# publications

title: Serotonergic Polypharmacology of 2-Halogenated Tryptamines
journal: bioRxiv
publication_date: 2026-04-20
doi: 10.64898/2026.04.16.718915
source_url: https://doi.org/10.64898/2026.04.16.718915
substance_tags: psilocybin,psilocin
topic_tags: Pharmacology,Receptor Pharmacology,Animal Study,Toxicity
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
authors:
Yacoub J, Bray E, Bayyat J, Glatfelter GC, Leake A, Buitrago EM, Maitland AD, Partilla J, Cavalco NG, Schalk SS, Lammers JC, Baumann MH, McCorvy J, Leahy JW, Gulick D, Witowski CG, von Salm JL.

abstract:
Serotonergic psychedelics such as N,N-dimethyltryptamine (DMT) and 4-phosphoryloxy-N,N-dimethyltryptamine (psilocybin) show therapeutic promise for psychiatric and neurodegenerative disorders but may be limited by liabilities from serotonin (5-HT)-2A mediated psychoactive effects and potential cardiotoxicity via 5-HT2B activation. To address these limitations, we designed and synthesized 2-halogenated derivatives of DMT and psilacetin to reduce 5-HT2A/5-HT2B activity while retaining engagement of therapeutically relevant targets, particularly 5-HT6, 5-HT2C, and 5-HT1B. This study demonstrated that 2-position halogenation decreased affinities, potencies, and efficacies at 5-HT2A and 5-HT1A receptors while preserving potent 5-HT6 agonism, especially for 2-Br-psilocin. The analogues exhibited reduced affinities at 5-HT2B and hERG ion channels, suggesting safer cardiac valve and cardiotoxic profiles. In C57BL/6J mice, 2-Br-psilacetin did not induce the head-twitch response and attenuated 2,5 dimethoxy-4-iodoamphetamine (DOI)-induced head-twitch behavior, suggesting a reduced potential for inducing psychedelic effects. Behavioral assays further revealed improvements in stress-induced affective measures and hippocampus-independent cued learning at intermediate doses. These findings identify 2-halogenated tryptamines as polypharmacological serotonergic ligands with reduced psychoactivity and cardiac valve and toxic liabilities, supporting their potential as next-generation psychedelic-inspired therapeutics.

raw_json:
{"europe_pmc_id":"PPR1214370","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


authors: Abramsky-Sze S, Marseille E, Matzopoulos R, Morlock R, Lerer L
abstract: [This corrects the article DOI: 10.3389/fpsyt.2025.1508811.].
journal: Frontiers in psychiatry
publication_date: 2025-12-31
doi: 10.3389/fpsyt.2026.1834094
pubmed_id: 42088004
source_url: https://pubmed.ncbi.nlm.nih.gov/42088004/
keywords: anxiety, depression, mental health, psilocybin, psychedelic mushroom, psychedelics
substance_tags: psilocybin
topic_tags: Depression,Anxiety
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":"42088004"}
title:
Correction: Characteristics and mental health of psychedelic mushroom and multi-psychedelic users relative to non-psychedelic users in American adults, 2020-2021.


title: Psychedelics and Autism Therapy: A Review of Current Research and Future Directions.
authors: Gondi CS, Gnanamony M, Gondi TP, Nersesyan L, Demirkhanyan L.
publication_date: 2026-04-17
doi: 10.3390/cimb48040417
pubmed_id: 42042077
source_url: https://doi.org/10.3390/cimb48040417
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
abstract:
Autism Spectrum Disorder (ASD) is a lifelong condition marked by challenges in social communication and repetitive behaviors. Current treatments, primarily behavioral therapies, often fail to address the core symptoms. Recent research has explored the potential of psychedelics, such as LSD, psilocybin, and MDMA, as a new therapeutic approach. While these substances primarily modulate the serotonin 5-HT2A receptor, their therapeutic effects also involve interactions with other serotonergic, dopaminergic, and glutamatergic pathways, collectively promoting neuroplasticity-the brain's ability to change and adapt. The specific receptors' activation leads to structural and functional changes in the brain that can enhance social behavior and emotional regulation. Studies show that psychedelics may reduce symptoms of conditions like treatment-resistant depression and PTSD, highlighting their therapeutic potential. For ASD specifically, psychedelics may improve psychological flexibility, reduce distress, and enhance social interaction. While promising, the use of these substances requires careful consideration. Psychedelics can induce intense experiences and altered states of consciousness, necessitating strict monitoring and support during therapy. Ethical guidelines, including informed consent, are crucial, especially for vulnerable populations. In conclusion, psychedelics hold significant promise for treating ASD and other psychiatric disorders by promoting neuroplasticity and modulating complex signaling pathways. Continued research and clinical trials, conducted with strong ethical oversight, are essential to realizing their full therapeutic potential.

topic_tags:
Depression,PTSD,Neuroplasticity,Mechanism of Action,Receptor Pharmacology,Consciousness,Emotional Processing,Psychological Flexibility,Clinical Trial,Review Article,Treatment-Resistant Depression,Drug Interactions

raw_json:
{"europe_pmc_id":"42042077","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin reshapes cortical inhibition through selective interneuron recruitment
journal: bioRxiv
publication_date: 2026-04-16
doi: 10.64898/2026.04.16.718963
source_url: https://doi.org/10.64898/2026.04.16.718963
substance_tags: psilocybin
topic_tags: Receptor Pharmacology,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
authors:
Davoudian PA, Jiang Q, Knox CA, Savalia NK, Shao L, Wilson J, Weiner AM, Chong CW, Liao C, Nothnagel JD, Sakurai T, Kwan AC.

abstract:
Psychedelics show therapeutic potential for treating psychiatric disorders. While studies have emphasized the roles of cortical pyramidal cells, GABAergic neurons also express serotonin receptors and are therefore likely targets of psychedelics. In this study, we determine the effect of psilocybin on the activity dynamics of major GABAergic cell types in the mouse medial frontal cortex. Psilocybin reduces the firing of somatostatin-expressing interneurons, but increases the activity of parvalbumin-expressing interneurons. This cell type-specific response is unlikely to involve vasoactive intestinal peptide-expressing interneurons. Instead, pharmacological blockade and conditional knockout experiments demonstrate that psilocybin acts on the 5-HT1A receptor at SST interneurons, which contributes to the drug's long-term behavioral effects. Collectively, the results reveal that the classic psychedelic psilocybin alters cortical inhibition in a cell type-specific manner.

raw_json:
{"europe_pmc_id":"PPR1215011","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


authors: Norris JJ.
publication_date: 2026-04-15
doi: 10.1177/02698811261436577
pubmed_id: 41989154
source_url: https://doi.org/10.1177/02698811261436577
substance_tags: psilocybin
topic_tags: Addiction,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 11:22:03
title:
Substance use predictors of arrest and self-reported criminal behavior in the United States: The role of psychedelics and rarely used drugs.

abstract:
BackgroundLittle research investigates the role of rarely used drugs in criminal offending. Moreover, given research suggesting that psychedelics reduce criminal offending, more research is needed to further document connections between psychedelics and crime.AimThis study examines the role of rarely used drugs in criminal behavior and extends previous research on psychedelics by incorporating additional substance use measures, including youth respondents, and analyzing self-reported crime as well as arrests.MethodsUsing data from the National Survey on Drug Use and Health (2014-2023) (n = 544,740), a nationally representative US survey, logistic regressions were performed testing whether substance use measures predicted arrest for various offenses and self-reported crimes after controlling for multiple covariates.ResultsUse of phencyclidine (PCP), a rarely used drug, was strongly associated with arrest for serious violent offenses, assault, and sex offenses, and with attacking three or more people. Another rarely used substance, gamma-hydroxybutyrate (GHB), was associated with arrest for several offenses. Among psychedelics, psilocybin was associated with reduced odds of several offenses, while DMT/AMT/Foxy and peyote were associated with increased odds. LSD and Salvia divinorum were associated with increased odds of some offenses but decreased odds of others. For minors, psychedelics were mainly associated with increased odds of arrest, as protective effects were almost entirely absent. Psychedelics were associated with reduced odds of arrest for whites far more than for minorities.ConclusionsPCP use was strongly associated with violent offending. This study's mixed findings on psychedelics indicate a need for further research to clarify causal connections between psychedelics and crime-related outcomes.

raw_json:
{"europe_pmc_id":"41989154","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Blinding Integrity in Psychedelic Randomized Clinical Trials: A Systematic Review.
journal: JAMA psychiatry
publication_date: 2026-06-30
doi: 10.1001/jamapsychiatry.2026.0255
pubmed_id: 41984443
source_url: https://pubmed.ncbi.nlm.nih.gov/41984443/
substance_tags: psilocybin
topic_tags: Clinical Trial,Randomized Controlled Trial,Systematic Review,Review Article
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":"41984443"}
authors:
Orsini DK, Wong S, Di Luch S, Chan B, Vasudeva S, Lovell GFM, Le GH, Jones BDM, Chisamore N, Mollica A, Johnson DE, Kaczmarek ES, Goel A, Burke MJ, Mansur R, McIntyre RS, Husain MI, Rosenblat JD

abstract:
Psychedelic drugs possess acute psychoactive effects that can compromise blinding integrity in randomized clinical trials (RCTs). Functional unblinding, when participants or raters correctly identify treatment allocation based on subjective effects, may bias outcomes through expectancy effects, challenging the validity of efficacy estimates and regulatory acceptance.
To systematically quantify the prevalence of blinding integrity assessment and the extent of functional unblinding in psychedelic RCTs for psychiatric disorders.
A systematic review was conducted in accordance with PRISMA guidelines across OVID, MEDLINE, Embase, and APA PsycINFO (January 1, 2020, to December 11, 2025), supplemented by manual searches of 3 prior reviews for studies prior to January 2020. Eligible studies included all RCTs investigating psychedelics as psychiatric interventions. Data extracted included blinding integrity assessment methods and results for participants and raters.
Of 112 RCTs (11 psilocybin, 17 lysergic acid diethylamide [LSD], 78 ketamine, 11 3,4-methylenedioxymethamphetamine [MDMA], 2 ayahuasca, 2 N,N-dimethyltryptamine [DMT], and 1 noribogaine), only 29.5% (n = 33) evaluated blinding integrity, yet 57.1% (n = 64) cited blinding as a limitation. Functional unblinding was substantial: psilocybin, LSD, and ayahuasca studies frequently reported blinding failure values of more than 90% among participants and raters, inert placebo-controlled MDMA trials exceeded 85%, and ketamine trials rarely assessed blinding (17.9%) but showed improved preservation with midazolam vs saline controls. No control strategy consistently achieved ideal blinding.
This first evaluation of blinding integrity in psychedelic RCTs indicates functional unblinding is pervasive among participants and raters raising concerns about the validity of efficacy findings. Few trials assess blinding or expectancy, highlighting the need for standardized, validated measures and innovative designs to separate true pharmacological effects from expectancy-driven responses.


publication_date: 2026-04-13
doi: 10.3389/fpubh.2026.1810904
pubmed_id: 42058096
source_url: https://doi.org/10.3389/fpubh.2026.1810904
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:
A phase 1 study of a second experience with Group Retreat Psilocybin Therapy for partial responders after a first experience.

authors:
Back AL, McGregor BA, Thorn LL, Harvey K, Blom D, Callan G, Guy J, Kumar S, Hershberg R, Layer M, Levin J, Myers S, Perez J, Salmonson K, Thompson P, Whinney J.

abstract:
IntroductionPsilocybin therapy has demonstrated efficacy for cancer-related anxiety and depression, but resource-intensive individual treatment models raise important questions for psychedelic public health about equitable access and scalability. In our prior Phase 1/2 study of group retreat psilocybin therapy for patients with metastatic cancer, we observed partial responders who did not achieve full therapeutic benefit. No published research has examined whether partial responders might benefit from a second psilocybin therapy experience.MethodsWe conducted a single-arm Phase 1 study to assess the safety of a second experience of Group Retreat Psilocybin Therapy for partial responders from our prior study. Protocol modifications addressed dose as a potential contributor to partial response: the initial dose was increased to 35 mg, and an optional 10 mg booster could be requested by participants who reported low subjective effect at 60-90 min and passed a safety check. Pre-retreat antidepressant tapering was not required. The intervention was delivered in a group retreat format with four primary facilitators and included three preparation sessions, a single psilocybin dosing day, and four integration sessions.ResultsThirteen participants (mean age 56 years, 70% female, 38% on concurrent antidepressants) completed the intervention. No serious adverse events occurred; mild adverse events included transient hypertension (n = 4), nausea (n = 3), and headache (n = 1). Seven participants (54%) received the booster dose. Mean Hospital Anxiety and Depression Scale (HADS) Total scores decreased from 15.08 (SD4.35) at baseline to 9.00 (SD4.62) at Day +8, with improvements maintained through 24-week follow-up (mean 10.42, SD6.93); 69% achieved HADS scores below the clinical threshold. The proportion of participants with a "complete" mystical experience (Mystical Experience Questionnaire ≥ 60%) increased from 38% in the first experience to 77% in the second, without an increase in challenging experiences (Challenging Experiences Questionnaire). Social support, social identification, and group cohesion scores showed progressive improvements that persisted at 24 weeks.DiscussionA second experience of group retreat psilocybin therapy was safe and feasible for partial responders with metastatic cancer. The protocol modifications-higher dose, optional booster, and no antidepressant tapering requirement-did not introduce new safety concerns and were associated with substantially enhanced mystical experiences and preliminary efficacy signals. These findings support further investigation of retreatment protocols for partial responders and contribute to developing scalable group-based models relevant to psychedelic public health, where the resource intensity of individual treatment remains a fundamental barrier to population-level access.

keywords:
Humans, Neoplasms, Hallucinogens, Treatment Outcome, Retreatment, Depression, Anxiety, Adult, Aged, Middle Aged, Female, Male, Psilocybin

topic_tags:
Depression,Anxiety,Headache / Migraine,Mystical Experience,Clinical Trial,Cancer Patients,Safety,Adverse Events

raw_json:
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title: Effects of a single dose of psilocybin on diet-induced weight loss in obese mice.
publication_date: 2026-04-13
doi: 10.1038/s41398-026-03995-7
pubmed_id: 41980923
source_url: https://doi.org/10.1038/s41398-026-03995-7
substance_tags: psilocybin
topic_tags: Neuroplasticity,Pharmacology,Mechanism of Action,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:
Keenan RJ, Haque RT, Jin X, Mustafa T, Homman-Ludiye J, Elysee K, Wee ZS, Simonds SE, Foldi CJ, Cowley MA.

abstract:
Prolonged obesity induces enduring structural changes within neural circuits that contribute to maintaining the body at an elevated/obese body weight. These circuits regulate various mechanisms which can inhibit extreme or persistent weight loss. Therefore, a potential therapeutic strategy to facilitate weight loss is to promote structural plasticity within the brain. Psychedelic compounds, such as psilocybin, promote neural plasticity caused by a rapid and persistent growth of dendritic spines, which can facilitate the remodelling of neural circuits. Preclinical and clinical studies using psychedelic compounds have demonstrated efficacy for various neuropsychiatric disorders, which are often comorbid with obesity, and share underlying neural mechanisms. Here, we evaluate the effects of a single dose of psilocybin on body weight, food intake and energy expenditure in diet-induced obese (DIO) mice switched onto a low-fat chow. Psilocybin exacerbated diet-induced weight loss over a four-week period in DIO mice and increased the susceptibility for mice to exhibit more profound weight loss. Psilocybin appears to exert these effects predominantly through modulating food intake, with no influence on energy expenditure. No differences were observed in body weight or food intake in DIO mice maintained on a high-fat diet, indicating psilocybin does not necessarily directly promote weight loss or reduce food intake. Rather, it may help facilitate weight loss, provided it is administered in combination with other weight loss promoting interventions. Additional experimentation is required to examine the precise mechanisms involved; however, this data supports further investigation into the use of psychedelic compounds as an adjunct therapy for obesity.

keywords:
Animals, Mice, Inbred C57BL, Mice, Mice, Obese, Obesity, Body Weight, Weight Loss, Hallucinogens, Energy Metabolism, Eating, Male, Diet, High-Fat, Psilocybin

raw_json:
{"europe_pmc_id":"41980923","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin Trends in States That Decriminalized Use.
authors: Black JC, Bau GE, Cook RR, Bemis EA, Monte AA.
publication_date: 2026-03-31
doi: 10.1001/jama.2026.1952
pubmed_id: 41817506
source_url: https://doi.org/10.1001/jama.2026.1952
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":"41817506","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2026-04-09
doi: 10.1038/s41467-026-71481-1
pubmed_id: 41963345
source_url: https://doi.org/10.1038/s41467-026-71481-1
substance_tags: psilocybin,psilocin
topic_tags: Mechanism of Action,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 11:22:00
title:
Sex-specific increased reactivity of the PVT and prolonged PVT→CeA circuit engagement following psilocin administration.

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

abstract:
The psychedelic psilocybin has shown therapeutic potential, yet underlying neural mechanisms remain poorly understood. We investigated the impact of psilocin-the active metabolite of psilocybin-on basal activity and reactivity within the paraventricular nucleus of the thalamus (PVT) and PVT projections to central amygdala (CeA) in rats. Psilocin administration increased PVT c-Fos expression and selectively engaged PVT→CeA neurons in females, but not males. Psilocin enhanced PVT reactivity to an aversive air-puff stimulus, with effects primarily driven by passive responders. In PVT→CeA neurons, psilocin prevented time-dependent reductions in stimulus-evoked activity and maintained reactivity across timepoints in females but not males. The sustained engagement of PVT→CeA circuitry was driven by active responders. These findings identify sex-specific modulation of thalamic-limbic circuitry and behavior by psilocin, implicating PVT→CeA circuitry in the neural and behavioral effects of psychedelic compounds, advancing our understanding of how psychedelics modulate emotional brain circuits to further inform potential therapeutic mechanisms.

keywords:
Paraventricular Hypothalamic Nucleus, Neurons, Animals, Rats, Rats, Sprague-Dawley, Proto-Oncogene Proteins c-fos, Hallucinogens, Female, Male, Central Amygdaloid Nucleus, Psilocybin

raw_json:
{"europe_pmc_id":"41963345","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Veysi A, Atanasovski D, Ardalan M, Motamed N, Eriksson E.
publication_date: 2026-04-09
doi: 10.1017/neu.2026.10075
pubmed_id: 41958297
source_url: https://doi.org/10.1017/neu.2026.10075
substance_tags: psilocybin
topic_tags: Depression,Neuroplasticity,Receptor Pharmacology,Transcriptomics
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 elicits a conserved glucocorticoid-responsive gene signature across five 5-HT2A receptor-rich brain regions in rat.

abstract:
ObjectivePsychedelics such as psilocybin are known for their hallucinogenic properties and have also been reported to produce long-lasting therapeutic effects in depression and possibly also other psychiatric disorders. Several lines of evidence suggest that psilocybin exerts its effects through activation of 5-HT2A receptors located postsynaptically to serotonergic neurons, for example, in the frontal cortex, parts of the limbic system, including the amygdala and hippocampus, and striatum. The present study was conducted to shed further light on psilocybin-induced changes in gene expression.MethodSamples from the medial prefrontal cortex, cingulate cortex, hippocampus, amygdala, and striatum were collected from 24 male Wistar rats 90 min after they had been injected with either saline or psilocybin (2 mg/kg) and subjected to multi-region transcriptional profiling using 3prime-RNASeq technology.ResultsNfkbia and Sgk1 were upregulated in all the studied regions, Ddit4 was upregulated in four regions, and Gpd1, Apold1, Sox9, Tsc22d3, and Slc2a1 were differentially expressed in two regions. Other cases of differentially expressed genes were region-specific.ConclusionWhereas psilocybin was not found to alter the expression of genes encoding enzymes, transporters, or receptors implicated in the serotonergic signalling, or those specifically involved in the regulation of the synaptic activity of other neurotransmitters, a common denominator for many of the genes impacted by psilocybin is that they have previously been found to be activated by glucocorticoids.

keywords:
Brain, Amygdala, Gyrus Cinguli, Hippocampus, Corpus Striatum, Prefrontal Cortex, Animals, Rats, Rats, Wistar, Receptor, Serotonin, 5-HT2A, Hallucinogens, Gene Expression Profiling, Male, Transcriptome, Psilocybin

raw_json:
{"europe_pmc_id":"41958297","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


journal: MMWR. Morbidity and mortality weekly report
publication_date: 2026-04-08
doi: 10.15585/mmwr.mm7513a2
pubmed_id: 41955162
source_url: https://pubmed.ncbi.nlm.nih.gov/41955162/
substance_tags: psilocin
topic_tags: Microdosing,Safety,Toxicity
study_type: Other
source_name: PubMed
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 06:54:12
raw_json: {"pubmed_id":"41955162"}
title:
Severe Illness Associated with Eating Mushroom-Containing Chocolate Products - United States, January-October 2024.

authors:
Rumph JT, Winquist A, Troeschel AN, Pulver S, Schnall AH, Ebersole J, Yeh M, Burt B, Federman SL, Klontz K, Dasenbrock C, Leahy HL, Brady S, Stuteville H, Patel K, Daniel J, Chang A

abstract:
In late spring 2024, CDC was alerted to an outbreak of poisoning potentially associated with eating Diamond Shruumz microdosing chocolate bars. Diamond Shruumz microdosing chocolate bars are edible products designed so that small doses of mushroom-derived psychoactive compounds and other psychoactive ingredients can be eaten in a presectioned serving. In response to this alert, CDC and the Food and Drug Administration coordinated a nationwide outbreak investigation to characterize the potential poisonings associated with eating Diamond Shruumz microdosing chocolate bars. A case of poisoning was defined as an illness with moderate or major clinical effects (i.e., symptoms) as defined by America's Poison Centers in a person who ate any Diamond Shruumz product or another mushroom-containing chocolate product during January-October 2024. In total, 180 cases were reported in 34 states. Among these, 73 persons were hospitalized, including 38 persons who required intensive care unit (ICU) admission, 29 who required endotracheal intubation, and two deaths. Eating Diamond Shruumz chocolate bars was associated with higher odds of hospitalization (odds ratio [OR] = 3.29; 95% CI = 1.51-7.40), ICU admission (OR = 6.30; 95% CI = 2.17-22.6), seizures (OR = 8.45; 95% CI = 3.00-27.9), and endotracheal intubation (OR = 8.04; 95% CI = 2.24-44.2), compared with eating other mushroom-containing chocolate products. Eating larger amounts of Diamond Shruumz chocolate bars was associated with an increased likelihood of hospitalization, ICU admission, and endotracheal intubation (p-value for trend tests [p-trend] = 0.023, 0.004, and <0.001, respectively). Diamond Shruumz products were recalled, and the public was advised not to eat, sell, or serve any Diamond Shruumz products and to discard any Diamond Shruumz products previously purchased. Testing of some Diamond Shruumz products identified substances present in psychoactive mushrooms, including muscimol, psilocin (a Schedule I controlled substance), kavalactones, and other substances in some, but not all, tested products. Consumers should be aware of the poisoning risk associated with eating Diamond Shruumz products and other mushroom-containing microdosing chocolate products due to variability in ingredient composition, the absence of standardized regulatory oversight for sampling and testing finished products, and the potential toxicity of compounds intended to produce psychoactive effects.


authors: Morel NS, Stenbaek DS, Lundberg J, Beckman M.
publication_date: 2026-04-08
doi: 10.1186/s12909-026-09124-8
pubmed_id: 41952163
source_url: https://doi.org/10.1186/s12909-026-09124-8
substance_tags: psilocybin
topic_tags: Depression,End-of-Life Distress,Randomized Controlled Trial
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:
Evaluation of a facilitator training program in a randomized controlled trial of psilocybin treatment for depression.

abstract:
BackgroundMajor depression is a prevalent condition among patients with life-threatening illnesses, such as cancer, and recent findings suggest that psilocybin may hold promising treatment potential. Contemporary trials of psilocybin generally employ a model that includes psychotherapeutic support consisting of preparation and integration sessions surrounding the dosing. However, there is limited research on the psychotherapeutic component of treatment, including the skills, professional qualifications and training needed to provide it.MethodsIn this study, nine nurses completed a 15-week online and on-site training program as facilitators in an ongoing randomized controlled trial of psilocybin treatment for depression. The training evaluation consisted of a subjective evaluation by the facilitators collected during and after completion of training, and an objective evaluation of the facilitators' verbal relational skills assessed with standardized role-plays before and after completion of training. The recorded role-plays were assessed using the relational components of the Motivational Interviewing Treatment Integrity (MITI) code 4.2 and analyzed with the Wilcoxon Signed Rank Test.ResultsThe facilitators' subjective evaluations indicated that the online and on-site training sessions had supported their knowledge- and skill acquisition. However, most facilitators reported that additional practical in-person training would have been necessary for them to feel adequately prepared to provide the treatment. The objective assessment of the facilitators' verbal relational skills showed a significant increase in one of twelve MITI variables and medium to large effect sizes for six of the measures pre- to post-training.ConclusionsThe training model used in this study showed potential to improve outcomes, though effects were modest and only demonstrated in role-play. The facilitators also indicated a need for additional training to feel adequately prepared. The exact requirements for the psychotherapeutic support surrounding the dosing in these treatments, including the specific skills and professional qualifications needed to provide it, remain unclear. Nonetheless, the results of this study suggest that different professionals may require distinct types of training to deliver these treatments effectively. Future studies should design training programs based on the facilitators' baseline skills and provide clear descriptions and objective measures of both the training intervention and outcome, along with adherence measures throughout treatment.Trial registrationEudraCT: 2023-505532-35-00; Clinicaltrails.gov ID: NCT06319378. Registered 8 November 2023.

keywords:
Humans, Hallucinogens, Program Evaluation, Adult, Female, Male, Psilocybin, Major Depressive Disorder

raw_json:
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title: Hallucinogenic Therapy in Alzheimer's Disease targeting Mitochondria-Associated Membranes.
authors: Minauro-Sanmiguel F, Vargas-Perez H.
publication_date: 2026-02-15
doi: 10.1016/j.neuroscience.2026.02.028
pubmed_id: 41707907
source_url: https://doi.org/10.1016/j.neuroscience.2026.02.028
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 11:22:02
abstract:
Mitochondrial dysfunction is increasingly recognized as a central driver of Alzheimer's disease (AD), contributing to neuroinflammation, synaptic failure, and energy collapse.Emerging preclinical evidence suggests that classic hallucinogens, such as psilocybin, lysergic acid diethylamide (LSD), N,N-dimethyltryptamine (DMT), mescaline, may restore mitochondrial integrity by activating Serotonin 2A (5-HT2A) and sigma-1(Sig-1R) receptors. In experimental models, these pathways are associated with enhanced mitochondrial biogenesis, reduced oxidative stress, and preservation of ER-mitochondrial coupling. DMT and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) specifically engage Sig-1R at mitochondria-associated membranes, improving calcium homeostasis and cellular resilience. While these mechanisms are mechanistically compelling, evidence for clinical efficacy in AD remains limited and largely preclinical. Accordingly, this framework is presented as a hypothesis-generating model suggesting that mitochondrial-centered psychedelic mechanisms warrant further investigation,provided that neuropsychiatric safety, patient selection, and translational feasibility are carefully addressed.

keywords:
Mitochondria, Animals, Humans, Alzheimer Disease, Receptors, sigma, Hallucinogens, Mitochondria Associated Membranes, Sigma-1 Receptor

topic_tags:
Neuroplasticity,Mechanism of Action,Receptor Pharmacology,Mitochondrial Function,Oxidative Stress,Resilience,Animal Study,Safety,Inflammation

raw_json:
{"europe_pmc_id":"41707907","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Catatonia Associated With First-Time Psilocybin Exposure: A Case Report.
authors: Singh J, Mruthyunjaya P.
publication_date: 2026-04-04
doi: 10.7759/cureus.106474
pubmed_id: 42093782
source_url: https://doi.org/10.7759/cureus.106474
substance_tags: psilocybin
topic_tags: Addiction,Brain Imaging,Aging,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 11:22:00
abstract:
In this case report, we highlight a 28-year-old male patient with predominantly retarded type of catatonia following a single incidence of psilocybin ingestion. This patient presented with a history of six months of mutism and inability to feed himself after consuming psilocybin for the first time. He did not have any history of psychiatric illness or substance use. Imaging and laboratory results were unremarkable. The goal of this case report is to document one of the earliest records of psilocybin-induced catatonia.

raw_json:
{"europe_pmc_id":"42093782","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin and human longevity.
authors: Lerer L.
publication_date: 2026-04-02
doi: 10.1038/s41514-026-00380-y
pubmed_id: 41932939
source_url: https://doi.org/10.1038/s41514-026-00380-y
substance_tags: psilocybin
topic_tags: Aging,Longevity,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:
Psilocybin extends lifespan in aged mice, and this has prompted extensive media speculation about possible human longevity benefits. We examined mortality among prominent psychedelic personalities, researchers, and advocates who claimed psychedelic use (n = 11) and compared them with cancer (n = 12) and aging researchers (n = 5). All groups exceeded population life expectancy, reflecting the effect of socioeconomic advantage on lifespan, but psychedelic personalities did not outlive cancer and aging researchers. These findings highlight the need for rigorous mechanistic and epidemiological studies before inferring human anti-aging effects of psychedelics.

raw_json:
{"europe_pmc_id":"41932939","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Complete biosynthesis of psychedelic tryptamines from three kingdoms in plants.
publication_date: 2026-03-31
doi: 10.1126/sciadv.aeb3034
pubmed_id: 41921002
source_url: https://doi.org/10.1126/sciadv.aeb3034
substance_tags: psilocybin,psilocin
topic_tags: Mechanism of Action,Aging,Spirituality
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:00
authors:
Berman P, Höfer J, Mehlman H, Almekias-Siegl E, Khersonsky O, Dong Y, Heinig U, Sulimani L, Hao LK, Cohen S, Peleg Y, Meir S, Rogachev I, Meiri D, Fleishman SJ, Aharoni A.

abstract:
Psychedelic indolethylamines with therapeutic potential are naturally produced in plants, fungi, and animals. Here, we elucidated the complete N,N-dimethyltryptamine (DMT) biosynthetic pathway in hallucinogenic plant species traditionally used in shamanic rituals for spiritual healing. Leveraging the similarities in their chemical structures, we reconstructed in one plant assay the full biosynthetic pathways of five renowned natural psychedelics; psilocin and psilocybin found in mushrooms, DMT from plants, and bufotenin and 5-methoxy-DMT secreted by the Sonoran Desert toad. We further engineered halogenated analogs of these molecules, which do not naturally occur in plants and exhibit prospective therapeutic potential for psychiatric conditions. Blending catalytic functions across the tree of life, coupled with metabolic engineering guided by rational protein design of mutant enzymes, enabled substantially more efficient in planta production of the indolethylamine components. This work establishes a versatile platform for concurrent biosynthesis and diversification of psychoactive indolethylamines, paving the way for their production in plants.

keywords:
Plants, Tryptamines, N,N-Dimethyltryptamine, Bufotenin, Hallucinogens, Biosynthetic Pathways, Psilocybin

raw_json:
{"europe_pmc_id":"41921002","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Qiao YX, Dai W, Yao YS, Wei QQ, Yue CX, Yin YY, Li YF, Zhang LM.
publication_date: 2026-04-11
doi: 10.1016/j.pnpbp.2026.111698
pubmed_id: 41974301
source_url: https://doi.org/10.1016/j.pnpbp.2026.111698
substance_tags: psilocybin,psilocin
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 astrocytes in the prefrontal cortex contribute to the rapid antidepressant-like effects of psilocybin in the chronic restraint stress mouse model.

abstract:
Psilocybin showed a rapid antidepressant response in several clinical trials, which offers new hope for treating depression. Astrocytes were associated with the etiology of depression and might contribute to the onset of psilocybin. In this study, we investigated the fast antidepressant effect of psilocybin and tested variations of GFAP (astrocytic markers) and C3 protein (markers of A1 astrocyte) expression after psilocybin treatment in the chronic restraint stress (CRS) mouse model. We next defined the modulating impact of psilocin (psilocybin's main active metabolite) on primary astrocytes as well as A1 astrocytes in vitro. The depletion of astrocytes was achieved by AAV injection to further verify the astrocytic role underlying the action of psilocybin. Psilocybin and ketamine (positive control) rapidly reversed the depressive-like behaviors in the CRS mice. Both psilocybin and ketamine inhibited the CRS-induced astrocytic loss and increased C3 protein in the prefrontal cortex (PFC). Psilocin up-regulated the activation and proliferation of primary astrocytes, and strengthened astrocytic ATP/lactate/glutamate release and mitochondrial function. Psilocin reversed A1 astrocyte-induced impairments in ATP/lactate/glutamate release and mitochondrial function. In vivo, depletion of astrocytes in the prelimbic (PrL) region of mPFC might affect the antidepressant action of psilocybin in unstressed mice. Our findings might be significant for a better understanding of astrocytic mechanisms in the action of psilocybin.

keywords:
Prefrontal Cortex, Astrocytes, Cells, Cultured, Animals, Mice, Inbred C57BL, Mice, Disease Models, Animal, Ketamine, Antidepressive Agents, Restraint, Physical, Depression, Stress, Psychological, Male, Psilocybin

topic_tags:
Depression,Mechanism of Action,Biomarkers,Mitochondrial Function,Clinical Trial,Animal Study,In Vitro Study

raw_json:
{"europe_pmc_id":"41974301","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: The Psychological Support Model in Psilocybin Research: Psychotherapy in Disguise?
authors: Jacobsen CF, Stenbæk DS, Poulsen S, Armand S.
publication_date: 2026-01-13
doi: 10.1176/appi.prcp.20250113
pubmed_id: 42022021
source_url: https://doi.org/10.1176/appi.prcp.20250113
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":"42022021","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Grant JE, Boutouis S, O'Brien M, Avila L, Neelapu M, Ehsan D.
publication_date: 2026-03-31
doi: 10.1097/wnf.0000000000000683
pubmed_id: 41973961
source_url: https://doi.org/10.1097/wnf.0000000000000683
substance_tags: psilocybin
topic_tags: Depression,Personality Change,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:
An Open-Label Study of Single-Dose Psilocybin for Borderline Personality Disorder With Co-Occurring Major Depressive Disorder.

abstract:
ObjectivesBorderline personality disorder (BPD) is often comorbid with major depressive disorder (MDD), and there has been a suggestion in the literature that this comorbidity may interfere with MDD treatment response. Our objective was to conduct a pilot study of psilocybin in adults with BPD and MDD.MethodsAdults aged 18 to 65 years with a DSM-5 diagnosis of MDD and BPD were enrolled in an open-label pilot study of a single dose of psilocybin. Assessments were conducted 1 week before dosing (baseline), on the dosing day (visit 2), and at 1, 2, and 4 weeks postdosing. The co-primary outcome measures were changes in depressive and BPD symptoms from baseline to study endpoint, and we used a paired-samples t test to examine changes in symptoms.ResultsNine participants (4 males; mean age=31.3 y) with MDD and BPD were enrolled. MDD symptoms significantly changed from baseline to visit 5: baseline (M=28.56, SD=4.53) and final visit (M=17.22, SD=10.39); t(8)=-4.217, P=0.003; Cohen d=1.41. BPD scores did not significantly change from baseline to study endpoint.ConclusionsThis small open-label study resulted in statistically significant improvement in MDD symptoms but not for BPD symptoms. These findings, which await larger clinical trials, suggest that BPD does not appear to interfere with response to depressive symptoms.

raw_json:
{"europe_pmc_id":"41973961","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psychedelic-assisted pharmacotherapy: clinical applications and regulatory considerations.
authors: Marazziti D, Gambini M, Gurrieri R, Russomanno G, Sità G, Pescini E, Digiuseppe FR, Mucci F.
publication_date: 2026-04-06
doi: 10.1080/14656566.2026.2654682
pubmed_id: 41944071
source_url: https://doi.org/10.1080/14656566.2026.2654682
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
abstract:
IntroductionAfter decades of regulatory marginalization, psychedelic compounds have reemerged as promising therapeutic tools in psychiatry, driven by unmet clinical needs in treatment-resistant mental disorders and by growing evidence of rapid and sustained effects on mood, cognition, and behavior.Areas coveredThis narrative review critically examined the current clinical and regulatory landscape of psychedelic-assisted therapies in psychiatry. We synthesize evidence from phase II-III clinical trials, regulatory agency documents, and international drug policy frameworks, focusing on ketamine/esketamine, MDMA, psilocybin, LSD, DMT/5-MeO-DMT, and ibogaine across major depressive disorder, treatment-resistant depression, PTSD, anxiety disorders, and substance use disorders. Particular attention will be given to regulatory pathways, scheduling constraints, access mechanisms, and compound-specific approval trajectories in the United States, European Union, and selected international jurisdictions.Expert opinionPsychedelic-assisted therapies are unlikely to follow a conventional prescription model and instead require specialist-delivered, psychotherapy-integrated care under appropriate regulatory and ethical safeguards. While late-stage trials support their potential in high-need populations, unresolved challenges, including long-term safety, scalability, workforce training, equity of access, and medico-legal accountability, must be addressed before broader clinical implementation.

keywords:
Animals, Humans, Substance-Related Disorders, Hallucinogens, Drug Approval, Mental Disorders, Psychotherapy

topic_tags:
Depression,Anxiety,PTSD,Addiction,Mechanism of Action,Clinical Trial,Review Article,Treatment-Resistant Depression,Safety

raw_json:
{"europe_pmc_id":"41944071","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: An international mega-analysis of psychedelic drug effects on brain circuit function.
publication_date: 2026-04-05
doi: 10.1038/s41591-026-04287-9
pubmed_id: 41942645
source_url: https://doi.org/10.1038/s41591-026-04287-9
substance_tags: psilocybin
topic_tags: Brain Imaging,Mechanism of Action,Aging
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:03
authors:
Girn M, Doss MK, Roseman L, Preller KH, Palhano-Fontes F, Pasquini L, Barrett FS, Mallaroni P, Mason NL, Timmermann C, McCulloch DE, Fisher PM, Winston BS, Moujaes F, Muller F, Liechti ME, Vollenweider FX, Ramaekers JG, Kuypers K, Araujo DB, Sporns O, Siegel J, Dosenbach N, Nutt DJ, Carhart-Harris RL, Stamatakis EA, Bzdok D.

abstract:
Psychedelic drugs are re-emerging as promising scientific and clinical tools. However, despite a rapidly expanding literature on their therapeutic value, the neural mechanisms underlying psychedelic effects remain unclear. Resting-state functional magnetic resonance imaging studies of acute psychedelic effects, conducted independently by several research groups, have so far yielded fragmented and sometimes inconsistent findings. Here, to help facilitate greater convergence, we conducted a 'mega-analysis' integrating 11 independent resting-state functional magnetic resonance imaging datasets across five psychedelic drugs (psilocybin, lysergic acid diethylamide, mescaline, N,N-dimethyltryptamine and ayahuasca) from research groups spanning three continents and five countries. By applying a uniform preprocessing pipeline and a Bayesian hierarchical modeling framework, we discovered several common features in the induced alterations to brain function across drugs and sites. Most prominently, we identified a core signature of increased functional connectivity between transmodal (default, frontoparietal and limbic) and unimodal networks (visual and somatomotor), with subnetwork specificity. Furthermore, key subcortical regions (thalamus, caudate and putamen) and the cerebellum exhibited altered coupling with sensorimotor networks. In contrast to several single-site reports, Bayesian modeling revealed weak-to-moderate and selective reductions in within-network functional connectivity, with substantial variability across drugs and networks. Together, these findings extend past work by demonstrating that psychedelics reconfigure large-scale cortical organization while selectively engaging subcortical circuitry. This study provides the most comprehensive synthesis of psychedelic brain action to date, helping resolve inconsistencies and offering a probabilistic map of how psychedelics alter large-scale brain organization. We hereby provide a cornerstone to benchmark and shepherd future psychedelic neuroimaging research.

keywords:
Brain, Nerve Net, Humans, Banisteriopsis, N,N-Dimethyltryptamine, Lysergic Acid Diethylamide, Hallucinogens, Magnetic Resonance Imaging, Brain Mapping, Bayes Theorem, Psilocybin

raw_json:
{"europe_pmc_id":"41942645","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Kazdan J, Ladha KS, Husain MI.
publication_date: 2026-03-31
doi: 10.1002/prp2.70238
pubmed_id: 41940853
source_url: https://doi.org/10.1002/prp2.70238
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:
Psychedelic Therapies for Comorbid Major Depressive Disorder and Chronic Pain: A Review of Putative Mechanisms of Action.

abstract:
Major Depressive Disorder (MDD) and chronic pain are independently debilitating conditions that frequently co-occur. This comorbidity poses a significant clinical challenge, resulting in greater symptom severity, higher disability, and worse prognosis than either condition alone. Current therapies often address each disorder in isolation, leaving individuals with comorbid MDD and chronic pain underserved. Serotonergic psychedelics such as psilocybin, N,N-dimethyltryptamine (DMT), and Lysergic Acid Diethylamide (LSD) have reemerged as promising therapeutic targets for a range of neuropsychiatric disorders. When combined with psychological support, psychedelics show rapid and sustained antidepressant potential, and preliminary evidence supports analgesic effects. Despite substantial overlap in the biological and psychological processes underlying MDD and chronic pain, research on psychedelics for this comorbidity remains largely unexplored. This narrative review examines putative mechanisms through which psychedelics target symptoms of both MDD and chronic pain. Mechanisms considered include serotonergic modulation via the 5-HT2A receptor, anti-inflammatory effects, neuroplastic changes, altered brain network dynamics, psychological effects, and the influence of set and setting. While most existing evidence comes from populations with either depression or pain alone, the breadth of proposed mechanisms supports psychedelics as a unified therapeutic approach for comorbid MDD and chronic pain. This review provides a compelling rationale for future clinical trials to evaluate psychedelic-assisted therapies for complex neuropsychiatric and medical conditions.

keywords:
Animals, Humans, Receptor, Serotonin, 5-HT2A, Hallucinogens, Antidepressive Agents, Comorbidity, Chronic Pain, Major Depressive Disorder

topic_tags:
Depression,Chronic Pain,Mechanism of Action,Receptor Pharmacology,Clinical Trial,Review Article,Inflammation

raw_json:
{"europe_pmc_id":"41940853","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Clinical Characteristics of Emergency Visits Related to Recreational Psychedelic Use.
authors: Bhatt KV, Friedman J, Benster L, Narasimhan R, Yang K, Mishra J, Weissman CR, Ramanathan D.
publication_date: 2026-03-31
doi: 10.1007/s10597-026-01620-x
pubmed_id: 41920509
source_url: https://doi.org/10.1007/s10597-026-01620-x
substance_tags: psilocybin
topic_tags: Anxiety,Review Article,Observational Study,Safety,Adverse Events
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:
Recreational psychedelic use is increasing, yet data on adverse events remains limited. This study characterized emergency department (ED) visits associated with recreational psychedelic use at UC San Diego Medical Center. We conducted a retrospective chart review of ED encounters (2010-2023). Cases were identified using ICD-10 hallucinogen-related codes and confirmed through manual review. Multivariable logistic regression was employed to identify factors associated with psychiatric hospitalization. We identified 232 cases, primarily related to LSD (35.0%), MDMA (30.2%), and psilocybin (24.0%). The cohort was predominantly young, white, and male. Common psychiatric symptoms included agitation (25.9%) and anxiety (24.6%). Common nonpsychiatric symptoms included nausea/vomiting (9.5%) and diaphoresis (5.2%). 11.2% of cases required psychiatric hospitalization. Factors associated with psychiatric hospitalization included concurrent cannabis use (OR = 10.9, 95% CI3.37-39.64), history of bipolar disorder (OR = 12.67, 95% CI2.35-70.43), and history of a primary psychotic disorder (OR = 17.10, 95% CI2.01-187.49). Psychedelic-associated emergency visits present with various clinical characteristics. While most recreational psychedelic presentations are effectively managed in the emergency department, specific factors predict severe outcomes. Concurrent cannabis use and pre-existing psychotic or bipolar disorders are associated with increased odds of psychiatric hospitalization, underscoring the importance of targeted risk assessment in patients with these vulnerabilities.

raw_json:
{"europe_pmc_id":"41920509","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Griškova-Bulanova I, Vejmola Č, Páleníček T.
publication_date: 2026-03-03
doi: 10.1152/jn.00519.2025
pubmed_id: 41779518
source_url: https://doi.org/10.1152/jn.00519.2025
substance_tags: psilocybin,psilocin
topic_tags: Brain Imaging,Mechanism of Action,Receptor Pharmacology,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
title:
Serotonergic modulation of cortical gamma synchronization: right-lateralized psilocin effects on 40 Hz auditory steady-state responses in rats.

abstract:
Auditory steady-state responses (ASSRs), particularly at 40 Hz, are promising biomarkers for psychiatric disorders involving dysregulated neural synchronization. Although most ASSR studies have focused on the glutamatergic system, the serotonergic system, specifically 5-HT2A receptor signaling, has received limited attention. Psilocin, the active metabolite of psilocybin and a known 5-HT2A receptor agonist, alters cortical oscillatory activity, but its effects on ASSR dynamics remain unclear. In this study, we examined psilocin's effects on ASSRs in eight adult male Wistar rats implanted with 21 cortical electrodes. The rats were exposed to 40 Hz and 80 Hz click-train stimulation before and 30 min after subcutaneous psilocin administration (4 mg/kg). EEG signals were analyzed using time-frequency decomposition to extract phase-locking index (PLI) and event-related spectral perturbation (ERSP) values from frontal and temporal regions of both hemispheres. Psilocin selectively decreased PLI at 40 Hz stimulation in the right temporal cortex, with no significant changes in the frontal or left temporal regions, nor in response to 80 Hz stimulation. ERSP analysis revealed a global reduction in spectral power after psilocin administration in response to 80 Hz stimuli, but no consistent effects at 40 Hz. These results indicate that psilocin induces region- and frequency-specific alterations in auditory neural synchronization, characterized by right-lateralized disruption of 40 Hz phase-locking. This highlights the sensitivity of low-gamma oscillations to serotonergic modulation and supports the use of ASSR paradigms in translational models of altered perceptual and cognitive states.NEW & NOTEWORTHY This is the first preclinical study to demonstrate that psilocin selectively disrupts auditory steady-state responses (ASSRs) in rats in a frequency- and region-specific manner. The findings indicate a right-lateralized reduction in phase-locking at 40 Hz, along with a global suppression of spectral power at 80 Hz. These results provide new insights into the serotonergic modulation of neural synchrony and support the use of ASSRs as a translational biomarker for altered perceptual states.

keywords:
Animals, Rats, Rats, Wistar, Hallucinogens, Cortical Synchronization, Acoustic Stimulation, Auditory Perception, Evoked Potentials, Auditory, Male, Functional Laterality, Serotonin 5-HT2 Receptor Agonists, Gamma Rhythm, Psilocybin

raw_json:
{"europe_pmc_id":"41779518","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Regulatory ambiguity and governance challenges for psilocybin mushrooms in Brazil.
authors: Nogueira M, García-Hernández S, Roberto GS, Rodrigues DC.
publication_date: 2026-02-17
doi: 10.1016/j.drugpo.2026.105198
pubmed_id: 41713116
source_url: https://doi.org/10.1016/j.drugpo.2026.105198
substance_tags: psilocybin
topic_tags: Mechanism of Action
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:
The legal status of psilocybin mushrooms in Brazil remains ambiguous, despite increasing global scientific and public interest in their therapeutic and ceremonial use. This commentary examines the regulatory uncertainty surrounding psilocybin mushrooms in Brazil and situates the debate within broader legal, drug policy, public health, and Indigenous rights discussions. Building on academic literature, media reports, jurisprudence, and insights drawn from the regulatory experience surrounding ayahuasca, our commentary argues that any future coherent approach to psilocybin regulation would need to integrate scientific evidence, Indigenous knowledge, and ethical governance. We underscore the importance of regulatory mechanisms that ensure Indigenous leadership in decision-making and protect traditional knowledge, consistent with international frameworks such as the World Health Organization's Global Traditional Medicine Strategy and the United Nations Declaration on the Rights of Indigenous Peoples. Despite the growing international momentum toward psychedelic reform, the absence of a coherent framework in Brazil continues to generate legal uncertainty and arbitrary enforcement. Accordingly, our reflection points to the need to open formal deliberative spaces by regulatory bodies, particularly the Brazilian Health Regulatory Agency (ANVISA) and the National Drug Policy Council (CONAD), to develop evidence-based, culturally sensitive, and constitutionally consistent policies for psilocybin regulation in Brazil.

keywords:
Humans, Hallucinogens, Public Health, Government Regulation, Legislation, Drug, Drug and Narcotic Control, Brazil, Psilocybe, Psilocybin

raw_json:
{"europe_pmc_id":"41713116","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2026-02-01
doi: 10.1016/j.psychres.2026.116992
pubmed_id: 41643299
source_url: https://doi.org/10.1016/j.psychres.2026.116992
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Emotional Processing,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 11:22:01
title:
Real-world effectiveness and safety of psychedelic-assisted psychotherapy: Outcomes from a large-scale compassionate use cohort in Switzerland.

authors:
Aboulafia-Brakha T, Buchard A, Mabilais C, Alaux S, Amberger C, Furtado L, Seragnoli F, Briefer JF, Thorens G, Sabé M, Szczesniak L, Iuga R, Zullino D, Penzenstadler L.

abstract:
BackgroundClassic serotonergic psychedelics such as LSD and psilocybin show promising antidepressant effects in controlled trials, but real-world data from routine clinical care remain limited.MethodsThis study retrospectively analysed routine data from adults with treatment-resistant depressive and/or anxiety disorders who received a first standardized Psychedelic-assisted Psychotherapy (PAP) cycle with 100 µg LSD or 25 mg psilocybin at a Swiss university hospital (May 2024-October 2025). Self-reported depression (BDI) and trait anxiety (STAI-T) were assessed at screening, one month before treatment, and 1-3 months post-treatment. In a subset of participants, cognitive emotion regulation (CERQ) was assessed pre- and post-treatment. Subjective drug effects and adverse events were recorded on the treatment day.ResultsThe sample consisted of 115 patients (56.5 % female; Mean age = 47.5 years). Depressive and anxiety symptoms significantly decreased over time (BDI: F(2178) = 63.50, p < 0.001, partial η² = 0.42; STAI-T: F(1.74,145.9) = 16.97, p < 0.001, partial η² = 0.17), with no main effect of substance. CERQ analyses indicated reduced self-blame, rumination and catastrophizing, and increased positive refocusing and reappraisal. Perceived intensity followed distinct temporal profiles for LSD and psilocybin, but comparable subjective drug effects and clinical outcomes. Adverse events were mostly mild and transient, with no serious complications or treatment discontinuations.ConclusionsIn this compassionate-use real-world cohort, a first fully-active dose PAP session with LSD or psilocybin was well tolerated and associated with significant improvements in depressive and anxiety symptoms. These findings support the feasibility and effectiveness of PAP in specialised routine care.

keywords:
Humans, Lysergic Acid Diethylamide, Hallucinogens, Treatment Outcome, Retrospective Studies, Anxiety Disorders, Psychotherapy, Adult, Middle Aged, Switzerland, Female, Male, Compassionate Use Trials, Depressive Disorder, Treatment-Resistant, Psilocybin, Outcome Assessment, Health Care

raw_json:
{"europe_pmc_id":"41643299","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Downar J, Lapenskie J, Anderson K, Parsons G, Polskaia N, Lalumiere G, Lawlor P.
publication_date: 2026-01-29
doi: 10.1177/02692163261416269
pubmed_id: 41617652
source_url: https://doi.org/10.1177/02692163261416269
substance_tags: psilocybin
topic_tags: Depression,Anxiety,End-of-Life Distress,Microdosing,Clinical Trial,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:
PSilocybin for psYCHological and existential distress in PALliative care (PSYCHED-PAL): A single arm unblinded clinical trial.

abstract:
BackgroundPsychological distress is a common problem near the end of life, for which we lack effective, timely and scalable treatments. No previous study has assessed whether microdose psilocybin can improve symptoms in this population.AimTo determine whether microdose psilocybin is safe, feasible and potentially efficacious in a palliative setting.DesignOpen label, single-arm clinical trial of a 3-week oral psilocybin intervention, starting with 1 mg daily in week 1, increased to 2 mg in week 2 and 3 mg in week 3.Clinicaltrialsgov NCT04754061.Setting/participantsTwo-center study in Ottawa, Canada of adults with advanced, incurable illness and an estimated prognosis of 1-12 months, experiencing severe psychological distress.ResultsWe enrolled 20 participants (59% of those screened) between January 2024 and April 2025, of which 17 began and 13/17 (76%) completed the intervention. Participants were 40-84 years old, 53% female, and 82% had cancer. There were no serious adverse events reported, and nine mild or moderate adverse events. Four participants withdrew due to disease progression or poor response. Of the 13 remaining participants, nine (69%) reported a meaningful global improvement (Patient Global Impression of Change ⩾ 5); 8 (62%) reported >50% improvement in Hamilton Depression Rating Scale scores, 7 (54%) reported >50% improvement in Hospital Anxiety and Depression Scale scores and 9 (72%) reported a meaningful improvement in Demoralization Scale II scores.ConclusionsMicrodose psilocybin is a safe, feasible and potentially efficacious treatment for psychological distress in people with advanced illness.

keywords:
Humans, Hallucinogens, Treatment Outcome, Palliative Care, Stress, Psychological, Existentialism, Adult, Aged, Aged, 80 and over, Middle Aged, Female, Male, Psilocybin, Psychological Distress

raw_json:
{"europe_pmc_id":"41617652","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Syed OA, Tsang B, Nestor SM, Lipsman N, Husain MI, Alam F, Giacobbe P.
publication_date: 2026-01-23
doi: 10.1016/j.neubiorev.2026.106573
pubmed_id: 41587629
source_url: https://doi.org/10.1016/j.neubiorev.2026.106573
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 11:22:00
title:
Methodological moderators of psilocybin-assisted therapy in depression: A systematic review and meta-analysis.

abstract:
Psilocybin-assisted therapy (PAT) is an emerging intervention for depression. Though several clinical trials report promising results for PAT in treating depression, there remains a need for consensus on optimal methodologies and standardization of PAT protocols. The objective of this review was to assess the efficacy of PAT in treating depressive symptoms and to systematically examine the influence of methodological moderators underlying antidepressant responses. We searched the electronic databases of PubMed, MEDLINE, PsychInfo and Embase for randomized-controlled trials (RCTs) using PAT as a treatment intervention for major depressive disorder. The primary outcomes were standardized mean difference (SMD) of change in depressive symptoms pre- versus post-treatment sessions, and the difference in antidepressant treatment effects among various PAT methodologies in a subgroup analysis. Seven RCTs involving 522 participants were analyzed. The overall random effects model found PAT to have a large and significant antidepressant effect. The subgroup analyses found larger effects, albeit non-significant differences in subgroup heterogeneity, associated with studies that administered psilocybin in bodyweight-adjusted doses and provided longer preparation, dosing, and integration sessions and provided non-manualized psychotherapy. This study presents the first systematic examination of PAT methodologies influencing antidepressant effects and provides preliminary insights for clinicians in designing future PAT protocols for depression.

keywords:
Humans, Hallucinogens, Antidepressive Agents, Depression, Randomized Controlled Trials as Topic, Psilocybin, Major Depressive Disorder

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

raw_json:
{"europe_pmc_id":"41587629","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Žuljević MF, Mijatović A, Orhanović R, Goasdoué G, Gujinović D.
publication_date: 2026-01-22
doi: 10.1016/j.jclinepi.2026.112170
pubmed_id: 41581835
source_url: https://doi.org/10.1016/j.jclinepi.2026.112170
substance_tags: psilocybin
topic_tags: 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:
Consistency of protocol and safety data reporting in clinical trial registrations and corresponding publications of interventions involving MDMA and psilocybin.

abstract:
Objectives3,4-methylenedioxymethamphetamine (MDMA) and psilocybin are being investigated as potential treatments for psychiatric disorders and have received increasing regulatory and media attention due to the methodological complexities and societal context of psychedelic substances. Therefore, we assessed the consistency of protocol registration and adverse event (AE) reporting in clinical trials of MDMA and psilocybin.Study design and settingWe conducted a cross-sectional analysis of all clinical trials on MDMA or psilocybin registered on ClinicalTrials.gov by March 12, 2025. For each trial, we assessed changes to primary outcome measures (POMs) and eligibility criteria over time and evaluated whether these changes were disclosed in corresponding publications. For completed trials with both posted results and published articles, we compared AE reporting between the article and the corresponding ClinicalTrials.gov registration.ResultsOut of 336 trials, major changes were recorded to POMs for 17.6% trials and to eligibility criteria for 28.6% trials, most of which occurred after participant recruitment began. Among completed trials, 72.0% did not report results on ClinicalTrials.gov, and most posted results exceeded the FDAAA-recommended 1-year reporting window. Only three of 29 trials with both posted results and publications showed full concordance in AE reporting, with most exhibiting both qualitative and quantitative discrepancies.ConclusionInconsistencies in protocol and AE reporting undermine the credibility and safety evaluation of MDMA and psilocybin trials. Greater transparency and stricter adherence to reporting standards are advised to ensure reliable evidence, protect participants, and maintain stakeholder and public trust.

keywords:
Humans, N-Methyl-3,4-methylenedioxyamphetamine, Hallucinogens, Cross-Sectional Studies, Research Design, Clinical Trials as Topic, Psilocybin

raw_json:
{"europe_pmc_id":"41581835","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Olejnik P, Kamińska K, Gołembiowska K, Kasarełło K.
publication_date: 2026-01-19
doi: 10.1007/s43440-026-00824-y
pubmed_id: 41557251
source_url: https://doi.org/10.1007/s43440-026-00824-y
substance_tags: psilocybin
topic_tags: Biomarkers,Clinical Trial,Animal Study,Inflammation,Immune Function
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 and chronic mild stress on microglial activation in rat spinal cord: an ex vivo analysis.

abstract:
INTRODUCTION: Psilocybin, a classic serotonergic psychedelic, has antidepressant, anxiolytic, anti-inflammatory, and analgesic properties. However, the immunomodulatory effects of psilocybin within the central nervous system, particularly on microglial activation, remain poorly understood. Therefore, this study aimed to investigate the effects of psilocybin on microglial activation markers and cytokine levels in the spinal cord isolated from rats subjected to chronic mild stress (CMS). METHODS: Tissues were isolated from four groups of adult male Wistar Han rats, each consisting of seven animals: not subjected to CMS (control), receiving two injections of saline (0.9% NaCl ip) or psilocybin (0.6 mg/kg ip) at 7-day intervals, and subjected to CMS, receiving two injections of NaCl (0.9% NaCl ip) or psilocybin (0.6 mg/kg ip) at 7-day intervals. Spinal cords were collected 1 week after the second dose of saline/psilocybin from the sacrificed rats and stored at -80 °C. The levels of microglial activation markers (iNOS and Arg1) and pro- and anti-inflammatory cytokines (TNF-α and IL-10) were analyzed using an enzyme-linked immunosorbent assay. RESULTS: The spinal cords isolated from CMS rats treated with psilocybin revealed significantly increased levels of Arg1 (p = 0.0306), TNF-α (p = 0.0357), and IL-10 (p = 0. 0081) compared to tissues from control rats administered with psilocybin. Additionally, although not statistically significant, iNOS levels showed an increasing trend in CMS rats treated with psilocybin compared to those in psilocybin-receiving controls (p = 0.0755). CONCLUSIONS: CMS activates the immune system/microglia non-specifically despite psilocybin administration. CLINICAL TRIAL NUMBER: Not applicable.

raw_json:
{"europe_pmc_id":"41557251","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Swieczkowski D, Kwaśny A, Sadko K, Cubała WJ.
publication_date: 2026-01-15
doi: 10.1016/j.euroneuro.2025.112746
pubmed_id: 41546918
source_url: https://doi.org/10.1016/j.euroneuro.2025.112746
substance_tags: psilocybin
topic_tags: Depression,Clinical Trial,Treatment-Resistant Depression,Safety
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:00
title:
Bridging the reporting gap: Application of the ReSPCT guidelines in psilocybin clinical trial protocols.

abstract:
Psilocybin-assisted therapies are increasingly studied for Major Depressive Disorder (MDD) and Treatment-Resistant Depression (TRD), and methodological rigor requires both pharmacological evaluation and consistent reporting of non-pharmacological variables that influence therapeutic outcomes. To address this need, the ReSPCT (Reporting of Setting in Psychedelic Clinical Trials) guidelines were recently introduced, providing a 30-item framework for standardized reporting of set and setting. This study aimed to evaluate how current psilocybin clinical trial protocols incorporate these elements and to identify domains requiring improvement. We systematically searched ClinicalTrials.gov and the EU Clinical Trials Information System (CTIS) for interventional psilocybin studies targeting MDD or TRD, including protocols listing depression as a primary condition. By June 21, 2025, 13 protocols (11 Phase II and 2 Phase III) met the inclusion criteria. Each protocol was assessed using the ReSPCT checklist, yielding a total of 390 item-level assessments rated on a four-point scale. Overall, 61 of 390 entries (15.6%) demonstrated full compliance, 252 (64.6%) partial compliance, and 77 (19.7%) provided no relevant information. Procedural elements, such as medical and experimental procedures (100% compliance), focus and main activities (92.3%), number of sessions (69.2%), and dosing regimens (53.8%), were consistently reported. In contrast, contextual and equity-related domains were markedly underreported: 84.6% of protocols lacked information on cultural competence and safety, 92.3% did not describe objects or decorations, and 84.6% failed to report access to nature. These findings indicate that while procedural safeguards are well documented, critical contextual and equity-relevant aspects remain insufficiently reported. Adopting ReSPCT guidelines may improve transparency and reproducibility.

keywords:
Humans, Hallucinogens, Clinical Protocols, Research Design, Clinical Trials as Topic, Depressive Disorder, Treatment-Resistant, Psilocybin, Major Depressive Disorder

raw_json:
{"europe_pmc_id":"41546918","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin Production With Genetically Modified Aspergillus nidulans Under Pressurized Conditions.
authors: Weiser S, Jung S, Bardl B, Kufs JE, Janevska S, Valiante V, Hoffmeister D, Regestein L.
publication_date: 2025-12-29
doi: 10.1002/bit.70137
pubmed_id: 41467547
source_url: https://doi.org/10.1002/bit.70137
substance_tags: psilocybin
topic_tags: 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
abstract:
Psilocybin, an indole alkaloid of psychedelic mushrooms, has the potential to sustainably improve the treatment of several psychiatric diseases. So far, the psilocybin demand for clinical trials has been met by chemical synthesis. In this study, we pursued the biotechnological approach to develop a psilocybin production process utilizing an overproduction strain of Aspergillus nidulans. The developed shake flask cultivation regime was characterized rheologically and was evaluated concerning the sensitivity to changes in oxygen availability and power input. Due to the strong impact of power input on viscosity and thus, (oxygen) mass transfer and mixing of the filamentous culture broth, the bioprocess was scaled up from shake flask to 7 L stirred tank reactor according to the specific power input. Utilizing a pressure reactor, the oxygen supply of the viscous culture broth was enhanced. Subsequently, the nitrogen limitation was addressed by supplementing the cultivation medium with additional ammonium sulfate to provide sufficient building blocks for protein biosynthesis. By producing 542 mg L-1 psilocybin within 68 h from glucose, a robust and efficient batch bioprocess for psilocybin production was developed to potentially contribute to the future supply of psilocybin for pharmaceutical purposes. Moreover, we demonstrated the suitability of pressurized bioprocesses to counteract oxygen limitations for shear-sensitive, filamentous organisms.

keywords:
Aspergillus nidulans, Oxygen, Culture Media, Bioreactors, Metabolic Engineering, Psilocybin, Microorganisms, Genetically-Modified

raw_json:
{"europe_pmc_id":"41467547","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Schindler EAD, Gottschalk CH, Pittman BP, D'Souza DC.
publication_date: 2025-12-28
doi: 10.1111/head.70024
pubmed_id: 41459830
source_url: https://doi.org/10.1111/head.70024
substance_tags: psilocybin
topic_tags: Headache / Migraine,Clinical Trial,Randomized Controlled Trial,Safety,Adverse Events
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:00
title:
Comparing single- and repeat-dose psilocybin with active placebo for migraine prevention in an exploratory randomized controlled clinical trial.

abstract:
ObjectiveThe goals of this study were to examine the therapeutic effects and safety of psilocybin given as a pulsed regimen for the prevention of migraine and to consider the blinding integrity of an active control agent.BackgroundThe administration of a single low dose of psilocybin was observed to have lasting therapeutic effects in one small pilot trial in migraine, although the ability of a pulse dose regimen, as practiced by patients with cluster headache, to potentially improve magnitude and/or duration of transitional preventive effects has not been studied. Furthermore, comparison to an active placebo agent that adequately mimics the acute subjective effects of psilocybin is required to improve blinding integrity and measure placebo effects.MethodsIn an exploratory randomized, double-blind, placebo-controlled, parallel group study, adults with migraine having at least two weekly migraine days at baseline (n = 18) participated in two drug administration sessions separated by 7 days during which they received zero, one, or two doses of psilocybin (10 mg; psi). Whenever participants did not receive psilocybin, they received diphenhydramine (25 mg; diph). Participant recruitment took place between September 2021 and August 2023. The primary outcome measure was a change in migraine frequency using headache diary data collected starting 2 weeks before and continuing through 8 weeks after the second drug session.ResultsIn the 2 weeks after completion of the two drug administration sessions, the change from baseline in migraine days/week was not significantly different among groups [diph-diph: -0.7 (95% confidence interval, -1.5 to 0.2); diph-psi: -2.0 (-3.0 to -1.0); psi-psi: -1.7 (-4.1 to 0.7); Χ2 (2) = 4.56, p = 0.102], despite large effect sizes against the placebo group in the those receiving one (diph-psi; d = 1.66) or two (psi-psi; d = 0.69) doses of psilocybin. Similar reductions in migraine frequency approximating 50% were seen in all groups over the 8 weeks measured. The difference in 50% response rate among groups over 2 weeks, however, approached significance (diph-diph: 17%; diph-psi: 80%; psi-psi: 80%; p = 0.087). Drug confidence ratings (i.e., blinding integrity) suggested that diphenhydramine partially substituted for the acute effects of psilocybin. No correlations were observed between changes in migraine frequency after psilocybin and drug confidence, acute general drug effects, or acute psychedelic effects. No serious or unexpected adverse events occurred.ConclusionThis exploratory study found similar reductions in migraine frequency with single-dose psilocybin, a two-dose pulse of psilocybin, or diphenhydramine placebo. Whereas blinding was incomplete in this study, this important topic is highlighted in the study design and findings. The potential for psilocybin to serve as a transitional treatment in migraine remains but will require careful planning in future studies to separate drug and non-drug effects. Furthermore, the inclusion of headache specialists in the design and execution of these future studies is necessary to preserve the viability of psilocybin treatment in headache medicine.

keywords:
Humans, Hallucinogens, Treatment Outcome, Double-Blind Method, Adult, Middle Aged, Female, Male, Migraine Disorders, Young Adult, Psilocybin

raw_json:
{"europe_pmc_id":"41459830","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Teopiz KM, Le GH, Wong S, McIntyre RS.
publication_date: 2025-12-05
doi: 10.1016/j.jad.2025.120836
pubmed_id: 41360373
source_url: https://doi.org/10.1016/j.jad.2025.120836
keywords: Animals, Humans, Rats, Dextromethorphan, Excitatory Amino Acid Antagonists, Reward, Anhedonia
substance_tags: psilocybin
topic_tags: Receptor Pharmacology,Systematic Review,Review Article,Animal Study,Healthy Volunteers
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:
The effect of dextromethorphan on reward-related behaviors: A systematic review of preclinical and clinical evidence.

abstract:
IntroductionExtant literature suggests that anhedonia, defined as a loss of the ability to feel pleasure or interest, is subserved by dysregulation of reward processing in the central nervous system. Dextromethorphan (DXM), an uncompetitive N-Methyl-d-Aspartate (NMDA) receptor antagonist and sigma-1 (σ1) receptor agonist, is a glutamatergic modulator with antidepressant properties. The effect of DXM on reward-related outcomes remains inadequately characterized. Herein, we conducted a systematic review of extant literature reporting on the effects of DXM on reward-related behaviors in both preclinical and clinical studies.MethodsA systematic search of the literature was conducted on online databases (PubMed, OVID, Scopus, Web of Science) of published articles from inception to January 2025. Preclinical and clinical studies that reported on the effect of DXM on reward outcomes were assessed.ResultsPreclinical studies (n = 13) indicate that administration of DXM attenuates reward-seeking behavior in rats as measured primarily by performance in the conditioned place preference test and behavioral sensitization. In a single human study (n = 1) evaluating DXM in healthy participants (n = 20), self-reported drug-liking for DXM (400 mg/70 kg) was significantly lower in comparison to psilocybin (20 mg and 30 mg) at 7 h after the dosing session.DiscussionExtant literature suggests that DXM administration attenuates reward-related behaviors in rats. There is a paucity of human studies investigating the effect of DXM on reward outcomes. Future research should prioritize the investigation of the effect of DXM on reward function using validated reward paradigms in persons with anhedonia.

raw_json:
{"europe_pmc_id":"41360373","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Allen J, Sun M, Baker TL, Dames S, Kryskow P, Christie BR, McDonald SJ, Shultz SR.
publication_date: 2025-11-04
doi: 10.1038/s41380-025-03329-x
pubmed_id: 41193674
source_url: https://doi.org/10.1038/s41380-025-03329-x
substance_tags: psilocybin
topic_tags: Neuroplasticity,Receptor Pharmacology,Animal Study,Inflammation
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 mitigates chronic behavioral and neurobiological alterations in a rat model of recurrent intimate partner violence-related brain injury.

abstract:
Intimate partner violence (IPV) poses a significant medical concern, predominantly affecting females. IPV-related brain injuries (IPV-BI), such as mild traumatic brain injury (mTBI) and non-fatal strangulation (NFS), sustained during physical attacks are common and often repetitive. Chronic neurobehavioral sequalae from IPV-BI are associated with neuroinflammation and impaired neuroplasticity, and effective treatment options are scarce, particularly in the context of IPV. However, psilocybin, a 5-HT2A receptor agonist with therapeutic potential in psychiatric disorders that share overlapping pathophysiology as BI, is a promising candidate. This study evaluated psilocybin's effects on behavior, cognition, and neurobiology in a novel rat model of recurrent IPV-BI. Female rats underwent daily mTBI (lateral impact) followed by NFS (90 s) for five days, followed by 16 weeks of recovery. Rats then received a single intraperitoneal injection of psilocybin (1 mg/kg) or saline, with behavioral testing 24 h later. To investigate whether psilocybin's effects were 5-HT2A receptor dependent, additional rats received pre-treatment with selective 5-HT2A receptor antagonist M100907 (1.5 mg/kg) one hour before psilocybin administration. Psilocybin recovered mTBI+NFS-induced abnormalities in the elevated plus-maze, increased sucrose preference when administered without M100907, and improved reversal learning in the water maze and spatial memory in the Y-maze. In the dorsal hippocampus, mTBI+NFS rats treated with saline, but not those treated with psilocybin, exhibited an increased number of microglial cells in the molecular layer and fewer reelin-positive cells in the subgranular zone. These findings suggest psilocybin's antidepressant, pro-cognitive, anti-inflammatory, and neuroplasticity-enhancing effects hold promise for improving chronic IPV-BI outcomes and highlight the critical role of 5-HT2A receptors in mediating psilocybin's therapeutic benefits.

keywords:
Brain, Animals, Rats, Rats, Sprague-Dawley, Brain Concussion, Disease Models, Animal, Behavior, Animal, Cognition, Female, Intimate Partner Violence, Psilocybin

raw_json:
{"europe_pmc_id":"41193674","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Syed OA, Petranker R, Fewster EC, Sobolenko V, Beidas Z, Husain MI, Lake S, Lucas P.
publication_date: 2024-12-23
doi: 10.1080/02791072.2024.2446445
pubmed_id: 39718337
source_url: https://doi.org/10.1080/02791072.2024.2446445
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 11:22:04
title:
Preferences, Perceptions, and Environmental Considerations of Natural and Synthetic Psychedelic Substances: Findings from the Global Psychedelic Survey.

abstract:
Although several studies have well described the characteristics of people who use psychedelics alongside their motivations and beliefs, little research has examined the preferences surrounding the source of psychedelic substances. In an anonymous online survey, we collected data from 6,379 consumers of 11 different psychedelic substances from 85 different countries, exploring their preferences and perceptions on natural and synthetic psychedelics. There was a strong preference of natural sources over synthetic alternatives for psilocybin (75%), DMT (56%), and mescaline (56%). Moreover, 50.8% of respondents believed that the source impacts the psychedelic's psychological and physiological effects, while 34.4% of respondents had a neutral stance on the topic. Despite the preference for natural sources, 67.7% of respondents agreed to switch to using synthetic alternatives to psychedelic substances if it would lessen the environmental impacts caused by the overharvesting of natural sources. This study presents novel insights into consumer preferences on the source of popular psychedelic substances. This international survey is limited to respondents primarily belonging to anglophone regions of the world.

keywords:
Humans, N,N-Dimethyltryptamine, Mescaline, Hallucinogens, Perception, Adolescent, Adult, Middle Aged, Female, Male, Young Adult, Consumer Behavior, Surveys and Questionnaires, Psilocybin

raw_json:
{"europe_pmc_id":"39718337","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2024-11-12
doi: 10.1080/02791072.2024.2428241
pubmed_id: 39535167
source_url: https://doi.org/10.1080/02791072.2024.2428241
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 11:22:04
title:
The Effect of Psilocybe cubensis on Spatial Memory and BDNF Expression in Male Rats Exposed to Chronic Unpredictable Mild Stress.

authors:
Ghaffarzadegan R, Karimi M, Hedayatjoo B, Behnoud H, Jasemi E, Mohammadi M, Roustaei S, Razmi A, Vaseghi S.

abstract:
Psilocybin-containing mushrooms, commonly known as magic mushrooms, drastically affect mental processing, cognitive functioning, and the mood state. In the present study, we investigated the effect of the Psilocybe cubensis extract on spatial memory and the brain-derived neurotrophic factor (BDNF) in rats exposed to chronic unpredictable mild stress (CUMS). The duration of CUMS was 4 weeks. Spatial learning and memory were measured using the Morris water maze apparatus. The Psilocybe cubensis extract was intraperitoneally injected (20 mg/kg) in different time periods: 5 min before training, 24 h before training, 48 h before training, 5 min after training, and 5 min before the probe test. Results showed that CUMS impaired spatial learning and memory, and decreased BDNF in the hippocampus. Psilocybe cubensis (24 and 48 h before training) restored spatial learning, while (48 h before training) restored spatial memory impairment in CUMS rats. Psilocybe cubensis (24 and 48 h before training) increased BDNF in CUMS rats. Psilocybe cubensis administrations (expect 48 h before training) impaired spatial learning and memory and decreased BDNF levels in controls. In conclusion, we suggested that Psilocybe cubensis may be beneficial for the improvement of memory deficits induced by CUMS, while the time of injection seems to be an important factor in its final effect.

keywords:
Hippocampus, Animals, Rats, Rats, Wistar, Memory Disorders, Disease Models, Animal, Brain-Derived Neurotrophic Factor, Hallucinogens, Stress, Psychological, Maze Learning, Male, Spatial Memory, Psilocybin

raw_json:
{"europe_pmc_id":"39535167","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Geraci J, Viirre E, Qorri B, Pani L.
publication_date: 2026-03-30
doi: 10.3389/fphar.2026.1777613
pubmed_id: 41988526
source_url: https://doi.org/10.3389/fphar.2026.1777613
substance_tags: psilocybin
topic_tags: Neuroplasticity,Brain Imaging,Pharmacology,Mechanism of Action,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 11:22:03
title:
Psychedelics and the quantum brain: a falsifiable hypothesis on Posner molecules and spin-dependent pharmacology.

abstract:
Classical serotonergic psychedelics (e.g., LSD, psilocybin, DMT) alter perception and neuroplasticity primarily via 5-HT2A receptor activation and downstream Ca2+-dependent signaling cascades. Here we propose a speculative yet falsifiable pharmacological hypothesis that these drug-induced biochemical cascades might interface with quantum-mechanical processes in the brain. We focus on nuclear spin dynamics in phosphate-containing biomolecules-calcium phosphate nanoclusters known as "Posner molecules" (Ca9(PO4)6) - as a candidate substrate for quantum coherence and entanglement in neural tissue. We distinguish the metaphorical "classical" analogies in psychedelic neuroscience from a literal quantum-level mechanism involving nuclear spin coherence and entanglement. The central hypothesis is that intense 5-HT2A-driven neural activity and Ca2+ flux during psychedelic exposure foster conditions under which 31P nuclear spins in phosphate groups may become entangled and shielded from decoherence within Posner molecules and subsequently influence neuronal signaling when these clusters dissolve and release bursts of Ca2+ in different neuronal compartments. Building on Fisher's Posner model of quantum cognition, we reframe Posner molecules as a potential quantum-coherence nexus in psychedelic action, de-emphasizing earlier microtubule-centric models and explore how such quantum effects, if they exist, might influence pharmacological outcomes. We outline translational implications of this hypothesis, including potential insights into inter-individual variability in treatment response and novel experimental paradigms for psychiatry. To ensure falsifiability, we propose concrete experimental directions in the short term (isotopically modified psychedelics and xenon environments), medium term (advanced quantum sensors such as nitrogen-vacancy magnetometry and ultrafast spectroscopy), and long term (entangled ligand studies or quantum neuroimaging modalities). While speculative, this interdisciplinary framework generates specific, disprovable predictions. Confirming or refuting the role of quantum-mechanical phenomena in psychedelic neuropharmacology would profoundly impact our understanding of mind-brain relationships and encourage high-reward innovation in psychiatric treatment and brain-targeted drug design.

raw_json:
{"europe_pmc_id":"41988526","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Albert OM, Arthur A.
publication_date: 2026-03-30
doi: 10.1177/20420986261436104
pubmed_id: 41930230
source_url: https://doi.org/10.1177/20420986261436104
substance_tags: psilocybin
topic_tags: Meta-Analysis,Review Article,Case Report,Observational Study,Healthcare Workers,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 11:22:02
title:
Psychedelic exposure in pregnancy: a scoping review to inform perinatal drug safety and clinical counseling.

abstract:
Psychedelic and psychedelic-adjacent substances, including 3,4-methylenedioxymethamphetamine (MDMA) and classic serotonergic hallucinogens, are undergoing renewed therapeutic investigation and remain in non-medical use. Inadvertent exposure during early, unrecognized pregnancy is clinically plausible, yet pregnancy-specific safety evidence is limited. To map and synthesize the extent, characteristics, and limitations of primary human evidence on prenatal exposure to MDMA, psilocybin, and classic hallucinogens (lysergic acid diethylamide (LSD), mescaline/peyote, and N,N-dimethyltryptamine (DMT)/ayahuasca), and to identify clinically relevant evidence gaps for perinatal counseling and pharmacovigilance. Peer-reviewed primary human studies (cohort, case-control, cross-sectional, case series, case reports, and brief reports) describing prenatal exposure with reported maternal, obstetric, neonatal, congenital anomaly, or child neurodevelopmental outcomes were included. Animal and preconception-only studies were excluded. MEDLINE, Embase, PsycINFO, CINAHL, and the Cochrane Library were searched from inception to March 2025. Supplementary methods included Google Scholar screening and citation tracking. Data were charted in duplicate using a standardized form and synthesized descriptively by substance and outcome domain. Consistent with scoping methodology, no formal risk-of-bias assessment or meta-analysis was undertaken. Twenty-three primary human sources (1968-2020) met inclusion criteria: MDMA (n = 11), LSD (n = 11), and mescaline/peyote (n = 1). No eligible primary human pregnancy outcome studies were identified for psilocybin or DMT/ayahuasca. The evidence base was heterogeneous and predominantly comprised small cohorts, teratology service follow-up reports, and case-based publications, frequently limited by self-reported exposure, polysubstance confounding, and inconsistent outcome definitions. Human evidence on prenatal psychedelic exposure remains sparse and methodologically constrained. Absence of data for several substances should not be interpreted as evidence of safety. Clinicians should counsel with explicit acknowledgment of uncertainty while supporting harm reduction and appropriate follow-up. Structured perinatal pharmacovigilance and ethically designed evidence-generation strategies are needed as therapeutic psychedelic research expands.

raw_json:
{"europe_pmc_id":"41930230","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Jurowski K, Kobylarz D, Noga M.
publication_date: 2026-03-30
doi: 10.1007/s00204-026-04365-4
pubmed_id: 41915186
source_url: https://doi.org/10.1007/s00204-026-04365-4
substance_tags: psilocybin,psilocin
topic_tags: 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:
In-silico toxicity study of tryptamine, psilocin, psilocybin, N,N-dimethyltryptamine, 5'-methoxy-N,N-dimethyltryptamine and O-acetylpsilocin.

abstract:
Understanding the toxicity of serotonergic tryptamines is becoming increasingly important from both clinical and forensic perspectives, yet experimental data for these compounds remain extremely limited. Despite their growing medical relevance and widespread non-medical use, there is still no systematic evaluation of their toxicological risks. This study presents the first comprehensive in silico assessment of key toxicological endpoints for six tryptamines of clinical and forensic interest: tryptamine, psilocin, psilocybin (4-PO-DMT),N, N-dimethyltryptamine (DMT), 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT),and O-acetylpsilocin (4-AcO-DMT). A multi-model computational approach was applied using STopTox, admetSAR 3.0, ADMETlab 3.0, ACD/Labs Percepta, Toxtree, ProTox 3.0, OCHEM, TEST, and VEGA QSAR, following OECD principles for QSAR model validation. The study covered acute systemic toxicity (LD50), organ-specific effects, cardiotoxicity (hERG inhibition), genotoxicity (Ames test), irritation potential, and estrogenic activity (ER-α binding). All compounds were classified as Cramer Class III (high toxicological concern). Predicted oral LD50 values were in the 100-500 mg/kg range, indicating moderate to high acute toxicity. Cardiovascular and gastrointestinal systems were consistently identified as primary targets (predicted effect ≥ 90%). DMT and 5-MeO-DMT showed the highest predicted hERG inhibition (20

raw_json:
{"europe_pmc_id":"41915186","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Reshaping human neurons.
authors: Maltman JL, González-Maeso J.
publication_date: 2026-03-30
doi: 10.7554/elife.110981
pubmed_id: 41914141
source_url: https://doi.org/10.7554/elife.110981
keywords: Neurons, Humans, Hallucinogens, Neuronal Plasticity, Psilocybin
substance_tags: psilocybin,psilocin
topic_tags: Neuroplasticity
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:
Human neurons derived from stem cells show increased structural complexity and stronger synaptic connections after exposure to psilocin, the active metabolite of the psychedelic psilocybin.

raw_json:
{"europe_pmc_id":"41914141","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Catchlove SJ, Oliver K, Savic M, Arunogiri S.
publication_date: 2026-03-29
doi: 10.1111/add.70403
pubmed_id: 41906885
source_url: https://doi.org/10.1111/add.70403
substance_tags: psilocybin
topic_tags: Depression,Addiction,Healthcare Workers
study_type: Qualitative 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:
Unlocking 'stuckness' and catalysing change: A qualitative study of clinician and service leader perspectives on psychedelic-assisted therapy for substance use and mental health problems.

abstract:
Background and aimsAustralia recently down-scheduled and authorised psychedelic-assisted therapies, including psilocybin, for certain mental health conditions. Evidence is emerging for potential application in substance use disorder treatment. However, regulatory developments have outpaced implementation readiness. While service leaders and clinicians are crucial to implementation, little research examines their perspectives on what psilocybin-assisted therapy is, how it works, and for whom. This study explored how these stakeholders conceptualise psychedelic-assisted therapy within their own professional setting, in the context of a broader implementation trial of psilocybin-assisted therapy for co-occurring depression and alcohol use disorder (AUD) in a routine alcohol and other drug (AOD) clinic.DesignA qualitative approach informed by the evidence-making intervention approach.SettingVictoria, Australia, prior to the implementation of psilocybin-assisted therapy in routine clinical services.ParticipantsTwo focus groups were conducted: one with clinicians (n = 9; nursing, psychology, psychiatry, pharmacy, and peer support professionals) and one with health service leaders (n = 9).MeasurementsFocus groups used a semi-structured guide, consisting of open-ended questions about understandings and perspectives on psilocybin-assisted therapy for co-occurring substance use and mental health problems. Verbatim transcripts underwent inductive thematic analysis, informed by the evidence-making intervention approach.FindingsThree enactments of psilocybin-assisted therapy emerged: (1) treatment of last resort for treatment-resistant conditions, which was emphasised by service leaders and aligned with regulatory frameworks; (2) tool to "unlock stuckness" in ongoing relational care when conventional therapies plateau, which was prominent among clinicians; and (3) catalyst for rapid progress applicable at any treatment stage. Clinicians emphasised the need for careful integration, robust support, and aftercare, alongside concerns about access and eligibility. Service leaders highlighted operational and ethical tensions within regulatory requirements. Both groups understood psilocybin-assisted therapy as a complex intervention dependent on interplay between medication, therapist skill, client readiness, and care context.ConclusionsPsilocybin-assisted therapy in Victoria, Australia is constituted through local implementation rather than existing as a singular intervention. Implementation approaches must be reflexive and adaptive, with attention to clinical and managerial dialogue, equity considerations, and contextual practice factors.

raw_json:
{"europe_pmc_id":"41906885","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psychedelics in NHS services: exploring a model for real-world implementation of psilocybin.
authors: Smith KA, Harcourt E, Cipriani A.
publication_date: 2026-03-29
doi: 10.1192/bjp.2026.10612
pubmed_id: 41906234
source_url: https://doi.org/10.1192/bjp.2026.10612
substance_tags: psilocybin
topic_tags: 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
abstract:
Psychedelics are increasingly described as a new therapeutic approach in a variety of mental disorders including depression. Oral psychedelics such as psilocybin have an acute effect evolving over 6-8 h and are generally given in combination with psychological support. There is debate on the exact role of this support and how and by whom it should be delivered. This has significant implications for real-world implementation in health services post-licensing. In this feature, we discuss these issues and outline a model for psychological support delivery in publicly funded health services such as the National Health Service. We also suggest further research to explore the exact role of support in psilocybin treatment and identify the essential elements to direct service plans for clinical implementation. These steps are important: over recent decades, there have been few new treatments for depression, moreover, psychedelic drugs are appealing to patients, and accumulating data suggest that their efficacy may be long-lasting. However, realistic plans for implementation must be based on high-quality evidence and the needs of the whole patient population. This will ensure that these treatments, if licensed, are available not only for those able to pay but to all on an equitable basis.

raw_json:
{"europe_pmc_id":"41906234","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Associations Between Psilocybin Use Motives and Cognitive, Affective, and Behavioural Self-Stigma.
authors: Knibb G, Ward R, Christiansen P, Roberts CA.
publication_date: 2026-03-27
doi: 10.1080/10826084.2026.2643418
pubmed_id: 41902789
source_url: https://doi.org/10.1080/10826084.2026.2643418
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 11:22:00
abstract:
Background: Self-stigma refers to the internalization of negative societal beliefs and has been associated with reduced self-efficacy, self-esteem and treatment avoidance among substance users. However, little research has explored antecedents of self-stigma such as substance use motives. This may be particularly salient for psilocybin which is used both as a therapeutic agent and a recreational substance and these different motivations for use may shape how users' behaviors are interpreted and internalized. Methods: The current study assessed associations between motives for psilocybin use and self-stigma across cognitive, affective and behavioral dimensions. Participants with prior experience of psilocybin (N = 239) completed an online questionnaire assessing their motives for using psilocybin and levels of self-stigma. A principal component analysis identified three components of psilocybin use motives, Social Recreation (ωt = 0.78), Experiential Enhancement (ωt = 0.80) and Therapeutic Growth (ωt = 0.73). Results: Hierarchical regression analyses demonstrated that greater Therapeutic Growth motives were associated with reduced self-stigma while greater Social Recreation motives were associated with increased self-stigma for all dimensions. No significant associations were found for Experiential Enhancement. Therapeutic Growth motives were also associated with increased frequency of psilocybin use. Conclusions: Although the variance explained was modest, these findings suggest that motives for psilocybin use may influence the extent to which users internalize stigma. This finding has implications for other substances and is important given the growing clinical interest in psilocybin.

raw_json:
{"europe_pmc_id":"41902789","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin Attenuates Cortical Representations of Aversion in the Mouse Auditory Cortex
authors: Johnson JD, Tian R, Etemadi Y, Li Z.
journal: bioRxiv
publication_date: 2026-03-26
doi: 10.64898/2026.03.26.714498
source_url: https://doi.org/10.64898/2026.03.26.714498
substance_tags: psilocybin
topic_tags: 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
abstract:
Psilocybin can produce sustained benefits in affective and trauma-related disorders, yet if and how it reshapes sensory representations of learned valence associations remains largely unclear. To address this, we used longitudinal two-photon calcium imaging in awake C57BL/6 mice to examine how psilocybin modulates layer 2/3 auditory cortex activity at single-cell and population levels. Evoked responses were measured for tones with or without prior associations with valenced stimuli, as well as for the valenced stimuli themselves. Most responsive neurons were selective for tones alone, while distinct subsets responded exclusively to reward or aversive stimuli, and a smaller population encoded both. Psilocybin selectively reduced responses to aversive stimuli and earlier-established aversive-associated tones, without affecting aversive association, reward responses, or responses to newly aversive-associated tones. At the population level, psilocybin acutely increased coordination across tone-responsive neurons, while later reducing it selectively among neurons encoding the aversive-associated tone. These results demonstrate that psilocybin preferentially dampens well consolidated aversive sensory representations in auditory cortex, rather than fresh associations, without broadly affecting auditory processing or new aversive learning.

raw_json:
{"europe_pmc_id":"PPR1217790","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


title: Psilocin fosters neuroplasticity in iPSC-derived human cortical neurons.
publication_date: 2026-03-26
doi: 10.7554/elife.104006
pubmed_id: 41891829
source_url: https://doi.org/10.7554/elife.104006
substance_tags: psilocybin,psilocin
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:
Schmidt M, Hoffrichter A, Davoudi M, Horschitz S, Lau T, Meinhardt MW, Spanagel R, Ladewig J, Köhr G, Koch P.

abstract:
Psilocybin is studied as innovative medication in anxiety, substance abuse and treatment-resistant depression. Animal studies show that psychedelics promote neuronal plasticity by strengthening synaptic responses and protein synthesis. However, the exact molecular and cellular changes induced by psilocybin in the human brain are not known. Here, we treated human cortical neurons derived from induced pluripotent stem cells with the 5-HT2A receptor agonist psilocin - the psychoactive metabolite of psilocybin. We analyzed how exposure to psilocin affects gene expression, neuronal morphology, synaptic markers and neuronal function. Psilocin provoked a 5-HT2A-R-mediated augmentation of BDNF abundance. Transcriptomic profiling identified gene expression signatures priming neurons to neuroplasticity. On a morphological level, psilocin induced enhanced neuronal complexity and increased expression of synaptic proteins, in particular in the postsynaptic compartment. Consistently, we observed an increased excitability and enhanced synaptic network activity in neurons treated with psilocin. In conclusion, exposure of human neurons to psilocin might induce a state of enhanced neuronal plasticity, which could explain why psilocin is beneficial in the treatment of neuropsychiatric disorders where synaptic dysfunctions are discussed.

keywords:
Cerebral Cortex, Neurons, Cells, Cultured, Humans, Brain-Derived Neurotrophic Factor, Hallucinogens, Gene Expression Profiling, Neuronal Plasticity, Induced Pluripotent Stem Cells, Psilocybin

topic_tags:
Depression,Anxiety,Neuroplasticity,Receptor Pharmacology,Biomarkers,Treatment-Resistant Depression,Transcriptomics

raw_json:
{"europe_pmc_id":"41891829","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Skalski P, Pękacka-Falkowska K, Pluto-Prądzyńska A, Owecki MK.
publication_date: 2026-03-25
doi: 10.3390/brainsci16040358
pubmed_id: 42041769
source_url: https://doi.org/10.3390/brainsci16040358
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 11:22:00
title:
Psilocybin in Neuropsychiatric Disorders: Seeking Valuable Evidence in History, Pure Science, Clinical Trials and Real-World Data (RWD).

abstract:
Background/Objectives: Psilocybin has re-emerged as a promising intervention for neuropsychiatric disorders including major depressive disorder, treatment-resistant depression, anxiety associated with life-threatening illness, obsessive compulsive disorder, and substance use disorders. However, conventional randomized controlled trials (RCTs)-the current gold standard in evidence-based medicine-may not adequately capture the therapeutic complexity of psilocybin, which depends not only on pharmacological action but also on contextual, psychological, and interpersonal factors. This critical narrative review aimed to evaluate the adequacy of existing clinical research frameworks for assessing psilocybin's therapeutic potential and to explore alternative methodologies that may better reflect real-world clinical conditions. Methods: Using the Web of Science Core Collection database, we identified and analysed the ten most cited clinical studies on psilocybin published between 2015 and 2025 inclusive. Additional literature was included through reference cross-checking, systematic reviews, meta-analyses, and interdisciplinary sources covering neurobiology, history, and real-world evidence (RWE). The review synthesizes clinical outcomes, methodological constraints, and epistemic considerations relevant to psychedelic-assisted therapy. Results: Evidence from highly cited trials demonstrates rapid and sustained antidepressant and anxiolytic effects of psilocybin, with notable benefits also observed in addiction treatment. However, significant methodological limitations were identified, including selection bias, challenges in placebo design and blinding, small sample sizes, and the underrepresentation of diverse populations. Psilocybin outcomes were strongly influenced by subjective experience and contextual factors such as set and setting. Emerging RWE studies revealed heterogeneous patterns of response and provided insights unattainable through RCTs alone. Conclusions: Psilocybin shows considerable therapeutic promise, but current RCT methodologies capture only part of its clinical effects. Comprehensive evaluation will require larger and more diverse clinical trials, long-term follow-up, standardized psychotherapeutic protocols, and the integration of RWE to reflect real-world practice. Psychedelic-assisted therapy should be conceptualized as a complex intervention that combines pharmacological and psychotherapeutic components.

topic_tags:
Depression,Anxiety,Addiction,End-of-Life Distress,Clinical Trial,Randomized Controlled Trial,Systematic Review,Review Article,Treatment-Resistant Depression

raw_json:
{"europe_pmc_id":"42041769","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Mäki-Marttunen V.
publication_date: 2026-03-25
doi: 10.1038/s42003-026-09912-4
pubmed_id: 41882058
source_url: https://doi.org/10.1038/s42003-026-09912-4
substance_tags: psilocybin
topic_tags: Brain Imaging,Mechanism of Action,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 11:22:00
title:
Psilocybin shapes the slow, global propagation of brain activity over the cortical layout of 5HT2a receptors.

abstract:
Uncovering the neural basis of psychedelics' potent effects on brain activity and conscious experience has great potential for understanding their therapeutic effects. Numerous studies using functional magnetic resonance imaging (fMRI) uncovered a strong effect of psychedelics on global properties of fMRI signal, but how they map to underlying neural phenomena remains to be further explored. In this article, we aimed to relate commonly reported findings from functional connectivity studies of psychedelics to changes in the spatio-temporal propagation of activity over the unimodal-transmodal cortical axis. We used data from an openly available dataset including baseline sessions, a control session with administration of methylphenidate, and psilocybin, a 5HT2a agonist. We found that faster propagation speed was related to increased total functional connectivity and a contraction of the principal gradient. The results support the view that these functional connectivity indices obtained from entire signal time courses reflect the modulation of specific global events of propagation. Furthermore, we found that the cortical distribution of 5HT2a receptors could contribute to the modulation of travelling wave propagation by psilocybin. These findings provide a link between macroscopic signatures of neuromodulatory activity, global brain events and receptor action, with relevance for understanding the mechanisms of psychedelic effects.

keywords:
Brain, Humans, Receptor, Serotonin, 5-HT2A, Hallucinogens, Magnetic Resonance Imaging, Brain Mapping, Serotonin 5-HT2 Receptor Agonists, Psilocybin

raw_json:
{"europe_pmc_id":"41882058","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin Prolongs the Neurovascular Coupling Response in Mouse Visual Cortex
journal: bioRxiv
publication_date: 2025-07-30
doi: 10.1101/2025.07.25.666803
source_url: https://doi.org/10.1101/2025.07.25.666803
substance_tags: psilocybin
topic_tags: Brain Imaging,Mechanism of Action,Receptor Pharmacology,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
authors:
Zirkel RT, Isaacson M, Liao C, Yi M, Yamaguchi K, Rivera D, Kuceyeski A, Nishimura N, Kwan AC, Schaffer CB.

abstract:
Psilocybin has profound therapeutic potential for various mental health disorders, but its mechanisms of action are unknown. Functional MRI studies have reported the effects of psilocybin on brain activity and connectivity; however, these measurements rely on neurovascular coupling to infer neural activity changes and assume that blood flow responses to neural activity are not altered by psilocybin. Using two-photon excited fluorescence imaging in the visual cortex of awake mice to simultaneously measure neural activity and capillary blood flow dynamics, we found that psilocybin administration prolonged the increase in visual stimulus-evoked capillary blood flow - an effect which was reduced by pretreatment with a 5-HT2A R antagonist - despite not causing changes in the stimulus-evoked neural response. Multi-modal widefield imaging also showed that psilocybin extends the stimulus-evoked vascular responses in surface vessels with no observed effect on the population neural response. Computational simulation with a whole-brain neural mass model showed that prolonged neurovascular coupling responses can lead to spurious increases in BOLD-based measures of functional connectivity. Together, these findings demonstrate that psilocybin broadens neurovascular responses in the brain and highlights the importance of accounting for these effects when interpreting human neuroimaging data of psychedelic drug action.

raw_json:
{"europe_pmc_id":"PPR1057821","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


title: Psilocybin: Chemical Foundations and Emerging Therapeutic Potential.
authors: Patil SA, Hunsberger HC.
publication_date: 2026-03-23
doi: 10.2174/0113895575429775260119043318
pubmed_id: 41879500
source_url: https://doi.org/10.2174/0113895575429775260119043318
substance_tags: psilocybin,psilocin
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:
Psilocybin, chemically known as (4-phosphoryloxy-N, N-dimethyltryptamine, 4-PODMT), is derived from the psychoactive mushroom genus, Psilocybe. Of the four active metabolites, psilocin readily enters systemic circulation. The psychoactive effects of psilocin are thought to arise through partial agonist effects at the 5-HT2A receptor. Psychedelic drugs, including psilocybin, are having a renaissance, especially in mental health disorders, addiction, and cancer-related depression. The beneficial effects of psilocybin are expanding into brain injury and lifespan due to its ability to enhance neuroplasticity. However, the large-scale synthesis of psilocybin was the main challenge for the scientific community after the FDA's breakthrough therapy designation in 2018 for Treatment- Resistant Depression (TRD) and for Major Depressive Disorder (MDD) in 2019. Synthesizing psilocybin is challenging due to the complex reactions, a multi-step process that requires strict temperature control, hazardous reagents, and purification difficulties. The very first Hoffman's synthetic method was successfully modified by several medicinal chemistry research groups to obtain it on a kilogram scale to conduct important clinical trials. This mini review comprises a brief history, chemistry, and pharmacology, along with the therapeutic use in depression of this naturally occurring psychedelic.

topic_tags:
Depression,Addiction,Neuroplasticity,Pharmacology,Receptor Pharmacology,Longevity,Clinical Trial,Review Article,Cancer Patients,Treatment-Resistant Depression

raw_json:
{"europe_pmc_id":"41879500","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Editorial: Psychedelic-assisted psychotherapies: from clinical trials to credibility.
authors: Evans M, Charrette A
journal: Frontiers in neuroscience
publication_date: 2025-12-31
doi: 10.3389/fnins.2026.1816932
pubmed_id: 41947857
source_url: https://pubmed.ncbi.nlm.nih.gov/41947857/
substance_tags: psilocybin
topic_tags: PTSD,Addiction,Brain Imaging,Aging,Emotional Processing,Clinical Trial
study_type: Clinical 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":"41947857"}
keywords:
DMT, PTSD, addiction, emotional processing, neuroimaging, psilocybin, psychedelic medicine, psychotherapy


title: Integrated 5-HT2A -TrkB and G protein signaling in serotonergic psychedelic responses
journal: bioRxiv
publication_date: 2026-03-22
doi: 10.64898/2026.03.19.712961
source_url: https://doi.org/10.64898/2026.03.19.712961
substance_tags: psilocin
topic_tags: Neuroplasticity,Pharmacology,Mechanism of Action,Receptor Pharmacology,In Vitro Study
study_type: In Vitro Study
source_name: bioRxiv
publication_status: preprint
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:02
authors:
Taddei-Tardón M, Medina-Rodríguez L, Maltman JL, Hudson S, Potukanuma S, Jiménez JH, Martín-Guerrero SM, González-Maeso J, López-Giménez JF.

abstract:
Serotonergic psychedelics have attracted considerable interest as promising therapeutic agents. However, the molecular mechanisms linking their acute hallucinogenic-like effects to longer-lasting neuroplastic responses remain incompletely understood, partly because of the scarcity of native neural models suitable for mechanistic studies. Here, we developed a neural stem cell-derived in vitro model capable of differentiating into neuronal and glial lineages and, after characterization, used it to investigate the molecular pharmacology of serotonergic psychedelics. A panel comprising tryptamines, phenethylamines and ergolines, including psychedelic compounds and selected non-psychedelic analogues, was evaluated alongside ketamine and TrkB agonists. Endpoints included dendritogenesis, synaptogenesis, immediate-early gene induction, BDNF expression and lactate production. TrkB silencing abolished dendritogenic responses to serotonergic psychedelics, ketamine and TrkB agonists, whereas 5-HT2A receptor silencing selectively impaired serotonergic psychedelic-induced plasticity and altered TrkB-dependent responses. Most serotonergic compounds also increased synaptogenesis and induced c-Fos and Egr-2 expression, although ligand-specific differences were evident, particularly for psilocin and the phenethylamines DOI and Ariadne. Uncoupling of G q/11 or G i/o protein-dependent signaling differentially modified neuroplastic and transcriptional responses, indicating a ligand and endpoint dependent contribution of both pathways. Serotonergic psychedelics further induced a 5-HT2A receptor dependent lactate response that was generally sensitive to disruption of either G q/11 or G i/o protein coupling. Taken together, these findings support a model in which serotonergic psychedelics recruit an integrated 5-HT2A -TrkB signaling network with distinct structural, transcriptional and metabolic outputs, and establish this neural stem cell-derived system as a valuable platform for screening and dissecting the signaling basis of psychedelic action.

raw_json:
{"europe_pmc_id":"PPR1218591","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


authors: Anchesi I, Raffaele I, Astorino MF, Lui M, Calabrò M, Cipriano GL.
publication_date: 2026-03-19
doi: 10.3390/ijms27062811
pubmed_id: 41898671
source_url: https://doi.org/10.3390/ijms27062811
keywords: Animals, Humans, Ibogaine, Hallucinogens, Neuronal Plasticity
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 11:22:03
title:
Beyond the Genomic Storm: Evaluating Tabernanthalog as a Potential Scaffold for Silent Neuroplasticity and Broad-Spectrum Therapy.

abstract:
The clinical renaissance of psychedelic medicine has highlighted the therapeutic potential of rapid-acting neuroplastogens, or "psychoplastogens," for psychiatric disorders. However, the widespread application of classical psychedelics-such as psilocybin and LSD-and the atypical dissociative ibogaine is severely limited by their hallucinogenic properties and, particularly in the case of ibogaine, life-threatening cardiotoxicity. Addressing these limitations, Tabernanthalog (TBG) has emerged as a frontrunner in the field. This non-hallucinogenic analog of ibogaine was rationally designed to eliminate interactions with the human ether-à-go-go-related gene (hERG, KCNH2) potassium channel, thereby mitigating cardiotoxic risks. While initially characterized for its anti-addictive and antidepressant-like properties, recent data from 2024-2025 have significantly expanded its therapeutic horizon. TBG demonstrates robust efficacy in preclinical models of neuropathic and visceral pain, as well as in the rescue of cognitive deficits associated with cancer-related cognitive impairment (CRCI). TBG has shown efficacy in reversing cognitive impairments induced directly by the presence of a tumor in preclinical models, rather than by chemotherapy-specific neurotoxicity. Crucially, emerging evidence suggests that TBG's mechanism extends beyond simple 5-HT2A receptor agonism. New findings point to a multi-target profile involving the inhibition of nicotinic acetylcholine receptors (nAChRs), positive modulation of NMDA receptors, and functional crosstalk with mGlu2 receptors. Furthermore, TBG appears to induce structural neuroplasticity without the widespread induction of immediate early genes (IEGs) seen with classical hallucinogens, suggesting a decoupling of therapeutic rewiring from the subjective psychedelic experience. This review synthesizes current preclinical evidence to discuss TBG as a promising chemical scaffold for next-generation neurotherapeutics targeting the intersection of psychiatry and neurology.

topic_tags:
End-of-Life Distress,Chronic Pain,Neuroplasticity,Receptor Pharmacology,Review Article,Animal Study,Cancer Patients,Safety,Toxicity,Drug Interactions,Genomics

raw_json:
{"europe_pmc_id":"41898671","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psychedelics and Mental Health in Endurance Athletes: A Cross-Sectional Study in Brazil.
authors: Portes MAM, Bertoglio LJ.
publication_date: 2026-03-19
doi: 10.1080/02791072.2026.2644865
pubmed_id: 41860795
source_url: https://doi.org/10.1080/02791072.2026.2644865
substance_tags: psilocybin
topic_tags: Depression,Anxiety,PTSD,Observational Study,Inflammation
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
abstract:
Psilocybin, N,N-dimethyltryptamine (DMT), lysergic acid diethylamide (LSD), and 3,4-methylenedioxymethamphetamine (MDMA) are psychedelic compounds with therapeutic potential for depression, anxiety, and post-traumatic stress. However, their relevance to endurance athletes, who face particular psychological and physical stressors, remains underexplored. This study combines a conceptual overview with cross-sectional survey data from Brazilian endurance athletes. Twenty-eight participants completed a questionnaire addressing mental health, use of supplements, medications, and psychoactive substances, as well as perceptions and attitudes toward psychedelics and psychedelic therapies. The mean age was 37 ± 10 years. Women more frequently reported pharmacological treatment for depression or anxiety. Overall, 64% reported a lack of mental health support in their athletic environments; 11% had prior psychedelic experience, while 79% expressed openness to psychedelic therapies if legal and supervised. However, 61% were unaware of existing evidence for psychedelics in treating mental health conditions. Their potential anti-inflammatory and analgesic properties were similarly unrecognized and unexpected. Misconceptions were common: 78% believed psychedelics to be addictive. Despite this, attitudes toward their therapeutic potential were generally positive. These findings reveal unmet mental health needs, significant knowledge gaps, and widespread misconceptions among endurance athletes, suggesting the value of targeted, evidence-based education to support informed consideration of psychedelic therapies.

raw_json:
{"europe_pmc_id":"41860795","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psychedelics in functional disorders: A scoping review.
authors: Bhagavan C, Carter O, Bryson A, Dandash O, Kanaan R.
publication_date: 2026-02-09
doi: 10.1016/j.pnpbp.2026.111642
pubmed_id: 41679377
source_url: https://doi.org/10.1016/j.pnpbp.2026.111642
keywords: Humans, Hallucinogens, Mental Disorders
substance_tags: psilocybin
topic_tags: Clinical Trial,Review Article,Observational Study,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 11:22:03
abstract:
Functional disorders, characterised by symptoms unexplained by organic disease, impose a significant burden on individuals and healthcare systems. Existing treatments are limited in efficacy, with no effective pharmacotherapies. There is growing evidence supporting the treatment potential of psychedelics in neuropsychiatric conditions, including several distinct functional disorders. This scoping review explores existing studies using classic psychedelics in functional disorders to identify current knowledge, highlight evidence gaps, and inform future research. Four databases (MEDLINE, PsycINFO, EMBASE, and Web of Science) and the World Health Organisation International Clinical Trials Registry Platform were searched, supplemented by citation searching, relevant websites, and search engine alerts. 62 reports were identified from 55 unique studies, comprising six surveys, six case studies of naturalistic psychedelics use, 33 completed clinical studies, and 10 registered trials. For completed studies, most refer to data from prior to 1976, few used comparator or control groups, and LSD was the most common psychedelic used. For registered trials planned or currently underway, most use comparator or control groups and all use psilocybin. Functional neurological symptoms represented the most common category of functional disorder studied. 60.7% demonstrated improvement. Adverse events encompassed several acute psychological and physical effects, including transient exacerbations of functional symptoms. Despite showing potential as a novel treatment, the evidence is limited by predominantly observational study designs, disparate methodologies, and a lack of long-term outcomes. Future research must adapt to the evolving complexities of trial designs in psychedelic research, implement standardised treatment protocols, explore mechanistic analyses, and incorporate comprehensive outcome and safety assessments.

raw_json:
{"europe_pmc_id":"41679377","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Ip CT, Olbrich S, de Bardeci M, Monn A, Ort A, Smallridge JW, Vollenweider F.
publication_date: 2026-01-26
doi: 10.1016/j.pnpbp.2026.111626
pubmed_id: 41611012
source_url: https://doi.org/10.1016/j.pnpbp.2026.111626
substance_tags: psilocybin
topic_tags: Brain Imaging,Default Mode Network,Consciousness,Biomarkers,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:
Psilocybin-induced alterations in EEG power, connectivity and network dynamics in healthy subjects: Correlations with subjective experience and implications for therapeutic applications.

abstract:
BackgroundRecent advancements in psychedelic research have highlighted psilocybin's potential therapeutic benefits for various mental disorders. Understanding its effects on brain function and identifying predictors of individual responses are essential for developing effective treatments.MethodsThis double-blind, randomized, crossover, and placebo-controlled study enrolled 25 healthy individuals (18 males, 7 females, average age 24.44 years). Participants underwent two sessions involving administration of either psilocybin (oral dose of 10-20 mg) or placebo. Ten-minute resting EEG recordings were taken at baseline and post-administration peaks, focusing on EEG power and connectivity in the default-mode network (DMN) and localized cortical networks in the frontal and parietal cortices. Additionally, we investigated whether baseline EEG features could predict subjective experiences during the psilocybin condition.ResultsPsilocybin significantly decreased EEG power in slow frequency bands (theta and alpha) and increased power in fast frequency bands (beta, gamma1, gamma2) compared to placebo. Connectivity analyses revealed increased connectivity in the DMN and localized parietal network under psilocybin. Subjective experiences, as measured by the Altered States of Consciousness Questionnaire, showed positive correlations with changes in EEG power and connectivity.ConclusionsPsilocybin induces significant changes in brain function, characterized by altered EEG power and connectivity. These changes correlate strongly with subjective experiences, supporting psilocybin's potential for treating mental disorders. The predictive value of baseline EEG features for subjective alterations suggests that specific brain activity patterns may serve as biomarkers for tailoring psilocybin therapy in clinical settings. This study enhances our understanding of psilocybin's neurophysiological impacts and informs future therapeutic applications.Clinical trials registrationhttps://clinicaltrials.gov/study/NCT03853577?cond=NCT03853577&rank=1 Registration number: NCT03853577.

keywords:
Brain, Nerve Net, Humans, Hallucinogens, Electroencephalography, Cross-Over Studies, Double-Blind Method, Adult, Female, Male, Young Adult, Brain Waves, Healthy Volunteers, Psilocybin, Default Mode Network

raw_json:
{"europe_pmc_id":"41611012","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2026-03-18
doi: 10.17269/s41997-026-01178-x
pubmed_id: 41857461
source_url: https://doi.org/10.17269/s41997-026-01178-x
substance_tags: psilocybin
topic_tags: Microdosing
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 retail stores in Canada: Changes in availability, commercialization, and geographic distribution.

authors:
Matsukubo J, Friesen EL, MacDonald-Spracklin R, Iseman R, Solmi M, Fiedorowicz JG, Fischer B, Myran DT.

abstract:
IntroductionThe use of psychedelics has increased in Canada in recent years. Although non-medical psilocybin use is prohibited under the Controlled Drugs and Substances Act, we previously documented the emergence of grey-market brick-and-mortar psilocybin retailers. This study examined changes in the number, composition, and geographic distribution of Canadian psilocybin retail stores between 2024 and 2025.MethodsWe conducted a repeated cross-sectional assessment of psilocybin retail stores with a physical storefront in Canada that were publicly visible and indexed through systematic Google and Google Maps searches between May 2024 and July 2025. Data were collected on store location, operating status, chain affiliation, and product offerings. Per capita availability and geographic clustering were calculated using Canadian census metropolitan area and dissemination area data.ResultsBetween 2024 and 2025, the number of psilocybin retail stores in Canada increased from a total of 57 to 75, a 33% increase in stores per 100,000 individuals (0.18 to 0.24). The proportion of Canadians residing within a 10-min walk of a psilocybin retail store increased from 1.4 to 1.7%. In this period, 30 of 57 outlets (52.6%) that were open in 2024 closed, while 48 new stores opened. In 2025, two large chains operated 44% of all stores in Canada. All but 2 stores (97%) were located in Ontario and British Columbia. In Toronto and Vancouver, Canada's first- and third-most populous cities, 9.5% and 29.0% of residents, respectively, lived within a 10-min walk of a psilocybin store. Psilocybin retail stores with a website sold a wide variety of products online, including dried mushrooms (98%), microdose capsules (100%), and infused edibles (89%). Sixty-nine percent offered products packaged to resemble commercial snack brands, such as Scooby-Doo Fruit Snacks and psilocybin-infused drinks styled after Arizona Iced Tea. Among outlets with online listings, 49% advertised the sale of additional psychoactive substances, most commonly N,N-dimethyltryptamine (93%) and cannabis (87%).Discussion and conclusionThe Canadian psilocybin retail market continues to expand substantially despite ongoing federal prohibition. The market is characterized by rapid turnover, increasing dominance of large chain operators, widespread sale of ordinary food brand-mimicking products, and marked geographic concentration in Ontario and British Columbia. The presence of a grey market may expose individuals to unregulated products and unverified health claims. Continued surveillance is warranted to monitor market evolution and to inform policy discussions regarding psilocybin regulation in Canada and elsewhere.

raw_json:
{"europe_pmc_id":"41857461","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin effects on brain functional connectivity: a systematic review of fMRI studies.
authors: Farré-Colomés À, Rublinetska O, Soto-Angona Ó.
publication_date: 2026-03-18
doi: 10.1007/s44192-026-00384-w
pubmed_id: 41854988
source_url: https://doi.org/10.1007/s44192-026-00384-w
substance_tags: psilocybin
topic_tags: Depression,Brain Imaging,Mechanism of Action,Aging,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
abstract:
Psilocybin-assisted therapies are innovative therapeutic approaches, particularly in the treatment of depression. However, there are sparse studies providing functional magnetic resonance imaging (fMRI) evidence elucidating the underlying biological mechanisms that support clinical outcomes. This review aims to comprehensively gather all the evidence reported in psilocybin studies using fMRI techniques. Independent extraction of articles was conducted by 2 authors using predefined data fields. 20 unique datasets were identified, with 5 including participants diagnosed with depression. Dropout rates were found to be high, and follow-up scanning timepoints were lacking in most of the studies. Most research has focused on the amygdala, the anterior cingulate cortex and the prefrontal cortex, as key regions involved in the effects of psilocybin. However, the current literature exhibits inconsistency in methods and designs. Further research is necessary to better define psilocybin’s impact on the human brain and its potential to enhance psychotherapy outcomes.

raw_json:
{"europe_pmc_id":"41854988","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Synthesis and Characterization of Psilocybin Metabolites and Deuterated Analogs.
authors: Williamson SE, Burkhartzmeyer EK, Faley MT, Ohana RF, Guzei IA, Valley M, Cali JJ, Sherwood AM.
publication_date: 2026-03-02
doi: 10.1021/acschemneuro.5c00879
pubmed_id: 41773421
source_url: https://doi.org/10.1021/acschemneuro.5c00879
keywords: Humans, Deuterium, Glucuronides, Receptors, Serotonin, Hallucinogens, Psilocybin
substance_tags: psilocybin,psilocin
topic_tags: Receptor Pharmacology,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
abstract:
To support ongoing clinical trials, the major human metabolites of psilocybin were synthesized on a preparative scale, specifically psilocin-O-glucuronide and 4-hydroxyindole-3-acetic acid (4-HIAA), along with putative minor metabolites and several deuterium-labeled derivatives. Psilocybin, psilocin, psilocin-O-glucuronide, and 4-HIAA were assayed for engagement at seven serotonin receptor subtypes using a BRET-based binding assay, which showed that only psilocin exhibited any discernible binding across the subtypes investigated. Given the high cost and challenging preparation of these compounds, our work offers a comprehensive guide for researchers to access these resources, advancing both basic and clinical research with psilocybin and its metabolites.

raw_json:
{"europe_pmc_id":"41773421","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Ziadi Y, Park T.
publication_date: 2026-03-16
doi: 10.1016/j.vhri.2026.101605
pubmed_id: 41842876
source_url: https://doi.org/10.1016/j.vhri.2026.101605
substance_tags: psilocybin
topic_tags: Depression,Randomized Controlled Trial,Treatment-Resistant Depression
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:
Cost-Effectiveness of Psilocybin-Assisted Therapy Versus Standard of Care for Patients With Treatment-Resistant Depression.

abstract:
BackgroundTreatment-resistant depression (TRD) imposes a substantial public health and economic burden. Although psilocybin-assisted therapy (PAT) has shown clinical promise, its economic value remains uncertain. This study evaluated the cost-effectiveness of PAT compared with the standard of care for TRD.MethodsA Markov model adopting a US healthcare perspective simulated patient transitions among health states (remission, response, non-response, and relapse) every 6-week cycle. Model inputs were derived from randomized controlled trials and relevant published literature. Outcomes included quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios. Sensitivity analyses were conducted to assess uncertainty in key parameters, dosing regimens, retreatment strategies, and psilocybin prices. Scenario analyses extended the time horizon to 30 years to examine treatment persistence and efficacy waning.ResultsCompared with the standard of care, PAT was more effective and less costly, yielding approximately $7000 in cost savings and a gain of 0.10 QALYs per patient. These economic advantages persisted across variations in key parameters, dosing strategies, retreatment assumptions, and psilocybin prices in sensitivity analyses. Extending the horizon to 30 years in scenario analyses increased cumulative savings to $215 900 with gains of 9.87 QALYs. PAT remained cost-effective under all efficacy-waning assumptions over the 30-year horizon.ConclusionThis modeling analysis provides preliminary evidence that PAT may be a cost-effective option for TRD management. Consistent findings across extended time horizons suggest that its economic value is largely driven by early clinical benefits that offset downstream chronic care costs. Longitudinal real-world evidence will be essential to validate these findings and inform sustainable integration into clinical practice.

raw_json:
{"europe_pmc_id":"41842876","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Lyons FE, Rockhill KM, Fox EJ, Bemis EA, Black JC, Monte AA, Dart RC.
publication_date: 2026-03-15
doi: 10.1080/02791072.2026.2644863
pubmed_id: 41834488
source_url: https://doi.org/10.1080/02791072.2026.2644863
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:
Psychedelic Terminology Preference in the 2024 National Survey Investigating Hallucinogenic Trends (NSIHT).

abstract:
Expanding regulation and increased use of psychedelic substances requires surveillance of behaviors and health outcomes in the United States. Widely comprehendible terminology is important for surveys. The objective of this study was to determine what psychedelic terminology is preferred among adults who used a psychedelic in the past 12 months. A cross-sectional survey measuring psychedelic use behaviors was administered. A rank-order question was included to assess preferences for seven terminology options ranked first to seventh. Median rank scores (lower medians indicating higher preference) were calculated across subgroups defined by age, education, and level of experience with psychedelic substances. A total of 2,306 respondents were included in the final sample. Among the total sample, specific substance names (e.g., psilocybin, ayahuasca) were most preferred (median rank = 3; 24.3% ranked first), followed by "psychedelics" (3; 19.4%). Other terms that ranked lower included by effect (3; 15.0%), "medicines" (4; 16.2%), "hallucinogen" (4; 13.7%), "entheogens" (5; 8.5%), or something else (6; 2.9%), and patterns were consistent across subgroups. Broader recommendations for terminology use are proposed to assist further survey development.

raw_json:
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title: Breaking the chains of depression: A systematic review and meta-analysis of psilocybin therapy.
authors: Khan FA, Pandupuspitasari NS, Tencomnao T, Chuchawankul S.
publication_date: 2025-12-16
doi: 10.1016/j.jad.2025.120882
pubmed_id: 41419063
source_url: https://doi.org/10.1016/j.jad.2025.120882
keywords: Humans, Hallucinogens, Psilocybin, Major Depressive Disorder
substance_tags: psilocybin
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
abstract:
Psilocybin, a naturally occurring hallucinogenic substance present in certain mushrooms, has drawn growing attention as a therapeutic breakthrough for several mental and psychiatric conditions. Psilocybin originated in spiritual and cultural traditions and has become the focus of extensive scientific research. This meta-analysis and systematic review aggregate results from the literature to evaluate the therapeutic function of psilocybin following PRISMA 2020. Although it is now used to treat addiction, end-of-life anxiety, and treatment-resistant depression, new research indicates that it could additionally be used to treat obsessive-compulsive disorder, eating disorders, and neurodegenerative diseases. Psilocybin's regulation of serotonin 5-HT2A receptors, which improves neuroplasticity, disrupts maladaptive cognitive processes and encourages emotional integration, is the backend of its therapeutic benefits. The meta-analysis results indicate that psilocybin has an outstanding capacity to reduce the symptoms of anxiety/MDD (SMD = -1.438, 95 % CI: -1.729 to -1.146, p

topic_tags:
Depression,Anxiety,Addiction,OCD,Eating Disorders,End-of-Life Distress,Neuroplasticity,Receptor Pharmacology,Emotional Processing,Spirituality,Meta-Analysis,Systematic Review,Review Article,Treatment-Resistant Depression

raw_json:
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authors: Wood BJ, Vest MF, Carfagno C, Bartley KR, Sharma P, Halberstadt AL, Blough BE, Murnane KS.
publication_date: 2026-03-02
doi: 10.1021/acsptsci.5c00484
pubmed_id: 41852641
source_url: https://doi.org/10.1021/acsptsci.5c00484
substance_tags: psilocybin
topic_tags: Anxiety,Mechanism of Action,Receptor Pharmacology,Clinical Trial,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 11:22:01
title:
Differential Effects of Acute and Chronic Fluoxetine on Psychedelic-Induced Behavior in Mice: Implications for Clinical Trials.

abstract:
Selective serotonin reuptake inhibitors (SSRIs) are widely prescribed for mood and anxiety disorders, the same conditions under which psychedelic-assisted therapies are gaining renewed interest. However, it remains unclear how SSRI treatment may influence sensitivity to psychedelics, particularly through the shared engagement of serotonergic pathways. Here, we used the head-twitch response (HTR), a well-established behavioral readout of 5-HT2A activation, to investigate how acute, chronic, and discontinued fluoxetine treatment modulates the behavioral effects of R(-)-DOI and psilocybin, where psilocybin was only evaluated in the acute fluoxetine paradigm. In male mice, acute fluoxetine at 10 mg/kg had no effect on DOI-induced HTR, whereas chronic fluoxetine (10 mg/kg for 14 days) produced a downward shift in the DOI dose-response function. This attenuated response following a 14 day discontinuation period was reversed, suggesting that the behavioral consequences of chronic SSRI exposure may return following cessation. Interestingly, acute 10 mg/kg fluoxetine attenuated the efficacy, but not potency, of psilocybin, suggesting that SSRI-psychedelic interactions may vary depending on the pharmacological properties of the psychedelic compound. Together, these findings demonstrate that SSRI treatment history can alter the behavioral efficacy of psychedelics in a way that may be compound specific. These results have important implications for psychedelic-assisted therapies in populations taking SSRIs and highlight the need for translational studies to inform cotreatment strategies and guide clinical trial design.

raw_json:
{"europe_pmc_id":"41852641","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: The renaissance of research on psychedelics in child and adolescent psychopharmacology.
authors: Crocq MA, Auby P.
publication_date: 2026-03-12
doi: 10.1186/s13034-026-01069-6
pubmed_id: 41826990
source_url: https://doi.org/10.1186/s13034-026-01069-6
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
abstract:
AIMS: The recent regulatory approval of esketamine in adults heralded the renaissance of research into psychedelic compounds. However, the relevance of this resurgence for children and adolescents remains unclear. This review examines the rationale for investigating psychedelics in pediatric psychopharmacology. METHODS: We reviewed recent literature, regulatory documents, and clinical trial registries addressing the psychiatric use of classic serotonergic psychedelics (e.g., psilocybin, LSD), the entactogen MDMA, and dissociative compounds such as ketamine and esketamine in adolescent and young populations. Although ketamine is not a classic serotonergic psychedelic, it represents a paradigm for innovative pharmacological approaches. RESULTS: Ongoing and planned trials primarily involve adolescents aged 16 years and older. Interest in these compounds is driven by significant unmet needs in child and adolescent psychiatry, where few medications are approved, and unsatisfactory therapeutic response is common. Potential targets include anorexia nervosa, core symptoms of autism spectrum disorders, obsessive-compulsive disorder, resistant depression, and severe PTSD. The fact that psychedelics may have long-lasting effects after only a few sessions raises the question of their effects on neuroplasticity. CONCLUSIONS: Although psychedelic research has entered a new phase in adult psychiatry, translation to pediatric populations requires caution due to developmental vulnerabilities and limited long-term safety data. Rigorous clinical trials, ethical safeguards, and regulatory oversight are essential before broader application in children and adolescents can be considered.

topic_tags:
Depression,PTSD,OCD,Eating Disorders,Neuroplasticity,Pharmacology,Clinical Trial,Review Article,Adolescents,Safety

raw_json:
{"europe_pmc_id":"41826990","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2026-03-11
doi: 10.1136/bmjopen-2025-107512
pubmed_id: 41819589
source_url: https://doi.org/10.1136/bmjopen-2025-107512
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 11:22:03
title:
Digital Intervention for Psychedelic Preparation (DIPP): protocol for a randomised controlled feasibility trial comparing meditation- and music-based programmes in healthy volunteers.

authors:
McAlpine R, Jaglinska M, Jedlovszky K, Kuc J, Castro A, Piot A, Timmermann C, Skipper JI, Sacchet MD, Kamboj SK.

abstract:
IntroductionPsychedelic-assisted therapy shows promise for treating various mental health conditions; however, its reliance on intensive psychological preparation limits its broader application. Digital health interventions have the potential to address this limitation by providing structured, accessible and scalable preparation solutions. This randomised controlled feasibility trial aims to evaluate the feasibility and preliminary efficacy of the Digital Intervention for Psychedelic Preparation (DIPP), a 21-day mobile-accessible programme designed to prepare individuals for psychedelic experiences.Methods and analysisThe study will recruit 40 non-treatment-seeking adults without a clinical diagnosis, randomly assigning them to one of two conditions: (1) DIPP-MEDITATE, which combines daily guided meditation with background music or (2) DIPP-MUSIC, which provides the same background music without guided meditation. Both groups will complete the 21-day digital intervention remotely. Following the intervention, participants will attend an in-person supervised psilocybin session, receiving a standardised 25 mg dose. Primary outcomes focus on feasibility metrics including recruitment efficiency, participant retention and adherence to the intervention protocol. Secondary outcomes assess subjective feasibility, acceptability and preliminary efficacy, specifically evaluating psychedelic preparedness, the quality of the psychedelic experience and changes in wellbeing, with follow-up assessments at 2 weeks, and at 3, 6 and 9 months post-session. Exploratory measures include neuroimaging, physiological, cognitive and psychological assessments, as well as voice note experience sampling through a chatbot (referred to as 'DIPP-bot') to monitor inner speech, thought and emotional states during the intervention and follow-up periods.Ethics and disseminationApproved by UCL Research Ethics Committee (ID: 19113/003), this study follows the Declaration of Helsinki. Results will be published in peer-reviewed journals and presented at conferences. Confidentiality will be maintained throughout.Trial registration numberNCT06815653.

keywords:
Humans, Hallucinogens, Meditation, Music Therapy, Feasibility Studies, Adult, Female, Male, Randomized Controlled Trials as Topic, Psilocybin, Digital Health

topic_tags:
Brain Imaging,Aging,Wellbeing,Emotional Processing,Randomized Controlled Trial,Review Article,Healthy Volunteers

raw_json:
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authors: Chauhan SB, Akhtar N, Jain C, Singh I.
publication_date: 2026-03-10
doi: 10.2174/0118715273434237251212095005
pubmed_id: 41833044
source_url: https://doi.org/10.2174/0118715273434237251212095005
substance_tags: psilocybin
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:
Strategic Neurodelivery of Psychedelic Compounds: Bridging Molecular Pharmacology with Therapeutic Innovation in CNS Disorders.

abstract:
Psychedelic compounds such as psilocybin, Lysergic Acid Diethylamide (LSD), N,Ndimethyltryptamine (DMT), and 3,4-methylenedioxymethamphetamine (MDMA) are emerging as novel therapeutics for neuropsychiatric disorders, including depression, Post-Traumatic Stress Disorder (PTSD), and addiction. Acting primarily through serotonin 5-HT2A receptor agonism, they activate intracellular cascades involving Brain-Derived Neurotrophic Factor (BDNF), Tropomyosin receptor kinase B (TrkB), and the mammalian target of rapamycin (mTOR) pathway, leading to enhanced neuroplasticity and synaptogenesis. Recent evidence demonstrates direct TrkB binding and sustained cortical remodeling, underlying their rapid and durable antidepressant effects. Advanced Drug Delivery Systems (DDS)-including liposomes, Solid Lipid Nanoparticles (SLNs), and Poly(lactic-co-glycolic acid) (PLGA) carriers-are being engineered to achieve controlled, braintargeted, and stimuli-responsive release while minimizing systemic toxicity. Integration with microfluidic fabrication, Artificial Intelligence (AI)-based dosing, and non-invasive routes such as intranasal and transdermal delivery improves precision and patient adherence. By merging neuropharmacology with materials science, these innovations are redefining psychedelic-assisted therapy through enhanced safety, personalized dosing, and translational potential for central nervous system disorders.

topic_tags:
Depression,PTSD,Addiction,Neuroplasticity,Pharmacology,Mechanism of Action,Receptor Pharmacology,Safety,Toxicity

raw_json:
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authors: Bradshaw AJ, Sharp C, Van Der Merwe B, Tremble KS, Dentinger BTM
journal: Proceedings. Biological sciences
publication_date: 2026-03-10
doi: 10.1098/rspb.2025.2270
pubmed_id: 41818815
source_url: https://pubmed.ncbi.nlm.nih.gov/41818815/
keywords: Psilocybe, diversity, psilocybin, psychedelic mushroom, southern Africa
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: 2026-07-01 11:20:34
raw_json: {"pubmed_id":"41818815"}
title:
Discovery of the closest free-living relative of the domesticated 'magic mushroom' Psilocybe cubensis in Africa.

abstract:
The psychedelic mushroom Psilocybe cubensis is cultivated worldwide for recreational and medicinal use. Described initially from Cuba in 1906, there has been substantial debate about its origin and diversification. The prevailing view is that P. cubensis was inadvertently introduced to the Americas when cattle were introduced to the continent from Africa and Europe (approx. 1500 CE), but that its progenitor was endemic to Africa. We report the discovery of the cryptic species Psilocybe ochraceocentrata, the closest wild relative of P. cubensis from sub-Saharan Africa. DNA sequences from type specimens of all known and accessible African species of Psilocybe, and multi-locus phylogenetic and molecular clock analyses, strongly support recognizing African specimens originally identified as P. cubensis as a new species that last shared a common ancestor with P. cubensis approximately 1.5 million years ago (approx. 710 000 to 2.55 million years ago, 95% highest posterior density), long predating cattle domestication. Both species are associated with large herbivore dung, suggesting coprophily in their common ancestor likely predisposed P. cubensis to its present specialization on domesticated cattle dung. Ecological niche modelling using bioclimatic variables for global records of these species indicates historical habitat suitability for the common ancestor of P. cubensis and P. ochraceocentrata across Africa, Asia and the Americas over the last 3 million years. This discovery sheds light on the wild origins of domesticated P. cubensis and provides new genetic resources for research on psychedelic mushrooms.


title: Psychedelic therapy and postpartum depression: priorities and prospects.
authors: Thuery G, Crossen F, Mc Loone D, Hinds C, Duffy R, Jairaj C, Harkin A, Kelly JR
journal: Therapeutic advances in psychopharmacology
publication_date: 2025-12-31
doi: 10.1177/20451253251408280
pubmed_id: 41816502
source_url: https://pubmed.ncbi.nlm.nih.gov/41816502/
keywords: 5-MeO-DMT, major depression, postpartum depression, psilocybin, psychedelics
substance_tags: psilocybin
topic_tags: Depression,Mechanism of Action,Aging,Review Article,Safety,Immune Function
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":"41816502"}
abstract:
Approximately 15% of pregnant women experience postpartum depression (PPD). Even with currently available antidepressant treatments, many women will continue to be impaired by symptoms. Psychedelic therapy offers a promising transdiagnostic therapeutic strategy for several mental health disorders, and early results from current trials suggest that serotonergic psychedelics may represent a viable therapeutic approach for PPD. However, there is marked variability in the therapeutic response to psychedelic therapy, and the benefit-risk ratio in this population is not yet clear. To inform the rationale for the use of serotonergic psychedelics in the treatment of PPD, this review summarises the existing knowledge of immune, endocrine and neural pathways underpinning PPD and explores how serotonergic psychedelics interact with these pathways in the context of maternal motivation, bonding and caregiving behaviours. Finally, special considerations for psychedelic therapy in the postpartum period are outlined and future perspectives explored. Despite the rationale and encouraging early findings, further research is required to determine efficacy and safety profiles. Future studies, particularly longitudinal trials, should include adaptations and safeguards tailored to the unique physiological, psychological and caregiving contexts of the postpartum period.


title: Psilocybin microdosing in the United States: Insights from a nationally representative survey.
authors: Priest M, Kilmer B, Ramchand R, Atshan S.
publication_date: 2026-03-07
doi: 10.1111/add.70368
pubmed_id: 41795902
source_url: https://doi.org/10.1111/add.70368
substance_tags: psilocybin
topic_tags: 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:
Background and aimsThere has been a resurgence of interest in using psilocybin to treat various mental health conditions. Although some adults in the United States (US) are using psilocybin, little is known about the epidemiology of its use, especially for microdosing (i.e., taking a fraction of a regular dose). This study aimed to present nationally representative survey results about people who microdose psilocybin in the US.MethodsA probability-based and nationally representative survey of individuals living in the US was fielded from December 2023 to January 2024. A population estimate of how many US adults have microdosed, recency of microdosing, and intentions for microdosing was calculated using sample weights designed to produce national estimates. Multinomial logit models were used to identify predictors of microdosing status across demographic characteristics.ResultsOf 4253 respondents who completed the screener, 554 reported using psilocybin in their lifetime. Among the 12.1% of US adults who used psilocybin in their lifetime, 26.5% (95% Confidence Interval [CI]: 21.5-32.1%) reported they microdosed the last time they used, 57.5% (95% CI: 51.5-63.2) reported they did not microdose, and 14.6% (95% CI: 10.8-19.5) did not know or were unsure. Among the 3.1% of adults who used psilocybin in the past year, 46.9% (95% CI: 35.3-58.8) reported they microdosed the last time they used, 45.6% (95% CI: 34.2-57.5) reported they did not microdose, and 6.1% (95% CI: 2.8-12.8) did not know or were unsure. Compared with those who did not microdose the last time they used psilocybin, those who did were 12 percentage points (p = 0.002) more likely to have used psilocybin for improved physical health and 25 percentage points (p

raw_json:
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title: The combination of exercise and psychedelics for the treatment of major depressive disorder.
authors: Fabiano N, Stubbs B, Lawrence DW, Rosenblat JD, Teixeira PJ, Wong S, Zhou C, Carhart-Harris R
journal: Discover mental health
publication_date: 2026-03-06
doi: 10.1007/s44192-026-00408-5
pubmed_id: 41793582
source_url: https://pubmed.ncbi.nlm.nih.gov/41793582/
keywords: Exercise, Depression, Major depressive disorder, Physical activity, Psilocybin, Psychedelic
substance_tags: psilocybin
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":"41793582"}
abstract:
Upwards of 50% of people do not respond to the primary treatment modalities for major depressive disorder (MDD), which has led to increased attention and use of alternative methods, including exercise and psychedelics. While interventions using either exercise or psychedelics have demonstrated largely positive results in isolation, their synergistic potential has yet to be explored. As such, this commentary provides an overview of exercise/psychedelics as a treatment for depression and their potential synergy and/or complementarity. From a biological perspective, psychedelics acutely enhance brain-derived neurotrophic factor (BDNF) signalling, while exercise provides sustained BDNF elevation; psychedelics enhance neuroplasticity largely in the cortex (with only modest effects in the hippocampus), while exercise boosts hippocampal neurogenesis; psychedelics increase glutamate release via stimulation of 5-HT receptors on pyramidal neurons, while exercise enhances glutamatergic transmission via the endocannabinoid system and reduction of systemic inflammation; both boost serotonin release; and psychedelics temporarily disrupt functional connectivity between the hippocampus and default mode network (DMN), while exercise normalizes this connectivity, which may sustain post-psychedelic gains. Through the lens of psychological and behaviour change, psychedelics appear to facilitate the adoption or maintenance of physical activity habits, increase psychological flexibility, and since exercise is associated with emotional resilience to acute stress, this may allow users to experience deeper immersion and exploration during their psychedelic experience, improving antidepressant outcomes. In summary, exercise and psychedelics have numerous potential complementary mechanisms, therefore, future research is warranted to explore the efficacy, tolerability, safety, and neurobiology of this combination.

topic_tags:
Depression,Neuroplasticity,Neurogenesis,Mechanism of Action,Receptor Pharmacology,Default Mode Network,Resilience,Emotional Processing,Psychological Flexibility,Safety,Inflammation


authors: Koning E, Gamberg S, Keshen A.
publication_date: 2026-03-05
doi: 10.3390/bs16030376
pubmed_id: 41898038
source_url: https://doi.org/10.3390/bs16030376
substance_tags: psilocybin
topic_tags: Eating Disorders,Neuroplasticity,Emotional Processing,Review Article,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 Treatment as an Adjunct to Cognitive Behavioral Therapy for Eating Disorders: Therapeutic Rationale & Considerations for Protocol Development.

abstract:
Eating disorders (EDs) remain challenging to treat, with high dropout and low remission rates in cognitive-behavioral therapy for EDs (CBT-ED). Psilocybin treatment (PT) demonstrates therapeutic potential to enhance CBT-ED by exerting several neurobiological, psychological, and experiential effects (e.g., antidepressant, neuroplasticity, emotional openness) that are hypothesized to increase psychotherapeutic engagement, reduce dropout, and improve clinical outcomes. This narrative review provides the first consolidation of theoretical evidence for PT/CBT-ED, proposes considerations for a concurrent intervention protocol, and presents clinical and research considerations to empirically test its feasibility, safety, and efficacy. This line of inquiry is expected to advance the development of approaches that improve ED treatment outcomes and, more broadly, advance the study of psychedelics as tools to enhance evidence-based psychotherapy models.

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title: 5 Years of bipolar disorder conversations on Reddit: Methods, key topics and future directions.
publication_date: 2026-03-05
doi: 10.1371/journal.pone.0338622
pubmed_id: 41790781
source_url: https://doi.org/10.1371/journal.pone.0338622
keywords: Humans, Bipolar Disorder, Internet
substance_tags: psilocybin
topic_tags: 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 11:22:03
authors:
Poh C, Head C, Nunez JJ, Lapadat L, Morton E, Collaborative RESearch Team to Study Psychosocial Issues in Bipolar Disorder (CREST.BD), Michalak EE.

abstract:
Bipolar disorder (BD) is a prevalent mood disorder that can be associated with serious personal, societal, and economic costs. Growing attention is being paid to the importance of including the experiences of people living with BD in research and healthcare system advancement. However, there is still much to be learned about what people with BD are prioritizing, and where their needs are not yet being met in research and clinical settings. For the past five years, the Collaborative RESearch Team to study psychosocial issues in Bipolar Disorder (CREST.BD) has facilitated the world's largest online BD question-and-answer event, an "Ask Me Anything" (AMA) hosted via Reddit. This event allows people internationally to submit BD-related questions to be answered by expert panelists. Altogether, 159 panelists with diverse expertise in BD have participated, and more than 2,000 questions addressed. After five years, the Reddit AMAs have become a large repository of questions that represent the needs and interests of individuals with BD and their supporters. This study used topic modeling, a natural language processing (NLP) method, to algorithmically extract key topics from AMA queries collected over five years. Queries were extracted using a python script and the Reddit API; BERTopic was used for topic modelling. Topic models of 10, 20, and an unrestricted number of topics were run; the 20 topic model was chosen as it best balanced specificity and breadth. The most common topic was BD misdiagnosis/differential diagnoses. Other topics included coping with daily struggles; understanding hypomania and suicidality; medication and use of substances such as psilocybin and ketamine; and supporting loved ones with BD. Future research in these areas would be beneficial for individuals with BD and their loved ones, and patients with BD may benefit from clinicians addressing these topics. Ethical issues are also discussed.

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authors: Thomas JE, Dellarole A, Caballero J.
publication_date: 2026-03-04
doi: 10.1093/ajhp/zxag062
pubmed_id: 41784123
source_url: https://doi.org/10.1093/ajhp/zxag062
substance_tags: psilocybin
topic_tags: PTSD,Randomized Controlled Trial,Systematic Review,Review Article,Veterans,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 11:22:03
title:
Efficacy and risks of psychedelics in treatment of posttraumatic stress disorder: A systematic review.

abstract:
PurposeThe purpose of this review is to evaluate which psychedelics have the most efficacy data to support their use in the treatment of posttraumatic stress disorder (PTSD). This review also aims to assess safety data and concerns related to psychedelic therapies and identify demographic characteristics that may influence clinical outcomes.SummaryA systematic review of the literature was conducted on PubMed, Web of Science, and Scopus to identify randomized controlled studies evaluating the use of psychedelic therapy in treatment of PTSD. Thirteen studies met our inclusion criteria and were included in the review. Six studies evaluated 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy, while 7 studies evaluated ketamine. Study findings regarding efficacy were mixed. Four of the 6 studies evaluating MDMA-assisted psychotherapy demonstrated statistically significant improvement in PTSD symptoms, while 3 of the 7 studies evaluating intravenous ketamine (ketamine IV) demonstrated statistically significant efficacy (eg, reduced PTSD symptoms, durable effect) in relation to comparators. Both therapies were generally well tolerated. The majority of studies were conducted in primarily civilian populations, with one MDMA study and 2 ketamine IV studies focused on veterans.ConclusionMDMA and ketamine IV currently have the greatest support in the literature for efficacy in PTSD. Studies suggest treatment with these agents under supervision may lead to improvements in PTSD symptoms, with the medications being generally well tolerated. However, caution should be used when interpreting study results due to limitations such as treatment expectancy effect and the potential for inadequate blinding. Randomized controlled studies of other psychedelics (eg, psilocybin, lysergic acid diethylamide) are needed to assess their utility in PTSD.

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title: Mushroom-Derived Carbon Nanosheets for Efficient Photothermal De-Icing Applications.
authors: Prusti SP, Salian R, Das AK, Kumbhakar P.
publication_date: 2026-01-21
doi: 10.1021/acs.langmuir.5c05324
pubmed_id: 41569282
source_url: https://doi.org/10.1021/acs.langmuir.5c05324
substance_tags: psilocybin,psilocin
topic_tags: 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:
The green synthesis of nanomaterials has emerged as a viable alternative to traditional techniques that reduce environmental risks and the production of harmful byproducts. In this work, biomaterial derived from wild mushrooms was used to synthesize psilocybin-derived carbon nanosheets (P-CNSs). The bioactive substance psilocybin serves as a sustainable precursor that ensures an environmentally friendly synthesis procedure. Spectroscopic measurements confirm the structural and functional properties of the P-CNSs. The naturally extracted P-CNSs demonstrated substantial photothermal conversion efficiency under both visible and infrared light. Their adaptability for thermal applications was shown by their medium-specific response. Furthermore, in photothermal de-icing, P-CNSs effectively melted ice under visible light exposure, making it a crucial application. Additionally, density functional theory (DFT) and time-dependent DFT calculations were performed to optimize the structures of psilocin, baeocystin, and norbaeocystin, which show the electronic transitions responsible for the appearance of absorption and fluorescence behavior. This work draws attention to the inclusion of psilocybin in green synthesis to produce an affordable and sustainable solution for environmental issues brought to the forefront by the advantages of environmentally benign manufacture and multipurpose use, especially in thermal control and environmental remediation.

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title: Psilocybin or Nicotine Patch for Smoking Cessation: A Pilot Randomized Clinical Trial.
authors: Johnson MW, Naudé GP, Hendricks PS, Garcia-Romeu A.
publication_date: 2026-03-01
doi: 10.1001/jamanetworkopen.2026.0972
pubmed_id: 41805956
source_url: https://doi.org/10.1001/jamanetworkopen.2026.0972
substance_tags: psilocybin
topic_tags: Addiction,Clinical Trial,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
abstract:
ImportanceAnnual tobacco-related death estimates are 480 000 in the US and 8 million worldwide, surpassing mortality for other abused substances. Most smoking cessation interventions result in modest long-term success.ObjectiveTo compare prolonged smoking abstinence rates in smokers receiving psilocybin plus cognitive behavioral therapy (CBT) with those receiving the nicotine patch plus CBT.Design, setting, and participantsIn this pilot randomized clinical trial, participants and investigators were unblinded to treatment condition, including an optional crossover after completion of the primary end point. Data were collected from psychiatrically healthy adult smokers from January 20, 2015, to May 8, 2023, at the Johns Hopkins Bayview Medical Center, an academic medical center and teaching hospital in Baltimore, Maryland.InterventionThe trial randomized cigarette smokers to receive either 1 high dose (30 mg/70 kg) of psilocybin or initiate 8 to 10 weeks of US Food and Drug Administration-approved nicotine patch treatment on the target quit date. Both groups received a 13-week manualized CBT program for smoking cessation.Main outcomes and measuresBiochemically verified prolonged smoking abstinence (primary) and 7-day point prevalence abstinence (secondary) at 6 months after the target quit date were compared between groups using intention-to-treat analysis.ResultsA total of 82 psychiatrically healthy adult smokers (mean [SD] age, 47.6 [12.0] years; 49 [59.8%] male) participated in the study, with 68 (82.9%) completing the 6-month follow-up. At 6-month follow-up, 17 participants receiving psilocybin (40.5%) exhibited biochemically verified prolonged abstinence compared with 4 participants using the nicotine patch (10.0%) (odds ratio, 6.12; 95% CI, 1.99-23.26; P =.003), and 22 participants receiving psilocybin (52.4%) exhibited biochemically verified 7-day point prevalence abstinence compared with 10 participants using the nicotine patch (25.0%) (odds ratio, 3.30; 95% CI, 1.32-8.70; P =.01). No serious adverse events were attributed to psilocybin or nicotine patch.Conclusions and relevanceIn this pilot randomized clinical trial, 1 dose of psilocybin with manualized CBT significantly increased long-term abstinence compared with nicotine patch treatment with CBT. Psilocybin abstinence rates were higher than typical treatments, suggesting promise for tobacco smoking cessation.Trial registrationClinicalTrials.gov Identifier: NCT01943994.

keywords:
Humans, Treatment Outcome, Pilot Projects, Smoking Cessation, Adult, Middle Aged, Female, Male, Psilocybin, Cognitive Behavioral Therapy, Tobacco Use Cessation Devices, Nicotine Replacement Therapy

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title: Psychedelics, Eleusis, and the Invention of Religious Experience.
authors: Mosurinjohn S, Ascough R
journal: Psychedelic medicine (New Rochelle, N.Y.)
publication_date: 2026-02-28
doi: 10.1177/28314425251361835
pubmed_id: 42130781
source_url: https://pubmed.ncbi.nlm.nih.gov/42130781/
substance_tags: psilocybin
topic_tags: Consciousness,Spirituality,Systematic Review,Review Article
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":"42130781"}
abstract:
This article corrects an idea in psychedelic science and culture that the ancient Eleusynian Mysteries used psychedelics, as claimed by Carl Ruck and co-authors in (1978), revitalized by Brian Muraresku's (2020), and popularized by social media heavyweights such as Joe Rogan.
It begins by exposing critical methodological flaws in the arguments, namely, a pattern of presenting claims, followed by mild circumstantial evidence, rhetorically solidifying the interpretation of this evidence into a "fact," on which is built each subsequent round of conjecture.
We then explore how the dogged pursuit of evidentiary mirages contributes to the project of establishing a western civilizational pedigree to dignify the use of stigmatized drugs and revitalize experiential religion.
Although the desire for legitimacy and meaning is understandable, the strategies used by the writers of this pseudo-history constitute a kind of religious fundamentalism. Their writing attempts to show that a relatively new practice is the old, true religion, in this case, the "religion with no name" that underlies every religious tradition. In doing so, they miss seriously relating to the many well-documented historical and living Indigenous histories of psychedelics, or seeing contemporary psychedelic practice in continuity with other, and maybe even older, nonpharmacological methods of changing consciousness. Overall, the "psychedelic Eleusis" discourse focuses on the purported Eleusynian drug and its phenomenology rather than focusing on practices for taking up the spiritual injunctions of those psychedelic experiences.
We conclude that, given how the psychedelic hypothesis is fundamentally flawed in its study of antiquity, it is a shaky foundation on which to build an argument for modern psychedelic use for therapeutic and spiritual practice. Since scholarly research is key to moving forward decriminalization, legalization, medical regulation, and other roles for psychedelics in society, it is crucial that scholars and popular audiences communicate effectively around psychedelic history and culture. Instead of committing to a specific (and erroneous) view of history, psychedelic scholarship must commit to academic discussion and debate.

keywords:
Eleusynian mysteries, ergot, psilocybin, psychedelic phenomenology, psychoactive substances, systematic review


title: Efficacy and Safety of Psychoactive Tryptamines in Addiction: A Systematic Review.
publication_date: 2026-02-23
doi: 10.1177/28314425251364182
pubmed_id: 42130778
source_url: https://doi.org/10.1177/28314425251364182
substance_tags: psilocybin
topic_tags: Addiction,Clinical Trial,Randomized Controlled Trial,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 11:22:01
authors:
van der Meer PB, Schukking N, Dik M, van Reemst A, Fuentes JJ, Kaptein AA, Schoones JW, Verboeket S, de Waal MM, Goudriaan AE, Kramers C, Schellekens A, Bossong MG, Somers M, Batalla A.

abstract:
BackgroundPsychedelics such as lysergic acid diethylamide (LSD) and psilocybin have shown a beneficial effect on substance use disorder (SUD) symptoms. In this systematic review, we aimed to assess the efficacy and safety of psychoactive tryptamines in patients with an SUD or non-substance-related disorder (i.e., gambling disorder) in order to provide a comprehensive overview of the available evidence and identify potential research gaps.MethodsA systematic literature search was performed in eight different databases up to February 2024. Clinical trials were included that assessed the efficacy and safety of psychoactive tryptamines other than psilocybin and ibogaine. A quality assessment of the included trials was done based on the revised Cochrane risk-of-bias tools.ResultsA total of four clinical trials (three randomized controlled trials and one single-arm clinical trial; n = 176 patients) were included, all in patients with alcohol use disorder. Dipropyltryptamine and diethyltryptamine were the two investigated psychoactive tryptamines. Abstinence ranged from 10% (duration of follow-up unknown) to 38% at 26 weeks of follow-up, and severity of alcohol use did not differ between the psychoactive tryptamine group and the control groups. Adverse effects were not well reported in the trials.ConclusionStudies assessing the efficacy of psychoactive tryptamines other than psilocybin and ibogaine in addiction are scarce and show limited evidence for effectiveness in the treatment of addictive disorders.

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title: [Perspectives opened up by the physiopathological understanding of psychiatric disorders].
authors: Girault N, Quiroga L, Jedrecy S, Bertin S, Djonouma N, Fossati P.
publication_date: 2026-02-28
pubmed_id: 41878960
source_url: https://europepmc.org/article/MED/41878960
keywords: Humans, Mental Disorders
substance_tags: psilocybin
topic_tags: Depression,Brain Imaging,Receptor Pharmacology,Aging,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
abstract:
Neuroimaging techniques have a rightful place in the field of psychiatry. They are essential for differential diagnosis, especially when the psychiatric presentation is atypical. Furthermore, they associate brain dysfunction with psychiatric disorders, but they cannot yet provide a definitive psychiatric diagnosis. However, from a therapeutic perspective, brain MRI is a very useful tool for neuronavigation techniques in combination with rTMS. From a neurobiological perspective, advances in genetics are allowing the development of genomic tests to guide antidepressant therapy and predict a diagnosis of bipolar disorder. In addition, psychedelics such as psilocybin offer promising alternatives for the treatment of depression. Similarly, ketamine, an antagonist of NMDA-type glutamatergic receptors, has shown efficacy in the management of suicidal crises and in the treatment of depressive disorders. Finally, antagonism of orexin receptors offer a new avenue for treating insomnia.

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title: Psilocybin and Ibogaine in Cocaine-Seeking: Extinction Enhancement Without Relapse Prevention.
publication_date: 2026-02-28
doi: 10.1111/adb.70111
pubmed_id: 41780506
source_url: https://doi.org/10.1111/adb.70111
substance_tags: psilocybin
topic_tags: Anxiety,Addiction,Animal Study,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:
Koutrouli IRA, Brejtr V, Schwendt M, Witek K, Charalambous C, Aleksič K, Miniariková N, Lhotková E, Toman M, Nikolič M, Jurok R, Cihlářová P, Mazoch V, Ryšánek P, Kuchař M, Šíchová K, Páleníček T.

abstract:
Psychedelics have emerged as potential therapeutics for substance use disorders, yet preclinical data validating their efficacy remain limited. Here, we investigated the effects of a clinically inspired dose-escalation protocol of psilocybin and ibogaine on extinction and cue-induced reinstatement in Wistar male rats following intravenous cocaine self-administration (IVSA). Rats were trained on a fixed ratio 1 (FR1) schedule with cocaine dose-escalation during the acquisition phase (0.25 mg/kg/infusion, followed by 0.5 mg/kg/infusion). Following acquisition, animals were randomised into treatment groups and then subjected to 10 days of extinction. Psilocybin (1.25 mg/kg and 5 mg/kg) or ibogaine (10 mg/kg and 40 mg/kg) was administered subcutaneously and intraperitoneally, respectively, on extinction days 1 and 5. A cue-induced reinstatement test was conducted 6 days after the last treatment. Both treatments significantly modulated behaviour during extinction; psilocybin reduced active lever pressing 1 day after the second dose, with a nonsignificant reduction already apparent after the first dose, while the effect of ibogaine was significant even after the first administration. However, neither compound significantly altered reinstatement behaviour, although psilocybin showed a trend toward attenuation. The applied treatment had no side effects on general locomotor activity or anxiety-like behaviour, as measured in the open field test 24 h after each administration. These findings support a role for psilocybin and ibogaine in facilitating extinction learning and suggest possible protective effects against relapse, warranting further research into their antiaddictive efficacy.

keywords:
Animals, Rats, Rats, Wistar, Cocaine-Related Disorders, Ibogaine, Cocaine, Dopamine Uptake Inhibitors, Hallucinogens, Self Administration, Behavior, Animal, Conditioning, Operant, Cues, Dose-Response Relationship, Drug, Male, Extinction, Psychological, Secondary Prevention, Drug-Seeking Behavior, Psilocybin

raw_json:
{"europe_pmc_id":"41780506","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Shokr MM, Fawzy MN, Abdelaziz AM.
publication_date: 2026-02-25
doi: 10.1016/j.mcn.2026.104076
pubmed_id: 41763341
source_url: https://doi.org/10.1016/j.mcn.2026.104076
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 11:22:03
title:
Pharmacological regulation of adult brain neuroplasticity: Synergistic roles of neuropeptide signaling, psychedelics, and synaptic modulators.

abstract:
Neuroplasticity refers to the ability of the brain to modify synaptic connections and reorganize neural circuits, underpinning cognitive function, emotional regulation, and recovery from injury. Recent advances have redefined adult neuroplasticity as more dynamic and therapeutically accessible than previously thought, spurring investigation into pharmacological interventions that can augment these adaptive processes. This review dissects current evidence for drug strategies targeting synaptic modulators (NMDA, AMPA, and GABA receptors), neuropeptide systems (including BDNF, oxytocin, vasopressin), and psychedelic compounds (psilocybin, LSD, ketamine), integrating insights from cellular, preclinical, and clinical studies. We detail how these agents modulate molecular pathways governing synaptic transmission, dendritic remodeling, and gene expression linked to neuronal growth and resilience. Highlighted findings include the rapid-acting antidepressant effects of NMDA antagonists, the structural and functional reorganization induced by classic psychedelics via 5-HT2A receptor activation, and the neurorestorative roles of neuropeptides in synaptic and network adaptation. Alongside these advances, we critically address safety, ethical considerations, and the risk of maladaptive plasticity, underscoring the importance of dosing, patient selection, and controlled therapeutic environments. Non-hallucinogenic neuroplastogens and combinatorial approaches that are still emerging offer new avenues to fine-tune plasticity with an improved safety profile. The collective evidence positions neuroplasticity-targeting pharmacology as a promising and complex frontier for the treatment of neuropsychiatric and neurodegenerative disorders in adulthood.

keywords:
Brain, Synapses, Animals, Humans, Neuropeptides, Hallucinogens, Signal Transduction, Synaptic Transmission, Neuronal Plasticity

topic_tags:
Neuroplasticity,Pharmacology,Mechanism of Action,Receptor Pharmacology,Resilience,Emotional Processing,Review Article,Animal Study,Safety

raw_json:
{"europe_pmc_id":"41763341","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Innovative Pharmacological Approaches to Eating Disorder Treatment.
authors: Keshen A, Touyz S, Lacroix E, Hay P, McElroy SL.
publication_date: 2025-09-23
doi: 10.1016/j.psc.2025.08.014
pubmed_id: 41708265
source_url: https://doi.org/10.1016/j.psc.2025.08.014
keywords: Humans, Central Nervous System Stimulants, Hallucinogens, Feeding and Eating Disorders
substance_tags: psilocybin
topic_tags: Eating Disorders,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
abstract:
This article explores innovative pharmacologic treatments for eating disorders, focusing on psychedelics, stimulant medications, and other emerging therapies. Preliminary evidence for psychedelics (eg, psilocybin) highlight their potential to enhance cognitive flexibility and support psychological interventions in some eating disorders (eg, anorexia nervosa). Stimulants like lisdexamfetamine offer benefits for binge-eating disorder, while medications for avoidant/restrictive food intake disorder and bulimia nervosa remain understudied. The study underscores the need for robust clinical trials to evaluate these approaches and advocates for integrating novel treatments into existing therapeutic frameworks to address the complex biological and psychological dimensions of eating disorders.

raw_json:
{"europe_pmc_id":"41708265","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Shiju S, Tirumala R, Marseille E.
publication_date: 2026-01-25
doi: 10.1016/j.rcsop.2026.100709
pubmed_id: 41674667
source_url: https://doi.org/10.1016/j.rcsop.2026.100709
substance_tags: psilocybin
topic_tags: Chronic Pain,Headache / Migraine,Microdosing,Review Article,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
title:
Self-medication with psychedelics: a scoping review and narrative synthesis of review-level evidence.

abstract:
BackgroundAs public and scientific interest in psychedelics grows, unsupervised use for health purposes is increasing. In the U.S., past-year hallucinogen use nearly doubled from 2015 to 2023. Many individuals report self-treating physical or psychological symptoms without medical supervision using psychedelics-a practice termed self-medication. Despite this trend, review-level syntheses remain scarce.AimThis scoping review aimed to map and synthesize review-level evidence on the self-medication of psychedelics, including which substances are used, for what health-related purposes, and what benefits and harms have been reported.MethodsWe conducted a scoping review of review-level evidence on self-medication with psychedelics, following the PRISMA PRISMA-ScR (2018) checklist. Searches in PubMed, PsycINFO, and Google Scholar (October-November 2024) used the terms ("self-medication" OR "self-treatment") AND "psychedelics." Eligible reviews examined unsupervised use of classical or non-classical psychedelics for physical, mental, or behavioral conditions. Four reviewers independently screened all records. Data extraction was conducted using Elicit AI and was manually verified by reviewers. Methodological quality was assessed using AMSTAR criteria.ResultsThree reviews met inclusion criteria (systematic, scoping, narrative). Psilocybin and LSD were most frequently reported, primarily for cluster headache and chronic pain. Outcomes included abortive relief, prophylactic relief, and prolonged remission, often from microdosed regimens. Approximately 40% achieved full remission; 70% reported preventive benefit. Adverse effects were rare and brief. Motivations for self-use centered on coping, desperation, and dissatisfaction with conventional care.ConclusionsPreliminary review-level evidence suggests that individuals self-medicating with psychedelics-particularly psilocybin and LSD-report symptom relief for conditions such as cluster headache, though findings remain limited by scarce and heterogeneous data. More rigorous research is needed to clarify effectiveness, safety, and real-world patterns of use.

raw_json:
{"europe_pmc_id":"41674667","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Xu T, Wong S, Le GH, Dri CE, Teopiz KM, Lu A, Lee S, Rhee TG, Yin L, Bargiota S, Ho R, McIntyre RS.
publication_date: 2026-02-04
doi: 10.1055/a-2794-6487
pubmed_id: 41643722
source_url: https://doi.org/10.1055/a-2794-6487
substance_tags: psilocybin
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:
Cardiac Consequences Associated with Psychedelic Use: A Systematic Review of Lysergic Acid Diethylamide, 3,4-Methylenedioxymethamphetamine, and 5-Hydroxytryptamine 2B-Mediated Valvular Heart Disease.

abstract:
Serotonergic psychedelics, such as lysergic acid diethylamide, and psilocybin, and the entactogen 3,4-methylenedioxymethamphetamine exhibit agonist activity at the 5-hydroxytryptamine 2B receptor, a signalling pathway known to mechanistically mediate drug-induced valvular heart disease. This systematic review evaluates whether chronic or repeated use of psychedelics and 3,4-methylenedioxymethamphetamine may contribute to valvular heart disease through sustained 5-hydroxytryptamine 2B receptor activation. A systematic search of Google Scholar, OVID and PubMed was conducted from inception to June 1, 2025. We sought to include studies that reported an association between psychedelics or 3,4-methylenedioxymethamphetamine at 5-hydroxytryptamine 2B binding and molecular, cellular, structural, and/or functional evidence of cardiac valvulopathy. Seventeen studies were included in this review. No studies were found on psilocybin, dimethyltryptamine or mescaline. Both lysergic acid diethylamide and 3,4-methylenedioxymethamphetamine have high affinity for 5-hydroxytryptamine 2B receptors and promote downstream signaling linked to mitogenic and fibrotic changes in valvular tissue. In vitro and structural studies show that lysergic acid diethylamide exhibits high affinity and induces β-arrestin-biased signaling in valvular interstitial cells, while 3,4-methylenedioxymethamphetamine displays moderate affinity and similar functional responses. In vivo studies confirm serotonin-induced valvulopathy, and chronic 3,4-methylenedioxymethamphetamine use has been associated with valvular abnormalities in humans. No clinical cases of lysergic acid diethylamide-induced valvulopathy have been reported, but preclinical data support its potential to engage fibrotic signaling pathways under sustained exposure. Preliminary converging mechanistic and preclinical evidence suggests that lysergic acid diethylamide and 3,4-methylenedioxymethamphetamine may promote cardiac valvulopathy via 5-hydroxytryptamine 2B receptor signalling. This is consistent with existing Food and Drug Administration concerns and supports the need for ongoing cardiac and valvular safety monitoring in psychedelic research.

keywords:
Animals, Humans, Heart Valve Diseases, N-Methyl-3,4-methylenedioxyamphetamine, Lysergic Acid Diethylamide, Receptor, Serotonin, 5-HT2B, Hallucinogens

topic_tags:
Mechanism of Action,Receptor Pharmacology,Systematic Review,Review Article,Animal Study,In Vitro Study,Safety

raw_json:
{"europe_pmc_id":"41643722","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2026-01-18
doi: 10.1016/j.genhosppsych.2026.01.001
pubmed_id: 41581334
source_url: https://doi.org/10.1016/j.genhosppsych.2026.01.001
substance_tags: psilocybin
topic_tags: Depression,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 11:22:02
title:
Early response to psilocybin in adults with treatment-resistant depression as a predictor for antidepressant efficacy.

authors:
Doyle Z, Chisamore N, Kaczmarek ES, Johnson DE, Brudner RM, Weiglein G, Blainey MG, Bawks J, Riva-Cambrin J, Sethi R, McIntyre RS, Rosenblat JD.

raw_json:
{"europe_pmc_id":"41581334","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Rached G, Campana A, Fiani D, Nguyen C, Van den Eynde V, Gillman PK, Barnett BS.
publication_date: 2026-01-16
doi: 10.1007/s40263-025-01256-7
pubmed_id: 41546846
source_url: https://doi.org/10.1007/s40263-025-01256-7
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:
Safety and Efficacy of Monoamine Oxidase Inhibitors in Patients Who Use Psychoactive Substances: Potential Drug Interactions and Substance Use Disorder Treatment Data.

abstract:
Monoamine oxidase inhibitors (MAOIs) remain an important option for patients with treatment-resistant depression (TRD) and other psychiatric conditions, despite potentially serious drug-drug interactions and associated dietary tyramine restrictions. However, they are rarely prescribed in patients with comorbid substance use disorders (SUDs) due to concerns about potential drug interactions and limited research in these populations. This narrative review investigates the use of MAOIs in patients who use psychoactive substances, exploring potential interactions while summarizing the relatively scant literature on using MAOIs as treatments for SUDs. It synthesizes data from 219 peer-reviewed publications investigating MAOI/psychoactive substance interactions or the use of MAOIs to treat SUDs or psychiatric conditions in patients with comorbid SUDs, including 20 randomized controlled trials, 18 non-randomized interventional trials, 32 observational studies/case series, 56 case reports, 85 preclinical studies, and 8 reviews, with publication years spanning from 1955 to 2025. Data from 28 non-peer-reviewed user-submitted reports from drug use/harm reduction forums are also included. Suspected cases of serotonin toxicity have been reported for MAOIs in combination with amphetamine, dextromethorphan, 3,4-methylenedioxymethamphetamine (MDMA), meperidine (pethidine), methadone, and tramadol. Hypertensive urgency/emergency has been reported for MAOIs in combination with alcohol (varieties containing significant amounts of tyramine), amphetamine, cocaine, dextroamphetamine, khat, methamphetamine, and psilocybin mushrooms. Other notable adverse events associated with MAOIs in combination with psychoactive substances include agitation (4-bromo-2,5-dimethoxyphenethylamine [2C-B] 5-methoxy-N,N-dimethyltryptamine [5-Meo-DMT]), N,N-dimethyltryptamine [DMT]), delirium/confusion (DMT, propoxyphene, and tramadol), edema (chlordiazepoxide), intracranial hemorrhage (amphetamine, khat, and methamphetamine), mania/psychosis (DMT), rhabdomyolysis (5-MeO-DMT, DMT, and propoxyphene), and sedation/stupor/loss of consciousness (amobarbital, amphetamine, cocaine, dextroamphetamine, and propoxyphene). Fatalities have been reported for MAOIs in combination with 5-MeO-DMT, amphetamine, dextroamphetamine, dextromethorphan (in overdose), MDMA, methamphetamine, meperidine, and tramadol (in overdose). Based on our findings, some substances, such as alcoholic beverages containing significant tyramine quantities (uncommon today), amphetamines, opioids with significant serotonergic reuptake inhibition, and some hallucinogens such as the empathogen/entactogen MDMA, can pose potentially fatal risks in combination with MAOIs. However, MAOI treatment of patients who use alcoholic beverages low in tyramine, caffeine, cannabis, nicotine, sedatives, some (primarily classic) hallucinogens, and some other substances can likely be appropriately managed with careful monitoring, although psychoactive substance dose and route of administration are important safety considerations. While there was initially hope MAOIs might effectively treat some SUDs, there are no robust human data to support their efficacy in this context. Given growing levels of substance use and an increasing number of novel illicit compounds being produced, more research on MAOI safety in patients with psychiatric conditions and comorbid psychoactive substance use/misuse is essential to determining their appropriateness in this complex patient population.

keywords:
Humans, Substance-Related Disorders, Psychotropic Drugs, Monoamine Oxidase Inhibitors, Drug Interactions

topic_tags:
Depression,Addiction,Receptor Pharmacology,Consciousness,Randomized Controlled Trial,Review Article,Case Report,Observational Study,Animal Study,Treatment-Resistant Depression,Safety,Adverse Events,Toxicity,Drug Interactions

raw_json:
{"europe_pmc_id":"41546846","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin shapes neural plasticity in selective brain networks.
authors: Lewis S.
publication_date: 2026-02-28
doi: 10.1038/s41583-025-01019-9
pubmed_id: 41495463
source_url: https://doi.org/10.1038/s41583-025-01019-9
substance_tags: psilocybin
topic_tags: Neuroplasticity
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":"41495463","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Jorgenson DM, Santos Leon E, Vakkalanka JP, Krispin S, Radke JB.
publication_date: 2026-01-05
doi: 10.1080/15563650.2025.2599402
pubmed_id: 41493095
source_url: https://doi.org/10.1080/15563650.2025.2599402
substance_tags: psilocybin
topic_tags: Depression,Observational Study,Adolescents,Toxicity
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:
Psychoactive mushroom edibles: trends and toxicities reported to the United States National Poison Data System®, 2023-2024.

abstract:
IntroductionPsychoactive mushroom edibles are gaining popularity, yet little is known of their clinical effects. These unregulated products are widely available, often with unlisted ingredients and inconsistent formulations, underscoring the need for more research to address public health concerns. We aimed to investigate recent trends in demographics and clinical effects associated with these products.MethodsWe conducted a retrospective observational analysis of psychoactive mushroom edible exposures reported to the United States National Poison Data System® between 2023 and 2024. We included both single and polysubstance cases from all ages, using the generic codes identifying edible preparations containing Amanita muscaria, psilocybin, or unspecified. We described demographic and clinical characteristics (e.g., management site, related clinical effects) stratified by mushroom type. Our primary outcome was medical admission, and secondary outcomes were the severity of reported toxicity (moderate or worse compared to minimal or non-toxic exposures). Multivariable logistic regression, odds ratios, and 95% confidence intervals were used to measure the association between demographic and clinical factors with each outcome.ResultsOf the 362 total psychoactive mushroom edible exposures identified, the majority were single-substance (78%) and intentional (58%). Factors associated with admission were polysubstance exposures (aOR: 2.58; 95% CI: 1.23-5.40), confusion (aOR: 3.06; 95% CI: 1.36-6.86), and central nervous system depression (aOR: 2.55; 95% CI: 1.29-5.06). These factors were also associated with moderate or worse toxicity (poly-substance exposure [aOR: 2.88; 95% CI: 1.35-6.13], confusion [aOR: 3.05; 95% CI: 1.14-8.13], and central nervous system depression [aOR: 4.92; 95% CI: 2.45-9.88]). No deaths were reported from exposure.DiscussionThe effects of mushroom edible ingestion are unpredictable, and clinical presentations vary widely. Polysubstance exposures involving mushroom edibles are associated with higher hospital admission rates and more severe toxicity.ConclusionPsychoactive mushroom edibles are an emerging public health concern that necessitates continued epidemiological and clinical monitoring as the trend evolves.

keywords:
Humans, Agaricales, Mushroom Poisoning, Psychotropic Drugs, Retrospective Studies, Databases, Factual, Adolescent, Adult, Aged, Middle Aged, Child, Child, Preschool, Infant, Poison Control Centers, United States, Female, Male, Young Adult, Psilocybin

raw_json:
{"europe_pmc_id":"41493095","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Syed OA, Nestor SM, Husain MI, Sinyor M, Alam F, Giacobbe P.
publication_date: 2025-12-28
doi: 10.1016/j.psychres.2025.116929
pubmed_id: 41485400
source_url: https://doi.org/10.1016/j.psychres.2025.116929
substance_tags: psilocybin
topic_tags: Addiction,Adolescents,Safety,Adverse Events
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:
Adverse events associated with classic psychedelics and MDMA: a real-world population-based study using the WHO pharmacovigilance database (VigiBase).

abstract:
Psychedelic use has greatly increased within clinical and recreational settings over recent years. While demonstrating a favorable safety profile within certain clinical populations, little empirical research has explored safety of psychedelic use within real-world samples. Using the World Health Organization (WHO) VigiBase, a comprehensive global pharmacovigilance database with voluntary spontaneous reporting of adverse events (AEs) from real-world clinical and recreational populations, we examined reports for classic psychedelics and MDMA. Most reports were made for MDMA (n = 1573) and LSD (n = 394), while psilocybin (n = 56), DMT (n = 18), and mescaline (n = 15) had fewer reports. The most common AEs for all substances were psychiatric in nature, specifically surrounding substance or drug abuse and dependence. Reports of overdose constituted 1.1 to 1.7 % of total AEs. Pregnancy-related and congenital disorders were rare. Compared to the acetaminophen control, LSD and MDMA were associated with significantly greater odds for the reported AEs of alcohol abuse (LSD: ROR=45.7, 95 % CI: 27.2 - 76.9; MDMA: ROR=19.2, 95 % CI: 12.2 - 30.4), substance use disorder (LSD: ROR=71.1, 95 % CI: 36.3 - 139.2; MDMA: ROR=129.9, 95 % CI: 78.4 - 215.5) and substance dependence (LSD: ROR=215.1, 95 % CI: 69.0 - 670.3; MDMA: ROR=76.8, 95 % CI: 25.5 - 231.8). These reports were also greater than those associated with the external positive control, oxycodone. Taken together, this exploratory study provides the first analysis of AEs associated with psychedelics reported to a global pharmacovigilance database and can inform their real-world safety. Findings should be considered in light of limitations surrounding co-use of other substances and potential deterrence towards reporting use of illicit substances.

keywords:
Humans, Substance-Related Disorders, N-Methyl-3,4-methylenedioxyamphetamine, Lysergic Acid Diethylamide, Hallucinogens, Adverse Drug Reaction Reporting Systems, Databases, Factual, Adolescent, Adult, Aged, Middle Aged, World Health Organization, Female, Male, Young Adult, Pharmacovigilance, Psilocybin

raw_json:
{"europe_pmc_id":"41485400","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Kirlić N, Atli M, Mistry S, Gold M, Goodwin GM.
publication_date: 2025-12-08
doi: 10.1097/jcp.0000000000002119
pubmed_id: 41362124
source_url: https://doi.org/10.1097/jcp.0000000000002119
substance_tags: psilocybin
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 Relationship Between Participant Pretreatment Clinical Presentation and the Quality of Psilocybin Experience: A Retrospective Analysis.

abstract:
Purpose/backgroundThe therapeutic effects of psilocybin treatment are thought to be influenced by the subjective dose-dependent psychedelic experience, as well as the individual participant's mindset and the treatment environment. However, the relative contribution of an individual's pretreatment clinical characteristics and their subjective psychedelic experience remains unclear. We examined the relationship between pretreatment participant factors and the acute effects of COMP360 psilocybin.Methods/proceduresParticipants (N=233) with treatment-resistant depression received a single dose of 25, 10, or 1 mg of COMP360 psilocybin (a synthesized, pharmaceutical-grade, proprietary formulation of psilocybin, developed by the sponsor, Compass Pathfinder Ltd., a subsidiary of Compass Pathways plc: ClinicalTrials.gov, NCT03775200). The psychedelic experience was assessed by the Five-Dimensional Altered States of Consciousness questionnaire (5D-ASC) and Emotional Breakthrough Inventory (EBI). We used hierarchical regression to measure the relative contribution of pretreatment clinical characteristics (along the cognitive-affective, somatic, and functional impairment domains) in addition to the drug dose to the subjective psychedelic experience.Findings/resultsDose was the strongest and most consistent predictor of the psychedelic experience. Some pretreatment characteristics contributed weakly to subjective experiences. Positive affect, lower generalized anxiety symptoms, higher executive functioning, and greater personality disorder symptoms had significant effects on different aspects of the subjective psychedelic experience.Implications/conclusionsThese findings challenge the assumption that pretreatment characteristics are major determinants of the acute psychedelic experience. While some traits may modestly modulate aspects of the experience, dose remains the largest driver.

keywords:
Humans, Hallucinogens, Retrospective Studies, Dose-Response Relationship, Drug, Adult, Middle Aged, Female, Male, Young Adult, Depressive Disorder, Treatment-Resistant, Psilocybin

topic_tags:
Depression,Anxiety,Mechanism of Action,Consciousness,Personality Change,Emotional Processing,Treatment-Resistant Depression

raw_json:
{"europe_pmc_id":"41362124","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Guo C, Luu NNT, Adwer MM, Hosseinzadeh H, Balan V, Yan Y, Lin Y.
publication_date: 2025-11-04
doi: 10.1016/j.ymben.2025.11.002
pubmed_id: 41202968
source_url: https://doi.org/10.1016/j.ymben.2025.11.002
substance_tags: psilocybin,psilocin
topic_tags: Depression,PTSD,Mechanism of Action,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:
Engineering artificial biosynthetic pathways for efficient microbial production of psilocybin and psilocin.

abstract:
Psychedelic-assisted therapy is emerging as a highly promising approach for treating depression, with psilocybin, a psychoactive compound in magic mushrooms, gaining the most recognition for its efficacy in treating post-traumatic stress disorder and treatment-resistant depression. However, its low natural abundance makes extraction costly, necessitating alternative production methods. While engineered microbial production has been explored, dependence on the CYP450 hydroxylase (PsiH) in the natural biosynthetic pathway remains a major bottleneck, limiting production efficiency. Here, we report the design, validation, and optimization of artificial biosynthetic pathways in Escherichia coli that bypass PsiH, enabling efficient psilocybin and psilocin production. De novo biosynthesis of psilocybin achieved record titers of 557.91 mg/L in shake flasks and 2.00 g/L in a bioreactor, outperforming previous microbial engineering efforts. This work demonstrates the great commercial potential of microbial psilocybin production via combinatorial metabolic engineering and synthetic biology approaches.

keywords:
Escherichia coli, Cytochrome P-450 Enzyme System, Biosynthetic Pathways, Metabolic Engineering, Psilocybin

raw_json:
{"europe_pmc_id":"41202968","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Meaning and Psychedelics in Palliative Care: A Narrative Review.
journal: Journal of pain and symptom management
publication_date: 2026-02-28
doi: 10.1016/j.jpainsymman.2025.10.015
pubmed_id: 41173063
source_url: https://pubmed.ncbi.nlm.nih.gov/41173063/
keywords: Demoralization, LSD, existential distress, meaning, palliative, psilocybin, psychedelic
substance_tags: psilocybin
topic_tags: End-of-Life Distress,Clinical Trial,Review Article,Safety
study_type: Clinical Trial
source_name: PubMed
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:20:35
raw_json: {"pubmed_id":"41173063"}
authors:
Alexander WB, Hansen ED, Anderson BT, Zarrabi AJ, Rogers AH, Loewen G, Ficarro ZR, Alexander MH, Schaefer D, Case AA

abstract:
Meaning is a primary existential concern in those with advanced illnesses and functions as an important coping mechanism. Loss of meaning contributes to existential distress, and, in particular, may manifest as demoralization, a syndrome of poor coping that is associated with negative outcomes. Psychedelics are unique psychoactive compounds that, among other properties, are proposed to enhance meaning. In the palliative setting, psychedelic therapies are under investigation for existential distress, including demoralization.
To synthesize the literature on meaning in palliative care, including the clinical impact of loss of meaning, particularly demoralization, and evidence for proposed interventions including existential psychological interventions and psychedelic therapies.
We conducted a narrative review based on a structured search within Pubmed. Articles were screened for those addressing prespecified questions derived from our objectives, and results were synthesized in narrative format.
Loss of meaning is a hallmark feature of demoralization syndrome, a prevalent and distinct condition linked with diminished quality of life, increased symptom burden, and increased suicide risk. Existential psychological interventions improve numerous psychosocial outcomes, although evidence for their efficacy in demoralization is limited. In psychedelic therapy, meaning-making is a typical feature, and existential interventions are commonly integrated. Finally, early clinical trial data indicate that psychedelic therapies show promise for existential distress, including demoralization.
Novel approaches are needed to address existential distress, especially when manifested as demoralization. Psychedelic therapy is a promising combined pharmacologic and psychological intervention that promotes meaning-making and shows potential for improving demoralization, warranting further investigation.


authors: Zhang J, Lin C, Lv X, Zhao H, Wang X.
publication_date: 2026-02-27
doi: 10.1016/j.biopsych.2026.02.011
pubmed_id: 41765343
source_url: https://doi.org/10.1016/j.biopsych.2026.02.011
substance_tags: psilocybin
topic_tags: Depression,PTSD,Addiction,Neuroplasticity,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 11:22:03
title:
Psychedelics and the Extracellular Matrix: Rewiring Neuroplasticity and Metaplasticity for Next-Generation Psychiatric Therapies.

abstract:
Classic psychedelics, such as psilocybin, lysergic acid diethylamide (LSD), and N,N-dimethyltryptamine (DMT), have emerged as potent modulators of neuroplasticity and metaplasticity in the adult brain, offering novel therapeutic strategies for neuropsychiatric disorders. Recent findings reveal that beyond their transient psychotropic effects, these compounds activate serotonin 5-HT2A receptors and downstream signaling cascades-including CaMKII (calcium/calmodulin-dependent protein kinase II), ERK (extracellular signal-regulated kinase), mTOR (mechanistic target of rapamycin), and BDNF (brain-derived neurotrophic factor) pathways-thereby inducing synaptogenesis, dendritic spine remodeling, and transcription of the immediate early genes. Critically, the brain's extracellular matrix (ECM), particularly perineuronal nets (PNNs), has been identified as a central regulator of synaptic stability and a key target of psychedelic action. Psychedelics transiently disrupt ECM integrity by loosening PNNs and reorganizing pericellular scaffolds, a process that reopens developmentally restricted critical periods of plasticity and restores circuit-level flexibility. These ECM-mediated metaplastic effects appear essential to the sustained therapeutic outcomes observed in the clinical studies of psychedelic-assisted therapy for depression, posttraumatic stress disorder, addiction, and potentially neurodegenerative diseases. This article synthesizes current cellular, molecular, and translational evidence highlighting the ECM as a dynamic and permissive substrate through which classic psychedelics exert long-lasting structural and functional brain changes, underscoring its potential as a target for precision interventions in neuropsychiatric care.

raw_json:
{"europe_pmc_id":"41765343","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psychedelic therapy and cultural humility.
authors: Gearin A, Docherty J, Sun X, Cheung EH, Tanuseputro P.
publication_date: 2026-02-26
doi: 10.1038/s41398-026-03913-x
pubmed_id: 41748534
source_url: https://doi.org/10.1038/s41398-026-03913-x
substance_tags: psilocybin
topic_tags: Depression,Anxiety,End-of-Life Distress,Pharmacology,Spirituality,Clinical Trial,Healthcare Workers
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
abstract:
ImportanceAs psychedelic-assisted therapies gain clinical legitimacy, their cultural portability remains underexamined. While promising results have emerged from trials on existential distress in life-limiting illness, most protocols reflect Euro-American values. The expansion of these therapies calls for a pivot toward cultural humility and renewed attention to what constitutes a "good death" in cultural worlds. This commentary explores these questions through the case of Chinese palliative care.ObservationsClinical trials of psilocybin and LSD assisted therapy demonstrate significant reductions in depression, anxiety, and demoralization among patients with life-limiting illness. However, psychosocial and cultural factors-including family-centered decision-making, spiritual beliefs, and stigma-will likely impact treatments in complex ways. The evolving healthcare framework of cultural humility emphasizes ongoing self-reflection, relational sensitivity towards power sharing, and openness to diverse worldviews and lived experiences of patients. This posture is particularly important in psychedelic therapy where patient experiences are sensitive to settings, relational processes, and meaning-making.Relevance and conclusionRegulatory openings in Australia and several European and U.S. jurisdictions are accelerating clinical interest in psychedelic therapy, yet the cultural life of these therapies present important challenges. The Chinese example illustrates how stigma, trust, and relational dimensions will likely crystallize differently, reminding researchers and clinicians that efficacy is not solely a biochemical or therapeutic question but also a cultural one. Addressing the translational gap of cultural diversity in psychedelic therapy can benefit from a stance of humility towards how situated beliefs, social norms, and clinical practices interact with psychedelic pharmacology.

keywords:
Humans, Lysergic Acid Diethylamide, Hallucinogens, Palliative Care, Culture, China, Australia, Psilocybin

raw_json:
{"europe_pmc_id":"41748534","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2026-02-26
doi: 10.1136/spcare-2025-005773
pubmed_id: 41184102
source_url: https://doi.org/10.1136/spcare-2025-005773
substance_tags: psilocybin
topic_tags: End-of-Life Distress,Emotional Processing,Safety,Adverse Events
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-assisted therapy for demoralisation in hospice patients: feasibility, safety and preliminary efficacy.

authors:
Beaussant Y, Sager Z, Brennan C, Kristan I, Ljuslin M, Mazzola E, Macdonald D, Murphy ME, Nigam K, Rinaldi AD, Sanders J, Schaefer KG, Sholevar R, Summer L, Waliji-Banglawala A, Yudilevich-Espinoza S, Tulsky JA.

abstract:
ObjectivesTo assess the feasibility, safety and preliminary efficacy of psilocybin-assisted therapy (PAT) for demoralisation in terminally ill patients receiving home hospice care.MethodsIn this open-label pilot trial, 4607 home hospice patients at a large community hospice were screened over 22 months; 66 were approached, 15 enrolled and 10 received psilocybin. Participants completed two home-based preparation sessions, a single 25 mg oral psilocybin session at an inpatient hospice facility, and two home-based integration sessions. Feasibility was assessed through recruitment, retention and acceptability. Safety was evaluated via adverse event monitoring, and preliminary efficacy was assessed using changes in demoralisation scores and other psychosocial measures.ResultsThe intervention was well tolerated, with no serious adverse events attributed to psilocybin. At week 3, demoralisation scores significantly decreased (mean reduction: 8.8 points, p=0.0196), despite ongoing clinical decline. Grief- and peace-related themes were prominent during psilocybin sessions. While six participants rated the treatment favourably on the Reaction to Research Participation Questionnaire global evaluation factor, three rated neutral on one or more items, suggesting that the emotional intensity and demands of the intervention may influence acceptability.ConclusionThis study provides initial evidence that PAT can be feasibly and safely integrated into hospice care for terminally ill patients. Further research is needed to optimise delivery and further assess therapeutic potential.

keywords:
Humans, Hallucinogens, Treatment Outcome, Hospice Care, Feasibility Studies, Pilot Projects, Adult, Aged, Aged, 80 and over, Middle Aged, Terminally Ill, Female, Male, Psilocybin

raw_json:
{"europe_pmc_id":"41184102","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Li T, Reynolds EE, Wang Z, Torrens-Spence MP, Weng JK, Wang Y.
publication_date: 2026-02-25
doi: 10.1038/s42003-026-09756-y
pubmed_id: 41748824
source_url: https://doi.org/10.1038/s42003-026-09756-y
substance_tags: psilocybin
topic_tags: End-of-Life Distress,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 11:22:03
title:
Calcium activation mechanism of a noncanonical aromatic L-amino acid decarboxylase from psilocybin mushroom Psilocybe cubensis.

abstract:
PcncAAAD is a noncanonical fungal aromatic L-amino acid decarboxylase (AAAD) featuring a unique appendage C-terminal domain (CTD) and two metal-binding sites. Unlike its mammalian and plant counterparts, PcncAAAD is activated by calcium, although the exact activation mechanism remains unclear. Here, we establish an in silico RMSD-based evaluation model through molecular dynamics simulations, validated by in vitro enzyme assays, to decipher the enzyme's calcium activation mechanism. The metal-binding site at the intra-monomer interface between the N-terminal domain and the CTD (site A) is found to play a primary role in the calcium activation of PcncAAAD, whereas the secondary site within the unique CTD (site B) contributes to the calcium-mediated stabilization of enzyme structure. Binding of calcium, but not sodium, exerts a profound influence on PcncAAAD activity by stabilizing a "lid-rim" structure underlying site A, which in turn maintains the integrity of the substrate-binding environment. In silico mutations disrupting site A or the lid-rim structure show severe structural distortion of the active site, leading to reduced or even eliminated activity as demonstrated by in vitro assays. These findings deepen our understanding of metal-activatable enzymes and hold promise for the rational design of engineered enzymes for the synthesis of aromatic amino acid derivatives.

keywords:
Agaricales, Calcium, Aromatic-L-Amino-Acid Decarboxylases, Binding Sites, Enzyme Activation, Molecular Dynamics Simulation

raw_json:
{"europe_pmc_id":"41748824","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Pilot study of psilocybin in patients with post-treatment lyme disease.
publication_date: 2026-02-24
doi: 10.1038/s41598-026-38091-9
pubmed_id: 41741501
source_url: https://doi.org/10.1038/s41598-026-38091-9
substance_tags: psilocybin
topic_tags: Chronic Pain,Headache / Migraine,Receptor Pharmacology,Clinical Trial,Adverse Events,Inflammation
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:
Garcia-Romeu A, Naudé GP, Rebman AW, So S, Yaffe A, Geithner I, Kozero EA, Yang T, Soloski MJ, Aucott JN.

abstract:
Lyme disease, caused by the bacterium Borrelia burgdorferi, is the most common vector-borne disease in the United States and Europe. Although antibiotics effectively treat most cases, an estimated 10-20% of patients develop post-treatment Lyme disease (PTLD), a chronic syndrome marked by fatigue, pain, cognitive difficulties, mood disturbance, and reduced quality of life. There are no established treatments for PTLD. The serotonin 2A receptor agonist psychedelic psilocybin has recently shown potential antidepressant and anxiolytic effects in clinical trials as well as preliminary evidence for anti-inflammatory effects in animals. This open-label, single-arm pilot study evaluated the effects of psilocybin in 20 participants with well-characterized PTLD. The 8-week intervention included two psilocybin sessions (15 mg in week 4; 15 or 25 mg in week 6) with psychological support. Participants (11 women, 9 men, mean age 44, median illness duration 5.7 years) showed significant improvements in PTLD symptom burden and quality of life from study enrollment through 1-month following the second dose of psilocybin (primary endpoint), with significant benefits sustained through 6 months. At the 6-month follow-up, general PTLD symptom burden (GSQ-30) was decreased 40% from baseline (p <.001; Cohen's dz = - 1.22, 95% CI [- 2.12, - 0.78]), and health-related quality of life improved across both SF-36 domains, with Mental (MCS) and Physical (PCS) component scores increasing 13% (p ≤.013; Cohen's dz = 0.46-0.59). Secondary outcomes assessing mood, fatigue, sleep quality, and pain also showed significant and sustained improvement through 6 months (all p ≤.003; Cohen's dz = 0.56-1.25). No serious adverse events (AEs) related to the study intervention occurred. The most common AEs attributed to psilocybin were transient hypertension (90%), headache (65%), tachycardia (35%), pain (20%), and fatigue (15%). Preliminary findings support that psilocybin-assisted treatment was feasible and well-tolerated among the sample. Clinical outcomes indicated potentially long-lasting benefits of psilocybin-assisted treatment, warranting further investigation for PTLD. Trial registration: ClinicalTrials.gov Identifier NCT05305105, registered 22/03/2022.

raw_json:
{"europe_pmc_id":"41741501","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psychedelic medicine: mechanisms, evidence, and translation to practice.
authors: Jacobs E, Zahid Z, Hinkle J, Nayak S, Yaden DB.
publication_date: 2026-02-22
doi: 10.1136/bmj-2024-081723
pubmed_id: 41730563
source_url: https://doi.org/10.1136/bmj-2024-081723
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
abstract:
Over the past 15 years, psychedelic treatments have garnered substantial clinical interest, with psilocybin and 3,4-methylenedioxymethamphetamine (MDMA) advancing to phase 3 trials for various psychiatric conditions. This state-of-the-art review examines the evidence for these treatments and their proposed mechanisms of action, and identifies key challenges in clinical translation. Psychedelic treatments combine limited drug administration with psychotherapy or psychological support, potentially working through various biological and psychological pathways, including effects on neural circuitry, emotional processing, and psychological flexibility, though the precise mechanisms are not completely understood. The strongest evidence supports psilocybin for treatment resistant depression and MDMA for post-traumatic stress disorder, with emerging data in substance use disorders and psychological distress in life threatening illness. Although psychedelics are well tolerated under controlled conditions, methodological limitations complicate interpretation of the evidence, including functional unblinding, variable psychotherapeutic protocols, and homogeneous trial populations. Current treatment models require extensive therapeutic support in specialized settings, posing challenges with scalability. While innovative approaches like group administration may improve accessibility, their comparative effectiveness remains to be established. Future priorities for the research field include standardizing adverse event assessment, developing evidence based implementation guidelines, and showing durable benefit in diverse patient populations. Whether psychedelic treatments can fulfil their therapeutic promise while meeting regulatory requirements and healthcare system constraints remains a defining question for the field.

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

topic_tags:
Depression,PTSD,Addiction,Mechanism of Action,Emotional Processing,Psychological Flexibility,Review Article,Adverse Events

raw_json:
{"europe_pmc_id":"41730563","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Rebuttal to "Questioning the recovery of dissociated traumatic memories under psilocybin".
authors: Knatz Peck S, Brewerton TD.
publication_date: 2026-02-16
doi: 10.1186/s40337-026-01532-x
pubmed_id: 41703646
source_url: https://doi.org/10.1186/s40337-026-01532-x
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 11:22:00
abstract:
In our original case report we provide detailed accounts of two research participants who reported the emergence of spontaneously recovered, previously forgotten traumatic memories of sexual assaults during psilocybin treatment. In their commentary of this article, Kangaslampi et al. argue that we preemptively label the experiences as dissociated traumatic memories in the absence of corroborating evidence and consideration of alternative explanations. Here we further address potential therapeutic effects associated with the classification of experiences and provide a rebuttal to the authors' criticisms on our chosen nomenclature.

raw_json:
{"europe_pmc_id":"41703646","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Khan Z, Weaver S, Dando RV, Schlag AK, Neill JC, Wainwright V.
publication_date: 2026-02-16
doi: 10.1177/10497323261419338
pubmed_id: 41700878
source_url: https://doi.org/10.1177/10497323261419338
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Aging,Clinical Trial,Cancer Patients
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:
Sense-Making Around Psilocybin in UK Women Experiencing Cancer-Related Existential Distress: An Interpretative Phenomenological Analysis.

abstract:
People with cancer often experience anxiety and depression following a diagnosis and can face barriers to accessing treatment for their mental health. An increasing number of patients are considering alternative approaches to managing their mental health symptoms, such as the psychedelic, psilocybin. A growing number of clinical trials show significant and enduring improvements in mood and quality of life following psilocybin-assisted therapy (PAT) in this patient group. While the lived experiences of patients undergoing PAT in clinical trials and medical contexts have been explored, the broad decision-making processes, perceptions of societal and self-acceptance of psilocybin, and the impact or otherwise of the legality of psilocybin outside of these settings have not. In this study, qualitative, semi-structured interviews were conducted to explore the attitudes and perceptions of using psilocybin by seven females in the United Kingdom with a current or previous diagnosis of cancer (four who had used psilocybin and three who had considered taking the drug). Data were analysed using Interpretative Phenomenological Analysis (IPA). Three group experiential themes were created: (i) somatic healing needs; (ii) outlawing nature: illegality as both a burden and boundary; and (iii) reconnecting self, nature, and mortality. Participants considered psilocybin a much-needed alternative to traditional treatments for the depression and anxiety they experienced in relation to their cancer diagnosis but felt its legal status was a significant barrier to access. As such, a compassionate access scheme here in the United Kingdom could transform the mental health of people with cancer.

raw_json:
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authors: Kase M, Kaup KK, Aru J.
publication_date: 2026-02-15
doi: 10.1177/02698811251412012
pubmed_id: 41699449
source_url: https://doi.org/10.1177/02698811251412012
substance_tags: psilocybin
topic_tags: Emotional Processing,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:
Effects of LSD, DMT and psilocybin on cognitive and psychological functions: A systematic review of the literature.

abstract:
We carried out a systematic review of modern-era (1990-2025) placebo-controlled studies assessing the acute and post-acute effects of lysergic acid diethylamide, dimethyltryptamine and psilocybin on cognitive and psychological functions. From February 28 to March 19, 2025, PubMed and APA PsychINFO were systematically searched for placebo-controlled studies examining the influence of psychedelics on empathy, reaction time, attention, inhibition, emotional processing, memory, cognitive flexibility, and related cognitive functions using experimental methods. Additional searches were done in Google Scholar. The systematic review included 32 studies. Psychedelics tended to enhance emotional empathy but had no effect on cognitive empathy. Psychedelics impaired, enhanced or had no effect on memory depending on the task and timing of the assessment. Dose-dependent impairments were seen in many of the reaction time, attention, and inhibition tasks, although some studies found no effects. Some studies found impaired recognition of negative stimuli under the acute effects of psychedelics. The findings regarding cognitive flexibility were mixed. Many studies had small samples, and it is hard to find a reliable placebo due to psychedelics' unique subjective effects. Future studies should use bigger samples and also study more longitudinal effects of psychedelics on cognitive and psychological functions.

raw_json:
{"europe_pmc_id":"41699449","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Management of obsessive-compulsive disorder in adults.
authors: Abramowitz JS, Abramovitch A, McKay D, Draffin A.
publication_date: 2026-02-15
doi: 10.1136/bmj-2024-083443
pubmed_id: 41698714
source_url: https://doi.org/10.1136/bmj-2024-083443
keywords: Humans, Obsessive-Compulsive Disorder, Implosive Therapy, Adult, Cognitive Behavioral Therapy
substance_tags: psilocybin
topic_tags: OCD,Review Article
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:
Obsessive-compulsive disorder (OCD) is a chronic, often debilitating psychiatric condition characterized by intrusive thoughts and behavioral or mental rituals. Although exposure and response prevention (ERP) remains the first line treatment, many individuals do not experience full remission, highlighting the need for innovation. This review provides a comprehensive and up-to-date synthesis of evidence based treatments for OCD in adults, as well as emerging psychological and biological approaches. It first describes established psychological and pharmacological therapies, highlighting recent findings and factors affecting treatment outcomes. It then examines innovations in psychological care including inhibitory learning informed ERP, acceptance and commitment therapy, inference based therapy, and telehealth delivery methods, as well as emerging biological treatments such as psilocybin, ketamine, and neuromodulation techniques. Cultural and identity related considerations are also discussed, emphasizing the importance of tailoring interventions for diverse populations.

raw_json:
{"europe_pmc_id":"41698714","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2026-02-15
doi: 10.1192/bjo.2025.10968
pubmed_id: 41693474
source_url: https://doi.org/10.1192/bjo.2025.10968
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:
Microdosing psilocybin for major depressive disorder: study protocol for a phase II double-blind placebo-controlled randomised partial crossover trial.

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

abstract:
BackgroundMajor depressive disorder (MDD) is the leading cause of disability worldwide, affecting roughly 322 million people. Recently, doses of psilocybin have shown promise in treating mood disorders, sparking interest in other dosing practices. According to anecdotal reports and observational studies, microdosing psilocybin yields benefits to mental health; however, rigorously controlled trials have failed to produce compelling evidence for this.AimsTo conduct a phase II, double-blind, placebo-controlled, randomised partial crossover trial to compare microdosing psilocybin to placebo for MDD, evaluating its safety, tolerability and preliminary antidepressant effects.MethodForty adults with MDD will be randomised to four doses of psilocybin (2 mg) or placebo (maltodextrin) once weekly over 4 weeks, then four doses of psilocybin (2 mg) once weekly for an additional 4 weeks. The primary efficacy end-point will be change in depression symptoms, as measured at baseline (0 weeks), after the experimental phase (4 weeks), and after the open-label phase (8 weeks). A battery of mood, well-being, attention, creativity, mindfulness and pro-sociality measures will be administered at each time point. Follow-ups will occur every 6 months for up to 2 years after the trial start date, as part of a long-term extension study.ResultsThe results of the primary outcome of this trial will be published as a manuscript in a peer-reviewed science or medical journal regardless of the magnitude or direction of effect.ConclusionsFindings will inform future research on microdosing psilocybin for MDD, regarding dose regimens, effect sizes and expectancy bias. Findings will also facilitate discussions on the comparable benefits of sub- versus threshold doses of psilocybin and the therapeutic value of radically altered perception.Trial registrationClinicalTrials.gov identifier: NCT05259943.

topic_tags:
Depression,Microdosing,Wellbeing,Creativity,Clinical Trial,Review Article,Observational Study,Safety

raw_json:
{"europe_pmc_id":"41693474","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: McNaughton N, Shadli SM, Beaglehole B, Glue P.
publication_date: 2026-02-14
doi: 10.1002/snz2.70002
pubmed_id: 41798779
source_url: https://doi.org/10.1002/snz2.70002
substance_tags: psilocybin
topic_tags: Depression,Anxiety,PTSD,OCD,Brain Imaging,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:
Hope for Neurotic Disorders: A Summary of New Zealand Research on the Development of Biomarkers and Novel Treatments.

abstract:
The neurotic disorders (e.g., depression, dysthymia, generalized anxiety disorder, panic disorder, agoraphobia, social anxiety, post-traumatic stress disorder, and obsessive-compulsive disorder) are costly and difficult to treat. Diagnosis is based on symptoms not biological causes. Here, we summarize New Zealand-based work developing EEG biomarkers and novel treatments. Working at the University of Otago, we have developed an anxiety disorder biomarker and shown its potential to detect anxiety resistant to conventional treatments. Others have started similar work on depression biomarkers. We have also found that ketamine is a novel treatment for treatment-resistant neurotic disorders in general and have provided a "double hit" hypothesis of the mechanisms involved. Muthukumaraswamy and coworkers at the University of Auckland and elsewhere have obtained similar results with ketamine, LSD, and psilocybin, and we, along with them, have demonstrated treatment-related effects on EEG. These linked developments, potentially supplemented with psychotherapy, should open the way to quicker acting, broad ranging, effective treatment of neurotic disorders. With the our recent more purely practical development of oral tablet delivery, which will allow home dosing, the future for the treatment of neurotic disorders looks bright.

raw_json:
{"europe_pmc_id":"41798779","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2025-11-01
doi: 10.1016/j.neuropharm.2025.110732
pubmed_id: 41187880
source_url: https://doi.org/10.1016/j.neuropharm.2025.110732
substance_tags: psilocybin
topic_tags: Microdosing,Creativity
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:
Microdosing psilocybin and its effect on creativity: Lessons learned from three double-blind placebo controlled longitudinal trials.

authors:
Prochazkova L, Marschall J, van Elk M, Rifkin BD, Schon NR, Fiacchino D, Fejer G, Kuchar M, Hommel B.

abstract:
BackgroundTaking very small doses of psychedelics (LSD, truffles) over an extended period became prevalent in Western societies for its alleged cognitive benefit, including enhanced creativity. However, in the absence of robust, double-blind-controlled quantitative studies, such claims remain anecdotal.MethodsHere we present results from 3 double-blind placebo-controlled longitudinal trials (one of which pre-registered) assessing the effects of microdosing psilocybin on convergent and divergent creativity in a well-controlled semi-naturalistic setting. To enhance statistical power and generalizability, data from all trials (N = 171) were pooled in a mega-analysis, resulting in one of the most robust laboratory-based studies on microdosing to date.ResultsWe found that active microdosing increased the ratio of original responses (originality/fluency), indicating higher quality of divergent thinking in the active microdosing condition. The unadjusted originality score was significantly more pronounced in the active microdosing condition, but only when relative dosage (dose/weight of participants) was considered. Importantly, these effects survived controlling for dose guess and demographic biases. No effects of active microdosing were found for other divergent-thinking scores or convergent thinking.ConclusionThe results suggest that the effects of truffle mirodosing are limited to the quality of divergent thinking. Moreover, our findings highlight the importance of controlling for placebo effects and prior psychedelic experience in assessing the impact of microdosing.

keywords:
Humans, Hallucinogens, Longitudinal Studies, Cross-Over Studies, Double-Blind Method, Thinking, Placebo Effect, Dose-Response Relationship, Drug, Adult, Female, Male, Young Adult, Creativity, Psilocybin

raw_json:
{"europe_pmc_id":"41187880","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Dolenec P, Pelčić G, Pilipović K, Mršić-Pelčić J, Hrkać AH.
publication_date: 2026-02-13
doi: 10.3390/ph19020316
pubmed_id: 41754856
source_url: https://doi.org/10.3390/ph19020316
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 11:22:03
title:
Ischemia-Induced Neurodegeneration in Glaucoma: Mechanistic Insights and Translational Opportunities for Psychoplastogen-Based Therapies.

abstract:
Glaucoma is increasingly recognized as an ischemic neurodegenerative disorder that extends beyond elevated intraocular pressure (IOP) to involve complex vascular, metabolic, and inflammatory mechanisms. Retinal ganglion cells are particularly vulnerable to ischemia-reperfusion injury, oxidative stress, and chronic neuroinflammation, leading to progressive disconnection from central visual pathways. Current therapies primarily target IOP reduction but fail to address ischemia-driven neurodegeneration or to restore lost neuronal connectivity. Ischemia triggers excitotoxicity, oxidative stress, and a maladaptive inflammatory response involving activated microglia and astrocytes, perpetuating neuronal injury and suppressing intrinsic regenerative capacity. Thus, restoring neural plasticity and mitigating neuroinflammation represent key unmet therapeutic needs. Psychoplastogens are a class of compounds capable of rapidly enhancing structural and functional neuroplasticity and have recently emerged as promising multitarget agents. Compounds such as ketamine, psilocybin, N,N-dimethyltryptamine (DMT), and some newly synthesized non-hallucinogenic analogs act through convergent signaling pathways involving BDNF-TrkB-mTOR, promoting dendritic growth, synaptogenesis, and glial modulation. Beyond their neurotrophic effects, psychoplastogens seem to exert potent immunomodulatory actions. In this review we will explore the interplay between ischemia, neurodegeneration, neuroinflammation, and impaired plasticity in glaucoma, integrating mechanistic insights from cerebral ischemia. We discuss emerging preclinical evidence supporting psychoplastogens as neurorestorative and anti-inflammatory agents, propose their potential application in ocular ischemic neurodegeneration, and outline translational challenges for future studies.

topic_tags:
Neuroplasticity,Mechanism of Action,Oxidative Stress,Review Article,Animal Study,Toxicity,Inflammation

raw_json:
{"europe_pmc_id":"41754856","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2026-02-13
doi: 10.1038/s41598-026-39483-7
pubmed_id: 41691031
source_url: https://doi.org/10.1038/s41598-026-39483-7
substance_tags: psilocybin
topic_tags: Pharmacology,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
title:
Network pharmacology and molecular simulation reveal the entourage effect mechanisms of psilocybin-producing mushrooms on the brain.

authors:
Murray Z, Lewies A, Wentzel JF, Schutte-Smith M, Erasmus E, Noreljaleel A, Visser H, Wilhelm A, Issahaku AR.

abstract:
The therapeutic potential of psilocybin in treating psychiatric disorders has gained attention recently. While most research has focused on isolated psilocybin, evidence suggests that whole mushroom extracts exhibit greater efficacy, implicating a possible entourage effect of additional bioactive compounds. This study aimed to elucidate the holistic neuropharmacological effects of psilocybin-producing mushroom compounds through a computational framework incorporating network pharmacology, molecular docking, and molecular dynamics. Fifteen mushroom-derived compounds were identified from literature, of which eight exhibited favorable pharmacokinetic profiles. Target prediction and network analysis identified 44 brain-localized proteins with partial biological connectivity. Functional enrichment and pathway analyses implicate key neurological pathways. The compounds exhibited strong docking scores to neurologically relevant targets. Several compounds formed stable salt bridges with the Asp155 residue of HTR2A, mirroring serotonin’s binding behavior. Molecular dynamics simulations further confirmed high residence stability of the compounds within the binding pockets of HTR2A and MAOA. These findings support a mechanistic rationale for the enhanced efficacy of whole mushroom extracts over isolated psilocybin and underscore the therapeutic potential of other constituent compounds. The study highlights the importance of multi-target interactions in mediating neuropsychiatric effects and provides a foundation for further investigations into the synergistic roles of these compounds in CNS modulation.

raw_json:
{"europe_pmc_id":"41691031","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Electrophysiological effects of psilocybin co-administered with midazolam.
publication_date: 2026-02-13
doi: 10.1038/s41398-026-03894-x
pubmed_id: 41688423
source_url: https://doi.org/10.1038/s41398-026-03894-x
substance_tags: psilocybin
topic_tags: Neuroplasticity,Brain Imaging,Consciousness
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:
Sutherland MH, Nicholas CR, Lennertz RC, Wenthur CJ, Krause BM, Sauder CJ, Riedner BA, Smith RF, Hutson PR, Raison CL, Banks MI.

abstract:
The serotonergic psychedelic psilocybin induces neural plasticity and profoundly alters consciousness. The benzodiazepine midazolam blunts neural plasticity and induces conscious sedation and amnesia at low doses. In our recent open label pilot study, we administered oral psilocybin (25 mg) along with intravenous midazolam at doses allowing a full psychedelic experience while blunting memory for the experience. We previously reported preliminary results from high density scalp electroencephalography (EEG) recorded during the dosing session. Here, we examined changes in EEG band power, normalized Lempel Ziv complexity (LZCn), and spectral exponent. We used linear mixed effects models that incorporated time and the subjective effects of midazolam and psilocybin, measured with the Observer's Assessment of Arousal and Sedation (OAA/S) and selected items from the Altered States of Consciousness (ASC) questionnaire, respectively. At 15-30 min, when midazolam but not psilocybin was at its targeted effect site concentration, we observed increased beta power and decreased spectral exponent. As the subjective effects of psilocybin commenced and over the next six hours, we observed increased LZCn and spectral exponent and decreased broadband power, with the most prominent power reductions in the delta, theta, and alpha frequency bands. OAA/S improved model fits for alpha power while ASC improved model fits for LZCn and spectral exponent. While recognizing limitations inherent to the small sample size and variability in dosages of midazolam, these data are further evidence that the effects of psilocybin are maintained in the presence of midazolam, supporting its utility in mechanistic studies of psilocybin's therapeutic activity.

keywords:
Humans, Midazolam, Hypnotics and Sedatives, Hallucinogens, Electroencephalography, Pilot Projects, Consciousness, Adult, Female, Male, Psilocybin

raw_json:
{"europe_pmc_id":"41688423","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


journal: Research Square
publication_date: 2026-02-11
doi: 10.21203/rs.3.rs-8733841/v1
source_url: https://doi.org/10.21203/rs.3.rs-8733841/v1
substance_tags: psilocybin
study_type: Clinical Trial
source_name: Europe PMC
publication_status: preprint
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:22:03
title:
Time-Dependent Effects of Rapid-Acting Antidepressants in iPSC-Derived Neurons from Treatment-Resistant Depression and Healthy Volunteers

authors:
Johnston J, Jones G, Peng S, Yuan P, Yavi M, Kadriu B, Henter I, Quintanilla B, Elkahloun AG, Moaddel R, Schulmann A, Akula N, Kvarta M, McMahon F, Zarate C.

abstract:
Abstract Rapid-acting antidepressants like ketamine and serotonergic psychedelics show promise for treatment-resistant depression (TRD), but the molecular mechanisms that contribute to their therapeutic effects remain unclear. Induced pluripotent stem cells (iPSCs) offer a platform to model human cortical neurons and investigate drug effects in a human-relevant system. Here, iPSCs from individuals with TRD and healthy volunteers (HVs) were differentiated into mature cortical-like neurons and treated for six and 24 hours with agents being investigated as rapid-acting antidepressants, including (2 R,6 R )-hydroxynorketamine (HNK), psilocybin, lysergic acid diethylamide (LSD), and 2,5-Dimethoxy-4-iodoamphetamine (DOI). Bulk and single-cell RNA sequencing assessed global and cell-type-specific transcriptomic responses. Synaptic proteins were evaluated via Western blotting and immunocytochemistry. To validate translational relevance, transcriptomic results were compared to CSF proteomics from ketamine-treated HVs. Despite differing initial pharmacological targets, overall gene expression across all compounds was highly correlated at matched timepoints compared to vehicle control, suggesting shared downstream effects. Both glutamatergic and serotonergic drugs converged on pathways involving inflammation, mTORC1 signaling, and cellular growth. At the single-cell level, HNK showed distinct cell-type specific alterations: upregulation in excitatory neurons and concomitant downregulation of inhibitory neuron populations. Differentially expressed genes from HNK-treated neurons also overlapped with CSF proteomic signatures from ketamine-treated individuals, supporting the model’s translational relevance. This study is the first to assess multiple putative rapid-acting antidepressants in parallel using an iPSC-derived neuron model. Both convergent and drug-specific changes in gene expression and pathway enrichment were observed across diverse compounds, supporting the use of human iPSC-derived neurons in antidepressant drug discovery. Clinical Trial Registry: www.clinical trials.gov, NCT02484456

topic_tags:
Depression,Neuroplasticity,Mechanism of Action,Clinical Trial,Healthy Volunteers,Treatment-Resistant Depression,Transcriptomics,Proteomics,Inflammation

raw_json:
{"europe_pmc_id":"PPR1154314","source":"PPR","pub_type":null,"publisher":"Research Square","importer":"Europe PMC"}


title: Chemical Design and Pharmacokinetics Enable Precision Psychedelic Therapeutics.
authors: Renner AC, Kargbo RB.
publication_date: 2026-01-11
doi: 10.1021/acsmedchemlett.5c00780
pubmed_id: 41704348
source_url: https://doi.org/10.1021/acsmedchemlett.5c00780
substance_tags: psilocybin
topic_tags: Pharmacology,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
abstract:
Recent psychedelic patent activity highlights a strategic shift from experiential framing toward chemically and pharmacokinetically precise neurotherapeutics. Four recent patent applications collectively span solid-state control of psilocybin, exposure-shaped intramuscular and infusion-based dosing, and chemically diversified monoaminergic scaffolds with defined transporter and receptor pharmacology. Together, these disclosures outline a platform-level evolution toward reproducible, mechanism-informed psychedelic medicines.

raw_json:
{"europe_pmc_id":"41704348","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2026-01-25
doi: 10.1021/acs.jmedchem.5c01797
pubmed_id: 41586631
source_url: https://doi.org/10.1021/acs.jmedchem.5c01797
substance_tags: psilocybin,psilocin
topic_tags: Pharmacology,Mechanism of Action,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:
Design, Synthesis, and Pharmacokinetic Profiling of Fluorinated Reversible N-Alkyl Carbamate Derivatives of Psilocin for Sub-Hallucinogenic Brain Exposure.

authors:
Banzato M, Colognesi M, Lucatello L, Comai S, Pasut G, Capolongo F, Orian L, Biasutto L, Signor A, Gabbia D, Manfredi PL, De Martin S, Mattarei A.

abstract:
Psilocybin, the phosphorylated prodrug of psilocin, holds therapeutic promise across a range of neuropsychiatric conditions, yet its clinical utility is constrained by acute psychoactive effects. Here, we report the rational design, synthesis, and evaluation of a focused library of fluorinated reversible N-alkyl carbamate derivatives of psilocin aimed at reducing acute psilocin exposure and thereby limiting hallucinogenic-like effects. Carbamate bond stability was systematically modulated by varying the number and positioning of fluorine atoms on the alkyl promoiety. The resulting compounds exhibited finely tuned hydrolysis under physiological conditions. A selected lead compound (4e) showed favorable oral bioavailability and efficient brain penetration while undergoing partial bioconversion to psilocin. Notably, 4e displayed intrinsic serotonergic activity at 5-HT2A and 5-HT2C receptors but induced attenuated psychotropic effects relative to psilocybin. Overall, these findings highlight fluorinated carbamate chemistry as a versatile platform to control psilocin exposure and serotonergic signaling, rather than the development of a classical pharmacologically inert prodrug.

keywords:
Brain, Animals, Humans, Mice, Rats, Carbamates, Hallucinogens, Prodrugs, Structure-Activity Relationship, Drug Design, Male, Halogenation, Psilocybin

raw_json:
{"europe_pmc_id":"41586631","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Habelt B.
publication_date: 2026-02-10
doi: 10.3389/fpsyg.2026.1779055
pubmed_id: 41756488
source_url: https://doi.org/10.3389/fpsyg.2026.1779055
substance_tags: psilocybin
topic_tags: Addiction,Brain Imaging,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 11:22:03
title:
The potential of event-related beta oscillations as biomarkers for neuromodulatory treatment efficacy.

abstract:
Electroencephalography (EEG) recently celebrated its 100-year anniversary, having revolutionized the study of cognitive function across species. Over the past century, neuroelectric measures such as resting-state EEG, event-related potentials (ERP), and event-related oscillations (ERO) have become indispensable not only for advancing our understanding of brain function but also for identifying valuable biomarkers for diagnosing neurological and psychiatric disorders and evaluating the efficacy of novel therapies. Compared to resting state activity and ERPs, EROs-oscillatory dynamics time-locked to and modulated by task events-remain relatively underutilized in evaluating treatment outcomes, despite growing evidence of their potential. Our recent findings from a rat model of alcohol addiction indicate that event-related beta oscillations are sensitive markers of cognitive function and recovery following therapeutic interventions. Both pharmacological treatment with psilocybin and targeted electrical stimulation induced a shift in dominant beta activity from higher to lower sub-bands during an auditory oddball task, underscoring the importance of sub-band-specific analyses beyond aggregate beta power as potential indicators of treatment efficacy acknowledging functional distinctions within the beta range. Despite these promising observations, systematic investigations of beta sub-band activity for diagnosis and treatment of neurological and psychiatric disorders remain scarce. Here, I propose that event-related beta oscillations are an underexplored yet highly promising biomarker for evaluating the efficacy of neuromodulatory interventions, including brain stimulation and neurofeedback, in both preclinical and clinical settings.

raw_json:
{"europe_pmc_id":"41756488","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Tom A, Reddy BSC, Sethi MIS, Math SB.
publication_date: 2026-02-04
doi: 10.1177/02537176261416347
pubmed_id: 41659196
source_url: https://doi.org/10.1177/02537176261416347
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:
India's Unique Legal Framework for Psilocybin Mushroom Research: An Unprecedented Opportunity in Psychiatric Therapeutics.

raw_json:
{"europe_pmc_id":"41659196","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Acute psilocin increased cortical activity in rat.
authors: Liu J, Wang Y, Xia K, Wu J, Zheng D, Cai A, Yan H, Su R.
publication_date: 2026-02-03
doi: 10.3389/fnins.2026.1593703
pubmed_id: 41716660
source_url: https://doi.org/10.3389/fnins.2026.1593703
substance_tags: psilocybin,psilocin
topic_tags: Depression,Brain Imaging,Mechanism of Action,Aging,Clinical Trial,Animal 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
abstract:
Psilocin, a naturally occurring hallucinogenic component of magic mushrooms, exerts notable psychoactive effects in both humans and rodents. However, the underlying mechanisms remain not fully understood. Blood-oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) is a valuable tool in many preclinical and clinical trials for investigating changes of brain activity and functional connectivity (FC) due to its noninvasive nature and widespread availability. However, fMRI effects of psilocin on rats have not been thoroughly explored. This study aimed to explore the impact of psilocin on rats' brain activity by combining BOLD fMRI and immunofluorescence (IF) of EGR1, an immediate early gene (IEG) closely related to depressive symptoms. Ten minutes after psilocin hydrochloride injection (2.0 mg/kg, i.p.), elevated brain activity was detected in the frontal, temporal, and parietal cortex (including the cingulate cortex and retrosplenial cortex), hippocampus, and striatum. Moreover, a region-of-interest (ROI) -wise FC analysis matrix indicated enhanced interconnectivity of several regions, such as the cingulate cortex, dorsal striatum, prelimbic, and limbic regions. Further seed-based analyses revealed increased FC of cingulate cortex with the cortical and striatal areas. In addition to the fMRI observations, acute psilocin led to an increase in the EGR1 level in most cortical and striatal regions, indicating a consistent activation throughout the cortical and striatal areas. In conclusion, the psilocin-induced hyperactive state in rats is congruent to that in humans, and the increased brain activity, enhanced functional connectivity and up-regulation of EGR1 may be responsible for its pharmacological effects.

raw_json:
{"europe_pmc_id":"41716660","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Retraction: Acute psilocybin increased cortical activities in rats.
authors: Frontiers Editorial Office.
abstract: [This retracts the article DOI: 10.3389/fnins.2023.1168911.].
publication_date: 2026-02-03
doi: 10.3389/fnins.2026.1787833
pubmed_id: 41716656
source_url: https://doi.org/10.3389/fnins.2026.1787833
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
raw_json:
{"europe_pmc_id":"41716656","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Christopher MW, Prentice BM, Garrett TJ.
publication_date: 2025-12-29
doi: 10.1021/jasms.5c00421
pubmed_id: 41467535
source_url: https://doi.org/10.1021/jasms.5c00421
substance_tags: psilocybin,psilocin
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:
Distinguishing 4- vs 5-Hydroxy-N,N-Dimethyltryptamine (Psilocin vs Bufotenine) Using Hydrogen-Deuterium Back-Exchange.

abstract:
Distinguishing metabolite isomers often relies on comparing relative data, such as relative chromatographic retention times and ion mobility arrival time orders, or relative product ion abundances. These approaches necessitate the need for quality reference data and/or chemical standards. An ideal method for differentiating isomers would leverage one of the absolute physiochemical properties of the isomers, and would have no reliance on instrument vendor, chromatographic column chemistry, or external reference data. For example, the pKa of an aromatic hydroxy hydrogen changes according to ring position across isomers (e.g., 4- vs 5-hydroxyindole). Herein, we leverage the difference in pKa to resolve 4- and 5-hydroxy positional isomers of hydroxy-N,N-dimethyltryptamine (psilocin and bufotenine), the structural moiety of compounds with profound effects on the serotonergic system. We first use hydrogen-deuterium exchange (HDX) to rapidly exchange the indole amine hydrogen and gradually exchange the indole hydroxy hydrogen atoms to deuterium atoms. We then back-exchange the indole amine deuterium atom back to a hydrogen atom on the LC column and monitor the kinetic exchange rates of the retained aromatic hydroxy deuterium atom using high resolution mass spectrometry (HRMS). HDX kinetics allow for facile differentiation of the two isomers, with only 4-hydroxy-N,N-dimethyltryptamine exchanging at an appreciable amount within hours. These results could ultimately be used to characterize a variety of unknown structural isomers.

keywords:
Deuterium, Deuterium Exchange Measurement, Isomerism, Psilocybin, Hydrogen Deuterium Exchange-Mass Spectrometry

raw_json:
{"europe_pmc_id":"41467535","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Bostancıklıoğlu M, Kaplan DS, Bal R, Yiğit E, Ulusal H, Temiz E.
publication_date: 2026-02-02
doi: 10.1016/j.biopsych.2026.01.016
pubmed_id: 41644029
source_url: https://doi.org/10.1016/j.biopsych.2026.01.016
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:
MDMA and Psilocybin Regulate Oligodendrocyte-Lineage Cell Numbers and Anxiety-Like Behaviors in a Rat Model of Fear.

abstract:
BackgroundPsilocybin and MDMA produce rapid, enduring therapeutic effects in posttraumatic stress disorder (PTSD); however, the underlying cellular mechanisms remain incompletely understood. In this study, we investigated whether adult myelin plasticity contributes to the therapeutic actions of psilocybin and MDMA in a rat model of contextual fear conditioning.MethodsAdult male Wistar rats (N = 210) received repeated low doses of psilocybin (0.5 mg/kg, intraperitoneally [i.p.], for 4 days) or MDMA (0.1 mg/kg/day, i.p., for 4 days). Behavioral tests assessed anxiety-like behaviors and spatial memory. Following local and global manipulations of myelin integrity, we assessed the drugs' effects on myelination by quantifying myelin sheath thickness; oligodendrocyte-lineage cell densities; and transcriptomic, proteomic, and metabolomic profiles in the dentate gyrus.ResultsBoth compounds reduced anxiety-like behaviors. These improvements coincided with oligodendroglial changes and multiomic signatures of myelin-related remodeling; however, mean g-ratio measures of myelin thickness did not differ significantly between intact fear-conditioned animals with or without psychedelic treatment. Myelin disruption abolished these anxiolytic effects, and integrative multiomics revealed convergent upregulation of myelin-related proteins following administration of psilocybin or MDMA. Psilocybin preferentially induced early oligodendroglial gene programs, while MDMA enhanced markers of mature myelin. Notably, 5-HT2A receptor blockade completely abolished the myelin and behavioral enhancements induced by both psilocybin and MDMA.ConclusionsPsilocybin and MDMA promote adult oligodendrocyte and myelin plasticity. Enhancing myelination may be a viable strategy to augment or sustain the therapeutic effects of psychedelic-assisted treatments for PTSD and related disorders.

topic_tags:
Anxiety,PTSD,Neuroplasticity,Mechanism of Action,Receptor Pharmacology,Biomarkers,Animal Study,Transcriptomics,Proteomics,Metabolomics

raw_json:
{"europe_pmc_id":"41644029","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2026-01-31
doi: 10.26402/jpp.2026.1.07
pubmed_id: 41931735
source_url: https://doi.org/10.26402/jpp.2026.1.07
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Microdosing,Animal Study,In Vitro 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 11:22:01
title:
Bioactive compounds from Psilocybe cubensis mycelial cultures with transient anxiolytic effects in mice.

authors:
Kala K, Bederska-Lojewska D, Lazur J, Gasior K, Maslanka A, Szewczyk A, Sulkowska-Ziaja K, Turek J, Szewczyk B, Pilc A, Muszynska B.

abstract:
The growing percentage of people suffering from drug-resistant depression increases interest in alternative therapies, particularly the usage of psychedelics such as psilocybin. The main source of psilocybin is the Psilocybe cubensis species. Due to the potential therapeutic benefits of psilocybin and the legal restrictions on its possession and use in the form of fungal fruiting bodies, this research work documents an attempt to obtain in vitro P. cubensis mycelium in which psilocybin and other biologically active substances acting on the central nervous system would be present. It was hypothesized that chronic microdosing with whole in vitro - cultured P. cubensis mycelium, containing psilocybin together with other neuroactive secondary metabolites, could exert anti-anxiety and antidepressant effects through their combined action. For this purpose, the anti-anxiety and antidepressant activity of mycelium microdosing in male C57BL/6J mice was investigated. The tail suspension test (TST), novelty suppressed feeding test (NSFT), sucrose preference test (SPT), locomotor activity (LA), and female urine sniffing test (FUST) were used to examine animal behavior. The chemical analysis was performed using high-performance liquid chromatography (HPLC) and thin-layer chromatography (TLC) method. Analysis of the studied extracts showed that psilocybin was present only in the mycelium of the Cambodian strain, at a concentration of 20.78 mg per 100 g dry weight. The experiment showed that mycelium supplementation significantly reduced anxious behavior in mice on day 22 but did not affect locomotor activity, depressive, anxiety-related, or anhedonic behaviors at later stages of the experimental protocol. Although the results suggest the potential of P. cubensis mycelial cultures in anxiety prevention, further studies using higher doses or alternative models are needed to confirm and extend these findings.

keywords:
Animals, Mice, Inbred C57BL, Mice, Mycelium, Anti-Anxiety Agents, Antidepressive Agents, Behavior, Animal, Anxiety, Female, Male, Psilocybe, Psilocybin

raw_json:
{"europe_pmc_id":"41931735","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Roser P.
publication_date: 2026-01-31
doi: 10.23785/tu.2026.01.006
pubmed_id: 41878754
source_url: https://doi.org/10.23785/tu.2026.01.006
substance_tags: psilocybin
topic_tags: Addiction,Receptor Pharmacology,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 11:22:02
title:
[Pharmacological post-acute treatment of alcohol use disorder: Established strategies and innovative approaches].

abstract:
IntroductionAlcohol use disorders are common and contribute significantly to the global burden of disease. The treatment of alcohol dependence includes the acute withdrawal phase and the post-acute rehabilitation phase. The primary goal of post-acute treatment is long-term abstinence, although reduction of alcohol consumption is also recognized as an intermediate goal. In addition to psychosocial and psychotherapeutic interventions, the use of medications is recommended. In Switzerland, four medications (acamprosate, naltrexone, nalmefene, and disulfiram) are approved for post-acute treatment. Their efficacy in reducing relapse risk, drinking days, and overall alcohol consumption is well established. Baclofen, topiramate, and gabapentin are used "off-label", but sufficient evidence of their effectiveness is still lacking. Innovative approaches such as cannabidiol, psilocybin, and glucagon-like peptide-1 receptor agonists show promising therapeutic potential, which needs to be confirmed in further clinical studies. The use of pharmacological interventions can help improve patient outcomes, reduce the need for inpatient treatment, and lower healthcare costs.

keywords:
Humans, Alcoholism, Disulfiram, Taurine, Naltrexone, Alcohol Deterrents, Treatment Outcome, Combined Modality Therapy, Switzerland, Secondary Prevention, Topiramate, Acamprosate

raw_json:
{"europe_pmc_id":"41878754","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Homon A, Laramie J, Hayward JJ, Trant JF
journal: ChemMedChem
publication_date: 2026-01-31
doi: 10.1002/cmdc.202500525
pubmed_id: 41765690
source_url: https://pubmed.ncbi.nlm.nih.gov/41765690/
keywords: 5‐HT receptors, psilocin derivatives, psychedelic, serotonin, total synthesis
substance_tags: psilocin
topic_tags: Receptor Pharmacology,Review Article,Animal Study,Inflammation
study_type: Review Article
source_name: PubMed
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:20:35
raw_json: {"pubmed_id":"41765690"}
title:
We Licked the Toads so You Don't Have to: A Comprehensive Analysis of the Chemical Syntheses of the Classical Psychedelics Bufotenin(e) and 5-Methoxy-N,N-Dimethyltryptamine.

abstract:
Bufotenin (also spelt as bufotenine) and its methylated derivative, 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), are potent psychedelics that are found in many plants but also excreted by some species of toads. The compounds are regulated differently around the world, and although used in traditional medicine, 20-century prohibition culture has slowed research into their utility for ameliorating psychological disorders and inflammatory and neurodegenerative diseases. However, the global trend toward legalization and a renewed interest in the therapeutic potential of psychedelics has increased the number of clinical and preclinical studies of these and related materials. This necessitates access to large amounts of these compounds, but they are not commercially available on scale, leaving researchers with a need to either contract out, or make their own. The first bufotenin synthesis was reported in 1935 by Hoshino and coworkers, and novel syntheses are still being disclosed in the 2020s. This is the first effort to collate and compare all extant academic and patent syntheses (as of fall 2024) into a single review so that researchers can identify the most appropriate route for their own purposes. We conclude by highlighting outstanding challenges that are ripe for solutions to reduce the cost of any future commercial-scale production.


authors: Halm S.
publication_date: 2026-01-31
doi: 10.1002/brb3.71265
pubmed_id: 41699879
source_url: https://doi.org/10.1002/brb3.71265
substance_tags: psilocybin
topic_tags: Depression,PTSD,Mechanism of Action
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:
Psychedelic- and Substance-Assisted Therapies in Global Mental Health: Bridging Cultures, Evidence, and Access.

abstract:
Psychedelic- and substance-assisted therapies, including MDMA, psilocybin, and ketamine, are gaining attention for conditions such as PTSD and depression, yet their development and implementation remain largely concentrated in high-income settings. This graphical abstract summarizes the central argument of the commentary: while these interventions may hold relevance for global mental health, particularly in conflict-affected and humanitarian contexts, their equitable use is constrained by cultural, ethical, regulatory, and resource-related challenges. Responsible implementation requires culturally grounded, ethically robust, and context-sensitive pathways rather than uncritical expansion.

keywords:
Humans, N-Methyl-3,4-methylenedioxyamphetamine, Ketamine, Hallucinogens, Mental Health, Stress Disorders, Post-Traumatic, Global Health, Psilocybin

raw_json:
{"europe_pmc_id":"41699879","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Participant Experiences of Therapeutic Touch in Psilocybin-Assisted Therapy.
authors: Ham R, Gardner J, Carter A, Liknaitzky P.
publication_date: 2026-01-31
doi: 10.1002/brb3.71262
pubmed_id: 41699875
source_url: https://doi.org/10.1002/brb3.71262
keywords: Humans, Hallucinogens, Therapeutic Touch, Adult, Middle Aged, Female, Male, Young Adult, Psilocybin
substance_tags: psilocybin
topic_tags: Emotional Processing,Clinical Trial,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 11:22:00
abstract:
IntroductionAlthough commonly used in psychedelic-assisted therapy, the role of therapeutic touch remains loosely defined and ethically sensitive. Gaining insight into how participants experience and interpret touch during psychedelic sessions is essential for informing safe and effective clinical practice.MethodsParticipants were sampled from a large randomized clinical trial of psilocybin-assisted therapy that permitted protocol-defined supportive touch. Longitudinal qualitative data (39 semi-structured interviews) were analyzed from n = 18 participants. Interviews covered expectations, experiences, and reflections on the use of touch during acute psychedelic states, before and after dosing. Thematic analysis was used to identify major themes.ResultsParticipants expressed varied preferences and responses to therapeutic touch. Most valued its availability, particularly after firsthand experience, describing its capacity to foster emotional connection, provide grounding during intense affective states, and modulate the depth of psychedelic experience. Several reported perceiving therapeutic benefit directly attributable to touch. Acceptability was consistently linked to the quality of the therapeutic relationship and robust consent processes. Some participants also identified potential for discomfort or distraction, underscoring the need for sensitivity to individual history and context.ConclusionsTherapeutic touch may support emotional safety and affect regulation during acute psychedelic states. Findings highlight the importance of explicit preparation, consent, and attunement when incorporating touch into psychedelic therapy. Further research should inform therapist training, individualized consent frameworks, and safety protocols to guide ethical and effective use in clinical practice.

raw_json:
{"europe_pmc_id":"41699875","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Patient perspectives on research gaps in cluster headache.
publication_date: 2026-01-20
doi: 10.1111/head.70031
pubmed_id: 41562498
source_url: https://doi.org/10.1111/head.70031
substance_tags: psilocybin
topic_tags: Headache / Migraine,Clinical Trial,Observational Study,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 11:22:02
authors:
Haghdoost F, Bahceci D, Delcourt C, Wijeratne T, Jensen RH, Cincinnato C, Tomlinson S, Wold B, Polito V, Carcel C, Ashraf U, Jenkins B, Petersen AS, Ray JC, Schindler EAD, Tsang B, Gianacas C, Rodgers A.

abstract:
ObjectiveThis study was undertaken to identify gaps in cluster headache management, highlight patient-prioritized research needs, and assess patient interest in, and preferences for, clinical trial participation.BackgroundMany people with cluster headache still lack effective treatment options to control or prevent attacks. There is a critical need for more studies, particularly clinical trials, in this field. To design and conduct successful trials, it is essential to identify priority research areas, allocate resources effectively, and ensure patient engagement and support.MethodsThis study was an online survey conducted among Australian adults with self-reported cluster headache. Participants were recruited using a multi-channel approach, including direct outreach by clinicians, support from patient advocacy groups, and broad social media distribution. It collected data on demographics, treatment experiences, and perspectives on future research, including research priorities, and preferred outcomes and interventions. Additionally, participants' interest in joining clinical trials was assessed to help identify potential candidates for future studies.ResultsOf the 219 individuals who began the survey, 17 (8%) were excluded due to providing no responses beyond demographic data or reporting no cluster headache diagnosis by a healthcare professional. The final sample consisted of 202 participants, with an average age of 46 years, 77% aged 25-54 years, 55% male, 72% had been living with cluster headache for more than 10 years, and 29% reported attacks occurring almost every month throughout the year. A quarter of participants had not followed up with a healthcare provider for cluster headache management when they completed the survey. Among those who sought care (n = 145 [72%]), general practitioners were the most frequently consulted (86%), followed by neurologists (66%). Treatments were considered "not at all effective" or "somewhat ineffective" by 35% of all participants, while 27% reported only partial effectiveness. The main treatment challenges were ineffectiveness (74%), side effects (54%), cost (53%), and difficulties with access (39%). Among the 202 participants, 126 (62%) indicated interest in participating in future cluster headache trials, while 26 (13%) responded with "maybe." Psilocybin was the highest-ranked treatment in terms of participants who were "very interested," with 66% selecting this option. The combined proportion of participants who were "very interested" or "interested" was 84% for combination therapies, 82% for psilocybin, 71% for medical devices, and 66% for anti-CGRP treatments.ConclusionParticipants with reported cluster headache highlighted inadequate treatment options, emphasized the need for further research, and expressed interest in future clinical trials, particularly those involving psilocybin or combination therapies.

keywords:
Humans, Cluster Headache, Biomedical Research, Adult, Middle Aged, Australia, Female, Male, Young Adult, Surveys and Questionnaires

raw_json:
{"europe_pmc_id":"41562498","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: The effect of psilocin on neurotransmitters release in the claustrum and on rat behavior.
authors: Kościuk Z, Szpręgiel I, Bysiek A, Gołembiowska K.
publication_date: 2026-01-04
doi: 10.1007/s43440-025-00817-3
pubmed_id: 41486340
source_url: https://doi.org/10.1007/s43440-025-00817-3
substance_tags: psilocybin,psilocin
topic_tags: Mechanism of Action,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:
BACKGROUND: The claustrum, a subcortical structure densely expressing 5-hydroxytryptamine 2 A (5-HT2A) receptors, has been implicated in sensory integration, emotional regulation, salience, and attention. Despite its hypothesized involvement in the effects of serotonergic psychedelics, the neurochemical impact of these substances on claustral neurotransmission remains unexplored. This study aimed to investigate how psilocin - a tryptamine and the active metabolite of psilocybin - and 4-Iodo-2, 5-dimethoxy-N-(2-methoxybenzyl)phenethylamine (25I-NBOMe) - a phenethylamine and new psychoactive substance (NPS) - modulate extracellular neurotransmitter levels in the rat claustrum, as well as to examine their effects on wet dog shake behavior, a well-established proxy for hallucinogenic activity. METHODS: Adult male Wistar Han rats were used for in vivo brain microdialysis experiments. Microdialysis probes were stereotaxically implanted into the claustrum. Rats received local administration of either psilocin (100 or 500 µM) or 25I-NBOMe (500 µM) through the microdialysis probe. Dialysate samples were collected and analyzed using high-performance liquid chromatography (HPLC) with electrochemical detection to quantify extracellular levels of dopamine (DA), noradrenaline (NA), serotonin (5-HT), glutamate (GLU), gamma-aminobutyric acid (GABA), and acetylcholine (ACh). A behavioral test defined as wet dog shakes (WDS) was conducted after drugs administration, to infer psychedelic-like activity. RESULTS: In vivo microdialysis performed in freely moving rats revealed that both substances markedly altered extracellular levels of DA, NA, 5-HT, GLU, GABA, and ACh. Psilocin, at both administered doses, was the only compound to significantly elevate NA and produced the most pronounced enhancement of cholinergic signaling across all neurotransmitter systems examined. By contrast, 25I-NBOMe induced a more substantial shift toward excitatory dominance, accompanied by the greatest increase in 5-HT release. Overall, psilocin generated a comparatively balanced excitatory-inhibitory neurochemical profile, reflecting its combined engagement of 5-HT2A and 5-HT1A receptors, whereas 25I-NBOMe produced an excitation-biased pattern consistent with its selective, high-affinity 5-HT2A agonism. CONCLUSIONS: These findings highlight the claustrum as a neurochemical convergence point for psychedelic action and demonstrate that psilocin engages this circuitry in a regulated, receptor-balanced manner, whereas 25I-NBOMe drives a markedly more excitatory and less compensated profile, underscoring their fundamentally distinct therapeutic and toxicological potentials.

keywords:
Animals, Rats, Rats, Wistar, Dopamine, Serotonin, Dimethoxyphenylethylamine, Neurotransmitter Agents, Hallucinogens, Microdialysis, Behavior, Animal, Male, Psilocybin, Claustrum

raw_json:
{"europe_pmc_id":"41486340","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin and Bipolar Depression: Promise and Prudence.
authors: Marques MG, Patarroyo-Rodriguez L, Singh B.
publication_date: 2026-01-03
doi: 10.1007/s40263-025-01255-8
pubmed_id: 41485178
source_url: https://doi.org/10.1007/s40263-025-01255-8
keywords: Animals, Humans, Hallucinogens, Antidepressive Agents, Bipolar Disorder, Psilocybin
substance_tags: psilocybin
topic_tags: Depression,Pharmacology,Aging,Clinical Trial,Safety,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
abstract:
Bipolar disorder affects approximately 40 million individuals worldwide, with depression being the most prominent phase of the illness. Owing to limited treatment options, bipolar depression remains a major public health concern, often causing significant functional impairment and increased suicide risk. Current therapies frequently lack rapid effectiveness, highlighting the need for novel approaches. Psilocybin, a psychedelic compound receiving growing interest for its potential rapid antidepressant effects, is under investigation in clinical trials combined with psychotherapy. Early studies in bipolar II disorder (n = 19) show encouraging results, but evidence is still limited, and important safety concerns such as affective switching and pharmacokinetic interactions persist. Additional challenges include regulatory restrictions, infrastructure demands, and uncertainties about the role of the psychedelic experience, especially given possible interference by common bipolar medications. Cautious, rigorous research is essential to determine psilocybin's safety, efficacy, and practical application in bipolar depression, particularly for bipolar I disorder and long-term outcomes.

raw_json:
{"europe_pmc_id":"41485178","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2025-12-28
doi: 10.1016/j.phrs.2025.108080
pubmed_id: 41475502
source_url: https://doi.org/10.1016/j.phrs.2025.108080
substance_tags: psilocybin
topic_tags: Pharmacology,Mechanism of Action,Receptor Pharmacology,Animal Study,Transcriptomics
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:
Low, non-psychedelic doses of psilocybin as a novel treatment for MASLD, obesity and type 2 diabetes via 5-HT2B receptor-dependent mechanisms.

authors:
Colognesi M, Gabbia D, Signor A, Sarill M, Centofanti L, Rinaldi A, Cascione L, Nunziata S, Banzato M, Mattarei A, Finzi G, Sonda S, Pendin D, Zanotto I, Comai S, Pasut G, Alajati A, Saponaro M, Bucciarelli L, Lunati ME, Guarato G, Goggi I, La Rosa S, Morano C, Paroni RC, Dei Cas M, Daniele G, Gentilucci M, Pappagallo M, Alimonti A, Manfredi PL, Folli F, De Martin S.

abstract:
The therapeutic potential of low, non-psychedelic doses of psilocybin, a fungal tryptamine alkaloid, was investigated in metabolic disorders including obesity, type 2 diabetes mellitus (T2DM), and liver steatosis. Mice fed a high-fat/high-fructose diet received chronic treatment with psilocybin (0.05 mg/kg) for 12 weeks. Body weight, liver histology, insulin sensitivity, and skeletal muscle function were assessed, and hepatic and muscle tissues underwent transcriptomic and lipidomic analyses. The role of three serotonin receptors (5-HT2A, 5-HT2B, and 5-HT2C) in psilocybin-induced metabolic effects was examined in human cell lines using pharmacological and CRISPR/Cas9-based genetic approaches. Low-dose psilocybin reduced body-weight gain, liver steatosis, hyperglycaemia, and insulin resistance without eliciting central nervous system effects. Multi-omics analyses revealed near-complete normalization of disrupted hepatic lipid and carbohydrate metabolism pathways. Psilocybin also improved muscle strength and function, potentially through restoration of leptin sensitivity. Mechanistic studies demonstrated that these metabolic benefits were independent of the canonical psychedelic target 5-HT2A and instead resulted from antagonism of the serotonin 5-HT2B receptor in the liver. Overall, chronic low-dose psilocybin exerts broad metabolic benefits via a hepatic 5-HT2B-dependent mechanism, distinct from its psychedelic effects, supporting its potential as a novel therapeutic strategy for liver steatosis, obesity, T2DM, and sarcopenia.

keywords:
Liver, Animals, Mice, Inbred C57BL, Humans, Mice, Diabetes Mellitus, Type 2, Insulin Resistance, Obesity, Receptor, Serotonin, 5-HT2B, Male, Lipid Metabolism, Serotonin 5-HT2 Receptor Agonists, Diet, High-Fat, Psilocybin

raw_json:
{"europe_pmc_id":"41475502","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Vollebregt R, Storm AEM, Lucassen PJ, Somers M.
publication_date: 2025-12-15
doi: 10.1016/j.neubiorev.2025.106529
pubmed_id: 41412413
source_url: https://doi.org/10.1016/j.neubiorev.2025.106529
keywords: Brain, Nerve Net, Animals, Humans, Hallucinogens, Psilocybin
substance_tags: psilocybin
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 experiences elicited by serotonergic psychedelics: Molecular mechanisms and functional connectivity changes in the brain.

abstract:
Classical psychedelics, like lysergic acid diethylamide (LSD), N,N-dimethyltryptamine (DMT), and psilocybin, can alter perception, emotion, and cognition, and have shown promise as 're-purposed' treatments for some psychiatric disorders. Recent trials have, e.g., demonstrated rapid and sustained symptom relief in treatment-resistant depression. While promising as a treatment, the neurobiological mechanisms underlying both the subjective and clinical effects remain incompletely understood. Also, their broader influence on (intra) cellular processes, neural circuits, and brain-wide connectivity is less well documented. Here, we review the molecular and network-level alterations induced by classical serotonergic psychedelics through a systematic review of experimental and (pre)clinical studies from 1990 onward. We focus on the short-term impact on receptor activity, intracellular signaling, and functional brain connectivity underlying the psychedelic experience. Most psychedelics primarily act as serotonin 5-HT₂A receptor agonists, initiating intracellular signaling pathways that modulate neuroplasticity, glutamate release, and cortical excitability. Psychedelics disrupt functional network connectivity, particularly within the default mode network, while enhancing global integration across brain regions. These effects are associated with subjective experiences of 'ego dissolution' and altered perception, which may contribute to their therapeutic effects. This review synthesizes findings at the molecular and systems level and their interaction during the psychedelic state. While no single model explains all effects, several overlapping theories begin to bridge receptor-level activity with large-scale brain connectivity changes. Improving our understanding of their neurobiological basis may help clarify how psychedelics act and allows for more tailored opportunities to enhance their therapeutic effects and clinical application in a stratified manner.

topic_tags:
Depression,Neuroplasticity,Mechanism of Action,Receptor Pharmacology,Default Mode Network,Emotional Processing,Systematic Review,Review Article,Treatment-Resistant Depression,Drug Interactions

raw_json:
{"europe_pmc_id":"41412413","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Dutton M, Schwenn P, Mitchell J, Hoffmann P, Bailey NW, Fitzgerald PB, Lagopoulos J, Can AT.
publication_date: 2025-12-16
doi: 10.1177/00048674251398677
pubmed_id: 41405025
source_url: https://doi.org/10.1177/00048674251398677
keywords: Humans, Hallucinogens, Australia, Depressive Disorder, Treatment-Resistant, Psilocybin
substance_tags: psilocybin
topic_tags: Depression,Mechanism of Action,Treatment-Resistant 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:
Psilocybin in the real world: Regulatory, ethical, and operational challenges in Australia's clinical landscape.

abstract:
Australia's reclassification of psilocybin as a Schedule 8 substance for treatment-resistant depression represents a significant shift in psychiatric policy. While this regulatory change positions Australia as a global leader in psychedelic medicine, its implementation has revealed substantial challenges. This article critically examines the regulatory, ethical and operational complexities surrounding the provision of psilocybin-assisted therapy in clinical practice. Key issues include limited prescriber access, absence of Australian Register of Therapeutic Goods-listed products, lack of standardised training pathways and significant cost barriers. Ethical considerations such as informed consent, cultural safety and therapeutic fidelity are also discussed, particularly in the context of trauma-informed care. This article proposes a series of structural recommendations to support safe and equitable deployment, including national training accreditation and fidelity monitoring tools. In addition, to maximise the efficacy of psilocybin-assisted therapy, we recommend that research explores the potential of neurobiologically informed stratification models to assist with treatment recommendations. These recommendations aim to enhance clinical integrity through evidence-based patient selection, improved safety, and to ensure that emerging psychedelic treatments are integrated responsibly within Australia's mental health system. By addressing these foundational gaps, Australia can move beyond regulatory novelty ensuring the therapeutic potential of these products is realised in a manner which is scientifically sound and upholds the integrity of psychiatric practice.

raw_json:
{"europe_pmc_id":"41405025","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


journal: The International journal on drug policy
publication_date: 2026-01-31
doi: 10.1016/j.drugpo.2025.105105
pubmed_id: 41389560
source_url: https://pubmed.ncbi.nlm.nih.gov/41389560/
keywords: Adverse, Challenging experiences, Childhood, Psilocybin, Psychedelics, Trauma
substance_tags: psilocybin
topic_tags: Anxiety,Safety
study_type: Qualitative Study
source_name: PubMed
publication_status: published
date_added: 2026-06-30 22:38:07
last_checked: 2026-07-01 11:20:35
raw_json: {"pubmed_id":"41389560"}
title:
Difficulties following naturalistic psychedelic use and associations with adverse childhood experiences.

authors:
Olofsson M, Osika W, Goldberg SB, Hendricks PS, Petrovic P, White T, Stenfors CUD, Chaturvedi S, Simonsson O

abstract:
Naturalistic psychedelic use can result in a range of difficulties that impair social, occupational, and other important areas of functioning. Yet, the prevalence, phenomenology, and etiology of these outcomes remain poorly understood. Recent qualitative research has shown that individuals with long-term difficulties after psychedelic use sometimes attribute their challenges to childhood trauma. Further studies are needed to investigate these relationships.
In this cross-sectional mixed-methods study of U.S. adults with lifetime psychedelic use (n = 3168), we examined the prevalence, duration, and nature of psychedelic-related difficulties, as well as associations with adverse childhood experiences (ACEs).
Of all participants (n = 3168), most (n = 2785, 87.9 %) reported no difficulties; 6.4 % (n = 203) reported post-acute difficulties that lasted for more than one day, and 1.3 % (n = 40) for more than one year. Among those who reported difficulties (n = 383), 47 % (n = 180) reported that their difficulties resolved in one day or less. The most frequently reported post-acute difficulties were general anxiety (33.9 %), negative changes in self-concept (25.9 %), and social disconnection (23.0 %). In covariate-adjusted regression models, 2 ACEs (aOR: 2.24, p = 0.007), 3 ACEs (aOR: 2.27, p = 0.006), and ≥4 ACEs (aOR: 2.84, p < 0.001) were associated with higher odds of psychedelic-related difficulties compared to 0 ACEs. ≥4 ACEs were also associated with higher odds of difficulties that lasted more than one day (aOR: 2.37, p = 0.015) and more than one week (aOR: 2.89, p = 0.042).
There are a range of difficulties that can follow psychedelic use and childhood adversity may represent a risk factor for persistent adverse effects.


title: Disengaged: A systematic review of community engagement in psychedelic-assisted therapy research.
authors: Reid MR, Song J, Boehnke KF, Buchanan NT, Aday JS.
publication_date: 2025-12-06
doi: 10.1016/j.neubiorev.2025.106516
pubmed_id: 41365426
source_url: https://doi.org/10.1016/j.neubiorev.2025.106516
keywords: Humans, Hallucinogens, Community-Based Participatory Research, Community Participation, Psilocybin
substance_tags: psilocybin
topic_tags: Mechanism of Action,Aging,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 11:22:03
abstract:
People of color have been significantly underincluded in psychedelic-assisted therapy (PAT) research, despite facing challenges commonly addressed in PAT and often more severe symptoms. It may be the case that people of color are underincluded because PAT researchers have not used approaches designed to promote sample diversity. Community-engaged research (CEnR) is a research paradigm that has demonstrated success in promoting participant diversity. We hypothesize that the absence of CEnR in psychedelic science may be a contributing factor to the lack of diversity in psychedelic studies. To examine the prevalence of CEnR practices in PAT research, we conducted a systematic review of the past 10 years of psilocybin, MDMA, and LSD clinical trials in the United States. We reviewed each study (N = 27) to assess whether researchers incorporated CEnR using the Continuum of Community Engagement and reached out to each individual study team to ensure comprehensiveness. Our analysis revealed that only 3/27 (11.11 %) studies incorporated CEnR. In the rare instances CEnR was integrated, PAT researchers used community consultation, which involves relatively little engagement with community members. To improve representation in PAT trials, we recommending incorporating the CEnR principles of 1) mapping and engaging local stakeholders, 2) leveraging existing university-hospital infrastructures, 3) co-designing research and outreach initiatives, 4) securing dedicated CEnR resources, and 5) establishing mechanisms for ongoing evaluation. This systematic review supports that there has been a paucity of community-engaged practices in PAT research, which can be addressed by incorporating our recommendations for implementing CEnR in PAT studies.

raw_json:
{"europe_pmc_id":"41365426","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: New treatments for OCD? Evidence for cannabinoids and psychedelics.
authors: Van Ameringen M, Patel V, Patterson B, Hopkinson P, Rahat M.
publication_date: 2025-11-25
doi: 10.1016/j.jpsychires.2025.11.021
pubmed_id: 41317726
source_url: https://doi.org/10.1016/j.jpsychires.2025.11.021
keywords: Humans, Cannabinoids, Hallucinogens, Obsessive-Compulsive Disorder
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 11:22:02
abstract:
The etiology of OCD is complex and appears to involve multiple biological pathways. Imbalances in central serotonin, dopamine, and glutamate activities are widely thought to play a causative role. Despite strong evidence supporting first-line OCD pharmacotherapies, approximately 40-60 % of OCD patients remain unresponsive and are considered treatment resistant (TR). Although a range of agents have been examined in TR-OCD, there is no gold-standard, indicating a need to broaden our clinical armamentarium. Cannabis has been used for centuries in many cultures for both medicinal and recreational purposes. Clinical interest in these agents has recently re-emerged. The current evidence for the use of cannabinoids in OCD is very small and includes survey-based, self-report studies with very few controlled trials. Additionally, after a long hiatus from psychiatric research, psychedelics have re-emerged as agents of interest within the past decade. A comprehensive scoping review of the OCD literature including published and grey literature was conducted and detailed in this paper. The current evidence associated with Cannabinoids, Psilocybin, Lysergic acid diethylamide (LSD), N,N-Dimethyltryptamine (N,N-DMT), and Methylenedioxyphenethylamine (MDMA) in the treatment of OCD is detailed. Much of the current evidence examining cannabinoids and psychedelics in OCD is from cross-sectional surveys and case reports, as well as some small clinical trials. There is a shortage of well-controlled, methodologically rigorous RCTs to properly test the efficacy of cannabinoids or psychedelics in OCD and related disorders. However, the current evidence appears to indicate a lack of evidence supporting the use of either synthetic or natural cannabinoids to treat OCD, but a stronger signal for the use of psilocybin in TR-OCD.

topic_tags:
OCD,Mechanism of Action,Receptor Pharmacology,Clinical Trial,Randomized Controlled Trial,Review Article,Case Report,Observational Study

raw_json:
{"europe_pmc_id":"41317726","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2025-11-27
doi: 10.1007/s40263-025-01248-7
pubmed_id: 41313392
source_url: https://doi.org/10.1007/s40263-025-01248-7
substance_tags: psilocybin
topic_tags: Eating Disorders,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 11:22:03
title:
Approved and Pipeline Pharmacological Interventions for Eating Disorders (2010-2025): 15 Years of Progress (or Lack Thereof).

authors:
Hirsch D, Reed J, Naqvi A, Ngor A, Dugan L, Costa K, Ganasi RS, Truman K, Danovitch I, IsHak WW, Hedrick R.

abstract:
Eating disorders (EDs) are complex psychiatric conditions characterized by disruptions in eating behaviors, body image concerns, and profound medical and psychosocial consequences. Despite their significant global prevalence, coupled with high morbidity and mortality rates, pharmacological treatment options remain limited. This review synthesizes evidence from clinical drug trials conducted between 1 January 2010 and 1 January 2025, supplemented with relevant literature, to evaluate the current and emerging pharmacological landscape for EDs. A systematic search of the U.S. Clinical Trials Registry (ClinicalTrials.gov) identified 43 eligible phase I-IV clinical trials for the treatment of anorexia nervosa (n = 12), binge eating disorder (n = 27), bulimia nervosa (n = 2), and rumination disorder (n = 2). Among 24 distinct compounds studied, only 1 agent, lisdexamfetamine dimesylate, received approval from the U.S. Food and Drug Administration (FDA) for an ED during this period. Notably, few agents have demonstrated positive results in late-stage trials and remain in development for EDs as of 2025. While some emerging agents show promise, such as solriamfetol and psilocybin, there remains a significant lack of evidence-based pharmacological interventions for anorexia nervosa and a dearth of progress in pharmacotherapy for bulimia nervosa. Overall, the past 15 years have witnessed limited advancements in pharmacotherapy for EDs. There remains an urgent need for rigorous clinical trials in this area in addition to increased prioritization of ED research at the public health level to overcome longstanding barriers in the treatment of EDs.

keywords:
Humans, Drug Approval, United States Food and Drug Administration, United States, Clinical Trials as Topic, Feeding and Eating Disorders

raw_json:
{"europe_pmc_id":"41313392","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: A Virtual Clinical Trial of Psychedelics to Treat Patients With Disorders of Consciousness.
publication_date: 2025-11-19
doi: 10.1002/advs.202511780
pubmed_id: 41261994
source_url: https://doi.org/10.1002/advs.202511780
substance_tags: psilocybin
topic_tags: Brain Imaging,Consciousness,Aging,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
authors:
Alnagger NLN, Cardone P, Martial C, Perl YS, Mindlin I, Sitt JD, Roseman L, Carhart-Harris R, Nutt D, Mallaroni P, Mason N, Ramaekers JG, Bonhomme V, Laureys S, Deco G, Gosseries O, Núñez P, Annen J.

abstract:
Disorders of consciousness (DoC), including unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS), have limited treatment options and are characterized by low complexity of brain activity. Recent research suggests that psychedelic drugs, which enhance the complexity of brain activity, could offer promising therapies. Here, individualized whole-brain computational models are developed for patients with DoC, optimized with empirical functional magnetic resonance imaging data and diffusion-weighted imaging data, upon which the administration of lysergic acid diethylamide (LSD) and psilocybin is simulated. An in silico perturbation protocol is applied to assess brain dynamics, first distinguishing between different states of consciousness, including DoC, anesthesia, and the psychedelic state. Then, brain dynamics are assessed before and after a simulation of psychedelic drugs on patients with DoC. Findings indicated that the simulation of LSD and psilocybin shifted the brain activity of patients with DoC closer to criticality (the point at a phase transition between order and chaos), with a greater effect in patients in the MCS. In patients with UWS, the treatment response correlated with structural connectivity, while in patients in the MCS, it aligned with baseline functional connectivity. These results offer a computational foundation for using psychedelics in DoC treatment and highlight the potential future role of computational modeling in drug discovery and personalized medicine.

keywords:
Brain, Humans, Consciousness Disorders, Lysergic Acid Diethylamide, Hallucinogens, Magnetic Resonance Imaging, Computer Simulation, Adult, Female, Male, Psilocybin

raw_json:
{"europe_pmc_id":"41261994","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Placebo Effects in the Treatment of Depression-Implications for the Psychedelic Renaissance.
authors: Ansari M, Elliott SI, Holmes SE, Sanacora G
journal: Neurologic clinics
publication_date: 2026-01-31
doi: 10.1016/j.ncl.2025.08.009
pubmed_id: 41232997
source_url: https://pubmed.ncbi.nlm.nih.gov/41232997/
keywords: Antidepressant, Ketamine, MDMA, Masking, Placebo, Psilocybin, Psychedelic, Unblinding
substance_tags: psilocybin
topic_tags: Depression,PTSD,Mechanism of Action,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 11:20:35
raw_json: {"pubmed_id":"41232997"}
abstract:
The development of novel, rapid-acting treatments and the resurgence of interest in the therapeutic potential of psychedelic-like compounds has stimulated excitement and enthusiasm within the pharmaceutical industry, and provided new hope for millions of individuals suffering with mental illness such as major depressive disorder and post-traumatic stress disorder. This review summarizes the scope and mechanisms of placebo related effects in depression treatment trials, with a particular focus on their implications for psychedelic-like compounds. We examine how expectancy, therapeutic setting, and trial design interact to shape outcomes and consider emerging approaches for mitigating, measuring, or even harnessing placebo-effects in future research.


journal: Neuropsychopharmacology Reports
publication_date: 2026-08-31
doi: 10.1002/npr2.70152
source_url: https://doi.org/10.1002/npr2.70152
substance_tags: psilocybin,psilocin
topic_tags: Depression,Anxiety,Receptor Pharmacology,Resilience,Animal Study,Treatment-Resistant Depression
study_type: Animal Study
source_name: Crossref
publication_status: published
date_added: 2026-07-01 06:48:03
last_checked: 2026-07-02 06:54:51
title:
Contribution of the Serotonin 5-HT2A Receptor to the Therapeutic Effect of Psilocin on Social Behavior Deficits in Mice Repeatedly Exposed to Social Defeat Stress

authors:
Ibi Daisuke, Takaba Rika, Yoshida Keisuke, Kawase Ririna, Kitagawa Hiroko, Matsushita Momoko, Ito Kana, Uno Shoya, Nishimura Fumiya, Kitagaki Shinji, Hiramatsu Masayuki

abstract:
ABSTRACT Psychedelics such as psilocybin and lysergic acid diethylamide (LSD) exert hallucinogenic effects through stimulation of serotonin 5-HT2A receptors (5-HT2ARs) in the cerebral cortex. In recent years, numerous reports have demonstrated that psychedelics are effective in treating various psychiatric disorders such as major depressive disorder (MDD), treatment-resistant depression (TRD), and anxiety-related disorders. We have previously reported that administration of psilocin, the active metabolite of psilocybin, produces antidepressant-like effects in mice. Furthermore, we found that this effect is mediated by 5-HT2AR activation. Since depression and other psychiatric disorders often lead to impairments in social behavior (e.g., social avoidance), the present study examined the effects of psilocin on social avoidance behavior in mice subjected to chronic social defeat stress (CSDS), a widely used model that closely models human psychosocial stress. Mice exposed to CSDS exhibited social avoidance behavior, whereas psilocin administration before the onset of CSDS had little effect on this behavior. In contrast, psilocin administration after the completion of CSDS ameliorated social avoidance in CSDS-exposed mice. This effect was blocked by pretreatment with a 5-HT2AR antagonist, indicating that psilocin exerts its therapeutic effects through 5-HT2AR activation. Taken together, psilocin exerts therapeutic effects on social avoidance behavior after stress through activation of 5-HT2AR, but not preventive effects when administered before stress, suggesting that psilocin may promote stress resilience rather than resistance.

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journal: Pharmacology, biochemistry, and behavior
publication_date: 2026-06-29
doi: 10.1016/j.pbb.2026.174231
pubmed_id: 42379524
source_url: https://pubmed.ncbi.nlm.nih.gov/42379524/
substance_tags: psilocin
study_type: Animal Study
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:03
last_checked: 2026-07-02 06:54:10
raw_json: {"pubmed_id":"42379524"}
title:
Chronic psilocin microdosing produces limited behavioral effects and does not enhance neurogenesis in rats.

authors:
Ladislavová L, Kútná V, Mazochová K, Šíchová K, Danda H, Lhotková E, Uttl L, Brejtr V, Syrová K, Mazoch V, Horsley R, Páleníček T

abstract:
Psilocin (4-hydroxy-N, N-dimethyltryptamine) is a substituted tryptamine alkaloid and a nonselective serotonergic agonist acting predominantly at 5-HT2A/C receptors, with substantial binding to 5-HT1A and 5-HT2B receptors. Microdosing is the practice of taking a very small, sub-perceptual dose, typically 5% to 10% of a full recreational dose, to improve mood, creativity, and focus without hallucinogenic effects. However, rigorous preclinical evidence for its behavioral and neurobiological effects remains limited. We therefore examined whether chronic psilocin microdosing alters behavior and dentate gyrus (DG) cell proliferation in adult male Wistar rats. Psilocin was administered subcutaneously at 0.05 or 0.075 mg/kg. Animals received six doses of psilocin or saline on alternate days over 18 days prior to the first behavioral assessment, and microdosing on alternate days continued between behavioral tasks for five weeks. To minimize acute drug effects, all behavioral assessments were performed 48 h after the preceding dose. Animals were tested sequentially in the Elevated Plus Maze, Hole-Board, Open Field, Social Interaction, and modified Forced Swim Test, with six-day intervals between tests. DG cell proliferation was quantified by BrdU and Ki-67 immunohistochemistry. Across this regimen, psilocin microdosing did not measurably affect locomotor activity, depressive-like behavior, sociability, or novelty seeking, and it did not increase DG proliferation by either marker. A small anxiogenic effect was detected in the Elevated Plus Maze. These data indicate that, under the present dosing schedule and endpoints, chronic psilocin microdosing produces limited behavioral effects and does not enhance hippocampal progenitor proliferation in rats.

keywords:
Anxiety, Behavioral testing, Depression, Hippocampal neurogenesis, Psilocin microdosing, Social interaction, Wistar rats

topic_tags:
Depression,Anxiety,Neurogenesis,Receptor Pharmacology,Biomarkers,Microdosing,Creativity,Animal Study,Drug Interactions


journal: PLOS One
publication_date: 2026-06-29
doi: 10.1371/journal.pone.0352246
source_url: https://doi.org/10.1371/journal.pone.0352246
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: Crossref
publication_status: published
date_added: 2026-07-01 06:48:03
last_checked: 2026-07-02 06:54:51
title:
Study Protocol for “Exploring the safety and therapeutic potential of psilocybin in the treatment of anorexia nervosa in adolescents and young adults”

authors:
Sjöström David, Schau Rybäck Olea, Claesdotter Knutsson Emma, Kajonius Petri, Jensen Sondén Oskar, Carlbring Per, Björkstrand Johannes, Movahed Rad Pouya

abstract:
Background Anorexia nervosa (AN) is a severe psychiatric disorder with high morbidity, mortality, and relapse rates, most commonly emerging during adolescence. Despite specialized psychological and nutritional treatments, outcomes remain suboptimal, with high rates of relapse and chronicity. Psilocybin has been investigated with preliminary efficacy in other psychiatric conditions characterized by rigidity and treatment resistance, but clinical evidence in AN-particularly in adolescents-is limited. Objective The psiAN study aims to evaluate the safety, tolerability, and feasibility of psilocybin therapy combined with psychological support in adolescents and young adults with relapsing AN, while exploring clinical, experiential, and neurobiological correlates of change. Methods A phase IIa, open-label, randomized controlled trial enrolling individuals aged 16-35 years with DSM-5 AN and a history of relapse. Participants are randomized to receive either two administrations of psilocybin (25 mg) with manualized psychological support plus treatment as usual (TAU), or TAU alone. Primary outcomes focus on safety and tolerability, assessed through adverse events, psychiatric monitoring, and medical parameters measured from first dosing to primary endpoint. Secondary outcomes include change in eating disorder symptom severity, relapse composite measures, mood, well-being, personality traits from baseline to primary endpoint with follow-up to 12 months. Functional magnetic resonance imaging (fMRI) and peripheral brain-derived neurotrophic factor are included as exploratory mechanistic measures. fMRI will evaluate pre- to post-intervention changes in structural and functional connectivity and task-related responses during a simplified Monetary Incentive Delay task (MIDT) and a Calorie-Cue Task (CCT). ClinicalTrials.gov Identifier: NCT07169747. Ethics and dissemination The study follows Good Clinical Practice (GCP), the Declaration of Helsinki, and EU Clinical Trials Regulation requirements, with staged inclusion of adolescents (16-17-year-olds) after a safety board review of adult data (18-35-year-olds). This protocol was prepared with reference to the SPIRIT 2025 guidelines (Chan et al., 2025) to enhance transparency and inform future trials.

topic_tags:
Eating Disorders,Brain Imaging,Aging,Wellbeing,Personality Change,Clinical Trial,Randomized Controlled Trial,Review Article,Adolescents,Safety,Adverse Events

raw_json:
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authors: Kramer HM, Hibicke M, Middleton J, Jaster AM, Kristensen JL, Nichols CD.
publication_date: 2025-11-12
doi: 10.1038/s41386-025-02272-3
pubmed_id: 41224969
source_url: https://doi.org/10.1038/s41386-025-02272-3
substance_tags: psilocybin
topic_tags: Neuroplasticity,Mechanism of Action,Receptor Pharmacology,Biomarkers,Animal Study
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:01
title:
Psychedelics produce enduring behavioral effects and functional plasticity through mechanisms independent of structural plasticity.

abstract:
Activation of serotonin 2A (5-HT2A) receptors is thought to underly the long-lasting antidepressant effects of psychedelics such as psilocybin, but beyond that, the molecular and cellular mechanisms involved are not well understood. Recent preclinical studies using mice have primarily examined relatively short time points after psychedelic administration, which does not address the long-lasting effects of psilocybin in humans (i.e., several months or more). We utilized a rat experimental system to demonstrate that both psilocybin and the selective 5-HT2A receptor agonist 25CN-NBOH reduce immobility in the forced swim test without a decrease in effect size for at least three months after a single administration of the psychedelic. There were no overt behavioral differences between psilocybin and 25CN-NBOH treated animals, suggesting 5-HT2A receptor activation is sufficient to produce long-lasting behavioral changes. Functional cellular plasticity in neurons from the medial prefrontal cortex (mPFC) of these animals was assessed using brain slice electrophysiology. Functional plasticity was evident for both psychedelics several months after treatment, and Layer 5 excitatory pyramidal neurons demonstrated significant changes in resting membrane potential, firing rates, and synaptic excitation. Recorded neurons were examined by microscopy for synaptic density and spine classification, which found no differences between control and psychedelic-treated. Gene expression studies for several presynaptic and postsynaptic markers in the mPFC indicated no differences in expression between groups. Together, our results indicate a single treatment with a psychedelic is sufficient to elicit very long-lasting behavioral and cellular changes through enduring function plasticity rather than structural plasticity.

keywords:
Prefrontal Cortex, Animals, Rats, Rats, Sprague-Dawley, Receptor, Serotonin, 5-HT2A, Hallucinogens, Behavior, Animal, Neuronal Plasticity, Male, Serotonin 5-HT2 Receptor Agonists, Psilocybin

raw_json:
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authors: Wolff M, Kangaslampi S.
publication_date: 2025-11-09
doi: 10.1016/j.jad.2025.120637
pubmed_id: 41224017
source_url: https://doi.org/10.1016/j.jad.2025.120637
substance_tags: psilocybin
topic_tags: Depression,Pharmacology,Biomarkers,Treatment-Resistant Depression
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
title:
Pharmacodynamic biomarker - or psychotherapeutic process? Comment on "The role of the psychedelic experience in psilocybin treatment for treatment-resistant depression".

raw_json:
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title: Psilocybin use in bipolar disorder: A comprehensive review.
authors: Do A, Cloutier L, Hébert-Tremblay L, Thauvin C.
publication_date: 2025-10-30
doi: 10.1016/j.jad.2025.120485
pubmed_id: 41177271
source_url: https://doi.org/10.1016/j.jad.2025.120485
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Addiction,Clinical Trial,Review Article,Safety,Adverse Events
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
abstract:
IntroductionBipolar disorder (BD) is a severe and persistent mental disorder characterized by recurrent mood episodes, with BD depression accounting for most of the illness burden. Although the mainstay treatment of BD consists of pharmacotherapy with mood stabilizers and atypical antipsychotics, a large proportion of patients with BD depression do not respond to adequate trials of medications. In addition, these medications can be associated with multiple, often significant adverse effects, highlighting the need for novel therapeutic agents that are acceptable, effective and safe for patients.MethodsWe performed a comprehensive narrative review on the use of psilocybin in BD, with a focus on clinical outcomes.ResultsTwo small clinical trials show that psilocybin combined with psychotherapy was safe and effective for the treatment of BDII depression with large treatment effects. No serious adverse events, including treatment-emergent mania/hypomania or increased suicidality, were reported in both trials. However, other studies have raised concerns about the safety of psilocybin in BD patients, including the development or worsening of manic symptoms, sleep disruptions and anxiety. Overall, the majority of BD patients believe that psilocybin could benefit their mental health problems, but their experiences varied depending on several contextual factors, such as polysubstance use, psilocybin dose, solo versus social experiences and pre-psilocybin sleep deprivation.ConclusionDespite its promising potential, the efficacy and safety of psilocybin in the treatment of BD depression remain unclear, and future research is essential to clarify its therapeutic value in BD.

keywords:
Humans, Hallucinogens, Treatment Outcome, Combined Modality Therapy, Bipolar Disorder, Psychotherapy, Psilocybin

raw_json:
{"europe_pmc_id":"41177271","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Ketamine, Psychedelics, and Psychotherapy: Reframing, Redefining, Renaming Treatment Models.
authors: Swainson J, Brietzke E, Khullar A, McIntyre RS, Soares CN
journal: Canadian journal of psychiatry. Revue canadienne de psychiatrie
publication_date: 2026-01-31
doi: 10.1177/07067437251389090
pubmed_id: 41148143
source_url: https://pubmed.ncbi.nlm.nih.gov/41148143/
substance_tags: psilocybin
topic_tags: Depression,Anxiety,PTSD,Mechanism of Action,Clinical Trial
study_type: Clinical Trial
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:20:35
raw_json: {"pubmed_id":"41148143"}
abstract:
There has been a renewed interest in the use of various psychedelic agents as potential therapies for multiple psychiatric conditions, including post-traumatic stress disorder (PTSD), major depressive disorder (MDD), generalized anxiety disorder (GAD), to name a few. This follows the recent accumulation of evidence for ketamine pharmacotherapy and a rapid proliferation of clinics/programs offering a variety of ketamine based treatments. A quick glance at the existing evidence, however, reveals a confusing scenario for patients, healthcare providers, and regulators. Overall, there are no standard definitions of what constitutes a psychotherapeutic intervention within a psychedelic-based or a ketamine-based treatment. More specifically, studies have not always distinguished between using a well-known, manualized psychotherapy, providing psychoeducation and psychological support, or providing a therapy specifically to integrate the drug experience in psychedelic trials. Also, it is difficult to determine the role of the psychedelic agent as a stand-alone treatment, and the relative importance (if any) of the psychedelic experience for the desired therapeutic effect. In this perspective, we discuss the evolving landscape of psychedelic-based and ketamine-based treatments, highlighting different therapeutic models, their methodologies, and the need for clearer definitions and rigorous clinical trials. The document proposes three new definitions to improve clarity in evaluating the effects of these agents and the role of psychotherapies. We suggest language that will distinguish: (1) when the drug is used for its pharmacologic effects as a stand-alone treatment, without requiring the psychedelic experience or combined psychotherapy; (2) when the treatment requires the acute psychological effects of the drug to assist psychotherapy and (3) When ketamine or a psychedelic agent is used in combination with a structured, manualized psychotherapy that could be implemented even in the absence of these agents. We hope that this new terminology and definitions will help distinguish the various therapeutic roles of these agents (as stand-alone treatments or in combination with psychotherapies), and facilitate study designs, regulatory pathways, and more informed patient care.Plain Language Summary TitleKetamine, Psychedelics, and Psychotherapy: Understanding treatment models to better inform practice.

keywords:
MDMA, PTSD, depression, ketamine, nomenclature, psilocybin, psychedelics, psychotherapy, terminology, therapy


title: Love (Drugs), Happiness, and Morality.
authors: Rakić V.
publication_date: 2025-10-26
doi: 10.1111/bioe.70043
pubmed_id: 41144801
source_url: https://doi.org/10.1111/bioe.70043
keywords: Humans, Meditation, Social Behavior, Happiness, Love, Morals
substance_tags: psilocybin
topic_tags: General
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
abstract:
Various authors, including myself, have argued that happiness and morality operate in a circularly supportive relationship. In this paper, love will be added to this relationship. The new triple correlation will be explored through the following lens: not only do love and happiness reinforce moral action, but they appear to be in a triple circularly supportive relationship. Moral behavior is frequently grounded in love; love encourages prosocial behavior; prosocial behavior increases happiness; happiness, in turn, enhances the inclination of most people to act morally most of the time. Argued from the opposite direction: happiness tends to encourage prosocial behavior in most people most of the time; prosocial behavior is conducive to the development of loving relationships; love induces us to behave morally toward the people we love. The argument presented here will also propose that this triple circular reinforcement can be significantly deepened and sustained through a careful use of love-enhancing substances, aided by guided meditation-particularly in the case of the psychedelic psilocybin. It will be concluded that humans will be motivated to use love drugs because they tend to increase their happiness. Consequently, a voluntary use of love drugs is a more effective means of moral (bio-)enhancement than is the prevention of "ultimate harm" that is based on compulsory moral enhancement.

raw_json:
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authors: Prochazkova L, Marschall J, Lippelt DP, Schon NR, Kuchař M, Hommel B.
publication_date: 2025-10-16
doi: 10.1016/j.neuropharm.2025.110722
pubmed_id: 41110634
source_url: https://doi.org/10.1016/j.neuropharm.2025.110722
substance_tags: psilocybin
topic_tags: Microdosing,Wellbeing,Emotional Processing
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Cognitive and subjective effects of psilocybin microdosing: Results from two double-blind placebo-controlled longitudinal trials.

abstract:
ObjectiveMicrodosing psychedelics has been widely reported to enhance focus and problem-solving, sparking interest in its potential to treat attentional disorders such as ADHD. However, existing studies largely rely on anecdotal evidence and lack adequate placebo control.MethodsThis study contributes to the literature by examining the longitudinal effects of microdosing psilocybin truffles in two randomized, double-blind, placebo-controlled trials conducted in semi-naturalistic settings. We assessed multiple domains, including cognitive control, memory, social cognition, subjective well-being and subjective experiences using a mix of quantitative and qualitative methods.ResultsContrary to expectations, microdosing did not significantly affect behavioral or subjective measures compared to placebo. While some initial effects were observed in social cognition, mood, and self-reported cognitive flexibility, these did not remain significant after correcting for multiple comparisons. Regardless of condition, participants predominantly reported their subjective experiences as positive yet negative bodily feelings were enhanced in the active condition. Notably, participants remained effectively blinded throughout the trials.DiscussionIn conclusion, our findings do not support the idea that microdosing psilocybin reliably enhances cognitive or emotional functioning beyond placebo. Future research should explore individual differences in response to microdosing and examine whether specific populations might benefit from targeted microdosing interventions.

keywords:
Humans, Hallucinogens, Longitudinal Studies, Double-Blind Method, Affect, Cognition, Adult, Female, Male, Young Adult, Psilocybin

raw_json:
{"europe_pmc_id":"41110634","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Contemplating versus having used psychedelics in bipolar disorder - What makes the difference?
authors: Vale LN, Ibrahim M, Fávaro-Pereira L, Soares JC, Meyer TD.
publication_date: 2025-10-16
doi: 10.1016/j.jad.2025.120437
pubmed_id: 41109422
source_url: https://doi.org/10.1016/j.jad.2025.120437
substance_tags: psilocybin
topic_tags: Personality Change,Clinical Trial,Observational Study
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
abstract:
In recent years psychedelics have gained popularity and potential promise in the field of mental health, but for patients diagnosed with bipolar disorder (BD), fears of emerging manic or psychotic symptoms have caused investigators to exclude them from psychedelic research. In this observational study, we explore the motivations, expectations, and personality characteristics of individuals with BD who have either used (i.e., experimenters) a classic psychedelic (i.e., psilocybin, LSD) or were considering using (i.e., contemplators) in the near future. We compared so-called experimenters to contemplators across various sociodemographic, psychological, and mental health variables. The groups did not differ in socio-demographic variables or mental health, however, experimenters demonstrated more positive attitudes towards psychedelics and more 'openness to experience.' Furthermore, certain motives for use were more strongly endorsed while contemplators expressed concerns about potential negative effects and outcomes. These findings highlight that previous psychedelic experience is associated with more positive perceptions and motivations for use, which might have also been shaped by the actual experience. While we do not advocate for unsupervised use of psychedelics outside of a clinical setting, the study provides some information what areas need to be discussed with individuals with BD who contemplate using psychedelics, even in the context of a clinical trial.

keywords:
Humans, Lysergic Acid Diethylamide, Hallucinogens, Motivation, Bipolar Disorder, Adult, Middle Aged, Female, Male, Young Adult, Psilocybin

raw_json:
{"europe_pmc_id":"41109422","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Compassionate use of psilocybin for treatment-resistant depression in Germany.
authors: Gründer G, Mertens LJ, Jungaberle A, Jungaberle H, Spangemacher M.
publication_date: 2025-09-17
doi: 10.1016/s2215-0366(25)00277-9
pubmed_id: 40976246
source_url: https://doi.org/10.1016/s2215-0366(25)00277-9
substance_tags: psilocybin
topic_tags: Depression,Treatment-Resistant Depression
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:02
raw_json:
{"europe_pmc_id":"40976246","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: The Use of Psilocybin in the Treatment of Depressive Disorders: A Narrative Review.
publication_date: 2026-01-30
doi: 10.7759/cureus.102694
pubmed_id: 41777966
source_url: https://doi.org/10.7759/cureus.102694
substance_tags: psilocybin
topic_tags: Depression,Receptor Pharmacology,Review Article,Drug Interactions
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
authors:
Siwek L, Nowocien M, Balajewicz B, Samborska A, Szukalska S, Karczewska M, Lichwala K, Wróblewski K, Wróblewska P.

abstract:
Psilocybin is a psychoactive chemical compound that exerts its effects through the activation of serotonergic receptors. It occurs naturally in mushrooms of the genus Psilocybe. Despite its potential medical applications, this substance is regarded as a drug with no recognized medical use. Depression constitutes a psychiatric disorder of substantial global burden, affecting millions of individuals worldwide, with epidemiological data indicating a continuing upward trend in its prevalence. It is a complex disease entity that, despite years of research, remains not fully understood and constitutes a significant therapeutic challenge. Its pathogenesis is based on the interaction of biological, environmental, and social factors. It is estimated that by the year 2030, depression will become the leading cause of disability. The concern associated with this projection, together with human curiosity, has formed the foundation of numerous scientific studies conducted in recent years, aimed at identifying a breakthrough therapeutic approach that would expand the range of treatment options available to psychiatrists. The aim of this paper is to present the most recent reports on attempts to use the controversial substance psilocybin in the treatment of depression. Owing to promising research results demonstrating high therapeutic efficacy in comparison with conventional, currently recommended treatments, psilocybin-assisted therapy offers hope for the development of a modern therapeutic approach that provides the expected clinical outcomes, with a proven and more sustained therapeutic effect in treated patients, as well as a minimal number or complete absence of adverse effects.

raw_json:
{"europe_pmc_id":"41777966","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Kristensen J.
publication_date: 2026-01-30
doi: 10.1038/s41398-026-03844-7
pubmed_id: 41620438
source_url: https://doi.org/10.1038/s41398-026-03844-7
substance_tags: psilocybin
topic_tags: Pharmacology,Mechanism of Action
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:02
title:
Regarding "The molecular mechanisms through which psilocybin prevents suicide: evidence from network pharmacology and molecular docking analyses".

raw_json:
{"europe_pmc_id":"41620438","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Improving Access to Psilocybin-Assisted Therapy: Barriers, Challenges, and Recommendations
authors: Tsang V, Roney C.
publication_date: 2024-08-26
source_url: https://europepmc.org/article/PMC/PMC11861878
substance_tags: psilocybin
topic_tags: General
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
raw_json:
{"europe_pmc_id":"PMC11861878","source":"PMC","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: High hopes? Precision psychedelic addiction medicine.
authors: Zafar RR, Kleine P, Kurtin D, Wall M, Erritzoe D.
publication_date: 2026-01-27
doi: 10.3389/fpsyt.2025.1681795
pubmed_id: 41684524
source_url: https://doi.org/10.3389/fpsyt.2025.1681795
substance_tags: psilocybin
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
abstract:
Despite decades of neuroscience research and significant investment in addiction neuroimaging, clinical outcomes for individuals with substance use and behavioural addictions remain poor. Only 1.8% of people with substance use disorders receive effective treatment, highlighting a major disconnect between mechanistic understanding and clinical utility. This paper calls for a reorientation of addiction neuroscience, from a predominantly diagnostic focus toward a theragnostic framework, in which biomarkers are used to stratify patients, guide treatment decisions, and predict outcomes. We argue that the integration of translational neuroimaging biomarkers, particularly fMRI, EEG, and PET, within psychedelic addiction research offers a unique and timely opportunity to catalyse this shift. Psychedelic compounds such as psilocybin represent a new class of therapeutics capable of engaging neuroplasticity, reward and emotional processing, and cognitive control networks central to addiction pathophysiology. We review how acute and pre-post neuroimaging paradigms can index pharmacodynamic effects and longer-term treatment response and propose a roadmap for embedding biomarkers in early and late phase clinical trials. Drawing on ongoing studies at the Centre for Psychedelic Research at Imperial College London, we outline how multimodal biomarkers are being co-developed alongside clinical trials in gambling and opioid use disorders to identify biotype-specific responses and build a deeply phenotyped treatment population. We argue that these biomarkers, if validated, could serve as regulatory-grade tools for drug theragnostic co-development, mirroring successful models in oncology and neurology. Importantly, we emphasise that realising this vision will require robust multi-stakeholder collaboration, including academia, industry, regulatory agencies, funders, healthcare systems, and patient groups alongside dedicated investment to build a scalable theragnostic infrastructure for addiction research and medicine. In conclusion, psychedelic therapy offers more than symptomatic relief, it presents a vehicle for transforming how we diagnose, treat, and understand addiction. By embracing theragnostic principles and prioritising biomarker integration, addiction medicine has the potential to move towards personalised and precision-guided care.

topic_tags:
Addiction,Neuroplasticity,Brain Imaging,Pharmacology,Biomarkers,Aging,Emotional Processing,Clinical Trial,Review Article,Cancer Patients

raw_json:
{"europe_pmc_id":"41684524","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: A Promise Without Panacea: Psychedelic-Assisted Therapies in Modern Psychiatry.
authors: Raza M, Kaur J.
publication_date: 2026-01-26
doi: 10.7759/cureus.102421
pubmed_id: 41769492
source_url: https://doi.org/10.7759/cureus.102421
substance_tags: psilocybin
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:02
abstract:
Psychedelic-assisted therapies have re-emerged as a subject of increasing scientific and clinical interest in psychiatry, particularly in the context of persistent treatment gaps for conditions such as treatment-resistant depression, post-traumatic stress disorder, and substance use disorders. Compounds, including psilocybin and 3,4-methylenedioxymethamphetamine, are being evaluated in controlled clinical trials and have demonstrated promising therapeutic effects when administered within structured psychotherapeutic frameworks. Emerging neurobiological evidence suggests that these agents may promote neural plasticity and facilitate cognitive and emotional flexibility, potentially enabling durable clinical improvement. Despite these advances, significant challenges remain, including regulatory uncertainty, methodological limitations in existing trials, ethical considerations related to patient vulnerability, and concerns regarding equitable access. This editorial examines the current state of psychedelic-assisted therapies, highlighting both their therapeutic potential and the critical considerations required for their responsible integration into mental health settings.

topic_tags:
Depression,PTSD,Addiction,Neuroplasticity,Emotional Processing,Clinical Trial,Treatment-Resistant Depression

raw_json:
{"europe_pmc_id":"41769492","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Gregory NS, Girard TE, Ram A, Casey AB, Malenka RC, Tawfik VL, Heifets BD.
publication_date: 2026-01-21
doi: 10.1038/s41467-026-68763-z
pubmed_id: 41565674
source_url: https://doi.org/10.1038/s41467-026-68763-z
substance_tags: psilocybin
topic_tags: Chronic Pain,Animal Study,Inflammation
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
No evidence of immediate or persistent analgesic effect from a single dose of psilocybin in three mouse models of pain.

abstract:
The psychedelic psilocybin may have lasting therapeutic effects for patients with chronic pain syndromes. Some preclinical data suggest these putative benefits derive from direct analgesic effects; however, this possibility has not been comprehensively tested in preclinical models. Here, we evaluated the analgesic properties of a single exposure to psilocybin at acute and chronic time points in Complete Freund's Adjuvant-induced inflammatory pain, spared nerve injury model of neuropathic pain, and acid-induced muscle pain. Across these models, we tested a range of doses (0.3, 2, and 10 mg/kg i.p.) in male and female mice using multiple behavioral assays evaluating sensory aspects (von Frey, cold plate, Hargreaves, thermal place preference, and muscle withdrawal threshold) and functional aspects of pain (marble burying). We further tested the effects of psilocybin on the affective dimension of pain in a surgical model of acute pain (mouse grimace scale). Except for cold sensitivity, we found no effect of psilocybin across pain models, behavioral assays, drug doses, or sex. The apparent reduction in cold sensitivity may be explained by profound hypothermia induced by psilocybin rather than true analgesia.

keywords:
Animals, Mice, Inbred C57BL, Mice, Pain, Neuralgia, Disease Models, Animal, Analgesics, Hallucinogens, Freund's Adjuvant, Pain Measurement, Behavior, Animal, Dose-Response Relationship, Drug, Female, Male, Psilocybin

raw_json:
{"europe_pmc_id":"41565674","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin triggers an activity-dependent rewiring of large-scale cortical networks.
publication_date: 2025-12-04
doi: 10.1016/j.cell.2025.11.009
pubmed_id: 41352354
source_url: https://doi.org/10.1016/j.cell.2025.11.009
substance_tags: psilocybin
topic_tags: Neuroplasticity,Default Mode Network,Animal Study
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
authors:
Jiang Q, Shao LX, Yao S, Savalia NK, Gilbert AD, Davoudian PA, Nothnagel JD, Tian G, Hung TS, Lai HM, Beier KT, Zeng H, Kwan AC.

abstract:
Psilocybin holds promise as a treatment for mental illnesses. One dose of psilocybin induces structural remodeling of dendritic spines in the medial frontal cortex in mice. The dendritic spines would be innervated by presynaptic neurons, but the sources of these inputs have not been identified. Here, using monosynaptic rabies tracing, we map the brain-wide distribution of inputs to frontal cortical pyramidal neurons. We discover that psilocybin's effect on connectivity is network specific, strengthening the routing of inputs from perceptual and medial regions (homolog of the default mode network) to subcortical targets while weakening inputs that are part of cortico-cortical recurrent loops. The pattern of synaptic reorganization depends on the drug-evoked spiking activity because silencing a presynaptic region during psilocybin administration disrupts the rewiring. Collectively, the results reveal the impact of psilocybin on the connectivity of large-scale cortical networks and demonstrate neural activity modulation as an approach to sculpt the psychedelic-evoked neural plasticity.

keywords:
Pyramidal Cells, Cerebral Cortex, Frontal Lobe, Nerve Net, Dendritic Spines, Animals, Mice, Inbred C57BL, Mice, Hallucinogens, Neuronal Plasticity, Male, Psilocybin

raw_json:
{"europe_pmc_id":"41352354","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Chwyl C, Spata A, Lucas W, Luoma JB.
publication_date: 2026-01-20
doi: 10.1186/s40359-025-03921-4
pubmed_id: 41566347
source_url: https://doi.org/10.1186/s40359-025-03921-4
substance_tags: psilocybin
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Mindset over molecule: comparing self-transcendent and mystical experiences across recreational psilocybin, MDMA, and cannabis use.

abstract:
BackgroundSelf-transcendent and mystical experiences may be key mechanisms underlying psychedelics' therapeutic effects, yet how these experiences differ across substances remains unclear. This study compared mystical and self-transcendent experiences across psilocybin, 3,4-Methylenedioxymethamphetamine (MDMA), and cannabis in a diverse, community-based sample, while accounting for covariates. Additionally, we examined the relative contributions of pharmacological versus psychological factors in shaping self-transcendent and mystical experiences.MethodsAdults aged 18 years and older (N = 397) were recruited with general, non-psychedelic-targeted advertisements on a crowdsourcing platform, and randomized to report on their most intense use experience with either cannabis, psilocybin or MDMA in the past five years. Participants completed measures of self-transcendent and mystical experiences, emotions, and variables previously found to predict mystical experiences (e.g., personality traits, motivations for use, intentions/expectations for the experience). Hierarchical multiple linear regressions examined the effects of substance type (cannabis/psilocybin/MDMA) on outcomes, both alone and while adjusting for contextual (set/setting) variables.ResultsMost of the sample reported recreational reasons for use (83%) and concurrently used other substances (75%). Psilocybin and MDMA corresponded to greater self-transcendent and mystical experiences than cannabis, even after controlling for contextual factors. However, effect sizes were generally small (standardized regression coefficients β = 0.14 - 0.34, ps.33). Notably, mindset-particularly surrendering to the experience and having spiritual/prosocial motivations-emerged as the strongest predictors, with models including these variables accounting for up to 58% of variance (compared to ≤ 10% for substance alone).ConclusionsFindings indicate a "mindset-over-molecule" pattern wherein psychological context ("set") is more strongly associated with psychedelic outcomes than substance type alone.

keywords:
Humans, Cannabis, N-Methyl-3,4-methylenedioxyamphetamine, Hallucinogens, Mysticism, Adolescent, Adult, Middle Aged, Female, Male, Young Adult, Psilocybin, Marijuana Use, Recreational Drug Use

topic_tags:
Mechanism of Action,Personality Change,Emotional Processing,Spirituality,Mystical Experience,Adolescents

raw_json:
{"europe_pmc_id":"41566347","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psychedelic Modulation of Excitation/Inhibition Balance: A Dual-Phase Neurodevelopmental Model.
authors: Kandilakis CL, Papatheodoropoulos C.
publication_date: 2026-01-06
doi: 10.1021/acschemneuro.5c00892
pubmed_id: 41498818
source_url: https://doi.org/10.1021/acschemneuro.5c00892
keywords: Brain, Animals, Humans, Hallucinogens, Neural Inhibition, Neuronal Plasticity, Neurodevelopment
substance_tags: psilocybin
topic_tags: Neuroplasticity,Mechanism of Action,Emotional Processing,Animal Study
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
abstract:
Psychedelics are a diverse class of psychoactive compounds that profoundly alter perception, cognition, and emotional states. Recently, classical serotonergic agents, such as psilocybin and lysergic acid diethylamide (LSD), along with atypical agents such as methylenedioxymethamphetamine (MDMA, ecstasy) and ibogaine, have attracted renewed attention due to their rapid and sustained clinical effects in psychiatric disorders. Preclinical and clinical studies indicate that serotonergic psychedelics acutely modulate glutamatergic and GABAergic transmission, enhance neuroplasticity, and reorganize brain network connectivity. However, a unified mechanistic framework linking these effects to enduring clinical outcomes remains elusive. Here, we propose a neurodevelopmental hypothesis in which psychedelics restore excitation/inhibition (E/I) balance, a fundamental property of both neurodevelopment and adult brain function. Acutely, psychedelics shift E/I dynamics through serotonergic and nonserotonergic mechanisms, creating a transient state of heightened plasticity similar to developmental sensitive periods. This permissive window facilitates the long-term reorganization of excitatory and inhibitory circuits with GABAergic interneurons as key mediators. By integrating established pharmacological effects with developmental principles, our dual-phase model links initial network excitability with subsequent neuroplasticity and circuit stabilization, providing a coherent framework for the rapid onset and sustained efficacy of psychedelic interventions across psychiatric disorders.

raw_json:
{"europe_pmc_id":"41498818","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Snapshot IP1 Detection Following 5-HT2A Receptor Stimulation in the Mouse Brain.
authors: de la Fuente Revenga M, González-Maeso J.
publication_date: 2026-01-01
doi: 10.1021/acschemneuro.5c00932
pubmed_id: 41481361
source_url: https://doi.org/10.1021/acschemneuro.5c00932
substance_tags: psilocybin
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:04
abstract:
The distinct subjective effects that define psychedelics such as lysergic acid diethylamide (LSD), psilocybin, or 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) as drug class are causally linked to the activation of the serotonin 2A receptor (5-HT2AR). However, some aspects of 5-HT2AR pharmacology remain elusive, such as what molecular drivers differentiate psychedelic from nonpsychedelic 5-HT2AR agonists. We developed an ex vivo platform to obtain snapshots of drug-mediated 5-HT2AR engagement of the canonical Gq/11 pathway in native tissue. This nonradioactive methodology captures the pharmacokinetic and pharmacodynamic events leading up to changes in inositol monophosphate (IP1) in the mouse brain. The specificity of this method was assessed in homogenates from the frontal cortex in DOI-treated wild-type and 5-HT2AR knockout (5-HT2AR-KO) animals compared to other brain regions, namely, striatum and cerebellum. The effect of DOI on mouse frontal cortex IP1 was time-bound, dose-dependent, and was correlated to head twitch response counts. We observed that IP1 levels in frontal cortex homogenates from mice treated with LSD and lisuride varying in magnitude, consistent with LSD's 5-HT2AR agonism and psychedelic nature and lisuride's lack thereof. 3,4-Methylenedioxymethamphetamine (MDMA) evoked an increase in the IP1 signal in the frontal cortex that was not matched by the serotonin precursor 5-hydroxytryptophan or the serotonin reuptake inhibitor fluoxetine. We attribute the differences in the readout primarily to the indirect stimulation of 5-HT2AR by MDMA via the release of serotonin from its presynaptic terminals. This methodology enables one to capture a snapshot of IP1 turnover in the mouse brain that can provide mechanistic insights into the study of psychedelics and Gq/11-coupled receptors.

keywords:
Brain, Animals, Mice, Inbred C57BL, Mice, Inositol Phosphates, Amphetamines, Lysergic Acid Diethylamide, Receptor, Serotonin, 5-HT2A, Hallucinogens, Male, Serotonin 5-HT2 Receptor Agonists

topic_tags:
End-of-Life Distress,Neuroplasticity,Pharmacology,Mechanism of Action,Receptor Pharmacology,Animal Study

raw_json:
{"europe_pmc_id":"41481361","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Presence of 4-Hydroxy-N-methyl-N-ethyltryptamine in Commercially Available Products.
authors: Barovic A, Pittiglio MK, Barrett JM, Aretz CDJ, Tesfatsion TT, Ramirez GA, Cruces W.
publication_date: 2026-01-06
doi: 10.1021/acsomega.5c10889
pubmed_id: 41585657
source_url: https://doi.org/10.1021/acsomega.5c10889
substance_tags: psilocin
topic_tags: General
study_type: Qualitative Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:02
abstract:
Novel psychoactive substances (NPS) remain an ongoing challenge for public health, forensic laboratories, and regulatory agencies, especially when they are chemically related to controlled tryptamines but are marketed as legal alternatives. In the United States, the Federal Analogue Act (FAA) was intended to restrict such substances; however, regulatory loopholes continue to be exploited. Herein, we present the characterization of a commercially available tablet marketed under the brand name Party Duck, alongside an unlabeled powder provided by our laboratory. Samples were analyzed using nuclear magnetic resonance (NMR) spectroscopy, gas chromatography/mass spectrometry (GC/MS), and liquid chromatography/mass spectrometry (LC/MS). All materials were identified to contain 4-hydroxy-N-methyl-N-ethyltryptamine (4-HO-MET), a synthetic psychedelic structure and pharmacologically similar to psilocin. The mean concentration of 4-HO-MET in the tablets was determined to be 2.82 or 1.45 mg/tablet, while the powder was confirmed qualitatively to contain the same compound. These findings demonstrate that 4-HO-MET is present in commercially available products and emphasize the importance of rigorous analytical methods for continuous monitoring of tryptamine derivatives in unregulated markets.

raw_json:
{"europe_pmc_id":"41585657","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Xia K, Gao T.
publication_date: 2025-12-31
doi: 10.12122/j.issn.1673-4254.2026.01.01
pubmed_id: 41540686
source_url: https://doi.org/10.12122/j.issn.1673-4254.2026.01.01
keywords: Humans, Hallucinogens, Antidepressive Agents, Depression, Psilocybin
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
title:
[Clinical application and mechanistic studies of psychedelics for treatment of depression: progress and future challenges].

abstract:
Depression is a complex and globally prevalent mental disorder, for which conventional antidepressant medications face limitations such as delayed onset and insufficient efficacy. Classic psychedelics, most notably psilocybin, have recently emerged as promising candidates for treatment of depression and demonstrated rapid, robust, and sustained antidepressant effects in controlled clinical settings. Their unique mechanisms of action and clinical prospects have become a key research focus in psychiatry and neuroscience. This review synthesizes the latest advances in the field over the past 5 years. Results from multiple randomized controlled trials indicate that a single or limited number of sessions of psychedelic-assisted psychotherapy can induce rapid and durable antidepressant effects in patients with treatment-resistant depression. At the mechanistic level, psychedelics rapidly promote the release of neurotrophic factors, enhance neuroplasticity, and facilitate brain network reorganization, thereby creating a critical "neuroplastic window" for psychotherapeutic intervention. However, the specific molecular and circuit-level mechanisms have not been fully understood with ongoing debate primarily over the 5-HT2A receptor-dependent hypothesis versus the TrkB neurotrophic pathway-dependent hypothesis. Despite the promising outlook, translational applications of these substances faces several key challenges, including psychedelic-related risks, incomplete mechanistic understanding, lack of standardized treatment protocols, and insufficient long-term safety data. Future research should focus on elucidating the underlying neurobiological mechanisms, developing non-hallucinogenic derivatives, establishing standardized treatment frameworks, and identifying precise biomarkers to advance this therapeutic approach toward safer, more standardized, and personalized clinical implementation.

topic_tags:
Depression,Neuroplasticity,Mechanism of Action,Receptor Pharmacology,Biomarkers,Randomized Controlled Trial,Review Article,Treatment-Resistant Depression,Safety

raw_json:
{"europe_pmc_id":"41540686","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: He MQ, Yang WQ, Phurbu D, Liu F, Li JX, Cao B, Zhao RL.
publication_date: 2026-01-18
doi: 10.3897/imafungus.17.167329
pubmed_id: 41607716
source_url: https://doi.org/10.3897/imafungus.17.167329
substance_tags: psilocybin
topic_tags: Genomics
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
﻿Systematic study of Panaeolus (Agaricales, Galeropsidaceae) sensu lato and psilocybin-producing traits of species from China.

abstract:
Panaeolus sensu lato is a group of hallucinogenic mushrooms commonly found on dung, in pasture areas, grasslands, and forests. Previous studies indicated that the Panaeolus s.l. clade (panaeo-clade) could be ranked as a family (Galeropsidaceae), pending further evidence. In this study, based on phylogenomic, multigene phylogenetic, molecular clock, and morphological analyses, the panaeo-clade is demonstrated to be a distinct family, separate from Bolbitiaceae. The taxonomic system of Galeropsidaceae is revised. The genera accepted in Galeropsidaceae are Panaeolus and Staktophyllus, whereas Crucispora and Panaeolopsis are synonymized under Panaeolus. Three subgenera are accepted in Panaeolus: subg. Bresadolomyces, subg. Panaeolina, and subg. Panaeolus. Subgenus Bresadolomyces is roughly equivalent to the traditional circumscription of subg. Copelandia but is extended to include species formerly placed in Crucispora. Subgenus Panaeolina comprises most species from China and Anellaria-like species. Subgenus Panaeolus mainly comprises the P. papilionaceus species complex and a western Asian clade represented by P. punjabensis. In this study, one new subgenus and eight new species are proposed. Species from China are documented with descriptions, photographs, and illustrations. Additionally, the psilocybin-producing traits of 14 species were tested using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS). Two species are confirmed to possess psilocybin-producing traits, namely the known species P. cinctulus and the new species P. subfoenisecii proposed in this study. The evolution of the coprophilous lifestyle and psilocybin-producing traits in Panaeolus is also discussed based on phylogenetic relationships and divergence times.

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publication_date: 2025-10-09
doi: 10.1016/j.jad.2025.120352
pubmed_id: 41075579
source_url: https://doi.org/10.1016/j.jad.2025.120352
substance_tags: psilocybin
topic_tags: Depression,Treatment-Resistant Depression
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
title:
Corrigendum to "The role of the psychedelic experience in psilocybin treatment for treatment-resistant depression" [Journal of Affective Disorders, Volume 372 (2025), Pages 523-532].

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

raw_json:
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authors: Sabbah SG, Li S, Wong S, Le GH, Badulescu S, Hawco C, Rosenblat JD, McIntyre RS.
publication_date: 2025-09-14
doi: 10.1016/j.jad.2025.120335
pubmed_id: 40962065
source_url: https://doi.org/10.1016/j.jad.2025.120335
substance_tags: psilocybin
study_type: Systematic Review
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:01
title:
Temporal dynamics in neuroimaging as correlates of therapeutic response to psilocybin in major depressive disorder: A systematic review and critical appraisal.

abstract:
BackgroundPsychedelics are emerging as promising treatments for major depressive disorder (MDD) and treatment-resistant depression (TRD). Functional magnetic resonance imaging (fMRI) offers a powerful tool to study neural mechanisms underlying therapeutic response.MethodsThis systematic review (PROSPERO #CRD42024557973) examined neuroimaging studies of psilocybin in MDD and TRD, with a focus on the temporal evolution of neuroimaging changes post-treatment. A secondary aim was to correlate imaging findings with validated clinical outcomes to assess their relevance in predicting treatment response.ResultsEleven eligible studies were included, using diverse fMRI modalities such as resting-state functional connectivity, task-based BOLD imaging, amplitude of low-frequency fluctuations (ALFF), dynamic functional connectivity, and magnetic resonance spectroscopy. Early (0-4 weeks) post-treatment changes included reduced network modularity and increased global brain integration, alongside modulation of affective circuits involving the amygdala, default mode network, and prefrontal regions. These changes were significantly associated with reductions in BDI, QIDS, and SHAPS scores, reflecting improvements in mood and anhedonia. Longer-term changes (5+ weeks) involved sustained reorganization of large-scale networks, particularly increased connectivity between the prefrontal and parietal cortices and salience network.ConclusionsAlthough these findings suggest psilocybin is associated with dynamic and temporally distinct neuroplastic changes linked to clinical improvement, several limitations must be acknowledged. Many studies reused overlapping datasets with high exploratory flexibility and risk of bias. The generalizability of results is therefore constrained. Future research should emphasize independent datasets, pre-registered imaging endpoints, and longitudinal designs to clarify the mechanisms underlying psychedelic therapy for depression.

keywords:
Brain, Humans, Hallucinogens, Magnetic Resonance Imaging, Treatment Outcome, Neuroimaging, Depressive Disorder, Treatment-Resistant, Psilocybin, Major Depressive Disorder

topic_tags:
Depression,Brain Imaging,Mechanism of Action,Default Mode Network,Aging,Systematic Review,Review Article,Treatment-Resistant Depression,Safety

raw_json:
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authors: Sobieraj J, Sleziak J, Szyszka M, Błażejewska M, Łukańko K, Soczomska P, Bodziony K, Piotrowski P.
publication_date: 2026-01-07
doi: 10.3389/fpubh.2025.1734137
pubmed_id: 41584153
source_url: https://doi.org/10.3389/fpubh.2025.1734137
substance_tags: psilocybin
topic_tags: Depression,Aging,Observational Study,Adolescents,Safety,Adverse Events
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:04
title:
Self-administered complementary and alternative methods of treating mental disorders among students in Wrocław: a cross-sectional study.

abstract:
IntroductionMental health disorders such as depression are a rising issue among university students. Some of them use complementary and alternative medicine (CAM) as self-administered therapy instead of or together with professional care. Defining the scale of the problem, its underlying reasons and possible implications are crucial for addressing it in clinical psychiatry and public health strategies.MethodsA cross-sectional survey on students from Wrocław universities was conducted between April 2024 and December 2024. The form developed specifically for this study contained questions about demographic status, respondents' mental health history, satisfaction with psychiatric or psychological help and factors affecting it. Survey also assessed experience and attitudes towards various CAM methods, including non-pharmacological like exercise, meditation, yoga and pharmacological such as herbs, e.g., st. John's wort (Hypericum perforatum), supplements, psychedelics, fly agaric (Amanita muscaria), marijuana and other non-conventional therapies. To evaluate current depressive symptoms, questions modelled on the Patient Health Questionnaire (PHQ-10) were used. 493 responses were included in the statistical analysis.Results46.5% of respondents had a history of mental disorders, with depression being the most prevalent (74.7%). While 45.3% of all students reported consultations with a psychiatrist and 44.8% usage of antidepressants, 96.1% applied CAM, mainly: physical exercise (81.4%), meditation (60.5%), yoga (39.1%). From herbs, the most popular were Melissa officinalis (53.0%) and Withania somnifera (24.8%), and from other substances: marijuana (31.3%), vitamins (22.5%) and psychedelics (10.4%). The main obstacles we identified in obtaining professional care were cost (80.7%), availability (35.7%) and fear of stigma (30.7%). Acceptance for classic therapies varied from 81.2% for psychotherapy and 75.9% for psychiatric drugs to 16.2% for electroconvulsive therapy (ECT). The factors affecting propensity to use particular CAM modalities included sex and severity of disorder. Females preferred herbs, probiotics and vitamins, while more males reported intake of A. muscaria. We found that among those students who engaged in professional health care services, there was significantly higher usage of marijuana, vitamins and probiotics. What's more, users of marijuana, ashwagandha and st. John's wort presented more intense depressive symptoms, based on PHQ-10. In the case of marijuana, its use is more prevalent among yoga practitioners and students with attention deficit hyperactivity disorder (ADHD). Consumption of psychedelics, marijuana and meditating is also connected to higher acceptance for novel therapies, such as ketamine and psilocybin, and practising yoga-for ketamine alone.ConclusionPrevalence of CAM use among students is high. One of the reasons we identified is limited access to professional psychiatric help. Use of CAM without supervision may potentially lead to adverse events. Psychiatrists treating students should consider those risks. Public health strategies should include educating students about CAM and classic therapies such as ECT, developing clinical guidelines for managing patients who use CAM and improving accessibility to mental health care for students. Future research should focus on studying the issue in other communities and populations, as well as precisely assessing the risks and potential benefits of particular CAM methods.

keywords:
Humans, Complementary Therapies, Cross-Sectional Studies, Mental Disorders, Students, Universities, Adolescent, Adult, Poland, Female, Male, Young Adult, Surveys and Questionnaires

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authors: Renner AC, Kargbo RB.
publication_date: 2025-12-15
doi: 10.1021/acsmedchemlett.5c00714
pubmed_id: 41531985
source_url: https://doi.org/10.1021/acsmedchemlett.5c00714
substance_tags: psilocybin
topic_tags: Brain Imaging,Pharmacology,Receptor Pharmacology,Biomarkers
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Advances in Psychedelic Therapeutics: Multimodal Iboga Analogs, EEG-Guided Psilocybin Dosing, and Optimized Harmine-DMT Formulations.

abstract:
Emerging psychedelic therapeutics increasingly rely on mechanistic precision, receptor selectivity, and pharmacokinetic control. Recent inventions introduce simplified iboga analogs with tunable polypharmacology, real-time EEG biomarkers that individualize psilocybin dosing, and standardized harmine-DMT ratios with high bioavailability. Together, these innovations form a coherent framework for safer, more reliable, and clinically actionable psychedelic medicines.

raw_json:
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authors: Mitchell J, Neitzke-Spruill L, Mathai DS, Robinson JO, Kavan Z, Averil LA, McGuire AL.
publication_date: 2025-12-31
doi: 10.1093/tbm/ibag027
pubmed_id: 42152689
source_url: https://doi.org/10.1093/tbm/ibag027
substance_tags: psilocybin
topic_tags: Depression,PTSD,Addiction,Clinical Trial,Treatment-Resistant Depression
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
title:
From trials to clinics: investigators' perspectives on translating psychedelic research into clinical care.

abstract:
BackgroundPsychedelics such as 3,4-methylenedioxymethamphetamine (MDMA) and psilocybin are showing promising results in clinical trials for the treatment of mental health disorders, including post-traumatic stress disorder, addiction, and treatment-resistant depression. US Food and Drug Administration approval may be on the horizon. Yet, little is known about how these treatments will move from tightly controlled clinical trials to routine clinical care.PurposeThis study examines how psychedelic clinical investigators anticipate this transition and what challenges they expect.MethodsWe conducted semi-structured interviews with 21 clinical investigators based at major academic psychedelic research centers across the United States. We transcribed and analyzed these conversations using inductive and deductive coding to identify major themes.ResultsInvestigators generally viewed psychedelic medicine as distinct from existing treatments, particularly in terms of drug effects, treatment models, and broader goals. They highlighted three major translational challenges: (i) uncertainty surrounding the role of psychotherapy, (ii) the cost of treatment and its scalability, and (iii) the effects of both hype and stigma on clinical uptake.ConclusionDespite these challenges, most investigators anticipated that psychedelic medicine could eventually fit into routine clinical care and may even improve it.

keywords:
Humans, N-Methyl-3,4-methylenedioxyamphetamine, Hallucinogens, Mental Disorders, Psychotherapy, Research Personnel, United States, Female, Male, Clinical Trials as Topic, Psilocybin, Translational Research, Biomedical

raw_json:
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title: Associations of Couples' Psychedelic Use with Shared Reality and Relational Well-Being.
authors: Cornelius T, Barba T.
publication_date: 2026-01-05
doi: 10.1080/02791072.2025.2607729
pubmed_id: 41496490
source_url: https://doi.org/10.1080/02791072.2025.2607729
substance_tags: psilocybin
topic_tags: Mechanism of Action,Wellbeing,Emotional Processing,Observational Study
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:02
abstract:
The resurgence in research with classic psychedelics (e.g. LSD, psilocybin) underscores their potential for improved well-being; however, the interpersonal context and mechanisms of psychedelic impacts remain unknown. In a sample of 798 participants (81 couples), this survey study tested whether use of a psychedelic with a romantic partner (v. not together) was associated with couples' shared understanding (i.e. shared reality) and changes in relational well-being. Multilevel dyadic analyses provided overwhelming support for hypotheses that taking a psychedelic together would be associated with greater shared reality and more positive relational changes (e.g. improved physical intimacy, emotional closeness, satisfaction). Shared reality mediated positive relational changes. Taking a psychedelic alone was indirectly associated with the decision to end a romantic relationship. Although limited by cross-sectional design and low dyadic participation, results emphasize the importance of a socially informed approach to the development of psychedelic therapies, with potential to increase treatment effectiveness and mitigate harms.

raw_json:
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title: Neuroscience: What doesn't kill you makes you stronger.
authors: Kucukdereli H, Douglass AM.
publication_date: 2025-12-31
doi: 10.1016/j.cub.2025.11.056
pubmed_id: 41494523
source_url: https://doi.org/10.1016/j.cub.2025.11.056
keywords: Animals, Humans, Anti-Anxiety Agents, Hallucinogens, Stress, Psychological, Psilocybin
substance_tags: psilocybin
topic_tags: Anxiety
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:01
abstract:
Small amounts of stress are thought to have beneficial effects. A new study reports a mechanism by which the psychedelic drug, psilocybin, causes acute release of stress hormones, despite its known long-term anti-anxiety effects.

raw_json:
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title: Psilocybin induces sex- and context-specific recruitment of the stress axis.
publication_date: 2025-12-08
doi: 10.1016/j.cub.2025.11.031
pubmed_id: 41371219
source_url: https://doi.org/10.1016/j.cub.2025.11.031
substance_tags: psilocybin
topic_tags: Depression,PTSD,Neuroplasticity,Mechanism of Action,Receptor Pharmacology,Animal Study
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
authors:
Cook SG, Lee S, Ference E, Shi Y, Baimoukhametova D, Rojas-Carvajal M, Hen R, Bains JS, Turi GF, Füzesi T.

abstract:
Following decades of prohibition, psychedelic drugs have reemerged as promising therapeutics for stress-related conditions, including depression and post-traumatic stress disorder. Still, their impact on stress-related brain regions and the hypothalamic-pituitary-adrenal (HPA) axis remains unclear. This work explores the acute effects of psilocybin on the primary regulators of the HPA axis: corticotropin-releasing hormone neurons in the paraventricular nucleus of the hypothalamus (CRHPVN). Here, using blood plasma measurements and in vivo single-fiber photometry, we demonstrate that psilocybin induces robust activation of the HPA axis via CRHPVN neurons, with more pronounced responses observed in female mice and a reliance on serotonergic 5-HT2A and 5-HT2C receptors. Ex vivo electrophysiology indicates that the 5-HT2A-receptor-mediated effects involve dual mechanisms: direct post-synaptic depolarization of CRHPVN neurons and increased presynaptic glutamate release. Our findings also reveal that psilocybin alters how CRHPVN neurons react to environmental changes, resulting in a surprising decrease in activity that contrasts with typical elevated stress responses. This context-specific modulation may be a key mechanism underlying the therapeutic potential of psychedelics to recalibrate maladaptive stress reactivity. Our findings emphasize the interplay between the serotonergic and stress systems and support the considerable influence of contextual factors, i.e., "setting," on the psychedelic experience. This study provides the first real-time in vivo evidence of neuronal activation of the stress system following psilocybin administration and has significant implications for optimizing the therapeutic efficacy of psychedelic-assisted therapy.

keywords:
Pituitary-Adrenal System, Hypothalamo-Hypophyseal System, Paraventricular Hypothalamic Nucleus, Neurons, Animals, Mice, Inbred C57BL, Mice, Corticotropin-Releasing Hormone, Hallucinogens, Female, Male, Psilocybin

raw_json:
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title: An open-label pilot study of psilocybin-assisted therapy for binge eating disorder.
publication_date: 2026-01-02
doi: 10.1186/s40337-025-01508-3
pubmed_id: 41485073
source_url: https://doi.org/10.1186/s40337-025-01508-3
substance_tags: psilocybin
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
authors:
Dallery J, Miller JL, Boissoneault J, Harvey L, Ives L, Knerr A, Blaes S, Ransom MN, Munson M, Gilligan JP, Silverman MH, Guzzo PR, Loeser B.

abstract:
Binge Eating Disorder (BED) is the most prevalent eating disorder and is associated with psychiatric comorbidities, health impairments, and decreased quality of life. Emerging evidence suggests that psilocybin-assisted therapy may promote cognitive and emotional flexibility and disrupt maladaptive behavioral patterns, making it a promising candidate for BED treatment. This open-label pilot study evaluated the feasibility, safety, and preliminary therapeutic effects of a single 25 mg dose of psilocybin administered in the context of Acceptance and Commitment Therapy (ACT)-based psychotherapy in adults with BED (N = 5). Primary outcomes included safety measures, and exploratory outcomes included self-reported binge eating frequency, depression, anxiety, psychological flexibility, anthropometric indices, and neuroimaging biomarkers assessed over a 14-week follow-up. Psilocybin was well tolerated, with no serious adverse events. Reductions in self-reported binge eating frequency were observed across all participants and sustained through week 14. Improvements were also noted in depression, anxiety, and psychological inflexibility. Three participants showed reductions in body mass index and waist circumference. Given the open label design and small sample size, causality cannot be inferred. fMRI analyses generated preliminary signals of change-such as increased functional activation from pre- to post-intervention in the middle frontal gyrus, angular gyrus, and supramarginal gyrus in response to processed versus unprocessed food cues. Psilocybin-assisted therapy was feasible and well-tolerated in individuals with BED. The clinical and neurobiological observations provide directions for future adequately powered trials.

topic_tags:
Depression,Anxiety,Eating Disorders,Brain Imaging,Biomarkers,Aging,Emotional Processing,Psychological Flexibility,Safety,Adverse Events

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publication_date: 2026-01-01
doi: 10.1001/jamanetworkopen.2025.54843
pubmed_id: 41563753
source_url: https://doi.org/10.1001/jamanetworkopen.2025.54843
substance_tags: psilocybin
study_type: Meta-Analysis
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:04
title:
Psychological Therapy Quantity and Depressive Symptom Reduction in Psychedelic-Assisted Therapy: A Systematic Review and Meta-Analysis.

authors:
Florineth GA, Klima I, Boeker AL, Catzeflis P, Wopfner A, Denier N, Bracht T, Adorjan K, Pfammatter M, Müller F, Soravia LM.

abstract:
ImportancePsychedelic-assisted therapy (PAT) is a novel intervention for depressive symptoms, typically delivered with additional psychological therapy sessions. Quantitative evidence on how this concomitant therapy contributes to treatment outcomes is limited, highlighting the need for a systematic synthesis.ObjectiveTo evaluate whether the quantity of psychological therapy is associated with symptom reduction in PAT for depressive symptoms.Data sourcesPubMed, PsycINFO, and Scopus databases were searched from inception to June 16, 2025.Study selectionThe analysis included controlled clinical trials involving adults with depressive symptoms who received PAT using classic serotonergic psychedelics (eg, psilocybin or lysergic acid diethylamide). Within these trials, psychedelic dosing sessions were embedded in therapeutic sessions before (preparation) and after (integration). Studies were excluded if they used microdosing as the primary intervention, involved naturalistic or purely pharmacological administration, or did not report therapy session count or duration. Qualitative studies, reviews, case reports, and conference abstracts were also excluded. Of the 226 records identified, 42 full texts were assessed by 2 independent reviewers, of which 12 met inclusion criteria.Data extraction and synthesisTwo reviewers independently extracted data and assessed risk of bias according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Multilevel random-effects meta-analysis and multilevel metaregressions were conducted using robust variance estimation.Main outcomes and measuresThe primary outcomes were standardized mean differences (Hedges g) in depressive symptoms at all available posttreatment time points. Metaregression analyses assessed associations of different metrics of psychological therapy quantity (duration in hours, number of sessions, and total duration in weeks) with treatment outcomes.ResultsThe 12 included trials had a total sample of 733 participants (365 female [49.8%]; mean [SD] age, 43.1 [6.2] years). PAT showed a large overall effect size in reducing depressive symptoms compared with control conditions (Hedges g = -0.84; 95% CI, -1.15 to -0.54; P

keywords:
Humans, Lysergic Acid Diethylamide, Hallucinogens, Treatment Outcome, Depression, Psychotherapy, Adult, Female, Male, Psilocybin

topic_tags:
Depression,Microdosing,Clinical Trial,Meta-Analysis,Systematic Review,Review Article,Case Report,Safety

raw_json:
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title: Reported Safety Practices of Publicly Advertised Psychedelic Retreats.
authors: McGuire AL, Neitzke-Spruill L, Robinson JO, Beit CS, Singh N, Mathai DS, Averill LA.
publication_date: 2026-01-01
doi: 10.1001/jamanetworkopen.2025.52505
pubmed_id: 41499117
source_url: https://doi.org/10.1001/jamanetworkopen.2025.52505
keywords: Humans, Hallucinogens, Qualitative Research, Advertising
substance_tags: psilocybin
topic_tags: Addiction,Safety
study_type: Qualitative Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:04
abstract:
ImportanceThe availability of psychedelic retreats has grown to meet the demand for access to these substances. Despite centuries of use among Indigenous communities, psychedelics can pose serious risks for some users.ObjectiveTo determine safety precautions that retreat organizations that offer psychedelic substances currently use.Design, setting, and participantsThis qualitative study included structured interviews conducted by phone or email with representatives from 49 organizations publicly advertising psychedelic retreat offerings from July to October 2023. Organizations were eligible if they marketed their services in English, offered at least 1 psychedelic substance, and made contact information available online. Organizations were selected using convenience sampling from a broader pool of organizations identified in a prior study. Data were analyzed from March 2024 to November 2025.Main outcomes and measuresThe main outcomes of interest included the types of drugs offered and presence of polysubstance use, collaboration with health care professionals, presence of health care professionals during retreats, disqualifying conditions, medication washout procedures, and integration practices. Descriptive statistics were used to characterize organizational practices and locations; content analysis was used to categorize medical exclusion criteria, medication washout protocols, involvement of health care professionals, integration offerings, and training of integration facilitators.ResultsOf 48 organizations that reported what substances they offered, all offered either ayahuasca, psilocybin, or both. Nineteen organizations (38.7%) offered more than 1 psychedelic substance. All organizations collected participant medical histories; 36 organizations (73.5%) excluded individuals with certain health conditions. Most (43 organizations [87.8%]) required or recommended medication washout for varying lengths of time, ranging from 1 day to more than 6 weeks. Most (34 organizations [69.4%]) worked with a licensed health care professional or someone with emergency response training, and 32 organizations (65.3%) had someone with those qualifications in attendance at retreats at least some of the time. All organizations offered some sort of integration support.Conclusions and relevanceThis qualitative study of the practices implemented by psychedelic retreat organizations found substantial variability in the implementation of safety precautions. Some practices related to medication washout and polysubstance use may pose increased risks to participants. Best practice guidelines are needed and should be codeveloped with Indigenous and nonclinical communities.

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