# publications

title: Effects of Psilocybin on Anxiety and Psychosocial Distress in Cancer Patients
authors: NYU Langone Health
journal: ClinicalTrials.gov
publication_date: 2020-10-19
source_url: https://clinicaltrials.gov/study/NCT00957359
keywords: Cancer, Psilocybin, 4-phosphoryloxy-N,N-dimethyltryptamine, Niacin, COMPLETED
substance_tags: psilocybin
study_type: Review Article
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT00957359","overall_status":"COMPLETED","phase":["EARLY_PHASE1"]}
abstract:
The primary objective of this double-blind, placebo-controlled pilot study is to assess the efficacy of psilocybin administration (4-phosphoryloxy-N,N-dimethyltryptamine), a serotonergic psychoactive agent, on psychosocial distress, with the specific primary outcome variable being anxiety associated with cancer. Secondary outcome measures will look at the effect of psilocybin on symptoms of pain perception, depression, existential/psychospiritual distress, attitudes towards disease progression and death, quality of life, and spiritual/mystical states of consciousness. In addition, a secondary objective of the study is to determine the feasibility of administering psilocybin to this patient population, with regards to the following issues: safety, patient recruitment, consent for treatment, and retention. The duration of the proposed investigation will be long enough to administer the drug one time to each of thirty-two patients and to conduct follow-up assessments. This study is separate but similar to a recently completed study at the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, run by a psychiatrist, Dr. Charles Grob. Although the outcomes measures would be similar to those used as in the Grob study, the proposed dose of psilocybin is higher at 0.3mg/kg and the total subjects for the study would be 32 instead of 12. The study utilizes a cross-over design at 7 weeks and includes prospective follow-up of 6 months duration. This study has been approved by the Bellevue Psychiatry Research Committee, the NYU Oncology PRMC Committee, the Food and Drug Administration (FDA) through the issuance of an IND (77,138), the New York University School of Medicine Institutional Review Board (NYU IRB), the Health and Hospitals Corporation (HHC)-New York University (NYU) Clinical Translational Science Institute (CTSI), the NYU Bluestone Center for Clinical Research, and the Drug Enforcement Agency (DEA) through the issuance of a schedule I license. It is hypothesized that a one time experience with psilocybin will occasion dramatic shifts in consciousness and awareness that will lead to short-term (ie hours to days) and long-term (up to 6 months in this study, following the administration of the second dosing, either psilocybin or placebo) improvement in anxiety, depression, and pain associated with advanced cancer. The exact mechanism of action is unclear but based on studies done in the 60's using serotonergic hallucinogens in patients with advanced cancer, improvements in anxiety levels, mood and pain were reported. However, a treatment model developed by the famous British psychiatrist Humphrey Osmond, offers one possibility. In this model, serotonergic hallucinogens' therapeutic mechanism lies in their ability to allow the individual to access novel dimensions of consciousness and their efficacy or lack thereof relies on whether a transcendent and mystical state of awareness is attained. Another possible mechanism relates to what Dobkin de Rios and Grob have described as 'managed altered states of consciousness,' where the power of suggestibility, occurring in a safe setting, allows one to transcend a particular state of consciousness (i.e. anxiety and depression associated with advanced illness) as a means to facilitate emotional discharge and to manage irreconcilable conflict.

topic_tags:
Depression,Anxiety,Chronic Pain,Mechanism of Action,Consciousness,Emotional Processing,Spirituality,Mystical Experience,Review Article,Cancer Patients,Safety


authors: University of Utah
journal: ClinicalTrials.gov
publication_date: 2024-11-11
source_url: https://clinicaltrials.gov/study/NCT05557643
keywords: Depression, Burnout, Professional, Psilocybin, Mindfulness-Based Stress Reduction (MBSR), COMPLETED
substance_tags: psilocybin
topic_tags: Depression
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT05557643","overall_status":"COMPLETED","phase":["PHASE1"]}
title:
PAPR: Psilocybin-assisted Psychotherapy + Mindfulness-Based Stress Reduction (MBSR) for Front-line Healthcare Provider COVID-19 Related Burnout

abstract:
This project is an open-label randomized study looking at an 8-week Mindfulness-Based Stress Reduction (MBSR) curriculum vs. an 8-week MBSR curriculum + a group psilocybin-assisted psychotherapy intervention for frontline healthcare providers struggling with symptoms of depression and burnout associated with the SARS-CoV-2 pandemic. Following consenting and enrollment a total of 24 participants will be randomized to receive either an 8-week MBSR curriculum or the same 8-week MBSR curriculum + a group psilocybin-assisted psychotherapy intervention. The group psilocybin-assisted psychotherapy intervention will involve 3 group preparatory sessions (2 hours each), a single 8 hour group psilocybin administration session with a 1:1 therapist to participant ratio (25mg psilocybin dose), and 3 group integration sessions (2 hours each).


authors: University of Pennsylvania
journal: ClinicalTrials.gov
publication_date: 2026-05-31
source_url: https://clinicaltrials.gov/study/NCT06810310
keywords: Opioid Use Disorder, Psilocybin (high dose), psilocybin (low dose), RECRUITING
substance_tags: psilocybin
topic_tags: Addiction,Brain Imaging,Mechanism of Action
study_type: Other
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT06810310","overall_status":"RECRUITING","phase":["PHASE2"]}
title:
Psilocybin: Capturing Brain Mechanisms of Motivation and Neurocognition in Individuals With Opioid Use Disorder

abstract:
The goal of this study is to test addiction-related brain circuitry (motivation/reward and inhibition) as well as neurocognitive circuitry prior to and following low or high dose psilocybin (PEX010 from Filament). Using fMRI, we will examine brain circuits relevant to drug relapse as well as neurocognitive flexibility circuits in individuals with opioid use disorder. We will randomize 24 males and females, aged 18 - 60, in the greater Philadelphia area, to either 1mg or 25 mg of psilocybin. Participants will come to our offices for screening visits - these are assessments, interviews, and some medical tests (such as a history and physical, as well as a fasting blood draw) to help us determine eligibility for our study. If eligible, they will be brought to our offices at 3535 Market Street in Philadelphia for about 7 visits. These visits include pre-dose psilocybin preparation therapy, baseline assessments and neuropsychological testing, psilocybin dosing, post dose therapy visits, and post dose assessments.


authors: University of California, Berkeley
journal: ClinicalTrials.gov
publication_date: 2025-10-20
source_url: https://clinicaltrials.gov/study/NCT05265546
keywords: Perception Disorders, Psilocybin, RECRUITING
substance_tags: psilocybin
topic_tags: Brain Imaging,Mechanism of Action,Aging
study_type: Other
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT05265546","overall_status":"RECRUITING","phase":["PHASE1"]}
title:
Investigating the Mechanisms of the Effects of Psilocybin on Visual Perception and Visual Representations in the Brain

abstract:
The long-term objective of this project is to characterize how psilocybin affects visual perception and the brain's representation of the visual environment. It is known that psilocybin alters aspects of visual perception, but the underlying brain mechanisms contributing to these effects are poorly understood. The proposed work will address these questions in a large, diverse sample of healthy human subjects by using functional magnetic resonance imaging (fMRI) to measure the brain's responses to visual stimuli. The proposed research will document which brain areas mediate the effects of psilocybin. The technique of fMRI will be employed to measure brain activity in different brain areas while subjects are performing a visual perceptual task.


authors: Optimi Health Corporation
journal: ClinicalTrials.gov
publication_date: 2023-03-19
source_url: https://clinicaltrials.gov/study/NCT05252598
substance_tags: psilocybin,psilocin
topic_tags: Depression,Anxiety,Microdosing,Wellbeing,Safety,Toxicity
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT05252598","overall_status":"WITHDRAWN","phase":["EARLY_PHASE1"]}
title:
Mood and Cognitive Effects of Low Doses of Psilocybin Observed in Healthy Subjects ("MELO"): A Blinded, Placebo-Controlled, Dose-Finding Study

abstract:
This study is seeking to find the optimal microdose or low dose of psilocybin (magic mushrooms) that provides general enhancements to mood, memory, sleep, and other measures of general well-being without any hallucinogenic effects. Psilocybin is a natural psychoactive alkaloid component of more than 200 species of naturally growing mushrooms that can be found throughout the world. Psilocybin use as a ceremonious ritual has been well documented in ancient Aztec and Mesoamerican history. Psilocybin was chemically isolated and synthesized in the 1950s by American scientists, who found that mushroom varieties offered varying ranges of natural psilocybin (from 0.2-1% of dry weight). The psychological benefits of psilocybin are well-documented, as are the safety profile, low toxicity, and significant lack of abuse or overdose potential in comparison to other scheduled and non-scheduled drug, including alcohol. Many clinical studies demonstrate the benefit of psilocybin on feelings of depression, mood, and overall feelings of well-being, particularly at higher doses greater than 25mg. At these doses, hallucinations and psychedelic effects also occur. A growing body of evidence suggests that extremely low doses, or microdoses, may offer similar psychological benefits to individuals without any hallucinogenic effect that may impair daily function. The purpose of this study is to examine an optimal small/microdose of psilocybin, taken orally, that may provide such benefits. Optimi,is committed to providing MELOCIN, an oral, pharmaceutical grade, but naturally derived, mushroom powder (Psilocybe cubensis), containing a specific dose of psilocybin and a controlled range of other natural compounds and excipients within the formulation. Clinical studies will inform the desired low to very low psilocybin dosing range for specific indications which do not elicit any psychedelic effects but are correlated to specific mood and cognition-related enhancements or improvements in otherwise healthy individuals. Primary objective: To assess the safety and tolerability of varying low doses and microdoses of Optimi psilocybin-containing mushroom powder in healthy humans. Secondary objective: To assess the magnitude of effects of varying low doses and microdoses of Optimi psilocybin-containing mushroom powder on general mood, physiological responses, cognitive performance, focus, and feelings of anxiety. Methodology: Double-blind, randomized, placebo-controlled trial examining effects of six oral doses of MELOCIN, a psilocybin-containing Psilocybe cubensis mushroom powder, with 0 (placebo), 1, 2, 5, 8 and 10mg of psilocybin, administered on six separate test days in a randomized fashion. Participants will be randomized to the order that doses are administered. Study days will be scheduled 6-9 days apart to avoid any carry-over effects of a previous dose. Each study day will require ingestion of 10 capsules, which will be a combination of placebo and Psilocybe cubensis powder containing the prescribed daily dose. On the placebo study day, participants will digest 9 placebo capsules and one Chaga mushroom (non-active, non-hallucinogenic) capsule such that the mushroom after-taste commonly present with hallucinogenic magic mushrooms is mimicked and still present to preserve the blinding of the study dosing regimen. Participants will be scheduled for 7 total weekly visits (6 dosing days, 1 follow up/close out visit) at the study clinic, each estimated to be 8-9 hours in duration. At each weekly study visit, participants will be continuously monitored and asked to complete cognitive, mood, and other psychological questionnaires and provide minimal blood work at 80-105 mins, 2.5 hrs, 5 hrs, and 7.5hrs post-drug administration in order to monitor the physiological and psychological effects of the dose provided that day. At the follow-up visit, final questionnaires will be completed and qualitative feedback on the experience will be collected

keywords:
Mood Disturbance, Mood Change, Sleep Disturbance, Drug Effect, Psychedelic Experiences, Health, Subjective, Psilocin Toxicity, Psilocybin Toxicity, Psilocybin Causing Adverse Effects in Therapeutic Use, Anxiety, Psilocybin, Melocin, Inonotus Obliquus Whole Extract, Chaga, WITHDRAWN


authors: Section for Affective Disorders; Northern Stockholm Psychiatry
journal: ClinicalTrials.gov
publication_date: 2024-04-18
source_url: https://clinicaltrials.gov/study/NCT04630964
keywords: Major Depressive Disorder, Depression, Psilocybin, Niacin, COMPLETED
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Neuroplasticity,Brain Imaging,Aging,Clinical Trial,Healthy Volunteers,Safety
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT04630964","overall_status":"COMPLETED","phase":["PHASE2"]}
title:
The Effect of Psilocybin on MDD Symptom Severity and Synaptic Density - A Single Dose Randomized, Double Blind, Placebo- Controlled Phase 2 Positron Emission Tomography Study

abstract:
PROTOCOL SYNOPSIS Title The effect of psilocybin on Major depressive disorder (MDD) symptom severity and synaptic density - a single dose randomized, double blind, placebo-controlled phase 2b positron emission tomography study Study Code PSIPET Name of Sponsor SLSO Organisationsnr: 232100-0016 Sponsor representative: Andreas Carlborg Norra Stockholms Psykiatri Vårdvägen 3 112 19 Stockholm Sweden Medical Monitor Inspira Medical AB Phase of Study Phase 2b Sample Size 30 randomized Name of Investigational Product (IP) Psilocybin, 3-\[2-(dimethylamino)ethyl\]-1H-indol-4-yl\] dihydrogen phosphate Name of Active Placebo Niacin EudraCT 2020-002790-94 Description of IP and Active Placebo PSIPET Protocol 5 200821 Page 14 Study Intervention Name: Psilocybin (active drug product) Niacin (active placebo product) Dosage formulation: One active capsule contains 25 mg of psilocybin One active placebo capsule contains 100 mg of niacin Capsule: Size 2 hydroxypropyl methylcellulose (HPMC), opaque Size 2 HPMC, opaque Unit dose strength: 25 mg 100 mg Route of Administration: Oral (solid dose) Oral (solid dose) Dosing instructions: One capsule administered with water One capsule administered with water Packaging and Labeling: Study Intervention will be provided in a high-density polyethylene (HDPE) bottle. Each bottle will contain one capsule (psilocybin or niacin) and will be labeled as required per Swedish requirement for blinded study. Study Description and Overview Thirty participants (males and females) ages 20 to 65 inclusive, who, at Screening, meet ICD-10 criteria for major depressive disorder (MDD), have a current depressive episode of at least 30-day duration, have a Screening Montgomery-Asberg Depression Rating Scale (MADRS) total score \>= 22 and meet all other inclusion/exclusion criteria will be randomized with a 1-to-1 allocation under double-blind conditions to receive a single 25 mg oral dose of psilocybin or a single 100 mg oral dose of niacin. Niacin will serve as an active placebo control that provides an acute physiological response (flushing) that is intended to aid in blinding of intervention allocation. All randomized participants will be included in the Full Analysis Set (FAS) population used in analyzing primary and secondary study endpoints. Only participants who meet depressive symptom severity criteria at web screening (MADRS self-rating (MADRS-S) score \> =19) and who do not show an unacceptably large degree of symptom improvement between the web screening and in-person screening (indexed by change in MADRS-S (improvement) 30% (MADRS representing web screening will be approximated to MADRS-S + 3) will be eligible for randomization. This is to minimize the risk for spontaneous remission before dosing. Participants deemed eligible following successful completion of all screening assessments including a structural Magnetic Resonance Imaging (MRI) examination will be determined as eligible. Eligible participants at Baseline will submit cerebrospinal fluid (CSF), submit blood samples, be examined with positron emission tomography (PET) and the radioligand \[11C\]UCB-J and receive one preparation session (see further below) to be eligible for randomization on Dosing (Day 0) to receive either psilocybin or niacin active-placebo. They will complete follow-up visits, including outcome measures assessments, on study Day 1, 8, 15, 42 and 365 (within corresponding visit windows). At day 15 the sampling of CSF, blood and \[11C\]UCB-J PET will be repeated. PSIPET Protocol 5 200821 Page 15 After day 42, all participants will be given follow-up visits at Norra Stockholms Psykiatri for up to one year after dosing, to study dedicated physicians or nurses at a frequency determined by the health care professional. If needed to reach/stay in remission, the participants will be provided antidepressant treatment in accordance with the regional guidelines for antidepressant treatment (https://psykiatristod.se/regionala-vardprogram/ depression). At least monthly the participants will be asked to provide on-line symptom rating data (via 1177.se). At the 365-day visit, symptoms will be evaluated using MADRS, Clinical Global Impression Improvement (CGI-I) and Severity (CGI-S) scales. After completing the study (one year or withdrawal), participants will be subject to standard care, including referral in accordance with regional guidelines. The study outcome measures will be used to assess depressive symptoms, clinical global functioning, functional disability, anxiety symptoms and health-related quality of life. Safety outcome measures will be collected at all assessment time points from the time of consent through the end of study. To enhance participant safety, the current study proposes to test psilocybin within a "set and setting" (SaS) protocol similar to the protocol that has been used in all modern studies of psilocybin in both diseased and normal healthy populations. The SaS protocol for this study includes: 1) a preparation with session Facilitators (licensed psychologists) prior to dosing; 2) administration of study medications in an aesthetically neutral room under the supervision of two Facilitators who are present throughout the session (with the exception of short, temporary allowances for facilitator breaks; e.g. bathroom breaks); and 3) three post-dose integration sessions during which participants are encouraged to discuss their intervention experience with the Facilitators. To evaluate the Facilitators' adherence to the study manual, and the role of Facilitators' and participants' in-session behaviors for treatment outcome, all five sessions in the trial with Facilitators present will be recorded. The SaS will be identical for those randomized to psilocybin or niacin active placebo. Study Duration The planned maximum study duration for each participant will be approximately one year, with variation primarily dependent on the length of the screening period, the number of days between baseline and dosing, and the visit windows provided for each post-dose assessment. For each participant, the study will be divided into two phases: Phase A or treatment phase (day 0 to and including day 42), and phase B or follow-up phase (day 43 -365). The primary objective of this study is to evaluate the efficacy of a single 25 mg oral dose of psilocybin for major depressive disorder (MDD) compared to an active placebo (niacin) in otherwise medically-healthy participants between the ages of 20 and 65, assessed as the difference between groups in changes in depressive symptoms. Primary Outcome Measure Change in blinded rater MADRS total score from Baseline to Day 8.


title: The Impact of Psilocybin on Pain in Fibromyalgia Patients: a Multicentre Trial.
authors: Maastricht University
journal: ClinicalTrials.gov
publication_date: 2025-09-14
source_url: https://clinicaltrials.gov/study/NCT06368492
keywords: Fibromyalgia, Psilocybin, Hypnosis script, RECRUITING
substance_tags: psilocybin
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT06368492","overall_status":"RECRUITING","phase":["NA"]}
abstract:
Rationale: Recent evidence shows that Lysergic Acid Diethylamide (LSD), even when administered in low, non-hallucinogenic doses, can produce analgesic effects and improve pain tolerance in a sample of healthy volunteers. Such results complement what was already observed with other serotonergic psychedelics such as psilocybin: survey studies and case series indicate that its use may lead to improvements in chronic pain conditions such as migraines, cluster headaches and phantom limb pain even at low, non-psychedelic doses. These effects have however not yet been investigated and confirmed in clinical populations under controlled experimental conditions. Fibromyalgia (FM) is a chronic condition characterised by widespread pain, hyperalgesia, anxiety, disturbed sleep patterns, impaired cognitive functioning and comorbid mood disorders. Most suggested therapies are only associated with small improvements in pain ratings and quality of life. Currently, there is no data concerning the effectiveness of serotonergic psychedelics in improving pain ratings in fibromyalgia patients. Objective: The present study will explore the effects that the administration of a placebo and 2 low psilocybin doses (5 mg or 10 mg) will have on pain perception in a group of fibromyalgia patients. Study design: The present study uses a double-blind, randomized, placebo-controlled design. All participants will receive a placebo and 2 doses of psilocybin (5 mg or 10 mg) and will undergo the Cold Pressor Test (CPT) and the Pain Pressure Threshold Task (PPT) o test its analgesic effects. Rationale: Recent evidence shows that Lysergic Acid Diethylamide (LSD), even when administered in low, non-hallucinogenic doses, can produce analgesic effects and improve pain tolerance in a sample of healthy volunteers. Such results complement what was already observed with other serotonergic psychedelics such as psilocybin: survey studies and case series indicate that its use may lead to improvements in chronic pain conditions such as migraines, cluster headaches and phantom limb pain even at low, non-psychedelic doses. These effects have however not yet been investigated and confirmed in clinical populations under controlled experimental conditions. Fibromyalgia (FM) is a chronic condition characterised by widespread pain, hyperalgesia, anxiety, disturbed sleep patterns, impaired cognitive functioning and comorbid mood disorders. It has high direct and indirect costs and it is considered challenging to treat. Most suggested therapies, in fact, are only associated with small improvements in pain ratings and quality of life. Currently, there is no data concerning the effectiveness of serotonergic psychedelics in improving pain ratings in fibromyalgia patients. Objective: The present study will explore the effects that the administration of a placebo and 2 low psilocybin doses (5 mg or 10 mg) will have on pain perception in a group of fibromyalgia patients. Study design: The present study uses a double-blind, randomized, placebo-controlled design. All participants will receive a placebo and 2 doses of psilocybin (5 mg or 10 mg) and will undergo the Cold Pressor Test (CPT) and the Pain Pressure Threshold Task (PPT) o test its analgesic effects. Study population: 35 fibromyalgia patients aged 18 to 65 years. Intervention: Placebo, 5 mg or 10 mg of psilocybin in randomized order. Main study parameters/endpoints: Primary outcomes will be subjective and objective measures of pain perception. Secondary measures will assess the effects that placebo and psilocybin will have on mood, cognition and psychedelic experience. Finally, participants will take part to an additional CPT after receiving hypnotic suggestions of analgesia to test whether such intervention may moderate pain ratings of individuals who took small doses of psilocybin. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Participants will visit the research lab 5 times during 5 weeks. Before the first study day, subjects will come for a screening visit during which they will also be familiarized with tests and study procedures. This includes a medical screening by a licensed physician (medical history review, laboratory screening, electrocardiogram recording). The study visits will consist of taking the study treatment (5 mg or 10 mg of psilocybin or placebo), taking part to the experimental tasks, taking blood samples, completing computer tasks and filling out questionnaires. Finally, participants will take part to a final online visit to administer post-study questionnaires.

topic_tags:
Anxiety,Chronic Pain,Headache / Migraine,Review Article,Case Report,Observational Study,Healthy Volunteers,Safety


authors: University of Colorado, Denver
journal: ClinicalTrials.gov
publication_date: 2026-04-20
source_url: https://clinicaltrials.gov/study/NCT06430541
keywords: Breast Cancer, Ovarian Cancer, Psilocybin, RECRUITING
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Clinical Trial,Observational Study
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT06430541","overall_status":"RECRUITING","phase":["PHASE1"]}
title:
Study of Psilocybin Assisted Psychotherapy to Address Fear of Recurrence in Patients Diagnosed With Early-stage Breast Cancer and Ovarian Cancer in Remission

abstract:
The goal of this clinical trial is to test whether psilocybin along with therapy in women with early breast cancer and ovarian cancer in remission can improve their fear of recurrence. The main question\[s\] it aims to answer \[is/are\]: Does psilocybin assisted therapy improve fear of cancer recurrence? Does psilocybin assisted therapy improve anxiety, depression, and quality of life? Participants will complete a series of survey measures, participate in preparatory therapy. After prep therapy is complete, they will receive a moderately high dose of psilocybin in a monitored and supportive environment. After the dosing day, they will complete 4 sessions of integrative therapy and complete survey measures.


authors: Yvan Beaussant, MD, MSci
journal: ClinicalTrials.gov
publication_date: 2025-12-15
source_url: https://clinicaltrials.gov/study/NCT06001749
substance_tags: psilocybin
topic_tags: Addiction,End-of-Life Distress,Chronic Pain,Receptor Pharmacology,Clinical Trial,Safety
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT06001749","overall_status":"RECRUITING","phase":["PHASE2"]}
title:
Feasibility Phase 2 Study of Psilocybin-Assisted Therapy for Opioid-Refractory Pain in Patients With Advanced Cancer

abstract:
The overall objective of this study is to assess the feasibility, safety and preliminary efficacy of psilocybin-assisted therapy to alleviate opioid-refractory pain in patients with advanced-cancer. The name of the study intervention used in this research study is: Psilocybin (a tryptamine derivative) This study is a phase 2 open label, single center, concurrent mixed-methods trial to assess the feasibility of a novel palliative-care informed psilocybin-assisted psychotherapy regimen to alleviate opioid-refractory pain in patients with advanced-cancer. Psilocybin works on the serotonin system in the brain which is linked to the regulation of mood, motivation and impulse control. Psilocybin is an "Investigational" drug, meaning that the study drug has not been approved by the U.S. Food and Drug Administration (FDA) as a treatment for any disease. However, investigators have permission from the FDA to use this drug in this research study. The research study procedures include screening for eligibility, an electrocardiogram, blood tests, and the study intervention includes preparation, evaluations, one psilocybin session and follow up visits. Participants will be followed for up to 12 weeks (approximately 3 months) after receiving the study treatment. It is expected that about 15 people will take part in this research study. Filament Health is supporting this research study by providing the study investigational medication, psilocybin. Cy Biopharma and Pancreatic Cancer North America are supporting this research study by providing funding.

keywords:
Opioid-Related Disorders, Pain Management, Pain Management and Care, Advanced Cancer, Advanced Cancers, Psilocybin, RECRUITING


authors: Brugmann University Hospital
journal: ClinicalTrials.gov
publication_date: 2024-08-06
source_url: https://clinicaltrials.gov/study/NCT06160232
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Addiction,Neuroplasticity,Mechanism of Action,Biomarkers,Clinical Trial,Safety
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT06160232","overall_status":"RECRUITING","phase":["PHASE2"]}
title:
Psilocybin-Assisted Therapy for Severe Alcohol Use Disorder: Feasibility, Clinical Efficacy & (Neuro)Cognitive Mechanisms

abstract:
Psilocybin-Assisted Therapy for Severe Alcohol Use Disorder: Protocol for a Double-Blind, Randomized, Placebo-Controlled, 7-month Parallel-Group Phase II Superiority Trial A substantial proportion of patients with alcohol use disorder does not respond to available treatments, which calls for the development of new alternatives. In parallel, psilocybin-assisted therapy for alcohol use disorder has recently yielded promising preliminary results. Building on extant findings, the proposed study aims to determine the feasibility and preliminary clinical efficacy of psilocybin-assisted therapy as a complementary intervention during inpatient rehabilitation for severe alcohol use disorder, and to characterize associated changes in the two key neurocognitive systems identified by dual-process models of addiction. In this double-blind, randomized, placebo-controlled, 7-month parallel-group phase II superiority trial, 62 participants aged 21-64 years will be enrolled to undergo psilocybin-assisted therapy within the context of a 4-week inpatient rehabilitation for severe alcohol use disorder. The experimental group will receive a high dose of psilocybin (30 mg), whereas the control group will receive an active placebo dose of psilocybin, both within the context of a brief standardized psychotherapeutic intervention. The primary clinical outcome is the between-group difference in terms of the change in percentage of heavy drinking days from baseline to four weeks post-hospital discharge, whilst safety and feasibility metrics will also be reported as primary outcomes. Key secondary assessments include between-group differences in terms of changes in 1) drinking behavior parameters up to six months post-hospital discharge, 2) phosphatidyl-ethanol blood concentration, an objective biomarker of alcohol consumption, 3) symptoms of depression, anxiety, trauma, and global functioning, 4) neuroplasticity and key neurocognitive mechanisms associated with addiction, 5) psychological processes and alcohol-related parameters.

keywords:
Severe Alcohol Use Disorder, Psilocybin (high dose), Active placebo (low dose of psilocybin), RECRUITING


authors: Gabriella Gobbi
journal: ClinicalTrials.gov
publication_date: 2026-02-24
source_url: https://clinicaltrials.gov/study/NCT07433452
keywords: Healthy Participants, Placebo - Control, Psilocybin, Psilocybin (drug), Placebo, NOT_YET_RECRUITING
substance_tags: psilocybin,psilocin
topic_tags: Brain Imaging,Receptor Pharmacology,Biomarkers,Healthy Volunteers
study_type: Other
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT07433452","overall_status":"NOT_YET_RECRUITING","phase":["PHASE1"]}
title:
The Effects of Psilocybin in Healthy Volunteers: Psychological, Biochemical and Electrophysiological Biomarkers.

abstract:
In this study, participants will received either psilocybin (the active ingredient found in certain mushrooms) or an inactive placebo (a look-alike tablet with no active drug). The psilocybin is supplied by Filament Health (Burnaby, British Columbia). After psilocybin ingestion, the body quickly converts it into psilocin, which is the form that produces the temporary psychological effects. Psilocin mainly works by interacting with serotonin receptors in the brain, especially a type called the 5-HT2A receptor. This study will be done in healthy volunteers using a single oral dose of 25 mg (one tablet by mouth), consistent with doses used in previous clinical research. The goal is to understand the biological, psychological, and high-density EEG (hd-EEG) changes that can happen after a one-time dose of psilocybin.


authors: Brigham and Women's Hospital
journal: ClinicalTrials.gov
publication_date: 2026-06-14
source_url: https://clinicaltrials.gov/study/NCT07296094
keywords: Alcohol Use Disorder, Psilocybin, NOT_YET_RECRUITING
substance_tags: psilocybin
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT07296094","overall_status":"NOT_YET_RECRUITING","phase":["PHASE2"]}
title:
Psilocybin-Assisted Psychotherapy for the Treatment of Severe Alcohol Use Disorder: A Double-Blind, Dose-Comparison Concurrent Control Randomized Trial

abstract:
This study aims to determine the safety and preliminary efficacy of psilocybin-assisted psychotherapy in improving alcohol-related outcomes among adults with severe alcohol use disorder in a a double-blind, dose-comparison concurrent control, randomized trial. Participants will undergo structured psychotherapy and will be randomized to two psilocybin sessions to receive either a full dose (30mg or 40mg) or low dose (10mg or 15mg). This study is a double-blind, dose-comparison concurrent control randomized trial designed to evaluate the effects of psilocybin-assisted psychotherapy on alcohol-related outcomes, neurocognitive processes related to craving and stress, and neural circuits involved in reward and regulation among adults with severe alcohol use disorder (AUD). Participants are recruited up to 3 months after completing inpatient alcohol withdrawal treatment to ensure medical stabilization prior to psilocybin administration. The study examines both preliminary efficacy and safety while also exploring mechanistic pathways through behavioral assessments and functional neuroimaging. Participants (N=36) are randomized in a 1:1 ratio to receive either a full-dose psilocybin (30 mg, with option to escalate to 40 mg on the second session) or a low-dose (10 mg, with option to escalate to 15 mg on the second session). All participants complete two dosing sessions spaced four weeks apart. The psychotherapy is delivered by a dyad of trained therapists before, during, and after the dosing sessions and is based on established therapeutic frameworks used in prior psilocybin-assisted therapy trials. The aim of the therapeutic support is to prepare participants for the psilocybin experience, facilitate psychological processing during and after dosing, and support integration of insights into daily life. A peer recovery coach is integrated into the study to support relapse prevention, enhance coping skills, and encourage engagement in ongoing addiction treatment. All participants are offered follow-up services at the institution's outpatient addiction treatment program (including the BWH Bridge Clinic), regardless of study arm. This combination of medical oversight, psychotherapy, and recovery support reflects an effort to embed the intervention within real-world addiction care settings. Alcohol-related outcomes are assessed repeatedly from baseline through 48 weeks after the second dosing session. The primary clinical outcome is the percentage of heavy drinking days during the 24-week follow-up period, measured using Timeline Follow-Back. Secondary alcohol outcomes include drinking quantity and frequency, relapse timing, direct alcohol biomarkers (phosphatidylethanol and ethylglucuronide), withdrawal symptoms, treatment expectancy, blinding integrity, and quality of life measures. Additional exploratory outcomes assess peer support engagement and 12-step attendance. Safety is evaluated throughout the study using structured assessments of adverse events, vital signs, and mood and anxiety symptoms. Because participants have severe AUD and recent withdrawal treatment, careful medical screening is conducted prior to each dosing session. The study includes multiple follow-up assessments up to 48 weeks after the second psilocybin dose, allowing characterization of both acute and longer-term safety. Two mechanistic components are incorporated. First, neurocognitive tasks assess cue-induced craving, attentional bias, stress reactivity, delayed discount, decision making, and distress tolerance. These measures evaluate whether psilocybin influences cognitive and affective processes known to contribute to alcohol use and relapse. Second, participants complete two fMRI scans-first within one week prior to the first dosing session and the second within one week after the second dosing session. The fMRI tasks evaluate neural response to alcohol-related cues and the ability to down-regulate craving, focusing on the nucleus accumbens (NAcc) and dorsolateral prefrontal cortex (DLPFC). Connectivity analyses examine changes in functional coupling between these regions during alcohol cue processing. Together, these approaches allow the study to evaluate whether full-dose psilocybin, compared to low-dose, produces greater reductions in heavy drinking and craving, whether the treatment is safe and tolerable for individuals with severe AUD, and whether changes in cognitive, emotional, and neural functioning help explain clinical outcomes. By recruiting individuals immediately following inpatient detoxification, the study also examines the feasibility of incorporating psilocybin-assisted therapy into a critical window of early recovery. Results will inform whether a larger, fully powered clinical trial is justified and will contribute to the broader understanding of psilocybin's therapeutic potential in alcohol use disorder.

topic_tags:
Anxiety,Addiction,Brain Imaging,Mechanism of Action,Biomarkers,Aging,Emotional Processing,Clinical Trial,Safety,Adverse Events


authors: University Hospital, Basel, Switzerland
journal: ClinicalTrials.gov
publication_date: 2021-04-26
source_url: https://clinicaltrials.gov/study/NCT03604744
keywords: Healthy, LSD, Psilocybin, COMPLETED
substance_tags: psilocybin,psilocin
topic_tags: Brain Imaging,Receptor Pharmacology,Consciousness,Aging
study_type: Other
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT03604744","overall_status":"COMPLETED","phase":["EARLY_PHASE1"]}
title:
Direct Comparison of Altered States of Consciousness Induced by LSD and Psilocybin in a Random-order Placebo-controlled Cross-over Study in Healthy Subjects

abstract:
LSD (lysergic acid diethylamide) and psilocybin (the active substance in "magic mushrooms") are widely used for recreational purposes. Both substances are also increasingly used in psychiatric and psychological research to induce and investigate alterations in waking consciousness and associated brain functions (functional brain imaging, "model psychosis"). However, it has never been studied whether there are differences in the alterations in mind produced by these two substances. Both LSD and psilocybin are thought to induce hallucinations primarily via stimulation of the 5-HT2A receptor. However, there are differences in the receptor activation profiles between the two substances that may also induce different subjective effects. LSD potently stimulates the 5-HT2A receptor but also 5-HT2B/C, 5-HT1 and D1-3 receptors. Psilocin (the active metabolite of the prodrug psilocybin) also stimulates the 5-HT2A receptor but additionally inhibits the 5-HT transporter. In contrast to LSD, psilocybin has no affinity for D2 receptors. Both substances are used in neuroscience as pharmacological tools. However, there are no modern studies comparing these two substances directly within the same clinical study and research subjects and using validated psychometric tools. Therefore, the investigators will compare the acute effects of LSD, psilocybin and placebo.


title: A Double-Blind Trial of Psilocybin-Assisted Treatment of Alcohol Dependence
authors: NYU Langone Health
journal: ClinicalTrials.gov
publication_date: 2022-11-07
source_url: https://clinicaltrials.gov/study/NCT02061293
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Addiction,Spirituality,Safety
study_type: Other
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT02061293","overall_status":"COMPLETED","phase":["PHASE2"]}
abstract:
Several lines of evidence suggest that classic hallucinogens such as psilocybin can facilitate behavior change in addictions such as alcohol dependence. The proposed investigation is a multi-site, double-blind active-controlled trial (n = 180, 90 per group) contrasting the acute and persisting effects of psilocybin to those of diphenhydramine in the context of outpatient alcoholism treatment. Two to four sites will participate in this study. Aims of the study are 1) to characterize the acute effects of PO psilocybin 25 mg/70 kg, 30 mg/70 kg, and 40 mg/70 kg in alcohol dependent patients; 2) to evaluate the effect of psilocybin treatment on drinking outcomes for 32 weeks after the first administration, relative to diphenhydramine control; 3) to test whether or not characteristics of the drug administration session experiences mediate effects of psilocybin on short-term (1 week) persisting effects and post-session drinking behavior, 4) to evaluate the explanatory value of changes in alcohol craving, self-efficacy, motivation, and other psychological domains in accounting for the observed experimental effect of psilocybin relative to diphenhydramine control, and 5) to evaluate pre-post changes in drinking in participants after they receive psilocybin in the third session. The total duration of psychosocial treatment in the double-blind period will be 12 weeks, and double-blind drug administration sessions will occur after 4 and 8 weeks. In the first psilocybin session, a dose of 25 mg/70 kg will be administered. Depending on the response in the first session, the dose for the second session may be increased to 30 mg/70 kg or 40 mg/70 kg, or held at 25mg/70kg. The dose of diphenhydramine will start at 50 mg, and may be increased to 100 mg or held at 50 mg in the second session, depending on response in the first session. Following completion of the double-blind period (34 weeks after randomization) all participants who meet interim safety criteria will be offered an additional session in which psilocybin will be administered. The drug will be administered during 8-hour sessions in an outpatient setting under close medical and psychiatric monitoring. The drug administration sessions will occur in the context of an extended version of Motivational Enhancement Therapy (Motivational Enhancement and Taking Action, META) with the addition of standardized preparation before and debriefing and follow-up after the psilocybin administration sessions. Extensive screening and baseline assessment will be completed, including thorough safety screening and assessment of participant characteristics that could potentially moderate treatment response. Within-session and short-term persisting effects will be assessed. Drinking outcomes and changes in several potential mediators of treatment effect, including motivation, self-efficacy, craving, depression, anxiety, and spiritual dimensions of the experience, will be measured until 50 weeks after the first drug administration session, for a total of 54 weeks from the initiation of treatment.

keywords:
Alcohol Dependence, Psilocybin, Diphenhydramine, Motivational Enhancement and Taking Action (META), COMPLETED


title: Psilocybin-Assisted vs Ketamine-Assisted Psychotherapy for Alcohol Use Disorder
authors: Peggy C Nopoulos
journal: ClinicalTrials.gov
publication_date: 2025-11-16
source_url: https://clinicaltrials.gov/study/NCT05421065
keywords: Alcohol Use Disorder, Psilocybin, Ketamine, ACTIVE_NOT_RECRUITING
substance_tags: psilocybin
topic_tags: Addiction
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT05421065","overall_status":"ACTIVE_NOT_RECRUITING","phase":["PHASE2"]}
abstract:
This pilot study will collect preliminary data that measures the effects of psilocybin-assisted psychotherapy vs ketamine-assisted psychotherapy on patients struggling with alcohol use. This pilot study will be a double blind, randomized, active-comparator controlled trial with two study arms. Subjects randomized to Arm 1 (n=10) will receive individual psychotherapy sessions plus a 25mg dose of psilocybin, while Arm 2 subjects (n=10) will receive individual psychotherapy sessions and a 200mg dose of ketamine. Psychotherapy sessions will involve integrative psychotherapy modalities. At baseline, subjects will be consented, randomized into one of the two arms, complete psychiatric and medical evaluations, and will undergo an MRI scan. The first two therapy sessions (week 1 and week 2) will be used to learn about the participant's life story, engage the patient, and evoke their reasons for wanting to change their pattern of alcohol use. At week 3, participants will undergo a psilocybin-assisted therapy session or a ketamine-assisted therapy session. The last 2 psychotherapy sessions will be focused on integration of their experiences in the drug administration session and will include a second MRI scan and more assessments. Therefore, each arm receives 4 psychotherapy sessions, and the primary difference between the groups is which drug participants receive. After the psychotherapy sessions are completed at the end of week 4, subjects will be followed weekly for 4 weeks. At the last follow-up (week 8), they will undergo a third MRI scan and a final assessment. At the conclusion of the study, those randomized to the ketamine group will be offered a psilocybin-assisted therapy session, and two follow-up/integration sessions in an open-label extension. The open-label extension will also include an additional 4 weeks of follow-up.


title: Psilocybin vs Ketamine for Alcohol Use Disorder
authors: University of Iowa
journal: ClinicalTrials.gov
publication_date: 2025-11-27
source_url: https://clinicaltrials.gov/study/NCT06405607
keywords: Alcohol Use Disorder, Alcohol Dependence, Alcohol Abuse, Psilocybin, Ketamine, RECRUITING
substance_tags: psilocybin
topic_tags: Addiction
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT06405607","overall_status":"RECRUITING","phase":["PHASE2"]}
abstract:
This study will collect data that measures the effects of a psychedelic intervention on patients struggling with alcohol use disorder (AUD). The study design will be a double blind, randomized, active-comparator trial with two study arms. Subjects randomized to Arm 1 (n=40) will receive individual psychotherapy sessions plus a 30 mg dose of psilocybin. Arm 2 subjects (n=40) will receive individual psychotherapy sessions and a 0.75 mg/kg dose of ketamine.


authors: University of Sydney
journal: ClinicalTrials.gov
publication_date: 2024-06-09
source_url: https://clinicaltrials.gov/study/NCT06444243
keywords: Alcohol Use Disorder, Alcohol Dependence, Depression, Anxiety, Psilocybin, Niacin, UNKNOWN
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Addiction,Wellbeing,Clinical Trial,Randomized Controlled Trial,Safety
study_type: Randomized Controlled Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT06444243","overall_status":"UNKNOWN","phase":["PHASE2"]}
title:
A Multi-centre, Double-blinded, Placebo-controlled, Randomised, Phase II Clinical Trial for Psilocybin-assisted Therapy for Alcohol Use Disorder

abstract:
To explore the effectiveness of psilocybin-assisted therapy on reducing alcohol consumption in a double-blind, randomised, phase II clinical trial. New strategies for treating Alcohol Use Disorder (AUD) are urgently needed. Recent evidence has shown promising results for psychedelic-assisted therapies, particularly psilocybin, which has demonstrated efficacy in reducing alcohol consumption and improving psychological well-being. This study aims to evaluate the clinical efficacy and tolerability of psilocybin-assisted therapy compared to a control (niacin) in reducing heavy drinking days (HDD) per week among individuals with AUD. Primary Objective To conduct a double-blind, randomised controlled trial with 90 participants diagnosed with Alcohol Use Disorder (AUD). The primary aim is to compare the efficacy of psilocybin-assisted therapy (two sessions of psilocybin, 25 mg per dosing session) versus control (niacin 250mg) and therapy in reducing alcohol consumption, specifically measuring the number of heavy drinking days (HDD) per week. Secondary Objectives To compare the efficacy of psilocybin-assisted therapy versus control in improving the characteristics of AUD and addressing common comorbidities associated with AUD, including depression and anxiety. Study Design The trial will employ a double-blind, randomised, controlled design. A sample of 90 individuals with AUD will undergo 14 weeks of treatment, which includes 12 therapy sessions and 2 dosing sessions with either psilocybin (25 mg) or control (niacin 250mg). Participants will be assessed for changes in alcohol consumption patterns and improvements in symptoms of depression and anxiety.


title: Psilocybin-assisted Interpersonal Therapy for Depression
authors: University of Otago
journal: ClinicalTrials.gov
publication_date: 2025-04-08
source_url: https://clinicaltrials.gov/study/NCT05581797
keywords: Depressive Disorder, Treatment-Resistant, Psilocybin-assisted psychotherapy, COMPLETED
substance_tags: psilocybin
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT05581797","overall_status":"COMPLETED","phase":["NA"]}
abstract:
This is a single-arm, open-label interventional study of psilocybin-assisted interpersonal therapy for treatment resistant depression. 20 participants will be recruited to take part in this 8-week intervention that involves 8 sessions of psychotherapy and 2 doses of psilocybin. Study Design Interventional, Single arm, open label 1\. Hypotheses: 1. It is feasible to deliver Psilocybin treatment integrated into interpersonal therapy for people with treatment resistant major depression (TRD). 2. It is feasible to recruit patients with TRD for this treatment in New Zealand. 2\. Participants The study will recruit 20 participants who have a current diagnosis of Treatment resistant Major Depressive Disorder. The participants will need to agree to cease psychotropic medications including antidepressants as part of the preparation for psilocybin dosing. 3\. Recruitment Participants will be recruited by referral from mental health services, primary care and community advertisements. 4\. Screening Screening involves a two-step process: 1. Participants will register their interest via a secure online Redcap website that will ask questions regarding initial eligibility. Those who pass the initial online screening and consent to further assessment of eligibility will be screened via telephone and review of online health records to determine whether they meet major inclusion/exclusion criteria, and thus whether they are eligible for an in-person screening session. 2. In-person screening will include a history and physical examination, ECG, a 30 cc blood draw for study measures and medical screening, a personal and family medical history questionnaire, psychiatric /psychological assessments and urine drug and pregnancy tests. These will be performed by clinical staff in the Clinical Research Unit (CRU, University of Otago, Christchurch Whatu Ora Waitaha). 5\. Clinical assessment Psychiatric screening will be conducted by structured assessments Structured Clinical Interview for DSM Disorders (SCID), (mood and substance use sections) by the study team. After this screening potential participants will be clinically assessed by a consultant psychiatrist on the team, who will oversee participants care throughout the study and will liaise with the participants current health provider regarding the study, antidepressant discontinuation, clinical progress and any support required at the conclusion of the study. Psychoactive drug-use history, history of antidepressant treatments, and information about employment status and current functioning (including mood and psychological and psychosomatic symptoms) will be obtained. Participants will be required to refrain from illicit drug use during the course of the study, and a urine test will be conducted before each psilocybin dosing session (e.g., testing for various opioids, stimulants and sedatives). Pregnant or nursing women are ineligible; female participants will receive a urine pregnancy test at intake and before each drug session and must agree to use effective methods of contraception during the study. 6\. Informed consent process Written informed consent will be obtained at the Clinical Research Unit at the start of the in-person screening. 7\. Intervention The study intervention is described in detail in the Interpersonal Therapy (IPT)+ Psilocybin Manual and is modified from Yale Manual for Psilocybin-assisted Therapy of Depression and Protocol for 'Effects of Psilocybin therapy for major depressive disorder: randomized clinical trial'. The intervention involves 8 sessions of psychotherapy and two doses of psilocybin over 10 weeks and one follow-up session at 18 weeks in the Clinical Research Unit, Dept of Psychological Medicine, University of Otago, Christchurch. During the study period (week 0-9) the participants will be under the care of the consultant psychiatrists and clinical team at the Clinical Research Unit, this includes the planned weekly contact as well as provision of urgent care during hours (via a duty clinician and psychiatrist), and the Crisis Resolution Team (CDHB) after hours. Following screening and baseline measurements antidepressants will be gradually discontinued and Interpersonal Therapy (IPT) will be commenced in preparation for psilocybin dosing. Antidepressant discontinuation will follow clinical guidelines and will be supervised by consultant psychiatrist on the team, who will oversee participants care throughout the study. The discontinuation schedule is initial dropping of dose by half followed by tapering over 2-6 weeks. The 3 IPT preparation sessions are designed around the beginning phase of IPT (timeline of stressors and mood episodes, interpersonal inventory and identification of psychotherapy focus). The next sessions will involve psilocybin dosing and debriefing (2 psilocybin dosing sessions and 1 debriefing). This will be followed by 5 integration sessions of IPT. The IPT integration sessions will formulate the psilocybin experience within an IPT framework. IPT utilises emotional processing to facilitate change and it is anticipated this will be intensified in the psilocybin sessions. Consultant psychiatrists will review each participant after completing psychotherapy to assess participants' ongoing treatment needs, including recommencing antidepressant medication if needed and referral to specialist mental health service if required.

topic_tags:
Depression,Addiction,Emotional Processing,Clinical Trial,Review Article,Treatment-Resistant Depression,Healthcare Workers


authors: Medical University of Vienna
journal: ClinicalTrials.gov
publication_date: 2026-03-23
source_url: https://clinicaltrials.gov/study/NCT07490353
substance_tags: psilocybin
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT07490353","overall_status":"RECRUITING","phase":["PHASE1"]}
title:
Elucidating the Relevance of the Psychedelic Experience to Psilocybin's Anti-Anhedonic Effects: A Randomized, Open-Label, Cross-Over Functional Magnetic Resonance Imaging Trial

abstract:
The goal of this clinical trial is to systematically categorize potential prohedonic effects of psilocybin in patients with anhedonia in depression. The main questions it aims to answer are: Primary Objectives 1. Systematically categorize prohedonic effects (antianhedonic effects in patients with anhedonia in depression, increase in well-being in all participants). 2. Test effects of psilocybin on brain network complexity measures during the hedonic experience using fMRI as a correlate for prohedonic (anti-anhedonic and well-being increasing) effects. 3. Elucidate relevance of the psychedelic experience to these effects (clinical, behavioral, and imaging) in a pharmacological challenge using the 5-HT2A/D2 antagonist risperidone and extensive characterization of the psychedelic experience. Secondary Objectives 4. Test the differential effects of the psychedelic experience on fMRI paradigms measuring symptoms shown to be altered in anhedonia, more specifically reward processing and sexual arousal. 5. Test the relevance of neuroplasticity (BDNF) and inflammatory parameters to anti-anhedonic, well-being promoting, and brain network dynamic complexity effects. 6. Test the effects of the psychedelic experience on BDNF and inflammatory parameters. Researchers will compare the effects of psilocybin in two separate sessions (one with psilocybin alone, one with co-administration of risperidone) in both patients with depression and anhedonia and healthy control participants. Participants will: * Take 25 mg of psilocybin p.o. in two sessions, in one of the two sessions they will take 1 mg risperidone p.o. before ingestion of psilocybin, to block psilocybin's acute psychedelic effects. * Undergo 3 MRI sessions, one before the first psilocybin session ('baseline') and one session each on the day after each respective psilocybin session. * Perform a variety of tasks during each fMRI session to asses the treatment's effects on anhedonia.

keywords:
Depression - Major Depressive Disorder, Anhedonia, Psilocybin (Usona Institute), Psilocybin, Risperidone 1 MG, Risperidone, Risperdal, MRI, RECRUITING

topic_tags:
Depression,Neuroplasticity,Brain Imaging,Receptor Pharmacology,Aging,Wellbeing,Clinical Trial,Inflammation


title: Beyond the Self and Back: Neuropharmacological Mechanisms Underlying the Dissolution of the Self
authors: University of Zurich
journal: ClinicalTrials.gov
publication_date: 2020-11-03
source_url: https://clinicaltrials.gov/study/NCT03736980
keywords: Healthy, Placebo, Psilocybine, COMPLETED
substance_tags: psilocybin
topic_tags: Brain Imaging,Mechanism of Action,Aging,Mystical Experience,Healthy Volunteers
study_type: Other
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT03736980","overall_status":"COMPLETED","phase":["NA"]}
abstract:
The aim of the study is to identify neural signatures, behavioral and phenomenological expressions of self-related processes including: sense of agency, semantic distinction between self and other, selflessness (altruism), social agency, embodied self (interoception), perceptual functioning of dissolved self including hallucinations and crossmodal processing, and finally the mystical type dissolution of the self. Four placebo-controlled, double blind sets of procedures using psilocybin with four independent study groups will be conducted. The number of subjects, testing procedures and dose of psilocybin for each group are as follows: group 1 (20 subjects, EEG, questionnaires, 0.200 mg/Kg body weight), group 2 (30 subjects, functional magnetic resonance imaging (fMRI), questionnaires, 0.200 mg/Kg body weight), group 3 (10 subjects, fMRI, questionnaires, 0.215 mg/Kg body weight), study group 4 (80 subjects, blood serum and saliva parameters, questionnaires, fMRI (only in 20 subjects from this group), 0.315 mg/Kg body weight). The groups 1, 2 and 3 involve healthy volunteers. The group 4 involves healthy volunteer long-term and short-term meditators during a 5-day group meditation retreat. Together, 140 subjects will participate in the study.


authors: Cybin Therapeutics Inc.
journal: ClinicalTrials.gov
publication_date: 2023-07-05
source_url: https://clinicaltrials.gov/study/NCT05594667
substance_tags: psilocybin
topic_tags: Depression,Receptor Pharmacology
study_type: Other
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT05594667","overall_status":"WITHDRAWN","phase":["PHASE2"]}
title:
Evaluating the Effect of Length of Time on Selective Serotonin Reuptake Inhibitors (SSRIs) on the Response to Psilocybin-assisted Therapy in Individuals With Mild-moderate Major Depressive Disorder (MDD)

abstract:
This study is an open-label, single-arm, within-subjects design in individuals with mild-moderate Major Depressive Disorder (MDD). All participants will receive a single dose of 25mg of psilocybin in a therapeutic setting. In order to investigate the effects of length of time on SSRI therapy, 30 participants with varying lengths of time on SSRI therapy will be enrolled, stratified into four groups: * Group 1: ≤ 1 year * Group 2: 1 to ≤ 5 years * Group 3: 5 to ≤ 10 years * Group 4: \> 10 years The majority of clinical investigations with psilocybin to date either exclude participants on SSRIs or taper them off SSRIs prior to psilocybin administration. While evidence derived from the use of larger doses of psilocybin suggests that its predominately serotonergic effects are safe when administered in controlled settings, research investigating the effects of psilocybin with individuals taking SSRIs is lacking, despite the prevalent and chronic use of SSRIs in individuals with depression. The aim of this study is to investigate the effect of length of time on SSRIs on psilocybin-assisted therapy response in individuals with MDD. Specifically, this feasibility study investigates participants who undergo a single-dose of psilocybin (25mg) in combination with pre- and post-dose therapy sessions. The follow-up period in the present study is 12 weeks (3 months).

keywords:
Depression, Major Depressive Disorder, Mild Depression, Moderate Depression, Depressive Disorder, Psilocybin, PEX010, WITHDRAWN


title: Psilocybin for the Treatment of Major Depressive Disorder
authors: Washington University School of Medicine
journal: ClinicalTrials.gov
publication_date: 2024-07-24
source_url: https://clinicaltrials.gov/study/NCT05675800
keywords: Major Depressive Disorder, Psilocybin, WITHDRAWN
substance_tags: psilocybin
topic_tags: Depression,Mechanism of Action
study_type: Other
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT05675800","overall_status":"WITHDRAWN","phase":["PHASE2"]}
abstract:
The goal of this study is to assess the effectiveness of psilocybin for the treatment of Major Depressive Disorder and potential therapeutic mechanisms. Enrolled participants will receive a single active dose of psilocybin, or a dose considered high enough to treat depression, administered orally with accompanying psychological support.


title: Pharmacokinetics of Psilocybin in Normal Adult Volunteers
authors: University of Wisconsin, Madison
journal: ClinicalTrials.gov
publication_date: 2020-04-14
source_url: https://clinicaltrials.gov/study/NCT02163707
keywords: Healthy, Psilocybin, COMPLETED
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Pharmacology,Clinical Trial
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT02163707","overall_status":"COMPLETED","phase":["PHASE1"]}
abstract:
Psilocybin is a naturally occurring psychedelic compound produced by more than 200 species of mushrooms, collectively known as psilocybin mushrooms. Psilocybin (4-phosphoroyloxy-N,N-dimethyltryptamine) is a hallucinogenic tryptamine that was first isolated from Psilocybe mushrooms in 1957. The objective of this Phase I clinical trial is to determine the pharmacokinetics of oral doses of psilocybin in normal, healthy adults. The study is performed in support of Phase II and Phase III studies of psilocybin for the treatment of refractory anxiety associated with incurable cancer, as well as other possible indications. Psilocybin is at present not an FDA-approved drug. The primary objective of this clinical trial is to determine the pharmacokinetics of an extemporaneous oral formulation of psilocybin in normal, healthy adults. This study is intended to add to the existing body of modern clinical research on psilocybin to support future multi-institutional Phase III clinical trials seeking to decrease anxiety and depression in patients with incurable cancer. The long-term goal of this research is to submit a successful new drug application for psilocybin to the FDA. Subjects will initially take one 0.3 mg/kg (approximately 20mg/70kg) oral dose of psilocybin to initiate an eight hour chaperoned outpatient experience. After eight hours of outpatient sampling, the subject will be transported across the street to the UW Institute for Clinical and Translational Research Clinical Research Unit (ICTR CRU) for an overnight stay and additional blood and urine sampling. Pre- and post-treatment psychologic preparation and debriefing interviews will be required. A minimum of four weeks after the first dose, the subject will receive a second oral dose of psilocybin at the higher dose of 0.45 mg/kg (approximately 30 mg/70 kg). This dosing will again take place in an attended, structured setting with timed blood and urine samples obtained both in the School of Pharmacy (0-8 hours) and in the UW Clinical Research Unit (8-24 hours). A minimum of four weeks after the second dose, the subject will receive a third oral dose of psilocybin at the highest dose of 0.6 mg/kg (approximately 40 mg/70 kg). This dose will again take place in an attended, structured setting with timed blood and urine samples obtained both in the School of Pharmacy (0-8 hours) and in the UW Clinical Research Unit (8-24 hours). 12-lead ECGs will be obtained at specified time points before and during each treatment period. Throughout the duration of drug action for each dose participants will be attended by two trained monitors, and a physician will available during the entire 24 hour treatment and sampling period. Subjects who have been administered the first dose but decline to receive any subsequent doses will remain evaluable. At that time their active study participation will end.


authors: Jennifer Mitchell
journal: ClinicalTrials.gov
publication_date: 2026-06-07
source_url: https://clinicaltrials.gov/study/NCT07386730
substance_tags: psilocybin
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT07386730","overall_status":"RECRUITING","phase":["PHASE1"]}
title:
A Double Blind, Randomized Trial Investigating the Safety, Feasibility, and Mechanisms of Psychedelics in Healthy Older Adults With Low Well-being as Moderated by Biomarkers for Preclinical Alzheimer's Disease

abstract:
This study is being conducted to understand changes in brain activity following administration of two different drugs (Psilocybin and Dextromethorphan) in older adults with low well-being. The main questions it aims to answer are, does psilocybin: 1. Acutely increase complexity of EEG activity in older adults with low well-being, as modulated by the presence of biomarkers of Alzheimer's disease (AD) pathology. 2. Longitudinally decrease plasma markers of neuroinflammation, as modulated by the presence of biomarkers of AD pathology. 3. Explore longitudinal changes in autonomic physiology via wearable recording devices as well as longitudinal structural and functional brain changes measured in the MRI Participants will be in the study for up to 3 months, which will include 3 to 4 in person visits and 3 to 4 remote visits. Most visits will be between 1 to 3 hours, but the dosing visit will last a minimum of 8 hours and could be as long as 12 hours. During the dosing visit, all participants will receive a single dose of the study drugs and dosages listed below. Researchers will compare participants who receive the following drug options: * A low-to-moderate dose of Psilocybin (5-10 mg) * A moderate-to-high dose of Psilocybin (25-30 mg) * A low-to-moderate dose of Dextromethorphan (30-60 mg) * A moderate-to-high dose of Dextromethorphan (80-90 mg)

keywords:
Anhedonia in Healthy Volunteers, Older Adults (50-90 Years), Psilocybin (drug), Dextromethorphan (DXM), RECRUITING

topic_tags:
Brain Imaging,Mechanism of Action,Biomarkers,Aging,Wellbeing,Animal Study,Healthy Volunteers,Older Adults,Safety,Inflammation


authors: University Health Network, Toronto
journal: ClinicalTrials.gov
publication_date: 2024-10-17
source_url: https://clinicaltrials.gov/study/NCT06506019
keywords: Bipolar Depression, Psilocybin, Functional MRI, RECRUITING
substance_tags: psilocybin,psilocin
study_type: Randomized Controlled Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT06506019","overall_status":"RECRUITING","phase":["PHASE1"]}
title:
Neurobiological Effects of Psilocybin in Treatment Resistant Bipolar Depression: An Emotional-Processing fMRI Pilot Study

abstract:
This study is an open-label, single-arm, proof-of-concept study, wherein treatment resistant bipolar depression (TRBD) participants will receive one 25 mg dose of oral psilocybin accompanied by preparatory, monitoring, and integration psychotherapy sessions (psilocybin-assisted psychotherapy, or PAP). Using fMRI (functional magnetic resonance imaging), the findings of this study will provide data on the neurobiological mechanism of psilocybin in TRBD. The primary objective is to understand the dynamic role of amygdala activity by evaluating the neurobiological effects of a single psychedelic dose (25 mg) of oral psilocybin in individuals with a moderate to severe major depressive episode and a primary diagnosis of Bipolar II Disorder, with 2 or more failed treatment trials (i.e., treatment resistant bipolar depression \[TRBD\]). Neurobiological effects will be determined by evaluating the association between post-treatment right amygdala activity during the facial affect task (determined by fMRI one day after the psilocybin dose) and antidepressant effects (determined by changes in the Montgomery-Åsberg Depression Rating Scale \[MADRS\] scores over time, during the one-week period post-psilocybin dose). This is a single-arm, open-label clinical trial wherein all participants will receive the same study intervention. Hypothesis: Increased right amygdala activity on fMRI with emotional stimuli one day after psilocybin treatment will be associated with greater antidepressant effects in the one-week period post-treatment in individuals with TRBD. Individuals with bipolar disorder (BD) spend a third of their lives in the midst of a depressive episode. BD is a severe and persistent mental illness with a lifetime prevalence of 2-3%. Bipolar depression remains a significant treatment challenge, with a paucity of evidence-based treatments. Only four pharmacological treatments for acute bipolar depression (cariprazine, olanzapine-fluoxetine combination, quetiapine, and lurasidone) are approved by the US Food and Drug Administration (FDA). Other medications often used for the treatment of BD are those primarily used to treat mania or psychosis (i.e., lithium; antipsychotics) or major depressive disorder (MDD) (i.e., antidepressants). Lamotrigine, which is recommended by international guidelines as a maintenance treatment for BD to prevent depressive recurrence, has limited efficacy for acute BD. Current medication options are also limited by adverse effects, including renal and thyroid impairment with long-term lithium therapy and weight gain and metabolic abnormalities with atypical antipsychotics. Furthermore, treatment outcomes remain poor, particularly for depressive episodes, with over one-third of patients failing to respond to two or more first-line treatments. Hence, there is a clear need for novel and efficacious treatments for BD. However, there is a limited understanding of the neurobiology of BD, which poses as a major barrier to identifying truly innovative treatments. Psilocybin is a chemical compound that naturally occurs in certain species of mushrooms, (for example, in the psilocybe genus, among others). It belongs to a class of drugs referred to as "psychedelics". Psilocybin is a tryptamine which is chemically similar to the neurotransmitter, serotonin, and the essential amino acid, tryptophan. It is considered a 5-hydroxytrptamineric (serotonergic) psychedelic along with other similar drugs such as dimethyltryptamine (DMT) and lysergic acid dieythamide (LSD). Psilocybin is a product for the pharmacologically active ingredient psilocin, which readily crosses the blood-brain barrier and acts as a potential partial agonist at serotonin 5HT2A and 5HT2c receptors in the brain. Typical effects of psilocybin include significantly altered states of consciousness, experienced through visual and auditory effects, changes in perception, distortions of time; and a range of effects including a sense of awe, novel perspectives, existential and personal insight, dramatically heightened empathy and feelings of compassion, strong emotions, and unitive experience. With proper screening and preparation, psilocybin has a safe physiological and psychological profile. Psilocybin is currently the preferred compound for use in clinical research involving 5-hydroxytrptaminergic psychedelics because it has a shorter duration of action and suffers from less notoriety and stigma than other similar drugs. Two recently completed clinical trials have assessed the effects of psilocybin on TRD in participants with BDII. The first study was a non-randomized controlled trial that demonstrated a single 25 mg dose of psilocybin with accompanying PAP led to a decrease in MADRS scores in all study participants (n=15) at the 3-week primary endpoint. The second study was a randomized controlled trial that included participants with both unipolar (n=27) and bipolar treatment-resistant depression (n=4), wherein all participants received at least one 25 mg dose of psilocybin with accompanying PAP (with the exception of one participant who dropped out of the study before receiving the study intervention). Participants had the opportunity to receive up to two additional 25 mg doses of psilocybin with accompanying PAP, if they were eligible to receive a repeat dose as per the study protocol. Both trials demonstrated that 25 mg of psilocybin resulted in a decrease of depressive symptoms in participants with treatment-resistant bipolar depression, without increased incidence of manic or hypomanic symptoms. Beyond the clinical benefits observed, psilocybin has provided several new insights into the neurobiology of depression, with dozens of additional, ongoing mechanistic studies underway. Neuroimaging studies evaluating the effects of psilocybin in treatment-resistant (unipolar) depression (TRD) have provided surprising neurobiological insights that have called into question several assumptions of mood disorders. In an open-label TRD trial evaluating the antidepressant and neurobiological effects of psilocybin, increased activity of the right amygdala was observed in response to fearful and happy faces post-treatment. Psilocybin's antidepressant effects were associated with increased right amygdala responses to negative emotional stimuli, an opposite effect to previous findings with selective serotonin reuptake inhibitors (SSRIs). Wherein SSRIs mitigate negative emotions, psilocybin might allow patients to feel, confront and work through them. These findings also suggest that neurobiological targets and mechanisms required to alleviate TRD, may be different from non-resistant depression, where SSRIs are often effective by reducing amygdala response to negative stimuli. Notably, the impact of psilocybin on amygdala function varies inter-individually depending on baseline mood state. More specifically, in healthy volunteers, psilocybin has been shown to decrease amygdala response to emotional stimuli, whereas in TRD, psilocybin was associated with increased amygdala response. Evaluating the effects of psilocybin in TRBD may improve the investigator's understanding of the neurobiology of bipolar depression by dynamically evaluating altered amygdala function and associated changes in depressive symptoms over time.

topic_tags:
Depression,Brain Imaging,Mechanism of Action,Receptor Pharmacology,Consciousness,Aging,Emotional Processing,Clinical Trial,Randomized Controlled Trial,Healthy Volunteers,Treatment-Resistant Depression


authors: Beersheva Mental Health Center
journal: ClinicalTrials.gov
publication_date: 2025-11-18
source_url: https://clinicaltrials.gov/study/NCT04882839
keywords: Obsessive-compulsive Disorder, psychotherapy assisted psilocybin, RECRUITING
substance_tags: psilocybin,psilocin
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT04882839","overall_status":"RECRUITING","phase":["PHASE2"]}
title:
Open Label, Phase 2 Study for Evaluating the Feasibility, Safety and Efficacy of Psychotherapy Assisted Psilocybin for Treatment of Severe Obsessive Compulsive Disorder (OCD) in Drug and/or Psychotherapy Resistant Patients.

abstract:
Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder characterized by recurrent distressing thoughts and substantial anxiety, accompanied by repetitive behaviors or mental rituals. Individuals with OCD often have diminished quality of life, and functional impairment. The disorder cause high personal, societal and economic costs. Current available treatments for OCD show moderate response rate and high rate of symptom relapse. The purpose of the current study is to explore new alternative options for the treatment of OCD that can widely and continuously benefit patients. Specifically, The aim of this study is to investigate the feasibility, safety and efficacy of psychotherapy assisted psilocybin for treatment of severe OCD. Previous research has shown safety of treatment and high efficacy in reduction of anxiety and depression symptoms. However, only one study has evaluated the use of psilocybin for OCD patients. The protocol includes 15 therapeutic sessions, of which 12 are one-hour sessions for psychological preparation and integration, and three are eight hours' experiential sessions under the influence of psilocybin. The research will include 15 participants diagnosed with severe OCD, with at least one treatment failure. Assessments will be based on comparing ratings of the main outcome measure (Y-BOCS), at baseline, at the middle and at end of treatment. Other assessments will include data on side effects- to evaluate safety, and possible spiritual variables underlying change in symptoms via standardized questionnaires. Background and research rationale: Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder characterized by recurrent distressing thoughts and substantial anxiety, accompanied by repetitive behaviours or mental rituals performed to control or alleviate this anxiety. Individuals with OCD often have diminished quality of life, functional impairment, and cause substantial caregiver burden and personal and societal economic costs. Lifetime prevalence of OCD ranges between 1.9%-2.5%, with patients often not responding to the offered pharmacological or psychological treatment, and in extreme cases may even undergo neurosurgical interventions. There are several possible physiological mechanisms leading to the development of OCD, which may indicate several possible effective treatment options. Nowadays there is a consensus that the dopaminergic and serotonergic pathways are central to the development of the disorder with the basal ganglia as the main area of its origin. Other brain areas involved in OCD are the orbitofrontal cortex and anterior cingulate cortex which are connected to the basal ganglia and are involved in regulating attention and awareness. Abnormal activity between these areas and other subcortical areas might explain why normally unconscious information processing, becomes consciousness, and requires additional resources for its regulation. It has also been suggested that the aversive emotional activity (anxiety, fear, disgust) experienced in OCD, relates to hyperactivity in the amygdala. The momentary relief brought on by the compulsive behaviour forms a positive feedback which perpetuate the disorder. The gold standard of care for OCD today is a combination of selective serotonin reuptake inhibitors (SSRIs) and cognitive behavioural therapy (CBT). Most patients will experience at least some symptomatic relief with these interventions; however, relapse of symptoms occur in 40%-60% of patients and around 25% of patients are unresponsive to treatment. Other existing treatments (either pharmacological or neurosurgical) possess a higher risk for serious side effects. It is important to note that even for those patients who are responsive to treatment there are still significant residual, impairing symptoms. It thus seems that there is a real and immediate need to explore new alternative options for the treatment of OCD that can widely and continuously benefit patients, with lower risk and fewer side effects. A new and promising prospect of treatment in mental health is the use of psychedelic substances, which interact with the serotonergic pathways and induce a powerful subjective experience with the potential for psychological transformation. Specifically, psilocybin has received attention in research as a promising alternative in the treatment of severe mental illness. Psilocybin is a prodrug which is quickly converted by the body to psilocin (4-OH-dimethyltryptamine), a 5-HT2A receptor partial agonist. Both psilocybin and psilocin, which have psychoactive properties, are naturally occurring in Psilocybe mushrooms and are structurally similar to the endogenous neurotransmitter serotonin. As a direct 5-HT2A agonist, psilocybin has a unique therapeutic potential compared with other pharmacological treatment for OCD such as SSRIs. Animal studies have shown increased cognitive flexibility, associative learning, cortical plasticity, and anti-depressive effects in response to 5-HT2A activation. The first current clinical research with psilocybin examined the safety and efficacy of psilocybin in the treatment of psychological distress in patients with terminal advanced-stage cancer. The double-blind, placebo-controlled research was conducted in the Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center (Torrance, California). Researchers concluded that psilocybin is safe and well tolerated at 0.2 mg/kg dose. Following this research two different research groups, in Johns Hopkins University, and in New York University, have received FDA approval to administrate a higher dose of psilocybin in a similar clinical population. These trails have shown promising results for safety, psychological distress reduction, and significant improvement in anxiety and depression. In their research, Griffiths and colleagues, examined the efficacy of psilocybin in reducing anxiety and depression in 51 patients suffering from a terminal end-stage cancer and experiencing symptoms of anxiety and depression. This randomized, double-blind, cross-over trial investigated the effects of a very low (placebo-like) dose (1 or 3 mg/70 kg) vs. a high dose (22 or 30 mg/70 kg) of psilocybin. No serious adverse events attributed to psilocybin administration occurred. There were transient moderate increases in systolic and/or diastolic blood pressure after psilocybin (in 34% of participants in the high-dose session and 17% of participants in the low-dose session), none of these episodes met criteria for medical intervention. Nausea or vomiting occurred in 15% of participants in the high-dose session. An episode of physical discomfort (any type) occurred in 21% of participants in the high-dose session and 8% in the low-dose session. Psychological discomfort (any type) occurred in 32% of participants in the high-dose session and 12% in the low-dose session. An episode of anxiety occurred in 26% of participants in the high-dose session and 15% in the low-dose session. One participant had a transient episode of paranoid ideation (2% of high-dose sessions). There were no cases of hallucinogen persisting perception disorder (HPPD) or prolonged psychosis. Across the two dose sequence groups, the overall rate of clinical response at 6 months was 78% and 83% for depression and anxiety, respectively, and the overall rate of symptom remission at 6 months for all participants was 65% and 57%, respectively. Ross and colleagues conducted a double-blind, placebo-controlled, crossover trial, with 29 patients with cancer-related anxiety and depression that were randomly assigned and received treatment with single-dose psilocybin (0.3 mg/kg) or niacin (active placebo), both in conjunction with psychotherapy (before and after drug administration). The most common adverse effects were non-clinically significant elevations in blood pressure and heart rate (76%), headaches/migraines (28%), nausea (14%), transient anxiety (17%), and transient psychotic-like symptoms (7%). The medical and psychiatric adverse effects attributable to psilocybin are all known, were transient, and tolerable. There were no cases of prolonged psychosis or HPPD, and no participants required psychiatric hospitalization. Psilocybin produced immediate, substantial, and sustained improvements in anxiety and depression, this effect was sustained at 6.5 months follow-up. These trails and others have shown safety of treatment and high efficacy in reduction of anxiety and depression symptoms with sustained effect at 6 months follow up. These findings taken together with the theoretical understanding of psilocybin mechanism of action and with the understanding of the neuro-psychological pathology of OCD, encourage investigating the potential of psilocybin as a novel significant treatment for this disorder. Research of beneficial effects of psilocybin for patients with OCD is in its infancy, but preliminary findings show potential efficacy in treatment of the disorder. Matsushima and colleagues, used a mice model for OCD and found that psilocybin (both syntactic and in mushroom form), significantly inhibited compulsive behaviour (marble burying) without affecting locomotor activity. In addition, several case reports showed beneficial effects of psilocybin for people with OCD. For example, Leonard and Rapoport (1987) and Moreno and Delgado (1997) reported that among drug-users with OCD, there was a worsening of symptoms under the influence of cocaine, but a remission of symptoms for hours/ days following psilocybin use. Wilcox (2014) described a case in which a patient with OCD self-medicated with psilocybin, once every three weeks, experienced a preserved effect of reduced anxiety, obsessive thoughts, and compulsive behaviour. In another case report, a patient suffering from a body dysmorphic disorder (spending about 4 hours a day examining himself in the mirror), has experienced a significant reduction in distress and a notable change in body perception following multiple dosing of psilocybin. Moreno et al. 2006 conducted a semi open-label trial examining the effect of psilocybin on nine participants with mild to severe OCD, which had at least one "treatment failure" defined as a lack of significant improvement after an adequate treatment. Doses were 25 (very low dose \[VLD\]), 100 (low dose \[LD\]), 200 (medium dose \[MD\]), and 300 (high dose \[HD\]) µg/kg. LD, MD, and HD were assigned in that order, and VLD was inserted randomly and in a double-blind fashion at any time after the first dose (LD). In measurements during the 24 hours after each dose all participants have experienced a significant relief in symptoms (23%-100% as measured by the Yale-Brown Obsessive-Compulsive Scale \[YBOCS\]) in at least one of the sessions. Two of the subjects reported that their symptomatic improvement lasted most of the following week after testing. One subject achieved long-term remission at the end of the 4 test sessions, as measured at 6-month follow-up. There was, however, no clear dose-response relationship to the change in YBOCS score and no correlation between YBOCS score reduction and the perceived intensity of the psychedelic experience. These preliminary findings stress the need for further research to examine the efficacy of psilocybin in the treatment of OCD. In addition, the only clinical trial to date did not include psychotherapy for patients while under the influence of psilocybin. Earlier studies have shown that a preliminary therapeutic relationship before psilocybin administration increases the probability for a "peak experience" during sessions. Furthermore, two more recent studies have emphasized the importance of psychotherapy during and before psilocybin sessions, touching on 'intent' and formulating an early and strong therapeutic relationship. There is also a reference to the, "psychedelic afterglow", an effect lasting for days and even weeks after a psychedelic session during which there is a unique window for a meaningful transformative psychotherapeutic intervention, most likely owing to the increased psychological plasticity following a psychedelic experience. The current study has two main goals: 1. Determine the safety and efficacy of psilocybin for patients suffering from OCD. 2. Elucidate the psychological mechanisms contributing to the beneficial effect of psilocybin on OCD symptoms. Research Plan: The current research aims to examine the feasibility, safety and efficacy of psychotherapy assisted psilocybin for treatment of severe OCD. The protocol includes 15 therapeutic sessions, of which 12 are one-hour sessions, and three are eight hours' experiential sessions (session 4,8,12) under the influence of psilocybin. In the first experiential session participants will receive a safety dose of 10mg/70kg. In the second and third sessions, participants will receive a therapeutic dose of 30mg/70kg. Three preparatory sessions will take place before the first experiential session, and three integration sessions will take place after each experiential session. The research will include 15 participants, and will include the following phases: Selection phase: Research team will screen participants via phone interviews. Participants answering the inclusion criteria will be invited to receive and sign consent forms. Research member will collect demographics and health status data and register the participants according to study protocol. Preparatory and final registration phase: It is known that SSRIs have a counter effect on psilocybin; therefore, to allow a full effect of psilocybin it is necessary to avoid drug interaction and discontinue previous treatment. In a period of 4 weeks participants will undergo medication withdrawal under psychiatric supervision. During the 4 weeks period each participant will have 2-4 sessions (as needed) with the research psychiatrist, to supervise their clinical state. At the end of 4 weeks, a psychiatric evaluation will take place to determine readiness to begin psilocybin treatment. Baseline assessment, and preparatory therapeutic sessions phase: During the 5-6 weeks from registration, participants will have three preparatory psychotherapy sessions with a couple of therapists assigned to their treatment. Prior to their first psychotherapy session, participants will complete the first-baseline assessment of research questionnaires. Treatment phase: The treatment phase includes three experiential sessions with psilocybin (sessions 4, 8, 12), and three integration sessions after each experiential session. During this phase participants will complete three assessments using research questionnaires (sessions 2, 10, 15). End of treatment and follow-up phase: Primary outcome assessment will take place at the end of the last therapeutic session (no.15). Additional assessments will take place at three months, and six months/one-year follow-up. Research procedure Participants will sign consent forms, before participating in the research treatment. The treatment is based on 15 therapy sessions: * Three preliminary sessions for establishing therapeutic alliance with the therapists and preparing the participant for the first experiential session. * An 8-hour experiential session with a safety dose of psilocybin (10mg/70 kg). (V4) * Participant will spend the night at the medical facility, under the supervision of a research member. * A1-hour session with the therapists, on the following morning (V5) * Two integration sessions, and preparation for the next experiential session. (V6, V7) * An 8-hour experiential session with a therapeutic dose of psilocybin (30mg/70 kg). (V8) * Participant will spend the night at the medical facility, under the supervision of a research member. * A1-hour session with the therapists, on the following morning (V9) * Two integration sessions, and preparation for the next experiential session. (V10, V11) * An 8-hour experiential session with a therapeutic dose of psilocybin (30mg/70 kg). (V12) * Participant will spend the night at the medical facility, under the supervision of a research member. * A1-hour session with the therapists, on the following morning (V13) * Two integration and summary sessions. (V14, V15) Possible discomfort: It is possible that psilocybin and the experience it induces will cause some emotional or physical discomfort. Investigators will address all possible discomforts and appropriate measures to contain them, in the research safety instructions. Research purpose: The main objective of this research is to use standardized measuring tools to explore the safety and efficacy of psilocybin assisted psychotherapy in treating severe OCD symptoms. A secondary aim is to explore possible variables underlying change in symptoms. Research objectives: The main objective is to assess efficacy of psilocybin assisted psychotherapy in treating severe OCD symptoms. This assessment will be based on comparing ratings of the main outcome measure (Y-BOCS), at baseline (session 2) at the middle and at end of treatment (session 10, 15 respectively). A score under 14 or a reduction of 35% in the overall score will be considered as remission (Lewin, Nadai, Park, Goodman, Murphy \& Stroch, 2011). Secondary objectives: assessing safety by collecting data on side effects, and assessing possible spiritual variables underlying change in symptoms via standardized questionnaires and semi constructed interviews. Safety: The general safety goal is to assess occurrence and frequency of adverse events during treatment. This includes suicide ideation and/or behaviour, and adverse physiological or psychological responses. The safety of psilocybin use was previously proven in several clinical research. Potential adverse effects: In general, psychedelic drugs have low levels of physiological toxicity, and previous research indicate no evidence of toxicity, organ damage or neurophysiological disfunctions. Possible physiological effects experienced under the influence of psychedelic substances may include: dizziness, weakness, tremor, paresthesia, nausea, thirst, blurred vision, dilated pupils, and hyperreflexia. These somatic effects are dynamic and relatively minor, even when the psychological effect (sensory, perceptual, and cognitive) is strong/intense. The significant risk associated with psilocybin intake, is a subjective experience of fear and anxiety, panic, dysphoria and/or paranoia. Recent clinical studies report a high safety level with no adverse effects. The high safety levels can be attributed to several control parameters described below, and to complying with safety guidelines in clinical psychotherapy with psychedelics. The use of psilocybin requires a significant psychotherapeutic holding of the subjective experience, that will provide a safe and supportive environment during the psychedelic experience. The safety guidelines in clinical psychotherapy with psychedelics describe the therapeutic presence and processes, as well as the set and settings needed to provide a supportive emotional and external environment. Safety measures: 1. Controlling the quality of psilocybin and ensuring it is manufactured under GMP conditions. 2. Controlling for appropriate and adjusted dosage. 3. Controlling a strict protocol for screening eligible participants to the study (for details see inclusion-exclusion criteria section) 4. Recruiting professional and experienced psychotherapists with the appropriate training for clinical psychotherapy with psychedelics. Professionals will undergo a unique training to work with the psychotherapy protocol written for the current research. 5. Psychotherapists will work in pairs (a man and a woman), to provide an optimal holding space for each participant. 6. A proximity of a medical team for case of emergency. 7. Providing preparatory and integration sessions before and after the psilocybin sessions. 8. Preparing and using a comfortable and friendly room for the therapeutic session. The physical environment in which the treatment takes place should be suitable to the physical as well as the emotional safety of the participant. This means creating a lenient environment, which provides a pleasant and welcoming atmosphere, and may elicit a sense of intimacy and connection. As opposed to the environment of a hospital, a space like this supports and strengthens the participant's sense of safety and connectedness, thus helping him/her contain the intense psychedelic experience. 9. Guidelines for psychotherapy process: these guidelines are based on the humanistic perspective, and concern the characteristic of the therapeutic process: * A supportive, accepting, and non-judgmental presence of the therapist. * The importance of the therapeutic alliance and trust between participant and therapists. * A non-directive approach, supportive and gentle presence that stays with the participant's unfolding experience. * Viewing the mind as multi-dimensional, making space for the diverse dimensions of the internal experience: physical, emotional, and spiritual. 10. Maintaining a well-documented monitoring of the study and the participants status during the study period. 11. Monitoring physiological measure (blood pressure, heart rate and body temperature) during the psychedelic sessions with psilocybin: before taking the drug, an hour and a half after taking the drug, and 8 hours after. In case of anomalies physiological measures will be monitor more frequently. 12. Consulting and collaborating with other research teams with similar research interests, in NYU and Imperial College in London, UK.

topic_tags:
Depression,Anxiety,Addiction,OCD,End-of-Life Distress,Headache / Migraine,Neuroplasticity,Mechanism of Action,Receptor Pharmacology,Consciousness,Emotional Processing,Spirituality,Clinical Trial,Case Report,Animal Study,Cancer Patients,Safety,Adverse Events,Toxicity,Drug Interactions


title: Psilocybin for Chronic Pelvic Pain (CPP) in Women: A Pilot Feasibility Study
authors: Oregon Health and Science University
journal: ClinicalTrials.gov
publication_date: 2025-10-09
source_url: https://clinicaltrials.gov/study/NCT06988319
keywords: Chronic Pelvic Pain, Psilocybin (Usona Institute), NOT_YET_RECRUITING
substance_tags: psilocybin
topic_tags: Chronic Pain,Safety,Adverse Events
study_type: Other
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT06988319","overall_status":"NOT_YET_RECRUITING","phase":["PHASE1"]}
abstract:
The primary aim is to determine the feasibility of enrolling and 15 women with chronic pelvic pain (CPP) that have failed one conventional for CPP to obtain preliminary safety data on a single administration of a moderate dose of pharmaceutical grade psilocybin (25 mg) in combination with psychotherapy sessions (two pre-dose preparatory and three post-dose integration sessions). Chronic pelvic pain (CPP) presents a significant challenge in healthcare, affecting approximately 15% of women in the United States and incurring annual healthcare costs upwards of $5.8 billion. This condition extends beyond persistent physical discomfort, profoundly impacting mental health and overall quality of life. Central to many chronic pain syndromes, CPP can lead to a heightened state of pain sensitivity known as central sensitization. This condition arises from neuroplastic changes within the central nervous system, leading to structural, functional, and chemical alterations in the brain that enhance neural reactivity, even in the absence of actual physical injuries. Central sensitization is characterized by widespread, multisite hyperalgesia and allodynia. These changes often co-occur with fatigue, mood and cognitive disturbances, sleep disruptions, and multisensory hypersensitivity, complicating the clinical picture and exacerbating the condition's impact on daily functioning. The use of psilocybin in chronic pain is a paradigm shift from conventional pain therapy where the goal is pain alleviation, to changing a person's relationship with pain, offering a re-alignment or 'reset' of one's view of their pain, this is an innovative approach. To date, there are no psilocybin studies evaluating CPP. This is a pilot feasibility and safety study to evaluate a single administration of psilocybin (25 mg) in women with CPP who have failed at least one conventional CPP therapy. The study will enroll 15 women, the primary aim is to assess feasibility that will be met when at least 80% of participants complete the study and attend 80% of 11 study visits (9/11 visits). Safety will be assessed by adverse event reports, safety labs, and vitals assessments.


authors: Anders Fink-Jensen, MD, DMSci
journal: ClinicalTrials.gov
publication_date: 2026-03-23
source_url: https://clinicaltrials.gov/study/NCT05416229
keywords: Alcohol Use Disorder, Psilocybin, Maltodextrin, COMPLETED
substance_tags: psilocybin,psilocin
topic_tags: Addiction,Brain Imaging,Biomarkers,Aging,Clinical Trial
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT05416229","overall_status":"COMPLETED","phase":["PHASE2"]}
title:
The QUANTUM Trip Trial - Psilocybin-assisted Therapy for Reducing Alcohol Intake in Patients With Alcohol Use Disorder: A Randomized, Double-blinded, Placebo-controlled Clinical Trial.

abstract:
Note: The trial is only eligible for citizens of Denmark. The purpose of this project is to assess the treatment efficacy of a single high dose of psilocybin administered within a protocol of psychological support to patients diagnosed with alcohol use disorder (AUD). To establish efficacy, we will investigate a single dose of psilocybin versus placebo in a randomised, double-blinded, placebo-controlled 12 weeks clinical trial. 90 patients, aged 20-70 years, diagnosed with alcohol use disorder and treatment seeking will be recruited from the community via advertisement and referrals from general practitioners and hospital units. The psilocybin or placebo is administered within a protocol of psychological support before, during and after the dosing. Outcome assessments will be carried out one, four, eight- and 12 weeks post dosing. The primary outcome is reduction in the percentage of heavy drinking days from baseline to follow-up at 12 weeks. Key secondary outcomes include 1) phosphatidyl-ethanol as an objective biomarker for alcohol consumption 2) plasma psilocin, the active metabolite, to establish a possible therapeutic range and 3) the acute subjective drug experience as a possible predictor of treatment outcome. Furthermore, we will investigate the neurobiological underpinnings of the possible treatment effects by use of functional magnetic resonance brain imaging one week post dosing.


title: Psilocybin in Alcohol Use Disorder With Comorbid Depression
authors: Centre Hospitalier Universitaire de Nīmes
journal: ClinicalTrials.gov
publication_date: 2025-03-18
source_url: https://clinicaltrials.gov/study/NCT06235411
substance_tags: psilocybin
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT06235411","overall_status":"COMPLETED","phase":["NA"]}
abstract:
Up to 40% of people with alcohol use disorder (AUD) experience depression. Depression is a risk factor for early relapse of AUD after withdrawal in a controlled environment. Promising data suggest the effectiveness of psilocybin, a psychedelic-type treatment, in depression and AUD. Following the acute effects of the psychedelic experience, which lasts approximately 6 hours, psilocybin action appears to be beneficial for preventing alcohol relapse in recently weaned people suffering from comorbid depression. Whilst the public perception of psilocybin therapy is poorly documented in France, the rapid changes in the legal status of psilocybin elsewhere, the positive media coverage of recent trials in depression, and the recent designation as an "innovative therapy" by the FDA could lead to the refusal of randomization of eligible participants. It is therefore essential to evaluate the feasibility and acceptability of psilocybin treatment and blinded randomized design in our clinical population of hospitalized patients with AUD and depressive symptoms. Recent data suggest that the effect size of psilocybin is much higher than other currently available treatments. However, this paradigm shift must be confirmed in our cohort of people with AUD and depressive symptoms, and in the context of treatment in addition to usual care, by an estimation of the expected effect size based on real data. This will allow the sample size to be accurately calculated for a large-scale randomized clinical trial. Finally, the potential mechanisms of action of psilocybin to prevent relapse in AUD with comorbid depression after withdrawal need to be documented. The objective of this pilot study is to evaluate the feasibility, acceptability, neural mechanisms and preliminary results of the effectiveness of psilocybin in the treatment of AUD and depressive symptoms after withdrawal, in addition to usual treatment. The study authors hypothesize that two oral administrations of 25 mg psilocybin at three-week intervals versus a control condition (1 mg psilocybin), in addition to the usual treatment, will be acceptable and feasible in recently withdrawn individuals suffering from AUD and depressive symptoms, between 14 and 60 days after their last alcohol consumption

keywords:
Alcohol-Related Disorders, Depressive Disorder, Addiction, Psilocybin therapy, Inactive Psilocybin therapy, Electroencephalogram, Blood samples for the analysis of immune and inflammatory profiles, stool samples, MRI functional and cerebral, COMPLETED

topic_tags:
Depression,Addiction,Mechanism of Action,Clinical Trial,Observational Study,Safety,Inflammation,Immune Function


title: Study of Psilocybin for Anorexia in Young Adults
authors: Marissa Raymond-Flesch, MD, MPH
journal: ClinicalTrials.gov
publication_date: 2026-03-02
source_url: https://clinicaltrials.gov/study/NCT06399263
substance_tags: psilocybin
topic_tags: Eating Disorders
study_type: Other
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT06399263","overall_status":"RECRUITING","phase":["PHASE2"]}
abstract:
This is a single site trial of psilocybin therapy for the treatment of refractory Anorexia Nervosa in young adults. The psilocybin therapy will include three preparatory sessions, psilocybin dosing session one (20mg), two integration sessions, psilocybin dosing session two (up to 25mg), and three final integration sessions. Eating disorder symptoms will be measured pre and post treatment. One to two family member(s) of each young adult participant will be enrolled in the study. One of which will be required to attend a portion of two preparatory sessions and a portion of two integration sessions and receive psychoeducation about supporting the young adult participant through preparation and integration for psilocybin therapy. Investigators hypothesize that psilocybin will increase cognitive flexibility and that this increase will predict long-term changes in cognitive rigidity, habitual eating, and exercise behaviors in patients with Anorexia Nervosa.

keywords:
Anorexia Nervosa, Psilocybin, PEX010, Preparation and Integration Sessions, Psilocybin Therapy, RECRUITING


title: The Safety and Efficacy of Psilocybin in Cancer Patients With Major Depressive Disorder
authors: Maryland Oncology Hematology, PA
journal: ClinicalTrials.gov
publication_date: 2021-10-14
source_url: https://clinicaltrials.gov/study/NCT04593563
keywords: Major Depressive Disorder, Psilocybin, UNKNOWN
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Clinical Trial,Cancer Patients,Safety
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT04593563","overall_status":"UNKNOWN","phase":["PHASE2"]}
abstract:
This is a Phase II, single-center, fixed dose, open label trial to explore the safety, tolerability and efficacy of a 25mg dose of psilocybin in cancer patients with MDD. The study population will include adult men and women, 18 years of age or above, with MDD, diagnosed with a malignant neoplasm. MDD is defined as those who meet DSM5 diagnostic criteria for a single or recurrent episode of MDD without psychotic features. A diagnosis of a malignant neoplasm is defined as having a diagnostic code from C00 to C97 according to the ICD-10. Recent randomized, placebo-controlled clinical trials of psilocybin therapy for anxiety and depression associated with cancer diagnosis showed significant improvement in study endpoints reflecting psychological distress, as compared to placebo. The effects of a single psilocybin therapy session endured for up to six months with no specific follow-up care. In this study, we aim to explore the safety and efficacy of psilocybin therapy in cancer patients, diagnosed with Major Depressive Disorder (MDD).


authors: University Health Network, Toronto
journal: ClinicalTrials.gov
publication_date: 2026-06-21
source_url: https://clinicaltrials.gov/study/NCT06416085
substance_tags: psilocybin
topic_tags: End-of-Life Distress,Clinical Trial,Safety
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT06416085","overall_status":"ACTIVE_NOT_RECRUITING","phase":["PHASE2"]}
title:
Psilocybin-assisted Existential, Attachment and RelationaL (PEARL) Therapy for Patients With Advanced Cancer: A Phase II Open-Label Trial

abstract:
The PEARL Pilot is a phase II open-label trial. Participants will receive a single high-dose (25 mg) of psilocybin in the context of Psilocybin-assisted Existential, Attachment and RelationaL (PEARL) therapy. Individuals with advanced cancer often experience high levels of distress due to physical suffering, difficult treatment decisions, social isolation, and fear of death. While there are many treatment options for the management of physical symptoms associated with cancer, there are relatively few standard treatment approaches to help patients deal with psychological and existential suffering. Over the past decade, research has shown that psychotherapies incorporating existential, attachment and relational approaches can address the specific needs and challenges of the advanced cancer population and thus help to reduce distress. Simultaneously, recent research has shown that psilocybin-assisted psychotherapy, in which, an individual ingests the psychoactive drug within the carefully monitored therapeutic setting, can reduce end-of-life distress and greatly benefit those with advanced disease. The multidisciplinary team has combined these two evidence-based approaches into what the team calls Psilocybin-assisted Existential, Attachment and RelationaL (PEARL) therapy. PEARL therapy combines elements from psilocybin-assisted psychotherapy, including preparatory therapy sessions, a high-dose drug session, and integration sessions, with important elements from manualized individual psychotherapies designed for patients with advanced cancer. This study will assess the feasibility, acceptability, and safety of PEARL therapy among patients with advanced cancer. This study will yield important information about the feasibility of this type of therapy and contribute to the growing research around the efficacy of psychedelic-assisted therapies. This type of therapy has the potential to improve quality of life among those with advanced disease and careful research is needed to build upon previous findings to outline the necessary components of therapy and guide public policy, legislation, and clinical guidelines.

keywords:
Advanced Cancer, Stage IV Solid Tumor Cancer, Stage IV Sarcoma of Bone, Stage IV Lymphoma, Stage IV Melanoma, Endocrine Cancer, Psilocybin, ACTIVE_NOT_RECRUITING


authors: Sheppard Pratt Health System
journal: ClinicalTrials.gov
publication_date: 2022-10-24
source_url: https://clinicaltrials.gov/study/NCT04433845
keywords: Treatment Resistant Depression, Psilocybin, UNKNOWN
substance_tags: psilocybin
topic_tags: Depression,Safety
study_type: Other
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT04433845","overall_status":"UNKNOWN","phase":["PHASE2"]}
title:
The Safety and Efficacy of Psilocybin in Participants With Type 2 Bipolar Disorder (BP-II) Depression.

abstract:
The primary objective of this study is to evaluate the efficacy of 25 mg of psilocybin under supportive conditions to adult participants with BP-II, current episode depressed, in improving depressive symptoms.


title: Psilocybin as a Treatment for Anorexia Nervosa: A Pilot Study
authors: Imperial College London
journal: ClinicalTrials.gov
publication_date: 2024-06-16
source_url: https://clinicaltrials.gov/study/NCT04505189
keywords: Anorexia Nervosa, Psilocybin, COMPLETED
substance_tags: psilocybin
topic_tags: Eating Disorders,Brain Imaging,Aging
study_type: Other
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT04505189","overall_status":"COMPLETED","phase":["PHASE1","PHASE2"]}
abstract:
The primary aim of this study is to assess the acceptability and efficacy of treating anorexia nervosa with psilocybin. The secondary aim of this study is to use Magnetic Resonance Imaging (MRI) and Electroencephalography (EEG) to examine the neuronal underpinnings of treatment with psilocybin in this patient group. Anorexia nervosa is the most fatal of all psychiatric conditions. With the current paucity of effective pharmacological and psychological treatments, and fewer than half of those diagnosed making a full recovery, there is a great need for new treatment avenues to be explored. For this study, we will recruit patients who have a primary diagnosis of anorexia nervosa as defined by DSM-V criteria, which has been established by their specialist ED team to have been present for at least 3 years, and who have found other forms of treatment ineffective. Over a period of 6 weeks, participants who are deemed eligible at screening will partake in 8 study visits, including three psilocybin dosing sessions with varying doses. The maximum dose of psilocybin a participant will receive in a single session is 25 mg. Across these 8 visits, there will also be 2 MRI scans, up to 5 EEG recordings and a range of psychological measures (questionnaires and interviews). There will be a follow-up period of 12 months following the final study visit.


title: Effects of Psilocybin in Anorexia Nervosa
authors: Johns Hopkins University
journal: ClinicalTrials.gov
publication_date: 2023-05-05
source_url: https://clinicaltrials.gov/study/NCT04052568
keywords: Anorexia Nervosa, Psilocybin, COMPLETED
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Eating Disorders,Safety
study_type: Other
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT04052568","overall_status":"COMPLETED","phase":["PHASE1"]}
abstract:
This open-label pilot study seeks to investigate the safety and efficacy of psilocybin in persons with chronic anorexia nervosa (AN). Psilocybin has previously been demonstrated to decrease depression and anxiety and increase long-term positive behavior change in other populations. The investigators seek to determine whether similar changes can be safely produced in people with AN when psilocybin is administered in a supportive setting with close follow-up. The investigators' primary hypotheses are that psilocybin is safe to administer in people with AN, that it will reduce measures of anxiety and depression, and that it will lead to increased quality of life. The investigators will also assess a number of exploratory measures related to eating disorder pathophysiology.


title: Microdosing Psychedelics to Improve Mood
authors: Rotem Petranker
journal: ClinicalTrials.gov
publication_date: 2025-12-29
source_url: https://clinicaltrials.gov/study/NCT05259943
keywords: Major Depressive Disorder, Psilocybin first, Placebo first, COMPLETED
substance_tags: psilocybin
topic_tags: Depression,Microdosing,Clinical Trial,Observational Study,Safety
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT05259943","overall_status":"COMPLETED","phase":["PHASE2"]}
abstract:
This trial aims to examine the safety and efficacy of small (2mg) sub-hallucinogenic doses of psilocybin in people with Major Depressive Disorder. This protocol is for a University of Toronto - sponsored, randomized, placebo-controlled crossover phase 2 study of the safety and efficacy of low doses of psilocybin in subjects with depressive symptoms who meet Diagnostic and Statistical Manual 5 (DSM-5) criteria for diagnosis of a major depressive disorder (MDD) and who are either unwilling to pursue standard treatment (psychotherapy and/or pharmacotherapy) or have previously been non-responsive to standard treatment. This feasibility study will assess whether microdosing has a short-term impact on participant ratings of depressive symptoms. Participants will be administered one dose of either placebo or psilocybin once weekly for four weeks, and then all participants will be administered a dose of psilocybin once weekly for four additional weeks. Short surveys will be collected once weekly three days after the administration of psilocybin/placebo, and follow-ups will occur for up to two years following the beginning of the trial. Using this design will maximize the experimental power to detect an effect if one exists and would inform future research on microdosing in terms of duration, effect size, and expectancy bias.


authors: Kevin Boehnke
journal: ClinicalTrials.gov
publication_date: 2025-04-15
source_url: https://clinicaltrials.gov/study/NCT05128162
keywords: Fibromyalgia, Psilocybin, Psychotherapy, COMPLETED
substance_tags: psilocybin
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT05128162","overall_status":"COMPLETED","phase":["PHASE2"]}
title:
A Phase 2a, Open-label, Pilot Study to Assess the Safety and Efficacy of Psilocybin Administration in Concert With Psychotherapy Among Adult Patients With Fibromyalgia

abstract:
The pressing need for effective fibromyalgia (FM) treatments, the known safety of psilocybin therapy, and the mechanistic plausibility for potential benefit provide a backdrop for investigating psilocybin therapy as a treatment for FM. The primary objective of this study is to evaluate the clinical benefit of oral psilocybin in concert with psychotherapy to treat chronic pain symptoms in patients with FM. Fibromyalgia is a chronic syndrome of widespread musculoskeletal pain that often manifests with a cluster of co-occurring symptoms, including sleep disturbances, fatigue, cognitive dysfunction, and mood problems including anxiety and depression. Recent studies have provided evidence of altered central pain pathways. Current management of FM typically takes a multidimensional approach including behavioral therapy, exercise, and medication. However, current medications provide only modest benefit and carry significant side effect burden, leading many people with FM to seek other alternatives. Psilocybin therapy (psilocybin delivered in concert with psychotherapy) may be a potentially safe and effective treatment for symptoms associated with FM. Indeed, psilocybin therapy has shown positive effects in treating cancer-related psychiatric distress, depression and anxiety, treatment-resistant depression, and nicotine or alcohol addiction. The United States Food and Drug Administration (FDA) has granted a Breakthrough Therapy designation for psilocybin in treatment-resistant depression and major depressive disorder. Psilocybin therapy is generally safe and well-tolerated when conducted under controlled conditions. While no clinical studies have explored psychedelic effects among people with FM, a recent review outlined potential mechanisms through which psychedelics could alleviate chronic pain symptoms.

topic_tags:
Depression,Anxiety,Addiction,Chronic Pain,Mechanism of Action,Clinical Trial,Review Article,Cancer Patients,Treatment-Resistant Depression,Safety,Adverse Events


authors: COMPASS Pathways
journal: ClinicalTrials.gov
publication_date: 2025-08-18
source_url: https://clinicaltrials.gov/study/NCT05733546
keywords: Major Depressive Disorder, Psilocybin, COMP360, ACTIVE_NOT_RECRUITING
substance_tags: psilocybin
topic_tags: Depression,Pharmacology,Clinical Trial,Safety
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT05733546","overall_status":"ACTIVE_NOT_RECRUITING","phase":["PHASE2"]}
title:
A Phase II, Multicentre, Randomised, Double-blind, Controlled Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Efficacy of COMP360 in Participants With Recurrent Major Depressive Disorder

abstract:
Safety, Tolerability, pharmacokinetics and efficacy of a single administration of COMP360 in participants with recurrent Major Depressive Disorder. This is a phase II, multi-centre, randomised, double-blind, controlled study. The study population will include participants aged ≥18 years with recurrent Major Depressive Disorder (MDD) with up to four prior treatment failures of an antidepressant in their current depressive episode. Overall, 102 participants will be randomised in a 1:1:1 ratio to receive COMP360 25 mg, COMP360 10mg or COMP360 1 mg. In this study the aim is to investigate the safety and tolerability of COMP360, administered with psychological support, in adult participants with MDD with one prior treatment failure. In addition, pharmacokinetics and efficacy of COMP360 will be investigated. The study will last up to 16 weeks including a three- to ten-week Screening Period and a six-week follow-up from investigational product (IP) administration.


authors: Ottawa Hospital Research Institute
journal: ClinicalTrials.gov
publication_date: 2024-08-08
source_url: https://clinicaltrials.gov/study/NCT04754061
keywords: Depression, Anxiety, Distress, Emotional, Psilocybin, RECRUITING
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT04754061","overall_status":"RECRUITING","phase":["PHASE1","PHASE2"]}
title:
PSilocybin for psYCHological and Existential Distress in PALliative Care (PSYCHED-PAL): A Multi-site, Open-label, Single Arm Phase I/II Proof-of-concept, Dose-finding, and Feasibility Clinical Trial

abstract:
The goal of this multi-centre phase I/II open-label, single-arm study is to determine the safety, feasibility, therapeutic dose, and preliminary efficacy of psilocybin microdosing to treat psychological distress among patients with advanced illness. Forty patients will receive psilocybin drug product (1-3mg per day, Mon-Fri) for 4 weeks to be administered via oral capsules by the participant. Feasibility (recruitment rate, rate of intervention and follow-up completion), safety (rate of adverse events), dosing, and preliminary efficacy (depression, anxiety, overall well-being, and global impression of change) will be measured. Patients with advanced illness report feeling a sense of hopelessness, loss of autonomy and relationships, and a lack of purpose in life. These feelings of psychological suffering have been described as "existential distress" and are associated with poor outcomes, including decreased medication adherence and quality of life, increased desire for hastened death and rates of suicide, and has been identified as a primary reason why individuals pursue medical assistance in dying (MAiD). Current treatments for psychological and existential suffering have low efficacy and are challenging to use in a palliative context. Pharmacological approaches for treating psychological suffering may reduce symptoms of depression and anxiety, but evidence to support their efficacy in palliative care (PC) is underwhelming. Antidepressant and anxiolytic medications also take time to work and can cause serious side effects such as falls and confusion, which can be substantial deterrents for patients. Similarly, results from randomized controlled trials (RCTs) and meta-analyses have demonstrated psychotherapeutic interventions show limited benefit in a PC population. Further, psychotherapy can be time consuming and slow to work, which is not ideal for patients with limited life expectancy. Given the burden of psychological and existential distress among patients followed by PC providers, there is a need to develop scalable, brief, and rapidly effective therapeutic approaches to reduce this distress. Psychedelic medications offer an innovative, safe, complementary approach to address psychological and existential suffering in patients receiving PC. Studies from the 1950's showed serotonergic hallucinogens ("psychedelics") improved depression and anxiety symptoms in cancer patients. However, legislative changes restricted the use of these medications in clinical care and research. Interest in psychedelic medications has been rekindled by two recently published RCTs that studied the use of psilocybin (a mushroom-derived 5HT2A agonist) during a single psychotherapeutic session in cancer patients with anxiety and/or depression. These trials demonstrated rapid, clinically meaningful, and long-lasting reductions in depressed mood and/or anxiety symptoms and improvements in quality of life and death acceptance. There is also evidence suggesting psilocybin microdosing - taking sub-hallucinogenic doses continuously over longer time periods, rather than a one-time hallucinogenic dose - can improve mood and anxiety. The effects of microdosing, however, have not been rigorously evaluated, particularly in patients with life limiting illness. Results from recent trials are encouraging but knowledge gaps remain. First, studies to date primarily enrolled patients with localized disease who experience different distress than that of patients with advanced disease who are near the end of life. Second, it is unclear if Canadians would find psilocybin an attractive option in the context of MAiD legalization, which provides an alternative option for patients with severe psychological suffering. Third, there is no empirical research on the therapeutic effects of psilocybin microdosing, as most studies have followed macrodosing protocols. While preliminary efficacy of macrodosing has been demonstrated, there are important barriers to administering this therapy in a PC context. Previous trials had slow recruitment rates, suggesting there may be barriers related to the acceptability of psilocybin macrodosing from the perspectives of patients and families. Macrodosing requires the patient to dedicate an entire day to participating in a guided hallucinogenic experience and remain in an acute care setting where they can be closely monitored. It also requires patients to engage in preparatory sessions with monitors and a post-therapy session. In a PC context, this time commitment may not be acceptable or feasible for patients who are nearing the end of life. Additionally, macrodosing requires at least two trained moderators to guide the patient through their psychedelic experience and facilitate the pre- and post-dosing sessions. In most PC settings, it is not feasible to have clinicians dedicate two days to a single patient, thus limiting the scalability of this intervention. Psilocybin microdosing has the potential to overcome barriers to the feasibility and acceptability of macrodosing. By removing the requirement for trained moderators, minimizing the time commitment required of patients, eliminating the hallucinogenic effects of the therapy, and allowing patients to receive treatment either as an inpatient or in the community, microdosing may be a more acceptable option to patients and families and allow psychedelic therapy to be scalable across various PC settings. Psilocybin microdosing is a novel, complementary therapy that, while still unproven for patients near the end of life, has the potential to fundamentally change the way psychological and existential distress is responded to in PC, improving the lives of the 30% of patients who experience this suffering at the end of life. Objective To determine if psilocybin microdosing is a safe and feasible treatment for psychological distress among patients nearing the end of life followed by palliative care providers. All participants will receive a 4-week psilocybin microdosing intervention. The secondary objective is to examine the preliminary efficacy of psilocybin microdosing. Sample Size As this is a feasibility study, no formal sample size calculation was performed to determine the number of patients required to reach a level of precision on any study endpoint. Rather, the goal of this study is to provide estimates, along with their margins of error, of the recruitment rate and efficacy outcomes which will inform a subsequent two-arm randomized controlled trial. Participating sites see approximately 5,300 patients per year. It is anticipated that 30% will have psychological distress. Assuming a minimum of 1 in 6 patients are eligible and 15% of eligible patients will enroll, the goal is to enroll a sample of 20 participants in up to 1-year period. Statistical Analysis Analyses will adopt an intent-to-treat approach. Because the goal of this trial is to demonstrate feasibility and preliminary measures of efficacy, the main analyses will include calculation of feasibility outcomes using descriptive statistics and 95% confidence intervals (CIs), as well as effect sizes with 95% CIs for primary and secondary efficacy measures, comparing patients' 4-week follow-up assessments to baseline assessments. Participants will also be stratified based on demographic and clinical characteristics to assess trends in outcomes. Notably, there is some evidence that selective serotonin reuptake inhibitors (SSRIs) in particular may attenuate the effects of psilocybin. As such, sub-analyses will evaluate outcomes in participants taking an SSRI medication versus those who are not. A sub-group analysis by setting of care (inpatient vs outpatient/community) will also be conducted. Analyses of safety data will include the mean and standard deviation of the peak effect observed (i.e. highest observed blood pressure, heart rate) and proportion of participants experiencing adverse mood and behaviour events. The incidence of delirium and serotonin syndrome will also be recorded. Details of Eligibility, Intervention Protocol, and Outcome Measures are provided elsewhere.

topic_tags:
Depression,Anxiety,End-of-Life Distress,Receptor Pharmacology,Aging,Microdosing,Wellbeing,Emotional Processing,Clinical Trial,Randomized Controlled Trial,Cancer Patients,Healthcare Workers,Safety,Adverse Events


title: Role of the Serotonin 5-HT2A Receptor in Mescaline-induced Altered States of Consciousness
authors: University Hospital, Basel, Switzerland
journal: ClinicalTrials.gov
publication_date: 2023-03-28
source_url: https://clinicaltrials.gov/study/NCT04849013
substance_tags: psilocybin
topic_tags: Receptor Pharmacology,Consciousness,Spirituality,Healthy Volunteers
study_type: Other
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT04849013","overall_status":"COMPLETED","phase":["PHASE1"]}
abstract:
Mescaline (the active substance in Peyote and San Pedro cacti) is a classic and long known serotonergic psychedelic substance (hallucinogen) that is widely used for recreational, spiritual, and/or ethno medical purposes. Despite its long history, modern data on the acute effects of mescaline on human is lacking. Mescaline produces prototypical psychedelic effects, similar as lysergic acid diethylamide (LSD) and psilocybin. The serotonin 2A (5-HT2A) receptor is thought to primarily mediate acute alterations of consciousness induced by LSD and psilocybin. However, the contributory role of the 5-HT2A receptor in mescaline-induced alterations of consciousness is unclear. Using 5-HT2A receptor antagonist ketanserin, the psychedelic experience induced by LSD and psilocybin can be attenuated and shortened. The present study therefore explores the role the 5-HT2A receptor in mescaline-induced altered states of consciousness using escalating doses of mescaline and the 5-HT2A receptor blocker ketanserin administered before a high dose of mescaline. Objective: The present MDR-study will characterize the subjective effects of different doses of mescaline using modern psychometric instruments and examine the contribution of the 5-HT2A receptor in the mescaline-induced alterations of consciousness. Design: Double-blind, placebo-controlled, 6-period cross-over design with six treatment conditions. 1) Placebo (Pla + Pla), 2) 100 mg mescaline (Pla + 100mg mescaline), 3) 200 mg mescaline (Pla + 200mg mescaline), 4) 400 mg mescaline (Pla + 400mg mescaline), 5) 800 mg mescaline (Pla + 800mg mescaline), and 6) 40mg ketanserin and 800mg mescaline (Ket + 800mg mescaline). Participants: 16 healthy participants aged ≥ 25 and ≤ 65 years (8 female, 8 male)

keywords:
Healthy, Placebo, Mescaline 100mg, Mescaline 200mg, Mescaline 400mg, Mescaline 800mg, Mescaline 800mg + Ketanserin 40mg, COMPLETED


authors: MycoMedica Life Sciences PBC
journal: ClinicalTrials.gov
publication_date: 2024-10-08
source_url: https://clinicaltrials.gov/study/NCT06326606
keywords: Healthy Volunteers, Psilocybin, MLS101, Placebo, COMPLETED
substance_tags: psilocybin
topic_tags: Pharmacology,Microdosing,Clinical Trial,Healthy Volunteers,Safety
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT06326606","overall_status":"COMPLETED","phase":["PHASE1"]}
title:
A Phase 1 Dose Escalation Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of MLS101 (psilocybin) in Healthy Participants

abstract:
MLS101 is being developed as a low dose psilocybin, that can be administered to treat various neurological and psychiatric conditions. The purpose of this clinical trial is to assess how safe and tolerated MLS101 is; to see how MLS101 is distributed and cleared by the body (pharmacokinetics); and to assess the psychedelic effects of MLS101 in healthy adult participants. In recent years, high-dose psilocybin has gained attention for its potential therapeutic benefits in many psychiatric indications, however existing clinical data for low psilocybin doses are limited. Microdoses are generally considered to be those absent of profound sensory and cognitive effects that would interfere with normal everyday functioning, but only a small number of prospective studies have evaluated microdoses and/or low doses in a controlled manner. As a foundational study of the therapeutic use of low doses of psilocybin, this study will evaluate the safety, tolerability, pharmacokinetics, and sensorial effects using a prospective, controlled, single ascending dose/multiple ascending doses in healthy volunteers.


authors: The Roots to Thrive Society for Psychedelic Therapy
journal: ClinicalTrials.gov
publication_date: 2023-07-24
source_url: https://clinicaltrials.gov/study/NCT05958758
substance_tags: psilocybin
topic_tags: End-of-Life Distress,Wellbeing,Resilience,Observational Study,Safety,Adverse Events
study_type: Observational Study
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT05958758","overall_status":"UNKNOWN","phase":["EARLY_PHASE1"]}
title:
An Open Label Pragmatic Feasibility Study on a Resilience Focused Community of Practice Program With Psilocybin-assisted Therapy (PaT) for End-of-Life Patients.

abstract:
The purpose of the study is to understand the feasibility of a resilience focused community of practice program that includes psilocybin-assisted therapy for End-of-Life Distress. The community of practice refers to a research informed group therapy process that runs over a 10-week period of time and includes one group administered psilocybin-assisted therapy session. Target population: The treatment team will treat a total of 64 patients who have: * a terminal diagnosis (experiencing end of life distress), * AND who are eligible for the RTT + Psilocybin-assisted Therapy Treatment program through the RTT Society. Treatment will take place at the Snuneymuxw Traditional Medicines Clinic, 1984 Woobank Rd, Nanaimo, B.C.Research data will be coordinated and held through RedCap, hosted by Island Health. Data collection centres on 1) understanding the feasibility; 2) collecting safety data; 3) exploring the mental health impacts of a community of practice as the vessel for psilocybin-assisted therapy for those with end-of-life distress. There is a mixed method approach for data collection, including: * Collect attendance * Biomedical measures taken during psilocybin sessions (blood pressure, pulse, medications to manage side effects). * Quantitative Health and Wellness Questionnaires of participants before, within, immediately after, and six months after completion. * Qualitative Surveys and Exit Interviews.

keywords:
End of Life, Psilocybin-assisted therapy within a community of practice model (group administered), UNKNOWN


title: Psilocybin for PTSD With or Without Psychotherapy: A Pilot Study of Safety and Efficacy
authors: Johns Hopkins University
journal: ClinicalTrials.gov
publication_date: 2026-06-21
source_url: https://clinicaltrials.gov/study/NCT06407635
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT06407635","overall_status":"ACTIVE_NOT_RECRUITING","phase":["PHASE1"]}
abstract:
The proposed open-label, controlled study at the Johns Hopkins Center for Psychedelic and Consciousness Research (CPCR) will test the following primary hypotheses in adult patients with chronic PTSD who are currently taking a serotonin reuptake inhibitor: psilocybin therapy will be feasible and safe for participants, significantly remediate PTSD symptoms, and enhance wellbeing and quality of life. In addition, the study will examine whether elements of evidence-based trauma-focused psychotherapy enhance treatment response when paired with psilocybin. This study uses a randomized controlled design to compare the safety and efficacy of 2 doses of psilocybin for PTSD. In addition, it will investigate the effects of trauma-focused psychotherapy (which includes standard psychological support) versus standard psychological support alone. Twenty participants will be recruited. Following the first psilocybin session, participants will be randomized to either the trauma-focused psychotherapy (which includes standard psychological support) treatment condition or the standard psychological support treatment condition (the latter being typical for the experimental administration of psilocybin therapy). Both groups will receive identical treatment prior to receiving the first dose of psilocybin, with one group receiving procedures related to trauma-focused psychotherapy (combined with standard psychological support) beginning after receipt of psilocybin. The study will include clinician and participant ratings of PTSD and mood symptoms pre- and post-drug session and monitor and participant ratings of subjective drug effects during and after each drug session. The intervention for both groups will consist of about 8 hours of preparatory meetings (over approximately 2 weeks), followed by 2 psilocybin sessions separated by approximately 2 weeks. The initial psilocybin dose will be 25 mg. The dose for the second session may be increased conditional on the strength of subjective effects, as measured by the Mystical Experiences Questionnaire (MEQ30), taken at the end of participants' first psilocybin session. This allows a dose to increase if, for example, concomitant serotonin reuptake inhibitors reduce subjective effects. Participants with a score ≥60% of the maximum on the MEQ30 will remain at a dose of 25 mg of psilocybin for the second session. Participants with an MEQ30 score below 60% will receive a dose of 40 mg for the second session. Elevation of dose will also be based on the clinical judgment of the principal investigator, study physician, and study staff that a higher dose can be safely administered. In addition, participants who prefer to not elevate the dose will remain at 25 mg for the second session. To support the participant's therapeutic integration of psilocybin experiences, following each psilocybin session, participants will meet with the session facilitator(s) at multiple scheduled time points. Additional contact hours will be scheduled if it is judged that the participant would benefit from additional meetings to discuss experiences from the session(s) or to prepare for the next session. This study is supported in part by philanthropic contributions from private individuals. These donors are not involved in the design, conduct, or analysis of the research.

keywords:
Post Traumatic Stress Disorder, Psilocybin, Trauma-focused psychotherapy, Standard psychological support, ACTIVE_NOT_RECRUITING

topic_tags:
PTSD,Receptor Pharmacology,Consciousness,Wellbeing,Mystical Experience,Randomized Controlled Trial,Healthcare Workers,Safety


authors: VA Office of Research and Development
journal: ClinicalTrials.gov
publication_date: 2026-06-04
source_url: https://clinicaltrials.gov/study/NCT07226232
keywords: Major Depression, Psilocybin, COMP360, NOT_YET_RECRUITING
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT07226232","overall_status":"NOT_YET_RECRUITING","phase":["PHASE3"]}
title:
A Multi-site Randomized Controlled Trial of Psilocybin for Treatment-Resistant Depression (TRD) in Veterans

abstract:
The purpose of this multi-site randomized controlled trial is to evaluate the efficacy and risks of psilocybin for the treatment of depression in U.S. military Veterans with and without (±) concurrent posttraumatic stress disorder. Treatment-resistant depression (TRD) is a serious mental health problem in Veterans, frequently comorbid with post-traumatic stress disorder (PTSD), and in need of novel and effective treatments. Clinical studies have revealed antidepressant effects of psilocybin for depression in civilians, but less is known about its efficacy and safety in Veterans. Very limited data is available on the effects of psilocybin in the treatment of PTSD. Thus, it is important to evaluate the safety and efficacy of psilocybin in the treatment of TRD with and without PTSD among Veterans. The purpose of this multi-site, double-blind, randomized controlled trial is to evaluate the efficacy and risks of psilocybin for the treatment of TRD in U.S. military Veterans with and without (±) concurrent PTSD. Eligible and consenting Veterans will two psilocybin dosing sessions along with preparation, administration, and integration psychological support provided by a facilitator. For the 1st psilocybin administration, participants will be randomized to one of two doses under blinded conditions. One month later, all participants will receive a 25mg dose at their 2nd psilocybin visit. Outcomes will be measured by an independent evaluator masked from all treatments at 2 and 4 weeks after each dosing session. Longer-term follow-up will be conducted over 6 months. Both expected and unanticipated adverse events will be collected by type, severity and relatedness to the study drug.

topic_tags:
Depression,PTSD,Randomized Controlled Trial,Treatment-Resistant Depression,Veterans,Safety,Adverse Events


authors: Yale University
journal: ClinicalTrials.gov
publication_date: 2026-03-10
source_url: https://clinicaltrials.gov/study/NCT06442423
substance_tags: psilocybin
topic_tags: Depression,Anxiety,PTSD,Addiction,OCD,Receptor Pharmacology,Clinical Trial,Safety,Adverse Events
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT06442423","overall_status":"RECRUITING","phase":["PHASE1"]}
title:
Safety, Feasibility, and Tolerability of Psilocybin Treatment for Individuals With Functional Impairment Related to Mood, Anxiety, Trauma and/or Addiction Symptoms: An Open-label Proof-of-concept Study

abstract:
The primary objective of this study is to investigate the safety, feasibility, and tolerability of psilocybin treatment in individuals with functional impairment due to psychiatric symptoms. The secondary objective of this study is to determine whether individuals with functional impairments due to psychiatric symptoms will experience statistically significant symptom reduction and functional improvement from baseline symptom measurements (Visit 3) to 1-week (Visit 7), 4-weeks (Visit 8), and 6-weeks (Visit 9) post dosing. The investigators will recruit individuals with mood, anxiety, trauma, addictive, or related symptomatology, and who have functional impairment associated with these symptoms. A DSM-5 diagnosis is not required (nor is it an exclusion). The investigators will allow for comorbidity and only exclude based on psychological and physiological safety considerations. Critically, this approach will allow us to assess the tolerability of our interventions in individuals who would typically be excluded from efficacy studies due to various comorbid DSM-5 conditions. The investigators will employ an open-label study where participants will be given one dose of oral psilocybin 25mg. The investigators will also have follow-up visits at 1, 4, and 6 weeks and an optional long-term follow-up at 3, 6, and 12 months. In this Phase 1b proof-of-concept clinical trial, the investigators aim to investigate the safety, feasibility, and tolerability of treatment of oral psilocybin in participants with functional impairment due to depressive, anxiety, trauma addictive, or other psychiatric symptomatology, allowing for comorbidity and diagnostic complexity to mirror potential real-world clinical scenarios. Secondarily, The investigators will assess improvement in functional status and symptomatology. The investigators will employ an open-label study design, with participants receiving one dose of oral psilocybin. This is an open-label clinical trial with a single treatment arm and no blinding. All participants will receive 25 mg of oral psilocybin. All dosing will be accompanied by non-directive support before, during, and after treatment sessions.The rationale for conducting this study lies in recognizing that the narrow inclusion and exclusion criteria commonly employed in clinical trials may raise issues of external validity. While previous research has predominantly focused on specific diagnostic categories, our study aims to address these limitations by exploring the safety, feasibility, and tolerability of psilocybin in a heterogeneous population. This study also recognizes the importance of symptom-related functional impairment as a cross-cutting construct relevant to all diagnostic categories.This is a Phase 1b open-label clinical trial to determine the feasibility, tolerability and safety of psilocybin to reduce psychiatric symptoms in participants experiencing functional impairment. Participants will receive one dose of oral psilocybin (25mg). Follow-up visits for assessments and measures at 1-week, 4-week, and 6-week post psilocybin dosing. Long-term follow-up visits assessments and measures for participants who consent to long-term follow-up (reassessments of study measures) for 3-month, 6-month, and 12-month post dosing. Psilocybin (4-hydroxy-N,N-dimethyltryptamine) occurs in nature in many species of mushrooms, including the genera Psilocybe, Conocybe, Gymnopilus, Panaeolus, and Strophparia. Its chemical formula is C12H17N2O4P. Psilocybin is a potent agonist at 5-HT2A/C receptors; potency of binding by related compounds to these receptors correlates with human potency as hallucinogens. Psilocybin is currently a Schedule I substance. Psilocybin will be orally administered in this study. Psilocybin will be administered in an opaque, size 2 gelatin capsule with approximately 180 ml of water to be orally ingested at Visit 5. The dose of psilocybin will be 25 mg. Descriptives for all safety measures (e.g., C-SSRS total and subscale scores, vitals, documented adverse events) will be compiled at all assessment intervals. Classification of adverse events will follow institute and regulatory body guidelines. Subsequent summary descriptives may focus on safety indices surrounding the dosing session and 1-week, 4 weeks, and 6-weeks after dosing. In addition, The investigators will perform descriptives and non-parametric analysis screen failure rates (including analysis of ineligibility), drop out rates pre and post dosing to determine feasibility and tolerability.

keywords:
Transdiagnostic, Depression - Major Depressive Disorder, Anxiety, PTSD Symptoms, PTSD, Substance Use, Substance Use Disorder (SUD), OCD, Psilocybin, RECRUITING


authors: Joshua Woolley, MD, PhD
journal: ClinicalTrials.gov
publication_date: 2026-04-28
source_url: https://clinicaltrials.gov/study/NCT05351541
substance_tags: psilocybin
topic_tags: Depression,Chronic Pain,Emotional Processing
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT05351541","overall_status":"ACTIVE_NOT_RECRUITING","phase":["PHASE1","PHASE2"]}
title:
A Double-blind, Randomized Trial Examining the Preliminary Efficacy of Psilocybin Therapy for People With Chronic Low Back Pain

abstract:
This study evaluates whether psilocybin therapy helps patients cope with chronic low back pain more effectively. Patients may be recruited at Stanford and University of California San Francisco (UCSF), study procedures will occur at UCSF. Each participant will receive a dose of psilocybin with possibly one or more other drugs. Participants will undergo two preparation sessions, a dosing session, three integration sessions to discuss their psilocybin experience, and several follow up sessions. Chronic pain is associated with higher levels of pain-related distress, depression, emotional dysfunction, helplessness, hopelessness, and suicidality. Psilocybin is a psychoactive drug that may be well-suited to easing the psychological and emotional symptoms of distress associated with chronic pain. Previous studies testing psilocybin therapy have shown improvements on multiple behavioral and psychiatric outcomes, but it is unknown whether psilocybin therapy similarly enables patients to cope with chronic pain more effectively. The investigators will determine whether psilocybin therapy improves patients' ability to cope with chronic low back pain. If psilocybin therapy is an effective treatment in this population, its use could be incorporated into interventions for chronic low back pain and other psychological conditions.

keywords:
Chronic Low-back Pain, Psilocybin therapy with Zolpidem and Modafinil, 4-phosphoryloxy- N,N-dimethyltryptamine, Psilocybin therapy with Zolpidem, Psilocybin therapy with Modafinil, Psilocybin therapy with Placebo, ACTIVE_NOT_RECRUITING


authors: Combat Stress
journal: ClinicalTrials.gov
publication_date: 2023-05-24
source_url: https://clinicaltrials.gov/study/NCT05876481
keywords: PTSD, Psilocybin, UNKNOWN
substance_tags: psilocybin
topic_tags: Depression,Anxiety,PTSD,Treatment-Resistant Depression,Veterans,Safety
study_type: Other
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT05876481","overall_status":"UNKNOWN","phase":["PHASE2"]}
title:
Evaluation of the Acceptability, Safety, Feasibility, and Efficacy of Psilocybin-assisted Psychotherapy (PaP) for the Treatment of Post-traumatic Stress Disorder (PTSD) in Military Veterans

abstract:
Post-Traumatic Stress Disorder (PTSD) is a mental health condition that occurs as a result of a traumatic experience. Symptoms include feeling anxious, flashbacks, nightmares and difficulty sleeping. Several studies indicate that psilocybin-assisted psychotherapy (PaP) may be an effective treatment for a number of mental health conditions. This has led to PaP being designated as a "breakthrough treatment" by the FDA in the US. Despite indications that PaP may hold benefits in treating individuals with posttraumatic stress disorder (PTSD), this remains to be investigated. As such, the present study aims to examine the acceptability, feasibility, safety, and efficacy of PaP (psilocybin administered with psychotherapy) in treating PTSD in military veterans. Recent studies have shown that Psilocybin-Assisted Psychotherapy (PaP) for individuals with treatment-resistant depression can result in outcomes that exceed routine psychotherapy. Psilocybin may have a catalytic effect on the psychotherapeutic process, enhancing introspection and interoception. PaP may similarly benefit the treatment of posttraumatic stress disorder (PTSD). Research indicates high treatment drop-out rates (approximately 30%) among PTSD patients, and moderate remission rates (approximately 44%) 40 months after completing treatment. Furthermore, some veterans with PTSD have poorer treatment responses than members of the general public. This suggests that alternative treatment approaches may be required to support veterans who do not benefit from standard evidence-based approaches. This study aims to explore the acceptability, feasibility, safety and efficacy of PaP for veterans with PTSD. A total of eight military veterans will be recruited. The study involves two non-directive preparatory sessions, two dosing sessions of psilocybin, followed by 12 sessions of Cognitive Processing Therapy. It is hypothesised that PaP will result in a significant reduction in PTSD symptoms, as indicated by PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders (DSM-5; PCL-5) scores from baseline to one-month follow-up.


title: Molecular Imaging Study of Harmine/DMT: a Basic Research Approach
authors: Insel Gruppe AG, University Hospital Bern
journal: ClinicalTrials.gov
publication_date: 2025-03-18
source_url: https://clinicaltrials.gov/study/NCT06252506
substance_tags: psilocybin
topic_tags: Brain Imaging,Pharmacology,Aging,Animal Study,Healthy Volunteers
study_type: Animal Study
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT06252506","overall_status":"COMPLETED","phase":["PHASE1"]}
abstract:
The few reports on effects of psychedelic substances on cerebral metabolic rate (CMRglc) indicate increases (psilocybin; human FDG-PET) or decreases (LSD, rat autoradiography; 5-MeO-DMT rat autoradiography). There are no reports of effects of DMT and/or harmine on cerebral energy metabolism. The primary objective of this study is thus to assess acute cerebrometabolic effects of harmine/DMT in healthy volunteers using quantitative FDG-PET, that is, to measure CMRglc before and after simultaneous treatment with an oral harmine and DMT formulation developed (and already applied) by the investigators' project partners at the University of Zurich. As a secondary objective, the researchers aim to correlate the time-dependent effects on CMRglc as assessed in the PET images with the time-dependent self-reported intensity of participants' psychedelic experience.

keywords:
Neuropharmacological Investigation of Ayahuasca Constituents DMT and Harmine, N,N-dimethyltryptamine (DMT) + harmine, Placebo, COMPLETED


authors: COMPASS Pathways
journal: ClinicalTrials.gov
publication_date: 2022-09-21
source_url: https://clinicaltrials.gov/study/NCT04519957
keywords: Treatment Resistant Depression, COMPLETED
substance_tags: psilocybin
topic_tags: Depression,Treatment-Resistant Depression,Safety
study_type: Other
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT04519957","overall_status":"COMPLETED","phase":[]}
title:
Multicentre Study To Assess Safety And Efficacy Of Psilocybin In Patients With Treatment-Resistant Depression Following Completion Of COMP001 And COMP003 Trials (P-TRD LTFU)

abstract:
The primary objective of this study is to assess the long-term efficacy of psilocybin with respect to use of new antidepressant treatment, hospitalisations for depression, suicidality, and depressive severity rated using the Montgomery and Asberg Depression Rating Scale (MADRS) over a total of 52 weeks (compared across the 1 mg, 10 mg and 25 mg psilocybin groups from COMP001). In this present study (COMP004), the aim is to follow up participants from COMP001 and COMP003 in a long-term follow up study, with both remote and digital assessments, to explore the long term efficacy and safety of the three different doses of psilocybin (1 mg, 10 mg, and 25 mg) administered to patients with TRD as a monotherapy in COMP001 and 25 mg psilocybin administered as an adjunct to an SSRI in COMP003. Patients previously treated in COMP001 will be followed for approximately 40 weeks and patients previosuly treated in COMP003 will be followed for approximately 49 weeks giving a total follow up period of 52 weeks from psilocybin dosing.


authors: Indiana University
journal: ClinicalTrials.gov
publication_date: 2026-03-29
source_url: https://clinicaltrials.gov/study/NCT07499583
keywords: Treatment Resistant Depression, Substance Use Disorders, Psilocybin, NOT_YET_RECRUITING
substance_tags: psilocybin
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT07499583","overall_status":"NOT_YET_RECRUITING","phase":["PHASE1","PHASE2"]}
title:
Psilocybin Assisted Psychotherapy for Treatment Resistant Depression and Co-occurring Substance Use Disorder

abstract:
The goal of this clinical trial is to learn if a single dose of psilocybin (5mg Vs 10mg Vs 25mg) alongside psychotherapy is safe and can help treat treatment resistant depression (TRD) with co-occurring substance use disorder (SUD) in veterans and first responders. We seek to answer: * Whether 5mgs, 10mgs and 25mgs of psilocybin are safe in individuals with co-occurring TRD and SUD * Whether psilocybin assisted psychotherapy will reduce substance use severity and depression symptoms * What neurobiological processes are associated with the effects of psilocybin assisted psychotherapy. The researchers will compare the effects of a single dose of psilocybin (either 5mgs or 10mgs or 25mg) alongside psychotherapy on substance use severity and depression symptoms over six weeks in veterans and first responders with TRD and co-occurring SUD. In this 14-week study, participants will: * Visit the clinic for two intake sessions * Complete seven psychotherapy sessions. This will include three sessions before psilocybin administration, an 8 to 10 hour dosing session, and three sessions following psilocybin administration * Complete short, repeated daily assessments for six weeks, in total, before and after psilocybin administration * Complete two brain scans before and after psilocybin administration This is a double-blind randomized clinical trial to examine the safety and efficacy of a single dose of psilocybin (5mg or 10mg or 25mg) in reducing substance use severity and depression symptoms in N=50 veterans and first responders with treatment resistant depression (TRD) and co-occurring substance use disorder (SUD). The study will be conducted at Goodman Hall outpatient clinic located at Indiana University, Department of Psychiatry. All participants will take part in two intake visits (one to conduct safety tests and establish eligibility, and one to collect baseline and covariate data). They will then participate in three preparatory psychotherapy sessions with a certified psilocybin counselor before receiving one of three, randomly assigned, psilocybin doses during an 8 to 10 hour administration session. Following psilocybin administration, participants will participate in three weekly integrative psychotherapy sessions. We will also conduct three, two-week bursts of Ecological Momentary Assessment (EMA) during weeks 1 and 2, weeks 5 and 6 and weeks 10 and 11 of study participation, to measure daily substance use patterns and depression symptoms both during stressful and non-stressful situations. A pre- and post- fMRI paradigm will additionally be conducted to determine psilocybin-related changes within and between the default mode network, the salience mode network and the central executive network, during both resting state and stress. We will also explore the extent to which elevations in subjective mystical and existential experience contributes to psilocybin's therapeutic and mechanistic effects. It is anticipated that all three doses of psilocybin will be safe and well-tolerated in this sample of veterans and first responders. We additionally expect that 25mgs of psilocybin compared with 5mgs will attenuate substance use severity and depressive symptoms six weeks following administration, and during both stressful and non-stressful situations. In addition, we expect that 25mg Vs 5mg psilocybin will decrease resting state functional connectivity within the default mode network (DMN) and modulate connectivity between the DMN, salience network, central executive network, and the amygdala during stress exposure.

topic_tags:
Depression,Addiction,Brain Imaging,Default Mode Network,Mystical Experience,Clinical Trial,Treatment-Resistant Depression,Veterans,Safety


authors: University of Calgary
journal: ClinicalTrials.gov
publication_date: 2025-12-29
source_url: https://clinicaltrials.gov/study/NCT06615908
keywords: Persisting Symptoms After Concussion, Psilocybin, magic mushrooms, PEX010, RECRUITING
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT06615908","overall_status":"RECRUITING","phase":["PHASE1"]}
title:
A Randomized Double-blinded Controlled Trial for the Treatment of Persisting Symptoms After Concussion With Psilocybin-assisted Therapy: A Safety and Feasibility Trial

abstract:
The goal of this randomized controlled trial is to evaluate the safety, feasibility, and efficacy of psilocybin assisted therapy as an intervention to reduce symptom burden in adult patients (aged 18-65) with persisting symptoms after concussion (PSaC). This trail will test the following 2 aims: AIM1: To test the safety and feasibility of an active psilocybin-assisted psychotherapy to an active control for patients with PSaC. AIM2: To evaluate the efficacy of an active psilocybin-assisted psychotherapy compared to an active control as a treatment for PSaC. Participants will be asked to: * Complete a 2-part screening process * Attend a baseline assessment * Complete a psychoeducation preparation session(s) * Attend psilocybin administration session (receive high dose \[25mg\] or low dose psilocybin \[1mg\]) * Complete 5 weekly sessions of Acceptance and commitment therapy (ACT) * Repeat outcome measures at 1-week, 4 weeks, 3 months, and 6 months post-psilocybin administration (online only at 6 months). The overall objective of this study is to evaluate the safety, feasibility, and efficacy of psilocybin assisted therapy administered with Acceptance and Commitment Therapy (ACT) as an intervention to reduce symptom burden in patients with persisting symptoms after concussion (PSaC). This trail will test the following 2 aims: AIM1: To test the safety and feasibility of an active/high dose (25mg) psilocybin-assisted psychotherapy to an active control (1mg) for adults with PSaC. Safety will be determined through the reporting of adverse events and response following psilocybin for each participant up to 6-months. Feasibility will be determined through recruitment, enrollment, and adherence rates. AIM2: To evaluate the efficacy of an active/high dose (25mg) psilocybin-assisted psychotherapy compared to an active control (1mg) as a treatment for PPCS at 1-week, 4 weeks, 3 months, and 6 months post-psilocybin administration. The primary efficacy outcome will be the change in PSaC burden (RPQ). The secondary efficacy outcomes will include measures of headache, dizziness, mood, anxiety, post-traumatic stress, cognitive flexibility, emotional regulation, and quality of life. A total of 40 male and female patients between the ages of 18-65 with a diagnosis of mild traumatic brain injury (American College of Rehabilitation Medicine 2023 criteria) who meet criteria for persisting symptoms after concussion (ICD-10) within 3 months to 5 years will be recruited from Calgary brain injury clinics and the community. All patients will undergo a thorough, 2-part screening procedure. Eligible participants will be randomly allocated 1:1 to either the high dose (20 participants) or low dose (20 participants) psilocybin groups. All participants will be asked to attend a baseline session consisting of clinical and behavioural outcome measures, followed by a pre-dosing psychoeducation session. Following the single dosing session, participants will complete 5 weekly ACT sessions. Outcome measure assessments will be repeated at 1-week, 4 weeks, 3 months, and 6 months post-dosing.

topic_tags:
Anxiety,PTSD,Headache / Migraine,Emotional Processing,Randomized Controlled Trial,Safety,Adverse Events


title: Optimizing Microdosing and Meditation
authors: National University of Natural Medicine
journal: ClinicalTrials.gov
publication_date: 2025-06-04
source_url: https://clinicaltrials.gov/study/NCT06560658
keywords: Meditation, Microdosing, Psilocybin, psilocybin microdosing, WITHDRAWN
substance_tags: psilocybin
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT06560658","overall_status":"WITHDRAWN","phase":["NA"]}
abstract:
The goal of this clinical trial is to test the feasibility of combining meditation with psilocybin microdosing in healthy adults. The main questions it aims to answer are: 1. Recruitment and retention feasibility 2. Acceptability, Safety and Tolerability 3. Exploratory Measures: 3.1: Explore potential changes in sleep quality and duration, heart rate variability, and other biometric outcomes captured by the Oura Ring (3rd generation). 3.2: Explore potential changes in quality of life scores 3.3: Explore potential differences in altered states of consciousness across groups 3.4: Explore qualitative data collected during sessions and at follow-up to assess satisfaction and receive feedback about the intervention. Every participant will receive the psilocybin microdosing intervention, however, half of the participants will be randomly selected to receive the meditation intervention. Research has shown that both meditation and high doses of psilocybin can produce enhanced feelings of well-being that persist. When combined, the synergistic effects might be more than the sum of the parts when treating mental health challenges like depression. The results for microdosing, on the other hand, are mixed, and there have yet to be studies on the synergy between microdosing and meditation. If the synergy between microdoses of psilocybin and meditation is significant, this suggests the possibility of a safe, effective, and low-cost intervention involving group-based meditation training and practice combined with a psilocybin microdosing protocol. The Oregon Psilocybin Services program provides a unique opportunity to test this possibility in the context of services now legally available to clients, allowing researchers to assess the safety and efficacy in a real-life context. Project aims and methods This study aims to test the feasibility of the model by assessing recruitment, retention, acceptability, safety, and preliminary efficacy of the intervention. In addition to an appropriate medical screening and intake we will collect questionnaire data using the Credibility/Expectancy Questionnaire (CEQ), PROMIS-29, Five Facet of Mindfulness Questionnaire (FFMQ), Pittsburgh Sleep Quality Index (PSQI), Altered States of Consciousness (11-ASC) rating scale, and a survey and structured interview. During a one week wash-in period, the intervention period, and for one month after the intervention, Oura rings will be used to collect over 20 biometric data points including sleep quality, respiration rate, heart rate variability, and more. Participants will consist of adults in Oregon that will be individually screened by a study investigator and then randomized into two arms. One arm will receive microdosing only consisting of one group preparation session and two microdosing sessions per week for two weeks. The other arm will receive the same microdosing protocol with the addition of morning online meditation practice Monday through Friday for both weeks, and will utilize meditation practices during their microdose sessions. The meditation sessions will include opportunities for the group to discuss their meditation experiences and a psychoeducational component to further improve outcomes. This content will provide participants with a better understanding of the ruminations that interrupt their focus while meditating and encourage greater distance from, and less distress concerning, those thoughts. Expected outcomes The authors hypothesize that the model will be feasible if we are able to recruit at least 20 out of 24 expected participants, have an 80% retention rate of participants during the two week intervention period, participants on average rate their satisfaction of the intervention as 3.0 or higher on a 5-point scale, there are no more than ten adverse events or more than one serious adverse event, and data from exploratory measures indicate that further investigation is warranted. Despite the U.S. Food and Drug Administration (FDA) granting Breakthrough Therapy status to psilocybin for the treatment of depression,56 it remains on the Drug Enforcement Agency's (DEA) Schedule I list of controlled substances alongside heroin and cocaine. While the DEA and the FDA have become increasingly more willing to grant waivers for research into psychedelic drugs, the proposed study does not require such a waiver to comply with the law. This is due to the unique construction of Oregon's Psilocybin Services Act (Chapter 475A of Oregon Statutes). The state law creates a program wherein licensed growers, inspected by licensed laboratories, can distribute psilocybin mushrooms to licensed service centers. It is only within the approved boundaries of these service centers and while supervised by a licensed facilitator that the mushrooms can be consumed by clients who must stay on site for a designated amount of time that depends on the dose. According to Oregon Health Authority Administrative rule 333-333-5130, facilitators of psilocybin service are prohibited from (1) practicing any other scope of practice they may have (e.g. naturopathic medicine) while facilitating, and (2) handling, selling, or transferring psilocybin at any time. Thus, while it is technically true that growers, services centers, and clients are liable for trafficking and possession of a Schedule I substance, the federal government has adopted a policy of allowing state programs such as this in a manner similar to their policy on cannabis. Complying with Oregon law means that study investigators are not administering or providing psilocybin, but instead are studying the facilitation of the services. At the request of the Institutional Review Board (IRB) of the National University of Natural Medicine (NUNM) for a similar study, this rationale was confirmed via direct communication with the regional DEA office who agreed with this interpretation of both federal and state law. Participants are given clear information on their liability in order to provide consent.

topic_tags:
Depression,Addiction,Consciousness,Microdosing,Wellbeing,Clinical Trial,Review Article,Observational Study,Safety,Adverse Events


authors: King's College London
journal: ClinicalTrials.gov
publication_date: 2021-07-21
source_url: https://clinicaltrials.gov/study/NCT04959253
keywords: Treatment Resistant Depression, Psilocybin assisted therapy, Placebo assisted therapy, UNKNOWN
substance_tags: psilocybin
topic_tags: Depression,Clinical Trial,Safety
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT04959253","overall_status":"UNKNOWN","phase":["PHASE2"]}
title:
A Randomised, Placebo Controlled Trial of Psilocybin in Treatment Resistant Depression: A Feasibility Study

abstract:
A single centre clinical trial to evaluate the feasibility, safety and efficacy of psilocybin, given under supportive conditions, in a randomised, blinded design in adult participants with treatment resistant major depressive disorder. The primary objective is to evaluate feasibility by measuring recruitment rates, dropout rates and by estimating the variance of the primary outcome measure (MADRS).


title: The Safety and Tolerability of COMP360 in Participants With Post-traumatic Stress Disorder
authors: COMPASS Pathways
journal: ClinicalTrials.gov
publication_date: 2025-06-12
source_url: https://clinicaltrials.gov/study/NCT05312151
keywords: Post Traumatic Stress Disorder, Psilocybin, COMP360, COMPLETED
substance_tags: psilocybin
topic_tags: PTSD,Safety
study_type: Other
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT05312151","overall_status":"COMPLETED","phase":["PHASE2"]}
abstract:
The Safety and Tolerability of COMP360 in Participants with Post-traumatic Stress Disorder The Safety and Tolerability of COMP360 administered under supportive conditions in participants with Post-traumatic Stress Disorder


authors: Robin Carhart-Harris, PhD, MA
journal: ClinicalTrials.gov
publication_date: 2026-06-03
source_url: https://clinicaltrials.gov/study/NCT06626139
substance_tags: psilocybin
topic_tags: Neuroplasticity,Wellbeing,Emotional Processing,Healthy Volunteers,Drug Interactions
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT06626139","overall_status":"RECRUITING","phase":["PHASE2"]}
title:
2 x 2 Factorial, Double-blind, Randomized Trial of 'Set and Setting': a Translational Study in Healthy Volunteers

abstract:
One hundred twenty healthy participants, ages 21 to 70, who experience moderate-to-lower-than-average mental well-being will be evenly randomized into four different study arms, using a 2x2 factorial design. Depending on the study arm, participants will either receive an inactive placebo or up to 25mg psilocybin (oral dose), in one of two set and setting conditions; drug administration contexts that are predicted to modulate drug effects. The purpose of this study is to evaluate any interaction effects between an oral dose of psilocybin and the surrounding context (set and setting). Recent research posits that psychedelic medicine is best employed as a combination treatment, i.e., as drug x psychological support or psychotherapy referred to for simplicity as 'psychedelic therapy'. It is assumed that positive outcomes via psychedelic therapy critically depend on a synergistic relationship between drug-induced brain and mind plasticity and supportive contextual factors (Carhart-Harris et al., 2018; Carhart-Harris and Friston, 2019). These contextual factors have been referred to as 'set and setting' (Leary et al., 1963) or 'extrapharmacological'- highlighting elements beyond the drug that contribute to relevant outcomes (Hartogsohn, 2016). The proposed experiment is a double-blind, randomized between-subjects 2 x 2 factorial study in 120 volunteers who experience low psychological well-being at baseline and have limited prior experience with psychedelics (1:1:1:1, n = 30 per condition). The main aim of the study is to assess the contribution of a select number of pre-defined contextual variables (both 'set' and 'setting') on the nature and trajectory of effects linked to a single dosing session with either psilocybin (oral, 25mg) or placebo (oral, inert). The study will have four primary outcomes, two pertaining to mental health, namely: changes in psychological well-being - as measured via the Warwick-Edinburgh Mental Wellbeing Scales (WEMWBS), from baseline to 4 weeks post dosing session (primary endpoint) and changes in the Watts Connectedness Scale (WCS) at consistent timepoints. The two primary outcomes indexing the quality of the acute experience will be: Emotional Breakthrough - measured via mean scores on the Emotional Breakthrough Inventory (EBI), and Challenging experience (CE) - defined and measured here as scores on the following four sub-factors of the Challenging Experience Questionnaire (CEQ): fear, insanity, isolation, and paranoia.

keywords:
Healthy Participants With Lower-than-average Mental Well-being, Psilocybin, Context 1, Context 2, Placebo, RECRUITING


authors: Johns Hopkins University
journal: ClinicalTrials.gov
publication_date: 2014-05-19
source_url: https://clinicaltrials.gov/study/NCT01988311
substance_tags: psilocybin
topic_tags: Brain Imaging,Aging
study_type: Other
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT01988311","overall_status":"COMPLETED","phase":["PHASE1"]}
title:
Pilot Study: Effects of Psilocybin on Behavior, Psychology and Brain Function in Long-term Meditators

abstract:
This is a pilot study to finalize methods for a larger study being planned for the future. This research is being done to characterize performance of tasks, brain functioning, and the effects of psilocybin in individuals with a long-term meditation practice. There are three different parts of the pilot study: 1. Effects of psilocybin on psychological function: This version of the pilot study will involve 1 or 2 day-long psilocybin sessions, and several meetings and data assessment visits. You will make a total of about 5 to 10 visits to our research unit (the BPRU on the Johns Hopkins Bayview Campus). 2. Performance on behavioral and cognitive tasks: This version of the pilot study will involve completing various behavioral and cognitive tasks at our research unit. You will make a total of about 1-10 visits to our research unit (the BPRU on the Johns Hopkins Bayview Campus). 3. Brain functioning: This version of the study will involve 1 to 3 brain imaging (MRI) measurements. You will make a total of about 2 to 5 visits to our research unit (the BPRU on the Johns Hopkins Bayview Campus). The MRI measurements will be taken at the F.M. Kirby Research Center at the Kennedy Krieger Institute (across the street from the Johns Hopkins Hospital). People who are between the ages of 25 and 80 years old, who have a current, regular meditation practice, and who meet the medical requirements may join.

keywords:
Psilocybin, Hallucinogens, Pharmacologic Actions, Central Nervous System Agents, Therapeutic Uses, Psychotropic Drugs, psilocybin, COMPLETED


authors: Nathan Brashares Sackett
journal: ClinicalTrials.gov
publication_date: 2025-08-27
source_url: https://clinicaltrials.gov/study/NCT06853912
substance_tags: psilocybin
topic_tags: PTSD,Addiction,Clinical Trial,Veterans,Safety
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT06853912","overall_status":"RECRUITING","phase":["PHASE2"]}
title:
A Phase 2 Single-site, Double-blind, Placebo-controlled, Randomized Clinical Trial With an Open-label Extension Phase to Examine the Safety, Subjective Experiences, Acute Effects, and Suitability of Psilocybin Combined With Psychological Support (Psi-PS) for Military Veterans and First Responders With Co-occurring Alcohol Use Disorder (AUD) and Posttraumatic Stress Disorder (PTSD)

abstract:
This study is a phase 2 single-site, double-blind, placebo-controlled, randomized clinical trial with an open-label extension phase to examine the safety of psilocybin (25 mg) combined with psychological support (Psi-PS) for treatment of approximately 40 military veterans and first responders (ages 21-65) with co-occurring alcohol use disorder (AUD) and posttraumatic stress disorder (PTSD). Psychological support is defined as providing safety, reassurance, active listening, and empathetic presence during the drug administration session in a nondirective manner. We hypothesize that Psi-PS may provide a safe treatment for participants. The primary objective of study is to characterize the safety of psilocybin combined with psychological support (Psi-PS) for individuals with co-occurring alcohol use disorder (AUD) and PTSD. There is growing evidence suggesting that psychedelic drugs, when paired with therapy, may constitute a safe and effective form of treating a diverse range of psychopathological issues such as alcohol use disorder (AUD) and PTSD (Bogenschutz et al., 2015, 2022; Dakwar et al., 2020; Grabski et al., 2022; Mitchell et al., 2021, 2023). However, to date, no studies have explored any form of psychedelic-assisted therapy in the treatment of patients with co-occurring AUD and PTSD, despite high rates of comorbidity. This study will be the first of its kind to evaluate the safety of psilocybin paired with therapy to target symptoms of comorbid AUD and PTSD. Data derived from this clinical trial will help shed light on whether Psi-PS may be safe for those suffering from both PTSD and AUD. Taken together, we propose the following primary, secondary, and exploratory objectives: 1. Primary Objective: Characterize the safety of psilocybin combined with psychological support (Psi-PS) for participants during the drug administration session (DAS) while the drug's acute effects are ongoing, approximately 24 hours after the DAS when the drug's acute effects have subsided, and approximately one-week post-DAS. 2. Exploratory Objective: (1) Explore the subjective experiences of Psi-PS within approximately 24 hours following the DAS, i.e., when the drug's acute effects have subsided, approximately one-week following the DAS, and at follow-up at approximately three-months. (2) Assess acute effects of Psi-PS on a range of variables at baseline and weeks 1, 2, 4, 12, and 24 post-DAS; (3) Further, assess suitability at baseline and approximately 4-weeks post-DAS. This study is a single-site, double-blinded, placebo-controlled, randomized clinical trial with an open-label extension phase assessing safety in two conditions: 1. Psi-PS (psilocybin combined with psychological support); and 2. placebo and nondirective psychological support. The study will last approximately 26-32 weeks and is composed of two preparation sessions; one Drug Administration Session (DAS), where 25 mg of oral psilocybin (PEX010) or inert placebo (PCB2) is administered in a clinical setting with two facilitators present; and three integration sessions. Placebo conditions will receive the same psychological support but will receive an inert placebo. 4-weeks after DAS, the study will be unblinded and those who received placebo will be offered Psi-PS for the open-label extension phase, following the same procedures. The intended sample size for the study is approximately 40 military veterans and first responders (ages 21-65) with co-occurring alcohol use disorder (AUD) and posttraumatic stress disorder (PTSD). Study drug shipments will arrive on-site pre randomized by the manufacturer, and double-blinding will be maintained throughout the study by using a placebo that is designed to have similar physical characteristics as the study drug. All participants will then be followed for a total of 6 months (24 weeks) following the DAS to assess durability of potential effects.

keywords:
Alcohol Use Disorder (AUD), PTSD, Psilocybin 25 mg, PEX010, PYEX, Maltodextrin (Placebo), RECRUITING


title: Psilocybin AsSisted pSychotherapy for the treatmENt of Gambling disordER: a Pilot Study
authors: Nantes University Hospital
journal: ClinicalTrials.gov
publication_date: 2026-02-04
source_url: https://clinicaltrials.gov/study/NCT07391332
substance_tags: psilocybin
topic_tags: Clinical Trial,Safety
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT07391332","overall_status":"NOT_YET_RECRUITING","phase":["PHASE2"]}
abstract:
The PASSENGER project aims to conduct a pilot feasibility study of the implementation of a randomized clinical trial on psilocybin-assisted psychotherapy for the treatment of gambling disorder. Feasibility will be assessed by estimating the ability to retain participants until the end of the protocol. Other objectives of the study will be to generate preliminary efficacy data, identify clinical factors potentially associated with the intensity of the psychedelic experience (which determines the expected therapeutic effect), and conduct a preliminary assessment of the safety of the treatment under study.

keywords:
Gambling Disorder, Psychotherapy assisted by high-dose psilocybin (25mg or 40mg where appropriate), Psychotherapy assisted by low-dose psilocybin (1 mg), NOT_YET_RECRUITING


title: Characterization of Altered Waking States of Consciousness in Healthy Humans
authors: University of Zurich
journal: ClinicalTrials.gov
publication_date: 2021-04-28
source_url: https://clinicaltrials.gov/study/NCT03853577
keywords: Altered Waking States of Consciousness in Healthy Humans, TMS/EEG, COMPLETED
substance_tags: psilocybin
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT03853577","overall_status":"COMPLETED","phase":["NA"]}
abstract:
Altered waking states of consciousness and its underlying functional organization have gained increasing interest in recent years, i.e. in identifying the neural basis of consciousness. To overcome fundamental shortcomings of current methods to objectively assess the level of consciousness, the investigators propose here to apply a novel and empirically validated measure called 'perturbational complexity index' (PCI) based on the integrated information theory (IIT). This involves a combination of transcranial magnetic stimulation (TMS) and highdensity electroencephalography (hd-EEG) to measure electrocortical responses as distributed cerebral interactions ('integration') and spatiotemporal pattern ('information'). Given the finding of subjectively expanded consciousness as induced here by psilocybin, the investigators hypothesize that the PCI may be higher in such states. This will be the first TMS/hd-EEG study to investigate quantitatively the level of consciousness in a pharmacologically altered waking state of consciousness. In this study the investigators will apply navigated TMS/high-density(hd)-EEG to directly stimulate defined cortical areas and investigate quantitatively the level of consciousness in psilocybin-induced altered brain states. For this purpose, PCI is the primary outcome in psilocybin versus placebo condition. Given the findings and the subjective feeling of an 'expanded' consciousness in such states, the investigators primarily hypothesize that psilocybin will induce a higher PCI as compared to placebo in TMS/hd-EEG measurements over all targeted cortical areas in the acute phase of treatment (80 minutes after substance intake). Measurements will be done over the premotor cortex (Brodmann-Areal BA06), the midline sensorimotor cortex (BA04) and the superior occipital gyrus/cuneus (BA19) and may be related to the experience of an altered sense of self, e.g. measures of selflessness and egodissolution. This study further seeks to characterize the effects of psilocybin compared to placebo on resting state EEG. To this aim, the current source density and the lagged phase synchronization of neuronal oscillations across distributed brain regions will be computed and correlated to reproduce interesting results in a recent work of Kometer and colleagues. More specifically, psilocybin decreased the current source density of neuronal oscillations within a neural network comprising the anterior and posterior cingulate cortices and parahippocampal regions. Even more, psilocybin-induced insightfulness and spiritual experience correlated with the lagged phase synchronization of delta oscillations between the retrosplenial cortex, the parahippocampus and the lateral orbitofrontal area, showing evidence for a direct association of spatiotemporal neuronal mechanism with enhanced insight into life and existence. The investigators therefore hypothesize that current source density of neuronal oscillations within the cingulate cortices and the parahippocampal regions (1.5-20 Hz) will be decreased and the lagged-phase synchronization of delta oscillations (1.5-4 Hz) between the retrosplenial cortex, the parahippocampus and the lateral orbitofrontal area will be correlated to insightfulness. Additionally, psychometric assessment of the sense of self, of perceptual alterations and of mood will be conducted before and after each TMS session (Hood's Mysticism-Scale; 5-Dimensional Altered States of Consciousness Rating Scale; Positive and Negative Affect Schedule). the investigators expect to find a relationship between substance induced changes in perception and mood as indexed by these questionnaires. Furthermore, the investigators will be conducting a probabilistic learning task (emotLearn) to examine the computational processes behind the interaction between reward learning and subconscious versus conscious emotional processing to estimate how emotional stimuli affect the learning rate in psilocybin compared to placebo condition. The investigators hypothesize that psilocybin decreases the conscious and subconscious learning rate by attenuating the processing of emotional cues. The study design will be randomized, double-blind, placebo-controlled with one-time application of a single dose for each substance (moderate psilocybin dose of 20mg versus mannitol), within-subject and single center at the Psychiatrische Universitätsklinik Zurich. The number of participants is 25 healthy subjects as determined by power analysis. Inclusion criteria are healthy male or female volunteers aged 18-40 years. Exclusion criteria are personal and family history of major psychiatric disease (e.g. major depression, bipolar disorder, psychotic disorder) as defined in the DSM-V, any major medical condition (e.g. neurologic, cardiovascular, metabolic disease), family history of seizure disorder, current psychopharmacological treatment or pregnant respectively breastfeeding women. The study comprises a total of 3 visits in 3 weeks - 1 screening visit and 2 investigational visits and a written follow-up 12 weeks after the last investigational visit per participant. On the investigational visits participants will receive placebo or psilocybin in a randomized and counterbalanced order. The screening visit consists of a psychiatric assessment, physical examination, routine lab/toxicology, electrocardiogram (ECG), EEG and cranial T1 weighted magnetic resonance tomography (MRT). Study duration will be 2-3 years. The research project was approved by the local ethics committee (KEK Zurich) in December 2018 as "Other clinical trial" as specified in the "Ordinance on Clinical Trials in Human Research" (KlinV, Chapter 2) without health-related intervention or investigational Medical Product (IMP) \[25\], Category B.

topic_tags:
Depression,Brain Imaging,Consciousness,Emotional Processing,Spirituality,Mystical Experience,Clinical Trial,Toxicity,Drug Interactions


authors: Yale University
journal: ClinicalTrials.gov
publication_date: 2024-11-19
source_url: https://clinicaltrials.gov/study/NCT03356483
substance_tags: psilocybin
topic_tags: OCD,Brain Imaging,Clinical Trial
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT03356483","overall_status":"COMPLETED","phase":["PHASE1"]}
title:
Psilocybin Treatment in Obsessive-Compulsive Disorder: a Preliminary Efficacy Study and Exploratory Investigation of Neural Correlates.

abstract:
This study aims to investigate the effects of oral psilocybin on OCD symptomatology and provide the first evidence of the neural mechanism that may mediate psilocybin's purported therapeutic effects on OCD. Aim 1: To investigate the effects of psilocybin on OCD symptomatology. OCD symptom severity will be assessed before treatment and 24 and 48 hours after treatment, one week after treatment, two weeks, one month, and three months after treatment. Hypothesis: We hypothesize that 0.25mg/kg of psilocybin will lead to greater symptom improvement than niacin (as the active-placebo-control agent) at the primary endpoint of 48 hours post-dosing and at all other assessment points. Aim 2: To explore the relationship between the psilocybin-induced brain connectivity changes and symptom change in OCD. Resting-state brain connectivity will be assessed before and 48 hours after treatment. Hypothesis: We hypothesize that (i) psilocybin will normalize abnormal fronto-striatal functional connectivity in patients with OCD; and (ii) normalization of these abnormalities will correlate with improvement in symptomatology after psilocybin treatment. This study will pilot a single-center, randomized, active-placebo-controlled, double-blind design to examine the clinical and neural effects on OCD, of either 0.25mg/kg of psilocybin or active placebo-control agent (niacin 250mg), given along with non-drug preparatory and follow-up support appointments to 30 study participants. The duration of the randomized study phase is from consent until two weeks after drug administration. Participants will be followed for 12 weeks (3 months) post-study drug administration. Eligible participants will be admitted as an inpatient for at least 3 nights / 4 days surrounding the initial drug administration (or more, at the option of the subject and the investigator). Participants will be randomized into active medication and active-placebo-control groups, and will be blinded as to their study condition. This admission 2 nights prior to the drug administration will allow the participant to adjust to sleeping on the unit and allow them to settle in to the research unit routine. A return for an fMRI scan (48 hours after the administration session) will be scheduled. The participants who received active-placebo-control will be offered the option to receive open-label psilocybin.

keywords:
Obsessive-Compulsive Disorder, Psilocybin (0.25mg/kg), "Magic Mushrooms", Niacin (250mg), Nicotinic acid, COMPLETED


authors: University of Washington
journal: ClinicalTrials.gov
publication_date: 2025-11-04
source_url: https://clinicaltrials.gov/study/NCT05847686
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Receptor Pharmacology,Clinical Trial,Cancer Patients,Safety,Adverse Events
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT05847686","overall_status":"COMPLETED","phase":["PHASE1","PHASE2"]}
title:
A Phase 1/2 Study of a Group Model of Psilocybin-Assisted Therapy for Cancer-Related Anxiety in Patients With Metastatic Cancer

abstract:
This phase I/II trial tests the safety and side effects of psilocybin in combination with therapy for the treatment of patients with metastatic cancer and symptoms of anxiety and/or depression. Psilocybin is a substance being studied in conjunction with therapy for the treatment of anxiety and depression in patients with cancer. In this study, the psilocybin being used is derived from the mushroom psilocybe cubensis using a patented process that results in a pharmaceutical grade version of psilocybin. Psilocybin acts by activating serotonin receptors on brain cells which can change perceptions and patterns of thinking in ways that may decrease anxiety. OUTLINE: Patients receive psilocybin orally (PO) and participate in group and individual therapy sessions on trial.

keywords:
Hematopoietic and Lymphatic System Neoplasm, Metastatic Malignant Solid Neoplasm, Counseling, Counseling Intervention, Psilocybin, CY-39, Indocybin, psilocybine, Questionnaire Administration, COMPLETED


authors: COMPASS Pathways
journal: ClinicalTrials.gov
publication_date: 2026-05-11
source_url: https://clinicaltrials.gov/study/NCT07570654
substance_tags: psilocybin
topic_tags: PTSD,Clinical Trial,Safety
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT07570654","overall_status":"NOT_YET_RECRUITING","phase":["PHASE2","PHASE3"]}
title:
A Phase 2b/3, Multicentre, Randomised, Double-blind, Controlled Trial, With an Open Label Extension, to Investigate the Efficacy, Safety, and Tolerability of COMP360 in Participants With Post-traumatic Stress Disorder

abstract:
The Redefine Study (COMP202) is testing COMP360 to see if it may reduce post-traumatic stress disorder (PTSD) symptoms when administered alongside monitoring and support from a trained study team. COMP360 is a lab-made form of the naturally occurring chemical compound psilocybin.

keywords:
PTSD - Post Traumatic Stress Disorder, PTSD, PTSD Symptoms, PTSD, Post Traumatic Stress Disorder, COMP360 psilocybin, NOT_YET_RECRUITING


authors: University Hospital, Basel, Switzerland
journal: ClinicalTrials.gov
publication_date: 2020-11-30
source_url: https://clinicaltrials.gov/study/NCT03912974
keywords: Healthy, Escitalopram, Placebo oral capsule, COMPLETED
substance_tags: psilocybin
topic_tags: Depression,Neuroplasticity,Receptor Pharmacology,Consciousness,Safety
study_type: Other
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT03912974","overall_status":"COMPLETED","phase":["PHASE1"]}
title:
Effects of Serotonin Transporter Inhibition on the Subjective Response to Psilocybin in Healthy Subjects

abstract:
Psilocybin is a classic serotonergic hallucinogen acting on the 5-HT2A receptor. It is used recreationally and in psychiatric research. Selective serotonin reuptake inhibitors (SSRIs) like escitalopram are first-line treatments for depression. They inhibit the serotonin transporter (SERT). This might cause a possible downregulation of postsynaptic 5-HT receptors, e.g. the 5-HT2A receptor. The aim of the study is to investigate the effects of psilocybin after escitalopram and Placebo pretreatment. Subjective and physiological effects as well as effects on gene expression will be assessed. Psilocybin (the active substance in "magic mushrooms") is a classic serotonergic hallucinogen acting on the serotonin 5-HT2A receptor. Psilocybin is used recreationally and in psychiatric research. First studies suggest efficacy in psychiatric disorders, such as depression. SSRIs like escitalopram are currently among the first-line treatments of this disorder. Escitalopram acts as a serotonin transporter (SERT) inhibitor. However, the link between this mechanism and its positive effects on mood remains to be established. Several studies suggest a possible downregulation of postsynaptic serotonin (5-HT) receptors such as the 5-HT2A receptor. The aim of the study is to assess whether SERT inhibition reduces expression of the gene coding for the 5-HT2A receptor and the response to psilocybin. Participants will be treated with escitalopram (10 mg in the 1st and 20 mg in the 2nd week) or placebo for 14 days. Pretreatment is followed the first study day. A single dose of psilocybin (25 mg) will be administered. Primary study endpoint are the subjective effects on consciousness (measured by the 5D-ASC total score). Secondary study endpoints include additional psychological measurements, plasma concentrations of psilocybin and escitalopram, hydroxytryptamine receptor (HTR) gene expression, as well as some safety measures (autonomic effects, ECG). The washout between the first study day and the second pretreatment will be at least 2 days. In the second pretreatment period, participants will be treated with placebo or escitalopram (cross-over) for another 14 days. This is followed by the second study day and administration of psilocybin (25 mg). Based on a power analysis the sample size is 24 participants (12 female and 12 male).


title: The Effects of Psilocybin on Self-Focus and Self-Related Processing in Treatment Resistant MDD
authors: Massachusetts General Hospital
journal: ClinicalTrials.gov
publication_date: 2024-01-23
source_url: https://clinicaltrials.gov/study/NCT05381974
keywords: Treatment-Resistant Major Depressive Disorder, Psilocybin, WITHDRAWN
substance_tags: psilocybin
topic_tags: Depression,Brain Imaging
study_type: Other
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT05381974","overall_status":"WITHDRAWN","phase":["PHASE2"]}
abstract:
This open-label fMRI study will assess the effects of a single dose of psilocybin on rumination and the neural correlates of rumination in individuals with treatment-resistant major depressive disorder.


title: Psilocybin Treatment of Major Depressive Disorder With Co-occurring Alcohol Use Disorder
authors: Johns Hopkins University
journal: ClinicalTrials.gov
publication_date: 2026-03-12
source_url: https://clinicaltrials.gov/study/NCT04620759
substance_tags: psilocybin
topic_tags: Depression,Addiction,Healthcare Workers
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT04620759","overall_status":"ACTIVE_NOT_RECRUITING","phase":["PHASE2"]}
abstract:
The purpose of this study is to determine whether psilocybin, a hallucinogenic drug, is effective in reducing depressive symptoms and amount of drinking in patients with co-occurring Major Depressive Disorder (MDD) and Alcohol Use Disorder (AUD). The objectives of this double-blind, placebo-controlled study are to test the hypotheses that a single high (25 mg) oral dose of psilocybin will lead to enduring reductions in depressive symptoms (as measured by the clinician-rated grid version of the Hamilton Depression Rating Scale, or GRID-HAMD) and amount of drinking (as measured using the Time Line Follow Back, or TLFB, procedure) compared to placebo in patients with co-occurring MDD and AUD. 90 male and female volunteers who are between the ages of 21 and 65 years old and who meet Diagnostic and Statistical Manual, Fifth Edition (DSM-5) criteria for MDD and AUD will be recruited from the community and complete all study procedures. Volunteers will be randomized to one of two study arms (psilocybin \[N=45\] or placebo \[N=45\]), and will complete a drug administration session paired with a brief Motivational Interviewing intervention for alcohol use. Volunteers will undergo assessments of depression and alcohol use before and after treatment. After primary endpoints are measured, all volunteers will receive a second, unblinded intervention with a single high dose of psilocybin (25 mg) to test a secondary hypothesis that two doses of psilocybin are more effective in treating MDD with co-occurring AUD than a single dose.

keywords:
Major Depressive Disorder, Alcohol Use Disorder, Psilocybin, 4-phosphoryloxy-N,N-dimethyltryptamine, Placebo, ACTIVE_NOT_RECRUITING


title: 5-HT2A Agonist Psilocybin in the Treatment of Tobacco Use Disorder
authors: Johns Hopkins University
journal: ClinicalTrials.gov
publication_date: 2026-06-28
source_url: https://clinicaltrials.gov/study/NCT05452772
substance_tags: psilocybin
topic_tags: Addiction,Mechanism of Action,Receptor Pharmacology,Clinical Trial
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-02 06:57:00
raw_json: {"nct_id":"NCT05452772","overall_status":"RECRUITING","phase":["PHASE2"]}
abstract:
This is a multi-site, double-blind, randomized clinical trial of the 5-HT2A receptor agonist psilocybin for smoking cessation. Four sites with experience in conducting psilocybin research will be involved in this trial: Johns Hopkins University (JHU), the University of Alabama at Birmingham (UAB), and New York University (NYU). The proposed study will treat 66 participants (22 at each site), randomized to receive either: 1) oral psilocybin (30 mg in session 1 and either 30 mg or 40 mg in session 2); or 2) oral niacin (150 mg in session 1 and either 150 mg or 200 mg in session 2), with sessions 1 week apart. This is a multi-site, double-blind, randomized clinical trial of the 5-HT2A receptor agonist psilocybin for smoking cessation. The investigators previously conducted an open-label pilot trial (N = 15) of psilocybin paired with cognitive behavior therapy (CBT). Data showed a biologically-verified 7-day point-prevalence abstinence rate of 67% at 12 months and 60% at 2.5 years (continuous abstinence rates: 53% and 47%, respectively). The investigators are now conducting an open-label randomized comparative efficacy trial of psilocybin vs. nicotine patch, both in combination with CBT. Interim results (N = 44; 22 per group) show greater biologically-verified abstinence rates at 12 months for psilocybin: 7-day point-prevalence: 59% vs. 27%; continuous abstinence: 36% vs. 9%. Despite these promising findings, the investigators have yet to conduct a double-blind study of psilocybin for smoking cessation. Furthermore, previous psilocybin study samples have been largely White with higher socioeconomic status (SES). The current trial will address these issues across four sites with experience in conducting psilocybin research: Johns Hopkins, the University of Alabama at Birmingham (UAB), and New York University (NYU). A diverse sample with regard to ethno-racial identity and SES will be recruited at each site. The proposed double-blind study will treat 66 participants (22 at each site), randomized to receive either: 1) psilocybin; 30 mg in session 1 and either 30 or 40 mg in session 2, with sessions 1 week apart; or 2) niacin; 150 mg in session 1 and either 150 mg or 200 mg in session 2, with sessions 1 week apart. Niacin was selected because it has been used as an active placebo in two previous randomized therapeutic trials of psilocybin, and the FDA has informed the investigators that niacin is the FDA's preferred active placebo for psilocybin. CBT will be administered to both groups and will allow the investigators to test psilocybin's efficacy above and beyond an established treatment approach. Biochemically-confirmed 7-day point-prevalence abstinence will be assessed throughout for up to 12 months. The investigators hypothesize that psilocybin (compared to niacin) will cause increased biologically-confirmed 7-day point-prevalence abstinence at 12-month follow-up. Based on pilot data, the investigators will test cognitive/psychological mediators of treatment response. The investigators hypothesize that psilocybin will be associated with improved cognitive control and decreased anticipation of withdrawal relief (from smoking) 1 day after the target quit date, which will be associated with greater 7-day point-prevalence abstinence at 12- month follow-up. This trial will provide a rigorous test of efficacy in a diverse study sample, and test relevant mechanisms, for an innovative smoking cessation treatment showing potential for substantial efficacy.

keywords:
Tobacco Use Disorder, Psilocybin, Active Experimental Group, Niacin, Active Comparator Group, RECRUITING


title: A Multicenter Phase 1 Safety and Tolerability Trial of Psilocybin in Healthy Older Adults
authors: University of Colorado, Denver
journal: ClinicalTrials.gov
publication_date: 2026-06-29
source_url: https://clinicaltrials.gov/study/NCT07516405
keywords: Healthy Volunteer, Older Adults (65-85 Years), Psilocybin (Usona Institute), RECRUITING
substance_tags: psilocybin
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-02 06:57:00
raw_json: {"nct_id":"NCT07516405","overall_status":"RECRUITING","phase":["PHASE1"]}
abstract:
This study plans to learn more about the safety and tolerability of psychedelic administration (psilocybin) in healthy older adults ages 65-85. The purpose of this study is to learn whether psilocybin, a psychedelic compound, can be given safely to older adults. We want to understand how psilocybin affects the body and mind, including blood pressure, heart rhythm, and mood. We also want to see how the body processes psilocybin (how quickly it is absorbed and cleared) and whether it affects thinking, memory, or wellbeing. * Primary Objective: Evaluate the safety and tolerability of psychedelic administration in two cohorts of healthy older adults. * Cohort 1a Psilocybin Moderate Dose: 2 doses of oral psilocybin (10mg and then 25mg) 30 days apart. * Cohort 1b Psilocybin High Dose: 2 doses of oral psilocybin (15mg and then 30mg) 30 days apart. * Secondary Objectives: Evaluate the pharmacokinetics of Psilocybin for each Cohort of healthy older adults. * Exploratory Objectives: Evaluate patient-reported outcomes related to Psilocybin administration (e.g., psychedelic experience and well-being) in each Cohort. Assess the relationships between the pharmacokinetic profile, safety endpoints, and patient-reported outcomes in each Cohort.

topic_tags:
Pharmacology,Aging,Wellbeing,Clinical Trial,Observational Study,Healthy Volunteers,Older Adults,Safety


authors: Centre for Addiction and Mental Health
journal: ClinicalTrials.gov
publication_date: 2026-05-06
source_url: https://clinicaltrials.gov/study/NCT05710237
keywords: Treatment-resistant Depression, Psilocybin 25 mg, Risperidone 1 MG, Placebo, COMPLETED
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT05710237","overall_status":"COMPLETED","phase":["PHASE2"]}
title:
Does Psilocybin Require Psychedelic Effects to Treat Depression? A4-Week, Double-Blind, Proof-of-Concept Randomized Controlled Trial

abstract:
Psilocybin, the chemical component of "magic mushrooms", has been administered with psychotherapy in several randomized clinical trials (RCTs) showing large and sustained antidepressant effects. In healthy volunteers, the psychedelic effects of psilocybin have been shown to be blocked by administration of serotonin (5HT)2A receptor antagonists such as risperidone. The purpose of this "double dummy" proof-of-concept trial is to evaluate whether psilocybin's antidepressant effects are dependent on its psychedelic effects. Sixty participants with treatment-resistant depression will be randomly assigned to one of three groups: 1) Psilocybin 25 mg plus risperidone 1 mg; 2) Psilocybin 25 mg plus placebo; and 3) Placebo plus risperidone 1 mg. The investigator's hypothesize that the combination of psilocybin and risperidone will be well tolerated, safe, and will block the psychedelic effects of psilocybin in patients diagnosed with treatment-resistant depression. This study is a three-arm, 4-week, double blind, proof-of concept RCT for investigating psilocybin-assisted psychotherapy (PAP) administered with risperidone in treating TRD. This three-arm "double dummy" design allows for an assessment of risperidone's anti-psychedelic effects, while allowing for an assessment of psilocybin's antidepressant effects alone and combined with risperidone, compared to an "active placebo" (i.e. placebo plus risperidone 1 mg). Overview of Study Design: A study team member will obtain informed consent from interested participants prior to study activities being initiated. Following this, participants will undergo a screening assessment where they will complete lab tests, and clinical and psychiatric assessments to determine eligibility. Following the screening visit, eligible participants will undergo a washout period where they will be tapered off concomitant medication over a period of 4 to 6 weeks. The length of the tapering period will depend on the type of medication the participant is being tapered off (based on the half-life of the medication) and the participant's preference for the length of the tapering period. Most medications will require a minimum of a 2-week tapering period before the baseline, with the exception of fluoxetine, which will require a minimum of 4-weeks. Additional time may be added at the discretion of the study investigator. During the tapering period, the study psychiatrist will see participants weekly (V1a, V1b, etc.) for at least 4 weeks to monitor for withdrawal and worsening of depressive symptoms and suicidality. Suicidality will be closely monitored using the Columbia Suicide Severity Rating Scale (C-SSRS). Participants and their family members/carers will be educated on the signs and symptoms of worsening depression and suicidality and will be given contact details of the study team in case of major decline in mental state. At the Baseline visit (V2), which occurs the day before the dosing session, participants will complete clinical measures, and undergo a preparatory session (up to 4 hours) with the study therapists. These sessions will build a therapeutic alliance, provide psychoeducation about, and set intentions for, the psilocybin session. To reduce participant burden, baseline can be broken up into multiple days, however all assessments must be completed within 7-days of the intervention. Ideally, baseline occurs the day before the intervention is administered. The psilocybin session (Day 0 \[V3\]) will last 5 to 6 hours and will be conducted in the existing psychedelic treatment suite developed at the Centre for Addiction and Mental Health (CAMH) Mood Disorder Service by Dr. Husain (PI). Two trained study therapists will be supporting each participant during the dosing session. Participants will receive psilocybin 25 mg plus risperidone 1 mg, or psilocybin 25 mg plus placebo, or placebo plus risperidone 1 mg. All participants will receive 10 hours of manualized supportive psychotherapy (which includes the 5-6 hour dosing session). After 5 hours of dose administration, participants will be evaluated for safety by the study psychiatrist and discharged home in the company of a caregiver or a family member. After the dosing session, participants will be seen for two 1-hour integration sessions (Day 1 \[V4\], Week 1 \[V5\]). Thereafter, participants will be followed-up after 2 \[V6\], 3 \[V7\] and 4 weeks \[V8\] post-dosing (see Figure 1). A study psychiatrist will be available throughout the duration of the RCT to respond to any concerns or changes in mental/physical state. Participants will not start other interventions for MDD during the study.

topic_tags:
Depression,Addiction,Receptor Pharmacology,Clinical Trial,Randomized Controlled Trial,Healthy Volunteers,Treatment-Resistant Depression,Safety


authors: Ohio State University
journal: ClinicalTrials.gov
publication_date: 2026-03-03
source_url: https://clinicaltrials.gov/study/NCT05554094
substance_tags: psilocybin
topic_tags: PTSD,Veterans,Safety
study_type: Other
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT05554094","overall_status":"ACTIVE_NOT_RECRUITING","phase":["PHASE2"]}
title:
Examining the Safety and Clinical Efficacy of Psilocybin Therapy for Veterans With PTSD: An Open-Label Proof-of-Concept Trial

abstract:
The primary aim of this study is to assess the safety and efficacy of psilocybin-assisted therapy in the treatment of post-traumatic stress disorder in United States military Veterans. The objective of this study is to determine the safety and efficacy of psilocybin assisted psychotherapy in the treatment of Veterans with PTSD. This study will recruit 15 United States Military Veterans, age 21 to 64, primarily from the Columbus and Central Ohio Region who meet the criteria for PTSD. After enrollment and informed consent, participants will receive two separate doses of psilocybin in conjunction with preparatory and post-psilocybin therapy sessions. Each psilocybin session will last approximately 8 hours and will be facilitated by two trained session facilitators. Before the first psilocybin session, participants will meet with one or both of the session facilitators for a total of 6-8 hours of contact time (or up to 4 meetings) before the first psilocybin session day. Two post psilocybin therapy session visits will follow Psilocybin Sessions 1 and 2. Psilocybin Sessions 1 and 2 will occur about two weeks apart. Follow-up visits will occur 1 and 2 weeks and 1, 3, and 6 months after the final psilocybin session, with additional contact hours scheduled as needed. Thus, the intervention and follow-up requires at least 13 visits over a period of about 8-10 months.

keywords:
PTSD, Stress Disorders, Traumatic, Stress Disorders, Post-Traumatic, Trauma and Stressor Related Disorders, Mental Disorder, Psilocybin, ACTIVE_NOT_RECRUITING


title: Repeat Dosing of Psilocybin in Headache Disorders
authors: Yale University
journal: ClinicalTrials.gov
publication_date: 2024-02-08
source_url: https://clinicaltrials.gov/study/NCT04218539
keywords: Migraine Headache, Psilocybin, Placebo, COMPLETED
substance_tags: psilocybin
topic_tags: Headache / Migraine,Biomarkers,Inflammation
study_type: Other
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT04218539","overall_status":"COMPLETED","phase":["PHASE1"]}
abstract:
In seeking to understand the capacity for psilocybin to reduce migraine headache burden, this study will investigate single and repeated dosing of psilocybin up to two doses. In seeking to identify an underlying mechanism in psilocybin's effects, neuroinflammatory markers for migraine headache will be measured. Migraine headache is a common medical condition and a top cause of disability worldwide. Treatment options for migraine headache are many and varied, though an approximated 10% of migraineurs is refractory to medication and thus, there is a need to develop alternative treatments. There is anecdotal evidence supporting lasting therapeutic effects after limited dosing of psilocybin and related compounds in headache disorders. The cause of this unique effect remains unknown, though the drug class has demonstrable anti-inflammatory activity, a biological process relevant to migraine and other headache disorders. In seeking to understand the capacity for psilocybin to reduce migraine headache burden, this study will investigate single and repeated dosing of psilocybin up to two doses. In seeking to identify an underlying mechanism in psilocybin's effects, neuroinflammatory markers for migraine headache will be measured. The results from this study will serve in the development of larger investigations seeking to understand the effects of psilocybin and related compounds in headache disorders.


title: Psilocybin in Patients With Fibromyalgia: EEG-measured Brain Biomarkers of Action
authors: Imperial College London
journal: ClinicalTrials.gov
publication_date: 2024-01-18
source_url: https://clinicaltrials.gov/study/NCT05548075
substance_tags: psilocybin
topic_tags: Neuroplasticity,Brain Imaging,Biomarkers,Observational Study
study_type: Observational Study
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT05548075","overall_status":"UNKNOWN","phase":[]}
abstract:
The purpose of this study is to assess brain activity under Psilocybin in a cohort of people with fibromyalgia. This mechanistic (Non-CTIMP) study will utilise a within-subjects design to examine a candidate brain biomarker of increased plasticity under Psilocybin. Up to 25mg of Psilocybin will be administered under standardised conditions on two occasions, separated by four weeks with in-dosing EEG recordings. The primary end-point will take place 8 weeks from the first dosing session after which patients will be remotely monitored monthly for 6 months.

keywords:
Fibromyalgia, Psilocybin, O-phosphoryl-4-hydroxy-N,N-dimethyltryptamine, Therapeutic support, UNKNOWN


title: Effects of Psilocybin in Major Depressive Disorder
authors: Johns Hopkins University
journal: ClinicalTrials.gov
publication_date: 2021-12-14
source_url: https://clinicaltrials.gov/study/NCT03181529
keywords: Major Depressive Disorder, Psilocybin, COMPLETED
substance_tags: psilocybin
topic_tags: Depression
study_type: Other
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT03181529","overall_status":"COMPLETED","phase":["PHASE2"]}
abstract:
The proposed pilot study will assess whether people with major depressive disorder experience psychological and behavioral benefits and/or harms from psilocybin. This study will investigate acute and persisting effects of psilocybin on depressive symptoms and other moods, attitudes, and behaviors. The primary hypothesis is that psilocybin will lead to rapid and sustained antidepressant response, as measured with standard depression rating scales.


authors: University of Nebraska
journal: ClinicalTrials.gov
publication_date: 2026-05-05
source_url: https://clinicaltrials.gov/study/NCT05220046
substance_tags: psilocybin
topic_tags: End-of-Life Distress,Wellbeing,Observational Study
study_type: Observational Study
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT05220046","overall_status":"ACTIVE_NOT_RECRUITING","phase":["PHASE1"]}
title:
An Exploratory Pilot Study of Palliadelic Treatment to Reduce Psychological Distress in People With Pancreatobiliary and Other Advanced Gastrointestinal Cancers

abstract:
The primary objective of this study is to evaluate the ability to recruit and retain participants, and to successfully conduct a psilocybin-based protocol, for a study of the treatment of distress related to stage IV or inoperable gastrointestinal cancers. Secondary objectives include pre/post, and longitudinal measurement of distress in intervention participants and a paired family member who is in an observational arm. Participants with stage IV or inoperable gastrointestinal cancers are eligible for intervention, paired family member recruited for observational arm. Following preparatory sessions in outpatient palliative care clinic or by telehealth (2-4 sessions lasting 60-90 minutes each), psilocybin will be administered as a 25mg capsule during an 8-hour monitored session. Integration sessions (2-3 sessions lasting up to 90 minutes each) will take place in the outpatient palliative care clinic or by phone or tele-heath. Primary and secondary objectives are complete at one-week post treatment, longitudinal exploratory measures collected up to 12 months post baseline. Parallel assessment of health care utilization, including choices regarding anti-cancer treatment and resource utilization, and family member distress, family communication, well-being and bereavement will be conducted at concurrent time points.

keywords:
Pancreas Cancer, Biliary Tract Cancer, Psychological Distress, Gastrointestinal Cancer, Psilocybin, mushroom, ACTIVE_NOT_RECRUITING


authors: Bruyère Health Research Institute.
journal: ClinicalTrials.gov
publication_date: 2026-01-26
source_url: https://clinicaltrials.gov/study/NCT07063862
keywords: Psychological Distress, Psilocybin, Placebo, RECRUITING
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT07063862","overall_status":"RECRUITING","phase":["PHASE3"]}
title:
PSilocybin Microdose for psYCHological and Existential Distress in PALliative Care (PSYCHED-PAL): A Multi-site Phase 3 Double-blind, Placebo-controlled, Parallel-arm Clinical Trial

abstract:
About 30-50% of patients with advanced illness experience depression, anxiety, or decreased sense of purpose and autonomy. Together, these are called psychological distress. Treatment options such as medication and therapy are available; however, they do not always work and can be time-consuming and expensive. We need treatments that work well, quickly, and can be available to all patients with advanced illness who have psychological distress. Psilocybin, a psychedelic medication (commonly called 'magic mushrooms') works well for improving psychological distress in people with cancer or chronic illness when given in high doses with specific forms of therapy. However, psilocybin has not been well-studied among people with advanced illness, and there are concerns about safety and side effects in people approaching the end of life. However, reports on psilocybin microdosing, which involves taking small doses that do not cause hallucinations and do not require therapy, suggest that this may be effective, safer, and more acceptable for people with advanced illness. We recently completed a small study of psilocybin microdosing. Our results showed psilocybin microdose improved psychological distress in most participants with advanced illness, without serious side effects. Our next step is to do a randomized clinical trial where some patients receive psilocybin microdose and some receive placebo (a drug that contains no medicinal ingredients). By comparing these two groups, we can remove the possibility that improvements in symptoms are only because patients thought they were getting treatment. We will enroll 120 patients from inpatient, outpatient, and community care settings across seven sites. Participants in the microdose psilocybin group will receive 2 or 3 mg of psilocybin daily, 4 days per week, for two consecutive weeks. The placebo group will receive placebo with the same treatment schedule. All participants will be offered microdose psilocybin after 2-week follow-up. If this study is successful, we have the potential to change how psychological distress is managed in patients with advanced illness. Patients with advanced illness report feeling a sense of hopelessness, loss of autonomy and relationships, and a lack of purpose in life. These feelings of psychological suffering have been described as "existential distress" and are associated with poor outcomes, including decreased medication adherence and quality of life, increased desire for hastened death and rates of suicide, and has been identified as a primary reason why individuals pursue medical assistance in dying (MAiD). Current treatments for psychological and existential suffering have low efficacy and are challenging to use in a palliative context. Pharmacological approaches for treating psychological suffering may reduce symptoms of depression and anxiety, but evidence to support their efficacy in palliative care (PC) is underwhelming. Antidepressant and anxiolytic medications also take time to work and can cause serious side effects such as falls and confusion, which can be substantial deterrents for patients. Similarly, results from randomized controlled trials (RCTs) and meta-analyses have demonstrated psychotherapeutic interventions show limited benefit in a PC population. Further, psychotherapy can be time consuming and slow to work, which is not ideal for patients with limited life expectancy. Given the burden of psychological and existential distress among patients followed by PC providers, there is a need to develop scalable, brief, and rapidly effective therapeutic approaches to reduce this distress. Psychedelic medications offer an innovative, safe, complementary approach to address psychological and existential suffering in patients receiving PC. Studies from the 1950's showed serotonergic hallucinogens ("psychedelics") improved depression and anxiety symptoms in cancer patients. However, legislative changes restricted the use of these medications in clinical care and research. Interest in psychedelic medications has been rekindled by two recently published RCTs that studied the use of psilocybin (a mushroom-derived 5HT2A agonist) during a single psychotherapeutic session in cancer patients with anxiety and/or depression. These trials demonstrated rapid, clinically meaningful, and long-lasting reductions in depressed mood and/or anxiety symptoms and improvements in quality of life and death acceptance. Although the exact mechanism by which psilocybin affects mood symptoms is unclear, functional MRI studies of the brain show psilocybin disrupts the functional connectivity between anterior hippocampus (involved in memory and anticipation of future events) and the default mode network (associated with anhedonia and rumination on negative themes). There is also evidence suggesting psilocybin microdosing - taking sub-hallucinogenic doses continuously over longer time periods, rather than a one-time hallucinogenic dose - can improve mood and anxiety. The effects of microdosing, however, have not been rigorously evaluated, particularly in patients with life limiting illness. Results from recent trials are encouraging but knowledge gaps remain. First, studies to date primarily enrolled patients with localized disease who experience different distress than that of patients with advanced disease who are near the end of life. Second, it is unclear if Canadians would find psilocybin an attractive option in the context of MAiD legalization, which provides an alternative option for patients with severe psychological suffering. Third, there is no empirical research on the therapeutic effects of psilocybin microdosing, as most studies have followed macrodosing protocols. While preliminary efficacy of macrodosing has been demonstrated, there are important barriers to administering this therapy in a PC context. Previous trials had slow recruitment rates, suggesting there may be barriers related to the acceptability of psilocybin macrodosing from the perspectives of patients and families. Macrodosing requires the patient to dedicate an entire day to participating in a guided hallucinogenic experience and remain in an acute care setting where they can be closely monitored. It also requires patients to engage in preparatory sessions with monitors and a post-therapy session. In a PC context, this time commitment may not be acceptable or feasible for patients who are nearing the end of life. Macrodosing requires at least two trained moderators to guide the patient through their psychedelic experience and facilitate the pre- and post-dosing sessions. In most PC settings, it is not feasible to have clinicians dedicate two days to a single patient, thus limiting the scalability of this intervention. Anecdotally, concerns about the safety of high-dose psilocybin in the terminally ill, as well as access to psychotherapy, may also be substantial barriers in this population. Moreover, randomized trials of psychedelic medications are methodologically challenging because patients cannot be blinded to having a psychedelic experience. This "functional unblinding" was one major reason why the US FDA chose not to approve psychedelic medication for the treatment of post-traumatic stress disorder in August 2024, despite strongly positive trial results. Psilocybin microdosing may be safer and more feasible than psilocybin macrodosing in palliative setting. Psychedelic microdosing involves taking 5-10% of a psychedelic dose of a substance such as psilocybin on a regular basis (daily or several times per week). It does not produce a psychedelic experience, nor does it involve psychotherapy, but large surveys and anecdotal reports suggest that microdosing produces substantial and sustained improvements in mood and anxiety symptoms without any important side effects. By removing the requirement for trained moderators, minimizing the time commitment required of patients, eliminating the hallucinogenic effects of the therapy, and allowing patients to receive treatment either as an inpatient or in the community, microdosing may be a more acceptable option to patients and families and allow psychedelic therapy to be scalable across various PC settings. We have completed a phase 2 dose-finding and proof of concept study for microdosing psilocybin in people with advanced illness receiving PC. Using progressively increasing microdoses of psilocybin over a 3-week period (from 1 mg to 3 mg daily), we found that a large proportion of participants experienced dramatic improvements in their psychological distress, with minimal side effects. This effect was durable after stopping the medication but diminished after 4 weeks. Given the encouraging findings from our phase 2 study, and the potential feasibility, scalability, and safety of psilocybin microdosing for a population with few effective options, proceeding to a phase 3 placebo-controlled trial is warranted. Objectives Primary Objectives: To determine the efficacy of microdose psilocybin for improving psychological distress among patients with advanced illness followed by a palliative care provider. Secondary Objectives: 1. Assess whether microdose psilocybin improves quality of life and desire to die among patients with advanced illness followed by a palliative care provider. 2. Determine the safety of long-term (up to 1 year) use of psilocybin microdose to treat psychological distress among patients with advanced illness followed by a palliative care provider. Open-Label Access and Extension Phase Following the primary study 2-week follow-up completion, all participants will have the option to participate in an open-label access phase. In this phase, participants will be offered open-label psilocybin for two consecutive weeks (same dosing and schedule as the primary study). Two weeks after the access phase has been completed, all participants will have the option to participate in the open-label extension period for up to 1 year. The open-label extension will follow a three-week dosing cycle, where all participants will take psilocybin microdoses for two consecutive weeks, and then no doses on the third week, before starting the cycle again. The open-label and open-label extension phase include safety and primary and secondary outcomes (see Outcome Measures), in line with the primary study protocol. Sample Size We require a sample size of 60 patients per arm (120 patients in total). This assumes a 20% loss to attrition/deterioration and 10% withdrawal (based on our phase 2 study). This sample would have 80% power to detect a change of 0.30 from 30% PGIC response (control) to 60% PGIC response (intervention) at last treatment day, corresponding to an effect size (Cohen's d) of 0.61. Statistical Analysis We will follow an intent-to-treat approach. We will use chi-square tests to compare the proportion of participants in the microdose psilocybin vs. placebo arm with a PGIC score of ≥5 at the last day of treatment and at 2-week follow-up, and to compare the proportion of participants who demonstrate a minimal clinically important difference (MCID) in secondary efficacy outcomes. To minimize type I error, a correction will be performed on the multiple secondary endpoint analyses. Safety and feasibility outcomes will be analyzed using descriptive statistics with 95% confidence intervals.

topic_tags:
Depression,Anxiety,PTSD,End-of-Life Distress,Receptor Pharmacology,Default Mode Network,Aging,Microdosing,Clinical Trial,Randomized Controlled Trial,Observational Study,Cancer Patients,Healthcare Workers,Safety,Adverse Events


title: Precision Functional Brain Mapping to Understand the Mechanisms of Psilocybin
authors: Washington University School of Medicine
journal: ClinicalTrials.gov
publication_date: 2025-10-30
source_url: https://clinicaltrials.gov/study/NCT04501653
keywords: Psilocybin, psilocin, Methylphenidate, Metadate, Methylin, Ritalin, Concerta, COMPLETED
substance_tags: psilocybin,psilocin
topic_tags: Brain Imaging,Mechanism of Action,Receptor Pharmacology,Aging,Healthy Volunteers
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT04501653","overall_status":"COMPLETED","phase":["EARLY_PHASE1"]}
abstract:
This project will employ functional brain imaging to study the mechanism and immediate and long-term effects of psilocybin, a serotonin receptor 2A agonist, on cortical and cortico-subcortical brain networks in healthy adults. Psilocybin shows promise as a safe, transformational therapeutic across several psychiatric conditions. However, little is know about its mechanism of action. This study aims to establish a neuroimaging paradigm for use in future clinical research testing the effectiveness of psilocybin in various clinical applications. In this study, we will assess both acute (during psilocybin exposure) and sustained (one week post-exposure) effects of 5-HT2A receptor agonism on brain circuits using resting state functional connectivity and precision functional mapping (PFM). Using a randomized, controlled crossover study design, a small number of healthy volunteers will receive either psilocybin or methylphenidate (MTP) and will undergo MRI (structural, task, blood flow, extended resting state). After two weeks, participants will return for a second exposure with the alternate of what they received in the first session. This study involves up to five separate imaging sessions. Functional connectivity will be measured using the following PFM approach: 1. Extended functional magnetic resonance imaging (fMRI) image acquisition 2. Aggressive data cleaning 3. Analysis designed to examine functional brain connectivity at the individual level This will allow us to map the effects of 5-HT2A receptor agonism on cortical and cortico-subcortical brain networks at the individual level with precision that is unparalleled in the current literature. This is the first step in developing a precision neuroimaging approach for mechanistic understanding of psilocybin's therapeutic effects. If successful, this pharmacoimaging paradigm will have potential utility across psychiatric conditions, allowing us to better understand whether and how psilocybin might "bend the curve" in treatment course, preventing persistent suffering, disability, and suicide.


title: Measurement of Persisting Changes in Emotional Brain Functioning Produced by Psilocybin
authors: Johns Hopkins University
journal: ClinicalTrials.gov
publication_date: 2019-09-09
source_url: https://clinicaltrials.gov/study/NCT02971605
keywords: Healthy, Psilocybin, COMPLETED
substance_tags: psilocybin
topic_tags: Mechanism of Action,Emotional Processing,Abuse Liability
study_type: Other
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT02971605","overall_status":"COMPLETED","phase":["PHASE1","PHASE2"]}
abstract:
The proposed pilot study will assess whether ingestion of a classic hallucinogen (psilocybin) leads to changes in emotion processing and neural circuitry that may predict repeated self-administration of this drug and underlie an atypical mechanism of abuse liability, which may vitally contribute to the understanding of the potential for abuse and the underlying mechanisms supporting abuse of classic hallucinogens.


title: Effects of Psilocybin in Post-Treatment Lyme Disease
authors: Johns Hopkins University
journal: ClinicalTrials.gov
publication_date: 2025-08-19
source_url: https://clinicaltrials.gov/study/NCT05305105
keywords: Post-Treatment Lyme Disease, Chronic Lyme Disease, Lyme Disease, Chronic, Psilocybin, COMPLETED
substance_tags: psilocybin
topic_tags: General
study_type: Other
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT05305105","overall_status":"COMPLETED","phase":["PHASE1"]}
abstract:
This study will examine the effects of psilocybin on Lyme disease symptom burden and quality of life in people with Post-Treatment Lyme Disease (PTLD). This pilot study will evaluate the therapeutic potential of psilocybin in people with well-documented current Post-Treatment Lyme Disease (PTLD). Study measures will assess the impact of psilocybin-assisted treatment on overall symptom burden and quality of life in 20 people with PTLD. This is an open-label proof-of-concept trial in which participants will complete an 8-week course of study treatment including two psilocybin sessions (15mg in week 4 and 15 or 25mg in week 6) with psychological support, and follow-up assessments 1, 3, and 6 months after the final psilocybin session.


authors: University of Chicago
journal: ClinicalTrials.gov
publication_date: 2025-12-22
source_url: https://clinicaltrials.gov/study/NCT05399498
keywords: Borderline Personality Disorder, Major Depressive Disorder, Psilocybin, COMPLETED
substance_tags: psilocybin
topic_tags: Depression,Personality Change,Safety
study_type: Other
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT05399498","overall_status":"COMPLETED","phase":["PHASE2"]}
title:
An Open Label Study of Single-Dose Psilocybin for Major Depressive Disorder With Co-occurring Borderline Personality Disorder

abstract:
The primary objective of the study is to evaluate the safety and efficacy of psilocybin in adults with major depressive disorder (MDD) and borderline personality disorder (BPD). The primary objective of the proposed study is to evaluate the safety and efficacy of psilocybin in adults with major depressive disorder (MDD) and borderline personality disorder (BPD). Ten subjects with MDD and BPD will receive a single 25 mg oral dose of psilocybin. The hypothesis to be tested is that psilocybin will result significant reduction in symptoms of both MDD and BPD after 1 week and sustained for 4 weeks compared to baseline (improvement in symptoms will be indicated by lower scores on established outcome measures of MDD and BPD symptoms that have been used in prior studies).


authors: University of Southern California
journal: ClinicalTrials.gov
publication_date: 2025-09-25
source_url: https://clinicaltrials.gov/study/NCT06233344
keywords: Mental Health, Psilocybin plus mindfulness training, Psilocybin, RECRUITING
substance_tags: psilocybin
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT06233344","overall_status":"RECRUITING","phase":["PHASE2"]}
title:
An Exploratory Study of Feasibility, Efficacy, and Mechanisms of Mindfulness-Assisted Psychedelic Therapy

abstract:
The goal of this clinical trial is to test psilocybin in combination with mindfulness training in healthy adults. The main question it aims to answer is "Does mindfulness training enhance the effects of psychedelic therapy (psilocybin) on mental health?" Interested individuals will complete an initial eligibility session and eligible participants will then be randomized into one of two groups: one dose of psilocybin (administered under the supervision of study therapists) combined with 8 weeks of weekly mindfulness training classes (Arm 1) or psilocybin alone (Arm 2). Both groups will complete baseline and post-treatment assessment sessions where they will complete questionnaires, computerized cognitive tests, and have an EEG (a measure of electrical activity in the brain). Both groups will also complete 2 follow-up surveys (at 8 weeks and 1 year after the post-treatment assessment) either online through REDCap or by phone or video call with a research assistant. Psilocybin is a psychoactive compound found in a variety of mushrooms that has been used for centuries to facilitate spiritual experiences. Recent evidence suggests that the combination of psilocybin with mindfulness training may enhance the therapeutic effects of these interventions for mental health; however, to date, only few studies have investigated a combination approach, and no studies have yet investigated the effects of psilocybin in combination with a formal mindfulness training program in participants with little or no prior meditation experience. We propose here to conduct a pilot study to evaluate the efficacy of psilocybin administration in combination with 8 weeks of mindfulness training. Participants (N = 40) will complete an initial eligibility session and eligible participants will then be randomized into one of two groups: psilocybin integrated with mindfulness training (MT) (Arm 1) and psilocybin alone (Arm 2). Both groups will complete baseline and post-treatment assessment sessions where they will complete questionnaires and cognitive assessments. Both groups will also complete 2 brief follow-up surveys (at 8 weeks and 1 year after the post-treatment assessment) either online through REDCap or by phone or video call with a research assistant. The primary feasibility outcome will be retention rate at the 8-week follow-up time point (percent of eligible enrolled participants who complete the 8-week follow-up). Secondary efficacy outcomes include change in psychological and mood measures, blood inflammatory \& neurotrophic markers and neurocognitive measures (EEG outcomes) from baseline to post-treatment. Safety outcomes will include the number of participants reporting adverse events and the mean severity of events. Logistic regression models will be used to examine the relationships between intervention group and the primary and secondary outcome variables. The results of this pilot study will be used to support a larger NIH and other external grant application as well as the extension of this intervention to clinical populations.

topic_tags:
Brain Imaging,Mechanism of Action,Biomarkers,Spirituality,Clinical Trial,Observational Study,Safety,Adverse Events,Inflammation


authors: NYU Langone Health
journal: ClinicalTrials.gov
publication_date: 2022-02-13
source_url: https://clinicaltrials.gov/study/NCT02421263
keywords: Religious or Spiritual Problem, Psilocybin, COMPLETED
substance_tags: psilocybin
topic_tags: Wellbeing,Spirituality,Mystical Experience,Randomized Controlled Trial
study_type: Randomized Controlled Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT02421263","overall_status":"COMPLETED","phase":["PHASE1"]}
title:
A Randomized Controlled Trial of the Effects of Psilocybin-Facilitated Experience on the Psychology and Effectiveness of Professional Leaders in Religion

abstract:
The current protocol is a pilot study of the effects and possible utility of psilocybin-facilitated experiences for professional religious leaders. We hypothesize that religious professionals, given their interests, training, and life experience, will be able to make nuanced discriminations of their psilocybin experiences, thus contributing to the scientific understanding of mystical-type experience. As we better characterize the phenomenology of psilocybin-induced mystical experiences, we may apply this knowledge to improve potential treatment studies in the future. A primary objective is to investigate changes in psychological functioning, spirituality, health, well-being, prosocial attitudes and behavior in professional religious leaders that may occur after receiving psilocybin under supportive conditions. A secondary objective is to determine whether participants who report having had the strongest mystical-type effects during psilocybin sessions will show the largest positive changes in the Interim Questionnaire. This randomized-controlled pilot study uses a wait-list control design. A wait-list design includes a control group that is assigned to a waiting list to receive an intervention after the active treatment group does. In this study, the active group will receive the psilocybin at weeks 5 and 9 and the wait-list control group will receive psilocybin at weeks 30 and 34. The wait-list control group serves the purpose of providing an untreated comparison for the active treatment group, while at the same time allowing the wait-list participants an opportunity to obtain the intervention at a later date. This study's procedures include screening, preparatory meetings, psilocybin sessions, and follow-up assessments. A large battery of behavioral and psychological measures will be assessed throughout. The study team will consent and enroll up to 86 subjects to obtain a total of 12 completer participants as well as 2-3 family members or friends per study participant who can assess said completers on the Observer Rating Form (COM-R). This number will account for screen-failures and dropouts as well. The 12 participants will be randomly assigned to either an immediate participation group (N=6) or a 6-month delayed participation group (N=6). Although statistical power calculations show that 12 participants will be sufficient to detect the major effects anticipated in this study, the sponsor of this study (The Council on Spiritual Practices) is concurrently funding Johns Hopkins University School of Medicine to conduct a methodologically identical study with 12 additional participants (IND #59009). This will permit the two sites to collaborate post study completion and combine the data from the two studies to provide statistical power to detect even more subtle effects of the psilocybin intervention. Twelve volunteers (6 from each group) will participate at Johns Hopkins and 12 at New York University. Randomization and data analysis will be conducted at New York University.


authors: University Hospital, Basel, Switzerland
journal: ClinicalTrials.gov
publication_date: 2026-04-28
source_url: https://clinicaltrials.gov/study/NCT05883540
substance_tags: psilocybin
topic_tags: Depression,Anxiety,End-of-Life Distress,Chronic Pain,Clinical Trial
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT05883540","overall_status":"RECRUITING","phase":["PHASE2"]}
title:
Lysergic Acid Diethylamide (LSD) in Palliative Care: a Randomised, Double-blind, Active-placebo Controlled Phase II Study (LPC-Study)

abstract:
Background: Terminally ill patients often experience significant psychosocial distress having depressed mood, death anxiety, pain, and an overall poor quality of life. Recent evidence from pilot studies suggests that serotonergic hallucinogens including lysergic acid diethylamide (LSD) and psilocybin produce significant and sustained reductions of depressive symptoms and anxiety, along with increases in quality of life, and life meaning in patients suffering from life-threatening diseases. Additionally, serotonergic hallucinogens may produce antinociceptive effects. Objective and Design: The study aims to evaluate effects of LSD on psychosocial distress in 60 patients suffering from an advanced or end-stage fatal disease with a life expectancy ≥12wks and ≤2yrs in an active placebo-controlled double-blind parallel study. Patients will be allocated in a 2:1 ratio to one of the two intervention arms receiving either two moderate to high doses of LSD (100 µg and 100 µg or 100 µg and 200 µg) as intervention and two low doses of LSD (25 µg and 25 µg) as active-placebo control.

keywords:
Palliative Care, Pain, Anxiety, Depression, Demoralization, Psychological Distress, Quality of Life, Caregiver Burden, Fear of Death, Existential Distress, Lysergic Acid Diethylamide Tartrate, LSD, RECRUITING


title: Psilocybin - Induced Neuroplasticity in the Treatment of Major Depressive Disorder
authors: Yale University
journal: ClinicalTrials.gov
publication_date: 2025-11-04
source_url: https://clinicaltrials.gov/study/NCT03554174
substance_tags: psilocybin
topic_tags: Depression,Neuroplasticity
study_type: Other
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT03554174","overall_status":"ACTIVE_NOT_RECRUITING","phase":["PHASE1"]}
abstract:
The primary goal of this pilot study is to investigate whether psilocybin alters neuroplasticity in people with major depressive disorder. The primary hypothesis is that psilocybin will result in neuroplastic changes that parallel improvement in symptoms of depression. In this placebo-controlled, blinded study, individuals with depression will participate in 2 experimental sessions approximately 4 weeks apart during which they will receive two of the following three interventions: 1) placebo, 2) low dose psilocybin (0.1 mg/kg), and 3) medium dose psilocybin (0.3 mg/kg).

keywords:
Major Depressive Disorder, Low Dose Psilocybin, Placebo, Medium Dose Psilocybin, ACTIVE_NOT_RECRUITING


authors: University of Calgary
journal: ClinicalTrials.gov
publication_date: 2026-05-13
source_url: https://clinicaltrials.gov/study/NCT06885996
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT06885996","overall_status":"NOT_YET_RECRUITING","phase":["PHASE2"]}
title:
Psilocybin-assisted Therapy for Post-Traumatic Stress Disorder in Survivors of Intimate Partner Violence

abstract:
The goal of this randomized controlled trial is to evaluate the efficacy of psilocybin administered with Acceptance and Commitment Therapy (ACT) as an intervention to reduce post-traumatic stress disorder (PTSD) symptom burden in adult (aged 18-65) survivors of intimate partner violence (IPV). This trail will test the following 2 aims: AIM1: To compare the efficacy of a therapeutic psilocybin dose at improving outcomes on the PCL-5 and CAPS-5 as compared to an active control psilocybin dose in IPV survivors with chronic PTSD. AIM2: To evaluate the efficacy of psilocybin on quality of life, cognitive function, motor ability, depression, anxiety, and cognitive flexibility. Participants will be asked to: * Complete a 2 part screening process * Attend a baseline assessment * Complete a psychoeducation preparation session(s) * Attend psilocybin administration session (receive high dose \[25mg\] or low dose psilocybin \[1mg\]) * Complete 5-6 weekly sessions of ACT * Repeat outcome measures at 1-week, 4 weeks, 3 months (online questionnaires only), and 6 months post-psilocybin administration. The overall objective of this study is to evaluate the efficacy of psilocybin administered with Acceptance and Commitment Therapy (ACT) as an intervention to reduce post-traumatic stress disorder (PTSD) symptom burden in survivors of intimate partner violence (IPV). This trail will test the following 2 aims: AIM1: To compare the efficacy of a therapeutic psilocybin dose (25mg) at improving outcomes on the PCL-5 and CAPS-5 as compared to an active control psilocybin dose (1mg) (allocation ratio 1:1) in IPV survivors with chronic PTSD. Mean baseline scores will be compared to scores at each follow-up timepoint (1-week, 4 weeks, 3 months (PCL-5 only), and 6 months post-psilocybin administration). AIM2: to evaluate the efficacy of psilocybin on quality of life, cognitive function, motor ability, depression, anxiety, and cognitive flexibility. Mean baseline scores will be compared to scores at each follow-up timepoint (1-week, 4 weeks, 3 months (online only), and 6 months post-psilocybin administration). The secondary efficacy outcomes will include measures of mood, anxiety, post-traumatic stress, cognitive flexibility, emotional regulation, and quality of life. Exploratory Aim: Exploratory objectives of this study include evaluating blood biomarkers reflective of inflammation, growth factors, brain injury, and oxidative stress relevant to PTSD and psilocybin's mechanisms of action. A total of 76 male and female patients between the ages of 18-65 with the last incident of IPV greater than 6 months prior with a score of 1 on the Composite Abuse Scale with repetition of abusive events, meeting DSM-5 criteria for PTSD and a minimum PCL-5 score of 33. All patients will undergo a thorough, 2-part screening procedure. Eligible participants will be randomly allocated 1:1 to either the high dose (38 participants) or low dose (38 participants) psilocybin groups. All participants will be asked to attend a baseline session consisting of clinical and behavioural outcome measures followed by a pre-dosing psychoeducation session. Following the single dosing session, participants will complete 5-6 weekly ACT sessions. Outcome measure assessments will be repeated at 1-week, 4 weeks, 3 months (online only), and 6 months post-dosing.

keywords:
Post Traumatic Stress Disorder PTSD, Intimate Partner Violence (IPV), Psilocybin, NOT_YET_RECRUITING

topic_tags:
Depression,Anxiety,PTSD,Mechanism of Action,Biomarkers,Oxidative Stress,Emotional Processing,Randomized Controlled Trial,Inflammation


authors: TRYP Therapeutics
journal: ClinicalTrials.gov
publication_date: 2024-11-18
source_url: https://clinicaltrials.gov/study/NCT05035927
keywords: Binge Eating Disorder, TRYP-0082, Psilocybin, Psychotherapy, COMPLETED
substance_tags: psilocybin
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT05035927","overall_status":"COMPLETED","phase":["PHASE2"]}
title:
A Phase 2a Safety and Feasibility Study Evaluating Psilocybin (TRP-8802) Administration in Concert With Psychotherapy in the Treatment of Binge Eating Disorder

abstract:
To better understand the potential benefits of psychedelics in overeating disorders, Tryp Therapeutics will conduct a safety and feasibility clinical trial using TRP8802 among individuals with Binge Eating Disorder. This is a single-center phase 2a open-label study to assess the safety and feasibility of a single dose of TRP8802 in subjects with BED. Subjects will undergo screening, preparation therapy sessions, dosing, integration therapy sessions, and follow-up for 12 weeks following the dose of TRP8802. The total participation in the study will be up to approximately 5 months. Binge eating disorder is the most common eating disorder and is associated with obesity and psychiatric comorbidities, including depression, and impulsive and compulsive disorders. Binge eating disorder is marked by severe disturbance to a person's control over their eating behaviors and high anxiety around food. Various programs using psilocybin paired with psychotherapy have shown positive effects in treating a variety of psychiatric and behavioral conditions, including cancer-related psychiatric distress, anxiety, treatment-resistant depression, and nicotine and alcohol addiction. Based on clinical precedents, relevant neuropharmacology, and mechanistic similarities, psilocybin is theorized to have the potential to be part of the treatment of overeating disorders. TRP-8802 could accomplish this by moderating overall anxiety, anxiety around food, perseveration, and repetitive and intrusive thoughts about food in people with BED. The primary objective of this study is to: 1\. Assess the safety of a single dose of TRP8802 in participants with binge eating disorder (BED) during the TRP8802 dosing session, and through 12 weeks following dosing (i.e., Week 14).

topic_tags:
Depression,Anxiety,Addiction,Eating Disorders,Pharmacology,Clinical Trial,Cancer Patients,Treatment-Resistant Depression,Safety


authors: NYU Langone Health
journal: ClinicalTrials.gov
publication_date: 2025-12-03
source_url: https://clinicaltrials.gov/study/NCT05398484
keywords: Advanced Cancer, Psilocybin 25 mgs, Niacin 100mg, Psychotherapy, RECRUITING
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Mechanism of Action,Clinical Trial,Randomized Controlled Trial,Safety
study_type: Randomized Controlled Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT05398484","overall_status":"RECRUITING","phase":["PHASE2","PHASE3"]}
title:
A Phase 2b, Randomized, Double-blind, Placebo-controlled, Multi-center Study of the Effects of Psilocybin-assisted Psychotherapy on Psychiatric and Existential Distress in Advanced Cancer

abstract:
The purpose of this research is to study the safety and effects of single-dose psilocybin 25mg versus an active placebo (single dose niacin 100mg) in the treatment of anxiety, depression, and existential distress (i.e., loss of meaning and hope; fear of death) in advanced cancer (i.e., stage 3 or 4). Study medications will be administered in conjunction with brief psychotherapy that is designed to treat anxiety, depression and existential distress in advanced cancer. This trial is designed to evaluate efficacy and psychological mechanisms of single-dose psilocybin-assisted psychotherapy (PAP) to treat psychiatric (anxiety, depression) and existential distress (demoralization, death anxiety), and quality-of-life (QOL), in 200 outpatients with late-stage or advanced cancer. The study will assess the strength and durability of therapeutic effects in a double-blind, parallel-design, placebo-controlled, two-center RCT comparing a single 25mg oral 'high' dose of psilocybin to a single 100mg dose of niacin (active placebo), both delivered in conjunction with a psychotherapy platform.


title: Psilocybin-assisted Cognitive Behavioral Therapy for Depression
authors: University of California, Los Angeles
journal: ClinicalTrials.gov
publication_date: 2026-05-18
source_url: https://clinicaltrials.gov/study/NCT05227612
keywords: Major Depressive Disorder, Psilocybin, Cognitive behavioral therapy, COMPLETED
substance_tags: psilocybin
topic_tags: Depression
study_type: Other
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT05227612","overall_status":"COMPLETED","phase":["PHASE1"]}
abstract:
The primary objectives of this clinical investigation are to (1) determine the acceptability and feasibility of joining psilocybin-assisted therapy with cognitive-behavioral therapy (PA-CBT) for patients with depression, (2) optimize CBT to most effectively integrate the psilocybin experience with psychotherapy and (3) examine the clinical benefit of psilocybin as an adjunct to cognitive-behavioral therapy (CBT) for major depressive disorder. This study will involve an open trial of PA-CBT where participants will receive two doses of psilocybin (10mg and then 25mg, separated by one month) plus 12 sessions of cognitive behavioral therapy.


authors: Yale University
journal: ClinicalTrials.gov
publication_date: 2025-12-28
source_url: https://clinicaltrials.gov/study/NCT07306364
substance_tags: psilocybin
topic_tags: Addiction,Chronic Pain,Mechanism of Action,Animal Study
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT07306364","overall_status":"NOT_YET_RECRUITING","phase":["PHASE2"]}
title:
Psilocybin in Chronic Low Back Pain: An Integrative Study of Lab-Based Mechanisms and Real-World Physical Therapy Outcomes

abstract:
The purpose of this research study is to investigate whether a single administration of psilocybin can improve interoceptive awareness (awareness of bodily sensations) in individuals with chronic low back pain undergoing physical therapy, and whether these improvements are linked to pain relief and better physical therapy outcomes. Preclinical and human studies suggest that psilocybin can temporarily disrupt rigid, maladaptive patterns of brain activity and promote longer-lasting changes in how the brain processes internal sensations. People with chronic pain who have used psilocybin qualitatively describe feeling more aware of their bodies, able to reinterpret pain sensations, and less distressed and disabled by their pain. Building on these mechanistic insights, this randomized, double-blind, placebo-controlled trial will evaluate a single dose of low- (10 mg), moderate-dose (25 mg), or placebo (niacin) administered prior to a standardized course of physical therapy (PT) in adults with chronic low back pain (CLBP). Participants in both treatment groups will receive a course of PT that is consistent with what would be delivered outside of involvement in the research study. That is, the study is evaluating psilocybin as an adjunct to PT delivered in a community outpatient PT clinic. By testing whether psilocybin-induced recalibration of brain networks can enhance engagement with and outcomes of PT, this study aims to establish a novel, non-opioid integrative strategy to relieve CLBP and restore functional recovery.

keywords:
Chronic Low Back Pain (CLBP), Physical Therapy, Psilocybin, Psilocybin 10 mg, Psilocybin 25 mg, Niacin 100 mg, NOT_YET_RECRUITING


title: Group Psilocybin-assisted Cognitive Behavioral Therapy for Major Depressive Disorder
authors: University of California, Los Angeles
journal: ClinicalTrials.gov
publication_date: 2026-05-03
source_url: https://clinicaltrials.gov/study/NCT07566104
substance_tags: psilocybin
topic_tags: Depression
study_type: Other
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT07566104","overall_status":"NOT_YET_RECRUITING","phase":["PHASE2"]}
abstract:
This study will seek to determine the (1) acceptability and (2) feasibility of psilocybin as an adjunct to cognitive-behavioral therapy, delivered as a group treatment (G-PACBT) for major depressive disorder and (3) explore the clinical effects of G-PACBT on depressive symptoms and psychosocial functioning.

keywords:
Depression - Major Depressive Disorder, Psilocybin, Cognitive Behavioral Therapy, Psilocybin (drug), Group Cognitive Behavioral Therapy, NOT_YET_RECRUITING


title: Psilocybin-facilitated Treatment for Chronic Pain
authors: University of Alabama at Birmingham
journal: ClinicalTrials.gov
publication_date: 2026-03-10
source_url: https://clinicaltrials.gov/study/NCT05068791
keywords: Fibromyalgia, Primary, Psilocybin, Dextromethorphan, RECRUITING
substance_tags: psilocybin
topic_tags: Chronic Pain,Personality Change,Emotional Processing,Mystical Experience,Safety
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT05068791","overall_status":"RECRUITING","phase":["EARLY_PHASE1"]}
abstract:
The primary purpose of this study is to preliminarily estimate the efficacy of psilocybin-facilitated treatment for fibromyalgia. Investigators will assess the impact of psilocybin-facilitated treatment on pain, fatigue, and other fibromyalgia symptoms, in addition to the level of functioning and quality of life. Investigators will also evaluate potential mediators of treatment (e.g., treatment expectations, pain characteristics, personality, beliefs/cognitions, emotions). Investigators hypothesize psilocybin treatment will significantly reduce symptom severity in fibromyalgia patients. Participants will be randomized to two groups: Psilocybin or Active Placebo. Those in the Psilocybin condition will receive.36 mg/kg of psilocybin. Based on previous research,.36 mg/kg of psilocybin is expected to balance the intention to increase the probability of having a full mystical-type experience against the odds of having a subjectively challenging psychological experience. Those in the Active Placebo condition will receive 2.6 mg/kg of dextromethorphan (DXM). DXM was selected as the placebo drug in the current study because its subjective and behavioral effects at higher doses can resemble those of classical hallucinogens. Participants will be blinded to what drug they are administered. Participants will be unblinded at the end of the study. Participants will attend between 7 to 9 study sessions to complete the protocol. Interested individuals who call research staff will undergo an initial telephone prescreen by a trained member of the research staff: the study aims, protocol, and any possible risks will be described and a series of questions will be asked to determine interest and eligibility for screening for the study. Initial eligibility may also be assessed via an online questionnaire through Qualtrics. Qualified participants will be scheduled for an in-person screening. In-person screening sessions will be conducted by the PI or trained research staff. Individuals will first undergo informed consent; the consent form will describe the necessary eligibility confirmation that takes place before proceeding with the full study. A physical examination, a detailed psychiatric interview, several self-report questionnaires, and a detailed medical history will be completed at the screening session, which takes place at the UAB Clinical Research Unit. Participants will also have their blood drawn for screening tests. Study staff will provide participants with a hand-held tablet device and instructions on how to complete the daily symptom questionnaire via the tablet. They will be asked to begin reporting daily symptoms on their tablet from home that evening. Eligible participants will be contacted by study staff by phone to inform them of their eligibility. All participants will undergo at least 2 weekly preparation sessions of approximately 2 hours each, with the possibility of 1-2 additional weekly preparatory sessions per the discretion of the investigator. These sessions are to educate participants on the study protocol, psilocybin administration, and study treatment rationale. Participants will be randomly assigned in a double-blind manner to the Psilocybin or Active Placebo group following their final preparation session. One week after the final preparation session, participants will be instructed to eat a low-fat breakfast prior to presenting for their drug administration session at 8:00 am, approximately 1 hour before drug administration. A urine sample will be collected to verify drug-free and non-pregnant status and participants will be encouraged to relax and reflect before drug administration. The drug administration session will take place over the course of 8 hours. The guide and secondary monitor will be present with and monitor participants throughout this session (at least one individual will always be present with the participant, even during brief intervals when the guide or monitor may be using the restroom). Participants will be monitored for physical symptoms of distress and encouraged to report any symptoms experienced. Blood pressure will be assessed pre-administration via automatic blood pressure monitor, and will also be assessed at 30, 60, 90, 120, 180, 240, 300, and 360 minutes post-administration. Eight hours after drug administration, when the major drug effects have subsided, participants will complete questionnaires assessing their experience. Participants will then be released into the care of a friend or family member oriented to be emotionally supportive of the participant (as arranged during preparation sessions) and instructed not to drive an automobile or engage in any other potentially dangerous activity for the remainder of the day. Participants will be provided with the guide's contact information by phone should they feel the need for support that evening. An immediate post-session meeting will be held the day following the drug administration session. Participants will meet with the guide for approximately 2 hours to discuss and reflect on their experience. A final study visit will take place approximately 6 weeks later; some questionnaires that were administered at Visit 1 will be administered again at the final visit. At the conclusion of the final study visit, participants will be debriefed.


authors: Johns Hopkins University
journal: ClinicalTrials.gov
publication_date: 2024-02-01
source_url: https://clinicaltrials.gov/study/NCT05242029
keywords: Opioid Use Disorder, Placebo, Psilocybin, WITHDRAWN
substance_tags: psilocybin
topic_tags: Addiction,Chronic Pain,Toxicity
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT05242029","overall_status":"WITHDRAWN","phase":["PHASE2"]}
title:
A Randomized, Double-Blind Study of Psilocybin for Opioid Use Disorder in Patients on Methadone Maintenance With Ongoing Opioid Use

abstract:
This study will investigate whether psilocybin administered under supportive conditions can reduce illicit opioid use and improve quality of life in individuals with Opioid Use Disorder (OUD) in Methadone Maintenance Treatment (MMT) who are concurrently using other opioids illicitly. This randomized double-blind placebo-controlled trial will investigate whether 2 doses of psilocybin administered under supportive conditions can reduce illicit opioid use (assessed by self-report and urine toxicology) and improve quality of life as measured by World Health Organization Quality of Life (WHOQOL-BREF) in individuals with OUD in MMT who are concurrently using other opioids illicitly. In addition, the investigators will investigate secondary outcomes including whether psilocybin under supportive conditions improves mood, reduces use of tobacco and other non-opioid drugs, improves chronic pain and sleep. Ninety-two participants aged 21-70 who meet Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for OUD, are enrolled in a MMT program for at least 3 months, and have urine toxicology positive for methadone and another opioid will be recruited from the community and complete all study procedures. Participants will be randomized to an active group or control group (46 per group). Participants will undergo a total of 2 dosing sessions (whether psilocybin or placebo). The active group will receive 40mg psilocybin first. All participants will receive a second dosing session at three months. The active group will be further randomized, with half receiving 40mg psilocybin, and half receiving placebo at three months to test a secondary hypothesis that two doses of psilocybin are more effective in treating OUD than a single dose.


authors: Brain and Cognition Discovery Foundation
journal: ClinicalTrials.gov
publication_date: 2023-07-26
source_url: https://clinicaltrials.gov/study/NCT05029466
keywords: Treatment Resistant Depression, Psilocybin, COMPLETED
substance_tags: psilocybin
topic_tags: Depression,Clinical Trial,Treatment-Resistant Depression,Safety,Adverse Events
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT05029466","overall_status":"COMPLETED","phase":["PHASE2"]}
title:
The Efficacy and Tolerability of Psilocybin in Participants With Treatment-Resistant Depression: a Phase 2, Randomized Feasibility Study

abstract:
The purpose of this study is to see if psilocybin, an investigational drug, is safe and well tolerated. Researchers also want to know if psilocybin can improve symptoms of depression. This study will see if psilocybin is safe and well tolerated by tracking changes in suicidal thoughts and behaviour, monitoring if any participants choose to stop participating in the study, and measuring any serious side effects, as well as how long they take to resolve. This study will also see if depression symptoms improve (or worsen) after psilocybin is administered. Additional information about participants' depressive symptoms and side effects will also be measured during the study. This randomized clinical trial will assess the feasibility, safety, and efficacy of single and repeat doses of psilocybin at point-of-care in persons with treatment-resistant depression as part of major depressive disorder or bipolar II disorder. The primary objective is to evaluate the feasibility of psilocybin in adults with treatment-resistant depression. The secondary objectives are to assess the efficacy and tolerability of psilocybin at point-of-care.


authors: Yvan Beaussant, MD, MSci
journal: ClinicalTrials.gov
publication_date: 2026-02-16
source_url: https://clinicaltrials.gov/study/NCT04950608
substance_tags: psilocybin
topic_tags: Depression,End-of-Life Distress,Cancer Patients,Safety
study_type: Other
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT04950608","overall_status":"COMPLETED","phase":["PHASE2"]}
title:
Pilot Study of Psilocybin-Assisted Therapy for Demoralization in Patients Receiving Hospice Care - PATH Study

abstract:
The overall objective of this study is to develop and pilot test a novel regimen of psilocybin-assisted psychotherapy for demoralization in patients receiving hospice care. -The name of the study drug involved in this study is Psilocybin The purpose of this research is to understand how psilocybin-assisted therapy may be adapted in the context of hospice care, in order to test its safety in people with terminal illness who experience demoralization, and to study how well it works to lessen symptoms of psychological and existential distress. * This research study involves a combined drug and psychotherapeutic (talk therapy) intervention. The research study procedures include screening for eligibility, and study intervention including preparation, evaluations, one psilocybin session and follow up visits. * The treatment regimen consists of a single administration of psilocybin with a supportive psychotherapy including 2 preparation sessions and 2 integration sessions * The name of the study drug involved in this study is Psilocybin. Psilocybin is a naturally occurring psychedelic drug produced by more than 200 species of mushrooms, which is manufactured for medical use to control potency and purity. * Participants will be followed for up to 24 weeks (approximately 6 months) after the study treatment. It is expected that about 15 people will take part in this research study. * This research study is a Feasibility Study, which mean it is the first time investigators are examining psilocybin-assisted therapy in the context of hospice care. Psilocybin is an "Investigational" drug, meaning that the study drug has not been approved by the U.S. Food and Drug Administration (FDA) as a treatment for any disease. However, the FDA has granted psilocybin the status of "breakthrough therapy" in the treatment of depression and the investigators have permission from the FDA to use this drug in this research study.

keywords:
Hospice, Psilocybin, Demoralization, Terminal Illness, Cancer-related Problem/Condition, Psychotherapy, Terminal Cancer, Cancer Terminal, COMPLETED


authors: COMPASS Pathways
journal: ClinicalTrials.gov
publication_date: 2025-12-17
source_url: https://clinicaltrials.gov/study/NCT05624268
keywords: Treatment Resistant Depression, Psilocybin, COMP360, ACTIVE_NOT_RECRUITING
substance_tags: psilocybin
topic_tags: Depression,Clinical Trial,Treatment-Resistant Depression,Safety
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT05624268","overall_status":"ACTIVE_NOT_RECRUITING","phase":["PHASE3"]}
title:
A Phase III, Multicentre, Randomised, Double-blind, Placebo-controlled Study to Investigate the Efficacy, Safety, and Tolerability of COMP360 in Participants With Treatment-resistant Depression

abstract:
Efficacy, Safety, and Tolerability of a single administration of COMP360 in participants with treatment-resistant depression (TRD) This is a phase III, international, multi-centre, randomised, parallel group, fixed single-dose, double-blind, placebo-controlled study. The study population will include participants aged ≥18 years with TRD. Overall, 255 participants will be randomised in a 2:1 ratio to receive COMP360 25 mg or placebo. The study comprises three parts (A, B, and C) and will last approximately 62 weeks including a three- to ten-week Screening Period. Part A will include a six-week follow-up from initial investigational product (IP) administration. In this study, the primary aim is to assess the efficacy and safety of a single dose of COMP360 25 mg versus placebo for reducing symptom severity in TRD, when administered with psychological support. This will be assessed in a 6-week, single-dose, double-blind, placebo-controlled part of the study (Part A). Durability of efficacy and long-term safety, and the efficacy and safety of re-treatment will be assessed in a 20-week single-dose, double-blind re-treatment part (Part B), and a 26-week open-label treatment part (Part C).


authors: University of California, San Diego
journal: ClinicalTrials.gov
publication_date: 2026-06-25
source_url: https://clinicaltrials.gov/study/NCT06814522
substance_tags: psilocybin
study_type: Other
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-02 06:57:00
raw_json: {"nct_id":"NCT06814522","overall_status":"RECRUITING","phase":["PHASE1","PHASE2"]}
title:
Psilocybin-Assisted Therapy for Physician Well-Being and Burnout: Feasibility, Safety, Clinical Effectiveness and Biomarkers of Response [PAT-B (Psilocybin-Assisted Therapy for Physician Well-Being and Burnout)]

abstract:
Through an open-label study involving a small group of UCSD physicians experiencing burnout, the investigators will evaluate the feasibility, safety, and preliminary effectiveness of PAT to reduce burnout symptoms. Physician burnout is a critical issue. Research shows that physician burnout is increasing, that physicians suffer higher rates of burnout than the general population, and that physician burnout is associated with poor mental health outcomes. Psilocybin is a naturally occurring alkaloid within certain fungi that elicits acute perceptual, cognitive, and emotional changes when ingested, due to action on neurotransmitter and neurocirculatory systems. The combination of psilocybin with psychological support, termed Psilocybin-Assisted Therapy (PAT), is a promising new mental health intervention shown to produce rapid and sustained improvements in psychological domains affected in burnout. PAT demonstrates preliminary efficacy as a treatment for depression and substance use disorders, is associated with brain changes measured with electroencephalography (EEG) and is a strong candidate treatment for physician burnout. The primary aim of this study is to investigate the safety, feasibility, and preliminary efficacy of PAT to enhance well-being in University of California, San Diego (UCSD) physicians experiencing burnout. A secondary aim is to identify neurophysiological changes associated with response to PAT. Physicians experiencing burnout will be recruited in an open-label trial involving preparatory therapy sessions, psilocybin treatment, and post-treatment integration. Burnout will be measured with the Stanford Professional Fulfillment Index (PFI).

keywords:
Burnout, Burnout, Healthcare Workers, Psilocybin, [3-[2-(dimethylamino)ethyl]-1H-indol-4-yl] dihydrogen phosphate, Psilocybin, RECRUITING

topic_tags:
Depression,Addiction,Brain Imaging,Biomarkers,Wellbeing,Emotional Processing,Healthcare Workers,Safety


title: Effects of Psilocybin in Patients With Amyotrophic Lateral Sclerosis
authors: Johns Hopkins University
journal: ClinicalTrials.gov
publication_date: 2026-01-11
source_url: https://clinicaltrials.gov/study/NCT06656702
keywords: Amyotrophic Lateral Sclerosis, Psilocybin, RECRUITING
substance_tags: psilocybin
topic_tags: Depression
study_type: Other
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT06656702","overall_status":"RECRUITING","phase":["EARLY_PHASE1"]}
abstract:
This study aims to study the feasibility of psilocybin therapy for patients with Amyotropic Lateral Sclerosis (ALS) with depressed mood. The secondary objective is to assess its impact on depression, quality of life, hopelessness, and functional status in this patient population. The proposed research's primary objective is to study the feasibility of psilocybin therapy for patients with ALS with depressed mood. The secondary objective is to assess its impact on depression, quality of life, hopelessness, and functional status in this patient population. The proposed proof-of-concept interventional trial will use a single-arm design. The study will be an open-label trial in a sample of up to 24 treatment-seeking patients with a diagnosis of ALS and depressed mood. Participants will complete an 8-week course of study treatment including two psilocybin sessions (15 mg in week 4 and 15 or 25 mg in week 6), with follow-up assessments 1, 3, and 6 months after the final psilocybin session.


title: Safety and Efficacy of Psilocybin for Body Dysmorphic Disorder
authors: New York State Psychiatric Institute
journal: ClinicalTrials.gov
publication_date: 2023-03-12
source_url: https://clinicaltrials.gov/study/NCT04656301
keywords: Body Dysmorphic Disorders, Psilocybin, COMPLETED
substance_tags: psilocybin
topic_tags: Depression,Brain Imaging,Receptor Pharmacology,Aging,Safety
study_type: Other
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT04656301","overall_status":"COMPLETED","phase":["PHASE2"]}
abstract:
In this pilot study 12 adult outpatients with body dysmorphic disorder that has not responded to at least one adequate trial of a serotonin reuptake inhibitor will be treated openly with a single oral dose of psilocybin. Followup visits to monitor safety and clinical outcome will be conducted over a 3 month period. In this pilot study, up to 12 adult outpatients with body dysmorphic disorder that has not responded to at least one adequate trial of a serotonin reuptake inhibitor will be treated openly with a single oral dose of psilocybin. Procedures will follow those previously established in depression studies of psilocybin. Patients will receive intensive preparation and support from two therapists, including 8-9 hours accompanying the patient on the day of medication administration in the Biological Studies Unit of New York State Psychiatric Institute. Followup visits to monitor safety and clinical outcome will be conducted at day 1, week1, and months 1,2, and 3 post-administration. Resting state function magnetic resonance imaging will be conducted prior to and one day after psilocybin administration to assess the effect of medication on brain circuits.


title: Psilocybin Administration With 5-HT1a Blockade
authors: Johns Hopkins University
journal: ClinicalTrials.gov
publication_date: 2026-06-24
source_url: https://clinicaltrials.gov/study/NCT07565493
substance_tags: psilocybin
topic_tags: Brain Imaging,Receptor Pharmacology,Consciousness,Observational Study,Healthy Volunteers
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 23:13:10
raw_json: {"nct_id":"NCT07565493","overall_status":"RECRUITING","phase":["EARLY_PHASE1"]}
abstract:
The purpose of this study is to assess the effects of 5-HT1A receptor blockade on the acute subjective effects of psilocybin, as measured through subjective survey measures and acute electroencephalography (EEG). Further, the investigators will assess the effects of psilocybin on post-acute sleep and dreaming through the use of sleep EEG and sleep and dream diaries. This double-blind, randomized, cross-over study (N = 18) will administer a moderate dose of psilocybin trihydrate (18 mg, equivalent to 15 mg psilocybin anhydrate), with pindolol (30 mg), or placebo to assess the effects of 5-HT1A receptor blockade on the acute subjective effects and the acute neurophysiological effects of psilocybin through the use of self-report measures and acute EEG. Participants will also complete sleep and dream diaries 10 days prior to and 10 days following each drug administration session as well as wear an at-home sleep EEG device for 5 days prior to and 5 days following each drug session. This study aims to understand the mechanistic basis of the perceptual changes in the altered state of consciousness induced by psilocybin as well as its effects on post-acute sleep and dreaming.

keywords:
Psychedelic Effects in Healthy Volunteers, Pindolol, Placebo, Microcrystalline cellulose placebo, Psilocybin, RECRUITING


authors: University Hospital, Basel, Switzerland
journal: ClinicalTrials.gov
publication_date: 2021-12-21
source_url: https://clinicaltrials.gov/study/NCT03153579
keywords: Patients, Anxiety Disorders, LSD, Placebo, COMPLETED
substance_tags: psilocybin
topic_tags: Depression,Anxiety,End-of-Life Distress,Clinical Trial
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT03153579","overall_status":"COMPLETED","phase":["PHASE2"]}
title:
LSD Treatment in Persons Suffering From Anxiety Symptoms in Severe Somatic Diseases or in Psychiatric Anxiety Disorders: a Randomized, Double-blind, Placebo-controlled Phase II Study

abstract:
Background: Lysergic acid diethylamide (LSD) was extensively investigated in humans in the 1950s and 1960s. Particularly, LSD attenuated anxiety in patients with cancer. Clinical research with LSD ended in the 1970s due to regulatory restrictions but its use for personal and recreational purposes continued. In recent years, there has been a renewed interest in the use hallucinogens in psychiatric research and practices. LSD and psilocybin were reused in experimental studies in healthy subjects and in the treatment for anxiety in patients with life-threatening diseases. Specifically, a pilot study documented that LSD can be used safely and may reduce anxiety in these patients. Larger well-designed and placebo-controlled studies are warranted. Similar studies have recently been completed with the hallucinogen psilocybin. Objective: To test the efficacy of LSD in patients with anxiety with or without life-threatening diseases. Design: Double-blind, placebo-controlled random-order cross-over trial using two LSD (200 µg) and two placebo sessions with subjects acting as their own control. Participants: 40 patients aged \> 25 years with anxiety disorder (according to DSM-IV or a state-trait anxiety inventory score \>40 in the STAI trait or state scale) with or without life-threatening illness. Main outcome measures: Reduction in anxiety (STAI), depression (Hamilton depression rating scale, HDRS and Beck depression inventory, BDI), and general psychopathological symptoms (Symptom Check List 90 items, SCL-90) at 2, 8, and 16 weeks after LSD- compared with placebo-assisted psychotherapy. Significance: Anxiety disorder (alone or in the context of life-threatening illness) is frequent and often insufficiently managed with available medications. This study will evaluate the potential benefits of single treatments with LSD in anxiety disorder.


title: Safety and Feasibility of Psilocybin in Methamphetamine Use Disorder in a Community-Based Sample
authors: University of Wisconsin, Madison
journal: ClinicalTrials.gov
publication_date: 2026-05-11
source_url: https://clinicaltrials.gov/study/NCT05322954
substance_tags: psilocybin
topic_tags: Addiction,Observational Study,Safety
study_type: Observational Study
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT05322954","overall_status":"TERMINATED","phase":["PHASE1"]}
abstract:
The purpose of this research study is to investigate the safety and feasibility of two (2) oral doses of psilocybin when combined with behavioral support for methamphetamine use disorder (MUD). Participants have a diagnosis of methamphetamine use disorder (MUD). Participants can expect to be actively engaged in the study for up to 26 weeks. The objective of this study is to determine the safety of psilocybin in adult participants with MUD. Eligible participants will be adults with methamphetamine use disorder recruited from the community. After physical and psychological screening, and at least 6 hours of psychological support for the psilocybin dosing, each participant will ingest 1 oral dose of psilocybin. All dosing sessions will be attended by 2 specially trained facilitators, in a dedicated Session Room at the University of Wisconsin School of Pharmacy. After eight hours of observation in the dosing room, the participant will stay overnight in the hospital Clinical Research Unit, and complete an integration session with at least one of the session facilitators before discharge to home. Approximately 4 weeks after the first dose, the participant will receive a second oral dose of psilocybin, with the same length of observation. Participants who decide not to proceed to the second dose will complete two additional integration sessions and study measures through the two-month follow-up. If you are interested in participating in this study, please fill out a brief 1-minute survey at the link in the "More Information" section at the bottom of this record.

keywords:
Methamphetamine Use Disorder, Substance-Related Disorders, Chemically-Induced Disorders, Substance Use Disorders, Stimulant-Use Disorder, Psilocybin, TERMINATED


authors: University Hospital, Ghent
journal: ClinicalTrials.gov
publication_date: 2024-09-18
source_url: https://clinicaltrials.gov/study/NCT06378229
keywords: Treatment Resistant Depression, Psilocybin, PEX010, RECRUITING
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Brain Imaging,Observational Study,Treatment-Resistant Depression,Safety,Toxicity
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT06378229","overall_status":"RECRUITING","phase":["PHASE2"]}
title:
Psilocybin-assisted Psychotherapy in the Treatment of Patients Hospitalized for Treatment-resistant Depression: an Open-label Feasibility Study with an Experiential and Systemic Focus

abstract:
The purpose of this study is to determine the safety and feasibility of performing psilocybin-assisted psychotherapy in patients hospitalized for treatment-resistant depression. The proposed study will assess the safety, feasibility, preliminary results and neurological aspects of psilocybin-assisted psychotherapy in the treatment of hospitalized patients with treatment-resistant depression. Screening, after signing the ICF, is done in patients newly admitted to the psychiatric service of Ghent University Hospital or patients referred for hospitalization through the outpatient clinic of the psychiatric service of Ghent University Hospital. Involved patients are hospitalized at the Anxiety, Compulsion and Mood Unit for 8 weeks. They will receive add-on treatment with psilocybin-supported psychotherapy in addition to standard treatment (daily group therapies, mainly non-verbal and activating). This consists of a preparatory phase (4 sessions of 1.5 hours before the first psilocybin session and 1 session of 1.5 hours before the second psilocybin session), the psilocybin sessions themselves (2 sessions, week 3 and week 6) and an integration phase (3 sessions of 1.5 hours after each psilocybin session). All sessions occur with the same 2 therapists throughout the entire course. Therapists are trained to provide experiential and systemic psychotherapeutic interventions. After hospitalization, weekly outpatient follow-up consultations continue until 12 weeks after the last psilocybin session. Subsequently, patients may still agree to a prospective, observational and naturalistic follow-up until 1 year after the last psilocybin session, during which they will be called monthly by a psychiatrist from the research team to inquire about current mental status and any therapies undertaken in the interim. During the study, patients are required to fill out questionnaires at regular intervals. Video-recordings will be made of certain parts of the preparation and integration sessions, for analysis with the client experience scale (EXP). The morning of each psilocybin session, female patients must provide a blood sample for a pregnancy test. The morning of each psilocybin session, all patients must provide a urine sample for toxicology screening. EEGs are also taken from patients the day before each psilocybin session, the morning of the first integration session after each psilocybin session and 12 weeks after the last psilocybin session (at the last outpatient consultation). At the start and at the end of the hospitalization phase, a semi-structured interview will be conducted with the patient to gauge expectations on the one hand and experiences on the other. Throughout the study, the patient's partner will be involved. The partner must complete a number of questionnaires at baseline and throughout the study and will have to be present at 3 EEGs. In addition, the partner will also participate in 1 preparatory session and 2 integration sessions. The partner will also be given the opportunity to spend the night of a psilocybin session with the patient in the hospital (rooming-in). At the start and at the end of the hospitalization phase, a semi-structured interview will be conducted with the partner to gauge expectations on the one hand and experiences on the other.


authors: Centre for Addiction and Mental Health
journal: ClinicalTrials.gov
publication_date: 2026-05-17
source_url: https://clinicaltrials.gov/study/NCT06299319
keywords: Obsessive-Compulsive Disorder, Psilocybin, PEX010, ENROLLING_BY_INVITATION
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT06299319","overall_status":"ENROLLING_BY_INVITATION","phase":["PHASE1"]}
title:
Evaluating the Feasibility, Clinical Effects, and Safety of Psilocybin-assisted Psychotherapy for Treatment-resistant Obsessive-compulsive Disorder: An Open-label Clinical Trial

abstract:
Psilocybin, the chemical component of "magic mushrooms", has been administered with psychotherapy in several randomized clinical trials (RCTs) showing large and sustained antidepressant effects. There is interest to see if similar effects may be provided in those with obsessive compulsive disorder (OCD). The purpose of this study is to evaluate the safety, feasibility, and clinical effects of psilocybin administration in those with OCD. Ten participants with treatment-resistant OCD will receive two doses of 25mg of psilocybin under supportive conditions, two weeks apart. The investigators hypothesize that two sessions of psilocybin 25mg administered under supportive conditions to participants with treatment-resistant OCD will lead to significant reductions in OCD symptoms. Literature suggests that up to 40 percent of individuals with OCD do not respond to conventional treatment and experience treatment resistant OCD (TROCD) (1, 2). Psilocybin, the chemical component of "magic mushrooms", has been administered with psychotherapy in several randomized clinical trials (RCTs) showing large and sustained antidepressant effects (3). Results of these trials have led to growing calls for transition to clinical use, as well as increased research for other mental health disorders. It is presumed that psilocybin's therapeutic effects are induced by the psychedelic "trip", which is dependent on serotonin 2A receptor (5-HT2AR) activation (4, 5). All studies have used psilocybin in conjunction with psychotherapy involving two therapists present during full-day dosing sessions. There is a need for more data in the TROCD population as there is only one clinical trial published for this specific population, followed by various case reports. Using a proof-of-concept, open-label, clinical trial approach, 10 participants with TROCD will receive 2 doses of 25mg of psilocybin, with two weeks between each dosing day. The objectives of this study are as follows: 1. To assess the safety, and feasibility, of psilocybin, administered with psychological support to adult participants with TROCD. Hypothesis 1: The investigators will be able to recruit and retain ten participants with TROCD for the duration of the trial and that psychedelic-assisted psychotherapy for obsessive compulsive disorder (PAP-OCD) will be safe in those with TROCD, as measured by monitoring adverse events and using the Columbia Suicide Severity Rating Scale (C-SSRS). 2. To assess the clinical effects of PAP in those with TROCD. Hypothesis 2: Two sessions of psilocybin (25mg) administered under supportive conditions to participants with TROCD will lead to significant reductions in OCD symptoms as measured by the Yale-Brown Obsessive Compulsive Scale (YBOCS) when comparing baseline to Week 3. 3. Provide pilot data on the effect of psilocybin and supportive therapy on TROCD in preparation of a future larger RCT. Overview of Study Design: All 10 participants will follow the same study design. Each participant will undergo a screening assessment where they will complete lab tests, and clinical and psychiatric assessments to determine eligibility. Following the screening visit, participants will undergo a washout period where they will be tapered off concomitant medications over a medication the participant is being tapered off (based on the half-life of the medication) and the participant's preference for the length of the tapering period. All medications will require a minimum of a 2-week tapering period with the exception of fluoxetine which will require a minimum of 4-weeks. Additional time may be added at the discretion of the study investigator. During this period, there will be weekly check-ins with the study physician. At study Visit 2 (Baseline, V2), participants will complete a series of questionnaires and assessments, preparatory therapy with trained study therapists, and undergo a brain functional magnetic resonance imaging (fMRI). The preparatory therapy sessions will build a therapeutic alliance, and provide psychoeducation about, and set intentions for, the psilocybin session. To reduce participant burden, baseline can be broken up into multiple days, however all assessments must be completed within 7-days of the first dose. At study Visit 3 (V3), neurophysiological measurements will be performed. Upon completion of V2 and V3, participants will undergo the first psilocybin dosing session at Visit 4 (V4) where they will receive an active dose (25mg) of psilocybin in conjunction with supportive therapy. The psilocybin session will last 5 to 6 hours and will be conducted in the existing psychedelic treatment suite developed at the Centre for Addiction and Mental Health (CAMH). Two trained study therapists will be supporting each participant during the dosing session. After 5 hours of dose administration, participants will be evaluated for safety by the study psychiatrist and discharged home in the company of a caregiver or a family member. On the day after the dosing session (Visit 5, V5) and one-week after the dosing session (Visit 6, V6), participants will be asked to complete the same questionnaires that were done at Baseline (V2) and will undergo an integrative therapy session with the trained study therapist. Between Visit 5 (V5) and Visit 7 (V7), during study Visit 6 (V6), the same neurophysiological measurements will be performed as during Visit 3 (V3). Follow-up assessments will also occur at 3, 6, 9 and 12 weeks (Visit 7, 8, 9 and 10) after the second psilocybin dosing session. The same questionnaires administered at Baseline (V2) will be repeated at each of these study visits.

topic_tags:
Addiction,OCD,Brain Imaging,Receptor Pharmacology,Aging,Clinical Trial,Randomized Controlled Trial,Case Report,Safety,Adverse Events


authors: University of Washington
journal: ClinicalTrials.gov
publication_date: 2025-03-17
source_url: https://clinicaltrials.gov/study/NCT05163496
substance_tags: psilocybin
topic_tags: Depression,Healthcare Workers
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT05163496","overall_status":"COMPLETED","phase":["PHASE3"]}
title:
A Randomized, Placebo-controlled Trial of Psychedelic-assisted Psychotherapy With Single Dose Psilocybin for Frontline Clinicians Experiencing COVID-related Symptoms of Depression and Burnout

abstract:
This study aims to investigate the effects of a single dose of psilocybin, delivered in the contextof pre- and post-dose psychotherapy, on symptoms of depression and burnout suffered by healthcare clinicians as a result of frontline work in the COVID pandemic. Aim 1: To assess short- and longer-term effects of psilocybin-assisted psychotherapy (PAP) on symptoms of depression experienced by physicians and nurses with frontline work exposure in the COVID pandemic. Hypothesis 1.1: Compared to active placebo, PAP will result in short term improvement in symptoms of depression 1 day and 1 week after the psilocybin dose session. Hypothesis 1.2: Compared to active placebo, PAP will result in longer term improvement of symptoms of depression 4 weeks after the medication dosing session. The primary outcome will be a comparison between the psilocybin 25 mg vs control groups of a combination of depression symptoms measured at 4 weeks post medication dose session. 1.1.2. Aim 2: To explore short- and longer-term effects of psilocybin-assisted psychotherapy (PAP) on symptoms of burnout experienced by physicians and nurses with frontline work exposure in the COVID pandemic. Hypothesis 2.1: Compared to active placebo, PAP will result in short term improvement in symptoms of burnout 1 day and 1 week after the psilocybin dose session.

keywords:
Burnout, Caregiver, Burnout, Professional, COVID-19, Depression, Post Traumatic Stress Disorder, Moral Injury, Psilocybin (Usona Institute), Psychedelic-assisted psychotherapy (PAP), Active placebo, PAP with placebo, COMPLETED


authors: James J. Peters Veterans Affairs Medical Center
journal: ClinicalTrials.gov
publication_date: 2026-05-03
source_url: https://clinicaltrials.gov/study/NCT07251491
substance_tags: psilocybin
study_type: Other
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT07251491","overall_status":"RECRUITING","phase":["PHASE1","PHASE2"]}
title:
Safety, Tolerability, Outcomes of Psilocybin for Depression (STOP Depression) in Veterans With Spinal Cord Injury

abstract:
The main goal of this study is to determine if psilocybin is safe for use in people with SCI. The study will measure how people with SCI respond to three psilocybin doses: low (5mg), medium (10mg), and high (25mg). The main question the study aims to answer is: does psilocybin increase the number and severity of adverse (bad) events reported by people with SCI? These may include pain, muscle spasms, symptoms of depression, and symptoms of low or high blood pressure. The investigators will also measure how well people with SCI tolerate the psychedelic experience, and compare responses between the low (5mg), medium (10mg), and high (25mg) doses. Participants will: * Agree to be enrolled in the study for up to 13 months. * Agree to complete the seven (7) visits that are included in the psilocybin-assisted therapy. * Agree to complete follow-up study visits, including in-person visits to the James J Peters VA Medical Center, located in the Bronx, New York and remote visits. * Agree to keep a log of how they are feeling and any change in the frequency or severity of adverse events. Background: Depression may be explained partly by decreased signaling of serotonin in the nervous system. Psilocybin, the active component of 'magic mushrooms', is a drug that activates serotonin pathways in the nervous system. Some scientists think psilocybin could help people with major depression, but it is not currently approved as a medicine in the United States. People with spinal cord injuries (SCI) often feel depressed, even more commonly than people without injuries. People with SCI have not been included in psilocybin studies. The goals of this study are first to see if psilocybin can be safely administered, and to determine if psilocybin can help improve symptoms of depression in people with SCI. Study Goals: The investigators will look at how safe psilocybin is for people with SCI, how people with SCI respond to different doses, and whether it helps reduce the severity of depression and other problems, like pain or muscle spasms. The study team will also check to see if psilocybin improves quality of life and wellbeing. The study will track these effects for a year after participants receive psilocybin. Study Plan: Thirty people with chronic SCI with a depressive disorder will be asked to join-15 with paraplegia and 15 with tetraplegia. They will be split into three groups to try different psilocybin doses: low (5mg), medium (10mg), and high (25mg). The study will take a stepwise approach to safety, but participants will not know the dose of psilocybin they receive. There will be at least 16 study visits, including medical and mental health check-ups, psilocybin assisted therapy, primary study endpoint and follow-up visits. What Will Be Measured: The study focus is to see if psilocybin is safe and tolerable in people with SCI. The study will track side effects, how people feel, and any changes in mood, pain, medication use, or body reactions. Doctors will check for problems like chest pain, high blood pressure, and changes in suicidal thoughts. The study team will also measure satisfaction with the therapy, experiences during the psilocybin sessions, and changes in depression. Why It Matters: Some people wrongly believe depression is just a normal part of living with SCI, so their depression may not be adequately treated. Also, people with SCI often can't join trials of new treatments because they have other health problems. Psilocybin could help treat depression and may improve many body functions affected by SCI if it is shown to be safe and effective.

keywords:
Spinal Cord Injury, Depression - Major Depressive Disorder, Veteran, Psilocybin (Usona Institute), Magic Mushrooms, RECRUITING

topic_tags:
Depression,Chronic Pain,Mechanism of Action,Receptor Pharmacology,Wellbeing,Veterans,Safety,Adverse Events


authors: COMPASS Pathways
journal: ClinicalTrials.gov
publication_date: 2026-01-11
source_url: https://clinicaltrials.gov/study/NCT05711940
keywords: Treatment Resistant Depression, Psilocybin, COMP360, ACTIVE_NOT_RECRUITING
substance_tags: psilocybin
topic_tags: Depression,Clinical Trial,Treatment-Resistant Depression,Safety
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT05711940","overall_status":"ACTIVE_NOT_RECRUITING","phase":["PHASE3"]}
title:
A Phase III, Multicentre, Randomised, Double-blind, Controlled Study to Investigate the Efficacy, Safety, and Tolerability of Two Administrations of COMP360 in Participants With Treatment-resistant Depression

abstract:
Efficacy, Safety, and Tolerability of two administrations of COMP360 in participants with treatment-resistant depression (TRD) This is a phase III, international, multi-centre, randomised, parallel group, fixed repeat dose, double-blind, controlled study. The study population will include participants aged ≥18 years with TRD. Overall, 568 participants are to be randomised in a 2:1:1 ratio to receive COMP360 25 mg, 10 mg or 1 mg. The study comprises three parts (A, B, and C) and will last approximately 62 weeks including a three- to ten-week screening period. Part A will include a nine-week follow-up from initial investigational product (IP) administration. Part B will include a further 17 weeks follow-up out to 26 weeks from initial IP administration. Part C will include a further 26 weeks follow-up out to 52 weeks from initial IP administration. In this study, the aim is to assess the efficacy of COMP360, administered with psychological support in adult participants with TRD, in improving symptoms of depression.


title: Open Label Psilocybin Brain Stimulation and Imaging Pilot Study
authors: Johns Hopkins University
journal: ClinicalTrials.gov
publication_date: 2026-04-19
source_url: https://clinicaltrials.gov/study/NCT06835699
keywords: Healthy Volunteers, Psilocybin 25 mgs, TMS, ACTIVE_NOT_RECRUITING
substance_tags: psilocybin
topic_tags: Brain Imaging,Aging,Healthy Volunteers
study_type: Other
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT06835699","overall_status":"ACTIVE_NOT_RECRUITING","phase":["PHASE1"]}
abstract:
This open-label pilot psilocybin administration study investigates the influence of psilocybin on brain function and cognitive control functions in clinically and psychiatrically healthy volunteers. Participants will undergo experimental drug administration sessions after careful screening and preparation. Participants will also have brain activity measured using electroencephalogram (EEG) also during non-invasive brain stimulation using Transcranial Magnetic Stimulation (TMS).


authors: Nova Mentis Life Science Corp
journal: ClinicalTrials.gov
publication_date: 2024-05-07
source_url: https://clinicaltrials.gov/study/NCT05832255
keywords: Fragile X Syndrome, Behavior, Cognitive Dysfunction, Psilocybin, 1.5 mg, SUSPENDED
substance_tags: psilocybin
study_type: Review Article
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT05832255","overall_status":"SUSPENDED","phase":["PHASE2"]}
title:
An Open-Label Investigation of the Effects of Sub-Perceptual Repeat Dosing of Psilocybin on the Behavioural and Cognitive Symptoms of Fragile X Syndrome in Adult Patients

abstract:
Diverse symptomatology makes Fragile X Syndrome (FXS) difficult to treat, and currently there are no approved prevention or treatment methods for FXS. Current therapies, including pharmaceutical and behavioural interventions, offer a patchwork of solutions that have limited efficacy and high toxicity. The current study aims to examine psilocybin as a safe treatment alternative with the ability to improve markers of cognition, communication, mood, behavior as well as markers of neuroinflammation, serotonin levels in exosomes, and neuroplasticity at sub-hallucinogenic doses (microdosing). The overall objective of this study is to assess the feasibility of low-dose psilocybin as a therapeutic option for individuals living with FXS and to improve diagnostic parameters of FXS, as well as therapeutic responses with the use of biomarkers. A total of 10 subjects who meet all the inclusion criteria and does not meet any of the exclusion criteria will be enrolled into the study. Any subjects prematurely terminated from the study will be replaced to ensure 10 subjects complete the study. A study coordinator will contact referring clinicians, caregivers, and subjects to pre-screen for initial eligibility. Those deemed eligible will be invited for an in-person screening along with the participating caregiver. The screening visit will be approximately two hours long and will consist of informed consent, diagnostic interview, physical examination, drugs of abuse test (DOA), ECG, medical/treatment history review, and demographic forms. A pregnancy test will be performed on females of child-bearing during screening, baseline, and end-of-study visits. All eligible subjects will enter the treatment arm of the study. Subjects and caregivers will return to the clinic for a baseline visit within three weeks of their screening completion. Baseline visit will include saliva/buccal swab collection, and clinician and self-report assessments for subjects and caregivers. These assessments will include the Vineland Adaptive Behavior Scales-Third Edition (VABS-3), Clinical Global Impressions-Improvement scale (CGI-I), Visual Analog Scale-Treatment Satisfaction (VAS-TS), the Anxiety, Depression and Mood Scale (ADAMS), and the Systematic Assessment For Treatment Emergent Events (SAFTEE). Digital assessments may also be performed at the baseline visit or at home at the discretion of the qualified investigator. Digital assessments will include the NIH Toolbox Cognitive Battery Modified for Intellectual Disabilities (NIH-TCB), the Trail Making Test (TMT), and the Multifaceted Empathy Test (MET). The study drug will be dispensed in blister packs to monitor adherence and improve subject compliance. Blister packs will be prepared and distributed at each subsequent visit. Subjects will return to the clinic for study visits on day 8, 15, 22, and 28 (study end date). Subjects and caregivers will complete the assessments described above. Subjects will provide additional saliva/buccal swab samples at day 15 and day 28.

topic_tags:
Depression,Anxiety,Neuroplasticity,Receptor Pharmacology,Biomarkers,Microdosing,Review Article,Healthcare Workers,Toxicity,Inflammation


authors: Empower Research Inc
journal: ClinicalTrials.gov
publication_date: 2024-06-23
source_url: https://clinicaltrials.gov/study/NCT06471959
keywords: Psilocybin, Psychotherapy, Group, PEX010, UNKNOWN
substance_tags: psilocybin,psilocin
topic_tags: Resilience,Healthcare Workers
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT06471959","overall_status":"UNKNOWN","phase":["PHASE1","PHASE2"]}
title:
Assessing the Feasibility of a Custom Psychedelic-assisted Group Program on Mental and Physical Health in First Responders

abstract:
This study is a two-group feasibility study of oral psilocybin combined with a 12-week group-based program, customized for firefighters. Trained facilitators will help create a trauma-informed space for the group (n = 6-8) to thrive and promote cognitive resilience. The topics covered throughout the 12 weeks include breath-work, mindfulness, self-compassion, embodiment, and Internal Family Systems work. Group 1 (control): 12-week group-based program, with a breathwork day at week 10 Group 2 (intervention): 12-week group-based program, with a 10mg dose of psilocybin (PEX010) at Week 10 Assessment timepoints: * Baseline * Mid-program (Week 6) * End of program (Week 12) * 6-month follow up All participants will undergo a 12-week, group-based program (one session per week, for 12 weeks). The first group session, as well as the Week 10 session will occur in-person. The remainder of the sessions will occur remotely. Each week, trained facilitators will help create a trauma-informed safe space for the group to thrive and promote cognitive resilience. The topics covered throughout the 12-week program include breath-work, mindfulness, self-compassion, embodiment, and Internal Family Systems work. During Week 10, participants will be provided with either psilocybin (active group) or complete a breathwork day (control group). For participants randomized to the active group, they will receive 10mg of psilocybin on Week 10. A clinician certified and trained in the therapeutic use of psilocybin will be on site for participants in the psilocybin group. During the dosing session, the clinicians will respond to whatever needs arise. This may include escorting them to the bathroom, giving them a drink of water. At least two staff (one facilitator and one clinician) will be on site during dosing days. The dose will be administered in clear capsules with approximately 500ml of water. Aside from the dose provided, the weekly session will continue as usual, with a focus on breath-work, embodiment, and gentle movement on dosing days. Psilocybin in the study comes in the form of the study drug, PYEX. PYEX is a drug substance which is a partially purified fraction of the extract of Psilocybe cubensis mushroom fruiting bodies. It is a mixture of indole alkaloids, other mushroom fruiting body components and stabilization excipients. The major indole alkaloids present include psilocybin and psilocin (dephosphorylated psilocybin). PEX010 is a capsule for oral administration and is manufactured with PYEX (12.5-14.0% psilocybin), excipients, and HPMC (hydroxypropyl methyl cellulose) capsules.


authors: Stanford University
journal: ClinicalTrials.gov
publication_date: 2026-05-05
source_url: https://clinicaltrials.gov/study/NCT07479550
keywords: Major Depression, Psilocybin (Usona Institute), Propofol, Placebo, NOT_YET_RECRUITING
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Brain Imaging,Wellbeing,Clinical Trial,Safety
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:27
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT07479550","overall_status":"NOT_YET_RECRUITING","phase":["PHASE2"]}
title:
A Phase 2 Randomized Study Examining the Safety, Feasibility, and Effectiveness of Masking Psilocybin Therapy With General Anesthesia in Major Depressive Disorder

abstract:
Major depressive disorder (MDD) affects millions of Americans and remains difficult to treat. Psilocybin, a psychedelic compound, has shown promise for reducing depression symptoms, but a key challenge in psychedelic research is that participants can usually tell whether they received the active drug - making it hard to conduct fully blinded studies. This study (Studying Psilocybin with Anesthesia Controlled by EEG \[SPACE\]) tests a new approach: administering psilocybin while participants are under general anesthesia, so that the noticeable psychological effects of psilocybin are masked. This allows both participants and outcome assessors to remain unaware of whether psilocybin or placebo was given, improving the scientific rigor of the research. Participants with MDD will be randomly assigned to receive either psilocybin or placebo across four dosing sessions conducted under general anesthesia. The study will assess whether this approach is safe and feasible, and will collect early data on whether it may reduce depression symptoms. Participants will receive four dosing sessions spaced one week apart. Each session involves taking an oral capsule containing either psilocybin (10 mg or 25 mg) or placebo, followed by general anesthesia with propofol. All sessions take place at Stanford Hospital under the supervision of a board-certified anesthesiologist. Between and after sessions, participants complete questionnaires about mood, sleep, wellbeing, and anxiety. Participants may also wear a consumer-grade EEG headband at home to track sleep patterns. The total study duration per participant is approximately 7 weeks, across around 25 visits, most of which are conducted remotely. Psilocybin is not FDA-approved and is administered under an FDA Investigational New Drug (IND) authorization for research purposes only.


authors: Yale University
journal: ClinicalTrials.gov
publication_date: 2026-04-30
source_url: https://clinicaltrials.gov/study/NCT06624137
substance_tags: psilocybin
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:28
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT06624137","overall_status":"RECRUITING","phase":[]}
title:
Computationally, Electrophysiologically, and Qualitatively Characterizing Serotonergic Psychedelics; Transdiagnostic Therapeutic and Pro-Psychotic Effects

abstract:
This is an observational study which does NOT directly administer a psychedelic substance but rather recruits participants who are already participating in another clinical trial in which they may receive a serotonergic psychedelic. The goal of this observational study is to learn how the brain's information processing changes during and following administration of serotonergic psychedelics (psilocybin, N,N-Dimethyltryptamine/DMT, Lystergic Acid Diethylamide/LSD, etc.) for people with and without mental illness receiving serotonergic psychedelics through any clinical trial at Yale University. The main questions it aims to answer are: 1. Do serotonergic psychedelics cause the brain to rely on new information more than previously learned information while under the influence? What about 1 day, 5-14 days, and 4-6 weeks after use? 2. Do serotonergic psychedelics cause long-lasting side-effects in how people perceive (see, hear, feel, etc.) the world and how easily people change their beliefs? 3. How does the brain's electrical activity change after using serotonergic psychedelics? How does the balance between excitation and inhibition change while under their effect? 4. Can changes in how the brain uses information predict who will benefit from a psychedelic and who will have side effects from psychedelics? Researchers will compare with people given placebos to see what changes in brain processing are unique to serotonergic psychedelics. Participants will have the opportunity to do some combination of the following: 1. Online computer assessments consisting of games and questionnaires that probe how participants think. 2. Magnetoencephalography (MEG) or electroencephalography (EEG) with eyes closed and with repeated clicks, images, or sensations delivered. 3. A magnetic resonance imaging (MRI) scan. 4. Semi-structured qualitative interviews about their experience after taking a serotonergic psychedelic recorded via Zoom. Mounting evidence suggests that serotonergic psychedelics (SPs; eg. psilocybin, LSD) reduce symptoms across many mental illnesses with rapid, sustained effects from single interventions. They also cause persisting, positive effects in the general population and those without mental illness. This improved wellness comes at the cost of acute psychosis-like effects, that sometimes persist in weakened forms or, rarely, as prolonged episodes of psychosis. Understanding the mechanism underlying these dual effects may help maximize therapeutic effect and minimize unwanted outcomes. The reason SPs cause therapeutic change and also cause psychotic-like effects regardless of whether one has a mental illness may be because they alter the basic machinery that the brain uses to process all information. SPs seem to shift processing-in both how we perceive (seeing, hearing, etc.) and learn-to rely more on new, incoming information over previously learned information. Essentially, SPs shift the brain into an extreme learning mode that allows it to modify harmful thought patterns associated with many mental illnesses, but that may also be similar to the brain states of early psychosis. Participants in this study will opt-in to complete various measures to be completed before, during, and after being administered a serotonergic psychedelic through a clinical trial at Yale University. How participant's brains process information will be assessed by: 1. Playing 3-4 computer games that measure how people see, hear, and learn. These will be completed 1-30 days before receiving the serotonergic psychedelic, the day they receive the serotonergic psychedelic (once psychologically acceptable and permitted by relevant trial researchers), the day after, 5-14 days after, and 4-6 weeks after. 2. MEG or EEG to measure the brain activity responsible for representing new vs. old information-and structural MRI to determine where the activity is coming from. The MEG/EEG will be done the day before, day of, and day after administration of the serotonergic psychedelic. The MRI can be done before, after, or during the trial. They behaviors that accompany these changes will be assessed by: 1. Validated, online questionnaires at the same time points as the computer games. 2. Semi-structured interviews about what participants' day-to-day experiences are like and how they have changed after taking a serotonergic psychedelic. These may be done 2-5 days after using a psychedelic, or at the same time that clinical trial staff do their interviews. Participants participating in a trial with single-arm placebo-controlled study design that includes a placebo arm may only complete these measures around a placebo administration. Those in a trial with a crossover design may complete these measures twice (except for day 1-30 and 4-6 week time points). Those opting to complete open-label administrations after study completion may complete relevant time points. The primary objectives are to: 1. Investigate how serotonergic psychedelics change brain reliance on new vs. old information in perception and belief-updating while under the influence. 2. Investigate how serotonergic psychedelic change brain reliance on new vs. old information in perception and belief updating at short and long-term follow-up. 3. Investigate whether serotonergic psychedelics cause side effects in people's perception, attention, and belief updating that are both healthy and psychosis-like. 4. Investigate how serotonergic psychedelics acutely alter excitation/inhibition (E/I) balance in the brain. 5. Investigate whether there are any persisting changes in resting state EEG power or E/I balance. The secondary objectives are to: 1. Investigate whether changes in brain information processing can explain therapeutic effects of serotonergic psychedelics. 2. Investigate whether changes in brain information processing can predict who will respond positively to serotonergic psychedelics. 3. Investigate whether changes in brain information processing can explain psychotic-like side effects of serotonergic psychedelics. 4. Investigate whether changes in brain information processing can predict who will have stronger psychotic-like side effects from serotonergic psychedelics. 5. Investigate whether acute or persisting changes in E/I balance predict therapeutic or psychotic effects of serotonergic psychedelics.

keywords:
OCD, Major Depressive Disorder (MDD), Alcohol Use Disorder (AUD), Healthy Volunteer, Migraine, PTSD, PTSD - Post Traumatic Stress Disorder, Addiction, Tobacco Use Disorder, Obsessive Compulsive Disorder (OCD), Opioid Use Disorder, Serotonergic Psychedelic, Placebo, RECRUITING

topic_tags:
Depression,PTSD,Addiction,OCD,Headache / Migraine,Brain Imaging,Aging,Wellbeing,Clinical Trial,Observational Study,Healthy Volunteers,Adverse Events


authors: Halucenex Life Sciences Inc.
journal: ClinicalTrials.gov
publication_date: 2023-06-28
source_url: https://clinicaltrials.gov/study/NCT05243329
keywords: Treatment Resistant Disorders, Post Traumatic Stress Disorder, Psilocybin, UNKNOWN
substance_tags: psilocybin
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:28
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT05243329","overall_status":"UNKNOWN","phase":["PHASE2"]}
title:
Investigating the Therapeutic Effects of Psilocybin in Treatment-Resistant Post-Traumatic Stress Disorder

abstract:
Post-traumatic stress disorder (PTSD) is a complex disorder expressed as a variety of neurobiological symptoms, including anxiety, re-experiencing, hyperarousal, and avoidance symptoms, along with comorbidities such as anxiety, depression, and increased risk for self-medicating substance abuse. Currently, there are only two approved medications in the United States (US) for PTSD, paroxetine and sertraline. Psychedelic medications, including psilocybin, have recently received breakthrough designation by the US Food and Drug Administration (FDA) for other psychiatric indications. Although no formal clinical trials have yet investigated psychedelic substances for the treatment of PTSD, the available evidence warrants such an investigation. The present study aims to investigate the effect of psilocybin on treatment-resistant PTSD. Post-traumatic stress disorder (PTSD) is a complex disorder expressed as a variety of neurobiological symptoms, including anxiety, re-experiencing, hyperarousal, and avoidance symptoms, along with comorbidities such as anxiety, depression, and increased risk for self-medicating substance abuse. Currently, there are only two approved medications in the United States (US) for PTSD, paroxetine and sertraline. These selective serotonin reuptake inhibitors (SSRIs) have limited efficacy. Furthermore, there is a lack of efficacious pharmacotherapy for treatment-resistant PTSD; PTSD remains a chronic and sometimes debilitating condition. New research into other treatment options for PTSD are warranted. Psychedelic medications, including psilocybin, have recently received breakthrough designation by the US Food and Drug Administration (FDA) for other psychiatric indications. Psilocybin has received breakthrough designation for treatment of depression. Research on psilocybin has shown that it facilitates fear extinction in mice and promotes neuroplasticity, increasing neurogenesis, spinogenesis and synaptogenesis. These properties may contribute to antidepressive and anxiolytic effects. Psilocybin also reduces activity in the amygdala during threat responses; decreased amygdala reactivity is correlated with positive mood. This is particularly relevant since individuals with PTSD showed increased reactivity in the amygdala, which may increase the ability to process traumatic memories. Although no formal clinical trials have yet investigated psychedelic substances for the treatment of PTSD, the available evidence warrants such an investigation. The present study aims to investigate the effect of psilocybin on treatment-resistant PTSD.

topic_tags:
Depression,Anxiety,PTSD,Neuroplasticity,Neurogenesis,Receptor Pharmacology,Clinical Trial,Animal Study,Safety


title: The Effects of Psilocybin on Self-Focus and Self-Related Processing in Major Depressive Disorder
authors: Sharmin Ghaznavi
journal: ClinicalTrials.gov
publication_date: 2025-05-05
source_url: https://clinicaltrials.gov/study/NCT06247839
keywords: Major Depressive Disorder, Psilocybin, RECRUITING
substance_tags: psilocybin
topic_tags: Depression,Brain Imaging,Aging
study_type: Other
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:28
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT06247839","overall_status":"RECRUITING","phase":["PHASE3"]}
abstract:
This open-label functional Magnetic Resonance Imaging (fMRI) study will assess the effects of a single dose of psilocybin on rumination and the neural correlates of rumination in individuals with major depressive disorder.


authors: Centre for Addiction and Mental Health
journal: ClinicalTrials.gov
publication_date: 2026-03-17
source_url: https://clinicaltrials.gov/study/NCT07211438
keywords: Treatment-Resistant Depression, Psilocybin, NOT_YET_RECRUITING
substance_tags: psilocybin
topic_tags: Depression,Clinical Trial,Randomized Controlled Trial,Treatment-Resistant Depression
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:28
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT07211438","overall_status":"NOT_YET_RECRUITING","phase":["PHASE2"]}
title:
Evaluating the Role of Psilocybin Monitors in Psilocybin Therapy for Treatment Resistant Depression: A Pilot Randomized Clinical Trial

abstract:
Psilocybin, the chemical component of "magic mushrooms", has been administered with psychological support in several randomized clinical trials (RCTs) showing large and sustained antidepressant effects. The purpose of this study is to determine the role of psilocybin monitors on the effects of psilocybin therapy in adults with treatment resistant depression. Psilocybin, the chemical component of "magic mushrooms", has been administered with psychological support in several randomized clinical trials (RCTs) showing large and sustained antidepressant effects. The purpose of this study is to determine the role of psilocybin monitors on the effects of psilocybin therapy in adults with treatment resistant depression.


authors: MycoMedica Life Sciences PBC
journal: ClinicalTrials.gov
publication_date: 2026-02-12
source_url: https://clinicaltrials.gov/study/NCT07050368
keywords: Healthy Volunteer, Psilocybin, Placebo, COMPLETED
substance_tags: psilocybin
topic_tags: Depression,Addiction,Brain Imaging,Pharmacology,Aging,Clinical Trial,Healthy Volunteers,Safety
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:28
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT07050368","overall_status":"COMPLETED","phase":["PHASE1"]}
title:
A Phase 1 Translational Study to Assess Brain Activity Using Functional Magnetic Resonance Imaging (fMRI) and to Evaluate the Safety, Tolerability, and Pharmacokinetics of Multiple Doses of MLS101 (Psilocybin) in Healthy Volunteers

abstract:
MLS101 is being developed as a low dose psilocybin, that can be administered to treat neurological and psychiatric conditions. The purpose of this trial is to investigate brain activity, safety, tolerability, and PK of multiple doses of MLS101 in healthy participants. In recent years, high-dose psilocybin has gained attention for it potential therapeutic benefit in many psychiatric conditions, however existing clinical data for low psilocybin doses are limited. The multiple-dose regimen proposed in this study is designed to optimize the pharmacology of MLS101 and elucidate whether it provides a longer period of positive effects, which could be used in future studies in chronic indications such as PMDD, obsessive compulsive disorder and opioid use disorder. Translational functional magnetic resonance imaging (fMRI) imaging will confirm the central nervous system (CNS) activity of priming and repeat low-dose psilocybin, which will serve as a computational evaluation of efficacy and complement the cognitive and perceptual scales and questionnaires.


title: Activating Neuroplasticity to ENHANCE the Perception Box Expanding Effects of Psilocybin
authors: University of Wisconsin, Madison
journal: ClinicalTrials.gov
publication_date: 2026-04-02
source_url: https://clinicaltrials.gov/study/NCT05866471
substance_tags: psilocybin
topic_tags: Neuroplasticity,Wellbeing,Clinical Trial,Safety
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:28
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT05866471","overall_status":"RECRUITING","phase":["PHASE1"]}
abstract:
This study will examine whether combining a single dose of psilocybin with non-invasive transcutaneous auricular vagus nerve stimulation (taVNS), a potential inducer of neuroplasticity and enhanced memory formation, will enhance the long-term beneficial behavioral effects of psilocybin when compared to sham taVNS or no VNS by allowing memory for insights gained during the psychedelic experience to remain vivid after they will have faded in subjects who receive psilocybin followed by sham taVNS or no VNS. One hundred and eight medically healthy adult volunteers with a modest decrement in wellbeing will receive a single open-label 25 mg dose of psilocybin administered within a "set and setting" (SaS) framework of psychological support provided by trained facilitators, such as has been successfully employed in prior psychedelic studies at UW-Madison. The SaS protocol will include 2-4 hours of preparation, a 6- to 8-hour psilocybin dosing session and an hour-long integration session 1 day and 9 days post dosing. All subjects will receive various combinations of active taVNS or sham taVNS prior to, or following, psilocybin dosing. Active and sham taVNS sessions will last 20 minutes and will occur twice daily (morning and afternoon/evening) for 7 consecutive days, using an "at home" protocol that has been used safely and effectively by study collaborators. taVNS is a non-invasive low-risk procedure. Subjects will be randomized with equal allocation to one of four conditions: 1) seven days of sham taVNS prior to psilocybin dosing and 7 days of active taVNS post- psilocybin dosing (Group 1: n=27); 2) seven days of sham taVNS prior to psilocybin dosing and 7 days of sham taVNS post- psilocybin dosing (Group 2: n=27); 3) seven days of sham taVNS prior to psilocybin dosing and psilocybin with psychosocial support post-dosing (Group 3: n=27); and 4) seven days of active taVNS prior to psilocybin dosing and 7 days of sham taVNS post- psilocybin dosing (Group 4: n=27). Importantly, participants in all groups will receive psychosocial support in addition to their randomization status (i.e., taVNS or sham taVNS prior to, or following psilocybin, or psychosocial support alone), as the provision of psychosocial support is the current standard of care for the use of psychedelics in FDA-regulated clinical trials (FDA2023). It is anticipated that a total sample of 108 subjects will be enrolled to provide 100 subjects who complete study activities/assessments sufficient to provide evaluable data for testing study primary and exploratory outcomes.

keywords:
Healthy, Psychedelic Experiences, Vagus Nerve Stimulation, Psilocybin, Psilocybine, Psilocibin, Filament Health Psilocybin, PEX010, Transcutaneous auricular Vagus Nerve Stimulation (taVNS), Psychosocial Support Alone, Sham taVNS, RECRUITING


authors: Lobe Sciences Ltd.
journal: ClinicalTrials.gov
publication_date: 2023-09-12
source_url: https://clinicaltrials.gov/study/NCT06035900
keywords: Side Effect of Drug, Psilocin, Psilocin Mucate, COMPLETED
substance_tags: psilocybin,psilocin
topic_tags: Addiction,Pharmacology,Clinical Trial,Safety,Adverse Events
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:28
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT06035900","overall_status":"COMPLETED","phase":["PHASE1"]}
title:
Phase 1, Open-Label, One-Treatment, Single-Dose, One-Period, Pharmacokinetic Study of Psilocin 4 mg as Its Mucic Acid Salt (L-130) Form, in Healthy Subjects Under Fasted Conditions

abstract:
Psilocin is the active metabolite of psilocybin a natural material found in several types of fungi. The bioavailability of psilocybin, the prodrug of psilocin, has been reported to be over 60%. However, pharmacokinetics and bioavailability of psilocin mucate has not been reported. This Phase I "First in Man" study of psilocin mucate is designed to determine its safety, pharmacokinetics, and bioavailability. The study is conducted under the supervision of physicians and psychiatrists who also will administer a mini-mental state evaluation and report observable anti-anxiolytic effect of the dosage. Safety and possible indications of efficacy will be tracked during the study period, a week following the dose administration and one month after. This study is designed to assess the bioavailability and pharmacokinetic parameters and to monitor the safety and tolerability of Psilocin 2 mg as its Mucic Acid Salt (L-130) form, a proprietary drug candidate of Lobe Sciences Ltd., in healthy subjects under fasted conditions. The study will be conducted in compliance with the protocol and applicable regulatory requirements, GCP and GLP principles and guidelines: Declaration of Helsinki as amended by the 64th WMA General Assembly, Fortaleza, Brazil, November 2013, FDA Guidelines for Bioavailability \& Bioequivalence Studies and OECD Principles of Good Laboratory Practice will be observed. The study population will consist of 10 Healthy Subjects aged between 21 and 50 years (inclusive), body mass index 18.5 to 30.0 kg/m2 inclusive (minimum of 50 kg weight for males and 45 kg for females), nonsmokers or quit smoking 24 hours prior to dosing. The investigational test product L-130 Capsules containing 2 mg of psilocin as its Mucic Acid Salt of Lobe Sciences Ltd. consisted of single oral dose containing 2 mg of Psilocin (equivalent to 4 mg as Psilocin Mucate salt). Each dose will be administered orally, with 240 mL of water in sitting position under sodium light to healthy subjects after an overnight fast of at least 10 hours in the morning of study dosing day. The study will be conducted as an open label study. Therefore, blinding will not be done. However, the bioanalysis will be performed blinded with regard to the sequence of product administration. Each subject will have a pre-dose sample of 8 ml collected and 13 additional 8 ml samples collected over a 24 hour period. The principal and/ or clinical investigator and study staff will monitor subjects throughout the hospitalization periods. Blood pressure and heart rate will be measured before dosing and at scheduled intervals after dosing. The principal and/ or clinical Investigator will be available throughout each hospitalization period. During outpatient phases, study staff will be available during regular working hours. Subjects' safety will be observed at scheduled intervals of before dosing (-1.00) and 0.50, 0.75, 1.00, 2.00, 3.00, 5.00, 8.00, 12.00, 16.00 and 24.00 hours after drug administration. Subjects will be queried on adverse events. In addition, voluntary reporting of adverse events by subjects will be reported. Mini Mental State Examination (MMSE) score will be assessed to dosed subjects by CI/PI approximately two hours after drug administration, and the results will be tabulated in the final report. Subjects will be asked to report changes in their mood, or other observations during and following the study period. Subjects will also be followed up by phone call after one week and four weeks of dosing to assess if they are experiencing changes in feeling or having improved mood, and the outcomes of the phone calls will be tabulated in the final report. Following the collection of blood samples and appropriate processing, each sample will be analyzed with a validated analytical method to determine the pharmacokinetic profile of psilocin mucate in plasma. All clinical laboratories test results of screening lab tests will be summarized by descriptive statistics. Follow up lab tests will also be summarized by descriptive statistics. The aim of the study is to assess the bioavailability and pharmacokinetic parameters and to monitor the safety and tolerability of the formulation in healthy subjects under fasting conditions after a single oral dose of L-130 Capsules containing 2 mg of psilocin as its Mucic Acid Salt. The final report will provide safety, tolerability and pharmacokinetics of the test product. The study will also report patient reported pharmacology.


authors: McMaster University
journal: ClinicalTrials.gov
publication_date: 2025-03-18
source_url: https://clinicaltrials.gov/study/NCT06225232
substance_tags: psilocybin
topic_tags: Addiction,Clinical Trial,Review Article,Safety
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:28
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT06225232","overall_status":"RECRUITING","phase":["PHASE2"]}
title:
An 8-week Phase 2 Clinical Trial to Evaluate the Safety, Tolerability and Efficacy of Psilocybin-assisted-psychotherapy in Adults With Cannabis Use Disorder: A Proof-of-Concept Study

abstract:
Cannabis is the most commonly used psychoactive substance in Canada (Lowry \& Corsi, 2020). A sub-group of cannabis users develop a condition known as Cannabis Use Disorder (CUD), which is defined as a regular pattern of cannabis use that causes performance difficulty at work, school and relationships (Hasin et al., 2013). A review of current treatments available for CUD indicate the lack of a pharmacological and psychological treatment with high success rates, which highlights the importance of exploring potential psychosocial interventions for the treatment of CUD. Given the evidence of psilocybin's therapeutic potential in the treatment of substance use disorders (de Veen et al., 2017), we aim to conduct a study using psilocybin-assisted-psychotherapy in the treatment of CUD. The study aims to evaluate the feasibility, safety, tolerability and potential therapeutic effect of 2 doses \[25 mg\] of psilocybin administered as part of an 8-week Motivational Enhancement Therapy (MET) and supportive therapy. This trial will be the first to evaluate the potential treatment effects of psilocybin on symptoms of CUD.

keywords:
Cannabis Use Disorder, Moderate, Cannabis Use Disorder, Severe, Psilocybin combined with Psychotherapy, RECRUITING


authors: Johns Hopkins University
journal: ClinicalTrials.gov
publication_date: 2024-06-17
source_url: https://clinicaltrials.gov/study/NCT02243813
keywords: Healthy, Psilocybin, COMPLETED
substance_tags: psilocybin
topic_tags: General
study_type: Other
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:28
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT02243813","overall_status":"COMPLETED","phase":["PHASE1"]}
title:
Effects of Psilocybin-facilitated Experience on the Psychology and Effectiveness of Professional Leaders in Religion

abstract:
The current protocol is a pilot study of the effects and possible utility of psilocybin-facilitated experiences for professional religious leaders.


title: The Effects of Psilocybin on Shared Experience in Film Processing
authors: Western University, Canada
journal: ClinicalTrials.gov
publication_date: 2024-09-26
source_url: https://clinicaltrials.gov/study/NCT06529939
keywords: Disorders of Consciousness, Psychedelic Experiences, Psilocybin, Placebo, NOT_YET_RECRUITING
substance_tags: psilocybin
topic_tags: Brain Imaging,Consciousness,Aging,Clinical Trial,Healthy Volunteers
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:28
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT06529939","overall_status":"NOT_YET_RECRUITING","phase":["NA"]}
abstract:
The goal of this clinical trial is to learn whether certain methods of detecting awareness in vegetative or minimally conscious patients (using neuroimaging) are sensitive to the effects of psilocybin (a psychedelic drug). One of these methods includes scanning peoples\' brains while they watch a film. When different individuals watch a film, their brains become synchronized with each other as they watch the plot unfold. Most importantly, if a seemingly unconscious patient also shows the same brain-synchronization, it means they might actually be conscious and aware. To approach this goal, the investigators will be carrying out this trial in healthy volunteers. This will help better understand whether psilocybin may be a potential treatment for restoring awareness in these patients. The main questions it aims to answer are: * Does psilocybin enhance or diminish brain synchrony during a film? * Do changes in brain synchrony reflect differences in each individual\'s conscious experience? Participants will be asked to: * Attend two brain scanning sessions and watch a series of film clips, perform a brief mental imagery task, and listen to music - once under a placebo, and once under psilocybin. * Play a series of games that assess their cognition (memory, reasoning, planning, etc.). * Perform a series of visual illusions tasks.


authors: Sunstone Medical
journal: ClinicalTrials.gov
publication_date: 2026-06-30
source_url: https://clinicaltrials.gov/study/NCT06902974
keywords: Post Traumatic Stress Disorder, PTSD, Psilocybin 25 mg, Psilocybin-assisted therapy, RECRUITING
substance_tags: psilocybin
topic_tags: PTSD,Clinical Trial,Safety
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:28
last_checked: 2026-07-02 06:57:00
raw_json: {"nct_id":"NCT06902974","overall_status":"RECRUITING","phase":["PHASE2"]}
title:
A Phase 2, Open-Label Study Investigating the Safety and Efficacy of Psilocybin-Assisted Therapy for Sexual Assault-Related Posttraumatic Stress Disorder (PTSD)

abstract:
A Phase 2, Open-Label Study to explore the efficacy, safety, and tolerability of psilocybin-assisted therapy in women with sexual assault-related Posttraumatic Stress Disorder (PTSD).


authors: Beersheva Mental Health Center
journal: ClinicalTrials.gov
publication_date: 2025-11-18
source_url: https://clinicaltrials.gov/study/NCT07183748
keywords: Treatment Resistant Depression, Psilocybin (drug), Placebo, RECRUITING
substance_tags: psilocybin
topic_tags: Depression,Biomarkers,Microdosing,Clinical Trial,Treatment-Resistant Depression,Safety,Inflammation
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:28
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT07183748","overall_status":"RECRUITING","phase":["PHASE2"]}
title:
A Double-blind, Phase II Feasibility Study to Assess the Safety and Efficacy of Psilocybin Microdosing Combined With Psychotherapy in Treatment-resistant Depression

abstract:
Objective: To assess the safety and efficacy of a six-week microdosing regimen of psilocybin combined with short-term, experience-based psychotherapy in patients with treatment-resistant depression who have not responded to previous pharmacological or long-term psychological interventions. Hypothesis: Compared to baseline, the group that begins with psilocybin will exhibit a more rapid reduction in depressive symptoms after six weeks, compared to the group that begins with placebo and receives only psychotherapy. Following the crossover between conditions, the placebo-first group will also show an accelerated reduction in these measures after the subsequent six weeks. Alternative hypothesis: No difference will be observed between groups in the rate of symptom reduction. Objective: To examine biological markers that may mediate potential improvements in depressive symptoms among participants receiving psilocybin microdosing compared to placebo. Hypothesis: Compared to baseline, six weeks of active psilocybin dosing will result in decreased levels of cortisol and inflammatory markers, and increased levels of oxytocin and BDNF in saliva. Objective: To assess psychological factors that may mediate potential improvements in depressive symptoms among participants receiving psilocybin microdosing compared to placebo. Hypothesis: Compared to baseline, six weeks of active psilocybin dosing will lead to increased cognitive flexibility, greater self-compassion, and enhanced present-moment awareness. Objective: To explore a subpopulation of women experiencing premenstrual symptom exacerbation (PMS) and the potential for improvement in depressive symptoms in the days preceding menstruation, if any. Hypothesis: Among women with worsened premenstrual symptoms, psilocybin will reduce premenstrual symptoms, specifically depressive symptoms, compared to baseline.


title: Safety and Efficacy of Psilocybin for the Treatment of Headache Disorders
authors: Yale University
journal: ClinicalTrials.gov
publication_date: 2023-12-14
source_url: https://clinicaltrials.gov/study/NCT02981173
substance_tags: psilocybin
topic_tags: Headache / Migraine,Safety
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:28
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT02981173","overall_status":"COMPLETED","phase":["PHASE1"]}
abstract:
The purpose of this study is to investigate the effects of an oral psilocybin pulse regimen in cluster headache. Subjects will be randomized to receive oral placebo, low dose psilocybin, or high dose psilocybin in three experimental sessions, each separated by 5 days. Subjects will maintain a headache diary prior to, during, and after the pulse regimen in order to document headache frequency and intensity before, during, and after the pulse regimen. After at least 6 months from the last experimental session, subjects may be invited for a second round, in which they will be randomized to receive either low dose or high dose psilocybin.

keywords:
Cluster Headache, 0.143 mg/kg Psilocybin or 10 mg Psilocybin, 0.0143 mg/kg Psilocybin or 1 mg Psilocybin, Placebo, COMPLETED


authors: TRYP Therapeutics
journal: ClinicalTrials.gov
publication_date: 2026-02-04
source_url: https://clinicaltrials.gov/study/NCT06206265
keywords: Irritable Bowel Syndrome, TRYP-0082, Psychotherapy, ACTIVE_NOT_RECRUITING
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Chronic Pain,Brain Imaging,Aging,Clinical Trial,Healthcare Workers,Safety
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:28
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT06206265","overall_status":"ACTIVE_NOT_RECRUITING","phase":["PHASE2"]}
title:
A Phase 2a, Open-label, Pilot Study to Assess the Safety and Efficacy of Oral Psilocybin (TRP-8802) Administration in Concert With Psychotherapy Among Adult Patients With Irritable Bowel Syndrome: A Randomized Delayed Treatment Control Design

abstract:
Participants with IBS (all subtypes) and with no exclusionary comorbid psychiatric or medical disorders will be enrolled in the study. This study will involve a randomized waitlist control design to investigate the rapid and sustained effects of TRP-8802 following two experimental sessions in which an oral dose of TRP-8802 is administered to participants with IBS. The study will include clinician and participant ratings of depression and anxiety pre- and post-drug-session, monitor and participant ratings of subjective drug effects during and after each drug session. This study comprises approximately a 28-day screening period (Days 28 to 1). After screening and enrollment, participants will be randomized to an immediate treatment group or a delayed treatment group ("waitlist control" condition). Participants in the immediate treatment group will proceed directly into three weeks of baseline and preparation (Days 1 to 18), a 2-dose administration period (Days 22 and 37), integration (Days 23, 30, 38, and 45), the End of Therapy (EOT) visit (Day 52). Participants in the delayed treatment group will wait 8 weeks after enrollment before beginning the study interventions and neuroimaging assessments. As a safety precaution, participants in the delayed treatment group will be assessed weekly via telephone calls or in-person visits during the wait period (i.e., telephone assessments during post-randomization weeks 1, 2, 3, 4, 5, 6, and 7; in-person assessment during post-randomization week 8) to assess suicide risk to determine if intervention is warranted. During week 8, IBS symptoms will also be assessed. At the end of the delay period, all participants in the delayed treatment group will complete the same intervention as the participants in the immediate treatment group. Validated and commonly used assessment tools will be used to evaluate symptoms at baseline and repeatedly after each session. The weekly average of worst daily pain score and weekly stool frequency and consistency for the 7 days immediately prior to EOT visit will be assessed for change from baseline and at the 3-, 6, and 12- month follow-up visits (Days 120, 240, 365).


title: Investigation of Psychedelic Effects in Psychoactive Substances
authors: Johns Hopkins University
journal: ClinicalTrials.gov
publication_date: 2026-02-22
source_url: https://clinicaltrials.gov/study/NCT06772753
substance_tags: psilocybin
topic_tags: Healthy Volunteers
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:28
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT06772753","overall_status":"RECRUITING","phase":["PHASE1"]}
abstract:
The aim of this double-blind, placebo-controlled, within-subjects study is to determine whether other psychoactive substances can produce experiences akin to those seen with classic psychedelics. Screening involves a medical and psychiatric examination, including blood draw, history and physical, interviews, and questionnaires. Eligible participants will then be asked to complete up to 6 experimental drug administration session during which the participants will potentially receive and report on the subjective effects of 6 different psychoactive substances or inactive placebo. Drug assignment for some sessions will be randomized (like flipping a count or rolling a pair of dice), and both participants and study staff will be blind to the drug condition on any given day. Participants will also complete 2 preparation sessions (4 hours total) before the first experimental session, and follow-up visits after each session to discuss and debrief on the participants subjective experience.

keywords:
Psychedelic Effects in Healthy Volunteers, Placebo, Psilocybin, Ketamine, Dextromethorphan (DXM), Dimethyltryptamine (DMT), Methylenedioxymethamphetamine (MDMA), Tetrahydrocannabinol (THC), RECRUITING


title: Psilocybin and MDMA for Post-traumatic Stress Disorder (PTSD)
authors: Johns Hopkins University
journal: ClinicalTrials.gov
publication_date: 2025-09-30
source_url: https://clinicaltrials.gov/study/NCT06989957
keywords: Posttraumatic Stress Disorder, Psilocybin, MDMA, RECRUITING
substance_tags: psilocybin
topic_tags: PTSD,Veterans,Safety
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:28
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT06989957","overall_status":"RECRUITING","phase":["PHASE1"]}
abstract:
The purpose of this study is to assess the safety and effectiveness of co-administered MDMA and psilocybin in military Veterans with a diagnosis of Posttraumatic Stress Disorder (PTSD). To apply or learn more, please view our website: https://hopkinspsychedelic.org/pamvet The proposed randomized, double-blind, active control study will compare a single experimental dose of co-administered MDMA + psilocybin (exact dosages not disclosed) with a single comparator dose of co-administered MDMA + psilocybin (exact dosages not disclosed). For the co-administered dosing session, MDMA will be given initially, followed by psilocybin 30 minutes later. Approximately 1.5 months after the first dosing session, a second single-blind (participant masked) dosing session will occur. The study will recruit adult Veterans with PTSD for ≥ 6 months.


title: Psychopharmacology of Psilocybin in Cancer Patients
authors: Johns Hopkins University
journal: ClinicalTrials.gov
publication_date: 2018-07-18
source_url: https://clinicaltrials.gov/study/NCT00465595
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Pharmacology,Consciousness,Spirituality,Healthy Volunteers,Cancer Patients
study_type: Other
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:28
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT00465595","overall_status":"COMPLETED","phase":["PHASE2"]}
abstract:
This research is being done to study the psychological effects of psilocybin in cancer patients. Psilocybin is a naturally occurring substance found in some mushrooms that some cultures have used for centuries in religious practices. This research is being done to study the psychological effects of psilocybin in cancer patients. Psilocybin is a naturally occurring substance found in some mushrooms that some cultures have used for centuries in religious practices. Psilocybin has not been approved for general medical use by the U.S. Food and Drug Administration (FDA). Its use in this study is investigational. Psilocybin is a mood-altering drug with effects similar to other hallucinogens like LSD and mescaline. Mescaline is the main psychoactive component of the peyote cactus used in Native American religious practices. Such substances have been used for centuries in some cultures as a way of inducing non-ordinary states of consciousness for religious and spiritual purposes. An earlier study that was done in our lab with healthy participants found that psilocybin, given in a comfortable and supportive setting, can provide an experience that is personally and spiritually meaningful for the participant. This study is being done to find out if psilocybin can also produce personally and spiritually meaningful experiences in cancer patients. This could be important because spirituality has been associated with increased psychological coping and decreased depression in serious illness. People with a diagnosis of cancer between the ages of 21 and 80 years old and who meet the medical requirements may join. About 44 people are expected to take part in this study.

keywords:
Depressive Symptoms, Anxiety, Cancer, psilocybin, O-phosphoryl-4-hydroxy-N,N-dimethyltryptamine, COMPLETED


authors: Gitte Moos Knudsen
journal: ClinicalTrials.gov
publication_date: 2022-08-09
source_url: https://clinicaltrials.gov/study/NCT04280055
keywords: Cluster Headache, Psilocybin, TERMINATED
substance_tags: psilocybin,psilocin
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:28
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT04280055","overall_status":"TERMINATED","phase":["PHASE1","PHASE2"]}
title:
Prophylactic Effects of Psilocybin on Chronic Cluster Headache: an Open-label Clinical Trial and Neuroimaging Study

abstract:
The purpose of this study is to investigate the prophylactic effects of psilocybin in chronic cluster headache. Subjects will receive a low dose of psilocybin during 3 sessions spaced by one week. Subjects will maintain a headache diary prior to, during, and after the administrations in order to document headache frequency, intensity and duration. Subjects will undergo a fMRI scanning before the first and after the last psilocybin session. Cluster headache (CH) is one of the most painful conditions known. CH affects 1 out 1000 and exists in two well-defined forms: episodic (ECH) and chronic (CCH). Ten to fifteen percent of patients have CCH and have less than three months of pain-free time during a year. Medical treatment for CH is divided into acute abortive treatment for the single attack and a prophylactic treatment. The most commonly used prophylactic, verapamil, decreases attack frequency but does not induce remission and very high doses are needed. Although most therapeutic options ameliorate CH, they may be problematic due to major side effects, unsatisfactory treatment response or availability. Thus, novel treatment options are needed. According to several studies, patients that self-medicate with low doses of the serotonin 2A receptor (5-HT2AR) agonist and psychedelic psilocybin report that this is effective as CH prophylaxis or even to induce remission. So far, no clinical trials to confirm this have been conducted, nor is there any objective measures of brain function in association with psilocybin intake in CH. There is, however, already some evidence from functional magnetic resonance (fMRI) imaging studies suggesting that CH patients have abnormal functional connectivity patterns involving the hypothalamus and distributed brain networks, but the implication of these abnormalities is unknown. The investigators are conducting a prospective pilot study, evaluating prophylactic effects of psilocybin in CCH using an open-label study design. They're also going to investigate psilocybin's active metabolite psilocin and brain function (fMRI) to identify possible brain mechanisms underlying CCH and treatment response, including the correlation of treatment response with psilocin levels and estimated 5-HT2AR occupancy and the extent to which brain network changes are affected by psilocybin and correlated with treatment response. Effects of psilocybin on headache frequency, duration and intensity will be assessed in a sample of 20 patients with CCH. Participants will fill out headache logs during the entire study period, in total 10 weeks. Before study inclusion, participants taking prophylactic medication will first go through a 2-week wash-out period to allow for elimination of the medicine. Inclusion is followed by a baseline observation period lasting four weeks, after which patients will first undergo a baseline rs fMRI scanning followed by the first dose of 0.14 mg/kg psilocybin p.o. Blood samples will be collected during the first psilocybin intervention to establish psilocin plasma concentrations, which will be used for estimating receptor occupancy. Participants will then undergo two additional psilocybin administrations spaced by one-week. The last psilocybin dose will be followed by 4 weeks of observation. One week after the last administration of psilocybin, participants will undergo a follow-up MRI scan. Participants will be contacted 3, 6 and 12 months after the last psilocybin dose to gain information about the duration of potential remission periods. All regular acute treatments are permitted during the study period and a systematic record hereof has to be noted in the headache diary. No other prophylactic medication is allowed during the trial and at least a two-week washout period before inclusion is required. Prophylactics are allowed again after the 4 weeks follow-up, with dose and type carefully recorded. Participants will fill out questionnaires during the observation period, in conjunction with psilocybin interventions and at follow-up.

topic_tags:
Chronic Pain,Headache / Migraine,Brain Imaging,Mechanism of Action,Receptor Pharmacology,Aging,Clinical Trial,Adverse Events


title: NeuroGuard: Psilocybin Trial for Preventing Chemo-induced Neuropathy
authors: M.D. Anderson Cancer Center
journal: ClinicalTrials.gov
publication_date: 2026-06-23
source_url: https://clinicaltrials.gov/study/NCT07227909
keywords: Psilocybin, Neuropathy, Psilocybin (drug), Standard of Care (SOC), NOT_YET_RECRUITING
substance_tags: psilocybin
topic_tags: Chronic Pain,Wellbeing,Mystical Experience,Healthcare Workers,Toxicity
study_type: Other
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:28
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT07227909","overall_status":"NOT_YET_RECRUITING","phase":["PHASE2"]}
abstract:
To learn if psilocybin can help to prevent or decrease the severity of chemotherapy-induced peripheral neuropathy (CIPN) in patients who are receiving chemotherapy for the treatment of breast, colorectal, and In this study, psilocybin is being compared to standard supportive care and to a placebo. Primary Objective 1\. To assess the efficacy of psilocybin in the prevention or mitigation of chemotherapy-induced peripheral neuropathy (CIPN) in individuals undergoing adjuvant neurotoxic chemotherapy (i.e., taxanes, platinum-based compounds) for breast, colorectal, and head \& neck cancers. The primary endpoint is the proportion of participants with a ≥25% increase (worsening) from baseline to Week 12 on the EORTC QLQ-CIPN20 sensory subscale. The primary comparison is 25 mg psilocybin vs pooled control (standard of care + 1 mg subperceptual psilocybin), tested two-sided at α=0.05. If significant, two confirmatory pairwise tests (25 mg vs SOC; 25 mg vs 1 mg) will be performed with Hochberg multiplicity control. Hypothesis: Prophylactic psilocybin administered in four doses (two pre-chemotherapy and two during chemotherapy) will reduce the severity of CIPN as measured by the proportion of participants reporting a 25% or greater increase in CIPN on the EORTC QLQ-CIPN20 sensory subscale compared to placebo or SOC. Secondary Objectives 1. Determine whether prophylactic psilocybin reduces rates of dose-liming modifications to chemotherapy as result of peripheral neurotoxicity. Dose modifications are defined by either a change in frequency or reduced chemotherapy dose during the 12-week study period. Dose modification decisions will be made by the participant's independent, primary clinician. 2. Determine whether prophylactic psilocybin decreases incidence and severity of CIPN as measured by the NCI-CTCAE criteria 3. Determine whether psilocybin-assisted psychotherapy improves measures of quality of life (e.g., sleep, pain, fatigue, functional status) and psychosocial well-being (e.g., mental health, finding meaning, and post-traumatic growth), as measured by the following: PROMIS-10, PROMIS-A, PROMIS-D, FACT-Cog, PSQI, BFI, MDASI, MEQ30 (mystical experience), Flourishing scale. 4. Determine whether psilocybin-assisted psychotherapy improves functional status per clinicianrated outcome measures. 5. Assess the effects of psilocybin-assisted psychotherapy on all-cause cancer treatment adherence determined by the likelihood that participants will follow the prescribed treatment (adherence) and continue the treatment for the duration prescribed (persistence) for these maintenance therapies.


title: Psilocybin-assisted Group Therapy for Demoralization in Long-term AIDS Survivors
authors: Joshua Woolley
journal: ClinicalTrials.gov
publication_date: 2021-01-06
source_url: https://clinicaltrials.gov/study/NCT02950467
substance_tags: psilocybin
topic_tags: Depression,End-of-Life Distress
study_type: Other
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:28
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT02950467","overall_status":"COMPLETED","phase":["PHASE1"]}
abstract:
The purpose of this study is to determine whether psilocybin-assisted group psychotherapy is a safe and feasible treatment for demoralization in long-term AIDS survivors (LTAS). This study is an open-label mixed-methods pilot study of an individual oral psilocybin drug session combined with ten sessions of an evidence-based, manualized brief group psychotherapy for existential distress in palliative care patients.

keywords:
Distress, Depression, Grief, Psilocybin, 4-phosphoryloxy-N,N-dimethyltryptamine, Indocybin, Modified brief Supportive Expressive Group Therapy, COMPLETED


authors: Centre Hospitalier Universitaire de Nīmes
journal: ClinicalTrials.gov
publication_date: 2025-08-19
source_url: https://clinicaltrials.gov/study/NCT06650800
substance_tags: psilocybin,psilocin
study_type: Other
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:28
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT06650800","overall_status":"COMPLETED","phase":["NA"]}
title:
Effect of Psilocybin on the Positive Valence System in Treatment-resistant Depression: a Pilot Clinical Neuroimaging Study

abstract:
The study hypothesis is that the antidepressant effect of psilocybin is mediated by a normalization of the functioning of the positive valence system. Depressive states, especially moderate to severe depressions that associate a certain level of anhedonia, produce an overvaluation of the cost of efforts and an infra-evaluation of the possible rewards derived from an action. Psilocybin would reduce anhedonia and the cost of efforts, facilitating the anticipation of reward. Thus, the antidepressant effect of psilocybin would be mediated by a greater anticipation of rewards (reduction of anhedonia) and a more optimistic estimation of the results of efforts (increase in motivation). Psilocybin-induced changes in the positive valence system will be observable on brain MRI images, particularly in the effort evaluation circuits: basolateral amygdala, dorsal anterior cingulate cortex, ventral pallidum, ventral striatum (VS), ventral tegmental area (VTA). The mesolimbic circuit (VS, VTA) is the anatomical substrate of anticipation of rewarding stimuli (food, sex, drugs). The amygdala also fulfills an associative function between environmental cues and rewarding stimuli. Structural and functional alterations in this circuit are associated with depressive symptoms such as anhedonia or distortions in the perception and memories of rewards. This hypothesis will be tested on a population of patients with moderate or severe depressive symptoms who meet the criteria for TRD. Depressive disorders are strongly associated with suicide risk and are the leading cause of disability in the world. Psilocybin is a natural alkaloid with psychedelic and hallucinogenic effects, produced by its active metabolite: psilocin. In recent years, there has been a resurgence of research aimed at using psilocybin in the treatment of psychiatric disorders, and in particular depression, combined or not with various psychotherapeutic programs. Psilocybin-assisted therapy is effective in treating cancer-associated depression and resistant depression. The Federal Drug Administration (FDA) has designated it as a "Breakthrough Therapy" in the treatment of treatment-resistant depression (TRD). Most researchers consider that the antidepressant effects of psilocybin are associated with the activation of the serotonin 5-HT2a receptor, with acute neuromodulation effects that modify the connectivity of cortico-striatal loops, but the mechanisms supporting this effect are unknown. The purpose of this study is to verify whether the antidepressant action of psilocybin is associated with an activation of the brain areas involved in the positive valence system, by comparing the activity of the neural circuits responsible for the evaluation of effort before and after taking psilocybin. The correlations between the activation of brain areas and the depression severity, behavioral activation and anhedonia scores will help establish a link with the response to treatment. Finally, the study authors wish to test the feasibility of a study with psilocybin in a French clinical population.

keywords:
Depressive Disorder, Depressive Disorder, Treatment-Resistant, Hallucinogens, Reinforcement, Psychology, Psilocybin, MRI, COMPLETED

topic_tags:
Depression,Brain Imaging,Mechanism of Action,Receptor Pharmacology,Aging,Treatment-Resistant Depression,Safety


authors: University of Calgary
journal: ClinicalTrials.gov
publication_date: 2026-06-01
source_url: https://clinicaltrials.gov/study/NCT06768944
substance_tags: psilocybin
topic_tags: Anxiety,Biomarkers,Wellbeing,Personality Change,Clinical Trial
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:28
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT06768944","overall_status":"RECRUITING","phase":["PHASE2"]}
title:
The Role of the Subjective Experience in Supporting Positive Effects Following Psilocybin: a Randomized, Controlled Clinical Trial Using Risperidone in Healthy Adults

abstract:
The purpose of this study is to determine the importance of the acute subjective experience induced by psilocybin (the primary component of "magic mushrooms") in facilitating positive outcomes. Participants in this study will be given psilocybin in combination with either a placebo or risperidone, an atypical antipsychotic that block the subjective effects of psilocybin. The overall goal of this clinical trial is to systematically explore the relationship between the subjective psychedelic experience, improvements in well-being, and the stress response following psilocybin administration. The investigators aim to determine whether blocking the acute subjective effects (via risperidone) will influence the acute or protracted effects of psilocybin as measured via self-report, biochemical, or psychophysiological measures. The study also aims to determine if individual variability in stress reactivity or regulation predicts acute (day of dosing) or protracted (1-week later) effects of psilocybin. A single site will recruit 128 participants aged 18 to 65 who do not meet criteria for any psychiatric diagnoses. A series of questionnaires, blood labs, and medical exams including electrocardiogram will determine inclusion into the study. Once accepted into the study, participants will complete baseline measures assessing biomarkers such as cortisol and brain-derived neurotrophic factor (BDNF) levels, cognitive flexibility, mood, well-being, personality traits, and anxiety levels. Participants will then be randomly assigned into one of the following groups: i) high dose psilocybin in combination with placebo pretreatment ii) high dose psilocybin in combination with risperidone pretreatment iii) low dose psilocybin in combination with placebo pretreatment iv) low dose psilocybin in combination with risperidone pretreatment Outcome measures will be assessed at 1-week and 1-month after each dosing session.

keywords:
Investigating the Importance of the Subjective Psychedelic Experience, Psilocybin high-dose, PEX010, high-dose psilocybin, Psilocybin low-dose, low-dose psilocybin, Risperidone 1 MG, Risperdal, Placebo, RECRUITING


authors: University of Washington
journal: ClinicalTrials.gov
publication_date: 2026-05-03
source_url: https://clinicaltrials.gov/study/NCT07565909
keywords: Depression, Anxiety, Psilocybin, Group Retreat Psilocybin Therapy, NOT_YET_RECRUITING
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Clinical Trial,Observational Study,Healthcare Workers,Safety,Adverse Events
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:28
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT07565909","overall_status":"NOT_YET_RECRUITING","phase":["PHASE2"]}
title:
A Phase 2 Sequential Dose-Finding Study of Preparation for Group Retreat Psilocybin Therapy for Healthcare Clinicians With Loss of Meaning in Their Work and Symptoms of Depression

abstract:
In this single-arm Phase 2 study, the researchers are assessing the feasibility of the group retreat format for clinicians and explores different 'doses' of preparation. A sequential dose-escalation design is used. The study will recruit healthcare clinicians (physicians, nurses, nurse practitioners, physician assistants) aged 25-70 years currently in clinical practice with moderate or greater symptoms of depression and loss of meaning during the past 5 years. Each participant will be in a group cohort of 8, and 3 cohorts will be tested at each dose level. The objectives are safety, feasibility, mechanism testing, and outcomes. This is a single-arm study that examines the feasibility of the group retreat format for clinicians and explores different 'doses' of preparation. Population: Healthcare clinicians (physicians, nurses, nurse practitioners, physician assistants) aged 25-70 years currently in clinical practice with moderate or greater symptoms of depression (PHQ-9 ≥10) and loss of meaning during the past 5 years. Study Design: Phase 2, non-randomized, sequential cohort dose-escalation study examining the optimal number of preparation sessions for group retreat psilocybin therapy. Three cohorts will receive different "doses" of preparation: Cohort 1 receives 7 total preparation sessions (6 virtual + 1 in-person), Cohort 2 receives 4 total preparation sessions (3 virtual + 1 in-person), and Cohort 3 receives 2 total preparation sessions (1 virtual + 1 in-person). Each cohort includes 3 retreats with 8 participants per retreat. Sample Size: 72 participants total (24 per cohort, distributed across 3 retreats of 8 participants each) Study Duration: 18-24 months from enrollment of first participant to completion of final data analysis. Individual participant involvement spans approximately 8-10 months including 6-month post-retreat follow-up. Primary Objectives: (1) Safety: Assess incidence and severity of challenging experiences and adverse events across preparation dose levels using the Challenging Experience Questionnaire (CEQ), adverse event monitoring, and psychiatric symptom scales (PHQ-9, GAD-7, C-SSRS). (2) Feasibility: Determine completion rates for preparation sessions at each dose level. Secondary Objectives: (1) Mechanism Testing: Examine relationship between preparation dose, group cohesion, and challenging experiences. (2) Clinical Outcomes: Explore effects on depression and burnout for future power calculations. (3) Participant Preference: Assess participant-reported optimal preparation length. Summary: Psilocybin therapy has demonstrated promising efficacy for symptoms of depression related to frontline work during the COVID pandemic for clinicians. The group retreat format offers potential advantages over individual treatment, including enhanced accessibility, reduced cost per participant, and potential therapeutic benefits from group cohesion and shared experience. However, a critical unanswered question concerns the optimal number of preparation sessions. A sequential dose-finding design is appropriate because: (1) the dose-response curve for preparation sessions in group format is unknown; (2) attrition/completion rate is a critical feasibility outcome, particularly for time-constrained healthcare clinicians; (3) the design allows protocol refinement between cohorts based on emerging data; (4) this approach is more scientifically honest about genuine uncertainty regarding optimal preparation dose than premature randomization; and (5) it seeks to establish a minimum effective dose of preparation for practical feasibility and future scalability.


authors: Anthony P King
journal: ClinicalTrials.gov
publication_date: 2026-06-24
source_url: https://clinicaltrials.gov/study/NCT07104916
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:28
last_checked: 2026-07-01 23:13:10
raw_json: {"nct_id":"NCT07104916","overall_status":"RECRUITING","phase":["PHASE2"]}
title:
A Pilot Mechanistic RCT of Psilocybin With Mindfulness-based Therapy vs Support for Posttraumatic Stress Disorder (PTSD)

abstract:
The goal of this study is to learn how psilocybin delivered with mindfulness-based therapy may help symptoms of posttraumatic stress disorder (PTSD). This is an assessor-blinded, randomized, controlled study in participants with PTSD. The study will investigate the changes in brain activity, connectivity, and microstructural neuroplasticity assessed using EEG/EMG and multimodal MRI measures after administration of one oral dose of psilocybin, accompanied either with standard "psychological support" only; or with standard support plus Mindfulness-based Cognitive Therapy (MBCT). Many patients with PTSD do not respond or have an incomplete response to treatment with currently available medications that are FDA-approved for PTSD, and/or do not respond to psychotherapies for PTSD. The use of psychedelics (e.g. psilocybin) is being investigated as a new approach to improve symptoms in patients with PTSD and depression, however their mechanism of action is still not well understood. Furthermore, while psychedelics are usually administered in the context of psychological support ("psychedelic assisted therapy", PAT) the kinds of support therapy used and possible interactions with drug with therapy effects is not well understood. This study will investigate the changes in brain activity, connectivity, and microstructural neuroplasticity, assessed using electroencephalography (EEG) / electromyography (EMG) and functional magnetic resonance imaging (fMRI) /diffusion-weighted magnetic resonance imaging (DWI), after administration of one oral dose of 25 mg synthetic Psilocybin delivered in the context of either non-directive psychological support only (the most common approach for PAT) or in combination with psychological support plus an active form of psychotherapy called Mindfulness-based Cognitive Therapy (MBCT). Up to 30 participants will be enrolled altogether. The initial phase of this study will be an open label administration of 25 mg synthetic Psilocybin combined with standard "PAT psychological support" plus MBCT in ten participants with PTSD, to allow us to pilot this new intervention package. In the next phase of the study, we will randomly assign twenty participants with PTSD into two groups: one group receiving 25 mg of synthetic Psilocybin (open label) combined with standard "PAT support" only, and one group receiving 25 mg of synthetic Psilocybin (open label) combined with standard "support" plus active form MBCT psychotherapy. In both groups, psychological support will be provided before, during and after the administration session. The MBCT group will also receive bi-weekly individual MBCT sessions and will be invited to complete daily homework, as per the MBCT protocol. Assessments performed at Baseline and on Day 2 and Day 28 after administration will include EEG/EMG, MRI, clinician-administered scales (CAPS-5, MADRS, C-SSRS) and self-report questionnaires to assess PTSD, depression and anxiety symptoms, cognitive testing, self-report questionnaires to evaluate the psychedelic effects of synthetic Psilocybin administration, and blood collection for the Gsα-AC biomarker assay.

keywords:
Post Traumatic Stress Disorder, Depression - Major Depressive Disorder, Psilocybin + MBCT therapy, Active Comparator: Psilocybin with Support Only, RECRUITING

topic_tags:
Depression,Anxiety,PTSD,Neuroplasticity,Brain Imaging,Mechanism of Action,Biomarkers,Aging,Randomized Controlled Trial,Healthcare Workers,Drug Interactions


title: The Efficacy of Psilocybin Therapy for Depression in Parkinson's Disease
authors: Yale University
journal: ClinicalTrials.gov
publication_date: 2026-06-28
source_url: https://clinicaltrials.gov/study/NCT07610369
substance_tags: psilocybin
topic_tags: Depression,Microdosing,Randomized Controlled Trial,Safety
study_type: Randomized Controlled Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:28
last_checked: 2026-07-02 06:57:00
raw_json: {"nct_id":"NCT07610369","overall_status":"NOT_YET_RECRUITING","phase":["PHASE2"]}
abstract:
The purpose of this study is to understand whether people with Parkinson's Disease and depression have improvement in their symptoms after psilocybin therapy. This is a randomized controlled trial of oral psilocybin therapy for depression in people with Parkinson's disease (PD). The primary goal is to examine efficacy of psilocybin therapy in this patient population. Investigators will enroll participants with clinically diagnosed early to moderate stage Parkinson's disease (Hoehn and Yahr Stage 1-3 during an "on" period), who meet criteria for moderate or greater depression severity and meet all other inclusion and exclusion criteria at screening. Participants will complete two drug administration sessions where they will each receive a dose of oral psilocybin ranging from low ("microdose") to high in a medically monitored setting with psychotherapeutic support. Participants will also complete a series of psychotherapy sessions before and after each drug administration session. Clinical assessments will be used to quantify changes in depression as well as other relevant outcomes (non-motor and motor symptoms of PD, cognitive performance, quality of life). Follow-up will continue to 3 months after the second session. Endpoints will evaluate efficacy, safety, and tolerability of study procedures. After posting of these trial results, this data will be combined with the data from the trial at UCSF (NCT06455293) for publication purposes.

keywords:
Depression, Parkinson's Disease (PD), Psilocybin (drug), 4-phosphoryloxy- N, N-dimethyltryptamine, NOT_YET_RECRUITING


