# publications

authors: Graham M, Ge Y, Pacula RL, Pessar SC, Wilkins C, Hall W, Hammond D.
publication_date: 2026-06-04
doi: 10.1016/j.drugpo.2026.105348
pubmed_id: 42247761
source_url: https://doi.org/10.1016/j.drugpo.2026.105348
substance_tags: psilocybin
topic_tags: Mechanism of Action,Clinical Trial,Observational Study,Adolescents,Adverse Events
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:01
title:
A cross-national comparison of nonmedical and medical use of psychedelic drugs in the international cannabis policy study.

abstract:
BackgroundWe know little about the extent psychedelic substances are consumed therapeutically and/or discussed with medical professionals despite renewed global interest in these substances.MethodsWe examined self-reported responses from the 2023 International Cannabis Policy Study (ICPS) in repeated cross-sectional surveys in Canada, the United States, Australia, and New Zealand. The survey included questions on lifetime, past year, and past month use of psilocybin, LSD, MDMA, and ketamine. It inquired about respondents' discussions with medical professionals, their self-reported medical use, and related adverse events. We estimate the mean proportion rate for each of these using logistic regression methods that adjust for demographics, country, and sampling weights.FindingsEstimated results suggest nineteen per cent of all ICPS respondents reported lifetime use of one of the four substances. Psilocybin was the most commonly estimated to be used in one's lifetime and in the past year, followed by LSD and MDMA. Estimated prevalences of ever using psilocybin were higher among respondents from Canada (16.3%, CI: 15.6-16.9%) than the USA (13.0%, CI: 12.3-13.6%) and New Zealand (12.1%, CI: 10.4-13.8%). Estimated rates of psilocybin ever use in Australia were significantly lower (7.8%, CI: 6.8-8.8%). An estimated 10-20% of respondents who report ever-use of a psychedelic asked their medical provider about medical use, and over a third who had used in the past year reported experiencing an adverse health effect. Estimated rates of past month use were low for all countries.InterpretationConsumer interest in therapeutic use of psilocybin, MDMA, LSD, and ketamine has surpassed the pace of clinical trials and therapeutic use provisions. These provisions do not necessarily equate to patient access and dual use motivations are not uncommon. Access via nonregulated pathways and self-initiated use in the absence of medical supervision may influence the proportion of individuals who experience adverse events.

keywords:
Humans, N-Methyl-3,4-methylenedioxyamphetamine, Ketamine, Lysergic Acid Diethylamide, Hallucinogens, Prevalence, Cross-Sectional Studies, Adolescent, Adult, Middle Aged, Canada, United States, Australia, New Zealand, Female, Male, Young Adult, Self Report, Psilocybin

raw_json:
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publication_date: 2026-05-25
doi: 10.1016/j.drugalcdep.2026.113218
pubmed_id: 42224931
source_url: https://doi.org/10.1016/j.drugalcdep.2026.113218
substance_tags: psilocybin
topic_tags: Anxiety,Safety
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:03
title:
Mystery shopper assessments of cannabis retailer practices and regulatory compliance in five U.S. states, 2025.

authors:
Berg CJ, LoParco CR, Rossheim ME, McCready DM, Langan L, Platt E, Romm KF, Johnson M, Speer MB, Burris S, Cavazos-Rehg PA.

abstract:
ObjectiveThis study used mystery shoppers to assess cannabis retail practices in 5 US states regulating legal nonmedical cannabis retail.MethodsThis mystery shopper study assessed 130 cannabis retailers in 5 cities (Los Angeles [LA], California; Las Vegas [LV], Nevada; Denver, Colorado; Portland, Oregon; Seattle, Washington) in summer 2025. Researchers recorded: 1) age verification; and 2) retail staff responses to inquiries about: a) use for anxiety, sleep, pregnancy-related nausea, etc.; b) use-related risks/cautions; c) interstate cannabis transport; and d) availability of derived intoxicating cannabis products (DICPs) and 'mushrooms' (psilocybin).ResultsMystery shoppers were asked for ID at 87.7% of retailers. When asked, most (>88%) retail staff responded that cannabis helps with anxiety and insomnia. While 40.8% warned against use for pregnancy-related nausea, 36.2% suggested it helps and 24.6% said it depends on the person/situation. Over half (58.5%) warned against driving post-use, but 50.0% said it depends (on person/situation). When asked about interstate transport, several indicated not to (42.3%) and/or it was illegal (39.2%); however, 44.6% indicated ways to pack cannabis to be undetectable, and 27.7% said not to worry about getting caught. Retail staff generally indicated DICPs are not as safe as delta-9 THC (27.7%) or are illegal (20.0%). The majority said mushrooms were illegal (67.7%), but 53.8% indicated they were easy to obtain, and 29.2% suggested their mental health benefits.ConclusionsCannabis retailer frequently made prohibited health claims and minimized risks, reinforcing public health concerns and the need for ongoing cannabis retail surveillance and stronger regulatory oversight and enforcement.

raw_json:
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title: A25-year analysis of Armillaria (honey mushroom) poisoning in Wisconsin.
authors: Feldman R, Audette M, Leacock PR, Theobald J.
publication_date: 2026-04-21
doi: 10.1016/j.ajem.2026.04.033
pubmed_id: 42066652
source_url: https://doi.org/10.1016/j.ajem.2026.04.033
substance_tags: psilocybin
topic_tags: Chronic Pain,Aging,Case Report,Adolescents,Toxicity
study_type: Case Report
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:03
abstract:
BackgroundWild mushroom foraging is common in the United States. Poisoning usually results from misidentification, though some "edible" mushrooms can also cause toxicity. Armillaria ("honey mushrooms") are widely foraged and generally considered edible, yet sporadic gastrointestinal illness has been reported. Their clinical effects remain poorly described. Poison center data provide real-world exposure characterization with standardized symptom documentation and mycologist collaboration. This study characterized the presentation, management, and outcomes of suspected or confirmed Armillaria ingestions reported to the Wisconsin Poison Center (WPC) over 25 years.MethodsWe conducted a retrospective case series of WPC records (2000-2025). Cases coded as Armillaria, "unknown mushroom," or "gastrointestinal irritant mushroom" were screened. Inclusion required mycologist confirmation or patient-reported Armillaria ingestion.ResultsEighteen cases were identified; 50% (n = 9) had mycologist confirmation. Exposures occurred August-October, with 78% in late September-mid-October. Most patients were adults (94%), median age 41.5 years. Fifteen (83%) developed gastrointestinal symptoms (vomiting, diarrhea, abdominal pain, nausea); all symptomatic patients had vomiting or diarrhea. Three (17%) remained asymptomatic. Symptom onset ranged 0.25-7.5 h (median 3.5), with resolution in 2-41 h (median 8.75). Five patients (28%) were evaluated in an emergency department; four were discharged and one had a brief admission for symptom control. No organ failure or deaths occurred. Illness occurred despite reported cooking. Concern for misidentification with toxic look-alikes was common; some cases reporting Armillaria were later identified as psilocybin-containing Gymnopilus.ConclusionsArmillaria ingestion produces a self-limited gastrointestinal toxidrome, typically with early onset but occasionally >6 h, which may complicate differentiation from amatoxin-containing species such as Galerina. If patients report Armillaria ingestion toxic look-alikes, including Gymnopilus, Galerina, Cortinarius, and muscarine-containing genera, should remain in the differential if appropriate toxidrome features are present. Confirmed cases generally have a favorable prognosis. Early poison center or toxicology consultation can assist with identification and management.

keywords:
Humans, Mushroom Poisoning, Vomiting, Retrospective Studies, Adolescent, Adult, Aged, Middle Aged, Poison Control Centers, Wisconsin, Female, Male, Armillaria, Young Adult

raw_json:
{"europe_pmc_id":"42066652","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2026-03-22
doi: 10.1016/j.jad.2026.121662
pubmed_id: 41881122
source_url: https://doi.org/10.1016/j.jad.2026.121662
substance_tags: psilocybin
topic_tags: Depression,Consciousness,Emotional Processing,Treatment-Resistant Depression
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:00
title:
The role of therapeutic alliance in psilocybin treatment for treatment-resistant depression: A post hoc path analysis.

authors:
Goodwin GM, Aaronson ST, Alvarez O, Carhart-Harris R, Croal M, Feifel D, Hellerstein DJ, Husain MI, Kelly JR, Kirlic N, Licht RW, Marwood L, Nowakowska A, Páleníček T, Repantis D, Schoevers RA, Simmons H, Soares JC, Somers M, Tsai J, Wahba M, Williams E, Young AH, Young MB, Zisook S, Malievskaia E.

abstract:
IntroductionThe contribution of patient support to psilocybin's antidepressant effects remains uncertain.MethodsRelationships between therapeutic alliance (Scale to Assess Therapeutic Relationship-Patient version; STAR-P), psychedelic experience (Five-Dimensional Altered States of Consciousness Questionnaire and Emotional Breakthrough Inventory; 5D-ASC and EBI) and clinical outcomes (Montgomery-Åsberg Depression Rating Scale; MADRS) were explored using correlation and path analysis for individuals with treatment-resistant depression receiving 25 mg psilocybin with monitoring and support (N = 79).ResultsChange from Baseline to Week 3 MADRS scores showed weaker correlations with pre-dosing therapeutic alliance (-0.178) than with measures of the psychedelic experience: EBI (-0.637), Oceanic Boundlessness (-0.508), and Visual Restructuralization (-0.516). Path analysis showed no nominally significant direct effects of therapeutic alliance on Week 3 MADRS scores, but there were nominally significant effects of therapeutic alliance on psychedelic experience (Oceanic Boundlessness (β = 0.28), Visual Restructuralization (β = 0.27), and Auditory Alterations (β = 0.25)). Only one indirect effect of therapeutic alliance on clinical outcome reached nominal significance (via Visual Restructuralization; β = -0.15). Stronger effects were seen on clinical outcomes for psychedelic experience (EBI (β = -0.59), Oceanic Boundlessness (β = -0.53), Visual Restructuralization (β = -0.54), and Auditory Alterations (β = -0.24)).ConclusionsThe therapeutic alliance appeared to facilitate the psychedelic experience, and these experiences in turn had stronger nominally significant direct effects on clinical outcomes. The effects of the alliance itself on therapeutic efficacy were either limited or absent.Trial registrationEudraCT number: 2017-003288-36; Clinicaltrials.gov identifier: NCT03775200.

keywords:
Humans, Hallucinogens, Treatment Outcome, Psychiatric Status Rating Scales, Adult, Middle Aged, Female, Male, Depressive Disorder, Treatment-Resistant, Psilocybin, Therapeutic Alliance

raw_json:
{"europe_pmc_id":"41881122","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin-assisted therapy for major depressive disorder: Perspective from meta-analysis.
authors: Kishi T, Sakuma K, Hatano M, Uchida H, Iwata N.
publication_date: 2026-03-21
doi: 10.1016/j.jad.2026.121675
pubmed_id: 41876058
source_url: https://doi.org/10.1016/j.jad.2026.121675
substance_tags: psilocybin
topic_tags: Depression,Randomized Controlled Trial,Meta-Analysis,Systematic Review,Review Article,Safety
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:00
abstract:
ObjectiveThis systematic review and meta-analysis of six randomized controlled trials aimed to investigate the temporal changes in the efficacy and safety of psilocybin treatment for major depressive disorder (MDD).MethodsSeparate meta-analyses were conducted for standard-dose psilocybin (25 mg/session, or 20-30 mg/70 kg/session) and low-dose psilocybin (10 mg/session or 15.05 mg/70 kg/session) subgroups. Control conditions included placebo, waiting-list control, niacin, or psilocybin 1 mg.ResultsStandard-dose psilocybin was superior to control in reducing depressive symptoms (standardized mean difference [SMD]: -1.05; 95% confidence intervals [CIs]: -1.60 to -0.50, p = 0.0002, I2 = 75%, K = 4). Sensitivity analysis excluding studies with waiting-list controls supported the superiority of standard-dose psilocybin compared with control without considerable heterogeneity (SMD: -0.70; 95% CI: -1.03 to -0.36, p

keywords:
Humans, Hallucinogens, Treatment Outcome, Randomized Controlled Trials as Topic, Psilocybin, Major Depressive Disorder

raw_json:
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title: Thirty Years of Ibogaine Research: A Literature Review on Clinical Perspectives.
authors: Kervadec E, Bezo A, Serreau R, Strika-Bruneau L, Fauvel B, Amirouche A, Benyamina A, Romeo B
journal: Journal of clinical psychopharmacology
publication_date: 2025-12-31
doi: 10.1097/jcp.0000000000002197
pubmed_id: 42228481
source_url: https://pubmed.ncbi.nlm.nih.gov/42228481/
keywords: ibogaine, opioid use disorder, posttraumatic stress disorder, psychedelics, substance use disorder
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: PubMed
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-02 06:54:10
raw_json: {"pubmed_id":"42228481"}
abstract:
Ibogaine has garnered interest for its potential therapeutic properties in substance use and psychiatric disorders. Unlike classic psychedelics such as psilocybin or LSD, ibogaine remains underexplored in clinical research. This review aimed to synthesize the clinical literature on ibogaine use in humans over the past 3 decades, focusing on outcomes and safety.
We conducted a narrative review of studies on ibogaine's clinical use published from 1990 to February 2025, including randomized controlled trials (RCTs), open-label, retrospective, and observational studies. Databases were searched for reports on efficacy and safety across various indications.
Twenty-four studies and 38 case reports/series were included. Most of the positive efficacy data come from uncontrolled, open-label, or retrospective studies, many conducted in nonclinical settings, with a high risk of bias. No double-blind RCT to date has demonstrated that ibogaine or noribogaine can effectively treat opioid use disorder (OUD). Only 1 small RCT reported significant effects for cocaine use disorder. Although observational data suggest that ibogaine may alleviate symptoms of OUD, PTSD, or polysubstance dependence, these findings remain exploratory. Moreover, serious ibogaine-related adverse events have been reported, especially cardiotoxicity due to QT prolongation, which represents a considerable risk given the currently unproven efficacy.
While ibogaine remains a compound of interest for neuropsychiatric research, current evidence is insufficient to support its clinical use. Further studies are needed to better demonstrate ibogaine's efficacy, optimize its safety profile, and determine how it could be integrated into psychiatric care, especially in relation to the emerging therapeutic use of classic psychedelics.

topic_tags:
PTSD,Addiction,Randomized Controlled Trial,Review Article,Case Report,Observational Study,Safety,Adverse Events,Toxicity


authors: Giri Y, Furst P, Loo CK, Clark SR, Tibrewal P
journal: The Australian and New Zealand journal of psychiatry
publication_date: 2026-06-30
doi: 10.1177/00048674261450390
pubmed_id: 42198984
source_url: https://pubmed.ncbi.nlm.nih.gov/42198984/
substance_tags: psilocybin
topic_tags: Depression,Treatment-Resistant Depression
study_type: Other
source_name: PubMed
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-02 06:54:10
raw_json: {"pubmed_id":"42198984"}
title:
Improving access to novel treatments for treatment-resistant depression: The potential role of specialist clinics in Australia.

abstract:
Treatment-resistant depression is a condition with significant morbidity, despite the current standard of treatment, including traditional pharmacotherapy, psychotherapy, augmentation strategies and electroconvulsive therapy. While novel therapies have emerged, such as ketamine/esketamine, transcranial magnetic stimulation and psilocybin-assisted therapy, the uptake of these treatments is relatively low, particularly within public mental health services. Commercial clinics across Australia offer these treatments, but can only be accessed by those able to pay, leaving those unable to pay with limited or no access. We compare novel treatments for treatment-resistant depression and examine barriers to their implementation within the Australian mental health system. We also propose specialist treatment-resistant depression clinics as a potential model to improve access and build clinical expertise. We identified challenges in identifying treatment-resistant depression, lack of training and expertise, and regulatory and economic barriers. We propose that the lack of public access to these novel treatments be initially addressed by the establishment of specialist treatment-resistant depression clinics in Australia, including in the public sector, which will drive training and the development of expertise within public mental health.

keywords:
Treatment-resistant depression, depression, esketamine, ketamine, mood disorder, personalisation, psilocybin, transcranial magnetic stimulation


journal: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
publication_date: 2026-06-30
doi: 10.1038/s41386-026-02428-9
pubmed_id: 42049943
source_url: https://pubmed.ncbi.nlm.nih.gov/42049943/
substance_tags: psilocybin
study_type: Clinical Trial
source_name: PubMed
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-02 06:54:10
raw_json: {"pubmed_id":"42049943"}
title:
Acute dose-dependent effects of 4-bromo-2,5-dimethoxyphenethylamine (2C-B) compared with 3,4-methylenedioxymethamphetamine (MDMA) and psilocybin in a double-blind, placebo-controlled study in healthy participants.

authors:
Arikci D, Borgulya J, Straumann I, Vizeli P, Luethi D, Thomann J, Rudin D, Vukalovic I, Eckert A, Liechti ME, Holze F

abstract:
Based on its in vitro profile and preliminary evidence, 4-bromo-2,5-dimethoxyphenethylamine (2C-B) may have psychoactive properties that are similar to 3,4-methylenedioxymethamphetamine (MDMA) and psilocybin, which are investigated for the treatment of posttraumatic stress disorder and depressive disorders. We compared acute effects of 2C-B (10, 20, and 30 mg), 125 mg MDMA, and 25 mg psilocybin in 24 healthy participants (12 women, 12 men) using a double-blind, randomized, placebo-controlled, crossover design. Outcome measures included acute subjective effects, autonomic effects, adverse effects, effects on emotional and cognitive empathy, plasma oxytocin and neurophysin I concentrations, and pharmacokinetics up to 9 h. 2C-B produced dose-dependent subjective effects, with the 30 mg dose exerting comparable "any drug effects" to MDMA but lower "any drug effects" than psilocybin. Only psilocybin induced "bad drug effects" and "anxiety" compared with placebo. The 30 mg dose of 2C-B induced psychedelic-type alterations of state of consciousness and increased emotional empathy similarly to MDMA. The average subjective effect duration of 30 mg 2C-B was 4.9 h and similar to MDMA (4.8 h) and shorter than psilocybin (6.1 h). MDMA produced the highest cardiovascular stimulation, followed by psilocybin and 2C-B. Only MDMA increased plasma oxytocin and neurophysin I concentrations. 2C-B exhibited dose-proportional pharmacokinetics, with a plasma elimination half-life of ~1.3 h. The 30 mg dose of 2C-B induced entactogenic and psychedelic effects similarly to MDMA and psilocybin, respectively. MDMA is more cardiostimulant than psilocybin and 2C-B. At the tested dose-level, psilocybin is more distressing than MDMA and 2C-B. These results may assist with dose-finding for future 2C-B research and provide a direct comparison with standard doses of the prototypical compounds MDMA and psilocybin. Trial registration: ClinicalTrials.gov identifier: NCT05523401.

topic_tags:
Depression,Anxiety,PTSD,Pharmacology,Consciousness,Emotional Processing,In Vitro Study,Healthy Volunteers


title: Psychedelics as a potential treatment for borderline personality disorder: A narrative review.
authors: Artna E, Sandhu G, Chisamore N, Lipsitz O, Kaczmarek ES, Johnson DE, Rosenblat JD, Sediqzadah S
journal: Psychiatry research
publication_date: 2026-06-30
doi: 10.1016/j.psychres.2026.117152
pubmed_id: 41955843
source_url: https://pubmed.ncbi.nlm.nih.gov/41955843/
substance_tags: psilocybin
topic_tags: Anxiety,Personality Change,Review Article,Safety
study_type: Review Article
source_name: PubMed
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-02 06:54:10
raw_json: {"pubmed_id":"41955843"}
abstract:
Borderline personality disorder (BPD) is a serious mental illness with high rates of morbidity and stigma; however, successful remission is frequently limited by a paucity of accessible treatment options. In an era of growing interest in psychedelics as novel psychiatric treatment modalities, patients with BPD are often excluded from research due to perceived safety risks, particularly pertaining to suicide and substance misuse. However, there is evolving evidence that psychedelic treatment may effectively target core BPD symptoms, in addition to those of the mood and anxiety disorders frequently comorbid with BPD. As such, characterizing the therapeutic potential of psychedelics in BPD represents an important opportunity to enhance patient outcomes. This narrative review aims to broadly analyze the existing literature on experiences with psychedelics in this population. Data were coalesced from multiple electronic databases (Ovid MEDLINE, PsychInfo, and Embase) to characterize the current evidence for psychedelic safety and effectiveness in individuals with BPD. The 22 studies included in this review encompass a broad range of study designs and outcomes involving ketamine, esketamine, and psilocybin. There is some preliminary evidence that these psychedelics may be implemented as safe and effective treatments to improve core BPD symptoms and socio-occupational functioning. However, further high-quality evidence focusing on BPD-specific outcomes is needed to better elucidate their potential role as a treatment modality.

keywords:
Borderline personality disorder, Esketamine, Hallucinogens, Ketamine, Psilocybin, Psychedelics, Psychotropics


title: Three cases of wood-lover paralysis: clinical insights from Victoria, Australia.
authors: Silvester A, Hampton S, May TW, Holmes GD, Leang YH
journal: Clinical toxicology (Philadelphia, Pa.)
publication_date: 2026-06-30
doi: 10.1080/15563650.2026.2640196
pubmed_id: 41910179
source_url: https://pubmed.ncbi.nlm.nih.gov/41910179/
keywords: Psilocybe subaeruginosa, respiratory failure, takostubo, weakness, wood-lover paralysis
substance_tags: psilocin
topic_tags: End-of-Life Distress,Case Report,Toxicity
study_type: Case Report
source_name: PubMed
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-02 06:54:10
raw_json: {"pubmed_id":"41910179"}
abstract:
Wood-lover paralysis is a rare complication of mushroom ingestion. The clinical spectrum is poorly characterized and published cases remain limited.
We describe three patients who developed acute muscle weakness following ingestion of mushrooms in Victoria, Australia. Written informed consent was obtained from these patients for publication of this case series.
Mild generalized weakness affecting gait, without other end-organ involvement.
Severe generalized weakness involving upper and lower limbs, associated with takotsubo cardiomyopathy.
Severe generalized weakness with respiratory failure, requiring intubation.All patients had a clear temporal relationship between mushroom ingestion and symptom onset. Mushroom samples from Cases 2 and Case 3 were identified as based on DNA sequence data. Serum toxicology detected psilocin in Case 1 and Case 3.
Our findings support a causal role for; however, no specific alkaloid has yet been proven to cause wood-lover paralysis.
These cases highlight the variable severity of wood-lover paralysis, ranging from mild weakness to life-threatening respiratory compromise, and add significantly to the current body of literature on this topic.


title: Recreational drug poisonings reported to six European poison centres from 2021 to 2024.
authors: Hondebrink L, Faber K, Kader A, Jagpal PS, Arif T, Hermanns-Clausen M
journal: Clinical toxicology (Philadelphia, Pa.)
publication_date: 2026-06-30
doi: 10.1080/15563650.2026.2628073
pubmed_id: 41778415
source_url: https://pubmed.ncbi.nlm.nih.gov/41778415/
substance_tags: psilocybin
topic_tags: Addiction
study_type: Other
source_name: PubMed
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-02 06:54:10
raw_json: {"pubmed_id":"41778415"}
abstract:
Recreational drug poisonings pose a growing public health concern. European-level data remain limited, although poison centres are well placed to monitor related health incidents. This study analysed temporal trends in recreational drug poisonings reported to six European poison centres.
Aggregated retrospective data were collected over four years (2021-2024) from poison centres in Austria, Freiburg (Germany), the Netherlands, Sweden, Switzerland, and the United Kingdom. Cases involving 11 recreational drugs (amfetamine, cocaine, delta-9-tetrahydrocannabinol, gamma-hydr-oxybutyrate, heroin, ketamine, lysergic acid diethylamide, 3,4-methylenedioxymetamfetamine, metamfetamine, poppers, and psilocybin) were included. Annual rates of recreational drug exposures were calculated relative to all poisoned patients, and trends were analysed using linear regression.
From 2021 to 2024, the six centres recorded 1,051,287 poisonings, of which 23,779 (2.3%) involved recreational drugs. The rate of recreational drug exposures increased from 1.8% ( = 4,581) in 2021 to 2.6% ( = 7,229) in 2024, mainly driven by the increases in Austria, Freiburg, and the United Kingdom. Rates ranged from 1.3% (Austria) to 2.8% (Netherlands) in 2021 and from 1.9% (Austria) to 3.6% (Freiburg) in 2024. Delta-9-tetrahydrocannabinol, cocaine, amfetamine, and 3,4-methylenedioxymetamfetamine were most frequently implicated. Increasing rates were observed for delta-9-tetrahydrocannabinol (Freiburg, Austria), cocaine (Freiburg, United Kingdom), amfetamine (Freiburg, Sweden), and ketamine (Austria, Freiburg, United Kingdom). In 2024, amfetamine poisonings peaked in Freiburg (0.63%) and Sweden (0.94%), cocaine in Freiburg (0.78%) and the United Kingdom (0.74%), and ketamine in the Netherlands (0.42%) and the United Kingdom (0.24%).
Although recreational drug poisonings comprised a small proportion of poison centre calls (∼3%), a significant increase was observed between 2021 and 2024, underscoring their value in toxicovigilance and early identification of emerging drug trends.
Delta-9-tetrahydrocannabinol, cocaine, amfetamine, and 3,4-methylenedioxymetamfetamine were most frequently reported, with notable national differences. Coordinated European monitoring of recreational drug poisonings may support timely public health interventions and prevention strategies.

keywords:
Delta-9-tetrahydrocannabinol, methylenedioxymetamfe­tamine, poison centre, poisoning rate, recreational drugs, toxicovigilance


journal: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
publication_date: 2026-06-30
doi: 10.1038/s41386-026-02361-x
pubmed_id: 41688761
source_url: https://pubmed.ncbi.nlm.nih.gov/41688761/
substance_tags: psilocybin
topic_tags: Neuroplasticity,Mechanism of Action,Receptor Pharmacology,Microdosing,Animal Study
study_type: Animal Study
source_name: PubMed
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-02 06:54:10
raw_json: {"pubmed_id":"41688761"}
title:
Psilocybin improves novel object recognition in a rat model of Fragile X Syndrome through the modulation of the BDNF/TrkB signaling pathway.

authors:
Ascone F, Buzzelli V, Mottarlini F, Di Trapano M, Miglioranza P, Rava A, Feo A, Spano F, Hausman M, Sugaya K, Caffino L, Fumagalli F, Trezza V

abstract:
Fragile X Syndrome (FXS) is the most common inherited intellectual disability and a leading monogenic cause of autism spectrum disorder (ASD). As a synaptic disorder, FXS involves the loss of Fragile X messenger ribonucleoprotein 1 (FMRP), leading to abnormal dendrite development and immature dendritic spines. Serotonergic signaling, essential for neuronal development and circuit remodeling, has been implicated in ASD and related conditions, including FXS, raising the possibility that serotonergic modulation could ameliorate neurodevelopmental impairments. This study investigated the therapeutic potential of psilocybin, a serotonergic compound, in the validated Fmr1-exon 8 rat model of FXS. Psilocybin microdosing rescued deficits in NOR. Importantly, its benefits on recognition memory persisted despite pretreatment with the 5HT2AR antagonist, volinanserin, or the 5HT1AR antagonist, WAY-100635, indicating that classical serotonergic receptor activation is not required. In contrast, pretreatment with the TrkB receptor antagonist, ANA-12, abolished psilocybin's effects, implicating BDNF/TrkB signaling as essential. At the molecular level, psilocybin normalized mature BDNF (mBDNF), increased TrkB, and restored downstream AKT signaling in the prefrontal cortex of Fmr1-exon 8 rats, pathways strongly linked to synaptic plasticity and cognitive function. These findings demonstrate that psilocybin rescues object recognition memory deficits in this rat model of FXS via BDNF/TrkB-AKT signaling rather than serotonergic receptor mechanisms. By dissociating therapeutic effects from hallucinogenic pathways, our results highlight psilocybin microdosing as a promising therapeutic strategy for neurodevelopmental disorders such as FXS and ASD.


authors: Fleury S, Nautiyal KM.
publication_date: 2026-06-30
doi: 10.1038/s41380-026-03488-5
pubmed_id: 41680332
source_url: https://doi.org/10.1038/s41380-026-03488-5
substance_tags: psilocybin
topic_tags: Receptor Pharmacology,Animal Study
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-02 06:54:51
title:
Correction: The serotonin 1B receptor is required for some of the behavioral effects of psilocybin in mice.

raw_json:
{"europe_pmc_id":"41680332","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Wittenkeller L, Gudelsky G, Winhusen TJ, Amato D
journal: British journal of pharmacology
publication_date: 2026-06-30
doi: 10.1111/bph.70181
pubmed_id: 40891276
source_url: https://pubmed.ncbi.nlm.nih.gov/40891276/
keywords: MDMA, addiction, psilocybin, psychedelics, psychedelic‐assisted therapy, substance use disorders
substance_tags: psilocybin
study_type: Clinical Trial
source_name: PubMed
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-02 06:54:10
raw_json: {"pubmed_id":"40891276"}
title:
Psychedelics as pharmacotherapeutics for substance use disorders: A scoping review on clinical trials and perspectives on underlying neurobiology.

abstract:
Psychedelics have garnered great attention in recent years as treatments for major depressive disorder (MDD) and treatment-resistant depression because of their ability to alter consciousness and afflicted cognitive processes with lasting effects. We aimed to characterise how psychedelics are currently being investigated to treat substance use disorders (SUDs). Additionally, we aimed to summarise the available literature on the dopaminergic consequences of classic psychedelics in the nucleus accumbens (NAc), a foundational component of SUDs, to understand how psychedelics may be therapeutically relevant for SUDs from a neurobiological perspective. Two scoping review approaches adhering to PRISMA-SCR guidelines were conducted. The first screened for ongoing clinical trials utilising psychedelics for SUD treatment registered at ClinicalTrials.gov. The second screened for in vivo microdialysis studies measuring psychedelic-induced changes in extracellular NAc dopamine in rats, found using PubMed, SCOPUS or Google Scholar. Thirty-four unique clinical trials were identified targeting alcohol, cannabis, cocaine, methamphetamine, nicotine, and opioid use disorders and mostly consisting of open-label trials lacking placebo-treated controls. The most common SUD investigated was alcohol use disorder (AUD). Following stringent exclusion criteria, four publications were identified that measured extracellular dopamine in the NAc following systemic administration of psilocybin or 3,4-methylenedioxymethamphetamine (MDMA). A sustained mild increase of dopamine was observed that was unique to high-dose psilocybin. In addition to known therapeutic mechanisms of psychedelics, findings herein suggest that psilocybin may support dopamine homeostasis through restoration of tonic dopamine levels. LINKED ARTICLES: This article is part of a themed issue Emerging Therapeutic Opportunities for Psychedelic and Related Drugs. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v183.14/issuetoc.

topic_tags:
Depression,Addiction,Mechanism of Action,Consciousness,Clinical Trial,Review Article,Treatment-Resistant Depression


title: Are we hallucinating or can psychedelic drugs modulate the immune system to control inflammation?
journal: British journal of pharmacology
publication_date: 2026-06-30
doi: 10.1111/bph.70138
pubmed_id: 40726049
source_url: https://pubmed.ncbi.nlm.nih.gov/40726049/
keywords: 5‐HT2A receptor, immune system, inflammation, neuroinflammation, psychedelic drugs
substance_tags: psilocybin
topic_tags: Receptor Pharmacology,Animal Study,Inflammation,Immune Function
study_type: Other
source_name: PubMed
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-02 06:54:10
raw_json: {"pubmed_id":"40726049"}
authors:
Qureshi O, Cowley J, Pegg A, Cooper AJ, Gordon J, Brady CA, Belli A, Butterworth S, Upthegrove R, Andrews N, Barnes NM

abstract:
Psychedelic drugs that activate 5-HT receptors have been long used for cultural, medicinal and recreational purposes. Interest in psychedelics for treating psychiatric disorders has resurged recently and is well documented; less well recognised are their anti-inflammatory properties. Growing evidence now demonstrates that psychedelics modulate immune responses, including inhibiting pro-inflammatory cytokine release. Furthermore, in vivo studies demonstrate that psychedelics, like (R)-DOI, reduce inflammation in animal models of acute and chronic inflammatory disease such as asthma. Likewise, some clinical studies with psychedelic drugs (e.g. psilocybin) demonstrate an impact upon circulating cytokine levels, supporting a translation from the animal models to the clinical arena. Such data emphasise the promise of therapeutic approaches targeting inflammation. Interestingly, recent research has also uncovered compounds that maintain therapeutic potential without likely causing psychedelic effects. These discoveries suggest that drugs informed by psychedelic drugs, but which do not evoke psychedelic experiences, which we term PIPI drugs (Psychedelic drug Informed but Psychedelic experience Inactive), could offer effective treatments for mental health and inflammation, presenting new avenues for therapeutic development. LINKED ARTICLES: This article is part of a themed issue Emerging Therapeutic Opportunities for Psychedelic and Related Drugs. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v183.14/issuetoc.


authors: Ippolito A, Vasudevan S, Hurley S, Gilmour G, Westhorpe F, Churchill G, Sharp T
journal: British journal of pharmacology
publication_date: 2026-06-30
doi: 10.1111/bph.70109
pubmed_id: 40545270
source_url: https://pubmed.ncbi.nlm.nih.gov/40545270/
keywords: 5‐HT, 5‐HT2A receptor, Gq and β‐arrestin2 signalling, biased agonism, psychedelic, serotonin
substance_tags: psilocin
topic_tags: Depression,Mechanism of Action,Receptor Pharmacology,Animal Study
study_type: Animal Study
source_name: PubMed
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-02 06:54:10
raw_json: {"pubmed_id":"40545270"}
title:
Evidence that 5-HT receptor signalling efficacy and not biased agonism differentiates serotonergic psychedelic from non-psychedelic drugs.

abstract:
Serotonergic psychedelic drugs are under investigation as therapies for various psychiatric disorders, including major depression. Although serotonergic psychedelic drugs are 5-HT receptor agonists, some such agonists are not psychedelic, potentially due to differences in 5-HT receptor ligand bias or signalling efficacy. Here, we investigated 5-HT receptor signalling properties of selected psychedelic and non-psychedelic drugs.
G-coupled (Ca and IP) and β-arrestin2 signalling effects of six psychedelic drugs (psilocin, 5-MeO-DMT, LSD, mescaline, 25B-NBOMe and DOI) and three non-psychedelic drugs (lisuride, TBG and IHCH-7079) were characterised using SH-SY5Y cells expressing human 5-HT receptors. Ligand bias and signalling efficacy were measured using concentration-responses curves, compared with 5-HT. The generality of findings was tested using rat C6 cells which express endogenous 5-HT receptors.
In SH-SY5Y cells, all psychedelic drugs were partial agonists at both 5-HT receptor signalling pathways and none showed significant ligand bias. In comparison, the non-psychedelic drugs were not distinguishable from psychedelic drugs in terms of ligand bias properties but exhibited the lowest 5-HT receptor signalling efficacy of all drugs tested. The latter result was confirmed in C6 cells.
In summary, all psychedelic drugs tested were unbiased, partial 5-HT receptor agonists. Importantly, the non-psychedelic drugs lisuride, TBG and IHCH-7079 were discriminated from psychedelic drugs, not through ligand bias but rather by low efficacy. Therefore, low 5-HT receptor signalling efficacy may explain why some 5-HT receptor agonists are not psychedelic, although a larger panel of drugs should be tested to confirm this idea.
This article is part of a themed issue Emerging Therapeutic Opportunities for Psychedelic and Related Drugs. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v183.14/issuetoc.


title: Psychedelics, entactogens and psychoplastogens for depression and related disorders.
authors: Hoyer D
journal: British journal of pharmacology
publication_date: 2026-06-30
doi: 10.1111/bph.70088
pubmed_id: 40518133
source_url: https://pubmed.ncbi.nlm.nih.gov/40518133/
substance_tags: psilocybin
study_type: Clinical Trial
source_name: PubMed
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-02 06:54:10
raw_json: {"pubmed_id":"40518133"}
abstract:
Currently, the most actively investigated rapidly acting antidepressants, anxiolytics and/or anti PTSD agents, include psychedelics e.g. psilocybin, LSD, N,N-dimethyltryptamine, ayahuasca; non-hallucinogenic entactogens, e.g. MDMA; psychoplastogens which rapidly promote neuroplasticity, e.g. ibogaine, ketamine and esketamine; and other atypicals e.g. dextromorphan/bupropion, esmethadone. Late-stage clinical trials support psychedelics and/or MDMA-assisted psychotherapy as rapidly acting treatments for major depressive disorder (MDD), treatment-resistant depression (TRD), PTSD or generalised anxiety disorders (GAD). Psilocybin, MDMA and LSD were granted FDA breakthrough status for TRD/MDD, PTSD and GAD, respectively, although FDA recently rejected the new drug application of MDMA in PTSD. Most of these drugs target the 5-HT and monoamine systems. Classical psychedelics act as 5-HT receptor agonists, although LSD, DMT and psilocybin target other 5-HT and/or dopamine receptors. Psychedelic-dependent 5-HT receptor agonism also has profound anti-(neuro)inflammatory effects. Advanced imaging studies suggest that brain 5-HT levels are reduced in depression. Functional magnetic resonance studies show that neural networks (cortico thalamic, salience, default mode) are profoundly impaired in depression. Such network defects are corrected upon psychedelic/entactogen treatment, offering a unique opportunity to serve as biomarkers for depression, anxiety and PTSD precision medicine trials. Psychedelics and entactogens target common end pathways, namely neuroplasticity/synaptogenesis, either directly via monoamine or glutamate receptors and/or indirectly, via BDNF and mTORC1 pathways. Together, these findings strongly support a biological basis for MDD, GAD, PTSD and related conditions, which can be considered as mixed biochemical, neurological and neuroimmune disorders, and are profoundly modified by psychedelics, entactogens and the newly developed psychoplastogens. LINKED ARTICLES: This article is part of a themed issue Emerging Therapeutic Opportunities for Psychedelic and Related Drugs. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v183.14/issuetoc.

keywords:
5‐HT (serotonin), Brain‐derived neurotrophic factor (BDNF), Empathogens, Entactogens, LSD (lysergic acid diethylamide), MDMA (3,4‐methylenedioxy methamphetamine), Post‐traumatic stress disorders (PTSD), Psychedelics, Psychoplastogens, Treatment resistant depression (TRD)

topic_tags:
Depression,Anxiety,PTSD,Neuroplasticity,Brain Imaging,Mechanism of Action,Receptor Pharmacology,Biomarkers,Aging,Clinical Trial,Treatment-Resistant Depression,Inflammation,Immune Function


title: Neuropsychopharmacology of hallucinogenic and non-hallucinogenic 5-HT receptor agonists.
authors: Sharp T, Ippolito A
journal: British journal of pharmacology
publication_date: 2026-06-30
doi: 10.1111/bph.70050
pubmed_id: 40405723
source_url: https://pubmed.ncbi.nlm.nih.gov/40405723/
keywords: 5‐HT, 5‐HT2A receptor, antidepressant, hallucinogens, psychedelics, serotonin
substance_tags: psilocin
topic_tags: Depression,Anxiety,Addiction,Neuroplasticity,Pharmacology,Receptor Pharmacology
study_type: Other
source_name: PubMed
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-02 06:54:10
raw_json: {"pubmed_id":"40405723"}
abstract:
Psychedelic drugs such as LSD and psilocin were once relegated to the fringes of medical research because of their association with counterculture movements and a perceived concern about harm through recreational use, and their consequent legal prohibition in the early 1970s. However, these drugs are now experiencing a renaissance in the field of psychiatry based on increasing evidence that they can produce long-lasting improvements in health across a wide variety of mental illnesses, including major depression, addictions and anxiety disorders. These drugs interact with many different 5-HT receptor subtypes but the powerful psychedelic experience, which (depending on set and setting) includes profound alterations in perception, mood and cognition, accompanied by vivid hallucinations, is now widely considered mediated by an agonist action at 5-HT receptors. However, the link between the psychedelic experience, 5-HT receptor agonism and therapeutic effects is currently uncertain. Indeed, recent research has revealed a new class of 5-HT receptor agonists which appear to retain the therapeutic potential of psychedelics drugs without inducing disorienting hallucinatory experiences. Biased signalling, partial agonism and non-selectivity at the 5-HT receptor are amongst the possible explanations for the differential properties of these drugs, whereas increased neuroplasticity offers a likely account of their common therapeutic effects. This article explores the neuropsychopharmacological properties of hallucinogenic and non-hallucinogenic 5-HT receptor agonists in the context of their promise as novel drug treatments in psychiatry. LINKED ARTICLES: This article is part of a themed issue Emerging Therapeutic Opportunities for Psychedelic and Related Drugs. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v183.14/issuetoc.


authors: Nutt DJ, Hunt P, Schlag AK, Fitzgerald P
journal: British journal of pharmacology
publication_date: 2026-06-30
doi: 10.1111/bph.17398
pubmed_id: 39701143
source_url: https://pubmed.ncbi.nlm.nih.gov/39701143/
substance_tags: psilocybin
topic_tags: Depression,PTSD,Mechanism of Action,Review Article,Treatment-Resistant Depression
study_type: Review Article
source_name: PubMed
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-02 06:54:10
raw_json: {"pubmed_id":"39701143"}
title:
The Australia story: Current status and future challenges for the clinical applications of psychedelics.

abstract:
The past decade has seen a huge increase in clinical research with psychedelic drugs and 3,4-methylenedioxymethamphetamine (MDMA), which have revealed great potential for treating mental health conditions. Given this progress in research, as well as the current unmet clinical need of millions of patients, in 2023, the Australian Therapeutic Goods Administration (TGA) approved the use of psilocybin for treatment-resistant depression and MDMA for PTSD to take effect from 1 July 2023. The campaign for TGA approval was led by a coalition comprising the Australian charity Mind Medicine Australia with support from Professor David Nutt, Drug Science, Professor Arthur Christopolous, Professor Chris Langmead (both from Monash University) and from large numbers of clinical, academic and patient groups. Under the rescheduling, current prescribing rights are limited to psychiatrists who have become authorised prescribers under the TGA's Authorised Prescriber Scheme, and psilocybin can only be used for treatment resistant depression and MDMA can only be used for PTSD. This paper reviews the background for this decision, its implications for approvals in other jurisdictions, as well as for the development pathways for other psychedelic drugs. LINKED ARTICLES: This article is part of a themed issue Emerging Therapeutic Opportunities for Psychedelic and Related Drugs. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v183.14/issuetoc.

keywords:
3,4‐methylenedioxymethamphetamine (MDMA), Australia, psilocybin, psychedelics, therapeutic goods administration (TGA)


title: Psilocybin as a novel treatment for chronic pain.
authors: Askey T, Lasrado R, Maiarú M, Stephens GJ
journal: British journal of pharmacology
publication_date: 2026-06-30
doi: 10.1111/bph.17420
pubmed_id: 39614355
source_url: https://pubmed.ncbi.nlm.nih.gov/39614355/
substance_tags: psilocybin
study_type: Review Article
source_name: PubMed
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-02 06:54:10
raw_json: {"pubmed_id":"39614355"}
abstract:
Psychedelic drugs are under active consideration for clinical use and have generated significant interest for their potential as anti-nociceptive treatments for chronic pain, and for addressing conditions like depression, frequently co-morbid with pain. This review primarily explores the utility of preclinical animal models in investigating the potential of psilocybin as an anti-nociceptive agent. Initial studies involving psilocybin in animal models of neuropathic and inflammatory pain are summarised, alongside areas where further research is needed. The potential mechanisms of action, including targeting serotonergic pathways through the activation of 5-HT receptors at both spinal and central levels, as well as neuroplastic actions that improve functional connectivity in brain regions involved in chronic pain, are considered. Current clinical aspects and the translational potential of psilocybin from animal models to chronic pain patients are reviewed. Also discussed is psilocybin's profile as an ideal anti-nociceptive agent, with a wide range of effects against chronic pain and its associated inflammatory or emotional components. LINKED ARTICLES: This article is part of a themed issue Emerging Therapeutic Opportunities for Psychedelic and Related Drugs. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v183.14/issuetoc.

keywords:
neuropathic pain, neuroplasticity, nociplastic pain, psilocybin, psychedelic drugs, serotonergic signalling

topic_tags:
Depression,Chronic Pain,Neuroplasticity,Mechanism of Action,Receptor Pharmacology,Emotional Processing,Review Article,Animal Study,Inflammation


title: Chemistry/structural biology of psychedelic drugs and their receptor(s).
authors: Gumpper RH, Nichols DE
journal: British journal of pharmacology
publication_date: 2026-06-30
doi: 10.1111/bph.17361
pubmed_id: 39354889
source_url: https://pubmed.ncbi.nlm.nih.gov/39354889/
substance_tags: psilocybin
topic_tags: Mechanism of Action,Receptor Pharmacology,Review Article
study_type: Review Article
source_name: PubMed
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-02 06:54:10
raw_json: {"pubmed_id":"39354889"}
abstract:
This brief review highlights some of the structure-activity relationships of classic serotonergic psychedelics. In particular, we discuss structural features of three chemotypes: phenethylamines, ergolines and certain tryptamines, which possess psychedelic activity in humans. Where they are known, we point out the underlying molecular mechanisms utilized by each of the three chemotypes of psychedelic molecules. With a focus on the 5-HT receptor subtype, a G-protein coupled receptor known to be the primary target of psychedelics, we refer to several X-ray and cryoEM structures, with a variety of ligands bound, to illustrate the underlying atomistic basis for some of the known pharmacological observations of psychedelic drug actions. LINKED ARTICLES: This article is part of a themed issue Emerging Therapeutic Opportunities for Psychedelic and Related Drugs. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v183.14/issuetoc.

keywords:
5‐HT2A agonists, 5‐HT2A receptor, LSD, Psychedelic chemotypes, crystal structures, docking, ergolines, phenethylamines, psilocybin, structural biology, structure‐activity relationships, therapeutic potential, tryptamines


publication_date: 2026-06-29
doi: 10.1007/s40211-026-00584-4
pubmed_id: 42377806
source_url: https://pubmed.ncbi.nlm.nih.gov/42377806/
keywords: Ayahuasca, Depression, Ketamine, Psilocybin, Psychedelic agents, Treatment resistance
substance_tags: psilocybin
study_type: Clinical Trial
source_name: PubMed
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-02 06:54:10
raw_json: {"pubmed_id":"42377806"}
title:
Psychedelics in treatment-resistant depression: a comprehensive review of mechanisms, clinical evidence, and recommendations.

authors:
Estela-Fernandez CA, Mohamed Yousif Elsheikh R, Beatrice DB, A Alhendal A, Irene Ewe C, Montesinos SY, Wensel J, Mishra AP, Yousif AA, Ali HT

abstract:
Major depressive disorder (MDD) is a heterogeneous, debilitating disorder. A distinct subgroup within the MDD spectrum is identified to have treatment-resistant depression (TRD). There is an impetus to find alternative treatments for TRD to reduce disease burden and improve quality of life. Psychedelics have been used in the treatment of various psychiatric disorders since the 1950s, with potential benefits in TRD.
Aiming to summarize the evidence of using psychedelics for TRD by exploring mechanisms and potential benefits, we conducted a literature search on different psychedelics with their mechanisms from clinical and preclinical evidence.
Psychedelics have been examined in many preclinical studies for efficacy and mechanisms with fewer clinical studies on patients with TRD. Besides serotonergic agonism, glutamate surge and monoamine release, psychedelics promote neuroplasticity, corticolimbic function, and epigenetic changes. Psilocybin, ketamine, and esketamine are the most researched agents of psychedelics in the context of TRD. Psilocybin-assisted therapy has been shown to induce short-term improvement in symptoms that can persist for weeks and months, with some meta-analyses consolidating such findings. Ketamine, as an atypical psychedelic, in many clinical trials of intravenous, subcutaneous, and oral forms, had rapid and robust effects in reducing depressive symptoms and relapses without decreasing cognitive function. Similarly, esketamine induced early and clinically meaningful improvements in function and productivity. Ayahuasca also showed fast and sustained effects with higher remission rates and good safety.
Psychedelics have significant potential in TRD with superior mechanisms over traditional antidepressants. Despite the encouraging findings of the existing studies, large, well-designed studies are needed to extend their use as part of standard recommendations.

journal:
Neuropsychiatrie : Klinik, Diagnostik, Therapie und Rehabilitation : Organ der Gesellschaft Osterreichischer Nervenarzte und Psychiater

topic_tags:
Depression,Neuroplasticity,Mechanism of Action,Aging,Epigenetics,Clinical Trial,Review Article,Animal Study,Treatment-Resistant Depression,Safety


authors: Wang Y, Wang H, Lin C, Wang X
journal: Proceedings of the National Academy of Sciences of the United States of America
publication_date: 2026-06-29
doi: 10.1073/pnas.2535785123
pubmed_id: 42341036
source_url: https://pubmed.ncbi.nlm.nih.gov/42341036/
keywords: chemical defense, chemical ecology, convergent evolution, hallucinogens
substance_tags: psilocybin
study_type: Other
source_name: PubMed
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-02 06:54:10
raw_json: {"pubmed_id":"42341036"}
title:
Chemical ecology and convergent evolution of natural hallucinogens: From ecological defense to conserved neural targets.

abstract:
Natural hallucinogenic compounds have arisen independently across plants, fungi, and animals, evolving into a diverse chemical arsenal that includes phenethylamines, indolealkylamines, and terpenoid scaffolds. Beyond clinical and cultural frameworks, their ecological origins and evolutionary trajectories may help explain why such potent modulators of perception, emotion, and cognition persist in nature. Here, integrating chemical ecology, comparative genomics, biosynthetic logic, and evolutionary biology, we propose that these molecules may function as defensive agents or symbiosis-associated manipulators of herbivore and pollinator behavior. A "building-block" biosynthetic logic links primary metabolism to convergent psychotropic scaffolds via a recurrent set of tailoring reactions, including decarboxylations and methylations. Recent advances illuminate mescaline biosynthesis in cacti, horizontal gene transfer of psilocybin clusters in fungi, and symbiont-derived alkaloids in grasses. We also assess the debate surrounding endogenous mammalian tryptamines, arguing that the leading hypothesis points toward sigma-1 receptor-mediated cytoprotection and stress responses, supported by convergent pharmacological and cellular evidence, rather than inherent hallucinogenic functions. Across kingdoms, natural hallucinogens appear to converge on conserved neural targets, including serotonergic and other neuromodulatory systems that are shared across phyla. From this perspective, human psychoactivity is likely an evolutionary by-product of molecules selected for ecological interactions with animals possessing deeply conserved receptor architectures. Framing hallucinogens through chemical ecology not only clarifies their origins but also highlights translational opportunities in target discovery, pathway engineering, and sustainable production, while emphasizing the need to integrate conservation, ethical sourcing, and benefit-sharing into the current hallucinogenic renaissance.

topic_tags:
Pharmacology,Mechanism of Action,Receptor Pharmacology,Epigenetics,Emotional Processing,Drug Interactions,Genomics


authors: Du Yingjie, Zhao Xiangting, Yao Yishan, Li Yunfeng, Wang Guyan, Zhang Liming
journal: Journal of Psychopharmacology
publication_date: 2026-06-27
doi: 10.1177/02698811261453819
source_url: https://doi.org/10.1177/02698811261453819
substance_tags: psilocybin
topic_tags: Depression,PTSD,Neuroplasticity,Neurogenesis,Mechanism of Action,Biomarkers,Animal Study
study_type: Animal Study
source_name: Crossref
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-02 06:54:51
title:
Psilocybin reduces fear memory and restores neuroplasticity in the hippocampus and medial prefrontal cortex

abstract:
Background: Posttraumatic stress disorder (PTSD) and major depressive disorder are often comorbid in humans. Psilocybin reportedly has beneficial therapeutic effects on depression, possibly by promoting neuroplasticity. PTSD is associated with the dysregulation of neuroplasticity in the hippocampus and medial prefrontal cortex (mPFC). We hypothesized that psilocybin might reduce fear memory by promoting neuroplasticity in the hippocampus and mPFC. Aims: We investigated the effects of psilocybin on fear memory and explored its underlying mechanisms. We generated a mouse model of PTSD via auditory-cued fear conditioning and treated the mice with either vehicle or psilocybin (2.5 mg/kg, intraperitoneal) on day 0. Fear memory was assessed by the percentage of freezing time in response to conditioned stimuli. Fear memory tests were conducted on days 1, 6, and 7, after which the mice were sacrificed. To investigate the role of neuroplasticity in mediating the effects of psilocybin on fear memory, we assessed structural neuroplasticity and neuroplasticity-associated marker protein levels in the hippocampus and mPFC 7 days after a single dose of psilocybin. Results: Psilocybin reduced the cue-induced fear response on days 1, 6, and 7. Psilocybin ameliorated the fear conditioning-induced decreases in neuroplasticity in the hippocampus and mPFC. Through Golgi-Cox staining, Western blotting, and immunofluorescence staining, we found that psilocybin increased dendritic branches and spine density, upregulated GluR1 and synapsin-1, enhanced brain-derived neurotrophic factor and mammalian target of rapamycin signaling, and promoted neurogenesis. Conclusions: A single dose of psilocybin reduces both the rapid and sustained fear memory in mice, at least in part by restoring neuroplasticity in the hippocampus and mPFC. These findings indicate that psilocybin has significant potential for use in the treatment of PTSD and other mental disorders characterized by fear memory.

raw_json:
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authors: Özaydın Y, Canlan Özaydın B
journal: Journal of psychopharmacology (Oxford, England)
publication_date: 2026-06-27
doi: 10.1177/02698811261456196
pubmed_id: 42365488
source_url: https://pubmed.ncbi.nlm.nih.gov/42365488/
substance_tags: psilocybin
topic_tags: Receptor Pharmacology,Microdosing,Meta-Analysis,Systematic Review,Review Article,Safety
study_type: Meta-Analysis
source_name: PubMed
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-02 06:54:10
raw_json: {"pubmed_id":"42365488"}
title:
Classical psychedelic microdosing, mood, and cognitive function: An umbrella review with narrative synthesis.

abstract:
Psychedelic microdosing-repeated sub-perceptual doses of lysergic acid diethylamide (LSD) or psilocybin-has attracted scientific interest as a potential mood and cognitive intervention. The evidence base remains methodologically heterogeneous and vulnerable to expectancy bias.
We conducted an umbrella review with narrative synthesis following Joanna Briggs Institute guidance and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 standards (International Prospective Register of Systematic Reviews [PROSPERO]: 2020 standards (PROSPERO: CRD420251077340). Six databases were searched through February 2026. Eligible studies were systematic reviews and/or meta-analyses examining microdosing effects (⩽20 μg LSD or ⩽3 mg psilocybin per session) on mood or cognitive outcomes in adults. Quality was appraised with A Measurement Tool to Assess Systematic Reviews-2; primary-study overlap was quantified via corrected covered area (CCA).
Three meta-analyses met quantitative criteria, drawing on 14 studies (13 unique samples, = 1614); three reviews contributed to narrative synthesis. Primary-study overlap was very high (CCA = 0.29). The sole significant pooled effect was a small decrease in cognitive control ( = -0.34, 95% CI: -0.62 to -0.06); all other domains were non-significant. No eligible meta-analysis provided pooled mood-outcome effect sizes within the microdose threshold; narrative evidence indicates that self-reported mood benefits are largely attenuated under placebo-controlled conditions. Short-term tolerability was acceptable, though cardiovascular signals and long-term risks via 5-HTB activation remain uncharacterized.
Current evidence does not support cognitive enhancement through microdosing; the only consistent controlled finding runs counter to popular claims: microdosing was associated with a small but reliable impairment of cognitive control. Observed mood benefits are not replicated under blinded conditions, consistent with expectancy-driven responding. Adequately powered, preregistered, expectancy-controlled trials are required before clinical recommendations can be made.

keywords:
AMSTAR-2, LSD, cognitive function, expectancy effects, mood, narrative synthesis, placebo, psilocybin, psychedelic microdosing, serotonin receptor partial agonist (5-HT2A), serotonin reuptake inhibitor, umbrella review


authors: Priest M, Kilmer B, Senator B, Setodji CM
journal: Rand health quarterly
publication_date: 2026-05-31
pubmed_id: 42368324
source_url: https://pubmed.ncbi.nlm.nih.gov/42368324/
substance_tags: psilocybin
topic_tags: Microdosing,Observational Study
study_type: Observational Study
source_name: PubMed
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-02 06:54:10
raw_json: {"pubmed_id":"42368324"}
title:
U.S. Psychedelic Use and Microdosing in 2025: Insights from a Probability-Based and Nationally Representative Survey.

abstract:
An increasing number of U.S. states are implementing or considering alternative policies to the prohibition of some psychedelic substances for nonclinical purposes. The authors present new data and analysis to inform these discussions with survey results on the use of 11 psychedelic substances and detailed information about the prevalence of microdosing (i.e., taking a fraction of a full dose, often on a schedule) for psilocybin, LSD, and MDMA.

keywords:
Controlled Substances and Illegal Drugs, Drug Markets and Supply, Drug Policy and Trends, Mental Health Treatment


title: The purpose of the psychosocial protocol in the psychedelic-assisted therapy: A scoping review.
authors: Giaffone de Paiva Ferreira F, Fernandes JAB, Filev R, da Silveira DX, Fidalgo TM.
publication_date: 2026-06-25
doi: 10.1177/02698811261453850
pubmed_id: 42363614
source_url: https://doi.org/10.1177/02698811261453850
substance_tags: psilocybin
topic_tags: Review Article,Observational Study
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-02 06:54:51
abstract:
With growing research on the use of psychedelics to treat mental health conditions, greater attention to the psychosocial procedures accompanying substance administration is warranted. This scoping review aims to categorize psychosocial protocols used in research involving psychedelics as psychiatric treatment according to their purpose, denomination, format, therapeutic orientation, formalization, and duration. Experimental and observational studies were identified through online search platforms, covering Ayahuasca, Dimethyltryptamine, 5-methoxy-N,N-dimethyltryptamine, Lysergic Acid Diethylamide, Ibogaine, Mescaline, 3,4-methylenedioxymethamphetamine, Psilocybin, and 4-hydroxy-N,N-diisopropyltryptamine, yielding 62 eligible studies that were also assessed for methodological quality. Seven categories were defined, reflecting distinct emphases on the substance, participant, research team, and sociocultural context. Although limited reporting and heterogeneity remain methodological challenges, these features reveal divergent research intentions and contextual constraints. The proposed parameters suggest a shared language to describe, compare, and examine psychosocial protocols across studies and reduce conceptual uncertainty in the field. This review may facilitate research decision-making and support the development of structured and replicable study designs, while predicting flexibility to accommodate individualized, culturally responsive, and population-specific care. Ultimately, researchers explicitly defining the intended purpose of psychosocial protocols may improve its transparent reporting, and evaluation. Future research should balance methodological rigor with attention to real-world studies, interdisciplinary perspectives, and demographic diversity for responsible advancing.

raw_json:
{"europe_pmc_id":"42363614","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Anthracaurisin A─Discovery of a Cytotoxic -Sesquiterpene Dimer from Patagonian.
journal: Journal of natural products
publication_date: 2026-06-25
doi: 10.1021/acs.jnatprod.6c00531
pubmed_id: 42273985
source_url: https://pubmed.ncbi.nlm.nih.gov/42273985/
substance_tags: psilocybin
topic_tags: General
study_type: Other
source_name: PubMed
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-02 06:54:10
raw_json: {"pubmed_id":"42273985"}
authors:
Petit B, Michrafy I, Nafie J, Dyer GE, Marshall EM, Riquelme C, Cabrera-Pardo JR, Strother JA, Loesgen S

abstract:
Fungal natural products, also called secondary metabolites (SMs), continue to inspire chemists and drug development. Around 30,000 fungal SMs are known, mainly from filamentous fungi of the phylum Ascomycota. Only 5% of all fungal species are described today, and even fewer have been cultured or chemically screened, which makes fungi an untapped reservoir for chemical discovery. The phylum Basidiomycota harbors chemically talented fungi such as the psilocybin producer (Agaricales, Hymenogastraceae), but other members like the genus (Agaricales, Omphalotaceae) remain largely genetically and chemically underexplored although new species are being discovered frequently. Here, we present the chemical and bioactivity exploration of a Chilean fungus. We discovered anthracaurisin A, the first fungal -sesquiterpene homodimer with potent cytotoxic activity and, isolated one new and several known illudins, and established their absolute configurations.


authors: Guidetti C, Fava M, Papakostas GI.
publication_date: 2026-06-24
doi: 10.1038/s41380-026-03722-0
pubmed_id: 42350785
source_url: https://doi.org/10.1038/s41380-026-03722-0
substance_tags: psilocybin
topic_tags: Depression,Brain Imaging,Biomarkers,Clinical Trial,Review Article,Treatment-Resistant Depression
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-02 06:54:51
title:
Novel approaches in depression treatment: from rapid-acting antidepressants to personalized interventions.

abstract:
Major depressive disorder (MDD) and treatment-resistant depression (TRD) are prevalent and debilitating conditions. Over 50% of patients have inadequate response to first-line serotonergic antidepressants and are left with suboptimal treatment options. Rapid-acting and individually tailored treatments for MDD remain major unmet needs. This review discusses promising rapid-acting treatments, including psychedelic and neuroplastogen compounds, currently under investigation for the treatment of MDD and TRD. Among these, psilocybin has advanced to late-stage trials. In addition, we examine the emerging role of repetitive transcranial magnetic stimulation (rTMS), including novel personalized interventions, such as the Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT) protocol, which has demonstrated rapid antidepressant effects and is now FDA-cleared for TRD, positioning it closest to clinical translation. We also highlight the ongoing ALTO-300 trial, which is evaluating an adjunctive treatment for MDD in patients identified by an EEG biomarker-representing another promising step toward personalized treatment. Finally, we review the results of a Phase 2 study reporting outcomes that vary by a specific genotype sequence, underscoring the potential for genetically guided personalized interventions. Despite these advances, key limitations, including unblinding in psychedelic trials, scalability challenges of intensive neuromodulation protocols, and the need for validated biomarkers, pose ongoing challenges for real-world implementation.

raw_json:
{"europe_pmc_id":"42350785","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Brar PS, Price RB, Ross S, Tofighi B, Sarpal DK
journal: Journal of psychopharmacology (Oxford, England)
publication_date: 2026-06-24
doi: 10.1177/02698811261456191
pubmed_id: 42345450
source_url: https://pubmed.ncbi.nlm.nih.gov/42345450/
keywords: DMT, LSD, mescaline, phenomenology, psilocybin, psychedelics, psychosis, schizophrenia
substance_tags: psilocybin
topic_tags: Depression,Mechanism of Action,Review Article,Safety
study_type: Review Article
source_name: PubMed
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-02 06:54:10
raw_json: {"pubmed_id":"42345450"}
title:
The intersection between psychedelics and schizophrenia spectrum disorders: Reevaluating risk and therapeutic potential.

abstract:
In the past decade, interest in studying psychedelic compounds as potential therapeutic agents has resurged. These studies carefully exclude individuals at risk for developing psychotic symptoms in response to psychedelic use. Given the potential for psychedelics to be established as treatments in psychiatry, it is important to more robustly understand their link with psychosis and schizophrenia spectrum disorders (SSDs). In this narrative review, we examine the historical and theoretical relationship between psychedelic drugs and SSDs, including the origins of the psychotomimetic hypothesis. For key psychedelic compounds, we review their phenomenological manifestations in relation to the experiential alterations characteristic of SSDs, revealing both areas of overlap and important qualitative differences that challenge the uniform psychotomimetic classification. We also review putative neural mechanisms underlying altered experiential states associated with psychedelic use and SSDs, with attention to serotonergic, dopaminergic, and glutamatergic contributions. Clinical evidence demonstrates that psychedelics can exacerbate pre-existing psychotic illness and may trigger psychosis in vulnerable individuals, though the magnitude of these risks remains inadequately quantified. However, phenomenological and mechanistic distinctions suggest that potential therapeutic applications may exist for carefully selected symptoms (negative symptoms, depression) in stable patients using low-dose, controlled approaches. Based on published work, we provide recommendations regarding psychosis-related risk and potential avenues for the treatment of SSDs as psychedelics gain traction as therapeutics.


title: Unintentional ingestion of recreational drugs among young children, 2000-2024.
authors: Uskovich K, Hays HL, Badeti J, Rine NI, Michaels NL, Ding K, Smith GA
journal: BMC public health
publication_date: 2026-06-23
doi: 10.1186/s12889-026-28233-z
pubmed_id: 42343328
source_url: https://pubmed.ncbi.nlm.nih.gov/42343328/
keywords: Pediatric, Poison, Recreational drugs, Toxicity
substance_tags: psilocybin
topic_tags: Addiction,Observational Study,Toxicity
study_type: Observational Study
source_name: PubMed
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 09:38:50
raw_json: {"pubmed_id":"42343328"}
abstract:
Previous studies of pediatric recreational drug exposures have often been limited in scope. Given the rapidly changing recreational drug supply and the related unintentional ingestion of these drugs by young children, a comprehensive study that includes recent data about these exposures is needed. The objective of this study is to investigate the characteristics and trends of unintentional ingestions of recreational drugs by children < 6 years old.
Using a retrospective cohort study design, National Poison Data System data from 2000 to 2024 were analyzed. United States Census Bureau data were used to calculate population-based ingestion rates. Rate ratios (RRs) with 95% confidence intervals (CIs) were calculated to assess the magnitude of relationships between key characteristics and outcomes, such as highest level of health care received and medical outcome.
There were 41,612 unintentional ingestions involving recreational drugs among children < 6 years old reported to United States poison centers from 2000 to 2024. Most were among children < 3 years old (57.6%), involved a single substance (95.9%), and occurred in a residence (96.4%). Although 50.6% of children experienced no or minor effects, 5.0% had a major effect and there were six deaths. Children < 3 years old were more likely to experience a major effect (RR: 1.54; 95% CI:1.39-1.71) or be admitted to a critical care unit (RR: 1.23; 95% CI: 1.16-1.30) than children 3-5 years old. Cannabinoids accounted for 84.7% of ingestions, followed by stimulants (8.4%), psychedelics (3.5%), opioids (2.8%), and dissociative agents (0.6%). Ingestions involving opioids (RR: 2.60; 95% CI: 2.36-2.86), stimulants (RR: 2.16; 95% CI: 2.01-2.31), and dissociative agents (RR: 1.59; 95% CI: 1.23-2.06) were more likely to be admitted to a critical care unit than the other substance categories combined. The recreational drug ingestion rate per 100,000 US children < 6 years old increased 3,307% from 1.05 in 2000 to 35.91 in 2024, with a rapid increase beginning in 2013, especially involving edible marijuana and psilocybin products.
The recreational drug ingestion rate among children < 6 years old reported to United States poison centers increased substantially from 2000 to 2024. Additional efforts are needed to prevent these unintentional ingestions in this vulnerable population.


title: Multi-metric evaluations of acute psychedelic effects on fMRI brain entropy.
authors: McCulloch DE, Olsen AS, Ozenne B, Larsen K, Stenbæk DS, Armand S, Madsen MK, Knudsen GM, Fisher PM.
publication_date: 2026-06-23
doi: 10.1038/s41467-026-74215-5
pubmed_id: 42343098
source_url: https://doi.org/10.1038/s41467-026-74215-5
substance_tags: psilocybin
topic_tags: Brain Imaging,Observational Study
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 23:10:52
abstract:
A prominent theory of psychedelics is that they increase brain entropy. Thirteen studies have evaluated psychedelic effects on fMRI brain entropy, each applying a distinct measure. Here we evaluated these metrics in an independent 28-participant healthy cohort with 121 pre- and post-psilocybin fMRI scans. We assessed relations between brain entropy and objective and subjective psychedelic drug effects using linear mixed-effects models. All metrics were evaluated using two parcellation strategies and 7 denoising pipelines. We observed consistent significant positive associations for Shannon entropy of the spatial eigendistribution of the time by voxel matrix, path-length, instantaneous correlations, brain-state switching, and sample entropy at short time-scales. We consistently did not observe significant effects for 8 of 14 entropy metrics and observe inconsistent positive effects for Lempel-Ziv complexity of the BOLD signal. Brain entropy quantifications showed limited inter-measure correlations. Our observations support a nuanced acute psychedelic effect on brain entropy, empirically demonstrating that these metrics do not reflect a singular construct.

raw_json:
{"europe_pmc_id":"42343098","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


journal: Clinical toxicology (Philadelphia, Pa.)
publication_date: 2026-06-22
doi: 10.1080/15563650.2026.2669671
pubmed_id: 42334445
source_url: https://pubmed.ncbi.nlm.nih.gov/42334445/
substance_tags: psilocybin
topic_tags: Addiction,Chronic Pain,Mechanism of Action,Safety,Toxicity
study_type: Other
source_name: PubMed
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:20:34
raw_json: {"pubmed_id":"42334445"}
title:
Cardiovascular effects associated with acute recreational drug toxicity presentations to the emergency department: a European drug emergencies network (Euro-DEN plus) study.

authors:
van den Busken WJ, Dines AM, Eyer F, Heyerdahl F, Hovda KE, Liechti ME, Miró Ò, Vallersnes OM, Wood DM, Yates C, Dargan PI, (on behalf of the Euro-DEN Plus Research Group), Gresnigt FMJ, Euro-DEN Plus Research Group

abstract:
Recreational drugs affect the cardiovascular system through distinct mechanisms; however, data regarding their cardiovascular impact in the emergency department setting is limited. This study aimed to assess the incidence of cardiovascular effects following recreational drug use in presentations to the emergency department, identify the main drug groups involved, and compare cases with and without cardiovascular effects.
Data were extracted from the European Drug Emergency Network (Euro-DEN Plus) dataset from October 2013 to December 2021. Recreational drugs were categorised into ten main drug groups: opioids, cocaine, crack cocaine, cannabis, 3,4-methylenedioxymethamfetamine, amfetamine-type stimulants, gamma-hydroxybutyrate and gamma-butyrolactone, hallucinogens, benzodiazepines, and ketamine.
Among 59,571 presentations, 13,905 (23.3%) involved cardiovascular effects. Cocaine (OR3.19, 95% CI2.99-3.39) and 3,4 methylenedioxymethamphetamine (OR1.18, 95% CI1.13-1.23) showed the strongest associations with cardiovascular features, including chest pain, palpitations, hypertension, and arrhythmias. Opioids (OR0.35, 95% CI0.31-0.38) and benzodiazepines (OR0.38, 95% CI0.32-0.44) were associated with less frequent cardiovascular features. Patients with cardiovascular features exhibited higher median values for temperature, heart rate, blood pressure, and respiratory rate (p
Cardiovascular effects were common in acute recreational drug toxicity. Cocaine and amfetamine-type stimulants increased the risk of chest pain and arrhythmias, with chest pain being a key indicator of acute coronary syndrome. Cardiovascular effects were more frequently observed with cocaine than with crack cocaine. Cannabis was positively associated with palpitations but not arrhythmias. Gamma-hydroxybutyrate and gamma-butyrolactone, opioids, and benzodiazepines were linked to hypotension. The presence of cardiovascular effects was associated with worse outcomes, underscoring the need for thorough cardiac assessment.
Cardiovascular effects were present in almost a quarter of emergency department presentations with acute recreational drug toxicity, particularly involving cocaine and 3,4 methylenedioxymethamphetamine.

keywords:
3,4 methylenedioxymeth­amphetamine, acute drug toxicity, amfetamine, amfetamine (amphetamine), amphetamine, cardio­vascular, cocaine, lysergide (lyseric acid diethylamide), midamafetamine (3,4 methylenedioxymethamphetamine, midomafetamine, psilocybine (psilocybin)


title: Blocking 5-HT2B receptors abolishes psilocybin's efficacy in the rat forced swim test.
authors: Seillier L, Seillier A, Zvolska MA, Šlamberová R.
publication_date: 2026-06-22
doi: 10.1177/02698811261458349
pubmed_id: 42334341
source_url: https://doi.org/10.1177/02698811261458349
substance_tags: psilocybin
topic_tags: Depression,Receptor Pharmacology,Animal Study
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:00
abstract:
BackgroundMajor depressive disorder is one of the most debilitating psychiatric disorders worldwide. First-line treatments such as selective serotonin reuptake inhibitors have significant limitations, including delayed onset of therapeutic effects and treatment resistance in about 30% of patients. Increasing evidence suggests that acute administration of serotonergic psychedelics, such as psilocybin, produces rapid and long-lasting antidepressant effects, including in treatment-resistant patients. However, it remains unknown which specific 5-HT receptor subtype mediates psilocybin's antidepressant activity.MethodsWe examined in Wistar rats whether pretreatment with the 5-HT2B receptor (5-HT2BR) antagonist RS-127445 (0.32, 1.0, or 3.2 mg/kg) blocked the rapid (day 1) and sustained (day 21) behavioral effects of a single psilocybin administration (0.32 mg/kg) in the forced swim test (FST), a test with predictive validity for antidepressant efficacy. We also measured the impact of RS-127445 on psilocybin-induced head-twitch response (HTR), a behavioral proxy in rodents for psychedelic properties.ResultsOur data showed that psilocybin produced both a rapid and sustained decrease in immobility and an increase in climbing behavior in the FST and significantly increased HTR counts. Although RS-127445 did not affect HTR counts at any tested dose, it dose-dependently reversed both the rapid and sustained psilocybin-induced reductions in immobility and increases in climbing behavior.ConclusionThese findings indicate that 5-HT2BRs are required for psilocybin's behavioral effects in the FST, but are not required for its HTR. The results add to evidence that psilocybin's predictive validity in the FST can be dissociated from its 5-HT2A-mediated psychedelic effects.

raw_json:
{"europe_pmc_id":"42334341","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Low ZXB.
publication_date: 2026-04-22
doi: 10.1016/j.pnpbp.2026.111717
pubmed_id: 42034276
source_url: https://doi.org/10.1016/j.pnpbp.2026.111717
keywords: Brain, Animals, Humans, Serotonin, Hallucinogens, Neuronal Plasticity, Autism Spectrum Disorder
substance_tags: psilocybin
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:03
title:
Serotonergic psychedelics for Autism spectrum disorder: Neurobiological mechanisms and translational prospects.

abstract:
Autism Spectrum Disorder (ASD) is characterized by persistent social-communication deficits, cognitive rigidity, and atypical sensory processing. Current pharmacological treatments, including risperidone and aripiprazole, provide only limited symptomatic relief and do not address the underlying neurobiological mechanisms. Converging evidence implicates dysregulated serotonergic signaling, impaired neuroplasticity, and chronic neuroimmune activation as central features of ASD pathophysiology. Serotonergic psychedelics, such as psilocybin and LSD, act as high-affinity 5-HT2A receptor agonists and have re-emerged as candidates for modulating these core pathways. In this Review, we synthesize molecular, cellular, and systems-level findings suggesting that psychedelics may transiently relax overly rigid cortical priors, reopen critical periods for social learning, and recalibrate dysfunctional neural circuits in ASD. These compounds enhance synaptic plasticity via BDNF and mTOR signaling, modulate cortical oscillations, and suppress neuroinflammation by shifting microglial phenotypes and suppressing pro-inflammatory cytokines. Systems-level frameworks, including the REBUS and anarchic brain hypotheses, contextualize how psychedelics induce globally integrated, less constrained brain states that may counteract the hyper-segregated connectivity commonly observed in ASD. While preclinical and early human studies report improvements in sociability, sensory responsiveness, and behavioural flexibility, rigorous clinical trials are urgently needed to establish safety, efficacy, and optimal developmental windows for intervention. We conclude by outlining a translational roadmap to guide future research, emphasizing the need for structured integration with behavioural therapies, attention to ASD heterogeneity, ethical considerations, and the potential to shift ASD treatment beyond symptomatic management toward disease-modifying intervention.

topic_tags:
Neuroplasticity,Mechanism of Action,Receptor Pharmacology,Clinical Trial,Review Article,Animal Study,Safety,Inflammation,Immune Function

raw_json:
{"europe_pmc_id":"42034276","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin restores behavioral and neuroplastic deficits induced by chronic stress in rats.
publication_date: 2026-04-18
doi: 10.1016/j.pnpbp.2026.111710
pubmed_id: 42009274
source_url: https://doi.org/10.1016/j.pnpbp.2026.111710
substance_tags: psilocybin
topic_tags: Depression,Neuroplasticity,Neurogenesis,Mechanism of Action,Biomarkers,Animal Study
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:00
authors:
Bysiek A, Szpręgiel I, Wojtas A, Maćkowiak M, Wawrzczak-Bargieła A, Leśkiewicz M, Trojan E, Kamińska K, Kumorek W, Bilecki W, Gołembiowska K.

abstract:
Psychedelics have emerged as a promising novel therapeutic approach for major depressive disorder (MDD). Altered activity and structural atrophy of the prefrontal cortex, hippocampus, and limbic structures are associated with depressive disorders. Psilocybin may reverse the loss of synaptic connections and restore the function of these brain regions. In this study, we investigated the effects of psilocybin on rat behavior, hippocampal neurogenesis, expression level of brain-derived neurotrophic factor (BDNF) and hypothalamic-pituitary-adrenal (HPA) axis activity. Psilocybin administered in two doses (0.6 mg/kg, s.c., 7 days apart) reversed anhedonia in stressed rats, produced antidepressant-like effects in the forced swim test (FST), and exerted anxiolytic activity in the light/dark box (LDB), elevated plus maze (EPM), and open field (OF) tests in stressed animals. Psilocybin induced hippocampal neurogenesis as evidenced by increasing the number of BrdU-positive cells (an exogenous marker of cell proliferation and survival), DCX-positive cells (a marker of immature neurons), and Ki-67-positive cells (an endogenous marker of cell proliferation) in stressed animals. Stress-induced reductions in BDNF expression levels appeared to be associated with normalization of HPA axis activity. These findings underscore the role of psilocybin-induced neuroplasticity in the antidepressant and anxiolytic mechanisms of psychedelics.

keywords:
Pituitary-Adrenal System, Hypothalamo-Hypophyseal System, Hippocampus, Animals, Rats, Rats, Wistar, Disease Models, Animal, Chronic Disease, Corticosterone, Brain-Derived Neurotrophic Factor, Hallucinogens, Antidepressive Agents, Stress, Psychological, Neuronal Plasticity, Male, Neurogenesis, Psilocybin, Doublecortin Protein

raw_json:
{"europe_pmc_id":"42009274","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Marketing by online tobacco retailers: An observational cross-sectional study.
authors: Apollonio DE, Dennehy CE, Tsourounis C, Wakefield T.
publication_date: 2026-06-18
doi: 10.18332/tid/220983
pubmed_id: 42325848
source_url: https://doi.org/10.18332/tid/220983
substance_tags: psilocybin
topic_tags: Addiction,Observational Study
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:03
abstract:
IntroductionUnderstanding retailer advertising has been identified as critical for developing effective policies to reduce tobacco product use, as these forms of advertising are among the tobacco industry's largest expenditures. Online retailer marketing has grown rapidly, and in this study, we sought to describe the marketing practices of these retailers.MethodsBetween March and July 2022, we conducted keyword searches (e.g. 'buy e-cigs', 'buy vapes') with the Brave search engine, embedded in the Brave browser, to identify online tobacco retailers, using the inclusion criteria: English-language websites of online retailers selling e-cigarette products that allowed online ordering and the sale of products to customers in the United States. Measures included name, address, and landing page characteristics, including products, brands, product types, seasonal specials, social media links, age gating, and whether the retailer sold non-tobacco products. Results are reported descriptively.ResultsWe identified 97 unique online tobacco retailers. Of these, 58 (60%) had set a restriction on browsing based on age. E-cigarettes, both disposable and reusable, were the most available products, followed by liquid nicotine ('vape juice'). Thirty-seven percent of online tobacco retailers sold cannabis products, and 38% of retailer websites listed other types of products for sale (e.g. bongs, dab rigs, cannabis apparel, psilocybin chocolates).ConclusionsOur findings indicated that online tobacco retailers heavily marketed flavored products, and a majority sold derived cannabis products. Future research should continue to investigate whether this marketing conflicts with stated federal regulatory goals, and whether the U.S. Food and Drug Administration should expand enforcement of existing regulations on tobacco and derived cannabis products.

raw_json:
{"europe_pmc_id":"42325848","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2026-06-18
doi: 10.1080/02791072.2026.2685527
pubmed_id: 42318842
source_url: https://doi.org/10.1080/02791072.2026.2685527
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Microdosing,Observational Study
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:02
title:
Psychedelic Use, Microdosing, Motives, and Information and Product Sources Among Young Adults in the United States.

authors:
Berg CJ, McCready DM, LoParco CR, Schubel LC, Romm KF, Thakkar S, Williams J, Cavazos-Rehg PA, Yang YT.

abstract:
Given the increases in psychedelic use, we examined correlates of psychedelic use and use motives among US young adults. In 2025, adults ages 18-34 (n = 3,227; Mage = 26.38, ~50% past-month cannabis use by design) completed an online survey. Multivariable regression assessed sociodemographics, mental health, and adverse childhood events (ACEs) in relation to: (1) past-year psychedelic use; and (2) among those reporting lifetime use: (a) lifetime microdosing and (b) use motives. Lifetime and past-year psychedelic use were 27.7% and 11.9% (commonly psilocybin/amanita, MDMA, and LSD); 48.8% used only for nonmedical purposes. Of those reporting lifetime use, 26.5% ever microdosed. Correlates of use-related outcomes varied: (1) lifetime use: older, male (vs female), Black (vs White), metropolitan/urban (vs rural), more depressive symptoms and ACEs; (2) microdosing: not having children, more anxiety symptoms and ACEs; (3) higher expansion motives: male, White (vs Asian), more anxiety symptoms and ACEs; (4) higher mood/social enhancement motives: more depressive symptoms; and (5) higher symptom management motives: male, Hispanic, more depressive symptoms and ACEs. Despite half using exclusively for nonmedical purposes, mental health symptoms and ACEs were associated with use, microdosing, and higher use motives. Understanding the role of mental health across sociodemographic groups is necessary to address possible adverse outcomes.

raw_json:
{"europe_pmc_id":"42318842","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: DESI-MSI-Based Multi-Organ Distribution Mapping of Psilocin in Zebrafish.
authors: Dong M, Zhang Y, Cao M, Shi T, Li L, Zong X, Wang C.
publication_date: 2026-06-17
doi: 10.3390/molecules31122143
pubmed_id: 42357539
source_url: https://doi.org/10.3390/molecules31122143
substance_tags: psilocybin,psilocin
topic_tags: Brain Imaging,Aging,Safety,Toxicity
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:00
abstract:
Psilocybin, a psychedelic drug with reported anxiolytic and antidepressant potential, is rapidly metabolized to its active metabolite psilocin. However, a lack of adequate toxicity studies and tissue distribution studies currently restricts its development and application. This study combined behavioral assays in zebrafish with desorption electrospray ionization mass spectrometry imaging (DESI-MSI) to systematically evaluate the acute neurotoxicity of psilocybin and characterize the in vivo spatial distribution of its active metabolite, psilocin. The novel tank test was used to evaluate zebrafish following a 4 h exposure to psilocybin at three different doses (20, 40, and 80 μM; n = 6 per group). Statistical analysis of the data was performed using ANOVA. Behavioral analyses revealed that exposure to psilocybin induced pronounced neurobehavioral alterations, including hyperactivity and disrupted swimming patterns, as evidenced by significant increases in the number of zone transitions and shuttle frequency. We established a DESI-MSI-based method for quantitative mapping and visualization of psilocin in zebrafish tissues. Methodological validation indicated that a linear relationship between ion intensity, spotted amount (R2 = 0.9947), and reproducibility (RSD < 15%) is suitable for quantitative analysis of psilocin in zebrafish tissues. Spatial distribution maps showed that following continuous exposure for 4 h, psilocin was widely distributed across multiple tissues, such as the eye, brain, heart, liver, and kidney, with marked accumulation in the brain and the periportal regions of the liver. Relative psilocin signal intensity revealed a dose-dependent increase in tissue drug levels. The dose-dependent increase in both behavioral hyperactivity and brain psilocin levels points to a consistent relationship, in line with a central site of action. Collectively, these findings demonstrate that DESI-MSI provides a visual and efficient strategy for studying drug distribution in biological tissues from exposed animals. The neurobehavioral toxicity phenotypes and distinct tissue distribution patterns of psilocin uncovered in this study offer critical insights into the biological effects and potential risks of this psychoactive substance.

keywords:
Brain, Animals, Zebrafish, Hallucinogens, Spectrometry, Mass, Electrospray Ionization, Behavior, Animal, Tissue Distribution, Psilocybin

raw_json:
{"europe_pmc_id":"42357539","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Dissociating the Hallucinogenic and Neuroplastic Effects of Psilocybin
authors: Baker JJ, Kogan E, Ma S, Lu J, Zuo Y.
journal: bioRxiv
publication_date: 2026-04-08
doi: 10.64898/2026.04.06.716778
source_url: https://doi.org/10.64898/2026.04.06.716778
substance_tags: psilocybin
topic_tags: Neuroplasticity,Mechanism of Action,Receptor Pharmacology
study_type: Other
source_name: bioRxiv
publication_status: preprint
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:00
abstract:
It is unclear how serotonin 2A receptors (5-HT2A Rs) in cortical layer 5 pyramidal neurons (L5 PyrNs) differentially contribute to psilocybin-induced hallucinations versus neuroplasticity. Here we show that psilocybin promotes synapse formation and maturation while accelerating the elimination of pre-existing synapses. Cell type-specific manipulation further demonstrated that 5-HT2A R signaling in L5 PyrNs is necessary and sufficient for psilocybin-induced synaptic remodeling but dispensable for the head-twitch response, a rodent proxy of hallucination.

raw_json:
{"europe_pmc_id":"PPR1215700","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


publication_date: 2026-06-16
doi: 10.1016/j.biopha.2026.119680
pubmed_id: 42308914
source_url: https://doi.org/10.1016/j.biopha.2026.119680
substance_tags: psilocybin
topic_tags: Anxiety,Pharmacology,Mechanism of Action,Biomarkers
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:02
title:
Anxiety-related platform in zebrafish (Danio rerio) larvae: An integrated analysis of behavioural and molecular assay in drug screening research.

authors:
Potoczna M, Kasica N, Chmielewska-Krzesińska M, Dybalska-Szczepanek J, Wąsowicz K, Sokołowska E, Podlasz P.

abstract:
Zebrafish larvae are increasingly used in behavioural pharmacology because of their translational relevance and suitability for anxiety- and stress-related studies. However, it remains unclear whether commonly used behavioural assays and molecular stress markers provide convergent evidence of anxiolytic-like drug activity. This study therefore aimed not to validate a single predictive screening platform, but to assess the concordance and interpretative value of behavioural and molecular endpoints in larval zebrafish anxiety-related drug screening. Reference compounds with established anxiolytic or antidepressant activity, including diazepam, amitriptyline, and fluoxetine, were used to anchor assay performance. TP003, a GABAergic modulator, and three serotonergic psychedelic compounds, DOI, 5-MeO-DMT, and psilocybin, were included to challenge the assays with pharmacologically diverse mechanisms relevant to stress- and anxiety-related responses. Diazepam showed the strongest cross-assay behavioural consistency compatible with an anxiolytic-like profile. However, this response was not accompanied by reduced cortisol levels or straightforward normalisation of stress-related gene expression. Amitriptyline reduced cortisol but produced only partial behavioural effects, whereas DOI affected selected behavioural preference endpoints and transcriptional markers without significantly reducing cortisol. Fluoxetine and 5-MeO-DMT altered locomotor activity in patterns requiring cautious interpretation, as reduced movement may reflect locomotor suppression or sedation rather than anxiolysis alone. These findings indicate that behavioural and molecular endpoints should not be treated as interchangeable measures of a single anxiety construct. Instead, combined behavioural and molecular assessment is most useful as a profiling framework to identify endpoint-dependent responses, detect sedative or nonspecific locomotor confounds, and support more cautious interpretation of putative anxiolytic-like effects in larval zebrafish.

raw_json:
{"europe_pmc_id":"42308914","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin's kinematic effect on manual dexterity.
authors: Klintefors P, Bhagavan C, Kanaan R, Bryson A, Berlowitz D, Attard Z, Carter O.
publication_date: 2026-06-16
doi: 10.1007/s00213-026-07106-8
pubmed_id: 42307775
source_url: https://doi.org/10.1007/s00213-026-07106-8
substance_tags: psilocybin
topic_tags: Healthy Volunteers,Safety
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:00
abstract:
RationaleClinical interest in psilocybin-assisted rehabilitation for motor disorders is growing. However, psilocybin's motor effects are under-researched, and quantifying them is essential for assessing treatment risks and outcomes.ObjectivesThis study aims to clarify whether acute effects of psilocybin disrupt established patterns of manual dexterity and coordination. Specifically, we evaluate the impact of psilocybin on velocity, smoothness and kinematic manifold stability.MethodsIn a randomised, blinded trial, healthy participants received three doses of psilocybin (5-20 mg) administered one week apart. Manual dexterity was assessed using the Box and Block Test (BBT) at baseline and 1.5, 3, and 4.5 hours post-drug administration. Task performance was analysed using a Bayesian mixed-effects model. For kinematic analysis, 21 hand landmarks were tracked from video recordings obtained at baseline and 1.5 hours post-administration. Principal component analysis (PCA) was the basis for evaluating the stability and dimensionality of latent structure.ResultsBBT performance showed a modest biphasic dose-response pattern at higher doses (10-20 mg), with slight impairment during peak effects and slight improvement 4.5 hours post-administration relative to baseline. Effect sizes were small compared to inter-individual baseline variability. Kinematic analyses revealed no substantial changes in movement smoothness or velocity. Dimensionality metrics indicated a stable coordination structure, although finger movements showed a subtle increase in complexity.ConclusionsLow to moderate doses of psilocybin did not meaningfully disrupt manual dexterity or the latent structure of hand coordination. These findings support the feasibility of combining psilocybin administration with active motor rehabilitation.

raw_json:
{"europe_pmc_id":"42307775","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Bhat A, Zolali E, Sakib MA, Rahimian M, McMahon LR, German N, Obeng S
journal: ACS chemical neuroscience
publication_date: 2026-06-16
doi: 10.1021/acschemneuro.6c00202
pubmed_id: 42257400
source_url: https://pubmed.ncbi.nlm.nih.gov/42257400/
keywords: 5-HT2A, long-acting, psilocybin, psychedelics, short-acting
substance_tags: psilocybin
topic_tags: Depression,Anxiety,PTSD,Addiction,Pharmacology,Receptor Pharmacology,Review Article
study_type: Review Article
source_name: PubMed
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:20:34
raw_json: {"pubmed_id":"42257400"}
title:
Short- and Long-Acting Psychedelics: Structure-Activity Relationships, Pharmacology, and Implications for Neuropsychiatric Therapeutics.

abstract:
Psychedelics have re-emerged as promising therapeutics for neuropsychiatric disorders, including depression, anxiety, post-traumatic stress disorder, and substance use disorders. While their beneficial effects are largely attributed to serotonin 2A (5-HT2A) receptor activation, psychedelics exhibit substantial diversity in chemical structure, receptor binding kinetics, metabolism, and duration of action. These differences underpin the distinction between short-acting psychedelics like -dimethyltryptamine (DMT) and 5-methoxy-DMT, and long-acting compounds like lysergic acid diethylamide (LSD) and mescaline. Short-acting psychedelics may offer advantages in clinical settings where brief therapeutic sessions are preferred, while long-acting agents may be relatively more effective for clinical outcomes. This review highlights the chemistry, structure-activity relationships, and pharmacology of both short- and long-acting psychedelics. We examine key functional group modifications that influence receptor binding affinity, efficacy, and duration. By integrating insights from synthetic chemistry, pharmacology, and clinical effects, this review provides a framework for rational psychedelic drug development aimed at producing next-generation antidepressants, anxiolytics, and substance use disorder treatments with controlled and predictable clinical effects.


publication_date: 2026-06-07
doi: 10.1073/pnas.2522000123
pubmed_id: 42258710
source_url: https://doi.org/10.1073/pnas.2522000123
substance_tags: psilocybin
topic_tags: Brain Imaging,Default Mode Network,Aging,Animal Study
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:02
title:
Psychedelics disrupt hierarchical cortical propagations in the default mode network of humans and mice.

authors:
Pines AR, Zhang X, Kochalka J, Vesuna SS, Kauvar IV, Rajasekharan D, Reneau TR, Akiki TJ, Hack LM, Siegel JS, Williams LM.

abstract:
Psychedelic drugs are poised to become mainstream treatments, yet we lack a circuit-level account of how they reshape brain activity. Emerging evidence suggests that multiple psychedelic compounds modulate activity in the brain's default mode network (DMN), often interpreted as either increased or decreased bottom-up hierarchical processing. Most imaging studies, however, quantify activity as if it were stationary, remaining agnostic to the ascending or descending movements of activity that defines hierarchical processing. Here, we adapt optical flow analyses to track frame-to-frame trajectories of DMN activity across four independent datasets (humans and mice; methylenedioxymethamphetamine, psilocybin, and lysergic acid diethylamide; nine drug-vs.-control contrasts). In functional magnetic resonance and calcium imaging, all psychedelics attenuate signal flow magnitude and bottom-up directionality within the DMN. Propagation attenuation is not attributable to data quality or previously documented effects of psychedelics and is uniquely associated with self-reported outcomes. This replicable and generalizable attenuation of bottom-up cortical propagations provides fundamental clarification of the effects of psychedelics on macroscale hierarchical processing.

keywords:
Brain, Cerebral Cortex, Animals, Humans, Mice, N-Methyl-3,4-methylenedioxyamphetamine, Lysergic Acid Diethylamide, Hallucinogens, Magnetic Resonance Imaging, Brain Mapping, Male, Psilocybin, Default Mode Network

raw_json:
{"europe_pmc_id":"42258710","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


journal: bioRxiv
publication_date: 2024-07-05
doi: 10.1101/2024.07.03.601959
source_url: https://doi.org/10.1101/2024.07.03.601959
substance_tags: psilocybin
topic_tags: Animal Study
study_type: Animal Study
source_name: bioRxiv
publication_status: preprint
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:03
title:
Psychedelics relax predictive processing in the post-acute period by remodeling cortico-cortical feedback circuits

authors:
West CL, Imai F, Bastos G, Hornick MA, Rachmany L, Duran A, Nadeem S, Ricci D, Rader Groves AM, Wargo JA, Van Leeuwen N, Sershen H, Yaragudri Vinod K, Peterka DS, Hamm JP.

abstract:
Serotonergic psychedelics (e.g., psilocybin, LSD) have potential to treat psychiatric disorders, with therapeutic effects lasting days to weeks after a single dose. Prominent theories suggest that psychedelics have a lasting effect on hierarchical brain circuits, reducing top-down influence on information processing to facilitate an unbiased, bottom-up reassessment of the world, but direct and concrete evidence for such an effect is lacking. Here we directly tested this hypothesis in both humans and mice, assessing predictive processing in the fronto-visual system in the days after a single psychedelic exposure. Individuals who recently (

raw_json:
{"europe_pmc_id":"PPR877954","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


title: Music Playlist Use in Clinical Trials of Psychedelic Assisted Psychotherapy: A Systematic Review.
authors: Cruz L, Beserra FR, Freind JMK, Rodrigues SE, Mograbi DC.
publication_date: 2026-06-14
doi: 10.1002/jclp.70167
pubmed_id: 42296474
source_url: https://doi.org/10.1002/jclp.70167
substance_tags: psilocybin
topic_tags: Depression,PTSD,Clinical Trial,Systematic Review,Review Article
study_type: Systematic Review
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:02
abstract:
Recent studies have shown promising results for psychedelics in the treatment of psychiatric disorders. Both in clinical and recreational settings, contextual elements, such as music, can influence the experience of users and may be linked to positive outcomes. This systematic review identifies how music is being selected and used in psychedelisc-assisted psychotherapy (PAP). The search adopted PRISMA criteria and was conducted using PubMed, PsycNet, Web of Science, Scopus and Cochrane as databases. The use of music in PAP was compared, considering aspects such as the creation of a playlist, playlist features and characteristics of the setting. A total of 36 articles were found, with 25 articles mentioning the use of music, predominantly addressing depressive disorders and post-traumatic stress disorder using psilocybin and 3,4-methylenedioxymethamphetamine (MDMA). There was considerable variation in terms of procedures, mostly because studies explored different disorders and substances, but also because there was no standardized protocol regarding music. Understanding which aspects are being privileged when choosing music for use in PAP may orient future clinical and research efforts.

raw_json:
{"europe_pmc_id":"42296474","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin-assisted cognitive behavioral therapy for major depressive disorder: A pilot trial.
publication_date: 2026-02-15
doi: 10.1016/j.jad.2026.121423
pubmed_id: 41707717
source_url: https://doi.org/10.1016/j.jad.2026.121423
substance_tags: psilocybin
topic_tags: Depression,Emotional Processing,Healthcare Workers,Adverse Events
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:00
authors:
Weintraub MJ, Jeffrey JK, Ichinose MC, Bergman RL, Shapiro B, Barnett G, Artin H, Lynn M, Salimian A, Grody S, Ramesh R, Eales L, Grob CS, Miklowitz DJ.

abstract:
BackgroundPsilocybin-assisted therapy has emerged as a promising treatment for major depressive disorder, but little attention has been paid to the psychotherapy that adjoins psilocybin. Providing an adjunctive psychotherapy that is manualized and evidence-based may make psilocybin treatment more acceptable, effective, and disseminable. We examined the acceptability, feasibility, and clinical outcomes of psilocybin paired with cognitive behavioral therapy (CBT) for major depressive disorder.MethodsParticipants were adults with major depressive disorder who presented with at least moderately severe depressive symptoms. All participants underwent psilocybin-assisted CBT (PA-CBT), which consisted of two psilocybin doses (10 mg and 25 mg separated by one month) interspersed with 12 psychotherapy sessions over four months. Participants' depressive symptoms, psychosocial functioning, and cognitive-affective responses were collected at the study's baseline, at the completion of PA-CBT, and three months post-treatment.ResultsSixteen participants were enrolled, and all were retained through the 7-month study. PA-CBT was rated as highly acceptable by participants and study clinicians, with no serious adverse events reported. Based on independent assessments, 13 of 16 participants showed at least moderate (≥ 25%) improvement in depressive symptoms by the end of treatment, and 9 had fully remitted. Pre-to-post treatment improvements in depressive symptoms and psychosocial functioning were sustained at the 3-month follow-up (Hedges' gs = 1.9-2.7). Changes in depressive severity during the treatment were associated with improvements in emotion regulation and positive and negative cognitive schemas.ConclusionsCBT appears to be a feasible, well-accepted, and beneficial adjunct to psilocybin treatment. Future randomized trials are needed to compare the efficacy of PA-CBT with other psilocybin-assisted therapy modalities.

keywords:
Humans, Hallucinogens, Treatment Outcome, Combined Modality Therapy, Feasibility Studies, Pilot Projects, Adult, Middle Aged, Female, Male, Psilocybin, Cognitive Behavioral Therapy, Major Depressive Disorder

raw_json:
{"europe_pmc_id":"41707717","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2026-02-11
doi: 10.1016/j.jad.2026.121385
pubmed_id: 41690631
source_url: https://doi.org/10.1016/j.jad.2026.121385
substance_tags: psilocybin
topic_tags: Depression,Treatment-Resistant Depression
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:00
title:
Examining the effects of psilocybin-assisted psychotherapy on anhedonia in treatment-resistant depression.

authors:
Kaczmarek ES, Rodrigues NB, Chisamore N, Doyle Z, Meshkat S, Blainey MG, Brudner R, Ali S, Teopiz KM, McIntyre RS, Rosenblat JD.

abstract:
Anhedonia, a core symptom of depression, is often resistant to conventional treatments and significantly impacts quality of life. This secondary analysis aimed to evaluate the effects of psilocybin-assisted psychotherapy (PAP) on anhedonia severity in individuals with treatment-resistant depression (TRD). Participants (n = 30) with TRD and a primary diagnosis of Major Depressive Disorder or Bipolar II Disorder received at least one 25 mg dose of oral psilocybin with psychotherapy as part of a randomized, waitlist-controlled trial (NCT05029466). The primary outcome of the present secondary analysis was changes in anhedonia, measured by the Snaith-Hamilton Pleasure Scale (SHAPS). Exploratory analysis examined whether changes in anhedonia were mediated through changes in overall depression severity, measured by the Montgomery-Asberg Depression Rating Scale (MADRS). A mixed ANOVA, adjusted for sex and age, revealed a statistically significant reduction in SHAPS scores following PAP at the 2-week primary endpoint (F(8, 143.48) = 3.43, p = 0.001, n = 29) with clinically significant improvements observed at 3-month and 6-month secondary endpoints. Our findings from this preliminary analysis suggest that PAP may offer a promising intervention for addressing anhedonia in TRD, but further research with larger, placebo-controlled trials are needed to confirm these effects and elucidate potential mediators. This study adds to a growing body of evidence supporting the therapeutic potential of PAP.

keywords:
Humans, Hallucinogens, Treatment Outcome, Combined Modality Therapy, Bipolar Disorder, Psychiatric Status Rating Scales, Psychotherapy, Adult, Middle Aged, Female, Male, Anhedonia, Depressive Disorder, Treatment-Resistant, Psilocybin, Major Depressive Disorder

raw_json:
{"europe_pmc_id":"41690631","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


journal: Clinical therapeutics
publication_date: 2026-06-12
doi: 10.1016/j.clinthera.2026.05.012
pubmed_id: 42288429
source_url: https://pubmed.ncbi.nlm.nih.gov/42288429/
keywords: Ayahuasca, Drug policy, Esketamine, Indigenous perspectives, Psilocybin, Psychedelics
substance_tags: psilocybin
topic_tags: Mystical Experience,Healthcare Workers,Safety
study_type: Other
source_name: PubMed
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:20:34
raw_json: {"pubmed_id":"42288429"}
title:
Barriers and Facilitators for Psychedelic Research and Regulation in Brazil: Insights From Diverse Stakeholders.

authors:
Guimarães AL, Beserra FR, Cruz L, Bienemmann B, Freind JMK, Guinle V, Rodrigues RS, Regalado JA, Mograbi DC

abstract:
The interest in psychedelics for health-related purposes has grown significantly over the past decade. However, there is an insufficient representation of stakeholders (eg, Indigenous groups, activists, policymakers) in discussions about research and regulation. Many psychedelics originate from traditional practices historically developed in low- and middle-income countries, but these regions are seldom represented in stakeholder perspectives research. The present study will examine the barriers, facilitators, and perspectives identified by a wide array of key stakeholders regarding the research and regulation of psychedelics in Brazil.
Twenty-six stakeholders, including Indigenous leaders, formal industry actors, clinicians, activists, policymakers, and informal sellers, were interviewed. The data were analyzed using inductive thematic analysis. Code-group co-occurrence indexing was used to capture the relevance of each theme across stakeholder groups.
Thematic analysis revealed 4 barriers ("accessibility," "regulation," "limited knowledge," and "risks"), 3 facilitators (1need for innovation," "scientific advancements," and "legal loopholes"), and 4 perspectives ("integration of ancestral knowledge," "idealization, mysticism and scientific rigor," "user autonomy," and "tangible social benefits"). Themes were similarly present among stakeholders' discourse, though with varying frequencies and weights, allowing comparisons of the particular relevance of themes for each group.
We detail cultural, political, scientific, and clinical barriers, facilitators, and perspectives for psychedelic research and regulation within a region with a rich history of traditional psychedelic use, and discuss their ethical, regulatory, and clinical implications.


publication_date: 2026-06-12
doi: 10.1016/j.ymben.2026.102490
pubmed_id: 42288133
source_url: https://doi.org/10.1016/j.ymben.2026.102490
substance_tags: psilocybin
topic_tags: Mechanism of Action,Genomics
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:00
title:
Genome-based optimization of psilocybin and N,N-dimethyltryptamine biosynthetic pathways in E. coli using CRISPR-associated transposases.

authors:
Abrahms ZN, Majdi M, Madsen SM, Morton CJ, Sen AK, Fried NB, Sawyer LE, Cegielski ER, Spezzano SJ, Jones JA.

abstract:
Stable, high-level biosynthesis of complex natural products requires precise control of heterologous pathway expression, yet transcriptional architectures optimized on plasmids often fail when transferred to the chromosome. Here, we present ePathIntegrate, a genome-centric pathway engineering strategy that leverages CRISPR-associated transposases (CASTs) to integrate and rebalance multigene metabolic pathways in Escherichia coli. Direct genomic transfer of plasmid-optimized psilocybin and N,N-dimethyltryptamine (DMT) pathways resulted in a loss of productivity, driven by context-dependent promoter behavior. To address this, we developed and characterized a library of mutant T7 promoters that restore mid-range transcriptional control on the genome. Applying ePathIntegrate enabled re-optimization of both pathways, yielding genome-encoded strains that achieve 1.88 g/L psilocybin and 1.62 g/L DMT in fed-batch bioreactors. Whole-genome sequencing of CAST-mediated strains further revealed (i) precise on-target integration, (ii) some off-target pathway integrations, and (iii) small mutations in a subset of strains, highlighting both the power and limitations of CAST-mediated strain engineering.

raw_json:
{"europe_pmc_id":"42288133","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Balancing safety and access in Oregon's psilocybin services.
authors: Cheung K, Propes C, Yaden DB.
publication_date: 2026-06-12
doi: 10.1016/j.drugpo.2026.105384
pubmed_id: 42288041
source_url: https://doi.org/10.1016/j.drugpo.2026.105384
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Wellbeing,Safety
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:00
abstract:
As jurisdictions across the U.S. consider enacting policies that facilitate access to psychedelics, they must determine how the desire to expand access to these substances should be weighed against the need to adequately protect safety. Oregon's psilocybin services program offers an important early case study of this balance in practice. Under the Psilocybin Services Act, adults over 21 are permitted to access psilocybin in Oregon at licensed service centers under facilitator supervision, with no referral from a medical practitioner, or clinical supervision, needed. Drawing on the first full year of data published by the Oregon Health Authority, this commentary examines how safety and access are being balanced through Oregon's policy. Reported adverse reactions in 2025 were relatively uncommon: however, Oregon's reporting framework sets a high threshold for reportable events. Access also remains limited, with most clients being of high-income and from outside Oregon. At the same time, the program has expanded supervised psilocybin use beyond strictly medical uses, with a proportion of clients reporting using psilocybin services for general health and wellness. Others report using psilocybin services for more medical-type motivations, such as for depression and anxiety. Overall, we argue that Oregon's broad eligibility criteria and supervision requirements may raise several safety concerns, particularly when clients with clinical symptoms seek services.

raw_json:
{"europe_pmc_id":"42288041","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Zhang T, Lin C, Wang X.
publication_date: 2026-05-24
doi: 10.1021/acsptsci.6c00146
pubmed_id: 42312173
source_url: https://doi.org/10.1021/acsptsci.6c00146
substance_tags: psilocybin
topic_tags: Pharmacology,Receptor Pharmacology,Animal Study,Safety
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:02
title:
Overcoming Pharmacokinetic and Peripheral Safety Challenges in Psychedelic Therapies: The Promise of Advanced Drug Delivery Systems.

abstract:
Classic serotonergic psychedelics-such as lysergic acid diethylamide (LSD), psilocybin, and N,N-dimethyltryptamine (DMT)-hold remarkable promise for treating neuropsychiatric disorders, yet their clinical translation is severely constrained by first-pass metabolism, erratic pharmacokinetics, unsuitable action profiles, and off-target peripheral serotonin effects. To overcome these barriers, advanced delivery systemssuch as transdermal and microneedle patches, intranasal sprays, sublingual films, and injectable formulationshave been developed, alongside molecular strategies including prodrugs, "off-switch" 5-HT receptor antagonists for session control, selective receptor bias, and adjunctive pharmacological approaches. These innovations help bypass hepatic metabolism, enable precise control over onset and duration of action, and minimize peripheral receptor activation. Preclinical and early clinical evidence shows gains in bioavailability, half-life extension, and conversion of fleeting psychedelic effects into manageable windows. These platforms offer a path to safer, patient-centered therapies. Despite regulatory and trial-design challenges, delivery innovations provide the essential pharmacokinetic toolkit to advance the field and clinical adoption.

raw_json:
{"europe_pmc_id":"42312173","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2026-06-11
doi: 10.1016/j.xcrm.2026.102867
pubmed_id: 42285092
source_url: https://doi.org/10.1016/j.xcrm.2026.102867
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Neuroplasticity,Mechanism of Action,Receptor Pharmacology,Safety,Inflammation
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:00
title:
Psilocybin restores behavior and 5-HT2A signaling while reducing microglial density after chronic traumatic brain injury in rats.

authors:
Allen J, Jupp B, Baker TL, Haskali MB, Brkljača R, Plummer Z, Sun M, Brand J, Christie BR, Debert CT, McDonald SJ, O'Brien TJ, Casillas-Espinosa PM, Shultz SR.

abstract:
Traumatic brain injury (TBI) causes persistent neurobehavioral deficits and increases the risk of psychiatric disorders, including depression, anxiety, and cognitive dysfunction linked to disrupted neuroplasticity, neuroinflammation, and serotonergic (5-HT) signaling. No effective pharmacotherapies exist for chronic TBI. Psilocybin, a psychedelic 5-HT2A receptor agonist, shows promise due to its neuroplasticity-enhancing, anti-inflammatory, and antidepressant effects. Here, male rats received fluid-percussion or sham injury, followed one year later by a single psilocybin (1 mg/kg) or saline injection. Behavioral testing began 24 h later, and positron emission tomography assessed 5-HT2A binding after two weeks. TBI produced persistent sensorimotor, learning and memory, and affective deficits; reduced 5-HT2A binding; and microglial alterations in the medial prefrontal cortex characterized by decreased process branching and enlarged soma size. Psilocybin treatment could improve sensorimotor function, restore 5-HT2A binding, and reduce microglial cell counts. These findings highlight psilocybin's therapeutic potential in chronic TBI and support further investigation of psychedelic treatments.

raw_json:
{"europe_pmc_id":"42285092","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Mingardi J, Molteni R, Bifari F.
publication_date: 2026-06-10
doi: 10.1016/j.phrs.2026.108290
pubmed_id: 42276399
source_url: https://doi.org/10.1016/j.phrs.2026.108290
substance_tags: psilocybin
topic_tags: Depression,Pharmacology
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:01
title:
Pharmacokinetic and pharmacodynamic rational for expanding the therapeutic landscape of psilocybin beyond depression.

raw_json:
{"europe_pmc_id":"42276399","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: The entropic brain today
journal: PsyArXiv
publication_date: 2025-12-11
source_url: https://osf.io/preprints/psyarxiv/ubzq3_v1
keywords: Psychiatry, Neuroscience, Social and Behavioral Sciences, Life Sciences
substance_tags: psilocybin
topic_tags: Consciousness,Aging,Wellbeing
study_type: Other
source_name: PsyArXiv
publication_status: preprint
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:30
raw_json: {"osf_id":"ubzq3_v1","version":1,"reviews_state":"accepted"}
abstract:
Introduced in 2014 and revised in 2018, the entropic brain hypothesis has accrued a wealth of supportive evidence. The hypothesis states that- along a dimension of breadth of conscious experience- ‘expansive states’ reliably exhibit increased brain entropy whereas the inverse applies for states of no or reduced consciousness. Examples of expansive states include those of expert meditation, flicker light stimulation, the near-death experience, atypical breathing, rapid-eye-movement sleep, the pre-ictal aura, unmedicated early psychosis and psychedelic drug states. Example states of no or reduced consciousness with low brain entropy, include disorders of consciousness, deep sleep, the anesthetized state, seizure, post-stroke, ageing, cognitive impairment, and neurodegenerative disorders. It is shown here that the entropic brain has convergent, correlative, predictive, discriminative and external validity. Regarding its predictive validity, increased brain entropy under psilocybin predicts subsequent improvements in mental health (improved well-being 1-month post-dose). Regarding its discriminative validity, changes in brain entropy selectively index the breadth of subjective experience versus alternative dimensions, such as arousal. Regarding portability/external validity, an entropy (temperature) function is used in generative artificial intelligence. In conclusion, the entropic brain is proving to be a useful model of conscious states.


title: The effects of psychedelics on attention deficit and hyperactivity disorder - a systematic review.
authors: Raikkerus H, Bujour A, Kennedy M, Tiihonen J.
publication_date: 2026-06-09
doi: 10.1017/neu.2026.10088
pubmed_id: 42265057
source_url: https://doi.org/10.1017/neu.2026.10088
substance_tags: psilocybin
topic_tags: Depression,Randomized Controlled Trial,Systematic Review,Review Article
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:02
abstract:
ObjectivesAttention deficit and hyperactivity disorder (ADHD) is a prevalent neuropsychiatric disorder (Drechsler et al., 2020). Recently, psychedelics have become of interest regarding developing treatment options for ADHD. The aim of this systematic review is to find all studies from the APA PsychInfo and MEDLINE databases, where psychedelics have been used for ADHD and assess whether further clinical studies are warranted.MethodsAPA PsychInfo and MEDLINE were searched on the 20th of August 2025 for studies discussing ADHD and lysergic acid diethylamide (LSD) or psilocybin or dimethyltryptamine (DMT) or mescaline or phencyclidine or 3,4-methylenedioxymethamphetamine (MDMA) or ketamine. Primary research articles in English where the effects of the psychedelics mentioned on ADHD in humans were included.ResultsN = 1023 results were identified. Six studies were included - one randomised controlled trial (RCT) finding no statistically important difference compared to placebo, 3 cross sectional studies where respondents reported positive effect of psychedelics and one where the statistically important improvement was measured by the Child Bipolar Questionnaire. In addition, one case study, where both, depressive symptoms and functioning improved with ketamine.ConclusionsThere is not sufficient evidence to give recommendations on psychedelic use for ADHD. In addition, it is not known whether patients, whose depressive symptoms have responded positively to ketamine, have also had ADHD. Also, no research was found on how psychedelics affect patient subgroups with different etiopathology causing their symptoms. Although only six studies filled the inclusion criteria, they bring out valuable implications for further research.

raw_json:
{"europe_pmc_id":"42265057","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Gillet M, Doudeau N, Vilain F, Sadat K, Morvan Y, Frajerman A.
publication_date: 2026-06-08
doi: 10.1177/07067437261457220
pubmed_id: 42262154
source_url: https://doi.org/10.1177/07067437261457220
substance_tags: psilocybin
topic_tags: Addiction,Observational Study
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:02
title:
Alcohol consumption and substance use among French medical students: A nationwide cross-sectional study: Consommation d'alcool et de substances chez les étudiants en médecine de France: une étude transversale nationale.

abstract:
ObjectivesMedical students are known to face significant psychological distress, making them vulnerable to substance use. There are few data on alcohol and drug consumption among medical students. The aim was to assess the prevalence of substance use, especially alcohol, in French medical students.MethodsThis cross-sectional nationwide study was conducted online from 10 June to 28 July 2024. A survey link was sent to French medical students and residents via official administrative emails. We assessed substance use (alcohol, tobacco, cannabis, cocaine, amphetamine, LSD, psilocybin, heroine, poppers, nitrous oxide and other). For alcohol consumption, we used the Alcohol Use Disorders Identification Test (AUDIT). Data analysis was performed, including recoding missing responses as zeros. Univariate and multivariate binary logistic regressions were performed with AUDIT as the dependent variable, categorized as binary (cutoff ≥8).ResultsWe included 8,312 students: 11% met criteria for hazardous drinking, and 5.5% for probable dependence according to the AUDIT; 23.3% respondents reported tobacco use, while cannabis use was reported by 13.4% with 1% using it more than 2 or 3 times a week. Among other substances, poppers (23.5%) and nitrous oxide (11.2%) were the most commonly reported. Multivariate analysis identified several factors associated with problematic alcohol use, such as male sex, younger age, financial difficulties, exposure to humiliation, harassment or sexual assault.ConclusionsAlcohol and psychoactive substance use remain prevalent among French medical students, at levels broadly comparable to those reported internationally. These findings underscore the need for targeted preventive and supportive actions within medical schools.

raw_json:
{"europe_pmc_id":"42262154","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Junior WSC, Bezerra KS, Matias EGC, Oliveira JIN, Fulco UL
journal: Physical chemistry chemical physics : PCCP
publication_date: 2026-06-30
doi: 10.1039/d6cp00943c
pubmed_id: 42300394
source_url: https://pubmed.ncbi.nlm.nih.gov/42300394/
substance_tags: psilocybin,psilocin
topic_tags: Depression,Receptor Pharmacology,Drug Interactions
study_type: Other
source_name: PubMed
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-02 06:54:10
raw_json: {"pubmed_id":"42300394"}
title:
MFCC-DFT mapping of ligand recognition at the 5-HT receptor: energetic analysis of the interactions between serotonin, psychedelics, and antipsychotics.

abstract:
Mental disorders represent a major global health problem, with depression being one of the most prevalent and disabling conditions worldwide. Growing evidence suggests that the serotonergic system, particularly the 5-HT receptor, plays an important role in modulating mood and cognitive processes, constituting a key pharmacological target for several psychoactive compounds. In this study, we investigated the molecular interaction profile between the 5-HT receptor and four pharmacologically relevant ligands, serotonin (5-HT), psilocybin/psilocin (PSILO), lysergic acid diethylamide (LSD), and lumateperone (LMTP). Interaction energies were evaluated using the molecular fragmentation with conjugated caps (MFCC) method combined with density functional theory (DFT) calculations. Crystallographic structures were used as initial models, and residue-level interaction energies were calculated to identify the amino acids that contribute most to ligand stabilization at the receptor binding site. The results reveal that the complexes exhibit total interaction energies ranging from -35.38 to -71.98 kcal mol under dielectric conditions representative of the protein environment. Key residues such as Asp155, Phe339, Leu229, and Val366 were identified as the main contributors to ligand stabilization in the studied systems, highlighting their role as structural anchors within the orthosteric binding pocket. Energy decomposition further revealed distinct interaction patterns associated with different regions of the ligand. Therefore, this study provides a detailed energetic characterization of ligand recognition in the 5-HT receptor and offers details that may contribute to the rational design of new serotonergic agents with potential for therapeutic applications.


title: Developing Methods for Observing Awe Narration in Psilocybin-Assisted Therapy.
publication_date: 2026-06-04
doi: 10.3390/healthcare14111589
pubmed_id: 42278842
source_url: https://doi.org/10.3390/healthcare14111589
substance_tags: psilocybin
topic_tags: Clinical Trial,Drug Interactions
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:00
authors:
Tarbi EC, Bhatia I, Balach N, Buehler S, Demeo-Meres M, Gramling C, Thambi T, Hart J, Reblin M, Rizzo DM, Gramling R, Agrawal M, Manetta E.

abstract:
Background: Understanding the benefits of psychedelic-assisted therapy (PAT) will require scientific attention to the causal interaction between the therapeutic context and process. Measuring what actually happens during PAT in large-scale studies will be an essential component of this work. Objective: We aim to develop and preliminarily evaluate the feasibility and reliability of a direct observation coding system for narrations of awe experiences during PAT, one hypothesized therapeutic mechanism. Methods: We analyzed 32 PAT clinical trial encounter recordings involving eight participants from a Phase 2 clinical trial study of psilocybin-assisted therapy in advanced cancer. Using a conceptually grounded structured codebook, two human coders independently identified start and stop times for moments exhibiting definitional characteristics of awe narration, including expressions of vastness, need for accommodation and ineffability. We used coder agreement and degree of confidence to refine the coding system. Results: During 16,760 total minutes of video, coders collectively recorded 246 moments of awe narration. Of those moments, 42% (104/246) were identified by one coder and 58% (142/246) by two coders. Coders felt substantially more confident in their judgments about a moment of awe when vastness was present compared to when vastness was absent (OR: 4.3; 95% CI: 2.4, 7.8). Iterative refinement of the coding system led to accommodation being operationalized as two distinct components: an initial cognitive disruption followed by variable engagement in the process of accommodation. Conclusions: Awe narration is directly observable using explicit definitional criteria. This work provides the empirical foundation for scalable coding systems of awe narration during PAT.

raw_json:
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authors: Ahmadian-Moghadam S, Roshan-Milani S, Saboory E.
publication_date: 2026-06-04
doi: 10.1038/s41398-026-04151-x
pubmed_id: 42248832
source_url: https://doi.org/10.1038/s41398-026-04151-x
substance_tags: psilocybin
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:00
title:
Prenatal stress, excitatory-inhibitory imbalance, and ADHD risk: a hypothesis-driven perspective on psilocybin-induced neuroplasticity.

abstract:
Attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental condition in which prenatal stress and long-lasting disruptions of excitatory-inhibitory (E/I) balance have been implicated as key vulnerability factors. Although established pharmacological and behavioral treatments are effective for many individuals, they are not universally successful and do not directly target upstream neurodevelopmental mechanisms. In this hypothesis-driven perspective, we examine whether psilocybin-induced neuroplasticity could theoretically modulate stress-related neurodevelopmental risk pathways relevant to ADHD. Rather than presenting psilocybin as an evidence-based intervention, we synthesize findings from related preclinical and clinical literatures to explore conceptual plausibility. Preclinical studies in non-ADHD models indicate that psilocybin can induce rapid and sustained synaptic plasticity, alter cortical E/I dynamics, and reverse stress-associated structural and functional alterations. Human clinical trials in adults-primarily in mood, trauma-related, and substance use disorders-demonstrate durable changes in emotional regulation, cognitive flexibility, and large-scale brain network organization, processes that overlap with neural systems implicated in ADHD. Research into the use of psilocybin for ADHD is in its early stages, with emerging, largely self-reported, and preliminary studies suggesting potential benefits for managing symptoms like inattention, impulsivity, and emotional dysregulation. We therefore frame psilocybin as a speculative (secondary/tertiary) approach that could, in principle, be explored to probe mechanisms of E/I rebalancing and neuroplasticity. Key mechanistic uncertainties-including the state-dependent effects of psilocybin on excitation and inhibition and the possibility of exacerbating existing imbalances-are explicitly discussed. Ethical and developmental considerations, particularly regarding vulnerable populations, are emphasized as critical constraints on translation. Finally, we propose a translational research roadmap encompassing preclinical prenatal-stress models, biomarker-driven pilot studies in ADHD, and multimodal outcome measures integrating neuroimaging, electrophysiology, and molecular indices. By clearly distinguishing established evidence from hypothesis, this perspective aims to stimulate rigorous and ethically grounded research rather than to advocate premature clinical application.

topic_tags:
Addiction,Neuroplasticity,Brain Imaging,Mechanism of Action,Biomarkers,Aging,Emotional Processing,Clinical Trial,Animal Study,Safety

raw_json:
{"europe_pmc_id":"42248832","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Domnauer C, Dentinger BTM.
publication_date: 2026-06-04
doi: 10.1080/00275514.2026.2670968
pubmed_id: 42247306
source_url: https://doi.org/10.1080/00275514.2026.2670968
substance_tags: psilocybin
topic_tags: Genomics
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:02
title:
Phylogenomic systematics of Lanmaoa (Boletaceae) reveals cryptic diversity, resolves global evolutionary relationships, and suggests a novel psychoactive lineage.

abstract:
The genus Lanmaoa is a globally distributed, economically important group of mushroom-forming fungi in the family Boletaceae containing edible and psychoactive species. Despite the growing interest in its hallucinogenic properties, the fundamental systematics of this genus remains poorly resolved due to limited taxon sampling and limited genetic characterization. This study combines a comprehensive sampling of all Lanmaoa species, including 21 type specimens, with whole genome sequencing of 53 specimens. A phylogeny of Lanmaoa is generated based upon an alignment of 1515 single-copy orthologs and recovers full statistical support at all major nodes, resolving evolutionary relationships in the genus. Phylogenomic analysis of previously unsequenced type specimens supports several taxonomic changes, including six novel combinations and the discovery of four novel species, two of which are described here-Lanmaoa fallax, sp. nov. and Lanmaoa carbonilivor, sp. nov.-resulting in a total recognition of 17 species in the genus. Genome mining of Lanmaoa asiatica fails to detect canonical biosynthetic genes associated with psilocybin or ibotenic acid production, suggesting the presence of a novel psychoactive compound. This study establishes a comprehensive genomic foundation for Lanmaoa systematics, enabling future research to more robustly explore the evolutionary history and secondary chemistry of the genus.

raw_json:
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authors: Reid MJ, Kettner H, Blanken TF, Weiss B, Carhart-Harris R.
publication_date: 2026-06-04
doi: 10.1007/s11920-026-01685-1
pubmed_id: 42243392
source_url: https://doi.org/10.1007/s11920-026-01685-1
substance_tags: psilocybin
topic_tags: General
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:02
title:
Correction to: Preliminary Evidence of Sleep Improvements Following Psilocybin Administration, and their Involvement in Antidepressant Therapeutic Action.

raw_json:
{"europe_pmc_id":"42243392","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Lu S, Zhang Z, Xue X, Jiang Y, Zhang C, Liu P, He D, Shen W, Yang S, Wang F.
publication_date: 2026-06-03
doi: 10.1016/j.heares.2026.109701
pubmed_id: 42289149
source_url: https://doi.org/10.1016/j.heares.2026.109701
substance_tags: psilocybin
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:02
title:
Current status and future prospects of research on psilocybin's regulation of neurotransmitters and their receptors related to the pathogenesis of tinnitus.

abstract:
Subjective tinnitus is a common auditory disorder characterised by the subjective perception of noise in the absence of external sound sources. Its prevalence has been rising annually due to noise exposure, medication misuse, and population ageing. Current tinnitus treatments employ antidepressants, anticonvulsants, and vasodilators, yet most demonstrate limited efficacy with significant side effects. There is an urgent clinical need for novel therapeutic agents targeting new mechanisms and pathways. In recent years, the natural psychedelic tryptamine psilocybin has garnered attention for its rapid and sustained therapeutic effects following single-dose administration in clinical trials for depression and end-of-life anxiety. Its mechanism involves selectively activating 5-HT2A receptors, triggering substantial glutamate release and subsequently upregulating brain-derived neurotrophic factor (BDNF). This markedly increases dendritic spine density and synaptic protein expression in the hippocampus and prefrontal cortex, thereby restoring neural plasticity. This review systematically integrates the aforementioned neuroplasticity mechanisms with cross-mechanisms of neuroplastic alterations associated with tinnitus, emphasising its synergistic regulatory effects on excitatory neurotransmitters and their receptors (glutamate, dopamine) as well as inhibitory neurotransmitters and their receptors (gamma-aminobutyric acid (GABA)).

topic_tags:
Depression,Anxiety,End-of-Life Distress,Neuroplasticity,Mechanism of Action,Receptor Pharmacology,Aging,Clinical Trial,Review Article,Adverse Events

raw_json:
{"europe_pmc_id":"42289149","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Kelly CM, Fradet M, Bostian CM, Donnelly A, Ellis S, Ostacher M, Aaronson S, Suppes T.
publication_date: 2026-06-03
doi: 10.1016/j.jad.2026.122063
pubmed_id: 42248535
source_url: https://doi.org/10.1016/j.jad.2026.122063
substance_tags: psilocybin
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:00
title:
Changes in anxiety, quality of life, and functioning following psilocybin-assisted therapy in veterans with treatment-resistant depression.

abstract:
BackgroundPsilocybin has demonstrated promise for improving depressive symptoms in treatment-resistant depression, but its effects on anxiety, quality of life, functioning, and posttraumatic stress symptoms are less well studied. This study reports exploratory findings from an open-label trial in Veterans with TRD.MethodsParticipants received a single 25-mg dose of psilocybin administered with psychological support. The primary endpoint was assessed 3 weeks post-dose, with follow-up extending to 12 months. Outcomes included anxiety severity (GAD-7), quality of life (Q-LES-Q-SF), functional impairment (WSAS), and posttraumatic stress disorder symptoms (PCL-5). Experiential outcomes were measured with the Mystical Experience Questionnaire (MEQ), Challenging Experiences Questionnaire (CEQ-30), and Emotional Breakthrough Inventory (EBI). Mixed-effects models were used to evaluate longitudinal changes, and correlation analyses examined associations between measures and changes in depressive symptoms on the Montgomery-Åsberg Depression Rating Scale.ResultsFifteen participants were included, with ten completing long-term follow-up. GAD-7 scores demonstrated sustained improvements through 12 months, with a 59% reduction from baseline at Week 3. Q-LES-Q-SF gains were significant through Week 12, with a 24% increase at Week 3, and WSAS improvements persisted through Month 6 before declining, with a 46% reduction at Week 3. These effects were no longer statistically significant after accounting for improvements in depression. Unadjusted PCL-5 reductions were observed at all timepoints. Exploratory analyses of acute subjective experiences did not correlate to treatment response.LimitationsThis study is limited by its small sample size and open-label design.ConclusionsPsilocybin with psychological support was associated with improvements in anxiety, quality of life, functioning, and PTSD symptoms which largely correlated to concurrent improvements in depressive symptoms.Clinical trialNCT04433858.

topic_tags:
Depression,Anxiety,PTSD,Emotional Processing,Mystical Experience,Clinical Trial,Treatment-Resistant Depression,Veterans

raw_json:
{"europe_pmc_id":"42248535","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Substance-induced manic psychosis in which delusions were corroborated by a chatbot - case report.
authors: Shah S, Morrin H.
publication_date: 2026-06-03
doi: 10.1186/s12888-026-08137-3
pubmed_id: 42243814
source_url: https://doi.org/10.1186/s12888-026-08137-3
substance_tags: psilocybin
topic_tags: Addiction,Spirituality,Case Report,Healthcare Workers,Safety,Drug Interactions
study_type: Case Report
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:03
abstract:
BackgroundThis case describes a substance-induced manic episode with psychotic features in which interaction with an AI (artificial intelligence) chatbot appeared to corroborate and reinforce the patient's delusional thought content and to contradict medical advice. Excerpts from the patient's interactions with the AI chatbot provide novel clinical insight into this phenomenon, which to date has primarily been reported in news media.Case presentationA man in his 30s presented to the emergency department with a one-week history of escalating behavioural disturbance, severe insomnia, pressured and overinclusive speech, and grandiose beliefs. Symptom onset followed heavy polysubstance use at a recreational event, including psilocybin (dried mushrooms and liquid preparation), ketamine, cocaine, and alcohol. During this period, the patient reported extensive interaction with an AI chatbot (ChatGPT). The AI chatbot reportedly affirmed his perceived "spiritual awakening," minimised the possibility that his presentation represented a manic episode, and provided medical advice, including discouragement of prescribed antipsychotic medication, though it cannot be determined to what extent, if any, these statements contributed to his existing presentation. Mental state examination was consistent with a manic episode with psychotic features, without evidence of perceptual disturbance. He was detained under mental health legislation for further assessment and commenced on olanzapine, with adjunctive sleep restoration and psychological interventions. Behavioural management included implementation of a care plan restricting AI chatbot use, as a form of environmental containment. Over several weeks, psychotic symptoms and behavioural disinhibition diminished, with subsequent improvement in insight.ConclusionsConcerns regarding potentially harmful interactions between AI chatbots and individuals with mental illness have largely been raised in news media. This case demonstrates that, in patients with psychotic symptoms, AI chatbots may reinforce delusional beliefs and impair the development of insight, and may also interfere with engagement with treatment by providing advice that conflicts with clinical recommendations. These observations raise clinical, ethical, and risk-management considerations regarding AI chatbot use during acute psychiatric illness. As AI chatbot use becomes increasingly widespread, clinicians should consider assessing their use and impact within clinical assessments and, where clinically indicated, implementing interventions to mitigate associated risks, ranging from psychoeducation to use-restriction strategies. Future population-level studies are required to establish the epidemiology of AI-associated mental health harms, and AI companies must bolster efforts to implement harm minimisation strategies and safeguards.

raw_json:
{"europe_pmc_id":"42243814","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Boehnke KF, Pouyan N, Aday JS.
publication_date: 2026-06-03
doi: 10.1007/s40265-026-02339-5
pubmed_id: 42243569
source_url: https://doi.org/10.1007/s40265-026-02339-5
substance_tags: psilocybin
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:02
title:
Classic Psychedelics for Chronic Pain: A Critical Review of the Literature and Practical Advice for Clinicians.

abstract:
Chronic pain is common, costly, and for many, remains inadequately treated by existing pharmacologic and non-pharmacologic approaches. In parallel with growing dissatisfaction with conventional therapies, classic serotonergic psychedelics, such as psilocybin, lysergic acid diethylamide (LSD), ayahuasca, N,N-dimethyltryptamine (DMT), and mescaline, administered alone or within psychedelic-assisted therapy models, have re-emerged as potential therapeutic tools for a range of health conditions, including chronic pain. In this review, we examine putative mechanisms of action relevant to pain, including effects on neuroplasticity, inflammation, large-scale brain network dynamics, and higher-order psychological processes, such as pain acceptance and cognitive flexibility. We also briefly overview findings from relevant preclinical models for pain. We then summarize recent observational studies and early-phase clinical trials that highlight preliminary signals of benefit across multiple pain conditions, including fibromyalgia, migraine, cluster headache, and other chronic pain syndromes. In addition, we critically evaluate safety considerations, contraindications, drug-drug interactions, and key regulatory challenges that will shape both research and clinical implementation of psychedelics for chronic pain. Finally, we offer pragmatic guidance for clinicians to work more skillfully with patients choosing to use these substances on their own. Although the existing literature suggests mechanistic plausibility and promising preliminary outcomes, the field is limited by small sample sizes, functional unblinding, and a lack of large, well-controlled randomized trials. We conclude by outlining critical methodological priorities and future research directions needed to rigorously evaluate the potential role of psychedelic compounds in the treatment of chronic pain.

topic_tags:
Chronic Pain,Headache / Migraine,Neuroplasticity,Mechanism of Action,Clinical Trial,Review Article,Observational Study,Animal Study,Healthcare Workers,Safety,Drug Interactions,Contraindications,Inflammation

raw_json:
{"europe_pmc_id":"42243569","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Barajas DA, Carter HCN, Tomedi MR, Lam HY, Deloatch TN, Reynolds GD, Castaneto MS, Ke P.
publication_date: 2026-05-31
doi: 10.1093/jat/bkag030
pubmed_id: 42203689
source_url: https://doi.org/10.1093/jat/bkag030
substance_tags: psilocybin,psilocin
topic_tags: Receptor Pharmacology,Toxicity
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:00
title:
Studies on enzymatic hydrolysis of psilocin-O-glucuronide for screening of psilocin in human urine by liquid chromatography-triple quadrupole tandem mass spectrometry.

abstract:
Psilocin is a psychedelic indole alkaloid and one of the major human metabolites of its phosphorylated precursor, psilocybin. Psilocin binds to the serotonin receptor, 5-HT2A, and dose-dependently induces hallucinogenic effects stronger than psilocybin. As a result, psilocin has been a drug of interest in the analytical toxicology community for years. In vivo, a majority of psilocin is metabolized to and excreted in urine as psilocin-O-glucuronide. Therefore, efficient conversion of psilocin-O-glucuronide to free psilocin directly impacts urine psilocin testing. Due to the chemical lability and light sensitivity of psilocin, the hydrolysis of psilocin-O-glucuronide requires relatively mild and carefully controlled reaction conditions, thus posing a significant challenge to analysts. In recent years, the development of recombinant β-glucuronidases offered a new approach for highly efficient deconjugation. However, to the best of our knowledge, little information on enzymatic hydrolysis of psilocin-O-glucuronide has been published since 2014. We utilized a certified LC-MS/MS-based psilocin screening method and investigated hydrolysis of psilocin-O-glucuronide in human urine catalyzed by one conventional β-glucuronidase (originating from E. coli) and three recombinant enzymes (IMCSZyme, Kura Biotech-BGTurbo, and Kura Biotech-B-One). The scope of our study included effects of enzyme concentration, pH, incubation time, and incubation temperature on the hydrolysis efficiency, as well as the comparison of modern enzymatic to traditional Brønsted-Lowry acidic and basic hydrolysis methods. The recombinant β-glucuronidases demonstrated remarkable superiority in hydrolysis efficiency compared to the E. coli-originated conventional β-glucuronidase. Kura Biotech-BGTurbo achieved the fastest hydrolysis completion at the lower temperatures (25-50°C) while IMCSZyme offered the most consistent performance across a wide range of incubation temperatures (25-80°C). Our findings provide quantifiable scientific references as a general guideline for other forensic toxicology laboratories to establish or optimize their own psilocin-O-glucuronide hydrolysis methods.

keywords:
Humans, Glucuronides, Glucuronidase, Hallucinogens, Chromatography, Liquid, Substance Abuse Detection, Hydrolysis, Tandem Mass Spectrometry, Psilocybin, Liquid Chromatography-Mass Spectrometry

raw_json:
{"europe_pmc_id":"42203689","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2026-06-02
doi: 10.3390/healthcare14111559
pubmed_id: 42278812
source_url: https://doi.org/10.3390/healthcare14111559
substance_tags: psilocybin
topic_tags: End-of-Life Distress,Mechanism of Action,Cancer Patients,Healthcare Workers
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:00
title:
Bringing Psilocybin-Assisted Therapy to Palliative Oncology: Early Lessons from Real-World Implementation.

authors:
Dorval M, Audet-Croteau V, Chang SL, Masse-Grenier M, Tremblay A, Bénard E, Chapdelaine A, Garel N, Guertin JR.

abstract:
Background/Objectives: Psilocybin-assisted therapy (PAT) is a promising intervention to alleviate existential distress among patients with advanced cancer receiving palliative care. However, evidence on how to integrate PAT into routine oncology and palliative care services remains scarce. This study aimed to examine real-world PAT implementation, identify factors influencing adoption, and estimate integration costs within oncology and palliative care services. Methods: We conducted a single-case implementation study in a large university-affiliated tertiary care center in Canada during the first year following its introduction. Semi-structured interviews with clinicians, managers, and other stakeholders explored barriers, facilitating conditions, and actions needed to support PAT implementation. A budget impact analysis estimated incremental costs associated with delivering PAT. Results: After one year, no patients had received PAT. Ten professionals representing diverse clinical and managerial roles participated in the interviews. While participants viewed PAT favorably, they emphasized the need to align the intervention with existing care pathways and clarify referral processes. Administrative and regulatory procedures, together with logistical constraints related to treatment delivery, were identified as key barriers, whereas perceived clinical relevance and institutional leadership were seen as important facilitators. From the health care system perspective, the estimated cost of delivering a complete PAT intervention ranged from 2648 to 5827 Canadian dollars (CAD) per patient, depending on the scenario examined, excluding the cost of the psilocybin itself. Conclusions: Despite perceived clinical relevance and relatively modest estimated costs, the absence of treated patients after one year highlights the gap between regulatory authorization and effective service uptake. These findings underscore the importance of structured implementation strategies, sustained institutional support, and alignment between regulatory frameworks and clinical workflows to ensure meaningful integration of PAT into routine oncology and palliative care services.

raw_json:
{"europe_pmc_id":"42278812","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Ona G, Llagostera C, Alvarez O, Dueñas RM, González D, Soto-Angona O.
publication_date: 2026-06-01
doi: 10.1080/14786419.2026.2683121
pubmed_id: 42228759
source_url: https://doi.org/10.1080/14786419.2026.2683121
substance_tags: psilocybin
topic_tags: Depression,OCD,Neuroplasticity,Review Article,Animal Study,Metabolomics
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:00
title:
Time to embrace the whole: considering the replacement of psilocybin with Psilocybe spp. in psychedelic research and therapy.

abstract:
Psilocybin, the main psychoactive compound in Psilocybe cubensis mushrooms, has gained considerable attention for its therapeutic potential. Current research focuses only on isolated psilocybin, neglecting the broader pharmacological and cultural use of the whole mushroom. This perspective advocates for an integrative approach that includes standardised P. cubensis extracts within the psychedelic research agenda. We review preclinical studies comparing whole-mushroom extracts with pure psilocybin, showing enhanced or distinct effects on synaptic proteins, metabolomic profiles, and behavioural outcomes, including in models of depression and obsessive-compulsive disorder. Furthermore, the use of whole extracts may promote more affordable, equitable, and publicly accessible treatment models, in contrast to high-cost synthetic psilocybin formulations. This article argues for the urgent need to explore whole-mushroom therapeutics, ensuring that decisions in psychedelic medicine are based on a full spectrum of evidence rather than solely on pharmaceutical feasibility.

raw_json:
{"europe_pmc_id":"42228759","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Trials, trips, and tribulations: pathways for implementing psychedelic therapy in Ireland.
publication_date: 2026-05-31
doi: 10.1093/ijnp/pyag028
pubmed_id: 42113605
source_url: https://doi.org/10.1093/ijnp/pyag028
keywords: Humans, Hallucinogens, Mental Disorders, Ireland, Clinical Trials as Topic, Psilocybin
substance_tags: psilocybin
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:01
authors:
Kelly JR, Sheridan C, Iusan P, Coakley L, Burke L, Brennan C, MacDonald A, Ivers JH, Trepel D, Tormey G, Finnegan M, Young GW, Harkin A.

abstract:
Classical serotonergic psychedelics, such as psilocybin, show emerging evidence of therapeutic potential across a range of mental health disorders, including depression, anxiety, and substance use disorders, with indications of transdiagnostic efficacy. While early-phase studies yielded encouraging results, recent larger-scale phase 3 trials, such as those evaluating psilocybin for treatment-resistant depression, have shown more modest effects, and further findings from ongoing trials are awaited. Despite the absence of regulatory approvals from the U.S. Food and Drug Administration and European Medicines Agency, a small but growing number of countries have permitted psychedelic therapies within regulated clinical settings. Across these divergent international approaches, the long-term trajectory and real-world impact of these therapies within public health systems remain uncertain. In anticipation of potential future approval, Ireland has an opportunity to draw on international experience and proactively plan for the integration of psychedelic therapies. Building on emerging evidence, international frameworks, and Ireland-specific policy and health system features, this paper examines the challenges of integrating psychedelic therapies into the Irish public healthcare system. These challenges span regulatory approval, Health Technology Assessment, service implementation, workforce capacity, and the evaluation of long-term patient outcomes. The aim is to inform policymakers, practitioners, and researchers about key system-level considerations.

topic_tags:
Depression,Anxiety,Addiction,Mechanism of Action,Aging,Clinical Trial,Treatment-Resistant Depression

raw_json:
{"europe_pmc_id":"42113605","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Rowe T, Hurzeler T, Towers E, Louie E, Morley KC.
publication_date: 2026-05-31
doi: 10.1002/brb3.71533
pubmed_id: 42348297
source_url: https://doi.org/10.1002/brb3.71533
substance_tags: psilocybin
topic_tags: Mechanism of Action,Emotional Processing,Systematic Review,Review Article,Drug Interactions
study_type: Systematic Review
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:03
title:
Psychedelic Therapy and the Role of Music: A Scoping Review of Quantitative Evidence on Subjective and Objective Outcomes.

abstract:
PurposePsychedelics have received considerable attention due to their potential in treating psychiatric disorders. The "setting" during psychedelic-assisted therapy (PAT) is recognized as playing a central role in the experience, during which music features prominently. Although music is theorized as directing and shaping psychedelic sessions, its precise contribution to acute experience and therapeutic outcomes is unclear. This scoping review aimed to map quantitative research on the interplay of psychedelics and music by consolidating existing evidence, identifying gaps, and where possible, reporting on effects of psychedelics and music on subjective (e.g., psychological) and objective (e.g., biological) outcomes.MethodFollowing PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, relevant papers were identified through electronic databases (MEDLINE, Embase, PsychINFO, Scopus) using terms associated with psychedelic compounds, psychedelic-assisted therapy, and music. Papers were restricted to quantitative studies published in peer-reviewed journals investigating human subjects within therapeutic and controlled experimental contexts, focusing on interactions between music and psychedelics.FindingA total of 19 papers (total human sample = 330) met inclusion criteria. Psilocybin and LSD were the most studied psychedelic compounds; no studies were found investigating MDMA and music. Characteristics of music conditions across studies have been limited. The findings suggest that music modulates the psychedelic experience through: (1) amplifying and intensifying emotions, (2) recruiting brain networks involved in meaning-attribution and visual imagery, and (3) increasing overall neural entropy.ConclusionConsiderable gaps remain in understanding mechanisms of action and how music is delivered to optimize therapeutic response, due in part to methodological inconsistencies and small sample sizes. This review underscores the critical role of music in shaping psychedelic experiences and therapeutic outcomes.

keywords:
Humans, Lysergic Acid Diethylamide, Hallucinogens, Music Therapy, Mental Disorders, Music, Psilocybin

raw_json:
{"europe_pmc_id":"42348297","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Therapeutic advances in fibromyalgia: one year in review 2026.
publication_date: 2026-06-17
doi: 10.55563/clinexprheumatol/xscnij
pubmed_id: 42328945
source_url: https://doi.org/10.55563/clinexprheumatol/xscnij
keywords: Humans, Fibromyalgia, Treatment Outcome, Quality of Life, Nociplastic Pain
substance_tags: psilocybin
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:02
authors:
Bazzichi L, Di Carlo M, Salaffi F, Farah S, Porta F, Ablin JN, Varrassi G, Galli F, Fornasari D, Carotti M, Alciati A, Pellegrino G, Batticciotto A, Lucini D, Casale R, Di Franco M, Sarzi-Puttini P, Iannuccelli C, Pain Study Group of the Italian Society of Rheumatology (SIR).

abstract:
Fibromyalgia (FM) is a chronic nociplastic pain syndrome characterised by widespread pain, fatigue, sleep disturbances and cognitive impairment, with a significant impact on health-related quality of life (HRQoL). Despite the availability of several therapeutic options, management remains challenging and often requires a personalised and multidimensional approach.Over the past year, growing attention has been directed toward both emerging pharmacological strategies and innovative non-pharmacological interventions. Among pharmacological treatments, low-dose naltrexone (LDN) continues to show potential benefits in modulating neuroinflammation and central sensitisation. Cannabinoids and other neuromodulatory agents have also been investigated, with preliminary evidence suggesting a role in symptom control. In addition, novel approaches involving serotonergic modulation, including psychedelic compounds such as psilocybin, are being explored in early-phase studies.Intravenous lidocaine remains a potential option in selected refractory patients, although recent evidence has not substantially expanded its clinical role. Similarly, interest in nutraceuticals and antioxidant compounds is increasing, particularly in relation to mitochondrial function and oxidative stress.Non-pharmacological interventions remain a cornerstone of FM management. Recent studies highlight the importance of structured physical activity, including supervised exercise programs and digitally supported rehabilitation. Emerging approaches such as neuromodulation techniques, including non-invasive brain stimulation and vagal nerve stimulation, are gaining attention. Complementary and body-oriented interventions are also being explored for their potential impact on pain perception and emotional well-being.Overall, current evidence supports a biopsychosocial and multimodal approach, integrating pharmacological and non-pharmacological strategies tailored to individual patient profiles. Future research should focus on better phenotyping of patients and on identifying predictors of treatment response to optimise personalised management.

topic_tags:
Chronic Pain,Mitochondrial Function,Oxidative Stress,Wellbeing,Emotional Processing,Review Article,Inflammation

raw_json:
{"europe_pmc_id":"42328945","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Rosa WE, Napolitano S, McAndrew N, Jenkins B, Lichtenthal WG, Applebaum AJ, Breitbart W, Agrawal M.
publication_date: 2025-07-29
doi: 10.1177/28314425251363983
pubmed_id: 42311441
source_url: https://doi.org/10.1177/28314425251363983
substance_tags: psilocybin
topic_tags: Depression,Aging,Clinical Trial,Observational Study
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:00
title:
Meaning-Centered Psychotherapy for Psilocybin-Assisted Therapy Among Patients with Advanced Cancer and Depression: Rationale and Preliminary Evaluation of MCP-PSIL.

abstract:
IntroductionPsilocybin shows encouraging outcomes for patients with cancer and major depressive disorder (MDD). However, there is insufficient evidence on the use of evidence-based psychotherapeutic interventions to consistently guide and standardize psilocybin preparation, dosing, and integration. Meaning-centered psychotherapy (MCP) is a manualized, brief psychotherapeutic intervention that enhances meaning and purpose among recipients. This article substantiates the rationale for using MCP as a psychotherapeutic intervention to accompany psychedelic-assisted therapy (PAT) with psilocybin for patients with cancer and MDD.Materials and methodsWe sampled seven patients with cancer and MDD who previously received PAT with psilocybin followed by group MCP in a phase 2 open-label trial, as well as six therapists who delivered the interventions. First, electronic open-ended response surveys were distributed to explore participant experiences during the phase 2 trial and elicit recommendations to adapt MCP for psilocybin. Second, the research team developed a 5-session model of MCP and psilocybin therapy (MCP-PSIL) based on survey responses. Finally, four focus groups were conducted (two with patients and two with therapists) to expand on patient experiences during the phase 2 trial and gather feedback on MCP-PSIL.ResultsSeven patients (ages 53-80 years) and six therapists (mental health professional experience ranging 9-44 years) participated in both surveys and focus groups. Focus groups underscored the value of experiences related to psilocybin, the group, and MCP, as distinct elements and in conjunction. Participants shared key recommendations to enhance combined psilocybin and MCP experiences and the 5-session MCP-PSIL model. The importance of the group format was also emphasized while noting that individual MCP may be indicated in certain circumstances.ConclusionFindings suggest that MCP is a natural therapeutic partner to guide patients throughout the PAT continuum. As MCP-PSIL is tested in the future, we anticipate MCP will leverage the PAT experience by building therapist capacity to optimize care while reducing avoidable distress for patients and maximizing their meaning-making opportunities.

raw_json:
{"europe_pmc_id":"42311441","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Poppe C, Lyck L, Bechtold L, Repantis D.
publication_date: 2026-05-31
doi: 10.1002/brb3.71544
pubmed_id: 42304595
source_url: https://doi.org/10.1002/brb3.71544
substance_tags: psilocybin
topic_tags: Depression,Mechanism of Action,Clinical Trial,Treatment-Resistant Depression
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:02
title:
Expectations and Motivations for Participation in Clinical Trials Utilizing Psychedelics for Treatment-Resistant Depression: A Qualitative Study.

abstract:
PurposeExpectations strongly shape participant experiences in clinical trials, contributing to placebo effects that complicate interpretation of outcomes. While quantitative tools exist to measure expectations, their subjective and multidimensional nature, especially for individuals with treatment-resistant depression (TRD), remains underexplored. This study aimed to explore the motivations and expectations of participants in psychedelic clinical trials.MethodSeventeen semi-structured interviews were conducted with individuals prior to screening for two TRD clinical trials involving 5-MeO-DMT or psilocybin at a German university hospital. Two matched follow-up interviews were also completed after trial participation. Data were analyzed thematically to identify overarching themes and subthemes.FindingsTwo main themes emerged: motivations and expectations, each with four subthemes. Motivations included hope, demoralization, prior psychedelic experience, and social motivation. Expectations involved anticipated symptom reduction, perceived mechanisms of change during the psychedelic experience, the role of setting, and retrospective expectations. Many participants viewed trial participation as a last resort due to chronic illness and previous treatment failures. In two cases, retrospective accounts suggested that initially cautious expectations were reinterpreted as stronger after participation.ConclusionExpectations in psychedelic trials are complex and may evolve over time. These findings highlight the need to systematically address expectancy in trial design, informed consent, and interpretation of clinical outcomes, particularly in treatment-resistant populations.

keywords:
Humans, Hallucinogens, Motivation, Qualitative Research, Adult, Middle Aged, Female, Male, Clinical Trials as Topic, Depressive Disorder, Treatment-Resistant, Psilocybin, Outcome Expectations

raw_json:
{"europe_pmc_id":"42304595","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Hallucinogen-Assisted Psychotherapy for Trauma Disorders: A Bionian Lens.
authors: Miller CWT, Kozak Z.
publication_date: 2026-05-31
doi: 10.1521/pdps.2026.54.2.308
pubmed_id: 42301163
source_url: https://doi.org/10.1521/pdps.2026.54.2.308
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Addiction,Mechanism of Action,Spirituality
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:02
abstract:
There has been an increasing interest in the use of classic psychedelics (such as psilocybin) and 3,4-methylenedioxymethamphetamine (MDMA) for treating mental health conditions. Individuals often describe psychedelic sessions as among the most significant experiences in their lives, emphasizing the sense of awe, connectedness, and spiritual transformation taking place. While the psychedelic literature from the past two decades has mostly focused on using these drugs in the treatment of major depressive, anxiety, and substance use disorders, researchers have also investigated the utility of classic psychedelics and MDMA for other conditions, including trauma- and stressor-related disorders. Trauma can profoundly affect biological systems, including stress hormone pathways and neural circuitry, often leading to hyperarousal and rigid cognitions. In this article, we discuss how some of the concepts posited by Wilfred Bion can be applied to neurobiological models of the mind and to the effects of these drugs. Relevant concepts from neurodevelopment are presented first, including how key areas can be significantly affected by early adversity. This is followed by a discussion of Bion's theory of containment and of how the K link (K denoting knowledge) is developed or disrupted, depending on one's experience. Finally, we present extant literature on the use of MDMA and classic psychedelics in trauma disorders, reflecting on how a Bionian lens can enrich our understanding of their therapeutic action.

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

raw_json:
{"europe_pmc_id":"42301163","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Reorganization of Human Brain Waves Across Diverse States of Consciousness
authors: Fotiadis P, Jang H, Dai R, Li D, Cofré R, Timmermann C, Mashour GA, Hudetz AG, Huang Z.
journal: bioRxiv
publication_date: 2026-05-31
doi: 10.64898/2026.05.27.728182
source_url: https://doi.org/10.64898/2026.05.27.728182
substance_tags: psilocybin
topic_tags: Mechanism of Action,Consciousness
study_type: Other
source_name: bioRxiv
publication_status: preprint
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:03
abstract:
Brain waves are ubiquitous phenomena of human brain activity. As they propagate, they coordinate neural communication, shaping conscious perception. Understanding how brain waves unfold across space and time is thus critical for uncovering the neural mechanisms that support and suppress consciousness. Here, we analyzed data from the Human Connectome Project alongside multiple independent human datasets of various states of consciousness collected during non-rapid eye movement sleep, propofol anesthesia, and psychedelic states produced by lysergic acid diethylamide, N,N-dimethyltryptamine, psilocybin, nitrous oxide, and ketamine. We then applied complex principal component analysis to map spatiotemporal propagation patterns of blood oxygen level-dependent activity across the human brain, under these diverse states of consciousness. We identified four dominant motifs of wave propagation: a global synchronized wave supporting unimodal-transmodal propagation, an anti-correlated unimodal-transmodal wave, an anti-correlated task-positive/task-negative wave, and an anti-correlated visual-somatomotor wave. Among them, the global wave exhibited the most pronounced state-dependent reconfiguration: in diminished states (sleep and anesthesia), the time needed for the wave to propagate across brain regions consistently increased and the distribution of regional contributions to the wave's power became more spatially concentrated and heterogeneous across individuals, indicating slower, more fragmented, and less stereotyped dynamics. In contrast, propagation duration decreased under psychedelic states, reflecting accelerated global wave dynamics alongside a trend towards more spatially distributed and uniform regional contributions, consistent with a more integrated global wave propagation pattern. Beyond this global mode, diminished states slowed propagation primarily along the unimodal-transmodal axis, whereas psychedelic states selectively accelerated propagation along the task-positive/task-negative axis. Together, our findings reveal that diminished (sleep and anesthesia) and psychedelic states alter the spatiotemporal structure of wave propagation across the brain in opposite and distinct ways, providing a unifying account of how macroscale brain dynamics are dynamically reshaped under pharmacological and endogenous perturbations of consciousness.

raw_json:
{"europe_pmc_id":"PPR1243454","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


authors: Houff J, Williams A, Allen O, Gisabella B, Pantazopoulos H, Del Arco A.
publication_date: 2026-05-31
doi: 10.1111/ejn.70574
pubmed_id: 42226515
source_url: https://doi.org/10.1111/ejn.70574
substance_tags: psilocybin
topic_tags: Addiction,Receptor Pharmacology,Biomarkers,Clinical Trial
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:00
title:
Psilocybin Decreases Preference for Large Rewards Accompanied by Increased Activity of Parvalbumin Neurons With Perineuronal Nets in the Medial Prefrontal Cortex.

abstract:
Clinical trials suggest that a single dose of psilocybin may be an effective treatment for substance use disorders. Choice impulsivity is a value-based decision-making bias that predicts drug-intake escalation and is commonly associated with substance use disorders. The dorsomedial prefrontal cortex regulates choice impulsivity and is enriched with 5-HT2A receptors that mediate effects of psilocybin. We hypothesized that psilocybin has long-term (≥ 48 h) effects on choice impulsivity in association with dorsomedial prefrontal cortex inhibitory interneurons with perineuronal nets (PNNs). Male Long Evans rats were trained in a delay discounting task where rats chose between delayed large rewards and immediate small rewards. Forty-eight hours after psilocybin or vehicle injections, delay discounting was assessed and rats' brains processed for microscopy analysis of extracellular matrix (PNNs) together with inhibitory parvalbumin (PV) interneurons and c-Fos as a marker of neuronal activity. Psilocybin acutely increased head-twitch responses. Psilocybin decreased large reward choices and increased the latency to large reward choices 48 h after administration. These effects were independent of delay and therefore not consistent with changes in impulsivity. Psilocybin also increased the density of triple-labelled neurons (PNN + PV + cFos) in the dorsomedial prefrontal cortex. These results suggest that psilocybin decreases appetitive motivation through the increased activation of PV interneurons with PNNs in the dorsomedial prefrontal cortex.

keywords:
Prefrontal Cortex, Neurons, Interneurons, Animals, Rats, Rats, Long-Evans, Parvalbumins, Hallucinogens, Impulsive Behavior, Reward, Male, Delay Discounting, Perineuronal Nets

raw_json:
{"europe_pmc_id":"42226515","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2026-05-31
doi: 10.1177/0271678x261454172
pubmed_id: 42220002
source_url: https://doi.org/10.1177/0271678x261454172
substance_tags: psilocybin
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:03
title:
Global increases in brain glucose metabolism following acute N,N-dimethyltryptamine and harmine administration in healthy volunteers: A randomised [18F]FDG-PET study.

authors:
Egger K, Bozsak R, Aicher HD, Sari H, Poetzsch SN, Rominger A, Martin-Soelch C, Smallridge JW, Dornbierer D, Quednow BB, Scheidegger M, Cumming P.

abstract:
Classical psychedelics such as N,N-dimethyltryptamine (DMT) modulate consciousness via serotonergic receptor agonism, and are increasingly investigated for their psychotherapeutic potential. When combined with the monoamine oxidase A (MAO-A) inhibitor harmine-mimicking the pharmacological profile of ayahuasca-oral DMT induces a psychedelic experience lasting 4-5 h. While some neuroimaging studies have characterized effects of DMT on functional connectivity and electroencephalography its impact on cerebral energy metabolism remains largely unexplored. We assessed the cerebral metabolic rate for glucose consumption (CMRglc) with [18F]fluorodeoxyglucose positron emission tomography ([18F]FDG-PET) and linear graphic analysis following buccal DMT + harmine (90 mg DMT, 120 mg harmine) versus placebo in a single-blind, crossover design in 14 healthy males. Scans were acquired during peak drug effects (100-170 min post-administration). Global CMRglc increased by 12.5% under DMT+harmine versus placebo (t = 2.58, p = 0.011). Vertex- and network-wise analyses revealed widespread cortical increases, particularly in higher-order brain networks. Exploratory analyses found a significant positive correlation between global CMRglc and harmine plasma levels, but not with DMT plasma levels, subjective intensity ratings. A psychedelic dose of DMT + harmine globally increased cerebral glucose metabolism, recapitulating a classic finding for psilocybin, and suggesting a potential metabolic signature of the psychedelic state. Clinical trial registry name and URL incl. registration number: Molecular Imaging Study of Harmine/DMT: a Basic Research Approach (HaD-PET) https://clinicaltrials.gov/study/NCT06252506.

topic_tags:
Brain Imaging,Pharmacology,Receptor Pharmacology,Consciousness,Aging,Clinical Trial,Healthy Volunteers

raw_json:
{"europe_pmc_id":"42220002","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Suggested Guidelines for Applying a Systemic Lens to Psychedelic-Assisted Psychotherapy.
authors: Lappan SN, Davis SD.
publication_date: 2025-12-08
doi: 10.1177/28314425251404021
pubmed_id: 42131862
source_url: https://doi.org/10.1177/28314425251404021
substance_tags: psilocybin
topic_tags: Depression,Anxiety,PTSD,Addiction,Emotional Processing
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:03
abstract:
Psychedelic-assisted psychotherapy has demonstrated efficacy in treating individual mental health conditions such as addiction, anxiety, depression, and post-traumatic stress disorder. However, current research predominantly focuses on individual experiences, overlooking the relational and systemic factors that influence healing and long-term therapeutic outcomes. This conceptual article proposes a systemic approach to psychedelic-assisted psychotherapy and research, integrating relational principles to explore the impact of psychedelic experiences on interpersonal dynamics, attachment patterns, and family systems. The proposed research design outlines a 10-session systemic research protocol involving preparation, psilocybin administration, and integration, with sessions that include significant relational figures, such as partners or family members. Outcome measures are outlined to assess relational quality, attachment security, communication patterns, emotional intimacy, and intergenerational trauma using validated psychometric tools. Systemic theories inform the therapeutic framework, including Bowenian family systems theory, structural family therapy, emotionally focused therapy, and contextual family therapy. By incorporating relational dynamics into psychedelic-assisted therapy, this article seeks to help bridge a critical gap in the existing literature and inform the development of integrative treatment models that promote long-term, systemic change beyond individual symptom reduction.

raw_json:
{"europe_pmc_id":"42131862","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Stocker K, Hartmann M, Barrett FS, Richards WA, Sepeda ND, Ley L, Becker AM, Holze F, Liechti ME.
publication_date: 2026-05-31
doi: 10.1002/mpr.70073
pubmed_id: 42035466
source_url: https://doi.org/10.1002/mpr.70073
substance_tags: psilocybin
topic_tags: Mystical Experience,Observational Study,Healthy Volunteers
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:01
title:
Integrating the Mystical Experience Questionnaire Into a Broader Psychometric Framework: English Validation of the Psychedelic Experience Scale and Comparison of Psilocybin and LSD Sessions Across Two Controlled Settings.

abstract:
ObjectivesFor English, the validated part of Psychedelic Experience Scale (PES48) is a four-factor structure called the Mystical Experience Questionnaire (MEQ30). The other validated part of the PES48 consists of four more factors: two more mystical factors (paradoxicality and connectedness, which together with the MEQ30 form the MEQ40), and two more non-mystical factors (visual experience and distressing experience). However, this latter four-factor part of the PES48 has thus far only been validated for the German version of the PES48. We investigated whether the overall eight-factor structure of the PES48 (which includes the MEQ30 four-factor structure) can also be validated, and thus potentially be put to good use in English.MethodsData from 280 English PES measurements (145 different healthy participants) from four placebo-controlled studies with low to high doses of psilocybin were included. The reliability of the eight subscales was evaluated using measures of internal consistency. The validity of the factor structure was assessed through model fit indices from confirmatory factor analysis. English results were then also compared with the German PES validation data set from Stocker et al. (2024).ResultsSix of the eight subscales (mystical, positive mood, transcendence of time and space, ineffability, connectedness, distressing experience) of the English PES48 show high internal consistency, one subscale (paradoxicality) shows good, and one (visual experience) acceptable internal consistency. Both MEQ models (MEQ30 and MEQ40) show similar fits (acceptable to good model fits). In English, both MEQ models show better fits than in German. All six MEQ40 scale means of the English data are higher compared to German data.ConclusionsThe findings suggest that the eight-factor PES48 is also a valid psychometric tool in English. With the MEQ40 part of the PES48, one can measure mystical experience with a still wider conceptual breath than with the MEQ30. Furthermore, one can also measure non-mystical visual and distressing states in an overall more comprehensive and broader conceptualization of the psychedelic experience. Higher MEQ40 scale means for the English than the German study participants could inspire future research into the role of setting in relation to mystical experience.

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

raw_json:
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publication_date: 2026-03-27
doi: 10.1007/s00406-025-02188-5
pubmed_id: 41902950
source_url: https://doi.org/10.1007/s00406-025-02188-5
substance_tags: psilocybin
topic_tags: Clinical Trial,Systematic Review,Review Article
study_type: Systematic Review
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:02
title:
Mapping cognitive-behavioral approach in psychedelic-assisted treatment: a systematic review across phases with classic and non-classic psychedelics.

authors:
Varela YM, de O Tavares VD, Delgado LM, de Faria HAT, Menezes LQ, Almeida RM, Agrícola P, de Carvalho BS, Bienemann B, Falchi-Carvalho M, Cavalcanti-Ribeiro P, Palhano-Fontes F, Fernandes-Osterhold G, de Araujo DB, Galvão-Coelho N.

abstract:
The use of psychedelics in the treatment of psychopathologies has been expanding, highlighting Psychedelic-Assisted Psychotherapy (PAP) as a promising resource in mental health care. This systematic review investigates. This systematic review investigates whether and how cognitive-behavioral therapies are integrated with psychedelic substances-both classical and atypical-for the treatment of mental disorders. A PRISMA-based search was conducted across four databases (Embase, PsycArticles, PubMed, and Web of Science) up to May 2025. The review included 9 clinical trials involving a total of 283 patients; these studies used ketamine (n = 5), psilocybin (n = 3), and 3,4-methylenedioxymethamphetamine (n = 1). Among the Cognitive Behavioral Approaches (CBAs) applied, traditional Cognitive Behavioral Therapy (CBT) was predominant (n = 6), followed by emerging modalities such as Mindfulness-Based Cognitive Therapy (MBCT) (n = 2) and Acceptance and Commitment Therapy (ACT) (n = 1). Considerable variability was observed across study designs, particularly in terms of the timing of psychotherapeutic interventions, which occurred before, during, or after the psychedelic experience, with or without concurrent support. The findings indicate that cognitive-behavioral strategies have been incorporated into psychedelic-assisted interventions in diverse ways, across different phases of treatment and with distinct therapeutic purposes. Nonetheless, the therapeutic approaches applied remain highly heterogeneous between studies, highlighting the need for further research to clarify how these models are implemented and characterized in practice.

raw_json:
{"europe_pmc_id":"41902950","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2026-03-12
doi: 10.1016/j.schres.2026.03.003
pubmed_id: 41830808
source_url: https://doi.org/10.1016/j.schres.2026.03.003
keywords: Animals, Humans, Hallucinogens, Depression, Schizophrenia, Major Depressive Disorder
substance_tags: psilocybin
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:03
title:
Psychedelics for treatment of negative symptoms and depressive symptoms in schizophrenia spectrum disorder: A narrative review.

authors:
Sabé M, Grof P, Sackett NB, Tai S, Kryskow P, Bershad A, Turkington D, Buonarroti M, De Pieri M, Baniotopoulos P, Eskinazi M, Böge K, Leucht S, Seragnoli F, Furtado L, Brakha TA, Curtis L, Kirschner M, Kaiser S, Penzenstadler L, Zullino D, Højlund M, Gallo J, Solmi M, Sapienza J, Bosia M, La Torre J.

abstract:
Serotonergic psychedelics are re-emerging as therapeutic candidates across psychiatry, particularly for treatment-resistant depression. Their rapid and sustained antidepressant effects, alongside evidence for neuroplastic, dopaminergic, and glutamatergic modulation, have prompted interest in whether they could address depressive and negative symptoms in schizophrenia spectrum disorders (SSDs). This narrative review summarizes mechanistic, preclinical, and early clinical findings relevant to psychedelic use in SSDs. Schizophrenia and major depressive disorder share disturbances in dopamine, glutamate, and neuroplasticity, and both involve large-scale network abnormalities. Schizophrenia is associated with widespread dysconnectivity, mesocortical hypodopaminergia, and striatal hyperdopaminergia linked to NMDA receptor hypofunction. Depression is characterized by fronto-limbic and default mode network hyperconnectivity, mesolimbic hypodopaminergia, and reduced cortical glutamatergic tone. Depressive symptoms within SSDs may reflect an intermediate phenotype combining depressive-like hyperconnectivity with schizophrenia-related global dysconnectivity, suggesting that psychedelics' capacity to transiently increase network flexibility and recalibrate maladaptive connectivity may be clinically relevant. Preclinical studies show increased dendritic spine density, enhanced BDNF expression, restored reward sensitivity, and modulation of network dynamics after psychedelic administration. Clinically, uncontrolled exposure appears associated with increased psychosis-related presentations, whereas limited case reports suggest controlled administration may be tolerated in carefully selected, clinically stable individuals with SSDs. To date, only one early-phase trial (MDMA in schizophrenia) is ongoing, and no randomized trials have evaluated psilocybin or LSD in SSDs. Overall, psychedelics are biologically and mechanistically plausible but remain unproven for depressive and negative symptoms in SSDs, which partially overlap. Carefully designed, safety-focused early-phase studies in clinically stable patients are therefore a prerequisite for broader clinical application.

topic_tags:
Depression,Neuroplasticity,Receptor Pharmacology,Default Mode Network,Review Article,Case Report,Animal Study,Treatment-Resistant Depression,Safety

raw_json:
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title: Psilocybin for psychiatric disorders: History, clinical trials, neuroimaging, and regulations.
publication_date: 2026-02-25
doi: 10.1111/pcn.70042
pubmed_id: 41749057
source_url: https://doi.org/10.1111/pcn.70042
keywords: Humans, Hallucinogens, Mental Disorders, Clinical Trials as Topic, Neuroimaging, Psilocybin
substance_tags: psilocybin
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:00
authors:
Yonezawa K, Hirata M, Takano H, Kusudo K, Tomiyama S, Harada L, Suzuki K, Nutt DJ, Uchida H, Tani H.

abstract:
Psilocybin, a classic psychedelic compound, has garnered renewed interest as a potential treatment for various psychiatric disorders. This review provides a comprehensive overview of psilocybin's history, recent clinical evidence, ongoing clinical trials, neuroimaging findings, and regulations. Historically used in spiritual and healing rituals, psilocybin was in the early 1970s subjected to strict legal restrictions that stalled research for decades. However, renewed scientific interest began in the 1990s, with studies demonstrating psilocybin's therapeutic potential for psychiatric disorders. Clinical trials have reported therapeutic effects of psilocybin in major depressive disorder (MDD), depressive symptoms associated with life-threatening illnesses, and in some substance use disorders. Moreover, several phase III clinical trials of psilocybin for depression are currently underway, though trial data for obsessive-compulsive disorder and bipolar depression are limited. Short-term side effects are reportedly generally mild and transient, but long-term effects still need further investigation. Neuroimaging research using magnetic resonance imaging and electroencephalography is still limited and focuses mainly on MDD. However, ongoing clinical trials include neuroimaging studies for psychiatric disorders beyond MDD, as well as positron emission tomography studies for MDD. Regulatory frameworks vary internationally. While many countries continue to classify psilocybin as a prohibited substance, use of psilocybin under controlled conditions is now permitted in Switzerland, parts of the United States, Canada, and Australia. Despite encouraging data, challenges remain, including the need for larger, blinded trials, standardized protocols, and clarification of long-term efficacy and safety. Psilocybin represents a novel therapeutic approach in psychiatric treatment, warranting further rigorous scientific and regulatory research.

topic_tags:
Depression,Addiction,OCD,End-of-Life Distress,Brain Imaging,Aging,Spirituality,Clinical Trial,Review Article,Safety,Adverse Events

raw_json:
{"europe_pmc_id":"41749057","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


journal: PsyArXiv
publication_date: 2025-11-01
doi: 10.1016/j.addbeh.2026.108652
source_url: https://osf.io/preprints/psyarxiv/jd2rk_v1
substance_tags: psilocybin
topic_tags: Depression,Addiction,Observational Study,Safety
study_type: Observational Study
source_name: PsyArXiv
publication_status: preprint
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:30
raw_json: {"osf_id":"jd2rk_v1","version":1,"reviews_state":"accepted"}
title:
Lifetime Psychedelic Use and Opioid Use Disorder Severity: Substance-Use Pattern Specific and Mental Health-Dependent Associations in a National Survey

abstract:
Background and Aims The ongoing opioid epidemic remains a major public health crisis in the United States, with over 100,000 opioid-related deaths annually. Mental health disorders are strongly associated with opioid use disorder (OUD), compounding risks of misuse and overdose. Emerging evidence indicates that psychedelics may be associated with reduced risk of OUD. This study aimed to estimate the associations between lifetime psychedelic use and OUD severity, accounting for mental health impairment, and to test whether these associations vary by mental health status. Design Cross-sectional analysis of the 2023 National Survey on Drug Use and Health using structural equation modeling with multiple-group moderation. Reporting follows STROBE guidelines for observational studies. Setting United States, nationally representative community survey. Participants 45,133 adults aged ≥18 years (55% female; mean age = 35.6 years, SD = 13.7). Measurements The primary dependent variable was OUD severity (no disorder, mild, moderate, severe). Independent variables were two psychedelic factors: mescaline/peyote (Psychedelic_F1) and LSD, psilocybin, MDMA, DMT (Psychedelic_F2). Mental health impairment was modeled as a latent construct (psychological distress, functional impairment, major depression) and also used to define high vs. low impairment groups. Covariates were age, sex, and household income. Findings Psychedelic_F1 was associated with lower OUD severity (β = -0.34, p =.001, 95%CI [-0.550, -0.153]), while the Psychedelic_F2 was associated with higher severity (β = 0.60, p <.001, 95%CI [0.429, 0.759]). Mental health impairment was positively associated with OUD severity (β = 0.21, p <.001, 95%CI [0.184, 0.256]). Multiple-group SEM indicated moderation by mental health impairment (Δχ²(6) = 22.29, p =.001): Psychedelic_F1 was associated with lower OUD severity only in the high mental health impairment group (β = -0.15, p =.041, 95%CI [-0.299, -0.006]), whereas the association of Psychedelic_F2 with higher OUD severity was attenuated in high mental health impairment (β = 0.38, p <.001, 95%CI [0.274, 0.521] vs. β = 0.48, p =.004, 95%CI [0.164, 0.847]). Conclusions In the United States, two distinct psychedelic use patterns were identified. The factor capturing lifetime mescaline/peyote use was associated with lower OUD severity, while the factor including LSD, psilocybin, MDMA, and DMT use was associated with higher severity. These associations differed by level of mental health impairment, with more favorable associations with OUD severity most evident among individuals with greater mental health impairment. More research on the context and intention of psychedelic use in the general public is warranted.

keywords:
Mental Health Impairment, Mescaline, National Survey on Drug Use and Health, Opioid Use Disorder, Peyote, Psychedelics, Social and Behavioral Sciences, Clinical Psychology, Substance Abuse and Addiction, Quantitative Methods, Quantitative Psychology


publication_date: 2026-02-17
doi: 10.1038/s41386-026-02356-8
pubmed_id: 41708994
source_url: https://doi.org/10.1038/s41386-026-02356-8
substance_tags: psilocybin
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:00
title:
Sex-dependent developmental changes in behavior, brain structure, functional connectivity, and sensory perception following exposure to psilocybin during adolescence.

authors:
Sahoo I, Masadi S, Maheswari A, Utama R, Abeer MI, Soltanpour S, Nasseef MT, Chukwuemeka T, Sinhal N, Pandit J, Ortiz RJ, Cavallaro N, Brengel E, Kulkarni PP, Gitcho MA, Ferris CF.

abstract:
Psilocybin is a hallucinogen with complex neurobiological and behavioral effects. Underlying these effects are changes in brain neuroplasticity. We hypothesized psilocybin given during adolescence, a time of heightened neuroplasticity, particularly in the forebrain, would affect emotional behavior and the associated underlying neuroanatomy, neurocircuitry, and epigenetics. Female and male mice were given vehicle or 3.0 mg/kg psilocybin every other day by oral gavage from postnatal days 40-50 for a total of five exposures. Between postnatal days 90-120 mice were imaged and evaluated for affective behavior and perception of rewarding and aversive stimuli. MRI data from voxel-based morphometry, diffusion weighted imaging, and BOLD resting state functional connectivity were registered to a mouse 3D MRI atlas with 139 brain regions providing site-specific differences in global brain structure and functional connectivity between experimental groups. The prefrontal cortex was measured for changes in proteins associated with epigenetics. Mice showed no significant differences in the light/dark box test, but female mice exposed to psilocybin showed reduced mobility in the open field as compared to controls. Mice with early psilocybin exposure showed reduced brain sensitivity to both rewarding and aversive odors during scanning sessions. There were regional reductions in brain volume and alteration in water diffusivity affecting males more than females. Global and regional functional connectivity were increased in both sexes with the prefrontal cortex showing enhanced connections to the hypothalamus, thalamus and midbrain. Males showed reduced levels of epigenetic and neuroplasticity protein markers in the prefrontal cortex. The pronounced changes in brain volume, water diffusivity - a surrogate marker of gray matter microarchitecture, increase in functional connectivity, altered perception of rewarding and aversive stimuli and altered levels of protein markers of neuroplasticity provide compelling evidence that exposure to psilocybin during adolescence has long term developmental consequences, particularly in males.

keywords:
Brain, Neural Pathways, Animals, Mice, Inbred C57BL, Mice, Hallucinogens, Magnetic Resonance Imaging, Sex Characteristics, Neuronal Plasticity, Female, Male, Psilocybin

topic_tags:
Neuroplasticity,Brain Imaging,Mechanism of Action,Biomarkers,Aging,Epigenetics,Emotional Processing,Animal Study

raw_json:
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authors: He Z, Wang Y, Chen J, Cheng J, Feng Y, Niu S, Yan J.
publication_date: 2026-02-11
doi: 10.1007/s00406-025-02165-y
pubmed_id: 41677823
source_url: https://doi.org/10.1007/s00406-025-02165-y
substance_tags: psilocybin
topic_tags: Depression,Meta-Analysis,Systematic Review,Review Article,Case Report,Safety
study_type: Meta-Analysis
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:00
title:
Therapeutic effects of psilocybin in major depressive disorder: a systematic review and meta-analysis exploring dose effects.

abstract:
BACKGROUND: Several recent trials indicate positive effects of psilocybin in patients with major depressive disorder. However, questions need to be addressed regarding the relationship between dosage and therapeutic outcomes, such as the recommended dose range and frequency for optimal practice as well as the dose-dependent adverse effects. OBJECTIVE: (1) to assess the effectiveness and tolerability of psilocybin on major depression; (2) to explore a suitable dosing regimen for psilocybin treatment concerning both dose and frequency. METHODS: Four databases (Cochrane Library, EMBASE, Pubmed, Web of Science) were searched up to February 23, 2024, to include primary studies evaluating the use of psilocybin in adults presenting major depressive disorder. All primary studies evaluating psilocybin in adults diagnosed with MDD were included. Case series, animal research, meta-analyses, and systematic reviews were excluded. The primary outcomes assessed were changes in depression scores, response rates, remission rates, and safety and tolerability profiles. Two reviewers performed study selection and data extraction independently based on the prepared criteria. The quality and potential risk of bias in each trial were evaluated using criteria outlined in the Cochrane Handbook. The review was registered in the PROSPERO (CRD420251115865). RESULTS: Seven trials including 464 participants were identified (one meeting abstract included). The overall quality of included trials is moderate, as assessed with Cochrane Handbook. Psilocybin presented significant effects in treating major depression with safety and tolerability. In a certain range, the higher dose and frequency resulted in a better effect. Our findings indicate the dose regimen of 35-50 mg/70kg and double-dosing may be a promising dosing strategy. CONCLUSION: The results support the potential application of psilocybin for treating major depressive disorder. Given that the included trials are limited by small sample sizes and short follow-up periods, further clinical studies with longer follow-up periods are needed to fully assess the efficacy and safety of high-dose psilocybin.

raw_json:
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title: Spatiotemporal mapping of brain organisation following the administration of 2C-B and psilocybin.
authors: Mallaroni P, Singleton SP, Mason NL, Satterthwaite TD, Ramaekers JG.
publication_date: 2026-02-02
doi: 10.1038/s41380-026-03447-0
pubmed_id: 41634136
source_url: https://doi.org/10.1038/s41380-026-03447-0
substance_tags: psilocybin
topic_tags: Brain Imaging,Pharmacology,Receptor Pharmacology,Biomarkers,Aging,Healthy Volunteers
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:00
abstract:
As psychedelic-assisted psychotherapy gains momentum, clinical investigation of next-generation psychedelics may lead to novel compounds tailored for specific populations. 2,5-dimethoxy-4-bromophenethylamine (2C-B) is a psychedelic phenethylamine reported to produce less dysphoria and subjective impairment than the psychedelic tryptamine psilocybin. Despite its popularity among recreational users and distinct pharmacodynamics, the neural correlates of 2C-B remain unexplored. Using 7 T resting-state functional MRI in 22 healthy volunteers, we mapped out the acute effects of matched doses of 20 mg 2C-B, 15 mg psilocybin and placebo across spatiotemporal benchmarks of functional brain organisation. In a within-subjects, double-blind, placebo-controlled crossover design, we evaluated the neuropharmacological and neurobehavioural correlates of an array of connectivity measures - including static (sFC) and global connectivity (gFC), dynamic connectivity variability (dFC), and spontaneous brain complexity. Compared to placebo, 2C-B and psilocybin selectively reduced intranetwork sFC, while broadly increasing between-network and subcortical-cortical connectivity. Compared to psilocybin, 2C-B exhibited less pronounced reductions in between-network dFC but elicited elevations in transmodal sFC. Both compounds yielded spatially divergent increases in gFC yet produced similar increases in brain complexity. Using PET density modelling, the spatial distribution of neural effects aligned with documented differences in monoaminergic transporter and serotonergic receptor binding affinity beyond 5-HT2A, highlighting the role of pharmacology in shaping functional dynamics. Lastly, we show behavioural markers of psychedelic effects are reflected by the decoupling of the transmodal axis of functional brain organisation. Together, our findings highlight 2C-B as a useful new addition to the study of psychedelic neuroscience and may motivate new pharmacotherapy strategies.

keywords:
Brain, Humans, Dimethoxyphenylethylamine, Hallucinogens, Magnetic Resonance Imaging, Brain Mapping, Cross-Over Studies, Double-Blind Method, Adult, Female, Male, Young Adult, Psilocybin

raw_json:
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authors: Stanger MK, Soffer HO, Bryan AD, Skrzynski CJ.
publication_date: 2024-06-16
doi: 10.1089/can.2024.0059
pubmed_id: 38885938
source_url: https://doi.org/10.1089/can.2024.0059
substance_tags: psilocybin
topic_tags: Observational Study,Adolescents
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:01
title:
Comparing Cannabis Use Motivations and Dependence Across Regular Cannabis Users Who Have or Have Not Recently Used Psilocybin.

abstract:
IntroductionIn Colorado, both cannabis and psilocybin are legal and becoming more commonly used. However, there is almost no research detailing the public health concerns regarding negative outcomes (e.g., dependence) of cannabis and psilocybin co-use and motives that may perpetuate these negative outcomes (e.g., coping, boredom).MethodsUsing data from a larger observational study on cannabis and metabolic processes, regular cannabis users (use ≥7 times/month; n = 97, 35.1% female, 89.7% WHITE) who used psilocybin in the past 3 months (n = 34) were compared with those who had not used psilocybin in the past 3 months (n = 63) on cannabis dependence as measured by the Marijuana Dependence Scale and endorsement of 12 cannabis motives from the Comprehensive Marijuana Motives Questionnaire. Correlations between motives and dependence were also examined and compared across groups.ResultsFindings revealed that individuals who had recently used psilocybin had greater cannabis dependence scores than those who had not used recently [F (1, 95) = 5.53, p = 0.02], and more strongly endorsed that their cannabis use was motivated by enjoyment [F (1, 91) = 4.31, p = 0.04], boredom [F (1, 91) = 9.10, p < 0.01], and availability [F (1, 91) = 9.46, p < 0.01]. Correlations between dependence scores and coping and boredom motives were also significantly positive for both groups (all p values

keywords:
Humans, Marijuana Abuse, Hallucinogens, Motivation, Adolescent, Adult, Colorado, Female, Male, Young Adult, Surveys and Questionnaires, Psilocybin, Marijuana Use

raw_json:
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title: Classic psychedelics and personality: An updated systematic review.
authors: Vicentini AB, de Paula CC, Silva Reis JA, Bouso JC, Hallak JEC, Dos Santos RG.
publication_date: 2026-05-30
doi: 10.1177/02698811261449386
pubmed_id: 42218644
source_url: https://doi.org/10.1177/02698811261449386
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:01
abstract:
BackgroundThe impact of classic psychedelics (5-HT2A receptor agonists) on personality traits has been studied for decades, and it has been hypothesized that the mechanisms underlying these changes are linked to agonism at cortical serotonergic 5-HT2A receptors. However, research results are contradictory. Therefore, the present paper aims to systematically evaluate the effects of psychedelics on personality, updating (2016-2024) a previous systematic review by Bouso and collaborators (2018). The International Prospective Register of Systematic Reviews ID for this study is CRD42024582704.MethodSystematic review using four databases (PubMed, LILACS, PsycINFO, and SciELO) including randomized controlled trials, open-label, and observational studies. Interventions included the consumption of any classic psychedelic (lysergic acid diethylamide, psilocybin, ayahuasca/dimethyltryptamine, mescaline), and the studies were required to use some instrument for personality assessment. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to conduct the data collection.ResultsOut of 6043 references screened, 48 studies were included: 14 experimental and 34 observational. The most consistent findings were increases in Openness and reductions in Neuroticism, especially with psilocybin and ayahuasca. Changes in other traits, such as Extraversion, Agreeableness, and Conscientiousness, were more variable. Microdosing was associated with modest reductions in Neuroticism and higher Absorption. Most studies used instruments based on the Five-Factor Model, reflecting its growing dominance.ConclusionsClassic psychedelics seem to promote lasting personality changes, most consistently increasing Openness and reducing Neuroticism. Future research would benefit from combining experimental and naturalistic designs, using longer follow-up periods and more diverse personality models to better understand the interplay between psychedelics and personality, thus providing a more accurate guide for clinical use.

topic_tags:
Mechanism of Action,Receptor Pharmacology,Microdosing,Personality Change,Randomized Controlled Trial,Systematic Review,Review Article,Observational Study

raw_json:
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title: Psychedelic-induced hypomania and mania: a systematic review and meta-analysis.
publication_date: 2026-05-28
doi: 10.1038/s41380-026-03657-6
pubmed_id: 42215638
source_url: https://doi.org/10.1038/s41380-026-03657-6
substance_tags: psilocybin
topic_tags: Depression,Addiction,Meta-Analysis,Systematic Review,Review Article,Observational Study,Safety
study_type: Meta-Analysis
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:01
authors:
Eskinazi M, Nasserdine R, Cusin RM, Baniotoupoulos P, Saccaro LF, De Pieri M, Corino T, Seragnoli F, Briefer JF, Aboulafia Brakha T, Richard-Lepouriel H, Penzenstadler L, Böge K, Kirchner M, Zullino D, Højlund M, Sapienza J, Bosia M, Catalan A, Vieta E, Solmi M, Sabé M.

abstract:
Serotonergic psychedelics are increasingly investigated as treatments for affective disorders. Concerns persist regarding their potential to induce hypomania or mania, particularly in individuals with bipolar spectrum vulnerability. Whether these substances precipitate transient mood switches or contribute to persistent bipolar illness or diagnostic transition remains unclear. We conducted a systematic review of human studies examining manic or hypomanic symptoms following exposure to serotonergic psychedelics (psilocybin, LSD, mescaline, DMT/ayahuasca) or MDMA (CRD420251160656). Databases and trial registries were searched through January 26, 2026. Eligible designs included randomized and non-randomized clinical studies, registry-based cohorts, cross-sectional surveys, and longitudinal observational studies. Outcomes included dysphoria/euphoria, manic or hypomanic symptoms and transition to bipolar disorder. Risk of bias was assessed using ROBINS-I, ROB2 or NIH tools. Twenty-three studies met inclusion criteria, four contributing to meta-analysis. Rates of psychedelic-associated dysphoria/euphoria, hypomania or mania ranged from 5.8% in controlled trials of psilocybin-assisted psychotherapy for major depressive disorders to 30% in naturalistic studies of individuals with bipolar disorder. When present, manic symptoms were typically acute and self-limited. Observational studies identified higher risks among individuals with bipolar I disorder, familial vulnerability, polysubstance use, and unsupervised or illegal use. Registry-based cohorts examining diagnostic transitions showed a prevalence of subsequent transition to bipolar disorder of 4% (95% CI2-8%; N = 7478; I² = 32.1%), with little evidence for a hallucinogen-specific signal. Overall, serotonergic psychedelics appear to pose a low but clinically meaningful relative risk of transient mood-related symptoms in susceptible individuals while remaining relatively safe in controlled clinical settings. Long-term outcomes and repeated exposure remain insufficiently studied, underscoring the need for rigorous longitudinal research.

raw_json:
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authors: Pei G.
publication_date: 2026-05-28
doi: 10.1038/s41421-026-00906-4
pubmed_id: 42215437
source_url: https://doi.org/10.1038/s41421-026-00906-4
substance_tags: psilocybin
topic_tags: Neuroplasticity,Receptor Pharmacology
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:01
title:
A spatiotemporal gating hypothesis for psilocybin plasticity: reconciling the 5-HT₂A-TrkB mechanistic paradox.

raw_json:
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title: Effects of psilocybin on sleep quality and brain microstructure in chronic cluster headache.
publication_date: 2026-05-28
doi: 10.1177/02698811261449380
pubmed_id: 42212900
source_url: https://doi.org/10.1177/02698811261449380
substance_tags: psilocybin
topic_tags: Headache / Migraine,Neuroplasticity,Receptor Pharmacology
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:00
authors:
Brendstrup-Brix K, Ozenne B, Fisher PM, Stenbæk DS, Petersen AS, Armand S, McCulloch DE, Marstrand-Joergensen MR, Ulv Larsen SM, Johansen A, Jensen RH, Knudsen GM, Madsen MK.

abstract:
BackgroundPatients with chronic cluster headache (CCH) suffer from poor sleep, which may impact their brain microstructure and parenchymal clearance of waste products. Psilocybin has shown promise for the treatment of CCH and has been linked to increased neuroplasticity with possible influences on brain microstructure.AimsTo investigate the effects of psilocybin on sleep, brain water diffusivity, and microstructure in CCH.MethodsEleven CCH patients underwent diffusion-weighted MRI and subjective sleep quality assessment with the Pittsburgh Sleep Quality Index (PSQI) before and 1 week after three psilocybin administrations (0.14 mg/kg) spaced 1 week apart. Measures taken prior to intervention were also compared to 24 healthy controls, and subjective sleep quality was related to brain microstructure and diffusivity across groups.ResultsWe found that sleep was poor in CCH patients, but improved after psilocybin treatment (CCH mean PSQI change (SD) = -2.50 (2.1), pFWER = 0.015). When analyzing brain microstructure and water diffusivity in conjunction, we found differences between CCH patients and controls, which were primarily driven by differences in grey matter. On average, psilocybin intervention in CCH patients was not associated with statistically significant changes in brain microstructure or water diffusivity. However, most patients exhibited lower white matter diffusivity and neurite volume after intervention. Subjective sleep quality showed borderline significant correlations of moderate effect size with brain microstructure and water diffusivity.ConclusionSubjective sleep quality improved in CCH patients after psilocybin and showed some evidence of an association with measures of brain microstructure and water diffusivity.Clinicaltrialsgov identifiers:Prophylactic Effects of Psilocybin on Chronic Cluster Headache (EPOCH; NCT04280055) and The Neurobiological Effect of 5-HT2AR Modulation (NeuroPharm2; NCT03289949).

raw_json:
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authors: Hampsey E, Martin K, Kalfas M, Benson L, Wihlborg S, Jelen L, Young AH, Rucker J.
publication_date: 2026-05-28
doi: 10.1177/02698811261453938
pubmed_id: 42212869
source_url: https://doi.org/10.1177/02698811261453938
substance_tags: psilocybin
topic_tags: Pharmacology,Systematic Review,Review Article
study_type: Systematic Review
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:00
title:
A systematic review of the pharmacokinetics of classical serotonergic psychedelic compounds in healthy adult subjects.

abstract:
IntroductionDespite renewed investigations into classical psychedelic compounds, their pharmacokinetic profiles remain incompletely understood.MethodsThis systematic review collated data from healthy adult volunteers on the pharmacokinetic properties of lysergic acid diethylamide (LSD), psilocybin, dimethyltryptamine (DMT), mescaline, and 5-methoxy-N,N-dimethyltryptamine (5-MEO-DMT).ResultsWe identified 32 eligible trials. LSD was the most studied compound, followed by DMT, split between intravenous (IV) and oral formulations. Psilocybin was also frequently studied. Mescaline was reported in two trials, with IV LSD, IV psilocybin, inhalation 5-MEO-DMT, and intranasal 5-MEO-DMT reported in single studies. Key findings include dose proportional Cmax values for LSD and psilocybin, alongside differences between oral and IV formulations of DMT that may be clinically significant.DiscussionThis systematic review highlights key variations in absorption, distribution, and elimination between the studied compounds that may have important implications in both clinical and research settings.

raw_json:
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authors: Lago M, Cerveira M, Simonet JX.
publication_date: 2026-05-27
doi: 10.3389/fnins.2026.1813281
pubmed_id: 42292331
source_url: https://doi.org/10.3389/fnins.2026.1813281
substance_tags: psilocybin
topic_tags: Neuroplasticity,Mechanism of Action,Emotional Processing,Case Report,Animal Study,Drug Interactions
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:00
title:
Transient multidomain functional improvement in advanced Alzheimer's disease following high-dose psilocybin-containing mushroom administration: a case report.

abstract:
BackgroundAdvanced Alzheimer's disease (AD) is generally regarded as a stage of irreversible functional decline. Psilocybin is known to transiently alter large-scale brain network dynamics and to induce plasticity-related mechanisms in preclinical models, yet clinical data in advanced dementia remain lacking.Case presentationWe report the case of an octogenarian Japanese-American woman with a 10-year history of Alzheimer's disease, including 5 years of marked hypofunction and predominantly monosyllabic speech. Baseline features included chronic urinary incontinence, executive dysfunction, dysphagia, dependent mobility, flat affect, and severe reduction in spontaneous communication. The patient received 5 g of orally administered psilocybin-containing mushrooms (Enigma strain). The acute phase was marked by autonomic activation, clinically suspected hyperthermia, profuse sweating, and a prolonged deep sleep-like state. Approximately 19 h post-administration, spontaneous autobiographical speech emerged. Over subsequent days and weeks, functional improvements included restoration of urinary continence, improved ambulation, autonomous dressing, increased emotional responsiveness, sustained social interaction, contextual memory retrieval, preserved working memory for social context, and spontaneous conversational engagement.ConclusionThis case documents transient multidomain functional improvement in advanced Alzheimer's disease following psilocybin administration. The findings do not imply disease reversal but suggest that residual functional capacity may persist in late-stage neurodegeneration and may become transiently accessible under specific neuromodulatory conditions.

raw_json:
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publication_date: 2026-05-27
doi: 10.15288/jsad.26-00013
pubmed_id: 42212774
source_url: https://doi.org/10.15288/jsad.26-00013
substance_tags: psilocybin
topic_tags: General
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:01
title:
Retail Availability of Intoxicating Cannabis and Mushroom Products Across Eleven U.S. Cities: Sales Persist Despite Prohibitions.

authors:
LoParco CR, Rossheim ME, Tillett KK, Cui Y, Johnson M, Speer M, Mihelich D, Amdeta H, Ndisebuye D, Berg CJ.

abstract:
ObjectiveRetail sales of intoxicants, including derived intoxicating cannabis products (DICPs) such as delta-8 tetrahydrocannabinol (THC) and hallucinogenic mushrooms, have rapidly increased throughout the US, despite their sale being federally illegal. This study assessed DICP and hallucinogenic mushroom availability in US smoke shops with differing DICP and psilocybin laws.MethodsIn May-October 2025, using Google's Incognito mode, we searched "smoke shop in [city, state]" across eleven cities in states (California, Colorado, Florida, Maryland, New York, Nevada, Oregon, Pennsylvania, Texas, Virginia, Washington) with differing legal contexts for THC and mushrooms (7 explicitly prohibited DICP sales, 2 decriminalized psilocybin, Amanita was not explicitly illegal in any). We called each store (n=1,023) to assess product availability. Bivariate tests assessed differences by state laws.Results73.0% (n=747/1,023) answered the phone and responded about DICP availability: 51.4% (n=384/747) reported selling DICPs (39.6% DICPs illegal vs. 80% not explicitly illegal, p

raw_json:
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publication_date: 2026-05-27
doi: 10.1016/j.euroneuro.2026.112879
pubmed_id: 42208423
source_url: https://doi.org/10.1016/j.euroneuro.2026.112879
substance_tags: psilocybin
topic_tags: Randomized Controlled Trial,Healthy Volunteers
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:00
title:
Blinding integrity in psychedelic research: Evidence from a comparative randomized controlled trial of psilocybin, MDMA, and methylphenidate in healthy volunteers.

authors:
Belinger L, Rieser NM, Engeli EJE, Becciolini L, Clamote M, Pribis M, Saissi F, Florineth GA, Hehl NL, Herdener M, Preller KH.

abstract:
Maintaining effective blinding is a major methodological challenge in psychedelic research. This study provides a comprehensive evaluation of blinding integrity in 120 healthy volunteers who received either psilocybin, MDMA, or methylphenidate (active placebo) in a double-blind, randomized controlled trial. Using a multi-level assessment incorporating forced-choice substance guesses, certainty ratings, decision factors, and subjective substance effects, the analyses characterize blinding integrity and its relation to the substance experience. Results indicate that overall blinding was insufficient, with psilocybin showing the highest rates of functional unblinding, MDMA moderate levels, and methylphenidate the lowest. As an active placebo, methylphenidate provided more effective blinding for MDMA than for psilocybin. Incorporating certainty levels of substance guesses revealed a more differentiated pattern, with lower functional unblinding rates. Decision factors and subjective substance experiences were associated with phenomenological substance effects. Prior substance experiences did not influence accuracy of forced-choice substance guesses. These findings provide empirical guidance for the design and reporting of blinding procedures in psychedelic trials and underscore the value of systematic, multi-level assessment of blinding integrity.

raw_json:
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title: Psilocybin-induced neurocardiogenic syncope: a case report.
authors: Atiq MA, Weisman E, Guerra RB, Martinez LL, Yaden DB, Barrett FS, Nayak S, Sayali C.
publication_date: 2026-05-27
doi: 10.1007/s00213-026-07079-8
pubmed_id: 42207275
source_url: https://doi.org/10.1007/s00213-026-07079-8
substance_tags: psilocybin
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:00
abstract:
BackgroundPsilocybin is among the serotonergic psychedelics closest to potential FDA approval, with growing evidence of therapeutic benefit across psychiatric conditions. As clinical trials expand, systematic characterization of adverse events (AEs) remains essential. While transient hypertensive responses are well documented, hypotensive events such as neurocardiogenic syncope (NCS) are rarely reported.Case presentationWe describe a healthy 35-year-old male enrolled in an open-label study investigating psilocybin-evoked changes in brain function during transcranial magnetic stimulation and electroencephalography (TMS-EEG). Approximately 60 minutes after receiving 25 mg oral psilocybin, and shortly after initiation of an eye-open resting-state EEG, he experienced prodromal lightheadedness followed by a brief loss of consciousness and postural tone. Immediate blood pressure was 93/51 mmHg with tachycardia and diaphoresis. Supportive measures, including leg elevation and oral hydration, led to rapid stabilization, and no further cardiovascular abnormalities occurred. The participant reported an emotionally intense experience, and contextual factors - including upright seated posture, restrictive EEG equipment, and anticipatory anxiety surrounding TMS - may have contributed to heightened autonomic arousal and susceptibility to NCS.ConclusionsThis case highlights a rare hypotensive AE during psilocybin administration and underscores the importance of vigilant cardiovascular monitoring, particularly during procedures that may amplify emotional arousal. Given that fewer than one-quarter of contemporary psychedelic trials report systematic AE assessment, transparent documentation of both hypertensive and hypotensive events is critical for defining psilocybin's safety profile as clinical applications expand.Parent trial registrationOpen Label Psilocybin Brain Stimulation and Imaging Pilot Study; ClinicalTrials.gov: NCT06835699. Date registered: 02/13/2025. The parent-study consent form explicitly permits publication of de-identified participant data, and separate institutional approval for this case report was obtained (IRB00543773).

topic_tags:
Anxiety,Brain Imaging,Consciousness,Aging,Emotional Processing,Clinical Trial,Case Report,Safety,Adverse Events

raw_json:
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title: Correction: Catatonia Associated With First-Time Psilocybin Exposure: A Case Report.
authors: Singh J, Mruthyunjaya P.
abstract: [This corrects the article DOI: 10.7759/cureus.106474.].
publication_date: 2026-05-26
doi: 10.7759/cureus.c439
pubmed_id: 42211293
source_url: https://doi.org/10.7759/cureus.c439
substance_tags: psilocybin
topic_tags: Case Report
study_type: Case Report
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:01
raw_json:
{"europe_pmc_id":"42211293","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2026-05-26
doi: 10.1159/000552272
pubmed_id: 42201843
source_url: https://doi.org/10.1159/000552272
substance_tags: psilocybin
topic_tags: Depression,Clinical Trial,Treatment-Resistant Depression
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:00
title:
Long-Term Efficacy of Psilocybin with Adjunct Psychotherapy in Treatment-Resistant Major Depression (EPIsoDE): 6- and 12-Month Naturalistic Follow-Up of a Phase 2b Trial.

authors:
Mertens LJ, Betzler F, Brand M, Evens R, Jungaberle A, Jungaberle H, Kärtner L, Majić T, Schmitz CN, Ströhle A, Scharf D, Spangemacher M, Wolff M, Assadi Z, Bahri S, Becher L, Färber LV, Harder H, Kirchen N, Kulakova E, Kunz LC, Meijer A, Rohrmoser B, Wellek S, Berger MM, Koslowski M, Gründer G.

abstract:
IntroductionPsilocybin shows promise for treatment-resistant depression (TRD), but long-term data are limited. This study examined the antidepressant effect of one or two psilocybin doses with adjunct psychotherapy in TRD until twelve months.MethodsThis is a naturalistic follow-up of a phase 2b, randomized, active placebo-controlled trial, where participants were randomized to receive two drug administrations six weeks apart, embedded within seven psychotherapeutic sessions: (1) active placebo (100 mg nicotinamide) then 25 mg psilocybin, (2) 5 mg psilocybin then 25 mg psilocybin, (3a) 25 mg psilocybin then 5 mg psilocybin, or (3b) 25 mg psilocybin twice. The controlled phase ended at twelve weeks, after which participants could pursue other treatments, with follow-ups at six- and twelve-months. The primary follow-up endpoint was change from baseline on the Hamilton Rating Scale for Depression (HAMD17).Results126/144 randomized participants (51 females, 40%) completed at least one follow-up visit. A generalized additive mixed regression model for change in HAMD17 scores showed a significant time effect across groups for both follow-up time points, with estimated average changes from baseline of -7.93 (95% CI: -9.17, -6.70, adj. p

raw_json:
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title: Epigenome-wide association study of psilocybin-induced methylome changes in alcohol use disorder.
authors: Urban MM, Zillich L, Rieser NM, Herdener M, Spanagel R, Vollenweider FX, Preller KH, Meinhardt MW.
publication_date: 2026-05-25
doi: 10.1038/s41398-026-03961-3
pubmed_id: 42192100
source_url: https://doi.org/10.1038/s41398-026-03961-3
substance_tags: psilocybin
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:00
abstract:
The serotonergic hallucinogen psilocybin has shown potential as a treatment for psychiatric conditions like alcohol use disorder (AUD) and depression in clinical studies. Epigenetic mechanisms, including DNA methylation, are hypothesized to contribute to its lasting therapeutic benefits. In this exploratory study, we present the first methylome-wide analysis of psilocybin-induced changes in a cohort of detoxified patients with AUD. The longitudinal study design included three assessment days in 37 patients with blood sampling and acquisition of psychometrics - at baseline, 24 h after administration of psilocybin (25 mg) or placebo (mannitol), and one month after treatment. As the primary endpoints (duration of abstinence and mean alcohol use) in this trial were not reached, our investigation included secondary psychometrics that differed significantly between groups: Beck's Depression Inventory and Beck's Hopelessness Scale. The epigenome-wide association study (EWAS) identified one CpG site in TLE4 (p = 1.1e-7) associated with psilocybin treatment. Screening for differentially methylated regions, we observed altered methylation in the gene RASGRP4 (pFDR = 3.2e-4). Network analysis revealed co-methylation modules related to psilocybin treatment, as well as modules associated with the reduction of depressive symptoms and drinking behavior. Gene ontology analysis indicated involvement of these modules in neuroplasticity and immune functions, suggesting that they may reflect abstinence-related recovery processes. Investigating candidate genes at nominal significance (p

keywords:
Humans, Alcoholism, Hallucinogens, Longitudinal Studies, DNA Methylation, Epigenesis, Genetic, Adult, Middle Aged, Female, Male, Genome-Wide Association Study, Psilocybin, Epigenome

topic_tags:
Depression,Addiction,Neuroplasticity,Mechanism of Action,Epigenetics,Observational Study,Genomics,Immune Function

raw_json:
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authors: Akbar RJ, Stringer AD, Wiah S, Dachepalli M, Daws SE, Inan S, Rawls SM.
publication_date: 2026-05-24
doi: 10.1097/fbp.0000000000000879
pubmed_id: 42186402
source_url: https://doi.org/10.1097/fbp.0000000000000879
substance_tags: psilocybin
topic_tags: Pharmacology,Mechanism of Action,Receptor Pharmacology
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:00
title:
Psilocybin induces stereotyped movements and reduces defensive responding in planarians through 5-hydroxytryptamine mechanisms.

abstract:
Psilocybin is a serotonergic 5-HT2A R agonist that causes psychedelic and anxiolytic effects in human users. To delineate conservation of psilocybin pharmacology, we investigated behavioral effects of psilocybin in planarians ( Dugesia dorotocephala ), the simplest living animal with cephalization that also has a well defined serotonin (5-hydroxytryptamine [5-HT]) system. We quantified stereotyped movements (e.g. head bops, twists, scrunches, and C-shapes) and defensive responding (negative phototaxis) and probed a 5-HT2A R mechanism for psilocybin using a selective 5-HT2A R antagonist (volinanserin). Psilocybin (0.01, 0.1, 1, and 10 nM) increased all stereotyped movements and, at higher concentrations, reduced motility. Volinanserin (1, 10, and 100 nM) did not induce any stereotyped movements or reduce motility. For combination experiments, volinanserin reduced cumulative stereotyped movements produced by psilocybin (0.01 nM) and specifically reduced psilocybin-evoked twists and head bops. Concentrations (

raw_json:
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title: Psilocybin modulates social behaviour in male and female mice in a time-dependent manner.
authors: Shadani S, McCoy K, Ong L, Greaves E, Conn K, Andrews ZB, Foldi CJ.
publication_date: 2026-05-24
doi: 10.1038/s41386-026-02450-x
pubmed_id: 42185639
source_url: https://doi.org/10.1038/s41386-026-02450-x
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Eating Disorders,Receptor Pharmacology,Animal Study,Drug Interactions
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:00
abstract:
With the resurgence of psychedelic research and growing evidence of their therapeutic potential, there is an urgent need to understand how these compounds act across biological sexes. Despite widespread interest in their use for conditions marked by social impairments, including depression, anxiety, and anorexia nervosa, the influence of sex as a biological variable on the prosocial effects of psychedelics remains poorly understood. Indeed, enhanced connectedness, sociability and empathy are common outcomes of psychedelic use and these have shaped human social structures for millennia. Here, we investigated the sex-specific effects of a single dose of psilocybin (1.5 mg/kg) in C57BL/6 J mice across multiple aspects of social behaviour. Psilocybin acutely enhanced huddling and induced hypothermia selectively in female mice and post-acutely (4 h) enhanced novelty-seeking and grooming in females, with no comparable effects in males. By 24 h, psilocybin-treated males showed reduced grooming and rearing alongside increased sociability directed toward a cage-mate. This was accompanied by blunted novelty-evoked nucleus accumbens dopamine responses that persisted to 7 days post-administration. At 7 days, psilocybin shifted female social preference toward familiarity over novelty, associated with prolonged nucleus accumbens dopamine release during familiar conspecific interactions, while males exhibited increased grooming, opposing the effect observed at 24 h. Both 5-HT1AR and 5-HT2AR contributed to psilocybin's behavioural effects in sex-specific ways. These findings reveal temporally dynamic, sex-differentiated patterns of social behaviour and dopaminergic modulation following psilocybin, underscoring the importance of sex-informed approaches in preclinical research and clinical application of psychedelic compounds.

raw_json:
{"europe_pmc_id":"42185639","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocin glucuronide in whole blood: a stable and useful biomarker of psilocybin intake.
authors: Bergh MS, Bogen IL, Vevelstad M, Øiestad ÅML.
publication_date: 2026-04-30
doi: 10.1093/jat/bkag015
pubmed_id: 41723823
source_url: https://doi.org/10.1093/jat/bkag015
substance_tags: psilocybin,psilocin
topic_tags: Biomarkers
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:00
abstract:
Detecting psilocybin use is challenging because it rapidly converts to its psychoactive metabolite psilocin, and both compounds are unstable in blood. Bufotenin, a structural isomer of psilocin, may exhibit comparable instability in blood. For reliable detection, we developed and validated an LC-MS/MS method to simultaneously quantify psilocin, bufotenin, and their metabolites, psilocin glucuronide (PSG) and 5-hydroxyindole-3-acetic acid (5-HIAA), in human whole blood. We prepared blood samples by protein precipitation and lipid removal filtration. Analytes were separated using a biphenyl column. The method was validated according to AAFS guidelines with LOQs of 2.4 nM for psilocin, PSG, and bufotenin, and 30 nM for 5-HIAA. We assessed analyte stability in whole blood under conditions relevant to forensic sample handling. Psilocin degraded by 46%-66% at room temperature and 66%-76% at 4°C after one day, increasing to 88%-99% and 94%-100% after three days. At -20°C, degradation slowed, with up to 51% loss after one month and ≥91% after three months. In contrast, PSG remained stable for 14 days at both room temperature and 4°C, and for at least one year at -20°C, making it a reliable biomarker of psilocybin intake. Bufotenin showed moderate stability, while 5-HIAA was unsuitable as a biomarker due to its endogenous presence. Our method enables direct quantification of PSG, offering a straightforward and accurate alternative to indirect approaches. We demonstrated the method's applicability by analyzing 23 forensic blood samples that screened positive for psilocin or PSG, with PSG quantified in nearly all cases, even when psilocin was below LOQ. These findings confirm PSG as a specific and stable biomarker of psilocybin use, and its integration into routine forensic workflows could significantly improve detection reliability.

keywords:
Humans, Glucuronides, Hydroxyindoleacetic Acid, Bufotenin, Hallucinogens, Chromatography, Liquid, Reproducibility of Results, Substance Abuse Detection, Tandem Mass Spectrometry, Limit of Detection, Biomarkers, Psilocybin, Liquid Chromatography-Mass Spectrometry

raw_json:
{"europe_pmc_id":"41723823","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2026-05-20
doi: 10.1007/s12264-026-01632-3
pubmed_id: 42168715
source_url: https://doi.org/10.1007/s12264-026-01632-3
substance_tags: psilocybin
topic_tags: Brain Imaging,Receptor Pharmacology,Aging
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:02
title:
Mescaline Alters Cerebellar Function, Global Connectivity, and Frequency-Selective Acoustic Gating: A BOLD fMRI Study in Awake Rats.

authors:
Cavallaro N, Rai P, Akins D, Soltanpour S, Nasseef MT, Ortiz RJ, Utama R, Cody CR, Mistry A, Brenhouse HC, Kulkarni PP, Ferris CF.

abstract:
Mescaline, a 5-HT2A agonist psychedelic used ceremonially for millennia, lacks neuroimaging characterization due to its Schedule 1 status. Using pharmacological and resting-state fMRI in awake rats, we report mescaline's first comprehensive neurobiological profile. Acutely, mescaline produced cerebellar-selective BOLD suppression, suggesting functional disconnection from forebrain structures. Paradoxically, resting-state analysis revealed global hyperconnectivity, with the cerebellum forming enhanced connections to the hippocampus, thalamus, somatosensory cortex, and midbrain. Mescaline abolished normal BOLD responses to rewarding olfactory stimuli, indicating disrupted sensory processing. Pre-pulse inhibition showed frequency-dependent acoustic gating effects: enhancement at 4 kHz (+ 27.6%) and 20 kHz (+ 27.3%), but impairment at 12 kHz (- 16.4%). These findings distinguish mescaline from LSD and psilocybin, implicating the cerebellum as a dysregulated sensory filter that floods forebrain circuits with unprocessed sensorimotor information-a potential mechanism underlying psychedelic-induced perceptual alterations.

raw_json:
{"europe_pmc_id":"42168715","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2026-05-20
doi: 10.1038/s41597-026-07312-1
pubmed_id: 42168232
source_url: https://doi.org/10.1038/s41597-026-07312-1
substance_tags: psilocybin
topic_tags: Brain Imaging,Aging,Observational Study,Drug Interactions
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:00
title:
PsiConnect: Multimodal Neuroimaging of Context-Dependent Brain and Behaviour Dynamics under Psilocybin.

authors:
Novelli L, Stoliker D, Barta T, Greaves MD, Chopra S, Jackson J, Kwee J, Pang JC, Williams ML, Razi A.

abstract:
PsiConnect is a large-scale neuroimaging study designed to investigate context-dependent neural and subjective effects of psilocybin using multimodal neuroimaging. It combines functional, structural, and diffusion-weighted MRI with EEG to examine brain activity in 62 participants before and after a 19 mg dose of psilocybin. The design includes resting-state scans and three naturalistic conditions: guided meditation, music listening, and movie watching. Half of the cohort underwent an 8-week meditation training program, enabling exploration of interactions among meditation, psilocybin, and brain function. fMRI data was obtained through multi-echo fMRI, enhancing signal-to-noise ratio and reducing susceptibility artifacts to improve reliability. A comprehensive battery of behavioural and self-report measures captured acute and longitudinal cognitive and subjective effects, with follow-ups to one year post-administration. The large sample, multimodal imaging, contextual diversity, and behavioural follow-ups enable study of psilocybin-induced brain and behaviour changes with unprecedented comprehensiveness and reliability. Data is curated according to open science principles to ensure accessibility and compatibility with established neuroimaging pipelines, making PsiConnect a valuable, reusable resource for cognitive and computational neuroscience.

raw_json:
{"europe_pmc_id":"42168232","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psychedelic-assisted therapy: a survey on the clinical methods of Swiss physicians.
authors: Beichmann K, Catzeflis P, Aicher HD, Seragnoli F, Calder A, Amrani A, Hasler G.
publication_date: 2026-05-19
doi: 10.1177/20451253261448745
pubmed_id: 42179908
source_url: https://doi.org/10.1177/20451253261448745
substance_tags: psilocybin
topic_tags: Depression,Anxiety,PTSD,Addiction,Chronic Pain,Observational Study
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:01
abstract:
BackgroundThe Swiss Federal Office of Public Health provides case-by-case exemptions allowing physicians to provide psychedelic-assisted therapy (PAT) using psilocybin, lysergic acid diethylamide (LSD), or 3,4-methylenedioxy-N-methamphetamine (MDMA).ObjectivesThe study provided an overview of PAT as currently provided in Switzerland under the regulatory framework of the Federal Office of Public Health (FOPH).DesignSwiss PAT practices were examined using an anonymous survey of physicians providing PAT. Questions included physicians' backgrounds, training, therapeutic orientation, treatment protocols, patient characteristics, and perceived benefits.MethodsParticipants were recruited from PAT professional associations and the research team network. Forty-one physicians providing PAT under FOPH exemptions contributed to the survey.ResultsRespondents used PAT primarily for depression, anxiety, post-traumatic stress disorder (PTSD), and chronic pain. Most physicians practiced in private practices, private outpatient clinics or shared practices (82%), with a minority in hospitals (18%). The most reported labels when providing PAT were body-oriented (61%), psychodynamic (59%), and eclectic (54%) approaches. Respondents provided PAT using psilocybin (85%), MDMA (71%), and LSD (65.9%). Choice of first substance was linked to diagnosis, with physicians preferring psilocybin for depression (54%) and substance use disorder (46%) and MDMA for PTSD (86%) and anxiety disorders (54%). A total of 90% reported always playing music during psychedelic sessions. Loss of orientation in time and space, feeling too cold, anxiety, and nausea where the most frequent adverse effects of PAT. 95% had emergency medication available, on average used during 2.4% of sessions. Challenges included legal constraints, high patient expectations, and financial barriers. Group therapy was common, with 9% reporting providing only group sessions, 42% providing both individual and group settings, and 47% providing only individual sessions. Only 9% reported never using co-sitters.ConclusionThis study offers valuable insights into the methods and experiences of physicians providing PAT in a legal clinical context, giving insight into the considerable variety of clinical methods. Cultural and regulatory differences may limit generalizability.

raw_json:
{"europe_pmc_id":"42179908","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Implementing psilocybin-assisted therapy in palliative care settings: A survey of stakeholders.
journal: Palliative medicine
publication_date: 2026-06-30
doi: 10.1177/02692163261446141
pubmed_id: 42154482
source_url: https://pubmed.ncbi.nlm.nih.gov/42154482/
substance_tags: psilocybin
topic_tags: End-of-Life Distress,Clinical Trial,Observational Study,Safety
study_type: Clinical Trial
source_name: PubMed
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-02 06:54:10
raw_json: {"pubmed_id":"42154482"}
authors:
Plourde L, Chang SL, Nguyen O, Garel N, Farzin H, Stephan JF, Fallu JS, Dorval M, P3A Research Group

abstract:
While the adoption of psilocybin-assisted therapy for existential distress offers promising support for patients with life-threatening illnesses, implementing this intervention into palliative care settings presents significant real-world challenges.
To examine palliative care stakeholders' knowledge and attitudes regarding psilocybin-assisted therapy, and identify barriers and facilitators to its implementation.
We conducted a cross-sectional online survey between April 15 and December 18, 2024. The survey assessed perceived knowledge, attitudes, and perceived barriers and facilitators to the effective integration of psilocybin-assisted therapy into palliative care settings.
One hundred and twenty-one adults involved in palliative care (physicians, other healthcare professionals, caregivers, and managers) were recruited from Canada's four most populous provinces: Québec, Ontario, Alberta, and British Columbia.
Forty-three percent of stakeholders reported having good knowledge of psilocybin's potential benefits and risks. Attitudes towards psilocybin-assisted therapy were predominantly non-favourable (61%), yet varied across occupational groups (
Translating the potential of psilocybin-assisted therapy for existential distress from clinical trials into palliative care settings requires careful consideration and collaboration with stakeholders. Given the significant divergence in perspectives between clinical and non-clinical groups, tailored interprofessional education could help build shared understanding and support effective implementation. Being conducted in Canada, transferability to different regulatory frameworks may be limited.

keywords:
attitude of health personnel, hallucinogens, palliative care, psilocybin, surveys and questionnaires


authors: Yang KH, Rasmussen M, Bhatt K, Satybaldiyeva N, Kepner W, Moore AA, Bergstrom J.
publication_date: 2026-05-17
doi: 10.1080/02791072.2026.2673845
pubmed_id: 42152600
source_url: https://doi.org/10.1080/02791072.2026.2673845
substance_tags: psilocybin
topic_tags: Receptor Pharmacology,Observational Study
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:02
title:
Association Between Lifetime Hallucinogen Use and Valvular Heart Disease: Findings from the All of Us Research Program.

abstract:
Recent literature suggests potential associations between hallucinogen use and valvular heart disease (VHD) due to prolonged activation of serotonin 5-HT2B receptors, which may lead to valvular fibrosis - a condition also linked to drugs including fenfluramine and pergolide. Despite these concerns, epidemiological studies exploring this association are lacking. This exploratory analysis investigated associations between lifetime hallucinogen use and VHD using cross-sectional data from US adults with linked electronic health record data in the NIH All of Us Research Program who completed the Lifestyle survey. This survey included questions about lifetime hallucinogen use (lysergic acid diethylamide [LSD], mushrooms/psilocybin, 3,4-Methylenedioxymethamphetamine [MDMA]/ecstasy, ketamine, phencyclidine [PCP]). Multivariable logistic regression models examined the association between hallucinogen use and VHD, adjusting for sociodemographic factors and other confounding health conditions. Our sample comprised 286,842 adults (mean age 50.8 [SD16.7], 61.4% female, 60.6% White). Among them, 13.2% reported lifetime hallucinogen use. Individuals with lifetime hallucinogen use had lower unadjusted VHD prevalence compared to those without lifetime hallucinogen use (3.6% vs. 4.7%, p

raw_json:
{"europe_pmc_id":"42152600","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2026-05-17
doi: 10.1177/00048674261450797
pubmed_id: 42145135
source_url: https://doi.org/10.1177/00048674261450797
substance_tags: psilocybin
topic_tags: General
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:02
title:
Corrigendum to: "Psilocybin in the real world: Regulatory, ethical, and operational challenges in Australia's clinical landscape".

raw_json:
{"europe_pmc_id":"42145135","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Geller JA, Pacilio R, Downey AE, Ragnhildstveit A, Raymond-Flesch M, Knatz-Peck S, Gukasyan N.
publication_date: 2026-05-13
doi: 10.1007/s11920-026-01679-z
pubmed_id: 42128951
source_url: https://doi.org/10.1007/s11920-026-01679-z
keywords: Humans, Hallucinogens, Anorexia Nervosa, Adolescent, Psilocybin
substance_tags: psilocybin
topic_tags: Eating Disorders,Review Article,Adolescents,Safety
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:00
title:
Psilocybin-Assisted Therapy for Adolescent Anorexia Nervosa: Clinical Considerations and Emerging Models of Care.

abstract:
Purpose of reviewThere is growing evidence that psychedelics and associated treatment modalities may offer therapeutic benefits across a range of psychiatric conditions. Anorexia nervosa (AN), a serious and often treatment-resistant illness associated with significant morbidity and mortality, is one such condition for which psilocybin-assisted therapy (PAT) may hold promise.Recent findingsTo date, research on PAT for AN has focused primarily on adults, despite the fact that AN frequently begins in adolescence, and early age of onset portends poorer prognosis, including more severe AN, more lifetime psychiatric comorbidity, and greater life difficulties. Given these risks, an exploration of the theoretical potential of PAT for adolescent populations is warranted. Important considerations include biological implications, developmental stage, and consent. Adaptations to the current models of psilocybin-assisted therapy in studies of adults are proposed, and emerging models that address the unique challenges of these patients are discussed.

raw_json:
{"europe_pmc_id":"42128951","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Kwiatos N, Ossel S, Mutti FG.
publication_date: 2026-04-30
doi: 10.1002/cbic.202500898
pubmed_id: 42107106
source_url: https://doi.org/10.1002/cbic.202500898
keywords: Saccharomyces cerevisiae, Amines, Biocatalysis, Metabolic Engineering, Bulk Drugs
substance_tags: psilocybin
topic_tags: Mechanism of Action,Receptor Pharmacology,Review Article,Genomics
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:02
title:
Synthesis of Amines for Active Pharmaceutical Ingredients Using the Whole-Cell Factory Saccharomyces Cerevisae.

abstract:
Whole-cell biocatalysis offers a sustainable alternative to traditional chemical synthesis for producing pharmaceutically relevant, often chiral, amines and amino acids. Saccharomyces cerevisiae has emerged as a privileged microbial chassis due to its robustness, ease of genetic manipulation, and GRAS status. This concise review summarizes recent advances in metabolic and genetic engineering of S. cerevisiae for amine biocatalysis, focusing on strategies to overcome bottlenecks such as enzyme gene expression, cofactor regeneration, and precursor channeling. The first section covers state-of-the-art methods for engineered strain construction, including genomic editing, optimization of gene expression (copy number, promoters, terminators, codon usage), and metabolic engineering (pathway balancing, compartmentalization, cofactor supply, transport proteins, auxiliary enzymes, and enzyme targeting via signal peptides), all enhancing product yields and enabling complex amine synthesis. The central section critically discusses compound families accessible via engineered S. cerevisiae, including various amines, amino alcohols, and amino acids such as l-carnitine, ergothioneine, halogenated tryptamine, serotonin, psilocybin, spermidine, l-ornithine, and mycosporine derivatives. Bioproduction of complex alkaloids, such as tropine derivatives (hyoscyamine and scopolamine) and ergot alkaloids, is also reviewed. Finally, current challenges and future perspectives are outlined, highlighting the integration of systems and synthetic biology tools to establish S. cerevisiae as a scalable platform for industrial amine production.

raw_json:
{"europe_pmc_id":"42107106","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Inaugural year of regulated psilocybin services in Oregon: safety, motivations, and utilization.
authors: Yu F, Tafur J, Moreno F, Dahmer S.
publication_date: 2026-05-12
doi: 10.3389/fpsyt.2026.1777387
pubmed_id: 42233004
source_url: https://doi.org/10.3389/fpsyt.2026.1777387
substance_tags: psilocybin
topic_tags: Wellbeing,Observational Study,Safety,Adverse Events
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:00
abstract:
ImportanceThe Oregon Psilocybin Services (OPS) program is the first statewide, regulated framework for legal psilocybin in the U.S. Analyzing inaugural-year utilization and safety is essential for informing policy and equity monitoring.MethodsWe conducted a descriptive analysis of statewide aggregate data from the OPS Public Dashboard (January 1-December 31, 2025). Outcomes included service volume, client demographics, motivations, and acute adverse events.ResultsIn 2025, 5,935 clients participated in 5,375 sessions. Volume peaked in Q2 (n=1,758) before stabilizing in Q4 (n=1,358). Service tourism was significant, with 32.6% of participants residing outside Oregon. The largest segment was aged 35-49 (~40%); women (57.4%) and LGBTQ+ individuals (27.2%) represented substantial portions of the annual cohort. Racial diversity was limited, with White participants representing 84.1%-91.5% quarterly, while Hispanic/Latino (7.1%) and African American (2.1%) participation lagged. Adverse events were rare, with annual behavioral and medical rates of 2.42 and 2.79 per 1,000 sessions, respectively.DiscussionFull-year data indicate stabilized utilization by a predominantly midlife adult population. While the program successfully reaches sexual and gender minorities, racial disparities persist. High service tourism suggests significant socioeconomic barriers. These findings underscore the program's dual role as a wellness modality and a functional alternative for addressing mental health distress.

raw_json:
{"europe_pmc_id":"42233004","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: van der Vaart A, LaPratt J, Swartz K, Shoultz A, Lauterbach M, Suppes T, Sackeim HA, Aaronson ST.
publication_date: 2026-05-12
doi: 10.4088/jcp.26m16338
pubmed_id: 42138588
source_url: https://doi.org/10.4088/jcp.26m16338
substance_tags: psilocybin
topic_tags: Depression,Randomized Controlled Trial,Safety,Adverse Events
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:00
title:
Efficacy and Safety of a Single Dose of Psilocybin for Chronic Suicidal Ideation: An Open-Label Trial.

abstract:
Objectives: To evaluate the efficacy, safety, and durability of a single 25-mg dose of a proprietary, synthetic formulation of psilocybin with psychological support for reducing chronic suicidal ideation in a treatment-resistant population.Methods: This was an open-label, single-arm study with a 12-week follow-up conducted between March 2022 and May 2025. Twenty adults with chronic suicidal ideation, major depressive disorder (DSM-5), and ≥2 prior antidepressant treatment failures received a single 25-mg dose of psilocybin administered within a structured preparatory and integration psychotherapy protocol. The primary outcome was change from baseline in the Modified Scale for Suicidal Ideation (MSSI) at week 3. Secondary outcomes included change in MSSI at weeks 1 and 12 and change in Montgomery-Asberg Depression Rating Scale (MADRS) scores at weeks 1, 3, and 12. Outcomes were analyzed using 1-way repeated-measures analysis of variance with Bonferroni-adjusted pairwise comparisons.Results: Significant reductions in MSSI scores were observed from baseline to week 3 (primary end point: mean difference [MD] = 13.95; 95% CI, 8.63-19.27; P <.001; d = 1.73). Improvements were rapid and durable, with significant reductions at week 1 (MD = 15.10; P <.001; d = 2.11) and week 12 (MD = 13.00; P <.001; d = 1.46). By week 12, 70% (n=14) of participants achieved MSSI ≤2. MADRS scores showed similar significant reductions at all postbaseline time points (MD range: 17.55-20.50; all P <.001; d = 1.63-1.97). No serious adverse events occurred.Conclusions: In this open-label single-arm study of adults with chronic suicidal ideation and prior treatment failures, a single administration of psilocybin with psychological support was associated with rapid, large-magnitude, and durable reductions in suicidal ideation and depressive symptoms through 12 weeks. These preliminary findings support further evaluation in larger randomized controlled trials.Trial Registration: ClinicalTrials.gov Identifier: NCT05220410.

keywords:
Humans, Chronic Disease, Hallucinogens, Treatment Outcome, Adult, Middle Aged, Female, Male, Suicidal Ideation, Depressive Disorder, Treatment-Resistant, Psilocybin, Major Depressive Disorder

raw_json:
{"europe_pmc_id":"42138588","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2026-05-12
doi: 10.1192/bjo.2026.12000
pubmed_id: 42125778
source_url: https://doi.org/10.1192/bjo.2026.12000
substance_tags: psilocybin
topic_tags: Depression,Microdosing,Clinical Trial
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:02
title:
Microdosing psilocybin for major depressive disorder: study protocol for a phase II double-blind placebo-controlled randomised partial crossover trial - CORRIGENDUM.

authors:
Beidas Z, Ragnhildstveit A, Blackman A, Anderson T, Fewster E, Syed OA, Sobolenko V, Kanca IK, Son T, Farb N, Petranker R.

raw_json:
{"europe_pmc_id":"42125778","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Jóźwiak-Bębenista M, Stasiak A, Sienkiewicz M, Kwiatkowski P, Kowalczyk E.
publication_date: 2026-05-08
doi: 10.3390/ijms27104229
pubmed_id: 42196212
source_url: https://doi.org/10.3390/ijms27104229
substance_tags: psilocybin,psilocin
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:00
title:
Psilocybin in Older Adults: Therapeutic Opportunities in Inflammation-Driven Disorders of Aging-From Depression to Neurodegeneration.

abstract:
Aging is associated with chronic, low-grade inflammation ("inflammaging"), which contributes to neuropsychiatric and neurodegenerative disorders such as depression, Alzheimer's disease, and Parkinson's disease. Conventional pharmacotherapies often provide limited benefit in older adults and are further complicated by polypharmacy and drug-drug interactions. Psilocybin, a serotonergic psychedelic acting primarily as a partial agonist at the 5-HT2A receptor and currently undergoing accelerated clinical development, has emerged as a potential multimodal therapeutic agent addressing these challenges. Acting via its active metabolite psilocin, 5-HT2A receptor-mediated signaling modulates cortical glutamatergic transmission, enhances tropomyosin receptor kinase B/brain-derived neurotrophic factor (TrkB/BDNF) pathways, and modulates neuroimmune cascades (includingnuclear factor kappa B (NF-κB), with convergent systems-level effects such as reorganization of the default mode network. Human studies report acute reductions in TNF-α with variable effects on IL-6 and CRP, consistent with an immunomodulatory profile. Pharmacokinetically, psilocybin shows properties advantageous in geriatric care: rapid onset, short half-life, and predominant phase-II glucuronidation, reducing interaction risk. Controlled studies demonstrate rapid antidepressant and anxiolytic effects in major depressive disorder, treatment-resistant depression, and existential distress, with emerging feasibility signals in neurodegeneration. Together, these findings support the hypothesis that a time-limited, mechanism-based intervention may improve mood and cognition while attenuating inflammation. This review integrates current evidence on psilocybin's neuroimmune and pharmacokinetic mechanisms relevant to aging, outlining its potential role in inflammation-related disorders and highlighting the need for targeted studies in older adults, who remain underrepresented in psychedelic research.

keywords:
Animals, Humans, Neurodegenerative Diseases, Inflammation, Hallucinogens, Depression, Aging, Aged, Psilocybin

topic_tags:
Depression,Pharmacology,Mechanism of Action,Receptor Pharmacology,Default Mode Network,Aging,Inflammaging,Review Article,Older Adults,Treatment-Resistant Depression,Safety,Drug Interactions,Inflammation,Immune Function

raw_json:
{"europe_pmc_id":"42196212","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Exploring new avenues: Psychedelic-assisted therapy for young people.
authors: Vamvakopoulou IA, Nicholls D, Nutt DJ, Di Simplicio M.
publication_date: 2026-05-07
doi: 10.1002/bcp.70579
pubmed_id: 42101062
source_url: https://doi.org/10.1002/bcp.70579
substance_tags: psilocybin
topic_tags: Depression,Anxiety,PTSD,Wellbeing,Review Article,Observational Study,Adolescents,Safety
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:02
abstract:
Rates of mental illness in young people are increasing, whereas the development of novel mental health treatments has not significantly progressed. Psychedelic-assisted therapy, using substances such as psilocybin and 3,4-methylenedioxymethamphetamine (MDMA), has shown potential in the treatment of mental illnesses in the adult population, including depression, anxiety and post-traumatic stress disorder. Interest has been growing around the potential use of psychedelic-assisted therapy to treat mental illness in adolescents. We present here a comprehensive review of all research focusing on children and young people, from experimental research of the 50s to observational and retrospective research focusing on traditional and Western non-medical use. The limited available research so far suggests that psychedelics appear to be safe overall and may have the potential to improve mental wellbeing in young people. However, young people may be at more risk of experiencing anxiety, challenging experiences and ego dissolution, but more thorough clinical research is warranted. Moving forward, we suggest that psychedelic-assisted therapy for young people should be administered within a rigorous ethical framework, where education of both the young people and their families is incorporated. Family involvement should be considered as part of the therapeutic framework. Lastly, avenues within the psychedelic space should be considered for young people, like the use of lower doses (psycholytic approach), which might lower the potential risks that are seen with high doses.

raw_json:
{"europe_pmc_id":"42101062","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Forsyth D, Faraone N, Lamarre SG, Currie S.
publication_date: 2026-05-06
doi: 10.3389/fnbeh.2026.1767175
pubmed_id: 42182826
source_url: https://doi.org/10.3389/fnbeh.2026.1767175
substance_tags: psilocybin
topic_tags: Mechanism of Action,Safety,Drug Interactions
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:00
title:
The magic of mushrooms: psilocybin influences behavior in the mangrove rivulus fish, Kryptolebias marmoratus.

abstract:
Non-human models, including fish, are increasingly important for investigating how pharmacological agents such as hallucinogens influence behavior, physiology, and cellular processes. These models help to reveal underlying mechanisms and to support assessments of toxicological impact, efficacy, and safety. In this study, we used isogenic lineages of the amphibious mangrove rivulus (Kryptolebias marmoratus), an emerging model fish known for high activity and socially dynamic interactions. This species often display aggression towards conspecifics making it well-suited to study behavioral effects of low doses of the psychoactive compound, psilocybin. We determined whether psilocybin could induce calming effects and reduce social aggression and activity. We socially stimulated fish using pairs of size-matched fish from different isogenic lineages and compared baseline social behavior following a waterborne dose of psilocybin. Waterborne psilocybin treatment resulted in a significant decrease in activity levels and in the frequency of swimming bursts (an aggressive behavior) towards a conspecific fish from a different lineage, with modest alterations on other behaviors. Our results also revealed considerable intraspecific variation in the behavioral response of these homozygous fish, suggesting the effects of psilocybin were largely independent of genotype. This study demonstrates that psilocybin reduces aggression and activity in an emerging fish model, adding to the evidence supporting its potential as a therapeutic agent for future clinical translation.

raw_json:
{"europe_pmc_id":"42182826","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Human brain changes after first psilocybin use.
publication_date: 2026-05-04
doi: 10.1038/s41467-026-71962-3
pubmed_id: 42086570
source_url: https://doi.org/10.1038/s41467-026-71962-3
substance_tags: psilocybin
topic_tags: Depression,Brain Imaging,Aging,Wellbeing
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:00
authors:
Lyons T, Spriggs M, Kerkelä L, Rosas FE, Roseman L, Mediano PAM, Timmermann C, Oestreich L, Pagni BA, Zeifman RJ, Hampshire A, Trender W, Douglass HM, Girn M, Godfrey K, Kettner H, Sharif F, Espasiano L, Gazzaley A, Wall MB, Erritzoe D, Nutt DJ, Carhart-Harris RL.

abstract:
Psychedelics have robust effects on acute brain function and long-term behavior but whether they also cause enduring functional and anatomical brain changes is largely unknown. In an exploratory, placebo-controlled, within-subjects, electroencephalography (EEG), and magnetic resonance imaging (MRI) study in 28 healthy, entirely psychedelic-naive participants, anatomical and functional brain changes are detected from one-hour to one-month after a single high-dose (25 mg) of psilocybin. Increases in cognitive flexibility, psychological insight, and well-being are seen at one-month. Diffusion tensor imaging (DTI) done before and one-month after 25 mg psilocybin reveals decreased axial diffusivity bilaterally in prefrontal-subcortical tracts that correlate with decreases in brain network modularity (fMRI) over the same month. Enduring functional brain changes are largely absent, but network modularity change (numerical decrease) negatively correlates with well-being change (significant increase), in line with previous findings in depression. Increased cortical signal entropy (EEG) at 1- and 2-hours post-dosing predicts improved psychological well-being at one-month. Next-day psychological insight mediates the entropy to well-being relationship. All effects are exclusive to 25 mg psilocybin; no effects occur with a 1 mg psilocybin placebo.

keywords:
Brain, Humans, Hallucinogens, Magnetic Resonance Imaging, Electroencephalography, Adult, Female, Male, Young Adult, Diffusion Tensor Imaging, Psilocybin, Psychological Well-Being, Cognitive Flexibility

raw_json:
{"europe_pmc_id":"42086570","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Prevalence and Reasons for Microdosing Cannabis, Psilocybin, LSD, and MDMA Among U.S. Adults.
authors: Yang KH, Satybaldiyeva N, Kepner W, Friedman J, Ping S, Leas EC.
publication_date: 2026-05-03
doi: 10.1016/j.amepre.2026.108381
pubmed_id: 42092643
source_url: https://doi.org/10.1016/j.amepre.2026.108381
substance_tags: psilocybin
topic_tags: Chronic Pain,Microdosing,Observational Study
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:00
abstract:
IntroductionMicrodosing involves consuming low doses of psychoactive substances, typically between 1/5th and 1/20th of a recreational dose. Despite increasing public attention to cannabis and psychedelics amid evolving drug policies, epidemiologic data on microdosing remain limited.MethodsA cross-sectional, web-based survey (Characterizing the Epidemiology of Cannabidiol Use Survey) of 1,523 U.S. adults was conducted in October-November 2023 and analyzed in 2024-2025 using the Ipsos KnowledgePanel. Participants reported lifetime microdosing of cannabis, psilocybin, lysergic acid diethylamide (LSD), and 3,4-methylenedioxymethamphetamine (MDMA). Lifetime prevalence, frequency, and reasons for microdosing were assessed, along with associations with demographics, mental health, quality of life, and cannabis and psychedelic policy environments. Survey weights were applied to generate nationally representative estimates.ResultsCannabis was the most commonly microdosed substance (9.4%; 95% CI=8.0, 10.7; 24.1 million adults), followed by psilocybin (5.3%; 95% CI=4.3, 6.3; 13.7 million adults), LSD (4.8%; 95% CI=3.8, 5.9; 12.4 million adults), and MDMA (2.2%; 95% CI=1.5, 2.9; 5.7 million adults). Cannabis (41.2%; 95% CI=33.3, 49.5) was primarily microdosed for medical purposes (e.g., to manage pain), whereas psilocybin (66.6%; 95% CI=56.9, 75.1), LSD (59.2%; 95% CI=46.5, 70.8), and MDMA (86.0%; 95% CI=68.8, 94.5) were more commonly microdosed for recreational purposes (e.g., to get less high). Across all substances, lifetime microdose use was more prevalent among respondents reporting poorer mental health and among those residing in jurisdictions that permitted recreational cannabis use and had decriminalized psychedelic possession.ConclusionsDespite cannabis, psilocybin, LSD, and MDMA remaining illegal at the federal level, a considerable number of U.S. adults reported having microdosed these substances in their lifetime. Microdosing was associated with poorer mental health and was more common among respondents who lived in environments with fewer restrictions on the use of cannabis and psychedelics. As policy reforms continue to expand, the prevalence of microdosing may increase, making ongoing surveillance essential for evidence-based public health responses.

raw_json:
{"europe_pmc_id":"42092643","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Hajivalizadeh S, Farahmand K, Kazemzadeh K, Hajivalizadeh G, Shamabadi A.
publication_date: 2026-04-30
doi: 10.1002/cnr2.70587
pubmed_id: 42178235
source_url: https://doi.org/10.1002/cnr2.70587
substance_tags: psilocybin
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:02
title:
Pharmacotherapeutic Management of Depression in Patients With Cancer: A Review of Mechanistic and Clinical Evidence.

abstract:
BackgroundDepression is a prevalent comorbidity in cancer, yet conventional treatments show inconsistent efficacy. This review sought to provide a mechanism-based framework for managing cancer-related depression by exploring its unique pathophysiology and evaluating promising pharmacotherapies based on their alignment with these biological pathways. This narrative review synthesized evidence on promising pharmacotherapies based on their ability to target the core biological mechanisms of cancer-related depression, including pro-inflammatory cytokine activity, hypothalamic-pituitary-adrenal axis hyperactivity, serotonin pathway disruption via indolamine-2,3-dioxygenase activation, and glutamate excitotoxicity.Recent findingsInterventions directly targeting inflammation (e.g., celecoxib) and glutamate modulation (e.g., ketamine) demonstrated encouraging early evidence. The effect of ketamine can also be due to its anti-inflammatory properties. Atypical antidepressants, such as mirtazapine, and the serotonergic psychedelic psilocybin also showed promising but preliminary benefits. In contrast, conventional selective serotonin reuptake inhibitors and tricyclic antidepressants yielded conflicting results. Other agents, including the psychostimulant methylphenidate, showed utility for specific symptoms like fatigue.ConclusionA personalized, mechanism-informed approach targeting the core pathophysiological cascade of inflammation, hypothalamic-pituitary-adrenal axis hyperactivity, and glutamate excitotoxicity is essential for effectively managing depression in patients with cancer. This represents a necessary paradigm shift away from a one-size-fits-all treatment model.

keywords:
Pituitary-Adrenal System, Hypothalamo-Hypophyseal System, Humans, Neoplasms, Antidepressive Agents, Depression

topic_tags:
Depression,Mechanism of Action,Receptor Pharmacology,Aging,Review Article,Cancer Patients,Toxicity,Inflammation

raw_json:
{"europe_pmc_id":"42178235","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Silva MH.
publication_date: 2026-04-30
doi: 10.1002/bdr2.70048
pubmed_id: 42163018
source_url: https://doi.org/10.1002/bdr2.70048
substance_tags: psilocybin,psilocin
topic_tags: Mechanism of Action,Receptor Pharmacology,Safety,Toxicity
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:00
title:
New Approach Methodologies and Open Access Tools Help Characterize Risks for DART, DNT, or Endocrine Effects From Exposure to Hallucinogens With Potential Pesticide Contaminants.

abstract:
BackgroundPsilocybe mushrooms (psilocybin/psilocin [PSI/PSC]) and ayahuasca (N,N-dimethyltryptamine [DMT]) are hallucinogenic serotonergic agonists. Pregnant and lactating women are frequently omitted from clinical studies; hence minimal developmental/reproductive/neurotoxicity (DART/DNT) and endocrine disruption (ED) data in humans are available. Hallucinogens contaminated with pesticides may have overlapping metabolic pathways affecting toxicity. An examination of potential adverse effects on pregnancy and development from exposure to hallucinogenic plants, hypothetically contaminated with organophosphates (OP) or organochlorines (OC), was performed using new approach methodologies (NAMs) and open access tools.MethodsCheminformatics Modules, Predicting Developmental Toxicity Potential Project, Toxicity Estimation Software Tool (TEST) using quantitative structure-activity relationships, Endocrine Disruptor Screening Program, California's Proposition 65 list, and ToxCast assays were investigated for DART/DNT and ED reported effects and/or predictions related to PSI/PSC, DMT, and sentinel pesticides (chlorpyrifos/chlorpyrifos-oxon and endosulfan). ToxCast data were inputs for Integrated Chemical Environment (ICE) PBTK adult and fetal models to generate adjusted human Administered Equivalent Doses (AdjAEDs) that were compared to regulatory dose ranges for hallucinogens and pesticides to assess model predictions.ResultsCheminformatics Modules, PregPred, and TEST-QSAR predicted that hallucinogens and pesticides have DART, DNT, and ED effects. No ToxCast data were reported for DMT and PSI was ToxCast inactive. PSC/pesticide overlapping metabolic pathways were CYP2C9 modulated by serotonin, thyroid hormones and sonic hedgehog, each associated with development. Clinical PSC and regulatory pesticide points of departure were generally within range of predicted fetal AdjAEDs.ConclusionsOpen access NAMs tools identified risks to fetal development from exposure to hallucinogens and pesticides.

keywords:
Humans, Hallucinogens, Pesticides, Risk Assessment, Quantitative Structure-Activity Relationship, Pregnancy, Female, Endocrine Disruptors

raw_json:
{"europe_pmc_id":"42163018","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Yngwe H, Plavén-Sigray P, Ekman CJ, Henje E, Berglund A, Tiger M, Beckman M, Lundberg J.
publication_date: 2026-04-30
doi: 10.1001/jamanetworkopen.2026.12589
pubmed_id: 42138922
source_url: https://doi.org/10.1001/jamanetworkopen.2026.12589
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Clinical Trial
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:00
title:
Short-Term and Late-Term Effects of Psilocybin on Symptoms in Major Depression: A Randomized Clinical Trial.

abstract:
ImportancePsilocybin has been proposed as a rapid-acting antidepressant (onset 6 weeks), but evidence from randomized clinical trials remains limited, particularly in the broader major depressive disorder (MDD) population.ObjectiveTo assess short-term and long-term antidepressant effects of psilocybin therapy in patients with MDD.Design, setting, and participantsThis double-blind, placebo-controlled randomized clinical trial of participants diagnosed with moderate to severe recurrent MDD was conducted at the Northern Stockholm Psychiatric Clinic between January 26, 2021, and February 19, 2024. Statistical analysis was performed from February 20, 2024, to June 20, 2025.InterventionsParticipants received a single dose of psilocybin (25 mg) or active placebo (niacin, 100 mg) and 5 psychotherapeutic support sessions during 17 days.Main outcomes and measuresThe primary end point was between-group difference in change in Montgomery-Åsberg Depression Rating Scale (MADRS) score from baseline to day 8. Secondary end points included MADRS scores on days 15, 42, and 365, as well as monthly self-reports (MADRS-S) of depressive symptoms, disability, quality of life, and anxiety throughout the 365-day follow-up.ResultsThe study included 35 participants (21 [60%] female; mean [SD] age, 41.0 [10.1] years) diagnosed with moderate to severe recurrent MDD, with 17 randomized to the psilocybin group and 18 to the niacin group. The study met its primary end point with a significant mean between-group difference (model estimated) in change in MADRS score on day 8 (-7.27; 95% CI, -12.89 to -1.65; P =.01) in favor of psilocybin. The between-group difference was significant also on days 15 (mean difference, -11.03; 95% CI, -16.65 to -5.42; P

keywords:
Humans, Hallucinogens, Antidepressive Agents, Treatment Outcome, Double-Blind Method, Psychiatric Status Rating Scales, Adult, Middle Aged, Female, Male, Psilocybin, Major Depressive Disorder

raw_json:
{"europe_pmc_id":"42138922","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


journal: Health technology assessment (Winchester, England)
publication_date: 2026-04-30
doi: 10.3310/gjhh0812
pubmed_id: 42116676
source_url: https://pubmed.ncbi.nlm.nih.gov/42116676/
keywords: ADHERENCE, ANOREXIA NERVOSA, ATTRITION, FEASIBILITY, OLANZAPINE, RECRUITMENT, SIDE EFFECTS
substance_tags: psilocybin
topic_tags: Eating Disorders,Randomized Controlled Trial,Healthcare Workers,Safety,Adverse Events
study_type: Randomized Controlled Trial
source_name: PubMed
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:20:34
raw_json: {"pubmed_id":"42116676"}
title:
Olanzapine for young people with anorexia nervosa: a synopsis of the main results from the OPEN open-label feasibility study.

authors:
Filiz ES, Stringer D, Kellermann V, Olive RR, Said O, Mutwalli H, Bektas S, Akkese MN, Ireland K, Beishon-Murley D, Khor JWT, Allman L, Kotze N, Carter B, Tyrrell-Bunge E, Rowlands K, Keeler JL, Ivin G, Simic M, Sually DS, Bentley J, Young AH, Madden S, Byford S, Landau S, Treasure J, Schmidt U, Nicholls D, Lawrence V, Himmerich H

abstract:
In clinical practice, olanzapine is commonly used in young people with anorexia nervosa, although the underpinning evidence-base is limited. However, its efficacy, tolerability, acceptability and adherence rate, and the patients', carers' and clinicians' views of olanzapine treatment are unclear. This synopsis article summarises the methods and results of the OPEN feasibility study, overarching the findings and drawing comprehensive conclusions from a quantitative feasibility outcome paper and two qualitative research papers.
The OPEN study assessed the feasibility of a future randomised controlled trial on olanzapine in young people with anorexia nervosa in an open-label, one-armed feasibility study. In this study, we aimed to include 55 patients with anorexia nervosa or atypical anorexia nervosa aged 12-24 who gained
Fifty-two people were pre-screened, 35 were eligible and 20 participants were recruited and started olanzapine. Of these, 15 continued olanzapine for ≥ 16 weeks. Participants experienced, on average, a decrease in their eating disorder psychopathology, and body weight and body mass index increased during treatment with olanzapine as an adjunct to treatment as usual. Important themes derived from semi-structured qualitative interviews with young people and their parents were: moving away from the illness towards recovery, evaluating information on olanzapine, consent and trust in shared decision-making and the ambivalence around recovery. The main themes expressed by clinicians included: acknowledging the concerns of young people with anorexia nervosa and their families, prioritising person-centred care, the limited service capacity and strict study eligibility criteria.
The study failed to meet the recruitment target and showed low adherence rates for treatment with olanzapine. Possible reasons for the recruitment difficulties and the low adherence rate include the high clinical workload of eating disorder services during and after the COVID-19 pandemic, the heterogeneity of eating disorder service setup across the country, and the reluctance of patients to agree to take olanzapine under the relatively restricted conditions of a clinical study.
A realistic time schedule for site-preparation, recruitment, treatment and follow-up, realistic recruitment targets and easy access to medical and laboratory examinations may improve the success of future feasibility studies and randomised controlled trials in this patient group.
The difficulties in conducting the OPEN study will inform the planning for future pharmacological and non-pharmacological studies in anorexia nervosa. Therefore, we developed a checklist with action points for the planning of pharmacological trials in eating disorders. Furthermore, novel pharmacological options such as typical and atypical psychedelic drugs (e.g. psilocybin and ketamine) might be more acceptable for people with anorexia nervosa as they do not have the side effect of immediate weight gain.
This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number NIHR130780.


title: Associations between psychedelic use and migraine history in Swedish twins.
authors: Simonsson O, Sun S, Wesseldijk LW, Ullén F, Osika W, Mosing MA
journal: Journal of psychopharmacology (Oxford, England)
publication_date: 2026-04-30
doi: 10.1177/02698811261449385
pubmed_id: 42113558
source_url: https://pubmed.ncbi.nlm.nih.gov/42113558/
keywords: LSD, migraine, psilocybin, psychedelics, twins
substance_tags: psilocybin
topic_tags: Headache / Migraine,Observational Study
study_type: Observational Study
source_name: PubMed
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:20:34
raw_json: {"pubmed_id":"42113558"}
abstract:
While psychedelics have shown initial promise in the treatment of migraine, experimental studies have relied on small and homogenous samples, which limit the reliability and generalizability of findings. These limitations underscore the complementary value of other research designs that leverage larger and more representative samples.
This cross-sectional study included three cohorts of twins from the Swedish Twin Registry and evaluated associations between psychedelic use and migraine history.
In this study, 50,726 twins answered questions related to the use of psychedelics. There were 1287 twins who reported psychedelic use, of whom 420 were monozygotic twins. While 271 twin pairs were discordant on psychedelic use, 40 twin pairs (16 male, 24 female) were discordant on both psychedelic use and migraine history. When restricting the analyses to monozygotic twins in the between-within logistic regression model, the between-pair association was significant, with pairs in which at least one twin reported psychedelic use showing lower odds of migraine history (adjusted odds ratio (aOR) = 0.50, = 0.041). The within-pair association was also significant, with twins who reported psychedelic use showing lower odds of migraine history compared to their co-twin (aOR = 0.38, = 0.008). Notably, subgroup analyses showed that these results were broadly the same when only males were included in the models, but no significant associations were observed in female-only models.
The findings from this twin study suggest that psychedelics may be linked to a lower likelihood of migraine, with potential differences by sex. This warrants further investigation and highlights the importance of sex-specific analyses in future studies.


title: Pilot Results for Psilocybin-Assisted Psychotherapy for Cocaine Use Disorder-A Critical Appraisal.
authors: Bonar EE.
publication_date: 2026-04-30
doi: 10.1001/jamanetworkopen.2026.11042
pubmed_id: 42096207
source_url: https://doi.org/10.1001/jamanetworkopen.2026.11042
substance_tags: psilocybin
topic_tags: Addiction
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:02
raw_json:
{"europe_pmc_id":"42096207","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin in the Treatment of Cocaine Use Disorder: A Randomized Clinical Trial.
publication_date: 2026-04-30
doi: 10.1001/jamanetworkopen.2026.11029
pubmed_id: 42096204
source_url: https://doi.org/10.1001/jamanetworkopen.2026.11029
substance_tags: psilocybin
topic_tags: Addiction,Clinical Trial
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:00
authors:
Hendricks PS, Lappan SN, Shelton RC, Lahti AC, Cropsey KL, Johnson MW, Bradley M, Simonsson O, Davis LL, Grossman DH, Ortiz CE.

abstract:
ImportanceCocaine use disorder is a serious public health problem and no medications have been proven effective for its treatment.ObjectiveTo evaluate psilocybin in the treatment of cocaine use disorder. It was hypothesized that psilocybin, compared with placebo, would yield a higher percentage of cocaine abstinent days, a greater likelihood of complete abstinence from cocaine, and a greater latency to first cocaine lapse through 180 days after end of treatment.Design, setting, and participantsRandomized, quadruple-blind, placebo-controlled clinical trial at a major medical research center in the Deep South of the US. Participants were individuals with cocaine use disorder who were motivated to quit and without significant comorbidities, recruited between May 2015 and August 2023 with data collection completed in May 2024.InterventionsParticipants were randomized (1:1) to receive a single oral dose of psilocybin (25 mg per 70 kg of body weight) or active placebo (100 mg diphenhydramine). All participants received manualized psychotherapy that incorporated cognitive-behavioral treatment approximately 1 month before and 1 month after an all-day investigational drug treatment session.Main outcomes and measuresPercentage of cocaine abstinent days, rates of complete cocaine abstinence, and time to first cocaine lapse through 180 days after end of treatment, assessed by timeline followback interview and confirmed with urinalysis. Hypotheses were formulated before data collection and analyses followed intention-to-treat principles.ResultsOf the 40 participants, 33 (82.5%) were men, the median (IQR) age was 50.0 (43.8-56.0) years, 33 (82.5%) were Black, and 7 (17.5%) were White. Most participants had lower socioeconomic status, with 26 participants (65%) having an annual income of $20 000 or less. Four participants were lost to follow-up, resulting in 36 participants who completed assessments through 180 days after end of treatment. Psilocybin recipients had a higher percentage of cocaine abstinent days (β = 28.95; 95% CI, 18.22-39.67; P

keywords:
Humans, Cocaine-Related Disorders, Treatment Outcome, Adult, Middle Aged, Female, Male, Psilocybin, Cognitive Behavioral Therapy

raw_json:
{"europe_pmc_id":"42096204","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Effects of psychedelic use on authoritarian attitudes revisited.
authors: Simonsson O, Lyons T, Marks J, Kettner H, Roseman L, Haijen E, Kaelen M, Carhart-Harris R.
publication_date: 2026-05-01
doi: 10.1177/02698811261443677
pubmed_id: 42068187
source_url: https://doi.org/10.1177/02698811261443677
substance_tags: psilocybin
topic_tags: Depression,Observational Study,Healthy Volunteers
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:01
abstract:
BackgroundPrevious research suggests that psychedelics may, under certain conditions, decrease authoritarian attitudes, but larger and more rigorously designed studies are needed to confirm these findings.AimsWe aimed to examine the effects of psychedelic use on authoritarian attitudes.MethodsUsing data from three separate studies with different designs and populations, we investigated the relationship between psychedelic use and authoritarian attitudes. Study 1 was a naturalistic observational study with participants who planned to use psychedelics at their own initiative, Study 2 was a single-arm study with healthy volunteers who received psilocybin, and Study 3 was a randomized, controlled trial with patients diagnosed with depression who received psilocybin or escitalopram.ResultsAcross the three studies, results showed no significant changes in authoritarian attitudes after psychedelic use.ConclusionsContrary to previous research, the latest evidence is not compelling that psychedelic use influences authoritarian attitudes in a reliable direction. Future research should recruit larger and more diverse samples, collect additional context-related data, and also investigate political outcomes other than authoritarian attitudes.

raw_json:
{"europe_pmc_id":"42068187","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Pharmacotherapy in Disorders of Consciousness: A Mechanism-Based Review.
authors: Gillet A, Geron C, Vitello MM, Lejeune N.
publication_date: 2026-03-23
doi: 10.1007/s40263-026-01274-z
pubmed_id: 41876835
source_url: https://doi.org/10.1007/s40263-026-01274-z
keywords: Animals, Humans, Consciousness Disorders, Dopamine Agents, GABA Agents
substance_tags: psilocin
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:01
abstract:
Disorders of consciousness pose major therapeutic challenges owing to the complexity of underlying brain dysfunctions. Current pharmacological interventions explored in disorders of consciousness target distinct molecular systems, including dopaminergic modulators (amantadine, levodopa, apomorphine, bromocriptine, selegiline, methylphenidate, and modafinil), GABAergic agents (zolpidem and baclofen), and other neuromodulatory compounds acting on glutamatergic, opioid, or serotonergic receptors (ketamine, remifentanil, and psilocin). These treatments aim to modulate disrupted neural circuits, including the mesocircuit, a thalamocortical-striatal network critically involved in consciousness and motor control. This review explores the pathophysiological mechanisms underlying disorders of consciousness and the pharmacological profile of these agents. It summarizes reported clinical improvements and discusses determinants of therapeutic response, highlighting the role of biomarkers derived from neurophysiological and neuroimaging assessments. Safety profiles associated with these treatments are also critically evaluated to guide clinical decision making. By integrating current knowledge on pharmacological modulation of key neural systems, including dopaminergic and GABAergic pathways, this article provides a comprehensive framework for understanding treatment strategies in disorders of consciousness.

topic_tags:
Addiction,Brain Imaging,Mechanism of Action,Receptor Pharmacology,Consciousness,Biomarkers,Aging,Review Article,Safety

raw_json:
{"europe_pmc_id":"41876835","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Trip killers: Addressing a critical knowledge gap in psychedelic research.
authors: O'Mahony B, Harrington C, Harkin A, Lally N
journal: Journal of psychopharmacology (Oxford, England)
publication_date: 2026-04-30
doi: 10.1177/02698811261431056
pubmed_id: 41869862
source_url: https://pubmed.ncbi.nlm.nih.gov/41869862/
keywords: 5-HT2A, LSD, antipsychotics, bad trips, psilocybin, psychedelic
substance_tags: psilocybin
study_type: Review Article
source_name: PubMed
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:20:34
raw_json: {"pubmed_id":"41869862"}
abstract:
Psychedelic drugs are increasingly under investigation as potential therapeutic agents for mental health conditions and are being increasingly used recreationally. Psychedelic use may result in an episode of intense psychological distress, commonly referred to as a "bad trip." Bad trips represent a potentially volatile, erratic, and dangerous situation, which may, in extreme cases, require presentation to accident and emergency departments and psychiatric hospital admission. Managing such cases requires careful consideration, with priority given to non-pharmacological strategies. When these measures prove insufficient, an alternative approach may be necessary, one that can effectively attenuate or terminate the psychedelic state and restore psychological stability. Despite clinical relevance, there is no systematic evaluation of pharmacological interventions to terminate such experiences. This review identifies and critically appraises candidate medications with potential utility as abortive agents, including serotonin antagonists, drugs for psychosis, and select drugs for anxiety and depression. We review these agents, their mechanisms of action, pharmacokinetics, safety profiles, and applicability in acute care settings. Binding strength at the molecular level, potency to functionally block receptor-mediated effects, and lack of side effects are key considerations. We conclude by proposing a provisional framework for the pharmacologic management of adverse psychedelic experiences and highlight key priorities for future research.

topic_tags:
Depression,Anxiety,Pharmacology,Mechanism of Action,Receptor Pharmacology,Aging,Review Article,Safety,Adverse Events


title: Psychological support in psychedelic-assisted therapy clinical trials: A systematic review.
authors: Brusky B, M'Bailara K, Alla F, Barrault M.
publication_date: 2026-03-19
doi: 10.1177/02698811261424204
pubmed_id: 41859988
source_url: https://doi.org/10.1177/02698811261424204
substance_tags: psilocybin
topic_tags: Clinical Trial,Systematic Review,Review Article,Healthcare Workers,Safety
study_type: Systematic Review
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:03
abstract:
RationaleThe nature and role of the psychological support provided in psychedelic-assisted treatments for psychiatric disorders are currently the object of debate. How this support is conceptualized-as a vector for therapeutic change or framework for risk minimization-has far-reaching consequences in terms of how these treatments should be regulated, delivered, and studied.ObjectivesTo determine whether psychological interventions in psychedelic trials meet accepted definitions of psychotherapy using a common factors framework. We assess whether self-described psychedelic-assisted psychotherapies align with psychotherapy criteria and whether trials where support is not defined as psychotherapy nonetheless embed psychotherapeutic elements.MethodsFollowing Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched PubMed and PsycINFO in January 2024 for all available clinical trials of psilocybin, MDMA, or lysergic acid diethylamide reporting any psychological support. Articles were assessed against a 4-item common factors framework.ResultsWe screened 224 records, reviewed 52 full-text documents, and included 29 clinical trials (449 patients). Of the 29 trials, 69% met all 4 factors. Of the 19 psychotherapy-labeled trials, 84% met all 4 factors. Of the 10 non-psychotherapy-labeled studies, 40% met 4 factors.ConclusionsFindings indicate that the psychological interventions in most therapeutic psychedelic trials qualify as psychotherapy. We highlight the clinical implications in terms of clinician training and treatment timeframe. We emphasize the ethical imperative to measure and address the intervention complexity inherent to psychedelic trials, to optimize clinical outcomes and safeguard patients.

raw_json:
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title: Enlightenment in a Pill-Testing the Efficacy of Psilocybin.
authors: Hudson JI, Pope HG.
publication_date: 2026-04-30
doi: 10.1001/jamapsychiatry.2026.0070
pubmed_id: 41848717
source_url: https://doi.org/10.1001/jamapsychiatry.2026.0070
substance_tags: psilocybin
topic_tags: General
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:01
raw_json:
{"europe_pmc_id":"41848717","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2026-04-30
doi: 10.1001/jamapsychiatry.2026.0132
pubmed_id: 41848690
source_url: https://doi.org/10.1001/jamapsychiatry.2026.0132
substance_tags: psilocybin
topic_tags: Depression,Clinical Trial,Treatment-Resistant Depression,Safety,Adverse Events
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:00
title:
Efficacy and Safety of Psilocybin in Treatment-Resistant Major Depression: The EPISODE Randomized Clinical Trial.

authors:
Mertens LJ, Koslowski M, Betzler F, Brand M, Evens R, Kärtner L, Jungaberle A, Jungaberle H, Majic T, Schmitz CN, Ströhle A, Scharf D, Spangemacher M, Wolff M, Assadi Z, Bahri S, Becher L, Färber LV, Kirchen N, Kulakova E, Kunz L, Meijer A, Rohrmoser B, Wellek S, Berger MM, Gründer G.

abstract:
ImportancePsilocybin shows promise in treating depression, although limitations of previous research warrant further research.ObjectiveTo investigate the efficacy and safety of oral psilocybin, 25 mg, with adjunct psychotherapy in treatment-resistant depression (TRD).Design, setting, and participantsThis was a 2-center, triple-blinded (investigator, participant, rater), phase 2b, active placebo-controlled randomized clinical trial. Participants were randomized to 4 groups in ratios 2:2:1:1, receiving 2 doses 6 weeks apart (week 0, week 6) as follows: (1) placebo (nicotinamide, 100 mg) then psilocybin, 25 mg; (2) psilocybin, 5 mg, then 25 mg; and (3) psilocybin, 25 mg, then 5 mg or psilocybin, 25 mg, twice embedded in psychotherapeutic sessions. Participants aged 25 to 65 years with TRD and withdrawn from antidepressant medication were recruited predominantly from 2 outpatient settings in Germany. Study data were analyzed from April 2024 to November 2025.InterventionsOral synthetic psilocybin, 25 mg; psilocybin, 5 mg; or nicotinamide, 100 mg administered with psychotherapeutic sessions.Main outcomes and measuresThe primary end point was treatment response (≥50% reduction on the Hamilton Rating Scale for Depression [HAMD17]) at week 6 before the second dose. Key secondary end points were response on the Beck Depression Inventory II (BDI-II) and mean change from baseline on the HAMD17 and BDI-II at week 6.ResultsA total of 144 participants (mean [SD] age, 42.6 [10.8] years; 85 male [59.0%]) were randomized, and 142 were included in the primary efficacy analysis: psilocybin, 25 mg (n = 47), psilocybin, 5 mg (n = 48), and nicotinamide (n = 47). Response rates on the primary end point were 17.0% in the group receiving psilocybin, 25 mg; 12.5% in the group receiving psilocybin, 5 mg; and 10.6% in the group receiving nicotinamide. The first hierarchical comparison was nonsignificant (psilocybin, 25 mg vs nicotinamide, adjusted odds ratio [OR], 1.73; 95% CI, 0.53-6.23; P =.19; 1-sided α P =.03); consequently, further formal testing was not performed. Analyses of key secondary end points (mean changes from baseline on HAMD17 and BDI-II) provided exploratory evidence of a clinically meaningful effect of psilocybin, 25 mg. Psilocybin, 25 mg, was linked to adverse events, predominantly acutely, and was associated with higher reports of suicidal ideation on dosing days (4% vs 1%-2% in comparator conditions). Two serious adverse reactions were reported after psilocybin, 25 mg, including 1 case of hallucinogen persisting perception disorder.Conclusion and relevanceIn this randomized clinical trial, psilocybin, 25 mg, with adjunct psychotherapy, was associated with a clinically meaningful reduction in depressive symptoms in individuals with TRD, although findings did not show a significant effect on the primary outcome. The treatment was well tolerated by most participants, although safety signals were observed. While overall this constituted an inconclusive trial, these results add to the existing evidence on the potential of psilocybin treatment for depression.Trial registrationClinicalTrials.gov Identifier: NCT04670081.

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

raw_json:
{"europe_pmc_id":"41848690","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Moreno FA, Allen KE, Wiegand CB, Dunne R, Prickett JI, Bayze B, Allen JJB.
publication_date: 2026-03-12
doi: 10.1177/02698811261424214
pubmed_id: 41825921
source_url: https://doi.org/10.1177/02698811261424214
substance_tags: psilocybin
topic_tags: OCD,Receptor Pharmacology,Clinical Trial,Safety,Adverse Events
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:00
title:
A randomized clinical trial of repeated doses of psilocybin for the treatment of obsessive-compulsive disorder.

abstract:
BackgroundCurrent treatments for obsessive-compulsive disorder (OCD), including serotonin reuptake inhibitors and cognitive-behavioral therapy, are often insufficient. Psilocybin, a 5HT2a agonist psychedelic, has shown promise for treating OCD, but rigorous evidence is still needed.AimsThis randomized clinical trial evaluated safety, tolerability, and benefit of multiple psilocybin doses in OCD patients.MethodsFifteen participants were randomized to receive 4 weekly sessions of high-dose (300 µg/kg), low-dose (100 µg/kg) psilocybin, or active placebo (lorazepam) in a double-blind Phase 1 (n = 5 per condition), followed by four additional high-dose sessions (single-blind Phase 2). OCD severity was assessed with the Yale-Brown Obsessive Compulsive Scale (YBOCS) following each session, and prospectively for 6 months. Safety was evaluated via adverse event systematic assessment, suicide severity rating, and psychosis screening.ResultsPsilocybin was generally well-tolerated, with no serious adverse events, or psychotic symptoms, and no significant changes in suicide severity scores. Psilocybin but not placebo significantly reduced YBOCS scores. At the end of 8-week treatment, after participants had received at least four high doses of psilocybin, 73.3% were responders (⩾35% reduction in YBOCS scores), with 40% in remission. These effects diminished but remained substantial at 6 months. Post hoc analysis of cumulative dosing correlated with YBOCS score reductions at the end of treatment.ConclusionsAdministration of up to eight doses of psilocybin in a clinical research setting appears to be safe and potentially effective for patients with OCD. Larger trials are needed to further support efficacy and refine treatment protocols.Clinical trial registrationClinicalTrials.gov ID NCT03300947.

raw_json:
{"europe_pmc_id":"41825921","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Montoy JCC, Wang RC, Coker AR, Anderson BT.
publication_date: 2026-02-19
doi: 10.1016/j.drugalcdep.2026.113059
pubmed_id: 41795251
source_url: https://doi.org/10.1016/j.drugalcdep.2026.113059
substance_tags: psilocybin
topic_tags: Observational Study,Adolescents,Drug Interactions
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:01
title:
Trends in first-time psychedelic and other hallucinogen use in the United States: Results from the National Survey on Drug Use and Health.

abstract:
Background and aimsPsychedelic drug use is increasing due in part to local legislative reforms. Understanding the patterns of first-time psychedelic drug use is imperative for informing consumers, healthcare providers, and policy makers.Design setting and participantsThe National Survey on Drug Use and Health (NSDUH) is a repeated cross-sectional nationally representative survey of civilians aged 12 and older. Use estimates are presented for 2002-2019 and 2021-2023; regression analyses did not span 2020 due to data incompatibility.MeasurementsPrimary analysis variables were binary indicators for a) lifetime use of hallucinogens (LSD, psilocybin, and MDMA) and b) first-time use of hallucinogens in the past year.FindingsAmong 1,005,421 respondents from 2002 to 2019 the prevalence of first-time use of any hallucinogen in the past year was 0.71 %; among 173,808 respondents from 2021 to 2023 0.79 % reported new hallucinogen use. From 2002-2019, an average of 0.39 % of participants used MDMA for the first time; 0.28 % used psilocybin for the first time; and 0.18 % used LSD for the first time each year. First-time use of any hallucinogen increased from 2002 to 2019 at an average odds ratio (OR) 1.009 (95 % confidence interval (CI) 1.001-1.016). New use varied by age group, with the age cohort x year interaction showing a decrease among the 12-17 age cohort (OR0.96 (95 %CI0.96-0.97)) and an increase among the 65 + cohorts (OR1.56 (95 %CI and 1.02 (95 %CI1.01-1.03), respectively). New LSD use increased (OR per additional year 1.08, 95 % CI1.07-1.09). Similar increases were not observed for psilocybin, MDMA, or hallucinogens overall. For 2021-2023, there was no change in new use of hallucinogens (OR0.97 [95 %CI0.86-1.08]).ConclusionsFirst-time psychedelic and hallucinogen increased only slightly over the period from 2002 to 2019 though there were notable age-group and substance-specific trends: new use generally decreased among adolescents and increased in among those aged 65 and older. Trends from 2021 to 2023 likewise did not suggest changes in overall new use, but continue to show changing patterns of use across substances and age groups.

keywords:
Humans, Substance-Related Disorders, N-Methyl-3,4-methylenedioxyamphetamine, Lysergic Acid Diethylamide, Hallucinogens, Health Surveys, Prevalence, Cross-Sectional Studies, Adolescent, Adult, Aged, Middle Aged, Child, United States, Female, Male, Young Adult, Psilocybin

raw_json:
{"europe_pmc_id":"41795251","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Courtes AC, Myers B, Daly N, Jones G, Soares JC, Zarate CA, Machado-Vieira R.
publication_date: 2026-02-24
doi: 10.1016/j.genhosppsych.2026.02.011
pubmed_id: 41762772
source_url: https://doi.org/10.1016/j.genhosppsych.2026.02.011
substance_tags: psilocybin
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:00
title:
Advancing cancer neuroscience through stress modulation: Interdisciplinary potential of psilocybin and ketamine.

abstract:
Psychological stress not only undermines quality of life for people with cancer but also fuels tumor growth. Emerging evidence from the nascent field of cancer neuroscience suggests that adrenergic signaling from direct tumor-neuron interactions drives cancer progression, resistance to treatment, and worse outcomes. Cancer neuroscientists are increasingly seeking to repurpose psychoactive medications (e.g., β-blockers and others) to augment primary cancer therapies. Preclinical models reveal that psychological stress can be a key activator of the sympathetic pathways that promote pathological tumor-neuron crosstalk. However, conventional antidepressants/anxiolytics used to address psychological distress are often less effective in this population. Conversely, while sample sizes are limited, psilocybin has achieved 60-80% long-term remission of cancer-related depression and anxiety and peri-palliative ketamine studies demonstrate rapid but short-lived symptom control. In preclinical models these agents appear to normalize hypothalamic-pituitary-adrenal (HPA) axis function while upregulating neurotrophic factors, mechanisms which putatively promote stress reductions and resilience. In this review, we propose that this neuroplastic recalibration may reduce sustained adrenergic tone, thereby interrupting the stress-driven tumor-neuron signaling that accelerates cancer progression. Integrating these rapid agents into oncology practice could thus disrupt maladaptive adrenergic signaling, enhance treatment adherence, and ultimately improve survival. Hospital-based psychiatrists are uniquely positioned to lead this effort by collaborating with oncologists, embedding biomarker-rich clinical trials, and monitoring both psychiatric and tumor-neuron interaction metrics. Advancing interdisciplinary research with ketamine and psilocybin will clarify whether targeting systemic stress indices represents a cancer-relevant endpoint beyond psychological symptom relief itself, while advancing research in cancer neuroscience mechanisms to improve oncologic outcomes.

keywords:
Humans, Neoplasms, Ketamine, Hallucinogens, Antidepressive Agents, Stress, Psychological, Psilocybin

topic_tags:
Depression,Anxiety,End-of-Life Distress,Mechanism of Action,Biomarkers,Resilience,Clinical Trial,Review Article,Animal Study,Cancer Patients,Drug Interactions

raw_json:
{"europe_pmc_id":"41762772","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2026-02-12
doi: 10.1016/j.psychres.2026.117010
pubmed_id: 41747432
source_url: https://doi.org/10.1016/j.psychres.2026.117010
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Clinical Trial,Healthy Volunteers
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:02
title:
Trip sitting or just sitting? Session facilitators substantially influence psychedelic experiences in clinical trials but not in healthy ones.

authors:
Goldy SP, Sepeda ND, Hilbert SN, Bari BA, Garcia-Romeu A, Gukasyan N, Barrett FS, Yaden DB, Nayak SM.

abstract:
Psychedelics' characteristic acute subjective effects predict therapeutic benefits, such as decreases in depression and anxiety. Thus, optimizing treatment involves better understanding which factors shape subjective effects. Session facilitators, who support participants before, during, and after psychedelic administration sessions, form an important part of the setting of these experiences. Yet, the extent to which session facilitators influence participants' acute subjective effects is unknown. To address this gap, we analyzed data from 9 psilocybin administration studies involving 298 participants, 670 dosing sessions, and 60 facilitators-the largest dataset of its kind. Using multilevel models, we examined whether facilitators contributed to variance in participants' acute subjective effects. Results showed that facilitators accounted for negligible variance (0.8 %) in healthy volunteers, but greater variance in clinical samples (13.6 %), after controlling for study and participant differences. These findings reveal that facilitators may play a clinically meaningful role in shaping psychedelic treatment outcomes in patient populations, relative to non-patients, comparable to or exceeding therapist effects in traditional psychotherapy (∼8 %). These results have direct implications for clinical trial design, training protocols, and the implementation of psychedelic treatments as they continue to scale.

keywords:
Humans, Hallucinogens, Psychotherapy, Adult, Middle Aged, Female, Male, Clinical Trials as Topic, Young Adult, Psilocybin

raw_json:
{"europe_pmc_id":"41747432","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2026-02-04
doi: 10.1177/02698811251413490
pubmed_id: 41645048
source_url: https://doi.org/10.1177/02698811251413490
substance_tags: psilocybin
topic_tags: Depression,Clinical Trial,Healthcare Workers,Safety
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:03
title:
Challenges with clinical trial participants in studies with classical psychedelics: A position statement from the National Network of Depression Centers' task group on psychedelics and related compounds.

authors:
Lewis BR, Reid MJ, Novick AM, Byrne K, Niciu MJ, Fonzo GA, Meyer TD, Feifel D, El-Mallakh RS, Soares J, Suppes T, Barrett FS.

abstract:
RationaleClassical psychedelics-a broad class of compounds that include psilocybin, lysergic acid diethylamide, dimethyltryptamine, and mescaline-have shown significant promise for the treatment of mental health conditions in recent clinical trials. Organizations such as the National Network of Depression Centers (NNDCs) can play a pivotal role in uniting researchers and clinicians working in this field to explore and synthesize existing evidence as well as characterize emerging challenges.ObjectivesWe outline several categories of challenges that have emerged in the context of clinical trials with psychedelic drugs, drawing from our collective empirical observations as well as the extant literature. While these challenges have been presented in the context of clinical trial environments, many of them are likely to persist if and when psychedelic treatments become approved and are implemented in psychiatric clinical practice.ResultsWe describe four categories of challenges in the context of clinical trial participants-(1) treatment nonresponse, (2) expectancy effects and functional unblinding, (3) post-session psychological difficulties, and (4) contagion effects-and provide management strategies for study teams to mitigate associated risks.ConclusionsClassical psychedelics show therapeutic promise as mental health treatments. Studying them properly presents unique and unprecedented challenges that require researchers to develop sophisticated strategies to navigate nonresponse, expectancy effects, functional unblinding, post-session psychological issues, and possible contagion effects to responsibly advance this field. The NNDC and similar organizations are well-positioned to guide best practices and ensure the responsible advancement of this promising field.

raw_json:
{"europe_pmc_id":"41645048","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Kerr-Gaffney J, Myrtle S, Askari F, Bird C, Modlin NL, Young AH, Rucker J.
publication_date: 2026-01-25
doi: 10.1177/02698811251408769
pubmed_id: 41588876
source_url: https://doi.org/10.1177/02698811251408769
substance_tags: psilocybin
topic_tags: Consciousness,Wellbeing,Personality Change,Clinical Trial,Healthy Volunteers
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:00
title:
Effects of psilocybin on personality, psychiatric symptoms, and values: Exploring mediating effects of the acute psychedelic experience.

abstract:
BackgroundChanges in well-being, personality, and personal values have been documented post-psilocybin; however, evidence from placebo-controlled trials is limited.AimsTo examine the effects of psilocybin versus placebo on psychiatric symptoms, personality, and personal values in healthy participants. Potential mediators were also explored.MethodsThis secondary analysis used data from a phase I, double-blind, randomised, placebo-controlled trial testing a single dose of 10 mg (n = 30) or 25 mg psilocybin (n = 30) versus an inert placebo (n = 29) in 89 healthy participants. Effects of psilocybin on personality (Neo Five-Factor Inventory; NEO-FFI), psychiatric symptoms (Symptom Checklist-90; SCL-90), and values (Life Changes Inventory; LCI) at short- (day 8) and long-term follow-up (day 85) were analysed using mixed-effects models. Group differences in cognitive flexibility (Intra-Extra Dimensional Set Shift task; IED) at day 8 were analysed using a Kruskal-Wallis test. Potential mediating effects of the acute psychedelic experience (Five-Dimensional Altered States of Consciousness Questionnaire; 5D-ASC) were explored.ResultsNo between-group differences were found on the NEO-FFI, SCL-90, or IED. Both psilocybin groups showed greater LCI absolute change scores at both follow-up points compared to placebo. The 5D-ASC oceanic boundlessness subscale partially mediated these changes. Oceanic boundlessness also fully or partially mediated differences across several LCI subscales, and auditory alterations mediated differences on one subscale.ConclusionsThe acute psychedelic experience, namely oceanic boundlessness and, to a lesser extent, auditory alterations, mediates self-reported changes in values in healthy volunteers. Findings from this exploratory study are tentative and should be replicated in larger samples.

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authors: Domi A, Lucente E, Cadeddu D, Bengtsson N, Smedler E, Adermark L.
publication_date: 2026-01-20
doi: 10.1016/j.neuropharm.2026.110854
pubmed_id: 41577180
source_url: https://doi.org/10.1016/j.neuropharm.2026.110854
substance_tags: psilocybin,psilocin
topic_tags: Depression,Neuroplasticity,Mechanism of Action,Receptor Pharmacology,Animal Study,Drug Interactions
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:00
title:
Psilocin mediates long-term synaptic depression in the prelimbic cortex through 5-HT2A receptor-independent mechanisms.

abstract:
Psilocybin is a naturally occurring psychedelic compound with potential antidepressant effects. Although it has long been used by humans, primarily for recreational purposes, the molecular mechanisms underlying its actions remain incompletely understood. Here, we examined the acute effects of psilocin, the active metabolite of psilocybin, on excitatory neurotransmission in the prefrontal cortex (PFC). Slice electrophysiological whole-cell and field potential recordings were conducted in the rat prelimbic cortex during bath application of psilocin. We observed a sex-independent long-term synaptic depression (LTD) of presynaptic origin. This effect was independent of 5-HT2A and metabotropic glutamatergic receptor group 2 and mediated through enhanced GABAergic tone. The effect was partially inhibited by 5-HT1A receptor antagonist and completely blocked in slices pre-treated with the neuronal receptor tyrosine kinase 2 (TrkB) receptor antagonist ANA-12. These findings suggest that psilocin exerts a complex modulatory influence on excitatory neurotransmission in the prelimbic PFC, involving GABAergic and serotonergic interactions, and producing sustained alterations in synaptic activity that persist beyond drug exposure. Psilocin-induced LTD, independent of 5-HT2A receptor activation, may be associated with the reduced prefrontal connectivity reported in humans after psilocin administration and could have implications for cognitive function.

keywords:
Prefrontal Cortex, Animals, Rats, Rats, Sprague-Dawley, Receptor, Serotonin, 5-HT2A, Hallucinogens, Excitatory Postsynaptic Potentials, Male, Long-Term Synaptic Depression, Psilocybin

raw_json:
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authors: Mills L, Rossell SL, Carruthers SP.
publication_date: 2026-01-19
doi: 10.1016/j.jad.2026.121220
pubmed_id: 41571194
source_url: https://doi.org/10.1016/j.jad.2026.121220
keywords: Humans, Hallucinogens, Depression, Bipolar Disorder, Social Media, Psilocybin, Mania
substance_tags: psilocybin
topic_tags: Depression,Safety
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:00
title:
Insights into psilocybin use among people with bipolar disorder: A thematic analysis of Reddit posts.

abstract:
Psilocybin has been reported to decrease depression symptoms among individuals with bipolar disorder (BD), but has also been associated with reports of mania, psychosis and increased depression. With increasing recreational use of psilocybin, and the potential for psilocybin to be used as a treatment for depression, a better understanding of the risks and benefits of this psychedelic among individuals with BD is warranted. Individuals have used social media sites like Reddit to share their experiences with psilocybin, providing an opportunity to understand a range of perspectives and experiences. The current study aimed to further explore psilocybin experiences as shared on Reddit, with a focus on posts related to BD. A thematic analysis of Reddit posts and comments was undertaken, with a focus on those identified with search terms, "bipolar" AND "psilocybin" OR "mushrooms". A total of 354 comments with a first-hand psilocybin experience were identified and included in the thematic analysis which revealed four core themes: (1) mania, (2) depression, (3) mixed experiences, and (4) broader perspectives. Psilocybin was reported to have benefits in some comments, including reduced depression symptoms and shifts in perspective about oneself and/or the world. However, reports of increased or new mania and psychosis symptoms were also reported, as well as increased depression. While psilocybin may benefit some individuals with BD, there may be potential for increased mania, psychosis and depression symptoms. Understanding the factors that contribute positive and negative outcomes among individuals with BD will be important in future research.

raw_json:
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authors: Garcia Garcia M, Belahda D, Graux C, Serrand C, Igounenc N, Sergent F, Mura T, Luquiens A.
publication_date: 2026-01-18
doi: 10.1016/j.jad.2026.121215
pubmed_id: 41558304
source_url: https://doi.org/10.1016/j.jad.2026.121215
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:01
title:
Insights from the psychedelic experience integration session: Verbatims differentiate 3-month abstinence in alcohol use disorder with depressive symptoms.

abstract:
BackgroundPsilocybin-assisted psychotherapy shows promise in alcohol use disorder (AUD), but therapeutic mechanisms remain poorly understood. Previous qualitative studies have described potential processes such as gaining insights, altered self-perception, connectedness, and changes in coping, yet findings remain limited and inconsistent in AUD, and little is known about early markers of therapeutic response.MethodsWe conducted a mixed quantitative-qualitative analysis of first integration sessions in the Psilocybin Alcohol Depression (PAD) randomized controlled trial. Only participants randomized to the 25 mg psilocybin group were included in this analysis. Recently detoxified patients with AUD and persisting depressive symptoms underwent semi-structured integration interviews the day after dosing. Transcripts were analyzed with IRaMuTeQ software using the Reinart descending hierarchical classification. Associations with abstinence at 3 months were examined.ResultsTwenty participants were included (55% male, median age 49); 55% were abstinent at 3 months. The corpus comprised 127,760 words, with 88% classified into two stable classes. Class 1 (44% of text segments) described sensory and emotional aspects of the psychedelic experience (physical sensations, visual phenomena, emotions, setting) and was predominantly elicited by non-responders. Class 2 (56%) reflected active cognitive processes and inner dialogue, including cognitive restructuring, distancing from habitual patterns, commitment to change, and work on pre-elicited intentions related to alcohol. Abstinence at 3 months was significantly associated with references to family connections, pleasant emotions, adaptive processing of fear, and revisiting alcohol-related triggers with new coping strategies, while non-abstinence was associated with negative emotions, physical pain, disappointment, and suppressive coping.ConclusionsResponders were distinguished by narratives of inner dialogue and adaptive coping, while non-responders emphasized sensory and affective descriptions and suppressive coping. Inner dialogue may constitute a distinct therapeutic mechanism, highlighting the importance of preparation and integration in psilocybin-assisted psychotherapy.

keywords:
Humans, Alcoholism, Hallucinogens, Treatment Outcome, Adaptation, Psychological, Depression, Psychotherapy, Adult, Middle Aged, Female, Male, Alcohol Abstinence, Psilocybin, Coping Skills

topic_tags:
Depression,Addiction,Chronic Pain,Mechanism of Action,Biomarkers,Emotional Processing,Randomized Controlled Trial

raw_json:
{"europe_pmc_id":"41558304","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2025-12-31
doi: 10.1177/02698811251389552
pubmed_id: 41479142
source_url: https://doi.org/10.1177/02698811251389552
substance_tags: psilocybin
topic_tags: Consciousness,Clinical Trial,Healthy Volunteers
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:00
title:
The effects of psilocybin on time perception in humans: A comparative analysis of subjective and objective measures.

authors:
Scholle P, Wenke Š, Nekovářová T, Zaytseva Y, Tylš F, Brunovský M, Horáček J, Andrashko V, Koudelka V, Viktorinová M, Viktorin V, Hájková K, Kuchař M, Páleníček T.

abstract:
BackgroundAlthough psychedelics have regained attention as potential treatment tools for various mental disorders, little research has examined their impact on temporal perception.AimsThis double-blinded placebo-controlled study aimed to investigate changes in temporal perception under psilocybin, both through performance during the Temporal Bisection Task (TBT) and through subjective self-report scales.MethodsTwenty-four healthy volunteers were assessed by comparing their performance on two parameters of the TBT -the Bisection Point (BP) and the Just Noticeable Difference (JND) with subjectively reported changes measured using the Hallucinogen Rating Scale (HRS) and the Altered States of Consciousness (ASC) questionnaires.ResultsWe observed a rightward shift in BP under psilocybin compared to placebo (t(23) = 2.27, p = 0.033, g = -0.37). This shift corresponded to reports of subjective time slowing down under psilocybin as measured by HRS and ASC. Psilocybin also increased JND compared to placebo (t(23) = 2.48, p = 0.021, g = -0.47), indicating decreased temporal precision. Consistent with previous findings, these effects were significant for durations longer than 2 seconds.ConclusionsBased on Bayesian framework of timing, we emphasised that psilocybin alters time perception through disruptions in cognitive functions, particularly working memory and attention. We also outlined directions for future research, which would allow us to not only understand time perception under psychedelics better, but help elucidate the role of serotonergic system on timing.Research ID:The research was conducted as part of a clinical trial registered at EudraCT database under the number 2012-004579-37.

raw_json:
{"europe_pmc_id":"41479142","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Diehl VJ, Calder AE, Hasler G.
publication_date: 2025-12-30
doi: 10.1177/02698811251397306
pubmed_id: 41472616
source_url: https://doi.org/10.1177/02698811251397306
substance_tags: psilocybin
topic_tags: Mechanism of Action,Mystical Experience,Observational Study
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:03
title:
The helioscope effect: A new framework for evaluating trauma-related memory processing in psychedelic experiences.

abstract:
BackgroundExisting tools assess psychedelic experiences, but none specifically measure altered processing of traumatic memories-a key mechanism in trauma-focused therapies and psychotherapy in general. The helioscope effect describes how psychedelics like psilocybin and 3,4-methylenedioxymethamphetamine (MDMA) enable revisiting challenging or traumatic experiences while remaining protected from re-actualization of trauma symptoms. This study introduces and evaluates the Helioscope Questionnaire, a novel scale for assessing memory-related processing during psychedelic experiences.MethodA cross-sectional, Internet-based survey was administered to 468 individuals (mean age = 32.9; 66.7% male) with self-reported psychedelic/MDMA use.ResultsThe final Helioscope Questionnaire comprised 21 items across 3 factors: protection, exposure, and avoidant-distress. A composite Helioscope Score (HS) was derived from protection and exposure subscales. Convergent validity was demonstrated through strong correlations with the Psychological Insight Questionnaire. Discriminant validity was evidenced by moderate associations with the Mystical Experience Questionnaire and a lack of significant correlations with the Challenging Experience Questionnaire. Predictive validity was supported by the HS predicting positive changes in mood and attitude on the Persisting Effects Questionnaire, whereas avoidant-distress predicted negative changes. The scale also demonstrated incremental validity by providing explanatory power beyond established psychedelic effect measures. Additionally, the presence of a trip sitter was associated with stronger HS scores, and MDMA use was linked to reduced avoidant distress.ConclusionsThe Helioscope Questionnaire offers a novel, psychometrically robust tool for assessing therapeutic mechanisms of psychedelic experiences, particularly in relation to processing of difficult memories. Further research in clinical populations is warranted to evaluate its utility in predicting treatment outcomes.

raw_json:
{"europe_pmc_id":"41472616","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2025-12-25
doi: 10.1177/02698811251397328
pubmed_id: 41451514
source_url: https://doi.org/10.1177/02698811251397328
substance_tags: psilocybin
topic_tags: Anxiety,Consciousness,Healthy Volunteers
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:03
title:
The 3D-ASCr scale: A revalidation of the core dimensions of the Altered States of Consciousness Rating Scale 5D(11)-ASC for psychedelic research.

authors:
Stocker K, Hartmann M, Schmid Y, Vogt SB, Becker AM, Ley L, Straumann I, Arikci D, Klaiber A, Erne L, Vizeli P, Holze F, Liechti ME.

abstract:
BackgroundThe Altered States of Consciousness Scale (3/5D-ASC or 11-ASC) is widely used to assess non-ordinary states of consciousness, particularly for psychedelic research. However, its original dimensional model (3D-ASC within 5D-ASC) and later 11-subscale structure (11-ASC) have a hierarchically incompatible higher/lower-order structure. Although the 11-ASC offers superior model fit, the 3D-ASC remains widely used for summarizing broader experiential domains.AimsWe wanted to provide an updated, psychometrically revalidated version of the ASC. We tested whether the 42-item 11-ASC could be integrated into a coherent three-dimensional framework. We further hypothesized that this revised model would outperform the original 66-item 3D-ASC while preserving its conceptual clarity.MethodsData from 901 5D-ASC questionnaires from 398 healthy participants across 16 randomized, mostly placebo-controlled psychedelic (lysergic acid diethylamide, psilocybin, mescaline, and N,N-dimethyltryptamine) studies were split for exploratory and confirmatory factor analysis. We compared the 3D-ASC and 11-ASC in terms of reliability and model fit, and tested whether the 11-ASC could be summarized within a three-dimensional model.ResultsTen of the 11 subscales formed three higher-order dimensions-Positive (PosE), Distressing (DisE), and Perceptual (PerE) effects-mirroring the 3D-ASC but with improved fit. We propose this as the 3D-ASCr scale. The Anxiety subscale could not be integrated due to consistent floor effects (low anxiety in the sample), but given its clinical relevance, it is retained within 3D-ASCr (as part of DisE or a standalone subscale).ConclusionThe 3D-ASCr is an updated version of the ASC and is recommended for use with classic serotonergic psychedelics in both clinical practice and research.

raw_json:
{"europe_pmc_id":"41451514","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: The serotonin 1B receptor is required for some of the behavioral effects of psilocybin in mice.
authors: Fleury S, Nautiyal KM.
publication_date: 2025-12-19
doi: 10.1038/s41380-025-03387-1
pubmed_id: 41422160
source_url: https://doi.org/10.1038/s41380-025-03387-1
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Neuroplasticity,Receptor Pharmacology,Emotional Processing,Animal Study
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:00
abstract:
Recent studies highlight the promising use of psychedelic therapies for psychiatric disorders, including depression. The persisting clinical effects of psychedelics such as psilocybin are commonly attributed to activation of the serotonin 2A receptor (5-HT2AR) based on its role in the acute hallucinatory effects. However, the active metabolite of psilocybin binds to many serotonin receptor subtypes, including the serotonin 1B receptor (5-HT1BR). Given the known role of 5-HT1BR in mediating depressive phenotypes and promoting neural plasticity, we hypothesized that it mediates the effects of psilocybin on neural activity and behavior. We first examined the acute neural response to psilocybin in mice lacking 5-HT1BR. We found that 5-HT1BR expression influenced brain-wide activity following psilocybin administration, measured by differences in the patterns of the immediate early gene c-Fos, across regions involved in emotional processing and cognitive function, including the amygdala and other subcortical limbic structures. Functionally, we demonstrated that 5-HT1BR mediates some of the acute and persisting behavioral effects of psilocybin. Although there was no effect of 5-HT1BR expression on the acute head twitch response, mice lacking 5-HT1BRs had attenuated hypolocomotion to psilocybin. We also measured the persisting effects of psilocybin on anhedonia and anxiety-like behavior using transgenic and pharmacological 5-HT1BR loss-of-function models. Although there were effects of sex and stress paradigms, we found that 5-HT1B is involved in mediating some of the longer-lasting behavioral responses to psilocybin. Finally, using a network analysis, we identified neural circuits through which 5-H1BR may modulate the response to psilocybin. Our findings suggest that the 5-HT1BR influences brain-wide neural changes following psilocybin administration and may contribute to its enduring antidepressant-like effects in mice.

keywords:
Brain, Animals, Mice, Inbred C57BL, Mice, Knockout, Mice, Receptor, Serotonin, 5-HT1B, Hallucinogens, Behavior, Animal, Depression, Male, Psilocybin

raw_json:
{"europe_pmc_id":"41422160","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Predictors of therapeutic response to psychedelic-assisted therapy: A systematic review.
authors: Viljoen G, Walter H, Bendau A, Koslowski M, Betzler F
journal: Journal of psychopharmacology (Oxford, England)
publication_date: 2026-04-30
doi: 10.1177/02698811251389581
pubmed_id: 41388888
source_url: https://pubmed.ncbi.nlm.nih.gov/41388888/
keywords: addictive disorders, depression, psilocybin, psychedelics, psychiatric disorders
substance_tags: psilocybin
study_type: Systematic Review
source_name: PubMed
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:20:34
raw_json: {"pubmed_id":"41388888"}
abstract:
Psychedelic-assisted therapy (PAT) has demonstrated substantial efficacy across a range of mental disorders. However, heterogeneity between patients confers differential responsiveness. This systematic review aims to explore factors which may predict therapeutic responses to PAT.
A systematic search was performed from inception through to March 2024 and studies that assessed predictors of response related to the use of classic psychedelics for mental disorders were included.
A total of 54 studies investigating potential predictors of treatment response to psychedelic-assisted therapy were included in the review. These studies encompassed adult populations diagnosed with substance-use disorders, major depressive disorder, anxiety disorders, obsessive-compulsive disorder, post-traumatic stress disorder and existential distress related to life-threatening illness as well as naturalistic samples reporting psychopathological symptoms without a formally confirmed diagnosis. The most frequently reported predictor of therapeutic response was the intensity of the acute psychedelic experience, particularly mystical-type experiences (MTEs), though this was not consistent across all disorders or time points. Factors related to set, setting and dose were frequently associated with the likelihood and intensity of MTEs.
The acute psychedelic experience, especially MTEs, was the most frequently reported predictor of therapeutic response. Future trials should explore a broader range of predictors, include longer-term follow-up and improve methodological consistency to strengthen the evidence base for reliable predictors of therapeutic response.

topic_tags:
Depression,Anxiety,PTSD,OCD,End-of-Life Distress,Mystical Experience,Systematic Review,Review Article


title: Landscape analysis of pre-registered clinical trials involving classical psychedelics.
authors: Uyar A, Forbrich L, Lueken U, Evens R.
publication_date: 2025-10-20
doi: 10.1177/02698811251371690
pubmed_id: 41121524
source_url: https://doi.org/10.1177/02698811251371690
substance_tags: psilocybin
topic_tags: Clinical Trial,Review Article
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:02
abstract:
Psychedelic clinical research is expanding rapidly. This review analyses the state and trends in psychedelic clinical trial registrations. A systematic search of ClinicalTrials.Gov was conducted on 11 November 2024, to identify registered interventional trials investigating (therapeutic) effects of serotonergic psychedelics (e.g. lysergic acid diethylamide [LSD], psilocybin, [5-MeO-]DMT). Analyses included a negative binomial regression to assess time trends and descriptive summaries of study characteristics. Outcomes included registration trends, substance distribution, study phase progression, sample and trial characteristics, geographical distribution and psychotherapy reporting. A total of 241 trials were identified, with registrations rising exponentially after 2006 and an acceleration post-2019. Two-thirds of trials are ongoing or planned. Psilocybin remains the most frequently studied substance and is most advanced towards approval, but short-acting psychedelics ([5-MeO-]DMT) have recently been introduced with a more focused clinical scope. Industry involvement is increasing, though university-led research still dominates. Reports of psychotherapy components increased following 2023 FDA recommendations, though no major improvements in intervention descriptions were observed. The rapid expansion of registered psychedelic clinical trials with diverse indications and substances reflects growing clinical interest. While university-led studies initiated early investigations and established a broad knowledge base, later industry involvement increasingly prioritizes scalability and economic considerations by adopting a focused approach towards clinical approval. Inconsistent reporting of psychotherapeutic components limits cross-study comparability and complicates systematic investigations into which combinations of therapeutic elements (type, timing, intensity) may optimize clinical outcomes. Future efforts should focus on complete and standardized trial reporting at study registration to minimize bias, reduce interpretative ambiguity and facilitate cross-trial comparisons.

raw_json:
{"europe_pmc_id":"41121524","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Bruno V, López-Canul M, Richardson B, Camarini R, Marcourakis T, Gobbi G.
publication_date: 2025-09-21
doi: 10.1177/02698811251368361
pubmed_id: 40984017
source_url: https://doi.org/10.1177/02698811251368361
substance_tags: psilocybin
topic_tags: Addiction,Animal Study
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:00
title:
High dose of psilocybin induces acute behavioral changes without inducing conditioned place preference in Sprague-Dawley rats.

abstract:
BackgroundIn recent years, there has been a resurgence of scientific interest in psychedelics, including psilocybin, for their potential in treating neuropsychiatric disorders. However, the reward-related effects of psilocybin and its impact on behavior remain underexplored.AimsWe aimed to evaluate the potential rewarding effects of high doses of psilocybin and its effects on rat behavior.MethodsSprague-Dawley rats were exposed to the conditioned place preference (CPP) paradigm. Over an 8-day period, rats were administered either psilocybin (10 mg/kg, i.p.) or vehicle (0.9% saline, i.p.) on odd conditioning days, while receiving vehicle (0.9% saline, i.p.) on even conditioning days. The potential rewarding effect induced by psilocybin was assessed 48 hours after the last psilocybin injection. Behavioral assessments, including head twitch, body shaking, grooming, body licking, defecation pellets, and rearing, were conducted during the CPP exposure.ResultsPsilocybin did not induce CPP in rats, highlighting its lack of reinforcing effects under these conditions. However, this regimen of administration led to modifications in the behavioral profile during CPP test by increasing head twitching, wet-wet-dog shaking, and defecation pellets and decreasing grooming, body licking, and rearing compared to the vehicle group. Importantly, 48 hours after the final psilocybin injection, no behavioral differences were observed between psilocybin and vehicle groups.ConclusionPsilocybin at this regimen (10 mg/kg, every other day) does not induce CPP, but induces changes in behavior, which disappear 48 hours after the last injection. More research is needed to better evaluate the addiction liability of psychedelics using different paradigms, doses, and protocols.

raw_json:
{"europe_pmc_id":"40984017","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2025-06-17
doi: 10.1192/bjp.2025.102
pubmed_id: 40528492
source_url: https://doi.org/10.1192/bjp.2025.102
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:04
title:
The Music for Subanesthetic Infusions of Ketamine randomised clinical trial: ketamine as a psychedelic treatment for highly refractory depression.

authors:
Greenway KT, Garel N, Dinh-Williams LL, Thibault Lévesque J, Kaelen M, Dagenais-Beaulé V, de la Salle S, Erritzoe D, Looper K, Turecki G, Rej S, Richard-Devantoy S.

abstract:
BackgroundKetamine exerts potent but transient antidepressant effects in treatment-resistant depression (TRD). Combinations of ketamine and psychotherapy have attracted interest, but no trial has investigated a psychedelic model of ketamine-psychotherapy for TRD to our knowledge.AimsThis secondary analysis of a randomised clinical trial (RCT) explores the therapeutic effects and experiential mechanisms of the Montreal Model of ketamine-psychotherapy for TRD, with or without music.MethodA two-centre, single-blinded, RCT conducted in Montreal, Canada, between January 2021 and August 2022 (NCT04701866). Participants received ketamine-psychotherapy for TRD - six subanaesthetic infusions over 4 weeks and psychological support - with either music or matched non-music support during ketamine doses, as per random group assignments. The primary therapeutic outcome was the Montgomery-Åsberg Depression Rating Scale, assessed by blinded raters. Psychedelic-like experiences, evaluated by the Mystical Experience Questionnaire and Emotional Breakthrough Inventory, and their session-by-session relationships with depression were explored with multilevel, time-lagged covariate models with autoregressive residuals.ResultsThirty-two participants with severe and highly comorbid TRD, including high rates of personality disorder and suicidality, received 181 ketamine infusions. Therapeutic outcomes and psychedelic experiences did not differ between music (n = 15) and non-music (n = 17) interventions. Both groups experienced significant reductions in clinician-rated and self-reported depression (d = 1.2 and d = 0.87, respectively; p < 0.001), anxiety (d = 0.8, p < 0.001) and suicidality (d = 0.4, p < 0.05) at 4 weeks, fully maintained at 8-week follow-up. Ketamine experiences were highly emotional and mystical. Converging analyses supported mystical-like ketamine experiences as mechanisms of its antidepressant effects.ConclusionsThis trial found large and notably sustained benefits of ketamine-psychotherapy for severe TRD, with or without music, and psychedelic experiences of comparable intensity to those observed with psilocybin. Mystical-like experiences may particularly contribute to ketamine's immediate and persistent psychiatric benefits.

keywords:
Humans, Ketamine, Hallucinogens, Antidepressive Agents, Treatment Outcome, Combined Modality Therapy, Music Therapy, Single-Blind Method, Adult, Middle Aged, Female, Male, Depressive Disorder, Treatment-Resistant

topic_tags:
Depression,Anxiety,Mechanism of Action,Personality Change,Emotional Processing,Mystical Experience,Clinical Trial,Randomized Controlled Trial,Treatment-Resistant Depression,Healthcare Workers

raw_json:
{"europe_pmc_id":"40528492","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Briggs D, Sease TB, Menou R, Perkins DR.
publication_date: 2026-04-29
doi: 10.3390/bs16050686
pubmed_id: 42193565
source_url: https://doi.org/10.3390/bs16050686
substance_tags: psilocybin
topic_tags: Emotional Processing,Mystical Experience,Psychological Flexibility
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:03
title:
Does Psychological Flexibility Correlate with Mystical Experiences: A Machine Learning Approach Including State of Surrender, Near-Death Experiences, and Psilocybin Consumption.

abstract:
Mystical experiences are characterized by a profound sense of interconnectedness and transcendence of ordinary reality. These experiences can facilitate feelings of connectedness with oneself and others and have been documented as leading to significant positive changes in thoughts, emotions, and behavior. The purpose of the present study was to evaluate the extent to which the four mindfulness facets of psychological flexibility (i.e., experiential acceptance, present-moment awareness, cognitive defusion, and self-as-context) were associated with self-reported mystical experiences while controlling for established covariates. Using a sample of 150 individuals recruited online, a regularized regression with an elastic net-a computationally efficient machine learning algorithm-was used to model the relationships among mystical experiences, State of Surrender, frequency of psychedelic use, near-death experiences, and facets of psychological flexibility. State of Surrender, experiential acceptance, cognitive defusion, and present-moment awareness emerged as the most robust predictors of mystical experiences. Collectively, these findings underscore the role of psychological processes, including surrender-related processes and facets of psychological flexibility, in predicting mystical experiences.

raw_json:
{"europe_pmc_id":"42193565","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: The Harmonious Dance: A Narrative Review on Psychedelics and Music in Therapeutic Settings.
authors: Wang H, Li X, Yu F, Wang X
journal: Current neuropharmacology
publication_date: 2026-04-27
doi: 10.2174/011570159x442471260422110855
pubmed_id: 42083530
source_url: https://pubmed.ncbi.nlm.nih.gov/42083530/
keywords: Psychedelics, default mode network, mental health, music therapy, psilocybin
substance_tags: psilocybin
study_type: Review Article
source_name: PubMed
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:20:34
raw_json: {"pubmed_id":"42083530"}
abstract:
The integration of psychedelics and music in therapeutic settings is gaining recognition for its potential to enhance mental health outcomes. This review synthesizes current evidence on the neurobiological mechanisms underlying this synergy, focusing on receptor-level pathways (e.g., 5-HT2A receptor agonism, BDNF-TrkB signaling) and neural circuit dynamics (e.g., default mode network desynchronization, thalamo-cortical connectivity) that mediate psychedelic action and mu-sic-induced emotional processing. By examining how music, acting as a "hidden therapist," ampli-fies the emotional and cognitive effects of psychedelics, we elucidate the mechanistic interplay that fosters deep psychological insights and emotional healing. Several key areas have been addressed, such as the exploration of dynamic brain activity in realistic music environments, the micro-neural mechanisms underlying basic musical elements, and the development of quantitative techniques for music therapy aimed at improving sleep quality and alleviating symptoms of anxiety and depression. Psychedelics increase neural plasticity and downregulate the default mode network, allowing music to guide emotional processing and facilitate profound therapeutic breakthroughs. The synergy be-tween music and psychedelics shows promise in treating conditions such as depression, Post-Traumatic Stress Disorder (PTSD), and addiction. The scientific contributions of this review include providing an integrated mechanistic framework for understanding psychedelic-music interactions and identifying key neurobiological targets for future therapeutic optimization. Future research should focus on optimizing therapeutic protocols and understanding the neurobiological mecha-nisms underlying this powerful combination to ensure its safe and effective integration into main-stream mental health care.

topic_tags:
Depression,Anxiety,PTSD,Addiction,Neuroplasticity,Mechanism of Action,Receptor Pharmacology,Default Mode Network,Emotional Processing,Review Article,Drug Interactions


publication_date: 2026-03-31
doi: 10.1002/cbic.70318
pubmed_id: 42011697
source_url: https://doi.org/10.1002/cbic.70318
keywords: Sesquiterpenes, Alkyl and Aryl Transferases, Psilocybe
substance_tags: psilocybin
topic_tags: Receptor Pharmacology,In Vitro Study
study_type: In Vitro Study
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:01
title:
Specific and Multi-Product Clade I and Clade IV Sesquiterpene Synthases Contribute to the Psilocybe cubensis Volatilome.

authors:
Schober S, Dorfmann L, Walther K, Blei F, Chadeayne AR, Gressler M, Bartram S, O'Connor SE, Hoffmeister D.

abstract:
Apart from the psychedelic psilocybin, the metabolite spectrum of Psilocybe "magic mushrooms" comprises sesquiterpenes, a class of natural products known to exhibit receptor-modulating bioactivities. However, the composition of the sesquiterpene profile has largely remained an open question. Here, we report the characterization of five Psilocybe cubensis sesquiterpene synthases, both in vitro using recombinantly produced enzymes and in vivo in Aspergillus niger. CubF is a clade I α-muurolol synthase. The investigated clade IV synthases were the near-identical CubG1 and CubG2 synthases, which catalyze mainly epi-isozizaene and β-duprezianene formation. Furthermore, CubH and CubI were identified as primarily making dauca-4(11),8-diene and β-barbatene, respectively. Gas chromatographic analyses of the headspaces of P. cubensis vegetative mycelium and fruiting bodies showed qualitative and quantitative differences, with sterpurene being among the major compounds in mycelium and dauca-4(11),8-diene in fruiting bodies. This fundamental knowledge of the P. cubensis terpenome may help distinguish the pharmacological effects of magic mushrooms versus pure psilocybin.

raw_json:
{"europe_pmc_id":"42011697","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Magnani L, Ghirotto L, Fesce F, Re T, Tanzi S, Amerio A, Costanza A.
publication_date: 2026-04-27
doi: 10.1136/spcare-2025-005689
pubmed_id: 41708300
source_url: https://doi.org/10.1136/spcare-2025-005689
substance_tags: psilocybin
topic_tags: Depression,Anxiety,End-of-Life Distress,Chronic Pain,Review Article,Cancer Patients,Inflammation
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:00
title:
Psilocybin-assisted psychotherapy for psycho-existential distress in advanced cancer: a narrative review.

abstract:
IntroductionThis article presents a narrative review of psilocybin-assisted psychotherapy as a promising intervention for addressing anxiety, depression and psycho-existential distress in patients with advanced cancer. This group of disorders, often resistant to conventional treatments, significantly impacts patients' quality of life and autonomy, as well as illness trajectories. Psilocybin, when administered in high doses within a structured therapeutic framework, seems to alleviate these symptoms safely and effectively, with potential additional benefits on pain and systemic inflammation.Methods and analysisA targeted literature search was conducted across major scientific databases-including PubMed, Scopus, PsycINFO, Cochrane Library and Embase-supervised by experts from various relevant disciplines to identify sources of particular importance.ResultsThe process also led to the acquisition of highly cited scientific works to compose a coherent theoretical framework through which to interpret the evidence initially collected. Emerged key themes include: the complex and treatment-resistant nature of psycho-existential disorders in cancer; the importance of set, setting and peak experiences for psilocybin efficacy, as well as the consequent therapeutic value of integrated approaches that include psychotherapy; and the methodological limitations in more recent experimental trials. The article also identifies palliative care as a uniquely appropriate context for psilocybin-assisted psychotherapy.Conclusionpsilocybin-assisted psychotherapy is a compelling therapeutic option warranting further investigation through rigorous, interdisciplinary research to promote an anthropologically/ethically grounded implementation in palliative settings, even beyond the oncology field.

keywords:
Humans, Neoplasms, Hallucinogens, Palliative Care, Depression, Stress, Psychological, Psychotherapy, Quality of Life, Psilocybin

raw_json:
{"europe_pmc_id":"41708300","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Rockhill KM, Bemis EA, Schow N, Olsen HA, Beekman K, Fox EJ, Monte AA, Black JC.
publication_date: 2026-04-26
doi: 10.2196/86059
pubmed_id: 42044375
source_url: https://doi.org/10.2196/86059
substance_tags: psilocybin
topic_tags: Addiction,Observational Study
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:04
title:
Fusing Specialized Surveys of Rare Populations to Larger Surveys for Generalized Inference: Cross-Sectional Survey Study.

abstract:
BackgroundMainstays of pharmacoepidemiology are large, representative, behavioral surveys, which focus on many drugs with few detailed behaviors. Smaller, targeted studies measure drug-specific patterns but without explicit generalizability assumptions; the evidence generated is narrow.ObjectiveIn this cross-sectional survey study, we outline an estimation framework based on data fusion and combine two surveys: a representative, anchor survey and an enriched survey about psychedelic drugs in the United States. Application of calibration weighting transports estimates from the enriched survey to the anchor survey.MethodsThe psychedelic-focused enriched survey was sampled twice from a commercial online panel of adults from April 19 to June 25, 2024, (n=2306; 40.4% female, 33.1 y median age) and January 24 to March 21, 2025 (n=2023; 39.6% female, 35.2 y median age). The anchor survey was sampled twice from a different online panel from March 13 to May 6 2024 (n=28,679 total; 2430 using psychedelics) and 14 August to 9 October 2024 (n=29,040 total; 2309 using psychedelics). Internal consistency (transport bias, the absolute difference between the weighted estimates from the anchor survey and weighted fused survey) and external validity (root-mean-square error, RMSE, of self-reported demographic, health, and substance use estimates to probability-based benchmarks) metrics were calculated. The methodology was applied to estimate reasons for using specific psychedelic drugs.ResultsWithout adjustments, the enriched surveys had lower percentages of male and White respondents, lower self-perceived health, and higher cigarette use. A total of 2048 weighting schemes were tested, with good internal consistency. Average transport biases with the final weighting scheme were: demographics, 0.09 percentage points; health characteristics, 0.35 percentage points; and substance use, 0.22 percentage points. Estimates after fusion were externally consistent with benchmarks. RMSE increased by 3.3% for demographic estimates (1.82 unweighted to 1.88 weighted); larger decreases were observed for health RMSE (7.30 to 3.38, 53.7% decrease) and for substance use RMSE (6.56 to 6.03, 8.1% decrease). Alcohol use substantially increased the RMSE, likely due to question differences (without alcohol, the RMSE decreased from 6.03 to 1.55). Using the fused dataset, recreational use of psilocybin (92.9%, 95% CI91.1, 94.7), LSD (93.2%, CI90.1, 96.4, and MDMA (93.3%, 91.0, 95.6) was more common than medical use (30.9%, CI27.6, 34.2; 26.4%, CI21.1, 31.7; and 21.1%, CI17.5, 24.7, respectively).ConclusionsBuilding upon past data fusion research, this study fused two surveys for the purpose of surveillance. This methodology, termed the "fused survey design," is a rigorous but accessible approach for surveilling rare behaviors like drug use, and we demonstrated constructs absent from anchor surveys may be measured with generalizable inference. This expands the surveillance epidemiology toolbox, giving researchers an actionable process to field enriched surveys with specialized questions that would be impractical to add to larger surveys due to space constraints and respondent fatigue.

keywords:
Humans, Hallucinogens, Cross-Sectional Studies, Pharmacoepidemiology, Adult, United States, Female, Male, Surveys and Questionnaires

raw_json:
{"europe_pmc_id":"42044375","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


journal: PsyArXiv
publication_date: 2025-12-17
doi: 10.47626/2237-6089-2025-1273
source_url: https://osf.io/preprints/psyarxiv/v7pxn_v1
substance_tags: psilocybin
topic_tags: Personality Change,Emotional Processing,Safety
study_type: Other
source_name: PsyArXiv
publication_status: preprint
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:30
raw_json: {"osf_id":"v7pxn_v1","version":1,"reviews_state":"accepted"}
title:
Exploring Psilocybin-Assisted Schema Therapy: A Conceptual Framework for Potential Therapeutic Synergies in Personality Disorders

abstract:
Personality disorders (PDs) are characterized by rigid and maladaptive patterns of self- and interpersonal functioning, leading to high clinical burden and limited treatment outcomes. Schema Therapy (ST), an integrative psychotherapy rooted in cognitive-behavioral principles, conceptualizes PDs in terms of Early Maladaptive Schemas (EMS)-pervasive cognitive-affective structures formed through unmet emotional needs-and schema modes, dynamic states organizing emotion, belief, and behavior. Evidence indicates moderate efficacy of ST, mainly for borderline personality disorder, with limited research on other Cluster B and C PDs. Emerging evidence suggests that psilocybin, a serotonergic psychedelic, can induce enduring personality change, supporting its potential use in treating PDs. Within a predictive coding framework, the REBUS (“Relaxed Beliefs Under Psychedelics”) and REBAS (“Revised Beliefs After Psychedelics”) models propose that psilocybin relaxes high-level priors, facilitating cognitive flexibility and revision of maladaptive self-beliefs. Conceptual parallels between EMS and high-level priors suggest that psychedelic-induced relaxation of entrenched beliefs may enhance responsiveness to ST’s experiential and cognitive interventions. Psilocybin-Assisted Schema Therapy (PAST) is proposed as a model in which psilocybin sessions are followed by integration combining psychedelic-induced cognitive flexibility with ST techniques, aimed at strengthening adaptive modes and reducing dysfunctional EMS and dysfunctional modes. PAST could be relevant in the future for enhancing outcomes and potentially reducing treatment duration in Cluster B and C PDs, pending empirical validation. Although current literature is insufficient to recommend psilocybin-assisted interventions for PDs, this theoretical article bridges computational neuroscience and clinical psychotherapy, outlining a framework for future studies on PAST feasibility, safety, and efficacy.

keywords:
Early Maladaptive Schemas, Personality Disorder, Predictive Coding, Psilocybin, Psychedelic-Assisted Therapy, Schema Therapy, Psychiatry


publication_date: 2026-04-23
doi: 10.1038/s42003-026-10065-7
pubmed_id: 42032175
source_url: https://doi.org/10.1038/s42003-026-10065-7
substance_tags: psilocybin
topic_tags: Chronic Pain,Receptor Pharmacology,Animal Study
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:00
title:
Psilocybin ameliorates neuropathic pain-like behaviour in mice and facilitates gabapentin-mediated analgesia.

authors:
Askey T, Allen-Ross D, Luzyanin D, Lasrado R, Gilmour G, Hunt SP, Tamagnini F, Ahmed M, Stephens GJ, Maiarú M.

abstract:
Chronic pain states remain challenging to control with current drug therapies. Here, we demonstrate that a single dose of psilocybin produces a sustained anti-nociceptive effect in chronic neuropathic pain models in male and female mice, mediated primarily by 5-HT2A receptors. Critically, psilocybin significantly potentiates the analgesic efficacy of gabapentin, a standard-of-care treatment, representing the first preclinical evidence that a psychedelic can serve as a pain-network primer for existing analgesics. This finding represents a novel therapeutic strategy with potential clinical application, particularly for the 30-50% of neuropathic pain patients who fail gabapentin monotherapy. Our data demonstrate that a single psilocybin injection produces sustained month-long changes that enhance gabapentin efficacy in a preclinical model of human pain. Together, these findings indicate that psilocybin both acutely enhances analgesia and induces lasting changes that amplify gabapentin efficacy weeks later. Such a translation is notable in chronic pain management, where most analgesics require chronic dosing and lose efficacy through tolerance. These findings establish psilocybin as a potential therapeutic addition for pain management by enabling longer-lasting changes in pain-processing networks and enhancing the utility of established treatments.

keywords:
Animals, Mice, Inbred C57BL, Mice, Neuralgia, Disease Models, Animal, Analgesics, Analgesia, Behavior, Animal, Female, Male, Psilocybin, Gabapentin

raw_json:
{"europe_pmc_id":"42032175","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Chaganti J, Siefried KJ, Vyakaranam VS, Acheson L, Brett J.
publication_date: 2026-04-23
doi: 10.3174/ajnr.a9364
pubmed_id: 42031666
source_url: https://doi.org/10.3174/ajnr.a9364
substance_tags: psilocybin
topic_tags: Addiction,Neuroplasticity,Brain Imaging,Biomarkers,Aging
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:00
title:
"Large-Scale and Local Functional Connectivity Changes Following Psilocybin Administration in Methamphetamine Use Disorder.

abstract:
Background and purposeMethamphetamine (MA) use disorder is associated with widespread disruption of large-scale brain networks involved in cognitive control, attention, and salience processing. Resting-state functional MRI (rs-fMRI) provides a means to characterize these alterations; however, little is known about the capacity for functional network reorganization following targeted intervention. The purpose of this study was to evaluate changes in large-scale and local functional connectivity following psilocybin administration in individuals with MA use disorder.Materials and methodsIn this exploratory prospective longitudinal study, participants with MA use disorder underwent rs-fMRI before and after psilocybin administration alongside psychotherapy. Large-scale functional connectivity was assessed across canonical resting-state networks, including the default mode, salience, dorsal attention, and executive control networks. Local connectivity was evaluated using regional homogeneity (ReHo). Connectivity changes were examined in relation to clinical measures of MA use, craving and psychological distress.ResultsFollowing intervention, significant reorganization of functional connectivity was observed within and between attentional, default mode, and salience networks. Improvements in network integration were accompanied by complementary shifts in local neural synchrony, with post-intervention increases in ReHo observed within frontal and sensorimotor regions. Greater MA reductions in use was associated with recovery of frontostriatal and attentional connectivity, whereas reductions in psychological distress correlated with strengthened integration of attentional and prefrontal-striatal circuits.ConclusionsPsilocybin administration was associated with measurable reorganization of both large-scale network connectivity and local functional coherence in individuals with MA use disorder. These findings provide preliminary evidence for distributed nature of brain network dysfunction in stimulant addiction and support the potential utility of multimodal rs-fMRI metrics as imaging biomarkers of network-level plasticity.

raw_json:
{"europe_pmc_id":"42031666","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Salinsky LM, Fox JL, Diaz KC, Timmons BC, Ferguson SM.
journal: Research Square
publication_date: 2026-04-22
doi: 10.21203/rs.3.rs-9306429/v1
source_url: https://doi.org/10.21203/rs.3.rs-9306429/v1
substance_tags: psilocybin
topic_tags: Addiction,Safety
study_type: Other
source_name: Europe PMC
publication_status: preprint
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:01
title:
Methamphetamine-Fentanyl Polysubstance Administration Produces Social Deficits and Corticolimbic Stress-Reward Circuit Adaptations

abstract:
Abstract Rationale and Objectives: Polysubstance use involving psychostimulants and opioids is increasingly prevalent and associated with elevated overdose risk, relapse vulnerability, and poor treatment outcomes. However, the neurobehavioral consequences of opioid-stimulant use remain poorly understood. We evaluated whether repeated methamphetamine-fentanyl polysubstance treatment disrupts social preference during withdrawal, whether psilocybin treatment restores sociability, and whether these manipulations alter corticolimbic expression of stress- and opioid-related genes. Methods Male and female rats received injections of methamphetamine and fentanyl or saline and were assessed for social preference at baseline and following 10 days of withdrawal. On withdrawal day 10, rats received psilocybin or saline and were reassessed for sociability 24 h later. CRHR1 and OPRM1 expression in the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc) were quantified by RT-qPCR. Results Withdrawal from 14-days of polysubstance treatment reduced social preference, replicating prior findings of withdrawal-associated social dysfunction. Psilocybin pretreatment did not restore social preference at the time point examined. In the mPFC, psilocybin bidirectionally altered CRHR1 expression depending on drug history, decreasing expression in saline-treated controls, while increasing expression following polysubstance treatment. In the NAc, polysubstance administration reduced CRHR1 expression. OPRM1 expression showed sex-dependent regulation with a marked reduction in the NAc of females following polysubstance treatment and evidence of sex-dependent effects in the mPFC. Conclusions Methamphetamine-fentanyl treatment produces persistent social deficits during withdrawal and region- and sex-dependent corticolimbic transcriptional adaptations in vivo. Although psilocybin did not restore sociability, it produced drug history-dependent regulation of cortical CRHR1.

raw_json:
{"europe_pmc_id":"PPR1181545","source":"PPR","pub_type":null,"publisher":"Research Square","importer":"Europe PMC"}


authors: Knox CA, Woodburn SC, Gilbert AD, Schlotzhauer JM, Kwan AC.
journal: bioRxiv
publication_date: 2026-04-21
doi: 10.64898/2026.04.21.720014
source_url: https://doi.org/10.64898/2026.04.21.720014
substance_tags: psilocybin
topic_tags: Neuroplasticity,Brain Imaging,Aging,Animal Study
study_type: Animal Study
source_name: bioRxiv
publication_status: preprint
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:00
title:
Structural plasticity and enhanced fear extinction following psilocybin in chronically stressed mice

abstract:
The classic psychedelic psilocybin elicits long-lasting neural plasticity and behavioral effects, but prior studies largely examined stress-naive animals. Using longitudinal imaging, we show that psilocybin increases dendritic spine density in frontal cortical neurons and facilitates fear extinction after chronic restraint stress, demonstrating psilocybin’s effects in a translationally relevant mouse model.

raw_json:
{"europe_pmc_id":"PPR1213850","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


authors: Sheheitli H, Hermosillo R, Grimsrud G, Madison T, Dominguez OM, Nelson S, Fair D, Nahas Z.
publication_date: 2026-04-21
doi: 10.1162/netn.a.537
pubmed_id: 42039092
source_url: https://doi.org/10.1162/netn.a.537
substance_tags: psilocybin
topic_tags: Brain Imaging,Biomarkers
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:02
title:
Metastability of resting-state bold fMRI as a reliable biomarker of individual brain dynamics: An interrogation of within-subject variability as a function of total acquisition time.

abstract:
Metastability of BOLD fMRI signals is a commonly used proxy of brain dynamics in behavioral and clinical studies. To date, little has been done to assess the confidence with which we can use estimates of metastability as reliable biomarkers of individual brain state. We analyze whole-brain and network-specific metastability for a highly sampled individual brain (84 sessions taken over 18 months) and quantify the within-subject reliability for the metrics as a function of the amount of data used, which we find to be comparable to that seen for static functional connectivity. As considerable variability is observed across networks in the required amount of data, we combine the networks' metrics in one novel feature vector that exhibits an order of magnitude improvement in reliability. We then test reproducibility by analyzing the Midnight Scan Club dataset (10 subjects imaged over 10 consecutive days). Finally, we examine the susceptibility to change of the proposed metastability measure in another dataset examining brain dynamics under the effect of psilocybin. We conclude that the networks' metastability feature vector exhibits strong within-subject reliability that renders it a promising candidate for the study of individual-specific biomarkers of brain dynamics and potential targets for precision neuromodulation.

raw_json:
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title: Wherefore the Magic? The Evolutionary Role of Psilocybin in Nature.
publication_date: 2026-04-21
doi: 10.1002/ece3.73522
pubmed_id: 42037650
source_url: https://doi.org/10.1002/ece3.73522
substance_tags: psilocybin
topic_tags: Mechanism of Action,Receptor Pharmacology,Drug Interactions
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:00
authors:
Matthews Nicholass KJ, Flis I, Hanley ME, Knight ME, Lane SM, Littlejohn G, Thom MDF, Billington RA, Boden R, Cummins R, Green BJ, Griffin C, Jones S, Salmon D, Sleep I, Smirnoff N, Ellis JS.

abstract:
Research into psychedelic compounds is in resurgence because of the exciting potential for their use in the treatment of psychiatric and mental health disorders. Despite this revival, remarkably little is known about their evolution. One of the most intriguing psychedelic compounds is psilocybin, the compound found in 'magic' mushrooms and used in ritual ceremonies in North America for generations. Associated with agaricomycete fungi across eight distantly related genera, psilocybin acts in a similar way to the neurotransmitter serotonin, yet how and why natural selection favoured its biosynthesis remains unclear. Given the resemblance to serotonin, a highly conserved neurotransmitter across invertebrates and vertebrates, modulation of invertebrate behaviour for defence is a likely explanation, but neither this nor alternative hypotheses have ever been formally tested. Here, we show that Drosophila larvae exposed to extracts from Psilocybe mushrooms exhibit reduced survival, pupation rates, and inhibited locomotion. Adults exposed during development show reduced thorax and wing size, along with small but significant deviations from perfect bilateral symmetry in wing venation, indicating developmental stress. However, mutants lacking the serotonin receptor that mediates psilocybin's effects in humans (5HT2A) showed the same response to Psilocybe extracts as wild-type flies. Furthermore, DNA metabarcoding revealed that although Psilocybe semilanceata demonstrates a distinct invertebrate community compared to most other grassland fungi, it overlapped with the non-psychedelic species Mycena epipterygia. This study provides a crucial first step toward understanding the evolutionary role of psilocybin-producing fungi and provides a grounding for future research into the molecular mechanisms, ecological interactions and evolutionary origins of psychedelic compounds in nature.

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authors: Baral A, Pan Y, Hlaing WM, Garcia-Romeu A, Pinheiro PS, Vidot DC.
publication_date: 2026-04-21
doi: 10.1007/s10552-026-02172-x
pubmed_id: 42017992
source_url: https://doi.org/10.1007/s10552-026-02172-x
substance_tags: psilocybin
topic_tags: Observational Study
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:02
title:
Classic psychedelic and cannabis use among U.S. cancer survivors aged ≥ 50 years: nationally representative estimates by cancer type/site.

abstract:
PurposeTo examine the prevalence of lifetime ("ever") cannabis and classic psychedelic use, and their co-use among U.S. adults aged ≥ 50 years with versus without a lifetime history of cancer, and to describe variation by cancer type/site among survivors.MethodsWe analyzed pooled 2015-2019 and 2021-2022 National Survey on Drug Use and Health (NSDUH) data of U.S. adults aged ≥ 50 years (Unweighted; n = 42,815 for 2015-2019; n = 21,144 for 2021-2022). Lifetime cannabis and classic psychedelic (LSD, psilocybin, peyote/mescaline) use and cancer history (physician-diagnosed, self-reported) were assessed. Weighted prevalence estimates and 95% CIs were computed, and subgroup analyses by cancer type/site were conducted.ResultsBetween 2015 and 2019, cannabis use was similar among cancer survivors (41.6%, 95% CI40.0-43.2) and individuals without cancer (42.6%, 95% CI42.0-43.2, p = 0.21). LSD (8.9, 95% CI8.1-9.7 vs 10.3, 95% CI9.8-10.8) and psilocybin (6.4, 95% CI5.6-7.3 vs 7.7, 95% CI7.4-8.1) were lower among cancer survivors. Any classic psychedelic use was 11.6% (95% CI10.6-12.5) among cancer survivors versus 12.9% (95% CI12.4-13.3) among those without cancer (p

keywords:
Humans, Neoplasms, Hallucinogens, Prevalence, United States Substance Abuse and Mental Health Services Administration, Aged, Middle Aged, United States, Female, Male, Cancer Survivors, Marijuana Use

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title: Prevalence and Correlates of Past-Year Psilocybin Use in the United States.
authors: Yang KH, Eun A, Palamar JJ.
publication_date: 2026-04-21
doi: 10.1176/appi.ajp.20251343
pubmed_id: 42014961
source_url: https://doi.org/10.1176/appi.ajp.20251343
substance_tags: psilocybin
topic_tags: General
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:01
raw_json:
{"europe_pmc_id":"42014961","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Drange S, Cohen J, Johansen SS, Dunkley B, Palner M.
publication_date: 2026-04-20
doi: 10.3389/fpsyt.2026.1819962
pubmed_id: 42094840
source_url: https://doi.org/10.3389/fpsyt.2026.1819962
substance_tags: psilocybin
topic_tags: OCD,Mechanism of Action,Microdosing,Wellbeing,Emotional Processing,Case Report,Observational Study
study_type: Case Report
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:00
title:
Case Report: Repeated low doses of psilocybin reduce perceived symptom severity but fail to restore cognitive flexibility in a case of severe obsessive-compulsive disorder: an observational case study of identical twins.

abstract:
BackgroundObsessive-Compulsive Disorder (OCD) can present significant challenges to individuals mental health, characterized by intrusive thoughts and repetitive maladaptive behaviors. Recent research into alternative treatments has highlighted psychedelics, notably psilocybin, for their potential therapeutic benefits in various psychiatric disorders, including OCD. This case study evaluated the impact of self-administered, low-doses of psilocybin, commonly referred to as microdosing, on symptom reduction and cognitive flexibility in OCD, with a focus on identical twins discordant for the condition.Case presentationThe study documents the experiences of one twin diagnosed with OCD who began a regimen of low-doses of psilocybin containing mushrooms, while the other twin, unaffected by OCD, served as a comparison. Case X was diagnosed with OCD by a general practitioner in the Danish healthcare system. Following years of severe OCD, case X began a self-medicated regimen consisting of psilocybin containing mushrooms, corresponding to 1-5 mg of psilocybin, every 3rd day. The other twin, case Y, who remained unaffected by OCD, and did not take psilocybin containing mushrooms. Cognitive flexibility was evaluated in both cases using a set-shift task. The affected twin reported a notable reduction in OCD symptoms, along with improvements in emotional regulation and overall well-being. However, despite these symptomatic improvements, deficits in cognitive flexibility remained present compared to the unaffected twin.ConclusionThis case study underscores the potential of low-doses of psilocybin as a promising avenue for mitigating symptoms of OCD. Nevertheless, the observed disparity in cognitive flexibility highlights the nuanced nature of OCD pathology, suggesting that while low-doses of psilocybin may alleviate certain symptoms, it may not fully address underlying cognitive impairments. Further research employing larger sample sizes and rigorous longitudinal designs is imperative to elucidate the mechanisms underlying the therapeutic effects of psilocybin low-doses in OCD, offering insights into its broader applicability as a treatment modality.

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