# publications

title: Processing Intergenerational Trauma With Psilocybin-Assisted Therapy
authors: Rachel Yehuda
journal: ClinicalTrials.gov
publication_date: 2025-09-07
source_url: https://clinicaltrials.gov/study/NCT06899165
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Biomarkers,Wellbeing,Resilience,Healthcare Workers,Safety
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":"NCT06899165","overall_status":"RECRUITING","phase":["PHASE2"]}
abstract:
This is an open-label psilocybin-assisted therapy study that will examine the safety and tolerability of psilocybin-assisted therapy in the offspring of genocide survivors with mood and anxiety disorders. The study will also investigate the efficacy of psilocybin-assisted therapy in reducing symptoms such as depression, anxiety and stress, as well as changes to the psychological effects of parental exposure to genocide, and changes to psychological resilience. This study is investigating whether Psilocybin-assisted therapy improves depression, anxiety and stress symptoms in the offspring (biological children) of genocide survivors. Intergenerational trauma is the concept that the effects of experiencing extreme stress can be perpetuated to future generations. A genocide here is defined by the extinction or threat of extinction of a racial, religious or ethnic group, by an oppressive regime. A genocide survivor here is defined by an individual who survived or escaped a genocide in their country of origin. Currently, there are no evidence-based treatments developed specifically for the syndrome associated with Intergenerational trauma. This study aims to assess the safety and tolerability of psilocybin-assisted therapy, and assess the efficacy of psilocybin-assisted therapy in reducing symptoms such as depression, anxiety and stress, as well as changes to the psychological effects of parental exposure to genocide, and changes to psychological resilience. Participants will be asked to attend one or more screening visits to assess eligibility. If eligible, participants will be treated with two separate doses of the study medication, Psilocybin, 3-4 weeks apart. This is an open-label research study, meaning all participants will receive Psilocybin (25mg). Two trained clinical practitioners will work with participants across preparation, dosing, and integration processes. Participants will complete assessments throughout the study until their participation has ended. Safety measures are in place to check the overall health and well-being of participants Participation will consist of: * Screening Period (up to 4 weeks): Phone screen, informed consent, eligibility assessment. * Tapering \& Enrollment Period (variable): Enrollment, supervised medical tapering where necessary as discussed with the study doctor, biomarker collection and psychometric baseline assessments. * Preparatory \& Treatment Period (up to 14 weeks): Three preparatory sessions with study clinicians, assessments; two dosing days at least three weeks apart, three weekly integration sessions with study clinicians following each dose, a 72-hour check-in call after each dosing day, assessments. * Follow-Up Period (up to 5 weeks): Follow-up one month after final integration session, assessments, clinical evaluation, biomarker collection

keywords:
Psychological Stress, Depression, Anxiety, Psilocybin, Psilocybin-Assisted Therapy, Integration sessions, RECRUITING


title: The Safety and Efficacy of Psilocybin in Participants With Treatment Resistant Depression
authors: COMPASS Pathways
journal: ClinicalTrials.gov
publication_date: 2023-04-23
source_url: https://clinicaltrials.gov/study/NCT03775200
keywords: Treatment Resistant Depression, Psilocybin, COMPLETED
substance_tags: psilocybin
topic_tags: Depression,Safety
study_type: Other
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:28
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT03775200","overall_status":"COMPLETED","phase":["PHASE2"]}
abstract:
The Safety and Efficacy of Psilocybin in Participants with Treatment Resistant Depression The Safety and Efficacy of Psilocybin in Participants with Treatment Resistant Depression - a dose-ranging study


title: Acute Dose-dependent Effects of DMT in Healthy Subjects: A Placebo-controlled Cross-over Study
authors: University Hospital, Basel, Switzerland
journal: ClinicalTrials.gov
publication_date: 2024-04-24
source_url: https://clinicaltrials.gov/study/NCT05384678
substance_tags: psilocybin
topic_tags: Consciousness,Spirituality
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":"NCT05384678","overall_status":"COMPLETED","phase":["PHASE1"]}
abstract:
N,N-dimethyltryptamine (DMT) is a psychoactive substance with similar effects such as LSD or psilocybin. However, DMT is less well characterized than the latter substances. The present study is a modern randomized cross-over trial, investigating different continuous intravenous DMT dose rates over a broad dose range. Thus, different doses will be tested and related to subjective and autonomic effects. N,N-dimethyltryptamine (DMT) is a naturally-occurring psychedelic substance widely used in recreational and spiritual settings (Ayahuasca). DMT is considered a tool to induce an altered state of consciousness of interest in psychological and psychiatric research. DMT is rapidly metabolized by monoamine oxidase (MAO) A. Therefore, it is inactive when administered orally and has a very short duration of action when administered parenterally (\

keywords:
Healthy, N,N-Dimethyltryptamine (54 mg), N,N-Dimethyltryptamine (108 mg), N,N-Dimethyltryptamine (162 mg), N,N-Dimethyltryptamine (216 mg), Placebo, N,N-Dimethyltryptamine (108 mg) + dose titration, COMPLETED


title: Psilocybin as a Treatment for Chronic Pain in Smokers
authors: Yale University
journal: ClinicalTrials.gov
publication_date: 2026-06-08
source_url: https://clinicaltrials.gov/study/NCT07118332
keywords: Smokers With Chronic Pain, Psilocybin (drug), NOT_YET_RECRUITING
substance_tags: psilocybin
topic_tags: Addiction,Chronic Pain,Headache / Migraine,Clinical Trial,Observational Study,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":"NCT07118332","overall_status":"NOT_YET_RECRUITING","phase":["EARLY_PHASE1"]}
abstract:
The purpose of this study is to understand whether psilocybin therapy is safe and well tolerated in improving chronic pain and increasing motivation to quit smoking for people who have chronic pain and smoke cigarettes. Psilocybin is a psychedelic drug and the active ingredient in "magic mushrooms." Psilocybin is currently being studied in clinical trials but has no current medical use in the United States. Some studies have shown that a dose of psilocybin can help people quit smoking. Other studies have shown that a dose of psilocybin may improve certain chronic pain conditions, such as migraine headaches. We believe that it may also be helpful for people who smoke and have chronic pain, but this has not been tested yet. This will be an open-label pilot study examining the feasibility and potential efficacy of psilocybin in individuals who smoke and have chronic pain. Following the screening visit, the potential participants will have 1) an adaptation/preparation session, 2) a treatment session, and 3) two post-treatment follow-up sessions: 1 and 4 weeks after the treatment session. During study participation, participants will also complete surveys 4 times per day on a mobile device for 5 weeks (1 week before the treatment session and 4 weeks post-treatment session). General Procedures: Potential participants will undergo extensive medical and psychiatric screening to minimize the risk of study participation. Psilocybin will be administered as a 25 mg oral dose under close medical and psychiatric monitoring. For the 24 hours before the treatment session, subjects will be asked to abstain from consuming alcoholic beverages and any illicit drugs, verified by urine drug screening and breathalyzer. Non-compliant subjects will be rescheduled or discharged from the study if they are repeatedly non-compliant. Subjects will be instructed to drink their typical number of caffeinated beverages and smoke cigarettes as usual to minimize caffeine and tobacco withdrawal, which could confound the study measures. Subjects will be instructed not to eat for 4 hours before the treatment sessions because a light snack will be provided before the beginning of the session, and lunch will be provided at the end.


authors: Ohio State University
journal: ClinicalTrials.gov
publication_date: 2025-10-29
source_url: https://clinicaltrials.gov/study/NCT06820723
keywords: Depression, Anxiety, Major Depressive Disorder, CYB003, Placebo, NOT_YET_RECRUITING
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":"NCT06820723","overall_status":"NOT_YET_RECRUITING","phase":["PHASE2"]}
title:
A Randomized, Double-Blind, Placebo-Controlled Mechanistic Study to Assess a Single Oral Dose of CYB003 in Participants With Major Depressive Disorder (MDD) and Moderate to Severe Anxiety

abstract:
The goal of this study is to learn how psychedelics may help symptoms of depression and anxiety. Participants with major depressive disorder experiencing symptoms of depression and anxiety will receive one dose of either a drug related to psilocybin or a placebo. Assessments include interviews, self-report questionnaires, EEG and fMRI to measure symptoms and brain function. Many patients with MDD do not respond or have an incomplete response to treatment with currently available antidepressants. The use of psychedelics (e.g. psilocybin) is being investigated as a new approach to improve depressive symptomatology, however their mechanism of action is still not well understood. Psilocin is the active metabolite of psilocybin responsible for the psychedelic effects of the parent compound. CYB003 is a synthetic, deuterated isotopomer of psilocin, being developed by Cybin for the treatment of MDD. The 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 CYB003. Up to 40 participants will be enrolled and randomized into two groups: one receiving 16 mg of CYB003, and one group receiving placebo. Psychological support will be provided before, during and after the administration session. Assessments performed at Baseline and on Day 2 and Day 21 after administration will include EEG/EMG, MRI, clinician (MADRS, HAM-A, C-SSRS) scales and self-report questionnaires to assess depression and anxiety symptoms, cognitive testing, self-report questionnaires to evaluate the psychedelic effects of CYB003 administration, and blood draw of the Gsα-AC biomarker assay.

topic_tags:
Depression,Anxiety,Neuroplasticity,Brain Imaging,Mechanism of Action,Biomarkers,Aging,Healthcare Workers


authors: Kyle Greenway
journal: ClinicalTrials.gov
publication_date: 2026-04-21
source_url: https://clinicaltrials.gov/study/NCT07373535
substance_tags: psilocybin
topic_tags: Depression,Wellbeing,Clinical Trial,Treatment-Resistant Depression,Safety
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:28
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT07373535","overall_status":"NOT_YET_RECRUITING","phase":["PHASE2"]}
title:
Toward Patient-Tailored Care for Treatment-Resistant Depression: A Pilot Patient-Preference Clinical Trial of Music and Mindfulness in Psilocybin-Assisted Psychotherapy

abstract:
The goal of this pilot clinical trial is to learn whether it is feasible to individually tailor psilocybin-assisted psychotherapy (PAP) for people with treatment-resistant depression (TRD) based on their personal preferences. The study also aims to explore whether two different psychotherapy styles, music-centered and mindfulness-centered, influence how people respond to psilocybin treatment. The main questions it aims to answer are: * Is it feasible to conduct a patient-preference randomized trial of psilocybin-assisted psychotherapy? * Does receiving a preferred psychotherapy style improve treatment experiences or outcomes? * How do music-centered and mindfulness-centered PAP approaches compare in their effects on improving mood and well-being? Researchers will compare music-centered PAP to mindfulness-centered PAP to see if aligning psychotherapy with individual preferences is a practical and potentially beneficial approach for improving treatment efficacy and tolerability. Participants will: * Be adults with treatment-resistant depression * Receive two 25 mg psilocybin (PEX010, Filament Health) sessions, spaced four weeks apart * Experience one session with music-centered psychotherapy and one with mindfulness-centered psychotherapy * Before treatment, rate their preference for the two psychotherapy approaches * Be randomly assigned to receive their preferred or non-preferred approach first, followed by the other * Complete preparation and integration sessions before and after each psilocybin session This feasibility trial will also collect information on participants' cultural and personal factors influencing psychotherapy preferences using a modified Cultural Formulation Interview, and explore physiological measures of therapeutic alliance, an important factor in psychotherapy outcomes. Depression is one of the top causes of disability worldwide. Psilocybin-assisted psychotherapy (PAP) is an emerging treatment for Treatment-Resistant Depression (TRD) that pairs one or two doses of psilocybin, a serotonergic psychedelic, with a brief course of psychotherapy. While multiple studies of PAP have found safe, rapid, and lasting antidepressant effects, much remains unknown about how to optimize this promising intervention's psychotherapy component. This pilot study aims to explore a novel strategy for improving the efficacy and tolerability of PAP: individually-tailoring its psychotherapy based on patient preferences for two important nonpharmacological treatment elements: music and mindfulness. These core treatment components were selected based on their ubiquitousness in psilocybin studies and their potential for significant patient preference effects. The investigators will conduct a patient-preference randomized clinical trial where 16 patients with TRD will receive two doses of psilocybin (PEX010, Filament Health, 25mg). For each patient, one psilocybin dose will be administered with music-centered psychological support and the other with mindfulness-centered psychological support. In the first 4-week phase, patients will be asked to rate their preferences for these different psychotherapeutic approaches. Patients will then be 50:50 randomized to first receive either their preferred or their non-preferred treatment approach. In a second 4-week crossover phase, patients will receive the other treatment approach. All patients will thus undergo both music-centered and mindfulness-centered PAP interventions, but in an order dictated by their preferences and randomization. Each treatment phase entails pre-treatment and post-treatment psychotherapy following standard protocols. Similar patient-preference clinical trial designs have shown that preferences can significantly influence the efficacy and tolerability of existing psychiatric treatments. The primary aim of this pilot trial is to examine this design's feasibility for exploring such preference effects in PAP, which the investigators hypothesize will be substantial. As secondary aims, the trial will generate preliminary estimates about the magnitude of preference effects, compare the music- and mindfulness-centered approaches, and yield qualitative data about the diverse sociocultural factors that influence patient preferences, including with a modified Cultural Formulation Interview administered at baseline. An additional exploratory aim is to examine novel physiological measures of therapeutic alliance, a crucial factor in psychiatric care. Depression affects millions of Canadians and new treatments are sorely needed. This line of research seeks to produce systematic approaches to tailoring the psychotherapy of PAP for TRD. Its ultimate goal is to improve this promising intervention's efficacy, safety, and applicability to diverse populations.

keywords:
Treatment-Resistant Major Depressive Disorder, Psilocybin 25mg, PEX010(25), Music-centered psilocybin-assisted therapy, Mindfulness-centered psilocybin-assisted therapy, NOT_YET_RECRUITING


authors: Keith Heinzerling
journal: ClinicalTrials.gov
publication_date: 2023-01-16
source_url: https://clinicaltrials.gov/study/NCT04410913
substance_tags: psilocybin
topic_tags: Anxiety,Addiction,Mystical Experience,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":"NCT04410913","overall_status":"ACTIVE_NOT_RECRUITING","phase":["PHASE2"]}
title:
Pilot Trial of Visual Healing®, a Nature-themed Virtual Immersive Experience, to Optimize Set and Setting in Psilocybin-assisted Therapy for Alcohol Use Disorder

abstract:
Twenty participants, age 18 or older, who meet Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for moderate to severe Alcohol Use Disorder will be randomized to open-label psilocybin (25 mg) therapy with the Visual Healing Set and Setting platform (N=10) versus psilocybin (25 mg) with a standard Set and Setting platform (N=10). The purpose of this study is to evaluate the feasibility, safety, and tolerability of adding Visual Healing, a nature-themed virtual immersive program, to psilocybin-assisted therapy among participants with alcohol use disorder. The objective of the study is to test a strategy for optimizing Set and Setting for psilocybin-assisted therapy of alcohol use disorder. Psilocybin shows promise in early trials for alcohol use disorder, but initial results suggest that patients with alcohol use disorder may be less likely to achieve a mystical experience with standard doses of psilocybin. Optimizing Set and Setting for the psilocybin experience may improve outcomes without requiring higher drug doses. The current study will complete a pilot randomized clinical trial to assess the feasibility, safety, and tolerability of Visual Healing Set and Setting (N=10) versus standard Set and Setting procedures (N=10) in participants with alcohol use disorder undergoing open-label psilocybin 25 mg therapy. In the Visual Healing condition, participants will view nature-themed video programs during the Prep session and during the Ascent phase of the psilocybin experience. Anecdotal reports and reviews suggest that viewing Visual Healing creates a tranquil and calming environment that fosters a stronger connection between the viewer and nature. Psilocybin increases the users feeling of connection to nature and having an intention to connect with nature during the psychedelic session is associated with better outcomes of psychedelic-assisted therapy in initial studies. Reducing pre-dosing anxiety/apprehension and enhancing connections to nature with Visual Healing may improve outcomes of psychedelic-assisted therapy without the need for higher psilocybin doses.

keywords:
Alcohol Use Disorder, Psilocybin plus Visual Healing Set and Setting, Psilocybin plus Standard Set and Setting, ACTIVE_NOT_RECRUITING


title: Safety and Efficacy of Psilocybin for the Treatment of Headache Disorders: Sub-Study I
authors: Yale University
journal: ClinicalTrials.gov
publication_date: 2023-10-11
source_url: https://clinicaltrials.gov/study/NCT03341689
keywords: Migraine Headache, High Dose Psilocybin, Low Dose Psilocybin, Placebo, COMPLETED
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":"NCT03341689","overall_status":"COMPLETED","phase":["PHASE1"]}
abstract:
The purpose of this study is to investigate the effects of oral psilocybin in migraine headache. Subjects will each receive a dose of placebo and a dose of psilocybin approximately 14 days apart. Subjects will be randomized to the order of treatment and they will be randomized to receive either low or high dose psilocybin. Subjects will maintain a headache diary prior to, during, and after the treatments in order to document headache frequency and intensity, as well as associated symptoms. This preliminary study will inform on the basic effects of psilocybin in migraine headache and inform on the design of larger, more definitive studies. The number of arms reflects the design of the enhanced blinding method. The final enrollment number reflects the number of subjects participating in study procedures.


authors: University Medical Center Groningen
journal: ClinicalTrials.gov
publication_date: 2026-05-07
source_url: https://clinicaltrials.gov/study/NCT06782724
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":"NCT06782724","overall_status":"RECRUITING","phase":["PHASE2"]}
title:
The Safety and Efficacy of Psilocybin Therapy Compared to Low-dose Control in Reducing Depressive Symptoms in Patients With COPD, ALS, MS, or APD.

abstract:
The goal of this clinical trial is to evaluate whether psilocybin therapy can effectively treat depression and psychological distress in adult patients with COPD, ALS, MS, or APD who have at least 6 months life expectancy. The main questions it aims to answer are: * Can psilocybin therapy safely reduce depressive symptoms compared to low-dose control? * Will the therapeutic effects be rapid and sustained over a 6-month period? Researchers will compare patients receiving two escalating doses of psilocybin (15mg followed by 25mg) against those receiving two low doses (1mg) to see if the higher doses lead to greater improvements in depression, anxiety, demoralization, and quality of life. Participants will: * Attend three preparation sessions with psychotherapists (1-2 hours each) * Undergo two supervised psilocybin dosing sessions (6-8 hours each) * Complete five integration therapy sessions following the dosing sessions * Participate in follow-up assessments at 6 weeks, 3 months, and 6 months * Have access to a digital care platform and peer support groups during the 6-month follow-up period * Optional: Control group participants may receive one high-dose psilocybin session (25mg) after the initial study period Rationale Patients with chronic obstructive pulmonary disorder (COPD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), or atypical and advanced Parkinsonian disorder (APD) often suffer from severe psychological distress with demoralization and death anxiety, which may culminate in to depressive disorder. Treatments of depression in palliative care currently involves psychotherapy and/or the use of antidepressants. However, these treatments have shown limited efficacy which urgently calls for new and innovative approaches. In recent years, a number of studies have shown very promising results of psilocybin therapy in alleviating psychological distress in patients with advanced cancer. The current study (PsyPal) aims to evaluate whether psilocybin therapy can also lead to rapid and sustained decreases in depressive symptoms, demoralization and other facets of psychological distress in patients who suffer from COPD, ALS, MS and APD. Objective The primary objective of the PsyPal study is to assess the safety and efficacy of psilocybin therapy compared to low-dose control in reducing depressive symptoms in patients with COPD, ALS, MS, or APD. Secondary objectives of PsyPal are to assess change in clinical functioning, end-of-life anxiety, psychological/existential distress, health-related quality of life, and how it impacts caregiver 's health- and economic burden. The safety objective of PsyPal is to evaluate the difference in adverse events between high and low dose groups before, during and after the dosing session. Exploratory objectives include the investigation of psychological mechanism, subjective effects, biomarkers (EEG and blood-based), cost-effectiveness, and the usefulness of a digital care platform, with a mixed methods approach. Main trial endpoints The main trial endpoint for PsyPal is the change in depression severity from baseline to 6 weeks after the second dose of psilocybin (high dose session). Adverse events and change in depression symptoms will also be assessed at 3- and 6-month follow-up to determine the safety and sustained effects of psilocybin therapy. Secondary trial endpoints Secondary trial endpoints will be assessed at baseline and 6 weeks after the second dose of psilocybin. These include response rate, anxiety, demoralization, health-related quality of life, experiential avoidance, coping with illness, death anxiety, the wish to hasten death, self-compassion, spirituality, attachment, pain, healthcare resource use, blood-based biomarkers, and functional brain changes. Some secondary endpoints will also be assessed at the 3- and 6-month follow-up, including anxiety, demoralization, health-related quality of life, experiential avoidance, and coping with illness. These endpoints aim to improve our understanding of the effects of psilocybin therapy, how psilocybin therapy works, and to see which patients show the best response. Finally, changes in (religious/spiritual) beliefs/understandings and the experience(s) with psilocybin therapy will be assessed through in-depth qualitative interviews with patients that are conducted 6 weeks after the second dose of psilocybin. Trial design PsyPal trial consists of a double-blind randomized low-dose controlled clinical trial with long term follow-up. Patients who are enrolled in the trial will be actively participating for ten weeks. After the primary endpoint, patients who received a low dose of psilocybin (1 mg) will be offered an optional single open label high-dose of psilocybin (25mg) together with three integration sessions. During long-term follow-up, patients will have access to a digital care platform and peer support groups. Trial population The trial population in PsyPal consists of patients with COPD, ALS, MS, or APD and co-morbid depression. The main further inclusion criteria for participation are an age of 18 or higher, having an identified caregiver or support person, and a life expectancy of at least 6 months. The main exclusion criteria are current use of antipsychotic drugs, suicidal ideations, schizophrenia or other psychotic disorders, bipolar I/II disorder, other major neurological conditions, cardiovascular conditions, diabetes, and/or moderate to severe hepatic impairment (i.e., liver failure). Other exclusion criteria are a first-degree relative on the schizophrenia spectrum, other psychotic disorders, or bipolar I disorder. Interventions Patients will receive psilocybin therapy consisting of three phases; 1) preparation, 2) dosing, and 3) integration: Preparation - The preparation phase consists of three psychotherapy sessions of 1-2 hours each. The purpose of these sessions is threefold: to build a therapeutic alliance between the patient and the therapist, to make a psychotherapeutic treatment plan for the patient using a process-based approach, and to educate patients about psilocybin's acute effects and how patients and therapists together can handle difficult experiences during the dosing sessions. Dosing - The dosing phase of PsyPal starts 1-3 days after the last preparation session. It consists of two escalating dosing sessions of 6-8 hours each. The patient first receives a moderate dose of psilocybin (15mg). Two weeks later, the patient receives a high dose of psilocybin (25mg). Patients in the control group will receive two doses of psilocybin (1mg). All dosing sessions take place under supervision of two trained therapists within a treatment room specifically designed for psilocybin therapy and with a medical doctor on call. Integration - The integration phase consists of five psychotherapeutic sessions of 1-2 hours each. There are two integration sessions following the first dosing session and three integration sessions following the second dosing session. The integration sessions are intended for further psychotherapeutic work, including working with the experience(s) that may have emerged during dosing sessions, and clinical assessment of the patient. Central topics may include the relationship with their life-limiting illness, death, meaning, sense of purpose, personal (religious/spiritual) beliefs, (social) relationships, and conflict resolution. The patient can also share thoughts and feelings about the PsyPal trial. Long-term follow-up After the intervention, patients will be returned to regular care and followed for a period of 6 months, tracking usage of healthcare resources, the digital care platform, and peer support groups. Qualitative aspects of the intervention will be evaluated for patients, caregivers and therapists. Long-term safety data of psilocybin therapy will be collected for the four patient populations.

keywords:
COPD (Chronic Obstructive Pulmonary Disease), ALS (Amyotrophic Lateral Sclerosis), MS (Multiple Sclerosis), Major Depressive Disorder (MDD), Atypical Parkinson Disease, Psilocybin therapy, RECRUITING

topic_tags:
Depression,Anxiety,End-of-Life Distress,Chronic Pain,Brain Imaging,Biomarkers,Spirituality,Clinical Trial,Safety,Adverse Events


authors: Khyber Medical University Peshawar
journal: ClinicalTrials.gov
publication_date: 2025-09-01
source_url: https://clinicaltrials.gov/study/NCT06746441
substance_tags: psilocybin,psilocin
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 11:22:33
raw_json: {"nct_id":"NCT06746441","overall_status":"COMPLETED","phase":["PHASE2"]}
title:
Effect of Psilocybin Only and Psilocybin Assisted Cognitive Behavioral Therapy in the Management of Major Depressive Disorder and Associated Metabolic, Immune, Inflammatory, Neuroplasticity and Electrical Activity Markers: a Randomized Controlled Trial

abstract:
This randomized controlled clinical trial evaluates the effectiveness of psilocybin and psilocybin-assisted cognitive behavioral therapy (CBT) in the management of Major Depressive Disorder (MDD). The study aims to compare the effects of psilocybin-only therapy, CBT, and psilocybin-assisted CBT on depression symptoms, neurochemical markers, inflammatory markers, and neuroplasticity in individuals with MDD. Participants will continue their routine depression medications and will be assessed for changes in depression scores, biochemical markers, and brain activity patterns using validated tools and tests. This single-masked randomized controlled trial investigates novel therapeutic interventions for Major Depressive Disorder (MDD). MDD is a leading cause of disability worldwide, with a significant proportion of patients being treatment-resistant or showing only partial response to conventional antidepressants. Emerging evidence suggests that psilocybin, a serotonergic psychedelic, has potential as a rapid-acting antidepressant. The study will recruit 60 participants meeting DSM-V criteria for MDD, randomized into four groups: Control group (Conventional therapy only), Psilocybin therapy group, Cognitive Behavioral Therapy (CBT) group, and Psilocybin-assisted CBT group. Participants will receive interventions over 10 weeks, with psilocybin administered in two heroic doses six weeks apart, and CBT delivered in 8-10 structured sessions. Biochemical and neurochemical markers such as CD4/CD8 ratio, TNF-α, IL-6, BDNF, and oxytocin will be measured, along with inflammatory markers (resistin and visfatin). Depression scores will be assessed using scales like HAM-D, MADRS, and BDI. EEG recordings will evaluate changes in brain activity pre- and post-intervention. The primary objective is to assess improvements in depression symptoms, while secondary objectives include evaluating changes in immune, inflammatory, and neurochemical markers and EEG activity. Data will be analyzed using ANOVA with Tukey's post-hoc tests to determine statistical significance.

keywords:
Major Depressive Disorder, Psilocybin, Psilocin (the active form of psilocybin metabolized in the body), Cognitive Behavioral Therapy (CBT), COMPLETED

topic_tags:
Depression,Neuroplasticity,Brain Imaging,Biomarkers,Clinical Trial,Randomized Controlled Trial,Inflammation,Immune Function


title: Psilocybin-assisted Psychotherapy in the Management of Anxiety Associated With Stage IV Melanoma.
authors: Multidisciplinary Association for Psychedelic Studies
journal: ClinicalTrials.gov
publication_date: 2023-12-25
source_url: https://clinicaltrials.gov/study/NCT00979693
keywords: Anxiety, Stage IV Melanoma, psilocybin, WITHDRAWN
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Aging,Spirituality,Mystical Experience,Safety,Immune Function
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":"NCT00979693","overall_status":"WITHDRAWN","phase":["PHASE2"]}
abstract:
This study is to find out about whether two sessions of psilocybin-assisted psychotherapy are safe and will help people who are anxious as a result of having stage IV melanoma and will involve two sessions of psychotherapy combined with either 4 or 25 mg psilocybin. The study will measure anxiety, depression, quality of life and spirituality before and after psilocybin-assisted psychotherapy, natural killer cells (a type of immune cell) will be counted from blood samples taken the day after psilocybin-assisted psychotherapy, and people will keep daily diaries reporting on how anxious they feel for each day in the study. Melanoma is a cancer arising from pigment-producing cells, or melanocytes. These cells are chiefly located in the skin, but they can also be found in other parts of the body, including eyes, ears and GI tract. A diagnosis of stage IV melanoma can create great stress and anxiety for an individual and his or her caregivers. Psilocybin (4-phosphoryloxy- N,N-dimethyl-tryptamine) is a psychedelic (hallucinogenic) compound found in certain species of mushrooms that can produce spiritual or mystical experiences and that has been used in psychotherapy prior to being made illegal. This study will be a randomized, active-placebo controlled pilot study of the safety and efficacy of psilocybin-assisted psychotherapy as a means of managing anxiety in association with stage IV melanoma. This study will examine whether two sessions of psilocybin-assisted psychotherapy scheduled seen to 14 days apart will reduce anxiety, improve quality of life and be safe in people with stage IV melanoma. Subjects in this study will have a 66% chance of receiving the full dose of 25 mg psilocybin and a 33% of receiving 4 mg psilocybin. The first dose is expected to change how people feel, think and see the world, while the lower dose is expected to have only slight effects. Each subject will receive these conditions at random, as if by coin-toss. The researchers, including the therapists, and the subject will not know whether they are assigned to get 25 or 4 mg psilocybin. The entire study can last up to three and a half months (14 weeks) but the main part of the study lasts six weeks. After the researchers determine that a person with stage IV melanoma and anxiety can be in the study, there will be two introductory psychotherapy sessions with the therapist-investigators. They will prepare the participant for psilocybin-assisted psychotherapy. The subject will have a day-long psilocybin-assisted psychotherapy session after introductory sessions, and he or she will remain overnight at the clinic. There will be a psychotherapy follow-up scheduled the day after each psilocybin-assisted session to help people work with the psilocybin-assisted psychotherapy, and there will be a psychotherapy session in between the first and second psilocybin-assisted psychotherapy sessions. Two weeks after the second psilocybin-assisted psychotherapy session, subjects will return for another follow-up visit. The subjects will answer questions or fill out questionnaires about anxiety, depression, quality of life, spirituality and sense of self at the start of the study, two weeks after the second psilocybin-assisted session and at least once during the study. Subjects will have blood draws to assess liver function before each psilocybin-assisted session and they will have a blood draw to assess natural killer (NK) cells the day after each psilocybin-assisted session. On the day after each psilocybin-assisted session, subjects will also complete a questionnaire about their experiences during the psilocybin-assisted session. Two weeks after the second experimental psilocybin-assisted session, subjects will learn if they got the full or active placebo dose of psilocybin. Any of the three subjects who receive the active placebo dose can take part in an "open-label" study phase that will last another six weeks. The open-label phase will be nearly identical to those used in the first study phase except that there will be one, and not two, introductory psychotherapy sessions, and the subject and therapists will know that the subject will be receiving 25 mg psilocybin. People who got the full dose of 25 mg psilocybin will not take part in the open-label study phase. If they are well enough to do so, subjects who received the full dose of psilocybin will have anxiety, depression, quality of life and spirituality measured again two months after the second experimental session. Subjects who received active placebo psilocybin will have anxiety, depression, quality of life and spirituality measured two months after the second open-label psilocybin-assisted session.


authors: University of Zurich
journal: ClinicalTrials.gov
publication_date: 2023-09-20
source_url: https://clinicaltrials.gov/study/NCT04141501
keywords: Alcohol Use Disorder, Psilocybin, Placebo oral capsule, COMPLETED
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":"NCT04141501","overall_status":"COMPLETED","phase":["PHASE2"]}
title:
Phase II, Randomized, Double Blind, Placebo Controlled, Parallel Group, Single Center Study of Psilocybin Efficacy and Mechanism in Alcohol Use Disorder

abstract:
Effects of serotonin 2A/1A receptor stimulation by psilocybin on alcohol addicted patients: a randomized double-blind placebo-controlled study Two billion people globally consume alcohol, leading in 2016 to 2.8 million deaths (5.2% of all deaths) and 99.2 million Disability Adjusted Life Years (DALYs) lost (4.2% of all DALYs). Of all the diseases, conditions, and injuries attributable to alcohol use, alcohol use disorders (AUDs) create the largest health burden globally. However, approved pharmacological treatments for alcoholism are limited in their effectiveness. A recent proof of- concept study testing psilocybin in ten alcohol dependent patients provides encouraging efficacy results and safety data. The investigators, therefore, propose to test the efficacy of psilocybin for treating alcohol use disorder and study its underlying neurobiological mechanisms in a randomized, placebo controlled, double blind study. To evaluate effects of psilocybin on alcohol use behaviour, clinical symptoms, neurocognitive and emotional measures in patients with alcohol use disorder. The present clinical trial aims at investigation the clinical and mechanistic effects of Psilocybin in Alcohol Addicted Patients. Patients with alcohol use disorder who have undergone withdrawal treatment within the last 6 weeks will be investigated in a single-centre, double-blind, placebo-controlled, parallel-group design clinical trial contrasting the acute and persisting effects of psilocybin to those of placebo. Patients will be randomly assigned to psilocybin or placebo group with a 1:1 allocation ratio. The study comprises a total of 6 visits during 6 weeks and two follow-up online surveys (3 and 6 months after treatment). In addition, two follow-up surveys that can be completed from home will guarantee monitoring of long-lasting changes in symptomology and ensure all potential side-effects can be captured. On the treatment visit, a single dose of psilocybin (25mg) or placebo will be administered. Patients will be monitored until all effects have worn off.

topic_tags:
Addiction,Mechanism of Action,Receptor Pharmacology,Aging,Emotional Processing,Clinical Trial,Observational Study,Safety


title: Low-Dose Psilocybin Therapy for Palliative Care Patients With Chronic Cancer Pain Requiring Opioids
authors: Roswell Park Cancer Institute
journal: ClinicalTrials.gov
publication_date: 2026-06-21
source_url: https://clinicaltrials.gov/study/NCT06827054
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":"NCT06827054","overall_status":"NOT_YET_RECRUITING","phase":["PHASE2"]}
abstract:
This phase II trial studies whether psilocybin with psychotherapy is safe and if it works for improving chronic pain in cancer patients who require opioids to manage their pain. Psilocybin is taken from the mushroom Psilocybe mexicana. Psilocybin acts on the brain to cause hallucinations (sights, sounds, smells, tastes, or touches that a person believes to be real but are not real). This may impact a patient's "total pain", a view that accounts for the psychological, spiritual, and social factors that contribute to their experience of pain. Psychotherapy uses methods such as discussion, listening, and counseling to help patients change the way they react to environmental triggers that may cause a negative reaction. Giving psilocybin with psychotherapy may be safe and helpful for improving chronic pain in cancer patients who require opioids to manage their pain. PRIMARY OBJECTIVE: I. To evaluate the safety, tolerability, and feasibility of low dose psilocybin therapy in patients with chronic cancer pain who require opioids. SECONDARY OBJECTIVE: I. To obtain preliminary evidence for efficacy of low dose psilocybin therapy in reducing pain and opioid requirement in participants with chronic cancer pain. EXPLORATORY OBJECTIVES: I. To evaluate potential mechanisms of action for psilocybin in pain control, including its effects on resting brain network activity, inflammation, and psychological changes processes. II. To obtain preliminary evidence for efficacy of psilocybin therapy on additional outcomes related to pain control, physical function, and opioid requirement in participants with chronic cancer pain. III. To obtain preliminary evidence for efficacy of low dose psilocybin therapy in alleviating psychological symptoms associated with chronic cancer pain. IV. To evaluate potential mechanisms of action for low dose psilocybin therapy in pain control, including its effects on the following: resting brain network activity, inflammation, psychological processes and psychedelic effects. OUTLINE: Patients attend two preparatory psychotherapy sessions. Patients then receive psilocybin orally (PO) twice a week (BIW) for 4 weeks (8 doses total) in the absence of unacceptable toxicity and attend three integration psychotherapy sessions over 1.5 hours each during psilocybin dosing sessions 2, 4, and 6. Patients may optionally attend additional psychotherapy sessions as needed during follow-up. Additionally, patients undergo functional magnetic resonance imaging (fMRI) and collection of blood and urine samples throughout the study. After completion of study intervention, patients are followed up at days 28-34, 56, and 84.

keywords:
Hematopoietic and Lymphatic System Neoplasm, Malignant Solid Neoplasm, Biospecimen Collection, Biological Sample Collection, Biospecimen Collected, Specimen Collection, Functional Magnetic Resonance Imaging, fMRI, Functional MRI, Interview, Psilocybine, CY-39, Indocybin, Psilocybin, Psychotherapy, talk therapy, Questionnaire Administration, NOT_YET_RECRUITING

topic_tags:
Addiction,End-of-Life Distress,Chronic Pain,Brain Imaging,Mechanism of Action,Aging,Spirituality,Clinical Trial,Cancer Patients,Safety,Toxicity,Inflammation


authors: Centre Hospitalier St Anne
journal: ClinicalTrials.gov
publication_date: 2025-10-06
source_url: https://clinicaltrials.gov/study/NCT07210112
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 11:22:33
raw_json: {"nct_id":"NCT07210112","overall_status":"NOT_YET_RECRUITING","phase":["PHASE2"]}
title:
Efficacy of Psilocybin and Trazodone Combination in Treatment-resistant Depression: a Randomized Controlled Proof-of-concept Study (PSILOTRAZ)

abstract:
Psilocybin, a serotonin receptor agonist in the brain, significantly and quickly improves depressive symptoms while inducing profound acute subjective effects. The benefit-risk ratio of psilocybin in treatment-resistant depression seems favorable, but needs to be confirmed. Moreover, the role of 5-HT2A receptors, involved in the psychedelic experience, on the therapeutic efficacy of psilocybin is still poorly understood. For example, pre-administration of trazodone, a 5-HT2A antagonist antidepressant, could annihilate the acute subjective effects of psilocybin without altering its beneficial effects (Rosenblat et al., 2023). We intend to test this hypothesis by comparing, in a randomized, double-blind, placebo-controlled study, the effect of two possible doses of trazodone (total or partial occupancy of 5-HT2A receptors) on the benefit/risk ratio of psilocybin. We hypothesize that the therapeutic effects of psilocybin are partially independent of 5-HT2A receptor activation and thus persist even after total or partial neutralization of its acute subjective effects. Treatment-resistant depression (TRD) is a frequent and potentially severe psychiatric disorder characterized by specific neurocognitive impairments. It has previously been demonstrated that psilocybin, a serotonin receptor agonist in the brain, significantly and quickly improved depressive symptoms while inducing profound acute subjective effects. The benefit-risk ratio of psilocybin in TRD seems favorable, but needs to be confirmed. Moreover, the role of 5-HT2A receptors, involved in the psychedelic experience, on the therapeutic efficacy of psilocybin is still poorly understood. For example, pre-administration of trazodone, a 5-HT2A antagonist antidepressant, could annihilate the acute subjective effects of psilocybin without altering its beneficial effects (Rosenblat et al., 2023). We intend to test this hypothesis in a randomized, double-blind, placebo-controlled phase II, monocentric, 4 parallel-group proof-of-concept study involving 112 adult subjects with a depressive episode who had failed to respond to at least two lines of antidepressant treatment. Patients will be randomized in a 1:1:1:1 ratio to one of the following treatment groups: * Group 1: Psilocybin PEX010 (25 mg) + trazodone placebo (pharmaceutical master preparation prepared according to GPP) * Group 2: Psilocybin PEX010 (25 mg) + trazodone 5 mg * Group 3: Psilocybin PEX010 (25 mg) + trazodone 30 mg * Group 4: PCB2 (Placebo of PEX010 (25)) + trazodone 30 mg Stratification factors: gender (M/F).

keywords:
Depression - Major Depressive Disorder, Treatment-resistant Depression (TRD), Psilocybin 25 mg per os, Trazodone 5mg, Trazodone 30 mg, Placebo of psilocybin, Placebo of trazodone, NOT_YET_RECRUITING

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


title: A Phase 2a Study of Group Retreat Psilocybin Therapy for Cancer-Related Anxiety and Depression
authors: University of Washington
journal: ClinicalTrials.gov
publication_date: 2026-05-28
source_url: https://clinicaltrials.gov/study/NCT07336238
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Clinical Trial,Observational Study,Cancer Patients,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":"NCT07336238","overall_status":"RECRUITING","phase":["PHASE2"]}
abstract:
This phase II trial tests the safety, side effects and how well group retreat psilocybin therapy works for the treatment of anxiety and depression in patients with solid tumors that have spread from where they first started (primary site) to other places in the body (metastatic) or with hematologic cancers for which no treatment is currently available (incurable). For patients with metastatic, incurable cancer, unrelieved anxiety and existential distress can cause profound suffering. Psilocybin therapy can relieve anxiety and existential distress by disrupting patterns of thinking that contribute to anxiety and depression. Psilocybin is a substance being studied in the treatment of anxiety or depression in patients with cancer. In this study, a pharmaceutical grade of psilocybin will be used that has been approved by the FDA for research, provided by Filament Health. Psilocybin acts on the brain by resetting the brain's activity and increasing connections between brain regions, particularly those involved in mood regulation and self-perception. In this study psilocybin is combined with structured discussions and reflections that enable patients to have new insights about their situation. In a prior study, group retreat psilocybin therapy was proven to be safe and this study tests a refined dosing regimen for symptoms of anxiety and depression in patients with metastatic solid tumors or incurable hematologic malignancies. OUTLINE: Patients attend group preparation therapy sessions on days -14 (virtual), -7 (virtual) and -1 (in person), and also attend an individual preparation therapy session on day -1 (in person). Patients receive psilocybin orally (PO) on day 0. Patients may receive an additional "booster" dose 60-90 minutes after the initial dose based on their subjective report combined with the physician's clinical judgement. Patients attend group integration therapy sessions on days 1 (in person), 8 (virtual), 15 (virtual), and 22 (virtual), and attend individual integration therapy sessions on days 1 (in person) and 8 (virtual). After completion of study treatment, patients are followed up at 2 weeks and at 1, 2, 3, and 6 months.

keywords:
Anxiety, Depression, Hematopoietic and Lymphatic System Neoplasm, Metastatic Malignant Solid Neoplasm, Psychotherapy, therapy, talk therapy, Psilocybin, psilocybine, Survey Administration, RECRUITING


authors: Usona Institute
journal: ClinicalTrials.gov
publication_date: 2026-05-03
source_url: https://clinicaltrials.gov/study/NCT04353921
keywords: Major Depressive Disorder, No intervention will be administered as part of this study., TERMINATED
substance_tags: psilocybin
topic_tags: Depression,Clinical Trial,Observational Study
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":"NCT04353921","overall_status":"TERMINATED","phase":[]}
title:
A One-Year Observational Follow-up Study of Participants With Major Depressive Disorder Following a Randomized, Double-Blind Single-Dose of Psilocybin or Niacin-Control

abstract:
This is a Phase 2 double-blind, long-term observational follow-up study of participants from Study PSIL201. Participants providing informed consent were enrolled into this study and completed web surveys and telephone interviews conducted by one central site at the following time intervals: months 3 and 6 (± 7 days for each assessment) and months 10 and 12 (± 14 days for each assessment).


authors: Section for Affective Disorders; Northern Stockholm Psychiatry
journal: ClinicalTrials.gov
publication_date: 2026-04-12
source_url: https://clinicaltrials.gov/study/NCT06319378
keywords: MDD, psilocybin 25 mg sod, psilocybin 1 mg sod, RECRUITING
substance_tags: psilocybin
topic_tags: Depression,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":"NCT06319378","overall_status":"RECRUITING","phase":["PHASE2"]}
title:
CAPSI - Cancer Related Major Depression Treated With a Single Dose of Psilocybin: A Multicenter Randomized Placebo Controlled Double Blind Clinical Trial

abstract:
The goal of this randomized placebo controlled trial is to compare the antidepressant effect of a single oral dose of psilocybin 25 mg compared to 1 mg in 100 patients with cancer related major depressive disorder. The main question it aims to answer is: 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 (psilocybin 1 mg) assessed as the difference between groups in changes in depressive symptoms, in the following Population: 20-80 (inclusive) years old, current depressive episode (according to Patient Health Questionnaire (PHQ-9) ≥10), \>1 month after cancer diagnosis, with at least 12 months of life expectancy, willingness to abstain from other psychotherapeutic or antidepressant treatments during the study (wash out time 5 half-lives).


title: Effects of Psilocybin on Behavior, Psychology and Brain Function in Long-term Meditators
authors: Johns Hopkins University
journal: ClinicalTrials.gov
publication_date: 2019-12-29
source_url: https://clinicaltrials.gov/study/NCT02145091
substance_tags: psilocybin
topic_tags: Brain Imaging,Pharmacology,Aging,Wellbeing,Spirituality
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":"NCT02145091","overall_status":"COMPLETED","phase":["PHASE1"]}
abstract:
This is a double-blind placebo-controlled study investigating the acute and persisting effects of psilocybin on meditation, spirituality, health, well-being, prosocial attitudes, and brain functioning. This study will use questionnaires and functional magnetic resonance imaging (fMRI) to examine the acute and persisting effects of psilocybin on brain function, meditation, spirituality, and psychology. The majority of the study procedures -- including screening, preparatory meetings, placebo and psilocybin sessions, and a large battery of behavioral and psychological measures -- will be conducted at the investigator's laboratory at the Behavioral Pharmacology Research Unit (BPRU) on the Johns Hopkins Bayview campus. The brain imaging procedures will be conducted at F.M. Kirby Research Center at the Kennedy Krieger Institute (KKI).

keywords:
Healthy, Moderately-high dose of psilocybin, O-phosphoryl-4-hydroxy-N,N-dimethyltryptamine, Moderately-low dose of psilocybin, Very-low dose of psilocybin, Placebo, Lactose, COMPLETED


title: Psilocybin-facilitated Treatment for Cocaine Use
authors: University of Alabama at Birmingham
journal: ClinicalTrials.gov
publication_date: 2026-05-17
source_url: https://clinicaltrials.gov/study/NCT02037126
keywords: Cocaine-Related Disorders, Psilocybin, psychedelic compound, Diphenhydramine, Benadryl, COMPLETED
substance_tags: psilocybin
topic_tags: Anxiety,Addiction,Brain Imaging,Mechanism of Action,Default Mode Network,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":"NCT02037126","overall_status":"COMPLETED","phase":["PHASE2"]}
abstract:
The primary purpose of this study is to evaluate the feasibility and estimate the efficacy of psilocybin-facilitated treatment for cocaine use. We also will monitor the impact of psilocybin-facilitated treatment on the use of other drugs and outcomes relevant to cocaine involvement. MRI assessment is a unique aspect of this study. As a potential biological mechanism of psilocybin's effect includes changes in default mode network functional connectivity (Carhart-Harris et al., 2012), we will determine if psilocybin's therapeutic effects are mediated by such changes. Moreover, as Glx (a brain metabolite that reflects glutamate) abnormalities have been shown to play a role in cocaine addiction, we will determine if psilocybin impacts Glx in the anterior cingulate cortex and hippocampus. Individuals who are eligible to participate and provide informed consent will complete baseline questionnaires and be randomly assigned in a double-blind manner to the Psilocybin or Active Placebo group. The first MRI assessment will take place shortly thereafter using a 3T head-only Magnetic Resonance Imaging and Spectroscopy scanner (Magnetom Allegra, Siemens medial Solutions, Malvern, PA), optimized for neuroimaging applications. Preparation sessions (see below) and the drug administration session will take place in a room at the Clinical Research Unit designed to be as comfortable, aesthetically pleasing (i.e., living-room like), and safe (e.g., no furniture with sharp corners or glass objects) as possible, with a directly adjacent, private restroom. All participants will undergo four weekly preparation sessions of approximately 2 hours each. The purpose of these sessions is to: 1) develop strong therapeutic alliance between the participants and the primary therapist (Dr. Hendricks) and secondary therapist; 2) establish comfort and rapport between participants and the remainder of the research team; 3) discuss participants' aspirations with regard to their drug administration experience (e.g., What do participants hope to gain from their experience?); 4) discuss the treatment rationale and putative mechanisms of action of psilocybin; 5) obtain a detailed personal history of the participant, with a focus on those factors contributing to their current difficulties; 6) prepare participants for drug administration, including a detailed account of all potential effects of the drug; 7) discuss all aspects of the drug administration protocol (i.e., logistics and procedures), including plans of action in the event that participants experience acute distress; and 8) administer cognitive-behavioral treatment for cocaine use. Any participant who demonstrates significant anxiety, discomfort, or unease regarding drug administration at the conclusion of the four preparation sessions will be provided up to two additional preparation sessions. If these sessions are unsuccessful at mitigating the participant's anxiety, discomfort, or unease, the participant will be removed from the study. Approximately one week after their 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 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 primary and secondary therapists will be present with participants throughout this session (at least one individual will always be present with the participant, even during brief intervals when one of the two therapists may be using the restroom). During this time, participants will be encouraged to lie down, use an eye mask to block external visual distraction, and use headphones through which a supportive music program will be played. Participants will be instructed to focus their attention on their inner experiences throughout the session. Any participant reporting significant distress will be provided reassurance verbally or physically (e.g., with a supportive touch to the hand or shoulder). In the event that psychological distress is insufficiently managed with reassurance alone, medication will be administered under the guidance of the study physician. Blood pressure will be assessed at regular intervals via automatic blood pressure monitor (e.g., pre-administration, and at 30, 60, 90, 120, 180, 240, 300, and 360 minutes post-administration), and medication for the treatment of acute hypertension will be administered should blood pressure remain elevated at \>200 systolic or \>110 diastolic. Seven 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 (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 primary therapist's pager number should they feel the need for support that evening. Within 2 days after the drug administration session, participants will meet with the therapists for approximately 1 hour to discuss and reflect on their experience. The therapists will assess for potential adverse effects at this time. The second MRI session will take place shortly thereafter. Participants will then meet with the guide once per week over the next 4 weeks with an emphasis on integration of their medication session experience in the context of achieving abstinence from cocaine; continued cognitive-behavioral treatment for cocaine use will be provided during these follow-up meetings. Long-term assessment visits will take place 3 and 6 months after the final therapy meeting. A battery of measures will be delivered at these times. At the conclusion of the 6-month assessment meeting, participants will be debriefed.


authors: The University of Texas Health Science Center, Houston
journal: ClinicalTrials.gov
publication_date: 2025-07-17
source_url: https://clinicaltrials.gov/study/NCT06706232
keywords: Bipolar II Disorder, Depression, Bipolar, Suicidality, Psilocybin, Therapeutic Support, RECRUITING
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 11:04:28
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT06706232","overall_status":"RECRUITING","phase":["PHASE2"]}
title:
Acceptability & Safety of Two Sequential Doses of Psilocybin in Bipolar Disorder II Depression and Suicidality

abstract:
The purpose of the study is to assess the safety and acceptability of up to two sequential administrations of 25 mg psilocybin with additional therapeutic support in decreasing suicidality in patients with Bipolar Disorder (BD II) depression. This study aims to determine whether psilocybin paired with psychotherapy is a safe, feasible, and acceptable treatment for Bipolar II (BD II) depression, specifically, individuals experiencing suicidal ideation (without having an active plan or intention to act). The design is a non-randomized clinical trial, where patients will receive up to 2 doses of 25mg psilocybin in the context of psychological support informed by mindfulness-based CBT and typical elements of psychedelic treatments (e.g., preparation, intention setting, integration). The investigators will measure suicidality, depression, and acute experiences using validated questionnaires at multiple time points in the study. If this study shows psilocybin to be a feasible, acceptable, and safe treatment option, this would have huge implications for improving outcomes because highly effective treatment for suicidality in patients with Bipolar Disorder is still lacking.


authors: Centre for Addiction and Mental Health
journal: ClinicalTrials.gov
publication_date: 2026-03-19
source_url: https://clinicaltrials.gov/study/NCT06731621
substance_tags: psilocybin
topic_tags: Depression,Consciousness,Clinical Trial,Treatment-Resistant Depression,Safety
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:28
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT06731621","overall_status":"RECRUITING","phase":["PHASE1"]}
title:
Psilocybin for Treatment-Resistant Depression in Autism: a Pilot Trial With Pre-Post Brain and Cognitive Measurement to Understand Mechanism

abstract:
We propose a first-of-its-kind open-label clinical trial to investigate the feasibility, tolerability, and safety of administering psilocybin in autistic adults with treatment-resistant depression (TRD). In this study, 20 participants (intellectually able and fluent-speech adults) with autism and co-occurring TRD will receive around 20 hours of manualized psychotherapy that has previously been used with psilocybin (Agin-Liebes et al., 2020). They will also receive psilocybin at 2 different time points, firstly a safety dose of 10mg, followed by a treatment dose of 25mg. This study design is in accordance with previous studies investigating the use of psilocybin with psilocybin-assisted therapy (PAT) to treat TRD (Carhart-Harris et al., 2016, 2018) Each participant will begin with a screening visit (V1), during which eligibility will be determined through clinical and psychiatric assessments of the participant's physical and mental health. Following confirmation of eligibility, the study procedures will begin. The participant will begin with a 2-4 week tapering period during which they will taper and discontinue any conventional antidepressants. Most conventional antidepressants will require a minimum 2-week tapering period, with the exception of fluoxetine, which will require a 4-week tapering period. Additional time may be added at the discretion of the study investigator. During the tapering period, there will be weekly check-ins with a study psychiatrist by in-person assessment or brief telephone calls to monitor for worsening depression and suicidality. Following the tapering period, participant eligibility will be re-assessed for the eligibility. At Study Visit 2 (Baseline, V2), participants will complete a series of questionnaires and assessments (Table 2) and preparatory therapy with trained study therapists. The participant will also receive a brain MRI scan lasting for about 45 minutes. At Study Visits 3 \& 4 (V3/V4), participants will receive oral doses of psilocybin (safety dose of 10 mg at V3, treatment dose of 25 mg at V4), to assess the tolerability and efficacy of psilocybin. These sessions will be held one week apart and will last 6 to 8 hours each. These sessions will take place in a pre-decorated treatment room at CAMH. Throughout the entire duration of the dosing sessions, participants will be monitored by a minimum of two trained therapists. At the end of each session, participants will be evaluated for safety by a study psychiatrist before being discharged. Participants will also rate the 11-Dimension Altered States of Consciousness (11D-ASC) at the end of each dosing day when the subjective effects of psilocybin have subsided to a negligible level. In addition, the participant will also receive a second brain MRI scan lasting for about 30 minutes (V3a) following V3 Safety dosing. To reduce participant burden, MRI scan can be completed on the following day or within 1-3 days following safety dosing (V3). The participants will also be required to complete the self-rated questionnaires at this additional MRI assessment. Visit 5 (V5) will be held one day after administration of the treatment dose (V4). During V5 the participants will complete post-treatment clinical and cognitive assessments, alongside the third and final MRI scan (of the main clinical trial design). Participants will also undergo a 1-hour integration therapy session to debrief their experiences the day before. Visit 6 (V6) will be held one week following the treatment dose (V4). During V6 a second 1-hour integration therapy session takes place and all post-treatment clinical assessments will be repeated. Subsequent clinical progress will be evaluated virtually at V7, V8, V9, which will respectively be held 2, 4, and 12 weeks following the treatment session (V4). 10 participants out of 20 participants in the main clinical trial could opt to receive 7 additional brain MRI scans besides the MRI scans at V2, V3a and V5 required in the main clinical trial. These 7 additional scans will be assessed at V1, in the middle of medication washout/tapering period V6, V7, V8, 8 weeks following the treatment dose (V4), and V9, respectively. At each optional MRI visit, self-rated assessments will also be collected.

keywords:
Treatment Resistant Depression, Autism Spectrum Disorder, Psilocybin, Psilocybin-Assisted Therapy, RECRUITING


authors: King's College London
journal: ClinicalTrials.gov
publication_date: 2019-08-12
source_url: https://clinicaltrials.gov/study/NCT03661125
keywords: Parkinson Disease Psychosis, Saracatinib, Placebo Oral Tablet, UNKNOWN
substance_tags: psilocybin
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":"NCT03661125","overall_status":"UNKNOWN","phase":["EARLY_PHASE1"]}
title:
A Randomised, Balanced, Double-blind Two-way Crossover Design Study to Evaluate the Effects of SRC Kinase Inhibitor, Saracatinib, on Brain Activity Associated With Visual Processing in Patients With Parkinson's Disease Psychosis.

abstract:
Parkinson's disease is often characterised by movement symptoms such as rigidity and bradykinesia, however, there are a number of non-motor symptoms that can have a significant impact on quality of life. One of the most common non-motor symptoms of Parkinson's disease is visual hallucinations (where someone sees things that don't exist outside their mind).. Recent findings led to the approval of a drug called Pimavanserin as a treatment for PD psychosis in the USA. Based on other recent studies, we believe that Saracatinib, a drug that interacts within the same system as Pimavanserin, is a potential treatment for PD psychosis. Saracatinib has shown to reduce the intensity of the psychedelic effect induced by psilocybin (a naturally occurring psychedelic found in psilocybe mushrooms) and attenuate social cognition and brain changes in healthy volunteers. The aim of this study is to test the effects of 14 days dosing of saracatinib or placebo on 30 volunteers with PD psychosis. We aim to to use neuroimaging combined with psychopharmacology to provide evidence that a putative new treatment approach can modulate abnormal visual cortex activation in patients with PD psychosis. If positive, this proof of mechanism study would provide a strong platform to pursue symptom modification studies with Saracatinib. Parkinson's disease (PD) is a neurodegenerative condition which has a 1% prevalence in the over 60s and also affects young adults. As well as motor symptoms such as akinesia or rigidity, many patients also experience non-motor symptoms of which psychosis is the most common (Chang and Fox, 2016). Current treatments for Parkinson's disease psychosis include atypical antipsychotics such as quetiapine, clozapine and pimavanserin (a 5-HT2a inverse agonist). Pimavanserin has recently been approved in the USA as a PD psychosis treatment; it has been shown to have an overall effect on reducing hallucinations as a whole, but not on visual hallucinations specifically. Functional neuroimaging evidence confirms dysfunctional ventral visual pathway activity in PD psychosis with altered metabolism, blood flow and brain activation following visual stimulation (Chang and Fox, 2016). Outside of the ventral visual pathways, two imaging studies in PD patients with visual hallucinations have shown altered connectivity within the default mode network, a brain system implicated in many neuropsychiatric conditions, pointing to more widespread abnormalities (Chang and Fox, 2016). Structural imaging studies show some atrophy within the ventral visual pathways, but also implicates brain regions outside of visual processing areas, including parietal, frontal, and cerebellar and hippocampal regions (Ffytche et al., 2017). Moreover, even though the serotoninergic dysfunction underpinning Parkinson's disease psychosis is not fully understood, animal studies with psychedelics have pointed to the dimerisation of the 5-HT2A and mGlu2 receptors and the over recruitment of specific downstream signalling pathways. Src kinase inhibition is a potential mechanism for blocking the hallucinogenic effects of 5-HT2A receptor agonism. Src kinase inhibitor, Saracatinib, has shown to reduce the intensity of the psychedelic effect induced by psilocybin (a naturally occurring psychedelic found in psilocybe mushrooms (Byock, 2018)) and attenuate social cognition and brain changes in healthy volunteers. We will test the effects of Saracatinib on brain activity associated with visual processing using a visual processing task, known to be sensitive to 5-HT2a receptor stimulation in previous studies with psilocybin (Carter et al., 2004), and a visual recognition task (Meppelink et al., 2009) with known sensitivity to PD psychosis, both scanned using the latest implementation of multi-echo blood oxygen level dependent (BOLD) functional Magnetic Resonance Imaging (fMRI). We aim to conduct a double-blind crossover design study, looking at the effects of Saracatinib and placebo treatment on 26 patients who have PD with psychosis. Existing data shows that 10 days of dosing with Saracatinib will achieve a steady state level that is known to be well tolerated in people with Alzheimer's disease (Nygaard et al., 2015). Therefore, participants will be given an oral dose of 100mg of Saracatinib or placebo as two 50mg tablets to be taken once daily for 14 days. Participants will return to the clinic on day 14 for their final dose of Saracatinib or placebo, fMRI and EEG scans, cognitive assessments, physical examination and blood screen. The participants will then move onto the second treatment arm where they will receive a further 14 days of dosing with saracatinib or placebo depending on the group they were in for the first treatment arm. There will be a minimum 2-week washout between treatment arms to avoid potential carry over effects.

topic_tags:
Brain Imaging,Pharmacology,Mechanism of Action,Receptor Pharmacology,Default Mode Network,Aging,Healthy Volunteers


authors: Filament Health Corp.
journal: ClinicalTrials.gov
publication_date: 2024-10-29
source_url: https://clinicaltrials.gov/study/NCT06666010
keywords: Stimulant Use Disorder, PEX010-Assisted Therapy, PEX010(01), NOT_YET_RECRUITING
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 11:04:28
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT06666010","overall_status":"NOT_YET_RECRUITING","phase":["PHASE2"]}
title:
A Registered Clinical Trial of PEX010-Assisted Therapy for Stimulant Use Disorder: A Safety, Feasibility and Efficacy Study

abstract:
The goal of this clinical trial is to learn if PEX010 is effective for the treatment of Stimulant Use Disorder in adults. The study will also assess the safety and feasibility of administering PEX010 to this population. The main questions it aims to answer are: Does PEX010 reduce stimulant use? What medical problems do participants experience when taking PEX010? Researchers will compare an active PEX010 dose containing 25 mg psilocybin to an active placebo arm, to see if PEX010 works to reduce stimulant use. Participants will: Take PEX010 or the active placebo once during the study, engage in cognitive behavioural therapy, and visit the clinic twice weekly for study intervention and follow-up assessments. In this randomized, controlled trial study participants will receive one capsule of PEX010 containing 25 mg or 1 mg of psilocybin, in conjunction with therapy. Following screening and baseline visits, participants will receive 2 preparation sessions, 1 PEX010 dosing session, 1 integration session, and 7 follow-up visits.


title: Effects of Psilocybin on Speech Fluency, Struggle, and Brain Activity in People Who Stutter
authors: NYU Langone Health
journal: ClinicalTrials.gov
publication_date: 2025-12-21
source_url: https://clinicaltrials.gov/study/NCT07296328
keywords: Stuttering, Psilocybin, Speech therapy, NOT_YET_RECRUITING
substance_tags: psilocybin
topic_tags: Mechanism of Action,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":"NCT07296328","overall_status":"NOT_YET_RECRUITING","phase":["PHASE2"]}
abstract:
This Phase 2a clinical trial is an open-label, single-group, within-subjects pilot study designed to evaluate the safety, feasibility, and preliminary efficacy of psilocybin as a therapeutic intervention for adults with developmental stuttering. This pilot study will assess whether further research to explore the potential benefits of psilocybin-assisted therapy for improving clinical outcomes in individuals who stutter, is warranted. The aims of this study include: * Aim 1: Assess the safety and feasibility of psilocybin as a therapeutic agent for stuttering. * Aim 2: Evaluate the effects of psilocybin on objective and subjective measures of stuttering severity, struggle, and well-being. * Aim 3: Explore the therapeutic neural mechanisms of psilocybin in stuttering.


authors: University Hospital, Basel, Switzerland
journal: ClinicalTrials.gov
publication_date: 2025-03-26
source_url: https://clinicaltrials.gov/study/NCT06899334
keywords: Healthy, LSD, Psilocybin, DMT, Placebo, RECRUITING
substance_tags: psilocybin
topic_tags: Pharmacology,Receptor Pharmacology,Consciousness,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":"NCT06899334","overall_status":"RECRUITING","phase":["PHASE1"]}
title:
Direct Comparison of Altered States of Consciousness Induced by LSD, Psilocybin, and DMT in a Randomized, Placebo-controlled, Cross-over Trial in Healthy Participants (LPD-Study)

abstract:
The primary objective of this study is to determine whether equivalent moderately high doses of LSD, psilocybin, and DMT produce qualitatively similar peak effects when the effect duration is standardized with ketanserin. A DMT infusion mimicking oral LSD and psilocybin administrations will be tested, as well as intravenously administered ketanserin. Lysergic acid diethylamide (LSD), psilocybin, and N,N-dimethyltryptamine (DMT) are serotonergic hallucinogens (psychedelics) and currently investigated as therapeutic tools for the treatment of various psychiatric disorders. They are usually administered in a dose range which induces an alteration of consciousness via the stimulation of the serotonin (5-HT)2A receptor. However, there are differences in the receptor activation profiles between the three substances that may induce different subjective effects. Moreover, they exhibit different pharmacokinetic qualities. In comparative studies of LSD and psilocybin blinding was impaired by the different duration of subjective effects. This study aims to ensure blinding by ending all experiences at the same time with the 5HT2A antagonist ketanserin. Moreover, no study has yet directly compared DMT to LSD and psilocybin. The DMT infusion will be modeled in accordance with the course of an oral LSD and psilocybin administration. Therefore, the LPD-study compares the acute and subacute effects of LSD, psilocybin, and DMT while standardizing the time course and the duration of action for all substances.


title: Neurobehavioral Mechanisms of Psilocybin-assisted Treatment for Alcohol Use Disorder
authors: NYU Langone Health
journal: ClinicalTrials.gov
publication_date: 2025-12-18
source_url: https://clinicaltrials.gov/study/NCT06349083
keywords: Alcohol Use Disorder, Psilocybin, Inactive Placebo, Supportive therapy sessions, RECRUITING
substance_tags: psilocybin
topic_tags: Addiction,Brain Imaging,Mechanism of Action,Biomarkers,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":"NCT06349083","overall_status":"RECRUITING","phase":["PHASE2"]}
abstract:
This is a double-blind, randomized, placebo-controlled Phase 2 mechanistic clinical trial designed to evaluate the therapeutic neural mechanisms of psilocybin in patients with alcohol use disorder (AUD), and to determine whether further studies are warranted to study the relationship of any such effects to clinical improvement in AUD symptoms. The primary aims are to evaluate the effects of psilocybin on AUD; measures will include 1) fMRI neural activation and functional connectivity, using a well-validated task to characterize neural and subjective response to negative affective and alcohol visual stimuli; 2) alcohol use data (self-report and blood biomarkers); and 3) self-report measures related the NE, IS, and EF domains.


authors: Healing Advocacy Fund
journal: ClinicalTrials.gov
publication_date: 2025-09-23
source_url: https://clinicaltrials.gov/study/NCT07189988
keywords: Alcohol Use Disorder, psilocybin, ACTIVE_NOT_RECRUITING
substance_tags: psilocybin
topic_tags: Depression,Anxiety,PTSD,Addiction,Wellbeing,Clinical Trial,Observational Study,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":"NCT07189988","overall_status":"ACTIVE_NOT_RECRUITING","phase":[]}
title:
Observational Pilot Study to Explore the Social and Health Impacts of a New Model of Care in Oregon: Psilocybin Services on Alcoholism

abstract:
The purpose for this study is to observe the real world experience of participants who are receiving psilocybin in the context of (alcoholism) Alcohol Use Disorder without intervening in the model of care. The study team will engage directly with the participants to examine the outcomes in participants who have been deemed eligible and appropriate to receive psilocybin services at Oregon's Innertrek Patient Service Center (PSC) and who are willing to participate in the People Science pilot study to share their experience concurrently. Since the participant will be making the informed decision to voluntarily take part in this concurrent observational study, there will be no "doctor-patient" relationship between the participant and the People Science Study Investigator. Study participants will receive the standard of care and medical management from Oregon's Innertrek Patient Service Center facilitators as deemed appropriate per their existing guidelines and practices. People Science will solely be operating as an observer, using an agnostic research data capture system to collect outcomes and follow participant experiences throughout the course of their treatment journey. The study will incorporate participant-reported outcome measures, questionnaires and surveys. The primary endpoint in collecting study data will be to observe the impact of the Psilocybin-Assisted care model on the frequency of heavy drinking days through quantitative and qualitative data analysis for people who struggle with alcohol use. Non-quantitative narratives will also be captured. Throughout the People Science study observations, participants will be in the direct care of the Oregon Patient Service Center facilitators. Findings from this study will contribute knowledge toward the understanding of the use of psilocybin in individuals with self-described alcoholism (AUD). Alcoholism or Alcohol Use Disorder (AUD) is a chronic and relapsing condition characterized by an inability to control alcohol consumption, leading to significant health, social, and economic consequences. Despite the availability of various treatment modalities, including pharmacotherapies and behavioral interventions, relapse rates remain high, with many individuals failing to achieve long-term abstinence or control. This has spurred interest in exploring novel therapeutic approaches and care models, including the potential use of psychedelic compounds such as psilocybin used in a supportive care environment. Psilocybin, a naturally occurring psychoactive substance found in certain species of mushrooms, has garnered attention for its potential therapeutic effects in treating mental health disorders such as depression, anxiety, and post-traumatic stress disorder. More recently, research has suggested that psilocybin may be beneficial in addressing substance use disorders, including Alcohol Use Disorder. The mechanism by which psilocybin exerts its effects appears to involve the modulation of neural circuits related to mood regulation, behavior, and self-reflection, which can facilitate profound psychological experiences that may promote lasting changes in behavior and cognition. Early clinical trials have shown promising results, indicating that psilocybin, when administered in a therapeutic setting, can reduce alcohol consumption and cravings in individuals with Alcohol Use Disorder. In a study published in Journal of American Medical Association of Psychiatry, researchers from New York University Grossman School of Medicine found that heavy alcohol consumption among people with alcohol use disorders was 83 percent lower among participants who had received psilocybin over an 8-month period following the psilocybin administration and almost half of participants who received psilocybin stopped drinking alcohol altogether. These studies highlight the potential for psilocybin to act as a catalyst for psychological insights and behavioral change when combined with psychotherapy or a calming and supportive environment, offering a new avenue for treatment-resistant cases of Alcohol Use Disorder. In Oregon, excessive alcohol consumption causes 2,000 deaths each year, making it the third leading cause of preventable death in the state. There is a glaring need for support for Oregonians facing alcohol and substance use disorders. Alongside more traditional treatment and harm reduction models, Psilocybin shows promise for treating alcohol and substance disorders. Oregon's state-regulated psilocybin program offers an opportunity to advance real world research on Psilocybin for treating alcohol and substance use disorders. In 2020, Oregon voters approved a ballot measure (Measure 109) to create the world's first state-regulated psilocybin program to improve the physical, mental, and social well-being of all people. The measure required that the Oregon Health Authority (OHA) create a licensing and regulatory framework for a safe, accessible and equitable program. After a two-year rule making period, licensed service centers are now open and providing psilocybin services to clients in Oregon. Psilocybin services are only delivered in licensed service centers, under the supervision of a trained facilitator, and psilocybin can only be consumed in the service center during that supervised session. There are no retail sales, no off-site consumption, possession, or production of psilocybin (outside of licensed manufacturers). The sponsor of this pilot research project is the Healing Advocacy Fund (HAF). HAF is a 501c3 non-profit organization that advocates for safe, affordable state-regulated access to psychedelic services. The Healing Advocacy Fund promotes regulations that create a state psilocybin program that is of high quality, accessible, and maximizes safety; educates stakeholders, policymakers, regulators, and the general public on the Oregon psilocybin program; and serves as a convener for the Oregon psilocybin ecosystem to collaboratively address goals and challenges, organize around shared needs, and deliver services to high standards and best practices. InnerTrek will provide the psilocybin services to individuals who struggle with alcohol use for the pilot. InnerTrek is a psilocybin patient service center located in Portland, Oregon and licensed by the Oregon Health Authority to offer both individual and group psilocybin services, including preparation, administration, and integration sessions. The position of the People Science research team in this setting is to observe the practices and experiences already occurring in the context of the State of Oregon's Psilocybin Services program at the InnerTrek Patient Service Center. People Science will create the questionnaires to be offered to the participants, as well as analyze data on the observation of participants' perspectives.


title: The Acute Effects of Psilocybin on Cognition, Memory, and Brain Function
authors: Manoj Doss
journal: ClinicalTrials.gov
publication_date: 2026-06-14
source_url: https://clinicaltrials.gov/study/NCT07079852
keywords: Healthy, Placebo, Psilocybin 15mg, NOT_YET_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 11:04:28
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT07079852","overall_status":"NOT_YET_RECRUITING","phase":["PHASE1","PHASE2"]}
abstract:
This study will test the effects of psilocybin on memory and cognition in healthy participants using computerized tasks and magnetic resonance imaging (MRI). In a double-blind, placebo-controlled, repeated measures design in healthy participants, this study will test the effects of psilocybin on memory and cognition in healthy individuals using computerized tasks and magnetic resonance imaging (MRI). A better understanding of the basic neurocognitive effects of psilocybin may allow for minimizing potential harms and maximizing potential benefits of psilocybin therapy.


title: Psilocybin and Affective Function in Chronic Lower Back Pain Depression
authors: Johns Hopkins University
journal: ClinicalTrials.gov
publication_date: 2025-10-13
source_url: https://clinicaltrials.gov/study/NCT06355414
keywords: Chronic Low-back Pain, Depression, Psilocybin, Methylphenidate, RECRUITING
substance_tags: psilocybin
topic_tags: Depression,Chronic Pain,Mechanism of Action,Observational Study,Safety
study_type: Observational Study
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":"NCT06355414","overall_status":"RECRUITING","phase":["PHASE1"]}
abstract:
This study seeks to provide insight on psilocybin's effects on mechanisms of chronic pain among patients with co-morbid chronic low back pain and depression (CLBP+D). Participants will receive either a single high-dose of psilocybin (25mg absolute dose) or methylphenidate (40mg absolute dose). Participants will be asked to complete assessments of pain, depressive symptoms, and more general questionnaires regarding the participants experiences during the experimental sessions and the associated enduring effects. This study will investigate the effects of a single experimental psilocybin (25 mg fixed dose) administration compared to a dose of methylphenidate (40 mg fixed dose). Assessments will be conducted during screening visits, before and after the drug session, at follow up visits up to 1-month after the drug session, as well as periodically throughout study participation via a multi-time-per-day survey application. Forty participants will complete all study visits including follow-up visits. Primary objectives: 1. Investigate the feasibility, safety, and acceptability of psilocybin for CLBP+D2. Investigate the effect of psilocybin on self-report of positive affect, negative affect, and pain catastrophizing 3. Investigate the effect of psilocybin on a behavioral task called positive affective pain inhibition Secondary objectives: 1. Investigate the durability (1-month follow-up) effects of psilocybin on self-report of positive affect, negative affect, and pain catastrophizing 2. Investigate the effect of psilocybin on dynamic associations between affective measures, pain, and function on a moment-to-moment basis.


authors: Centre for Addiction and Mental Health
journal: ClinicalTrials.gov
publication_date: 2025-04-24
source_url: https://clinicaltrials.gov/study/NCT06518720
keywords: Treatment Resistant Depression, Chronic Pain, Psilocybin 25 mg, PEX010, RECRUITING
substance_tags: psilocybin
topic_tags: Depression,Chronic Pain,Clinical Trial,Randomized Controlled 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":"NCT06518720","overall_status":"RECRUITING","phase":["PHASE2"]}
title:
Treatment With Psilocybin for Chronic Neuropathic Pain and Depression (TRANSCEND): 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. The purpose of this study is to assess the feasibility, tolerability, and preliminary efficacy of psilocybin therapy for adults with chronic neuropathic pain and co-morbid treatment resistant depression.


authors: University of California, San Francisco
journal: ClinicalTrials.gov
publication_date: 2024-09-24
source_url: https://clinicaltrials.gov/study/NCT05065294
substance_tags: psilocybin
topic_tags: Depression,Healthcare Workers,Safety
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":"NCT05065294","overall_status":"ACTIVE_NOT_RECRUITING","phase":["PHASE2"]}
title:
An Open-Label Pilot Study Examining the Feasibility, Safety, and Effectiveness of Psilocybin Therapy for Depression in Bipolar II Disorder

abstract:
The purpose of this study is to determine the safety, tolerability, and feasibility of psilocybin therapy in people with Bipolar II Disorder. The primary goal of this study is to examine the safety, tolerability, and feasibility of psilocybin therapy in people with Bipolar II Disorder (BD II). Fourteen participants, ages 18 to 70 with clinically diagnosed BD II with active depression, in active outpatient mental health treatment, and who meet all other inclusion and exclusion criteria at screening will be enrolled. After baseline assessments, participants will engage in preparatory visits with trained facilitators, followed by an initial drug administration of oral psilocybin,supervised by the facilitators and a clinician who will conduct safety monitoring throughout. Participants will complete assessment and integration sessions with the facilitators subsequently in order to help process the experience. Participants who tolerated the first dosage may be asked to complete a second psilocybin dosing session, involving the same preparation, procedures, integration, and supervision as the first. Primary outcome measures will assess safety, tolerability, and feasibility of study procedures. Efficacy will be measured by change in depression as measured by the MADRS three weeks after the final psilocybin administration. Exploratory outcome measures will assess changes in sleep, quality of life, and therapeutic engagement.

keywords:
Bipolar II Disorder, Psilocybin therapy, 4-phosphoryloxy-N,N-dimethyltryptamine, ACTIVE_NOT_RECRUITING


title: Psilocybin for Treatment of Obsessive Compulsive Disorder
authors: University of Arizona
journal: ClinicalTrials.gov
publication_date: 2024-08-29
source_url: https://clinicaltrials.gov/study/NCT03300947
substance_tags: psilocybin
topic_tags: Anxiety,OCD,Mechanism of Action
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 11:22:34
raw_json: {"nct_id":"NCT03300947","overall_status":"COMPLETED","phase":["PHASE1"]}
abstract:
This study will evaluate whether psilocybin, a hallucinogenic drug, improves symptoms of obsessive compulsive disorder (OCD), whether it is safely tolerated as treatment of OCD, and will investigate the mechanisms by which it works. The study seeks to improve our ability to treat and improve the lives of people who have obsessive-compulsive disorder (OCD) by exploring the benefits of psilocybin, a mind-altering drug that changes activity in brain areas believed to be involved in OCD. Anecdotal reports and results from previous research support this idea. This two-phase study will enroll patients with symptomatic OCD who are not taking mind-altering medications or street drugs. During Phase One, neither participants nor the investigators will know which drugs or doses are administered. This information will be available if it is medically necessary to reveal which drugs and doses were administered. Five subjects in each group will receive study drug a total of four times, separated by one week. During Phase Two, participants will not know which drugs or doses they receive, but the investigators will know. All participants will receive psilocybin at some point during study participation. Participants will be randomly assigned to one of the following groups: 1. Low dose (100 µg/kg) psilocybin, 2. High dose (300 µg/kg) psilocybin, or 3. Lorazepam (1 mg), a calming medication. Lorazepam is used often for anxiety and will be used to mask which drug participants receive. Participants will spend approximately 12 hours at the research site under observation during each visit, until they are free of the mind-altering effects of the drug and are determined by the psychiatrist to be safe to go home accompanied by a responsible adult. The effects of low versus high doses, and the additive effects of repeated doses will be analyzed and will be compared to the effects of lorazepam.

keywords:
Obsessive-compulsive Disorder (OCD), Psilocybin 100 mcg/kg, Psilocybine, "magic mushrooms", Psilocybin 300 mcg/kg, Lorazepam 1 mg, Ativan, Intensol, COMPLETED


title: Evaluation of Psilocybin in Anorexia Nervosa: Safety and Efficacy
authors: University of California, San Diego
journal: ClinicalTrials.gov
publication_date: 2022-07-24
source_url: https://clinicaltrials.gov/study/NCT04661514
keywords: Anorexia Nervosa, Psilocybin, COMPLETED
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Addiction,Eating Disorders,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":"NCT04661514","overall_status":"COMPLETED","phase":["PHASE2"]}
abstract:
The primary aim of this study is to assess the safety and tolerability of one 25 mg dose of psilocybin in participants with anorexia nervosa based on adverse events (AEs), changes in vital signs, electrocardiograms (ECGs) and clinical laboratory tests. The secondary objectives are to explore the efficacy of a single 25 mg dose of psilocybin on eating disorder symptoms and behaviors, body image, anxiety, food related obsessions and rituals, and body weight. Because there are no proven treatments that normalize core symptoms in adult anorexia nervosa, a disorder with high chronicity, many individuals seek out alternative approaches to care. Recent evidence has suggested that anxiety, obsessive compulsive disorder, and diminished reward or motivation play key roles in the development and maintenance of dysfunctional eating, and poor outcome. In recent years, a growing number of studies have demonstrated the safety and preliminary efficacy of psilocybin in clinical trials for a range of psychiatric illnesses including treatment resistant depression, obsessive compulsive disorder, addiction, and anxiety. Psilocybin may represent a promising new treatment for anorexia nervosa. However, no studies have tested psilocybin in this eating disorder population. Accordingly, this study aims to establish the safety, tolerability and dosing of psilocybin in adult patients with anorexia nervosa, as well as gather pilot data on possible efficacy. For this study, the investigators will recruit adults who currently have a DSM-V diagnosis of anorexia nervosa. Participants will undergo medical and psychological screening and those who are deemed eligible will partake in a maximum of 7 study visits, lasting from 4-8 weeks. On dosing day, participants will receive a single 25 mg dose of psilocybin along with psychotherapeutic support, which includes preparation and integration sessions surrounding the experience. There will be a follow-up period of one month following the psilocybin session during which a range of psychological measures (questionnaires and interviews) will be collected.


title: Acute Effects of MDMA Co-administration on the Response to Psilocybin in Healthy Subjects
authors: University Hospital, Basel, Switzerland
journal: ClinicalTrials.gov
publication_date: 2026-06-24
source_url: https://clinicaltrials.gov/study/NCT06884514
substance_tags: psilocybin
study_type: Qualitative Study
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":"NCT06884514","overall_status":"COMPLETED","phase":["PHASE1"]}
abstract:
The acute subjective effects of serotonin (5-HT)2A receptor stimulation with psilocybin in humans are mostly positive. However, negative effects such as anxiety, paranoid thinking, or loss of trust towards other people are common effects, depending on the dose administered, the personality traits of the person consuming it (set), or the environment in which psilocybin is taken (setting). Negative psychedelic effects may cause acute distress to the subject and acute anxiety has been linked to less favorable long-term outcomes in patients experimentally treated with psilocybin or similar substances for the treatment of depression. The 5-HT and oxytocin releaser 3,4-methylenedioxymethamphetamine (MDMA) reliably induces positive mood, euphoria, comfort, empathy, and feelings of trust. If administered in combination with psilocybin, MDMA may increase positive subjective drug effects including positive mood, empathy, and trust and reduce negative emotions and anxiety associated with psilocybin and overall produce a more positive over negative experience. The present study will assess subjective and autonomic effects of psilocybin alone and in combination with MDMA. Psilocybin is a classic serotonergic psychedelic. Clinically, the acute effects of psilocybin last shorter than those of lysergic acid diethylamide (LSD) but are qualitatively very similar. Currently, psilocybin is the most investigated psychedelic substance among the classic psychedelics including LSD, psilocybin, mescaline, and dimethyltryptamine (DMT). Psilocybin is capable of inducing exceptional subjective effects such as a dream-like alteration of consciousness, affective changes, psychological insight, visual imagery, pseudo-hallucinations and ego-dissolution. The acute subjective effects elicited by psilocybin are mostly positive in humans. However, psychedelic substances like psilocybin may also cause unpleasant subjective effects like negative thoughts, rumination, anxiety, panic, paranoia, loss of trust towards other people and perceived loss of control, depending on the dose of psilocybin used, the personality traits of the person consuming it (i.e. 'set'), the environment in which it is consumed (i.e. 'setting'), and other factors. Acute negative psychological effects are considered the main risk of psychedelic substance use in humans. Inducing an overall positive acute response to the psychedelic is critical because several studies showed that a more positive experience is predictive of a greater therapeutic long-term effect of the psychedelic. The present study uses 3,4-methylenedioxymethamphetamine (MDMA) as a pharmacological tool to optimize the effects of psilocybin by inducing positive mood. MDMA is an amphetamine derivative which, unlike prototypical amphetamines, predominantly enhances serotonergic neurotransmission via release of 5-HT through the serotonin transporter (SERT). Furthermore, MDMA is known to trigger oxytocin release which may contribute to its effects to increase trust, prosociality, and enhanced empathy. The state of well-being induced by MDMA including increased activation and emotional excitation is known to be associated with a better response to psychedelics. Due to its psychological profile, MDMA could be a reliable pharmacological tool to serve as an optimizer of a psychedelic experience by inducing positive emotions.

keywords:
Healthy, Psilocybin, 3,4-Methylenedioxymethamphetamine, Psilocybin placebo, 3,4-Methylenedioxymethamphetamine placebo, COMPLETED

topic_tags:
Depression,Anxiety,Addiction,Receptor Pharmacology,Consciousness,Wellbeing,Personality Change,Emotional Processing,Safety


title: A Randomized, Double-Blind Study of Single-Dose Psilocybin for Major Depressive Disorder (MDD)
authors: Usona Institute
journal: ClinicalTrials.gov
publication_date: 2026-04-21
source_url: https://clinicaltrials.gov/study/NCT03866174
substance_tags: psilocybin
topic_tags: Depression,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":"NCT03866174","overall_status":"COMPLETED","phase":["PHASE2"]}
abstract:
One hundred participants, ages 21 to 65, who meet Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for major depressive disorder (MDD) will be stratified by study site and 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. The purpose of this study is to evaluate the potential efficacy of a single 25 mg oral dose of psilocybin for MDD compared to the active placebo in otherwise medically-healthy participants, assessed as the difference between groups in changes in depressive symptoms from Baseline to Day 43 post-dose. Major depressive disorder (MDD) has become a health crisis of epidemic proportions in the modern world. One in six individuals in the United States will experience an episode of major depression in his or her lifetime, and it is estimated that major depression will rank second after cardiac disease as a cause of international medical morbidity by the year 2020. Depression is associated with greater disability than are most other chronic illnesses and is a risk factor for mortality. Additionally, depression predicts the later development of a number of medical conditions, including cardiac and cerebrovascular disease, hypertension, diabetes, obesity, metabolic syndrome, dementia, and cancer. Unfortunately, most patients with depression do not experience a complete resolution of symptoms with antidepressant treatment. Partial-but incomplete-response to antidepressants is associated with an increased risk of full symptomatic relapse (even when on therapy) and a worse long-term disease course. Combined with the high prevalence and significant disability associated with MDD, the fact that currently available treatments are not fully adequate highlights the tremendous need to identify novel treatment strategies. Data suggest that psilocybin may have behavioral effects relevant to the treatment of depression and recent studies also suggest that psilocybin may possess antidepressant properties. To further assess the effects of psilocybin on MDD signs and symptoms, this trial will enroll 100 participants, ages 21 to 65, who meet criteria for MDD. Participants will be stratified by study site and 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. To enhance participant safety, a Set and Setting (SaS) protocol will be utilized similar to the protocol that has been used in all modern studies of psilocybin. The SaS protocol for this study includes: 1) a period of preparation with session Facilitators prior to dosing; 2) administration of study medications in an aesthetically pleasing room under the supervision of two Facilitators who are present throughout the session; and 3) three post-dose integration sessions during which participants are encouraged to discuss their intervention experience with the Facilitators. The SaS protocol will be identical for those randomized to psilocybin or active placebo. The primary objective of this study is to evaluate the potential efficacy of a single 25 mg oral dose of psilocybin for MDD compared to the active placebo (niacin), assessed as the difference between groups in changes in depressive symptoms from Baseline to Day 43 post-dose.

keywords:
Depressive Disorder, Major, Psilocybin, Psilocybine, Psilocibin, Indocybin, Niacin, Vitamin B3, Set and Setting (SaS) Protocol, COMPLETED


authors: Anna Rose Childress, Ph.D.
journal: ClinicalTrials.gov
publication_date: 2025-10-28
source_url: https://clinicaltrials.gov/study/NCT06786325
keywords: Opioid Use Disorder, Psilocybin, PEX010, RECRUITING
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":"NCT06786325","overall_status":"RECRUITING","phase":["PHASE2"]}
title:
A Wellcome Leap for the Opioid Crisis: Can the 5HT2A Agonist Psilocybin Improve Brain, Behavioral, and Clinical Outcomes in Opioid Use Disorder (OUD)?

abstract:
Investigators will recruit 36 individuals on MAT for OUD for a double-blind, placebo-controlled design to determine whether PEX010 (25-mg/d) shows preliminary efficacy on neural correlates of neurocognition and on clinical outcomes. Participants will be randomized to either (single dose) 25-mg (PEX010-25 group) or 1-mg (PPEX010-1 group) PEX010 in a 2:1 ratio. Brain and behavioral testing sessions will precede Psilocybin (PSI) dosing day by 24-48 hours and will follow PSI dosing by 1 week. After an initial 6 phases, participants will come into the lab to submit a urine screen 2x/week and to complete a short survey in order to collect data on drug use, MAT adherence, and mental health symptoms. The investigators hypothesize the PEX010-25 (vs. PEX010-1) group will have better clinical outcomes (e.g., lower average percent positive urine drug screens, more late relapses, higher MAT adherence). There are research follow ups every three months out to one year post dose. The Opioid Crisis: Currently in its third wave, the opioid epidemic involves the prevalence of lethal levels of fentanyl in drugs, leading to a surge in opioid-related deaths. Reports indicate a record-breaking number of over 107,000 drug-related overdose deaths in 2021-2022, with opioids contributing to more than 75% of these fatalities. Beyond fatal overdoses, nearly 1 million non-fatal overdoses occurred in 2017, carrying significant, long-lasting consequences. Those who experience non-fatal overdoses are more prone to subsequent overdoses and have a higher likelihood of death within a year, primarily due to drug-related issues. The escalating cases of opioid use disorder (OUD) emphasize the critical need for innovative treatments to address the associated challenges, including neurocognitive difficulties and poor clinical outcomes. While medication-assisted treatment (MAT) like methadone or buprenorphine effectively alleviates withdrawal symptoms and reduces overdose risk, illicit drug use persists, and non-adherence to MAT remains a challenge. The opioid overdose crisis demands urgent attention and necessitates the development of treatments capable of making a significant impact. Psilocybin: In response to the need for improved treatments, there's a growing interest in psychedelic-assisted treatment (PAT), particularly involving psilocybin (PSI). Clinical trials support the use of PAT in controlled medical contexts, with 105 trials registered in the past 20 years covering various mental health and other conditions. PSI (at single doses in the proposed range) has shown preliminary promise for depression, alcohol use disorder, and tobacco-use disorder. However, its potential benefits for OUD remain unknown. This proposal aims to determine whether PSI enhances critical OUD clinical outcomes, such as relapse, overdose, and MAT adherence. Importantly, the investigators will test how PSI produces its benefits through its impact on brain and bio-behavioral targets, thus linking potential biomarkers to clinical outcomes. Cognitive Flexibility: The ability to change thoughts, emotions, and behaviors in response to changes in circumstance (to "flex") has strong survival value. When the brain cannot "flex", one can experience a range of mishaps, from small (turning left rather than right 'out of habit') to much larger ones. Being 'stuck' is a problem that appears in many disorders. For example, individuals with depression may get 'stuck' in dark ruminating thoughts; individuals with OCD may get 'stuck' in repetitive thoughts and behaviors; people with substance use disorders get 'stuck' over-responding to drug reward signals and pursue the drug despite negative consequences. Recent research shows that PSI facilitates intermediate and long-term improvements in cognitive flexibility, raising the hope that it can 're-set' the brain and enable new thoughts, emotions, and behaviors. Cognitive flexibility is often measured by tasks that quantify how successfully one can shift between changing mental rules to complete a task. Using such tasks, there is evidence of cognitive flexibility deficits in people with OUD, but research has not specifically examined the impact of improved cognitive flexibility on OUD clinical outcomes. To date, one study showed that neurocognitive training in executive function (EF), including cognitive flexibility, is associated with reduced opioid use, while a non-OUD study found that higher baseline cognitive flexibility was related to better substance use treatment retention. This proposal will be the first to test whether putative PSI-related improvements in cognitive flexibility will lead to more favorable OUD clinical outcomes. Other Executive Functions: Importantly, cognitive flexibility is a complex capability that depends on the integrated action of several other basic executive functions (EFs): attention, working memory, and inhibition of thoughts, feelings, or actions. Further, each of these basic EFs, together with cognitive flexibility, are needed for effective and efficient planning and decision-making. Individuals who use drugs demonstrate impairment in a variety of these fundamental EFs. In OUD populations, deficits are evident across most EF domains, including working memory, attention, inhibition, and decision-making, which may relate to or underly their cognitive inflexibility. Studies have found that performance on EF tasks (and the neural underpinnings of EF in the prefrontal cortex \[PFC\]) indeed correlate with clinical outcomes such as treatment non-adherence (e.g., working memory) and drug use/relapse (e.g., poor inhibition) in substance-use disorders generally, and with reduced abstinence in OUD. Whether these multiple EF deficits predate, or even predispose, drug use - they are likely compounded by drug exposure, including non-fatal opioid overdoses that produce hypoxic-related brain injuries, leading to further neurocognitive deficits. In sum, there is good preliminary evidence for deficits in the several component EFs underlying cognitive flexibility in OUD. By measuring these separately, the current proposal will be able to determine which of these targets are most impacted by PSI, and their relative importance for outcome prediction. What's "special" about psilocybin? PSI has likely been in use by humans for millennia, originally as a religious or spiritual agent due to its dramatic subjective effects, including hallucinations and mystical experiences. However, scientists have more recently understood that some of the effects - such as increased sense of connectedness, openness, and change in perspective - can produce long-lasting change and improved mental health. Indeed, psychometric instruments capturing non-ordinary states of consciousness and psychological constructs have reliably predicted clinical treatment outcomes, including substance use disorder outcomes. Some theorists have proposed that these dramatic drug effects may reflect a profound initial 'loosening' of top-down control over limbic and sensory regions, resulting in improved flexibility and adaptive behavior. Though the current proposal will not be able to test all features of this hypothesis, the investigators will capture the special acute phenomenology of the drug state and test for the fundamental feature of flexibility. Further, the investigators will determine the relative role of the basic EF components of flexibility and test the importance of all these factors (alone and in combination) for obtaining clinical benefit from the drug. This study will provide a critical foundation for understanding the potential of 5HT2A agonists in OUD, with treatment implications for several other disorders where cognitive inflexibility, 'getting stuck', is a core feature.

topic_tags:
Depression,Addiction,OCD,Receptor Pharmacology,Consciousness,Biomarkers,Emotional Processing,Spirituality,Mystical Experience,Clinical Trial,Observational Study,Safety


authors: NYU Langone Health
journal: ClinicalTrials.gov
publication_date: 2026-03-04
source_url: https://clinicaltrials.gov/study/NCT06760533
substance_tags: psilocybin
topic_tags: Randomized Controlled Trial
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 11:22:33
raw_json: {"nct_id":"NCT06760533","overall_status":"NOT_YET_RECRUITING","phase":["EARLY_PHASE1"]}
title:
Pilot Proof of Concept Study Evaluating the Potential Psilocybin Assisted Psychotherapy (PAP) as a Therapeutic Tool for Patients Suffering From Severe Irritable Bowel Syndrome.

abstract:
This study will serve as a pilot randomized controlled trial to assess the feasibility of Psilocybin-Assisted Psychotherapy (PAP) in Treating Irritable Bowel Syndrome (IBS). Patients with severe IBS will undergo 3 pre-psychotherapy sessions with two licensed and trained psychedelic therapists, then will be randomized to undergo a guided psychotherapy session with single 25 mg oral "high" dose of psilocybin or a single 100 mg dose of niacin (active placebo) and attend 4 post-therapy integration sessions.

keywords:
IBS - Irritable Bowel Syndrome, Psilocybin 25 mg, Psychotherapy Treatment Session, Niacin 100 mg, NOT_YET_RECRUITING


authors: University of Alabama at Birmingham
journal: ClinicalTrials.gov
publication_date: 2026-03-10
source_url: https://clinicaltrials.gov/study/NCT05227742
keywords: Demoralization, Psilocybin, Placebo, WITHDRAWN
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":"NCT05227742","overall_status":"WITHDRAWN","phase":["EARLY_PHASE1"]}
title:
Exploratory Study of the Effects of Low-Dose Psilocybin on Sensory Processing, Neurophysiological Arousal, and Emotional Health

abstract:
The purpose of the present study is to evaluate the feasibility, initial signals of efficacy, and potential mechanisms of action of "microdoses" of psilocybin (i.e., low doses of psilocybin that are not believed to produce mystical-type, transcendent, hallucinogenic, or other overtly salient subjective effects that limit functionality) in the treatment of moderate to severe demoralization (feelings of hopelessness and meaningless that frequently accompany medical illness and other life hardship). Individuals who call research staff will undergo an initial telephone screen that will determine eligibility. Week 1: Baseline Intake Appointment. Those who are eligible to participate on the basis of the telephone screen and provide informed consent will then complete a standard demographic questionnaire, a detailed psychiatric interview, and provide a urine sample for confirmation of substance abstinence and pregnancy status. Participants will then be administered a detailed medical history interview and physical examination including EKG and blood panel. Week 2: Orientation. Participants who are medically eligible to participate will be scheduled for a psychoeducational orientation session that further explains the rationale of the study, and summarizes the study logistics. Participants will complete a number of baseline questionnaires and neuropsychological assessments at this time. Week 3: Drug administration #1. In a between-groups design, participants will be randomized to receive 0 mg, 1 mg, 2.5 mg, or 5 mg of psilocybin at five weekly 6-hour long drug administration sessions. Dose will remain constant for each participant at each drug administration session. At Drug Administration #1 and all subsequent drug administration sessions, participants will complete visual analogue scale (VAS) questions drawn from different sources that include drug abuse liability measures. These VAS questions will be administered at drug administration baseline and every 30 minutes thereafter through the end of acute effects at 6-hrs post-baseline. Research staff will complete a number of observational assessments at similar intervals. Blood pressure will be assessed at regular intervals via automatic blood pressure monitor (i.e., at baseline and at 30, 60, 90, 120, 180, 240, and 360 min post-baseline), and medication for the treatment of acute hypertension will be administered should blood pressure exceed 200 systolic and/or 110 diastolic. At peak drug effects (2 hr post-baseline), a number of measures will be administered, each differing by drug administration session. At Drug Administration #1, participants will undergo two electroencephalogram (EEG) tasks (with assessments at baseline serving as pre-drug control values). At 6-hr post-baseline, participants will complete self-report measures assessing the subjective experience. These questionnaires will be administered at the conclusion of each drug administration session. Participants will then be administered a brief semi-structured qualitative interview designed to probe the nature of their experience. All participants will be required to arrange for transportation home from the CRU; participants will not be allowed to drive themselves after drug administration sessions. Week 4: Drug Administration #2. This session will be identical to Drug Administration #1, however, at peak drug effects, participants will complete two new EEG tasks (with assessments at baseline serving as pre-drug control values). Week 5: Drug Administration #3. This session will be identical to prior drug administration sessions, however, at peak drug effects, a neuropsychological measure will be administered. Week 6: Drug Administration #4. This session will be identical to prior drug administration sessions, however, at peak drug effects, participants will complete another neuropsychological measure. Week 7: Drug Administration #5. This session will be identical to prior drug administration sessions, however, at peak drug effects, participants will complete another neuropsychological measure. At the conclusion of this measure, subjects will undergo an EEG assessment (with an assessment at baseline serving as a pre-drug control value). Week 8: Study Termination. This session will comprise completion of the same questionnaires that were previously completed at baseline as well as a semi-structured qualitative interview. EKG will be repeated at study termination. It is noted that over the duration of the study, every day participants will be asked to complete some brief self-report measures and a resting state EEG via a smartphone app.

topic_tags:
Brain Imaging,Mechanism of Action,Microdosing,Emotional Processing,Mystical Experience,Observational Study,Abuse Liability


authors: Lakshmi N Yatham
journal: ClinicalTrials.gov
publication_date: 2026-04-30
source_url: https://clinicaltrials.gov/study/NCT06943573
keywords: Bipolar II Depression, psilocybin (25 mg), psilocybin 1mg micro-dose, NOT_YET_RECRUITING
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:28
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT06943573","overall_status":"NOT_YET_RECRUITING","phase":["PHASE3"]}
title:
Psilocybin-Assisted Therapy for Treatment-Resistant Depression in Bipolar II Disorder: A Randomized Controlled Trial

abstract:
This study is a 12-week (in addition to up to 30 days of screening) randomized, double-blind, placebo-controlled, parallel-group trial. The primary objective of this study is to assess the effectiveness, safety, and tolerability of single-dose psilocybin (25 mg)-assisted therapy in comparison to active placebo (1 mg micro-dose) psilocybin-assisted therapy in patients with bipolar II depression who have not responded to adequate trials with at least two first or second-line treatments for bipolar II depression (i.e. quetiapine, lithium, lamotrigine, sertraline, or venlafaxine as monotherapy or adjunctive therapy, or bupropion adjunctive therapy). The active placebo is a substance that looks identical to the study medication but contains less therapeutic ingredients, and thus is less capable of producing the transformative and meaningful aspects of psychedelic experience compared to the 25 mg dose. Participants will have a total of 11 study visits over a period of up to 16 weeks, which includes 5 therapy sessions from trained study therapists. Bipolar disorders (BD) are lifelong conditions characterized by recurrent episodes of depression and (hypo)mania. Statistics Canada data indicate over a million Canadians are affected by this illness. Bipolar II disorder is characterised by recurrent episodes of hypomania and depression and individuals with BD-II are symptomatic about 50% of the time despite treatment. The majority of this time is spent being depressed thus there is an urgent need to develop new treatments that are safe and effective. Psilocybin, a naturally occurring psychedelic compound found in mushrooms, has been noted to result in an increase in psychological well-being in healthy volunteers as well as have antidepressant effects when administered in conjunction with psychological support. Two recent open-label pilot trials of Psilocybin-Assisted Therapy (PAT) in treatment-resistant depression, including BD-II participants, demonstrated high response rates and excellent tolerability, thereby providing strong justification for the current study.

topic_tags:
Depression,Wellbeing,Randomized Controlled Trial,Healthy Volunteers,Treatment-Resistant Depression,Safety


title: Psilocybin With Intracranial Neural Sensing
authors: Joshua Woolley, MD, PhD
journal: ClinicalTrials.gov
publication_date: 2025-06-05
source_url: https://clinicaltrials.gov/study/NCT06919640
keywords: Chronic Pain, Psilocybin, ENROLLING_BY_INVITATION
substance_tags: psilocybin
topic_tags: Chronic Pain
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":"NCT06919640","overall_status":"ENROLLING_BY_INVITATION","phase":["PHASE1"]}
abstract:
This is an open-label, single-arm, pilot study exploring the neural, sensory, and cognitive effects of a single, medium dose of psilocybin in patients with chronic pain who already have implanted sensing-capable deep brain stimulation (DBS) devices. Outcomes include multi-site neural recording from previously placed ambulatory sensing-capable DBS devices, quantitative sensory and cognitive testing, and self-reports of pain. We hypothesize that psilocybin will change functional connectivity, decrease clinical and task-based pain reports, and improve cognitive functions. This is an open-label, single-arm, pilot study exploring the neural, sensory, and cognitive effects of a single, medium dose of psilocybin in patients with chronic pain who already have implanted sensing-capable deep brain stimulation (DBS) devices. Outcomes include multi-site neural recording from previously placed ambulatory sensing-capable DBS devices, quantitative sensory and cognitive testing, and self-reports of pain. We hypothesize that psilocybin will change functional connectivity, decrease clinical and task-based pain reports, and improve cognitive functions.


title: Safety for Home Administration of Microdose Psilocybin Use
authors: Johns Hopkins University
journal: ClinicalTrials.gov
publication_date: 2026-02-22
source_url: https://clinicaltrials.gov/study/NCT06450210
keywords: Psychedelic Experiences, psilocybin trihydrate, Placebo, RECRUITING
substance_tags: psilocybin
topic_tags: Microdosing,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":"NCT06450210","overall_status":"RECRUITING","phase":["PHASE1"]}
abstract:
The goal of this laboratory study is to establish whether and which microdoses of psilocybin are safe to administer at home to healthy participants. Eligible participants will be given ascending doses of psilocybin trihydrate and a single, interspersed, randomized placebo on separate days in double-blind fashion. The participants will be asked to complete questionnaires and undergo safety assessments. This study aims to enroll 20 healthy participants who will complete all study procedures. Participants will undergo a standard screening procedure. Baseline measures will be completed before the first dose. Participants will then be given ascending doses of psilocybin trihydrate (1.2 mg, 2.0 mg, 3.0 mg, and 4.2 mg) and a single, interspersed, randomized placebo on separate days in double-blind fashion at the research site. A1 mg dose of psilocybin anhydrate is equivalent to a 1.19 mg dose of psilocybin trihydrate (used in this study). For each session, participants will be assessed with criteria for the safety of home dosing. If any dose meets criteria for at-home dosing, and a lower dose did not fail these criteria, that dose will be identified as the safe dose for the given participant. After administration of all doses of psilocybin to all participants, if a safe at-home dose was identified for all participants, that will be considered the highest safe dose for at-home administration to be used for future studies. Visit summary: Initial screening: Medical and psychological screening (Approx. 4 hours though portions of this may be completed remotely). Dosing sessions: There will be 5 double-blind laboratory dosing sessions involving administration of ascending doses of psilocybin and a single, interspersed, randomized placebo dose. Baseline questionnaires will be completed on the day of the first dosing visit, and safety assessments will be administered during and at the end of each session.


title: Exploration of Synaptotrophic Effects of Psilocybin in Opioid Use Disorder (OUD)
authors: Yale University
journal: ClinicalTrials.gov
publication_date: 2025-05-28
source_url: https://clinicaltrials.gov/study/NCT06160284
keywords: Opioid Use Disorder, Psilocybin, RECRUITING
substance_tags: psilocybin
topic_tags: Addiction,Brain Imaging,Aging,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":"NCT06160284","overall_status":"RECRUITING","phase":["PHASE1"]}
abstract:
This study will examine the synaptotrophic effects of psilocybin among medically healthy, detoxified OUD subjects. Eligible OUD participants will undergo pre- and post- psilocybin administration PET scans with the \[11C\]-UCB-J radiotracer while inpatient. Participants will undergo screening as outpatients at the Clinical Neuroscience Research Unit (CNRU). Once deemed eligible, OUD subjects will be studied as inpatients. However, they will have the option of scheduling their second \[11C\]-UCB-J PET as an outpatient (pending these participants' agreement to undergo outpatient visits twice per week to provide urine toxicology to monitor abstinence before PET). The only portion of the study that will be available as outpatient for OUD subjects will be the 1-2 weeks before the second \[11C\]-UCB-J PET scan. The subject will still be admitted for 1-2 weeks, which will include: inpatient detoxification, baseline \[11C\]-UCB-J PET scan, psilocybin administration, and overnight observation after psilocybin administration. However, they may be discharged the day following psilocybin administration and return 2x weekly for urine toxicology testing between discharge and the second \[11C\]-UCB-J PET to confirm abstinence. Structural magnetic resonance imaging (MRI) scans will be obtained for anatomical registration/partial volume correction from all subjects. Functional MRI (fMRI) scans will be completed pre- and post-psilocybin administration to evaluate changes in resting state connectivity. All subjects will participate in a battery of behavioral assessments for exploratory correlations with \[11C\]-UCB-J. Inpatient subjects who smoke cigarettes will have the option of using nicotine gum and/or nicotine patch while on the unit in order to prevent or minimize nicotine withdrawal. The \[11C\]-UCB-J PET scans will be done at the Yale PET Center 1-2 weeks before (baseline) and after psilocybin administration. This is a single-center study at Yale, that will have study activities completed at the following areas: * Clinical Neuroscience Research Unit (CNRU) of the Connecticut Mental Health Center (CMHC) * Yale Positron Emission Tomography (PET) Imaging Center * Yale Magnetic Resonance Research Center (MRRC)


authors: Johns Hopkins University
journal: ClinicalTrials.gov
publication_date: 2026-03-15
source_url: https://clinicaltrials.gov/study/NCT04123314
substance_tags: psilocybin
topic_tags: Depression,Receptor Pharmacology
study_type: Other
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:28
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT04123314","overall_status":"RECRUITING","phase":["EARLY_PHASE1"]}
title:
Pilot Study of Serotonin 2A Receptor (5-HT2A) Agonist Psilocybin for Depression in Patients With Mild Cognitive Impairment or Early Alzheimer's Disease

abstract:
This open-label pilot study examines whether the hallucinogenic drug, psilocybin, given under supportive conditions, is safe and effective for depression in people with Mild Cognitive Impairment (MCI) or early Alzheimer's Disease (AD). This study will also assess whether psilocybin may improve quality of life in those individuals. This is a pilot study evaluating the potential efficacy of psilocybin to produce improvement in depression compared to pre-treatment in people with Mild Cognitive Impairment (MCI) or early Alzheimer's Disease (AD) and clinically significant symptoms of depression. The study will be an open-label trial in a sample of up to 20 treatment-seeking participants with a diagnosis of MCI or early AD. Participants will complete an 8-week course of study treatment including two psilocybin sessions (15 mg/70 kg in week 4 and 15 or 25 mg/70 kg in week 6), with follow-up assessments up to 6 months after the final psilocybin session. The study will assess changes in depressed mood at 1 week after the second psilocybin session compared to pre-treatment, and quality of life in participants from pre- to post-treatment.

keywords:
Depressive Symptoms, Depression, Alzheimer Disease, Mild Cognitive Impairment, Psilocybin, RECRUITING


authors: Milan Scheidegger
journal: ClinicalTrials.gov
publication_date: 2023-09-20
source_url: https://clinicaltrials.gov/study/NCT05780216
keywords: Healthy Participants, DMT + harmine, Placebo, COMPLETED
substance_tags: psilocybin
topic_tags: Brain Imaging,Receptor Pharmacology,Consciousness,Aging,Healthy Volunteers,Drug Interactions
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":"NCT05780216","overall_status":"COMPLETED","phase":["EARLY_PHASE1"]}
title:
Mindfulness and Psychedelics: A Combined Neurophenomenological and Pharmacological Approach to the Characterization of Mindfulness States in Experienced Meditators

abstract:
The investigators are doing this project to investigate potential neurophysiological synergy effects between mindfulness meditation and psychedelics. Previous studies have found that both mindfulness and psychedelics like psilocybin modulate neural activity and connectivity of the same brain network. However, little is known about the potential interactions between mindfulness meditation and psychedelics. The indigenous plant preparation "Ayahuasca" is particularly interesting for the combination with mindfulness meditation. It contains two components, N,N-dimethyltryptamine (DMT) and harmine, which are very similar to the body's own messenger substance serotonin and increase its effect in the body. The investigators would now like to find out how these corresponding networks change in experienced meditators after DMT/Harmine-enhanced mindfulness meditation and how this affects their subjective experience. For this functional MRI imaging will be performed, as well as psychometric assessments and detailed experiential interviews before and after a three-day meditation retreat. Participants will be randomly assigned to one of two groups. One group receives DMT and harmine during the sitting meditation on the second day, the other group receives a corresponding placebo. Neither the participants nor the investigator know who will receive a placebo or the combination of DMT/harmine on the day of the experiment. The pre- and post-measurements of the MRI imaging and psychometric questionnaires of the DMT/Harmine group are compared with those of the placebo control group. By examining the synergistic effects of mindfulness meditation and DMT/harmine, the aim of this study is to contribute to a comprehensive understanding of the neurophenomenology of rare and inaccessible phenomena of consciousness.


authors: Alan Davis
journal: ClinicalTrials.gov
publication_date: 2026-05-13
source_url: https://clinicaltrials.gov/study/NCT07216404
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Clinical Trial,Observational Study,Cancer Patients,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":"NCT07216404","overall_status":"RECRUITING","phase":["PHASE2"]}
title:
Exploring the Safety, Acceptability, and Efficacy of Psilocybin Among Non-Small Cell Lung Cancer Patients With Major Depressive Disorder: A Proof-of-Concept Trial (DREAM LUNG STUDY)

abstract:
This phase II trial tests the safety and side effects of psilocybin in combination with therapy for the treatment of major depressive disorder in patients with non-small cell lung cancer. A cancer diagnosis is life-changing, resulting in significant levels of psychological symptoms, including a combination of depression, anxiety, stress, including feelings of existential distress (i.e., loss of meaning, demoralization, despair). Among all cancer patients, those diagnosed with lung cancer have the highest prevalence of mood disorders, such as depression (up to 40%) leading to profound deterioration in quality of life, prolonged hospital stays, poorer treatment adherence, decreased survival rates, and high rates of suicide (5- and 3-times higher than the general population and other cancer patients, respectively). Psilocybin is substance being studied in the treatment of anxiety or depression in patients with advanced cancer. It is taken from the mushroom Psilocybe mexicana. Psilocybin acts on the brain to cause hallucinations (sights, sounds, smells, tastes, or touches that a person believes to be real but are not real). Psilocybin in combination with therapy may be safe and effective in treating major depressive disorder in patients with non-small cell lung cancer. PRIMARY OBJECTIVE: I. To determine the safety and acceptability of psilocybin-assisted psychotherapy with non-small cell lung cancer (NSCLC) patients. SECONDARY OBJECTIVE: I. To determine the efficacy of psilocybin-assisted therapy in the reduction of depression and the impact of treatment on quality of life, cancer-related stress, and existential distress. OUTLINE: Patients participate in two preparation therapy sessions over 4 hours each on days 7 and 14, then patients receive psilocybin orally (PO) on day 21 and participate in a single dosing therapy session for over 8-10 hours on study. Patients also complete two post-dosing therapy sessions over 2 hours each on days 22 and 28 on study. Patients additionally undergo blood and urine sample collection throughout the study. After completion of study treatment, patients are followed up at 4 and 12 weeks.

keywords:
Lung Non-Small Cell Carcinoma, Unipolar Depression, Biospecimen Collection, Biological Sample Collection, Biospecimen Collected, Specimen Collection, Counseling, Counseling Intervention, Interview, Psilocybin, [3-[2-(dimethylamino)ethyl]-1H-indol-4-yl] dihydrogen phosphate, Survey Administration, RECRUITING


title: Targeting Reward Circuits: Psilocybin as a Novel Therapy for Residual Anhedonia
authors: NYU Langone Health
journal: ClinicalTrials.gov
publication_date: 2026-05-26
source_url: https://clinicaltrials.gov/study/NCT07607938
keywords: Anhedonia, Emotional Blunting, Psilocybin, Placebo, NOT_YET_RECRUITING
substance_tags: psilocybin
topic_tags: Brain Imaging,Emotional Processing
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":"NCT07607938","overall_status":"NOT_YET_RECRUITING","phase":["PHASE1"]}
abstract:
The primary objective is to evaluate whether a single dose of psilocybin (25 mg), compared to placebo, can restore fronto-striatal reward circuit function and thereby improve anhedonia and emotional blunting in individuals with residual symptoms despite ongoing SSRI or SNRI treatment. This will be assessed using precision functional mapping (PFM), task-based fMRI, and clinical rating scales (DARS).


authors: Centre for Addiction and Mental Health
journal: ClinicalTrials.gov
publication_date: 2026-02-24
source_url: https://clinicaltrials.gov/study/NCT06041152
keywords: Amnestic Mild Cognitive Impairment, Psilocybin, Placebo, ACTIVE_NOT_RECRUITING
substance_tags: psilocybin
topic_tags: Neuroplasticity,Brain Imaging,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":"NCT06041152","overall_status":"ACTIVE_NOT_RECRUITING","phase":["PHASE2"]}
title:
Does Psilocybin Change Synaptic Density in the Brains of Patients With Amnestic Mild Cognitive Impairment

abstract:
The goal of this pilot, exploratory, clinical trial is to investigate the effects of psilocybin on synaptic vesicular density (SVD) as measured by the positron emission tomography (PET) radiotracer, 18F-SynVesT-1, in participants with amnestic Mild Cognitive Impairment (aMCI) and healthy participants. The investigators hypothesize that SVD levels in the brain will be higher following the ingestion of psilocybin in comparison to placebo, and that increases in SVD will be associated with improvements in cognition. 10 participants (6 with aMCI, and 4 sex and age matched healthy volunteers) will: * Be randomized to receive either: 1. Two 25 mg macrodoses of psilocybin separated by 1 week. 2. Two placebo doses separated by 1 week. * Receive a baseline 18F-SynVesT-1 PET scan, clinical, and neuropsychological assessments. * Receive a 18F-SynVesT-1 PET scan one week after the last dose of treatment. * Depending on available funds, receive a third PET scan at any time within 4 weeks of the screening visit to quantify tauopathy with the \[18F\]T807 radiotracer. * Receive clinical and neuropsychological testing 1, 4, and 12 weeks after the last treatment. Researchers will compare placebo vs. experimental groups to see if psilocybin will increase SVD, and if increases in SVD are associated with cognitive improvements. The proposed study will investigate the effects of on synaptic vesicular density (SVD) levels as measured by the positron emission tomography (PET) radiotracer, 18F-SynVesT-1, and cognition (i.e., global cognition, executive function, and memory domains) in amnestic Mild Cognitive Impairment (aMCI) and healthy participants. Participants will be randomized to receive either two 25mg doses of psilocybin separated by one week, or two placebo doses separated by one week. Brain scans, clinical, and cognitive assessments will be conducted one week before, and one week, four weeks, and 12 weeks post dosing.


authors: Sheppard Pratt Health System
journal: ClinicalTrials.gov
publication_date: 2024-08-08
source_url: https://clinicaltrials.gov/study/NCT04433858
keywords: Treatment Resistant Depression, Psilocybin, COMP360, ACTIVE_NOT_RECRUITING
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 11:04:28
last_checked: 2026-07-01 11:22:33
raw_json: {"nct_id":"NCT04433858","overall_status":"ACTIVE_NOT_RECRUITING","phase":["PHASE2"]}
title:
An Open Label Study of the Safety and Efficacy of Psilocybin in Participants With Treatment-Resistant Depression (P-TRD)

abstract:
The primary objective of this study is to evaluate the efficacy of psilocybin (25 mg) administered under supportive conditions to adult participants with severe TRD, in improving depressive symptoms.


authors: University Health Network, Toronto
journal: ClinicalTrials.gov
publication_date: 2024-04-01
source_url: https://clinicaltrials.gov/study/NCT06341426
substance_tags: psilocybin
topic_tags: Depression,Clinical Trial,Observational Study,Treatment-Resistant Depression,Safety,Adverse Events
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:28
last_checked: 2026-07-01 11:22:34
raw_json: {"nct_id":"NCT06341426","overall_status":"RECRUITING","phase":["PHASE2"]}
title:
Psilocybin-Assisted Psychotherapy for Treatment-Resistant Depression: A Randomized Phase II Clinical Trial Comparing One Versus Two Psychedelic Doses of Psilocybin (PSI-1V2)

abstract:
The purpose of this study is to see if one or two doses of psilocybin is more effective in relieving depressive symptoms in patients with treatment-resistant depression (TRD). Researchers also want to know if a second dose of psilocybin is safe and well-tolerated. This study will see if psilocybin is effective, safe, and well-tolerated by tracking changes in depressive symptoms, suicidality, and side effects. This study will also see if a second dose of psilocybin has an effect on quality of life, functioning, cognition (thinking, reasoning, remembering), and how long depressive symptoms improve (or worsen) after psilocybin is administered. During the past decade, there has been increased interest in the use of psilocybin as a novel treatment for mental health disorders, including treatment-resistant depression (TRD). Recent studies have suggested that psilocybin has the potential to relieve depressive symptoms when combined with psychotherapy (i.e., psilocybin-assisted psychotherapy \[PAP\]). Each psilocybin dosing session requires the use of extensive resources, including two specialized therapists supporting the patient for 6-8 hours per dosing session. If two doses of psilocybin prove to be more effective than a single dose of psilocybin in relieving depressive symptoms, then two doses should be the standard intervention for future trials and clinical application. However, if a second dose of psilocybin does not offer increased anti-depressant benefit from the first dose, then a second dose of psilocybin would only increase the risk of adverse side effects and cost of treatment. Therefore, the purpose of this study is to determine whether a second dose of psilocybin provides better efficacy, safety and tolerability than a single dose. The investigators hypothesize that two doses of psilocybin will be more beneficial compared to a single dose, and that there will be no significant difference between the groups (one dose versus two doses) in safety or tolerability. The primary objective of assessing antidepressant efficacy will be evaluated by the change in the Montgomery-Åsberg Depression Rating Scale (MADRS) between baseline and Week 8. Safety and tolerability will be assessed using standardized adverse effects monitoring, in addition to close participant monitoring during the dosing day (e.g., blood pressure changes, dissociative and psychotomimetic effects, treatment-emergent manic symptoms, and suicidality). Secondary objectives include evaluating the effects of one versus two psilocybin doses on suicidality, quality of life, functioning, cognition, and duration of clinical benefits during the six month observational follow-up period. Exploratory objectives include evaluating predictors of response, such as static and dynamic clinical factors and expectancy effects, and cost-effectiveness of one versus two psilocybin doses.

keywords:
Major Depressive Disorder, Depression, Treatment-Resistant Depression, Mood Disorders, Single Psychedelic Dose Psilocybin, Two Psychedelic Doses Psilocybin, RECRUITING


authors: MycoMedica Life Sciences PBC
journal: ClinicalTrials.gov
publication_date: 2025-06-11
source_url: https://clinicaltrials.gov/study/NCT06643637
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 11:04:28
last_checked: 2026-07-01 11:22:34
raw_json: {"nct_id":"NCT06643637","overall_status":"COMPLETED","phase":["PHASE1"]}
title:
A Phase 1 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Multiple Doses of MLS101 (Psilocybin) in Healthy Participants

abstract:
MLS101 is being developed as a low dose psilocybin, that can be administered to treat 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 it potential therapeutic benefit in many psychiatric conditions, 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 psilocybin microdoses, this study will assess the safety, tolerability, pharmacokinetics and sensorial effects using a prospective, controlled, multiple dose regimen in healthy volunteers.


authors: Felix Mueller
journal: ClinicalTrials.gov
publication_date: 2025-04-13
source_url: https://clinicaltrials.gov/study/NCT05570708
substance_tags: psilocybin
topic_tags: Consciousness,Safety,Drug Interactions
study_type: Other
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:28
last_checked: 2026-07-01 11:22:34
raw_json: {"nct_id":"NCT05570708","overall_status":"ENROLLING_BY_INVITATION","phase":["NA"]}
title:
The Role of Personal Experience for the Therapeutic Attitude in the Context of Substance-assisted Therapy Training

abstract:
The study investigates two groups of participants of the SÄPT therapist's training starting in October 2022. The overall objective is to investigate the risks and benefits of personal experience (PE) with substance-induced altered states of consciousness for physicians or psychotherapists in the context of a training course for substance-assisted therapy. Specifically, the study aims to assess changes in therapeutic attitude and other factors important in interactions between patients and therapists (such as empathy and cognitive flexibility).

keywords:
Personal Experience of Substance-assisted Therapy Using Psilocybin, MDMA, and LSD, MDMA, LSD, psilocybin, ENROLLING_BY_INVITATION


authors: University of North Carolina, Chapel Hill
journal: ClinicalTrials.gov
publication_date: 2026-05-05
source_url: https://clinicaltrials.gov/study/NCT06303739
keywords: Refractory Depression, Treatment Resistant Depression, psilocybin, ACTIVE_NOT_RECRUITING
substance_tags: psilocybin
topic_tags: Depression,Clinical Trial,Observational Study,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 11:22:34
raw_json: {"nct_id":"NCT06303739","overall_status":"ACTIVE_NOT_RECRUITING","phase":["PHASE3"]}
title:
Induction Protocol for Psilocybin-Assisted Therapy in Treatment-Resistant Depression (TRD): A Pilot Study

abstract:
The goal of this clinical trial is to test how well psilocybin-assisted therapy works in treating people with depression. The main questions this study aims to answer are: * Does psilocybin with assisted therapy help improve symptoms for people with depression? * How long do the effects of this treatment last? Participants will: * Take part in a couple of screening and preparation visits. * Be given psilocybin in one or two treatment sessions. * Attend a series of follow-up sessions over the following year. * Complete forms and surveys to test how their symptoms have changed and what they thought of their experience. Researchers will also compare whether one treatment or two treatments help improve symptoms more for participants. Major depressive disorder (MDD) ranks fourth in global disease burden and has significant morbidity, mortality, societal and financial costs. However, few adequate and effective treatments exist with 60% of MDD patients not responding sufficiently to an initial oral antidepressant treatment. These patients who experience treatment resistant depression (TRD), defined as an intolerance or lack of response to two antidepressants of different classes, have limited treatment options beyond the antidepressant treatments that often yield insufficient results or relapse. Psilocybin, a novel treatment, has been found to relieve symptoms of TRD, but there are limited studies on specific dosing and long term treatment follow-up. In this study, the investigators will look closer at the effectiveness of one treatment with psilocybin versus two treatments with psilocybin, as well as the long term effectiveness over the first 12 months after treatment.


title: Group Psilocybin-Assisted Therapy for Post-Traumatic Stress Disorder
authors: University of New Mexico
journal: ClinicalTrials.gov
publication_date: 2026-05-21
source_url: https://clinicaltrials.gov/study/NCT07506395
keywords: PTSD, Psilocybin, RECRUITING
substance_tags: psilocybin
topic_tags: PTSD,Clinical Trial,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 11:22:34
raw_json: {"nct_id":"NCT07506395","overall_status":"RECRUITING","phase":["PHASE1"]}
abstract:
This study is a community-informed, pragmatic, open-label, phase 1 clinical trial of group-format psilocybin-assisted therapy (GPAT) for individuals with post-traumatic stress disorder (PTSD). The primary objectives of this phase 1 study are to assess the safety and feasibility of (GPAT) for individuals with (PTSD) and to evaluate preliminary effects on PTSD severity. This study is a community-informed, pragmatic, open-label, phase 1 clinical trial of group-format psilocybin-assisted therapy (GPAT) for individuals with post-traumatic stress disorder (PTSD). The primary objectives of this phase 1 study are to assess the safety and feasibility of (GPAT) for individuals with (PTSD) and to evaluate preliminary effects on PTSD severity. These will be assessed by the following outcome measures: * Proportion of participants completing the study protocol * Incidence of adverse events (AEs), serious adverse events (SAEs) and AEs of special interest using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 * Mean change in the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) and PTSD checklist for DSM-5 (PCL-5). The CAPS-5 and PCL-5 are based on the DSM-5 not the DSM-5-TR.


authors: Usona Institute
journal: ClinicalTrials.gov
publication_date: 2026-05-31
source_url: https://clinicaltrials.gov/study/NCT06308653
substance_tags: psilocybin
topic_tags: Depression,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 11:22:34
raw_json: {"nct_id":"NCT06308653","overall_status":"ACTIVE_NOT_RECRUITING","phase":["PHASE3"]}
title:
A Phase 3, Randomized, Double-Blind, Multicenter Study to Evaluate the Efficacy, Safety, and Tolerability of Psilocybin in Adults With Major Depressive Disorder (MDD)

abstract:
Approximately 240 eligible adult participants (≥18 years old) who meet Diagnostic and Statistical Manual of Mental Disorders (DSM-5-TR) criteria for Major Depressive Disorder (MDD) will be enrolled. Participants will be randomly assigned to receive a single oral dose of Psilocybin 25 mg, Psilocybin 5 mg, or inactive placebo. The purpose of this study is to evaluate the efficacy, safety, and tolerability of Psilocybin 25 mg versus placebo in adults with MDD, as assessed by the difference between groups in change in depressive symptoms from Baseline to Day 43 post-dose, and to characterize the durability of initial treatment effect and subsequent response to optional Psilocybin 25 mg re-administration(s) during the 1-year Follow-up Period. Double-blind Period: Participants who show stable depression symptoms between Screening and Trial Baseline will be randomly assigned to receive a single oral dose of Psilocybin 25 mg, Psilocybin 5 mg, or inactive placebo. Investigational Product (IP) will be administered in the context of a "Set and Setting" (SaS) Protocol for psychosocial support, comprised of 1) a period of preparation with Facilitators prior to dosing; 2) administration of IP in an aesthetically pleasing room under the supervision of two Facilitators; and 3) post-dose integration sessions during which participants will discuss their dosing experience with the Facilitators. Trial outcome measures will assess depressive symptoms, functional disability, health-related quality of life, and clinical global impression of disease severity. Long-term Follow-up Period: After the initial 6-week Double-blind Period and completion of the post-dosing Trial Day 43 assessments, all participants will proceed into a 1-year Follow-up Period. During the 1-year Follow-up Period, participants will be followed regularly by clinic staff to assess MDD symptom severity, functional disability, and health-related quality of life; long-term safety data will also be collected. In addition to scheduled clinic visits, clinic staff will contact participants by telephone every two weeks to assess for changes in MDD symptom severity, concomitant medications, adverse events (AEs), and suicidal ideation and behavior. Participants who meet the pre-defined MDD severity criteria and meet all re-administration eligibility criteria may be offered re-administration(s) of open-label Psilocybin 25 mg administered under a "Set and Setting" (SaS) Protocol. Psychosocial support, including psychoeducation, is also incorporated in the long-term Follow-up Period.

keywords:
Depressive Disorder, Major, Psilocybin 25 mg, Psilocybine, Psilocibin, Indocybin, Inactive Placebo, Microcrystalline Cellulose (MCC), Placebo, Psilocybin 5 mg, Psilocybine, Psilocibin, Indocybin, Active Comparator, Psychosocial Support, ACTIVE_NOT_RECRUITING


authors: Psyence Australia Pty Ltd
journal: ClinicalTrials.gov
publication_date: 2026-03-02
source_url: https://clinicaltrials.gov/study/NCT07072728
substance_tags: psilocybin
topic_tags: Depression,Anxiety,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 11:22:34
raw_json: {"nct_id":"NCT07072728","overall_status":"RECRUITING","phase":["PHASE2"]}
title:
A Phase 2b Double-blind, Randomized, Low-dose Comparator-controlled Clinical Trial to Assess the Efficacy and Safety of NPX-5 in Psilocybin-assisted Psychotherapy for the Treatment of Adjustment Disorder Associated With Cancer.

abstract:
This study is assessing the efficacy and safety of NPX-5 in psilocybin-assisted psychotherapy for the treatment of adjustment disorder due to cancer diagnosis. Who is it for? This study is for people who are aged between 18 and 80 years old and suffer from anxiety after adjusting to an acutely stressful event of their cancer diagnosis. This is called adjustment disorder. Study details Participants in this study will be randomly allocated by chance (similar to flipping a coin) to one of three groups: a 25mg NPX-5 dose group, a 10 mg NPX-5 dose group or a 1mg NPX-5 dose group. Participants will be allocated a dose that will be administered during their psilocybin-assisted psychotherapy (PAP) dosing session. The PAP dosing session will run approximately 8 hours, with NPX-5 administered at Day 14 (dosing day). At Week 10, non-responders that continue to meet the study eligibility criteria may commence an additional PAP cycle (at 25 mg NPX-5). A maximum of 2 PAP cycles may be administered. Long term follow up will comprise of a study visit at 3 months post Week 10 (of the final cycle) to assess safety and tolerability of NPX-5. It is hoped that this research will develop important scientific knowledge that could contribute to the development of a potential new treatment for anxiety and depression after adjusting to an acutely stressful event such as a cancer diagnosis. This is a randomized, double-blind, low-dose comparator-controlled Phase IIb study to investigate the efficacy and safety of PAP with 25 mg, 10 mg and 1 mg \[low-dose comparator) NPX-5, for the treatment of adjustment disorder symptoms in participants diagnosed with cancer. The referring oncologist will indicate that the participant is physically capable of undergoing psychedelic encounter and is likely to have a minimum life expectancy of 6 months. At least 87 adult participants (age 18 to 80 at screening) with a diagnosis of AjD due to cancer diagnosis will be enrolled in this study. Participants will be randomly assigned with a ratio of 1:1:1 to receive Psilocybin-Assisted Psychotherapy (PAP) with either 25 mg, 10 mg or 1 mg NPX-5. Both the site staff treating participants and the participants themselves will be blinded to the treatments being administered. The study consists of a combination of clinic visits and telehealth phone calls to support this vulnerable participant population. The clinic will have experience with conducting PAP. All study visits be carried out by suitably qualified individuals and wherever possible, the same therapist will meet with study participants for in-person and telehealth appointments. Participants will undertake a screening visit between Day -45 and Day -2 to determine eligibility to participate in the study. Those participants that meet the eligibility criteria will attend the study site on Day 1 when continued eligibility will be assessed and baseline assessments performed. Participants must complete three preparation sessions with the therapist prior to dosing session. Two of these sessions can be completed remotely via telehealth and have flexible timing, provided there is at least one day between each session. One preparation session must be done in person in the dosing room, ideally during a site visit on Day 13. Additionally, at least one preparation session must include the sitter or secondary therapist. The primary therapist has the discretion to include the sitter or secondary therapist in more preparation or integration sessions based on their assessment. The clinic site visits will comprise Day 1, Day 13 (day prior dosing session), Day 14 (dosing session), Day 15 (integration session) and Day 70/Week 10 (follow-up) post-randomization. There will be ± 3 days for a dosing session allowed. Subsequently, all relevant visits will be adjusted accordingly. In addition, participants will be required to attend following telehealth appointments: * Two telehealth appointments for preparatory sessions within 2 weeks prior to dosing session. * One telehealth appointment for integration therapy session in the two weeks following the dosing session. * Follow up telehealth appointments on Day 28 (Week 4), Day 42 (Week 6). * Final study follow-up telehealth appointment at 3 months post the Day 70 (Week 10) visit of the final PAP cycle for final safety assessments. Non responders (for criteria see Section 5.5.2) at Day 70 (Week 10) that continue to meet the study eligibility criteria, may commence an additional PAP cycle (at 25 mg NPX-5). These participants will repeat the schedule described above, including the visit the day prior to dosing session, the actual dosing session, and the integration sessions. A maximum of 2 PAP cycles may be administered.

keywords:
Adjustment Disorder, Adjustment Disorder With Anxious Mood, Cancer, Cancer Cachexia, Cancer of Endometrium, Cancer of Kidney, Cancer of Prostate, Cancer of the Breast, Cancer of Stomach, Cancer Melanoma Skin, Cancer Pancreas, Psilocybin therapy, RECRUITING


authors: University of California, San Francisco
journal: ClinicalTrials.gov
publication_date: 2025-06-09
source_url: https://clinicaltrials.gov/study/NCT05317689
keywords: Healthy, Psilocin, Psilocybin, Sublingual Psilocin, ACTIVE_NOT_RECRUITING
substance_tags: psilocybin,psilocin
topic_tags: Healthcare Workers,Safety
study_type: Other
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:28
last_checked: 2026-07-01 11:22:34
raw_json: {"nct_id":"NCT05317689","overall_status":"ACTIVE_NOT_RECRUITING","phase":["PHASE1"]}
title:
Comparison of the Effects of PEX20 (Oral Psilocin), PEX30 (Sublingual Psilocin), and PEX10 (Oral Psilocybin) in Healthy Adults

abstract:
To compare the physiological and psychological effects of psilocin taken orally by pill or sublingually by dissolving a tablet under the tongue to those of psilocybin taken by pill in healthy adults. The primary goal of this study is to compare the physiological and psychological effects of psilocin taken orally by pill or sublingually dissolved under the tongue to those of psilocybin taken by pill. Twenty participants, ages 25 to 50, with one previous experience with psychedelics, and who meet all other inclusion and exclusion criteria at screening will be enrolled. After baseline assessments, participants will engage in preparatory visits with trained facilitators, followed by drug administration, supervised by the facilitators and a clinician who will conduct safety monitoring throughout. Participants will then complete assessment and integration sessions with the facilitators in order to help process the experience. The same preparation, procedures, integration, and supervision will be repeated up to three more times with each participant.


authors: Usona Institute
journal: ClinicalTrials.gov
publication_date: 2023-08-14
source_url: https://clinicaltrials.gov/study/NCT05478278
substance_tags: psilocybin
topic_tags: Pharmacology,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 11:22:34
raw_json: {"nct_id":"NCT05478278","overall_status":"COMPLETED","phase":["PHASE1"]}
title:
A Phase 1, Two-Part Study in Healthy Volunteers to Evaluate The Effect of Psilocybin on Cardiac Repolarization and The Effect of Food on Psilocybin Pharmacokinetics

abstract:
This study is comprised of two parts. The purpose of the first part of this study is to evaluate the effects of a supratherapeutic dose of psilocybin on cardiac repolarization. The purpose of the second part of the study is to evaluate the effects of food on the pharmacokinetics of psilocybin. Part one of this study will be a double-blind, single-dose, randomized, placebo-controlled, 4-treatment, 4-period, 12-sequence crossover design in 36 healthy volunteers (adult male and/or female subjects). Subjects will be randomly assigned to 1 of 12 different treatment administration sequences, whereby each sequence will include 3 double-blind treatments (therapeutic dose of psilocybin, supratherapeutic dose of psilocybin, and placebo) and 1 open-label positive control treatment (moxifloxacin). Part two of this study will be an open-label, randomized, 2-period, 2-sequence crossover design in 24 healthy volunteers (adult male and/or female subjects). Each assigned treatment will be administered under fasting or fed conditions as a single dose on Day 1 of the respective study period.

keywords:
QTc Interval, Pharmacokinetics, Psilocybin, Psilocybine, Psilocibin, Indocybin, Moxifloxacin, Avelox, Moxeza, Micro-Crystalline Cellulose, COMPLETED


title: Safety and Efficacy of Psilocybin for the Treatment of Headache Disorders: Sub-Study II
authors: Yale University
journal: ClinicalTrials.gov
publication_date: 2023-10-11
source_url: https://clinicaltrials.gov/study/NCT03806985
substance_tags: psilocybin
topic_tags: Headache / Migraine,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 11:22:34
raw_json: {"nct_id":"NCT03806985","overall_status":"TERMINATED","phase":["PHASE1"]}
abstract:
The purpose of this study is to investigate the effects of oral psilocybin in post-traumatic headache. Subjects will be randomized to receive placebo, low dose psilocybin, or high dose psilocybin on two separate test days approximately 14 days apart. Subjects will maintain a headache diary prior to, during, and after the treatments in order to document headache frequency and intensity, as well as associated symptoms. Blood samples will be drawn at various timepoints to measure levels of inflammatory peptides.

keywords:
Post-Traumatic Headache, Placebo oral capsule, Low Dose Psilocybin, High Dose Psilocybin, TERMINATED


authors: Sunstone Medical
journal: ClinicalTrials.gov
publication_date: 2026-05-05
source_url: https://clinicaltrials.gov/study/NCT05947383
keywords: Cancer, Major Depressive Disorder, Psilocybin, Placebo, ACTIVE_NOT_RECRUITING
substance_tags: psilocybin
topic_tags: Depression,Clinical Trial,Observational Study,Cancer Patients,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 11:22:34
raw_json: {"nct_id":"NCT05947383","overall_status":"ACTIVE_NOT_RECRUITING","phase":["PHASE2"]}
title:
A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of up to Two Doses of Psilocybin for the Treatment of Major Depressive Disorder in Adults With Cancer

abstract:
This is a Phase 2, single-center study to explore the efficacy, safety, and tolerability of up to two 25-mg doses of psilocybin administered at an interval of 9 to 10 weeks in patients with MDD and cancer. This two-part study will administer a fixed dose (25 mg) of psilocybin in a double-blind, randomized, placebo-controlled portion (Dosing Session 1) and subsequently allow rollover into an open-label portion (Dosing Session 2; fixed dose of psilocybin, 25 mg) for patients who do not achieve remission of MDD symptoms after the first dose. In Dosing Session 1, groups of two to four patients will be randomized, as a cohort, to receive either psilocybin 25 mg or niacin 100 mg (active placebo) in a group session, with each patient supported by their dedicated study therapist and monitored by a second therapist via video feed. In Dosing Session 2, all eligible participants (i.e., patients who have not achieved remission defined as MADRS \< 10 at V7) will receive psilocybin 25 mg in an open-label fashion using the group session model. The study population will include adult men and women who are 18 years of age or older and have diagnoses of both MDD and a malignant neoplasm. MDD is defined as the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) 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 International Classification of Diseases, 10th edition (ICD-10). Participants will be recruited through referrals from specialized psychiatric and oncology services as well as through patient self-referrals. The majority of participants will have no prior exposure to psilocybin or so-called "magic mushrooms"; however, participants with prior recreational experience with psilocybin or "magic mushrooms" are eligible.


authors: Unity Health Toronto
journal: ClinicalTrials.gov
publication_date: 2026-06-25
source_url: https://clinicaltrials.gov/study/NCT06386003
keywords: Post Traumatic Stress Disorder, PTSD, Chronic PTSD, Psilocybin, RECRUITING
substance_tags: psilocybin
topic_tags: PTSD,Healthcare Workers,Safety
study_type: Other
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":"NCT06386003","overall_status":"RECRUITING","phase":["PHASE2"]}
title:
Psilocybin-Assisted Massed Cognitive Processing Therapy for Chronic Posttraumatic Stress Disorder: An Open-label Trial

abstract:
This is an open-label trial evaluating feasibility, tolerability, safety and efficacy of psilocybin assisted cognitive processing therapy for chronic Posttraumatic Stress Disorder (PTSD). Current front-line treatments for Posttraumatic stress disorder (PTSD) are ineffective for up to half of patients, with serious medical and societal consequences. It is imperative to improve the efficacy of front-line treatment options, such as cognitive processing therapy (CPT). CPT is an effective treatment for PTSD, including when delivered intensively (i.e., multiple sessions over 7 days). However, a substantial proportion of patients continue to meet criteria for PTSD or have residual PTSD symptoms post-treatment. Psilocybin-assisted CPT may be a potential solution, as preliminary evidence supports the potential of psilocybin to alleviate symptoms of PTSD. Fifteen participants will receive a single dose of psilocybin 25mg combined with 12 sessions of massed CPT, and 2 psychotherapy sessions related to psilocybin over 7 days. Participants will complete clinician-administered scales, self-reported mental health questionnaires, and use a wearable device. After the 1-week interventional period, participants will enter a 12-weeks follow-up period.


authors: Centre Hospitalier Universitaire de Nīmes
journal: ClinicalTrials.gov
publication_date: 2025-08-20
source_url: https://clinicaltrials.gov/study/NCT06647056
keywords: Psychogenic Nonepileptic Seizures, Psilocybin, MRI, COMPLETED
substance_tags: psilocybin
topic_tags: Default Mode Network,Emotional Processing
study_type: Other
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:28
last_checked: 2026-07-01 11:22:34
raw_json: {"nct_id":"NCT06647056","overall_status":"COMPLETED","phase":["NA"]}
title:
Evaluation of the Effect of a Single Dose of Psilocybin on Neural Correlates of Cognitive Control in Patients With Psychogenic Nonepileptic Seizures

abstract:
Psychogenic non-epileptic seizures (PNES) are functional paroxysmal motor disorders that may be clinically suggestive of epilepsy but are not associated with the electroencephysiological and electroencephalographic changes of epilepsy. Thus, hyper-connectivity of the regions of the default mode network (DMN) linked to executive control could be involved in the impairment of cognitive control capacities in patients suffering from PNES. Also, the HYCORE study (NCT02329626), showed that dysregulation of frontal regions involved in attentional and emotional regulation is correlated with motor symptoms in patients with functional neurological disorders. The researchers of this study hypothesized that psilocybin would improve cognitive control in patients with PNES.


title: Safety and Tolerability of Psilocybin in Post-Traumatic Stress Disorder
authors: Johns Hopkins University
journal: ClinicalTrials.gov
publication_date: 2024-01-04
source_url: https://clinicaltrials.gov/study/NCT05562973
keywords: Post-Traumatic Stress Disorder, Psilocybin, WITHDRAWN
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: 2026-07-01 11:22:34
raw_json: {"nct_id":"NCT05562973","overall_status":"WITHDRAWN","phase":["PHASE1"]}
abstract:
The purpose of this study is to evaluate the safety, tolerability, and potential efficacy of psilocybin-assisted psychotherapy to reduce post-traumatic stress disorder (PTSD) severity in a sample of individuals with PTSD. The proposed Phase I study aims to evaluate the safety, tolerability, and potential efficacy of psilocybin-assisted psychotherapy to reduce PTSD severity in a sample of individuals with PTSD. A sample of up to 30 individuals with PTSD will be recruited. All participants will receive the intervention, which will consist of three psilocybin sessions with an interval of approximately 2 weeks between each session. A3+3 Phase I trial design will be used to evaluate a range of possible dose sequences with doses ranging from 15 mg up to 45 mg. Safety, tolerability, and efficacy endpoints will be evaluated 2 weeks following each psilocybin session and at 1-month, 3-month, and 6-month follow-ups.


authors: Centre for Addiction and Mental Health
journal: ClinicalTrials.gov
publication_date: 2026-02-11
source_url: https://clinicaltrials.gov/study/NCT07405606
substance_tags: psilocybin
topic_tags: Depression,Addiction,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 11:22:34
raw_json: {"nct_id":"NCT07405606","overall_status":"NOT_YET_RECRUITING","phase":["PHASE2"]}
title:
Psilocybin-assisted Therapy for Comorbid Major Depressive Disorder and Alcohol Use Disorder: A Pilot Randomized Clinical Trial

abstract:
The goal of this clinical trial is to determine the safety and efficacy of psilocybin assisted Therapy (PAT) in individuals with comorbid Major Depressive Disorder (MDD) and Alcohol Use Disorder (AUD). The main question it aims to answer is: \- What is the feasibility and safety of administering PAT in adults with MDD-AUD by evaluating recruitment, retention, tolerability, and safety? Researchers will compare the psilocybin (25 mg) and placebo groups to see if there are any significant differences in frequency of dropouts or serious adverse events. Participants will: * be randomized to receive either psilocybin (25 mg) or placebo * visit the site (in-person and remotely) for a total of 14 times to complete study tasks * receive psilocybin-assisted therapy (PAT) at five various timepoints

keywords:
Major Depressive Disorder (MDD), Alcohol Use Disorder (AUD), Psilocybin 25 mg, Placebo, NOT_YET_RECRUITING


authors: Imperial College London
journal: ClinicalTrials.gov
publication_date: 2025-12-04
source_url: https://clinicaltrials.gov/study/NCT06798636
substance_tags: psilocybin
topic_tags: Depression,Mechanism of Action,Emotional Processing,Safety
study_type: Other
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:28
last_checked: 2026-07-01 11:22:34
raw_json: {"nct_id":"NCT06798636","overall_status":"RECRUITING","phase":["EARLY_PHASE1"]}
title:
Investigating the Effects of a Psychedelic-augmented Mental Imagery-based Intervention for Young People With Self-harm Behaviour: an Experimental Medicine Study

abstract:
Approximately 20% of young people experience self-harm behaviour in their lives. Self-harm can occur across different mental health disorders, and lead to negative outcomes and risk of suicide. Current treatments are long, costly and do not suit all young people, making it essential to research alternative treatments. Therapy combined with psychedelic drugs has recently been shown to be helpful in a variety of mental health disorders, including depression. This research project will explore the mechanisms by which combining a low dose of psychedelic psilocybin with a cognitive technique may target self-harm behaviour in young people (aged 16-25). Previous research has shown that mental images of self-harm are common among individuals who self-harm and can increase the urge to self-harm. Imagery Re-Scripting (ImRS) is a cognitive technique that guides an individual to replace mental imagery driving self-harm with an alternative image that will instead discourage self-harm and promote alternative coping strategies. However, during ImRS individuals may fear bringing negative mental images and emotions to mind, hindering the process. Psychedelic substances can increase the ability to tolerate difficult emotions, make thinking styles more flexible and individuals more open to change. Based on this, the aim is to test if enhancing a cognitive technique with a low dose psychedelic can modify the cognitive mechanisms maintaining self- harm behaviour. The aim is to examine the effect of a sub-hallucinogenic dose of psilocybin in combination with ImRS on cognitive processes, such as experiencing vivid mental images, and whether it can reduce these mental images and associated negative emotions in young people with recent self-harm behaviour above the effects of ImRS alone. The hypothesis is that psilocybin could facilitate confronting the emotions that arise during ImRS and make it easier to generate new helpful mental imagery. These experimental data could lay the foundation for future treatment development targeting self-harm in young people.

keywords:
Self Harm, Psilocybin 5 mg with cognitive behavioural therapy intervention, Psilocybin, Placebo with cognitive behavioural therapy intervention, RECRUITING


title: The Therapeutic Potential of Psilocybin in Anorexia Nervosa in Young Adults
authors: Region Skane
journal: ClinicalTrials.gov
publication_date: 2026-03-05
source_url: https://clinicaltrials.gov/study/NCT07169747
keywords: Anorexia Nervosa, Psilocybin, RECRUITING
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:28
last_checked: 2026-07-01 11:22:34
raw_json: {"nct_id":"NCT07169747","overall_status":"RECRUITING","phase":["PHASE2"]}
abstract:
The goal of this clinical trial is to learn if psilocybin, given with psychological support, is safe and helps treat anorexia nervosa in young adults. Anorexia nervosa is a serious eating disorder that currently has no approved medicine. Psilocybin is a psychedelic substance that may help the brain form new connections, which could make it easier for people with anorexia nervosa to develop healthier ways of thinking. The main questions this study aims to answer are: * Is psilocybin with psychological support safe and well-tolerated? * Does psilocybin with psychological support help lower symptoms of anorexia nervosa? * How might psilocybin work in the brain to support recovery from anorexia? This study will compare psilocybin with psychological support to Treatment as Usual (TAU). Participants in the study will be randomly placed into one of the two groups. There will be 40 patients with anorexia nervosa included, 20 per group. TAU includes the standard care people receive for anorexia nervosa in a specialized eating disorder clinic in Region Skåne, Sweden. Participants will: * Be between 16 and 35 years old and have anorexia nervosa * Take psilocybin (25 mg) by mouth two times, four weeks apart * Receive psychological support before, during, and after each dosing session (including preparation and integration sessions) * Complete questionnaires, have brain scans (magnetic resonance imaging) and blood tests to learn more about how psilocybin may work * Share their personal experiences as part of a qualitative interview This study hopes to learn if psilocybin, when given with the right support, can be a helpful and safe option for people living with anorexia nervosa. Background and Rationale Anorexia Nervosa (AN) is one of the most lethal psychiatric disorders, with mortality rates approximately five times higher than that of the general population. AN affects multiple organ systems due to severe weight loss and malnutrition and hence leads to a substantial decline in health-related quality of life. While psychotherapies have shown partial efficacy, data suggest that only 46% of patients recover within four years, and 20% remain chronically ill. Relapse rates exceed 50% among those who recover, underscoring the need for more effective treatments. Research suggests that several psychological factors, such as challenges in regulating emotions, black-and-white thinking, mental rigidity, and a limited capacity for mentalization may contribute to the persistence of severe, chronic anorexia nervosa. The age of onset for AN typically shows a bimodal distribution, peaking at 14 and 18 years of age, motivating the design of including patients as young as 16 years old in this study. Psilocybin, a serotonergic psychedelic compound, primarily acts as an agonist of the 5-HT2A receptor, inducing profound effects on cognition, emotion, perception, and self-awareness. Although research on psilocybin remains limited, clinical trials across psychiatric disorders suggest its potential therapeutic benefit. For example personality changes such as increased openness, have been observed to persist up to a year following a single high dose. The inclusion of 16-17-year-olds in this study is particularly novel, as research on psychedelic therapy in adolescents and young adults remains scarce. Emerging evidence highlights how psychedelics may benefit AN patients, such as enhanced serotonin signaling and cognitive flexibility. The ability of psychedelics to foster cognitive flexibility, a well-documented phenomenon, is considered a key factor in therapeutic processes. This is especially relevant for AN, where rigid thinking and behavior contribute to treatment resistance. One pilot study demonstrated that a 25 mg psilocybin dose, combined with psychological support, was well-tolerated by female AN patients with a body mass index (BMI) \>16. The study reported significant reductions in eating disorder symptoms at one month post-treatment, with only mild and transient adverse events. Recent studies indicate that psilocybin induces significant changes in brain function and network organization across key regions. Notably, psilocybin disrupts connectivity in the default mode network by causing desynchronization across spatial scales. These findings suggest a neurobiological basis for psilocybin´s therapeutic effect. However, further research is needed to elucidate long-term effects, particularly in clinical context. Functional magnetic resonance imaging (fMRI) has demonstrated utility in detecting neuronal abnormalities in AN. This study's use of fMRI before and after psilocybin treatment will provide critical insights into the neurobiological impacts of psilocybin on AN. Brain-Derived Neurotrophic Factor (BDNF) is a protein that plays a crucial role in neuroplasticity. Preclinical studies show that psilocybin promotes neuritogenesis and synaptic plasticity, potentially via increased cortical BDNF expression. Given that individuals with AN exhibit reduced serum BDNF levels, this study will assess changes in BDNF pre- and post-treatment to elucidate psilocybin's impact on neurobiological mechanisms. These insights may advance treatment optimization and efficacy predictions for AN patients. Study Objectives Primary Objective is to assess the safety and tolerability of psilocybin 25 mg in young adults (16-35 years old) with anorexia nervosa. Secondary objectives include evaluating the efficacy of psilocybin with psychological support in reducing AN symptom compared to treatment as usual (TAU), investigate potential mechanisms of action through self-report questionnaires, neuroimaging and BDNF analysis, and conduct qualitative analysis of subjective experiences. Neuroimaging will investigate changes in brain resting state connectivity (measured by fMRI), and commonly used task-based fMRI paradigms. The task-based paradigms will involve food-related conditions, commonly used in the population (Celeghin et al., 2023; Bronleigh et al., 2022) as well as established paradigms involved in processing reward anticipation (Knutson et al., 2000; Ventorp et al 2022) Trial Design and Procedures This is a phase II, open-label, randomized controlled trial with two arms: 1. Active treatment arm; Two dosing sessions with psilocybin 25mg with psychological support alongside TAU. 2. Active comparator control arm; TAU only. The study will include 40 participants, 20 in each group. If the active treatment arm is determined to be safe, tolerable, and preliminarily effective during the follow-up assessment, participants in the control group will have the option to switch to the active treatment while maintaining their usual specialized care. The switch to psilocybin treatment will follow the same preparation, dosing, and integration protocols as outlined for the intervention group. This design minimizes ethical concerns regarding withholding a potentially effective treatment. Participants will be randomly assigned (1:1) to either the intervention or control group. Block randomization stratified by age group (16-18 and 19-35 years) will ensure balanced representation. Given the small sample size of 40 participants (20 per group), the statistical power to detect between-group differences is inherently limited, irrespective of blinding. As such, the trial is appropriately designed as a pilot study, with a primary focus on assessing safety, feasibility, and tolerability. To enhance interpretation, qualitative and neurobiological measures are also included. A formal power calculation was not conducted, in line with the exploratory nature of the study. The sample size was determined based on practical feasibility and aligns with current recommendations for early-phase trials of novel interventions. A post-hoc power analysis will be conducted to evaluate whether the sample size was sufficient to detect clinically meaningful changes in the primary outcomes. Details on location and Data Collection Methods All procedures will be conducted at the University Hospital for Psychiatry, Baravägen 1, Lund, except the fMRI assessments which are performed at the The National 7 Tesla (7T) Facility in Lund. All assessments will be carried out by qualified personnel appointed by the principal investigator, including medical doctors, nurses, and psychologists. The National 7T Facility will appoint qualified personnel for fMRI assessment. The duration of the entire trial is from the first screening of the first patient to the last follow up of the last patient. For each patient participant, the duration of the trial is from the screening to the last follow up at week 52 (12 month). Patient rehospitalization and additional interventions data are collected in patient journal registers. Pre-Study Activity Following ethical approval, a focus group will be conducted with patients with anorexia nervosa in two different groups, one aged 16-18 and one 19-35 years. The purpose is to provide study information, gather feedback on the clarity and ethical aspects of the protocol, and identify ways to improve potential benefit. Input from this focus group will inform study quality, recruitment materials, communication strategies and ethical aspects of psilocybin research experienced by the population. Any amendments based on this will be processed according to CTIS protocol. Screening Phase Screening includes psychiatric and medical history, inclusion/exclusion criteria assessment, safety blood tests (glucose, liver, kidney), electrocardiogram (ECG), informed consent (with a 2-week consideration period), pregnancy test and urine toxicology (U-tox). The time from screening to the first psilocybin dose must not exceed 8 weeks, regardless of washout status. Potential participants will be screened by a psychiatric clinician appointed by the principal investigator to ensure eligibility and understanding of the study requirements. Preparation Phase Preparation Session 1 \& Baseline Assessment (Week -1): Psychoeducation about psilocybin, breathing and relaxation techniques, rapport-building with therapists, and discussion of expectations and concerns. Includes full baseline assessments (list provided as attachment to protocol: * Expectation of Treatment Scale (ETS-BF) * Readiness and Motivation Questionnaire (RMQ) * General Change Mechanisms Questionnaire (GCMQ) * Patient Health Questionnaire (PHQ-9) * Generalized Anxiety Disorder scale (GAD-7) * Eating Disorder Examination Questionnaire (EDE-Q ) * Columbia-Suicide Severity Rating Scale (C-SSRS) * Brief Psychiatric Rating Scale - Extended (BPRS+) * Life Satisfaction Scale (LS) * Positive and Negative Affect Schedule (PANAS) * Harmony in Life Scale (HILS) * Ten Item Personality Inventory (TIPI) * Honesty-Humility Scale (HH) Vital signs, ECG, fasting glucose, urine drug screening, fMRI, BMI, metric assessment of body size perception and blood sampling for BDNF and safety labs are also conducted. Preparation Session 2 (Week 0): 7-10 days after Preparation 1, and 2-3 days before psilocybin dosing. Dosing and Integration Phase Dosing Session 1 (Week 0): Psilocybin 25 mg under therapeutic support with ECG and blood pressure/pulse monitoring. Integration Session 1 (Day after Dosing 1): Reflection, fMRI, blood sampling (including glucose, liver, kidney, BDNF), and reassessments with RMQ, GCMQ, PHQ-9, GAD-7, C-SSRS, BPRS+, LS, PANAS, HILS, TIPI, ECG and blood pressure/pulse. Psychedelic Experience related scales; Altered States of Consciousness Rating Scale (5D-ASC), Mystical Experience Questionnaire (MEQ-4), Meaningful Life Experience Rating (MLE). Integration Session 2 (Week 1): Continued psychological integration support. Integration Session 3 (Week 2-3): Summary of first dosing experience and preparation for second dosing. Dosing Session 2 (Week 4): Second psilocybin 25 mg administration under identical conditions as first dosing session. Integration Session 4 (Day after Dosing 2): Reflection, blood sampling (including glucose, liver, kidney, BDNF), and reassessments with RMQ, GCMQ, PHQ-9, GAD-7, C-SSRS, BPRS+, LS, PANAS, HILS, TIPI, ECG and blood pressure/pulse. Psychedelic Experience related scales; Altered States of Consciousness Rating Scale (5D-ASC), Mystical Experience Questionnaire (MEQ-4), Meaningful Life Experience Rating (MLE). Integration Session 5 (Week 5-6): Final integration session and preparation for long-term follow-up. Primary Endpoint (Week 8) Includes full safety and outcome evaluations: * fMRI * blood sampling (including glucose, liver, kidney, glucose, BDNF) * Vital signs, ECG, U-tox * BMI * Metric assessment of body size perception * Adverse Event/Serious Adverse Event (AE/SAE) monitoring * Readiness and Motivation Questionnaire (RMQ) * General Change Mechanisms Questionnaire (GCMQ) * Patient Health Questionnaire (PHQ-9) * Generalized Anxiety Disorder scale (GAD-7) * Eating Disorder Examination Questionnaire (EDE-Q ) * Columbia-Suicide Severity Rating Scale (C-SSRS) * Brief Psychiatric Rating Scale - Extended (BPRS+) * Life Satisfaction Scale (LS) * Positive and Negative Affect Schedule (PANAS) * Harmony in Life Scale (HILS) * Ten Item Personality Inventory (TIPI) * Honesty-Humility Scale (HH) Intensive Follow-Up Phase (Week 8-24) Follow-up visits at Week 12, 16, and 20 include: * Eating Disorder Examination Questionnaire (EDE-Q ) * Columbia-Suicide Severity Rating Scale (C-SSRS) * Brief Psychiatric Rating Scale - Extended (BPRS+) * AE/SAE monitoring * BMI, blood pressure, ECG * Fasting glucose, U-tox 6-Month Follow-Up (Week 24) Same as primary endpoint assessments, including: * blood sampling (including glucose, liver, kidney, BDNF) * Vital signs, ECG, U-tox * BMI * Metric assessment of body size perception * AE/SAE monitoring * Readiness and Motivation Questionnaire (RMQ) * General Change Mechanisms Questionnaire (GCMQ) * Patient Health Questionnaire (PHQ-9) * Generalized Anxiety Disorder scale (GAD-7) * Eating Disorder Examination Questionnaire (EDE-Q ) * Columbia-Suicide Severity Rating Scale (C-SSRS) * Brief Psychiatric Rating Scale - Extended (BPRS+) * Life Satisfaction Scale (LS) * Positive and Negative Affect Schedule (PANAS) * Harmony in Life Scale (HILS) * Ten Item Personality Inventory (TIPI) * Honesty-Humility Scale (HH) Extended Follow-Up Phase (Week 24-52) 9-Month Follow-Up (Week 36) * Eating Disorder Examination Questionnaire (EDE-Q ) * Columbia-Suicide Severity Rating Scale (C-SSRS) * Brief Psychiatric Rating Scale - Extended (BPRS+) * AE/SAE monitoring * BMI, blood pressure, ECG * Fasting glucose, U-tox 12-Month Final Follow-Up (Week 52) * Eating Disorder Examination Questionnaire (EDE-Q ) * Columbia-Suicide Severity Rating Scale (C-SSRS) * Brief Psychiatric Rating Scale - Extended (BPRS+) * Patient Health Questionnaire (PHQ-9) * Generalized Anxiety Disorder scale (GAD-7) * Ten Item Personality Inventory (TIPI) * Meaningful Life Experience Rating (MLE). * AE/SAE monitoring * BMI, blood pressure, ECG * Fasting glucose, U-tox Participants who show signs of psychological or physical deterioration at any point during the study between follow-ups are instructed to contact the research team at any time and will be offered additional assessment and support. Description of Psilocybin Administration and Psychological support Psychological support includes a non-directive preparation and integration pre- and post-dosing sessions according to protocol manual, alongside support for the patient on the dosing session day. The study follows the guidelines for safe research with psychedelics. Preparation session will include psychoeducation of the effects of psilocybin, breathing techniques, getting to know the two therapists (one male and one female). A standardized preparation script will ensure consistency across participants. The two integration sessions following each dosing session last 1-2 h and focus on exploring the session's effects and offer support in integrating the experience. Integration sessions will include structured discussions about insights gained, with therapists facilitating connections between the experience and the participant's therapeutic goals. The therapists couple will contain at least one licensed healthcare personnel (psychologist, nurse, physiotherapist or physician). The assistant therapist can be non-licensed healthcare personnel experienced with the anorexia nervosa population, such as a healthcare assistant. All psychological support therapists must have done all specific 5-day training in the psiAN manual. Dosing session day The dosing session, lasting 6-8 hours, is supported by the therapists introduced during preparation sessions. The psilocybin's acute effects persist for 4-6 hours, recorded via video and audio. Participants, lie down with an optional eye mask, experience the session in a comfortable room with a pre-selected music playlist, respecting individual preferences. Therapists provide support and guidance if requested but with minimal psychotherapeutic focus. Therapists will follow pre-established protocols for de-escalation and grounding in case of distressing experiences. Parents are introduced at the session's end with participant approval. During the dosing session, a medically trained study doctor will be available, equipped for emergencies in the unlikely event of serious adverse events related to psilocybin risks. Biological Sampling Procedures Blood samples will be collected for the analysis of Brain-Derived Neurotrophic Factor (BDNF) as the primary biomarker and for tolerance and safety measurements. Additionally, we aim to collect one tube of additional whole blood per occasion for future analysis. BDNF samples will be taken at five key time points: (1) before treatment (baseline), (2) and (3) at first integration session after Psilocybin 25mg dosing, (4) at 8 weeks, and (5) during the 6-month follow-up. This ensures comprehensive longitudinal data collection. Blood samples of glucose, kidney and liver status will be measured at the same time points as above for safety and tolerance reasons. None of these blood samples are collected or stored. All blood samples are done by a standard peripheral venous sampling method performed by a nurse at the research facility at the university hospital clinic for psychiatry at Baravägen 1, Lund. Procedures will be implemented to minimize discomfort during blood collection, such as using pediatric needles for younger participants when necessary. Blood collection and processing will follow standardized protocols to ensure sample integrity. Discontinuation from the Clinical Trial A participant will be discontinued entirely from the clinical trial (i.e., all further participation and follow-up will end) only under the following condition: Withdrawal of informed consent at any time, for any reason, without the need to justify. Discontinuation from the Intervention (Dosing) Participants may be discontinued from the intervention (i.e., psilocybin administration - first or second dose), without being excluded from the trial. Participants will be encouraged to continue with follow-up assessments unless they explicitly withdraw consent. This approach allows for continued safety and data collection in accordance with the intention-to-treat principle. Reasons for discontinuing intervention may include: * Development or discovery of exclusion criteria after inclusion (e.g. new psychiatric diagnosis, pregnancy). * Emergence of a serious adverse event (SAE) or medical condition that, in the investigator's judgment, makes continued treatment unsafe. * Initiation of treatment with prohibited medication according to protocol. * Failure to adhere to critical aspects of the study protocol (e.g. repeated missed visits, non-compliance with preparation or safety procedures). * Investigator decision in consultation with the medical monitor. The reason for discontinuation will be documented. Participants will be offered a final follow-up visit when appropriate. Non-compliance to fMRI will not lead to study exclusion nor discontinuation of the intervention. Methods for Measurement of Endpoints for Clinical Safety Continuous clinical safety monitoring will be performed by licensed healthcare professionals at Lund University Hospital throughout the trial, from baseline to the final 12-month follow-up. The safety evaluations cover physical, biochemical, and psychological parameters relevant to psilocybin administration. Measurements for assessing clinical safety will include blood samples of hepatic and renal function, glucose, urine toxicology, cardiovascular parameters, assessment of suicidality, assessment of mental health symptoms and and assessment of Adverse Events/Serious Adverse Events/Suspected Unexpected Serious Adverse Reactions (AE/SAE/SUSARs). Assessment of Adverse Events Participants are instructed to contact the research team during daytime hours for urgent concerns. Outside of study hours, they are directed to seek emergency services. Events will be assessed by the clinical team for causality, intensity, and seriousness and potential relationship to treatment (psilocybin 25mg). The investigator is responsible for determining whether there is a causal relationship between the AE/SAE and use of the investigational medicinal product. Consideration should be given to whether there is a reasonable possibility of establishing a causal relationship between the adverse event and the investigational medicinal product based on the analysis of the available evidence. All AE can be categorized as either likely related, possibly related, unlikely related or not related. Those AEs which are suspected of having a causal relationship to the investigational medicinal product will be followed up until the subject has recovered or is well taken care of and on the way to good recovery. Each adverse event shall be classified by an investigator as mild, moderate or severe. Follow-up of Adverse Events Follow-up visits will be scheduled for all participants experiencing AEs to ensure resolution and ongoing safety. Participants with unresolved AEs at the end of the trial will be monitored until resolution or stabilization. For SAEs, additional follow-ups will be scheduled at least every two weeks until resolution. The frequency can be changed by the Safety Review Committee or Principal Investigator. Procedures in Case of Emergencies and Overdose Emergency protocols are in place, including immediate medical care and monitoring. In case of an overdose, the participant will be transferred to an emergency facility. Emergency kits, including benzodiazepines for anxiety or seizures, will be available during all dosing sessions. Pregnancy Management Participants who can become pregnant must use a highly effective form of contraception during the study and for two months after the last psilocybin dose. Approved methods include hormonal contraception, IUDs, sterilization, vasectomized partner, or abstinence. Urine pregnancy tests will be done at screening, before each psilocybin session, and as needed during follow-up. Psilocybin's effects on pregnancy are unknown. To reduce possible risks, strict contraception and testing protocols are required. Interim Analysis Following two administration sessions of 25mg psilocybin, a panel of three senior psychiatrists, who are not part of the research team, will conduct an evaluation of the safety data and adherence to the protocol. This analysis will be repeated after a total of 20 psilocybin administrations have been completed. After 25 patients over 18 have been through dosing sessions, patients 16-17 will be recruited. Methods for Measurement of Endpoints for Clinical Efficacy Composite Relapse Endpoint: BMI Decrease: Measured at baseline, 8 weeks, and 6 months using calibrated equipment and standardized protocols. Hospitalization Data: Collected through patient reports and confirmed by medical records. Symptom Deterioration: Assessed using validated tools such as the EDE-Q6.0 and clinical interviews conducted by trained staff. Clinical Intervention Use: Recorded in patient files, including initiation of new treatments during follow-up. Statistics Analysis Population Both the Intention-to-treat (ITT) and per-protocol populations will be analyzed. ITT analysis will include all participants who are randomized, regardless of protocol adherence, to ensure generalizability. Per-protocol analysis will focus on participants who completed the study as planned, ensuring the assessment of efficacy under ideal conditions. Statistical Analyses Primary Baseline Analyses: The primary analyses will involve descriptive statistics for demographic and baseline characteristics, ensuring comparability across groups, and control for follow-up measurements. Primary Endpoints analysis We will analyze differences in the number of participants and severity experiencing adverse event/serious adverse event (AE/SAE) between the groups standardized forms for AE/SAE capturing: Event description, Start and end dates, Severity (e.g., mild, moderate, severe), Relatedness to intervention (assessed by safety review committee), Action taken. The primary statistical methods will be: Descriptive Frequencies and Percentages. Comparing Proportions (Most Common for "Incidence") (Chi-squared test (or Fisher's Exact Test): Fisher's exact test is preferred for small cell counts (\ 1 would indicate a higher risk in the intervention group. Comparing Severity and Relatedness is assessed with Mann-Whitney U test or Student t-test to compare severity distributions between groups. Secondary Endpoints: For secondary endpoints (e.g., changes in fMRI connectivity, BDNF, rating scales), group comparisons, including t-test, Analysis of Variance (ANOVA), and Repeated Measures ANOVA will be utilized. When controlling for variables such as individual differences, ANCOVA or Multivariate Analysis of Covariance (MANCOVA) will be utilized. Principal component analysis (PCA) or independent component analysis (ICA) may be applied to identify patterns in fMRI data. Endpoints include longitudinal between- and within-person analyses. When dichotomous (binary) outcome variables: Binary outcomes (e.g., remission, response rates) will be analyzed using logistic regression models, adjusting for baseline characteristics such as age, baseline BMI, and symptom severity. The odds ratios and 95% confidence intervals will be reported. When continuous (dimensional) variables (e.g., BMI, BDNF levels, cognitive flexibility) will be analyzed using linear mixed-effects models, and regression models of various types. Other: Exploratory Subgroup Analyses: Exploratory subgroup analyses will assess treatment effects across different strata (e.g., age groups, baseline severity) using interaction terms in regression models or stratified analyses to explore heterogeneity in treatment responses. Other: Sensitivity Analyses: Sensitivity analyses will address missing data using methods such as multiple imputation or maximum likelihood estimation. These methods ensure robustness of the findings by accounting for the potential impact of missing data on primary and secondary outcomes. Adjustment of Significance and Confidence Interval A Bonferroni correction or false discovery rate (FDR) adjustment will be applied for multiple comparisons to control Type I error. Results will be presented with 95% confidence intervals, and significance will be set at a two-tailed p-value of \

topic_tags:
Anxiety,Eating Disorders,Neuroplasticity,Brain Imaging,Mechanism of Action,Receptor Pharmacology,Default Mode Network,Consciousness,Biomarkers,Aging,Personality Change,Emotional Processing,Mystical Experience,Clinical Trial,Randomized Controlled Trial,Review Article,Animal Study,Adolescents,Healthcare Workers,Safety,Adverse Events,Toxicity,Drug Interactions


title: The Neurobiological Effect of 5-HT2AR Modulation
authors: Gitte Moos Knudsen
journal: ClinicalTrials.gov
publication_date: 2024-12-15
source_url: https://clinicaltrials.gov/study/NCT03289949
keywords: Basic Science, Psilocybine, Psilocybin, Ketanserin, Ketensin, RECRUITING
substance_tags: psilocybin
topic_tags: Brain Imaging,Mechanism of Action,Receptor Pharmacology,Aging,Healthy Volunteers
study_type: Other
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:28
last_checked: 2026-07-01 11:22:34
raw_json: {"nct_id":"NCT03289949","overall_status":"RECRUITING","phase":["PHASE1"]}
abstract:
The investigators wish to investigate neurobiological effects of serotonin 2A receptor modulation in healthy volunteers, contrasting effects of an agonist (psilocybin) and an antagonist (ketanserin). Magnetic resonance imaging (MRI) and positron emission tomography (PET) will be used as neuroimaging tools. This project applies an experimental medicine strategy coupled with human functional and molecular neuroimaging to elucidate the effects of 5-HT2A receptor (5-HT2AR) modulation on brain function and mood in healthy individuals. We compare psilocybin (5-HT2AR agonist) and ketanserin (5-HT2AR antagonist) effects on brain function to identify neural mechanisms mediating the clinical effects of psilocybin and, more broadly, to establish this comparative strategy as a pathway for delineating pharmacological effects on the brain in humans.


title: Effects of Psilocybin and Spiritual Practice on Persisting Changes in Attitudes and Behavior
authors: Johns Hopkins University
journal: ClinicalTrials.gov
publication_date: 2016-02-23
source_url: https://clinicaltrials.gov/study/NCT00802282
keywords: Healthy, psilocybin, Intensity of support for spiritual practice, Number of sessions, COMPLETED
substance_tags: psilocybin
topic_tags: Spirituality,Healthy Volunteers
study_type: Other
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:28
last_checked: 2026-07-01 11:22:34
raw_json: {"nct_id":"NCT00802282","overall_status":"COMPLETED","phase":["PHASE1"]}
abstract:
This study will investigate the effects of psilocybin dose and the frequency and intensity of support activities for spiritual practice (e.g., meditation) on a battery of attitudinal and behavioral outcome measures in 75 healthy volunteers who are interested in pursuing a program of spiritual practices with the intention applying spiritual insights and knowledge to everyday life. After screening and study enrollment, each volunteer will be assigned to one of five groups that vary in dose, frequency and intensity of support for spiritual practice, and number of psilocybin sessions (either 2 or 3 sessions). The psilocybin dose manipulation will be double-blind. Volunteers will be told that in each of sessions 1, 2, and 3, he/she could receive a very low, low, moderate, moderately high, or high dose of psilocybin. They will be told that each participant will receive 2 or more dose levels of psilocybin over the 2 or 3 sessions, and all participants will have one or more sessions in which he or she receives a moderately high or high dose of psilocybin. The duration of each volunteer's participation will be approximately 6 to 8 months. Each volunteer will receive several hours of preparation with the study guides in the month prior to the first psilocybin session; the first two sessions will be separated by one month. Various measures will be assessed before, during and immediately after sessions. A battery of longitudinal measures will be evaluated immediately after study enrollment, 3 weeks after the second psilocybin session, and 4 months after the second psilocybin session (6 months after study enrollment). For purposes of controlling expectancies through the 6 month follow-up evaluation, volunteers and guides will not know which volunteers or how many volunteers will be scheduled for a third session.


authors: Apex Labs Ltd.
journal: ClinicalTrials.gov
publication_date: 2023-11-28
source_url: https://clinicaltrials.gov/study/NCT06141876
keywords: Post-traumatic Stress Disorder, Depression, APEX-002-A02, psilocybin, Placebo, UNKNOWN
substance_tags: psilocybin
topic_tags: Depression,Anxiety,PTSD,Addiction,OCD,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 11:22:34
raw_json: {"nct_id":"NCT06141876","overall_status":"UNKNOWN","phase":["PHASE2"]}
title:
A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability and Efficacy of Psilocybin-Assisted Psychotherapy in Treating Severe Depression Among Adults With Post-Traumatic Stress Disorder (PTSD).

abstract:
Post-Traumatic Stress Disorder (PTSD) is a mental disorder that may develop in people who have been exposed to a traumatic event, including actual or threatened death, serious injury, or sexual violence. Exposure to a traumatic event is defined as directly experiencing the event, learning about the event, or repeated exposure to details of the event. PTSD is often accompanied by other psychiatric and physical comorbidities, both of which are associated with elevated healthcare costs. Depression, psychosis and suicide rates are consistently reported in greater proportion of PTSD patients. Despite the overwhelming impact of PTSD and comorbid depression, there is a shortfall of effective treatments with few side effects that target the broad range of symptoms, including depression. Psilocybin has been studied for the treatment of depression, anxiety, tobacco and alcohol use disorders, obsessive-compulsive disorder, end of life depression and anxiety, demonstrating safety and efficacy for a variety of indications, with no significant adverse events occurring during the course of treatment and follow-up. Notably, in a participant group distinguished by long-standing, moderate to severe major depressive disorder, two doses of psilocybin-assisted therapy were found to be as effective in antidepressant effects as 6 weeks of daily escitalopram, a commonly used SSRI. Promising results found in these studies have led to psilocybin recently receiving breakthrough designation from the US FDA for its potential therapeutic effect in the treatment of depression. Based on previous research, psilocybin has demonstrated a favorable safety profile and has shown preliminary efficacy against depression as well as other symptoms that typically affect patients with PTSD. Unlike traditional SSRIs which are associated with treatment-resistance and addiction, psilocybin requires few doses to improve a wide-range of symptoms and has not been linked with physical dependence. Furthermore, the effect of other psychedelics can vary greatly and may potentially exacerbate existing conditions.


authors: King's College London
journal: ClinicalTrials.gov
publication_date: 2026-04-16
source_url: https://clinicaltrials.gov/study/NCT05723276
keywords: Functional Neurological Disorder, Psilocybin, ACTIVE_NOT_RECRUITING
substance_tags: psilocybin
topic_tags: Brain Imaging,Default Mode Network,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 11:22:34
raw_json: {"nct_id":"NCT05723276","overall_status":"ACTIVE_NOT_RECRUITING","phase":["NA"]}
title:
Probing the Functional Magnetic Resonance Imaging Response to Psilocybin in Functional Neurological Disorder (PsiFUND)

abstract:
The goal of this study is to learn about the brain network response in people who have functional neurological disorder who are administered with a single dose of the psychedelic psilocybin with therapeutic support. The main question it aims to answer is: Can the default mode network, a brain network thought to be relevent in FND, be modified by the administration of psilocybin based on functional magnetic resonance imaging before and after the dose?


authors: University of Helsinki
journal: ClinicalTrials.gov
publication_date: 2017-12-20
source_url: https://clinicaltrials.gov/study/NCT03380442
keywords: Severe Depression, Psilocybin, Ketamine (Ketalar), UNKNOWN
substance_tags: psilocybin
topic_tags: Depression,Brain Imaging,Mechanism of Action,Biomarkers,Aging,Emotional Processing
study_type: Other
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:28
last_checked: 2026-07-01 11:22:34
raw_json: {"nct_id":"NCT03380442","overall_status":"UNKNOWN","phase":["PHASE2"]}
title:
Psilocybin and Depression - Assessing the Long-term Effects of a Single Administration of Psilocybin on the Psychiatric Symptoms and Brain Activity of Patients With Severe Depression

abstract:
The main aim of the study is to investigate the possible long-term therapeutic effects of psilocybin on the symptoms of severe depression, as well as the brain mechanisms underlying these changes. Depression severity is assessed before and after (i.e., 1 week, 3 months and 6 months after) a single dose of psilocybin and compared to respective scores of a group receiving an active placebo, ketamine. Brain activity (using functional magnetic resonance imaging) is measured before and one week after drug administration in order to determine whether changes in brain networks related to emotional and self-referential processing correlate with any observed changes in depression scores. Further, blood samples will be obtained from the participants and analyzed in order to reveal gene expression and molecular level correlates underlying rapid antidepressant effects, and to identify biomarkers that predict treatment outcome.


authors: University of Calgary
journal: ClinicalTrials.gov
publication_date: 2024-05-06
source_url: https://clinicaltrials.gov/study/NCT05995769
keywords: Alcohol Use Disorder, Alcoholism, Psilocybin, magic mushrooms, PEX010, RECRUITING
substance_tags: psilocybin
topic_tags: Addiction,Brain Imaging,Mechanism of Action,Aging,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 11:22:34
raw_json: {"nct_id":"NCT05995769","overall_status":"RECRUITING","phase":["PHASE2"]}
title:
Mechanisms Supporting Psilocybin-assisted Psychotherapy for Alcohol Use Disorder: A Randomized, Controlled Clinical Trial

abstract:
The aim of this study is to determine if a single dose of psilocybin administered with motivational enhancement therapy (MET) can reduce heavy drinking in patients with an alcohol use disorder (AUD). The primary objective of this study is to determine if psilocybin administered with a standardized psychotherapeutic intervention, motivational enhancement therapy (MET), can reduce heavy drinking in a patient population with an alcohol use disorder (AUD). Patients with an AUD will be randomly allocated to either a high dose (25mg; active treatment) or a low dose (1mg; active control) psilocybin arm. All participants will receive 5 sessions of MET, starting at 24hrs post-dosing. Heavy drinking will be assessed as percent heavy drinking days using the Time Line Follow Back (TLFB) at baseline and 1-, 4-, and 12-weeks post-dosing. A total of 128 male and female patients between the ages of 22-65 with a moderate to severe AUD diagnosis will be recruited from the community. Participants will undergo a thorough screening procedure and eligible participants will be randomly allocated to the high (N=64) or low (N=64) psilocybin doses. All participants will complete a baseline session consisting of clinical, behavioral, and neuroimaging measures. Following the single dosing session, participants will complete 5 weekly MET sessions. Neuroimaging measures will be assessed again at 1-week post-doing. Clinical and behavioral outcomes will be measured at 1-, 4-, and 12-weeks post-dosing


authors: Emory University
journal: ClinicalTrials.gov
publication_date: 2025-07-22
source_url: https://clinicaltrials.gov/study/NCT05506982
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 11:22:34
raw_json: {"nct_id":"NCT05506982","overall_status":"COMPLETED","phase":["PHASE1"]}
title:
The Safety, Feasibility, and Acceptability of Psilocybin Combined With Multidisciplinary Palliative Care in Demoralized Cancer Survivors With Chronic Pain (P-PC)

abstract:
This phase I trial evaluates the side effects of psilocybin and how well it works under supportive care conditions in cancer survivors living with demoralization and chronic pain. Cancer patients often experience demoralization, which is characterized by feelings of hopelessness, loss of meaning, and existential distress. Psilocybin psychotherapy, together with multidisciplinary palliative and supportive care, may help treat the anxiety, depression, and chronic pain felt by cancer survivors - defined here as cancer patients from time of diagnosis through the end-of-life. PRIMARY OBJECTIVE: I. To determine the safety, feasibility, and acceptability of a single administration of 25 mg psilocybin (psilocybin) provided under supportive conditions with multidisciplinary palliative care support (P-PC) in adult cancer survivors living with concurrent demoralization and chronic pain. EXPLORATORY OBJECTIVE: I. To evaluate for changes in demoralization, anxiety, depression, quality of life, pain, other symptoms, mysticism, awe, post-traumatic growth, social isolation, and psychosocial functioning from baseline to end-of-treatment to 3.5-month follow up. OUTLINE: Patients receive psilocybin orally (PO) and undergo observation for up to 8 hours on day 14. After completion of study intervention, patients are followed up on days 15, 21, 42, 56, and 98.

keywords:
Hematopoietic and Lymphoid Cell Neoplasm, Malignant Solid Neoplasm, Psilocybin, CY-39, Indocybin, Psychotherapy, talk therapy, Quality-of-Life Assessment, Quality of Life Assessment, Questionnaire Administration, COMPLETED

topic_tags:
Depression,Anxiety,End-of-Life Distress,Chronic Pain,Mystical Experience,Clinical Trial,Cancer Patients,Safety,Adverse Events


title: A Phase 1 Study Comparing the Pharmacokinetics and Safety of Intravenous and Oral Psilocybin
authors: University of Wisconsin, Madison
journal: ClinicalTrials.gov
publication_date: 2023-05-14
source_url: https://clinicaltrials.gov/study/NCT05467761
keywords: Healthy, Oral Psilocybin, IV Psilocybin, WITHDRAWN
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 11:22:34
raw_json: {"nct_id":"NCT05467761","overall_status":"WITHDRAWN","phase":["PHASE1"]}
abstract:
The purpose of this research study is to compare an oral dose of psilocybin and an intravenous (IV) infusion of psilocybin to assess differences in how the drug is absorbed by the body, the psychedelic experience, and any side effects when taken by healthy adult participants. Participants can expect to be in the study for approximately 12 weeks. Psilocybin, when delivered to screened and prepared participants in a controlled environment, has shown strong evidence of positive effects in treating cancer-related psychiatric distress, depression and anxiety, treatment-resistant depression, and nicotine or alcohol addiction. Psilocybin therapy is generally safe and well-tolerated when conducted under controlled conditions. Psilocybin is very rapidly transformed to the active metabolite psilocin, which is considered the active agent from psilocybin administration. Oral and IV psilocybin are expected to have similar pharmacokinetic and psychedelic effects, as well as safety profiles, while IV psilocybin will achieve more consistent blood levels than are possible with oral psilocybin.

topic_tags:
Depression,Anxiety,Addiction,Pharmacology,Clinical Trial,Cancer Patients,Treatment-Resistant Depression,Safety,Adverse Events


title: Psilocybin for Enhanced Analgesia in Chronic nEuropathic PAIN
authors: Unity Health Toronto
journal: ClinicalTrials.gov
publication_date: 2025-03-29
source_url: https://clinicaltrials.gov/study/NCT06731335
keywords: Chronic Neuropathic Pain, Pain Management, Psilocybin, Psychotherapy, Active Placebo, RECRUITING
substance_tags: psilocybin
topic_tags: Chronic Pain,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 11:04:28
last_checked: 2026-07-01 11:22:34
raw_json: {"nct_id":"NCT06731335","overall_status":"RECRUITING","phase":["PHASE2"]}
abstract:
This is a feasibility study to examine the use of use of Psilocybin (magic mushrooms) to alleviate pain in chronic neuropathic pain. While theoretical mechanisms demonstrate promise, there is no clinical evidence. This vacuum of clinical evidence has been occupied by a "psychedelic hype bubble" with media communications touting psychedelics as a 'miracle cures'. The mismatch between evidence and perception creates an urgent need for RCT to fill this significant gap. This trial aims to address this gap by conducting a pilot trial assessing the feasibility, tolerability, and preliminary efficacy of psilocybin for chronic neuropathic pain to inform a future larger, multi-centre study. The purpose is to conduct a randomized control double-blinded trial of psilocybin and active placebo (dextromethorphan). At this time, the aim of the trial is to recruit 30 participants from St. Michael's Hospital, to learn whether it will be feasible to plan a larger study in the future. Brief title PEACE-PAIN Trial Indication Adult patients suffering from chronic neuropathic pain Condition(s) of focus of study Moderate-to-severe chronic neuropathic pain Number of participants 30 Primary outcome Feasibility (recruitment success, consent rate, adherence, patient withdrawal, missing data, adverse outcomes) Secondary outcome Change in pain intensity and pain interference Study design Study type: An intervention trial Allocation: Randomized Intervention model: 2-Arm Parallel Group Primary purpose: Feasibility Phase: Phase II Masking Participants, all study team including outcome assessors Test Products, Dose, and Mode of Administration Treatment arm: Psilocybin 25mg + placebo PO single dose plus psychological support Placebo arm: Dextromethorphan 400mg PO single dose plus psychological support Follow-Up Days: 1, 7, 14, 30, and 90


title: A Pilot Mechanistic Study of Psilocybin-Assisted Therapy as a Treatment for Depression
authors: Washington University School of Medicine
journal: ClinicalTrials.gov
publication_date: 2026-05-19
source_url: https://clinicaltrials.gov/study/NCT07582120
keywords: Depression, Psilocybin (Usona Institute), NOT_YET_RECRUITING
substance_tags: psilocybin
topic_tags: Depression,Biomarkers,Psychological Flexibility,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 11:22:34
raw_json: {"nct_id":"NCT07582120","overall_status":"NOT_YET_RECRUITING","phase":["PHASE2"]}
abstract:
Depression is the leading cause of disability worldwide, affecting an estimated 300 million people. Despite available treatments, response rates remain modest, and treatment resistance is common. Novel treatments are needed that act rapidly, produce lasting effects and work differently than existing antidepressants. In clinical trials, psilocybin has shown promise as a treatment for depression due to its rapid onset of antidepressant effects and sustained benefits. This study will use MRI scanning of the brain and other biological measures (biomarkers) to investigate how psilocybin affects brain activity and psychological flexibility before, during, and after receiving psilocybin in participants with depressive symptoms.


title: Psilocybin-Assisted Therapy for Prolonged Grief
authors: University of Virginia
journal: ClinicalTrials.gov
publication_date: 2026-06-22
source_url: https://clinicaltrials.gov/study/NCT06724289
substance_tags: psilocybin
topic_tags: Brain Imaging,Aging,Spirituality,Mystical Experience,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 11:22:34
raw_json: {"nct_id":"NCT06724289","overall_status":"RECRUITING","phase":["EARLY_PHASE1"]}
abstract:
The primary purpose of this study is to explore the feasibility of conducting a clinical trial on the effects of psilocybin for individuals with prolonged grief disorder (PGD). The study aims to investigate whether a single dose of 25 mg psilocybin can reduce the symptoms of grief and trauma associated with Prolonged Grief Disorder (PGD). It is hypothesized that psilocybin will significantly reduce the symptoms of PGD, and that the treatment will facilitate subjective mystical, spiritual, or insightful experiences, which in turn may contribute to the alleviation of grief and trauma symptoms. Neuroimaging will be used to help researchers better understand the relationship between grief and brain functions, comparing pre- and post-dose scans. Participants will undergo two MRI (magnetic resonance imaging) where they are asked to look at images (this is called a functional MRI or fMRI).

keywords:
Prolonged Grief Disorder, Psilocybin 25 mg, Functional Magnetic Resonance Imaging (fMRI), RECRUITING


title: Psilocybin for Treatment of Alcohol Use Disorder: a Feasibility Study
authors: Anders Fink-Jensen, MD, DMSci
journal: ClinicalTrials.gov
publication_date: 2024-07-11
source_url: https://clinicaltrials.gov/study/NCT04718792
keywords: Alcohol Use Disorder (AUD), Psilocybin, ACTIVE_NOT_RECRUITING
substance_tags: psilocybin,psilocin
topic_tags: Addiction,Pharmacology,Receptor Pharmacology,Safety,Adverse Events
study_type: Other
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:28
last_checked: 2026-07-01 11:22:34
raw_json: {"nct_id":"NCT04718792","overall_status":"ACTIVE_NOT_RECRUITING","phase":["PHASE2"]}
abstract:
The purpose of this project is to assess the feasibility and safety of administering a single dose of psilocybin to patients diagnosed with alcohol use disorder (AUD). In addition the investigators will establish the pharmacokinetic properties of the active metabolite psilocin. This is the first step in a research project that has the overall aim to evaluate the efficacy of a single administration of psilocybin as an intervention for treatment of AUD. The investigators will evaluate the feasibility and safety of administering psilocybin to 10 patients diagnosed with AUD. Following informed consent, patients will be screened for eligibility as per in- and exclusion criteria and baseline values will be recorded as per outcome measures. All patients will receive a single administration of 25 mg of psilocybin. As per safety guidelines patients will be monitored the entire dosing session by study staff familiar with the psychedelic effects of psilocybin. In addition, the patients will meet before and after the dosing session with a psychologist connected to the study for preparation and post-session debriefing, respectively. During dosing session, the investigators will collect blood plasma psilocin levels in order to establish pharmacokinetics and an estimated brain 5-HT2AR occupancy. When the effects of psilocybin subside, the investigators will ask the patients to fill out questionnaires encapsulating the psychedelic experience. One week after drug administration the patients are required to meet for an end-of-study assessment of outcome measures including adverse events.


authors: NWTraumatherapies
journal: ClinicalTrials.gov
publication_date: 2022-11-15
source_url: https://clinicaltrials.gov/study/NCT05042466
keywords: Trauma, Nervous System, Trauma, psilocybin, UNKNOWN
substance_tags: psilocybin
study_type: Other
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:28
last_checked: 2026-07-01 11:22:34
raw_json: {"nct_id":"NCT05042466","overall_status":"UNKNOWN","phase":["PHASE1"]}
title:
NW Trauma Therapies, Chronic Illness of Chronic Depression, PTSD, MS, HIV, and SARS-CoV-2, Long Haulers Syndrome. Treatment of Unregulaaible Trauma by the Treatment of Enhanced Micro Dosing the Levels of 0.15, Thru 0.33, With a Maintenance Dose of 1 Gram Per Month for Neural Pathway Increase of Non Synthesized Psilocybin, Using the Actual Plant to Regulate the Highjacked Nervous System.

abstract:
The on-boarding of unregulatable trauma in the United States has reached 20%, which is 1/5 of the population. A population of this magnitude, by definition has now reached an epidemic classification. The population with chronic illness as stated: PTSD, Chronic Depression, MS, HIV, and SARS-CoV-2- Long Haulers Syndrome. These chronic conditions/illnesses many lead to death and are often the cause or perpetuate unregulated trauma and create an unstable population. Psychiatrists have testified before congress that the SSSRI medications are not fully functional cures and are not working for patients. Enchanced Psilocybin micro-dosing at the levels of 0.15g. ranging to 0.33g. every other day an 0.50g. for monthly maintenance of neural pathway production is proving to shave back the highjacked nervous system, thus stopping or rerouting the ruminating neurotransmitters, by rerouting thru new neural pathways. The body has a additional natural pathway in place then to decrease/stop these thoughts by have open pathways to process the thought differently. Serotonin is a neurotransmitter and which is the most famous of all the neurotransmitters. Serotonin is very similar in its compound structure to the plant medicine family of psilocybin, serotonin and psilocybin work very similarly with the 5h2A receptor in the human cortex ( the outer cortex of the brain ). Enhanced Microdosing of psilocybin at the levels of 0.15 to 0.33 and of 1 gram to 1.5 grams monthly for maintenance of the newly opened neural pathways is postulated to be a mental health game changer. Psilocybin helps shave back the highjacked nervous system which is a condition known as the diagnosis (SSD) Somatic Symptom Disorder. This research is believed accurate by proof on previous studies to process the subconscious held in the subconscious and shave back the somatic feelings resulting from the trauma of the individuals who have on-boarded chronic disease(s) of Trauma,PTSD, Unregulated Chronic Depression, MS, Cancer, HIV, and SARS-CoV-2- Long Haulers Syndrome. Patients will work with a team: The Administrator Of Study, participants will be onboarded into the study by a Psychiatrist, Therapist LCPC, Micro Dosing Advisor/On-Boarding Provider, going forward referred to as a PMOP ( PLANT MEDICINE ON-BOARDING PROVIDER. The PMOP will administrate, chart dosing and file reports with the Psychiatrist, General Provider, Psychologist, or the LCPC Therapist. Adding a PMOP to Western Medicine could be the key to making treatment available at a functional cost. The dosage will be ( enhanced micro-dosing which is 1 gram to 1.5 grams of psilocybin every other day for 5 days then moving into a M/W/F dose ranging in the enhanced micro-dose levels of 0.15G. thru 0..33 for 8 weeks. Patients will be accepted in the study they must present with one of the following diagnosed conditions, chronic illness' of Trauma, PTSD, Unregulated Chronic Depression, MS, HIV, Cancer, or SARS-CoV-2- Long Haulers Syndrome. As participants with unregulated trauma can tend to have a severely compromised un-functional compromised immune system. This compromised low functioning compromised immune system creates additional health crisis and can cost a great deal of money for the patients and the healthcare system. As testified to congress, the SSRI's are not fully able to manage the on boarding of severe trauma resulting often in PTST/Trauma, these pharmaceuticals tend to become in effective for treatment within 6 months to a year. The SSRI's and pharmaceuticals available for treatment currently have a success rate of 35 %. These diagnosis' of mental compromise are currently being managed at great human cost and financial cost for a decade or more for many patients. Working in conjunction with the General Provider, Psychiatrist, Psychologist, and LCPC Therapist, with a PMOP ( Enhanced Micro Dosing Provider),The PMOP On-Boarding Provider will tailor the dose of plant medicine which this study postulates will result in a positive treatment and will result in improved (Quality of Life) and in the cases of terminal illness, result in (Dying Well)" A mind without rumination. As Stated, this study is looking for evidence this Plant Medicine Psilocybin would become a path to shave back the SSRI's and treat with dosing of of M/W/F of enhance Microdosing at the levels of 0.15g. thru 0.33G. The Monthly dose of 1 to 1.5 grams of Plant Medicine for maintenance of the increase in newly opened neural pathways. This Study will introduce Non Synthetic Psilocybin every other day for 8 weeks, and the 1G to 1.1.5 G once time per month. The on-boarding of unregulatable trauma in the United States has reached 20%, which is 1/5 of the population. A population of this magnitude, by definition has reached an epidemic classification. The population with chronic illness as stated: Trauma, PTSD, Chronic Depression, MS, Caner, HIV, and SARS-CoV-2- Long Haulers Syndrome, these conditions are severe and the treatments are often not effective. These chronic illnesses which can result in unregulated trauma and create an unstable portion of the population. Psychiatrists have testified before congress that the SSRI's medications are not functional cures and are often not working for patients. Psilocybin micro-dosing by many studies is proving to shave back the highjacked nervous system, stopping or rerouting the neural pathways lessening or stopping the ruminating neurotransmitters. This is the 1st study to support the treatment in the Enhanced Microdosing levels in the range of 0.15g. to 0.33g, and adding a dose of 1g. to 1.5 g. monthly for maintence. The body has a natural path to stop these thoughts by a neurotransmitter called serotonin This famous neurotransmitter Serotonin, is very similar to the plant medicine family of psilocybin, Serotonin and Psilocybin work very similarly with the 5h2A receptor in the human cortex ( the outer cortex of the brain ). Enhanced Microdosing of 0.15 to 0.33 with month dose of 1 gram to 1.5 grams of psilocybin is postulated to shave back and reroute the highjacked nervous system known as the diagnosis (SSD) Somatic Symptom Disorder. This research is believed accurate by proof on previous studies to reverse back the somatic feelings resulting from the trauma of the individuals who are on boarding chronic diseases of PTSD, Chronic Depression, MS, HIV, Cancer, and SARS-CoV-2- Long Haulers Syndrome. Ross Allison Administrator NPI#1437519899

topic_tags:
Depression,PTSD,End-of-Life Distress,Mechanism of Action,Receptor Pharmacology,Microdosing,Immune Function


authors: University of Washington
journal: ClinicalTrials.gov
publication_date: 2025-10-13
source_url: https://clinicaltrials.gov/study/NCT06644170
substance_tags: psilocybin
topic_tags: Anxiety,Receptor Pharmacology,Wellbeing,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 11:22:34
raw_json: {"nct_id":"NCT06644170","overall_status":"COMPLETED","phase":["PHASE1"]}
title:
A Phase 1 Study of a Second Psilocybin Group Retreat for Partial Responders With Anxiety Associated With Metastatic Cancer

abstract:
This phase I trial tests the safety and side effects of a second episode of psilocybin-assisted group therapy and how well it works in treating anxiety and distress in patients with cancer that has spread from where it first started (primary site) to other places in the body (metastatic) and had a partial response to their first retreat. Up to 50% of patients with metastatic cancer have clinically significant anxiety and unaddressed anxiety and distress may add to the suffering caused by cancer itself. Psilocybin, a psychedelic drug, is made using an extract from the psilocybe mushroom, also known as "magic mushrooms". Psilocybin binds to serotonin receptors (natural body chemicals that control moods) on brain cells producing intense changes in mood, including anxiety. This may change perceptions and patterns of thinking in ways that may decrease anxiety. Group therapy may reduce stress and improve the well-being and quality of life of patients with metastatic cancer. A second episode of psilocybin-assisted group therapy may be safe, tolerable and or effective in treating anxiety and distress in partial responders with metastatic cancer. OUTLINE: Patients receive psilocybin orally (PO) with optional booster dose on day 0. Patients attend an individual prep visit on day -1 and an individual integration visit on day 1. Patients also attend group preparation visits on days -14, -7 and -1 and group integration visits on days 1, 8, 22 and 36. After completion of study treatment, patients are followed up at 2, 3, and 6 months.

keywords:
Hematopoietic and Lymphatic System Neoplasm, Metastatic Malignant Solid Neoplasm, Behavioral Intervention, Psychedelic therapy, Group Therapy, Psilocybin, Questionnaire Administration, COMPLETED


authors: Gustavo Vazquez
journal: ClinicalTrials.gov
publication_date: 2026-03-17
source_url: https://clinicaltrials.gov/study/NCT06818994
keywords: Demoralization, Safety, Psilocybin-assisted Psychotherapy, RECRUITING
substance_tags: psilocybin
topic_tags: Depression,Anxiety,End-of-Life Distress,Aging,Clinical Trial,Cancer Patients,Safety,Adverse Events
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:28
last_checked: 2026-07-01 11:22:34
raw_json: {"nct_id":"NCT06818994","overall_status":"RECRUITING","phase":["PHASE1"]}
title:
Safety and Efficacy of Psilocybin-assisted Psychotherapy for Demoralization Syndrome in Patients Diagnosed With Advanced Stage Cancer: a Pilot Study

abstract:
Demoralization syndrome is frequently present in palliative care and oncology patients. In particular, up to a third of patients diagnosed with cancer will experience demoralization due to their illness. The relevance of demoralization syndrome in oncology is tied to this syndrome's association with other mental health ailments such as depression, anxiety, suicidal ideation, and quality of life. Unfortunately, so far no pharmacological strategy has been devised for demoralization, and only a few psychotherapeutic approaches have been trialed in this population, though no psychotherapeutic treatments have been tested for demoralization specifically. The new wave of psychedelic research has been showing encouraging results in a broad spectrum of psychiatric diagnosis, including depression and anxiety in patients diagnosed with cancer and other life-threatening diseases. To date, no clinical trials have been published in which the potential therapeutic effects of psychedelics are explored for the treatment of demoralization syndrome. The aim of this open label pilot study is to assess the safety and efficacy of psilocybin-assisted psychotherapy as a treatment for demoralization syndrome in patients diagnosed with cancer. Fifteen participants between the ages of 18 to 70 years with advanced stage cancer and demoralization syndrome will be enrolled in a treatment program which will include 6 psychotherapeutic sessions and one psilocybin (25 mg) dosing session. Our outcome of interest will be a decrease in demoralization, as measured by the Demoralization Scale at baseline and at the end of the study, and adverse events registration. Other measures of interest include Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, and the Columbia Suicide Severity Rating Scale. Those patients with partial response a month after the psilocybin intervention will be offered the possibility of a second psilocybin 25 mg dosing session.


authors: Charles Raison
journal: ClinicalTrials.gov
publication_date: 2025-05-22
source_url: https://clinicaltrials.gov/study/NCT06512194
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Aging,Wellbeing,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 11:22:34
raw_json: {"nct_id":"NCT06512194","overall_status":"RECRUITING","phase":["PHASE2"]}
title:
An Investigation of Strategies to Understand and Optimize the Antidepressant Effects of Psilocybin (The OPTIMIZE Study)

abstract:
This study will examine the effects of a single dose of psilocybin, administered with psychological support, on symptoms of depression. It will also assess whether different post-dosing interventions, including a non-invasive technique called transcutaneous auricular Vagus Nerve Stimulation (taVNS), influence various psychological and behavioral outcomes. In addition, the study will explore objective measures of real-world social behavior and identify early behavioral responses that may be associated with long-term treatment outcomes. One hundred forty-one adults ages 18 to 70 experiencing a major depressive episode of at least 60 days duration of moderate or greater severity at screening will be enrolled to obtain evaluable data on approximately 120 subjects. All subjects will receive a single 25 mg dose of psilocybin using a "set and setting" therapeutic approach that will include 1) several hours of preparatory sessions prior to dosing and 2) the presence of two facilitators throughout the dosing session; and 3) several post dosing integration sessions with a facilitator. Following the psilocybin dosing session, subjects will be randomized to 1) taVNS (7 days of twice daily taVNS), 2) sham taVNS (7 days of twice daily sham taVNS), or 3) no taVNS. Both taVNS and sham sessions will include guided prompts encouraging participants to reflect on key aspects of their psychedelic experience, accompanied by music previously used during the psilocybin dosing session. Participants will complete assessments at multiple time points to evaluate depression, anxiety, well-being, functional disability, quality of life, social behavior, suicidal ideation, and adverse events before and after psilocybin dosing.

keywords:
Depression, Psilocybin, Psilocybine, Psilocibin, Usona Institute Psilocybin, Transcutaneous Auricular Vagus Nerve Stimulation (taVNS), taVNS, Sham taVNS, RECRUITING


title: Pilot Study of Psilocybin-assisted Treatment for Cannabis Use Disorder
authors: Johns Hopkins University
journal: ClinicalTrials.gov
publication_date: 2026-03-17
source_url: https://clinicaltrials.gov/study/NCT06660381
keywords: Cannabis Use Disorder, Psilocybin, RECRUITING
substance_tags: psilocybin
topic_tags: Biomarkers
study_type: Other
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:28
last_checked: 2026-07-01 11:22:34
raw_json: {"nct_id":"NCT06660381","overall_status":"RECRUITING","phase":["PHASE1"]}
abstract:
This pilot study will evaluate the therapeutic potential of psilocybin in people with Cannabis Use Disorder (CUD). This study will examine the impact of psilocybin treatment on cannabis use and related variables in 12 people with CUD. This is an open-label proof-of-concept trial in which participants will complete a 12-week course of study treatment including two psilocybin sessions with psychological support, and follow-up assessments 3 and 6 months after the first psilocybin session. This pilot study will evaluate the therapeutic potential of psilocybin to produce significant reduction in cannabis use compared to pre-treatment in a sample of 12 treatment-seeking patients with Cannabis Use Disorder (CUD). Upon enrollment, participants will complete a 12-week course of study treatment including two psilocybin sessions, with follow-up assessment 3 and 6 months after the first psilocybin session. After 4 weekly preparatory meetings including a targeted cognitive behavioral therapy (CBT) intervention for CUD, participants will receive a moderately high dose (25mg) of psilocybin in week 5 of the 12-week counseling, and either another moderately high dose (25mg) or a high dose (35mg) in week 7. After each psilocybin session, participants will complete a follow-up meeting within 3 days (i.e. integration meeting), as well as continued weekly meetings through week 12. Participants will complete post-session assessments in approximately weeks 12 (End of Treatment), 17 (3 months after 1st psilocybin session, and 29 (6 months after 1st psilocybin session). Some study meetings may be held virtually via a secure web-based video conference platform (e.g., Zoom). Self-reported cannabis use and biomarkers of recent use will be assessed at baseline (screening), weekly throughout the 12-week intervention, and at approximately weeks 17 (3 months after 1st psilocybin session), and 29 (6 months after 1st psilocybin session).


title: Psilocybin vs Escitalopram for Major Depressive Disorder: Comparative Mechanisms
authors: Imperial College London
journal: ClinicalTrials.gov
publication_date: 2024-10-23
source_url: https://clinicaltrials.gov/study/NCT03429075
keywords: Depressive Disorder, Major, Psilocybin + Placebo, Psilocybin + Escitalopram, COMPLETED
substance_tags: psilocybin
topic_tags: Depression,Mechanism of Action,Receptor Pharmacology,Clinical Trial
study_type: Clinical Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:28
last_checked: 2026-07-01 11:22:34
raw_json: {"nct_id":"NCT03429075","overall_status":"COMPLETED","phase":["PHASE2"]}
abstract:
This is a randomised double-blind clinical trial. The aim is to compare the efficacy and mechanisms of action of psilocybin, the primary psychoactive substance in 'magic mushrooms', with the selective serotonin reuptake inhibitor (SSRI) escitalopram for major depressive disorder (MDD).


title: Behavioral and Neural Mechanisms Supporting Psilocybin-assisted Therapy for Phantom Limb Pain
authors: University of California, San Diego
journal: ClinicalTrials.gov
publication_date: 2026-01-08
source_url: https://clinicaltrials.gov/study/NCT05224336
keywords: Phantom Limb Pain, Psilocybin, Placebo Niacin, COMPLETED
substance_tags: psilocybin
topic_tags: Chronic Pain,Mechanism of Action
study_type: Other
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:28
last_checked: 2026-07-01 11:22:34
raw_json: {"nct_id":"NCT05224336","overall_status":"COMPLETED","phase":["PHASE1"]}
abstract:
This double-blind placebo-controlled pilot study seeks to investigate whether psilocybin can be safely administered to people with chronic phantom limb pain (PLP) in a supportive setting with close follow-up, and its effects on pain symptoms and other moods, attitudes, and behaviors. The investigators' primary hypotheses are that psilocybin is safe to administer in people with PLP and that it will reduce scores on measures of pain. The investigators will also assess a number of secondary measures related to the behavioral and neural responses to pain after psilocybin treatment.


authors: University Hospital, Basel, Switzerland
journal: ClinicalTrials.gov
publication_date: 2025-04-10
source_url: https://clinicaltrials.gov/study/NCT05695495
substance_tags: psilocybin
topic_tags: Consciousness,Spirituality
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 11:22:34
raw_json: {"nct_id":"NCT05695495","overall_status":"COMPLETED","phase":["PHASE1"]}
title:
Acute Dose-dependent Effects of DMT-bolus Applications in Healthy Subjects: A Placebo-controlled Cross-over Study (DMT BDR-Study).

abstract:
N,N-dimethyltryptamine (DMT) is a psychoactive substance with similar effects such as LSD or psilocybin. However, DMT is less well characterized than the latter substances. The present study is a modern randomized cross-over trial, investigating different intravenous DMT boluses over a broad dose range. Thus, different doses will be tested and related to subjective and autonomic effects. N,N-dimethyltryptamine (DMT) is a naturally-occurring psychedelic substance widely used in recreational and spiritual settings (Ayahuasca). DMT is considered a tool to induce an altered state of consciousness of interest in psychological and psychiatric research. DMT is rapidly metabolized by monoamine oxidase (MAO) A. Therefore, it is inactive when administered orally and has a very short duration of action when administered parenterally (\

keywords:
Healthy, N,N-Dimethyltryptamine (5mg), N,N-Dimethyltryptamine (10mg), N,N-Dimethyltryptamine (15mg), N,N-Dimethyltryptamine (20mg), N,N-Dimethyltryptamine (25mg), Placebo (saline), COMPLETED


authors: Centre for Addiction and Mental Health
journal: ClinicalTrials.gov
publication_date: 2026-05-31
source_url: https://clinicaltrials.gov/study/NCT06512220
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 11:22:34
raw_json: {"nct_id":"NCT06512220","overall_status":"RECRUITING","phase":["PHASE2"]}
title:
Imaging the Effects of Serotonin 2A Receptor Modulation on Synaptic Density in Treatment-resistant Depression (SYNVEST)

abstract:
Limit: 5000 characters. 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 certain medications such as risperidone. The purpose of this study is to use an established SV2A radiotracer produced at our Centre to determine the feasibility of integrating PET imaging in to psilocybin trials. The preliminary imaging data will assess whether psilocybin's antidepressant effects are related to changes in synaptic density in adults with TRD, and whether any changes in synaptic density are associated with psilocybin's actions on the 5-HT2AR.

keywords:
Treatment Resistant Depression, Psilocybin 25 mg, PEX010, Risperidone 1 MG, MAR-Risperidone, RECRUITING

topic_tags:
Depression,Neuroplasticity,Brain Imaging,Receptor Pharmacology,Aging,Clinical Trial,Randomized Controlled Trial,Healthy Volunteers,Treatment-Resistant Depression


title: Mechanistic Studies of Psilocybin in Headache Disorders
authors: Yale University
journal: ClinicalTrials.gov
publication_date: 2025-07-23
source_url: https://clinicaltrials.gov/study/NCT06464367
keywords: Migraine, Psilocybin, Placebo, RECRUITING
substance_tags: psilocybin
topic_tags: Headache / Migraine,Neuroplasticity,Brain Imaging,Biomarkers,Clinical Trial,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 11:22:34
raw_json: {"nct_id":"NCT06464367","overall_status":"RECRUITING","phase":["EARLY_PHASE1"]}
abstract:
In previous clinical trial work, the investigators observed lasting reductions in headache burden after limited dosing of psilocybin. This purpose of this study is to examine potential sources for this observed effect. This study will measure brain resting state functional connectivity (fMRI), central synaptic density (SV2A PET), peripheral markers of inflammation, circadian rhythm (actigraphy), and sleep (sleep EEG) in both migraine and healthy control participants before and one week after the administration of psilocybin or an active control agent.


title: Effects of Psilocybin in Advanced-Stage Cancer Patients With Anxiety
authors: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
journal: ClinicalTrials.gov
publication_date: 2025-03-12
source_url: https://clinicaltrials.gov/study/NCT00302744
substance_tags: psilocybin
topic_tags: Depression,Anxiety,End-of-Life Distress,Chronic Pain,Consciousness,Spirituality,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 11:22:34
raw_json: {"nct_id":"NCT00302744","overall_status":"COMPLETED","phase":["PHASE1","PHASE2"]}
abstract:
Psychiatric Research Study For Cancer Patients The Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center is conducting a study designed to measure the effectiveness of the novel psychoactive medication psilocybin on the reduction of anxiety, depression, and physical pain. The significance of this study is that it is addressing the important issues of psychological and spiritual well being of people who have advanced cancer. In 2001, the National Cancer Policy Board of the Institute of Medicine and National Research Council issued a report (Improving Palliative Care for Cancer: Summary and Recommendations) that specifically recommended research be conducted using novel agents and methods. Psilocybin is a novel agent which produces a profound alteration in your state of consciousness. It is the main active ingredient found in "magic mushrooms". Our specific aim is to learn whether this psychoactive drug, psilocybin, might be effective in reducing anxiety, depression and physical pain, and therefore improving your quality of life. This pilot study will start with 12 people ages 18-70. For each participant there will be two overnight admissions to the hospital. In one session you will be given a placebo and in the other you will get the active medication, but no one will know which drug is administered when. This is called a double blind study. You will be asked to fill out questionnaires about how you feel, your pain levels and your moods. There will also be at least two psychotherapy meetings before the study sessions, so that you are fully aware of what to expect and to have all your questions answered. We cannot take you in the study if you have central nervous system (CNS) cancers, kidney disease, diabetes, abnormal liver function tests, epilepsy, cardiovascular disease including untreated high blood pressure (BP greater than 140/90), and pregnancy. The psychiatric exclusions are: you or an immediate family member with a history of a major psychiatric disorder, a current substance abuse problem, or an anxiety or a mood disorder within 1 year prior to the onset of symptoms of your current illness. We also cannot take you in the study if you are taking certain medications, such as: anti-seizure, insulin and oral hypoglycemics, and cardiovascular drugs (except anti-hypertensive medications). Some antidepressant (SSRIs) medications cannot be taken within the two weeks prior to the session (except for Prozac, which cannot be taken in the last 5 weeks prior to the session). You will get a MRI of the brain prior to admission (if you haven't had one in the prior two months), at the study's expense, to be sure there is no CNS involvement. You can provide us, or the study will pay for, lab work from the prior 2 weeks (CBC, liver function and renal function). The history and physical, neurological exam, EKG, and a urine pregnancy test (if you are a woman with child-bearing potential), will be done on admission by the house staff doctors. You will be allowed to take your own medications while in the hospital, and will be encouraged to bring to the hospital personal photos, small memorabilia, and some of your favorite music that can be played during the sessions.

keywords:
Anxiety, Psilocybin (drug), 4-phosphoryloxy-N,N-dimethyltryptamine, Niacin, nicotinamide, vitamin B3, MRI, COMPLETED


authors: University Health Network, Toronto
journal: ClinicalTrials.gov
publication_date: 2026-06-22
source_url: https://clinicaltrials.gov/study/NCT07048743
keywords: Caregiver Distress, Psilocybin, RECRUITING
substance_tags: psilocybin
topic_tags: Depression,Anxiety,End-of-Life Distress,Spirituality,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 11:22:34
raw_json: {"nct_id":"NCT07048743","overall_status":"RECRUITING","phase":["PHASE2"]}
title:
Psilocybin-assisted Existential, Attachment and Relational (PEARL) Therapy for Caregivers of Patients With Advanced Cancer: A Phase II Open-Label Trial

abstract:
The PEARL-C1 trial 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. Caregivers of patients with advanced cancer often experience high levels of distress but there is currently little evidence-based guidance on how to help caregivers who experience depression, anxiety, anticipatory grief, spiritual suffering, caregiving burden and/or impaired quality of life. 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 related distress. Simultaneously, recent research has shown that psilocybin-assisted psychotherapy, in which an individual ingests the psychoactive drug within a carefully monitored therapy, can reduce end-of-life distress and greatly benefit those with advanced disease. The multidisciplinary team has combined these two evidence-based approaches into 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 and their families facing advanced cancer. This study will assess the feasibility, acceptability, and safety of PEARL therapy among caregivers of patients with advanced cancer. This study will contribute to the growing research around the efficacy of psychedelic-assisted therapies for the psychological distress associated with advanced disease and mortality. This type of therapy has the potential to improve quality of life among caregivers of those with advanced disease, to build upon previous findings to help outline the necessary components of therapy, and to inform public policy and clinical guidelines.


title: Effects of Psilocybin in Obsessive Compulsive Disorder
authors: Johns Hopkins University
journal: ClinicalTrials.gov
publication_date: 2026-04-01
source_url: https://clinicaltrials.gov/study/NCT05546658
keywords: Obsessive-Compulsive Disorder, Psilocybin, ACTIVE_NOT_RECRUITING
substance_tags: psilocybin
topic_tags: Depression,Anxiety,OCD,Mechanism of Action,Safety
study_type: Other
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:28
last_checked: 2026-07-01 11:22:34
raw_json: {"nct_id":"NCT05546658","overall_status":"ACTIVE_NOT_RECRUITING","phase":["EARLY_PHASE1"]}
abstract:
This study will test the feasibility, safety, and evidence for efficacy of psilocybin administration in participants with obsessive compulsive disorder (OCD). This will serve as a preliminary proof of concept study for future larger studies aimed to investigate the utility, cognitive mechanisms, and neural correlates of this intervention. Participants in this study will receive two doses of psilocybin approximately two weeks apart. Assessments will be conducted during screening visits, psilocybin sessions, and at follow up visits up to 6 months after the final psilocybin session. Thirty participants will complete all study visits including follow-up visits. Primary objectives: 1. Investigate the feasibility, safety, and acceptability of psilocybin for OCD. 2. Investigate the effect of psilocybin on OCD symptoms and concomitant depression and anxiety symptoms. 3. Investigate the effect of psilocybin on quality of life. Secondary objectives: 1. Investigate the effect of psilocybin on metacognition of episodic memory and decision-making. 2. Investigate the effect of psilocybin on model-based learning. 3. Investigate the effect of psilocybin on the ERN. 4. Investigate the effect of psilocybin on affect and social connection. 5. Investigate the effect of psilocybin on movement and communications.


authors: University of Wisconsin, Madison
journal: ClinicalTrials.gov
publication_date: 2025-10-14
source_url: https://clinicaltrials.gov/study/NCT04161066
keywords: Opioid Use Disorder, Psilocybin with facilitated counseling, RECRUITING
substance_tags: psilocybin
topic_tags: Addiction,Chronic Pain,Clinical Trial,Observational Study,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 11:22:34
raw_json: {"nct_id":"NCT04161066","overall_status":"RECRUITING","phase":["PHASE1"]}
title:
Phase I Study of the Safety and Adjunctive Effects of Psilocybin in Adults With Opioid Use Disorder Maintained on a Buprenorphine/Naloxone Formulation

abstract:
Primary Aim: In participants with OUD, to characterize adverse events associated with adding two psilocybin doses to a stable buprenorphine-naloxone formulation. Secondary Aim: To evaluate the effect of psilocybin treatment on the effectiveness of a buprenorphine-naloxone maintenance therapy. Secondary Aim: To evaluate the effect of concurrent buprenorphine-naloxone use on the effects of psilocybin therapy. Descriptive Aim: To describe any changes in self-efficacy, quality of life, pain. The primary objective of this clinical trial is to determine the safety of psilocybin in adult patients with opioid use disorder concurrently taking buprenorphine-naloxone. Eligible participants will be adults with active opioid use disorder (OUD) who are willing to begin and maintain a daily dose of buprenorphine-naloxone throughout study participation. Initiation, stabilization, and maintenance of buprenorphine-naloxone will be overseen by a qualified study medical provider. After psychological screening and at least 6 hours of preparatory counseling and preparation for the psilocybin dosing, set, and setting, each participant will ingest 1 oral dose of psilocybin. All dosing sessions will be attended by 2 specially trained facilitators, in a dedicated Clinical Research Facility. After eight hours of observation in the dosing room, the participant will be kept overnight in the hospital Clinical Research Unit, and complete an integration session with a psychologist 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 have been administered the first dose but decline to receive the second dose will remain evaluable. At study termination, their active study participation will end, but completion of the 28 day post-dose follow up will be requested. The primary endpoint is the assessment of the safety of concurrent administration of a buprenorphine-naloxone formulation and psilocybin as determined by physiological measures (ECG, respiratory rate, blood pressure, body temperature, and blood oxygen saturation) and validated clinical and self-report measures (Clinical Opiate Withdrawal Scale (COWS), Opioid Craving Scale (OCS), Timeline Follow-Back (TLFB)). 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.


authors: Wake Network, Inc.
journal: ClinicalTrials.gov
publication_date: 2022-06-29
source_url: https://clinicaltrials.gov/study/NCT04989972
keywords: Anxiety and Depression, PSIL428, Oyster mushroom, WITHDRAWN
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Wellbeing,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 11:22:34
raw_json: {"nct_id":"NCT04989972","overall_status":"WITHDRAWN","phase":["PHASE2"]}
title:
Randomized Double Blind Placebo Controlled Assessing the Efficacy of Micro-dosed Psilocybin in Reducing Anxiety and or Depression Levels in Adults

abstract:
To investigate the efficacy of a 16 week treatment with PSIL428 patient reported anxiety levels in otherwise healthy individuals suffering from depression and or anxiety symptoms. Randomized, double-blind, placebo-controlled study assessing the efficacy of micro-dosed psilocybin on reducing anxiety and/or depression levels in adults Study summary: The Institute for Health Metrics and Evaluation reported that Anxiety disorders currently affect an estimated 275 million people worldwide, about one in 13 people (7.3 percent). COVID-19 has accelerated the rate of new anxiety diagnoses and exacerbated pre-existing diagnoses of anxiety in individuals worldwide. The effectiveness of full dose psilocybin for treatment of anxiety and depression has been shown in a number of clinical trials. While there is a significant evidence of clinical efficacy of full dose psilocybin, acute effects of the dose result in a significant impairment - perceptual and sensory distortions incapacitating the patient for the duration of drug activity. Recent work suggests while not producing perceptual changes, micro-dosing may indeed be associated with improved mood and enhanced well-being. The practice of micro-dosing is gaining popularity in the general population, while clinical data on its safety and efficacy is lacking. This will be a novel randomized, double-blind, placebo-controlled study aimed at establishment of safety and anxiolytic efficacy of psilocybin PSIL428 administered in a micro-dosing regimen (2-5% of a full therapeutic dose) to adults suffering from depression or anxiety. The primary outcome of this study is the change in anxiety and/or depression levels from screening to week 16. Participant anxiety levels will be monitored through Beck Anxiety inventory, depression levels - through Beck Depression Inventory forms on a bi-weekly basis across the course of the study. Study Drug PSIL428 is an experimental intervention and the active ingredient psilocybin is botanically derived. Similar interventions are currently undergoing Phase IIb/III clinical trials in international jurisdictions. It is being assessed for treatment of depressive disorders. Typically psilocybin used in full therapeutic doses associated with significant acute adverse effects. The proposed trial would utilize psilocybin in different dosing regimen - as micro-dosing - ingesting of sub-perceptual doses of the drug equal to 2-10% of the full dose. The micro-dosing practice is gaining significant popularity world-wide, however evidence-based data around it is minimal. Risks and benefits associated with the trial are not definitively established, however existing pre-clinical and clinical data around full-dose use of the drug carries a favorable risk-benefit potential. The trial will be conducted in accordance with the most recently acceptable version of the Declaration of Helsinki, Good Clinical Practice (GCP) according to International Conference on Harmonization (ICH) guidelines, and applicable Standard Operating Procedures (SOPs). The trial will be conducted under a protocol reviewed and approved by an IRB; the trial will be conducted by scientifically and medically qualified persons; the benefits of the study are in proportion to the risks; the rights and welfare of the subjects will be respected; each subject will give his or her written informed consent before any protocol-driven tests or evaluations are performed. The investigators are responsible for obtaining informed consent in adherence to GCP and according to applicable regulations prior to entering the subject into the trial. A positive change in Beck Anxiety and/or Beck Depression numeric levels between PSIL428 and placebo groups will mark our primary outcome achievement of confirming beneficial effects of micro-dose-administered psilocybin on study participants' overall anxiety and/or depression levels


authors: Suzanne "Sue" Sisley MD
journal: ClinicalTrials.gov
publication_date: 2026-03-08
source_url: https://clinicaltrials.gov/study/NCT07275970
keywords: PTSD, Psychedelic, RECRUITING
substance_tags: psilocybin
topic_tags: PTSD,Pharmacology,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 11:22:34
raw_json: {"nct_id":"NCT07275970","overall_status":"RECRUITING","phase":["PHASE1"]}
title:
An Open-Label, Phase 1 Study of the Safety Pharmacokinetic Profile, and Preliminary Efficacy, of Organic Whole Psilocybin-Containing Mushrooms in Patients Suffering From PTSD

abstract:
This study will examine the safety and preliminary efficacy of psilocybin mushrooms to treat adults with PTSD. Up to 24 participants will take part in this study. Each participant will ingest psilocybin from dried mushrooms in a chocolate formulation.


title: Psilocybin-facilitated Smoking Cessation Treatment: A Pilot Study
authors: Johns Hopkins University
journal: ClinicalTrials.gov
publication_date: 2025-05-24
source_url: https://clinicaltrials.gov/study/NCT01943994
substance_tags: psilocybin
topic_tags: Addiction,Mechanism of Action,Spirituality,Randomized Controlled Trial
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 11:22:34
raw_json: {"nct_id":"NCT01943994","overall_status":"COMPLETED","phase":["NA"]}
abstract:
One of the most promising lines of investigation for the therapeutic use of hallucinogens in the 1960s and 1970s was in the treatment of drug dependence. The investigators propose to examine psilocybin administration combined with a structured smoking cessation treatment program in nicotine dependent individuals in order to provide preliminary data on the efficacy of this combined treatment for smoking cessation. Prior work in the investigators laboratory has shown that under carefully prepared and supportive conditions, psilocybin administration can facilitate highly salient experiences with enduring personal meaning and spiritual significance. It is plausible that embedding such highly meaningful experiences into a drug dependence cessation attempt may provide an enduring motivation for remaining abstinent. Cigarette smoking is a good model system for studying drug dependence because users are less likely to be challenged by the many social and economic impairments that often accompany dependence on other drugs such as cocaine, heroin, or alcohol. More specifically, the investigators propose to conduct a randomized controlled comparative efficacy study in which either psilocybin or transdermal nicotine patch are administered under highly supportive conditions to individuals who are nicotine-dependent cigarette smokers, who have had multiple unsuccessful quit attempts, and who continue to desire to quit smoking. Other than nicotine dependence, participants will be healthy. Fifteen participants have already completed a preliminary open-label pilot-study with no control condition. Eighty additional participants will be enrolled and randomized to either psilocybin (n=40), or nicotine patch (n=40) treatment. Participants will receive a 13-week course of cognitive behavioral therapy for smoking cessation, with Target Quit Date set for week 5. After several preparation meetings with study monitors, participants will have either a single day-long psilocybin session using a high dose (30 mg/70 kg), or a standard 8 to 10-week course of nicotine patch treatment. Participant smoking status will be assessed repeatedly for 8 weeks after the Target Quit Date, including biological verification of smoking status through breath and urine samples. Smoking status will also be assessed at three follow up sessions approximately 3, 6, and 12 months after the Target Quit Date. Additionally, 50 of these participants (25 per treatment condition) will undergo MRI scanning before and after Target Quit Date to assess the brain-based mechanisms associated with these treatments. Individuals assigned to the nicotine patch study treatment condition will be eligible to undergo an optional high dose psilocybin session after completing the 6-month follow-up meeting.

keywords:
Nicotine Dependence, Psilocybin-assisted treatment, O-phosphoryl-4-hydroxy-N,N-dimethyltryptamine, Nicotine Replacement Therapy (NRT), Transdermal Nicotine Patch, Nicoderm CQ, COMPLETED


title: Safety Profile of 25 mg Psilocybin in Individuals With Cocaine Use Disorder
authors: University of California, Los Angeles
journal: ClinicalTrials.gov
publication_date: 2026-04-06
source_url: https://clinicaltrials.gov/study/NCT06102434
keywords: Cocaine Use Disorder, Psilocybin, SUSPENDED
substance_tags: psilocybin
topic_tags: Addiction,Brain Imaging,Aging,Healthcare Workers,Safety
study_type: Other
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:28
last_checked: 2026-07-01 11:22:34
raw_json: {"nct_id":"NCT06102434","overall_status":"SUSPENDED","phase":["EARLY_PHASE1"]}
abstract:
The purpose of this study is to establish the safe administration of psilocybin in individuals with cocaine use disorder in terms of cardiovascular (e.g., heart rate) and subjective (e.g., mood) effects. The study's subject population consists of men and women between the ages of 21 and 55 from the Los Angeles area that meet criteria for cocaine use disorder and express an interest in ceasing cocaine use. 25 mg oral psilocybin will be administered to 10 individuals (separately) during a single laboratory visit. The laboratory visit will take place from 9 am until 3 pm within a comfortable, living room like environment. Within this study session room, participants will be accompanied by two clinicians. Participants will then consume the psilocybin capsule, and thereafter will be encouraged to lie down on a couch and introspect on the experience. At one-hour intervals following ingestion, participants will be tested briefly for changes in heart rate, blood pressure, and subjective effects. No blood draws, behavioral assessments, or neuroimaging is included in the study. Following the laboratory visit, investigators will check-in on participants remotely, after 48 hours, and 10, 50, and 90 days from the psilocybin session.


title: Precision Phenotyping of Behavioral Risk and Response to Electromagnetic and Psychedelic Therapies
authors: University of New Mexico
journal: ClinicalTrials.gov
publication_date: 2026-03-19
source_url: https://clinicaltrials.gov/study/NCT07484906
substance_tags: psilocybin
study_type: Observational Study
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:28
last_checked: 2026-07-01 11:22:34
raw_json: {"nct_id":"NCT07484906","overall_status":"WITHDRAWN","phase":["PHASE2"]}
abstract:
PRE-EMPT will assemble a study group of 150 civilian and Veteran participants from three populations (low risk, intermediate risk, and high risk for self-harm). The investigators will obtain clinical assessments, MRI, and blood levels for circular RNA (circRNA). The teams will then administer three interventions (neurofeedback, transcranial magnetic stimulation, and psilocybin assisted therapy), and repeat the tests above. A team with expertise in artificial intelligence will then use our data to try to find patterns that identify who is at high risk versus low risk with a high degree of accuracy. For U.S. Service Members, deployment and combat exposure can result in significant mental strain, with high rates of disability and suicide. Unfortunately our ability to predict and treat those at high risk of intentional self-harm is limited. PRE-EMPT (Precision Phenotyping of Behavioral Risk and Response to Electromagnetic and Psychedelic Therapies) seeks to transform the assessment and treatment of the spectrum of depression, posttraumatic stress, and self-harm. PRE-EMPT will utilize multimodal neuroimaging, blood-based biomarkers, and predictive analytics to devise highly accurate models of behavioral risk, and to characterize response to three neuroplasticity-enhancing interventions. Background: Rates of suicide have increased 37% since the year 2000 despite concerted governmental and institutional programs to address root causes such as stigma and lack of access. Suicide was the number one cause of active-duty fatality from 2014 to 2019, highlighting the vulnerability of Service Members and Veterans. Suicide is a highly multifactorial event and may be conceptualized as a state in which individuals cannot come up with any other option to endure difficult circumstances or intense feelings, representing failures of cognitive control (CC) and emotion regulation (ER). Similarly, the heritability of suicide risk is well known, and transcriptomics, or the study of transcript molecules such as RNA that regulate gene expression, has potential to reveal mechanisms of risk not fully explained by DNA analysis. Better methods of classifying suicide risk according to objective and measurable factors are needed to proactively identify persons at risk and provide interventions tailored to risk. Research Plan: PRE-EMPT will assemble a cohort of 150 civilian and Veteran participants from three populations (low risk, intermediate risk, and high risk for self-harm). The investigators will obtain baseline clinical assessments, structural and functional MRI utilizing tasks pioneered by our team to assess cognitive control (CC) and emotion regulation (ER), and peripheral circular RNA (circRNA) levels to characterize the molecular brain states associated with behavioral risk. In parallel, investigators will mine publicly available databases to identify network nodes and use deep learning techniques on multivariate patterns of brain activation, structural topography, and functional connectivity. The clinical, imaging, and transcriptomic data will be fused and jointly analyzed to increase the accuracy of risk prediction models. PRE-EMPT in three separate arms will then prospectively assess three promising and innovative interventions for their potential to reduce suicidal ideation and alter activity in key neural networks: 1) neurofeedback (NF) using real-time fMRI with simultaneous electroencephalography (EEG), 2) accelerated intermittent theta burst stimulation (aiTBS) with dose optimization through electric field modeling; and 3) psilocybin assisted therapy (PSI), with flexible dosing plan to maximize the depth of psychedelic experience. Assessments will be repeated at post-treatment and at 1, 3, and 6 months after intervention. These therapies were chosen based on our team's prior work in all three interventions demonstrating rapid action and large effects. Each clinical arm will contribute independent insights into mediators of efficacy for the specific interventions and risk groups, while pooling data to identify predictors across the risk spectrum. Specific Aim 1: To construct a neurobehavioral model from structural and functional MRI, clinical, and transcriptomic data that accurately predicts behavioral risk. Specific Aim 2: To test three potential rapid-acting therapies for suicidal ideation and identify mechanistic mediators of response.

keywords:
Suicidal Ideation, fMRI Neurofeedback, Accelerated theta burst stimulation, Psilocybin assisted therapy, WITHDRAWN

topic_tags:
Depression,PTSD,Neuroplasticity,Brain Imaging,Mechanism of Action,Biomarkers,Aging,Emotional Processing,Observational Study,Veterans,Safety,Transcriptomics


title: Psilocybin-Enhanced Psychotherapy for Methamphetamine Use Disorder
authors: Portland VA Research Foundation, Inc
journal: ClinicalTrials.gov
publication_date: 2026-04-21
source_url: https://clinicaltrials.gov/study/NCT04982796
keywords: Amphetamine-Related Disorders, Psilocybin, Treatment-as-usual, ACTIVE_NOT_RECRUITING
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 11:04:28
last_checked: 2026-07-01 11:22:34
raw_json: {"nct_id":"NCT04982796","overall_status":"ACTIVE_NOT_RECRUITING","phase":["PHASE1","PHASE2"]}
abstract:
This is a proof-of-concept randomized clinical trial of psilocybin-enhanced psychotherapy versus treatment-as-usual among individuals being treated for methamphetamine use disorder. The trial will take place with individuals admitted to a residential rehabilitation treatment program. The treatment protocol will consist of 4 preparatory therapy visits, 2 psilocybin sessions (25-30mg), and 8 total integration therapy visits. Primary aims assess acceptability, feasibility, and safety with a primary endpoint at the conclusion of the study intervention. An additional aim assesses preliminary efficacy for methamphetamine use disorder and overall functioning at follow-up assessments 60 and 180 days after discharge from the residential treatment program.


authors: University of Zurich
journal: ClinicalTrials.gov
publication_date: 2022-04-28
source_url: https://clinicaltrials.gov/study/NCT03715127
keywords: Depressive Disorder, Major, Psilocybine oral capsule, Placebo oral capsule, COMPLETED
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 11:22:34
raw_json: {"nct_id":"NCT03715127","overall_status":"COMPLETED","phase":["PHASE2"]}
title:
Phase II, Randomized, Double Blind, Placebo Controlled, Parallel Group, Single Center Study of Psilocybin Efficacy in Major Depression

abstract:
Effects of serotonin 2A/1A receptor stimulation by psilocybin on mood and emotion processing in major depressive disorder: a randomized double-blind placebo-controlled study Major depressive disorder (MDD) is one of the world's greatest contributor to the global burden of disease and MDD affects around 17% of the Swiss population (Tomonaga et al. 2013). It is a chronic condition and can cause the affected person to suffer greatly and function poorly at work, at school and in the family. More than 1'000 suicides were recorded in Switzerland in 2014, about 90% of these fatalities were related to depression or other psychiatric problems. Suicide is the second leading cause of death in individuals 15-24 years of age (Insel \& Charney 2003). Current pharmacotherapies, including monoaminergic-acting antidepressants, require prolonged administration (weeks if not months) for clinical improvement. This lag time, as well as a high non-response rate, emphasizes the need for better and faster-acting antidepressant medications. However, psychopharmacological research has largely failed to produce novel and more efficacious treatment options for MDD since decades. Advanced pharmaceutical antidepressants should ideally facilitate the psychotherapeutic process for patients, reduce the time onset of antidepressant efficacy, and prime neuroplastic adaptations relevant to symptom improvement. Such novel therapeutics are much needed and would address this detrimental public health problem, particularly in treatment-resistant patients. Early clinical studies using the psychotropic compound psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine) as an adjunct in psychotherapy reported a significant improvement of clinical symptoms in depression and anxiety disorder (Leuner 1961, 1981). Psilocybin is the main psychoactive principle of the group of hallucinogenic fungi (Hofmann 1968), commonly known as magic mushrooms, and acts as partial agonist at cortical and sub-cortical serotonin 5-HT2A and 5-HT1A receptors. At moderate doses, psilocybin produces a dream-like state of consciousness (Kraehenmann et al. 2016) characterized by perceptual alterations, enhanced mood, facilitated autobiographic memory recollection, and a change of perspective on the self (Leuner 1981; Studerus et al. 2011). Recent clinical studies applying placebo-controlled designs support and extend these early findings by showing that a single dose of psilocybin leads to a fast and sustained reduction in anxiety and depression as well as an improvement of quality of life in advanced cancer patients (Griffiths 2015, Grob et al. 2011). Furthermore, a recent open-label feasibility study showed rapid-onset, sustained symptom improvements over 3 weeks in a small sample of treatment-resistant depressed patients following two psilocybin treatment sessions (Carhart-Harris et al. 2016). Accumulating evidence from pharmacological and neuroimaging studies suggests that psilocybin may produce its antidepressant effects via activation of 5-HT2A receptors located in prefrontal-limbic structures that are also implicated in the pathophysiology of depression (Kraehenmann \& Vollenweider et al. 2015; Vollenweider und Kometer 2010; Disner et al. 2011). In addition, molecular studies suggest that the enduring symptom improvement after a single dose of psilocybin may be mediated through downstream effects on the glutamate system and a subsequent activation of neuroplastic factors such as brain-derived neurotrophic factor (BDNF) (Catlow et al. 2013, Barre et al. 2016). The present clinical trial aims at investigating the putative antidepressant effects of a single moderate dose of psilocybin (0.215 mg/kg) in patients suffering from MDD by applying a randomized, double-blind, placebo-controlled design. The specific aims of this project are: 1. To investigate whether psilocybin in combination with short-term focused psychotherapy will reduce core symptoms in patients with MDD. 2. Using functional magnetic resonance imaging (fMRI) to longitudinally assess whether a single dose of psilocybin will post-acutely change the negative emotion processing bias in patients with MDD and whether the change in emotion processing bias will predict subsequent symptom improvement. In addition, the investigators will analyze whether psilocybin will lead to sustained changes in functional neuronal network connectivity (FC), e.g. in amygdala-prefrontal FC. 3. To investigate whether psilocybin will increase BDNF plasma concentration and whether the change in BDNF is related to changes in fMRI markers and the subsequent mood improvement. Recent reviews indicate that impaired neuroplasticity is at the core of the pathophysiology moods and stress-related disorders. Current available antidepressants have been developed with the aim of providing symptom relief rather than targeting neuroplastic impairments. In contrast to this, the present proposal builds on promising new findings that single dose of psilocybin, presumably via a 5-HT2A receptor driven glutamatergic mechanism, leads to a rapid enhancement in neuronal resilience and a to a change in the function of neuronal networks underlying depressive symptoms and behavior. Targeting neuroplasticity with such novel approaches appears to be important for reversing cognitive schemata and emotion processing biases, fostering enduring improvements in mood and cognitive flexibility (Krystal et al. 2009). Expected value: this is the first randomized, double-blind, placebo-controlled clinical trial (RCT) of psilocybin treatment in MDD. Using state-of-the art behavioral, neuroimaging, and neuroplasticity methodology, the results of this study will help elucidate urgently needed new treatment mechanisms in MDD. Should it turn out that a single moderate dose of psilocybin vs. placebo in conjunction with psychotherapy may rapidly and sustainedly reduce depressive symptoms, this will be a major breakthrough in finding a novel and fast acting treatment strategy in depressed patients. Therefore, the results of this study will have high impact on the field of pharmacological research into novel antidepressant medication.

topic_tags:
Depression,Anxiety,Neuroplasticity,Brain Imaging,Mechanism of Action,Receptor Pharmacology,Consciousness,Biomarkers,Aging,Resilience,Emotional Processing,Clinical Trial,Randomized Controlled Trial,Review Article,Cancer Patients


authors: Emory University
journal: ClinicalTrials.gov
publication_date: 2026-05-25
source_url: https://clinicaltrials.gov/study/NCT07332143
substance_tags: psilocybin
topic_tags: Depression,PTSD,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 11:22:34
raw_json: {"nct_id":"NCT07332143","overall_status":"NOT_YET_RECRUITING","phase":["PHASE2"]}
title:
The Safety and Acceptability of Psilocybin With Support and With Massed Prolonged Exposure Therapy for PTSD

abstract:
This pilot study will examine the safety, tolerability, acceptability, and efficacy of combination psilocybin + psychotherapy to decrease PTSD symptoms. Participants will be randomized into two different treatment groups, allowing the investigators to directly compare PE augmented with psilocybin and psilocybin-assisted psychotherapy. The Primary objective is to pilot and investigate tolerability, safety, and acceptability of psilocybin-assisted supportive therapy and psilocybin-assisted massed prolonged exposure (PE) therapy and conduct exploratory analyses related to comparative effectiveness of these treatments, including preliminary outcomes from pre-treatment to 1-month follow-up on post-traumatic stress disorder (PTSD) symptoms. Safety and tolerability of the treatment will be assessed and evaluated using the Swiss Psychedelic Side Effects Inventory (SPSI), Psychedelic-assisted Therapy After Effects (PATAE), and the Accessibility Questionnaire (AQ). The study will also evaluate the effect of psilocybin and massed exposure therapy using Subjective Units of Distress (SUDS) during imaginal exposure sessions; to assess self-reported PTSD and depression symptoms across treatment and investigate effect on fear extinction learning and fear extinction recall as assessed via fear potentiated startle. Given that this is a pilot study with small sample, analyses will be preliminary.

keywords:
PTSD, psilocybin, 3-[2-(Dimethylamino)ethyl]-1H-indol-4-yl dihydrogen phosphate, Supportive Therapy, Prolonged Exposure Therapy, NOT_YET_RECRUITING


authors: University of Colorado, Denver
journal: ClinicalTrials.gov
publication_date: 2026-05-21
source_url: https://clinicaltrials.gov/study/NCT06230757
substance_tags: psilocybin
topic_tags: Depression,Randomized Controlled Trial,Treatment-Resistant Depression
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 11:22:34
raw_json: {"nct_id":"NCT06230757","overall_status":"COMPLETED","phase":["PHASE2"]}
title:
Effects of Psilocybin With Psychological Support on Anhedonia in Treatment-resistant Depression: a Randomized Controlled Pilot Trial

abstract:
The purpose of this study is to evaluate the efficacy of psilocybin on the symptom of anhedonia in individuals with treatment-resistant major depressive disorder.

keywords:
Major Depressive Disorder, Anhedonia, Treatment Resistant Depression, Psilocybin 25mg, Placebo (active placebo), Ultra Low Dose Psilocybin, COMPLETED


title: Efficacy in Relapse Prevention: Psilocybin in Alcohol Use Disorder With Depressive Symptoms
authors: Centre Hospitalier Universitaire de Nīmes
journal: ClinicalTrials.gov
publication_date: 2026-06-30
source_url: https://clinicaltrials.gov/study/NCT07638553
substance_tags: psilocybin
topic_tags: Depression,Addiction,Safety
study_type: Other
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":"NCT07638553","overall_status":"RECRUITING","phase":["PHASE3"]}
abstract:
Up to 40% of individuals with alcohol use disorder (AUD) experience depression, which increases the risk of early relapse. Depression can cause relapse to occur 3 times faster in individuals with AUD who experience depressive symptoms at discharge. No treatments have been approved for individuals with both AUD and depression. Psilocybin, a psychedelic, shows promising results in treating both depression and addiction. It may be particularly effective for preventing relapse in people with AUD who also have depressive symptoms after detoxification, offering quicker action than traditional antidepressants. The Psilocybin Alcohol Depression (PAD) pilot study, launched in February 2024, has provided critical insights for avoiding methodological flaws and demonstrated that psilocybin-assisted psychotherapy (PAP) is both feasible and acceptable. Preliminary efficacy analyses were conducted: at 12 weeks, the 25 mg group showed significantly greater reductions in drinking days (p = 0.038) and craving frequency (p = 0.045). Relapse rates were 35% in the 25 mg group and 50% in the control group (HR = 0.52 \[0.16-1.65\]). In the ERPPAD trial, the study authors will compare high-dose PAP with low-dose PAP in preventing relapse in individuals with AUD and depressive symptoms. The hypothesis is that high-dose PAP will be more effective than low-dose in preventing relapse over 6 months.

keywords:
Alcohol Use Disorder, Depressive Sympotoms, Psilocybin, Psilocybin (high dose), Psilocybin (low dose), RECRUITING


title: Engaging Mood Brain Circuits With Psilocybin: a Randomized Neuroimaging Trial in Depression
authors: Sunnybrook Health Sciences Centre
journal: ClinicalTrials.gov
publication_date: 2026-03-29
source_url: https://clinicaltrials.gov/study/NCT06072898
substance_tags: psilocybin
topic_tags: Depression,Brain Imaging,Aging,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 11:22:34
raw_json: {"nct_id":"NCT06072898","overall_status":"RECRUITING","phase":["PHASE2"]}
abstract:
The goal of this neuroimaging clinical trial is to test whether psilocybin produces significant immediate changes in functional brain activity in networks associated with mood regulation and depression compared to placebo in patients with depression. The trial aims to determine if psilocybin: 1. Changes connectivity within brain networks associated with mood and depression 2. Changes blood flow in brain regions associated with mood and depression Participants will be attend two treatment sessions where they receive an oral medication and supportive psychotherapy. At each session, participants will undergo an MRI scan after drug administration but prior to psychotherapy. Participants will be randomly to assigned to one of two groups that will receive, 1) microcrystalline cellulose (25mg) at the first visit and psilocybin (25mg) at the second visit, or 2) psilocybin (25mg) at both visits, respectively. Differences between groups will be compared to understand what effects on brain activity are specific to psilocybin.

keywords:
Depressive Disorder, Major Depressive Disorder, Psilocybin, Microcrystalline cellulose, MCC, Supportive psychotherapy, RECRUITING


authors: Yale University
journal: ClinicalTrials.gov
publication_date: 2026-06-03
source_url: https://clinicaltrials.gov/study/NCT05370911
keywords: Obsessive-Compulsive Disorder, Psilocybin, ACTIVE_NOT_RECRUITING
substance_tags: psilocybin
topic_tags: OCD,Mechanism of Action
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 11:22:34
raw_json: {"nct_id":"NCT05370911","overall_status":"ACTIVE_NOT_RECRUITING","phase":["PHASE1"]}
title:
Effects of Repeated Dosing of Psilocybin on Obsessive-Compulsive Disorder: A Randomized, Waitlist-Controlled Study

abstract:
This study aims to investigate the effects of repeated dosing of oral psilocybin on obsessive-compulsive disorder (OCD) symptomatology in a randomized, waitlist-controlled design with blinded independent ratings, and assess psychological mechanisms that may mediate psilocybin's therapeutic effects on OCD. Aim 1: To examine the effects of two doses of psilocybin on OCD symptoms among participants in the immediate treatment condition, compared to participants in the waitlist control/delayed treatment condition. The investigators hypothesize that participants in the immediate treatment group will report statistically significantly greater symptom improvement from baseline 4 days post-second dose, compared to participants in the waitlist control/delayed treatment group at the same interval during their waitlist phase. Aim 2: To examine the effects of two doses of psilocybin on OCD symptoms, compared to one dose. The investigators hypothesize that two doses of oral psilocybin will reduce OCD symptoms to a statistically significantly greater extent than one dose. This study aims to investigate the effects of repeated dosing of oral psilocybin on OCD symptomatology and assess psychological mechanisms that may mediate psilocybin's therapeutic effects on OCD. This study will employ a randomized, waitlist-controlled design with blinded independent ratings, with participants randomized to receive either immediate treatment (two doses oral psilocybin separated by one week) or delayed treatment (7 weeks post-randomization). An adaptive dose selection strategy will be implemented, with the first dose being standardized at 25 mg of psilocybin, and the second dose being either the same or a higher dosage (i.e., 30 mg) on the basis of a clinically significant response from baseline or not, respectively, 4 days post-first dose. This study is conducted entirely on an outpatient basis with the possibility of remote/virtual follow-up visits after each dosing session. The dosing sessions last the entire day, and participants will be medically cleared prior to being permitted to return home with assistance (e.g., driven by a family member or friend, or ride share).


authors: University of Zurich
journal: ClinicalTrials.gov
publication_date: 2025-11-18
source_url: https://clinicaltrials.gov/study/NCT06081179
substance_tags: psilocybin
topic_tags: Receptor Pharmacology,Healthy Volunteers
study_type: Other
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:28
last_checked: 2026-07-01 11:22:34
raw_json: {"nct_id":"NCT06081179","overall_status":"COMPLETED","phase":["PHASE1"]}
title:
Does Serotonin System Stimulation Increase Pro-social Behavior? - A Comparative Pharmacological Neuroscientific Study in Healthy Humans

abstract:
The study looks into whether administering psychedelic substances that stimulate the serotonin system influences pro-social behavior when compared to administering substances that stimulate the dopamine system in healthy individuals. Psychedelic substances have been shown to be powerful modulators of social perception and behavior during the acute experience. This is of particular interest given that social relationships play a key role in the development and resolution of psychiatric symptoms. However, the neuropharmacological mechanism underlying pro-social effects and time-dependent changes currently remain unclear. This study therefore aims at answering two key questions: 1) Does stimulation of the serotonin system induce lasting effects on pro-social behavior? and 2) Are these effects specific to serotonergic stimulation? The following proposed study will assess these questions by investigating objective, ecologically valid measures of pro-social cognition four weeks after different pharmacological challenges (MDMA, an entactogen and releaser of serotonin, norepinephrine, and dopamine; psilocybin: a classical psychedelic and serotonin 2A receptor agonist, methylphenidate: an amphetamine and norepinephrine-dopamine re-uptake inhibitor) in healthy volunteers.

keywords:
Healthy, Psilocybin, magic mushrooms, 3,4 Methylenedioxymethamphetamine, MDMA, Ecstasy, Methylphenidate, Ritalin, COMPLETED


title: Acute Effects of 2C-B Compared With MDMA and Psilocybin in Healthy Subjects
authors: University Hospital, Basel, Switzerland
journal: ClinicalTrials.gov
publication_date: 2025-03-04
source_url: https://clinicaltrials.gov/study/NCT05523401
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 11:22:34
raw_json: {"nct_id":"NCT05523401","overall_status":"COMPLETED","phase":["PHASE1"]}
abstract:
4-bromo-2,5-dimethoxyphenethylamine (2C-B) is a psychoactive substance with reportedly similar acute effects to both the prototypical empathogen 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) and the classic psychedelic substance psilocybin (contained in "magic, hallucinogenic mushrooms"). Pharmacologically, MDMA mainly releases serotonin (5-HT) via the serotonin transporter (SERT) and psilocybin mainly acts as direct agonist at 5-HT2A receptors. 2C-B interacts with both the 5-HT2A receptor and SERT which is in line with its reported mixed effects profile. However, scientific studies are lacking. There is an increased interest in psychiatric research on the therapeutic properties of MDMA and psilocybin and also on mixed empathogenic-psychedelic substances. 2C-B is a phenethylamine and belongs to the so-called 2C drugs, a group of novel psychoactive substances (NPS) with some structural similarity to the classic psychedelic mescaline. 2C-B is relatively widely used as recreational substance often replacing or mimicking classic substances such as LSD or MDMA. 2C-B also ranks high among the substances found as substitutes or adulterants of tablets sold as MDMA or Ecstasy. Users report that 2C-B has similar acute effects to MDMA when used at low (5-10 mg) and medium doses (10-25 mg) and more psychedelic effects when used at a high doses (25-40 mg). Additionally, in two open labeled studies the effects have been defined by the researchers as entactogenic (MDMA-like) with psychedelic/hallucinogenic properties when administering 20 mg and on the other hand as psychedelic-psychostimulant like when administering a mean dose of 16 mg (4 used 10 mg, 5 used 15 mg and 7 used 20 mg). Subjective effects peaked at 1-2h and lasted 5h. The 2C drugs act mainly as agonists on the 5-HT2A receptor very similar to classic psychedelics like LSD or psilocybin. Furthermore, 2C-B may interact with monoaminergic systems more similar to MDMA and may share some empathogenic or even stimulant-type actions. 2C-B also inhibits the SERT similar to MDMA, however, only at low potency in vitro. Thus, taken together, the pharmacology of 2C-B in vitro is somewhat inconclusive but would be consistent with both MDMA- and psychedelic-type actions in vivo in humans. Increases in blood pressure and heart rate are moderate and regarded as lower than those of MDMA. No severe cases were observed. The safety profile of 2C-B is considered to be similar to MDMA. Psilocybin is a classic serotonergic psychedelic. Psilocybin is a prodrug which is activated to psilocin within the body. The psychoactive action of psilocin primarily involves an interaction with the serotonin 5-HT2A receptor. Currently, psilocybin is the most investigated psychedelic substance among the classic psychedelics. In particular, there are high hopes of using psilocybin in patients with treatment resistant major depression and pharmaceutical companies are currently conducting phase III studies. MDMA is an amphetamine derivative which, unlike prototypical amphetamines, predominantly enhances serotonergic neurotransmission via release of 5-HT through the SERT and it less potently also releases dopamine and norepinephrine through the dopamine transporter (DAT) and norepinephrine transporter (NET), respectively. Furthermore, MDMA is known to trigger oxytocin release which may contribute to its effects to increase trust, prosociality, and enhanced empathy and is therefore referred to as an "entactogen" or "empathogen". Being granted as a "breakthrough therapy" by the FDA, MDMA is currently investigated in substance-assisted psychotherapy for treatment of PTSD. By using a placebo-controlled double-blind cross-over design the study will provide insight into the effects profiles of recreationally used psychoactive substances relevant for psychiatric research. Therefore the study will compare the acute subjective, physiological and endocrine effects of low (10 mg), medium (20 mg) and high (30 mg) doses of 2C-B with standard doses of MDMA (125 mg) and psilocybin (25 mg) in healthy subjects. Finally, the study will also allow to newly directly compare MDMA and psilocybin effects at representative doses and within the same subjects which will provide for a better characterization of these substances increasingly used in psychiatric research.

keywords:
Healthy, 4-bromo-2,5-dimethoxyphenethylamine (10 mg), 2C-B, 4-bromo-2,5-dimethoxyphenethylamine (20 mg), 4-bromo-2,5-dimethoxyphenethylamine (30 mg), 3,4-methylenedioxymethamphetamine, MDMA, Psilocybin, Placebo, COMPLETED

topic_tags:
Depression,PTSD,Pharmacology,Receptor Pharmacology,Clinical Trial,In Vitro Study,Safety,Drug Interactions


title: Effects and Therapeutic Potential of Psilocybin in Alcohol Dependence
authors: University of New Mexico
journal: ClinicalTrials.gov
publication_date: 2023-09-25
source_url: https://clinicaltrials.gov/study/NCT01534494
keywords: Alcohol Dependence, Psilocybin, COMPLETED
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Spirituality,Safety
study_type: Other
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:28
last_checked: 2026-07-01 11:22:34
raw_json: {"nct_id":"NCT01534494","overall_status":"COMPLETED","phase":["PHASE2"]}
abstract:
This trial is an open-label pilot study (N = 10) designed to assess the effects of psilocybin in alcohol dependent participants, demonstrate the feasibility of the integrated behavioral/pharmacologic intervention, and provide preliminary outcome and safety data. Participants will receive psilocybin orally in two all-day administration sessions, conducted in a secure outpatient psychiatric setting, in a dose range that has been well-tolerated in recent studies. Psilocybin administration will occur in the context of a behavioral intervention including a total of 12 sessions over 12 weeks, incorporating Motivational Enhancement Therapy (MET (Miller, Zweben et al. 1992; Miller 1995), based on Motivational Interviewing (Miller and Rollnick 2002)) with booster sessions, as well as preparation before and debriefing after the psilocybin administration sessions. The MET will incorporate attention to spirituality as well as drinking behavior as a primary subject of change. 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 during treatment and for 24 weeks after the end of treatment. The investigators hypothesize that drinking will decrease following the psilocybin sessions, and that increases in motivation, self-efficacy, and spirituality (primary contrast 12 weeks vs. baseline) will be observed among study participants.


authors: Kevin Murnane
journal: ClinicalTrials.gov
publication_date: 2025-10-06
source_url: https://clinicaltrials.gov/study/NCT06899594
keywords: Methamphetamine Use Disorder, Psilocybin 25 mg, RECRUITING
substance_tags: psilocybin
topic_tags: Addiction,Emotional Processing,Review Article,Safety
study_type: Review Article
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:28
last_checked: 2026-07-01 11:22:34
raw_json: {"nct_id":"NCT06899594","overall_status":"RECRUITING","phase":["EARLY_PHASE1"]}
title:
A Pilot Study in North Louisiana to Assess the Tolerability of Psilocybin as Well as Its Capacity to Promote Abstinence From Methamphetamine

abstract:
The primary purpose of this study is to preliminarily determine if the use of psilocybin to promote abstinence from methamphetamine is feasible and well tolerated in populations such as those found in Northern Louisiana. Investigators will assess the impact of psilocybin-facilitated treatment on methamphetamine abstinence, craving, negative affect, cognitive function and quality of life. Components of the psilocybin experience will also be measured (persisting effects, quality of life, challenging experiences, etc). Investigators will assess feasibility and tolerability as rates of retention and challenging experiences, among other factors. This is an open-label pilot study evaluating the feasibility and tolerability of a single 25 mg psilocybin dose in promoting abstinence from methamphetamine. Participants will attend 10 to 12 study visits over a period of up to six months. Participants will be recruited from a population receiving treatment for methamphetamine dependence at a local residential treatment facility. Recruitment will involve informative presentations to current clients and counselor-facilitated referrals based on provided inclusion criteria. Prescreening will utilize information collected by the treatment center during the client's admission process. Individuals who meet prescreening criteria will be invited to an in-person screening visit, conducted after obtaining informed consent. The screening visit will include a clinical review, a detailed psychiatric interview, self-report questionnaires, a comprehensive medical history, and safety laboratory testing, including blood draws. Once eligibility is confirmed, participants will proceed with study enrollment and complete baseline assessments, which will measure substance use, quality of life, and executive function. Three preparatory sessions will follow over a two-week period to establish trust and rapport between participants and session monitors, educate participants on the study protocol, and prepare them for the psilocybin session. Two preparatory sessions may be conducted via telehealth to enhance feasibility, while the third will be conducted in person with both the primary and secondary monitors present. A medical examination will be performed within the week preceding psilocybin administration. Within a week of the third preparatory session, participants will attend a psilocybin administration session. Participants will arrive at the study location by 9:30 AM and undergo safety screenings, including breathalyzer testing, before psilocybin administration at approximately 10:00 AM. Participants will have been instructed to consume a low-fat breakfast prior to arrival. During the session, cardiovascular measures (e.g., heart rate, blood pressure) will be monitored upon arrival, hourly throughout the session, and as clinically indicated. The psilocybin session, lasting approximately 6-8 hours, will be monitored by both the primary and secondary session monitors, ensuring that at least one individual is present with the participant at all times. At the conclusion of the session, participants will complete questionnaires assessing their subjective experiences. Participants will then be released into the care of treatment center staff, who will provide emotional support. Participants will also receive contact information for the primary monitor to access support if needed. Post-session integration will include two telehealth sessions: the first within one day of the psilocybin session and the second approximately 7 days later (±3 days). These sessions will provide opportunities to discuss insights or challenges arising from the psilocybin experience, with an emphasis on promoting adaptive cognitive and behavioral changes. Follow-up assessments will occur via telehealth at 30 and 60 days post-psilocybin, with an in-person assessment conducted at 120 days. The final visit will include a urine drug screen.


authors: Imperial College London
journal: ClinicalTrials.gov
publication_date: 2024-11-05
source_url: https://clinicaltrials.gov/study/NCT06258031
substance_tags: psilocybin
study_type: Observational Study
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:28
last_checked: 2026-07-01 11:22:34
raw_json: {"nct_id":"NCT06258031","overall_status":"COMPLETED","phase":["PHASE1"]}
title:
PsilOCD: Evaluating the Effects of the 5-HT2A Agonist Psilocybin on the Neurocognitive and Clinical Correlates of Compulsivity (A Pharmacological-Challenge Feasibility Study)

abstract:
The purpose of this study is to assess the impact of psilocybin on cognitive inflexibility and neural plasticity in a cohort of people with obsessive-compulsive disorder (OCD). This mechanistic study will utilise a within-subjects design, administering up to 10mg of psilocybin to participants with OCD (DSM-5 criteria) on two separate instances spaced four weeks apart. To ensure consistency and participant safety, dosing will occur under medical supervision with psychological support from two experienced therapists. Before and after each session, participants will engage in virtual preparation and integration sessions led by their therapists. Cognitive tasks will be administered in the days following each dosing session. Additionally, acute post-dosing EEG recordings will be conducted, and blood samples will be taken after each dosing session. OCD symptoms will also be assessed seven times throughout the trial by an external blinded psychiatrist, serving as a secondary outcome. Collectively, these measures aim to evaluate changes in cognitive inflexibility, decision-making abilities, neuroplasticity (peripheral blood markers and EEG measures), inflammation (peripheral blood markers), and symptomatology following each dosing session.

keywords:
Obsessive-Compulsive Disorder, Psilocybin (COMP360), O-phosphoryl-4-hydroxy-N,N-dimethyltryptamine, COMPLETED

topic_tags:
OCD,Neuroplasticity,Brain Imaging,Receptor Pharmacology,Biomarkers,Observational Study,Safety,Inflammation


authors: University Hospital, Basel, Switzerland
journal: ClinicalTrials.gov
publication_date: 2026-04-01
source_url: https://clinicaltrials.gov/study/NCT06180759
substance_tags: psilocybin
topic_tags: Chronic Pain,Headache / Migraine,Clinical Trial,Case Report,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 11:22:34
raw_json: {"nct_id":"NCT06180759","overall_status":"COMPLETED","phase":["PHASE1"]}
title:
Acute Analgesic Effects of DMT on Experimentally Induced Acute Nociceptive Pain, Hyperalgesia and Allodynia in Healthy Participants

abstract:
N,N-dimethyltryptamine (DMT) is a classical psychedelic with similar effects like LSD or psilocybin. Preliminary evidence from case series and small open-label trials suggests that psychedelics may be promising candidates for the treatment of several pain-related diseases such as chronic pain, migraine, cluster headache or phantom limb pain. However, data from rigorously conducted and randomized clinical trials are lacking. Additionally, the potential acute analgesic properties of psychedelics remain poorly characterized. Therefore, the investigators will evaluate the efficacy of DMT on different pain qualities within a model of electrically induced pain in healthy participants. The analgesic effects will be compared to racemic ketamine (active control) and placebo within a cross-over design. Preliminary evidence from case series and small open-label trials suggests that psychedelics may be promising candidates for the treatment of several pain-related diseases such as chronic pain, migraine, cluster headache or phantom limb pain. However, data from rigorously conducted and randomized clinical trials are lacking. Additionally, the potential acute analgesic properties of psychedelics remain poorly characterized. For instance, it is unclear whether psychedelics possess acute antinociceptive effects or if they rather modulate secondary pain phenomena such as hyperalgesia, allodynia, and/or functional pain. Here, the investigators will employ a validated electrical stimulation model in healthy volunteers that produces acute nociceptive pain but also features of chronic pain such as hyperalgesia and allodynia. The model is established for the detailed assessment of the analgesic effect of known analgesics or new compounds. Thus, the investigators will evaluate the efficacy of N,N-dimethyltryptamine (DMT), a classical and naturally-occurring psychedelic, on different pain qualities within this model. DMT differs from other classical psychedelics in its very short elimination half-life. Due to its rapid metabolization by monoaminoxidases (MAO), DMT is not orally bioavailable in the absence of MAO-inhibitors and thus has to be administered continuously and intravenously. Recently, the investigators tested several continuous intravenous administration regimes of DMT that lead to the induction of a constant and rapidly adaptable psychedelic state. The regime allows to induce stable DMT effect that can be terminated rapidly. Due to this controllability, a continuous infusion of intravenous DMT is most suitable to assess time and concentration-dependent analgesic effects within the used pain model. The analgesic efficacy of DMT will be compared to ketamine, a known analgesic (positive control), and placebo.

keywords:
Healthy, Intravenous infusion of DMT, Intravenous infusion of ketamine, Intravenous infusion of placebo, COMPLETED


authors: National Council of Scientific and Technical Research, Argentina
journal: ClinicalTrials.gov
publication_date: 2021-12-15
source_url: https://clinicaltrials.gov/study/NCT05160220
keywords: Cognitive Change, Creativity, Mood Change, Sleep, Psilocybin, Placebo, COMPLETED
substance_tags: psilocybin
topic_tags: Brain Imaging,Mechanism of Action,Microdosing,Wellbeing,Creativity
study_type: Other
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:28
last_checked: 2026-07-01 11:22:34
raw_json: {"nct_id":"NCT05160220","overall_status":"COMPLETED","phase":["NA"]}
title:
Double-blind Placebo-controlled Naturalistic Study of Microdosing With Psilocybin: Effects on Brain Activity, Behavior, Cognition, Creativity, and Mental Health

abstract:
This study seeks to understand the neural, cognitive and behavioral effects of low doses of psilocybin administered in the form of dried mushroom material (0.5 g of Psilocybe cubensis) consumed in natural settings following a placebo-controlled double-blind experimental design. Sub-threshold doses of serotonergic psychedelics are frequently consumed as cognitive enhancers, and due to their purported positive effects on mood, energy and creativity ("microdosing"). The acute and short-term effects of psilocybin (the psychoactive compound of Psilocybe cubensis mushrooms) on several variables will be investigated, comprising spontaneous and evoked electrophysiological brain activity, perception and cognitive function (cognitive flexibility, attention, inhibitory control, conscious access, visual perception), creativity (problem solving, divergent and convergent thinking), behavior (actigraphy and sleep patterns, natural language production) and several domains related to well-being and mental health of the participants. This study is simultaneously naturalistic (i.e. recruited subjects are intrinsically motivated to microdose, as they have decided to embark in a microdosing protocol) and controlled by expectations, following a double-blind placebo-controlled design. Participants will microdose according to the following schedule: Two sessions (0.5 g dried Psilocybin mushrooms vs. dried edible mushroom material without psychoactive effects as a placebo condition) will be conducted. A third party will be in charge of generating their active dose and placebo capsules, and they will also implement a blinding procedure. Each session will span one week of measurements. Subjects will be given a smartwatch to monitor activity and sleeping patterns at the beginning of the week. At days 3 and 5, subjects will take capsules with active mushroom material or placebo, and then several variables will be recorded. Experiments will be conducted in a setting that is natural and comfortable for the participants, e.g. their homes. The main outcome measures consist of resting state activity recorded with EEG, evoked response potentials and performance during cognitive tasks, behavioral variables obtained with actigraphy and automated sleep scoring, natural language analysis, and several measurs self-reported via standarized questionnaires. After completion, this study will provide direct evidence concerning the efficacy of microdosing for cognitive enhancement under natural conditions, i.e. those most frequently used by individuals who microdose, as well as provide information concerning the potential underlying neurobiological mechanisms.


title: Low-Income Group Psilocybin Assisted Therapy for Depression: A Feasibility Study
authors: Matthew Hicks
journal: ClinicalTrials.gov
publication_date: 2025-06-04
source_url: https://clinicaltrials.gov/study/NCT06372197
keywords: Depression, Psilocybin, COMPLETED
substance_tags: psilocybin
topic_tags: Depression,Mechanism of Action,Consciousness,Clinical Trial,Observational Study,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 11:22:34
raw_json: {"nct_id":"NCT06372197","overall_status":"COMPLETED","phase":["NA"]}
abstract:
Due to psilocybin-assisted therapy's success in previous research, growing cultural awareness and use of psilocybin and other psychedelics, the Oregon Psilocybin Services Act passed by ballot measure in 2020 and began offering services in 2023. While the program has had many successes, a significant problem it faces is affordability and no research to date has investigated the therapy in a low-income population. Psychedelic research in recent decades has used the model of two therapists to one client to demonstrate an abundance of caution and safety to regulators, but no evidence has demonstrated this model to be safer or more effective than one with less practitioner oversight. This feasibility study would be the first investigation of Oregon Psilocybin Services as a model of care and among the first few to use a group therapy model. This study aims to test the feasibility of the model by assessing recruitment, retention, acceptability and safety of the treatment. In addition to an appropriate medical screening and intake the following questionnaire data will be collected: the Adverse Childhood Events (ACE) questionnaire, Credibility/Expectancy Questionnaire (CEQ), Hamilton Depression Inventory, PROMIS-29, Altered States of Consciousness (11-ASC) rating scale, and a survey and structured interview. Participants will consist of adults in Oregon with an income at or below 200% of the federal poverty level. Inclusion criteria will include DSM-5 diagnosis of major depression. Participants will be individually screened by a study investigator and placed into groups of five to six participants. Treatment will consist of two group preparation sessions, two psilocybin sessions, and two group integration sessions. An additional follow-up visit to collect further data will take place three months after conclusion of the treatment. The proposed study will provide valuable information for designing future clinical trials investigating the efficacy, mechanisms, and cost-effectiveness of psilocybin-assisted group therapy for depression in low-income populations.


authors: NYU Langone Health
journal: ClinicalTrials.gov
publication_date: 2026-01-22
source_url: https://clinicaltrials.gov/study/NCT06796062
keywords: Opioid Use Disorder, Psilocybin, RECRUITING
substance_tags: psilocybin
topic_tags: Addiction,Clinical Trial,Randomized Controlled Trial,Safety
study_type: Randomized Controlled Trial
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:28
last_checked: 2026-07-01 11:22:34
raw_json: {"nct_id":"NCT06796062","overall_status":"RECRUITING","phase":["PHASE2"]}
title:
A Phase 2 Trial of Psilocybin as an Adjunctive Treatment for OUD Patients Who Continue to Use Illicit Opioids Despite Adherence to Methadone Treatment

abstract:
This is a double-blind, adaptive, 2-stage, multi-site, phase 2 randomized controlled clinical trial designed to evaluate effects of moderate and high dose psilocybin, relative to low-dose psilocybin control, in OUD patients who continue to use illicit opioids in spite of adherence to standard-of-care treatment with methadone. Up to 480 participations will be consented to yield 240 randomized participants. This study is part of the NIH HEAL Initiative (https://heal.nih.gov/). In Stage 1, subjects will be randomly assigned to one of three groups: psilocybin 30 mg (high dose), psilocybin 20 mg (medium dose), and psilocybin 1 mg (control condition). By the end of Stage 1, an interim statistical analysis will be performed. The study will proceed to Stage 2 if at least one of the active dosages of psilocybin demonstrates 1) acceptable safety, based on analysis of safety data from Stage 1; and 2) conditional power of at least 25%, based on effect size estimates for the primary opioid use outcome (weeks of biologically-verified abstinence during 24 weeks of follow-up). Using a priori decision rules, the interim analysis will determine which of the active treatment groups (30 mg, 20 mg, or both) will be retained in Stage 2 of the trial. Stage 2 will continue the study, using the same treatment and assessment protocols, but retaining only the active dosage or dosages with a high probability of demonstrating efficacy relative to the psilocybin 1 mg control condition. The primary aims are to 1) Evaluate safety and efficacy outcomes in Stage 1 subjects in order to optimize design of the Stage 2, 2) Determine whether treatment with a single high (30 mg) or medium (20 mg) dose of psilocybin improves OUD treatment outcomes, relative to psilocybin 1 mg (control condition), in patients who continue to use illicit opioids despite adherence to methadone treatment, 3) Evaluate the effects of high-dose psilocybin and medium dose psilocybin on self-reported OUD-related neuropsychopathology, and 4) Identify likely responders to psilocybin treatment by using machine learning to model post-treatment OUD outcomes, based on pretreatment characteristics including all relevant clinical data, evaluations, and questionnaires.


authors: M.D. Anderson Cancer Center
journal: ClinicalTrials.gov
publication_date: 2026-06-23
source_url: https://clinicaltrials.gov/study/NCT06801041
keywords: Depression, Anxiety, Cancer, Psilocybin, RECRUITING
substance_tags: psilocybin
study_type: Other
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:28
last_checked: 2026-07-01 11:22:34
raw_json: {"nct_id":"NCT06801041","overall_status":"RECRUITING","phase":["PHASE2"]}
title:
TRIPS - Treatment to Improve Depression and/or Anxiety Using Psilocybin-assisted Psychotherapy in Cancer Survivors

abstract:
This clinical research study is to learn about the feasibility, safety, and effects of psilocybin-assisted psychotherapy for cancer survivors with depression and/or anxiety. Primary Objective: To examine the feasibility, safety, effect size estimates of psilocybin-assisted psychotherapy for cancer survivor patients with depression and/or anxiety. Feasibility will be measured as: At least 20% of eligible patients consent (inclusion rate), at least 60% of consented patients completing the two doses of treatment (treatment completion rate), and at least 80% and 65% consenting patients completing assessments at the 2- and 6-month follow-ups (adherence rates), respectively. Secondary Objectives: 1. Determine whether psilocybin-assisted psychotherapy improves measures of quality of life (e.g., sleep, pain, functional status) and psychosocial well-being (e.g., finding meaning and post-traumatic growth), as measured by the following: PHQ-9, GAD-7, PROMIS-10, PROMIS-A, PROMIS-D, MEQ30 (mystical experience), Flourishing scale, mDES, PIQ (altered states), and Posttraumatic Growth Inventory. 2. Determine whether psilocybin-assisted psychotherapy improves functional status per clinician-rated outcome measures. 3. Measure the change in inflammatory markers (IL6, TNF, and CRP) and in frequency and activation status of peripheral immune cell populations assessed by immune monitoring through flow cytometry. 4. Examine changes in central nervous system plasticity through the use of fMRI, specifically changes in 5-HT2A-rich and higher-order functional networks, as well as a global increase in brain network integration. 5. Evaluate the Impact on MDASI measurements.

topic_tags:
Depression,Anxiety,Chronic Pain,Neuroplasticity,Brain Imaging,Receptor Pharmacology,Biomarkers,Wellbeing,Mystical Experience,Healthcare Workers,Safety,Inflammation,Immune Function


authors: Johns Hopkins University
journal: ClinicalTrials.gov
publication_date: 2026-02-22
source_url: https://clinicaltrials.gov/study/NCT06005662
keywords: Opioid Use Disorder, Psilocybin, Buprenorphine, WITHDRAWN
substance_tags: psilocybin
topic_tags: Addiction,Clinical Trial,Healthy Volunteers,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 11:22:34
raw_json: {"nct_id":"NCT06005662","overall_status":"WITHDRAWN","phase":["PHASE2"]}
title:
Inpatient Buprenorphine Induction With Psilocybin for Opioid Use Disorder: a Randomized Double-blind Trial

abstract:
This study will examine the effect of a single high dose of psilocybin therapy (30 mg) versus a very low dose (1 mg) as an adjunctive therapy to individuals undergoing standard-of-care buprenorphine treatment for Opioid use disorder (OUD). Effects of adjunctive psilocybin will be determined for longitudinal outcomes of opioid abstinence, compliance with buprenorphine maintenance, quality of life, and mood. The proposed study is a double-blind, controlled investigation of the effect of 1 high-dose psilocybin (30 mg) session compared to a very low dose session (1 mg) following standard-of-care buprenorphine induction on drug abstinence, quality of life, craving, tobacco use, and treatment retention in healthy participants with an active OUD diagnosis. Use of buprenorphine follow standard of care, and the investigators are investigating the additive power of adjunctive psilocybin to enhance opioid abstinence, treatment adherence, quality of life, and mood. The study will consist of a brief (6-8 day) inpatient phase for standard buprenorphine induction as well as experimental psilocybin administration, an 8-week outpatient phase involving standard buprenorphine maintenance and experimental follow-up meetings, and long-term follow-up sessions for 4 months after. During the inpatient phase, participants will be inducted onto sublingual (SL) buprenorphine (using a buprenorphine/naloxone combination product) while admitted to the Bayview Clinical Research Unit. During this time, participants will also undergo 2-3 preparatory sessions, and will undergo an experimental drug administration session under supportive conditions, during which the participants will receive either a very low dose (1 mg) or a single high (30mg) oral dose of psilocybin under double-blind conditions. At the end of the inpatient phase, participants will be discharged to complete the 8-week outpatient phase, during which participants will undergo visits at 1, 2, 3, 4, 6, and 8 weeks post-dosing session for monitoring of adverse events, clinical status, treatment adherence, and to receive a weekly supply of buprenorphine. All buprenorphine procedures will be open label and will follow standard-of-care practices. This trial utilizes a Bayesian sequential methodology, employing a maximum sample size of 90 participants and calculating Bayes factors (starting at 20 participants and assessed after each 10) to assess evidence for the null and experimental hypotheses, enabling potential early stopping for efficacy or futility based on predetermined thresholds (Bayes factor of 6 and 1/6). This will be calculated for the primary outcome of opioid abstinence at 8-weeks


authors: National Institute of Mental Health, Czech Republic
journal: ClinicalTrials.gov
publication_date: 2022-05-19
source_url: https://clinicaltrials.gov/study/NCT05383313
keywords: Treatment Resistant Depression, Psilocybin, Ketamine Hydrochloride, Midazolam Ph. Eur 9.0, UNKNOWN
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 11:22:34
raw_json: {"nct_id":"NCT05383313","overall_status":"UNKNOWN","phase":["PHASE2"]}
title:
Psilocybin Versus Ketamine - Fast Acting Antidepressant Strategies in Treatment-resistant Depression

abstract:
The main goal is to compare the antidepressant effects of psilocybin and ketamine in patients with TRD versus the antidepressant inactive substance midazolam. The primary endpoint will be the antidepressant effect on the Montgomery- Asberg Depression Rating Scale (MADRS) 24 hours after treatment, the key secondary endpoints being the duration of antidepressant effect, the number of responses and remissions, and the time to standard antidepressant treatment during 3 months of observation. The exploratory part of the study aims to monitor changes in the functional brain states using simultaneous EEG / fMRI, before treatment versus 1 day and 1 week after. Based on literature data and recent data from healthy volunteers who participated in a previous study with psilocybin, the investigator will correlate antidepressant effects of drugs (using psychometric scales and reactions to emotionally salient stimuli (eye tracker)) with entropy and functional connectivity measures. Finally the investigator will explore the role of plasmatic neurobiological biomarkers in depression (BDNF, prolactin, ACTH and oxytocin). The main aim of the study is to verify the efficacy and safety of a single dose of psilocybin 20 mg in the treatment of TRD in adults in a randomized clinical trial with active comparator ketamine 200 mg (rapid onset acting antidepressant) and negative control midazolam 5 mg (drug with no antidepressant properties). Primary objective: 1) verification of the rapid antidepressant effect of psilocybin compared to ketamine using the MADRS scale at 24 hours. Secondary objectives: 1) on days 3, 7 and 14 and 3, 4, 5, 6, 8 and 12 weeks after application of the substances, evaluate / compare: a) the duration of effects of both substances using the MADRS scale b) antidepressant effects according to the subjective evaluation of patients - QIDS scale. c) response rate (50% reduction on the MADRS scale) and remission (MADRS? 10). 2) time to return of depressive symptoms defined according to the criteria for the use of antidepressants within 12 weeks 3) safety profile of study medication Exploratory objectives: 1) Evaluate the antidepressant effect depending on: a) the intensity of acute psychological effects assessed using the subjective scale of 5D-ASCs and the objective scale of BPRS, b) depending on the retrospective assessment of persistent effects using the Persisting effects scale, c) the degree of eye contact with negative and neutral emotion faces measured by eye-tracking before and after treatment (on days 1 and 7). 2) To evaluate the neurobiology of the antidepressant effect in relation to: a) plasma levels of the major metabolite of psilocin, markers of neuroplasticity, antidepressant effect and stress (BDNF, prolactin, oxytocin, ACTH) at 90 min, 3, and 6 h after administration of study medication compared to pre-administration levels, b) changes in resting-state brain activity (connectivity, entropy) measured by simultaneous EEG / fMRI functional imaging methods before and after 1 and 7 days after treatment.

topic_tags:
Depression,Neuroplasticity,Brain Imaging,Biomarkers,Aging,Emotional Processing,Clinical Trial,Healthy Volunteers,Treatment-Resistant Depression,Safety


title: Retrospective Observational Study of Intensity Effects in Psychedelic-assisted Treatment
authors: University Hospital, Geneva
journal: ClinicalTrials.gov
publication_date: 2025-10-01
source_url: https://clinicaltrials.gov/study/NCT07164287
substance_tags: psilocybin
topic_tags: Depression,Anxiety,PTSD,Addiction,Observational Study,Treatment-Resistant Depression,Safety
study_type: Observational Study
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:28
last_checked: 2026-07-01 11:22:34
raw_json: {"nct_id":"NCT07164287","overall_status":"ACTIVE_NOT_RECRUITING","phase":[]}
abstract:
This retrospective observational study examines the effects of psychedelic-assisted psychotherapy (PAP) with lysergic acid diethylamide (LSD) or psilocybin in patients with treatment-resistant depressive, anxiety, or addictive disorders. Data will be analyzed from patients treated at the University Hospitals of Geneva between June 2020 and April 2025 who obtained individual authorizations from the Swiss Federal Office of Public Health for use of LSD or psilocybin under compassionate use criteria. The main objective is to assess the effects of psychedelic-assisted psychotherapy with LSD or psilocybin on changes in depressive symptoms, anxiety symptoms. Secondary objectives include evaluating the association between psychedelic session intensity and the administered dose of LSD or psilocybin, changes in depressive symptoms, anxiety symptoms, and problematic substance use, as well as their association with intensity effects. Additionally physiological effects during session will be assessed. All data are retrospectively collected from clinical records with prior patient consent. This study aims to generate evidence on the feasibility, safety, and therapeutic potential of PAP in real-world clinical practice. The overall project is a retrospective observational study evaluating the effects of psychedelic-assisted psychotherapy (PAP) with LSD or psilocybin in treatment-resistant depressive, anxiety, and addictive disorders. Data from 200 patients treated at Geneva University Hospitals will be included, with the primary aim of assessing relationships between psychedelic dose, subjective intensity of experience, and clinical outcomes. Subset Analysis: Cardiovascular Outcomes In addition to the main objectives, a subset analysis will be conducted to evaluate cardiovascular effects of LSD and psilocybin. Routinely collected data from 30 patients with treatment-resistant depression or anxiety disorders will be included. Population: 30 patients who underwent their first psychedelic session (LSD100-200 µg or psilocybin 15-25 mg). Measurements: Heart rate and self-rated anxiety (visual analogue scale) recorded at seven time points between 30 and 300 minutes post-administration on the treatment day. A further subset analysis investigated the role of early maladaptive schemas (EMS) in psychedelic-assisted psychotherapy. Populations: 192 patients who routinely completed the Young Schema Questionnaire - Rasch version (YSQ-R) before treatment were included; of these, 97 initiated PAP with LSD or psilocybin and 74 contributed longitudinal outcomes. Measurements: Baseline EMS profiles (YSQ-R) measured at Baseline (screening or preparation visit, before first psychedelic session), immediately after each psychedelic session (sessions 1-3, up to 9 months) and 1 month after each psychedelic session (sessions 1-3, up to 12 months after baseline).

keywords:
Major Depressive Disorder (MDD), Anxiety Disorders, Substance Use Disorder (SUD), PTSD - Post Traumatic Stress Disorder, Lysergic Acid Diethylamide (LSD) or psilocybin, ACTIVE_NOT_RECRUITING


authors: University of Wisconsin, Madison
journal: ClinicalTrials.gov
publication_date: 2026-04-02
source_url: https://clinicaltrials.gov/study/NCT06692192
keywords: Psilocybin, Psilocybine, Psilocibin, Midazolam, Saline, RECRUITING
substance_tags: psilocybin
topic_tags: Neuroplasticity,Brain Imaging,Wellbeing,Emotional Processing,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 11:22:34
raw_json: {"nct_id":"NCT06692192","overall_status":"RECRUITING","phase":["PHASE1"]}
title:
Role of Experience, Conscious Awareness, and Plasticity in Psilocybin's Behavioral Effects - Follow-Up Study (The RECAP 2 Study)

abstract:
The goal of this clinical trial is to learn about the role that inducing neuroplasticity (the brain's ability to adapt and change) plays in the behavioral effects of psilocybin in people who have experienced a mild decline in emotional wellbeing. Researchers will compare different doses of psilocybin combined with midazolam or placebo to see what dose induces increased wellbeing. Participants will: * Receive one of four possible combinations of medications * Undergo an MRI * Complete questionnaires * Undergo transcranial magnetic stimulation (TMS) and EEG The purpose of this study is to investigate the role that inducing neuroplasticity plays in the behavioral effects of psilocybin in people with modest decrements in emotional wellbeing.


authors: Central Institute of Mental Health, Mannheim
journal: ClinicalTrials.gov
publication_date: 2025-01-19
source_url: https://clinicaltrials.gov/study/NCT04670081
keywords: Treatment-resistant Depression, Psilocybin, Nicotinamide, COMPLETED
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 11:04:28
last_checked: 2026-07-01 11:22:34
raw_json: {"nct_id":"NCT04670081","overall_status":"COMPLETED","phase":["PHASE2"]}
title:
A Phase II Randomized, Double-blind, Active Placebo-controlled Parallel Group Trial to Examine the Efficacy and Safety of Psilocybin in Treatment-resistant Major Depression

abstract:
The study aims to investigate the safety and efficacy of oral psilocybin administered under supportive conditions in treatment-resistant major depression (TRD). The study is a bi-centric, prospective, randomized, active placebo-controlled study investigating the effects of 25 mg and 5 mg (p.o.) psilocybin versus placebo (100 mg nicotinamide) in a psychotherapeutic context in 144 patients with TRD from moderate to severe degree (ICD-10 F32/F33). After giving written informed consent and down-titration of their monoaminergic medication under supervision of the treating psychiatrist and the study team, patients will be randomly assigned to one of four trial arms using an online randomization tool: 1) receiving placebo (100 mg nicotinamide) at the first session and the full dose (25 mg) at the second; 2) receiving the presumably sub-effective dose (5 mg) at the first session and the full dose (25 mg) at the second; 3a) receiving the full dose (25 mg) at the first session and 5 mg at the second; 3b) receiving the full dose at both sessions. The two dosing sessions are accompanied by three preparatory and four integration sessions. Drug administration must occur under psychotherapeutic conditions. Two trained therapists (one male, one female) will be assigned to each patient and be present during each dosing, preparatory and integration sessions. We will follow the safety guidelines provided by Johnson et al. (2), including a thorough preparation, establishment of trust/rapport, a safe and pleasing physical environment and sufficient interpersonal support. For safety reasons and close monitoring, patients will stay hospitalized for one night after each dosing session (i.e. in-patient setting).


authors: COMPASS Pathways
journal: ClinicalTrials.gov
publication_date: 2023-11-08
source_url: https://clinicaltrials.gov/study/NCT04739865
keywords: Treatment Resistant Depression, Psilocybin, COMP360, 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 11:04:28
last_checked: 2026-07-01 11:22:34
raw_json: {"nct_id":"NCT04739865","overall_status":"COMPLETED","phase":["PHASE2"]}
title:
The Safety and Efficacy Of Psilocybin as an Adjunctive Therapy in Participants With Treatment Resistant Depression

abstract:
The Safety and Efficacy of Psilocybin as an Adjunctive Therapy in Participants with Treatment-Resistant Depression A recent open label study of the effects of psilocybin in participants with treatment-resistant depression (TRD) showed rapid significant decrease of depressive symptoms after treatment with psilocybin coupled with psychological support. Over 40% of participants sustained response at 3 months. In this study, the aim is to explore effectiveness of 25 mg of psilocybin as an adjunctive therapy in participants with TRD.


authors: University of Texas at Austin
journal: ClinicalTrials.gov
publication_date: 2025-11-25
source_url: https://clinicaltrials.gov/study/NCT06132178
substance_tags: psilocybin
topic_tags: Depression,Brain Imaging,Biomarkers,Aging,Clinical Trial,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 11:22:34
raw_json: {"nct_id":"NCT06132178","overall_status":"RECRUITING","phase":["PHASE2"]}
title:
Assessing the Safety, Tolerability, and Efficacy of Psilocybin Therapy Followed by Accelerated Intermittent Theta Burst (aiTBS) Repetitive Transcranial Magnetic Stimulation (rTMS) for Treatment-Resistant Major Depressive Disorder

abstract:
The purpose of this study is to determine the safety and feasibility of sequencing psilocybin therapy with a short-duration, aiTBS protocol (Stanford Accelerated Intelligent Neuromodulation Therapy, or SAINT) in individuals with treatment-resistant major depressive disorder. This will be a phase II 2x2 design (device and dose) clinical trial. 100 participants, ages 22-76, with treatment-resistant MDD will be randomized to treatment with either: a) 25mg of COMP360 (N=50); or b) 1mg of COMP360 (low-dose comparator; N=50) with appropriate psychological preparation, support, and integration sessions with trained therapists. This will then be directly followed by one of two subsequent treatment conditions: i) the active accelerated intermittent theta burst (aiTBS) rTMS treatment known as Stanford Neuromodulation Therapy (SNT) and/or Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT) targeted to a functional magnetic resonance imaging (fMRI) functional connectivity-guided personalized left dorsolateral prefrontal cortex target using neuronavigation and delivered over 10 sessions daily for 5 consecutive days at 90% of coil-to-target depth-corrected resting motor threshold50,51; or ii) sham iTBS delivered in the same fashion. Individuals will undergo screening, a baseline clinical assessment and neurobiological assessment of functional magnetic resonance imaging (fMRI) and electroencephalographic (EEG) recordings. Individuals will then return on a subsequent day to begin the course of psilocybin therapy. Preparation sessions will occur on the first two out of five days (\~1.5-2 hrs each day), psilocybin dosing will occur on the third day (\~6-8 hours), integration session (\~1 hour) and post-dosing assessments will occur on the fourth day, and a final integration session (\~1 hour) and post-psilocybin clinical and neurobiological assessments will occur on the last of the five days. The following week, the individual will return to the lab to begin the course of active or sham SNT, for 10 hrs. a day (10 min once per 60 min, 50-minute inter-session interval, repeated 10 times daily) for 5 days. This is the protocol now FDA-cleared for treatment of treatment-resistant MDD, known as Stanford Neuromodulation Therapy and commercialized by Magnus Medical (see support letter from Magus Medical). In the third week, the individual will return to complete post-SNT clinical assessments and to complete a post-SNT neurobiological (fMRI and EEG) assessment. Individuals will complete long-term follow-up clinical assessments at 1 month, 2 months, 3 months, 4 months, 6 months, 9 months, and 12 months post-initiation of first treatment (psilocybin administration) to assess durability of clinical response and identify potential points of depression relapse over a sustained period of time. Aims: To determine the safety and feasibility of sequencing psilocybin therapy with a short-duration, aiTBS protocol (Stanford Accelerated Intelligent Neuromodulation Therapy, or SAINT) in individuals with treatment-resistant major depressive disorder. To determine if the combination of psilocybin therapy followed by SAINT demonstrates superior efficacy relative to either treatment alone acutely (primary acute endpoint will be \~14 days after the initiation of the treatment sequence) and over time (additional endpoints at 2 weeks, 4 weeks, 2 months, 3 months, 4 months, 5 months, 6 months, 9 months, and 12 months following cessation of the treatment protocol). To determine the neurobiological changes following the combination treatment (assessment points at baseline, 2 days post-psilocybin, and \~14 days post-psilocybin/2-4 days post cessation of accelerated theta burst), and if the magnitude or nature of such changes are different from those demonstrated in either treatment alone. Investigate how psychedelic treatment may impact blood biomarkers of inflammation (e.g., inflammatory cytokines) and how select functional genetic polymorphisms may moderate the effect of the psychedelic treatment on subsequent functional brain changes.

keywords:
Treatment Resistant Depression, MDD, Major Depressive Disorder, Recurrent Depression, Depression, Psilocybin, COMP360, Accelerated intermittent theta burst (aiTBS) rTMS treatment, Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT), Stanford Neuromodulation Therapy (SNT), Low-dose psilocybin, low-dose COMP360, Sham Accelerated intermittent theta burst (aiTBS) rTMS treatment, Sham Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT), Sham Stanford Neuromodulation Therapy (SNT), RECRUITING


title: Visual Surround Suppression and Perceptual Expectation Under Psilocybin
authors: University of Minnesota
journal: ClinicalTrials.gov
publication_date: 2025-06-26
source_url: https://clinicaltrials.gov/study/NCT04424225
substance_tags: psilocybin
topic_tags: Mechanism of Action
study_type: Other
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:28
last_checked: 2026-07-01 11:22:34
raw_json: {"nct_id":"NCT04424225","overall_status":"TERMINATED","phase":["PHASE1"]}
abstract:
The prospective pilot study will address the critical need for more precise characterizations of the acute visual effects of the drug psilocybin by measuring the impact of acute psilocybin intoxication on a perceptual task known as visual surround suppression, compared to an active placebo control. The proposed pilot study will address the critical need for more precise characterizations of the acute visual effects of the drug psilocybin by measuring the impact of acute psilocybin intoxication on a perceptual task known as visual surround suppression, compared to an active placebo control. The data collected in the proposed experiment will make important contributions to knowledge of how psilocybin impacts contextual processing in the brain. Moreover, this will in turn inform the neurobiology of visual surround suppression in general, providing the first investigation of links between surround suppression and serotonergic pathways in humans. Furthermore, the impact of psilocybin on surround suppression will complement recent discoveries of differences in surround suppression present in certain clinical populations. Taken together, these points suggest that this relatively simple and straightforward study could have significant payoff in its contribution to knowledge, not only of the effects of psilocybin but also of key brain processes underpinning human vision and context processing more broadly.

keywords:
Perception Disturbance, Visual Suppression, Psychedelic Experiences, Psilocybin, Niacin, Vitamin B3, TERMINATED


authors: University of Wisconsin, Madison
journal: ClinicalTrials.gov
publication_date: 2023-05-18
source_url: https://clinicaltrials.gov/study/NCT04842045
substance_tags: psilocybin
topic_tags: Depression,Addiction,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 11:22:34
raw_json: {"nct_id":"NCT04842045","overall_status":"COMPLETED","phase":["PHASE1"]}
title:
Recall of Experience and Conscious Awareness in Psilocybin Treatment of Depression (The RECAP Study): Pilot Phase in Healthy Adult Volunteers

abstract:
The primary objective of the RECAP Study Program is to investigate the role played by conscious experience in the antidepressant effects of the psychedelic agent psilocybin. This pilot dosing study (PILOT RECAP) is designed to determine the optimal dose of midazolam that allows a psychedelic experience to occur while inducing amnesia for the experience. This is an essential step required for subsequent evaluation of the role of memory for the psychedelic experience in the antidepressant effects of psilocybin in the full RECAP study. The PILOT RECAP Study will investigate the effect of co- administering the amnestic agent midazolam with a single 25 mg dose of psilocybin on the induction of a psychedelic experience and subsequent memory for the experience with the goal of identifying an optimal dosing regimen of midazolam that will allow a psychedelic experience to occur while also inducing amnesia for the experience. Identifying this midazolam dosing regimen will allow us in a subsequent stage of the RECAP program to test whether memory for the psychedelic experience is required/important for psilocybin to produce longer-term antidepressant effects. This is a phase 1 study in psychiatrically and medically healthy volunteers. Given this, there is no disease background for PILOT RECAP per se. However, the purpose of PILOT RECAP is to identify an optimal midazolam dosing schedule to be used in a subsequent study (RECAP) in patients with major depressive disorder (MDD). The investigational treatment for PILOT RECAP is a single 25 mg dose of psilocybin combined with repeated intravenous (IV) boluses of midazolam dosed at levels known to maintain conscious experience while inducing subsequent amnesia for the experience upon its conclusion. Because PILOT RECAP is the first study to examine this drug combination, no data are currently available on this approach. Psilocybin + midazolam will be administered within a "Set and Setting" (SaS) protocol that provides psychoeducation and therapeutic support prior to, during, and following psychedelic dosing, and that has been standard procedure for recent studies of psilocybin in humans. It is believed that this SaS approach enhances clinical efficacy and safety. SaS is an integral component of the PILOT RECAP intervention. The PILOT RECAP study will not enroll vulnerable populations. During this study, participants are asked to: * Refrain from use of psychotropic medications. Use of such medications prior to psilocybin/midazolam dosing will result in a participant being discontinued from the study. * Refrain from use of any illegal psychoactive substances from screening until study termination. * Refrain from using legal psychoactive substance for the following defined time periods (the exception is caffeine): * Tobacco and Nicotine: from screening until study termination * Alcohol: 72 hours prior to the Dosing Visit

keywords:
Psychedelic Experiences, Amnesia, Psilocybin and Midazolam, Psilocybine, Psilocibin, benzodiazepine, COMPLETED


authors: M.D. Anderson Cancer Center
journal: ClinicalTrials.gov
publication_date: 2026-06-23
source_url: https://clinicaltrials.gov/study/NCT06200155
substance_tags: psilocybin
study_type: Other
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:28
last_checked: 2026-07-01 11:22:34
raw_json: {"nct_id":"NCT06200155","overall_status":"RECRUITING","phase":["PHASE2"]}
title:
TRIP - TReatment to Improve Depression and/or Anxiety Using Psilocybin-Assisted Psychotherapy in Patients With Advanced Cancer on Maintenance Therapy

abstract:
To learn about the feasibility, safety, and effects of psilocybin-assisted psychotherapy on depression and/or anxiety in participants who are being treated for advanced cancer. Primary Objective To examine the feasibility, safety, effect size estimates of psilocybin-assisted psychotherapy for participants with depression and/or anxiety who are being actively treated for advanced cancer. Feasibility will be measured as: At least 20% of eligible participants consent and at least 60% of consented participants complete the two doses of treatment. Secondary Objectives 1. Determine whether psilocybin-assisted psychotherapy improves measures of quality of life (e.g., sleep, pain, functional status) and psychosocial well-being (e.g., finding meaning and post-traumatic growth), as measured by the following: PHQ-9, GAD-7, PROMIS-10, PROMIS-A, PROMIS-D, MEQ30 (mystical experience), Flourishing scale, mDES, 5D-ASC (altered states), and Posttraumatic Growth Inventory. 2. Determine whether psilocybin-assisted psychotherapy improves functional status per clinician-rated outcome measures. 3. Assess the effects of psilocybin-assisted psychotherapy on 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. 4. Measure the change in inflammatory markers (IL6, TNF, and CRP) and in frequency and activation status of peripheral immune cell populations assessed by immune monitoring through flow cytometry. 5. Examine changes in central nervous system plasticity through the use of fMRI, specifically changes in 5-HT2A-rich and higher-order functional networks, as well as a global increase in brain network integration. 6. Evaluate the Impact on MDASI measurements.

keywords:
Depression, Anxiety, Psilocybin-Assisted Psychotherapy, Advanced Cancer, Psilocybin, Niacin, RECRUITING

topic_tags:
Depression,Anxiety,Chronic Pain,Neuroplasticity,Brain Imaging,Receptor Pharmacology,Biomarkers,Wellbeing,Mystical Experience,Healthcare Workers,Safety,Inflammation,Immune Function


authors: Beckley Psytech Limited
journal: ClinicalTrials.gov
publication_date: 2022-10-11
source_url: https://clinicaltrials.gov/study/NCT04905121
keywords: Short Lasting Unilateral Neuralgiform Headache Attacks, Psilocybin, TERMINATED
substance_tags: psilocybin
topic_tags: Headache / Migraine,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 11:22:34
raw_json: {"nct_id":"NCT04905121","overall_status":"TERMINATED","phase":["PHASE1"]}
title:
An Exploratory Open-Label, Phase 1b, Ascending Dose Study to Evaluate the Effects of Oral 3-[2-(Dimethylamino)Ethyl]-1h-indol-4-yl Dihydrogen Phosphate (Psilocybin, BPL-PSILO) on Cognition in Patients With Chronic Short-Lasting Unilateral Neuralgiform Headache Attacks (SUNHA)

abstract:
This exploratory open-label phase 1b, ascending dose study is to evaluate the effects of psilocybin on cognition in patients with Chronic Short-Lasting Unilateral Neuralgiform Headache Attacks (SUNHA) The study aims to: Determine the safety and tolerability of psilocybin when administered to patients with chronic SUNHA Determine the effects of psilocybin on cognition when administered to patients with chronic SUNHA Explore the change in frequency, duration, and intensity of headache attacks with escalating doses of psilocybin in patients with chronic SUNHA


authors: Johns Hopkins University
journal: ClinicalTrials.gov
publication_date: 2026-06-07
source_url: https://clinicaltrials.gov/study/NCT07610135
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 11:22:34
raw_json: {"nct_id":"NCT07610135","overall_status":"NOT_YET_RECRUITING","phase":["PHASE1","PHASE2"]}
title:
PRISMatic: A Phase 1b Randomized, Double-Armed, Parallel-Group, Placebo-Controlled Trial of Psilocybin Efficacy With or Without Pimavanserin Pretreatment

abstract:
Twenty healthy adults (≥21 years old) will be enrolled to evaluate the efficacy of a single oral dose of psilocybin (25 mg) administered with or without pretreatment using oral pimavanserin (34 mg) or placebo. Outcome assessments will occur at 1 week and 1 month following psilocybin administration. The purpose of this study is to clarify the receptor-level mechanisms underlying psilocybin's effects on mood and well-being, along with the associated neurophysiologic signatures. These mechanisms will be examined using psychometric scales, autonomic and fMRI-based neurophysiologic markers, and integrated pharmacokinetic/pharmacodynamic modeling.

keywords:
Mood (Psychological Function), Well Being, Mood, Healthy, Psilocybin, Pimavanserin, Nuplazid, Inactive Placebo, NOT_YET_RECRUITING

topic_tags:
Brain Imaging,Pharmacology,Mechanism of Action,Receptor Pharmacology,Biomarkers,Wellbeing,Clinical Trial


title: Psilocybin Therapy for Depression and Anxiety in Parkinson's Disease: a Pilot Study
authors: Joshua Woolley, MD, PhD
journal: ClinicalTrials.gov
publication_date: 2024-12-31
source_url: https://clinicaltrials.gov/study/NCT04932434
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Safety,Adverse Events
study_type: Other
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:28
last_checked: 2026-07-01 11:22:34
raw_json: {"nct_id":"NCT04932434","overall_status":"COMPLETED","phase":["PHASE2"]}
abstract:
The purpose of this study is to determine the safety, tolerability, and feasibility of psilocybin therapy for depression and anxiety in people with Parkinson's disease. This is an open-label single-arm pilot study of oral psilocybin therapy for depression and anxiety in people with Parkinson's Disease (PD). The primary goal is to examine safety, tolerability, and feasibility of the intervention in this patient population. We will enroll people ages 40 to 75 with clinically diagnosed early stage Parkinson's Disease (Hoehn and Yahr Stage 1-3 during an "off" period), who meet DSM-5 criteria for a depressive or anxious disorder and meet all other inclusion and exclusion criteria at screening. After baseline assessments, participants will complete preparation sessions designed to provide information about the psilocybin experience and to build rapport/trust with the study team. Next, participants will complete a first psilocybin administration session, receiving a low-moderate dose of 10 mg oral psilocybin in a supervised setting with safety monitoring by a physician. Participants who do not experience significant adverse events during or following the session will complete a second psilocybin administration session approximately two weeks later. During the second psilocybin administration session, participants will receive a moderate-high dose of 25 mg oral. The second session will involve the same procedures and level of monitoring as the first. Participants will subsequently complete multiple follow-up sessions designed to assess PD and psychiatric symptoms as well as to provide support as they process their psilocybin experiences. Follow-up will continue to 3 months after the second psilocybin administration session. Primary endpoints will assess safety, tolerability, and feasibility of study procedures. Exploratory efficacy endpoints will assess changes in depressive symptoms, anxious symptoms, and related measures of function.

keywords:
Parkinson Disease, Depression, Anxiety, Psilocybin therapy, 4-phosphoryloxy-N,N-dimethyltryptamine, COMPLETED


authors: University of California, Berkeley
journal: ClinicalTrials.gov
publication_date: 2025-10-20
source_url: https://clinicaltrials.gov/study/NCT06367738
keywords: Aging, Psilocybin, RECRUITING
substance_tags: psilocybin
study_type: Observational Study
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:28
last_checked: 2026-07-01 11:22:34
raw_json: {"nct_id":"NCT06367738","overall_status":"RECRUITING","phase":["PHASE1"]}
title:
Investigating the Persisting Effects of a Single Dose of Psilocybin on Structural Plasticity in Healthy Older Adults

abstract:
Participants in this study will undergo a series of non-invasive tests and activities designed to understand how a single dose of psilocybin might influence cognition and emotional well-being in healthy older adults. After providing written informed consent, eligible participants, aged between 60 and 85, will be randomly assigned to receive a dose of psilocybin ranging from a microdose to a moderate-to-high dose. Anatomical magnetic resonance imaging (MRI) and diffusion weighted imaging (DWI) will be used to assess changes in brain structure, while functional magnetic resonance imaging (fMRI) will be used to quantify changes in functional brain activity. The investigators will use cognitive exams, perceptual tasks, brain imaging, peripheral psychophysiology, and surveys to investigate the persisting effects of psilocybin on cognition, predictive coding, and affect in healthy older adults (60-85 years old). The investigators will measure changes in these measures by comparing baseline to one-week and one-month post-treatment. Participants will be randomly assigned to receive a dose of psilocybin in a range from microdose to moderate-to-high dose (1-30 milligrams). Anatomical magnetic resonance imaging (MRI) and diffusion weighted imaging (DWI) will be used to assess changes in brain structure, while functional magnetic resonance imaging (fMRI) will be used to quantify changes in functional brain activity. The investigators will assess whether changes in these brain measures underlie observed changes in cognition, predictive coding and affect.

topic_tags:
Neuroplasticity,Brain Imaging,Aging,Microdosing,Wellbeing,Emotional Processing,Observational Study,Older Adults


title: Efficacy and Safety of COMP360 Psilocybin Therapy in Anorexia Nervosa: a Proof-of-concept Study
authors: COMPASS Pathways
journal: ClinicalTrials.gov
publication_date: 2024-12-03
source_url: https://clinicaltrials.gov/study/NCT05481736
keywords: Anorexia Nervosa, Psilocybin, COMP360, COMPLETED
substance_tags: psilocybin
topic_tags: Eating Disorders,Safety
study_type: Other
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:28
last_checked: 2026-07-01 11:22:34
raw_json: {"nct_id":"NCT05481736","overall_status":"COMPLETED","phase":["PHASE2"]}
abstract:
Efficacy and Safety of COMP360 Psilocybin therapy in Anorexia Nervosa: a Proof-of-concept Study This study aims to explore the efficacy and safety of COMP360 25 mg as compared to COMP360 1 mg (control condition) administered with psychological support in participants with Anorexia Nervosa


title: Safety and Psychological Effects of Psilocybin and D-Serine Formulation in Healthy Volunteers
authors: Hadassah Medical Organization
journal: ClinicalTrials.gov
publication_date: 2026-02-04
source_url: https://clinicaltrials.gov/study/NCT07079930
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 11:22:34
raw_json: {"nct_id":"NCT07079930","overall_status":"RECRUITING","phase":["PHASE1"]}
abstract:
The goal of this open-label, dose-escalation, prospective study is to evaluate the safety and psychological effects of a Psilocybin and D-Serine formulation in healthy volunteers. The main objectives are: 1. To assess the psychological and physiological effects of psilocybin administered with D-Serine in healthy adults. 2. To determine whether D-Serine modulates or attenuates the psychedelic effects of psilocybin. 3. To evaluate the safety and tolerability of psilocybin and D-Serine co-administration. Study population includes: 10 healthy male or female volunteers aged 25-60 years with no history of psychiatric or major medical disorders and no current evidence of such disorders. The study includes two cohorts. The first cohort of 5 participants will receive 15 mg of Psilocybin and 5 g of D-Serine. Safety data will be collected and submitted in an interim report to the Ethics Committee. If no safety concerns arise, the second cohort will receive an increased dose of 25 mg of Psilocybin and 7 g of D-Serine to help determine the optimal dose for a future Phase IIa clinical trial. This is a first-in-human, Phase I, exploratory clinical trial designed to evaluate the safety, tolerability, and initial psychological and physiological responses to a single administration of psilocybin in combination with D-Serine in healthy adult volunteers. The rationale for this combination stems from preclinical evidence indicating that D-Serine, a naturally occurring co-agonist at the NMDA receptor, may attenuate the acute psychedelic effects of psilocybin while preserving its neuroplastic and therapeutic properties. Preclinical studies demonstrated that D-Serine reduced the psilocybin-induced head-twitch response (HTR) in rodent models and enhanced the expression of synaptic plasticity markers (e.g., GAP43, PSD95, SV2A, synaptophysin) across multiple brain regions, with effects sustained up to 12 days post-treatment. These findings suggest that the combination may improve the safety and tolerability of psilocybin, particularly for populations sensitive to its psychoactive effects. The trial will consist of four sequential components: Screening Phase - to assess eligibility. Preparation Phase - to establish therapeutic rapport and baseline assessments. Administration Phase - involving a single oral administration of the investigational combination (psilocybin + D-Serine). Follow-up Phase - including in-person follow-up visits on Day 2, Day 7, Day 28, and Day 84 post-treatment to monitor safety outcomes, subjective responses, and potential delayed effects.

keywords:
Healthy Volunteers, Psilocybin and D-Serine, Physical Examination, Vital signs, ECG test, Comprehensive Blood Panel, SMAC-20, Complete Blood Count, CBC, Urinalysis, Urine Toxicology Screen, A pregnancy Urine test, Electroencephalogram, EEG, Plasma Amino Acid Levels, Plasma Inflammation Markers, Plasma Brain-Derived Neurotrophic Facto, Plasma BDNF, Mini International Neuropsychiatric Interview, MINI, Family Psychiatric History Assessment, FPHA, Beck Depression Inventory, BDI, State-Trait Anxiety Inventory, STAI, Profile of Mood States, POMS, Subjective Units of Distress Scale, SUDS, Five-Dimensional Altered States of Consciousness questionnaire, 5D-ASC, Integration, RECRUITING

topic_tags:
Depression,Anxiety,Neuroplasticity,Brain Imaging,Receptor Pharmacology,Consciousness,Biomarkers,Clinical Trial,Observational Study,Animal Study,Healthy Volunteers,Safety,Toxicity,Inflammation


authors: Johns Hopkins University
journal: ClinicalTrials.gov
publication_date: 2025-07-27
source_url: https://clinicaltrials.gov/study/NCT06067737
keywords: Opioid Use Disorder, Psilocybin, buprenorphine, RECRUITING
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 11:22:34
raw_json: {"nct_id":"NCT06067737","overall_status":"RECRUITING","phase":["PHASE2"]}
title:
Outpatient Buprenorphine Induction With Psilocybin for Opioid Use Disorder: a Randomized Double-blind Trial

abstract:
This study will examine the effect of a single high dose of psilocybin therapy (30 mg) versus a very low dose (1 mg) as an adjunctive therapy to individuals undergoing standard-of-care outpatient buprenorphine treatment for Opioid use disorder (OUD). The participants will have previously undergone buprenorphine induction before. Effects of adjunctive psilocybin will be determined for longitudinal outcomes of opioid abstinence, compliance with outpatient buprenorphine maintenance, quality of life, and mood. The proposed study is a double-blind, controlled investigation of the effect of 1 high-dose psilocybin (30 mg) session compared to a very low dose session (1 mg) in the period immediately following standard-of-care outpatient buprenorphine induction on drug abstinence, quality of life, craving, tobacco use, and treatment retention in healthy participants with an active OUD diagnosis and a history of being prescribed buprenorphine previously. Use of buprenorphine is standard of care for OUD, and the investigators are investigating the additive power of adjunctive psilocybin to enhance opioid abstinence, treatment adherence, quality of life, and mood. Of note, this trial is designed with a parallel and complementary structure to IRB00344281 (BIPOD: Buprenorphine Induction with Psilocybin for Opioid use Disorder: A Randomized Controlled Clinical Trial"). The current proposed trial ("BIPOD-Out") differs in that it is tailored specifically to identify participants who have previously been prescribed and tolerated buprenorphine but subsequently relapsed. The study will recruit participants who have very recently (past 3 weeks) undergone standard of care outpatient buprenorphine induction or are interested in undergoing buprenorphine induction by a study team physician and offer experimental psilocybin administration, as utilized in several other studies at this center. As noted above (and unlike in IRB00344281), participants naïve to buprenorphine will be excluded from this study. Outpatient buprenorphine induction will be followed by an 8-week outpatient phase involving standard of care buprenorphine maintenance with participants referred to further buprenorphine treatment in the community and followed in long-term follow-up for 4 to 6 months. The study team will recruit participants who have recently (past 3 weeks) been inducted onto sublingual (SL) buprenorphine (a buprenorphine/naloxone combination product) in the outpatient setting, and also participants interested in participating in a buprenorphine induction conducted by one of the study team physicians. Once buprenorphine induction is complete and participants are deemed eligible, participants will undergo 2-4 preparatory sessions (described below), followed by an experimental drug administration session under supportive conditions, during which the participants will receive either a very low dose (1 mg) or a single high (30mg) oral dose of psilocybin under double-blind conditions. Participants will then complete an 8-week outpatient phase, during which a study team clinician will provide standard of care outpatient buprenorphine maintenance. Participants will undergo outpatient visits at 1, 2, 3, 4, 6, and 8 weeks post-dosing session at the Behavioral Pharmacology Research Unit for monitoring of adverse events, clinical status, treatment adherence, and to receive a weekly supply of buprenorphine. All buprenorphine procedures will be open label and will follow standard-of-care practices.

topic_tags:
Addiction,Pharmacology,Clinical Trial,Randomized Controlled Trial,Healthy Volunteers,Healthcare Workers,Adverse Events


authors: University of British Columbia
journal: ClinicalTrials.gov
publication_date: 2025-12-03
source_url: https://clinicaltrials.gov/study/NCT05585229
keywords: Opioid Dependence, Chronic Pain, Psilocybin-assisted Psychotherapy, PEX010, RECRUITING
substance_tags: psilocybin
topic_tags: Addiction,Chronic Pain,Mechanism of Action,Safety,Adverse Events,Contraindications
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 11:22:34
raw_json: {"nct_id":"NCT05585229","overall_status":"RECRUITING","phase":["PHASE2"]}
title:
Standardized Natural Psilocybin-assisted Psychotherapy for Tapering of Opioid Medication in Patients With Chronic Pain: an Open-label Feasibility Study

abstract:
This is an open-label pilot trial to assess the safety and feasibility of a novel 8-week psilocybin-assisted psychotherapy intervention to facilitate successful tapering/discontinuation of opioid pain medication in adult patients receiving long-term opioid therapy for chronic pain. Participation will last approximately 8 months and includes one or two psilocybin-assisted therapy sessions. The study will evaluate the incidence and severity of adverse events during and after treatment, the number of participants who drop out of the study for intervention-related reasons, and the self-reported benefits and harms of the intervention. The purpose of this pilot study is to establish the safety and tolerability of a therapeutic intervention using psilocybin-assisted psychotherapy as a novel treatment for opioid tapering in a sample of patients with chronic pain. Participants will be patients who have failed previous attempts to reduce their use of opioid medication and who have no medical or psychological contraindications for psilocybin administration. This pilot study involves an 8-week open-label, non-randomized therapeutic intervention and a 6-month follow-up period. To provide a supportive context for the drug experience, participants will receive preparatory and integrative sessions following an acceptance and commitment therapy model for psychedelic therapy. The physician-supervised opioid taper will begin following the first psilocybin dosing session (25mg) after an integration session with therapists, and a second optional psilocybin dosing session (37.5mg) will be facilitated one month later. Assessments will be completed at baseline, and at follow-up points at 1-month, 3-months and 6-months post-intervention to evaluate both acute and long-term effects of the intervention. Primary outcomes of interest are rates of adverse events, retention rates, and patient perceptions of intervention tolerability. Preliminary efficacy of the treatment will be evaluated by tracking opioid reduction rates and long-term maintenance of these reductions. Other measures of interest include qualities of the psychedelic experience, opioid cravings and withdrawal, chronic pain symptoms, and psychological mechanisms.


title: Consciousness and Psilocybin Effects on Well-Being: The CoPEWell Study
authors: University of Wisconsin, Madison
journal: ClinicalTrials.gov
publication_date: 2026-04-30
source_url: https://clinicaltrials.gov/study/NCT07360301
substance_tags: psilocybin
topic_tags: Consciousness,Wellbeing,Psychological Flexibility
study_type: Other
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:28
last_checked: 2026-07-01 11:22:34
raw_json: {"nct_id":"NCT07360301","overall_status":"NOT_YET_RECRUITING","phase":["PHASE1"]}
abstract:
This study is exploring how psilocybin (a psychedelic drug) may improve mood and wellbeing. Many people report feeling better after taking psilocybin, but it is not clear why. The CoPEWell study will test whether these improvements come from the psychedelic experience itself (the "trip") or from direct effects on the brain. To study this, up to 120 participants will be enrolled to receive psilocybin either while awake or asleep and can expect to be on study for up to 4 months. Primary Objectives: 1. To evaluate the effect of psilocybin on wellbeing when administered while awake vs. while asleep 2. To evaluate the effect of psilocybin on wellbeing administered while asleep vs. placebo administered while asleep Secondary Objectives: 3. To evaluate the effect of psilocybin on psychological flexibility when administered while awake vs. while asleep 4. To evaluate the effect of psilocybin on psychological flexibility administered while asleep vs. placebo administered while asleep 5. To evaluate the effect of psilocybin on social connectedness when administered while awake vs. while asleep 6. To evaluate the effect of psilocybin on social connectedness administered while asleep vs. placebo administered while asleep 7. To evaluate the effect on wellbeing/life satisfaction/purpose/meaning explicitly ascribed to psilocybin administered while awake vs. while asleep 8. To evaluate the effect on wellbeing/life satisfaction/purpose/meaning explicitly ascribed to psilocybin administered while asleep vs. saline placebo administered while asleep

keywords:
Well-Being, Psychological, Psychedelic Experiences, Psilocybin, intravenous psilocybin, Saline Placebo, Clonidine, Clonidine ER, NOT_YET_RECRUITING


authors: Icahn School of Medicine at Mount Sinai
journal: ClinicalTrials.gov
publication_date: 2025-05-13
source_url: https://clinicaltrials.gov/study/NCT06592833
keywords: Major Depressive Disorder, Psilocybin, Pimavanserin, Nuplazid, Placebo, RECRUITING
substance_tags: psilocybin
topic_tags: Depression,Mechanism of Action,Receptor Pharmacology
study_type: Other
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:28
last_checked: 2026-07-01 11:22:34
raw_json: {"nct_id":"NCT06592833","overall_status":"RECRUITING","phase":["PHASE2"]}
title:
Investigating the Role of Serotonin in the Mechanism of Action of Psilocybin in Patients With Major Depressive Disorder

abstract:
This is an interventional, parallel arm assignment treatment study in individuals with Major Depressive Disorder (MDD). Each individual will be treated with a single dose of pimavanserin or placebo plus a single dose of psilocybin. Evaluations will be taken before dosing and following dosing at several timepoints up to 5 weeks post-dosing. In this study, the researchers want to probe the role of the 5-HT2A receptor in mediating the subjective effects of psilocybin. While previous studies have shown that blockage of the 5-HT2A receptor reduces the psychedelic experience in humans, an animal study revealed that blockage of the 5-HT2A receptor abolished the psychedelic effects without affecting the antidepressant response. This suggests that the pathway responsible for the antidepressant response is dissociated from the psychedelic experience pathway, which is mediated by 5-HT2A signaling.


title: SV2A Marker of Synaptogenesis in a Clinical Trial of Psilocybin for Depression
authors: Washington University School of Medicine
journal: ClinicalTrials.gov
publication_date: 2023-01-29
source_url: https://clinicaltrials.gov/study/NCT05601648
keywords: Major Depressive Disorder, Anhedonia, Psilocybin, WITHDRAWN
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 11:22:34
raw_json: {"nct_id":"NCT05601648","overall_status":"WITHDRAWN","phase":["PHASE2"]}
abstract:
Participants with depression will be given a single dose of psilocybin and supportive psychotherapy before, during, and after drug administration. Participants will undergo positron emission tomography (PET) imaging before and one week after psilocybin using a marker of synaptic density. This design allows us to assess the relationship between neurotrophic, and antidepressant effects produced by psilocybin. The investigators are studying the neurotrophic effects of psilocybin using 11C-UCB-J, a PET marker for synaptogenesis. Psilocybin is a naturally occurring psychedelic and exerts perceptual effects via 5-HT2A receptor agonism. Psilocybin has gained a great deal of attention as a tool for psychiatric treatment, with clinical trials demonstrating symptom relief after a single dose that is immediate and persists for months. Recognizing the therapeutic potential of psilocybin, the US Food and Drug Administration granted breakthrough therapy status to the Usona Institute for Phase 2 testing of psilocybin in depression. Animal models suggest that psychedelics exert antidepressant effects by producing a rapid and powerful neurotrophic response in the brain. The investigators will enroll patients with major depressive disorder and anhedonia. Participants will be given a single dose of psilocybin and supportive psychotherapy before, during, and after drug administration. Participants will undergo PET imaging before and one week after drug using 11C-UCB-J, a radiotracer that binds to SV2A - a marker of synaptic density and synaptogenesis. This design allows the investigators to assess the relationship between neurotrophic, and antidepressant effects produced by psilocybin.

topic_tags:
Depression,Neuroplasticity,Brain Imaging,Receptor Pharmacology,Biomarkers,Aging,Clinical Trial,Animal Study


title: Psilocybe Cubensis Mushrooms With or Without Fluoxetine for Refractory Depression
authors: Federal University of Latin American Integration
journal: ClinicalTrials.gov
publication_date: 2026-03-26
source_url: https://clinicaltrials.gov/study/NCT06898606
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 11:04:28
last_checked: 2026-07-01 11:22:34
raw_json: {"nct_id":"NCT06898606","overall_status":"RECRUITING","phase":["PHASE1","PHASE2"]}
abstract:
This Phase 2a pilot, exploratory, randomized, double-blind, placebo-controlled, parallel-group trial will estimate whether concurrent fluoxetine alters the antidepressant effect, acute psychedelic experience, or safety of a psychedelic-assisted psychotherapy session in adults with treatment-resistant major depressive disorder (TRD). Eligible participants (ages 25-64) have DSM-5-TR MDD, moderate-severe, MADRS ≥20, and partial response in the current episode (≥1 adequate antidepressant trial of 6-12 weeks with \

keywords:
Depressive Disorder, Psilocybin and Psilocyn, Placebo, Psychotherapy-assisted session, Fluoxetine, RECRUITING


title: A Pilot Study of Psilocybin Enhanced Group Psychotherapy in Patients With Cancer
authors: University of Utah
journal: ClinicalTrials.gov
publication_date: 2024-03-19
source_url: https://clinicaltrials.gov/study/NCT04522804
keywords: Cancer, Psilocybin, COMPLETED
substance_tags: psilocybin
topic_tags: Safety
study_type: Other
source_name: ClinicalTrials.gov
publication_status: clinical trial
date_added: 2026-07-01 11:04:28
last_checked: 2026-07-01 11:22:34
raw_json: {"nct_id":"NCT04522804","overall_status":"COMPLETED","phase":["EARLY_PHASE1"]}
abstract:
This pilot project is an open-label trial that will offer psilocybin in a group format to assess the feasibility of offering psilocybin therapy in a group setting with a decreased therapist to subject ratio. Study intervention will involve a group of six patients with one therapist per subject for a 1:1 ratio, thus significantly reducing the total number of therapist hours per subject compared to standard individual therapy protocols. Two groups of six will be treated on this trial. After the enrollment and treatment of the first group of six patients, accrual will be placed on hold to ensure subject safety. If stopping rules are not met (Section 11), the next group of six patients will be enrolled and treated on study. The study intervention will include a total of seven group therapy sessions including three 2-hour preparatory sessions, one 8-hour psilocybin session, and one two-hour integration session. The group therapy sessions will occur on a weekly basis, followed one week later by the psilocybin session. The first integration group session will occur 1-2 days following the psilocybin session.


