# publications

authors: Gattuso JJ, Wilson C, Hannan AJ, Renoir T.
publication_date: 2023-11-28
doi: 10.1111/jnc.16017
pubmed_id: 38019032
source_url: https://doi.org/10.1111/jnc.16017
keywords: Animals, Humans, Hallucinogens, Drug Evaluation, Preclinical, Mental Disorders, Psilocybin
substance_tags: psilocybin
study_type: Systematic Review
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Psilocybin as a lead candidate molecule in preclinical therapeutic studies of psychiatric disorders: A systematic review.

abstract:
Psilocybin is the main psychoactive compound found in hallucinogenic/magic mushrooms and can bind to both serotonergic and tropomyosin receptor kinase b (TrkB) receptors. Psilocybin has begun to show efficacy for a range of neuropsychiatric conditions, including treatment-resistant depression and anxiety disorders; however, neurobiological mechanisms are still being elucidated. Clinical research has found that psilocybin can alter functional connectivity patterns in human brains, which is often associated with therapeutic outcomes. However, preclinical research affords the opportunity to assess the potential cellular mechanisms by which psilocybin may exert its therapeutic effects. Preclinical rodent models can also facilitate a more tightly controlled experimental context and minimise placebo effects. Furthermore, where there is a rationale, preclinical researchers can investigate psilocybin administration in neuropsychiatric conditions that have not yet been researched clinically. As a result, we have systematically reviewed the knowledge base, identifying 82 preclinical studies which were screened based on specific criteria. This resulted in the exclusion of 44 articles, with 34 articles being included in the main review and another 2 articles included as Supporting Information materials. We found that psilocybin shows promise as a lead candidate molecule for treating a variety of neuropsychiatric conditions, albeit showing the most efficacy for depression. We discuss the experimental findings, and identify possible mechanisms whereby psilocybin could invoke therapeutic changes. Furthermore, we critically evaluate the between-study heterogeneity and possible future research avenues. Our review suggests that preclinical rodent models can provide valid and translatable tools for researching novel psilocybin-induced molecular and cellular mechanisms, and therapeutic outcomes.

topic_tags:
Depression,Anxiety,Mechanism of Action,Receptor Pharmacology,Systematic Review,Review Article,Animal Study,Treatment-Resistant Depression

raw_json:
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publication_date: 2023-08-23
doi: 10.1080/02791072.2023.2251133
pubmed_id: 37615379
source_url: https://doi.org/10.1080/02791072.2023.2251133
substance_tags: psilocybin
topic_tags: Anxiety,Addiction,Receptor Pharmacology,Review Article,Safety,Adverse Events
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
title:
Beyond Psilocybin: Reviewing the Therapeutic Potential of Other Serotonergic Psychedelics in Mental and Substance Use Disorders.

authors:
Wong S, Yu AY, Fabiano N, Finkelstein O, Pasricha A, Jones BDM, Rosenblat JD, Blumberger DM, Mulsant BH, Husain MI.

abstract:
There has been a resurgence of interest in the use of psychedelic therapies for several mental and substance use disorders. Psilocybin, a "classic" serotonergic psychedelic, has emerged as one of the primary compounds of interest in clinical research. While research on psilocybin's potential mental health benefits has grown, data on the safety and efficacy of other serotonergic psychedelics remain limited. A comprehensive scoping review on the use of mescaline, ibogaine, ayahuasca, N,N-dimethyltryptamine (DMT), and lysergic acid diethylamide (LSD) in the treatment of mental and substance disorders was conducted. Independent reviewers screened titles, abstracts, and full texts and conducted data extraction. Seventy-seven studies met the inclusion criteria. There were 43 studies of LSD, 24 studies of ayahuasca, 5 studies of DMT, 5 studies of ibogaine, and 5 studies of mescaline. Commonly reported benefits included improved mood and anxiety symptoms, improved insight, reduced substance use, improved relationships, and decreased vegetative symptoms. Commonly reported adverse effects were psychological, neurological, physical, and gastrointestinal in nature. Serious adverse events (homicide and suicide) were reported in published studies of LSD. In conclusion, there is only low-level evidence to support the safety and efficacy of non-psilocybin serotonergic psychedelics in individuals with mental and substance use disorders.

keywords:
Humans, Banisteriopsis, Substance-Related Disorders, N,N-Dimethyltryptamine, Mescaline, Lysergic Acid Diethylamide, Ibogaine, Serotonin Agents, Hallucinogens, Mental Disorders, Psilocybin

raw_json:
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authors: Palamar JJ, Rutherford C, Le A, Keyes KM.
publication_date: 2023-08-20
doi: 10.1080/02791072.2023.2240322
pubmed_id: 37605471
source_url: https://doi.org/10.1080/02791072.2023.2240322
substance_tags: psilocybin
topic_tags: Addiction,Observational Study,Adolescents,Safety
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
title:
Seasonal Variation of Use of Common Psychedelics and Party Drugs Among Nightclub/Festival Attendees in New York City.

abstract:
Few epidemiological studies have focused on seasonal variation in the use of common psychedelics and party drugs among nightclub and festival attendees, typically those who attend electronic dance music (EDM) events. We sought to determine whether the use of different drug types varies seasonally within this population. Across 15 seasons from summer 2017 through fall 2022, we surveyed 3,935 adults entering randomly selected nightclubs and festivals in New York City regarding their past-month use of cocaine, MDMA (3,4-methylenedioxymethamphetamine, commonly known as ecstasy), lysergic acid diethylamide (LSD), psilocybin (shrooms), and ketamine. Multivariable models were used to compare adjusted odds ratios for drug use within each season with the grand mean of combined seasons. Summer was associated with higher odds for use of LSD (aOR 2.72; 95% CI, 1.88-3.93) and psilocybin (aOR 1.65; CI, 1.12-2.43), independent of increases in psilocybin use over time (p <.001). A significant increase in use of ketamine (p =.014) and significant decreases in use of cocaine (p =.002) and ecstasy (p =.002) were found across time, but multivariable models did not detect seasonal variations. Summer is a risk factor for use of common psychedelics among people who attend EDM events. Therefore, the summer months may be the best time to disseminate information about harm reduction for psychedelic drug users.

keywords:
Humans, Substance-Related Disorders, N-Methyl-3,4-methylenedioxyamphetamine, Ketamine, Lysergic Acid Diethylamide, Cocaine, Hallucinogens, Seasons, Holidays, Dancing, Adolescent, Adult, Middle Aged, New York City, Female, Male, Young Adult, Surveys and Questionnaires, Psilocybin, Illicit Drugs, Recreational Drug Use

raw_json:
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authors: Korman BA.
publication_date: 2023-07-30
doi: 10.1080/02791072.2023.2242358
pubmed_id: 37525416
source_url: https://doi.org/10.1080/02791072.2023.2242358
substance_tags: psilocybin
topic_tags: Addiction,Observational Study,Adolescents
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
On the mushrooming reports of "quiet quitting": Employees' lifetime psilocybin use predicts their overtime hours worked.

abstract:
Despite the recent and sharp rise in psychedelic research, few studies have investigated how classic psychedelic use relates to employees' work-related outcomes. This is surprising given that the increased use, decriminalization, and legalization of classic psychedelics in the United States (U.S.) has the potential to impact both employees and their organizations. Addressing this gap, the current study explores how employees' lifetime psilocybin use relates to the amount of overtime they work, thereby offering insight into what current trends in psilocybin use could mean for businesses. Using pooled, cross-sectional data from the National Survey on Drug Use and Health (2002-2014) on 217,963 adults employed in the U.S. full-time, this study tests whether lifetime psilocybin use is associated with employees' number of overtime hours worked in the past week. After adjusting for sociodemographics and other substance use, a significant negative association is found between employees' lifetime psilocybin use and the amount of overtime they reported working. Specifically, the findings suggest that lifetime psilocybin use in the U.S. full-time working population is associated with an estimated 44,348,400 fewer overtime hours worked per year and may help explain recent findings linking employees' lifetime psilocybin use to a reduction in sick leave taken.

keywords:
Humans, Substance-Related Disorders, Hallucinogens, Cross-Sectional Studies, Adolescent, Adult, Middle Aged, Employment, Workload, United States, Female, Male, Young Adult, Psilocybin

raw_json:
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publication_date: 2023-07-13
doi: 10.1080/02791072.2023.2232379
pubmed_id: 37449499
source_url: https://doi.org/10.1080/02791072.2023.2232379
substance_tags: psilocybin
topic_tags: Mystical Experience,Observational Study
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
title:
Translation and Initial Psychometric Evaluation of Spanish Versions of Three Psychedelic Acute Effects Measures: Mystical, Challenging, and Insight Experiences.

authors:
Davis AK, Timmermann C, Ortiz Bernal AM, Lancelotta R, Nayak S, Sepeda ND, Nikolaidis A, Griffiths RR.

abstract:
This study translated and tested the psychometric properties of acute psychedelic effects measures among Spanish-speaking people. The Psychological Insight Questionnaire (PIQ), Challenging Experiences Questionnaire (CEQ), and Mystical Experiences Questionnaire (MEQ) were translated before being incorporated into a web-based survey. We recruited native Spanish-speakers (N = 442; Mage = 30.8, SD = 10.9; Latino/Latina = 62%; Hispanic = 91.4%; male = 71.5%) to assess their previous experience with one of two psychedelics (LSD = 58.4%; Psilocybin = 41.6%) and their acute and enduring effects. Confirmatory factor analysis (confirming factor structure based on the English version) revealed a good fit for the MEQ, PIQ and the CEQ. Repeating our analysis in each drug subsample revealed consistency in factor structure for each assessment tool. Construct validity was supported by significant positive associations between the PIQ and MEQ, and between the PIQ and MEQ and changes in cognitive fusion and negative associations between changes in prosocial behaviors. As a signal of predictive validity, persisting effects (PEQ) were strongly related to scores on the MEQ and PIQ. Findings demonstrate that the Spanish versions of these measures can be reliably employed in studies of psychedelic use or administration in Spanish-speaking populations.

keywords:
Humans, Lysergic Acid Diethylamide, Hallucinogens, Factor Analysis, Statistical, Reproducibility of Results, Psychometrics, Mysticism, Translations, Adult, Female, Male, Young Adult, Surveys and Questionnaires, Psilocybin, Hispanic or Latino

raw_json:
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title: Within-subject comparison of near-death and psychedelic experiences: acute and enduring effects.
authors: Martial C, Carhart-Harris R, Timmermann C.
publication_date: 2024-08-29
doi: 10.1093/nc/niae033
pubmed_id: 39220326
source_url: https://doi.org/10.1093/nc/niae033
substance_tags: psilocybin
topic_tags: Consciousness,Mystical Experience,Observational Study
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
abstract:
Mystical-like states of consciousness may arise through means such as psychedelic substances, but may also occur unexpectedly during near-death experiences (NDEs). So far, research studies comparing experiences induced by serotonergic psychedelics and NDEs, along with their enduring effects, have employed between-subject designs, limiting direct comparisons. We present results from an online survey exploring the phenomenology, attribution of reality, psychological insights, and enduring effects of NDEs and psychedelic experiences (PEs) in individuals who have experienced both at some point during their lifetime. We used frequentist and Bayesian analyses to determine significant differences and overlaps (evidence for null hypotheses) between the two. Thirty-one adults reported having experienced both an NDE (i.e. NDE-C scale total score ≥27/80) and a PE (intake of lysergic acid diethylamide, psilocybin/mushrooms, ayahuasca, N,N-dimethyltryptamine, or mescaline). Results revealed areas of overlap between both experiences for phenomenology, attribution of reality, psychological insights, and enduring effects. A finer-grained analysis of the phenomenology revealed a significant overlap in mystical-like effects, while low-level phenomena (sensory effects) were significantly different, with NDEs displaying higher scores of disembodiment and PEs higher scores of visual imagery. This suggests psychedelics as a useful model for studying mystical-like effects induced by NDEs, while highlighting distinctions in sensory experiences.

raw_json:
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authors: Yao Y, Zhang YZ, Liang JQ, Liu F, Li ZF, Li HJ, Xu F.
publication_date: 2024-07-03
doi: 10.1016/j.toxicon.2024.107849
pubmed_id: 38971474
source_url: https://doi.org/10.1016/j.toxicon.2024.107849
keywords: Humans, Agaricales, Mushroom Poisoning, Tryptamines, Phylogeny, China, Psilocybin
substance_tags: psilocybin,psilocin
topic_tags: Aging
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:00
title:
Mushroom poisoning of Panaeolus subbalteatus from Ningxia, northwest China, with species identification and tryptamine detection.

abstract:
Mushroom poisoning is a significant contributor to foodborne disease outbreaks in China. This study focuses on two Panaeolus subbalteatus poisoning incidents accompanied by epidemiological investigations, species identification, and toxin detection in Ningxia, northwest China. In these two poisoning incidents, some patients exhibited gastrointestinal or neurological symptoms approximately 0.5 h after ingestion of a large amount of wild mushroom. Specifically, in Case 1, one of the three patients experienced nausea, vomiting, and numbness in the throat and limbs; in Case 2, one patient reported dizziness and an abnormal sense of direction. Through morphological and phylogenetic analyses, mushroom specimens were identified as P. subbalteatus. Psilocybin and psilocin were detected in mushroom samples, and only psilocin was detected in biological samples by liquid chromatography-triple quadrupole-linear ion trap mass spectrometry screening. The average psilocybin and psilocin contents in mushroom samples were 1532.2-1760.7 and 114.5-136.0 mg/kg (n = 3), respectively. Moreover, only psilocin was detected in blood and urine samples, with average concentrations 0.5-1.2 ng/mL (n = 3) and 2.5-3.1 ng/mL (n = 3), respectively. These findings provide technical support for managing similar incidents in the future.

raw_json:
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authors: Frye MA, Singh B, Breitinger SA, Oesterle TS.
publication_date: 2024-08-25
doi: 10.4088/jcp.24cr15378
pubmed_id: 39196888
source_url: https://doi.org/10.4088/jcp.24cr15378
substance_tags: psilocybin
topic_tags: Addiction,Receptor Pharmacology
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
title:
Selective Serotonin Reuptake Inhibitor Discontinuation for Psilocybin Treatment and Contributions to Alcohol Addiction Relapse: A Cautionary Tale.

keywords:
Humans, Alcoholism, Recurrence, Hallucinogens, Adult, Male, Psilocybin, Selective Serotonin Reuptake Inhibitors

raw_json:
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publication_date: 2024-08-20
doi: 10.1136/bmj-2023-078607
pubmed_id: 39168500
source_url: https://doi.org/10.1136/bmj-2023-078607
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Comparative oral monotherapy of psilocybin, lysergic acid diethylamide, 3,4-methylenedioxymethamphetamine, ayahuasca, and escitalopram for depressive symptoms: systematic review and Bayesian network meta-analysis.

authors:
Hsu TW, Tsai CK, Kao YC, Thompson T, Carvalho AF, Yang FC, Tseng PT, Hsu CW, Yu CL, Tu YK, Liang CS.

abstract:
ObjectiveTo evaluate the comparative effectiveness and acceptability of oral monotherapy using psychedelics and escitalopram in patients with depressive symptoms, considering the potential for overestimated effectiveness due to unsuccessful blinding.DesignSystematic review and Bayesian network meta-analysis.Data sourcesMedline, Cochrane Central Register of Controlled Trials, Embase, PsycINFO, ClinicalTrial.gov, and World Health Organization's International Clinical Trials Registry Platform from database inception to 12 October 2023.Eligibility criteria for selecting studiesRandomised controlled trials on psychedelics or escitalopram in adults with depressive symptoms. Eligible randomised controlled trials of psychedelics (3,4-methylenedioxymethamphetamine (known as MDMA), lysergic acid diethylamide (known as LSD), psilocybin, or ayahuasca) required oral monotherapy with no concomitant use of antidepressants.Data extraction and synthesisThe primary outcome was change in depression, measured by the 17-item Hamilton depression rating scale. The secondary outcomes were all cause discontinuation and severe adverse events. Severe adverse events were those resulting in any of a list of negative health outcomes including, death, admission to hospital, significant or persistent incapacity, congenital birth defect or abnormality, and suicide attempt. Data were pooled using a random effects model within a Bayesian framework. To avoid estimation bias, placebo responses were distinguished between psychedelic and antidepressant trials.ResultsPlacebo response in psychedelic trials was lower than that in antidepression trials of escitalopram (mean difference -3.90 (95% credible interval -7.10 to -0.96)). Although most psychedelics were better than placebo in psychedelic trials, only high dose psilocybin was better than placebo in antidepression trials of escitalopram (mean difference 6.45 (3.19 to 9.41)). However, the effect size (standardised mean difference) of high dose psilocybin decreased from large (0.88) to small (0.31) when the reference arm changed from placebo response in the psychedelic trials to antidepressant trials. The relative effect of high dose psilocybin was larger than escitalopram at 10 mg (4.66 (95% credible interval 1.36 to 7.74)) and 20 mg (4.69 (1.64 to 7.54)). None of the interventions was associated with higher all cause discontinuation or severe adverse events than the placebo.ConclusionsOf the available psychedelic treatments for depressive symptoms, patients treated with high dose psilocybin showed better responses than those treated with placebo in the antidepressant trials, but the effect size was small.Systematic review registrationPROSPERO, CRD42023469014.

keywords:
Humans, Banisteriopsis, N-Methyl-3,4-methylenedioxyamphetamine, Lysergic Acid Diethylamide, Hallucinogens, Treatment Outcome, Administration, Oral, Bayes Theorem, Depression, Randomized Controlled Trials as Topic, Psilocybin, Escitalopram

topic_tags:
Depression,Clinical Trial,Randomized Controlled Trial,Meta-Analysis,Systematic Review,Review Article,Adverse Events

raw_json:
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title: Psilocybin Facilitates Fear Extinction: Importance of Dose, Context, and Serotonin Receptors.
authors: Woodburn SC, Levitt CM, Koester AM, Kwan AC.
publication_date: 2024-07-31
doi: 10.1021/acschemneuro.4c00279
pubmed_id: 39087917
source_url: https://doi.org/10.1021/acschemneuro.4c00279
substance_tags: psilocybin
topic_tags: PTSD,Receptor Pharmacology,Animal Study
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
abstract:
A variety of classic psychedelics and MDMA have been shown to enhance fear extinction in rodent models. This has translational significance because a standard treatment for post-traumatic stress disorder (PTSD) is prolonged exposure therapy. However, few studies have investigated psilocybin's potential effect on fear learning paradigms. More specifically, the extents to which dose, timing of administration, and serotonin receptors may influence psilocybin's effect on fear extinction are not understood. In this study, we used a delay fear conditioning paradigm to determine the effects of psilocybin on fear extinction, extinction retention, and fear renewal in male and female mice. Psilocybin robustly enhances fear extinction when given acutely prior to testing for all doses tested. Psilocybin also exerts long-term effects to elevate extinction retention and suppress fear renewal in a novel context, although these changes were sensitive to dose. Analysis of sex differences showed that females may respond to a narrower range of doses than males. Administration of psilocybin prior to fear learning or immediately after extinction yielded no change in behavior, indicating that concurrent extinction experience is necessary for the drug's effects. Cotreatment with a 5-HT2A receptor antagonist blocked psilocybin's effects for extinction, extinction retention, and fear renewal, whereas 5-HT1A receptor antagonism attenuated only the effect on fear renewal. Collectively, these results highlight dose, context, and serotonin receptors as crucial factors in psilocybin's ability to facilitate fear extinction. The study provides preclinical evidence to support investigating psilocybin as a pharmacological adjunct for extinction-based therapy for PTSD.

keywords:
Animals, Mice, Inbred C57BL, Mice, Receptors, Serotonin, Hallucinogens, Fear, Conditioning, Classical, Dose-Response Relationship, Drug, Female, Male, Extinction, Psychological, Psilocybin

raw_json:
{"europe_pmc_id":"39087917","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Salvetti G, Saccenti D, Moro AS, Lamanna J, Ferro M.
publication_date: 2024-08-17
doi: 10.3390/brainsci14080829
pubmed_id: 39199520
source_url: https://doi.org/10.3390/brainsci14080829
substance_tags: psilocybin
study_type: Meta-Analysis
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Comparison between Single-Dose and Two-Dose Psilocybin Administration in the Treatment of Major Depression: A Systematic Review and Meta-Analysis of Current Clinical Trials.

abstract:
Current pharmacological treatments for major depressive disorder (MDD) are often only partially effective, with many patients experiencing no significant benefit, leading to treatment-resistant depression (TRD). Psilocybin, a classical serotonergic psychedelic, has emerged as a notable emerging treatment for such disorders. The aim of this systematic review and meta-analysis is to summarize and discuss the most recent evidence about the therapeutic effects of single-dose and two-dose psilocybin administration on the severity of depressive symptoms, as well as compare the efficacy of these interventions among patients with a primary diagnosis of MDD or TRD. Articles were collected from EBSCOhost and PubMed following the PRISMA guidelines, yielding 425 articles with 138 duplicates. After screening 287 records, 12 studies met the eligibility criteria and were included in the review. A quantitative analysis of the studies indicates that psilocybin is highly effective in reducing depressive symptoms severity among patients with primary MDD or TRD. Both single-dose and two-dose psilocybin treatments significantly reduced depressive symptoms severity, with two-dose administration sometimes yielding more pronounced and lasting effects. However, it is unclear if this was solely due to dosage or other factors. Future research should include standardized trials comparing these dosing strategies to better inform clinical practice.

topic_tags:
Depression,Clinical Trial,Meta-Analysis,Systematic Review,Review Article,Treatment-Resistant Depression

raw_json:
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authors: Khajavinia A, Michel D, Ezeaka UC, Purves RW, Laprairie RB, El-Aneed A.
publication_date: 2024-07-03
doi: 10.1016/j.chroma.2024.465123
pubmed_id: 38981146
source_url: https://doi.org/10.1016/j.chroma.2024.465123
substance_tags: psilocybin,psilocin
topic_tags: Depression,Anxiety,PTSD,Pharmacology,Animal Study,Safety,Drug Interactions
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:00
title:
Addressing a major interference in the quantification of psilocin in mouse plasma: Development of a validated liquid chromatography tandem mass spectrometry method.

abstract:
Psilocybin is a psychedelic compound found in some hallucinogenic "magic mushrooms". Psilocin is the active metabolite of Psilocybin, and it is the subject of several studies for the treatment of psychological disorders, such as anxiety, depression, and post-traumatic stress disorder. As such, the pharmacokinetic properties of psilocin should be evaluated to ensure its safety and efficacy as part of the drug development process. Based on the previously published studies, reversed-phase liquid chromatography (LC) was tested for psilocin quantification. The analysis, however, showed a major interference in mouse plasma that was not, to the best of our knowledge, reported previously. We, therefore, aimed to identify and separate the interference, using various chromatographic columns, mobile phase conditions, and mass spectrometers (MS) instruments. Chromatographic separation was achieved on an ultra high performance liquid chromatography (UHPLC) system, and a quadrupole-linear ion trap equipped with an electrospray ionization (ESI) source was used in positive ion mode with multiple reaction monitoring (MRM). Several chromatographic conditions and column chemistries, including C-18 and Phenyl-hexyl were initially tested, and failed to separate the interference. Exact mass measurement and MS/MS analysis were used to determine the structure of the interfering compound, which was confirmed to be tryptophan. Using the identified structure of the interfering compound, a fast and reliable hydrophilic interaction liquid chromatography (HILIC)-MS/MS method was developed and validated, that was capable of separating psilocin from the interference while achieving a 0.5 ng/ml lower limit of quantification (LLOQ). The validated method was successfully applied to a pharmacokinetic study where psilocin was orally administered to C57BL/6 mouse subjects. Psilocin concentration in all the analyzed mouse plasma samples was successfully determined.

keywords:
Animals, Mice, Inbred C57BL, Mice, Hallucinogens, Chromatography, Liquid, Chromatography, High Pressure Liquid, Reproducibility of Results, Male, Tandem Mass Spectrometry, Chromatography, Reverse-Phase, Psilocybin

raw_json:
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authors: Chen MH, Cheng SL, Kao YC, Tseng PT, Hsu CW, Yu CL, Yang FC, Thompson T, Hsu TW, Liang CS.
publication_date: 2024-08-12
doi: 10.3389/fpsyt.2024.1439347
pubmed_id: 39193583
source_url: https://doi.org/10.3389/fpsyt.2024.1439347
substance_tags: psilocybin
topic_tags: Depression,Clinical Trial,Meta-Analysis,Review Article
study_type: Meta-Analysis
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
The association between diverse psychological protocols and the efficacy of psilocybin-assisted therapy for clinical depressive symptoms: a Bayesian meta-analysis.

abstract:
ObjectivePsilocybin-assisted therapy has shown promising efficacy on clinical depressive symptoms. However, diverse psychological support or psychotherapy was performed with psilocybin treatment. This study aimed to explore the association of psychological protocols with the efficacy of psilocybin-assisted therapy for depressive symptoms.MethodFive major databases were systemic searched for clinical trials addressing psilocybin-assisted therapy for patients with clinical depressive symptoms. A Bayesian random-effects meta-analysis and meta-regression were performed. The effect size was mean difference (with 95% credible interval) measured by 17-Item Hamilton Depression Rating Scale.ResultsThere were 10 eligible studies including 515 adult patients with clinically diagnosed depression. The psychological protocols could be categorized into four types: (i) manualized directive psychotherapy(k=1); (ii) manualized nondirective psychological support(k=3), (iii) non-manualized nondirective psychological support(k=5); and (iv) non-manualized supportive psychotherapy(k=1). The pooled standard mean difference of psilocybin-assisted therapy was 10.08 (5.03-14.70).ConclusionCompared with manualized nondirective psychological support, the other three psychological approaches did not differ significantly. The improvement of depressive symptoms was not associated with the psychological protocols in adult patients receiving psilocybin-assisted therapy.Systemic review registrationOpen Science Framework: identifier (osf.io/3YUDV).

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authors: VanderZwaag B, Garcia-Romeu A, Garcia-Barrera MA.
publication_date: 2024-08-06
doi: 10.1177/20451253241264812
pubmed_id: 39132012
source_url: https://doi.org/10.1177/20451253241264812
substance_tags: psilocybin
topic_tags: Depression,Addiction,Aging,Observational Study,Safety
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Exploring psychedelic use in athletes and their attitudes toward psilocybin-assisted therapy in concussion recovery.

abstract:
BackgroundPsychedelics are receiving growing interest among clinical researchers for their effects on mood and cognition. Psilocybin is one of the most widely studied classic psychedelics which has shown good safety and clinical benefit for major depression and substance use disorders. Athletes frequently sustain concussions and often experience myriad symptoms, including cognitive and mood issues, which can persist for weeks or months in 10%-30% of athletes. Psilocybin may be a potential symptom management option for athletes with persisting concussion symptoms.ObjectivesThis study sought to summarize athlete psychedelic use, among other substances, and to examine the willingness of the sports community to engage in or support psilocybin-assisted therapy (PAT) for concussion recovery and management of persisting concussion symptoms.MethodsIn total, 175 (n = 85 athletes; n = 90 staff) respondents completed an online survey distributed in Canada and the United States which queried sport involvement and demographics, substance use, concussion history, and knowledge and willingness about psilocybin. The reporting of this study conforms to the Checklist for Reporting Results of Internet E-Surveys (CHERRIES) statement.DesignSubstance use rates were summarized across athletes and team staff members and a path analysis was used for each sample to identify predictors of willingness to use PAT (athletes) or support PAT (staff) for concussion recovery. Participants were also asked to identify perceived barriers to the implementation of PAT for sports-related concussions, and to indicate their overall willingness.ResultsPsychedelics were the third most used substance in the past year among athletes (35.8%) while regular psychedelic use was quite low in athletes (7.5%). A path analysis conducted in RStudio found that attitudes toward psilocybin and knowledge of psilocybin were significant predictors for both athletes and staff members of their willingness to use or support PAT for concussion recovery. Athletes reported likely engaging in PAT (61.2%) and staff (71.1%) reported that they would support their athletes using PAT.ConclusionThe results of this study suggest that the sports community may be receptive to PAT and athletes would be willing to engage in it for concussion recovery and/or the management of persisting post-concussion symptoms (PPCS). Future research should examine the effects of psilocybin for PPCS to inform whether there is any impact while addressing concerns regarding long-term effects of psilocybin use.

raw_json:
{"europe_pmc_id":"39132012","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin-assisted therapy and HIV-related shame.
authors: Mehtani NJ, Johnson MO, Hendricks PS, Mitchell J, Anderson BT.
publication_date: 2024-08-01
doi: 10.1038/s41598-024-68908-4
pubmed_id: 39095420
source_url: https://doi.org/10.1038/s41598-024-68908-4
substance_tags: psilocybin
topic_tags: Addiction,Clinical Trial
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
abstract:
As a proposed mediator between stigma-related stressors and negative mental health outcomes, HIV-related shame has been predictive of increased rates of substance use and difficulties adhering to antiretroviral treatment among people with HIV. These downstream manifestations have ultimately impeded progress toward national goals to End the HIV Epidemic, in part due to limited success of conventional psychotherapies in addressing HIV-related shame. In a pilot clinical trial (N = 12), receipt of psilocybin-assisted group therapy was associated with a large pre-post decrease in HIV-related shame as measured by the HIV and Abuse Related Shame Inventory, with a median (IQR) change of - 5.5 (- 6.5, - 3.5) points from baseline to 3-months follow-up (Z = - 2.6, p = 0.009, r = - 0.75). A paradoxical exacerbation of sexual abuse-related shame experienced by two participants following receipt of psilocybin raises critical questions regarding the use of psilocybin therapy among patients with trauma. These preliminary findings carry potential significance for the future of HIV care.

keywords:
Humans, HIV Infections, Pilot Projects, Shame, Adult, Middle Aged, Female, Male, Social Stigma, Psilocybin

raw_json:
{"europe_pmc_id":"39095420","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: CURRENT STATE OF PSILOCYBIN-ASSISTED THERAPY IN MOOD DISORDERS.
authors: Kaiserman A, Vanderjist L, Kornreich C.
publication_date: 2024-07-31
doi: 10.24869/psyd.2024.174
pubmed_id: 39546645
source_url: https://doi.org/10.24869/psyd.2024.174
keywords: Humans, Hallucinogens, Mood Disorders, Psilocybin
substance_tags: psilocybin
topic_tags: Depression,Anxiety,End-of-Life Distress,Neuroplasticity,Receptor Pharmacology,Review Article
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
abstract:
Psychedelics are currently undergoing a scientific renaissance, with modern studies investigating therapeutic efficacy of psychedelic-assisted therapy in a range of psychiatric conditions. In particular, psilocybin-assisted therapy (PAT) has been suggested to have positive effects on patients suffering from depression and psychiatric distress associated with life-threatening disease - contexts with growing needs for alternative treatments - in a therapeutic setting involving fewer doses and less important adverse effect compared to that of classic psychotrope administration. Psychedelics are partial agonists of the serotonin 2A (5-HT2A) G protein-coupled receptors, whose activation likely mediates the acute psychoactive effects. Furthermore, psychedelics seem to induce a hyper-plastic state which allows for adaptation of inflexible pathological thinking patterns. Post-acutely, they are suggested to induce rapid, robust and sustained neuroplasticity. Eight clinical PAT trials have been conducted between January 1st 2001 and March 31st 2023 and are reviewed here. Five of them evaluate the effect on depressive symptomatology in an otherwise general population. The other three evaluate effect on depression and anxiety in patients suffering from somatic life-threatening disease. The studies reviewed here show that PAT is safe and feasible to administer in current clinical models. Preliminary efficacy shows significant improvements in depressive and anxious symptomatology which are immediate and partially sustained. One study comparing PAT to selective serotonergic reuptake inhibitors showed no significant difference of efficacy between the two treatments. Preliminary results regarding efficacy of PAT on mood disorders are promising, but further research is warranted for stronger inferences, with a particular focus on larger, multicentric studies, more diverse populations and a stronger control for expectancy and unblinding.

raw_json:
{"europe_pmc_id":"39546645","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: [The nursing role in psychedelic-assisted psychotherapy].
authors: Amberger C, Szczesniak L
journal: Revue de l'infirmiere
publication_date: 2023-12-31
doi: 10.1016/j.revinf.2024.07.014
pubmed_id: 39209402
source_url: https://pubmed.ncbi.nlm.nih.gov/39209402/
substance_tags: psilocybin
topic_tags: Consciousness
study_type: Other
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:36
raw_json: {"pubmed_id":"39209402"}
abstract:
In this article, we aim to highlight the specific role of nurses in the interdisciplinary model of psychedelic-assisted psychotherapy. We argue that the plural competencies of our profession are at the heart of future issues in psychiatry and the use of psychedelics.

keywords:
LSD, conscience, consciousness, nursing role, psilocybin, psilocybine, psychedelics, psychotherapy, psychothérapie, psychédélique, rôle infirmier


title: Psilocybin desynchronizes the human brain.
publication_date: 2024-07-16
doi: 10.1038/s41586-024-07624-5
pubmed_id: 39020167
source_url: https://doi.org/10.1038/s41586-024-07624-5
substance_tags: psilocybin
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:00
authors:
Siegel JS, Subramanian S, Perry D, Kay BP, Gordon EM, Laumann TO, Reneau TR, Metcalf NV, Chacko RV, Gratton C, Horan C, Krimmel SR, Shimony JS, Schweiger JA, Wong DF, Bender DA, Scheidter KM, Whiting FI, Padawer-Curry JA, Shinohara RT, Chen Y, Moser J, Yacoub E, Nelson SM, Vizioli L, Fair DA, Lenze EJ, Carhart-Harris R, Raison CL, Raichle ME, Snyder AZ, Nicol GE, Dosenbach NUF.

abstract:
A single dose of psilocybin, a psychedelic that acutely causes distortions of space-time perception and ego dissolution, produces rapid and persistent therapeutic effects in human clinical trials1-4. In animal models, psilocybin induces neuroplasticity in cortex and hippocampus5-8. It remains unclear how human brain network changes relate to subjective and lasting effects of psychedelics. Here we tracked individual-specific brain changes with longitudinal precision functional mapping (roughly 18 magnetic resonance imaging visits per participant). Healthy adults were tracked before, during and for 3 weeks after high-dose psilocybin (25 mg) and methylphenidate (40 mg), and brought back for an additional psilocybin dose 6-12 months later. Psilocybin massively disrupted functional connectivity (FC) in cortex and subcortex, acutely causing more than threefold greater change than methylphenidate. These FC changes were driven by brain desynchronization across spatial scales (areal, global), which dissolved network distinctions by reducing correlations within and anticorrelations between networks. Psilocybin-driven FC changes were strongest in the default mode network, which is connected to the anterior hippocampus and is thought to create our sense of space, time and self. Individual differences in FC changes were strongly linked to the subjective psychedelic experience. Performing a perceptual task reduced psilocybin-driven FC changes. Psilocybin caused persistent decrease in FC between the anterior hippocampus and default mode network, lasting for weeks. Persistent reduction of hippocampal-default mode network connectivity may represent a neuroanatomical and mechanistic correlate of the proplasticity and therapeutic effects of psychedelics.

keywords:
Brain, Hippocampus, Nerve Net, Humans, Methylphenidate, Hallucinogens, Magnetic Resonance Imaging, Brain Mapping, Ego, Space Perception, Time Perception, Adolescent, Adult, Middle Aged, Female, Male, Young Adult, Healthy Volunteers, Psilocybin, Default Mode Network

topic_tags:
Neuroplasticity,Brain Imaging,Default Mode Network,Aging,Clinical Trial,Animal Study,Healthy Volunteers,Adolescents

raw_json:
{"europe_pmc_id":"39020167","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Brain Networks, Neurotransmitters and Psychedelics: Towards a Neurochemistry of Self-Awareness.
authors: Mograbi DC, Rodrigues R, Bienemann B, Huntley J
journal: Current neurology and neuroscience reports
publication_date: 2024-07-31
doi: 10.1007/s11910-024-01353-y
pubmed_id: 38980658
source_url: https://pubmed.ncbi.nlm.nih.gov/38980658/
keywords: Interoception, LSD, agency, emotional regulation, metacognition, psilocybin
substance_tags: psilocybin
topic_tags: Mechanism of Action,Emotional Processing,Review Article
study_type: Review Article
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:36
raw_json: {"pubmed_id":"38980658"}
abstract:
Self-awareness can be defined as the capacity of becoming the object of one's own awareness and, increasingly, it has been the target of scientific inquiry. Self-awareness has important clinical implications, and a better understanding of the neurochemical basis of self-awareness may help clarifying causes and developing interventions for different psychopathological conditions. The current article explores the relationship between neurochemistry and self-awareness, with special attention to the effects of psychedelics.
The functioning of self-related networks, such as the default-mode network and the salience network, and how these are influenced by different neurotransmitters is discussed. The impact of psychedelics on self-awareness is reviewed in relation to specific processes, such as interoception, body ownership, agency, metacognition, emotional regulation and autobiographical memory, within a framework based on predictive coding. Improved outcomes in emotional regulation and autobiographical memory have been observed in association with the use of psychedelics, suggesting higher-order self-awareness changes, which can be modulated by relaxation of priors and improved coping mechanisms linked to cognitive flexibility. Alterations in bodily self-awareness are less consistent, being potentially impacted by doses employed, differences in acute/long-term effects and the presence of clinical conditions. Future studies investigating the effects of different molecules in rebalancing connectivity between resting-state networks may lead to novel therapeutic approaches and the refinement of existing treatments.


authors: Lake S, Lucas P.
publication_date: 2024-06-25
doi: 10.1016/j.drugpo.2024.104507
pubmed_id: 38936219
source_url: https://doi.org/10.1016/j.drugpo.2024.104507
substance_tags: psilocybin
topic_tags: Observational Study
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
title:
The Global Psychedelic Survey: Consumer characteristics, patterns of use, and access in primarily anglophone regions around the world.

abstract:
ObjectivesDespite advancements in policies governing psychedelic substances globally, our understanding of real-world psychedelic use and its variations across international jurisdictions remains limited. We implemented the Global Psychedelic Survey (GPS) to capture information about psychedelic consumer characteristics, access, and usage patterns around the world.MethodsThe GPS was administered online in Spring 2023 to English-speaking adults (≥21 years) who use(d) psychedelics. We categorized survey responses into major catchment regions (Canada/US, Europe/UK, Australia/NZ, All Other). We used descriptive and bivariable statistics to characterize consumers' socio-demographic characteristics, psychedelic access sources, and usage patterns. We examined regional differences in psychedelic use patterns using multinomial logistic regression.ResultsWe analyzed 6379 responses from 85 countries including Canada/US (n = 4434), Europe/UK (n = 771), Australia/NZ (n = 864), and Other (n = 310). Psilocybin, LSD, and MDMA were the most used psychedelics and personal growth was the most common use motive across all catchments. There were significant regional differences in psychedelic use patterns, including types of psychedelics used (e.g., less ibogaine use in Europe/UK and Australia/NZ relative to Canada/US), frequency of use (e.g., lower frequency use in Australia/NZ relative to Canada/US), motivations for use (e.g., less therapeutic use in Europe/UK and Other relative to Canada/US), and types of dosing regimens (e.g., more "micro"-dosing in Canada/US).DiscussionIn this large sample of adult psychedelic consumers from regions around the world, infrequent psychedelic use centered around life enhancement was common. Respondents indicated preference for legal access via quality-controlled sources. Jurisdictional differences in access and usage patterns likely reflect region-specific regulations and traditional practices. Further research should explore opportunities to increase representation of non-White respondents in psychedelic research via translation of studies into several languages and incorporation of culturally reflective, community-based study development.

keywords:
Humans, Hallucinogens, Adult, Middle Aged, Female, Male, Young Adult, Surveys and Questionnaires, Recreational Drug Use

raw_json:
{"europe_pmc_id":"38936219","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2024-06-17
doi: 10.1177/02698811241257839
pubmed_id: 38888164
source_url: https://doi.org/10.1177/02698811241257839
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Wellbeing,Clinical Trial,Observational Study,Safety,Adverse Events
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Developing the Open Psychedelic Evaluation Nexus consensus measures for assessment of supervised psilocybin services: An e-Delphi study.

authors:
Korthuis PT, Hoffman K, Wilson-Poe AR, Luoma JB, Bazinet A, Pertl K, Morgan DL, Cook RR, Bielavitz S, Myers R, Wolf RC, McCarty D, Stauffer CS.

abstract:
BackgroundVoter initiatives in Oregon and Colorado authorize legal frameworks for supervised psilocybin services, but no measures monitor safety or outcomes.AimsTo develop core measures of best practices.MethodsA three-phase e-Delphi process recruited 36 experts with 5 or more years' experience facilitating psilocybin experiences in various contexts (e.g., ceremonial settings, indigenous practices, clinical trials), or other pertinent psilocybin expertise. Phase I, an on-line survey with qualitative, open-ended text responses, generated potential measures to assess processes, outcomes, and structure reflecting high quality psilocybin services. In Phase II, experts used seven-point Likert scales to rate the importance and feasibility of the Phase I measures. Measures were priority ranked. Qualitative interviews and analysis in Phase III refined top-rated measures.ResultsExperts (n = 36; 53% female; 71% white; 56% heterosexual) reported currently providing psilocybin services (64%) for a mean of 15.2 [SD13.1] years, experience with indigenous psychedelic practices (67%), and/or conducting clinical trials (36%). Thematic analysis of Phase I responses yielded 55 candidate process measures (e.g., preparatory hours with client, total dose of psilocybin administered, documentation of touch/sexual boundaries), outcome measures (e.g., adverse events, well-being, anxiety/depression symptoms), and structure measures (e.g., facilitator training in trauma informed care, referral capacity for medical/psychiatric issues). In Phase II and III, experts prioritized a core set of 11 process, 11 outcome, and 17 structure measures that balanced importance and feasibility.ConclusionService providers and policy makers should consider standardizing core measures developed in this study to monitor the safety, quality, and outcomes of community-based psilocybin services.

keywords:
Humans, Hallucinogens, Adult, Middle Aged, Oregon, Colorado, Female, Male, Surveys and Questionnaires, Psilocybin

raw_json:
{"europe_pmc_id":"38888164","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: The cyclical revival of psychedelics in psychiatric treatment.
authors: Appiani FJ, Caroff SN.
publication_date: 2024-06-19
doi: 10.1080/03007995.2024.2368725
pubmed_id: 38880945
source_url: https://doi.org/10.1080/03007995.2024.2368725
keywords: Humans, Hallucinogens, Psychotherapy, Psilocybin
substance_tags: psilocybin
topic_tags: Depression,Clinical Trial,Treatment-Resistant Depression,Safety
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:03
abstract:
There is an increasing demand for effective treatments for depression, particularly for individuals grappling with treatment-resistant depression. Over recent years, a surge of interest has focused on exploring the safety and efficacy of psilocybin as a potential treatment for depression. However, preliminary findings from phase 2 studies have been inconclusive, prompting critical examination of issues such as maintaining blinding and the role of adjunctive psychotherapy. The maintenance of double-blinding and the role of adjunctive psychotherapy introduce biases that complicate the attainment of conclusive results in clinical research. Examining historical data reveals a recurrent pattern linked to the use of psychoactive substances, which starts with an excess of optimism and ends with general addictive behaviors and a heightened risk of serious public health problems. Considering these findings, a cautious and measured approach is imperative, given that the efficacy and safety of psilocybin treatment have yet to be unequivocally established. The potential for excessive optimism among researchers is a notable concern, as unwarranted enthusiasm may inadvertently facilitate the widespread adoption of this treatment without sufficient empirical support. In navigating the complexities of depression treatment, it is necessary to strike a balance between innovation and prudence to ensure evidence-based advancement of therapeutic approaches.

raw_json:
{"europe_pmc_id":"38880945","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Is microdosing a placebo? A rapid review of low-dose LSD and psilocybin research.
authors: Polito V, Liknaitzky P.
publication_date: 2024-06-13
doi: 10.1177/02698811241254831
pubmed_id: 38877715
source_url: https://doi.org/10.1177/02698811241254831
substance_tags: psilocybin
topic_tags: Microdosing,Randomized Controlled Trial,Review Article,Safety
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
abstract:
Some recent research and commentary have suggested that most or all the effects reported by people who microdose psychedelics may be explained by expectations or placebo effects. In this rapid review, we aimed to evaluate the strength of evidence for a placebo explanation of the reported effects of microdosing. We conducted a PubMed search for all studies investigating psychedelic microdosing with controlled doses and a placebo comparator. We identified 19 placebo-controlled microdosing studies and summarised all positive and null findings across this literature. Risk of bias was assessed using the Cochrane risk-of-bias tool for randomised trials. The reviewed papers indicated that microdosing with LSD and psilocybin leads to changes in neurobiology, physiology, subjective experience, affect, and cognition relative to placebo. We evaluate methodological gaps and challenges in microdosing research and suggest eight reasons why current claims that microdosing is predominately a placebo are premature and possibly wrong: (1) there have been only a small number of controlled studies; (2) studies have had small sample sizes; (3) there is evidence of dose-dependent effects; (4) studies have only investigated the effects of a small number of doses; (5) the doses investigated may have been too small; (6) studies have looked only at non-clinical populations; (7) studies so far have been susceptible to selection bias; and (8) the measured impact of expectancy is small. Considering the available evidence, we conclude that it is not yet possible to determine whether microdosing is a placebo.

keywords:
Humans, Lysergic Acid Diethylamide, Hallucinogens, Placebo Effect, Dose-Response Relationship, Drug, Randomized Controlled Trials as Topic, Psilocybin

raw_json:
{"europe_pmc_id":"38877715","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Protocols and practices in psilocybin assisted psychotherapy for depression: A systematic review.
publication_date: 2024-05-30
doi: 10.1016/j.jpsychires.2024.05.051
pubmed_id: 38850581
source_url: https://doi.org/10.1016/j.jpsychires.2024.05.051
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
authors:
Chisamore N, Johnson D, Chen MJQ, Offman H, Chen-Li D, Kaczmarek ES, Doyle Z, McIntyre RS, Rosenblat JD.

abstract:
BackgroundPsilocybin-assisted psychotherapy (PAP) is a promising treatment option for depression, with randomized controlled trials (RCTs) providing preliminary support for its safety and efficacy. However, there is a lack of consistency across existing treatment protocols and psychotherapeutic approaches. The objective of this review is to summarize and compare current psychotherapy methods of PAP in treating depression and distress in life-threatening illnesses. We sought to comprehensively summarize published psychotherapy protocols from clinical trials to provide insights for future practices.MethodsA systematic search of four databases (Embase, MEDLINE, PsycINFO, CINAHL) for data relating to psychotherapy protocols was conducted by two independent reviewers.ResultsIn total, our search identified 1869 articles; after removing duplicates, we screened 1107 articles. We included 70 articles in the full-text review and determined that 28 were eligible for the final review. All protocols include sessions before (preparatory) and after (integration) the psychedelic dosing session with supportive monitoring. However, there was substantial variability and inconsistencies in all other aspects of therapy protocols (e.g., duration and number of sessions, model of therapy). Additionally, significant limitations were identified in the frequent need for more clarity in the description of therapeutic approaches.ConclusionIn published clinical trials, PAP has consisted of preparation, supportive dosing, and integration sessions. Beyond this basic framework, significant heterogeneity and lack of clarity were identified in reported psychotherapy protocols, meaning a validated and universally agreed upon protocol for PAP currently does not exist. Future studies should more clearly define and report psychotherapeutic components to identify the safest and most efficacious approaches to PAP.

keywords:
Humans, Hallucinogens, Clinical Protocols, Depression, Depressive Disorder, Psychotherapy, Psilocybin

topic_tags:
Depression,End-of-Life Distress,Clinical Trial,Randomized Controlled Trial,Systematic Review,Review Article,Safety

raw_json:
{"europe_pmc_id":"38850581","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psychedelic-assisted psychotherapy: where is the psychotherapy research?
authors: Aday JS, Horton D, Fernandes-Osterhold G, O'Donovan A, Bradley ER, Rosen RC, Woolley JD
journal: Psychopharmacology
publication_date: 2024-07-31
doi: 10.1007/s00213-024-06620-x
pubmed_id: 38782821
source_url: https://pubmed.ncbi.nlm.nih.gov/38782821/
substance_tags: psilocybin
topic_tags: Depression,Addiction,Mechanism of Action,Clinical Trial,Review Article,Safety
study_type: Clinical Trial
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:36
raw_json: {"pubmed_id":"38782821"}
abstract:
Psychedelic-assisted psychotherapy (PAP) has emerged as a potential treatment for a variety of mental health conditions, including substance use disorders and depression. Current models of PAP emphasize the importance of psychotherapeutic support before, during, and after ingestion of a psychedelic to maximize safety and clinical benefit. Despite this ubiquitous assumption, there has been surprisingly little empirical investigation of the "psychotherapy" in PAP, leaving critical questions about the necessary and sufficient components of PAP unanswered.
As clinical trials for psychedelic compounds continue the transition from safety- and feasibility-testing to evaluating efficacy, the role of the accompanying psychotherapy must be better understood to enhance scientific understanding of the mechanisms underlying therapeutic change, optimize clinical outcomes, and inform cost-effectiveness.
The present paper first reviews the current status of psychotherapy in the PAP literature, starting with recent debates regarding "psychotherapy" versus "psychological support" and then overviewing published clinical trial psychotherapy models and putative models informed by theory. We then delineate lessons that PAP researchers can leverage from traditional psychotherapy research regarding standardizing treatments (e.g., publish treatment manuals, establish eligibility criteria for providers), identifying mechanisms of change (e.g., measure established mechanisms in psychotherapy), and optimizing clinical trial designs (e.g., consider dismantling studies, comparative efficacy trials, and cross-lagged panel designs). Throughout this review, the need for increased research into the psychotherapeutic components of treatment in PAP is underscored.
PAP is a distinct, integrative, and transdisciplinary intervention. Future research designs should consider transdisciplinary research methodologies to identify best practices and inform federal guidelines for PAP administration.

keywords:
Psilocybin, Psychedelic, Psychedelic-assisted psychotherapy, Psychotherapy, Psychotherapy models, Review


title: Is it now time to prepare psychiatry for a psychedelic future?
authors: Nutt D, Crome I, Young AH.
publication_date: 2024-07-31
doi: 10.1192/bjp.2024.76
pubmed_id: 38764044
source_url: https://doi.org/10.1192/bjp.2024.76
substance_tags: psilocybin
topic_tags: Depression,PTSD,Treatment-Resistant Depression
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:03
abstract:
Australia has just rescheduled two drugs controlled under the United Nations Psychotropic Drug Conventions, psilocybin and MDMA, as treatments for treatment-resistant depression and post-traumatic stress disorder respectively. This feature explores the reasons for these developments, the opportunities and challenges they provide to psychiatry communities and how along with health systems these communities might respond to these developments.

keywords:
Humans, N-Methyl-3,4-methylenedioxyamphetamine, Hallucinogens, Stress Disorders, Post-Traumatic, Psychiatry, Australia, Depressive Disorder, Treatment-Resistant, Psilocybin

raw_json:
{"europe_pmc_id":"38764044","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2024-04-29
doi: 10.1007/s00213-024-06585-x
pubmed_id: 38687360
source_url: https://doi.org/10.1007/s00213-024-06585-x
substance_tags: psilocybin
topic_tags: Receptor Pharmacology,Safety,Toxicity,Drug Interactions
study_type: Qualitative Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Content analysis of Reddit posts about coadministration of selective serotonin reuptake inhibitors and psilocybin mushrooms.

authors:
Sakai K, Bradley ER, Zamaria JA, Agin-Liebes G, Kelley DP, Fish A, Martini V, Ferris MC, Morton E, Michalak EE, O'Donovan A, Woolley JD.

abstract:
RationaleTreatments with the serotonergic psychedelic psilocybin are being investigated for multiple neuropsychiatric disorders. Because many patients with these disorders use selective serotonin reuptake inhibitors (SSRIs), understanding interactions between psilocybin and SSRIs is critical for evaluating the safety, efficacy, and scalability of psilocybin-based treatments. Current knowledge about these interactions is limited, as most clinical psilocybin research has prohibited concomittant SSRI use.ObjectivesWe aimed to explore potential interactions between psilocybin and SSRIs by characterizing peoples' real-world experiences using psilocybin mushrooms and SSRIs together.MethodsWe conducted a systematic search of Reddit for posts describing psilocybin mushroom and SSRI coadministration. We identified 443 eligible posts and applied qualitative content analysis to each.Results8% of posts reported negative physical or psychological effects resulting from coadministration. These included 13 reports that may reflect serotonin toxicity, and 1 concerning for a psychotic/manic episode. 54% of posts described reduced intensity of the acute psilocybin experience, but 39% reported unchanged intensity with SSRI coadministration.ConclusionsPsilocybin's interactions with SSRIs are likely complex and may depend on multiple factors. Prospective studies are needed to evaluate whether psilocybin treatments are reliably safe and effective in the setting of SSRI use.

keywords:
Humans, Agaricales, Hallucinogens, Drug Interactions, Psilocybin, Selective Serotonin Reuptake Inhibitors

raw_json:
{"europe_pmc_id":"38687360","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Tipado Z, Kuypers KPC, Sorger B, Ramaekers JG.
publication_date: 2024-04-20
doi: 10.1016/j.euroneuro.2024.04.011
pubmed_id: 38648694
source_url: https://doi.org/10.1016/j.euroneuro.2024.04.011
substance_tags: psilocybin
topic_tags: Mechanism of Action,Receptor Pharmacology
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
title:
Visual hallucinations originating in the retinofugal pathway under clinical and psychedelic conditions.

abstract:
Psychedelics like LSD (Lysergic acid diethylamide) and psilocybin are known to modulate perceptual modalities due to the activation of mostly serotonin receptors in specific cortical (e.g., visual cortex) and subcortical (e.g., thalamus) regions of the brain. In the visual domain, these psychedelic modulations often result in peculiar disturbances of viewed objects and light and sometimes even in hallucinations of non-existent environments, objects, and creatures. Although the underlying processes are poorly understood, research conducted over the past twenty years on the subjective experience of psychedelics details theories that attempt to explain these perceptual alterations due to a disruption of communication between cortical and subcortical regions. However, rare medical conditions in the visual system like Charles Bonnet syndrome that cause perceptual distortions may shed new light on the additional importance of the retinofugal pathway in psychedelic subjective experiences. Interneurons in the retina called amacrine cells could be the first site of visual psychedelic modulation and aid in disrupting the hierarchical structure of how humans perceive visual information. This paper presents an understanding of how the retinofugal pathway communicates and modulates visual information in psychedelic and clinical conditions. Therefore, we elucidate a new theory of psychedelic modulation in the retinofugal pathway.

keywords:
Visual Pathways, Animals, Humans, Hallucinations, Lysergic Acid Diethylamide, Hallucinogens, Charles Bonnet Syndrome

raw_json:
{"europe_pmc_id":"38648694","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Kaminski D, Reinert JP.
publication_date: 2023-10-29
doi: 10.1177/10600280231205645
pubmed_id: 37902038
source_url: https://doi.org/10.1177/10600280231205645
keywords: Humans, Substance-Related Disorders, Hallucinogens, Mental Disorders, Psilocybin
substance_tags: psilocybin
topic_tags: Anxiety,Headache / Migraine,Clinical Trial,Systematic Review,Review Article,Safety
study_type: Systematic Review
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
The Tolerability and Safety of Psilocybin in Psychiatric and Substance-Dependence Conditions: A Systematic Review.

abstract:
ObjectiveThe objective of this systematic review is to determine the tolerability and safety of psilocybin in a variety of psychiatric and substance-dependence conditions.Data sourcesA systematic review was conducted using Embase, PubMed, Cochrane Central, and Web of Science through September 2023 using the following terminology: "psilocybin" AND "mental-disease" OR "substance-dependence" AND "disease-therapy," in addition to other synonymous key words.Study selection and data extractionLiterature reporting acute effects and safety data following the use of psilocybin as the pharmacologic intervention in a clinical trial in adult patients with a psychiatric or substance-dependence condition were included. Following the application of inclusion and exclusion criteria, 16 studies were ultimately included in this review.Data synthesisThe most common treatment-emergent adverse effects reported were transient nausea and headache. Transient anxiety was reported as a frequent psychiatric effect, and 3 participants received a benzodiazepine for refractory anxiety during the psilocybin session. Psilocybin demonstrated modest increases in blood pressure and heart rate, and 1 participant received an antihypertensive for sustained hypertension during the psilocybin session. No cases of psilocybin-induced psychosis or Hallucinogen Persisting Perception Disorder were reported.Relevance to patient care and clinical practiceTreatment resistance remains a concern for psychiatric patients and novel therapies are needed to help alleviate the burden of morbidity and mortality. Psilocybin demonstrates promising acute and long-term safety that may allow for its use in psychiatric or substance-dependence conditions as an alternative to standards of care or in treatment-resistant patients.ConclusionsPsilocybin has demonstrated tolerability and safety in recent literature that has investigated its therapeutic potential in a variety of psychiatric or substance-dependence conditions.

raw_json:
{"europe_pmc_id":"37902038","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: How psilocybin affects the brain.
authors: O'Leary K.
publication_date: 2024-07-29
doi: 10.1038/d41591-024-00055-9
pubmed_id: 39080488
source_url: https://doi.org/10.1038/d41591-024-00055-9
substance_tags: psilocybin
topic_tags: General
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:03
raw_json:
{"europe_pmc_id":"39080488","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Bader H, Farraj H, Maghnam J, Abu Omar Y.
publication_date: 2024-06-30
doi: 10.5306/wjco.v15.i7.908
pubmed_id: 39071471
source_url: https://doi.org/10.5306/wjco.v15.i7.908
substance_tags: psilocybin
study_type: Meta-Analysis
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Investigating the therapeutic efficacy of psilocybin in advanced cancer patients: A comprehensive review and meta-analysis.

abstract:
BackgroundPsilocybin, a naturally occurring psychedelic compound found in certain species of mushrooms, is known for its effects on anxiety and depression. It has recently gained increasing interest for its potential therapeutic effects, particularly in patients with advanced cancer. This systematic review and meta-analysis aim to evaluate the effects of psilocybin on adult patients with advanced cancer.AimTo investigate the therapeutic effect of psilocybin in patients with advanced cancer.MethodsA comprehensive search of electronic databases was conducted in PubMed, Cochrane Central Register of Controlled Trials, and Google Scholar for articles published up to February 2023. The reference lists of the included studies were also searched to retrieve possible additional studies.ResultsA total of 7 studies met the inclusion criteria for the systematic review, comprising 132 participants. The results revealed significant improvements in quality of life, pain control, and anxiety relief following psilocybin-assisted therapy, specifically results on anxiety relief. Pooled effect sizes indicated statistically significant reductions in symptoms of anxiety at both 4 to 4.5 months [35.15 (95%CI: 32.28-38.01)] and 6 to 6.5 months [33.06 (95%CI: 28.73-37.40)]. Post-administration compared to baseline assessments (P < 0.05). Additionally, patients reported sustained improvements in psychological well-being and existential distress following psilocybin therapy.ConclusionThe findings provided compelling evidence for the potential benefits of psilocybin-assisted therapy in improving quality of life, pain control, and anxiety relief in patients with advanced cancer.

topic_tags:
Depression,Anxiety,Chronic Pain,Wellbeing,Meta-Analysis,Systematic Review,Review Article,Cancer Patients

raw_json:
{"europe_pmc_id":"39071471","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin and Motor Function: A Triple-Blind, Dose-Finding Study in Healthy Participants.
publication_date: 2024-07-22
doi: 10.1176/appi.prcp.20240047
pubmed_id: 39669539
source_url: https://doi.org/10.1176/appi.prcp.20240047
substance_tags: psilocybin
topic_tags: Brain Imaging,Aging,Healthy Volunteers,Safety
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
authors:
Bhagavan C, Kanaan R, Carter O, Nielsen G, Berlowitz D, Issak S, Braat S, Zaloumis S, Attard Z, Oliver G, Mayne D, McKernon D, Roebuck G, Rucker J, Butler M, Bryson A.

abstract:
BackgroundThere has been a resurgence of research into the potential therapeutic benefits of psychedelics for neuropsychiatric disorders. Classic psychedelics, such as psilocybin, exert complex effects on higher cognitive functions such as perception and awareness, but their impact on motor function remains unexplored. Moreover, there is a theoretical rationale for using psychedelics to promote motor retraining in certain neuropsychiatric conditions associated with motor dysfunction. This protocol paper outlines the first study to investigate the feasibility and safety of performing movement tasks during the acute effects of psilocybin in healthy participants. The findings from this study will further our understanding of the impact of psychedelics on motor function, and inform future studies that combine classic psychedelics with motor retraining in clinical populations.Methods12 healthy participants will each receive three doses of psilocybin (between 5 and 20 mg) in a randomized order, with each dose administered at least 1 week apart. Participants, the trial physiotherapists, and statisticians will remain blinded to the psilocybin dose. A battery of measures assessing motor function will be completed during the acute drug effects. In addition, measures of safety, pre- and post-dose resting-state brain activity via functional magnetic resonance imaging, and participants' subjective experience will be assessed.

raw_json:
{"europe_pmc_id":"39669539","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2024-07-16
doi: 10.1038/s41598-024-66817-0
pubmed_id: 39019922
source_url: https://doi.org/10.1038/s41598-024-66817-0
substance_tags: psilocybin
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Longitudinal experiences of Canadians receiving compassionate access to psilocybin-assisted psychotherapy.

authors:
de la Salle S, Kettner H, Thibault Lévesque J, Garel N, Dames S, Patchett-Marble R, Rej S, Gloeckler S, Erritzoe D, Carhart-Harris R, Greenway KT.

abstract:
Recent clinical trials have found that the serotonergic psychedelic psilocybin effectively alleviates anxiodepressive symptoms in patients with life-threatening illnesses when given in a supportive environment. These outcomes prompted Canada to establish legal pathways for therapeutic access to psilocybin, coupled with psychological support. Despite over one-hundred Canadians receiving compassionate access since 2020, there has been little examination of these 'real-world' patients. We conducted a prospective longitudinal survey which focused on Canadians who were granted Section 56 exemptions for legal psilocybin-assisted psychotherapy. Surveys assessing various symptom dimensions were conducted at baseline, two weeks following the session (endpoint), and optionally one day post-session. Participant characteristics were examined using descriptive statistics, and paired sample t-tests were used to quantify changes from baseline to the two-week post-treatment endpoint. Eight participants with Section 56 exemptions (four females, Mage = 52.3 years), all with cancer diagnoses, fully completed baseline and endpoint surveys. Significant improvements in anxiety and depression symptoms, pain, fear of COVID-19, quality of life, and spiritual well-being were observed. Attitudes towards death, medical assistance in dying, and desire for hastened death remained unchanged. While most participants found the psilocybin sessions highly meaningful, if challenging, one reported a substantial decrease in well-being due to the experience. These preliminary data are amongst the first to suggest that psilocybin-assisted psychotherapy can produce psychiatric benefits in real-world patients akin to those observed in clinical trials. Limited enrollment and individual reports of negative experiences indicate the need for formal real-world evaluation programs to surveil the ongoing expansion of legal access to psychedelics.

keywords:
Humans, Hallucinogens, Longitudinal Studies, Prospective Studies, Depression, Anxiety, Psychotherapy, Quality of Life, Adult, Aged, Middle Aged, Canada, Female, Male, Compassionate Use Trials, Psilocybin, North American People

topic_tags:
Depression,Anxiety,End-of-Life Distress,Chronic Pain,Mechanism of Action,Wellbeing,Spirituality,Clinical Trial,Observational Study

raw_json:
{"europe_pmc_id":"39019922","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Acute Effects of Hallucinogens on Functional Connectivity: Psilocybin and Salvinorin-A.
authors: Bagdasarian FA, Hansen HD, Chen J, Yoo CH, Placzek MS, Hooker JM, Wey HY.
publication_date: 2024-06-24
doi: 10.1021/acschemneuro.4c00245
pubmed_id: 38916752
source_url: https://doi.org/10.1021/acschemneuro.4c00245
substance_tags: psilocybin
topic_tags: Addiction,Brain Imaging,Mechanism of Action,Receptor Pharmacology,Default Mode Network,Aging
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
abstract:
The extent of changes in functional connectivity (FC) within functional networks as a common feature across hallucinogenic drug classes is under-explored. This work utilized fMRI to assess the dissociative hallucinogens Psilocybin, a classical serotonergic psychedelic, and Salvinorin-A, a kappa-opioid receptor (KOR) agonist, on resting-state FC in nonhuman primates. We highlight overlapping and differing influence of these substances on FC relative to the thalamus, claustrum, prefrontal cortex (PFC), default mode network (DMN), and DMN subcomponents. Analysis was conducted on a within-subject basis. Findings support the cortico-claustro-cortical network model for probing functional effects of hallucinogens regardless of serotonergic potential, with a potential key paradigm centered around the claustrum, PFC, anterior cingulate cortices (ACC), and angular gyrus relationship. Thalamo-cortical networks are implicated but appear dependent on 5-HT2AR activation. Acute desynchronization relative to the DMN for both drugs was also shown. Our findings provide a framework to understand broader mechanisms at which hallucinogens in differing classes may impact subjects regardless of the target receptor.

keywords:
Brain, Thalamus, Prefrontal Cortex, Nerve Net, Neural Pathways, Animals, Macaca mulatta, Diterpenes, Clerodane, Hallucinogens, Magnetic Resonance Imaging, Male, Psilocybin, Default Mode Network

raw_json:
{"europe_pmc_id":"38916752","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Serotoninergic antidepressants combination in psilocybin-assisted psychotherapy: a case report.
publication_date: 2024-07-15
doi: 10.3389/fpsyt.2024.1394962
pubmed_id: 39086732
source_url: https://doi.org/10.3389/fpsyt.2024.1394962
substance_tags: psilocybin
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
authors:
Do A, Michaud V, Stephan JF, Moreau M, Benoît É, Bérubé FA, Bibaud-De Serres A, Taillefer A, Vincent P.

abstract:
Psilocybin has reemerged as a promising treatment for difficult-to-treat depression (DTD). Although there is limited evidence regarding interactions between psilocybin and other psychotropic drugs, clinical trials require that patients discontinue their antidepressants before study entry to isolate the benefits of psilocybin and to minimize the risk of adverse events. We present the first case of an adult patient with DTD who received psilocybin-assisted psychotherapy (PAP) in combination with two serotoninergic antidepressants (duloxetine and vortioxetine). Since he displayed a partial response after the first PAP session, he agreed to discontinue duloxetine (but refused to stop vortioxetine) before the second PAP session to see if it could improve the therapeutic efficacy of psilocybin. However, his anxiety and depressive symptoms worsened. Psilocybin was well-tolerated in both PAP sessions; mild headaches were the main adverse effects experienced by the patient, and there were no cardiovascular safety concerns. This case report suggests that serotoninergic antidepressants combination with psilocybin appears to be safe and that antidepressant discontinuation prior to PAP may not be necessary. Since the continuation of antidepressants during PAP has the potential to improve treatment acceptability and accessibility, future research should assess whether psilocybin can be administered concurrently with antidepressants.

topic_tags:
Depression,Anxiety,Headache / Migraine,Receptor Pharmacology,Clinical Trial,Case Report,Safety,Adverse Events,Drug Interactions

raw_json:
{"europe_pmc_id":"39086732","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin for the treatment of Alzheimer's disease.
authors: Zheng S, Ma R, Yang Y, Li G.
publication_date: 2024-07-09
doi: 10.3389/fnins.2024.1420601
pubmed_id: 39050672
source_url: https://doi.org/10.3389/fnins.2024.1420601
substance_tags: psilocybin,psilocin
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:00
abstract:
Alzheimer's disease (AD) stands as a formidable neurodegenerative ailment and a prominent contributor to dementia. The scarcity of available therapies for AD accentuates the exigency for innovative treatment modalities. Psilocybin, a psychoactive alkaloid intrinsic to hallucinogenic mushrooms, has garnered attention within the neuropsychiatric realm due to its established safety and efficacy in treating depression. Nonetheless, its potential as a therapeutic avenue for AD remains largely uncharted. This comprehensive review endeavors to encapsulate the pharmacological effects of psilocybin while elucidating the existing evidence concerning its potential mechanisms contributing to a positive impact on AD. Specifically, the active metabolite of psilocybin, psilocin, elicits its effects through the modulation of the 5-hydroxytryptamine 2A receptor (5-HT2A receptor). This modulation causes heightened neural plasticity, diminished inflammation, and improvements in cognitive functions such as creativity, cognitive flexibility, and emotional facial recognition. Noteworthy is psilocybin's promising role in mitigating anxiety and depression symptoms in AD patients. Acknowledging the attendant adverse reactions, we proffer strategies aimed at tempering or mitigating its hallucinogenic effects. Moreover, we broach the ethical and legal dimensions inherent in psilocybin's exploration for AD treatment. By traversing these avenues, We propose therapeutic potential of psilocybin in the nuanced management of Alzheimer's disease.

topic_tags:
Depression,Anxiety,Neuroplasticity,Mechanism of Action,Receptor Pharmacology,Emotional Processing,Creativity,Review Article,Safety,Inflammation

raw_json:
{"europe_pmc_id":"39050672","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin fungi microdose treatment in major depressive disorder: a case report
authors: Zarankin M, Pellegrini MS, Zenteno F.
publication_date: 2024-07-09
doi: 10.53680/vertex.v35i164.544
pubmed_id: 39024488
source_url: https://doi.org/10.53680/vertex.v35i164.544
keywords: Humans, Agaricales, Hallucinogens, Male, Young Adult, Psilocybin, Major Depressive Disorder
substance_tags: psilocybin
topic_tags: Depression,Microdosing,Wellbeing,Emotional Processing,Case Report,Safety,Drug Interactions
study_type: Case Report
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
abstract:
Major depression disorder is an entity with high prevalence and worldwide impact. Current treatments present a non-response rate of 15-30%, and certain adverse effects are seen like apathy syndrome and lack of emotional response. It is stated that the treatment with psilocybin fungi allows the possibility of dose reduction and suspension of classic psychotropic drugs and entails changes on an emotional and behavioral level that result benefic in patients with major depressive syndrome. We present a case of a 19 years old patient with major depressive syndrome diagnosis. Accompaniment and patient advice was made appealing to the right of autonomy, on the psilocybin microdose self-administration process, aiming to reducing health risks and potentiate probable beneficial effects, with weekly evaluations, for a period of 7 months; using clinical anamnesis, laboratory tests and the Hamilton depression scale. As a result of this intervention, a symptomatic complete remission was proven, alongside with the suspension of conventional pharmacological treatment without discontinuation symptoms and improvements at the communicational level, social interaction and general well-being. These findings support the idea that psilocybin microdose treatments are promising tools in depression treatments. Scientific studies are needed in order to certify these findings.

raw_json:
{"europe_pmc_id":"39024488","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: The Black Book of Psychotropic Dosing and Monitoring.
authors: DeBattista C, Schatzberg AF.
publication_date: 2024-06-30
doi: 10.64719/pb.4493
pubmed_id: 38993656
source_url: https://doi.org/10.64719/pb.4493
substance_tags: psilocybin
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:07
abstract:
Introduction Since the last edition of the Black Book, several innovative agents have been approved or are poised to be approved in the coming year. These include novel antidepressants, the first muscarine agonist for the treatment of schizophrenia, the first psychedelic which may be approved for the treatment of PTSD (Post Traumatic Stress Disorder), and the first disease modifying drug for the treatment of Alzheimer's disease. Three new antidepressants have come to the market in the past 18 months. The first of those, Auvelity, the combination of bupropion and dextromethorphan, takes advantage of a pharmacokinetic and pharmacodynamic synergism between the two drugs.85 Dextromethorphan has several pharmacodynamic properties including actions on the NMDA receptor and the Sigma 1 receptor, adding to the indirect norepinephrine agonist properties of bupropion. How Dextromethorphan is rapidly metabolized via the CYP2D6 isoenzyme to dextrophan that may have mu opioid agonist properties. The combination with bupropion, a CYP2D6 inhibitor, inhibits the metabolism of dextromethorphan allowing for more consistent therapeutic levels. The combination of dextromethorphan 45 mg twice per day and bupropion SR105 mg twice daily appears to be more effective than an equivalent dose of bupropion alone both in speeding up antidepressant response and achieving remission. However, it's not clear at this time how the combination would compare with a more typical dose of bupropion of 300-450 milligrams a day range. The phase III program for Auvelity, showed that the drug was well tolerated with the most common side effects being dizziness, headache, and dry mouth.86 Another novel antidepressant agent approved in 2023 is zuranolone (Zurzuvae). Zuranolone is an oral analog of IV brexanalone, and like brexanolone, was approved for the treatment of post-partum depression.83 The advantages of zuranolone over brexanalone are many. While brexanolone is a 60-hour intravenous infusion that must be administered in a health care facility, zuranolone is a once/day oral medication that is usually taken at home. Like brexanolone, and unlike most antidepressants, zuranolone has a short course of treatment, lasting just 14 days. Zuranolone's, as does brexanolone, is thought to act primarily as allosteric modulator of the GABA-a receptors. Despite only 14 days of treatment, zuranolone produced in depression in post-partum patients a clinically and significantly meaningful improvement at day 15 and continued to day 45 or 1 month past the end of treatment. Zuranolone is a schedule IV drug. The most common side effect in clinical trials was somnolence with 36% of participants reporting this side effect vs only 6% of those on placebo.84 Other common side effects included dizziness, diarrhea and fatigue. While the FDA declined to approve zuranolone as monotherapy or as an adjunctive treatment to standard antidepressants in major depression itself, there are positive studies in non-post-partum major depression albeit with smaller effect sizes and less consistent duration of activity. It is likely that zuranolone will continue to be studied in other depressive syndromes such as depression with anxious distress. The third "new" antidepressant approved late 2023 was gepirone (Exxua). Gepirone is not exactly a new or novel antidepressant and originally sought approval in the US about 20 years ago.88 There had been two positive studies of gepirone during the original NDA application but also a number of failed, negative, or non-informative studies as well. Thus, the FDA declined to originally approve the drug. However, failed and negative trials are common with antidepressants and after much internal debate, the FDA ultimately agreed to approve the drug based on the positive trials and a relatively favorable side effect profile. Gepirone, like buspirone, is a partial agonist of the 5HT1a receptor and a 5HT2 antagonist. As such, gepirone does not tend to be associated with sexual side effects, weight gain, or sedation. The most common side effects are dizziness, nausea, and insomnia which tend to improve in many patients over time. Second generation antipsychotics (SGAs) continue to be the only class of agents [other than esketamine (Spravato)] approved in adjunctive treatment of resistant major depression. In addition to olanzapine (combined with fluoxetine; Symbyax), aripiprazole (Abilify), quetiapine (Seroquel), brexpiprazole (Rexulti), cariprazine (Vraylar) became the latest SGA to be approved in 2022.90 Adjunctive cariprazine at 1.5 mg daily was significantly more effective than adjunctive placebo in patients with MDD who had failed to achieve an adequate response with an antidepressant alone after 6 weeks of treatment. Interestingly, a 3 mg dose of cariprazine was less consistently effective.91 The major advantage of cariprazine over some of the other approved adjunctive SGA's is easy dosing, with the starting 1.5 mg dose being the optimal therapeutic dose for most people, and a lower metabolic side effect burden with most subjects having limited or no weight gain in short term trials. The most common side effect were akathisia/restlessness, fatigue, and nausea. Lumateperone (Caplyta) is also has positive phase III data in the adjunctive treatment of major depression and is expective file for approval in late 2024. Another recent major development in psychopharmacology is the reemergence of psychedelics in the treatment of psychiatric disorders. The first of these is MDMA (phenethylamine 3,4-methylenedioxymethamphetamine) assisted psychotherapy for the treatment of PTSD. A New Drug Application (NDA) was accepted by the FDA for MDMA in the treatment of PTSD in late 2023.87 Because the drug is being fast tracked as a "breakthrough" treatment by the FDA, it was expected to see approval in the summer of 2024. The phase II and III data for MDMA assisted psychotherapy in the treatment of PTSD have been quite consistent and impressive. However, independent reviews have pointed to significant deficiencies in these studies including the bias introduced because of functional unblinding; virtually all patients in psychedelic studies can guess whether they got the active drug or placebo. The functional unblinding, the lack of standardization of adjunctive psychotherapy as well as the abuse potential of MDMA, may delay an FDA approval. The typical regimen in these trials included 3 preparatory psychotherapy sessions followed by once/month dosing sessions (lasting about 8 hours) and using doses of 120-160 mg in a split dose. There were typically 3 monthly dosing sessions, each followed by 3 integrative psychotherapy sessions to help subjects process and understand their experiences during the dosing sessions. In the most recent phase 3 trials, over 70% of subjects no longer met criteria for PTDS compared to 46% of those treated with psychotherapy and placebo alone.89 The only approved medications for treating PTSD are two SSRIs, paroxetine and sertraline. These drugs effect only some dimensions of PTSD with only 20-30% achieving a remission level response with these drugs. Thus, MDMA assisted psychotherapy appears to achieve much higher levels of remission and response than has been true for the SSRIs. Since MDMA is not taken continuously, side effects from MDMA tend to be short lived. Side effects have included muscle tightness, nausea, diminished appetite, excessive sweating, feeling cold and dizziness among others. Since MDMA is currently a schedule I drug, it is likely that a rigorous Risk Evaluation Mitigation (REMs) program will be put in place and a limited number of centers and clinicians will be designated to perform MDMA assisted psychotherapy for PTSD. In addition to MDMA, psilocybin-assisted psychotherapy is in phase 3 trials for treating resistant depression but unlikely to be available before late 2025 at the earliest. An argument can be made that there has not been a truly novel antipsychotic since the introduction of clozapine in the US in 1990. All first-generation antipsychotics have been dopamine 2 antagonists and second-generation drugs have involved some ratio of 5HT2 antagonism to D2 blockade. In 2023, the FDA accepted the application of xenomaline/tropsium (KarXT) which may become the first muscarinic M1M4 agonist approved for the treatment of schizophrenia.82,83 Tropsium is added as a muscarine antagonist to block the peripheral cholinergic effects of a muscarine agonist. Xenomaline/tropsium appears to be effective in treating both positive and negative symptoms of schizophrenia. In a phase 3 study of 407 patients with schizophrenia, xenomaline/tropsium at doses of xenomaline/50 mg/tropsium 20 mg twice daily up to 125 mg/30 mg twice daily was significantly more effective than placebo in treating both and negative symptoms over 5 weeks of treatment. As would be expected, the side effect profile of xenomaline/tropsium is very different that all currently available antipsychotics. There is no risk of EPS as it is not a dopamine antagonist, and xenomaline/tropsium is not associated with significant metabolic effects. The side effects are cholinergic in nature and include constipation, dry mouth, and nausea. A decision is expected in September of 2024. The year 2023 also saw the approval of the first disease modifying drug in the treatment of Alzheimer's disease, lecanemab (Lequembi). While acetylcholinesterase inhibitors and memantine have been available for decades, these drugs modestly improve cognition in Alzheimer's disease patients and do not alter the progressive course of the illness. Lecanemab is an IV monoclonal antibody that targets the removal of beta-amyloid in the brain as well proto-fibrils that are also known to be toxic to neuronal tissue. When given early in the course of the illness, patients treated with Lecanemab showed 27% less decline on some measures of cognition and function than did patients treated with a placebo over 18 months (about 1 and a half years). It is not known whether treatment for longer than 18 months would show lesser or greater decline over time. However, there are simulation studies that suggest that Lecanemab may modestly reduce the number of patients who progress to severe Alzheimer's disease and require institutional care. The standard dose is 10 mg/kg given via IV over one hour every 2 weeks for 18 months. Lecanemab is typically administered in an infusion center so that side effects can be monitored. The most serious side effects of Lecanemab are amyloid related imaging abnormalities (ARIA) that are associated with brain edema and microhemorrhages. ARIA can occur in up to 15% of patients. More common side effects are headache and nausea. While it remains to be seen how useful these new agents will be in clinical practice, they do represent an approach to treating neuropsychiatric disorders that are a notable departure from the pharmacotherapy of the past half century. It seems likely that some patients who have not been able to respond to or tolerate traditional pharmacotherapy will find hope in these new medications.

keywords:
Humans, Bupropion, Dextromethorphan, Psychotropic Drugs, Antidepressive Agents, Drug Monitoring, Dose-Response Relationship, Drug

topic_tags:
Depression,Anxiety,PTSD,Addiction,Headache / Migraine,Brain Imaging,Pharmacology,Receptor Pharmacology,Aging,Clinical Trial,Review Article,Healthcare Workers,Safety,Adverse Events

raw_json:
{"europe_pmc_id":"38993656","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2024-07-02
doi: 10.1186/s13063-024-08268-6
pubmed_id: 38956594
source_url: https://doi.org/10.1186/s13063-024-08268-6
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Engaging Mood Brain Circuits with Psilocybin (EMBRACE): a study protocol for a randomized, placebo-controlled and delayed-start, neuroimaging trial in depression.

authors:
Poulin JM, Bigford GE, Lanctôt KL, Giacobbe P, Schaffer A, Sinyor M, Rabin JS, Masellis M, Singnurkar A, Pople CB, Lipsman N, Husain MI, Rosenblat JD, Cao X, MacIntosh BJ, Nestor SM.

abstract:
BackgroundMajor depressive disorder (MDD) is a leading cause of disability worldwide across domains of health and cognition, affecting overall quality of life. Approximately one third of individuals with depression do not fully respond to treatments (e.g., conventional antidepressants, psychotherapy) and alternative strategies are needed. Recent early phase trials suggest psilocybin may be a safe and efficacious intervention with rapid-acting antidepressant properties. Psilocybin is thought to exert therapeutic benefits by altering brain network connectivity and inducing neuroplastic changes that endure for weeks post-treatment. Although early clinical results are encouraging, psilocybin's acute neurobiological effects on neuroplasticity have not been fully investigated. We aim to examine for the first time how psilocybin acutely (intraday) and subacutely (weeks) alters functional brain networks implicated in depression.MethodsFifty participants diagnosed with MDD or persistent depressive disorder (PDD) will be recruited from a tertiary mood disorders clinic and undergo 1:1 randomization into either an experimental or control arm. Participants will be given either 25 mg psilocybin or 25 mg microcrystalline cellulose (MCC) placebo for the first treatment. Three weeks later, those in the control arm will transition to receiving 25 mg psilocybin. We will investigate whether treatments are associated with changes in arterial spin labelling and blood oxygenation level-dependent contrast neuroimaging assessments at acute and subacute timepoints. Primary outcomes include testing whether psilocybin demonstrates acute changes in (1) cerebral blood flow and (2) functional brain activity in networks associated with mood regulation and depression when compared to placebo, along with changes in MADRS score over time compared to placebo. Secondary outcomes include changes across complementary clinical psychiatric, cognitive, and functional scales from baseline to final follow-up. Serum peripheral neurotrophic and inflammatory biomarkers will be collected at baseline and follow-up to examine relationships with clinical response, and neuroimaging measures.DiscussionThis study will investigate the acute and additive subacute neuroplastic effects of psilocybin on brain networks affected by depression using advanced serial neuroimaging methods. Results will improve our understanding of psilocybin's antidepressant mechanisms versus placebo response and whether biological measures of brain function can provide early predictors of treatment response.Trial registrationClinicalTrials.gov Identifier: NCT06072898. Registered on 6 October 2023.

keywords:
Brain, Humans, Antidepressive Agents, Magnetic Resonance Imaging, Treatment Outcome, Affect, Neuronal Plasticity, Time Factors, Adult, Middle Aged, Female, Male, Randomized Controlled Trials as Topic, Young Adult, Psilocybin, Major Depressive Disorder

topic_tags:
Depression,Neuroplasticity,Brain Imaging,Mechanism of Action,Biomarkers,Aging,Randomized Controlled Trial,Inflammation

raw_json:
{"europe_pmc_id":"38956594","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Treating Anxiety and Depression With Psilocybin Therapy.
authors: Hanstein AP, Felchlin C.
publication_date: 2024-06-30
pubmed_id: 39079732
source_url: https://europepmc.org/article/MED/39079732
keywords: Humans, Hallucinogens, Treatment Outcome, Depression, Anxiety, Psilocybin
substance_tags: psilocybin
topic_tags: Depression,Anxiety
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:03
raw_json:
{"europe_pmc_id":"39079732","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Your brain on shrooms - how psilocybin resets neural networks.
authors: Kozlov M.
publication_date: 2024-06-30
doi: 10.1038/d41586-024-02275-y
pubmed_id: 39020195
source_url: https://doi.org/10.1038/d41586-024-02275-y
keywords: Brain, Nerve Net, Humans, Hallucinogens, Psilocybin
substance_tags: psilocybin
topic_tags: General
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
raw_json:
{"europe_pmc_id":"39020195","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Foldi CJ, Liknaitzky P, Williams M, Oldfield BJ.
publication_date: 2020-02-03
doi: 10.3389/fnins.2020.00043
pubmed_id: 32116500
source_url: https://doi.org/10.3389/fnins.2020.00043
substance_tags: psilocybin
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
title:
Rethinking Therapeutic Strategies for Anorexia Nervosa: Insights From Psychedelic Medicine and Animal Models.

abstract:
Anorexia nervosa (AN) has the highest mortality rate of any psychiatric disease, yet available pharmacological treatments are largely ineffective due, in part, to an inadequate understanding of the neurobiological drivers that underpin the condition. The recent resurgence of research into the clinical applications of psychedelic medicine for a range of mental disorders has highlighted the potential for classical psychedelics, including psilocybin, to alleviate symptoms of AN that relate to serotonergic signaling and cognitive inflexibility. Clinical trials using psychedelics in treatment-resistant depression have shown promising outcomes, although these studies are unable to circumvent some methodological biases. The first clinical trial to use psilocybin in patients with AN commenced in 2019, necessitating a better understanding of the neurobiological mechanisms through which psychedelics act. Animal models are beneficial in this respect, allowing for detailed scrutiny of brain function and behavior and the potential to study pharmacology without the confounds of expectancy and bias that are impossible to control for in patient populations. We argue that studies investigating the neurobiological effects of psychedelics in animal models, including the activity-based anorexia (ABA) rodent model, are particularly important to inform clinical applications, including the subpopulations of patients that may benefit most from psychedelic medicine.

topic_tags:
Depression,Eating Disorders,Pharmacology,Mechanism of Action,Clinical Trial,Animal Study,Treatment-Resistant Depression

raw_json:
{"europe_pmc_id":"32116500","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Innovative and Emerging Treatments for Anorexia Nervosa.
authors: Downey AE, Gorrell S.
publication_date: 2024-06-27
doi: 10.1176/appi.focus.20230041
pubmed_id: 38988458
source_url: https://doi.org/10.1176/appi.focus.20230041
substance_tags: psilocybin
topic_tags: Eating Disorders,Clinical Trial
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
abstract:
Unlike psychopharmacologic interventions for other psychiatric conditions, few medications have emerged as helpful in improving eating disorder cognitions and evidence-based psychotherapies fail many patients. Novel treatments are urgently needed to address anorexia nervosa (AN), which is increasingly prevalent and difficult to treat. This article provides an overview of preliminary investigations into cannabidiol, psilocybin therapy, ketamine and the ketogenic diet, transcranial magnetic stimulation, and vagus nerve stimulation in individuals with AN. These pilot studies underscore the need for larger clinical trials that include more participant diversity in order to rapidly translate findings to real-world clinical practice.

raw_json:
{"europe_pmc_id":"38988458","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin therapy for females with anorexia nervosa: a phase 1, open-label feasibility study.
authors: Peck SK, Shao S, Gruen T, Yang K, Babakanian A, Trim J, Finn DM, Kaye WH.
publication_date: 2023-07-23
doi: 10.1038/s41591-023-02455-9
pubmed_id: 37488291
source_url: https://doi.org/10.1038/s41591-023-02455-9
substance_tags: psilocybin
topic_tags: Eating Disorders,Clinical Trial,Safety,Adverse Events
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
abstract:
Anorexia nervosa (AN) is a deadly illness with no proven treatments to reverse core symptoms and no medications approved by the US Food and Drug Administration. Novel treatments are urgently needed to improve clinical outcomes. In this open-label feasibility study, 10 adult female participants (mean body mass index 19.7 kg m-2; s.d. 3.7) who met Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for AN or pAN (partial remission) were recruited to a study conducted at an academic clinical research institute. Participants received a single 25-mg dose of synthetic psilocybin in conjunction with psychological support. The primary aim was to assess safety, tolerability and feasibility at post-treatment by incidences and occurrences of adverse events (AEs) and clinically significant changes in electrocardiogram (ECG), laboratory tests, vital signs and suicidality. No clinically significant changes were observed in ECG, vital signs or suicidality. Two participants developed asymptomatic hypoglycemia at post-treatment, which resolved within 24 h. No other clinically significant changes were observed in laboratory values. All AEs were mild and transient in nature. Participants' qualitative perceptions suggest that the treatment was acceptable for most participants. Results suggest that psilocybin therapy is safe, tolerable and acceptable for female AN, which is a promising finding given physiological dangers and problems with treatment engagement. ClinicalTrials.gov identifier NCT04661514.

keywords:
Humans, Body Mass Index, Treatment Outcome, Feasibility Studies, Anorexia Nervosa, Adult, Female, Psilocybin

raw_json:
{"europe_pmc_id":"37488291","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Potential Differences in Psychedelic Actions Based on Biological Sex.
authors: Shadani S, Conn K, Andrews ZB, Foldi CJ
journal: Endocrinology
publication_date: 2024-06-30
doi: 10.1210/endocr/bqae083
pubmed_id: 38980913
source_url: https://pubmed.ncbi.nlm.nih.gov/38980913/
keywords: cognition, estrogen, learning, psilocybin, psychedelics, serotonin, sex differences
substance_tags: psilocybin
topic_tags: Mechanism of Action,Receptor Pharmacology,Review Article,Drug Interactions
study_type: Review Article
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:36
raw_json: {"pubmed_id":"38980913"}
abstract:
The resurgence of interest in psychedelics as treatments for psychiatric disorders necessitates a better understanding of potential sex differences in response to these substances. Sex as a biological variable (SABV) has been historically neglected in medical research, posing limits to our understanding of treatment efficacy. Human studies have provided insights into the efficacy of psychedelics across various diagnoses and aspects of cognition, yet sex-specific effects remain unclear, making it difficult to draw strong conclusions about sex-dependent differences in response to psychedelic treatments. Compounding this further, animal studies used to understand biological mechanisms of psychedelics predominantly use one sex and present mixed neurobiological and behavioral outcomes. Studies that do include both sexes often do not investigate sex differences further, which may hinder the translation of findings to the clinic. In reviewing sex differences in responses to psychedelics, we will highlight the direct interaction between estrogen (the most extensively studied steroid hormone) and the serotonin system (central to the mechanism of action of psychedelics), and the potential that estrogen-serotonin interactions may influence the efficacy of psychedelics in female participants. Estrogen influences serotonin neurotransmission by affecting its synthesis and release, as well as modulating the sensitivity and responsiveness of serotonin receptor subtypes in the brain. This could potentially influence the efficacy of psychedelics in females by modifying their therapeutic efficacy across menstrual cycles and developmental stages. Investigating this interaction in the context of psychedelic research could aid in the advancement of therapeutic outcomes, especially for conditions with sex-specific prevalence.


authors: Singleton SP, Kuceyeski A.
publication_date: 2024-06-30
doi: 10.1016/j.bpsc.2024.05.003
pubmed_id: 38969436
source_url: https://doi.org/10.1016/j.bpsc.2024.05.003
keywords: Brain, Humans, Hallucinogens, Magnetic Resonance Imaging, Connectome, Psilocybin
substance_tags: psilocybin
topic_tags: Brain Imaging,Aging
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
title:
Bridging Psilocybin-Induced Changes in the Brain's Dynamic Functional Connectome With an Individual's Subjective Experience.

raw_json:
{"europe_pmc_id":"38969436","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Neumann J, Dimov K, Azatsian K, Hofmann B, Gergs U.
publication_date: 2024-06-11
doi: 10.1016/j.toxlet.2024.06.006
pubmed_id: 38876450
source_url: https://doi.org/10.1016/j.toxlet.2024.06.006
substance_tags: psilocybin,psilocin
topic_tags: Depression,Receptor Pharmacology,Animal Study,In Vitro Study
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:00
title:
Effects of psilocin and psilocybin on human 5-HT4 serotonin receptors in atrial preparations of transgenic mice and humans.

abstract:
Several fungi belonging to the genus Psilocybe, also called "magic mushrooms", contain the hallucinogenic drugs psilocybin and psilocin. They are chemically related to serotonin (5-HT). In addition to being abused as drugs, they are now also being discussed or used as a treatment option for depression. Here, we hypothesized that psilocybin and psilocin may act also on cardiac serotonin receptors and studied them in vitro in atrial preparations of our transgenic mouse model with cardiac myocytes-specific overexpression of the human 5-HT4 receptor (5-HT4-TG) as well as in human atrial preparations. Both psilocybin and psilocin enhanced the force of contraction in isolated left atrial preparations from 5-HT4-TG, increased the beating rate in isolated spontaneously beating right atrial preparations from 5-HT4-TG and augmented the force of contraction in the human atrial preparations. The inotropic and chronotropic effects of psilocybin and psilocin at 10 µM were smaller than that of 1 µM 5-HT on the left and right atria from 5-HT4-TG, respectively. Psilocybin and psilocin were inactive in WT. In the human atrial preparations, inhibition of the phosphodiesterase III by cilostamide was necessary to unmask the positive inotropic effects of psilocybin or psilocin. The effects of 10 µM psilocybin and psilocin were abrogated by 10 µM tropisetron or by 1 µM GR125487, a more selective 5-HT4 receptor antagonist. In summary, we demonstrated that psilocin and psilocybin act as agonists on cardiac 5-HT4 receptors.

keywords:
Heart Atria, Myocytes, Cardiac, Animals, Mice, Transgenic, Humans, Mice, Receptors, Serotonin, 5-HT4, Hallucinogens, Heart Rate, Myocardial Contraction, Female, Male, Serotonin 5-HT4 Receptor Agonists, Psilocybin

raw_json:
{"europe_pmc_id":"38876450","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Ramos L, Vicente SG.
publication_date: 2024-06-05
doi: 10.1080/13803395.2024.2363343
pubmed_id: 38842300
source_url: https://doi.org/10.1080/13803395.2024.2363343
keywords: Humans, Hallucinogens, Depression, Emotions, Cognition, Adult, Psilocybin
substance_tags: psilocybin
topic_tags: Depression,Mechanism of Action,Emotional Processing,Creativity,Review Article
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
The effects of psilocybin on cognition and emotional processing in healthy adults and adults with depression: a systematic literature review.

abstract:
IntroductionPsilocybin, a naturally occurring serotonergic agonist in some mushroom species, has shown promise as a novel, fast-acting pharmacotherapy seeking to overcome the limitations of conventional first-line antidepressants. Studying psilocybin effects on cognition and emotional processing may help to clarify the mechanisms underlying the therapeutic potential of psilocybin and may also support studies with people suffering from depression. Thus, this review aims to provide a comprehensive overview of the current literature regarding the effects of psilocybin on these two key areas in both healthy and depressed populations.MethodA systematic search was performed on 29 January 2024, in the PubMed, EBSCOhost, Web of Science and SCOPUS databases. After duplicates removal, study selection was conducted considering pre-specified criteria. Data extraction was then performed. The quality assessment of the studies was carried out using the Cochrane Collaboration tools for randomized (RoB 2.0) and non-randomized (ROBINS-I) controlled trials.ResultsTwenty articles were included, with 18 targeting healthy adults and two adults with depression. Results point to impairments within attentional and inhibitory processes, and improvements in the domains of creativity and social cognition in healthy individuals. In the population with depression, only cognitive flexibility and emotional recognition were affected, both being enhanced. The comparison of outcomes from both populations proved limited.ConclusionsPsilocybin acutely alters several cognitive domains, with a localized rather than global focus, in a dose- and time-dependent manner. However, the significant methodological constraints call for further research, in the context of depression and with standardized protocols, with longitudinal studies also imperative.

raw_json:
{"europe_pmc_id":"38842300","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Brockett AT, Francis NA.
publication_date: 2024-05-28
doi: 10.1152/jn.00124.2024
pubmed_id: 38810366
source_url: https://doi.org/10.1152/jn.00124.2024
substance_tags: psilocybin
topic_tags: Brain Imaging,Aging,Animal Study
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Psilocybin decreases neural responsiveness and increases functional connectivity while preserving pure-tone frequency selectivity in mouse auditory cortex.

abstract:
Psilocybin is a serotonergic psychedelic believed to have therapeutic potential for neuropsychiatric conditions. Despite well-documented prevalence of perceptual alterations, hallucinations, and synesthesia associated with psychedelic experiences, little is known about how psilocybin affects sensory cortex or alters the activity of neurons in awake animals. To investigate, we conducted two-photon imaging experiments in auditory cortex of awake mice and collected video of free-roaming mouse behavior, both at baseline and during psilocybin treatment. In comparison with pre-dose neural activity, a 2 mg/kg ip dose of psilocybin initially increased the amplitude of neural responses to sound. Thirty minutes post-dose, behavioral activity and neural response amplitudes decreased, yet functional connectivity increased. In contrast, control mice given intraperitoneal saline injections showed no significant changes in either neural or behavioral activity across conditions. Notably, neuronal stimulus selectivity remained stable during psilocybin treatment, for both tonotopic cortical maps and single-cell pure-tone frequency tuning curves. Our results mirror similar findings regarding the effects of serotonergic psychedelics in visual cortex and suggest that psilocybin modulates the balance of intrinsic versus stimulus-driven influences on neural activity in auditory cortex.NEW & NOTEWORTHY Recent studies have shown promising therapeutic potential for psychedelics in treating neuropsychiatric conditions. Musical experience during psilocybin-assisted therapy is predictive of treatment outcome, yet little is known about how psilocybin affects auditory processing. Here, we conducted two-photon imaging experiments in auditory cortex of awake mice that received a dose of psilocybin. Our results suggest that psilocybin modulates the roles of intrinsic neural activity versus stimulus-driven influences on auditory perception.

keywords:
Auditory Cortex, Neurons, Animals, Mice, Inbred C57BL, Mice, Hallucinogens, Acoustic Stimulation, Auditory Perception, Male, Psilocybin

raw_json:
{"europe_pmc_id":"38810366","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Fang Q, Chan VKY, Chan SSM, Jiao Y, Wang J, Li X.
publication_date: 2024-05-21
doi: 10.1016/j.psychres.2024.115960
pubmed_id: 38781672
source_url: https://doi.org/10.1016/j.psychres.2024.115960
keywords: Humans, Hallucinogens, Treatment Outcome, Depressive Disorder, Treatment-Resistant, Psilocybin
substance_tags: psilocybin
topic_tags: Depression,Meta-Analysis,Systematic Review,Review Article,Treatment-Resistant Depression,Safety
study_type: Meta-Analysis
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
title:
Efficacy and safety of psilocybin on treatment-resistant depression: A systematic review and meta-analysis.

raw_json:
{"europe_pmc_id":"38781672","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psychedelic therapy in depression and substance use disorders.
authors: Korkmaz ND, Cikrikcili U, Akan M, Yucesan E.
publication_date: 2024-05-20
doi: 10.1111/ejn.16421
pubmed_id: 38773750
source_url: https://doi.org/10.1111/ejn.16421
substance_tags: psilocybin
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:03
abstract:
Psychoactive substances obtained from botanicals have been applied for a wide variety of purposes in the rituals of different cultures for thousands of years. Classical psychedelics from N,N'-dimethyltryptamine, psilocybin, mescaline and various lysergamides cause specific alterations in perception, emotion and cognition by acting through serotonin 5-HT2A receptor activation. Lysergic acid diethylamide, the first famous breakthrough in the field, was discovered by chance by Albert Hoffman in the Zurich Sandoz laboratory in 1943, and studies on its psychoactive effects began to take place in the literature. Studies in this area were blocked after the legislation controlling the use and research of psychedelic drugs came into force in 1967, but since the 1990s, it has started to be a matter of scientific curiosity again by various research groups. In particular, with the crucial reports of psychotherapy-assisted psilocybin applications for life-threatening cancer-related anxiety and depression, a new avenues have been opened in the treatment of psychiatric diseases such as treatment-resistant depression and substance addictions. An increasing number of studies show that psychedelics have a very promising potential in the treatment of neuropsychiatric diseases where the desired efficiency cannot be achieved with conventional treatment methods. In this context, we discuss psychedelic therapy, encompassing its historical development, therapeutic applications and potential treatment effects-especially in depression, trauma disorders and substance use disorders-within the framework of ethical considerations.

keywords:
Animals, Humans, Substance-Related Disorders, Lysergic Acid Diethylamide, Hallucinogens, Depression, Depressive Disorder, Psilocybin

topic_tags:
Depression,Anxiety,Addiction,End-of-Life Distress,Receptor Pharmacology,Emotional Processing,Cancer Patients,Treatment-Resistant Depression

raw_json:
{"europe_pmc_id":"38773750","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: What is needed for the roll-out of psychedelic treatments?
authors: Xenakis SN, Shannon SM.
publication_date: 2024-05-06
doi: 10.1097/yco.0000000000000946
pubmed_id: 38726805
source_url: https://doi.org/10.1097/yco.0000000000000946
substance_tags: psilocybin
topic_tags: PTSD,Clinical Trial,Review Article
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:03
abstract:
Purpose of reviewThe pace of psychedelic treatments continues to increase. Regulation and coherent clinical guidance have not been established. A philosophical divide limits effective resolution of a practice delivery quandary: is this primarily a pharmacological or psychotherapeutic intervention?Recent findingsLykos (formerly MAPS) has submitted its new drug application (NDA) request to the FDA for 3-4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for PTSD and is expecting a response by the summer of 2024. Australia endorsed psilocybin and MDMA for regulated use in 2023. Multiple phase II and III clinical trials are also being conducted in the United States and Europe to study the use of psilocybin. Currently, Colorado and Oregon have legalized psilocybin in different manners. In Colorado, plants containing psilocybin, ibogaine, dimethyltryptamine (DMT) and mescaline (other than peyote) are now legal to possess, share and cultivate. Guidelines for regulated treatment with psilocybin containing mushrooms are in process with service delivery to begin early in 2025. In Oregon, clients must complete a preparation session with a licensed facilitator before consuming psilocybin products at a licensed service center. A prescription is not required. It is expected that other states will follow suit with a ballot measure likely in Massachusetts this year. Additionally, in the United States, the DEA, state boards, pharmaceutical distributors, and professional liability carriers all share mounting concerns about the in-home use of compounded ketamine used as a psychedelic therapeutic via remote prescribing.SummaryPsychedelic treatments are rapidly entering the mainstream of medical care delivery in the United States. Clinical guidelines are urgently needed to ensure well tolerated practice and coherent regulation. The delivery of this guidance is limited by a core philosophical disagreement. Resolution of this conflict will be needed to deliver coherent clinical guidelines. Current research and clinical experience provide a solid foundation for practical clinical guidance and the introduction of psychedelics into healthcare.

keywords:
Humans, N-Methyl-3,4-methylenedioxyamphetamine, Hallucinogens, Stress Disorders, Post-Traumatic, Psychotherapy, United States, Psilocybin

raw_json:
{"europe_pmc_id":"38726805","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: A taxonomy of regulatory and policy matters relevant to psychedelic-assisted therapy in Australia.
authors: Hatfield SP, Thornton NL, Greenstien K, Glozier N.
publication_date: 2024-04-15
doi: 10.1177/00048674241240597
pubmed_id: 38628079
source_url: https://doi.org/10.1177/00048674241240597
keywords: Humans, N-Methyl-3,4-methylenedioxyamphetamine, Hallucinogens, Health Policy, Australia, Psilocybin
substance_tags: psilocybin
topic_tags: Review Article
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
abstract:
ObjectivesThe Australian government recently rescheduled psilocybin and 3,4-methylenedioxymethamphetamine for limited clinical uses. This change has raised various regulatory concerns and challenges for the field of psychedelic-assisted therapy. To provide clarity, we aimed to comprehensively catalogue the matters relating to psychedelic-assisted therapy that are or could be regulated.MethodsWe conducted a desktop review of the literature and current regulatory sources, semi-structured interviews with professionals who had expertise in fields relating to psychedelic-assisted therapy and a framework analysis to generate a taxonomy of relevant regulatory matters. In relation to each matter, we further identified what type of regulation (if any) currently applies to that matter, any uncertainty as to how the matter should be addressed in clinical practice in the context of current regulation and whether there are conflicting views as to how the matter could or should be further regulated.ResultsThe taxonomy is structured into six main regulatory domains, three of which have a substantial proportion of matters with uncertainty or conflicting views: Service Establishment, Practitioner, and Treatment Delivery. Key examples of such matters include the location of services and facilities required, which professionals are eligible to become psychedelic therapists, and with what qualifications and experience. Matters in the remaining three domains, Patient Evaluation, Drug Supply and Service Oversight, appear by comparison relatively settled, with regulation either well-established or thought unnecessary.ConclusionsThe taxonomy provides a roadmap for health services establishing and implementing a psychedelic-assisted therapy program, or for government and other policymakers when determining areas that may require further regulation.

raw_json:
{"europe_pmc_id":"38628079","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Mortaheb S, Fort LD, Mason NL, Mallaroni P, Ramaekers JG, Demertzi A.
publication_date: 2024-04-05
doi: 10.1016/j.bpsc.2024.04.001
pubmed_id: 38588855
source_url: https://doi.org/10.1016/j.bpsc.2024.04.001
substance_tags: psilocybin
topic_tags: Brain Imaging,Consciousness,Aging,Healthy Volunteers
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Dynamic Functional Hyperconnectivity After Psilocybin Intake Is Primarily Associated With Oceanic Boundlessness.

abstract:
BackgroundPsilocybin is a widely studied psychedelic substance that leads to the psychedelic state, a specific altered state of consciousness. To date, the relationship between the psychedelic state's neurobiological and experiential patterns remains undercharacterized because they are often analyzed separately. We investigated the relationship between neurobiological and experiential patterns after psilocybin by focusing on the link between dynamic cerebral connectivity and retrospective questionnaire assessment.MethodsHealthy participants were randomized to receive either psilocybin (n = 22) or placebo (n = 27) and scanned for 6 minutes in an eyes-open resting state during the peak subjective drug effect (102 minutes posttreatment) in ultrahigh field 7T magnetic resonance imaging. The 5-Dimensional Altered States of Consciousness Rating Scale was administered 360 minutes after drug intake.ResultsUnder psilocybin, there were alterations across all dimensions of the 5-Dimensional Altered States of Consciousness Rating Scale and widespread increases in averaged brain functional connectivity. Time-varying functional connectivity analysis unveiled a recurrent hyperconnected pattern characterized by low blood oxygen level-dependent signal amplitude, suggesting heightened cortical arousal. In terms of neuroexperiential links, canonical correlation analysis showed higher transition probabilities to the hyperconnected pattern with feelings of oceanic boundlessness and secondly with visionary restructuralization.ConclusionsPsilocybin generates profound alterations at both the brain and the experiential levels. We suggest that the brain's tendency to enter a hyperconnected-hyperarousal pattern under psilocybin represents the potential to entertain variant mental associations. These findings illuminate the intricate interplay between brain dynamics and subjective experience under psilocybin, thereby providing insights into the neurophysiology and neuroexperiential qualities of the psychedelic state.

keywords:
Brain, Nerve Net, Humans, Hallucinogens, Magnetic Resonance Imaging, Consciousness, Adult, Female, Male, Young Adult, Connectome, Psilocybin

raw_json:
{"europe_pmc_id":"38588855","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2024-02-19
doi: 10.1038/s41380-024-02477-w
pubmed_id: 38378926
source_url: https://doi.org/10.1038/s41380-024-02477-w
substance_tags: psilocybin
topic_tags: Neuroplasticity,Mechanism of Action,Oxidative Stress,Animal Study,Metabolomics
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Effect of chemically synthesized psilocybin and psychedelic mushroom extract on molecular and metabolic profiles in mouse brain.

authors:
Shahar O, Botvinnik A, Shwartz A, Lerer E, Golding P, Buko A, Hamid E, Kahn D, Guralnick M, Blakolmer K, Wolf G, Lotan A, Lerer L, Lerer B, Lifschytz T.

abstract:
Psilocybin, a naturally occurring, tryptamine alkaloid prodrug, is currently being investigated for the treatment of a range of psychiatric disorders. Preclinical reports suggest that the biological effects of psilocybin-containing mushroom extract or "full spectrum" (psychedelic) mushroom extract (PME), may differ from those of chemically synthesized psilocybin (PSIL). We compared the effects of PME to those of PSIL on the head twitch response (HTR), neuroplasticity-related synaptic proteins and frontal cortex metabolomic profiles in male C57Bl/6j mice. HTR measurement showed similar effects of PSIL and PME over 20 min. Brain specimens (frontal cortex, hippocampus, amygdala, striatum) were assayed for the synaptic proteins, GAP43, PSD95, synaptophysin and SV2A, using western blots. These proteins may serve as indicators of synaptic plasticity. Three days after treatment, there was minimal increase in synaptic proteins. After 11 days, PSIL and PME significantly increased GAP43 in the frontal cortex (p = 0.019; p = 0.039 respectively) and hippocampus (p = 0.015; p = 0.027) and synaptophysin in the hippocampus (p = 0.041; p = 0.05) and amygdala (p = 0.035; p = 0.004). PSIL increased SV2A in the amygdala (p = 0.036) and PME did so in the hippocampus (p = 0.014). In the striatum, synaptophysin was increased by PME only (p = 0.023). There were no significant effects of PSIL or PME on PSD95 in any brain area when these were analyzed separately. Nested analysis of variance (ANOVA) showed a significant increase in each of the 4 proteins over all brain areas for PME versus vehicle control, while significant PSIL effects were observed only in the hippocampus and amygdala and were limited to PSD95 and SV2A. Metabolomic analyses of the pre-frontal cortex were performed by untargeted polar metabolomics utilizing capillary electrophoresis - Fourier transform mass spectrometry (CE-FTMS) and showed a differential metabolic separation between PME and vehicle groups. The purines guanosine, hypoxanthine and inosine, associated with oxidative stress and energy production pathways, showed a progressive decline from VEH to PSIL to PME. In conclusion, our synaptic protein findings suggest that PME has a more potent and prolonged effect on synaptic plasticity than PSIL. Our metabolomics data support a gradient of effects from inert vehicle via chemical psilocybin to PME further supporting differential effects. Further studies are needed to confirm and extend these findings and to identify the molecules that may be responsible for the enhanced effects of PME as compared to psilocybin alone.

keywords:
Brain, Frontal Lobe, Animals, Mice, Inbred C57BL, Mice, Agaricales, Hallucinogens, Neuronal Plasticity, Male, Psilocybin

raw_json:
{"europe_pmc_id":"38378926","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Stoliker D, Novelli L, Vollenweider FX, Egan GF, Preller KH, Razi A.
publication_date: 2024-01-05
doi: 10.1016/j.biopsych.2024.01.002
pubmed_id: 38185235
source_url: https://doi.org/10.1016/j.biopsych.2024.01.002
substance_tags: psilocybin
topic_tags: Brain Imaging,Mechanism of Action,Default Mode Network,Aging,Emotional Processing,Clinical Trial
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Neural Mechanisms of Resting-State Networks and the Amygdala Underlying the Cognitive and Emotional Effects of Psilocybin.

abstract:
BackgroundSerotonergic psychedelics, such as psilocybin, alter perceptual and cognitive systems that are functionally integrated with the amygdala. These changes can alter cognition and emotions that are hypothesized to contribute to their therapeutic utility. However, the neural mechanisms of cognitive and subcortical systems altered by psychedelics are not well understood.MethodsWe used resting-state functional magnetic resonance images collected during a randomized, double-blind, placebo-controlled clinical trial of 24 healthy adults under 0.2 mg/kg psilocybin to estimate the directed (i.e., effective) changes between the amygdala and 3 large-scale resting-state networks involved in cognition. These networks are the default mode network, the salience network, and the central executive network.ResultsWe found a pattern of decreased top-down effective connectivity from these resting-state networks to the amygdala. Effective connectivity decreased within the default mode network and salience network but increased within the central executive network. These changes in effective connectivity were statistically associated with behavioral measures of altered cognition and emotion under the influence of psilocybin.ConclusionsOur findings suggest that temporary amygdala signal attenuation is associated with mechanistic changes to resting-state network connectivity. These changes are significant for altered cognition and perception and suggest targets for research investigating the efficacy of psychedelic therapy for internalizing psychiatric disorders. More broadly, our study suggests the value of quantifying the brain's hierarchical organization using effective connectivity to identify important mechanisms for basic cognitive function and how they are integrated to give rise to subjective experiences.

keywords:
Amygdala, Nerve Net, Neural Pathways, Humans, Hallucinogens, Magnetic Resonance Imaging, Double-Blind Method, Emotions, Cognition, Rest, Adult, Female, Male, Young Adult, Connectome, Psilocybin, Default Mode Network

raw_json:
{"europe_pmc_id":"38185235","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin's Potential Mechanisms in the Treatment of Depression: A Systematic Review.
authors: Lee HJ, Tsang VW, Chai BS, Lin MC, Howard A, Uy C, Elefante JO.
publication_date: 2023-06-28
doi: 10.1080/02791072.2023.2223195
pubmed_id: 37385217
source_url: https://doi.org/10.1080/02791072.2023.2223195
keywords: Brain, Animals, Humans, Hallucinogens, Antidepressive Agents, Depression, Psilocybin
substance_tags: psilocybin
study_type: Systematic Review
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
abstract:
Evidence suggests that psilocybin has therapeutic benefit for treating depression. However, there is little consensus regarding the mechanism by which psilocybin elicits antidepressant effects. This systematic review summarizes existing evidence. Ovid MEDLINE, EMBASE, psychINFO, and Web of Science were searched, for both human and animal studies, using a combination of MeSH Terms and free-text keywords in September 2021. No other mood disorders or psychiatric diagnoses were included. Original papers in English were included. The PRISMA framework was followed for the screening of papers. Two researchers screened the retrieved articles from the literature search, and a third researcher resolved any conflicts. Of 2,193 papers identified, 49 were selected for full-text review. 14 articles were included in the qualitative synthesis. Six supported psilocybin's mechanism of antidepressant action via changes to serotonin or glutamate receptor activity and three papers found an increase in synaptogenesis. Thirteen papers investigated changes in non-receptor or pathway-specific brain activity. Five papers found changes in functional connectivity or neurotransmission, most commonly in the hippocampus or prefrontal cortex. Several neuroreceptors, neurotransmitters, and brain areas are thought to be involved in psilocybin's ability to mitigate depressive symptoms. Psilocybin appears to alter cerebral blood flow to the amygdala and prefrontal cortex, but the evidence on changes in functional connectivity and specific receptor activity remains sparse. The lack of consensus between studies suggests that psilocybin's mechanism of action may involve a variety of pathways, demonstrating the need for more studies on psilocybin's mechanism of action as an antidepressant.

topic_tags:
Depression,Neuroplasticity,Mechanism of Action,Receptor Pharmacology,Systematic Review,Review Article

raw_json:
{"europe_pmc_id":"37385217","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Bienemann B, Barbosa AR, Cruz LVMD, Multedo M, Mograbi D.
publication_date: 2023-06-21
doi: 10.1080/02791072.2023.2226414
pubmed_id: 37348116
source_url: https://doi.org/10.1080/02791072.2023.2226414
keywords: Humans, Hallucinogens, Adult, Middle Aged, Female, Male, Young Adult, Self Report, Psilocybin
substance_tags: psilocybin
topic_tags: Mystical Experience
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
title:
Health Benefits and Positive Acute Effects of Psilocybin Consumption: A Quantitative Textual Analysis of User Self-Reported Data.

abstract:
There has been growth in the use of psychedelics by the global population in recent years. In addition to recreational and ritualistic use, recent research into psychedelics has brought advances for treating mental disorders. Understanding the specific circumstances in which psilocybin leads to positive outcomes may have important implications for the future of its clinical use and for harm reduction initiatives. This study aimed to investigate the positive effects from the consumption of psilocybin through public online self-reports. We sought to investigate health benefits promoted by the consumption of the substance, positive acute effects, and contextual details of these experiences. We analyzed 846 reports with the assistance of the IRaMuTeQ textual analysis software, adopting the procedures of Descending Hierarchical Classification, Correspondence Factor Analysis, and Specificities Analysis. The texts were grouped in 5 clusters, describing the content of mental experiences, cognitive processes, somatic experiences, perceptual alterations, and context of administration. The findings of this study reinforce central axes of the psychedelic experience, such as the presence of somatic and visual alterations, connectedness and feeling one with the world and effects of setting, as well as the beneficial character of mystical experiences this substance promotes, and the importance of the ego-dissolution phenomenon.

raw_json:
{"europe_pmc_id":"37348116","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Jones GM, Ricard JA, Nock MK.
publication_date: 2024-06-23
doi: 10.3389/fpsyt.2024.1169686
pubmed_id: 38979507
source_url: https://doi.org/10.3389/fpsyt.2024.1169686
substance_tags: psilocybin
topic_tags: Clinical Trial,Observational Study
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Race and ethnicity moderate the associations between lifetime psilocybin use and past year hypertension.

abstract:
BackgroundHypertension is a major source of morbidity and mortality worldwide, particularly for racial and ethnic minorities who face higher rates of hypertension and worse health-related outcomes. Recent research has reported on protective associations between classic psychedelics and hypertension; however, there is a need to explore how race and ethnicity may moderate such associations.MethodsWe used data from the National Survey on Drug Use and Health (2005-2014) to assess whether race and ethnicity moderate the associations between classic psychedelic use - specifically psilocybin - and past year hypertension.ResultsHispanic identity moderated the associations between psilocybin use and past year hypertension. Furthermore, individuals who used psilocybin and identified as Non-Hispanic White had reduced odds of hypertension (aOR: 0.83); however, these associations were not observed for any other racial or ethnic groups in our study for individuals who used psilocybin.ConclusionOverall, our results demonstrate that the associations between psychedelics and hypertension may vary by race and ethnicity. Longitudinal studies and clinical trials can further advance this research and determine whether such differences exist in causal contexts.Project registrationhttps://osf.io/xsz2p/?view_only=0bf7b56749034c18abb2a3f8d3d4bc0b.

raw_json:
{"europe_pmc_id":"38979507","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2024-06-21
doi: 10.1038/s41467-024-49741-9
pubmed_id: 38909051
source_url: https://doi.org/10.1038/s41467-024-49741-9
substance_tags: psilocybin,psilocin
topic_tags: Mechanism of Action
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:00
title:
Increased reactivity of the paraventricular nucleus of the hypothalamus and decreased threat responding in male rats following psilocin administration.

authors:
Effinger DP, Hoffman JL, Mott SE, Magee SN, Quadir SG, Rollison CS, Toedt D, Echeveste Sanchez M, High MW, Hodge CW, Herman MA.

abstract:
Psychedelics have experienced renewed interest following positive clinical effects, however the neurobiological mechanisms underlying effects remain unclear. The paraventricular nucleus of the hypothalamus (PVN) plays an integral role in stress response, autonomic function, social behavior, and other affective processes. We investigated the effect of psilocin, the psychoactive metabolite of psilocybin, on PVN reactivity in Sprague Dawley rats. Psilocin increased stimulus-independent PVN activity as measured by c-Fos expression in male and female rats. Psilocin increased PVN reactivity to an aversive air-puff stimulus in males but not females. Reactivity was restored at 2- and 7-days post-injection with no group differences. Additionally, prior psilocin injection did not affect PVN reactivity following acute restraint stress. Experimental groups sub-classified by baseline threat responding indicate that increased male PVN reactivity is driven by active threat responders. These findings identify the PVN as a significant site of psychedelic drug action with implications for threat responding behavior.

keywords:
Paraventricular Hypothalamic Nucleus, Animals, Rats, Rats, Sprague-Dawley, Proto-Oncogene Proteins c-fos, Hallucinogens, Behavior, Animal, Stress, Psychological, Female, Male, Psilocybin

raw_json:
{"europe_pmc_id":"38909051","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: The influence of psilocybin on subconscious and conscious emotional learning.
authors: Casanova AF, Ort A, Smallridge JW, Preller KH, Seifritz E, Vollenweider FX.
publication_date: 2024-05-18
doi: 10.1016/j.isci.2024.110034
pubmed_id: 38883812
source_url: https://doi.org/10.1016/j.isci.2024.110034
substance_tags: psilocybin
topic_tags: Mechanism of Action,Receptor Pharmacology,Emotional Processing
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
abstract:
Serotonergic psychedelics hold promise as a treatment modality for various psychiatric disorders and are currently applied in psychedelic-assisted psychotherapy. We investigated the learning effects of the serotonin receptor agonist psilocybin in a probabilistic cue-reward task with emotional cues in the form of neutral or fearful faces, presented either consciously or subconsciously. This study represents the first investigation into reinforcement learning with psilocybin. Across different dosages, psilocybin preserved learning effects and was statistically noninferior compared to placebo, while suggesting a higher exploratory behavior. Notably, the 20 mg group exhibited significantly better learning rates against the placebo group. Psilocybin induced inferior results with subconscious cues compared to placebo, and better results with conscious neutral cues in some conditions. These findings suggest that modulating serotonin signaling in the brain with psilocybin sufficiently preservers reinforcement learning.

raw_json:
{"europe_pmc_id":"38883812","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: At the Forefront: Social Workers' Role in Psilocybin Treatment for Depression and Substance Misuse.
authors: Parker C, Wood BM.
publication_date: 2024-05-31
doi: 10.1093/sw/swae019
pubmed_id: 38697188
source_url: https://doi.org/10.1093/sw/swae019
substance_tags: psilocybin
topic_tags: Depression,Addiction,Mechanism of Action,Clinical Trial,Adverse Events
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
abstract:
This article underscores the critical role of social workers in harnessing the potential therapeutic benefits of psilocybin for treating major depressive disorder (MDD) and substance use disorder (SUD). Contemporary treatments for MDD often have side effects, and the success rate for SUD treatments remains low. The pervasiveness of MDD, combined with the challenges in treating SUD, highlights a need for innovative treatments. This article provides an overview of the resurgence of literature over the past two decades that illuminates the therapeutic promise of psilocybin for mental health treatment; clinical trials elucidate the efficacy of psilocybin-assisted therapy in mitigating MDD and demonstrate great promise in reducing SUD symptoms. The long-lasting posttreatment effect emphasizes its potential as a novel treatment modality. Furthermore, psilocybin's recognition as a "breakthrough therapy" by the U.S. Food and Drug Administration (FDA) and the accelerating pace of psychedelic reform bills indicate growing acceptance and interest in its therapeutic capacities. Psilocybin-assisted therapy emerges as a potent treatment option, showcasing remarkable effectiveness even after a single dose. Recommendations and pathways for social workers to be involved in psilocybin-assisted therapy investigation, advocacy, and implementation are provided.

keywords:
Humans, Substance-Related Disorders, Hallucinogens, Professional Role, Social Work, United States, Social Workers, Psilocybin, Major Depressive Disorder

raw_json:
{"europe_pmc_id":"38697188","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Bryson N, Alexander R, Asnis-Alibozek A, Ehlers MD.
publication_date: 2024-05-16
doi: 10.1021/acschemneuro.4c00058
pubmed_id: 38758589
source_url: https://doi.org/10.1021/acschemneuro.4c00058
substance_tags: psilocybin,psilocin
topic_tags: Depression,Receptor Pharmacology,Clinical Trial,Animal Study
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
RE104: Synthesis and Activity of a Novel Serotonergic Psychedelic Prodrug of 4-Hydroxy-N,N-diisopropyltryptamine.

abstract:
Results from randomized clinical trials of psilocybin in depressive disorders highlight the therapeutic potential of serotonergic psychedelic compounds in mental health disorders. The synthetic 5-hydroxytryptamine 2A receptor agonist 4-hydroxy-N,N-diisopropyltryptamine (4-OH-DiPT) is structurally similar to psilocin but is reported to have a shorter duration (2-3 h) of psychedelic effects, suggesting the potential for psilocybin-like therapeutic activity with reduced clinical resource burden. Here, we describe the preclinical and translational characterization of RE104, a 4-OH-DiPT prodrug comprising a glutarate moiety designed to cleave rapidly in situ and thus provide reasonable bioavailability of the active drug. Plasma concentration of 4-HO-DiPT over time in PK experiments in rats was correlated with head-twitch intensity. The half-life of 4-OH-DiPT was 40 min after subcutaneous administration of RE104 in rats. In a forced swim test, a single dose of RE104 (1 mg/kg) significantly reduced mean immobility time at 1 week compared with vehicle (P < 0.001), confirming translational antidepressant potential. Taken together, these data with RE104 show that the glutarate ester can act as an efficient prodrug strategy for 4-HO-DiPT, a unique short-duration psychedelic with potential in depressive disorders.

keywords:
Animals, Rats, Rats, Sprague-Dawley, Tryptamines, Hallucinogens, Antidepressive Agents, Prodrugs, Male

raw_json:
{"europe_pmc_id":"38758589","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Impact of Psilocybin on Peripheral Cytokine Production.
authors: DiRenzo D, Barrett FS, Perin J, Darrah E, Christopher-Stine L, Griffiths RR.
publication_date: 2024-06-16
doi: 10.1089/psymed.2023.0039
pubmed_id: 40051582
source_url: https://doi.org/10.1089/psymed.2023.0039
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
abstract:
BackgroundPsilocybin is a psychedelic drug with potential therapeutic effects in patients with mood and substance use disorders. Little is known about its impact on the immune system.MethodsMultiplex immunoassay pro-inflammatory cytokine panels (Meso-Scale Discovery, Rockville, MD) were used to examine the serum from participants in three separate randomized controlled clinical trials (randomized controlled trials [RCTs]) wherein a range of doses of psilocybin were administered (methods reported previously). Participants represented a range of clinical histories including those with no-known health problems/long-term meditation practice (n = 35), depression (n = 25), anxiety, and cancer (various types; n = 31). Linear mixed models with random effects for each participant were fit to determine relative cytokine levels both immediately before and at various time points after psilocybin administration, adjusted for multiple comparisons. Serum extracted during a waitlist, where applicable, was not included.ResultsSera from 91 participants were included from our three prior RCTs. In our linear models of pooled data, sera collected ≤1-week postpsilocybin revealed increased levels of interleukin (IL)-8 (β = 0.164, 95% confidence interval [0.10 to 0.23]; p = 0.042). At ≥4-week time points compared to baseline, there were no changes in cytokine levels. In our linear models of individual studies, no changes in cytokine levels at each time point were observed.ConclusionThis preliminary study suggests that a transient increase in cytokine production ≤1-week postpsilocybin may be found, although not consistently across patient populations. More broadly, peripheral cytokine production is possibly altered by psilocybin administration. ClinicalTrials.gov Identifier: NCT01988311.

topic_tags:
Depression,Anxiety,Addiction,Clinical Trial,Randomized Controlled Trial,Inflammation,Immune Function

raw_json:
{"europe_pmc_id":"40051582","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Downey AE, Bradley ER, Lerche AS, O'Donovan A, Krystal AD, Woolley J.
publication_date: 2024-06-16
doi: 10.1089/psymed.2023.0051
pubmed_id: 40051581
source_url: https://doi.org/10.1089/psymed.2023.0051
substance_tags: psilocybin
topic_tags: Aging,Clinical Trial,Review Article,Observational Study,Safety,Adverse Events
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
A Plea for Nuance: Should People with a Family History of Bipolar Disorder Be Excluded from Clinical Trials of Psilocybin Therapy?

abstract:
BackgroundAs the field of psychedelic therapy grows, it is vital to consider who can safely engage with psilocybin therapy. In most modern clinical trials of psilocybin therapy, individuals with a family history of bipolar disorder (BD) have been excluded from participation because of their genetic predisposition for developing BD.ReviewCase studies and survey data shed light on the risks of psilocybin therapy among those with a family history of BD in the absence of data from modern clinical trials. We review existing evidence that could inform risk stratification for these individuals, including genetic proximity to the affected relative, BD type, age at onset in the relative, and participant age. Hypothesizing that the risk of developing BD may predict the risk of developing serious adverse events when engaging with psilocybin therapy, we propose a risk stratification tool to be utilized when determining the relative risks of psilocybin therapy to those with a family history of BD in the context of clinical trials.ConclusionBalancing the need for effective treatments against the potential for serious adverse events in those undergoing psilocybin therapy with a family history of BD, we argue for caution in psychedelic clinical trials but not outright exclusion of these individuals. Our risk stratification tool allows for more nuanced inclusion and exclusion criteria.

raw_json:
{"europe_pmc_id":"40051581","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Licit use of illicit drugs for treating depression: the pill and the process.
authors: Torrado Pacheco A, Moghaddam B.
publication_date: 2024-06-16
doi: 10.1172/jci180217
pubmed_id: 40047885
source_url: https://doi.org/10.1172/jci180217
substance_tags: psilocybin
topic_tags: Depression,Anxiety,PTSD,Addiction,Clinical Trial,Review Article,Animal Study,Healthcare Workers
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:03
abstract:
Psilocybin, MDMA, and ketamine have emerged as potentially effective treatments for rapid amelioration of the symptoms of mood and related psychiatric disorders. All clinical data collected so far with regard to psilocybin or MDMA, which have reported positive outcomes for treating depression, anxiety, posttraumatic stress disorder, and drug or alcohol use disorders, have involved clinician-assisted intervention. While the case for ketamine is assumed to be different, the first report of the successful use of ketamine in psychiatry for treating depression was in combination with psychotherapy, and an emerging literature suggests that the subjective state of individual experiences with ketamine predicts clinical outcome. This Review will focus on (a) a brief review of the literature, showing that the context or the process of drug administration has been an integrative component of published work; (b) the importance of clinical trials to compare the efficacy of the drug ("pill") as a stand-alone treatment versus drug in combination with clinician-assisted psychological support ("process"); and (c) suggestions for future approaches in animal models that take into account the role of systems and behavioral neuroscience in explaining a potential role for context, experience, and expectancy in drug effect.

keywords:
Animals, Humans, N-Methyl-3,4-methylenedioxyamphetamine, Ketamine, Depression, Psilocybin, Illicit Drugs

raw_json:
{"europe_pmc_id":"40047885","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2024-03-31
doi: 10.1016/j.jad.2024.03.165
pubmed_id: 38570038
source_url: https://doi.org/10.1016/j.jad.2024.03.165
substance_tags: psilocybin
study_type: Systematic Review
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
title:
Spectral signatures of psilocybin, lysergic acid diethylamide (LSD) and ketamine in healthy volunteers and persons with major depressive disorder and treatment-resistant depression: A systematic review.

authors:
Le GH, Wong S, Badulescu S, Au H, Di Vincenzo JD, Gill H, Phan L, Rhee TG, Ho R, Teopiz KM, Kwan ATH, Rosenblat JD, Mansur RB, McIntyre RS.

abstract:
BackgroundElectrophysiologic measures provide an opportunity to inform mechanistic models and possibly biomarker prediction of response. Serotonergic psychedelics (SPs) (i.e., psilocybin, lysergic acid diethylamide (LSD)) and ketamine represent new investigational and established treatments in mood disorders respectively. There is a need to better characterize the mechanism of action of these agents.MethodsWe conducted a systematic review investigating the spectral signatures of psilocybin, LSD, and ketamine in persons with major depressive disorder (MDD), treatment-resistant depression (TRD), and healthy controls.ResultsKetamine and SPs are associated with increased theta power in persons with depression. Ketamine and SPs are also associated with decreased spectral power in the alpha, beta and delta bands in healthy controls and persons with depression. When administered with SPs, theta power was increased in persons with MDD when administered with SPs. Ketamine is associated with increased gamma band power in both healthy controls and persons with MDD.LimitationsThe studies included in our review were heterogeneous in their patient population, exposure, dosing of treatment and devices used to evaluate EEG and MEG signatures. Our results were extracted entirely from persons who were either healthy volunteers or persons with MDD or TRD.ConclusionsExtant literature evaluating EEG and MEG spectral signatures indicate that ketamine and SPs have reproducible effects in keeping with disease models of network connectivity. Future research vistas should evaluate whether observed spectral signatures can guide further discovery of therapeutics within the psychedelic and dissociative classes of agents, and its prediction capability in persons treated for depression.

keywords:
Humans, Ketamine, Lysergic Acid Diethylamide, Hallucinogens, Electroencephalography, Depressive Disorder, Treatment-Resistant, Healthy Volunteers, Psilocybin, Major Depressive Disorder

topic_tags:
Depression,Brain Imaging,Mechanism of Action,Biomarkers,Systematic Review,Review Article,Healthy Volunteers,Treatment-Resistant Depression

raw_json:
{"europe_pmc_id":"38570038","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Kargbo RB.
publication_date: 2024-05-07
doi: 10.1021/acsmedchemlett.4c00181
pubmed_id: 38894903
source_url: https://doi.org/10.1021/acsmedchemlett.4c00181
substance_tags: psilocybin,psilocin
topic_tags: Pharmacology,Emotional Processing
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Advancements in Psychoactive Alkaloid Delivery, Neuroenhancement, and Psychedelic Therapies: Exploring the Frontiers of Modern Pharmacology.

abstract:
This Patent Highlight explores advancements in pharmacology, focusing on the novel delivery and application of psychoactive substances. It highlights the development of transdermal formulations for psychoactive alkaloids, neuroenhancement techniques to augment emotional responses, and the intravenous infusion of psilocybin or psilocin for various therapeutic purposes. Additionally, it delves into the characterization and potential uses of crystalline forms of tryptamine derivatives. These innovations signify significant progress in drug delivery systems, neurostimulation methods, and the therapeutic use of psychedelic compounds, potentially revolutionizing the treatment of psychological and neurological disorders.

raw_json:
{"europe_pmc_id":"38894903","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Szafoni S, Gręblowski P, Grabowska K, Więckiewicz G.
publication_date: 2024-06-10
doi: 10.3389/fpsyt.2024.1406888
pubmed_id: 38919636
source_url: https://doi.org/10.3389/fpsyt.2024.1406888
substance_tags: psilocybin
topic_tags: Depression,Addiction,OCD,Mechanism of Action,Clinical Trial,Safety
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Unlocking the healing power of psilocybin: an overview of the role of psilocybin therapy in major depressive disorder, obsessive-compulsive disorder and substance use disorder.

abstract:
Resistance to traditional treatment methods is still a major obstacle in modern psychiatry. As a result, several studies are currently being conducted to find effective alternatives to traditional therapies. One of these alternatives is psilocybin, a psychedelic substance that has been tested in clinical trials as an adjunct to psychotherapy. These studies focus on patients with major depressive disorder (MDD), obsessive-compulsive disorder (OCD) and substance use disorder (SUD), particularly alcohol and nicotine dependence. This article looks at the current understanding of psilocybin, including data from clinical trials conducted, psilocybin's mechanism of action, its safety and the level of risk associated with it.

raw_json:
{"europe_pmc_id":"38919636","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Study protocol for "Psilocybin in patients with fibromyalgia: brain biomarkers of action".
publication_date: 2024-06-03
doi: 10.3389/fpsyt.2024.1320780
pubmed_id: 38983371
source_url: https://doi.org/10.3389/fpsyt.2024.1320780
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
authors:
Bornemann J, Close JB, Ahmad K, Barba T, Godfrey K, Macdonald L, Erritzoe D, Nutt D, Carhart-Harris R.

abstract:
BackgroundChronic pain is a leading cause of disability worldwide. Fibromyalgia is a particularly debilitating form of widespread chronic pain. Fibromyalgia remains poorly understood, and treatment options are limited or moderately effective at best. Here, we present a protocol for a mechanistic study investigating the effects of psychedelic-assisted-therapy in a fibromyalgia population. The principal focus of this trial is the central mechanism(s) of psilocybin-therapy i.e., in the brain and on associated mental schemata, primarily captured by electroencephalography (EEG) recordings of the acute psychedelic state, plus pre and post Magnetic Resonance Imaging (MRI).MethodsTwenty participants with fibromyalgia will complete 8 study visits over 8 weeks. This will include two dosing sessions where participants will receive psilocybin at least once, with doses varying up to 25mg. Our primary outcomes are 1) Lempel-Ziv complexity (LZc) recorded acutely using EEG, and the 2) the (Brief Experiential Avoidance Questionnaire (BEAQ) measured at baseline and primary endpoint. Secondary outcomes will aim to capture broad aspects of the pain experience and related features through neuroimaging, self-report measures, behavioural paradigms, and qualitative interviews. Pain Symptomatology will be measured using the Brief Pain Inventory Interference Subscale (BPI-IS), physical and mental health-related function will be measured using the 36-Item Short Form Health Survey (SF-36). Further neurobiological investigations will include functional MRI (fMRI) and diffusion tensor imaging (changes from baseline to primary endpoint), and acute changes in pre- vs post-acute spontaneous brain activity - plus event-related potential functional plasticity markers, captured via EEG.DiscussionThe results of this study will provide valuable insight into the brain mechanisms involved in the action of psilocybin-therapy for fibromyalgia with potential implications for the therapeutic action of psychedelic-therapy more broadly. It will also deliver essential data to inform the design of a potential subsequent RCT.

topic_tags:
Chronic Pain,Neuroplasticity,Brain Imaging,Mechanism of Action,Biomarkers,Aging,Randomized Controlled Trial,Observational Study

raw_json:
{"europe_pmc_id":"38983371","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Wang CK, Kim G, Aleksandrova LR, Panenka WJ, Barr AM.
publication_date: 2024-06-02
doi: 10.3389/fphar.2024.1387158
pubmed_id: 38887548
source_url: https://doi.org/10.3389/fphar.2024.1387158
substance_tags: psilocybin
study_type: Systematic Review
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:03
title:
A scoping review of the effects of mushroom and fungus extracts in rodent models of depression and tests of antidepressant activity.

abstract:
One of the most important developments in psychopharmacology in the past decade has been the emergence of novel treatments for mood disorders, such as psilocybin for treatment-resistant depression. Psilocybin is most commonly found in different species of mushroom; however, the literature on mushroom and fungus extracts with potential antidepressant activity extends well beyond just psilocybin-containing mushrooms, and includes both psychedelic and non-psychedelic species. In the current review, we systematically review the preclinical literature on mushroom and fungus extracts, and their effects of animal models of depression and tests of antidepressant activity. The PICO structure, PRISMA checklist and the Cochrane Handbook for systematic reviews of intervention were used to guide the search strategy. A scoping search was conducted in electronic databases PubMed, CINAHL, Embase and Web of Science. The literature search identified 50 relevant and suitable published studies. These included 19 different species of mushrooms, as well as seven different species of other fungi. Nearly all studies reported antidepressant-like effects of treatment with extracts. Treatments were most commonly delivered orally, in both acute and chronically administered studies to predominantly male rodents. Multiple animal models of depression were used, the most common being unpredictable chronic mild stress, while the tail suspension test and forced swim test were most frequently used as standalone antidepressant screens. Details on each experiment with mushroom and fungus species are discussed in detail, while an evaluation is provided of the strengths and weaknesses of these studies.

topic_tags:
Depression,Pharmacology,Systematic Review,Review Article,Animal Study,Treatment-Resistant Depression

raw_json:
{"europe_pmc_id":"38887548","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Effect of oral tryptamines on the gut microbiome of rats-a preliminary study.
authors: Xu M, Kiss AJ, Jones JA, McMurray MS, Shi H.
publication_date: 2024-06-02
doi: 10.7717/peerj.17517
pubmed_id: 38846751
source_url: https://doi.org/10.7717/peerj.17517
substance_tags: psilocybin
topic_tags: Depression,Mechanism of Action,Microbiome
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:03
abstract:
BackgroundPsilocybin and related tryptamines have come into the spotlight in recent years as potential therapeutics for depression. Research on the mechanisms of these effects has historically focused on the direct effects of these drugs on neural processes. However, in addition to such neural effects, alterations in peripheral physiology may also contribute to their therapeutic effects. In particular, substantial support exists for a gut microbiome-mediated pathway for the antidepressant efficacy of other drug classes, but no prior studies have determined the effects of tryptamines on microbiota.MethodsTo address this gap, in this preliminary study, male Long Evans rats were treated with varying dosages of oral psilocybin (0.2 or 2 mg/kg), norbaeocystin (0.25 or 2.52 mg/kg), or vehicle and their fecal samples were collected 1 week and 3 weeks after exposure for microbiome analysis using integrated 16S ribosomal DNA sequencing to determine gut microbiome composition.ResultsWe found that although treatment with neither psilocybin nor norbaeocystin significantly affected overall microbiome diversity, it did cause significant dose- and time-dependent changes in bacterial abundance at the phylum level, including increases in Verrucomicrobia and Actinobacteria, and decreases in Proteobacteria.Conclusion and implicationsThese preliminary findings support the idea that psilocybin and other tryptamines may act on the gut microbiome in a dose- and time-dependent manner, potentially identifying a novel peripheral mechanism for their antidepressant activity. The results from this preliminary study also suggest that norbaeocystin may warrant further investigation as a potential antidepressant, given the similarity of its effects to psilocybin.

keywords:
Feces, Animals, Rats, Rats, Long-Evans, Tryptamines, Antidepressive Agents, Administration, Oral, Male, Gastrointestinal Microbiome, Psilocybin

raw_json:
{"europe_pmc_id":"38846751","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Long-COVID symptoms improved after MDMA and psilocybin therapy: A case report.
authors: Chopra H, Furnish T, Verduzco-Gutierrez M, Jevotovsky DS, Castellanos J.
publication_date: 2024-05-27
doi: 10.1002/ccr3.8791
pubmed_id: 38813452
source_url: https://doi.org/10.1002/ccr3.8791
substance_tags: psilocybin
topic_tags: Case Report,Safety
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
abstract:
Key clinical messageLong-COVID syndrome lacks effective holistic treatment options. We present a case of a 41-year-old fully vaccinated female with Long-COVID syndrome who obtained significant symptomatic relief after self-medicating with psilocybin and MDMA.AbstractLong-COVID, a syndrome persisting after the acute phase of coronavirus disease 2019 (COVID-19), lacks effective holistic treatment options. We present a case of a 41-year-old fully vaccinated female with Long-COVID syndrome who obtained significant symptomatic relief by self-prescribing psilocybin and MDMA. Future research is needed to assess safety and efficacy.

raw_json:
{"europe_pmc_id":"38813452","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Structural pharmacology and therapeutic potential of 5-methoxytryptamines.
publication_date: 2024-05-07
doi: 10.1038/s41586-024-07403-2
pubmed_id: 38720072
source_url: https://doi.org/10.1038/s41586-024-07403-2
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Pharmacology,Receptor Pharmacology,Animal Study,In Vitro Study,Drug Interactions
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
authors:
Warren AL, Lankri D, Cunningham MJ, Serrano IC, Parise LF, Kruegel AC, Duggan P, Zilberg G, Capper MJ, Havel V, Russo SJ, Sames D, Wacker D.

abstract:
Psychedelic substances such as lysergic acid diethylamide (LSD) and psilocybin show potential for the treatment of various neuropsychiatric disorders1-3. These compounds are thought to mediate their hallucinogenic and therapeutic effects through the serotonin (5-hydroxytryptamine (5-HT)) receptor 5-HT2A (ref. 4). However, 5-HT1A also plays a part in the behavioural effects of tryptamine hallucinogens5, particularly 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), a psychedelic found in the toxin of Colorado River toads6. Although 5-HT1A is a validated therapeutic target7,8, little is known about how psychedelics engage 5-HT1A and which effects are mediated by this receptor. Here we map the molecular underpinnings of 5-MeO-DMT pharmacology through five cryogenic electron microscopy (cryo-EM) structures of 5-HT1A, systematic medicinal chemistry, receptor mutagenesis and mouse behaviour. Structure-activity relationship analyses of 5-methoxytryptamines at both 5-HT1A and 5-HT2A enable the characterization of molecular determinants of 5-HT1A signalling potency, efficacy and selectivity. Moreover, we contrast the structural interactions and in vitro pharmacology of 5-MeO-DMT and analogues to the pan-serotonergic agonist LSD and clinically used 5-HT1A agonists. We show that a 5-HT1A-selective 5-MeO-DMT analogue is devoid of hallucinogenic-like effects while retaining anxiolytic-like and antidepressant-like activity in socially defeated animals. Our studies uncover molecular aspects of 5-HT1A-targeted psychedelics and therapeutics, which may facilitate the future development of new medications for neuropsychiatric disorders.

keywords:
Animals, Humans, Mice, Methoxydimethyltryptamines, 5-Methoxytryptamine, Lysergic Acid Diethylamide, Receptor, Serotonin, 5-HT1A, Receptor, Serotonin, 5-HT2A, Anti-Anxiety Agents, Hallucinogens, Antidepressive Agents, Cryoelectron Microscopy, Structure-Activity Relationship, Models, Molecular, Male, Serotonin Receptor Agonists

raw_json:
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authors: Soliman PS, Curley DE, Capone C, Eaton E, Haass-Koffler CL.
publication_date: 2024-04-28
doi: 10.1007/s00213-024-06598-6
pubmed_id: 38683460
source_url: https://doi.org/10.1007/s00213-024-06598-6
substance_tags: psilocybin
topic_tags: Randomized Controlled Trial,Systematic Review,Review Article
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
title:
In the new era of psychedelic assisted therapy: A systematic review of study methodology in randomized controlled trials.

abstract:
Recent years have seen a resurgence in randomized, placebo controlled trials (RCTs) utilizing non-classical psychedelics (e.g. 3,4-methyl enedioxy methamphetamine [MDMA]), and classical psychedelics (e.g. psilocybin, lysergic acid diethylamide [LSD], and N,N-dimethyltryptamine [DMT/ayahuasca]) in conjunction with assisted therapy (AT) for psychiatric disorders. A notable methodological challenge in psychedelic AT, however, is the complexity of blinding procedures. The lack of efficacious blinding can introduce considerable response bias, reduce internal validity, and compromise participant retention. This systematic review examines design and blinding techniques in RCTs utilizing psychedelics and placebo for the treatment of psychiatric disorders. The aim of this work is to identify factors that may inform future RTC design for conducting psychedelics research. We conducted a systematic review of PubMed, MEDLINE, CINAHL, Cochrane Central Register of Controlled Trials (CENTRAL), Psycinfo, Embase, and Web of Science Core Collection to examine: (1) placebo selection, (2) study design, and (3) integrity of blinding measures. Sixteen publications were identified as meeting the criteria for a systematic review. Our findings suggest that traditional placebo administration is insufficient to control for expectancy confounds. Consequently, experimental methodology that limits personnel unblinding and the use of an active placebo are important considerations when designing prospective clinical studies involving psychedelics.

keywords:
Humans, Hallucinogens, Double-Blind Method, Mental Disorders, Research Design, Randomized Controlled Trials as Topic

raw_json:
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authors: Agor D, Knettel BA, Daici K, Meanley S.
publication_date: 2024-02-18
doi: 10.1016/j.cnur.2024.01.005
pubmed_id: 38670693
source_url: https://doi.org/10.1016/j.cnur.2024.01.005
substance_tags: psilocybin
topic_tags: Aging,Review Article,Older Adults
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
title:
The Intersection of Mental Health and Sexual and Gender Minority Identities for Older Adults Living with Human Immunodeficiency Virus: A Narrative Review.

abstract:
The transition of HIV into a chronic illness has brought to the forefront the pressing need to address the complex web of social determinants of HIV outcomes. A structured literature search and narrative review of studies describing intervention strategies for mental health among sexual/gender minority (SGM) older adults living with HIV (OALWH) published in the last decade identified 2 studies for inclusion. This narrative review identifies age-sensitive and culturally adapted therapies, mindfulness and meditation-based stress reduction, group therapy, digital mental health resources, and psilocybin-assisted group therapy as emerging intervention models tailored to meet the unique needs of SGM OALWH.

keywords:
Humans, HIV Infections, Mental Health, Aged, Middle Aged, Female, Male, Sexual and Gender Minorities

raw_json:
{"europe_pmc_id":"38670693","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Mechanisms of therapeutic change after psychedelic treatment in OCD.
authors: Maloney G, Ching T, Kichuk SA, Pittenger C, Kelmendi B.
publication_date: 2024-04-06
doi: 10.1016/j.psychres.2024.115907
pubmed_id: 38615521
source_url: https://doi.org/10.1016/j.psychres.2024.115907
keywords: Humans, Hallucinogens, Obsessive-Compulsive Disorder, Psilocybin, Imagery, Psychotherapy
substance_tags: psilocybin
topic_tags: OCD,Mechanism of Action,Emotional Processing
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
abstract:
Novel treatments are required for the 30-50% of individuals with obsessive-compulsive disorder (OCD) who remain resistant to first-line pharmacological and psychotherapeutic treatments. Recent pilot data suggest benefit from psilocybin-assisted psychotherapy (PAP) and from imagery rescripting (ImRs). We explore psychological mechanisms of change underpinning both interventions that appear to allow for reprocessing of negative emotions and core beliefs associated with past aversive events. A next critical step in PAP is the development of psychotherapeutic frameworks grounded in theory. We propose that basing PAP on an ImRs framework may provide synergistic benefits in symptom reduction, modification of core beliefs, and value-based living.

raw_json:
{"europe_pmc_id":"38615521","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Treating Bipolar Depression Using Psilocybin-Validity Threats Regarding Efficacy and Safety-Reply.
authors: Aaronson ST, van der Vaart A, Sackeim HA.
publication_date: 2024-05-31
doi: 10.1001/jamapsychiatry.2024.0423
pubmed_id: 38598225
source_url: https://doi.org/10.1001/jamapsychiatry.2024.0423
keywords: Humans, Hallucinogens, Treatment Outcome, Reproducibility of Results, Bipolar Disorder, Psilocybin
substance_tags: psilocybin
topic_tags: Depression,Safety
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
raw_json:
{"europe_pmc_id":"38598225","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Treating Bipolar Depression Using Psilocybin-Validity Threats Regarding Efficacy and Safety.
authors: Fried EI, Cristea IA, Naudet F.
publication_date: 2024-05-31
doi: 10.1001/jamapsychiatry.2024.0420
pubmed_id: 38598200
source_url: https://doi.org/10.1001/jamapsychiatry.2024.0420
keywords: Humans, Hallucinogens, Treatment Outcome, Reproducibility of Results, Bipolar Disorder, Psilocybin
substance_tags: psilocybin
topic_tags: Depression,Safety
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
raw_json:
{"europe_pmc_id":"38598200","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2024-05-31
source_url: https://europepmc.org/article/PMC/PMC11847495
substance_tags: psilocybin
topic_tags: Depression,Mechanism of Action
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:03
title:
Psilocybin for dementia prevention? The potential role of psilocybin to alter mechanisms associated with major depression and neurodegenerative diseases

authors:
Haniff Z, Bocharova M, Mantingh T, Rucker J, Velayudhan L, Taylor D, Young A, Aarsland D, Vernon A, Thuret S.

raw_json:
{"europe_pmc_id":"PMC11847495","source":"PMC","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Assessing expectancy and suggestibility in a trial of escitalopram v. psilocybin for depression.
authors: Szigeti B, Weiss B, Rosas FE, Erritzoe D, Nutt D, Carhart-Harris R.
publication_date: 2024-01-21
doi: 10.1017/s0033291723003653
pubmed_id: 38247730
source_url: https://doi.org/10.1017/s0033291723003653
substance_tags: psilocybin
topic_tags: Depression
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
abstract:
BackgroundTo investigate the association between pre-trial expectancy, suggestibility, and response to treatment in a trial of escitalopram and investigational drug, COMP360, psilocybin, in the treatment of major depressive disorder (ClinicalTrials.gov registration: NCT03429075).MethodsWe used data (n = 55) from our recent double-blind, parallel-group, randomized head-to-head comparison trial of escitalopram and investigational drug, COMP360, psilocybin. Mixed linear models were used to investigate the association between pre-treatment efficacy-related expectations, as well as baseline trait suggestibility and absorption, and therapeutic response to both escitalopram and COMP360 psilocybin.ResultsPatients had significantly higher expectancy for psilocybin relative to escitalopram; however, expectancy for escitalopram was associated with improved therapeutic outcomes to escitalopram, expectancy for psilocybin was not predictive of response to psilocybin. Separately, we found that pre-treatment trait suggestibility was associated with therapeutic response in the psilocybin arm, but not in the escitalopram arm.ConclusionsOverall, our results suggest that psychedelic therapy may be less vulnerable to expectancy biases than previously suspected. The relationship between baseline trait suggestibility and response to psilocybin therapy implies that highly suggestible individuals may be primed for response to this treatment.

keywords:
Humans, Citalopram, Hallucinogens, Treatment Outcome, Suggestion, Double-Blind Method, Adult, Middle Aged, Female, Male, Anticipation, Psychological, Psilocybin, Escitalopram, Major Depressive Disorder

raw_json:
{"europe_pmc_id":"38247730","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2024-05-31
doi: 10.1001/jamapsychiatry.2023.4685
pubmed_id: 38055270
source_url: https://doi.org/10.1001/jamapsychiatry.2023.4685
substance_tags: psilocybin
topic_tags: Depression,Safety
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Single-Dose Synthetic Psilocybin With Psychotherapy for Treatment-Resistant Bipolar Type II Major Depressive Episodes: A Nonrandomized Open-Label Trial.

authors:
Aaronson ST, van der Vaart A, Miller T, LaPratt J, Swartz K, Shoultz A, Lauterbach M, Sackeim HA, Suppes T.

abstract:
ImportanceBipolar II disorder (BDII) is a debilitating condition frequently associated with difficult-to-treat depressive episodes. Psilocybin has evidence for rapid-acting antidepressant effects but has not been investigated in bipolar depression.ObjectiveTo establish the safety and efficacy of psilocybin in patients with BDII in a current depressive episode.Design, setting, and participantsThis was a 12-week, open-label nonrandomized open-label trial conducted at Sheppard Pratt Hospital. Participants aged 18 to 65 years with BDII, a current depressive episode longer than 3 months, and documented insufficient benefit with at least 2 pharmacologic treatments during the current episode were invited to participate. Of 70 approached, 19 met inclusion criteria and were enrolled. The trial was conducted between April 14, 2021, and January 5, 2023.InterventionsA single dose of synthetic psilocybin, 25 mg, was administered. Psychotropic medications were discontinued at least 2 weeks prior to dosing. Therapists met with patients for 3 sessions during pretreatment, during the 8-hour dosing day, and for 3 integration sessions posttreatment.Main outcomes and measuresThe primary outcome measure was change in Montgomery-Åsberg Depression Rating scale (MADRS) at 3 weeks posttreatment. Secondary measures included MADRS scores 12 weeks posttreatment, the self-rated Quick Inventory of Depression Symptoms-Self Rating (QIDS-SR), and the self-rated Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF), each completed at baseline and all subsequent visits. Safety measures included the Columbia Suicide Severity Rating Scale (CSSRS) and the Young Mania Rating Scale (YMRS) completed at each visit.ResultsOf the 15 participants in this study (6 male and 9 female; mean [SD] age, 37.8 [11.6] years), all had lower scores at week 3, with a mean (SD) change of -24.00 (9.23) points on the MADRS, (Cohen d = 4.08; 95% CI, -29.11 to -18.89; P

keywords:
Humans, Hallucinogens, Treatment Outcome, Combined Modality Therapy, Bipolar Disorder, Psychotherapy, Adult, Middle Aged, Female, Male, Young Adult, Depressive Disorder, Treatment-Resistant, Psilocybin, Major Depressive Disorder

raw_json:
{"europe_pmc_id":"38055270","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin in Bipolar II Study Provides Preliminary Data on Safety.
authors: Yaden DB, Gukasyan N, Nayak SM.
publication_date: 2024-05-31
doi: 10.1001/jamapsychiatry.2023.4680
pubmed_id: 38055240
source_url: https://doi.org/10.1001/jamapsychiatry.2023.4680
keywords: Humans, Hallucinogens, Bipolar Disorder, Randomized Controlled Trials as Topic, Psilocybin
substance_tags: psilocybin
topic_tags: Randomized Controlled Trial,Safety
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
raw_json:
{"europe_pmc_id":"38055240","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Iorgu AM, Vasilescu AN, Pfeiffer N, Spanagel R, Mallien AS, Inta D, Gass P.
publication_date: 2023-11-06
doi: 10.1007/s00406-023-01699-3
pubmed_id: 37934233
source_url: https://doi.org/10.1007/s00406-023-01699-3
substance_tags: psilocybin
topic_tags: Receptor Pharmacology,Biomarkers,Toxicity
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Psilocybin does not induce the vulnerability marker HSP70 in neurons susceptible to Olney's lesions.

abstract:
S-ketamine, a N-methyl-D-aspartate receptor (NMDAR) antagonist, and psilocybin, a 5-hydroxy-tryptamine (serotonin) 2A receptor (5-HT2AR) agonist, are reported as effective rapid-acting antidepressants. Both compounds increase glutamate signalling and evoke cortical hyperexcitation. S-ketamine induces neurotoxicity especially in the retrosplenial cortex (Olney's lesions). Whether psilocybin produces similar neurotoxic effects has so far not been investigated. We performed an immunohistochemical whole-brain mapping for heat shock protein 70 (HSP70) in rats treated with psilocybin, S-ketamine, and MK-801. In contrast to S-ketamine- and MK-801-treated animals, we did not detect any HSP70-positive neurons in retrosplenial cortex of rats treated with psilocybin. Our results suggest that psilocybin might be safer for clinical use compared to S-ketamine regarding neuronal damage.

keywords:
Cerebral Cortex, Neurons, Animals, Rats, Rats, Sprague-Dawley, Ketamine, Dizocilpine Maleate, Excitatory Amino Acid Antagonists, Hallucinogens, Male, HSP70 Heat-Shock Proteins, Psilocybin

raw_json:
{"europe_pmc_id":"37934233","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Lasch A, Schweikert T, Dora E, Kolb T, Schurig HL, Walther A.
publication_date: 2023-05-18
doi: 10.1055/a-2046-5202
pubmed_id: 37207669
source_url: https://doi.org/10.1055/a-2046-5202
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Addiction,Mechanism of Action,Clinical Trial,Review Article
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
[Psilocybin-Assisted Treatment of Depression, Anxiety and Substance use Disorders: Neurobiological Basis and Clinical Application].

abstract:
Successful therapy of mental disorders is very important in view of the high level of suffering of those affected. Since established pharmaceutical and psychotherapeutic approaches do not lead to the desired improvement in all cases, complementary or alternative treatment methods are intensively researched. Psilocybin-assisted psychotherapy seems particularly promising, and has been approved in the USA for larger clinical trials. Psilocybin belongs to the group of psychedelics and influences psychological experiences. In assisted therapy, psilocybin is administered in controlled doses under medical supervision to patients with different mental disorders. In the studies conducted so far, longer-term positive effects could be shown after just one or a few doses. In order to provide a better understanding of the potential therapeutic mechanisms, this article will first describe neurobiological and psychological effects of psilocybin. To better assess the potential of psilocybin-assisted psychotherapy for various disorders, clinical studies conducted so far with patients administered psilocybin are reviewed.

keywords:
Humans, Substance-Related Disorders, Hallucinogens, Depression, Anxiety, Anxiety Disorders, Psychotherapy, Psilocybin

raw_json:
{"europe_pmc_id":"37207669","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Wang SM, Kim S, Choi WS, Lim HK, Woo YS, Pae CU, Bahk WM.
publication_date: 2023-11-29
doi: 10.9758/cpn.23.1134
pubmed_id: 38627070
source_url: https://doi.org/10.9758/cpn.23.1134
substance_tags: psilocybin
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Current Understanding on Psilocybin for Major Depressive Disorder: A Review Focusing on Clinical Trials.

abstract:
Previous studies suggested effectiveness of psilocybin in the field of mental health. FDA designated psilocybin as a "breakthrough therapy" for the treatment of treatment-resistant depression (TRD) in 2018. This paper provided a review of psilocybin's potential role in treatment of depression by focusing on published clinical trials. Studies showed that psilocybin, an agonist on 5-HT2A receptors, manifests antidepressant and anxiolytic effects by increasing glutamate transmission, reducing brain inflammation, decreasing default mode network activity. In terms of clinical trials, eleven studies (six open-label and five double blinded randomized clinical trials [DB-RCTs]) trials exploring psilocybin's impact on depression were found. Among open-label studies, a pilot study on TRD patients demonstrated significant reductions in depressive symptoms after two psilocybin sessions. Psilocybin also improved cognitive bias associated with depression. Extension studies confirmed sustained improvements and high remission rates. Among five DB-RCTs, two showed that psilocybin led to significant reductions in anxiety and depression in cancer patients, and the improvements sustained for over six months. In MDD, psilocybin showed rapid reductions in depression, with higher remission rates compared to escitalopram in a DB-RCT. Another DB-RCT showed that psilocybin induced higher decrease in depression around 6 hours after their administrations than placebo. The last DB-RCT showed that in patients with TRD, a single dose of psilocybin 25 mg, but not psilocybin 10 mg, resulted in superior antidepressant effect than psilocybin 1 mg. Overall, psilocybin showed promise in treating depression and anxiety, with notable safety profiles. Further research should explore optimal dosages and long-term effects.

topic_tags:
Depression,Anxiety,Receptor Pharmacology,Default Mode Network,Clinical Trial,Randomized Controlled Trial,Review Article,Cancer Patients,Treatment-Resistant Depression,Safety,Inflammation

raw_json:
{"europe_pmc_id":"38627070","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Vohryzek J, Luppi A, Atasoy S, Deco G, Timmermann C, Carhart-Harris RL, Kringelbach ML.
journal: bioRxiv
publication_date: 2024-05-30
doi: 10.1101/2024.05.30.596410
source_url: https://doi.org/10.1101/2024.05.30.596410
substance_tags: psilocybin
topic_tags: Mechanism of Action,Consciousness
study_type: Other
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
title:
Time-resolved coupling between connectome harmonics and subjective experience under the psychedelic DMT

abstract:
Exploring the intricate relationship between brain's structure and function, and how this affects subjective experience is a fundamental pursuit in neuroscience. Psychedelic substances offer a unique insight into the influences of specific neurotransmitter systems on perception, cognition and consciousness. Specifically, their impact on brain function propagates across the structural connectome, a network of white matter pathways linking different regions. To comprehensively grasp the effects of psychedelic compounds on brain function, we used a theoretically rigorous framework known as connectome harmonic decomposition. This framework provides a robust method to characterize how brain function intricately depends on the organized network structure of the human connectome. We show that the connectome harmonic repertoire under DMT is reshaped in line with other reported psychedelic compounds; psilocybin, LSD and ketamine. Furthermore, we show that the repertoire entropy of connectome harmonics increases under DMT, as with those other psychedelics. Importantly, we demonstrate for the first time that measures of energy spectrum difference and repertoire entropy of connectome harmonics indexes the intensity of subjective experience of the participants in a time-resolved manner reflecting close coupling between connectome harmonics and subjective experience.

raw_json:
{"europe_pmc_id":"PPR860621","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


title: Medical Uses and Adverse Effects of Psilocybin.
authors: Ghaznavi S, Bernardez LM, Stern TA.
publication_date: 2024-05-27
doi: 10.4088/pcc.23f03652
pubmed_id: 38815272
source_url: https://doi.org/10.4088/pcc.23f03652
keywords: Humans, Hallucinogens, Mental Disorders, Psilocybin
substance_tags: psilocybin
topic_tags: Healthcare Workers
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:03
abstract:
The Psychiatric Consultation Service at Massachusetts General Hospital sees medical and surgical inpatients with comorbid psychiatric symptoms and conditions. During their twice-weekly rounds, Dr Stern and other members of the Consultation Service discuss diagnosis and management of hospitalized patients with complex medical or surgical problems who also demonstrate psychiatric symptoms or conditions. These discussions have given rise to rounds repors that will prove useful for clinicians practicing at the interface of medicine and psychiatry.Prim Care Companion CNS Disord 2024;26(3):23f03652. Author affiliations are listed at the end of this article.

raw_json:
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title: Attitudes of European psychiatrists on psychedelics: a qualitative study.
authors: Žuljević MF, Breški N, Kaliterna M, Hren D
journal: Frontiers in psychiatry
publication_date: 2023-12-31
doi: 10.3389/fpsyt.2024.1411234
pubmed_id: 38855648
source_url: https://pubmed.ncbi.nlm.nih.gov/38855648/
keywords: psychedelics, MDMA, attitudes, psilocybin, psychedelic therapy, psychiatrists
substance_tags: psilocybin
topic_tags: General
study_type: Qualitative Study
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:37
raw_json: {"pubmed_id":"38855648"}
abstract:
It is important to understand how mental health practitioners view recent findings on psychedelic-assisted psychotherapy (PAP) as there is potential this treatment may be incorporated into clinical practice. The aim of our study was to explore how psychiatrists who are not involved in psychedelic research and who are located in the European region perceive psychedelics and PAP.
We conducted online semi-structured interviews with 12 psychiatry specialists and psychiatry trainees from 8 European countries. Data were analyzed using a general inductive approach informed by codebook thematic analysis.
Based on the interviews, we developed four main themes and 14 sub-themes, including (1) Psychedelics hold potential, (2) Psychedelics are dangerous, (3) Future of psychedelics is uncertain, and (4) Psychiatry is ambivalent toward psychedelics.
Our respondents-psychiatrists acknowledged the potential of PAP but remained cautious and did not yet perceive its evidence base as robust enough. Education on psychedelics is lacking in medical and psychiatric training and should be improved to facilitate the involvement of mental health experts in decision-making on PAP.


publication_date: 2024-05-20
doi: 10.1186/s13063-024-08174-x
pubmed_id: 38773523
source_url: https://doi.org/10.1186/s13063-024-08174-x
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
title:
Effect of MDMA-assisted therapy on mood and anxiety symptoms in advanced-stage cancer (EMMAC): study protocol for a double-blind, randomised controlled trial.

authors:
Bhagavan C, Glue P, Evans W, Reynolds L, Turner T, King C, Russell BR, Morunga E, Mills JL, Layton G, Menkes DB.

abstract:
BackgroundSymptoms of anxiety and depression are common in patients with terminal illness and multiple challenges exist with timely and effective care in this population. Several centres have reported that one dose of the serotonergic psychedelic psilocybin, combined with therapeutic support, improves these symptoms for up to 6 months in this patient group. Drawing upon related therapeutic mechanisms, 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy may have the potential to achieve similar, positive mental health outcomes in this group. Preliminary evidence also supports the tolerability of MDMA-assisted therapy for anxiety and depression in advanced-stage cancer.MethodsUp to 32 participants with advanced-stage cancer and associated depression and anxiety will be randomised in a 1:1 ratio into one of two blinded parallel treatment arms. The intervention group will receive 120 mg (+ 60 mg optional supplemental dose) MDMA-assisted therapy. The psychoactive control group will receive 20 mg oral (+ 10 mg optional supplemental dose) methylphenidate-assisted therapy. For each medication-assisted therapy session, participants will undergo two 90-min therapeutic support sessions in the week preceding, and one 90-min support session the day after the experimental session. A battery of measures (mood, anxiety, quality of life, mystical experience, spiritual wellbeing, attitudes towards death, personality traits, holistic health and wellbeing, connectedness, demoralisation, expectations, qualitative data and safety measures) will be assessed at baseline and through to the end of the protocol. Participants will be followed up until either 12 months post-randomisation or death, whichever occurs first.DiscussionThis study will examine the effect of MDMA-assisted therapy on symptoms of anxiety and depression in advanced-stage cancer. Potential therapeutic implications include establishing the safety and effectiveness of a novel treatment that may relieve mental suffering in patients with life-threatening illness.Trial registrationTrial registered on Australian New Zealand Clinical Trials Registry.Registration numberACTRN12619001334190p. Date registered: 30/09/2019. URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=378153&showOriginal=true&isReview=true.

keywords:
Humans, Neoplasms, N-Methyl-3,4-methylenedioxyamphetamine, Methylphenidate, Hallucinogens, Neoplasm Staging, Treatment Outcome, Double-Blind Method, Depression, Affect, Anxiety, Time Factors, Quality of Life, Male, Randomized Controlled Trials as Topic

topic_tags:
Depression,Anxiety,End-of-Life Distress,Mechanism of Action,Aging,Wellbeing,Personality Change,Spirituality,Mystical Experience,Clinical Trial,Randomized Controlled Trial,Review Article,Safety

raw_json:
{"europe_pmc_id":"38773523","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Harari R, Chatterjee I, Getselter D, Elliott E.
publication_date: 2024-04-08
doi: 10.1016/j.isci.2024.109686
pubmed_id: 38660396
source_url: https://doi.org/10.1016/j.isci.2024.109686
substance_tags: psilocybin,psilocin
topic_tags: Depression,Anxiety,Neuroplasticity,Mechanism of Action,Receptor Pharmacology,Animal Study
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:00
title:
Psilocybin induces acute anxiety and changes in amygdalar phosphopeptides independently from the 5-HT2A receptor.

abstract:
Psilocybin, and its metabolite psilocin, induces psychedelic effects through activation of the 5-HT2A receptor. Psilocybin has been proposed as a treatment for depression and anxiety but sometimes induces anxiety in humans. An understanding of mechanisms underlying the anxiety response will help to better develop therapeutic prospects of psychedelics. In the current study, psilocybin induced an acute increase in anxiety in behavioral paradigms in mice. Importantly, pharmacological blocking of the 5-HT2A receptor attenuates psilocybin-induced head twitch response, a behavioral proxy for the psychedelic response, but does not rescue psilocybin's effect on anxiety-related behavior. Phosphopeptide analysis in the amygdala uncovered signal transduction pathways that are dependent or independent of the 5-HT2A receptor. Furthermore, presynaptic proteins are specifically involved in psilocybin-induced acute anxiety. These insights into how psilocybin may induce short-term anxiety are important for understanding how psilocybin may best be used in the clinical framework.

raw_json:
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authors: Schindler EAD, Sewell RA, Gottschalk CH, Flynn LT, Zhu Y, Pittman BP, Cozzi NV, D'Souza DC.
publication_date: 2024-04-01
doi: 10.1016/j.jns.2024.122993
pubmed_id: 38581739
source_url: https://doi.org/10.1016/j.jns.2024.122993
substance_tags: psilocybin
topic_tags: Headache / Migraine,Clinical Trial,Randomized Controlled Trial,Safety,Adverse Events
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Psilocybin pulse regimen reduces cluster headache attack frequency in the blinded extension phase of a randomized controlled trial.

abstract:
BackgroundIn a recent randomized, double-blind, placebo-controlled study, we observed a nonsignificant reduction of attack frequency in cluster headache after pulse administration of psilocybin (10 mg/70 kg, 3 doses, 5 days apart each). We carried out a blinded extension phase to consider the safety and efficacy of repeating the pulse regimen.MethodsEligible participants returned to receive a psilocybin pulse at least 6 months after their first round of study participation. Participants kept headache diaries starting two weeks before and continuing through eight weeks after the first drug session. Ten participants completed the extension phase and all ten were included in the final analysis.ResultsIn the three weeks after the start of the pulse, cluster attack frequency was significantly reduced from baseline (18.4 [95% confidence interval 8.4 to 28.4] to 9.8 [4.3 to 15.2] attacks/week; p = 0.013, d' = 0.97). A reduction of approximately 50% was seen regardless of individual response to psilocybin in the first round. Psilocybin was well-tolerated without any unexpected or serious adverse events.DiscussionThis study shows a significant reduction in cluster attack frequency in a repeat round of pulse psilocybin administration and suggests that prior response may not predict the effect of repeated treatment. To gauge the full potential of psilocybin as a viable medicine in cluster headache, future work should investigate the safety and therapeutic efficacy in larger, more representative samples over a longer time period, including repeating the treatment.Clinical trials registrationNCT02981173.

keywords:
Humans, Cluster Headache, Hallucinogens, Treatment Outcome, Double-Blind Method, Adult, Middle Aged, Female, Male, Psilocybin

raw_json:
{"europe_pmc_id":"38581739","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Copa D, Erritzoe D, Giribaldi B, Nutt D, Carhart-Harris R, Tagliazucchi E.
publication_date: 2024-02-26
doi: 10.1016/j.jad.2024.02.089
pubmed_id: 38423367
source_url: https://doi.org/10.1016/j.jad.2024.02.089
keywords: Humans, Magnetic Resonance Imaging, Depression, Psilocybin, Escitalopram, Major Depressive Disorder
substance_tags: psilocybin
topic_tags: Depression,Brain Imaging,Aging,Treatment-Resistant Depression
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Predicting the outcome of psilocybin treatment for depression from baseline fMRI functional connectivity.

abstract:
BackgroundPsilocybin is a serotonergic psychedelic drug under assessment as a potential therapy for treatment-resistant and major depression. Heterogeneous treatment responses raise interest in predicting the outcome from baseline data.MethodsA machine learning pipeline was implemented to investigate baseline resting-state functional connectivity measured with functional magnetic resonance imaging (fMRI) as a predictor of symptom severity in psilocybin monotherapy for treatment-resistant depression (16 patients administered two 5 mg capsules followed by 25 mg, separated by one week). Generalizability was tested in a sample of 22 patients who participated in a psilocybin vs. escitalopram trial for moderate-to-severe major depression (two separate doses of 25 mg of psilocybin 3 weeks apart plus 6 weeks of daily placebo vs. two separate doses of 1 mg of psilocybin 3 weeks apart plus 6 weeks of daily oral escitalopram). The analysis was repeated using both samples combined.ResultsFunctional connectivity of visual, default mode and executive networks predicted early symptom improvement, while the salience network predicted responders up to 24 weeks after treatment (accuracy≈0.9). Generalization performance was borderline significant. Consistent results were obtained from the combined sample analysis. Fronto-occipital and fronto-temporal coupling predicted early and late symptom reduction, respectively.LimitationsThe number of participants and differences between the two datasets limit the generalizability of the findings, while the lack of a placebo arm limits their specificity.ConclusionsBaseline neurophysiological measurements can predict the outcome of psilocybin treatment for depression. Future research based on larger datasets should strive to assess the generalizability of these predictions.

raw_json:
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authors: Zeller M, Parent S, Schultheiss N.
publication_date: 2024-04-30
source_url: https://europepmc.org/article/PMC/PMC11151301
substance_tags: psilocin
topic_tags: General
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:03
title:
Structural characterization and comparative analysis of polymorphic forms of psilocin (4-hy­droxy-N,N-di­methyl­tryptamine)

raw_json:
{"europe_pmc_id":"PMC11151301","source":"PMC","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2024-05-13
doi: 10.3389/fpsyt.2024.1386321
pubmed_id: 38807690
source_url: https://doi.org/10.3389/fpsyt.2024.1386321
substance_tags: psilocybin
topic_tags: Brain Imaging,Default Mode Network,Consciousness,Aging,Mystical Experience,Review Article
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
title:
Alterations in brain network connectivity and subjective experience induced by psychedelics: a scoping review.

authors:
Yu Z, Burback L, Winkler O, Xu L, Dennett L, Vermetten E, Greenshaw A, Li XM, Milne M, Wang F, Cao B, Winship IR, Zhang Y, Chan AW.

abstract:
Intense interest surrounds current research on psychedelics, particularly regarding their potential in treating mental health disorders. Various studies suggest a link between the subjective effects produced by psychedelics and their therapeutic efficacy. Neuroimaging evidence indicates an association of changes in brain functional connectivity with the subjective effects of psychedelics. We conducted a review focusing on psychedelics and brain functional connectivity. The review focused on four psychedelic drugs: ayahuasca, psilocybin and LSD, and the entactogen MDMA. We conducted searches in databases of MEDLINE, Embase, APA PsycInfo and Scopus from inception to Jun 2023 by keywords related to functional connectivity and psychedelics. Using the PRISMA framework, we selected 24 articles from an initial pool of 492 for analysis. This scoping review and analysis investigated the effects of psychedelics on subjective experiences and brain functional connectivity in healthy individuals. The studies quantified subjective effects through psychometric scales, revealing significant experiences of altered consciousness, mood elevation, and mystical experiences induced by psychedelics. Neuroimaging results indicated alterations in the functional connectivity of psychedelics, with consistent findings across substances of decreased connectivity within the default mode network and increased sensory and thalamocortical connectivity. Correlations between these neurophysiological changes and subjective experiences were noted, suggesting a brain network basis of the psychedelics' neuropsychological impact. While the result of the review provides a potential neural mechanism of the subjective effects of psychedelics, direct clinical evidence is needed to advance their clinical outcomes. Our research serves as a foundation for further exploration of the therapeutic potential of psychedelics.

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authors: M Ro Rsted E, Jensen AA, Smits G, Frydenvang K, Kristensen JL.
publication_date: 2024-04-21
doi: 10.1021/acs.jmedchem.4c00082
pubmed_id: 38648420
source_url: https://doi.org/10.1021/acs.jmedchem.4c00082
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Receptor Pharmacology,Clinical Trial
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
title:
Discovery and Structure-Activity Relationships of 2,5-Dimethoxyphenylpiperidines as Selective Serotonin 5-HT2A Receptor Agonists.

abstract:
Classical psychedelics such as psilocybin, lysergic acid diethylamide (LSD), and N,N-dimethyltryptamine (DMT) are showing promising results in clinical trials for a range of psychiatric indications, including depression, anxiety, and substance abuse disorder. These compounds are characterized by broad pharmacological activity profiles, and while the acute mind-altering effects can be ascribed to their shared agonist activity at the serotonin 2A receptor (5-HT2AR), their apparent persistent therapeutic effects are yet to be decidedly linked to activity at this receptor. We report herein the discovery of 2,5-dimethoxyphenylpiperidines as a novel class of selective 5-HT2AR agonists and detail the structure-activity investigations leading to the identification of LPH-5 [analogue (S)-11] as a selective 5-HT2AR agonist with desirable drug-like properties.

keywords:
Animals, Humans, Rats, Lysergic Acid Diethylamide, Piperidines, Receptor, Serotonin, 5-HT2A, Structure-Activity Relationship, Drug Discovery, Serotonin 5-HT2 Receptor Agonists

raw_json:
{"europe_pmc_id":"38648420","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2024-05-03
doi: 10.1136/bmj.q1025
pubmed_id: 38704154
source_url: https://doi.org/10.1136/bmj.q1025
substance_tags: psilocybin
topic_tags: Depression,Meta-Analysis,Systematic Review,Review Article
study_type: Meta-Analysis
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
title:
EXPRESSION OF CONCERN: Efficacy of psilocybin for treating symptoms of depression: systematic review and meta-analysis.

raw_json:
{"europe_pmc_id":"38704154","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2024-01-31
pubmed_id: 38309742
source_url: https://europepmc.org/article/MED/38309742
keywords: Humans, Neoplasms, Hallucinogens, Depression, Adult, Psilocybin
substance_tags: psilocybin
topic_tags: Depression
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
title:
Psychedelic psilocybin-assisted therapy reduces depressive symptoms in adults with cancer and depression.

raw_json:
{"europe_pmc_id":"38309742","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Ruan Y, Yuan R, He J, Jiang Y, Chu S, Chen N.
publication_date: 2024-04-30
doi: 10.1038/s41420-024-01974-9
pubmed_id: 38693106
source_url: https://doi.org/10.1038/s41420-024-01974-9
substance_tags: psilocybin
topic_tags: Depression,Neuroplasticity,Mechanism of Action,Epigenetics,Review Article
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
title:
New perspective on sustained antidepressant effect: focus on neurexins regulating synaptic plasticity.

abstract:
Depression is highly prevalent globally, however, currently available medications face challenges such as low response rates and short duration of efficacy. Additionally, depression mostly accompany other psychiatric disorders, further progressing to major depressive disorder without long-term effective management. Thus, sustained antidepressant strategies are urgently needed. Recently, ketamine and psilocybin gained attention as potential sustained antidepressants. Review of recent studies highlights that synaptic plasticity changes as key events of downstream long-lasting changes in sustained antidepressant effect. This underscores the significance of synaptic plasticity in sustained antidepressant effect. Moreover, neurexins, key molecules involved in the regulation of synaptic plasticity, act as critical links between synaptic plasticity and sustained antidepressant effects, involving mechanisms including protein level, selective splicing, epigenetics, astrocytes, positional redistribution and protein structure. Based on the regulation of synaptic plasticity by neurexins, several drugs with potential for sustained antidepressant effect are also discussed. Focusing on neurexins in regulating synaptic plasticity promises much for further understanding underlying mechanisms of sustained antidepressant and the next step in new drug development. This research represents a highly promising future research direction.

raw_json:
{"europe_pmc_id":"38693106","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Efficacy of psilocybin for treating symptoms of depression: systematic review and meta-analysis.
authors: Metaxa AM, Clarke M.
publication_date: 2024-04-30
doi: 10.1136/bmj-2023-078084
pubmed_id: 38692686
source_url: https://doi.org/10.1136/bmj-2023-078084
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
abstract:
ObjectiveTo determine the efficacy of psilocybin as an antidepressant compared with placebo or non-psychoactive drugs.DesignSystematic review and meta-analysis.Data sourcesFive electronic databases of published literature (Cochrane Central Register of Controlled Trials, Medline, Embase, Science Citation Index and Conference Proceedings Citation Index, and PsycInfo) and four databases of unpublished and international literature (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, ProQuest Dissertations and Theses Global, and PsycEXTRA), and handsearching of reference lists, conference proceedings, and abstracts.Data synthesis and study qualityInformation on potential treatment effect moderators was extracted, including depression type (primary or secondary), previous use of psychedelics, psilocybin dosage, type of outcome measure (clinician rated or self-reported), and personal characteristics (eg, age, sex). Data were synthesised using a random effects meta-analysis model, and observed heterogeneity and the effect of covariates were investigated with subgroup analyses and metaregression. Hedges’ g was used as a measure of treatment effect size, to account for small sample effects and substantial differences between the included studies’ sample sizes. Study quality was appraised using Cochrane’s Risk of Bias 2 tool, and the quality of the aggregated evidence was evaluated using GRADE guidelines.Eligibility criteriaRandomised trials in which psilocybin was administered as a standalone treatment for adults with clinically significant symptoms of depression and change in symptoms was measured using a validated clinician rated or self-report scale. Studies with directive psychotherapy were included if the psychotherapeutic component was present in both experimental and control conditions. Participants with depression regardless of comorbidities (eg, cancer) were eligible.ResultsMeta-analysis on 436 participants (228 female participants), average age 36-60 years, from seven of the nine included studies showed a significant benefit of psilocybin (Hedges’ g=0.66, 95% confidence interval (CI) 0.46 to 0.86, P

keywords:
Humans, Hallucinogens, Antidepressive Agents, Treatment Outcome, Depression, Randomized Controlled Trials as Topic, Psilocybin

topic_tags:
Depression,Clinical Trial,Randomized Controlled Trial,Meta-Analysis,Systematic Review,Review Article,Healthcare Workers,Safety

raw_json:
{"europe_pmc_id":"38692686","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin for depression.
authors: De Giorgi R, Ede R.
publication_date: 2024-04-30
doi: 10.1136/bmj.q798
pubmed_id: 38692675
source_url: https://doi.org/10.1136/bmj.q798
keywords: Humans, Hallucinogens, Depressive Disorder, Psilocybin
substance_tags: psilocybin
topic_tags: Depression
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:03
raw_json:
{"europe_pmc_id":"38692675","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Zhao X, Du Y, Yao Y, Dai W, Yin Y, Wang G, Li Y, Zhang L.
publication_date: 2024-04-27
doi: 10.1177/02698811241249436
pubmed_id: 38680011
source_url: https://doi.org/10.1177/02698811241249436
substance_tags: psilocybin
topic_tags: Depression,Neuroplasticity,Neurogenesis,Mechanism of Action,Animal Study
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Psilocybin promotes neuroplasticity and induces rapid and sustained antidepressant-like effects in mice.

abstract:
BackgroundPsilocybin offers new hope for treating mood disorders due to its rapid and sustained antidepressant effects, as standard medications require weeks or months to exert their effects. However, the mechanisms underlying this action of psilocybin have not been identified.AimsTo investigate whether psilocybin has rapid and sustained antidepressant-like effects in mice and investigate whether its potential mechanisms of action are related to promoted neuroplasticity.MethodsWe first examined the antidepressant-like effects of psilocybin in normal mice by the forced swimming test and in chronic corticosterone (CORT)-exposed mice by the sucrose preference test and novelty-suppressed feeding test. Furthermore, to explore the role of neuroplasticity in mediating the antidepressant-like effects of psilocybin, we measured structural neuroplasticity and neuroplasticity-associated protein levels in the prefrontal cortex (PFC) and hippocampus.ResultsWe observed that a single dose of psilocybin had rapid and sustained antidepressant-like effects in both healthy mice and chronic CORT-exposed mice. Moreover, psilocybin ameliorated chronic CORT exposure-induced inhibition of neuroplasticity in the PFC and hippocampus, including by increasing neuroplasticity (total number of dendritic branches and dendritic spine density), synaptic protein (p-GluA1, PSD95 and synapsin-1) levels, BDNF-mTOR signalling pathway activation (BDNF, TrkB and mTOR levels), and promoting neurogenesis (number of DCX-positive cells).ConclusionsOur results demonstrate that psilocybin elicits robust, rapid and sustained antidepressant-like effects which is accompanied by the promotion of neuroplasticity in the PFC and hippocampus.

keywords:
Hippocampus, Prefrontal Cortex, Animals, Mice, Inbred C57BL, Mice, Disease Models, Animal, Corticosterone, Brain-Derived Neurotrophic Factor, Antidepressive Agents, Behavior, Animal, Depression, Neuronal Plasticity, Male, TOR Serine-Threonine Kinases, Psilocybin, Doublecortin Protein

raw_json:
{"europe_pmc_id":"38680011","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psychedelics and the 'inner healer': Myth or mechanism?
authors: Peill J, Marguilho M, Erritzoe D, Barba T, Greenway KT, Rosas F, Timmermann C, Carhart-Harris R.
publication_date: 2024-04-11
doi: 10.1177/02698811241239206
pubmed_id: 38605658
source_url: https://doi.org/10.1177/02698811241239206
substance_tags: psilocybin
topic_tags: Depression,Mechanism of Action,Randomized Controlled Trial
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:03
abstract:
BackgroundReference to an intrinsic healing mechanism or an 'inner healer' is commonplace amongst psychedelic drug-using cultures. The 'inner healer' refers to the belief that psychedelic compounds, plants or concoctions have an intrinsically regenerative action on the mind and brain, analogous to intrinsic healing mechanisms within the physical body, for example, after sickness or injury.AimsHere, we sought to test and critique this idea by devising a single subjective rating item pertaining to perceived 'inner healing' effects.MethodsThe item was issued to 59 patients after a single high (25 mg, n = 30) or 'placebo' (1 mg, n = 29) dose of psilocybin in a double-blind randomised controlled trial of psilocybin for depression.ResultsInner healer scores were higher after the high versus placebo dose of psilocybin (t = 3.88, p

keywords:
Humans, Hallucinogens, Double-Blind Method, Depression, Dose-Response Relationship, Drug, Adult, Middle Aged, Female, Male, Young Adult, Psilocybin

raw_json:
{"europe_pmc_id":"38605658","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Safety and risk assessment of psychedelic psychotherapy: A meta-analysis and systematic review.
authors: Romeo B, Kervadec E, Fauvel B, Strika-Bruneau L, Amirouche A, Verroust V, Piolino P, Benyamina A
journal: Psychiatry research
publication_date: 2024-04-30
doi: 10.1016/j.psychres.2024.115880
pubmed_id: 38579460
source_url: https://pubmed.ncbi.nlm.nih.gov/38579460/
keywords: Adverse events, LSD, Meta-analysis, Psilocybin, Psychedelic, Side effects
substance_tags: psilocybin
topic_tags: Anxiety,Headache / Migraine,Meta-Analysis,Systematic Review,Review Article,Safety,Adverse Events
study_type: Meta-Analysis
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:37
raw_json: {"pubmed_id":"38579460"}
abstract:
Psychotherapies assisted by psychedelic substances have shown promising results in the treatment of psychiatric disorders. The aim of this systematic review and meta-analysis was to evaluate safety data in human subjects. We carried out a search on MEDLINE, Embase and PsycINFO databases between 2000 and 2022. Standardized mean differences between different dose ranges and between acute and subacute phases were calculated for cardiovascular data after psychedelic administration. Risk differences were calculated for serious adverse events and common side effects. Thirty studies were included in this meta-analysis. There were only nine serious adverse events for over 1000 administrations of psychedelic substances (one during the acute phase and 8 during the post-acute phase). There were no suicide attempts during the acute phase and 3 participants engaged in self-harm during the post-acute phase. There was an increased risk for elevated heart rate, systolic and diastolic blood pressure for all dose range categories, as well as an increased risk of nausea during the acute phase. Other common side effects included headaches, anxiety, and decreased concentration or appetite. This meta-analysis demonstrates that psychedelics are well-tolerated, with a low risk of emerging serious adverse events in a controlled setting with appropriate inclusion criteria.


publication_date: 2024-03-27
doi: 10.1016/j.psychres.2024.115886
pubmed_id: 38574699
source_url: https://doi.org/10.1016/j.psychres.2024.115886
substance_tags: psilocybin
study_type: Meta-Analysis
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:03
title:
Efficacy and safety of psychedelics for the treatment of mental disorders: A systematic review and meta-analysis.

authors:
Yao Y, Guo D, Lu TS, Liu FL, Huang SH, Diao MQ, Li SX, Zhang XJ, Kosten TR, Shi J, Bao YP, Lu L, Han Y.

abstract:
We aim to systematically review and meta-analyze the effectiveness and safety of psychedelics [psilocybin, ayahuasca (active component DMT), LSD and MDMA] in treating symptoms of various mental disorders. Web of Science, Embase, EBSCO, and PubMed were searched up to February 2024 and 126 articles were finally included. Results showed that psilocybin has the largest number of articles on treating mood disorders (N = 28), followed by ayahuasca (N = 7) and LSD (N = 6). Overall, psychedelics have therapeutic effects on mental disorders such as depression and anxiety. Specifically, psilocybin (Hedges' g = -1.49, 95% CI [-1.67, -1.30]) showed the strongest therapeutic effect among four psychedelics, followed by ayahuasca (Hedges' g = -1.34, 95% CI [-1.86, -0.82]), MDMA (Hedges' g = -0.83, 95% CI [-1.33, -0.32]), and LSD (Hedges' g = -0.65, 95% CI [-1.03, -0.27]). A small amount of evidence also supports psychedelics improving tobacco addiction, eating disorders, sleep disorders, borderline personality disorder, obsessive-compulsive disorder, and body dysmorphic disorder. The most common adverse event with psychedelics was headache. Nearly a third of the articles reported that no participants reported lasting adverse effects. Our analyses suggest that psychedelics reduce negative mood, and have potential efficacy in other mental disorders, such as substance-use disorders and PTSD.

keywords:
Humans, Banisteriopsis, N-Methyl-3,4-methylenedioxyamphetamine, Lysergic Acid Diethylamide, Hallucinogens, Mental Disorders, Psilocybin

topic_tags:
Depression,Anxiety,PTSD,Addiction,OCD,Eating Disorders,Headache / Migraine,Personality Change,Meta-Analysis,Systematic Review,Review Article,Safety,Adverse Events

raw_json:
{"europe_pmc_id":"38574699","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Erritzoe D, Barba T, Spriggs MJ, Rosas FE, Nutt DJ, Carhart-Harris R.
publication_date: 2024-03-21
doi: 10.1177/02698811241237870
pubmed_id: 38520045
source_url: https://doi.org/10.1177/02698811241237870
substance_tags: psilocybin
topic_tags: Depression,Receptor Pharmacology,Wellbeing,Clinical Trial,Safety,Drug Interactions
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Effects of discontinuation of serotonergic antidepressants prior to psilocybin therapy versus escitalopram for major depression.

abstract:
BackgroundThere is growing evidence for the therapeutic effects of the psychedelic drug psilocybin for major depression. However, due to the lack of safety data on combining psilocybin with selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) and concerns that there may be a negative interaction on efficacy, participants enrolling in psychedelic trials are usually required to discontinue SNRI/SNRIs prior to enrolling.AimsUsing data from a recent clinical trial examining the comparative efficacy the psychedelic drug psilocybin (P) combined with approximately 20 h of psychological support to a 6-week (daily) course of the SSRI escitalopram plus matched psychological support for major depressive disorder, we explored the effects of discontinuing SSRI/SNRIs prior to study enrolment on study outcomes.MethodsExploratory post hoc analyses using linear mixed effects model were performed to investigate the discontinuation effect on various validated depression symptom severity scales and well-being. The impact of SSRI/SNRIs discontinuation on the acute psychedelic experience was also explored.Results/outcomesIn the psilocybin group, there was a reduced treatment effect on all outcome measures for SSRI/SNRIs discontinuers compared with unmedicated patients at trial entry. However, no effects of discontinuation on measures of the acute psychedelic experience were found.ConclusionDiscontinuation of SSRI/SNRIs before psilocybin might diminish response to treatment; however, as we did not test SSRI/SNRI continuation in our trial, we cannot infer such causation. Moreover, the exploratory nature of the analyses makes them hypothesis generating, and not confirmatory. A controlled trial of SSRI/SNRI discontinuation versus continuation prior to psilocybin is urgently required.

keywords:
Humans, Hallucinogens, Treatment Outcome, Drug Therapy, Combination, Adult, Middle Aged, Female, Male, Psilocybin, Escitalopram, Selective Serotonin Reuptake Inhibitors, Major Depressive Disorder

raw_json:
{"europe_pmc_id":"38520045","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin Exposures Reported to U.S. Poison Centers: National Trends Over a Decade.
authors: Farah R, Kerns AF, Murray AC, Holstege CP.
publication_date: 2024-02-25
doi: 10.1016/j.jadohealth.2024.01.027
pubmed_id: 38416101
source_url: https://doi.org/10.1016/j.jadohealth.2024.01.027
substance_tags: psilocybin
topic_tags: Adolescents
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
abstract:
PurposeWe describe trends in psilocybin exposures among adolescents and young adults as reported to US poison centers over the past decade.MethodsWe queried the National Poison Data System for cases involving psilocybin during January 1, 2013-December 31, 2022. Persons aged 13-25 years were included. We examined exposures to psilocybin by demographics, clinical effects, level of care, and medical outcome.ResultsDuring the 10-year study period, 4,055 psilocybin-involved exposures were reported among adolescents and young adults, 2,667 (65.8%) being single substance exposures. Most single substance cases received medical attention (adolescents: 75.3% [n = 1,176], young adults: 72.1% [n = 797]). We did not find significant change in the number of cases during 2013-2018. Cases started increasing in 2019. In 2022, cases more than tripled among adolescents and more than doubled among young adults, compared to 2018 (p <.0001).DiscussionContinued national surveillance is critical to determine the impact of psilocybin exposures on youth as it becomes increasingly available.

keywords:
Humans, Poisons, Databases, Factual, Adolescent, Poison Control Centers, United States, Young Adult, Psilocybin

raw_json:
{"europe_pmc_id":"38416101","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Expectancy Effects in Psychedelic Trials.
authors: Szigeti B, Heifets BD.
publication_date: 2024-02-19
doi: 10.1016/j.bpsc.2024.02.004
pubmed_id: 38387698
source_url: https://doi.org/10.1016/j.bpsc.2024.02.004
keywords: Humans, Hallucinogens, Placebo Effect, Clinical Trials as Topic, Anticipation, Psychological
substance_tags: psilocybin
topic_tags: Clinical Trial,Review Article
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
abstract:
Clinical trials of psychedelic compounds like psilocybin, lysergic acid diethylamide (LSD), and N,N-dimethyltrptamine (DMT) have forced a reconsideration of how nondrug factors, such as participant expectations, are measured and controlled in mental health research. As doses of these profoundly psychoactive substances increase, so does the difficulty in concealing the treatment condition in the classic double-blind, placebo-controlled trial design. As widespread public enthusiasm for the promise of psychedelic therapy grows, so do questions regarding whether and how much trial results are biased by positive expectancy. First, we review the key concepts related to expectancy and its measurement. Then, we review expectancy effects that have been reported in both micro- and macrodose psychedelic trials from the modern era. Finally, we consider expectancy as a discrete physiological process that can be independent of, or even interact with, the drug effect. Expectancy effects can be harnessed to improve treatment outcomes and can also be actively managed in controlled studies to enhance the rigor and generalizability of future psychedelic trials.

raw_json:
{"europe_pmc_id":"38387698","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Shafiee A, Arabzadeh Bahri R, Rafiei MA, Esmaeilpur Abianeh F, Razmara P, Jafarabady K, Amini MJ
journal: Journal of psychopharmacology (Oxford, England)
publication_date: 2024-04-30
doi: 10.1177/02698811241234247
pubmed_id: 38385351
source_url: https://pubmed.ncbi.nlm.nih.gov/38385351/
keywords: BDNF, LSD, MDMA, Psychedelics, brain-derived neurotrophic factor, psilocybin
substance_tags: psilocybin
topic_tags: Neuroplasticity,Mechanism of Action,Meta-Analysis,Systematic Review,Review Article
study_type: Meta-Analysis
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:37
raw_json: {"pubmed_id":"38385351"}
title:
The effect of psychedelics on the level of brain-derived neurotrophic factor: A systematic review and meta-analysis.

abstract:
Recent interest in the potential therapeutic effects of psychedelics has led to investigations into their influence on molecular signaling pathways within the brain.
Integrated review and analysis of different studies in this field.
A systematic search was conducted across international databases including Embase, Scopus, Web of Science, and PubMed from inception to 9 July 2023. Eligibility criteria encompassed published and peer-reviewed studies evaluating changes in brain-derived neurotrophic factor (BDNF) levels after psychedelic consumption.
A total of nine studies were included in our study. The meta-analysis demonstrated significantly higher BDNF levels in psychedelic consumers compared to healthy controls, with a pooled standardized mean difference of 0.26 (95% CI: 0.10-0.42, = 38.51%,
More precisely, the documented rise in BDNF levels indicates a neurobiological mechanism by which psychedelics could enhance synaptic plasticity and foster the growth of neurons. Given the limited data available on this topic, the conclusions remain uncertain. Consequently, we highly recommend additional research with more extensive sample sizes to yield more reliable evidence in this field.


authors: Schmid Y, Bershad AK
journal: Biological psychiatry. Cognitive neuroscience and neuroimaging
publication_date: 2024-04-30
doi: 10.1016/j.bpsc.2024.02.001
pubmed_id: 38341085
source_url: https://pubmed.ncbi.nlm.nih.gov/38341085/
substance_tags: psilocybin
topic_tags: Neuroplasticity,Mechanism of Action,Mystical Experience,Animal Study
study_type: Animal Study
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:37
raw_json: {"pubmed_id":"38341085"}
title:
Altered States and Social Bonds: Effects of MDMA and Serotonergic Psychedelics on Social Behavior as a Mechanism Underlying Substance-Assisted Therapy.

abstract:
There has been renewed interest in the use of 3,4-methylenedioxy-methamphetamine (MDMA) and serotonergic psychedelics in the treatment of multiple psychiatric disorders. Many of these compounds are known to produce prosocial effects, but how these effects relate to therapeutic efficacy and the extent to which prosocial effects are unique to a particular drug class is unknown. In this article, we present a narrative overview and compare evidence for the prosocial effects of MDMA and serotonergic psychedelics to elucidate shared mechanisms that may underlie the therapeutic process. We discuss 4 categories of prosocial effects: altered self-image, responses to social reward, responses to negative social input, and social neuroplasticity. While both categories of drugs alter self-perception, MDMA may do so in a way that is less related to the experience of mystical-type states than serotonergic psychedelics. In the case of social reward, evidence supports the ability of MDMA to enhance responses and suggests that serotonergic psychedelics may also do so, but more research is needed in this area. Both drug classes consistently dampen reactivity to negative social stimuli. Finally, preclinical evidence supports the ability of both drug classes to induce social neuroplasticity, promoting adaptive rewiring of neural circuits, which may be helpful in trauma processing. While both MDMA and serotonergic psychedelics produce prosocial effects, they differ in the mechanisms through which they do this. These differences affect the types of psychosocial interventions that may work best with each compound.

keywords:
3,4-methylenedioxy-methamphetamine (MDMA), Lysergic acid diethylamide (LSD), Psilocybin, Psychedelic-assisted therapy, Psychedelics, Social behavior, Social processing


title: National and regional trends in seizures of shrooms (psilocybin) in the United States, 2017-2022.
authors: Palamar JJ, Fitzgerald ND, Carr TH, Rutherford C, Keyes KM, Cottler LB.
publication_date: 2024-02-05
doi: 10.1016/j.drugalcdep.2024.111086
pubmed_id: 38326175
source_url: https://doi.org/10.1016/j.drugalcdep.2024.111086
keywords: Humans, Hallucinogens, United States, Psilocybin
substance_tags: psilocybin
topic_tags: General
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
abstract:
BackgroundPsilocybin, the principle psychoactive component in "shrooms", is regaining acceptance in therapeutic settings, leading to media coverage of medical benefits associated with use. Possession is also becoming increasingly decriminalized throughout the United States. There is a lack of data on prevalence of shroom use, but trends in law enforcement seizure data can provide one indicator of shroom availability in US communities. We determined whether seizures of shrooms have shifted between 2017 and 2022.MethodsThis study examined national and regional trends in counts and total weight of shroom seizures reported to High Intensity Drug Trafficking Areas in the US between 2017 and 2022 (N=4526).ResultsThere were 402 seizures in 2017 compared to 1396 in 2022 with the plurality occurring in the Midwest (36.0%), followed by the West (33.5%). Between 2017 Quarter 1 (Q1) and 2022 Quarter 4 (Q4), the number of seizures increased by 368.9% (AQPC=7.0; 95 CI: 5.9-8.1) and there were significant increases in all four regions. In terms of weight, 226.0kg was seized in 2017 vs. 844.0kg in 2022, and the greatest total weight in seizures was in the West (1864.2kg, 42.6%), followed by the South (1831.9kg, 41.8%). Between 2017 Q1 and 2022 Q4, the total weight seized in the US increased by 2749.7% (AQPC=6.2, 95% CI: 0.3-12.4) and there were significant increases in all four regions.ConclusionsSeizures of shrooms have increased, suggesting that availability may be escalating; thus, increases in prevention efforts and harm reduction education are warranted.

raw_json:
{"europe_pmc_id":"38326175","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Holze F, Singh N, Liechti ME, D'Souza DC.
publication_date: 2024-01-31
doi: 10.1016/j.bpsc.2024.01.007
pubmed_id: 38301886
source_url: https://doi.org/10.1016/j.bpsc.2024.01.007
keywords: Humans, Lysergic Acid Diethylamide, Hallucinogens, Serotonin 5-HT2 Receptor Agonists, Psilocybin
substance_tags: psilocybin
topic_tags: Depression,Pharmacology,Receptor Pharmacology,Review Article,Safety
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:03
title:
Serotonergic Psychedelics: A Comparative Review of Efficacy, Safety, Pharmacokinetics, and Binding Profile.

abstract:
Psychedelic compounds, including psilocybin, LSD (lysergic acid diethylamide), DMT (N,N -dimethyltryptamine), and 5-MeO-DMT (5-methoxy-N,N-dimethyltryptamine), all of which are serotonin 2A receptor agonists, are being investigated as potential treatments. This review aims to summarize the current clinical research on these 4 compounds and mescaline to guide future research. Their mechanism(s) of action, pharmacokinetics, pharmacodynamics, efficacy, and safety were reviewed. While evidence for therapeutic indications, with the exception of psilocybin for depression, is still relatively scarce, we noted no differences in psychedelic effects beyond effect duration. Therefore, it remains unclear whether different receptor profiles contribute to the therapeutic potential of these compounds. More research is needed to differentiate these compounds in order to inform which compounds might be best for different therapeutic uses.

raw_json:
{"europe_pmc_id":"38301886","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: A Brief Historical Overview of Psychedelic Research.
authors: Geyer MA.
publication_date: 2023-11-22
doi: 10.1016/j.bpsc.2023.11.003
pubmed_id: 38000715
source_url: https://doi.org/10.1016/j.bpsc.2023.11.003
substance_tags: psilocybin
topic_tags: Mechanism of Action,Receptor Pharmacology,Mystical Experience,Animal Study
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
abstract:
Classical serotonergic psychedelics such as lysergic acid diethylamide or the naturally occurring compounds psilocybin and mescaline produce profound changes in mood, thought, intuition, sensory perception, the experience of time and space, and even the experience of self. Research examining psychedelic compounds has had a complex and turbulent evolution. Many cultures throughout the world have used psychedelic plants not only for mystical, ritualistic, or divinatory purposes but also for curing illnesses. Much of the genesis and progress of modern investigations into the effects and underlying mechanisms of action of psychedelics have been intertwined with studies of the neurotransmitter serotonin. Early hypotheses that serotonergic systems mediate psychedelic effects were supported initially by preclinical animal studies and subsequently confirmed by pharmacological studies in healthy humans. The use of psychedelic compounds as putative psychotomimetics that reproduce some features of naturally occurring psychotic disorders met with some limited success. More recent studies are exploring psychedelics as potential psychotherapeutic agents. Recent indications that even 1 or 2 psychedelic treatments produce robust and sustained reductions in clinical symptoms in a variety of psychiatric disorders have prompted an enormous resurgence of interest in the nature and mechanisms contributing to their effects.

keywords:
Animals, Humans, Serotonin, Lysergic Acid Diethylamide, Hallucinogens, History, 19th Century, History, 20th Century, History, 21st Century, Psilocybin

raw_json:
{"europe_pmc_id":"38000715","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


journal: Research Square
publication_date: 2023-07-06
doi: 10.21203/rs.3.rs-3138705/v1
source_url: https://doi.org/10.21203/rs.3.rs-3138705/v1
substance_tags: psilocybin,psilocin
topic_tags: Depression,Anxiety,Receptor Pharmacology,Animal Study
study_type: Animal Study
source_name: Europe PMC
publication_status: preprint
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Ethopharmacological evaluation of antidepressant-like effect of serotonergic psychedelics in C57BL/6J male mice

authors:
Takaba R, Ibi D, Yoshida K, Hosomi E, Kawase R, Kitagawa H, Goto H, Achiwa M, Mizutani K, Maede K, González-Maeso J, Kitagaki S, Hiramatsu M.

abstract:
Serotonergic psychedelics such as psilocybin, lysergic acid diethylamide, and DOI exert a hallucinatory effect through serotonin 5-HT2A receptor (5-HT2A) activation. Recent studies have revealed that serotonergic psychedelics have therapeutic potential for neuropsychiatric disorders, including major depressive and anxiety-related disorders. However, the involvement of 5-HT2A in mediating the therapeutic effects of these drugs remains unclear. In this study, we ethopharmacologically analyzed the role of 5-HT2A in the occurrence of anxiolytic-and antidepressant-like effects of serotonergic psychedelics such as psilocin, an active metabolite of psilocybin, DOI, and TCB-2 in mice. Mice with acute intraperitoneal psychedelic treatment exhibited significantly shorter immobility times in the forced swimming test (FST) and tail-suspension test (TST) than vehicle-treated control mice 24 h post-treatment. These effects were eliminated by pretreatment with volinanserin, a 5-HT2A antagonist. Surprisingly, the decreasing immobility time in the FST in response to acute psilocin treatment was sustained for at least three weeks. In the novelty-suppressed feeding test (NSFT), the latency to feed, an indicator of anxiety-like behavior, was decreased by acute administration of psilocin; however, pretreatment with volinanserin did not diminish this effect. In contrast, DOI and TCB-2 did not affect the NSFT performance in mice. Furthermore, psilocin, DOI, and TCB-2 treatment did not affect the spontaneous locomotor activity or head-twitch response, a hallucination-like behavior in rodents. These results suggest that 5-HT2A contributes to the antidepressant effects of serotonergic psychedelics rather than an anxiolytic effects.

raw_json:
{"europe_pmc_id":"PPR688165","source":"PPR","pub_type":null,"publisher":"Research Square","importer":"Europe PMC"}


title: Comparing Neural Correlates of Consciousness: From Psychedelics to Hypnosis and Meditation.
publication_date: 2023-07-16
doi: 10.1016/j.bpsc.2023.07.003
pubmed_id: 37459910
source_url: https://doi.org/10.1016/j.bpsc.2023.07.003
substance_tags: psilocybin
topic_tags: Brain Imaging,Mechanism of Action,Consciousness,Aging
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
authors:
Moujaes F, Rieser NM, Phillips C, de Matos NMP, Brügger M, Dürler P, Smigielski L, Stämpfli P, Seifritz E, Vollenweider FX, Anticevic A, Preller KH.

abstract:
BackgroundPharmacological and nonpharmacological methods of inducing altered states of consciousness (ASCs) are becoming increasingly relevant in the treatment of psychiatric disorders. While comparisons between them are often drawn, to date no study has directly compared their neural correlates.MethodsTo address this knowledge gap, we directly compared 2 pharmacological methods (psilocybin 0.2 mg/kg orally [n = 23] and lysergic acid diethylamide [LSD] 100 μg orally [n = 25]) and 2 nonpharmacological methods (hypnosis [n = 30] and meditation [n = 29]) using resting-state functional connectivity magnetic resonance imaging and assessed the predictive value of the data using a machine learning approach.ResultsWe found that 1) no network reached significance in all 4 ASC methods; 2) pharmacological and nonpharmacological interventions of inducing ASCs showed distinct connectivity patterns that were predictive at the individual level; 3) hypnosis and meditation showed differences in functional connectivity when compared directly and also drove distinct differences when jointly compared with the pharmacological ASC interventions; and 4) psilocybin and LSD showed no differences in functional connectivity when directly compared with each other, but they did show distinct behavioral-neural relationships.ConclusionsOverall, these results extend our understanding of the mechanisms of action of ASCs and highlight the importance of exploring how these effects can be leveraged in the treatment of psychiatric disorders.

keywords:
Brain, Humans, Lysergic Acid Diethylamide, Hallucinogens, Magnetic Resonance Imaging, Hypnosis, Meditation, Consciousness, Adult, Female, Male, Young Adult, Connectome, Machine Learning, Psilocybin

raw_json:
{"europe_pmc_id":"37459910","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: In vitro and in vivo metabolism of psilocybin's active metabolite psilocin.
publication_date: 2024-04-28
doi: 10.3389/fphar.2024.1391689
pubmed_id: 38741590
source_url: https://doi.org/10.3389/fphar.2024.1391689
substance_tags: psilocybin,psilocin
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:00
authors:
Thomann J, Kolaczynska KE, Stoeckmann OV, Rudin D, Vizeli P, Hoener MC, Pryce CR, Vollenweider FX, Liechti ME, Duthaler U.

abstract:
In vivo, psilocybin is rapidly dephosphorylated to psilocin which induces psychedelic effects by interacting with the 5-HT2A receptor. Psilocin primarily undergoes glucuronidation or conversion to 4-hydroxyindole-3-acetic acid (4-HIAA). Herein, we investigated psilocybin's metabolic pathways in vitro and in vivo, conducting a thorough analysis of the enzymes involved. Metabolism studies were performed using human liver microsomes (HLM), cytochrome P450 (CYP) enzymes, monoamine oxidase (MAO), and UDP-glucuronosyltransferase (UGT). In vivo, metabolism was examined using male C57BL/6J mice and human plasma samples. Approximately 29% of psilocin was metabolized by HLM, while recombinant CYP2D6 and CYP3A4 enzymes metabolized nearly 100% and 40% of psilocin, respectively. Notably, 4-HIAA and 4-hydroxytryptophol (4-HTP) were detected with HLM but not with recombinant CYPs. MAO-A transformed psilocin into minimal amounts of 4-HIAA and 4-HTP. 4-HTP was only present in vitro. Neither 4-HIAA nor 4-HTP showed relevant interactions at assessed 5-HT receptors. In contrast to in vivo data, UGT1A10 did not extensively metabolize psilocin in vitro. Furthermore, two putative metabolites were observed. N-methyl-4-hydroxytryptamine (norpsilocin) was identified in vitro (CYP2D6) and in mice, while an oxidized metabolite was detected in vitro (CYP2D6) and in humans. However, the CYP2D6 genotype did not influence psilocin plasma concentrations in the investigated study population. In conclusion, MAO-A, CYP2D6, and CYP3A4 are involved in psilocin's metabolism. The discovery of putative norpsilocin in mice and oxidized psilocin in humans further unravels psilocin's metabolism. Despite limitations in replicating phase II metabolism in vitro, these findings hold significance for studying drug-drug interactions and advancing research on psilocybin as a therapeutic agent.

topic_tags:
Pharmacology,Mechanism of Action,Receptor Pharmacology,Clinical Trial,Animal Study,In Vitro Study,Drug Interactions

raw_json:
{"europe_pmc_id":"38741590","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Review of Psilocybin Use for Depression among Cancer Patients after Approval in Oregon.
authors: Bellman V.
publication_date: 2024-04-26
doi: 10.3390/cancers16091702
pubmed_id: 38730654
source_url: https://doi.org/10.3390/cancers16091702
substance_tags: psilocybin
topic_tags: Depression,End-of-Life Distress,Review Article,Cancer Patients
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
abstract:
Despite the legalization of psilocybin therapy for depression in terminal illnesses such as advanced cancer through Oregon's Measure 109 in 2020, significant challenges have impeded its implementation. This review synthesizes the empirical data supporting the utilization of psilocybin therapy for addressing cancer-related depression, including an evaluation of its purported benefits and potential adverse effects. It provides a comprehensive examination of therapeutic strategies, dosing regimens, and barriers to ensuring responsible and equitable access. Salient issues explored include the development of ethical protocols, integration within healthcare systems, ensuring statewide availability, resolving legal ambiguities, and defining clinical standards. Oregon's pioneering role serves as a case study, highlighting the necessity of addressing regulatory, logistical, and ethical obstacles to ensure the establishment of rigorous and equitable psilocybin care models.

raw_json:
{"europe_pmc_id":"38730654","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Seibold PS, Dörner S, Fricke J, Schäfer T, Beemelmanns C, Hoffmeister D.
publication_date: 2024-04-24
doi: 10.1186/s40694-024-00173-6
pubmed_id: 38664850
source_url: https://doi.org/10.1186/s40694-024-00173-6
substance_tags: psilocybin
topic_tags: Pharmacology,Mechanism of Action,In Vitro Study,Transcriptomics
study_type: In Vitro Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Genetic regulation of L-tryptophan metabolism in Psilocybe mexicana supports psilocybin biosynthesis.

abstract:
BackgroundAlthough Basidiomycota produce pharmaceutically and ecologically relevant natural products, knowledge of how they coordinate their primary and secondary metabolism is virtually non-existent. Upon transition from vegetative mycelium to carpophore formation, mushrooms of the genus Psilocybe use L-tryptophan to supply the biosynthesis of the psychedelic tryptamine alkaloid psilocybin with the scaffold, leading to a strongly increased demand for this particular amino acid as this alkaloid may account for up to 2% of the dry mass. Using Psilocybe mexicana as our model and relying on genetic, transcriptomic, and biochemical methods, this study investigated if L-tryptophan biosynthesis and degradation in P. mexicana correlate with natural product formation.ResultsA comparative transcriptomic approach of gene expression in P. mexicana psilocybin non-producing vegetative mycelium versus producing carpophores identified the upregulation of L-tryptophan biosynthesis genes. The shikimate pathway genes trpE1, trpD, and trpB (encoding anthranilate synthase, anthranilate phosphoribosyltransferase, and L-tryptophan synthase, respectively) were upregulated in carpophores. In contrast, genes idoA and iasA, encoding indole-2,3-dioxygenase and indole-3-acetaldehyde synthase, i.e., gateway enzymes for L-tryptophan-consuming pathways, were massively downregulated. Subsequently, IasA was heterologously produced in Escherichia coli and biochemically characterized in vitro. This enzyme represents the first characterized microbial L-tryptophan-preferring acetaldehyde synthase. A comparison of transcriptomic data collected in this study with prior data of Psilocybe cubensis showed species-specific differences in how L-tryptophan metabolism genes are regulated, despite the close taxonomic relationship.ConclusionsThe upregulated L-tryptophan biosynthesis genes and, oppositely, the concomitant downregulated genes encoding L-tryptophan-consuming enzymes reflect a well-adjusted cellular system to route this amino acid toward psilocybin production. Our study has pilot character beyond the genus Psilocybe and provides, for the first time, insight in the coordination of mushroom primary and secondary metabolism.

raw_json:
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publication_date: 2024-04-24
doi: 10.1186/s12888-024-05768-2
pubmed_id: 38658877
source_url: https://doi.org/10.1186/s12888-024-05768-2
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
The 'PSILAUT' protocol: an experimental medicine study of autistic differences in the function of brain serotonin targets of psilocybin.

authors:
Whelan TP, Daly E, Puts NA, Smith P, Allison C, Baron-Cohen S, Malievskaia E, Murphy DGM, McAlonan GM.

abstract:
BackgroundThe underlying neurobiology of the complex autism phenotype remains obscure, although accumulating evidence implicates the serotonin system and especially the 5HT2A receptor. However, previous research has largely relied upon association or correlation studies to link differences in serotonin targets to autism. To directly establish that serotonergic signalling is involved in a candidate brain function our approach is to change it and observe a shift in that function. We will use psilocybin as a pharmacological probe of the serotonin system in vivo. We will directly test the hypothesis that serotonergic targets of psilocybin - principally, but not exclusively, 5HT2A receptor pathways-function differently in autistic and non-autistic adults.MethodsThe 'PSILAUT' "shiftability" study is a case-control study autistic and non-autistic adults. How neural responses 'shift' in response to low doses (2 mg and 5 mg) of psilocybin compared to placebo will be examined using multimodal techniques including functional MRI and EEG. Each participant will attend on up to three separate visits with drug or placebo administration in a double-blind and randomized order.ResultsThis study will provide the first direct evidence that the serotonin targets of psilocybin function differently in the autistic and non-autistic brain. We will also examine individual differences in serotonin system function.ConclusionsThis work will inform our understanding of the neurobiology of autism as well as decisions about future clinical trials of psilocybin and/or related compounds including stratification approaches.Trial registrationNCT05651126.

keywords:
Brain, Humans, Serotonin, Receptor, Serotonin, 5-HT2A, Hallucinogens, Magnetic Resonance Imaging, Electroencephalography, Case-Control Studies, Double-Blind Method, Autistic Disorder, Adolescent, Adult, Female, Male, Randomized Controlled Trials as Topic, Young Adult, Psilocybin

topic_tags:
Brain Imaging,Mechanism of Action,Receptor Pharmacology,Aging,Clinical Trial,Randomized Controlled Trial,Adolescents

raw_json:
{"europe_pmc_id":"38658877","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Downey AE, Chaphekar AV, Woolley J, Raymond-Flesch M.
publication_date: 2024-04-23
doi: 10.1186/s40337-024-01005-z
pubmed_id: 38659049
source_url: https://doi.org/10.1186/s40337-024-01005-z
substance_tags: psilocybin
topic_tags: Eating Disorders,Headache / Migraine,Clinical Trial,Review Article,Healthcare Workers,Safety
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Psilocybin therapy and anorexia nervosa: a narrative review of safety considerations for researchers and clinicians.

abstract:
BackgroundClinical trials using psilocybin therapy to treat anorexia nervosa (AN) are currently underway. The safety and tolerability of psilocybin is of utmost importance in individuals with AN who may present unique medical vulnerabilities. The purpose of this review is to describe how the common physiologic adverse effects of psilocybin may impact medical complications experienced by individuals with AN in clinical trials of psilocybin therapy.Main bodyThe physiologic underpinnings of common adverse effects following psilocybin administration are described, including tachycardia, hypertension, electrocardiogram changes, nausea, headache, and lightheadedness. These anticipated physiologic changes are described in relation to the common medical correlates seen in individuals with AN. Risk mitigation strategies for each adverse effect are proposed.ConclusionEarly evidence suggests that psilocybin therapy is well-tolerated in individuals with AN. Understanding the unique medical complications of AN, and how they may be impacted by common physiologic adverse effects of psilocybin administration, leads to tailored risk mitigation strategies to enhance safety and tolerability of this novel intervention.

raw_json:
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publication_date: 2024-04-22
doi: 10.1038/s41598-024-59897-5
pubmed_id: 38654063
source_url: https://doi.org/10.1038/s41598-024-59897-5
substance_tags: psilocybin
topic_tags: Brain Imaging,Aging
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
title:
Author Correction: Psilocybin enhances insightfulness in meditation: a perspective on the global topology of brain imaging during meditation.

authors:
Singer B, Meling D, Hirsch-Hoffmann M, Michels L, Kometer M, Smigielski L, Dornbierer D, Seifritz E, Vollenweider FX, Scheidegger M.

raw_json:
{"europe_pmc_id":"38654063","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Wang JR, Mendez Araque SJ, Micciche G, McMillan A, Coughlin E, Mattiola R, English D, Kaliebe K.
publication_date: 2024-04-17
doi: 10.3389/fpsyt.2024.1301960
pubmed_id: 38699449
source_url: https://doi.org/10.3389/fpsyt.2024.1301960
substance_tags: psilocybin
topic_tags: Anxiety,End-of-Life Distress,Wellbeing,Observational Study,Healthcare Workers,Safety
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Palliative care patients' attitudes and openness towards psilocybin-assisted psychotherapy for existential distress.

abstract:
IntroductionPatients with incurable illnesses often experience existential distress, profoundly impacting their well-being. Current medical approaches have limitations in addressing these burdens. Psilocybin, a promising psychedelic compound, may offer therapeutic benefits. This pilot survey study aimed to investigate the attitudes and openness toward psilocybin-assisted psychotherapy (PAT) among patients with incurable illnesses. The objective is to assess patients' attitudes toward PAT and identify potential barriers and concerns, including exploring the association between beliefs in psilocybin's therapeutic benefits and interest in receiving this treatment.MethodsThe survey study was conducted at the Tampa General Hospital Palliative Care Outpatient office in the United States. Participants were 32 English-fluent patients, aged 18 or older, with incurable illnesses. The survey included demographic questions, a validated tool to measure existential distress, and questions about knowledge and concerns regarding psilocybin. Attitudes toward PAT and interest in its future use were assessed using Likert scale responses.ResultsAmong the 31 analyzed participants, 51.6% expressed interest in future psilocybin treatment, while 32.3% did not indicate interest. Belief in the psilocybin's therapeutic benefits for stress and anxiety significantly correlated with interest in use. Concerns included risk of psychosis, lack of trained providers, and potential for exploitation. No demographic factors were associated with interest or levels of distress.ConclusionsThis pilot study provides insights into the attitudes and concerns toward PAT among patients with incurable illnesses. Over half of participants expressed interest. However, concerns regarding its use were identified, with patients' concern for the risk of exploitation associated with PAT as an especially novel concern documented in this patient population. This highlighted the need for further education of risks and benefits or PAT by trained clinicians and rigorous training of clinicians with the establishment of safeguards against exploitation. Further research is necessary to explore the potential benefits of PAT and related non-psilocybin psychedelic compounds in addressing existential distress among patients with incurable illnesses.

raw_json:
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authors: Lerer E, Botvinnik A, Shahar O, Grad M, Blakolmer K, Shomron N, Lotan A, Lerer B, Lifschytz T.
publication_date: 2024-04-17
doi: 10.3389/fphar.2024.1391412
pubmed_id: 38698823
source_url: https://doi.org/10.3389/fphar.2024.1391412
substance_tags: psilocybin
topic_tags: Neuroplasticity,Receptor Pharmacology,Animal Study,Drug Interactions
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
title:
Effects of psilocybin, psychedelic mushroom extract and 5-hydroxytryptophan on brain immediate early gene expression: Interaction with serotonergic receptor modulators.

abstract:
Background: Immediate early genes (IEGs) are rapidly activated and initiate diverse cellular processes including neuroplasticity. We report the effect of psilocybin (PSIL), PSIL-containing psychedelic mushroom extract (PME) and 5-hydroxytryptophan (5-HTP) on expression of the IEGs, cfos, egr1, and egr2 in mouse somatosensory cortex (SSC). Methods: In our initial experiment, male C57Bl/6j mice were injected with PSIL4.4 mg/kg or 5-HTP200 mg/kg, alone or immediately preceded by serotonergic receptor modulators. IEG mRNA expression 1 hour later was determined by real time qPCR. In a replication study a group of mice treated with PME was added. Results: In our initial experiment, PSIL but not 5-HTP significantly increased expression of all three IEGs. No correlation was observed between the head twitch response (HTR) induced by PSIL and its effect on the IEGs. The serotonergic receptor modulators did not significantly alter PSIL-induced IEG expression, with the exception of the 5-HT2C antagonist (RS102221), which significantly enhanced PSIL-induced egr2 expression. 5-HTP did not affect IEG expression. In our replication experiment, PSIL and PME upregulated levels of egr1 and cfos while the upregulation of egr2 was not significant. Conclusions: We have shown that PSIL and PME but not 5-HTP (at a dose sufficient to induce HTR), induced a significant increase in cfos and egr1 expression in mouse SSC. Our findings suggest that egr1 and cfos expression may be associated with psychedelic effects.

raw_json:
{"europe_pmc_id":"38698823","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Sloshower J, Zeifman RJ, Guss J, Krause R, Safi-Aghdam H, Pathania S, Pittman B, D'Souza DC.
publication_date: 2024-04-16
doi: 10.1038/s41598-024-58318-x
pubmed_id: 38632313
source_url: https://doi.org/10.1038/s41598-024-58318-x
substance_tags: psilocybin
topic_tags: Depression,Mechanism of Action,Psychological Flexibility,Clinical Trial,Observational Study
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Psychological flexibility as a mechanism of change in psilocybin-assisted therapy for major depression: results from an exploratory placebo-controlled trial.

abstract:
Several phase II studies have demonstrated that psilocybin-assisted therapy shows therapeutic potential across a spectrum of neuropsychiatric conditions, including major depressive disorder (MDD). However, the mechanisms underlying its often persisting beneficial effects remain unclear. Observational research suggests that improvements in psychological flexibility may mediate therapeutic effects. However, no psychedelic trials to date have substantiated this finding in a clinical sample. In an exploratory placebo-controlled, within-subject, fixed-order study, individuals with moderate to severe MDD were administered placebo (n = 19) followed by psilocybin (0.3 mg/kg) (n = 15) 4 weeks later. Dosing sessions were embedded within a manualized psychotherapy that incorporated principles of Acceptance and Commitment Therapy. Depression severity, psychological flexibility, mindfulness, and values-congruent living were measured over a 16-weeks study period. Psychological flexibility, several facets of mindfulness, and values-congruent living significantly improved following psilocybin and were maintained through week 16. Additionally, improvements in psychological flexibility and experiential acceptance were strongly associated with reductions in depression severity following psilocybin. These findings support the theoretical premise of integrating psilocybin treatment with psychotherapeutic platforms that target psychological flexibility and add to emerging evidence that increasing psychological flexibility may be an important putative mechanism of change in psilocybin-assisted therapy for MDD and potentially, other mental health conditions.

keywords:
Humans, Hallucinogens, Depression, Acceptance and Commitment Therapy, Psilocybin, Major Depressive Disorder

raw_json:
{"europe_pmc_id":"38632313","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Norring SA, Spigarelli MG.
publication_date: 2024-04-09
doi: 10.2147/dddt.s443177
pubmed_id: 38618282
source_url: https://doi.org/10.2147/dddt.s443177
keywords: Humans, Hallucinogens, Research Design, Marketing, United States, Psilocybin, Drug Development
substance_tags: psilocybin
topic_tags: Clinical Trial,Observational Study
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
The Promise of Therapeutic Psilocybin: An Evaluation of the 134 Clinical Trials, 54 Potential Indications, and 0 Marketing Approvals on ClinicalTrials.gov.

abstract:
IntroductionPsilocybin, a tryptamine psychedelic, has been touted in the media both historically and recently as a potential game-changing mental health therapeutic. ClinicalTrials.gov has over one hundred and thirty psilocybin clinical trials listed covering the last twenty years. The single most important aspect of any therapeutic is to gain approval for marketing and thus enter the real-world phase of development. A typical new chemical entity progresses from inception to US Food and Drug Administration (FDA) approval in approximately 12 years and seeks approval for a single indication.MethodsAn observational study was conducted with the available information on the ClinicalTrials.gov site to observe the extent of progress made demonstrating the clinical utility of psilocybin.ResultsThe results showed 134 psilocybin trials typically unblinded studies of 10-20 participants, recruited over years at a single site. Additionally, there have been only three advanced trials (1 Phase 2/3 and 2 Phase 3) submitted, and only in the last two years.DiscussionThe hundreds of psilocybin clinical trials initiated over the past twenty years comprising a myriad of potential indications may actually be slowing this potential game-changing mental health therapeutic agent's approval and is costing excessive amounts of capital. To fully evaluate the actual potential of psilocybin, purposeful clinical trials need to be designed well, executed efficiently, and analyzed utilizing sequential and statistically valid processes for each potential indication. This will require a change from the current exploratory forays to defined, well-funded, sequential pharmaceutical development practices, including adequate and appropriate blinding of studies, statistical design to determine the number of participants and more importantly, professional expertise in conducting multicenter trials. Unfortunately, these results demonstrate little real progress towards FDA approval of psilocybin and a field with no clear direction forward.

raw_json:
{"europe_pmc_id":"38618282","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psychedelic Psychiatry
authors: Nutt D.
publication_date: 2022-08-31
source_url: https://europepmc.org/article/PMC/PMC9565852
substance_tags: psilocybin
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
abstract:
The last decade has seen a remarkable resurgence of interest in psychedelic drugs such as psilocybin (from magic mushrooms) LSD and DMT (dimethyl tryptamine - the active ingredient of ayahuasca). This has been driven by the discovery that these psychedelics all act agonists of 5-HT2A receptors. Human imaging studies have revealed this action leads to profound alterations in brain measures of activity particularly in terms of increased entropy of EEG MEG and fMRI signals and reduced within-network, but increased between-network, connectivity. In addition they all can increase synaptic growth and brain plasticity. These findings not only explain the subjective nature of the psychedelic experience but also have implications for the treatment of internalising disorders such as depression addiction anorexia and OCD that are characterised by increased within network connectivity especially of the default mode network. Subsequent trials, particularly of psilocybin, in these disorders has revealed significant clinical benefits from even just a single administration. A number of companies have now been set up to extend these discoveries with regulatory-level trials that could result in market authorisations within a few years. My talk will explore these brain mechanisms and clinical data and discuss the potential place of psychedelic medicine in the future of psychiatry. Disclosure I am an advisor to Compass pathways and Beckley Psytec two companies that are developing psychedelics for depression and other psychiatric indications. Several members of my research group receive support from these companies and also from Small Pharma.

topic_tags:
Depression,Addiction,OCD,Eating Disorders,Neuroplasticity,Brain Imaging,Mechanism of Action,Receptor Pharmacology,Default Mode Network,Aging

raw_json:
{"europe_pmc_id":"PMC9565852","source":"PMC","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Cultivation, chemistry, and genome of Psilocybe zapotecorum
authors: Miller DR, Jacobs JT, Rockefeller A, Singer H, Bollinger IM, Conway J, Slot JC, Cliffel DE.
journal: bioRxiv
publication_date: 2023-11-01
doi: 10.1101/2023.11.01.564784
source_url: https://doi.org/10.1101/2023.11.01.564784
substance_tags: psilocybin,psilocin
topic_tags: Genomics
study_type: Other
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
abstract:
Psilocybe zapotecorum is a strongly blue-bruising psilocybin mushroom used by indigenous groups in southeastern Mexico and beyond. While this species has a rich history of ceremonial use, research into its chemistry and genetics have been limited. Herein, we detail mushroom morphology and report on cultivation parameters, chemical profile, and the full genome sequence of P. zapotecorum. First, growth and cloning methods are detailed that are simple, and reproducible. In combination with high resolution microscopic analysis, the strain was barcoded, confirming species-level identification. Full genome sequencing reveals the architecture of the psilocybin gene cluster in P. zapotecorum, and can serve as a reference genome for Psilocybe Clade I. Characterization of the tryptamine profile revealed a psilocybin concentration of 17.9±1.7 mg/g, with a range of 10.6-25.7 mg/g (n=7), and similar tryptamines (psilocin, baeocystin, norbaeocystin, norpsilocin, aeruginascin, 4-HO-tryptamine, and tryptamine) in lesser concentrations for a combined tryptamine concentration of 22.5±3.2 mg/g. These results show P. zapotecorum to be a potent - and variable - Psilocybe mushroom. Chemical profiling, genetic analysis, and cultivation assist in demystifying these mushrooms. As clinical studies with psilocybin gain traction, understanding the diversity of psilocybin mushrooms will assure that psilocybin therapy does not become synonymous with psilocybin mushrooms.

raw_json:
{"europe_pmc_id":"PPR752679","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


authors: Wilkes R, Roberts DM, Liknaitzky P, Brett J.
publication_date: 2024-03-31
doi: 10.1080/15563650.2024.2346612
pubmed_id: 38753585
source_url: https://doi.org/10.1080/15563650.2024.2346612
substance_tags: psilocybin
topic_tags: Clinical Trial,Observational Study,Adolescents,Healthcare Workers,Safety,Toxicity
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
title:
The psychedelic call: analysis of Australian Poisons Information Centre calls associated with classic psychedelics.

abstract:
IntroductionThe global use of certain classical psychedelics has increased in recent years, but little is known about their spectrum of toxicity within Australia. We aim to describe calls to New South Wales Poisons Information Centre relating to exposures to classical psychedelics including lysergic acid diethylamide, psilocybin, N,N-dimethyltryptamine, ayahuasca, mescaline and ibogaine.MethodsThis is a retrospective observational study of calls to New South Wales Poisons Information Centre between January 2014 and December 2022. We identified exposures to classical psychedelics within New South Wales Poisons Information Centre database and measured the annual number of exposures, source of call (hospital, health care worker, member of the public), co-ingested substances, clinical features and advice given.ResultsThere were 737 calls related to relevant psychedelic exposures; 352 (47.8 per cent) to lysergic acid diethylamide, 347 (47.0 per cent) to psilocybin, 28 (3.8 per cent) to N,N-dimethyltryptamine, 4 (0.5 per cent) to ayahuasca, 4 (0.5 per cent) to mescaline and 2 (0.3 per cent) to ibogaine. Cases were predominantly male (77.2 per cent) and aged between 20 and 74 years (65.6 per cent). Psychedelic calls more than doubled from 45 in 2014 to 105 in 2022 and 625 (85 per cent) of all calls were either from or referred to hospital. Co-ingestion of psychedelics with another substance occurred in 249 (33.8 per cent) of calls and the most frequent clinical features related to single substance psychedelic exposures were hallucinations (27.6 per cent), gastrointestinal symptoms (21.7 per cent) and tachycardia (18.1 per cent). Seizures occurred in 2.9 per cent of single substance psychedelic exposures.DiscussionIncreasing incidence of psychedelic exposure calls, including those reporting significant toxicity, likely reflects increasing community use. This may in part be driven by increasing interest in psychedelic assisted psychotherapy trials subsequently increasing public awareness.ConclusionRelatively high poisoning severity contrasts with safety within clinical trials of psychedelic assisted psychotherapy that may relate to the uncontrolled nature of community use which is mitigated within clinical trial environments. Education about safe use may be useful.

keywords:
Humans, Banisteriopsis, Lysergic Acid Diethylamide, Hallucinogens, Retrospective Studies, Adolescent, Adult, Aged, Middle Aged, Child, Poison Control Centers, New South Wales, Female, Male, Young Adult, Psilocybin

raw_json:
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authors: Tap SC.
publication_date: 2024-03-31
doi: 10.1111/adb.13386
pubmed_id: 38600715
source_url: https://doi.org/10.1111/adb.13386
substance_tags: psilocybin
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
title:
The potential of 5-methoxy-N,N-dimethyltryptamine in the treatment of alcohol use disorder: A first look at therapeutic mechanisms of action.

abstract:
Alcohol use disorder (AUD) remains one of the most prevalent psychiatric disorders worldwide with high economic costs. Current treatment options show modest efficacy and relapse rates are high. Furthermore, there are increases in the treatment gap and few new medications have been approved in the past 20 years. Recently, psychedelic-assisted therapy with psilocybin and lysergic acid diethylamide has garnered significant attention in the treatment of AUD. Yet, they require significant amounts of therapist input due to prolonged subjective effects (~4-12 h) leading to high costs and impeding implementation. Accordingly, there is an increasing interest in the rapid and short-acting psychedelic 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT). This paper offers a first look at potential therapeutic mechanisms for AUD by reviewing the current literature on 5-MeO-DMT. Primarily, 5-MeO-DMT is able to induce mystical experiences and ego-dissolution together with increases in psychological flexibility and mindfulness. This could decrease AUD symptoms through the alleviation of psychiatric mood-related comorbidities consistent with the negative reinforcement and self-medication paradigms. In addition, preliminary evidence indicates that 5-MeO-DMT modulates neural oscillations that might subserve ego-dissolution (increases in gamma), psychological flexibility and mindfulness (increases in theta), and the reorganization of executive control networks (increases in coherence across frequencies) that could improve emotion regulation and inhibition. Finally, animal studies show that 5-MeO-DMT is characterized by neuroplasticity, anti-inflammation, 5-HT2A receptor agonism, and downregulation of metabotropic glutamate receptor 5 with clinical implications for AUD and psychiatric mood-related comorbidities. The paper concludes with several recommendations for future research to establish the purported therapeutic mechanisms of action.

keywords:
Animals, Humans, Alcoholism, N,N-Dimethyltryptamine, Methoxydimethyltryptamines, Hallucinogens, Alcohol Drinking

topic_tags:
Addiction,Neuroplasticity,Mechanism of Action,Receptor Pharmacology,Emotional Processing,Mystical Experience,Psychological Flexibility,Review Article,Inflammation

raw_json:
{"europe_pmc_id":"38600715","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Acute Adverse Effects of Therapeutic Doses of Psilocybin: A Systematic Review and Meta-Analysis.
authors: Yerubandi A, Thomas JE, Bhuiya NMMA, Harrington C, Villa Zapata L, Caballero J.
publication_date: 2024-03-31
doi: 10.1001/jamanetworkopen.2024.5960
pubmed_id: 38598236
source_url: https://doi.org/10.1001/jamanetworkopen.2024.5960
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
abstract:
ImportancePsilocybin has been studied in the treatment of depression and anxiety disorders. Clinical studies have mainly focused on efficacy, with systematic reviews showing favorable efficacy; however, none have primarily focused on psilocybin safety.ObjectiveTo evaluate the acute adverse effects of psilocybin at therapeutic doses in the treatment of depression and anxiety.Data sourcesMEDLINE via PubMed, Web of Science, and ClinicalTrials.gov were searched for publications available between 1966 and November 30, 2023.Study selectionRandomized, double-blind clinical trials that reported adverse effects of psilocybin in patients treated for depression and anxiety were screened.Data extraction and synthesisData were independently extracted by 2 authors and verified by 2 additional authors following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. The inverse variance method with the Hartung-Knapp adjustment for the random-effects model was used, with a continuity correction of 0.5 for studies with 0 cell frequencies. Sensitivity analysis was conducted by sequentially removing 1 study at a time to assess the robustness of the results.Main outcomes and measuresThe primary outcome was considered as the adverse effects of psilocybin at high and moderate (ie, therapeutic) dose regimens and compared with placebo, low-dose psilocybin, or other comparator in the treatment of depression and/or anxiety.ResultsSix studies met the inclusion criteria with a total sample of 528 participants (approximately 51% female; median age 39.8 years; IQR, 39.8-41.2). Seven adverse effects were reported in multiple studies and included in the analysis. Among these, headache (relative risk [RR], 1.99; 95% CI1.06-3.74), nausea (RR, 8.85; 95% CI, 5.68-13.79), anxiety (RR, 2.27; 95% CI, 1.11-4.64), dizziness (RR, 5.81; 95% CI, 1.02-33.03), and elevated blood pressure (RR, 2.29; 95% CI, 1.15- 4.53) were statistically significant. Psilocybin use was not associated with risk of paranoia and transient thought disorder.Conclusions and relevanceIn this meta-analysis, the acute adverse effect profile of therapeutic single-dose psilocybin appeared to be tolerable and resolved within 48 hours. However, future studies need to more actively evaluate the appropriate management of adverse effects.

keywords:
Humans, Dizziness, Anxiety, Anxiety Disorders, Adult, Female, Male, Randomized Controlled Trials as Topic, Drug-Related Side Effects and Adverse Reactions, Psilocybin

topic_tags:
Depression,Anxiety,Headache / Migraine,Clinical Trial,Randomized Controlled Trial,Meta-Analysis,Systematic Review,Review Article,Safety,Adverse Events

raw_json:
{"europe_pmc_id":"38598236","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Tolle HM, Farah JC, Mallaroni P, Mason NL, Ramaekers JG, Amico E.
publication_date: 2024-03-31
doi: 10.1162/netn_a_00349
pubmed_id: 38562294
source_url: https://doi.org/10.1162/netn_a_00349
substance_tags: psilocybin
topic_tags: Brain Imaging,Default Mode Network,Aging,Healthy Volunteers
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
The unique neural signature of your trip: Functional connectome fingerprints of subjective psilocybin experience.

abstract:
The emerging neuroscientific frontier of brain fingerprinting has recently established that human functional connectomes (FCs) exhibit fingerprint-like idiosyncratic features, which map onto heterogeneously distributed behavioral traits. Here, we harness brain-fingerprinting tools to extract FC features that predict subjective drug experience induced by the psychedelic psilocybin. Specifically, in neuroimaging data of healthy volunteers under the acute influence of psilocybin or a placebo, we show that, post psilocybin administration, FCs become more idiosyncratic owing to greater intersubject dissimilarity. Moreover, whereas in placebo subjects idiosyncratic features are primarily found in the frontoparietal network, in psilocybin subjects they concentrate in the default mode network (DMN). Crucially, isolating the latter revealed an FC pattern that predicts subjective psilocybin experience and is characterized by reduced within-DMN and DMN-limbic connectivity, as well as increased connectivity between the DMN and attentional systems. Overall, these results contribute to bridging the gap between psilocybin-mediated effects on brain and behavior, while demonstrating the value of a brain-fingerprinting approach to pharmacological neuroimaging.

raw_json:
{"europe_pmc_id":"38562294","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Sandbrink JD, Johnson K, Gill M, Yaden DB, Savulescu J, Hannikainen IR, Earp BD.
publication_date: 2024-02-04
doi: 10.1080/21507740.2024.2303154
pubmed_id: 38315212
source_url: https://doi.org/10.1080/21507740.2024.2303154
keywords: Humans, Hallucinogens, Decision Making, Mental Disorders, Public Policy, Psilocybin
substance_tags: psilocybin
topic_tags: Wellbeing
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Strong Bipartisan Support for Controlled Psilocybin Use as Treatment or Enhancement in a Representative Sample of US Americans: Need for Caution in Public Policy Persists.

abstract:
The psychedelic psilocybin has shown promise both as treatment for psychiatric conditions and as a means of improving well-being in healthy individuals. In some jurisdictions (e.g., Oregon, USA), psilocybin use for both purposes is or will soon be allowed and yet, public attitudes toward this shift are understudied. We asked a nationally representative sample of 795 US Americans to evaluate the moral status of psilocybin use in an appropriately licensed setting for either treatment of a psychiatric condition or well-being enhancement. Showing strong bipartisan support, participants rated the individual's decision as morally positive in both contexts. These results can inform effective policy-making decisions around supervised psilocybin use, given robust public attitudes as elicited in the context of an innovative regulatory model. We did not explore attitudes to psilocybin use in unsupervised or non-licensed community or social settings.

raw_json:
{"europe_pmc_id":"38315212","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2024-01-31
doi: 10.1016/j.arr.2024.102211
pubmed_id: 38307424
source_url: https://doi.org/10.1016/j.arr.2024.102211
substance_tags: psilocybin
topic_tags: Neuroplasticity,Mechanism of Action,Receptor Pharmacology,Spirituality,Safety
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
title:
Psychedelics for alzheimer's disease-related dementia: Unveiling therapeutic possibilities and pathways.

authors:
Sinha JK, Trisal A, Ghosh S, Gupta S, Singh KK, Han SS, Mahapatra M, Abomughaid MM, Abomughayedh AM, Almutary AG, Iqbal D, Bhaskar R, Mishra PC, Jha SK, Jha NK, Singh AK.

abstract:
Psychedelics have traditionally been used for spiritual and recreational purposes, but recent developments in psychotherapy have highlighted their potential as therapeutic agents. These compounds, which act as potent 5-hydroxytryptamine (5HT) agonists, have been recognized for their ability to enhance neural plasticity through the activation of the serotoninergic and glutamatergic systems. However, the implications of these findings for the treatment of neurodegenerative disorders, particularly dementia, have not been fully explored. In recent years, studies have revealed the modulatory and beneficial effects of psychedelics in the context of dementia, specifically Alzheimer's disease (AD)-related dementia, which lacks a definitive cure. Psychedelics such as N,N-dimethyltryptamine (DMT), lysergic acid diethylamide (LSD), and Psilocybin have shown potential in mitigating the effects of this debilitating disease. These compounds not only target neurotransmitter imbalances but also act at the molecular level to modulate signalling pathways in AD, including the brain-derived neurotrophic factor signalling pathway and the subsequent activation of mammalian target of rapamycin and other autophagy regulators. Therefore, the controlled and dose-dependent administration of psychedelics represents a novel therapeutic intervention worth exploring and considering for the development of drugs for the treatment of AD-related dementia. In this article, we critically examined the literature that sheds light on the therapeutic possibilities and pathways of psychedelics for AD-related dementia. While this emerging field of research holds great promise, further studies are necessary to elucidate the long-term safety, efficacy, and optimal treatment protocols. Ultimately, the integration of psychedelics into the current treatment paradigm may provide a transformative approach for addressing the unmet needs of individuals living with AD-related dementia and their caregivers.

keywords:
Humans, Alzheimer Disease, N,N-Dimethyltryptamine, Lysergic Acid Diethylamide, Hallucinogens, Psilocybin

raw_json:
{"europe_pmc_id":"38307424","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2024-01-17
doi: 10.1016/j.jad.2024.01.142
pubmed_id: 38244804
source_url: https://doi.org/10.1016/j.jad.2024.01.142
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
A comparison between psilocybin and esketamine in treatment-resistant depression using number needed to treat (NNT): A systematic review.

authors:
Wong S, Kwan ATH, Teopiz KM, Le GH, Meshkat S, Ho R, d'Andrea G, Cao B, Di Vincenzo JD, Rosenblat JD, McIntyre RS.

abstract:
BackgroundInadequate outcomes with monoamine-based treatments in depressive disorders are common and provide the impetus for mechanistically-novel treatments. Esketamine is a proven treatment recently approved for adults with Treatment-Resistant Depression (TRD) while psilocybin is an investigational treatment. Translation of the clinical meaningfulness for these foregoing agents in adults with TRD is required. Herein we evaluate the Number Needed to Treat (NNT) and Harm (NNH) of esketamine and psilocybin in adults with TRD.MethodsWe conducted a systematic review of randomized controlled trials, comparing the clinical efficacy of oral psilocybin to the co-commencement of intranasal esketamine with an oral antidepressant in adults with TRD.Results25 mg psilocybin had a significant reduction in depressive symptoms at 21-days post-dose, the NNT was 5 [95 % CI = 3.1, 18.5]. Psilocybin-induced nausea had a significant NNH = 5. Fixed-dosed esketamine at 56 mg and 84 mg had a significant effect at 28-days post-dose, (NNT of 7 [95 % CI56mg = 3.5, 46.7], [95 % CI84mg = 3.6, 142.2]). Esketamine-induced headache, nausea, dizziness, and dissociation had NNHs

keywords:
Humans, Ketamine, Hallucinogens, Antidepressive Agents, Treatment Outcome, Administration, Intranasal, Adult, Randomized Controlled Trials as Topic, Depressive Disorder, Treatment-Resistant, Psilocybin

topic_tags:
Depression,Headache / Migraine,Randomized Controlled Trial,Systematic Review,Review Article,Treatment-Resistant Depression

raw_json:
{"europe_pmc_id":"38244804","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Ghofrani-Jahromi Z, Nouri-Darehno S, Rahimi-Danesh M, Talaee N, Jasemi E, Razmi A, Vaseghi S.
publication_date: 2024-01-17
doi: 10.1037/bne0000579
pubmed_id: 38236234
source_url: https://doi.org/10.1037/bne0000579
substance_tags: psilocybin,psilocin
topic_tags: Anxiety,PTSD,Chronic Pain,Animal Study
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Psilocybe cubensis extract potently prevents fear memory recall and freezing behavior in short- but not long-term in a rat model of posttraumatic stress disorder.

abstract:
Psilocybe cubensis is a species of psilocybin mushroom (magic mushroom) of moderate potency whose principal active compounds are psilocybin and psilocin. Recent studies have shown the significant procognitive and mood-enhancer effects of Psilocybe cubensis. However, evidence is so limited, especially in preclinical studies. We aimed to investigate the effect of Psilocybe cubensis extract on posttraumatic stress disorder (PTSD)-like behavior, pain perception, locomotor activity, and anxiety in a rat model of PTSD. Male rats were exposed to three consecutive shocks (0.8 mA, 3 s interval) paired with three sounds broadcasted 3 s before delivering shocks (75 dB, 3 s). After 1, 3, or 21 days, freezing rate was measured in the fear-conditioning apparatus. Open filed test and hot plate were used to assess locomotor activity and anxiety, and pain subthreshold, respectively. Psilocybe cubensis was injected intraperitoneal at the dose of 25 mg/kg (single administration) before (pretrain) or after (posttrain) shocks, or before the test (pretest). Results showed psilocybin potently alleviated PTSD symptom is short- but not long-term after the induction of PTSD. Psilocybe cubensis decreased locomotor activity only in a short period after administration. Psilocybe cubensis also increased pain subthreshold and decreased anxiety. In conclusion, Psilocybe cubensis effects on PTSD-like behavior and locomotor activity seem to be remained in short-term, while Psilocybe cubensis effects on pain subthreshold and anxiety remained long-term. This is the first study evaluating the effect of Psilocybe cubensis on PTSD-like behavior in rats in three different time protocols (1, 3, and 21 days after fear conditioning). (PsycInfo Database Record (c) 2024 APA, all rights reserved).

keywords:
Animals, Rats, Rats, Wistar, Disease Models, Animal, Anxiety, Fear, Mental Recall, Stress Disorders, Post-Traumatic, Male, Psilocybin

raw_json:
{"europe_pmc_id":"38236234","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2024-01-16
doi: 10.1038/s41380-023-02391-7
pubmed_id: 38233467
source_url: https://doi.org/10.1038/s41380-023-02391-7
substance_tags: psilocybin
topic_tags: Anxiety,Brain Imaging,Mechanism of Action,Receptor Pharmacology,Aging
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
High-resolution tracking of unconfined zebrafish behavior reveals stimulatory and anxiolytic effects of psilocybin.

authors:
Braun D, Rosenberg AM, Rabaniam E, Haruvi R, Malamud D, Barbara R, Aiznkot T, Levavi-Sivan B, Kawashima T.

abstract:
Serotonergic psychedelics are emerging therapeutics for psychiatric disorders, yet their underlying mechanisms of action in the brain remain largely elusive. Here, we developed a wide-field behavioral tracking system for larval zebrafish and investigated the effects of psilocybin, a psychedelic serotonin receptor agonist. Machine learning analyses of precise body kinematics identified latent behavioral states reflecting spontaneous exploration, visually-driven rapid swimming, and irregular swim patterns following stress exposure. Using this method, we found that acute psilocybin treatment has two behavioral effects: [i] facilitation of spontaneous exploration ("stimulatory") and [ii] prevention of irregular swim patterns following stress exposure ("anxiolytic"). These effects differed from the effect of acute SSRI treatment and were rather similar to the effect of ketamine treatment. Neural activity imaging in the dorsal raphe nucleus suggested that psilocybin inhibits serotonergic neurons by activating local GABAergic neurons, consistent with psychedelic-induced suppression of serotonergic neurons in mammals. These findings pave the way for using larval zebrafish to elucidate neural mechanisms underlying the behavioral effects of serotonergic psychedelics.

keywords:
Brain, Animals, Zebrafish, Ketamine, Anti-Anxiety Agents, Hallucinogens, Behavior, Animal, Anxiety, Larva, Swimming, Serotonin Receptor Agonists, Serotonergic Neurons, GABAergic Neurons, Dorsal Raphe Nucleus, Psilocybin, Selective Serotonin Reuptake Inhibitors

raw_json:
{"europe_pmc_id":"38233467","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Endocrinology-informed neuroimaging in eating disorders: GLP1, orexins, and psilocybin.
authors: Steward T.
publication_date: 2023-12-18
doi: 10.1016/j.molmed.2023.12.001
pubmed_id: 38123380
source_url: https://doi.org/10.1016/j.molmed.2023.12.001
substance_tags: psilocybin
topic_tags: Eating Disorders,Brain Imaging,Receptor Pharmacology,Aging
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
abstract:
The neurobiology of eating disorders [EDs; anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED)] remains poorly understood. Here, I describe how neuroimaging, accompanied by peripheral endocrine measures, can provide insights into the neurobiological drivers of eating disorders. Orexins/hypocretins, glucagon-like peptide-1 receptor (GLP1R) agonists, and psilocybin are highlighted as avenues for investigation.

keywords:
Humans, Binge-Eating Disorder, Neuroimaging, Orexins, Feeding and Eating Disorders, Glucagon-Like Peptide-1 Receptor, Psilocybin, Glucagon-Like Peptide-1 Receptor Agonists

raw_json:
{"europe_pmc_id":"38123380","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2023-12-17
doi: 10.1002/cncr.35010
pubmed_id: 38105655
source_url: https://doi.org/10.1002/cncr.35010
substance_tags: psilocybin
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Psilocybin-assisted group therapy in patients with cancer diagnosed with a major depressive disorder.

authors:
Agrawal M, Richards W, Beaussant Y, Shnayder S, Ameli R, Roddy K, Stevens N, Richards B, Schor N, Honstein H, Jenkins B, Bates M, Thambi P.

abstract:
BackgroundDepression is common in patients with cancer and is associated with lower treatment adherence and reduced quality of life. Antidepressants and psychotherapy have limited success in improving depression among patients with cancer. This study explored the safety, feasibility, and efficacy of psilocybin-assisted therapy in patients with cancer and major depressive disorder.MethodsThis phase 2, open-label trial enrolled patients with curable and noncurable cancer and major depressive disorder at a single community oncology practice site. A single 25-mg dose of psilocybin was administered simultaneously to cohorts of three to four participants with individual (4.25 hours in 1:1 therapist-to-patient ratio) and group therapeutic support (3.75 hours) before, during, and after psilocybin administration. Outcomes included depression severity, anxiety, pain, demoralization, and disability.ResultsThirty participants completed the study. No psilocybin-related serious adverse events occurred; treatment-related adverse events (e.g., nausea, headache) were generally mild and expected. There were no laboratory or electrocardiogram abnormalities. No suicidality was reported. Efficacy was suggested with a robust reduction in depression severity scores from baseline to posttreatment of 19.1 points (95% CI, 22.3 to -16.0; p

keywords:
Humans, Neoplasms, Antidepressive Agents, Psychotherapy, Group, Quality of Life, Psilocybin, Major Depressive Disorder

topic_tags:
Depression,Anxiety,Chronic Pain,Headache / Migraine,Clinical Trial,Observational Study,Cancer Patients,Safety,Adverse Events

raw_json:
{"europe_pmc_id":"38105655","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Innovations in group-based psilocybin-assisted therapy of major depression in patients with cancer.
authors: Thrul J, Kozak Z, Carducci MA, Garcia-Romeu A, Yaden DB.
publication_date: 2023-12-17
doi: 10.1002/cncr.35127
pubmed_id: 38105654
source_url: https://doi.org/10.1002/cncr.35127
keywords: Humans, Neoplasms, Depression, Anxiety, Psilocybin, Major Depressive Disorder
substance_tags: psilocybin
topic_tags: Depression,Anxiety
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
raw_json:
{"europe_pmc_id":"38105654","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2023-12-17
doi: 10.1002/cncr.35024
pubmed_id: 38105653
source_url: https://doi.org/10.1002/cncr.35024
keywords: Humans, Neoplasms, Psychotherapy, Psychotherapy, Group, Psilocybin, Major Depressive Disorder
substance_tags: psilocybin
topic_tags: Depression,Aging,Clinical Trial,Cancer Patients,Safety,Drug Interactions
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Acceptability of psilocybin-assisted group therapy in patients with cancer and major depressive disorder: Qualitative analysis.

authors:
Beaussant Y, Tarbi E, Nigam K, Miner S, Sager Z, Sanders JJ, Ljuslin M, Guérin B, Thambi P, Tulsky JA, Agrawal M.

abstract:
BackgroundThe present study explored the acceptability of psilocybin-assisted group therapy from the perspective of patients with cancer and depression who participated in a clinical trial assessing the safety and efficacy of this novel intervention.MethodsGuided by the conceptual framework of acceptability, the authors conducted semi-structured interviews with participants of the psilocybin trial. Data were analyzed using template and thematic analyses.ResultsParticipants' (n = 28) perspectives on the acceptability of the group and simultaneous sessions was generally positive, both in terms of safety and efficacy: first, the groups contributed to increase participants' sense of safety and preparedness as they were engaging in the therapy; and second, the groups fostered a sense of connection and of belonging, which served to enrich and deepen the meaning of participants' experience, ultimately opening a dimension of self-transcendence and compassion. Other subthemes related to factors influencing the acceptability of the group approach included: 1) the importance of the therapeutic framework, 2) the complementary value of individual sessions, 3) disruptive factors related to the group and/or simultaneous setting, and 4) opportunities and challenges related to group size and how to structure interactions.ConclusionsThis study enhances understanding of what promotes acceptability of the psilocybin-assisted therapy group model for the treatment of MDD in cancer patients.Plain language summaryWe conducted exit interviews with participants of a phase 2 trial of psilocybin-assisted therapy (PAT) conducted in a community cancer center, to assess the acceptability of a novel psilocybin delivery model combining simultaneous individual therapy and group sessions. Our findings support the acceptability of this intervention and suggest that in addition to being feasible, it might also enhance participants' perceived safety and efficacy compared to uniquely individual or group delivery models of PAT. Our analysis highlights critical factors conditioning acceptability and suggests new ways PAT may be scaled and integrated into cancer care.

raw_json:
{"europe_pmc_id":"38105653","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Simonsson O, Osika W, Stenfors CUD, Goldberg SB, Honk L, Hendricks PS
journal: Psychological medicine
publication_date: 2024-03-31
doi: 10.1017/s0033291723003082
pubmed_id: 37859627
source_url: https://pubmed.ncbi.nlm.nih.gov/37859627/
keywords: compassion, meditation, mindfulness, psilocybin, psychedelics
substance_tags: psilocybin
topic_tags: Observational Study
study_type: Observational Study
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:37
raw_json: {"pubmed_id":"37859627"}
title:
Longitudinal associations between psychedelic use and meditation practices in the United States and the United Kingdom.

abstract:
Previous research has proposed that there may be potential synergies between psychedelic and meditation interventions, but there are still knowledge gaps that merit further investigation.
Using a longitudinal observational research design with samples representative of the US and UK adult population with regard to sex, age, and ethnicity ( = 9732), we investigated potential associations between self-reported psychedelic use and meditation practice.
The follow-up survey was completed by 7667 respondents (79% retention rate), with 100 respondents reporting psychedelic use during the 2-month study period (1.3% of follow-up respondents). In covariate-adjusted regression models, psychedelic use during the study period was associated with greater increases in the number of days of mindfulness meditation practice in the past week ( = 0.40, = 0.004). Among those who reported psychedelic use during the study period, covariate-adjusted regression models revealed that the subjective experience of insight during respondents' most intense psychedelic experience in that period was also associated with greater increases in the number of days of mindfulness and loving-kindness or compassion meditation practice in the past week ( = 0.42, = 0.021; = 0.38, = 0.017). Notably, more days of loving-kindness or compassion meditation practice in the past week at baseline was associated with less severe subjective feelings of death or dying during respondents' most intense psychedelic experience in the study period ( = -0.29, = 0.037).
Psychedelic use might lead to greater engagement with meditation practices such as mindfulness meditation, while meditation practices such as loving-kindness or compassion medication might buffer against certain challenging experiences associated with psychedelic use.


authors: Kelly TJ, Bonniwell EM, Mu L, Liu X, Hu Y, Friedman V, Yu H, Su W, McCorvy JD, Liu QS.
publication_date: 2023-09-25
doi: 10.1038/s41386-023-01744-8
pubmed_id: 37752222
source_url: https://doi.org/10.1038/s41386-023-01744-8
substance_tags: psilocybin
topic_tags: Depression,PTSD,Neuroplasticity,Mechanism of Action,Receptor Pharmacology,Animal Study
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
title:
Psilocybin analog 4-OH-DiPT enhances fear extinction and GABAergic inhibition of principal neurons in the basolateral amygdala.

abstract:
Psychedelics such as psilocybin show great promise for the treatment of depression and PTSD, but their long duration of action poses practical limitations for patient access. 4-OH-DiPT is a fast-acting and shorter-lasting derivative of psilocybin. Here we characterized the pharmacological profile of 4-OH-DiPT and examined its impact on fear extinction learning as well as a potential mechanism of action. First, we profiled 4-OH-DiPT at all 12 human 5-HT GPCRs. 4-OH-DiPT showed strongest agonist activity at all three 5-HT2A/2B/2C receptors with near full agonist activity at 5-HT2A. Notably, 4-OH-DiPT had comparable activity at mouse and human 5-HT2A/2B/2C receptors. In a fear extinction paradigm, 4-OH-DiPT significantly reduced freezing responses to conditioned cues in a dose-dependent manner with a greater potency in female mice than male mice. Female mice that received 4-OH-DiPT before extinction training had reduced avoidance behaviors several days later in the light dark box, elevated plus maze and novelty-suppressed feeding test compared to controls, while male mice did not show significant differences. 4-OH-DiPT produced robust increases in spontaneous inhibitory postsynaptic currents (sIPSCs) in basolateral amygdala (BLA) principal neurons and action potential firing in BLA interneurons in a 5-HT2A-dependent manner. RNAscope demonstrates that Htr2a mRNA is expressed predominantly in BLA GABA interneurons, Htr2c mRNA is expressed in both GABA interneurons and principal neurons, while Htr2b mRNA is absent in the BLA. Our findings suggest that 4-OH-DiPT activates BLA interneurons via the 5-HT2A receptor to enhance GABAergic inhibition of BLA principal neurons, which provides a potential mechanism for suppressing learned fear.

keywords:
Neurons, Animals, Humans, Mice, Serotonin, gamma-Aminobutyric Acid, RNA, Messenger, Fear, Female, Male, Extinction, Psychological, Basolateral Nuclear Complex, Psilocybin

raw_json:
{"europe_pmc_id":"37752222","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Evidence versus expectancy: the development of psilocybin therapy.
authors: Rucker JJ.
publication_date: 2024-03-31
doi: 10.1192/bjb.2023.28
pubmed_id: 37246405
source_url: https://doi.org/10.1192/bjb.2023.28
substance_tags: psilocybin
topic_tags: Depression,Clinical Trial,Treatment-Resistant Depression
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
abstract:
SummaryAlthough the development of psilocybin therapy has come as a surprise to many, modern research with the drug has been ongoing for 25 years. Psilocybin therapy is composed of psilocybin dosing sessions embedded within a wider process of psychoeducation, psychological support and integration. Early phase clinical trial evidence is promising, particularly for treatment-resistant depression. However, masking probably fails and expectancy effects may be a part of the mechanism of change. Disambiguating between drug and expectancy effects is a necessary part of the development process, yet this is difficult if masking fails. Hitherto, masking and expectancy have not been routinely measured in psilocybin or other medication trials. Doing so represents an opportunity for research and may influence psychiatry more widely. In this opinion piece I summarise the clinical development process of psilocybin therapy thus far, discussing the hope, the hype, the challenges and the opportunities along the way.

raw_json:
{"europe_pmc_id":"37246405","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Thomas KL, Jesse R, Mehtani NJ, Mitchell JM, Anderson BT
journal: Journal of psychoactive drugs
publication_date: 2023-12-31
doi: 10.1080/02791072.2023.2201244
pubmed_id: 37061961
source_url: https://pubmed.ncbi.nlm.nih.gov/37061961/
keywords: 5-MeO-DMT, DMT, LSD, MDMA, ayahuasca, ibogaine, mescaline, policy, psilocybin, psychedelic
substance_tags: psilocybin
topic_tags: Clinical Trial
study_type: Clinical Trial
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:37
raw_json: {"pubmed_id":"37061961"}
title:
Commentary: Evidence-Informed Recommendation to Achieve Approximate Parity in the Allowed Number of Doses for Common Psychedelics.

abstract:
In recent years, policymakers have proposed and implemented regulatory changes promoting the deprioritization, decriminalization, or state-level legalization of one or more psychedelic substances, usually referencing data from clinical trials as reasons to support liberalizing drug control policies. As psychedelic policies continue to be drafted, personal possession limits may be considered for inclusion in those regulations. If "allowable amount" limits are to be written into law to set personal possession limits, then such amounts should be more consistently related to psychedelic doses found to be safe and efficacious in clinical trials, existing data on moderate-high doses commonly used in various naturalistic settings, and the few studies that estimate psychedelic dose equivalence based on the intensity of subjective effects. In this commentary, we provide an evidence-informed table of typical moderate-high doses for seven commonly used psychedelic substances. These estimates of comparable moderate-high doses can be used to inform "allowable amount" values for psychedelic substances. When such limits are written into legislation, the adoption of evidence-informed comparable limits akin to those presented here would be an important first step toward ensuring greater parity and consistency in drug policy, relative to limits that have little or no scientific basis.


title: Use of Prescribed and Non-Prescribed Treatments for Cluster Headache in a Swedish Cohort.
authors: Smedfors G, Jennysdotter Olofsgård F, Steinberg A, Waldenlind E, Ran C, Belin AC.
publication_date: 2024-03-30
doi: 10.3390/brainsci14040348
pubmed_id: 38672000
source_url: https://doi.org/10.3390/brainsci14040348
substance_tags: psilocybin
topic_tags: Chronic Pain,Headache / Migraine,Observational Study,Adverse Events
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
abstract:
BackgroundCluster headache (CH) is a debilitating condition, but current therapies leave CH patients in pain. The extent of this problem in Sweden is unknown.MethodsAn anonymized questionnaire was sent to 479 Swedish CH patients to investigate patterns and perceived effects of treatments.ResultsThree hundred fourteen answers were analyzed. The population was representative regarding age of onset and sex. Less than half (46%) were satisfied with their abortive treatments, 19% terminated functioning abortive treatments due to side effects. Additionally, 17% of chronic CH patients had not tried the first-line preventive drug verapamil. A small subset had tried illicit substances to treat their CH (0-8% depending on substance). Notably, psilocybin was reported effective as an abortive treatment by 100% (n = 8), and with some level of effect as a preventive treatment by 92% (n = 12). For verapamil, some level of preventive effect was reported among 68% (n = 85).ConclusionsOur descriptive data illustrate that many Swedish CH patients are undertreated, lack functional therapies, and experience side effects. Further studies are warranted to search for new treatment strategies as well as a revision of current treatment guidelines with the aim of reducing patient disease burden to the greatest extent possible.

raw_json:
{"europe_pmc_id":"38672000","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Deciphering psilocybin: Cytotoxicity, anti-inflammatory effects, and mechanistic insights.
authors: Laabi S, LeMmon C, Vogel C, Chacon M, Jimenez VM.
publication_date: 2024-02-22
doi: 10.1016/j.intimp.2024.111753
pubmed_id: 38401463
source_url: https://doi.org/10.1016/j.intimp.2024.111753
substance_tags: psilocybin,psilocin
topic_tags: Depression,Mechanism of Action,Animal Study,Toxicity,Inflammation
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:00
abstract:
A decade of clinical research has indicated psilocybin's effectiveness in treating various neuropsychiatric disorders, such as depression and substance abuse. The correlation between increased pro-inflammatory cytokines and the severity of neuropsychiatric symptoms, along with the known anti-inflammatory potential of some psychedelics, suggests an immunomodulatory role for psilocybin. This study aims to understand the mechanism of action of psilocybin by investigating the cytotoxic and immunomodulatory effects of psilocybin and psilocin on both resting and LPS-activated RAW264.7 murine macrophages. The study evaluated the cytotoxicity of psilocybin and psilocin using an LDH assay across various doses and assessed their impact on cytokine production in RAW264.7 cells, measuring cytokine expression via ELISA. Different doses, including those above and below the LC50, were used in both pre-treatment and post-treatment approaches. The LDH assay revealed that psilocybin is almost twice as cytotoxic as psilocin, with an LC50 of 12 ng/ml and 28 ng/ml, respectively. In resting macrophages, both psilocybin and psilocin triggered significant release of TNF- α after 4 h, with the lowest doses inducing higher levels of the cytokine than the highest doses. IL-10 expression in resting cells was only triggered by the highest dose of psilocin in the 4-hour incubation group. In LPS-stimulated cells, psilocin reduced TNF- α levels more than psilocybin in pre-treatment and post-treatment, with no significant effects on IL-10 in pre-treatment. Psilocin, but not psilocybin, induced a significant increase of IL-10 in post-treatment, leading to the conclusion that psilocin, but not psilocybin, exerts anti-inflammatory effects on classically activated macrophages.

keywords:
Animals, Mice, Lipopolysaccharides, Tumor Necrosis Factor-alpha, Anti-Inflammatory Agents, Interleukin-10, Cytokines, Psilocybin

raw_json:
{"europe_pmc_id":"38401463","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Methyl transfer in psilocybin biosynthesis.
authors: Hudspeth J, Rogge K, Dörner S, Müll M, Hoffmeister D, Rupp B, Werten S.
publication_date: 2024-03-27
doi: 10.1038/s41467-024-46997-z
pubmed_id: 38548735
source_url: https://doi.org/10.1038/s41467-024-46997-z
keywords: Agaricales, Hallucinogens, Phylogeny, Psilocybe, Psilocybin
substance_tags: psilocybin
topic_tags: Depression,Mechanism of Action,Epigenetics,Transcriptomics
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
abstract:
Psilocybin, the natural hallucinogen produced by Psilocybe ("magic") mushrooms, holds great promise for the treatment of depression and several other mental health conditions. The final step in the psilocybin biosynthetic pathway, dimethylation of the tryptophan-derived intermediate norbaeocystin, is catalysed by PsiM. Here we present atomic resolution (0.9 Å) crystal structures of PsiM trapped at various stages of its reaction cycle, providing detailed insight into the SAM-dependent methylation mechanism. Structural and phylogenetic analyses suggest that PsiM derives from epitranscriptomic N6-methyladenosine writers of the METTL16 family, which is further supported by the observation that bound substrates physicochemically mimic RNA. Inherent limitations of the ancestral monomethyltransferase scaffold hamper the efficiency of psilocybin assembly and leave PsiM incapable of catalysing trimethylation to aeruginascin. The results of our study will support bioengineering efforts aiming to create novel variants of psilocybin with improved therapeutic properties.

raw_json:
{"europe_pmc_id":"38548735","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Natural Product Synthesis in the 21st Century: Beyond the Mountain Top.
authors: Shenvi RA.
publication_date: 2024-02-13
doi: 10.1021/acscentsci.3c01518
pubmed_id: 38559299
source_url: https://doi.org/10.1021/acscentsci.3c01518
substance_tags: psilocybin
topic_tags: Wellbeing
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
abstract:
Research into natural products emerged from humanity's curiosity about the nature of matter and its role in the materia medica of diverse civilizations. Plants and fungi, in particular, supplied materials that altered behavior, perception, and well-being profoundly. Many active principles remain well-known today: strychnine, morphine, psilocybin, ephedrine. The potential to circumvent the constraints of natural supply and explore the properties of these materials led to the field of natural product synthesis. This research delivered new molecules with new properties, but also led to fundamental insights into the chemistry of the nonmetal elements H, C, N, O, P, S, Se, and their combinations, i.e., organic chemistry. It also led to a potent culture focused on bigger molecules and races to the finish line, perhaps at the expense of actionable next steps. About 20 years ago, the field began to contract in the United States. Research that focused solely on chemical reaction development, especially catalysis, filled the void. After all, new reactions and mechanistic insight could be immediately implemented by the chemistry community, so it became hard to justify the lengthy procurement of a complex molecule that sat in the freezer unused. This shift coincided with a divestment of natural product portfolios by pharmaceutical companies and an emphasis in academic organic chemistry on applications-driven research, perhaps at the expense of more fundamental science. However, as bioassays and the tools of chemical biology become widespread, synthesis finds a new and powerful ally that allows us to better deliver on the premise of the field. And the hard-won insights of complex synthesis can be better encoded digitally, mined by data science, and applied to new challenges, as chemists perturb and even surpass the properties of complex natural products. The 21st century promises powerful developments, both in fundamental organic chemistry and at the interface of synthesis and biology, if the community of scientists fosters its growth. This essay tries to contextualize natural product synthesis for a broad audience, looks ahead to its transformation in the coming years, and expects the future to be bright.

raw_json:
{"europe_pmc_id":"38559299","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2024-03-25
doi: 10.1038/s41598-024-55726-x
pubmed_id: 38531905
source_url: https://doi.org/10.1038/s41598-024-55726-x
keywords: Brain, Humans, Hallucinogens, Meditation, Brain Mapping, Psilocybin
substance_tags: psilocybin
topic_tags: Brain Imaging,Biomarkers,Aging
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Psilocybin enhances insightfulness in meditation: a perspective on the global topology of brain imaging during meditation.

authors:
Singer B, Meling D, Hirsch-Hoffmann M, Michels L, Kometer M, Smigielski L, Dornbierer D, Seifritz E, Vollenweider FX, Scheidegger M.

abstract:
In this study, for the first time, we explored a dataset of functional magnetic resonance images collected during focused attention and open monitoring meditation before and after a five-day psilocybin-assisted meditation retreat using a recently established approach, based on the Mapper algorithm from topological data analysis. After generating subject-specific maps for two groups (psilocybin vs. placebo, 18 subjects/group) of experienced meditators, organizational principles were uncovered using graph topological tools, including the optimal transport (OT) distance, a geometrically rich measure of similarity between brain activity patterns. This revealed characteristics of the topology (i.e. shape) in space (i.e. abstract space of voxels) and time dimension of whole-brain activity patterns during different styles of meditation and psilocybin-induced alterations. Most interestingly, we found that (psilocybin-induced) positive derealization, which fosters insightfulness specifically when accompanied by enhanced open-monitoring meditation, was linked to the OT distance between open-monitoring and resting state. Our findings suggest that enhanced meta-awareness through meditation practice in experienced meditators combined with potential psilocybin-induced positive alterations in perception mediate insightfulness. Together, these findings provide a novel perspective on meditation and psychedelics that may reveal potential novel brain markers for positive synergistic effects between mindfulness practices and psilocybin.

raw_json:
{"europe_pmc_id":"38531905","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Synthesis and bioactivity of psilocybin analogues containing a stable carbon-phosphorus bond.
authors: Vandevelde M, Simoens A, Vandekerckhove B, Stevens C.
publication_date: 2024-02-20
doi: 10.1039/d4md00043a
pubmed_id: 38516602
source_url: https://doi.org/10.1039/d4md00043a
substance_tags: psilocybin,psilocin
topic_tags: Receptor Pharmacology
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:00
abstract:
Psilocybin analogues have been synthesized comprising a non-hydrolysable P-C bond to evaluate the biological activity and the selectivity towards 5-HT2AR, 5-HT2BR and the TNAP receptor. No activity was observed towards the phosphatase, however all compounds showed good binding affinity for 5-HT2AR and 5-HT2BR and one compound showed a higher selectivity towards 5-HT2AR than psilocin.

raw_json:
{"europe_pmc_id":"38516602","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Ethical considerations for psychedelic-assisted therapy in military clinical settings.
authors: Hoener S, Wolfgang A, Nissan D, Howe E.
publication_date: 2024-03-19
doi: 10.1136/jme-2023-108943
pubmed_id: 37253556
source_url: https://doi.org/10.1136/jme-2023-108943
keywords: Humans, N-Methyl-3,4-methylenedioxyamphetamine, Hallucinogens, Military Personnel, Psilocybin
substance_tags: psilocybin
topic_tags: Depression,PTSD,Clinical Trial,Safety
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
abstract:
Psychedelic treatments, particularly 3,4-methylenedioxymethamphetamine (MDMA)-assisted and psilocybin-assisted therapies, have recently seen renewed interest in their clinical potential to treat various mental health conditions. Clinical trials for both MDMA-assisted and psilocybin-assisted therapies have shown to be highly efficacious for post-traumatic stress disorder and major depression. Recent research trials for psychedelic-assisted therapies (PAT) have demonstrated that although they are resource-intensive, their effects are rapid-acting, durable and cost-effective. These results have generated enthusiasm among researchers seeking to investigate psychedelic therapies in active-duty service members of the US military, particularly those with treatment refractory mental health conditions. At the same time, psychedelics remain in early stages of clinical investigation, have not yet achieved regulatory approval for general clinical use and may confer unique psychological and neurobiological effects that could raise novel ethical considerations when treating active-duty service members. Should psychedelics achieve regulatory approval, military relevant considerations may include issues of access to these treatments, appropriate procedures for informed consent, confidentiality standards, and possible unanticipated mental health risks and other psychological sequelae. A service member's deployability, as well as their ability to return to full military duty following PAT, may also be of unique concern. The authors argue that MDMA-assisted therapy currently represents a promising treatment that should be more rapidly investigated as a clinical therapy for service members while still taking a measured approach that accounts for the many military-specific uncertainties that remain.

raw_json:
{"europe_pmc_id":"37253556","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Five New Species of Gymnopilus from Xizang Autonomous Region of China and Surrounding Areas.
authors: Yang WQ, Li JX, He MQ, Wang SH, Zhu XY, Phurbu D, Yun JM, Zhao RL.
publication_date: 2024-03-17
doi: 10.3390/jof10030220
pubmed_id: 38535228
source_url: https://doi.org/10.3390/jof10030220
substance_tags: psilocybin
topic_tags: General
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
abstract:
The species of Gymnopilus (Hymenogastraceae, Agricales) are commonly recognized as wood-decaying fungi. Certain members of this genus have been identified as psilocybin-producing mushrooms. Gymnopilus exhibits a diverse range and has a global distribution. In this study, a total of seventy-eight specimens were gathered from ten provinces in China. A comprehensive molecular phylogenetic analysis was conducted, employing gene sequences including ITS, nrLSU, nrSSU, rpb1, rpb2, and tef1-α. Additionally, morphological examinations were also carried out. The phylogenetic topology of Gymnopilus from this study generally agreed with previous studies and facilitated the identification of all those specimens. As a result, eleven species, including five newly discovered ones named Gy. gyirongensis, Gy. variisporus, Gy. tomentosiceps, Gy. tenuibasidialis, and Gy. aurantipileatus, were recognized. Significantly, four of the five newly identified species are native to the Xizang Autonomous Region, emphasizing their specialization in this distinctive habitat. This research contributes to our comprehension of Gymnopilus diversity and lays the groundwork for the conservation and sustainable utilization of Gymnopilus resources.

raw_json:
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title: Safety pharmacology of acute psilocybin administration in healthy participants.
authors: Straumann I, Holze F, Becker AM, Ley L, Halter N, Liechti ME.
publication_date: 2024-03-15
doi: 10.1016/j.nsa.2024.104060
pubmed_id: 40656108
source_url: https://doi.org/10.1016/j.nsa.2024.104060
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Addiction,Pharmacology,Healthy Volunteers,Safety
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
abstract:
Psilocybin is being studied for its therapeutic potential in various mental health disorders, such as depression, anxiety, and addiction. Initial studies suggested that psilocybin is generally safe when used under controlled conditions, but more research is needed to better understand its safety profile. We report safety pharmacology data from a pooled analysis of three randomized crossover studies that included 85 healthy participants and 113 single-dose administrations of psilocybin. Single oral doses included 15 mg, 20 mg, 25 mg, and 30 mg psilocybin dihydrate. We investigated subjective effects, blood pressure, heart rate, body temperature, acute and subacute adverse effects, reports of flashbacks, and liver and kidney function before and after the studies. The 20, 25, and 30 mg doses of psilocybin produced stronger effects than the 15 mg dose. Psilocybin at all doses induced higher "good drug effects" than "bad drug effects." Only the 25 and 30 mg doses increased anxiety. Psilocybin elevated autonomic effects only moderately. Tachycardia (>100 beats/min) was observed with 7% of all psilocybin administrations. Body temperature >38° was reached in 7%, 9%, 17%, and 32% of the participants with the 15, 20, 25, and 30 mg doses, respectively. Kidney and liver function parameters were unaltered at the end of the study. Five participants (6%) reported transient flashback phenomena. No serious adverse reactions occurred. These findings suggest that a single administration of psilocybin is safe with regard to acute psychological and physical harm in healthy participants in a controlled research setting.

raw_json:
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title: Pioneering Methods in Brain Optimization and Mental Health Treatment.
authors: Kargbo RB.
publication_date: 2024-02-12
doi: 10.1021/acsmedchemlett.4c00058
pubmed_id: 38505858
source_url: https://doi.org/10.1021/acsmedchemlett.4c00058
substance_tags: psilocybin,psilocin
topic_tags: General
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
abstract:
This Patent Highlight explores ground-breaking advancements in neurostimulation, psychedelic therapy, and brain function optimization from recent innovations. It examines methods for altering brain states through AI-driven non-invasive neurostimulation, potentially contributing to personalized brain therapy. The publication also delves into the therapeutic potential of N-isopropyl tryptamines and tryptamine derivatives. Furthermore, it discusses the therapeutic applications of psilocybin and psilocin crystalline forms in mental health and central nervous system disorders. By comparing and contrasting these diverse approaches, this work highlights their mechanistic insights, therapeutic implications, and contributions to the evolving fields of neuroscience and mental health.

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authors: Song-Smith C, Jacobs E, Rucker J, Saint M, Cooke J, Schlosser M.
publication_date: 2024-03-13
doi: 10.1136/bmjopen-2023-083595
pubmed_id: 38485474
source_url: https://doi.org/10.1136/bmjopen-2023-083595
substance_tags: psilocybin
topic_tags: Observational Study
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
title:
UK medical students' self-reported knowledge and harm assessment of psychedelics and their application in clinical research: a cross-sectional study.

abstract:
ObjectiveTo capture UK medical students' self-reported knowledge and harm assessment of psychedelics and to explore the factors associated with support for changing the legal status of psychedelics to facilitate further clinical research.DesignCross-sectional, anonymous online survey of UK medical students using a non-random sampling method.SettingUK medical schools recognised by the General Medical Council.Participants132 medical students who had spent an average of 3.8 years (SD=1.4; range: 1-6) in medical school.ResultsMost students (83%) reported that they were aware of psychedelic research and only four participants (3%) said that they were not interested in learning more about this type of research. Although medical students' harm assessment of psychedelics closely aligned with that of experts, only 17% of students felt well-educated on psychedelic research. Teachings on psychedelics were only rarely encountered in their curriculum (psilocybin: 14.1 (SD=19.9), scale: 0 (never) to 100 (very often)). Time spent at medical schools was not associated with more knowledge about psychedelics (r=0.12, p=0.129). On average, this sample of medical students showed strong support for changing the legal status of psychedelics to facilitate further research into their potential clinical applications (psilocybin: 80.2 (SD=24.8), scale: 0 (strongly oppose) to 100 (strongly support)). Regression modelling indicated that greater knowledge of psychedelics (p

keywords:
Humans, Hallucinogens, Cross-Sectional Studies, Students, Medical, Self Report, United Kingdom, Psilocybin

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publication_date: 2024-03-13
doi: 10.1371/journal.pone.0300501
pubmed_id: 38483940
source_url: https://doi.org/10.1371/journal.pone.0300501
keywords: Humans, Treatment Outcome, Adult, Psilocybin, Therapeutic Alliance, Major Depressive Disorder
substance_tags: psilocybin
topic_tags: Depression,Mystical Experience,Clinical Trial
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
The therapeutic alliance between study participants and intervention facilitators is associated with acute effects and clinical outcomes in a psilocybin-assisted therapy trial for major depressive disorder.

authors:
Levin AW, Lancelotta R, Sepeda ND, Gukasyan N, Nayak S, Wagener TL, Barrett FS, Griffiths RR, Davis AK.

abstract:
We examined if the therapeutic alliance between study participants and intervention facilitators in a psilocybin-assisted therapy (PAT) trial changed over time and whether there were relationships between alliance, acute psilocybin experiences, and depression outcomes. In a randomized, waiting list-controlled clinical trial for major depressive disorder in adults (N = 24), participants were randomized to an immediate (N = 13) or delayed (N = 11) condition with two oral doses of psilocybin (20mg/70kg and 30mg/70kg). Ratings of therapeutic alliance significantly increased from the final preparation session to one-week post-intervention (p =.03, d =.43). A stronger total alliance at the final preparation session predicted depression scores at 4 weeks (r = -.65, p =.002), 6 months (r = -.47, p =.036), and 12 months (r = -.54, p =.014) post-intervention. A stronger total alliance in the final preparation session was correlated with higher peak ratings of mystical experiences (r =.49, p =.027) and psychological insight (r =.52, p =.040), and peak ratings of mystical experience and psychological insight were correlated with depression scores at 4 weeks (r = -.45, p =.030 for mystical; r = -.75, p <.001 for insight). Stronger total alliance one week after the final psilocybin session predicted depression scores at 4 weeks (r = -.85, p <.001), 3 months (r = -.52, p =.010), 6 months (r = -.77, p <.001), and 12 months (r = -.61, p =.001) post-intervention. These findings highlight the importance of the therapeutic relationship in PAT. Future research should explore therapist and participant characteristics which maximize the therapeutic alliance and evaluate its relationship to treatment outcomes. Trial registration: Registration: Clinicaltrials.gov NCT03181529. https://classic.clinicaltrials.gov/ct2/show/NCT03181529.

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authors: Hibicke M, Billac G, Nichols CD.
publication_date: 2024-03-11
doi: 10.1089/psymed.2023.0037
pubmed_id: 40051761
source_url: https://doi.org/10.1089/psymed.2023.0037
substance_tags: psilocybin,psilocin
topic_tags: Longevity
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Preadministration of Lorazepam Reduces Efficacy and Longevity of Antidepressant-Like Effect from a Psychedelic.

abstract:
IntroductionPsychedelics such as psilocybin have been shown to have persistent antidepressant effects, but with considerable individual variability in optimal dosing. Intravenous (IV) dosing is rapid onset and quickly titrated, possibly preceded by an anxiolytic for patient comfort. We explored the viability of IV psilocin with and without preadministration of lorazepam for possible future inpatient therapeutic utility.MethodsMale Wistar-Kyoto rats were given saline (S), psilocin (P), or psilocin and lorazepam (P+L). Saline was given intraperitoneally (IP), psilocin was given IV to a second group, and lorazepam was given IP, then psilocin was given IV30 min later to a final group. Rats were tested in the forced swim test (FST) 3 and 14 weeks after injection.ResultsP rats were more active than S rats at both time points. P + L rats were more active in the FST than S rats at 3, but not 14, weeks. P + L rats were less active than P rats at 14 weeks, and less active than themselves at 3 weeks. S rats' behavior was not different at 3 and 14 weeks. Similarly, P rats behaved the same at both time points.ConclusionsIV psilocin persistently decreased immobility in the FST, but lorazepam reduced psilocin's antidepressant-like efficacy and longevity.

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authors: Barnett BS, Arakelian M, Beebe D, Ontko J, Riegal C, Siu WO, Weleff J, Pope HG
journal: Psychedelic medicine (New Rochelle, N.Y.)
publication_date: 2024-02-29
doi: 10.1089/psymed.2023.0036
pubmed_id: 40051760
source_url: https://pubmed.ncbi.nlm.nih.gov/40051760/
keywords: hallucinogen, psychedelic assisted therapy, psychedelics, psychiatrist, survey
substance_tags: psilocybin
topic_tags: Depression,Addiction,Clinical Trial,Observational Study,Treatment-Resistant Depression,Safety
study_type: Clinical Trial
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:37
raw_json: {"pubmed_id":"40051760"}
title:
American Psychiatrists' Opinions About Classic Hallucinogens and Their Potential Therapeutic Applications: A7-Year Follow-Up Survey.

abstract:
Psilocybin, a classic hallucinogen, may eventually be approved by the United States Food and Drug Administration for treatment-resistant depression. However, we are aware of only one published national survey of American psychiatrists regarding their opinions about hallucinogens and hallucinogen-assisted therapy, conducted by our group in 2016. Here, we report a repeat survey, using virtually identical methods, assessing whether American psychiatrists display greater optimism about the therapeutic use of hallucinogens in 2022-23.
We e-mailed our survey instrument to 1,000 randomly selected American Psychiatric Association members-250 resident-fellows and 750 attending psychiatrists-in late 2022 and early 2023. We calculated descriptive statistics and used a non-parametric trend test to compare the current survey responses with those from 2016. We also constructed a multivariate logistic regression model to assess attributes of respondents that predicted moderate/strong agreement with plans to incorporate hallucinogen-assisted therapy into their own practice.
The response rate was 13.1% ( = 131). Respondents were demographically similar to the 2016 respondents. A majority moderately/strongly believed that hallucinogens show promise in treating psychiatric conditions (80.9%) and substance use disorders (SUDs) (60.8%). Large majorities also moderately/strongly supported research into hallucinogens' therapeutic potential for psychiatric conditions (93.9%) and SUDs (88.6%), as well as federal funding of associated clinical trials (84.7% and 80.9%, respectively). Comparisons to 2016 showed significantly increased optimism regarding the therapeutic promise of hallucinogens and decreased concern about risks, with 50.4% of respondents reporting moderate/strong intentions to incorporate hallucinogen-assisted therapy into their practice.
Our data reveal a striking positive shift in attitudes toward the therapeutic potential of hallucinogens among American psychiatrists since 2016, with a majority of responding psychiatrists planning to incorporate hallucinogen-assisted therapy into their practice if regulatory approval is granted.


title: The Mystical Experience Questionnaire 4-Item and Challenging Experience Questionnaire 7-Item.
authors: Strickland JC, Garcia-Romeu A, Johnson MW.
publication_date: 2024-03-11
doi: 10.1089/psymed.2023.0046
pubmed_id: 40051759
source_url: https://doi.org/10.1089/psymed.2023.0046
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Mystical Experience
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
abstract:
BackgroundThe Mystical Experience Questionnaire (MEQ-30) and Challenging Effects Questionnaire (CEQ) are two of the most widely used, validated instruments to probe subjective effects of psychedelic drugs. However, these assessments are lengthy and can be a burden to study participants or patients if administered during acute psychedelic effects, after resolution of psychedelic effects when participants are often fatigued, or in studies with multiple other assessments. The development of briefer measures can advance research and patient assessment.Methods and materialsThis study developed and assessed the validity of brief versions of the MEQ-30 and CEQ (MEQ-4 and CEQ-7) using data collected online from individuals reporting psychedelic use with therapeutic intent in nonstudy settings (N = 1160). Respondents completed full and brief versions as well as mood questionnaires indexing mental health symptoms before their psychedelic experience and now.ResultsFull and brief version total scores showed strong correspondence for the MEQ (r = 0.89) and CEQ (r = 0.90). Brief versions also showed strong correspondence to full-scale subscale scores. MEQ and CEQ scores were higher for classic psychedelics (e.g., lysergic acid diethylamide, psilocybin) than for 3,4-Methylene-dioxymethamphetamine in this sample with both full and brief versions, consistent with previous full-version findings showing drug and dose-related differences using the MEQ. Also consistent with prior findings, higher mystical experience scores on both full and brief MEQ versions were associated with greater reductions in depression and anxiety, whereas challenging experiences on both full and brief CEQ versions showed limited association with changes in mental health variables.ConclusionThe notably strong association of brief scales with full versions combined with associations with therapeutic outcomes provide initial support for the MEQ-4 and CEQ-7. These findings, combined with substantial reductions in participant/patient burden, support the use of the MEQ-4 and CEQ-7 for a wide variety of research and patient treatment settings.

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title: Scoping Review: The Role of Psychedelics in the Management of Chronic Pain.
authors: Robinson CL, Fonseca ACG, Diejomaoh EM, D'Souza RS, Schatman ME, Orhurhu V, Emerick T.
publication_date: 2024-03-10
doi: 10.2147/jpr.s439348
pubmed_id: 38496341
source_url: https://doi.org/10.2147/jpr.s439348
substance_tags: psilocybin
study_type: Meta-Analysis
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
abstract:
IntroductionAmid a lack of effective chronic pain treatments, psychedelics have gained attention as a potential solution, although their Schedule 1 classification poses challenges. Psychedelics, such as lysergic acid diethylamide (LSD) and psilocybin, have gained popularity as alternatives and adjuncts for chronic pain treatment. Studies suggest that they may modulate pain processing through agonism primarily at the serotonin receptor, 5-HT2A. One of the first of its nature, we present an artificial intelligence (AI)-powered scoping review primarily focusing on evaluating psychedelics for chronic pain conditions such as cluster headache, phantom limb pain, and fibromyalgia.MethodsIn accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, we used an AI-powered comprehensive search strategy utilizing the ChatGPT4.0 Bing chat to search Medline, Embase, Cochrane, and Google Scholar for articles addressing chronic pain. The query was performed on June 1, 2023, focusing on psychedelics for chronic, non-cancer pain including headache disorders. Inclusion criteria were English-only, peer-reviewed articles involving human participants >18 years, focusing on chronic pain conditions (eg, phantom limb pain and cluster headache), using LSD, 2.5-dimethoxy-4-bromophenethylamine (2C-B), N, N-dimethyltryptamine (DMT), psilocybin, or mescaline. Exclusion criteria were reviews, editorials, and opinion articles and studies focusing on tetrahydrocannabinol/cannabis and/or ketamine.ResultsA total of 186 unique database entries were retrieved, of which nine studies were included in the scoping review. These included four case reports/series, an open-label study, a cohort study, two online surveys, and a randomized, double-blind, placebo-controlled trial. They comprised three studies addressing phantom limb pain, four addressing cluster headaches, and two addressing fibromyalgia, spinal cord injury, complex regional pain syndrome, and lumbar radiculopathy.ConclusionPsychedelics may have potential in alleviating pain symptoms secondary to a multitude of chronic pain conditions. However, further randomized, double-blind, placebo-controlled trials are needed to further explore and evaluate the role of psychedelics in chronic, non-cancer pain.

topic_tags:
Chronic Pain,Headache / Migraine,Receptor Pharmacology,Meta-Analysis,Systematic Review,Review Article,Case Report,Observational Study

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publication_date: 2024-02-13
doi: 10.1016/j.medj.2024.01.005
pubmed_id: 38359838
source_url: https://doi.org/10.1016/j.medj.2024.01.005
substance_tags: psilocybin
topic_tags: Depression,Addiction,Clinical Trial,Treatment-Resistant Depression,Safety,Adverse Events
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Psilocybin-assisted psychotherapy for treatment resistant depression: A randomized clinical trial evaluating repeated doses of psilocybin.

authors:
Rosenblat JD, Meshkat S, Doyle Z, Kaczmarek E, Brudner RM, Kratiuk K, Mansur RB, Schulz-Quach C, Sethi R, Abate A, Ali S, Bawks J, Blainey MG, Brietzke E, Cronin V, Danilewitz J, Dhawan S, Di Fonzo A, Di Fonzo M, Drzadzewski P, Dunlop W, Fiszter H, Gomes FA, Grewal S, Leon-Carlyle M, McCallum M, Mofidi N, Offman H, Riva-Cambrin J, Schmidt J, Smolkin M, Quinn JM, Zumrova A, Marlborough M, McIntyre RS.

abstract:
BackgroundPsilocybin-assisted psychotherapy (PAP) has been associated with antidepressant effects. Trials to date have typically excluded participants with complex presentations. Our aim was to determine the feasibility of PAP in a complex population, including high levels of treatment resistance in major depressive and bipolar disorder and patients with baseline suicidality and significant comorbidity. We also evaluated flexible repeated doses over a 6-month period.MethodsAdults with treatment-resistant depression as part of major depressive or bipolar II disorder without psychosis or a substance use disorder were eligible to participate. Subjects were randomized to immediate treatment or waitlist control, with all eventually receiving PAP. Participants had one, two, or three psilocybin sessions with a fixed dose of 25 mg. Each dose was accompanied by preparation and integration psychotherapy sessions. Acceptability, safety, tolerability, and efficacy were evaluated (this study was registered at ClinicalTrials.gov: NCT05029466).FindingsParticipants were randomized to immediate treatment (n = 16) or delayed treatment (n = 14). 29/30 were retained to the week-2 primary endpoint. Adverse events were transient, with no serious adverse events. Greater reductions in depression severity as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) were observed in the immediate treatment arm compared to the waitlist period arm with a large hedge's g effect size of 1.07 (p

keywords:
Humans, Antidepressive Agents, Psychotherapy, Adult, Depressive Disorder, Treatment-Resistant, Psilocybin, Major Depressive Disorder

raw_json:
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title: New evidence for flexible psilocybin dosing in patients with treatment-resistant depression.
authors: Aaronson ST, Kozak Z.
publication_date: 2024-02-13
doi: 10.1016/j.medj.2024.01.014
pubmed_id: 38359837
source_url: https://doi.org/10.1016/j.medj.2024.01.014
keywords: Humans, Depression, Bipolar Disorder, Depressive Disorder, Treatment-Resistant, Psilocybin
substance_tags: psilocybin
topic_tags: Depression,Clinical Trial,Treatment-Resistant Depression
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
abstract:
Psilocybin has demonstrated efficacy for treating depression; however, psychiatrically complex patients have been excluded from trials. A recent clinical trial by Rosenblat at al.1 demonstrates feasibility of a flexible dosing schedule of psilocybin in individuals with severely treatment-resistant depression (TRD), including those with co-morbid conditions or bipolar II disorder (BPII), potentially expanding the current treatment paradigm.

raw_json:
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title: Where do the symptoms come from in depression? Topography and dynamics matter.
authors: Çatal Y, Northoff G.
publication_date: 2024-03-04
doi: 10.1093/braincomms/fcae067
pubmed_id: 38515441
source_url: https://doi.org/10.1093/braincomms/fcae067
substance_tags: psilocybin
topic_tags: Depression,Treatment-Resistant Depression
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:03
abstract:
This scientific commentary refers to 'Brain dynamics predictive of response to psilocybin for treatment-resistant depression', by Vohryzek et al. (https://doi.org/10.1093/braincomms/fcae049).

raw_json:
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title: Neuroimaging features of psilocybin-induced toxic-metabolic encephalopathy in an adolescent.
authors: Ho C, Crawford JR.
publication_date: 2024-03-04
doi: 10.1136/bcr-2024-259721
pubmed_id: 38442973
source_url: https://doi.org/10.1136/bcr-2024-259721
keywords: Humans, Brain Diseases, Metabolic, Adolescent, Psilocybin
substance_tags: psilocybin
topic_tags: Brain Imaging,Aging,Adolescents
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
raw_json:
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authors: Velit-Salazar MR, Shiroma PR, Cherian E.
publication_date: 2024-03-02
doi: 10.3390/brainsci14030248
pubmed_id: 38539636
source_url: https://doi.org/10.3390/brainsci14030248
substance_tags: psilocybin
topic_tags: Depression,PTSD,Emotional Processing,Systematic Review,Review Article
study_type: Systematic Review
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
title:
A Systematic Review of the Neurocognitive Effects of Psychedelics in Healthy Populations: Implications for Depressive Disorders and Post-Traumatic Stress Disorder.

abstract:
ObjectiveThis study aims to provide an overview of pharmacological trials that examine the neurocognitive effects of psychedelics among healthy individuals and patients with post-traumatic stress disorder (PTSD) or major depressive disorder (MDD).MethodsThe Preferred Reporting Items for Systematic Reviews (PRISMA) was used as a guide to structure and report the findings for this review. A literature search included the MEDLINE database up until December 2022. We included randomized or open-label human studies of MDMA, psilocybin, mescaline, LSD, DMT, or cannabis reporting non-emotionally charged neurocognitive outcomes ("cold cognition") measured through validated neuropsychological tests.ResultsA total of 43 full-text papers on MDMA (15), cannabis (12), LSD (6), psilocybin (9), DMT/ayahuasca (1), and mescaline (0) were included, mostly on healthy subjects. A single article on MDMA's effects on cognition in subjects with PTSD was included; there were no studies on psychedelics and neurocognition in MDD. Most of the studies on healthy subjects reported detrimental or neutral effects on cognition during the peak effect of psychedelics with a few exceptions (e.g., MDMA improved psychomotor function). Performance on the type of neurocognitive dimension (e.g., attention, memory, executive function, psychomotor) varies by type of psychedelic, dosage, and cognitive testing.ConclusionsSmall samples and a lack of uniformed methods across studies preclude unequivocal conclusions on whether psychedelics enhance, decrease, or have no significant effect on cognitive performance. It is foreseen that psychedelics will soon become an available treatment for various psychiatric disorders. The acute and long-term effects on cognition caused by psychedelics should be assessed in future studies.

raw_json:
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title: Psychedelic Therapy: A Primer for Primary Care Clinicians-Psilocybin.
authors: Tabaac BJ, Shinozuka K, Arenas A, Beutler BD, Cherian K, Evans VD, Fasano C, Muir OS.
publication_date: 2024-02-29
doi: 10.1097/mjt.0000000000001724
pubmed_id: 38518269
source_url: https://doi.org/10.1097/mjt.0000000000001724
substance_tags: psilocybin
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
abstract:
BackgroundThe primary psychoactive drug in magic mushrooms, psilocybin, induces profound alterations in consciousness through the 5-HT2A receptor. This review consolidates current research findings to elucidate the pharmacology, safety profile, and clinical applications of psilocybin.Areas of uncertaintyDespite initial concerns that psilocybin could cause psychosis, contemporary research has demonstrated that psilocybin is generally safe. The most common adverse effects are nausea and headache, yet both tend to be transient. Serious adverse events can generally be avoided in controlled settings such as clinical trials. However, in the largest clinical trial to date, there were a total of 7 reported cases of suicidal ideation, up to 12 weeks after receiving a single 25 mg dose of psilocybin. That being said, all 7 cases did not respond to the treatment. Although selective serotonin reuptake inhibitors may blunt the hallucinogenic qualities of psilocybin, preliminary research suggests that they may enhance its antidepressant effects.Therapeutic advancesIn clinical trials, psilocybin has shown promise for treating major depressive disorder and treatment-resistant depression. Initial studies indicated that 42%-57% of patients underwent remission after psilocybin-assisted therapy, which suggests that psilocybin is more effective than existing antidepressant medications. Clinical data have also demonstrated that psilocybin can manage substance use disorders and end-of-life anxiety with clinical outcomes that are sustained for months and sometimes years after 1 or 2 doses.LimitationsHowever, larger Phase II trials with more than 100 depressed participants have shown a much smaller remission rate of 25%-29%, though these studies still observed that psilocybin causes a significant reduction in depressive symptoms.ConclusionsAside from ketamine, psilocybin is the most clinically well-researched psychedelic drug, with trials that have enrolled hundreds of participants and multiple therapeutic applications. Phase III trials will determine whether psilocybin lives up to the promise that it showed in previous clinical trials.

keywords:
Humans, Hallucinogens, Antidepressive Agents, Primary Health Care, Clinical Trials as Topic, Psilocybin, Major Depressive Disorder

topic_tags:
Depression,Anxiety,Addiction,End-of-Life Distress,Headache / Migraine,Pharmacology,Receptor Pharmacology,Consciousness,Clinical Trial,Review Article,Treatment-Resistant Depression,Healthcare Workers,Safety,Adverse Events

raw_json:
{"europe_pmc_id":"38518269","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psychedelic Therapy: A Primer for Primary Care Clinicians-Historical Perspective and Overview.
authors: Tabaac BJ, Shinozuka K, Arenas A, Beutler BD, Cherian K, Evans VD, Fasano C, Muir OS.
publication_date: 2024-02-29
doi: 10.1097/mjt.0000000000001727
pubmed_id: 38518266
source_url: https://doi.org/10.1097/mjt.0000000000001727
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
abstract:
BackgroundPsychedelic drugs have recently emerged as plausibly effective pharmacological agents for the management of depression, anxiety, and other neuropsychiatric conditions, including those that are treatment-resistent. The latter half of the 20th century marked a revolution in the treatment of mental illnesses, exemplified by the introduction of selective serotonin reuptake inhibitors and other pharmacological agents. Nevertheless, mental illness remains a major public health crisis, affecting nearly one billion individuals worldwide.Areas of uncertaintyBecause of the decades-long status of several psychedelics as Schedule I drugs, there have not been very many large, double-blind, randomized controlled trials of psychedelics. Owing to small sample sizes, there may be rare yet serious adverse events that have not been reported in the clinical trials thus far.Therapeutic advancesEsketamine, a dissociative hallucinogen drug, was approved for the management of major depressive disorder by the Food and Drug Administration in 2019. As of January 2024, two Phase III trials of 3,4-methylenedioxymethamphetamine (MDMA), a synthetic drug that inhibits the serotonin transporter, have been completed; the results indicate that MDMA is superior to existing pharmacological treatments for post-traumatic stress disorder. A phase III trial of psilocybin, a naturally occurring serotonin receptor partial agonist, is currently underway. The following series details the current state of research in psychedelic therapeutics, including lysergic acid diethylamide (LSD), N-N-dimethyltryptamine (DMT) and ayahuasca, psilocybin, ibogaine, MDMA, and ketamine.LimitationsWhile initial clinical trials of psychedelics for depression were very promising, trials of psilocybin with larger sample sizes (100+ participants) suggest that its remission rate is 25%-29%. This is about the same as the remission rate of antidepressants, which is roughly 30% according to the landmark STAR*D trial.ConclusionsPsychedelic drugs and structural derivatives offer a great deal of promise for the management of a wide range of psychiatric morbidities. It is imperative that clinicians become familiar with these novel agents and learn how to integrate psychedelic therapy with the rest of their care through open communication and referral.

keywords:
Humans, N-Methyl-3,4-methylenedioxyamphetamine, Hallucinogens, Primary Health Care, Randomized Controlled Trials as Topic, Psilocybin, Major Depressive Disorder

topic_tags:
Depression,Anxiety,PTSD,Receptor Pharmacology,Clinical Trial,Randomized Controlled Trial,Healthcare Workers,Adverse Events

raw_json:
{"europe_pmc_id":"38518266","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Wood ME, Brown GJ, Karschner EL, Seither JZ, Brown JT, Knittel JL, Walterscheid JP.
publication_date: 2024-02-29
doi: 10.1093/jat/bkae002
pubmed_id: 38287693
source_url: https://doi.org/10.1093/jat/bkae002
substance_tags: psilocybin,psilocin
topic_tags: Safety,Toxicity
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Screening and confirmation of psilocin, mitragynine, phencyclidine, ketamine and ketamine metabolites by liquid chromatography-tandem mass spectrometry.

abstract:
A safe and productive workplace requires a sober workforce, free from substances that impair judgment and concentration. Although drug monitoring programs already exist, the scope and loopholes of standard workplace testing panels are well known, allowing other substances to remain a source of risk. Therefore, a high-throughput urine screening method for psilocin, mitragynine, phencyclidine, ketamine, norketamine and dehydronorketamine was developed and validated in conjunction with a urine and blood confirmation method. There are analytical challenges to overcome with psilocin and mitragynine, particularly when it comes to drug stability and unambiguous identification in authentic specimens. Screening and confirmation methods were validated according to the American National Standards Institute/Academy Standards Board (ANSI/ASB) Standard 036, Standard Practices for Method Validation in Forensic Toxicology. An automated liquid handling system equipped with dispersive pipette extraction tips was utilized for preparing screening samples, whereas an offline solid-phase extraction method was used for confirmation sample preparation. Both methods utilized liquid chromatography-tandem mass spectrometry to achieve limits of detection between 1-5 ng/mL for the screening method and 1 ng/mL for the confirmation method. Automation allows for faster throughput and enhanced quality assurance, which improves turnaround time. Compared to previous in-house methods, specimen volumes were substantially decreased for both blood and urine, which is an advantage when volume is limited. This screening technique is well suited for evaluating large numbers of specimens from those employed in safety-sensitive workforce positions. This method can be utilized by workplace drug testing, human performance and postmortem laboratories seeking robust qualitative screening and confirmation methods for analytes that have traditionally been challenging to routinely analyze.

keywords:
Humans, Ketamine, Secologanin Tryptamine Alkaloids, Phencyclidine, Chromatography, Liquid, Tandem Mass Spectrometry, Psilocybin

raw_json:
{"europe_pmc_id":"38287693","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Rouaud A, Calder AE, Hasler G.
publication_date: 2024-01-11
doi: 10.1177/02698811231225609
pubmed_id: 38214279
source_url: https://doi.org/10.1177/02698811231225609
keywords: Humans, Fibrosis, Lysergic Acid Diethylamide, Hallucinogens, Cardiotoxins, Psilocybin
substance_tags: psilocybin
topic_tags: Receptor Pharmacology,Microdosing,Review Article,Safety
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:03
title:
Microdosing psychedelics and the risk of cardiac fibrosis and valvulopathy: Comparison to known cardiotoxins.

abstract:
Though microdosing psychedelics has become increasingly popular, its long-term effects on cardiac health remain unknown. Microdosing most commonly involves ingesting sub-threshold doses of lysergic acid diethylamide (LSD), psilocybin, or other psychedelic drugs 2-4 times a week for at least several weeks, but potentially months or years. Concerningly, both LSD and psilocybin share structural similarities with medications which raise the risk of cardiac fibrosis and valvulopathy when taken regularly, including methysergide, pergolide, and fenfluramine. 3,4-Methylenedioxymethamphetamine, which is also reportedly used for microdosing, is likewise associated with heart valve damage when taken chronically. In this review, we evaluate the evidence that microdosing LSD, psilocybin, and other psychedelics for several months or more could raise the risk of cardiac fibrosis. We discuss the relationship between drug-induced cardiac fibrosis and the 5-HT2B receptor, and we make recommendations for evaluating the safety of microdosing psychedelics in future studies.

raw_json:
{"europe_pmc_id":"38214279","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Sekssaoui M, Bockaert J, Marin P, Bécamel C.
publication_date: 2024-01-10
doi: 10.1038/s41386-024-01794-6
pubmed_id: 38212441
source_url: https://doi.org/10.1038/s41386-024-01794-6
substance_tags: psilocybin
topic_tags: Depression,Mechanism of Action,Receptor Pharmacology,Animal Study
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:03
title:
Antidepressant-like effects of psychedelics in a chronic despair mouse model: is the 5-HT2A receptor the unique player?

abstract:
Major depressive disorder (MDD) is one of the most disabling psychiatric disorders in the world. First-line treatments such as selective serotonin reuptake inhibitors (SSRIs) still have many limitations, including a resistance to treatment in 30% of patients and a delayed clinical benefit that is observed only after several weeks of treatment. Increasing clinical evidence indicates that the acute administration of psychedelic agonists of the serotonin 5-HT2A receptor (5-HT2AR), such as psilocybin, to patients with MDD induce fast antidepressant effects, which persist up to five weeks after the treatment. However, the involvement of the 5-HT2AR in these antidepressant effects remains controversial. Furthermore, whether the hallucinogenic properties of 5-HT2AR agonists are mandatory to their antidepressant activity is still an open question. Here, we addressed these issues by investigating the effect of two psychedelics of different chemical families, DOI and psilocybin, and a non-hallucinogenic 5-HT2AR agonist, lisuride, in a chronic despair mouse model exhibiting a robust depressive-like phenotype. We show that a single injection of each drug to wild type mice induces anxiolytic- and antidepressant-like effects in the novelty-suppressed feeding, sucrose preference and forced swim tests, which last up to 15 days. DOI and lisuride administration did not produce antidepressant-like effects in 5-HT2A-/- mice, whereas psilocybin was still effective. Moreover, neither 5-HT1AR blockade nor dopamine D1 or D2 receptor blockade affected the antidepressant-like effects of psilocybin in 5-HT2A-/- mice. Collectively, these findings indicate that 5-HT2AR agonists can produce antidepressant-like effects independently of hallucinogenic properties through mechanisms involving or not involving the receptor.

keywords:
Animals, Humans, Mice, Serotonin, Lisuride, Receptor, Serotonin, 5-HT2A, Hallucinogens, Antidepressive Agents, Psilocybin, Major Depressive Disorder

raw_json:
{"europe_pmc_id":"38212441","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2023-12-21
doi: 10.1016/j.euroneuro.2023.12.006
pubmed_id: 38141403
source_url: https://doi.org/10.1016/j.euroneuro.2023.12.006
substance_tags: psilocybin
topic_tags: Biomarkers,Clinical Trial,Healthy Volunteers,Safety,Adverse Events
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
title:
Safety and tolerability of inhaled N,N-Dimethyltryptamine (BMND01 candidate): A phase I clinical trial.

authors:
Falchi-Carvalho M, Wießner I, Silva SRB, O Maia L, Barros H, Laborde S, Arichelle F, Tullman S, Silva-Costa N, Assunção A, Almeida R, Pantrigo ÉJ, Bolcont R, Costa-Macedo JV, Arcoverde E, Galvão-Coelho N, Araujo DB, Palhano-Fontes F.

abstract:
Psychedelics are being increasingly examined for their therapeutic potential in mood disorders. While the acute effects of ayahuasca, psilocybin, and lysergic acid diethylamide (LSD) last over several hours, inhaled N,N-Dimethyltryptamine (DMT) effects last around 10 min, which might provide a cost- and time-effective alternative to the clinical application of oral psychedelics. We aimed at investigating the safety and tolerability of inhaled DMT (BMND01 candidate). We recruited 27 healthy volunteers to receive a first, lower dose and a second, higher dose (5/20 mg, 7.5/30 mg, 10/40 mg, 12.5/50 mg, or 15/60 mg) of inhaled DMT in an open-label, single-ascending, fixed-order, dose-response study design. We investigated subjective experiences (intensity, valence, and phenomenology), physiological effects (blood pressure, heart rate, respiratory rate, blood oxygen saturation, body temperature), biochemical markers (liver, kidney, and metabolic functions), and adverse events during the acute and post-acute effects of DMT. DMT dose-dependently increased intensity, valence and perceptual ratings. There was a mild, transient, and self-limited increase in blood pressure and heart rate. There were no changes in safety blood biomarkers and no serious adverse events. DMT dose-dependently enhanced subjective experiences and positive valence. Inhaled DMT might be an efficient, non-invasive, safe route of administration, which might simplify the clinical use of this substance. This is the first clinical trial to test the effects of inhaled DMT (BMND01 candidate).

keywords:
Humans, N,N-Dimethyltryptamine, Lysergic Acid Diethylamide, Hallucinogens, Blood Pressure, Psilocybin

raw_json:
{"europe_pmc_id":"38141403","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Gomonit MM, Skillman B, Swortwood MJ.
publication_date: 2023-12-21
doi: 10.1111/1556-4029.15454
pubmed_id: 38140718
source_url: https://doi.org/10.1111/1556-4029.15454
substance_tags: psilocybin,psilocin
topic_tags: Pharmacology
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:00
title:
Quantification of psilocin in human whole blood using liquid chromatography-tandem mass spectrometry (LC-MS/MS).

abstract:
There has been burgeoning interest in psilocybin-use for the treatment of various neurological and neurodegenerative diseases. Psilocybin is mistakenly perceived as the principal pharmacologically active compound due to its high concentrations found in magic mushrooms; however, it is the prodrug of psilocin. Despite the expanding body of clinical research seeking to understand the pharmacodynamic/pharmacokinetic properties of psilocin, and its role in inducing dramatic changes to cognitive function, there has not been a corresponding increase in the development of sensitive analytical methods that can quantify psilocin in different biological fluids. Existing analytical methods have been developed using plasma, serum, and urine as the matrix of choice, but with the unknown blood-to-plasma ratio of psilocin, any pharmacokinetic conclusions drawn solely on plasma data may be misleading. Thus, the main objective of this study is to develop the first analytical method that utilizes SPE and LC-MS/MS to quantify psilocin in human whole blood. The SPE procedure yielded a high recovery efficiency (≥89%) with minimal matrix effects. The method was validated according to ANSI/ASB036 guidelines. Linearity was between 0.7-200 ng/mL and encompassed previously reported ranges found in plasma/serum. Bias, within- and between-run precision for all quality controls met ANSI/ASB036 acceptability criteria. Endogenous/exogenous interferences and carryover were negligible. Psilocin stability was assessed at 4°C over 48 h and was considered stable. Although a proof-of-concept study will need to be performed to characterize the method, this analytical workflow was able to detect and quantify psilocin in human whole blood at low limits of quantification.

keywords:
Humans, Chromatography, Liquid, Tandem Mass Spectrometry, Psilocybin, Liquid Chromatography-Mass Spectrometry

raw_json:
{"europe_pmc_id":"38140718","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Capaldi JM, Shabanian J, Finster LB, Asher A, Wertheimer JC, Zebrack BJ, Shirazipour CH.
publication_date: 2023-01-11
doi: 10.1080/17437199.2022.2162947
pubmed_id: 36632776
source_url: https://doi.org/10.1080/17437199.2022.2162947
substance_tags: psilocybin
topic_tags: PTSD,Review Article
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
title:
Post-traumatic stress symptoms, post-traumatic stress disorder, and post-traumatic growth among cancer survivors: a systematic scoping review of interventions.

abstract:
The detrimental effects of Post-Traumatic Stress Symptoms (PTSS) and Post-Traumatic Stress Disorder (PTSD) and the benefits of Post-Traumatic Growth (PTG) are well established for cancer survivors. Increased cancer survival rates necessitate an understanding of how these two paradoxical outcomes, PTSS/PTSD and PTG, are targeted through interventions. This systematic scoping review aims to (a) examine existing evidence on interventions targeting PTSS/PTSD and/or PTG among cancer survivors and (b) identify knowledge gaps to inform future research. Following the six steps of a scoping review, 76 articles met the inclusion criteria. Quantitative articles were examined using descriptive analysis. Frequency counts of the collated data were tabulated into summary tables. Qualitative articles were reviewed using meta-synthesis. Most articles were quantitative (n = 52) and targeted PTG (n = 68) through promising intervention approaches such as psychotherapy, mindfulness, physical activity, and psilocybin-assisted therapy. Three key implications for future research and practice were synthesized: (1) mechanistic considerations for intervention design that provide a roadmap for rigorous and theoretically-grounded research; (2) the need for improved representation of cancer survivors in trials; and (3) potential facilitators of intervention efficacy. Together, these findings can direct future research to optimize interventions to reduce PTSS/PTSD and promote PTG achievement among cancer survivors.

keywords:
Humans, Neoplasms, Stress Disorders, Post-Traumatic, Psychotherapy, Cancer Survivors, Posttraumatic Growth, Psychological

raw_json:
{"europe_pmc_id":"36632776","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin and the Development of Serotonin Toxicity.
authors: Amarnani AD, Free MF, Baweja R.
publication_date: 2024-02-28
doi: 10.4088/pcc.23cr03648
pubmed_id: 38442068
source_url: https://doi.org/10.4088/pcc.23cr03648
keywords: Humans, Serotonin, Psilocybin
substance_tags: psilocybin
topic_tags: Receptor Pharmacology,Toxicity
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:03
raw_json:
{"europe_pmc_id":"38442068","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin, an Effective Treatment for Major Depressive Disorder in Adults - A Systematic Review.
authors: Watford T, Masood N.
publication_date: 2023-10-15
doi: 10.9758/cpn.23.1120
pubmed_id: 38247407
source_url: https://doi.org/10.9758/cpn.23.1120
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
abstract:
Psilocybin is a classical psychedelic which has been utilised for healing purposes for millenia. However, with its classification as a Schedule I substance, research into this compound is scarce with few FDA-approved clinical studies. Despite this, profound findings into its antidepressant effects (largely through its action on 5-HT1a receptors) in mental illnesses such as major depressive disorder have rapidly increased interest back into their potential therapeutic benefits. This systematic review provides an analysis of the studies examining the clinical use of psilocybin for major depressive disorder. In total 6 studies were selected, including 319 participants, with half being randomised controlled trials and half open label trials. In every study psychological support was included as an integral part of the treatment. It was found that every study significantly favoured the use of psilocybin in reducing depressive symptoms, with few side effects. This gives psilocybin an advantage over commonly prescribed selective serotonin reuptake inhibitors (SSRIs), which carry more risk and cause more adverse effects. This drug therefore shows promise for being used as a clinical treatment for major depressive disorder, however future research should develop a paradigm for its use, with the timing of sessions and type of psychological support specified to allow for more precise analysis of the clinical effects of the drug. Additionally, more studies into its clinical efficacy are needed for appropriate detection of any publication bias. With this, psilocybin could prove to be revolutionary in treating depression and become an alternative medication to SSRIs.

topic_tags:
Depression,Receptor Pharmacology,Randomized Controlled Trial,Systematic Review,Review Article,Safety,Adverse Events

raw_json:
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authors: Glynos NG, Aday JS, Kruger D, Boehnke KF, Lake S, Lucas P
journal: Frontiers in psychiatry
publication_date: 2023-12-31
doi: 10.3389/fpsyt.2024.1349565
pubmed_id: 38455520
source_url: https://pubmed.ncbi.nlm.nih.gov/38455520/
keywords: MDMA, SUD, psilocybin, psychedelics, substance use, survey
substance_tags: psilocybin
topic_tags: Addiction,Observational Study
study_type: Observational Study
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:37
raw_json: {"pubmed_id":"38455520"}
title:
Psychedelic substitution: altered substance use patterns following psychedelic use in a global survey.

abstract:
Recent research suggests that psychedelics may have potential for the treatment of various substance use disorders. However, most studies to date have been limited by small sample sizes and neglecting to include non-North American and European populations.
We conducted a global, cross-sectional online survey of adults (n = 5,268, 47.2% women) self-reporting past or current psychedelic use and investigated whether psychedelic use was associated with changes in use of other substances.
Nearly three-quarters (70.9%; n = 3,737/5,268) reported ceasing or decreasing use of one or more non-psychedelic substances after naturalistic psychedelic use. Among those with previous use, 60.6% (n = 2,634/4,344) decreased alcohol use, 55.7% (n = 1,223/2,197) decreased antidepressant use, and 54.2% (n = 767/1,415) decreased use of cocaine/crack. Over a quarter of the sample indicated that their decrease in substance use persisted for 26 weeks or more following use of a psychedelic. Factors associated with decreased use included a motivation to either decrease one's substance use or self-treat a medical condition. Importantly, 19.8% of respondents also reported increased or initiated use of one or more other substances after psychedelic use, with illicit opioids (14.7%; n = 86/584) and cannabis (13.3%; n = 540/4,064) having the highest proportions. Factors associated with increased substance use included having a higher income and residing in Canada or the US.
Although limited by cross-sectional study design, this large observational study will help inform future studies aiming to investigate the relationship between substance use patterns and psychedelic use.


authors: Bhatt KV, Weissman CR.
publication_date: 2024-02-19
doi: 10.1038/s44184-023-00053-8
pubmed_id: 38609500
source_url: https://doi.org/10.1038/s44184-023-00053-8
substance_tags: psilocybin
topic_tags: Review Article
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
The effect of psilocybin on empathy and prosocial behavior: a proposed mechanism for enduring antidepressant effects.

abstract:
Psilocybin is a serotonergic psychedelic shown to have enduring antidepressant effects. Currently, the mechanism for its enduring effects is not well understood. Empathy and prosocial behavior may be important for understanding the therapeutic benefit of psilocybin. In this article we review the effect of psilocybin on empathy and prosocial behavior. Moreover, we propose that psilocybin may induce a positive feedback loop involving empathy and prosocial behavior which helps explain the observed, enduring antidepressant effects.

raw_json:
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title: Development of a digital intervention for psychedelic preparation (DIPP).
authors: McAlpine RG, Sacchet MD, Simonsson O, Khan M, Krajnovic K, Morometescu L, Kamboj SK.
publication_date: 2024-02-18
doi: 10.1038/s41598-024-54642-4
pubmed_id: 38374177
source_url: https://doi.org/10.1038/s41598-024-54642-4
keywords: Humans, Pentamidine, Hallucinogens, Mental Health, Consciousness, Psilocybin
substance_tags: psilocybin
topic_tags: Consciousness,Safety
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
abstract:
Psychedelic substances induce profound alterations in consciousness. Careful preparation is therefore essential to limit adverse reactions, enhance therapeutic benefits, and maintain user safety. This paper describes the development of a self-directed, digital intervention for psychedelic preparation. Drawing on elements from the UK Medical Research Council (MRC) framework for developing complex interventions, the design was informed by a four-factor model of psychedelic preparedness, using a person-centred approach. Our mixed-methods investigation consisted of two studies. The first involved interviews with 19 participants who had previously attended a 'high-dose' psilocybin retreat, systematically exploring their preparation behaviours and perspectives on the proposed intervention. The second study engaged 28 attendees of an ongoing psilocybin retreat in co-design workshops, refining the intervention protocol using insights from the initial interviews. The outcome is a co-produced 21-day digital course (Digital Intervention for Psychedelic Preparation (DIPP)), that is organised into four modules: Knowledge-Expectation, Psychophysical-Readiness, Safety-Planning, and Intention-Preparation. Fundamental components of the course include daily meditation practice, supplementary exercises tied to the weekly modules, and mood tracking. DIPP provides a comprehensive and scalable solution to enhance psychedelic preparedness, aligning with the broader shift towards digital mental health interventions.

raw_json:
{"europe_pmc_id":"38374177","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


abstract: [This corrects the article DOI: 10.3389/fpsyt.2023.1278823.].
publication_date: 2024-02-15
doi: 10.3389/fpsyt.2024.1372373
pubmed_id: 38435972
source_url: https://doi.org/10.3389/fpsyt.2024.1372373
substance_tags: psilocybin
topic_tags: OCD,Safety
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
title:
Corrigendum: Safety, feasibility, tolerability, and clinical effects of repeated psilocybin dosing combined with non-directive support in the treatment of obsessive-compulsive disorder: protocol for a randomized, waitlist-controlled trial with blinded ratings.

authors:
Ching THW, Amoroso L, Bohner C, D'Amico E, Eilbott J, Entezar T, Fitzpatrick M, Fram G, Grazioplene R, Hokanson J, Jankovsky A, Kichuk SA, Martins B, Patel P, Schaer H, Shnayder S, Witherow C, Pittenger C, Kelmendi B.

raw_json:
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title: Effect of a single psilocybin treatment on Fos protein expression in male rat brain.
authors: Funk D, Araujo J, Slassi M, Lanthier J, Atkinson J, Feng D, Lau W, Lê A, Higgins GA.
publication_date: 2024-01-03
doi: 10.1016/j.neuroscience.2024.01.001
pubmed_id: 38184069
source_url: https://doi.org/10.1016/j.neuroscience.2024.01.001
substance_tags: psilocybin
topic_tags: Depression,Addiction,Mechanism of Action,Biomarkers,Emotional Processing,Animal Study
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
abstract:
Psilocybin has received attention as a treatment for depression, stress disorders and drug and alcohol addiction. To help determine the mechanisms underlying its therapeutic effects, here we examined acute effects of a range of behaviourally relevant psilocybin doses (0.1-3 mg/kg SC) on regional expression of Fos, the protein product of the immediate early gene, c-fos in brain areas involved in stress, reward and motivation in male rats. We also determined the cellular phenotypes activated by psilocybin, in a co-labeling analysis with NeuN, a marker of mature neurons, or Olig1, a marker of oligodendrocytes. In adult male Sprague-Dawley rats, psilocybin increased Fos expression dose dependently in several brain regions, including the frontal cortex, nucleus accumbens, central and basolateral amygdala and locus coeruleus. These effects were most marked in the central amygdala. Double labeling experiments showed that Fos was expressed in both neurons and oligodendrocytes. These results extend previous research by determining Fos expression in multiple brain areas at a wider psilocybin dose range, and the cellular phenotypes expressing Fos. The data also highlight the amygdala, especially the central nucleus, a key brain region involved in emotional processing and learning and interconnected with other brain areas involved in stress, reward and addiction, as a potentially important locus for the therapeutic effects of psilocybin. Overall, the present findings suggest that the central amygdala may be an important site through which the initial brain activation induced by psilocybin is translated into neuroplastic changes, locally and in other regions that underlie its extended therapeutic effects.

keywords:
Brain, Locus Coeruleus, Amygdala, Animals, Rats, Rats, Sprague-Dawley, Proto-Oncogene Proteins c-fos, Male, Psilocybin

raw_json:
{"europe_pmc_id":"38184069","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


