# publications

title: The Potential Role of Psilocybin in Traumatic Brain Injury Recovery: A Narrative Review.
authors: Palmer C, Ferber AT, Greenwald BD.
publication_date: 2025-05-25
doi: 10.3390/brainsci15060572
pubmed_id: 40563744
source_url: https://doi.org/10.3390/brainsci15060572
substance_tags: psilocybin
topic_tags: Depression,Addiction,Neuroplasticity,Clinical Trial,Review Article,Inflammation
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:
Background: This narrative review explores psilocybin's potential use as a therapeutic agent in patients with traumatic brain injury (TBI). Methods: We engaged in a search of PubMed, ScienceDirect, and Cochrane's databases for information on the effects of psilocybin. We also reviewed articles where psilocybin was used in patients with TBI. Articles from 2000-2025 were included. Results: A total of 29 articles met our initial inclusion criteria. Additionally, 13 articles were obtained from reference lists and 3 more articles on the legality of psilocybin from public websites. Conclusions: Assisted psilocybin use may have benefits in TBI by reducing inflammation, promoting neuroplasticity and neuroregeneration, and alleviating associated mood disorders. Positive findings in related fields, like treatment for depression and addiction, highlight the necessity for more extensive clinical trials on psilocybin's role in TBI recovery.

raw_json:
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authors: Peck SK, Brewerton TD, Fisher H, Trim J, Shao S, Modlin NL, Kim J, Finn DM, Kaye WH.
publication_date: 2025-05-25
doi: 10.1186/s40337-025-01274-2
pubmed_id: 40420197
source_url: https://doi.org/10.1186/s40337-025-01274-2
substance_tags: psilocybin
topic_tags: PTSD,Eating Disorders,Mechanism of Action,Review Article,Safety
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
title:
Therapeutic emergence of dissociated traumatic memories during psilocybin treatment for anorexia nervosa.

abstract:
BackgroundPsychedelic treatment is a rapidly emerging therapeutic approach for a host of chronic, difficult to treat psychiatric disorders, including anorexia nervosa (AN). Trauma and its sequelae, such as dissociation, often contribute to comorbidity and treatment refractoriness.AimsIn this report, we describe the therapeutic emergence of previously dissociated traumatic memories of sexual assault in 2 of 10 research participants with AN while receiving psilocybin treatment.MethodsTen female adults who met DSM-5 criteria for AN or pAN (partial remission) participated in an open pilot study evaluating the safety, tolerability and preliminary efficacy of psilocybin-assisted psychotherapy. Participants received a 25-mg dose of investigational drug COMP360, a proprietary pharmaceutical-grade synthetic psilocybin formulation developed by COMPASS Pathfinder Ltd. administered in conjunction with psychological support. Participants also received two integration therapy sessions on days 1 and 7 after dosing, and they were reassessed at 1 and 3 months. Participants were interviewed using a semi-structured interview to understand qualitative perspectives of treatment and its effect on AN.Results/outcomesBoth patients described in this report significantly benefited from the emergence and processing of previously dissociated information (dissociative amnesia), and both patients subsequently attained remission of their AN psychopathology at 3-month follow-up as determined by global scores on the Eating Disorder Examination Questionnaire (EDE-Q) and clinically meaningful weight gain.Conclusions/interpretationPT may hold promise not only in the treatment of eating disorders but also trauma-related disorders, including PTSD and dissociative amnesia. Potential mechanisms of psilocybin's facilitation of remembering and processing traumatic material is reviewed.

raw_json:
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authors: Wang Z, Robbins B, Zhuang R, van Bruggen R, Sandini T, Li XM, Zhang Y.
publication_date: 2025-05-25
doi: 10.1038/s41598-025-03383-z
pubmed_id: 40419666
source_url: https://doi.org/10.1038/s41598-025-03383-z
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
title:
Psilocybin mitigates behavioral despair and cognitive impairment in treatment-resistant depression model using wistar kyoto rats.

abstract:
Major depressive disorder (MDD) is a leading cause of disability that affects over 300 million people globally. Despite multiple antidepressant trials, approximately one-third of MDD patients remain symptomatic, progressing to treatment-resistant depression (TRD). This persistence possibly is due to the multifaceted etiology of TRD, encompassing biological, psychological, and environmental factors. Chronic stress, prevalent in modern life, significantly contributes to mental health disorders and complicates TRD treatment. This study investigated psilocybin as a potential TRD treatment using a diathesis-stress animal model. Twenty-two male Wistar-Kyoto (WKY) rats were divided into control and stress groups, with the stress group further subdivided to receive either sham treatment or psilocybin as early intervention. Behavioral assessments demonstrated a significant and sustained beneficial effect of psilocybin on behavioral despair and cognitive impairment. Biochemical analyses revealed psilocybin-induced increases in thyroid-stimulating hormone (TSH) levels without significant changes in the hypothalamic-pituitary-adrenal (HPA) axis. The ability of psilocybin to counter stress-induced TSH reductions suggested that TSH may serve as a proxy marker of therapeutic response, although its causal role in mood regulation remains unclear. Additionally, following psilocybin administration, changes in cannabinoid receptor type I (CB1R) suggest a potential modulation of psilocybin intervention on the component of the endocannabinoid system (ECS), though causal links remain unconfirmed without antagonist studies. These findings highlight the potential of psilocybin to treat TRD through the targeting of previously unexplored biological pathways.

keywords:
Animals, Rats, Inbred WKY, Rats, Disease Models, Animal, Antidepressive Agents, Behavior, Animal, Stress, Psychological, Male, Depressive Disorder, Treatment-Resistant, Psilocybin, Cognitive Dysfunction

topic_tags:
Depression,Mechanism of Action,Receptor Pharmacology,Biomarkers,Animal Study,Treatment-Resistant Depression

raw_json:
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authors: Han C, Baek H, Lim JY, Kim E, Tran CK, Freeman E, Chen Z, Yoo SH, Burish MJ.
publication_date: 2025-05-22
doi: 10.1186/s10194-025-02008-0
pubmed_id: 40410667
source_url: https://doi.org/10.1186/s10194-025-02008-0
substance_tags: psilocybin
topic_tags: Chronic Pain,Headache / Migraine,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 11:22:05
title:
Ergotamine enhances circadian amplitude and diurnally mitigates nitroglycerin-induced mechanical hypersensitivity.

abstract:
BackgroundCluster headache and migraine have a circadian timing of attacks and are linked to the trigeminovascular system. Recently the trigeminal ganglion was found to have a strong circadian rhythm, with the serotonin 2A receptor identified as a clock-controlled gene. Ergotamine is an acute treatment for cluster headache and migraine, acts on the trigeminal ganglion, and is a serotonin 2A receptor agonist. The circadian properties of ergotamine are unknown.MethodsWe performed real-time bioluminescence monitoring and qPCR of Per2::LucSV reporter mouse fibroblast cultures after treatment with ergotamine. We examined receptor effects by treating Per2::LucSV fibroblast cultures with ergotamine and one of several serotoninergic, adrenergic, and/or dopaminergic receptor antagonists. Next, we treated Per2::LucSV reporter mouse trigeminal ganglion explants with ergotamine and monitored circadian reporter rhythms; finally we measured hindpaw sensitivity in a nitroglycerin chronic headache mouse model and administered ergotamine at two different times to examine a chronotherapeutic effect on pain behavior.ResultsErgotamine caused a more than two-fold increase in the amplitude of Per2::LucSV fibroblasts without a change in period length; amplitude enhancement was also seen for expression of Clock, Bmal1, Period3, Cryptochrome2, Rev-erbα, and Rev-erbβ. Ergotamine's effect on circadian amplitude was dampened by the serotonin-1B/1D receptor antagonist GR127935, the serotonin-1D receptor antagonist BRL1557, the serotonin-1A/1B/2A/2B/2C, alpha1A-adrenergic, and dopamine D1-4 receptor antagonist asenapine, and the serotonin-2C receptor antagonist SB242084. In contrast to serotonin receptor antagonists, ergotamine's effects on clock amplitude were unchanged by other serotonin antagonists or by selective adrenergic or dopaminergic receptor antagonists, suggesting that ergotamine's amplitude effect is mediated by serotonin receptor activation. Furthermore, trigeminal ganglion explant cultures treated with ergotamine showed a significant increase in amplitude without a change in period. Finally, in the nitroglycerin chronic headache mouse model, ergotamine significantly raised hindpaw thresholds when administered during the daytime (ZT4) but not at night (ZT16).ConclusionsErgotamine has substantial circadian rhythm modification effects in both cellular and animal models. Ergotamine's circadian effects appear to be mediated through serotonin 1D and 2C receptors, providing a rationale for why sub-psychedelic doses of psilocybin (which induces psychedelic responses through the serotonin 2A receptor) might be effective. Ergotamine's peak effect on hindpaw thresholds at ZT4 suggests that ergotamine may be more effective at certain times of day.

keywords:
Trigeminal Ganglion, Animals, Mice, Inbred C57BL, Mice, Hyperalgesia, Disease Models, Animal, Nitroglycerin, Ergotamine, Circadian Rhythm, Male, Migraine Disorders

raw_json:
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title: In Vitro Psilocybin Synthesis by Co-Immobilized Enzymes.
authors: Schäfer T, Sherwood A, Kirkland T, Krüger T, Worbs J, Kniemeyer O, Gressler M, Hoffmeister D.
publication_date: 2025-04-20
doi: 10.1002/chem.202501037
pubmed_id: 40202903
source_url: https://doi.org/10.1002/chem.202501037
keywords: Escherichia coli, Enzymes, Immobilized, Methyltransferases, Biocatalysis, Psilocybe, Psilocybin
substance_tags: psilocybin
topic_tags: Depression,Clinical Trial,In Vitro 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 11:22:00
abstract:
Advanced clinical trials investigate the Psilocybe magic mushroom natural product psilocybin as a treatment against major depressive disorder. Currently, synthetic material is used to meet the demand for legitimate pharmaceutical purposes. Here, we report an in vitro approach to biocatalytically produce psilocybin on a solid-phase matrix charged with five covalently bound biosynthetic enzymes. These enzymes include three Psilocybe enzymes: IasA*, an engineered l-tryptophan decarboxylase/aromatic aldehyde synthase, the 4-hydroxytryptamine kinase PsiK and the norbaeocystin methyltransferase PsiM, along with Escherichia coli nucleosidase MtnN and adenine deaminase Ade. In a proof-of-principle experiment, this enzyme-charged resin allowed for quantitative turnover of 4-hydroxy-l-tryptophan into psilocybin. This facile process i) represents a sustainable approach with reusable enzymes, ii) circumvents the drawbacks of in vivo processes while harnessing the selectivity of enzymatic catalysis and iii) helps access an urgently needed drug candidate.

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authors: Gao JL, Wu XP, Zhou YL, Yu WJ, Fan YG.
publication_date: 2025-05-19
doi: 10.3389/fmicb.2025.1540570
pubmed_id: 40463436
source_url: https://doi.org/10.3389/fmicb.2025.1540570
substance_tags: psilocybin,psilocin
topic_tags: Pharmacology
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
title:
Additions to the Inocybe sect. Leptocybe (Agaricales) in China: new species from tropical rainforests, new geographical distributions, and toxin detection.

abstract:
Inocybe is a cosmopolitan genus of ectomycorrhizal fungi within the family Inocybaceae. Members of this genus are recognized as a group of toxic mushrooms linked to poisoning incidents worldwide. Clarifying this species diversity and toxin profiles within this genus is critical for both taxonomy and public health. In this study, we describe two newly identified species, I. bicystidiata sp. nov. and I. microcarpa sp. nov., based on phylogenetic analysis and morphological evidence. Phylogenetically, the two new species belong to I. sect. Leptocybe. Inocybe bicystidiata is characterized by nodulose basidiospores with saddle-shaped projections and the coexistence of thick-walled pleurocystidia and thin-walled paracystidia on the lamellar side. Inocybe microcarpa is characterized by very small basidiomata, spinose basidiospores with forked projections, absence of pleurocystidia, and thin-walled cheilocystidia. Ecologically, both of these new species occur in tropical rainforests dominated by Parashorea chinensis, which is considered as their presumed host. In addition, new geographic data are reported for three previously documented species of I. sect. Leptocybe, I. acutata, I. juji, and I. peppa, based on newly obtained specimens. Comprehensive ultra-performance liquid chromatography-mass spectrometry (UPLC-MS)/MS toxin screening revealed no detectable levels of muscarine, psilocybin, psilocin, bufotenine, or baeocystin in 10 examined species of sect. Leptocybe. This contrasts with the known toxin-producing Inocybe lineages, suggesting a divergent secondary metabolism in this clade.

raw_json:
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title: Can the gut-brain axis provide insight into psilocybin's therapeutic value in reducing stress?
authors: Kit A, Conway K, Makarowski S, O'Regan G, Allen J, Shultz SR, Bodnar TS, Christie BR.
publication_date: 2025-05-18
doi: 10.1016/j.ynstr.2025.100732
pubmed_id: 40496249
source_url: https://doi.org/10.1016/j.ynstr.2025.100732
substance_tags: psilocybin
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:01
abstract:
There is growing interest in exploring the therapeutic potential and mechanisms of action of psilocybin on stress-related neuropsychiatric disorders, including depression, generalized anxiety disorder (GAD), post-traumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD), addiction, and disordered eating. Despite promising progressions in preclinical and clinical research, the neurobiological and physiological mechanisms underlying the therapeutic effects of psilocybin remain complex, involving multiple systems with numerous homeostatic feedback signaling pathways throughout the body. This review paper explores how psilocybin mechanistically interacts with the gut microbiota, enteric nervous system, hypothalamic-pituitary axis, and how psilocybin influences the bidirectional communication between peripheral and neuronal systems. Shifting towards a more integrated paradigm to unravel the mechanisms through which psilocybin affects the bidirectional gut-brain axis holds the promise of significantly advancing our understanding of psilocybin-based therapies from preparation of treatment, administration, to proceeding long-term integration. Such an understanding can extend beyond the treatment of psychiatric disorders, further encompassing a broader spectrum of inflammatory-related disorders.

topic_tags:
Depression,Anxiety,PTSD,Addiction,OCD,Mechanism of Action,Review Article,Animal Study,Microbiome,Inflammation

raw_json:
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authors: Viña SM.
publication_date: 2025-05-15
doi: 10.3390/healthcare13101158
pubmed_id: 40427994
source_url: https://doi.org/10.3390/healthcare13101158
substance_tags: psilocybin
topic_tags: Observational Study
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:04
title:
The Relationships Between Healthcare Access, Gender, and Psychedelics and Their Effects on Distress.

abstract:
Background: Structural inequalities in healthcare access may influence how individuals experience the psychological effects of psychedelic substances, potentially limiting positive outcomes among vulnerable populations. Objectives: This study uses data from the National Survey on Drug Use and Health (2008-2019; N = 484,732) to examine how public and private health insurance moderate the association between psychedelic use and psychological distress. Methods: Ordinary least squares (OLS) regression models indicate that private health insurance is associated with lower psychological distress, while public insurance is associated with higher distress. Results: Psychedelic use moderates these associations, reinforcing the protective pattern linked to private insurance and intensifying distress among those with public coverage. These patterns vary by gender: among men, psychedelic use does not significantly alter the association between insurance type and distress; among women, however, psilocybin and lysergic acid diethylamide (LSD) use are associated with lower distress among those with private insurance, but with higher distress among those with public insurance. Conclusions: These findings indicate that while psychedelics may interact with existing healthcare conditions, they do not mitigate structural inequalities and may, in some cases, exacerbate them.

raw_json:
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title: Aesthetic quality of psychedelic experience is linked to insight and psychological outcomes.
authors: Hooper JF, Gyongyosi EL, Hutchison KE, Mueller RL.
publication_date: 2025-05-14
doi: 10.3389/fpsyg.2025.1533055
pubmed_id: 40443723
source_url: https://doi.org/10.3389/fpsyg.2025.1533055
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Mechanism of Action,Emotional Processing,Mystical Experience,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 11:22:04
abstract:
IntroductionThe aesthetic qualities of psychedelic experiences have long been documented, but their specific contribution to therapeutic outcomes remains understudied. Aesthetic experiences may facilitate emotional breakthroughs and cognitive shifts, potentially playing a crucial role in the lasting psychological benefits observed following psychedelic use.MethodsThis cross-sectional study surveyed 96 individuals who reported using classic psychedelics (e.g., psilocybin, LSD, DMT, mescaline) within the past year. Participants completed validated measures including the Mystical Experience Questionnaire (MEQ), Emotional Breakthrough Inventory (EBI), Psychological Insight Scale (PIS), Challenging Experience Questionnaire (CEQ), and a novel measure of aesthetic experience (PAEQ). Linear regression and Spearman correlations were used to assess associations between aesthetic experience and psychological outcomes.ResultsAesthetic experience was significantly associated with greater emotional breakthrough (r =.40), psychological insight (r =.48), behavioral change (r =.55), and mystical experience (r =.49) (all p <.001). Aesthetic experience was also inversely associated with fear (r = -.24, p <.05) and paranoia (r = -.36, p <.001). Regression models indicated aesthetic quality predicted improvements in depression, anxiety, and quality of life, independent of age, gender, or mystical experience.DiscussionThese findings suggest that aesthetic aspects of psychedelic experiences are not merely perceptual enhancements but may actively contribute to therapeutic outcomes. The inverse relationship between aesthetic quality and challenging experiences highlights the potential utility of optimizing the aesthetic environment in psychedelic-assisted therapy. Future research should further validate the PAEQ and explore causal mechanisms using longitudinal and experimental designs.

raw_json:
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authors: Lazar M, Brownstien M, Botvinnik A, Shevakh C, Shahar O, Lifschytz T, Lerer B.
publication_date: 2025-04-30
doi: 10.1093/ijnp/pyaf022
pubmed_id: 40156912
source_url: https://doi.org/10.1093/ijnp/pyaf022
substance_tags: psilocybin
topic_tags: Anxiety,OCD,Neuroplasticity,Animal Study,Drug Interactions
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:
Premorbid characteristics of the SAPAP3 mouse model of obsessive-compulsive disorder: behavior, neuroplasticity, and psilocybin treatment.

abstract:
BackgroundSAPAP3-knockout (SAPAP3-KO) mice develop excessive self-grooming behavior at 4-6 months of age, serving as a model for obsessive-compulsive disorder (OCD). Given that anxiety often precedes OCD diagnosis in humans, this study investigated whether juvenile SAPAP3-KO mice exhibit anxiety-like behaviors before developing the self-grooming phenotype, and whether such behaviors respond to psilocybin (PSIL) treatment. The study also examined 4 key neuroplasticity-related synaptic proteins-GAP43, PSD95, synaptophysin, and SV2A-as SAPAP3 is a postsynaptic scaffold protein that interacts with PSD95 and may affect synaptic function.MethodsTwo studies were conducted using male and female juvenile (10-13 weeks) SAPAP3-KO mice. Study 1 compared behavioral phenotypes between homozygous (HOM), heterozygous, and wild-type (WT) mice. Study 2 evaluated a different sample of HOM and WT mice and assessed the effect of PSIL (4.4 mg/kg) on identified behavioral differences. Both studies included comprehensive behavioral testing focused on anxiety-like behavior, social interaction, and cognitive function. Additionally, levels of 4 synaptic proteins were measured by western blots in the frontal cortex, hippocampus, amygdala, and striatum of juvenile and adult SAPAP3-KO mice.ResultsIn both studies, juvenile HOM SAPAP3-KO mice showed significant anxiety-like behaviors compared to WT mice, spending less time in open field center, and elevated plus maze open arms. They also buried fewer marbles and found fewer buried Oreos than WT mice. Psilocybin treatment did not improve these behavioral manifestations. Analysis of synaptic proteins revealed significant increases in GAP43, synaptophysin, and SV2A across multiple brain regions in adult male HOM mice and of SV2A in the frontal cortex of HOM females compared to WT, but not in juvenile mice of either sex.ConclusionsJuvenile SAPAP3-KO mice exhibit anxiety-like behaviors before developing the characteristic excessive self-grooming phenotype, paralleling the prodromal anxiety often seen in human OCD. Unlike in adult SAPAP3-KO mice, these manifestations were not responsive to PSIL treatment. The age-dependent increases in synaptic proteins observed in adult (but not juvenile) male SAPAP3-KO mice HOM for the deletion and to a lesser extent in female homozygotes, may represent compensatory plasticity changes in response to the phenotype. These results provide insights into the developmental trajectory of OCD-like behaviors and associated neuroplastic adaptations.

keywords:
Animals, Mice, Knockout, Mice, Disease Models, Animal, GAP-43 Protein, Synaptophysin, Nerve Tissue Proteins, Hallucinogens, Behavior, Animal, Grooming, Anxiety, Obsessive-Compulsive Disorder, Neuronal Plasticity, Female, Male, Disks Large Homolog 4 Protein

raw_json:
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title: Targeting Phantom Pain with Psilocybin: Toward Integration with Adaptive Sensory Technologies.
authors: Kargbo RB.
publication_date: 2025-04-09
doi: 10.1021/acsmedchemlett.5c00182
pubmed_id: 40365378
source_url: https://doi.org/10.1021/acsmedchemlett.5c00182
substance_tags: psilocybin
topic_tags: Chronic Pain
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
abstract:
Psilocybin demonstrates a clinically meaningful reduction in phantom and residual limb pain. Adaptive sensory environments (ASEs) separately offer biosensor-guided modulation of psychological states during psychoactive therapy. This Patent Highlight explores the pharmacological findings of a psilocybin trial and discusses future integration with ASE systems to precision and scale psychedelic-assisted interventions.

raw_json:
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title: Race/ethnicity moderates the associations between lifetime psilocybin use and opioid use disorder.
authors: Jones G.
publication_date: 2025-05-06
doi: 10.1371/journal.pone.0321461
pubmed_id: 40334252
source_url: https://doi.org/10.1371/journal.pone.0321461
substance_tags: psilocybin
topic_tags: Addiction,Observational Study,Adolescents
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
abstract:
BackgroundOpioid use disorder (OUD) is a debilitating health condition that is associated with significant morbidity and mortality in the U.S. While preliminary studies have demonstrated that psilocybin is associated with lowered odds of OUD, current research in this domain suffers from a lack of investigation into the impact of race/ethnicity on this association.ObjectiveTo assess the impact of race and ethnicity on the association between psilocybin use and lowered odds of OUD using data from the National Survey on Drug Use and Health (2002-2019) (N = 706,891).MethodI used survey-weighted multivariable logistic regression to test whether race/ethnicity moderates the association between psilocybin use and lowered odds of OUD. Subsequently, I stratified my sample by race and ethnicity and assessed the associations between psilocybin and OUD for individual racial and ethnic groups (White, Black, Indigenous, Asian, Multiracial, Hispanic). My analysis plan was pre-registered.ResultsRace and ethnicity significantly moderated the association between psilocybin and OUD. Furthermore, when I stratified my sample by race and ethnicity, only White participants and Hispanic participants demonstrated a link between psilocybin and lowered odds of OUD (White aOR: 0.84; Hispanic aOR: 0.68). For Black, Asian, Indigenous, and Multiracial participants, psilocybin did not share a significant association with OUD.ConclusionRace and ethnicity moderate the associations between psilocybin and OUD. Future longitudinal, experimental, and qualitative research is needed to better understand the pattern of associations I observed in this study.

keywords:
Humans, Opioid-Related Disorders, Adolescent, Adult, Middle Aged, United States, Female, Male, Young Adult, Psilocybin, Ethnicity, Racial Groups

raw_json:
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title: Exploring the Role of Psychedelics in Modulating Ego and Treating Neuropsychiatric Disorders.
authors: Wang H, Wang X
journal: ACS chemical neuroscience
publication_date: 2025-05-06
doi: 10.1021/acschemneuro.5c00247
pubmed_id: 40254808
source_url: https://pubmed.ncbi.nlm.nih.gov/40254808/
substance_tags: psilocybin
topic_tags: Depression,Anxiety,PTSD,Addiction,Default Mode Network,Aging,Emotional Processing
study_type: Other
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":"40254808"}
abstract:
This viewpoint explores the therapeutic potential of psychedelics in treating neuropsychiatric disorders, particularly through the modulation of brain entropy and the experience of ego dissolution. Psychedelics disrupt rigid neural patterns, facilitating enhanced connectivity and fostering profound emotional breakthroughs that may alleviate symptoms of disorders like depression, anxiety, PTSD, and addiction. Despite their promising potential, the clinical application of psychedelics presents significant challenges, including the need for careful patient screening, managing adverse experiences, and addressing ethical considerations, all of which are essential for their safe integration into therapy.

keywords:
Default mode network, Ego, Lysergic acid diethylamide, Neuropsychiatric diseases, Psilocybin, Psychedelics


authors: Kratina S, Strike C, Schwartz R, Nayfeh A, Jopling S, Lo C, Rush B.
publication_date: 2025-05-05
doi: 10.1371/journal.pone.0318343
pubmed_id: 40327705
source_url: https://doi.org/10.1371/journal.pone.0318343
keywords: Humans, Hallucinogens, Terminal Care, Stress, Psychological, Psilocybin, Scoping Reviews As Topic
substance_tags: psilocybin
topic_tags: Depression,Anxiety,End-of-Life Distress,Mechanism of Action,Systematic Review,Review Article,Safety
study_type: Systematic Review
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
title:
A protocol for a scoping review of variations among psychedelic interventions for psychological suffering associated with the end-of-life.

abstract:
Psychedelic substances are increasingly recognized for their therapeutic potential to ease psychological suffering linked to end-of-life issues. However, amid renewed scientific and public interest, policy remains restrictive. Existing reviews have made progress in synthesizing the results of studies of psychedelic interventions, especially psilocybin, and particularly with regard to their outcomes related to anxiety and depression, long-term effects and safety. Despite this progress, a wide range of both substances (such as ayahuasca, psilocybin, ketamine) and therapeutic approaches (such as psychedelics alone, or psychotherapy assisted with a psychedelic) in the use of psychedelic interventions specifically for end-of-life populations, has not been adequately covered by reviews to date. The aim of this scoping review is to identify and learn from the variety of psychedelic substances and therapeutic approaches that exists within the research on therapeutic psychedelic interventions reported in populations coping with psychological suffering associated with life-threatening illness and the end of life itself. We will follow Arksey and O'Malley's (2005) framework for scoping reviews while incorporating updated methodological guidance. The Preferred Reporting Items for Systematic Review and Meta-Analyses extension for scoping reviews (PRISMA-ScR) guideline will be used to organize the search and identification of research focusing on psychedelic interventions, psychological suffering, and end-of-life issues. Health science databases such as Medline, Embase, APA PsychINFO, and CINAHL will be searched. The search will be limited to empirical published data on 'end-of-life', 'psychedelics', and 'psychological suffering'. Data extracted from selected studies will cover intervention details, participant characteristics, measured outcomes, and theorised mechanisms. The insights gained from this review will be used to inform future research and discussions on how psychedelics can be integrated into care strategies for populations coping with end-of-life concerns. This scoping review does not require ethics approval.

raw_json:
{"europe_pmc_id":"40327705","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: A landscape analysis of psychedelic retreat organizations advertising online.
authors: Neitzke-Spruill L, Beit CS, Robinson JO, Singh N, Kambala S, Ramesh R, McGuire AL.
publication_date: 2025-05-01
doi: 10.1371/journal.pone.0321648
pubmed_id: 40315211
source_url: https://doi.org/10.1371/journal.pone.0321648
keywords: Humans, Hallucinogens, Advertising, Internet, Psilocybin
substance_tags: psilocybin
topic_tags: Mechanism of Action,Wellbeing,Safety
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:
Research into psychedelics' clinical potential has corresponded to a growth in public interest and adult use. One common pathway to accessing psychedelics is through psychedelic retreats. While individual retreats have been characterized in the anthropological literature, no systematic evaluation of the psychedelic retreat industry exists. Assessing the characteristics of the psychedelic retreat industry is critical to understanding the associated ethical, legal, and social implications and ensuring consumer safety. To this end, we conducted a landscape analysis of online, publicly available information to capture and characterize a broad range of organizations offering psychedelic retreats and marketing to English-speaking consumers. From July 2023 to December 2023, we identified 298 psychedelic retreat organizations. Some identified as religious organizations, but the majority focused on general wellness. Organizations offered various psychedelic substances with ayahuasca being the most common, followed by psilocybin and San Pedro. Organizations held retreats across the globe at various price points. In total, there were 440 distinct physical locations where retreat experiences were held; 130 were inside the United States (U.S.) and 310 were outside the U.S. Further research into the practices of psychedelic retreat organizations is recommended to help reduce harm and support consumer education.

raw_json:
{"europe_pmc_id":"40315211","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: From molecules to meaning: unpacking the antidepressant mechanisms of psychedelic drugs.
authors: Acero VP, Flatt TA, Gooch PM, Gaughan SJ, Levin AW, Davis AK
journal: Expert review of clinical pharmacology
publication_date: 2025-04-30
doi: 10.1080/17512433.2025.2515866
pubmed_id: 40470809
source_url: https://pubmed.ncbi.nlm.nih.gov/40470809/
substance_tags: psilocybin
topic_tags: Depression,Pharmacology,Mechanism of Action,Spirituality,Review Article
study_type: Review Article
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":"40470809"}
abstract:
Psychedelic compounds are emerging treatments for depression, capable of producing rapid and lasting symptom reduction after 1-2 administrations in the context of psychotherapy - a stark contrast to traditional antidepressants. Despite promising outcomes, the mechanisms underlying psychedelics' reported antidepressant effects remain poorly understood and are often framed in fragmented ways. Clarifying these mechanisms is crucial for guiding future research and clinical innovation with psychedelics.
This review critically examines current evidence on the mechanisms by which psychedelics may exert antidepressant effects. We highlight key mechanisms of action within biological, psychological, social, and spiritual domains that we believe are among the most compelling and deserving of further investigation. Throughout, we compare these mechanisms to those proposed for traditional antidepressants, identifying points of overlap and divergence.
Although mechanistic research is valuable, an overemphasis on identifying discrete pathways may limit psychedelic science. Psychedelics likely work through complex, interwoven biological, psychological, and experiential processes that cannot be fully reduced to single mechanisms. Future research should move beyond frameworks and metrics used to validate conventional antidepressants to explore how suprapharmacological factors - set, setting, therapy modality, and integration - shape outcomes. Embracing this complexity is essential to realizing psychedelics' full therapeutic potential for depression.

keywords:
Psychedelic-assisted therapy for depression, psilocybin, LSD, DMT, ayahuasca, and 5-MeO-DMT for depression, psychedelic mechanism of action, psychedelic pharmacology, psychedelic transdiagnostic mechanisms, psychedelics for depression


authors: Weintraub MJ, Miklowitz DJ, Jeffrey JK.
publication_date: 2025-04-30
doi: 10.1097/pra.0000000000000853
pubmed_id: 40440674
source_url: https://doi.org/10.1097/pra.0000000000000853
substance_tags: psilocybin
topic_tags: Depression,Clinical Trial,Healthcare Workers
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:
Divergent Effects of Psilocybin for 2 Patients Participating in a Psilocybin-assisted Cognitive Behavioral Therapy Trial for Major Depressive Disorder.

abstract:
We present divergent experiences of 2 patients who participated in a clinical trial of psilocybin-assisted cognitive behavioral therapy for major depressive disorder. Both patients participated in an open trial involving 2 drug administration sessions separated by one﻿ month (10 and 25 mg, respectively) along with﻿ 12 sessions of cognitive behavioral therapy. The first of the 2 patients had powerful and beneficial experiences on psilocybin that led to immediate and sustained antidepressant effects over the 7-month study. The second participant reported significant challenges with psilocybin and minimal to no antidepressant effects following the drug administration. We present the clinicians' experiences who treated both patients. Finally, we theorize and discuss areas of future research to elucidate how psilocybin can yield the greatest psychiatric benefit, the conditions within the patient that can lead to (or inhibit) psychiatric benefit, and the psychosocial environment that can best facilitate psilocybin therapy﻿.

keywords:
Humans, Hallucinogens, Treatment Outcome, Combined Modality Therapy, Psilocybin, Cognitive Behavioral Therapy, Major Depressive Disorder

raw_json:
{"europe_pmc_id":"40440674","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2025-04-30
doi: 10.3389/fnins.2025.1554049
pubmed_id: 40376612
source_url: https://doi.org/10.3389/fnins.2025.1554049
substance_tags: psilocybin,psilocin
topic_tags: Brain Imaging,Aging,Animal Study
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Dose-dependent changes in global brain activity and functional connectivity following exposure to psilocybin: a BOLD MRI study in awake rats.

authors:
Fuini E, Chang A, Ortiz RJ, Nasseef T, Edwards J, Latta M, Gonzalez E, Woodward TJ, Axe B, Maheswari A, Cavallaro N, Bradshaw HB, Kulkarni PP, Ferris CF.

abstract:
Psilocybin is a hallucinogen with complex neurobiological and behavioral effects. This is the first study to use MRI to follow functional changes in brain activity in response to different doses of psilocybin in fully awake, drug naive rats. We hypothesized that psilocybin would show a dose-dependent increase in activity in the prefrontal cortex and thalamus, while decreasing hippocampal activity. Female and male rats were given IP injections of vehicle or psilocybin in doses of 0.03 mg/kg, 0.3 mg/kg, and 3.0 mg/kg while fully awake during the imaging session. These levels were validated by measuring psilocybin and its metabolite, psilocin. Changes in BOLD signal were recorded over a 20 min window. Data for resting state functional connectivity were collected approximately 35 min post injection. All data were registered to rat 3D MRI atlas with 169 brain areas providing site-specific changes in global brain activity and changes in functional connectivity. Treatment with psilocybin resulted in a significant dose-dependent increase in positive BOLD signal. The areas most affected by the acute presentation of psilocybin were the somatosensory cortex, basal ganglia and thalamus. Males and females showed different sensitivity to psilocybin dose, with females exhibiting greater activation than males at 0.3 mg/kg, especially in thalamic and basal ganglia regions. There was a significant dose-dependent global increase in functional connectivity, highlighted by hyperconnectivity to the cerebellum. Brain areas hypothesized to be involved in loss of sensory filtering and organization of sensory motor stimuli, such as the cortico-striato-thalamo-cortical circuit and the claustrum, showed increased activation at higher doses of psilocybin. Indeed, the general neuroanatomical circuitry associated with the psychedelic experience was affected but the direction of the BOLD signal and pattern of activity between neural networks was inconsistent with the human literature.

raw_json:
{"europe_pmc_id":"40376612","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2025-04-21
doi: 10.1038/s41386-025-02091-6
pubmed_id: 40258990
source_url: https://doi.org/10.1038/s41386-025-02091-6
substance_tags: psilocybin
topic_tags: Depression,Clinical Trial,Treatment-Resistant Depression,Safety,Adverse Events,Drug Interactions
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:04
title:
Rapid and sustained antidepressant effects of vaporized N,N-dimethyltryptamine: a phase 2a clinical trial in treatment-resistant depression.

authors:
Falchi-Carvalho M, Palhano-Fontes F, Wießner I, Barros H, Bolcont R, Laborde S, Ruschi B Silva S, Montanini D, C Barbosa D, Teixeira E, Florence-Vilela R, Almeida R, K A de Macedo R, Arichelle F, J Pantrigo É, V Costa-Macedo J, da Cruz Nunes JA, de Araújo Costa Neto LA, Nunes Ferreira LF, Dantas Corrêa L, da Costa Bezerra RB, Arcoverde E, Galvão-Coelho N, B Araujo D.

abstract:
Depression affects over 185 million people worldwide, with approximately one-third classified as treatment-resistant depression (TRD). Current treatments, such as oral antidepressants, often take around 3 weeks to become effective, with no immediate anti-suicidal benefits. The field urgently needs innovative therapies that provide rapid relief. Psychedelics like psilocybin and ayahuasca have shown promising antidepressant effects; however, their long duration (several hours) makes them costly and impractical for public health systems. N,N-Dimethyltryptamine (DMT), an endogenous psychedelic also found in ayahuasca, offers a viable alternative with a short duration of action (10-20 min) and non-invasive inhalation administration. Unlike ayahuasca, which contains monoamine oxidase inhibitors, vaporized DMT acts quickly and poses fewer pharmacological interaction risks. This open-label trial evaluated inhaled DMT for TRD for the first time, within the framework of interventional psychiatry. Fourteen patients (Nfemale = 6) participated in a fixed-order, dose-escalation study (15 mg and 60 mg). The treatment was safe, well-tolerated, and produced manageable psychedelic effects with no serious adverse events. A subpopulation using antidepressants showed similar safety outcomes. Results showed rapid and sustained antidepressant effects, with an average reduction of 21.14 points on the Montgomery-Asberg Depression Rating Scale by day 7 (p

keywords:
Humans, N,N-Dimethyltryptamine, Antidepressive Agents, Treatment Outcome, Administration, Inhalation, Adult, Aged, Middle Aged, Female, Male, Depressive Disorder, Treatment-Resistant

raw_json:
{"europe_pmc_id":"40258990","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin and ketamine affect novel neuropeptides gene expression in the rat hypothalamus.
publication_date: 2025-04-16
doi: 10.1177/02698811251330783
pubmed_id: 40243003
source_url: https://doi.org/10.1177/02698811251330783
substance_tags: psilocybin
topic_tags: Mechanism of Action,Receptor Pharmacology,Consciousness,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:
Pałasz A, Pukowiec M, Bogus K, Suszka-Świtek A, Filipczyk Ł, Mordecka-Chamera K, Worthington JJ, Sygidus M, Wojtas A, Bysiek A, Gołembiowska K.

abstract:
ObjectivePsychedelics are able to trigger highly intense and profound alterations in self-consciousness, perception, affective, and cognitive processes. Indeed, recent studies show that ketamine and psilocybin could be used as fast-acting antidepressants. However, the molecular and neurochemical mechanisms of these psychedelics and their actions at the level of diverse brain structures remains so far unclear. Hypothalamic neuropeptides are involved in a wide spectrum of neuronal activities being responsible for the central control of all fundamental autonomic functions.MethodsThe purpose of this exploratory pilot study was to assess the gene expression of both classical and novel neuropeptides, including nesfatin-1, phoenixin (PNX), spexin (SPX), neuromedin U (NMU), neuropeptide S (NPS), and their known receptors in the hypothalamus of male Wistar-Han rats subjected to single injections of psilocybin (dose 2 or 10 mg/kg) and ketamine (dose10 mg/kg). Total mRNA was isolated from homogenized tissue and real-time PCR was used for estimation of related gene expression.ResultsIt was found that a single administration of the higher dose of psilocybin increased the mRNA expression of most noncanonical neuropeptides examined in the study, with only the case of NMU there with a decrease in gene expression. Interestingly, psilocybin administration also increased mRNA expression of the serotonin receptors: 5-HT1A, 5-HT2A, and 5-HT2B, but not 5HT-2C. In contrast, the effect of ketamine on the expression of neuropeptides was much more limited compared to psilocybin, only increasing transcripts of NUCB2, GPR173, and POMC were demonstrated.ConclusionsThese results suggest for the first time that selected psychedelics may enhance the signaling of 5-HT2A receptors or inhibit NMDA receptor activity, affecting neuropeptide signaling and serotonin transmission in the rat hypothalamus, which may contribute to a better understanding of psychedelic action in the brain.

keywords:
Hypothalamus, Animals, Rats, Rats, Wistar, Ketamine, Neuropeptides, Calcium-Binding Proteins, DNA-Binding Proteins, Nerve Tissue Proteins, RNA, Messenger, Hallucinogens, Pilot Projects, Gene Expression, Male, Psilocybin, Nucleobindins

raw_json:
{"europe_pmc_id":"40243003","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2025-04-01
doi: 10.1016/j.neubiorev.2025.106132
pubmed_id: 40185376
source_url: https://doi.org/10.1016/j.neubiorev.2025.106132
keywords: Brain, Animals, Humans, Hallucinogens, Mental Disorders, Neuronal Plasticity
substance_tags: psilocybin
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:04
title:
Neuroplasticity and psychedelics: A comprehensive examination of classic and non-classic compounds in pre and clinical models.

authors:
Agnorelli C, Spriggs M, Godfrey K, Sawicka G, Bohl B, Douglass H, Fagiolini A, Parastoo H, Carhart-Harris R, Nutt D, Erritzoe D.

abstract:
Neuroplasticity, the ability of the nervous system to adapt throughout an organism's lifespan, offers potential as both a biomarker and treatment target for neuropsychiatric conditions. Psychedelics, a burgeoning category of drugs, are increasingly prominent in psychiatric research, prompting inquiries into their mechanisms of action. Distinguishing themselves from traditional medications, psychedelics demonstrate rapid and enduring therapeutic effects after a single or few administrations, believed to stem from their neuroplasticity-enhancing properties. This review examines how classic psychedelics (e.g., LSD, psilocybin, N,N-DMT) and non-classic psychedelics (e.g., ketamine, MDMA) influence neuroplasticity. Drawing from preclinical and clinical studies, we explore the molecular, structural, and functional changes triggered by these agents. Animal studies suggest psychedelics induce heightened sensitivity of the nervous system to environmental stimuli (meta-plasticity), re-opening developmental windows for long-term structural changes (hyper-plasticity), with implications for mood and behavior. Translating these findings to humans faces challenges due to limitations in current imaging techniques. Nonetheless, promising new directions for human research are emerging, including the employment of novel positron-emission tomography (PET) radioligands, non-invasive brain stimulation methods, and multimodal approaches. By elucidating the interplay between psychedelics and neuroplasticity, this review informs the development of targeted interventions for neuropsychiatric disorders and advances understanding of psychedelics' therapeutic potential.

topic_tags:
Neuroplasticity,Brain Imaging,Mechanism of Action,Biomarkers,Aging,Longevity,Review Article,Animal Study

raw_json:
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journal: PsyArXiv
publication_date: 2024-10-21
source_url: https://osf.io/preprints/psyarxiv/s6bzc_v1
substance_tags: psilocybin
topic_tags: Creativity,Observational Study
study_type: Observational Study
source_name: PsyArXiv
publication_status: preprint
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:30
raw_json: {"osf_id":"s6bzc_v1","version":1,"reviews_state":"accepted"}
title:
The Afterglow Inventory (AGI) - validation of a new instrument for measuring subacute effects of classic serotonergic psychedelics

abstract:
Background: Classic psychedelics such as psilocybin and LSD are anecdotally associated with the phenomenon of "psychedelic afterglow," a set of predominantly pleasant, temporary psychological effects reported after the acute effects have subsided. Since post-acute effects are crucial for the therapeutic use of psychedelics, an instrument to systematically assess subacute "afterglow" effects is needed. Aims: To create and validate a questionnaire to quantify subacute "afterglow" effects of psychedelics. Methods: An international online survey was conducted in English and German. Participants who had consumed a psychedelic (N = 1,323) or another non-psychedelic substance (control group, N = 157) within the past four weeks were included. An initial list of 97 items was progressively reduced to 24 items. Results: A5-factor structure best fit the data and showed high internal consistency. The factors included 1) Vitality, 2) Transpersonal Aspects, 3) Inspiration/Creativity, 4) Interpersonal Relationships, and 5) Relationship to Nature. The final 24-item version of the Afterglow Inventory (AGI) effectively differentiated between the psychedelic group and the control group. The overall AGI score positively correlated with the intensity (r = 0.165; p < 0.001) and positive valence (r = 0.251; p < 0.001) of the acute psychedelic effects. Conclusions: The AGI is a novel scale for quantifying positive subacute ("afterglow") effects of psychedelics. The use of the AGI could lead to a better understanding of the interplay between acute, subacute, and long-term effects of psychedelics. Insights could also be gained into how different substances, dosages, and extra-pharmacological factors, such as psychotherapy, might influence outcomes.

keywords:
Psychiatry, Neuroscience, Life Sciences, Social and Behavioral Sciences, Quantitative Methods, Psychometrics, Cognitive Psychology, Health Psychology


title: Psilocybin for disorders of consciousness: A case-report study.
publication_date: 2025-03-07
doi: 10.1016/j.clinph.2025.02.264
pubmed_id: 40147181
source_url: https://doi.org/10.1016/j.clinph.2025.02.264
keywords: Brain, Humans, Consciousness Disorders, Hallucinogens, Electroencephalography, Psilocybin
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 11:22:01
authors:
Cardone P, Núñez P, Alnagger NLN, Martial C, van der Lande GJM, Sandell R, Carhart-Harris R, Gosseries O.

abstract:
ObjectiveWith very few treatments available, post-comatose disorders of consciousness (DoC) pose one of the hardest challenges in modern neurology. Following promising clinical trial results in psychiatry, and a deepening understanding of their brain mechanisms, psychedelics have been suggested as a novel therapeutic drug for DoC patients, given that they increase the entropy or complexity of spontaneous activity in healthy participants. However, no attempts have been so far performed in patients with DoC.MethodsIn this case report, we describe the first-ever administration of psilocybin, a classic psychedelic (i.e., agonist at the 5-HT2A receptor), to a patient in a minimally conscious state plus. We report the behavioural effects and changes in neurophysiology measured with EEG.ResultsWe report no increase in overt behavioural repertoire with validated scales, yet new spontaneous behaviour not previously seen, and increased brain complexity, as measured by the Lempel-Ziv complexity index, with changes in the underlying periodic rhythms.ConclusionsThis study contributes to future investigations exploring the use of psychedelics in DoC, enriching the discussion surrounding the role of psychedelics in medicine, and the link between brain complexity and consciousness.SignificanceThis is the first-ever report of a classic psychedelic used as a treatment for post-comatose DoC.

topic_tags:
Brain Imaging,Mechanism of Action,Receptor Pharmacology,Consciousness,Clinical Trial,Case Report,Healthy Volunteers

raw_json:
{"europe_pmc_id":"40147181","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Classic Psychedelics for the Treatment of Depression: Potential Benefits and Challenges.
authors: Ghaznavi S, Richter SG.
publication_date: 2025-03-23
doi: 10.1007/s40265-025-02172-2
pubmed_id: 40128500
source_url: https://doi.org/10.1007/s40265-025-02172-2
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
abstract:
There has been a recent resurgence in research on psychedelics as therapeutic agents for psychiatric conditions. This leading article outlines the studies to date of classic psychedelic treatments for treatment-resistant depression and major depression, including psilocybin, ayahuasca, dimethyltryptamine (DMT), and O-methyl-bufotenine (5-Me-O DMT). We discuss the potential of expanding treatment options for depression based on the data available, as well as the difficulties and limitations of research on psychedelics that make assessing that potential more challenging.

keywords:
Humans, Banisteriopsis, N,N-Dimethyltryptamine, Hallucinogens, Antidepressive Agents, Depressive Disorder, Treatment-Resistant, Psilocybin, Major Depressive Disorder

raw_json:
{"europe_pmc_id":"40128500","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Polysubstance Use Profiles Among the General Adult Population, United States, 2022.
authors: Rockhill KM, Black JC, Iwanicki J, Abraham A.
publication_date: 2025-03-19
doi: 10.2105/ajph.2024.307979
pubmed_id: 40112266
source_url: https://doi.org/10.2105/ajph.2024.307979
substance_tags: psilocybin
topic_tags: Addiction,Observational Study,Adolescents
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:04
abstract:
Objectives. To characterize present-day polysubstance use patterns in the general adult population. Methods. From a 2022 nationally representative survey in the United States, we defined polysubstance use as last 12-month use of 2 or more drugs (n = 15 800). Latent class analyses included medical (as indicated) and nonmedical (not as directed) use of prescription opioids, stimulants, benzodiazepines, and antidepressants; recreational use of cannabis, psilocybin or mushrooms, other psychedelics, cocaine, methamphetamine, and illicit opioids; and concomitant use with alcohol, cannabis, prescriptions, or recreational drugs. Results. The national prevalence of polysubstance use was 20.9% (95% confidence interval = 20.5%, 21.3%), broken down into the following 4 latent classes: (1) medically guided polysubstance use (11.5% prevalence, 6.1% substance use disorder [SUD]): prescribed drug use, some cannabis, and no concomitant use; (2) principal cannabis use variety (4.0% prevalence, 31.9% SUD): high probability of cannabis use with various drugs concomitantly used; (3) self-guided polysubstance use (3.4% prevalence, 14.5% SUD): nonmedical use of prescriptions and concomitant use; and (4) indiscriminate coexposures (2.1% prevalence, 58.9% SUD): concomitant drug use with indiscriminate drug preference. Conclusions. Different polysubstance profiles show adults with untreated SUDs, and there are 2 previously unrecognized classes. Prevention and treatment strategies addressing polysubstance use should take a personalized perspective and tailor to individuals' use profile. (Am J Public Health. 2025;115(5):747-757. https://doi.org/10.2105/AJPH.2024.307979).

keywords:
Humans, Substance-Related Disorders, Prevalence, Adolescent, Adult, Aged, Middle Aged, United States, Female, Male, Young Adult, Illicit Drugs, Recreational Drug Use

raw_json:
{"europe_pmc_id":"40112266","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2025-03-16
doi: 10.1016/j.phrs.2025.107699
pubmed_id: 40107634
source_url: https://doi.org/10.1016/j.phrs.2025.107699
substance_tags: psilocybin
topic_tags: Chronic Pain,Receptor Pharmacology,Animal Study,Safety,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:
IUPHAR Article: Psilocybin induces long-lasting effects via 5-HT2A receptors in mouse models of chronic pain.

authors:
Koseli E, Buzzi B, Honaker T, Rakholia Y, Lewis M, Gaines-Smith M, Jaster AM, Gonzalez-Maeso J, Damaj MI.

abstract:
Chronic pain is a debilitating disease with current treatments lacking efficacy and safety, therefore discovery of new treatments is crucial. Initial studies suggest that psychedelics may be feasible for targeting pain, however clinical and preclinical controlled studies are necessary to further investigate that possibility. In this study we assessed the effects of two classical psychedelics psilocybin and 2,5-Dimethoxy-4-iodoamphetamine (DOI) in two models of chronic pain after systemic administration in male and female mice. Psilocybin and DOI dose-dependently reversed mechanical and cold hypersensitivity in the chemotherapy-induced peripheral neuropathy (CIPN) mouse model with different time-course of action. Similarly, psilocybin and DOI dose-dependently reversed thermal hypersensitivity in the chronic inflammatory mouse model of Complete Freud's Adjuvant (CFA). The effects of Psilocybin and DOI in both models were mediated by activation of 5-HT2A receptors (5-HT2AR). Overall, the present study suggests that classical psychedelics psilocybin and DOI are effective in reducing pain-like behaviors via 5-HT2AR activation in two mouse models of chronic pain.

keywords:
Animals, Mice, Inbred C57BL, Mice, Hyperalgesia, Disease Models, Animal, Amphetamines, Receptor, Serotonin, 5-HT2A, Hallucinogens, Female, Male, Serotonin 5-HT2 Receptor Agonists, Chronic Pain, Psilocybin

raw_json:
{"europe_pmc_id":"40107634","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Opinion Mining of Erowid's Experience Reports on LSD and Psilocybin-Containing Mushrooms.
authors: Al-Imam A, Lora R, Motyka MA, Marletta E, Vezzaro M, Moczko J, Younus M, Michalak M.
publication_date: 2025-03-03
doi: 10.1007/s40264-025-01530-z
pubmed_id: 40032797
source_url: https://doi.org/10.1007/s40264-025-01530-z
substance_tags: psilocybin
topic_tags: Emotional Processing
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
abstract:
BackgroundPsychedelics are gaining attention for their therapeutic potential in modern and personalized medicine. Online forums such as Erowid provide valuable user insights, but analyses of these experiences using natural language processing (NLP) remain scarce.ObjectiveThis study aims to utilize NLP, including sentiment and lexicon analysis, to examine user-generated experience reports on psilocybin-containing mushrooms and LSD from the Erowid forum.MethodsData from 2188 Erowid users (1161 psilocybin mushrooms and 1027 LSD) was collected via automated web scraping with XPath, CSS selectors, and Selenium WebDriver. The dataset included report titles, substances, and demographics. Sentiment analysis utilized BERT, RoBERTa, and VADER models. Preprocessing involved tokenization, lemmatization, part-of-speech tagging, and stop-word filtering. Lexicon analysis identified themes through recurring n-grams, visualized using Python.ResultsUser demographics revealed comparable ages for psilocybin mushrooms (23.8 ± 0.9 years) and LSD users (20.0 ± 0.6 years), with a predominance of male users. The BERT model predominantly labeled experiences as negative (unfavorable), particularly for mushroom users (p = 0.001). VADER indicated more positive experiences for mushroom users (p < 0.001), while RoBERTa mainly classified experiences as negative or neutral. Significant gender differences were found only with VADER, where more male users expressed positive opinions about psilocybin mushrooms (74.09% versus 65.52%, p < 0.021). The VADER model yielded more polarized results, whereas RoBERTa's cautious classifications indicate its suitability for analyzing lengthy and complex psychedelic reports. Further, RoBERTa outperformed other transformer-based models, achieving the highest accuracy. Lexicon analysis revealed emotional, sensory, and temporal themes, with psilocybin reports emphasizing introspection and time dilation phenomenon, while LSD reports highlighted memory issues and cognitive disorientation.ConclusionsSentiment analysis showed that VADER produced more polarized results, while RoBERTa offered cautious classifications with the highest accuracy. Lexicon analysis revealed shared themes, with mushroom reports focusing on introspection and time dilation perception, while those of LSD emphasized cognitive disturbances. This study highlights the value of these analyses in understanding psychedelic experiences, informing harm reduction, and guiding policy-making.

keywords:
Humans, Agaricales, Lysergic Acid Diethylamide, Hallucinogens, Natural Language Processing, Adult, Female, Male, Young Adult, Data Mining, Psilocybin

raw_json:
{"europe_pmc_id":"40032797","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Romeo B, Kervadec E, Fauvel B, Strika-Bruneau L, Amirouche A, Bezo A, Piolino P, Benyamina A
journal: Neuroscience and biobehavioral reviews
publication_date: 2025-04-30
doi: 10.1016/j.neubiorev.2025.106086
pubmed_id: 40031999
source_url: https://pubmed.ncbi.nlm.nih.gov/40031999/
substance_tags: psilocybin
topic_tags: Addiction,Mystical Experience,Meta-Analysis,Systematic Review,Review Article
study_type: Meta-Analysis
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":"40031999"}
title:
The intensity of the psychedelic experience is reliably associated with clinical improvements: A systematic review and meta-analysis.

abstract:
Psychedelic-assisted therapies have demonstrated promising results in treating mental disorders, with results suggesting that the subjective intensity and quality of psychedelic experiences plays a significant role in mediating therapeutic effects. However, the strength of this association across diagnoses and treatment settings remains underexplored.
We searched MEDLINE, Embase, and PsycINFO databases for studies examining the correlation between the intensity of the psychedelic experience and clinical outcomes in patients treated with classical psychedelics. Meta-correlations were performed, and standardized mean differences of psychedelic experience intensity scores were compared between clinical responders and non-responders using random-effects models. Subgroup analyses were conducted based on diagnosis, study design, setting (clinical vs. naturalistic), and substance used.
A significant positive correlation was found between the intensity of mystical experiences and clinical improvement across all studies (r =.33, p
The intensity of psychedelic experiences is significantly and reliably associated with therapeutic outcomes, particularly in mood disorders. Clinical settings and prospective study designs strengthen this relationship, emphasizing the importance of controlled environments and therapeutic support to fully benefit from the therapeutic potential of psychedelics.

keywords:
Addiction, Intensity of psychedelic experience, LSD, Meta-analysis, Mood disorders, Psilocybin, Psychedelics


publication_date: 2025-02-27
doi: 10.1177/02698811251319457
pubmed_id: 40018886
source_url: https://doi.org/10.1177/02698811251319457
substance_tags: psilocybin,psilocin
topic_tags: Addiction,Pharmacology,Receptor Pharmacology,Clinical Trial,Safety
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:
Single-dose psilocybin therapy for alcohol use disorder: Pharmacokinetics, feasibility, safety and efficacy in an open-label study.

authors:
Jensen ME, Stenbæk DS, Messell CD, Poulsen ED, Varga TV, Fisher PM, Nielsen MKK, Johansen SS, Volkow ND, Knudsen GM, Fink-Jensen A.

abstract:
BackgroundPsilocybin, a serotonin 2A receptor agonist with psychedelic properties, shows promise as a novel treatment for alcohol use disorder (AUD). While current studies involve two dosing sessions, the effects of a single dose have not been investigated.AimsTo investigate the pharmacokinetics, feasibility, safety and efficacy of single-dose psilocybin therapy in AUD.MethodsThis open-label, single-group study investigated single-dose psilocybin therapy in 10 treatment-seeking adults (8 men and 2 women; median age 44 years) with severe AUD. The treatment involved two preparation sessions, a high-dose psilocybin session (25 mg) and two integration sessions. Pharmacokinetics were determined by noncompartmental analysis, and changes in alcohol consumption, craving and self-efficacy, were assessed using a linear mixed model.ResultsNotable between-participant pharmacokinetic variations were observed, with peak plasma psilocin concentrations ranging from 14 to 59 µg/L. Alcohol consumption significantly decreased over the 12 weeks following psilocybin administration. Heavy drinking days were reduced by 37.5 percentage points (95% CI: -61.1 to -13.9, p = 0.005), and drinks per day decreased by 3.4 drinks (95% CI: -6.5 to -0.3, p = 0.03). This was corroborated by reports of rapid and sustained reductions in craving and increases in self-efficacy.ConclusionsDespite pharmacokinetic variations, a single 25 mg psilocybin dose was safe and effective in reducing alcohol consumption in AUD patients. Larger randomised, placebo-controlled, single-dose AUD trials are warranted.Clinical trial registrationhttps://clinicaltrials.gov/study/NCT04718792.

keywords:
Humans, Alcoholism, Hallucinogens, Treatment Outcome, Feasibility Studies, Alcohol Drinking, Adult, Middle Aged, Female, Male, Serotonin 5-HT2 Receptor Agonists, Craving, Psilocybin

raw_json:
{"europe_pmc_id":"40018886","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psychedelic-assisted Therapy as a Promising Treatment for Irritable Bowel Syndrome.
authors: Mauney E, King F, Burton-Murray H, Kuo B.
publication_date: 2025-02-16
doi: 10.1097/mcg.0000000000002149
pubmed_id: 39998940
source_url: https://doi.org/10.1097/mcg.0000000000002149
keywords: Humans, Irritable Bowel Syndrome, Hallucinogens, Chronic Pain, Psilocybin
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 11:22:04
abstract:
Irritable bowel syndrome (IBS) is prevalent and can be disabling. Many patients remain symptomatic despite behavioral and medical therapies. Psychedelic-assisted therapy (PAT), in which serotonergic agents like psilocybin are administered in a psychotherapeutic context, has shown promise for refractory psychiatric disorders, including major depressive disorder and post-traumatic stress disorder. Emerging evidence suggests PAT may also be beneficial for chronic pain conditions, including fibromyalgia, low back pain, and migraines. IBS is highly comorbid with depression, anxiety, and other chronic pain disorders, suggesting shared cognitive and neurological roots and potentially shared therapeutic targets. In this editorial, we discuss 3 lines of evidence for PAT as a treatment for IBS, under the overarching themes of (1) psychological mechanisms (the findings from historic studies of psychedelics for chronic pain and the elements of psychobiological dysfunction targeted by PAT), (2) central nervous system mechanisms (default mode network modulation and induction of neuroplasticity), and (3) the neurointestinal pathophysiology of IBS that may be modified by PAT. We argue that this evidence suggests PAT is worthy of study as a new therapy for IBS, and potentially for other disorders of gut-brain interaction (DGBI). Successful application of PAT to gastrointestinal disease would represent a major step beyond mind-body dualism, with potential implications for other functional somatic disorders.

topic_tags:
Depression,Anxiety,PTSD,Chronic Pain,Headache / Migraine,Neuroplasticity,Mechanism of Action,Default Mode Network,Drug Interactions

raw_json:
{"europe_pmc_id":"39998940","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Dave M, Shore R, Cupido T, Haley C, Clinkard D.
publication_date: 2025-02-17
doi: 10.1097/eja.0000000000002138
pubmed_id: 39967455
source_url: https://doi.org/10.1097/eja.0000000000002138
keywords: Humans, Lysergic Acid Diethylamide, Anesthetics, Hallucinogens, Anesthesia, Psilocybin
substance_tags: psilocybin
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:01
title:
Anaesthetic implications of psilocybin and lysergic acid diethylamide: what is old is now new: A narrative review on psychedelics and anaesthesia.

abstract:
Psychedelic drugs, known for their perception-altering properties, are gaining popularity in the treatment of mental health and pain disorders. As exploratory studies demonstrate clinical efficacy with few adverse events, it is expected that more patients will ingest psychedelic drugs. For therapeutic reasons, as with any drug, anaesthesiologists must be aware of its physiological effects and contraindications to ensure the safe provision of anaesthesia. Psilocybin is a 5HT 1A and 5HT 2A serotonin receptor agonist thought to act on excitatory and inhibitory neurons in the brain. Acute ingestion causes sympathetic nervous system activation, which can precipitate haemodynamic instability. Activation of the 5HT serotonin receptors can also place the patient at risk of serotonin syndrome. Chronic use increases plasma concentrations of cortisol, which has implications on prophylactic stress-dosing of glucocorticoids preoperatively. Lysergic acid diethylamide (LSD), a synthetic psychoactive substance, is also a 5HT2 A agonist. LSD has been shown to potentiate opioid analgesics, and monoamine oxidase (MAO) inhibition. Historical reports suggest that LSD has anticholinesterase activity and can prolong neuromuscular block with depolarising muscle relaxants. Mescaline is a poorly understood psychedelic with similar autonomic effects. Historical studies have shown decreased neuromuscular transmission and an association with malignant hyperthermia. When managing patients who have consumed psychedelics drugs, it is important to consider delaying surgery whenever possible, to allow acute intoxication to wane. A high degree of suspicion and an understanding of management principles is vital to the safe conduct of anaesthesia. Future research should explore therapeutic doses of psychedelic drugs to understand physiologic effects at various concentrations.

topic_tags:
Addiction,Chronic Pain,Receptor Pharmacology,Aging,Review Article,Safety,Adverse Events,Contraindications

raw_json:
{"europe_pmc_id":"39967455","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Noback M, Kenton JA, Klein AK, Hughes ZA, Kruegel AC, Schmid Y, Halberstadt AL, Young JW.
publication_date: 2025-01-31
doi: 10.1016/j.neuropharm.2025.110334
pubmed_id: 39900138
source_url: https://doi.org/10.1016/j.neuropharm.2025.110334
substance_tags: psilocybin
topic_tags: Receptor Pharmacology,Microdosing,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 11:22:04
title:
Low (micro)doses of 2,5-dimethoxy-4-propylamphetamine (DOPR) increase effortful motivation in low-performing mice.

abstract:
Treating amotivated states remains difficult. Classical psychedelic drugs (5-HT2A receptor agonists) such as LSD and psilocybin have shown therapeutic potential in treating such symptoms, but their development has been hindered by their undesirable hallucinogenic effects. There is increasing evidence that administration of psychedelics at dose levels too low to evoke a hallucinogenic effect ("microdoses") may have therapeutic value in contexts of mood and cognition. 2,5-Dimethoxy-4-propylamphetamine (DOPR) is a psychedelic phenethylamine compound acting as a 5-HT2A receptor agonist. We used a combination of behavioral assays to determine the motivational and hallucinogenic-like effects of DOPR and identify the dose ranges at which each of these effects were observed. In mice, the motivational effects of psychedelic compounds were assessed using the progressive ratio breakpoint task (PRBT, n = 80), a translational assay sensitive to changes in motivation. Psychedelic-like effects were gauged using the mouse head-twitch response (HTR, n = 72) assay, a preclinical readout of psychedelic potential. Significant improvements in PRBT performance were seen at doses as low as 0.0106 mg/kg in animals with low baseline PRBT scores while high-performing PRBT mice were unaffected. DOPR only induced significant HTR at doses ≥0.1 mg/kg. Together, these results indicate that the psychedelic DOPR may increase motivation in those with a low motivated state. Importantly, these effects may be attainable at low doses below the threshold required to induce psychedelic subjective effects. Hence, the ability of low doses of DOPR and other psychedelic drugs to alleviate amotivated states in rodents manipulated to induce disease-relevant states should be investigated.

keywords:
Animals, Mice, Inbred C57BL, Mice, Amphetamines, Hallucinogens, Motivation, Dose-Response Relationship, Drug, Male, Serotonin 5-HT2 Receptor Agonists

raw_json:
{"europe_pmc_id":"39900138","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Catalyst for change: Psilocybin's antidepressant mechanisms-A systematic review.
authors: Liebnau J, Betzler F, Kerber A.
publication_date: 2025-01-19
doi: 10.1177/02698811241312866
pubmed_id: 39829391
source_url: https://doi.org/10.1177/02698811241312866
keywords: Brain, Humans, Hallucinogens, Antidepressive Agents, Cognition, Psilocybin, Emotional Regulation
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 11:22:02
abstract:
BackgroundRecent clinical trials suggest promising antidepressant effects of psilocybin, despite methodological challenges. While various studies have investigated distinct mechanisms and proposed theoretical opinions, a comprehensive understanding of psilocybin's neurobiological and psychological antidepressant mechanisms is lacking.AimsSystematically review potential antidepressant neurobiological and psychological mechanisms of psilocybin.MethodsSearch terms were generated based on existing evidence of psilocybin's effects related to antidepressant mechanisms. Following Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, 15 studies were systematically reviewed, exploring various therapeutic change principles such as brain dynamics, emotion regulation, cognition, self-referential processing, connectedness, and interpersonal functioning.ResultsWithin a supportive setting, psilocybin promoted openness, cognitive and neural flexibility, and greater ability and acceptance of emotional experiences. A renewed sense of connectedness to the self, others, and the world emerged as a key experience. Imaging studies consistently found altered brain dynamics, characterized by reduced global and within default mode network connectivity, alongside increased between-network connectivity.ConclusionsTogether, these changes may create a fertile yet vulnerable window for change, emphasizing the importance of a supportive set, setting, and therapeutic guidance. The results suggest that psilocybin, within a supportive context, may induce antidepressant effects by leveraging the interplay between neurobiological mechanisms and common psychotherapeutic factors. This complements the view of purely pharmacological effects, supporting a multileveled approach that reflects various relevant dimensions of therapeutic change, including neurobiological, psychological, and environmental factors.

topic_tags:
Depression,Brain Imaging,Mechanism of Action,Default Mode Network,Aging,Emotional Processing,Clinical Trial,Meta-Analysis,Systematic Review,Review Article

raw_json:
{"europe_pmc_id":"39829391","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: ALSUntangled #77: Psilocybin.
publication_date: 2024-12-21
doi: 10.1080/21678421.2024.2441274
pubmed_id: 39709547
source_url: https://doi.org/10.1080/21678421.2024.2441274
keywords: Animals, Humans, Amyotrophic Lateral Sclerosis, Hallucinogens, Psilocybin
substance_tags: psilocybin
topic_tags: Neurogenesis,Mechanism of Action,Review Article,Case Report,Safety,Adverse Events,Inflammation
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:
Bakshi B, Yerraguntla S, Armon C, Barkhaus P, Bertorini T, Bowser R, Breevoort S, Bromberg M, Brown A, Carter GT, Chang V, Crayle J, Fullam T, Greene M, Heiman-Patterson T, Jackson C, Jhooty S, Mallon E, Cadavid JM, Mcdermott CJ, Pattee G, Pierce K, Ratner D, Sun Y, Wang O, Wicks P, Wiedau M, Bedlack R.

abstract:
ALSUntangled reviews alternate and off-label treatments prompted by patient interest. Here, we review psilocybin, a chemical derived from mushrooms and belonging in the category of drugs known as psychedelics. Psilocybin has plausible mechanisms for slowing ALS progression because of its ability to cross the blood brain barrier and effect neurogenesis and inflammation. Currently, there are no pre-clinical ALS models, case reports, or trials for psilocybin and ALS in the context of disease modifying therapy. Depending on dosing, there can be a high risk of psychological side effects including hallucinations and physical harm. Based on the above information, we do not currently support the use of psilocybin as a means to slow ALS progression.

raw_json:
{"europe_pmc_id":"39709547","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Menon V, Ramamurthy P, Venu S, Andrade C.
publication_date: 2024-12-02
doi: 10.1111/acps.13778
pubmed_id: 39627679
source_url: https://doi.org/10.1111/acps.13778
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 11:22:01
title:
Randomized Controlled Trials of Psilocybin-Assisted Therapy in the Treatment of Major Depressive Disorder: Systematic Review and Meta-Analysis.

abstract:
IntroductionThere is growing interest in the use of psychedelic-assisted therapy (PAT) for major depressive disorder (MDD), including treatment-resistant depression. We used randomized controlled trial (RCT) data to compare summary estimates of change in depression ratings with PAT versus comparator treatments in MDD. We also compared response and remission rates, and adverse effects.MethodsWe searched MEDLINE, EMBASE, Cochrane Central Register for Controlled Trials (CENTRAL), and SCOPUS from inception till April 2024. Our primary efficacy outcome was 1-week (or nearest) between-group change in depression ratings. Secondary efficacy outcomes were changes in depression ratings at days 2, 14, and 42 (or nearest) and study-defined response and remission rates at week 1 (or nearest). Safety outcomes were reported adverse effects. We pooled outcomes in random-effects meta-analyses using standardized mean difference (SMD; Hedges g) for continuous outcomes and risk ratio (RR) for categorical outcomes.ResultsWe found 6 eligible RCTs (pooled N = 427), all on psilocybin. The pooled SMD for 1-week between-group change in depression ratings was -0.72 [95% CI, -0.95 to -0.49; I2 = 17%; 5 RCTs; n = 403], favouring PAT; results were similar at days 2, 14, and 42. The response [RR = 3.42; 95% CI, 2.35-4.97; I2 = 0%; 4 RCTs; n = 373] and remission [RR = 3.66; 95% CI, 2.26-5.92; I2 = 0%; 4 RCTs; n = 373] rates also favored PAT. The PAT group had a small but significantly increased risk of developing any adverse event [RR = 1.20; 95% CI, 1.01-1.42; I2 = 43%; 4 RCTs; n = 373] and a significantly higher risk of experiencing headache [RR = 1.78; 95% CI, 1.10-2.86; I2 = 52%; 4 RCTs; n = 373] and dizziness [RR = 6.52; 95% CI, 1.19-35.87; I2 = 0%; 3 RCTs; n = 269]. Low heterogeneity characterized most analyses and findings were similar in sensitivity analyses.ConclusionAntidepressant effects of psilocybin-assisted therapy are superior (with at least medium effect sizes) to comparator interventions for at least up to 6 weeks postintervention.

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

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

raw_json:
{"europe_pmc_id":"39627679","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Neurochemical characterization of 5-HT2AR partial agonists with simultaneous PET-MRI.
publication_date: 2024-11-28
doi: 10.1177/0271678x241302937
pubmed_id: 39610321
source_url: https://doi.org/10.1177/0271678x241302937
substance_tags: psilocybin
topic_tags: Brain Imaging,Receptor Pharmacology,Aging
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
authors:
Bagdasarian FA, Larsen K, Larsen K, Deng HP, Fisher PM, Mandeville JB, Sander CY, Wey HY, Hansen HD.

abstract:
Understanding neuromodulatory effects of serotonin 2A receptor (5-HT2AR) agonists with diverse pharmacological profiles is relevant to advancing psychedelic-related drug applications. We performed simultaneous positron emission tomography (PET) and pharmacological magnetic resonance imaging (phMRI) in anesthetized nonhuman primates (NHP; N = 3) to examine partial agonists with varying 5-HT2AR affinities and selectivity profiles: psilocybin (30, 60, and 90 µg/kg), lisuride (5 µg/kg), and 25CN-NBOH (15 µg/kg). Receptor occupancy was assessed with [11C]MDL-100907 PET, and cerebral blood volume (CBV) changes were measured with phMRI. Mixed partial agonists psilocybin and lisuride evoked biphasic CBV responses, whereas the selective 25CN-NBOH produced monophasic CBV increases. Cortical occupancy for psilocybin plateaued at 60 µg/kg (32%), whereas a lower dose of lisuride (5 µg/kg) resulted in similar occupancy (31%). Administration of 25CN-NBOH resulted in lower occupancy (7%) but larger changes in CBV compared to psilocybin and lisuride. The associations between CBV and 5-HT2AR occupancy appear linear for lisuride and 25CN-NBOH, but not for psilocybin. We speculate that the temporal and spatial differences in hemodynamic responses of the three agonists could stem from mixed affinity profiles. This work provides an understanding of pharmacological impacts of mixed serotonergic agonists being pursued as therapeutics for psychiatric conditions, offering valuable insights for future drug applications and development strategies.

keywords:
Brain, Animals, Macaca mulatta, Benzylamines, Lisuride, Receptor, Serotonin, 5-HT2A, Hallucinogens, Positron-Emission Tomography, Magnetic Resonance Imaging, Cerebrovascular Circulation, Male, Serotonin 5-HT2 Receptor Agonists, Psilocybin

raw_json:
{"europe_pmc_id":"39610321","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Floris G, Dabrowski KR, Zanda MT, Daws SE.
journal: bioRxiv
publication_date: 2024-05-31
doi: 10.1101/2024.05.28.596205
source_url: https://doi.org/10.1101/2024.05.28.596205
substance_tags: psilocybin
topic_tags: Addiction,Mechanism of Action,Receptor Pharmacology,Animal Study,Inflammation
study_type: Animal Study
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:01
title:
Psilocybin reduces heroin seeking behavior and modulates inflammatory gene expression in the nucleus accumbens and prefrontal cortex of male rats

abstract:
Preclinical and human studies indicate psilocybin may reduce perseverant maladaptive behaviors, including nicotine and alcohol seeking. Such studies in the opioid field are lacking, though opioids are involved in more >50% of overdose deaths. Psilocybin is an agonist at the serotonin 2A receptor (5-HT2A R), a well-documented target for modulation of drug seeking, and evidence suggests 5-HT2A R agonists may dampen motivation for opioids. We sought to investigate the therapeutic efficacy of psilocybin in mediating cessation of opioid use and maintenance of long-lasting abstinence from opioid seeking behavior in a rat model of heroin self-administration (SA). Psilocybin or 5-HT2A R antagonists ketanserin and volinanserin were administered systemically to rats prior to SA of 0.075 mg/kg/infusion of heroin, or relapse following forced abstinence. Psilocybin did not alter heroin taking, but a single exposure to 3.0 mg/kg psilocybin 4-24 hours prior to a relapse test blunted cue-induced heroin seeking. Conversely, 5-HT2A R antagonists exacerbated heroin relapse. To begin to elucidate mechanisms of psilocybin, drug-naïve rats received psilocybin and/or ketanserin, and tissue was collected from the prefrontal cortex (PFC), a region critical for drug seeking and responsive to psilocybin, 24 hours later for RNA-sequencing. 3.0 mg/kg psilocybin regulated ∼2-fold more genes in the PFC than 1.0 mg/kg, including genes involved in the cytoskeleton and cytokine signaling. Ketanserin blocked >90% of psilocybin-regulated genes, including the IL-17a cytokine receptor, Il17ra. Psychedelic compounds have reported anti-inflammatory properties, and therefore we performed a gene expression array to measure chemokine/cytokine molecules in the PFC of animals that displayed psilocybin-mediated inhibition of heroin seeking. Psilocybin regulated 4 genes, including Il17a, and a subset of genes correlated with relapse behavior. Selective inhibition of PFC IL-17a was sufficient to reduce heroin relapse. We conclude that psilocybin reduces heroin relapse and highlight IL-17a signaling as a potential downstream pathway of psilocybin that also reduces heroin seeking.

raw_json:
{"europe_pmc_id":"PPR860490","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


title: Identifying Three Psilocybin Use Patterns by Frequency and Quantity.
authors: Gray BA, Bolts OL, Fidler D, Prince M.
publication_date: 2024-08-22
doi: 10.15288/jsad.23-00312
pubmed_id: 39177101
source_url: https://doi.org/10.15288/jsad.23-00312
substance_tags: psilocybin
topic_tags: Adolescents
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
abstract:
ObjectivePatterns of psilocybin use in nonclinical settings are not well described in the literature. Psilocybin use can involve infrequent, large (i.e., macro) doses that produce hallucinogenic effects. In addition, some people report psilocybin use at particularly small (i.e., micro), sub-perceptual doses. Given the heterogeneity in reported use metrics, we sought to determine whether there are identifiable patterns of psilocybin use based on participants' self-described typical use frequencies and quantities and to describe how demographic characteristics are associated with each pattern of use.MethodParticipants were recruited from online communities via Reddit.com. We used latent profile analysis to discern psilocybin use patterns defined by frequency and quantity of use. The analytic sample consisted of 664 participants (75.6% U.S. residents; 83.1% White; 67.2% male).ResultsThe chipper profile (18%) was associated with approximately 1 to 4 annual uses and using between 0.75 g and 1.0 g of dehydrated, psilocybin-containing mushrooms. The tripper profile (64%) was associated with approximately 2 to 6 annual uses and self-reported use quantities between 2 and 4 g. The micro-doser profile (18%) was related to substantively higher psilocybin use frequencies than the other profiles (between 2 and 4 times a week) and a lower range of preferred quantities (between 0.25 g and 0.75 g). In addition, profiles differed by certain demographic measurements, lifetime psilocybin use, and timing of psilocybin use.ConclusionsPsilocybin use in nonclinical settings is heterogeneous. We identified three profiles that differed on frequency and quantity of use and their associated demographic characteristics. Next steps are to identify factors that affect one's likelihood of experiencing particular use outcomes and to explore use variability.

keywords:
Humans, Substance-Related Disorders, Hallucinogens, Adolescent, Adult, Middle Aged, Female, Male, Young Adult, Psilocybin

raw_json:
{"europe_pmc_id":"39177101","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Dwyer J, Johnston RB, O'Callaghan C, Kallianis V, Ross ML
journal: Frontiers in psychiatry
publication_date: 2024-12-31
doi: 10.3389/fpsyt.2025.1541528
pubmed_id: 40370591
source_url: https://pubmed.ncbi.nlm.nih.gov/40370591/
substance_tags: psilocybin
topic_tags: End-of-Life Distress,Healthcare Workers
study_type: Other
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":"40370591"}
title:
Music as a collaborating actor: new insights into the nature and role of music in psychedelic-assisted psychotherapy.

abstract:
Music has been identified as a central feature of psychedelic-assisted psychotherapy (PAP) and has hitherto been understood to amplify the psychedelic experience in a predictable way that has been codified into music recommendations and playlists.
To re-evaluate the nature and role of music within the participant's world during psychedelic-assisted psychotherapy.
Phenomenological analysis of participants' descriptions of music during a randomised control trial of PAP at end of life involving two doses and a semi-structured interview following each dose.
Music undergoes a profound change during PAP that radically transforms it from everyday recorded music into a series of internally generated multisensory and deeply personal experiences that arrive fully formed and are instantly known by the participant. Some of these are constituted into actors that collaborate with the participant and the psychotherapist in their ongoing psychotherapy endeavours. This stands in stark contrast with the everyday properties of music described by those in the placebo group.
An alternate understanding of music in PAP is suggested that radically departs from the view that music is "administered" as part of PAP. There are profound implications for the practise of PAP and further research.
Australian New Zealand Clinician Trials Registry identifier, ACTRN12619001225101.

keywords:
end-of-life, music therapy, palliative care, psilocybin, psychedelic assisted psychotherapy, psychotherapy


title: The phenomenology of psilocybin: transformative insights for research and clinical practice.
authors: Metastasio A, Prevete E, Venturini S, Garofalo A, Cecconello B, De Pisapia N, Corazza O.
publication_date: 2025-04-24
doi: 10.3389/fpsyg.2025.1455902
pubmed_id: 40351574
source_url: https://doi.org/10.3389/fpsyg.2025.1455902
substance_tags: psilocybin
topic_tags: Emotional Processing
study_type: Qualitative Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
abstract:
IntroductionConsidering the increasing evidence supporting psilocybin's efficacy in therapeutic settings, it is essential to deepen our understanding of its subjective meanings and effects to enhance its integration into psychotherapy. Current knowledge is primarily based on psychometric assessments or unstructured personal reports, leaving a gap in the qualitative analysis of subjective psychedelic experiences and the resulting changes.ObjectiveThis study aimed to describe the subjective psychedelic experience with psilocybin in a structured, objective, and non-judgmental way (Epoche), while exploring its potential clinical applications.MethodsA phenomenological qualitative approach, integrating interpretative phenomenological analysis (IPA) and the dynamic analysis (PHD) method, was used to analyze self-reported psilocybin experiences. Participants who met the inclusion criteria of being healthy adults and who had experienced psilocybin without any other substances were recruited through convenience sampling. Semi-structured interviews explored dimensions such as emotions, bodily sensations, perception of time and space, relationships, values, and enduring transformation. Data were analyzed using thematic coding.ResultsTen interviews were carried out with voluntary participants. All the interviewees reported enhanced emotional and interpersonal sensitivity, increased empathy, a deeper connection to others, and a heightened ability to resolve personal issues as well as long-lasting insights into their lives and values. Participants also showed profound changes in behavior, attitudes, and interests, indicative of the potential for psilocybin to catalyze significant personal growth and development.ConclusionThis study highlights the transformative potential of psilocybin experiences and their relevance to psychotherapeutic practices. By employing phenomenological methods, we offer a structured understanding of these states, which could be used in future to provide guidance for their integration into therapy by giving a better insight into psychedelic experience.

raw_json:
{"europe_pmc_id":"40351574","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Exploring Factors Affecting Psychological Flexibility After Psychedelic Experiences.
authors: Romeo B, Kervadec E, Fauvel B, Strika-Bruneau L, Amirouche A, Verroust V, Piolino P, Benyamina A
journal: Journal of psychoactive drugs
publication_date: 2025-04-24
doi: 10.1080/02791072.2025.2495937
pubmed_id: 40277080
source_url: https://pubmed.ncbi.nlm.nih.gov/40277080/
keywords: LSD, Psychedelic, acceptance and commitment therapy, psilocybin, psychological flexibility
substance_tags: psilocybin
topic_tags: Mystical Experience,Psychological Flexibility,Observational Study
study_type: Observational Study
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":"40277080"}
abstract:
Neurobiological effects and psychological models propose that psychedelics may promote psychological flexibility, suggesting a transdiagnostic effect by disrupting maladaptive patterns. The objective of this study was therefore to investigate the determinants of psychological flexibility change following a psychedelic use. This retrospective online survey included French individuals who had undergone a significant psychedelic experience. Participants were assessed for mystical experience intensity with the MEQ-30, and psychological flexibility via the AAQ-II, at three retrospective time points. Data analysis comprised descriptive statistics, correlation analysis, ANCOVA to evaluate the impact of psychedelic use variables on psychological flexibility, and linear regression to identify predictors of psychological flexibility changes. Data showed a positive correlation between mystical experience intensity and improvements in psychological flexibility, especially 1-month post-experience (


authors: Williams ML, Rudin D, Schmid Y, von Salm J.
publication_date: 2025-04-22
doi: 10.3389/fpsyt.2025.1600812
pubmed_id: 40336703
source_url: https://doi.org/10.3389/fpsyt.2025.1600812
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
title:
Editorial: Beyond psilocybin: exploring the clinical potential of alternative and novel psychedelics.

raw_json:
{"europe_pmc_id":"40336703","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: [Treatment with psychedelics: potential benefits in Parkinson's disease].
authors: Penzenstadler L, Baudois S, Lingenberg A, Catalano Chiuvé S, Tomkova E, Fleury V.
publication_date: 2025-03-31
doi: 10.53738/revmed.2025.21.915.47180
pubmed_id: 40275842
source_url: https://doi.org/10.53738/revmed.2025.21.915.47180
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:
Psychedelics, such as psilocybin and lysergic acid diethylamide, modulate neuroplasticity and brain connectivity via 5-HT2A receptors. Their efficacy has been demonstrated in depression and anxiety, where they are particularly interesting because of their rapid and long-lasting effect. They could also be beneficial for addictions, post-traumatic stress, and obsessive-compulsive disorder. This article explores their therapeutic potential in Parkinson's disease (PD), both symptomatically in PD depression, anxiety, and impulse control disorders, and in terms of neuroprotection. Psychedelics actually stimulate synaptogenesis, increase brain-derived neurotrophic factor, and exert anti-inflammatory effects. Although promising, these treatments require clinical trials to confirm their safety and efficacy in PD.

keywords:
Humans, Parkinson Disease, Lysergic Acid Diethylamide, Hallucinogens, Neuroprotective Agents, Depression, Anxiety, Psilocybin

topic_tags:
Depression,Anxiety,PTSD,Addiction,OCD,Neuroplasticity,Receptor Pharmacology,Clinical Trial,Safety,Inflammation

raw_json:
{"europe_pmc_id":"40275842","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Cohen J, Sulimani L, Procaccia S, Lerenthal Y, Milay L, Taran I, Shapira A, Meiri D.
publication_date: 2025-04-21
doi: 10.1038/s41598-025-97710-z
pubmed_id: 40263354
source_url: https://doi.org/10.1038/s41598-025-97710-z
substance_tags: psilocybin
topic_tags: In Vitro Study,Metabolomics
study_type: In Vitro 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:
Comprehensive analysis of 42 psilocybin-producing fungal strains reveals metabolite diversity and species-specific clusters.

abstract:
Psilocybin-producing fungi have garnered attention due to accumulating evidence regarding the therapeutic potential of their principal component psilocybin. This diverse group of fungi harbors a wealth of less-studied metabolites, however, thus far most research has addressed them as a cohesive group. By optimizing an approach for extraction and analysis, we examined the metabolomes of 42 distinct fungi strains and show that the breadth and diversity of metabolites within and between 9 species. We integrated and validated the reproducible and reliable extraction of fruiting bodies followed by chromatographic separation, quantification and identification of their known and yet to be identified secondary metabolites. The optimal extraction of fruiting bodies for high yield of indole alkaloids was achieved using a 1:20 tissue:solvent ratio, 25:75 H2O:MeOH (pH = 9), for 1.5 h, followed by the quantification of 8 tryptophan-derived indolamines by HPLC-DAD and the identification of putative metabolite hydroxypsilocybin by HPLC-MS/MS. The metabolomic analysis revealed the diversity of metabolites within and between species. Finally, we developed and present a method that mimics the in vivo process of dephosphorylation that occurs upon ingestion for in vitro setups. Overall, our study summarizes a standardized approach for both in vitro and in vivo studies involving psilocybin-producing fungi, showcasing the unique metabolome of each strain and the rich diversity of these fungi, encompassing promising pharmaceutical potential.

keywords:
Fungi, Hallucinogens, Chromatography, High Pressure Liquid, Species Specificity, Tandem Mass Spectrometry, Metabolomics, Metabolome, Psilocybin

raw_json:
{"europe_pmc_id":"40263354","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2025-04-21
doi: 10.1017/s147895152500032x
pubmed_id: 40259688
source_url: https://doi.org/10.1017/s147895152500032x
keywords: Humans, Neoplasms, Hallucinogens, Stress, Psychological, Psilocybin, Psychological Distress
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 11:22:00
title:
Evaluating the effectiveness of psilocybin in alleviating distress among cancer patients: A systematic review.

authors:
Lapid MI, Pagali SR, Randall AL, Donovan KA, Bronars CA, Gauthier TA, Bock J, Lim SD, Carey EC, Sokolowski E, Ulrich AM, Hassett LC, Kung S, Whitford KJ, Olivier KR, D'Andre SD.

abstract:
ObjectivesPsychological and existential distress is prevalent among patients with life-threatening cancer, significantly impacting their quality of life. Psilocybin-assisted therapy has shown promise in alleviating these symptoms. This systematic review aims to synthesize the evidence on the efficacy and safety of psilocybin in reducing cancer-related distress.MethodsWe searched MEDLINE, APA PsycINFO, Cochrane database, Embase, and Scopus from inception to February 8, 2024, for randomized controlled trials (RCTs), open-label trials, qualitative studies, and single case reports that evaluated psilocybin for cancer-related distress. Data were extracted on study characteristics, participant demographics, psilocybin and psychotherapy intervention, outcome measures, and results. Two authors independently screened, selected, and extracted data from the studies. Cochrane Risk of Bias for RCTs and Methodological Index for Non-Randomized Studies criteria were used to evaluate study quality. This study was registered with PROSPERO (CRD42024511692).ResultsFourteen studies met the inclusion criteria, comprising three RCTs, five open-label trials, five qualitative studies, and one single case report. Psilocybin therapy consistently showed significant reductions in depression, anxiety, and existential distress, with improvements sustained over several months. Adverse effects were generally mild and transient.Significance of resultsThis systematic review highlights the potential of psilocybin-assisted therapy as an effective treatment for reducing psychological and existential distress in cancer patients. Despite promising findings, further large-scale, well-designed RCTs are needed to confirm these results and address existing research gaps.

topic_tags:
Depression,Anxiety,End-of-Life Distress,Randomized Controlled Trial,Systematic Review,Review Article,Case Report,Cancer Patients,Safety

raw_json:
{"europe_pmc_id":"40259688","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


journal: Wellcome Open Res
publication_date: 2025-04-21
doi: 10.12688/wellcomeopenres.22543.2
source_url: https://doi.org/10.12688/wellcomeopenres.22543.2
substance_tags: psilocybin
topic_tags: Brain Imaging,Mechanism of Action,Aging
study_type: Other
source_name: Europe PMC
publication_status: preprint
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:01
title:
Probing the functional magnetic resonance imaging response to psilocybin in functional neurological disorder (PsiFUND): study protocol

authors:
Butler M, Bird C, Maggio C, Durden A, Modlin N, Campbell-Coker K, Edwards M, Pick S, Millman LM, Lowery E, Bhagavan C, Kanaan R, Golder D, Mildon B, Mehta M, Rucker J, Nicholson TR.

abstract:
Background: Functional neurological disorder (FND) is a common cause of neurological symptoms including seizures and movement disorders. It can be debilitating, is associated with high health and social care costs, and can have a poor prognosis. Functional magnetic resonance imaging (fMRI) has suggested FND is a multi-network disorder. Converging evidence suggests that other mechanisms including dissociation, interoception, and motor agency may be abnormal in people with FND. Psychedelics are currently under investigation for numerous neuropsychiatric disorders and have been shown to disrupt functional brain networks. Administering psychedelics to people with FND will help us to probe mechanistic theories of the disorder. Protocol In this open-label neuroimaging study, we will administer 25mg oral psilocybin with psychological support to people with chronic FND (target n = 24). Participants will undergo resting-state and task-based (Libet’s clock, a measure of motor agency) fMRI sequences which will be compared in a pre-post manner. Additional mechanistic outcomes including measures of interoception (heartbeat tracking task), somatisation, illness perceptions, suggestibility, and dissociation will be collected. Data on expectancy, preparedness, and subjective experience of the psychedelic experience will also be gathered. Participants will be followed up for three months following psilocybin administration. fMRI changes in networks will be analysed using seed-based approaches, and additional exploratory analysis of resting-state imaging will take place. Discussion The study will help us to probe the mechanisms thought to potentially underpin FND. As the first modern study of psychedelics in FND, it will also help us to understand whether psychedelic administration alongside psychological support might be safe and feasible in this patient population.

raw_json:
{"europe_pmc_id":"PPR1007277","source":"PPR","pub_type":null,"publisher":"Wellcome Open Res","importer":"Europe PMC"}


authors: Thaoboonruang N, Lohitnavy O, Ya K, Lohitnavy M.
publication_date: 2025-04-20
doi: 10.1038/s41598-025-98202-w
pubmed_id: 40258947
source_url: https://doi.org/10.1038/s41598-025-98202-w
keywords: Animals, Humans, Mice, Rats, Hallucinogens, Models, Biological, Male, Psilocybe, Psilocybin
substance_tags: psilocybin,psilocin
topic_tags: Depression,Pharmacology,Clinical Trial,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 11:22:00
title:
Development of a PBPK model of psilocybin/psilocin from Psilocybe cubensis (magic mushroom) in mice, rats, and humans.

abstract:
Psilocybin is an active alkaloid found in magic mushrooms (Psilocybe cubensis). It is classified as a Class I Psychoactive Substance due to its psychoactive properties. Recent research has suggested that psilocybin holds potential for treating major depressive disorder. The objective of this study was to develop a physiologically based pharmacokinetic (PBPK) model for psilocybin and its active metabolite, psilocin, in mice, rats, and humans. This model aims to explore the disposition of psilocin within the body, including its distribution to the target organ, the brain. Psilocybin is assumed to undergo complete conversion to psilocin before the latter enters systemic circulation. The PBPK model effectively characterizes the concentration-time profiles under various dosing scenarios and routes of administration in mice, rats, and humans. The human model has the potential for guiding therapeutic strategies and enhancing clinical trial designs for the therapeutic use of psilocybin.

raw_json:
{"europe_pmc_id":"40258947","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Mimms C, Sotelo K, Khaliq AS.
publication_date: 2025-04-17
doi: 10.7759/cureus.82532
pubmed_id: 40385821
source_url: https://doi.org/10.7759/cureus.82532
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 11:22:02
title:
Comparative Efficacy and Functional Outcomes of Psychedelic-Assisted Therapies in Treatment-Resistant Depression: A Systematic Review of Recent Clinical Trials.

abstract:
This systematic review explores the comparative efficacy and functional outcomes of psychedelic-assisted therapies in the management of treatment-resistant depression (TRD). Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a comprehensive literature search was conducted across PubMed, Scopus, and Web of Science for randomized controlled trials (RCTs) published in the last 12 months. Ten RCTs were included, evaluating agents such as ketamine, esketamine, and psilocybin. Most studies demonstrated significant reductions in depressive symptom severity, with oral and intranasal esketamine and high-dose psilocybin showing sustained antidepressant effects. Functional improvements, such as workplace productivity and cognitive stability, were reported in select trials, notably those involving esketamine. Risk of bias was low in four studies and moderate in six due to open-label or observational extensions. Overall, psychedelic therapies were well tolerated, with favorable safety profiles and minimal cognitive adverse effects. These findings support the integration of psychedelic-assisted therapies as viable alternatives or adjuncts in the treatment of TRD and highlight the importance of assessing both clinical and functional endpoints for a more holistic understanding of therapeutic benefit.

topic_tags:
Depression,Clinical Trial,Randomized Controlled Trial,Systematic Review,Review Article,Observational Study,Treatment-Resistant Depression,Safety

raw_json:
{"europe_pmc_id":"40385821","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2025-04-16
doi: 10.1089/pmr.2024.0108
pubmed_id: 40385526
source_url: https://doi.org/10.1089/pmr.2024.0108
substance_tags: psilocybin
topic_tags: End-of-Life Distress,Safety
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:
Roadmap for Equitable Access and Responsible Use of Psilocybin-Assisted Psychotherapy in Palliative Care.

authors:
Dorval M, Chang SL, Farzin H, Nguyen O, Stephan JF, Tapp D, Deschamps P, Joly Y, Moureaux F, Foxman R, Masse-Grenier M, Fallu JS, Fallu JS, P3A Research Group.

abstract:
Psilocybin-assisted psychotherapy represents a promising addition to palliative care interventions, potentially improving quality of life by addressing existential distress. Despite its safety and effectiveness, this therapy remains limited in Canada, underscoring the need for improved access to ease suffering from life-threatening illnesses. However, important questions remain regarding how to integrate psilocybin-assisted psychotherapy into existing health care frameworks, navigate regulatory challenges, and ensure equitable access for all patients. These unanswered questions highlight the complexity of expanding access and the need for thoughtful, informed approaches to its implementation. To address this, the P3A team (Psilocybin at End of Life: Audacity, Acceptability, Access) held a forum on March 22, 2024, in Quebec, Canada, to explore actionable steps for the responsible use and equitable access to psilocybin-assisted psychotherapy. A total of 57 participants with knowledge in palliative care, including professional and patient associations, patients, health care professionals, researchers, and policymakers, attended the event, which featured presentations, a panel discussion, and small-group workshops. This report provides 16 recommendations across six previously identified key topics: (1) patient eligibility and equity, (2) regulatory framework and respect for autonomy, (3) logistical and organizational aspects, (4) professional education and training, (5) public awareness and information, and (6) research. The elements and recommendations discussed in this article could offer valuable insights for expanding access to psilocybin-assisted psychotherapy in other jurisdictions, particularly in global contexts where similar barriers to care exist.

raw_json:
{"europe_pmc_id":"40385526","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2025-04-14
doi: 10.1136/bmjopen-2024-095992
pubmed_id: 40233965
source_url: https://doi.org/10.1136/bmjopen-2024-095992
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 11:22:01
title:
Psilocybin-Assisted suppoRtive psychoTherapy IN the treatment of prolonged Grief (PARTING) trial: protocol for an open-label pilot trial for cancer-related bereavement.

authors:
Beesley VL, Kennedy TJ, Maccallum F, Ross M, Harvey R, Rossell SL, Sarris J, Perkins D, Neale RE, Bennett-Levy J, Johnson S, Beebe H, Roset N, Strobel J, Parker S.

abstract:
IntroductionProlonged grief disorder (PGD) represents a substantial public health issue, especially in oncology settings where it affects up to 30% of bereaved carers. Current best-practice treatments are lengthy, and up to 50% of participants have persistent PGD. Building on encouraging recent research with psychedelic-assisted therapies, the Psilocybin-Assisted suppoRtive psychoTherapy IN the treatment of prolonged Grief (PARTING) trial is the first study to consider psilocybin-assisted psychotherapy as a potential treatment for prolonged grief.Methods and analysisPARTING is an open-label pilot trial of psilocybin-assisted psychotherapy for approximately 15 people with cancer-related PGD. It aims to investigate feasibility, safety, acceptability, participant experience and participant-reported therapeutic effects. Over a 5-week intervention period, participants will undergo three preparation sessions before receiving a psychoactive (25 mg) dose of psilocybin alongside non-directive supportive guidance, followed by four integration sessions. All sessions will be delivered by a psychologist and either a nurse or Indigenous Therapist. An artificial intelligence-assisted tool will be used to create an artwork of participants' psychedelic experience.Outcomes will be investigated over a 12-month follow-up period. Feasibility will be assessed through recruitment/retention rates and completion of follow-up assessments. Safety will be evaluated via adverse events over 12 months and the comparison of physiological measures (vital signs, biochemistry, haematology, ECG) recorded during screening and 1 day after the psilocybin dose. Qualitative thematic analysis of semistructured interviews with participants and trial therapists will assess acceptability and the therapeutic potential of the treatment. Diagnostic clinical interviews for PGD and quantitative participant-reported measures of therapeutic effects are also being collected. Participant-reported measures include grief severity, depression, anxiety, grief avoidance, psychological flexibility, connectedness, and quality of life.Ethics and disseminationEthics approval has been obtained from QIMR Berghofer Medical Research Institute Human Research Ethics Committee (P3801). Dissemination of results will occur via conference presentations, peer-reviewed publications and media.Trial registration numberAustralian New Zealand Clinical Trials Registry (ACTRN12623000827639).

keywords:
Humans, Neoplasms, Hallucinogens, Pilot Projects, Bereavement, Grief, Psychotherapy, Research Design, Psilocybin

topic_tags:
Depression,Anxiety,Aging,Psychological Flexibility,Clinical Trial,Review Article,Cancer Patients,Safety,Adverse Events

raw_json:
{"europe_pmc_id":"40233965","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Hu S, Lin C, Wang H, Wang X.
publication_date: 2025-03-06
doi: 10.1021/acsptsci.5c00094
pubmed_id: 40242584
source_url: https://doi.org/10.1021/acsptsci.5c00094
substance_tags: psilocybin
topic_tags: Eating Disorders,Wellbeing,Emotional Processing,Safety
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:
Psychedelics and Eating Disorders: Exploring the Therapeutic Potential for Anorexia Nervosa and Beyond.

abstract:
Anorexia nervosa (AN) is a severe psychiatric disorder characterized by extreme food restriction, an intense fear of weight gain, and a distorted body image, leading to significant morbidity and mortality. Conventional treatments such as cognitive-behavioral therapy (CBT) and pharmacotherapy often prove inadequate, especially in severe cases, highlighting the need for novel therapeutic approaches. Recent research into psychedelics, such as psilocybin and 3,4-methylenedioxymethamphetamine (MDMA), offers promising avenues for treating anorexia nervosa by targeting its neurobiological and psychological underpinnings. These psychedelics disrupt maladaptive neural circuits, enhance cognitive flexibility, and facilitate emotional processing, offering potential relief for patients unresponsive to traditional therapies. Early studies have shown positive outcomes with psychedelics, including reductions in anorexia nervosa symptoms and improvements in psychological well-being. However, further research is needed to establish their long-term safety, efficacy, and integration into clinical practice. Addressing the legal, ethical, and safety challenges will be crucial in determining whether psychedelics can transform the treatment landscape for anorexia nervosa and other eating disorders.

raw_json:
{"europe_pmc_id":"40242584","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Tunstad PA, Kvam TM, Uthaug MV, Stewart LH, Andersen KAA, Grønnerød C
journal: Frontiers in pharmacology
publication_date: 2024-12-31
doi: 10.3389/fphar.2025.1556299
pubmed_id: 40276609
source_url: https://pubmed.ncbi.nlm.nih.gov/40276609/
keywords: N,N-dimethyltryptamine (DMT), lysergic acid diethylamide (LSD), psilocybin, psychedelics, survey
substance_tags: psilocybin
topic_tags: Wellbeing,Emotional Processing,Observational Study
study_type: Observational Study
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:20:36
raw_json: {"pubmed_id":"40276609"}
title:
Contextual and experiential aspects of the psychedelic experience predicting improvement in subjective wellbeing: results from a Norwegian internet convenience sample.

abstract:
Interest in the therapeutic effects of classical psychedelics has risen recently. However, little epidemiological knowledge exists about the use of classical psychedelics in Scandinavian countries. Additionally, there is a limited understanding of what factors drive self-reported improvement in wellbeing. The aim of this study was to investigate the relationship between the use of classical psychedelics and outcomes related to subjective wellbeing in an adult, Norwegian-speaking sample. We examined how contextual and phenomenological variables were associated with self-reported subjective wellbeing.
Using an anonymous internet survey, we recruited Norwegian speaking subjects who have had a memorable experience after taking a classic psychedelic substance. Data are presented by using descriptive statistics about the sample and two hierarchical regression analyses. The first regression analysis examined contextual variables, and the second examined variables related to acute phenomena during the experience.
The survey showed that 85% of the sample reported a small to large positive change in subjective wellbeing after their experience with classical psychedelics. Integration, ego dissolution, and emotional breakthrough had a clear, positive predictive effect on the participants' self-reported subjective wellbeing. Variables with lower but significant effects were the degree of challenging experiences, settings associated with nature or ceremony, and a therapeutic or seeking intention.
The use of classical psychedelics leads to an increase in subjective wellbeing for the majority of the participants. This relationship seems dependent upon various experiential aspects of acute subjective drug effects. These findings should be viewed as hypothesis-generating rather than confirmatory due to the study's limitations.


authors: Ardini M, Angelucci F, Rea F, Paluzzi L, Gabriele F, Palerma M, Di Leandro L, Ippoliti R, Pitari G.
publication_date: 2025-04-09
doi: 10.1186/s13062-025-00632-z
pubmed_id: 40211327
source_url: https://doi.org/10.1186/s13062-025-00632-z
keywords: Humans, Methyltransferases, Fluorometry, Molecular Docking Simulation
substance_tags: psilocybin
topic_tags: Spirituality,Clinical Trial,Drug Interactions
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:04
title:
Functional and structural characterization of the human indolethylamine N-methyltransferase through fluorometric, thermal and computational docking analyses.

abstract:
BackgroundThe "psychedelic renaissance" is sparking growing interest in clinical research, along with a rise in clinical trials. Substances such as 3,4-methylenedioxymethamphetamine (MDMA), psilocybin and N,N-dimethyltryptamine (DMT) are involved. The focus of this paper is on indolethylamine N-methyltransferase (INMT), a crucial enzyme in the biosynthesis of key compounds, including DMT, which meets science, medicine and spirituality. The presence of DMT in animals and plants raises many questions about its biological role. Meanwhile, the distribution of INMT in various organs and its involvement in diseases like cancer and mental disorders also fuel investigations worldwide. However, INMT remains largely unexplored, particularly its enzymatic mechanism and structural properties, leaving a significant gap in potential applications.ResultsThis study examines for the first time the catalytic activity of the human INMT (hINMT) using a simple fluorometric steady-state assay employing the substrate quinoline. The findings are supported by thermal shift and docking analyses, providing valuable information about optimal chemical conditions and potential binding sites for substrates. The thermal shift assays indicate that recombinant hINMT is unstable and requires acidic or near-neutral pH and low salt levels. These experiments also allow for the estimation of dissociation constants for its natural coenzymes SAM and SAH, helping to determine the appropriate setup for the fluorometric assays and calculate kinetic constants, which are comparable to other methyltransferases. The docking indicates that quinoline occupies the same site as the natural substrate tryptamine, further validating the fluorometric approach.ConclusionsThe paper provides a foundation for thoroughly studying hINMT under consistent conditions, which is crucial for obtaining reliable kinetic data and maintaining molecular stability for future structural analysis. This represents a valid alternative over previous endpoint radioactive-based and chromatography-mass spectrometry assays, which can provide only apparent steady-state parameters. Given the polymorphisms observed in hINMT and their potential association with psychiatric disorders, e.g., schizophrenia, and cancer, this strategy could serve as an invaluable tool for understanding the structure-function relationship of enzyme mutants and their role in diseases. Furthermore, these findings for the first time provide insights into the interaction modalities of hINMT with its substrates and lay the groundwork for inhibition experiments aimed at practical applications.

raw_json:
{"europe_pmc_id":"40211327","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Eklund J, Bremberg U, Larsson J, Torkelsson E, Wennerberg J, Zandelin S, Odell LR.
publication_date: 2025-03-19
doi: 10.1021/acs.jmedchem.4c02612
pubmed_id: 40108981
source_url: https://doi.org/10.1021/acs.jmedchem.4c02612
keywords: Microsomes, Liver, Animals, Humans, Prodrugs, Drug Stability, Psilocybin
substance_tags: psilocybin,psilocin
topic_tags: In Vitro Study
study_type: In Vitro 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:
Synthesis and In Vitro Profiling of Psilocin Derivatives: Improved Stability and Synthetic Properties.

abstract:
As interest in using psilocybin therapy for treating mental health disorders intensifies, the need for efficient production methods becomes increasingly important. Current medical-grade psilocybin production is inefficient and relies on a complicated multistep synthesis. This study has explored and evaluated psilocin ester prodrugs and psilocin salts as potential alternatives to psilocybin, focusing on their ease of synthesis, chemical stability, and metabolic profiles. A diverse library of 15 psilocin ester prodrugs and six psilocin salts was synthesized and evaluated. The study successfully identified several psilocin ester prodrugs and psilocin salts that exhibited desirable characteristics, including storage and handling stability, rapid metabolic conversion to psilocin, and easy synthesis, with potential advantages over psilocybin. This research introduces viable options through psilocin ester compounds and psilocin salts, offering promising avenues for future development.

raw_json:
{"europe_pmc_id":"40108981","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: A multi-institutional investigation of psilocybin’s effects on mouse behavior
journal: bioRxiv
publication_date: 2025-04-08
doi: 10.1101/2025.04.08.647810
source_url: https://doi.org/10.1101/2025.04.08.647810
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Animal Study
study_type: Animal Study
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:02
authors:
Lu OD, White K, Raymond K, Liu C, Klein AS, Green N, Vaillancourt S, Gallagher A, Shindy L, Li A, Wallquist K, Li R, Zou M, Casey AB, Cameron LP, Pomrenze MB, Sohal V, Kheirbek MA, Gomez AM, Lammel S, Heifets BD, Malenka R.

abstract:
ABSTRACT Studies reporting novel therapeutic effects of psychedelic drugs are rapidly emerging. However, the reproducibility and reliability of these findings could remain uncertain for years. Here, we implemented a multi-institutional collaborative approach to define the robust and replicable effects of the psychedelic drug psilocybin on mouse behavior. Five laboratories performed the same experiments to test the acute and persistent effects of psilocybin (2 mg/kg, IP) on various behaviors that psychedelics have been proposed to affect, including anxiety-related approach-avoidance, exploration, sociability, depression-related behaviors, fear extinction, and social reward learning. Through this coordinated approach, we found that psilocybin had several robust and replicable acute effects on mouse behavior, including increased anxiety- and avoidance-related behaviors and decreased fear expression. Surprisingly, however, we found that psilocybin did not have replicable effects 24 hours post psilocybin administration on reducing anxiety- and depression-like behaviors or facilitating fear extinction learning. Additionally, we were unable to observe psilocybin-induced alterations in social preference or social reward learning. Overall, our comprehensive characterization of psilocybin’s acute and persistent behavioral effects using ∼200 total male and female mice per experiment spread across five independent labs demonstrates with unique certainty several acute drug effects and suggests that psilocybin’s persistent effects in mice may be more modest and inconsistent than previously suggested. We believe this unusual multi-laboratory, highly coordinated research effort serves as a model for facilitating the generation of replicable results and consequently will reduce efforts based on unreliable and spurious results.

raw_json:
{"europe_pmc_id":"PPR1001669","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


title: The Emergence of Psilocybin in Psychiatry and Neuroscience.
authors: Omidian H, Omidian A.
publication_date: 2025-04-08
doi: 10.3390/ph18040555
pubmed_id: 40283990
source_url: https://doi.org/10.3390/ph18040555
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
abstract:
Psilocybin, a naturally occurring psychedelic compound, has garnered renewed scientific interest for its potential in treating psychiatric and neurological disorders. This review systematically examines the latest research on psilocybin's pharmacokinetics, pharmacodynamics, clinical efficacy, and safety profile. Emerging evidence supports its efficacy in conditions such as major depressive disorder (MDD), treatment-resistant depression (TRD), anxiety, alcohol use disorders (AUD), and cancer-related distress. Despite promising outcomes, significant barriers remain, including methodological constraints, regulatory hurdles, and limited population diversity in clinical trials. Advances in biosynthetic production and optimized psychotherapeutic integration are necessary to ensure scalability and accessibility. Future research should focus on long-term safety, dosing precision, and neurobiological mechanisms to refine its therapeutic applications. This review provides a critical foundation for advancing evidence-based clinical integration of psilocybin.

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

raw_json:
{"europe_pmc_id":"40283990","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: The compulsive eating paradigm: can psychedelics help in treating obesity?
authors: Ammineni D, Park R.
publication_date: 2025-04-06
doi: 10.1186/s40337-024-01186-7
pubmed_id: 40197427
source_url: https://doi.org/10.1186/s40337-024-01186-7
substance_tags: psilocybin
topic_tags: Addiction,Mechanism of Action,Psychological Flexibility
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:04
abstract:
Obesity is a multifactorial disorder involving a behavioural aetiology in subsets of patients that traditional therapeutic approaches have failed to address. Drawing parallels with addiction, the rewarding aspects of a chronic energy-dense diet can compromise dopaminergic reward circuits, eventually causing individuals to become habitually responsive to food-related stimuli despite adverse health consequences. The maladaptive prediction of reward and motivational salience that becomes associated with food-related stimuli can exert top-down influence on perception and attention, promoting compulsive eating behaviour. Emerging research suggests that psychedelics, e.g., psilocybin and LSD, induce non-ordinary mental states where the influence of such behaviours could potentially be reduced and modified. Based on current evidence, mechanisms have been proposed which suggest that psychedelics might relax the top-down influence of high-level predictions encoded within neuronal hierarchies and sensitise them to bottom-up information flow. Additionally, psychedelics are thought to open a window of psychological flexibility, allowing people to potentially become open to new cognitive and behavioural strategies that can be offered via assisted psychotherapy. Therefore, psychedelics-assisted psychotherapy may encourage beneficial changes to eating behaviour, in those with maladaptive eating habits. While promising in theory, new research is needed to assess the potential efficacy of psychedelics-assisted psychotherapy in treating compulsive eating behaviour.

raw_json:
{"europe_pmc_id":"40197427","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin has a narrow therapeutic window as an antidepressant treatment.
authors: Seillier L, Čechová B, Seillier A, Šlamberová R.
publication_date: 2025-04-14
doi: 10.1016/j.pnpbp.2025.111368
pubmed_id: 40246053
source_url: https://doi.org/10.1016/j.pnpbp.2025.111368
substance_tags: psilocybin
topic_tags: Depression,Adverse Events,Drug Interactions
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
abstract:
Psilocybin, a naturally occurring psychedelic compound in magic mushrooms, shows promise as a novel intervention with a single administration inducing rapid and long-lasting antidepressant effects. However, there are limited studies on the optimal dosing required for the beneficial effects of psilocybin given its side effects. To address this gap, we investigated in Wistar rats whether a single psilocybin administration (0.1, 0.32, 1.0, and 3.2 mg/kg) had antidepressant-like effects in the forced swim test (FST), a pro-social effect in the social interaction test (SIT), and the ability to alter pleasure using the sucrose preference test (SPT). We also examined the dose-response relationships of psilocybin on the head-twitch response (HTR), locomotor activity, body temperature, and weight gain. Furthermore, we explored whether the brain-derived neurotrophic factor (BDNF) levels in the hippocampus and prefrontal cortex (PFC) paralleled the behavioral changes observed after psilocybin. In the FST, psilocybin induced dose-dependent inverted-U-shaped responses with only the intermediate dose of 0.32 mg/kg producing short and long-term antidepressant-like effects. A similar pattern was observed for the SIT, the SPT, and the HTR. In contrast, the high doses of psilocybin (1.0 and 3.2 mg/kg), while deprived of anti-depressant-like activity, significantly reduced body temperature, locomotor activity, and body weight gain. BDNF levels in the hippocampus and PFC increased dose-dependently after psilocybin, but linearly suggesting a dissociation between high BDNF levels and the observed antidepressant-like behaviors. Our results indicated that there is a narrow window for the therapeutic potential of psilocybin, with 0.32 mg/kg effectively producing antidepressant-like effects without the accompanying adverse effects observed only at higher doses.

keywords:
Hippocampus, Prefrontal Cortex, Animals, Rats, Rats, Wistar, Disease Models, Animal, Brain-Derived Neurotrophic Factor, Hallucinogens, Antidepressive Agents, Body Temperature, Motor Activity, Swimming, Dose-Response Relationship, Drug, Male, Psilocybin

raw_json:
{"europe_pmc_id":"40246053","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2025-03-30
doi: 10.1016/j.pnpbp.2025.111353
pubmed_id: 40174857
source_url: https://doi.org/10.1016/j.pnpbp.2025.111353
substance_tags: psilocybin
topic_tags: Adolescents
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:04
title:
Sporadic use of classic psychedelics and neuropsychological performance: A cross-sectional analysis.

authors:
Reiche S, Hirschfeld T, Gröticke AL, Traub M, Hafiz NJ, Haas R, Sedlaczek L, Ortlieb L, Leistenschneider G, Basedow LA, Lohse A, Bermpohl F, Riemer TG, Majić T.

abstract:
BackgroundEvidence on the neuropsychological consequences of classic psychedelics like psilocybin, LSD, and ayahuasca is conflicting, and little is known about how sporadic use of psychedelics under naturalistic conditions may affect cognitive functioning. Given the growing interest in the therapeutic potential of psychedelics and the rise in non-medical use, further exploration into their neuropsychological effects is needed.MethodsThis cross-sectional, exploratory study employed a comprehensive neuropsychological test battery to assess cognitive domains such as executive function, memory, attention, and visuospatial abilities among individuals with mild to moderate lifetime use of psychedelics. Analyses compared all users to non-users, moderate users to matched controls, and adjusted dose-response analyses were conducted within the users group.ResultsFrom 2611 screened individuals, N = 136 participants (84 psychedelic users and 52 controls) were included. Participants were aged 18-50 years. Neuropsychological performance was broadly equivalent between users and controls. However, matched-pair analyses showed that psychedelic users had a modest advantage in executive functions, especially superior performance on the Wisconsin Card Sorting Test (WCST) (p

keywords:
Humans, Hallucinogens, Cross-Sectional Studies, Cognition, Attention, Neuropsychological Tests, Adolescent, Adult, Middle Aged, Female, Male, Young Adult, Executive Function

raw_json:
{"europe_pmc_id":"40174857","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: The effect of low-dose psilocybin on brain neurotransmission and rat behavior.
authors: Bysiek A, Wojtas A, Szpręgiel I, Wawrzczak-Bargieła A, Maćkowiak M, Gołembiowska K.
publication_date: 2025-03-26
doi: 10.1016/j.pnpbp.2025.111347
pubmed_id: 40157708
source_url: https://doi.org/10.1016/j.pnpbp.2025.111347
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Addiction,OCD,Neuroplasticity,Pharmacology,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
abstract:
Psilocybin has various therapeutic effects in mental and psychological disorders, including depression and mood disorders, obsessive-compulsive disorders, substance addiction and anxiety. Pharmacodynamic properties of psilocybin depend on doses used and time after administration. The psilocybin dose range varies depending on whether it is used therapeutically or for recreational purposes in humans, but most animal studies require larger doses to induce an effect on brain neurotransmission and animal behavior. The aim of this study was to investigate the effect of psilocybin on the release of cortical neurotransmitters and rat behavior when it was administered subcutaneously at doses of 0.1, 0.3 and 0.6 mg/kg. Psilocybin affected the release of dopamine, noradrenaline, serotonin and acetylcholine in the frontal cortex as measured by microdialysis in freely moving rats. Psilocybin increased the release of aminergic transmitters in a non-linear manner with the dose of 0.3 mg/kg being the weakest. Psilocybin also increased the release of γ-aminobutyric acid, but glutamate release was enhanced only for the first 2 h after drug injection and was followed by a decrease for the rest of the experimental period. In contrast to 25I-NBOMe, an agonist of 5-HT2A receptors, psilocybin did not produce hallucinogenic activity expressed as wet dog shakes and did not disrupt sensorimotor gating in the acoustic startle response test. Furthermore, psilocybin showed anxiolytic effect in the light dark box test 1 h after administration. It also modulated the hypothalamic-pituitary-adrenal axis activity as it transiently increased serum corticosterone level, decreased serotonin, but increased dopamine turnover rates in the hypothalamus and inhibited the content of noradrenaline and adrenaline in the adrenal glands. The changes in the neurotransmitter release seem to play a role in psilocybin behavioral effects. The lack of hallucinogenic activity and disruptive effect on sensorimotor gating by psilocybin lower doses indicates that psychotomimetic effects did not occur. Psilocybin in contrast to 25I-NBOMe, ketamine and MDMA did not produce oxidative damage of DNA in the frontal cortex and hippocampus. Thus, the single low doses of psilocybin may have some beneficial properties and fewer harmful effects.

keywords:
Brain, Animals, Rats, Rats, Wistar, Dopamine, Serotonin, Hallucinogens, Microdialysis, Behavior, Animal, Synaptic Transmission, Dose-Response Relationship, Drug, Male, Psilocybin

raw_json:
{"europe_pmc_id":"40157708","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Exploring the potential of psychedelic-assisted psychotherapy for moral injury: A scoping review.
authors: Kurkova V, Winkler O, Greenshaw A, Jetly R, Swainson J, Lodewyk K, Saghafi P, Dennett E, Burback L.
publication_date: 2025-03-17
doi: 10.1016/j.pnpbp.2025.111333
pubmed_id: 40113127
source_url: https://doi.org/10.1016/j.pnpbp.2025.111333
keywords: Humans, Hallucinogens, Morals, Stress Disorders, Post-Traumatic, Psychotherapy
substance_tags: psilocybin
topic_tags: Depression,Anxiety,PTSD,Addiction,End-of-Life Distress,Personality Change,Review Article
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:04
abstract:
This scoping review addresses the need to comprehensively explore the potential of psychedelic-assisted psychotherapy (PAP) to facilitate recovery from moral injury. Moral injury (MI), characterized by profound psychological distress arising from morally challenging experiences, has garnered increased attention as a complex mental health concern with significant functional sequelae, especially in the context of post-traumatic stress disorder (PTSD). There is growing interest in exploring alternative therapeutic approaches, with psychedelics emerging as an exciting potential intervention, as moral injury impacts treatment resistance, suicidality, social isolation, and overall functioning. Ten studies were included from 11,734 publications. Studies utilized psilocybin, MDMA, or LSD. None focused specifically on moral injury. Diagnoses included PTSD, alcohol use disorder, insomnia, human Immunodeficiency virus-related demoralized men, barbiturate dependence, anxiety associated with life-threatening illness, major depression, and PTSD comorbid with generalized anxiety disorder, panic disorder, and borderline personality disorder. Studies reported rapid, increasing, and sustained self-compassion over time, alongside increases in self-forgiveness and self-acceptance, reduction in demoralization, and decreased drinking scores. Though in other diagnostic contexts, PAP has shown efficacy in addressing symptoms commonly associated with moral injury, particularly within the context of PTSD. It holds promise as an intervention for MI and requires further exploration.

raw_json:
{"europe_pmc_id":"40113127","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


journal: PsyArXiv
publication_date: 2024-09-30
doi: 10.1002/prp2.70097
source_url: https://osf.io/preprints/psyarxiv/uxhv7_v1
substance_tags: psilocybin
topic_tags: Depression,PTSD,Randomized Controlled Trial,Review Article
study_type: Randomized Controlled Trial
source_name: PsyArXiv
publication_status: preprint
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:30
raw_json: {"osf_id":"uxhv7_v1","version":1,"reviews_state":"accepted"}
title:
From efficacy to effectiveness: evaluating psychedelic randomised controlled trials for trustworthy evidence-based policy and practice.

abstract:
The recent review of a new drug application for MDMA-assisted therapy for post-traumatic stress disorder by the United States’ Food and Drug Administration (FDA) highlighted epistemological and methodological challenges for evidence assessments. Similar challenges will also be faced in reviews of other compounds in early- and late-stage development, like psilocybin for depression. The regulatory demand for two successful phase 3 randomised controlled trials (RCTs) seems problematic, given a current lack of agreement on what constitutes “success”, particularly when psychoactive drug administration is concomitant with (psycho)therapy. These complex arrangements challenge the internal validity of estimated average treatment effect through comparison with conventional control conditions. This paper reviews the assumptions behind RCTs’ current “gold-standard” status in the hierarchy of evidence-based medicine (EBM). Recapitulating known epistemic limits of randomisation and blinding, it emphasises the urgent need to avoid the extrapolation fallacy. The resulting argument is that the degree of trustworthiness that efficacy - reported in RCTs - will reliably predict effectiveness - in target populations outside RCTs - depends on what type of psychedelic treatments will be regulated. If “stand-alone” drugs for large scale prescription and consumption, trustworthiness should be graded low. On the other hand, for regulation of drug-assisted (psycho)therapies, the degree of trustworthiness can be considered high. The reason being that these two treatment approaches are based on different causal claims with distinct external validities. Therefore, careful assessment of support factors in each is recommended to prevent detrimental consequences, from potential rejection of effective therapies up to medical reversal of eventually approved drugs.

keywords:
bias, causal, EBM, EBM+, effectiveness, efficacy, evidence, extrapolation fallacy, mechanism, medical reversal, psychedelics, RCT, Psychiatry, Neuroscience, Social and Behavioral Sciences, Clinical Psychology, Life Sciences, Theory and Philosophy of Science, Health Psychology


title: De Novo Biosynthesis of Antidepressant Psilocybin in Escherichia coli.
authors: Huang Z, Yao Y, Di R, Zhang J, Pan Y, Liu G.
publication_date: 2025-03-31
doi: 10.1111/1751-7915.70135
pubmed_id: 40177917
source_url: https://doi.org/10.1111/1751-7915.70135
substance_tags: psilocybin
topic_tags: Depression,End-of-Life Distress,Mechanism of Action,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 11:22:00
abstract:
Psilocybin, a tryptamine-derived alkaloid, has been granted Breakthrough Therapy designation by the U.S. FDA for treatment-resistant depression, underscoring its clinical importance. Therefore, sustainable and economic production is urgently needed. Manufacturing of psilocybin in Escherichia coli has drawn great attention. However, due to the low expression and activity of the eukaryotic cytochrome P450 enzyme PsiH in the psilocybin biosynthetic pathway, de novo synthesis of psilocybin in prokaryotic cells has been hampered. To overcome this dilemma, we herein demonstrated de novo synthesis of psilocybin in E. coli by constructing PsiH variants with N-terminal domain modifications and expressing the entire biosynthetic pathway at a concordantly low temperature. Improving the supply of precursor and engineering the P450 electron transfer chain resulted in a 33-fold increase in the titre of norbaeocystin (105.3 mg/L), a key intermediate of psilocybin biosynthesis, and a 17-fold increase in the titre of psilocybin (14 mg/L). Further enhancement of psilocybin production was achieved by converting norbaeocystin to psilocybin by overexpressing an extra copy of the methyltransferase gene psiM. Finally, 79.4 mg/L of psilocybin was produced by optimising flask fermentation conditions, a 100-fold improvement over the starting strain. Our work demonstrates the successful fungal P450 engineering to improve the catalytic activity in E. coli and will advance the sustainable production of the important antidepressant psilocybin in prokaryotic microbial cells.

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

raw_json:
{"europe_pmc_id":"40177917","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin Dispensaries and Advertising-Buyer Beware.
authors: Hutson PR.
publication_date: 2025-03-31
doi: 10.1001/jamanetworkopen.2025.2858
pubmed_id: 40168028
source_url: https://doi.org/10.1001/jamanetworkopen.2025.2858
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 11:22:02
raw_json:
{"europe_pmc_id":"40168028","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin Dispensaries and Online Health Claims in Canada.
authors: Matsukubo J, Dickson S, Xiao J, Friesen EL, Solmi M, Fiedorowicz JG, Fischer B, Myran DT.
publication_date: 2025-03-31
doi: 10.1001/jamanetworkopen.2025.2853
pubmed_id: 40168023
source_url: https://doi.org/10.1001/jamanetworkopen.2025.2853
substance_tags: psilocybin
topic_tags: Anxiety,Microdosing,Clinical Trial
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:
ImportanceThere is growing societal interest in and use of psilocybin. While psilocybin in Canada is illegal outside of clinical trials, there have been anecdotal reports of increasing access via unregulated online purchases and retail dispensaries.ObjectiveTo describe access to and the characteristics of psilocybin dispensaries across Canada and the health claims and warnings made on dispensary websites.Design, setting, and participantsThis cross-sectional study used systematic web searches and media reports to identify psilocybin dispensaries operating in Canada in May 2024. Data analysis was performed from June 17 to August 29, 2024.Main outcomes and measuresDescriptive and geospatial analyses were used to identify the psilocybin dispensary characteristics, product types, and store distribution. Content analysis assessed the nature and frequency of health claims and warnings on websites.ResultsAs of May 2024, 57 psilocybin dispensaries were identified in Canada (0.18 dispensaries per 100 000 individuals aged ≥15 years) in 15 of Canada's 42 major urban cities (35.7%). Approximately 815 628 (2.6%) of Canadians lived within 1 km of a dispensary. Only 4 of 13 provinces and territories had a dispensary, with most in Ontario and British Columbia. Of the 57 stores, 35 (61.4%) were part of a chain (≥2 stores owned by a single company) and 52 (91.2%) had an online presence. Stores sold a wide variety of products, including dried mushrooms (100.0%), microdosing capsules (97.8%), psilocybin-infused chocolate (91.3%) and gummies (93.4%), and most stores (65.2%) sold products mimicking popular food brands. Among stores with websites, 86.4% claimed mental health benefits of psilocybin (eg, alleviating anxiety). While 86.4% of websites provided health warnings, relevant warnings, such as those about use while driving (9.1%), during pregnancy (13.6%), or in individuals with a history of psychosis, schizophrenia, or bipolar disorder (31.8%) were rare.Conclusions and relevanceIn this study, psilocybin retailers, who were present in over a third of major Canadian cities, made a variety of unverified health claims and lacked warnings of potential harms, suggesting the need for greater regulatory measures to protect the public.

keywords:
Humans, Hallucinogens, Cross-Sectional Studies, Commerce, Internet, Adult, Canada, Female, Psilocybin

raw_json:
{"europe_pmc_id":"40168023","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2025-03-13
doi: 10.1016/j.eclinm.2025.103149
pubmed_id: 40144690
source_url: https://doi.org/10.1016/j.eclinm.2025.103149
substance_tags: psilocybin
topic_tags: Addiction,Clinical Trial,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
title:
Psilocybin-assisted therapy for relapse prevention in alcohol use disorder: a phase 2 randomized clinical trial.

authors:
Rieser NM, Bitar R, Halm S, Rossgoderer C, Gubser LP, Thévenaz M, Kreis Y, von Rotz R, Nordt C, Visentini M, Moujaes F, Engeli EJE, Ort A, Seifritz E, Vollenweider FX, Herdener M, Preller KH.

abstract:
BackgroundDespite the promising therapeutic effects of psilocybin, its efficacy in preventing relapse after withdrawal treatment for alcohol use disorder (AUD) remains unknown. This study aims to assess whether a single dose of psilocybin combined with brief psychotherapy could reduce relapse rates and alcohol use in AUD patients.MethodsThis single-center, double-blind, randomized clinical trial was conducted in Switzerland. We recruited participants with AUD between June 8, 2020, and August 16, 2023 who completed withdrawal treatment within six weeks prior to enrollment. Participants were randomized (1:1) to receive either a single oral dose of psilocybin (25 mg) or placebo (mannitol), combined with brief psychotherapy. The primary outcomes were abstinence and mean alcohol use at 4-week follow-up. Participants completed the timeline followback to assess daily alcohol use. The trial is registered on ClinicalTrials.gov (NCT04141501).FindingsWe included 37 participants who completed the 4-week follow-up (female:male = 14:23; psilocybin = 18, placebo = 19) in the analysis. There were no significant differences between groups in abstinence duration (p = 0.55, psilocybin mean = 16.80 days, 95% CI: 14.31-19.29; placebo mean = 13.80 days, 95% CI: 10.97-16.63; Cohen's d = 0.151) or mean alcohol use per day (p = 0.51, psilocybin: median = 0.48 standard alcohol units, range: 0-3.99, placebo: median = 0.54 standard alcohol units, range: 0-5.96; Cohen's d = 0.11) at 4-week or 6-month follow-up (abstinence: Cohen's d = 0.10, alcohol use: Cohen's d = 0.075). Participants in both groups reported reduced craving and temptation to drink alcohol after the dosing visit, with an additional reduction observed in the psilocybin group. Thirteen adverse events occurred in the psilocybin and seven in the placebo group. One serious adverse event occurred in the psilocybin and four in the placebo group, all related to inpatient withdrawal treatments.InterpretationA single dose of psilocybin combined with five psychotherapy sessions may not be sufficient to reduce relapse rates and alcohol use in severely affected AUD patients following withdrawal treatment. However, given the limited sample size of our study, larger trials are needed in the future to confirm these findings.FundingSwiss National Science Foundation under the framework of Neuron Cofund, Swiss Neuromatrix Foundation, and Heffter Young Investigator Fellowship Award.

raw_json:
{"europe_pmc_id":"40144690","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Kim SH, Yang S, Jung J, Choi J, Kang M, Joo JY.
publication_date: 2025-03-19
doi: 10.1002/advs.202413786
pubmed_id: 40112231
source_url: https://doi.org/10.1002/advs.202413786
keywords: Humans, Lysergic Acid Diethylamide, Hallucinogens, Mental Disorders, Psilocybin, Deep Learning
substance_tags: psilocybin
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
title:
Psychedelic Drugs in Mental Disorders: Current Clinical Scope and Deep Learning-Based Advanced Perspectives.

abstract:
Mental disorders are a representative type of brain disorder, including anxiety, major depressive depression (MDD), and autism spectrum disorder (ASD), that are caused by multiple etiologies, including genetic heterogeneity, epigenetic dysregulation, and aberrant morphological and biochemical conditions. Psychedelic drugs such as psilocybin and lysergic acid diethylamide (LSD) have been renewed as fascinating treatment options and have gradually demonstrated potential therapeutic effects in mental disorders. However, the multifaceted conditions of psychiatric disorders resulting from individuality, complex genetic interplay, and intricate neural circuits impact the systemic pharmacology of psychedelics, which disturbs the integration of mechanisms that may result in dissimilar medicinal efficiency. The precise prescription of psychedelic drugs remains unclear, and advanced approaches are needed to optimize drug development. Here, recent studies demonstrating the diverse pharmacological effects of psychedelics in mental disorders are reviewed, and emerging perspectives on structural function, the microbiota-gut-brain axis, and the transcriptome are discussed. Moreover, the applicability of deep learning is highlighted for the development of drugs on the basis of big data. These approaches may provide insight into pharmacological mechanisms and interindividual factors to enhance drug discovery and development for advanced precision medicine.

topic_tags:
Depression,Anxiety,Pharmacology,Mechanism of Action,Epigenetics,Review Article,Transcriptomics,Microbiome

raw_json:
{"europe_pmc_id":"40112231","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: A Rapid Review of Psychedelic-Assisted Therapy in the Context of Palliative Care.
authors: Miller M, Meyers M, Martin A, Napolitano S, Dorsen C, Penn A, Rosa WE.
publication_date: 2024-12-18
doi: 10.1097/njh.0000000000001096
pubmed_id: 39699865
source_url: https://doi.org/10.1097/njh.0000000000001096
keywords: Humans, Hallucinogens, Palliative Care
substance_tags: psilocybin
topic_tags: End-of-Life Distress,Spirituality,Review Article,Safety
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:04
abstract:
Psychedelic-assisted therapy (PAT) involves supported experiences with psychedelic medicines in carefully curated environments. Early evidence suggests possible utility of PAT for addressing psychosocial-spiritual-existential concerns, yet gaps remain in understanding findings related to PAT's role in palliative care. This rapid review aims to synthesize current literature on applications of PAT in the context of palliative care. Through a systematic process, we identified 34 articles published between January 2021 and July 2024. Protocols varied yet included common components of participant screening, preparation, dosing, and integration. Psilocybin was the most commonly studied compound. Results support safety and initial efficacy of PAT for psycho-spiritual-existential outcomes among carefully screened and highly homogonous samples of patients with serious illness (predominantly cancer). Current efforts and challenges around integrating PAT into systems of palliative care were highlighted. Additional work is needed to (1) explore PAT's safety and efficacy within more diverse samples and contexts, (2) train palliative care providers on PAT, (3) determine systems of care delivery best suited for translation of PAT into practice, and (4) begin developing policy solutions to support safe and equitable access to PAT. Because many patients lack access to basic psychosocial-spiritual-existential care, careful consideration is needed around integration of PAT. The psychedelic substances which are the topic of this article are not currently FDA approved for use in the United States.

raw_json:
{"europe_pmc_id":"39699865","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2025-03-31
doi: 10.1002/prp2.70079
pubmed_id: 39996441
source_url: https://doi.org/10.1002/prp2.70079
substance_tags: psilocybin,psilocin
topic_tags: Addiction,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
title:
Psilocin, A Psychedelic Drug, Exerts Anticonvulsant Effects Against PTZ- and MES-Induced Seizures in Mice via 5-HT1A and CB1 Receptors: Involvement of Nitrergic, Opioidergic, and Kynurenine Pathways.

authors:
Balabandian M, Manavi MA, Lesani A, Mohammad Jafari R, Shafaroodi H, Heidari N, Mirnajafi-Zadeh J, Foroumadi A, Afrooghe A, Dehpour AR.

abstract:
Epilepsy, a chronic neurological disorder affecting around 65 million people globally, is characterized by recurrent, unprovoked epileptic seizures. Psilocin, the active metabolite of psilocybin, a well-known psychedelic compound, has recently gained attention for its potential antidepressant and anxiolytic properties. This study aims to investigate the anticonvulsant effects of psilocin. The study utilizes behavioral seizure models and electrophysiological recordings in mice to assess the anticonvulsant efficacy of psilocin. The pentylenetetrazole (PTZ) test for clonic seizures and the maximal electroshock (MES) test for generalized tonic-clonic seizures are employed. Cortical electrical activity is monitored to provide insights into the compound's effects on neuronal activity. The involvement of kynurenine pathway, opioidergic and nitrergic systems, as well as cannabinoid receptors using agonist/antagonist paradigms. Western blotting was employed to evaluate the expression levels of key receptors and enzymes implicated in psilocin's anticonvulsant effects. The findings indicate a possible modulation of seizure activity by psilocin, with modest doses (3 mg/kg, i.p.) demonstrating potential anticonvulsant effects. Remarkably, the administration of 1-MT, L-NAME, naltrexone, sildenafil, and AM-251 led to a diminishment of the anticonvulsant effects of psilocin, underscoring the involvement of the kynurenine pathway, nitrergic and opioidergic systems, cGMP, and the CB1 receptor in mediating the anticonvulsant effects of psilocin, respectively. Based on western blotting analysis, the upregulation of 5-HT1A but not 5-HT2A and the downregulation of IDO and CB1 expression following psilocin administration were observed. Acute administration of psilocin exerts anticonvulsant effects that might be mediated at least in part through the kynurenine pathway, opioidergic, serotonergic, and nitrergic systems.

keywords:
Animals, Mice, Seizures, Disease Models, Animal, Nitric Oxide, Pentylenetetrazole, Kynurenine, Receptor, Cannabinoid, CB1, Receptor, Serotonin, 5-HT1A, Anticonvulsants, Hallucinogens, Electroshock, Signal Transduction, Male, Psilocybin

raw_json:
{"europe_pmc_id":"39996441","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Quantitative analysis of recreational psychoactive mushroom gummies in Portland, Oregon.
authors: Correia MS, Gonzaga MJ, Temple C, Gerona RR.
publication_date: 2025-02-19
doi: 10.1080/15563650.2025.2450240
pubmed_id: 39977248
source_url: https://doi.org/10.1080/15563650.2025.2450240
keywords: Humans, Agaricales, Psychotropic Drugs, Chromatography, Liquid, Oregon, Psilocybin, Illicit Drugs
substance_tags: psilocybin,psilocin
topic_tags: Safety
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
abstract:
IntroductionIn November 2020, Oregon passed Measures 109 and 110 altering the legal landscape for psychoactive substances by regulating psilocybin use and decriminalizing possession of Schedule I substances. This coincided with the growth of the commercial nootropic (cognitive enhancers) mushroom industry, including products such as mushroom gummies marketed for "legal highs." Despite these product claims, concerns have been raised about their safety profile. Our study aimed to assess the accuracy of labeling of these products and quantify their psychoactive contents.MethodsEight gummy products were procured from seven different smoke and vape shops in Portland, Oregon. Gummy samples were homogenized and analyzed using liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Products were screened for psychoactive compounds, including psilocybin, psilocin, and their analogues, as well as for purported Amanita muscaria derivatives. Quantitative analysis of identified compounds was performed using isotope dilution.ResultsNeither ibotenic acid nor muscimol, the active components of Amanita muscaria, were detected in the two products claiming to contain Amanita muscaria extracts. However, these products contained psilocin and tryptamine derivatives. One product labeled as psilocybin-free tested positive for psilocybin. Another sample claiming to be nootropic contained undisclosed Δ9-tetrahydrocannabinol. Overall, seven of the eight products contained psilocin, and six contained 4-acetoxy-N,N,dimethyltryptamine. Other detected compounds included various tryptamine congeners and kavalactones.DiscussionLabeling was inaccurate and inconsistent in many of the products examined. Users are likely to experience psychoactive symptoms considering the concentrations of xenobiotics determined. Serotonergic effects are expected from products containing tryptamine derivatives, including those inaccurately labeled as containing Amanita muscaria extracts.ConclusionsThe labeling of psychoactive mushroom gummies we tested was overall inaccurate. Products suggesting Amanita muscaria content instead contained serotonergic tryptamines, including some which falsely claimed to be free of psilocybin.

raw_json:
{"europe_pmc_id":"39977248","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Irrmischer M, Puxty D, Yıldırım BO, Deijen JB, Engelbregt H.
publication_date: 2025-01-06
doi: 10.1007/s00213-024-06733-3
pubmed_id: 39775022
source_url: https://doi.org/10.1007/s00213-024-06733-3
substance_tags: psilocybin
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:01
title:
Moderating factors in psilocybin-assisted treatment affecting mood and personality: A naturalistic, open-label investigation.

abstract:
RationalePsychedelic-assisted therapy is increasingly applied within mental health treatment.ObjectivesThis study focused on factors moderating changes in the acute and long-term effects of an individual psilocybin-assisted program on depression, anxiety, PTSD and personality structures by including demographic factors, subjective experience and degree of mystical type experiences during the dosing, as well as emotional breakthrough and personal growth after the program.MethodsAt baseline, 1 week and 3 months after the psilocybin program participants completed the Generalized Anxiety Disorder Assessment (GAD-7), Patient Health Questionnaire (PHQ-9), PTSD Checklist for DSM-5 (PCL-5) and NEO Five-Factor Inventory-3 (NEO-FFI-3). In addition, after the dosing the Mystical Experiences Questionnaire (MEQ-30), Posttraumatic Growth Inventory (PTGI) and Emotional Breakthrough Inventory (EBI) were administered. Moderation effects were established using linear mixed-model analysis.ResultsA single high dose of psilocybin in combination with therapy was found to lower symptoms of anxiety, depression, PTSD and neuroticism over a period of 3-months. Scores on openness and conscientiousness increased after the treatment only. Participants reported mystical type experiences, emotional breakthrough and personal growth. These subjective experiences together with demographic factors were moderating the observed positive changes.ConclusionsFindings indicate that individual psilocybin-assisted therapy has the potential for beneficial effects on mood and personality characteristics. Moreover, the study highlights the importance of subjective experiences and demographic factors in moderating this effect. This study adds to the ongoing research on psilocybin-assisted therapy by investigating contributing factors for optimizing this evolving type of therapy.

keywords:
Humans, Hallucinogens, Treatment Outcome, Depression, Affect, Anxiety, Personality, Stress Disorders, Post-Traumatic, Adult, Middle Aged, Female, Male, Young Adult, Surveys and Questionnaires, Psilocybin

topic_tags:
Depression,Anxiety,PTSD,Personality Change,Emotional Processing,Mystical Experience,Observational Study

raw_json:
{"europe_pmc_id":"39775022","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Sutherland I, Ho MF, Croarkin PE.
publication_date: 2025-01-05
doi: 10.1089/cap.2024.0082
pubmed_id: 39761065
source_url: https://doi.org/10.1089/cap.2024.0082
substance_tags: psilocybin
topic_tags: Depression,Anxiety,PTSD,Pharmacology,Adolescents,Treatment-Resistant Depression,Safety
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:
Psychedelic Treatments in Adolescent Psychopharmacology: Considering Safety, Ethics, and Scientific Rigor.

abstract:
Interest in psychedelic therapies for adults is rapidly growing, with substances like 3,4-methylenedioxymethamphetamine for posttraumatic stress disorder, psilocybin for treatment-resistant depression, and lysergic acid diethylamide for generalized anxiety disorder showing promise. However, research on these therapies in children and adolescents is limited, with no recent trials. Despite this lack of scientific exploration, adolescents may still experiment with these substances for both recreational and therapeutic purposes as accessibility continues to increase. This raises significant concerns, as adolescents are a vulnerable population requiring heightened caution and safety measures. Therefore, we advocate for structured, safe, and well-controlled exploration of psychedelic therapies in adolescents.

keywords:
Humans, N-Methyl-3,4-methylenedioxyamphetamine, Lysergic Acid Diethylamide, Hallucinogens, Anxiety Disorders, Stress Disorders, Post-Traumatic, Psychopharmacology, Adolescent, Psilocybin

raw_json:
{"europe_pmc_id":"39761065","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin-Assisted Therapy for Brain Cancer Related Existential Distress: A Case-Report.
authors: Stephan JF, Karam S.
publication_date: 2024-09-11
doi: 10.1089/jpm.2024.0277
pubmed_id: 39264873
source_url: https://doi.org/10.1089/jpm.2024.0277
substance_tags: psilocybin
topic_tags: End-of-Life Distress,Cancer Patients,Adverse Events
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:
Introduction: Psilocybin-assisted therapy (PAT) has gained traction in palliative care as a treatment for existential distress in the last decade. Patients with brain cancer have been excluded from studies, yet they stand to benefit as much as other patients with cancer-related psychological distress. Case description: In this report, we discuss the case of a patient with end-of-life distress secondary to stage 4 astrocytoma that received PAT through Health Canada's Special Access Program. The patient had a positive response to PAT without adverse events. Discussion: Standard treatment for existential distress is often inefficacious and PAT is rarely available, especially for patients with brain cancer. We highlight the importance of making PAT more available as many patients with unresolved existential distress resort to medical assistance in dying without ever knowing of the existence of PAT. Conclusion: PAT was effective in partially alleviating the patient's existential distress. Access to PAT needs to be expanded urgently.

keywords:
Humans, Astrocytoma, Brain Neoplasms, Hallucinogens, Palliative Care, Stress, Psychological, Canada, Psilocybin, Psychological Distress

raw_json:
{"europe_pmc_id":"39264873","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Neural mechanisms of psychedelic visual imagery.
authors: Stoliker D, Preller KH, Novelli L, Anticevic A, Egan GF, Vollenweider FX, Razi A.
publication_date: 2024-06-10
doi: 10.1038/s41380-024-02632-3
pubmed_id: 38862674
source_url: https://doi.org/10.1038/s41380-024-02632-3
substance_tags: psilocybin
topic_tags: Neuroplasticity,Brain Imaging,Mechanism of Action,Receptor Pharmacology,Aging,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 11:22:03
abstract:
Visual alterations under classic psychedelics can include rich phenomenological accounts of eyes-closed imagery. Preclinical evidence suggests agonism of the 5-HT2A receptor may reduce synaptic gain to produce psychedelic-induced imagery. However, this has not been investigated in humans. To infer the directed connectivity changes to visual connectivity underlying psychedelic visual imagery in healthy adults, a double-blind, randomised, placebo-controlled, cross-over study was performed, and dynamic causal modelling was applied to the resting state eyes-closed functional MRI scans of 24 subjects after administration of 0.2 mg/kg of the serotonergic psychedelic drug, psilocybin (magic mushrooms), or placebo. The effective connectivity model included the early visual area, fusiform gyrus, intraparietal sulcus, and inferior frontal gyrus. We observed a pattern of increased self-inhibition of both early visual and higher visual-association regions under psilocybin that was consistent with preclinical findings. We also observed a pattern of reduced inhibition from visual-association regions to earlier visual areas that indicated top-down connectivity is enhanced during visual imagery. The results were analysed with behavioural measures taken immediately after the scans, suggesting psilocybin-induced decreased sensitivity to neural inputs is associated with the perception of eyes-closed visual imagery. The findings inform our basic and clinical understanding of visual perception. They reveal neural mechanisms that, by affecting balance, may increase the impact of top-down feedback connectivity on perception, which could contribute to the visual imagery seen with eyes-closed during psychedelic experiences.

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

raw_json:
{"europe_pmc_id":"38862674","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psychedelic Microdosing among Young Adults from Southern California.
authors: Harlow AF, Hendricks PS, Leventhal AM, Barrington-Trimis JL.
publication_date: 2024-02-09
doi: 10.1080/02791072.2024.2313684
pubmed_id: 38341607
source_url: https://doi.org/10.1080/02791072.2024.2313684
substance_tags: psilocybin
topic_tags: Addiction,Microdosing,Personality Change,Adolescents
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:05
abstract:
Despite common depictions in the media, there is little scientific evidence on microdosing psychedelic drugs. We assessed awareness, prevalence, and dosing practices of microdosing psychedelic drugs among young adults 18-22 years old from Southern California (2018-2019). We examined whether sociodemographic factors, personality traits, mental health, or other substance use behaviors were correlated with having ever microdosed. Among 2,396 participants, 293 (12%) had heard of microdosing and 74 (3%) ever microdosed. Among those who had heard of microdosing, 79% correctly defined microdosing as taking an amount of a psychedelic much lower than a standard dose, whereas 15% misperceived microdosing as a standard psychedelic dose. Psilocybin was the most common drug ever microdosed (70%), followed by lysergic acid diethylamide (LSD, 57%). Among those who ever microdosed, ~18% reported using psychoactive doses far higher than would be generally considered a microdose. White race, male/masculine gender identity, bisexual identity, past 6-month other drug use, greater attention deficit/hyperactivity disorder symptoms, mindfulness, and sensation-seeking were positively associated with having ever microdosed in multivariable models. Young adult microdosing merits further attention from scientific and public health professionals to help prevent misperceptions and potential adverse consequences as well as explore its potential therapeutic applications.

keywords:
Humans, Substance-Related Disorders, Lysergic Acid Diethylamide, Hallucinogens, Health Knowledge, Attitudes, Practice, Dose-Response Relationship, Drug, Adolescent, California, Female, Male, Young Adult, Psilocybin

raw_json:
{"europe_pmc_id":"38341607","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: The remarkable reimagining of psilocybin.
authors: Filer CN.
publication_date: 2023-11-01
doi: 10.1080/14786419.2023.2272285
pubmed_id: 37919964
source_url: https://doi.org/10.1080/14786419.2023.2272285
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":"37919964","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Utilizing Psychedelics to Enhance Well-Being: A Systematic Review.
authors: Thomson S, Thomacos N.
publication_date: 2025-03-30
doi: 10.1080/02791072.2025.2484380
pubmed_id: 40163076
source_url: https://doi.org/10.1080/02791072.2025.2484380
substance_tags: psilocybin
topic_tags: Wellbeing,Emotional Processing,Randomized Controlled Trial,Systematic Review,Review Article
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:04
abstract:
Psychedelic-assisted therapy is gaining recognition for its potential to enhance human functioning. While most research has focused on psychedelic' therapeutic use for mental illness, this review applies the PERMA Theory of Well-Being to systematically examine their role in enhancing well-being in healthy individuals. The final search of five academic databases was conducted on February 4, 2024, including studies published from 1994. After applying the inclusion criteria (controlled or naturalistic experimental design with an outcome measurement at least 7 days post-consumption), 19 studies were included. Encompassing 949 participants, two studies involved 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), seven ayahuasca, two lysergic acid diethylamide (LSD), and eight psilocybin. Results consistently indicate psychedelic consumption is related to enduring enhancements in PERMA's five elements of well-being, including positive emotions, engagement, relationships, meaning, and accomplishment. While discussion of adverse effects was frequently absent, no serious adverse effects were reported in six studies. Future research should address the limitations of the included studies by conducting larger-scale, longitudinal randomized controlled trials that incorporate a comprehensive assessment of well-being. Nevertheless, the findings of this systematic review call for a paradigm shift, moving beyond a disease-focused lens to recognizing psychedelics' capacity to enhance well-being in healthy individuals, ultimately fostering human flourishing.

raw_json:
{"europe_pmc_id":"40163076","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Pharmacokinetics of Psilocybin: A Systematic Review.
publication_date: 2025-03-24
doi: 10.3390/pharmaceutics17040411
pubmed_id: 40284409
source_url: https://doi.org/10.3390/pharmaceutics17040411
substance_tags: psilocybin,psilocin
topic_tags: Pharmacology,Systematic Review,Review Article,Animal Study,In Vitro Study,Drug Interactions
study_type: Systematic Review
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
authors:
Meshkat S, Al-Shamali H, Perivolaris A, Tullu T, Zeifman RJ, Zhang Y, Burback L, Winkler O, Greenshaw A, Husain MI, C Reichelt A, Vermetten E, Jha MK, Jetly R, Loebenberg R, Bhat V.

abstract:
Background: Psilocybin has shown promise in therapeutic applications for mental disorders. Understanding the pharmacokinetics of psilocybin and its active metabolite psilocin is crucial for optimizing its clinical use and minimizing adverse effects. Methods: This systematic review involved a comprehensive search across MEDLINE, APA PsycINFO, and Embase databases, from inception to December 2024, identifying original studies that investigated the pharmacokinetics of psilocybin. Results: Fourteen studies met the inclusion criteria: eight laboratory-based and six clinical studies. Laboratory studies used animal models or in vitro systems, while clinical studies included 112 healthy human participants. Psilocybin is rapidly dephosphorylated to psilocin, which is absorbed with Tmax values ranging from 1.8 to 4 h following oral administration. Cmax varied dose-dependently, from 8.2 ± 2.8 ng/mL (plasma) to 871 ng/mL (urine). One study reported psilocin bioavailability at 52.7 ± 20%. The volume of distribution was extensive, ranging from 277 ± 92 L to 1016 L, suggesting significant tissue distribution. Psilocin metabolism is primarily mediated by CYP2D6 and CYP3A4, with secondary contributions from monoamine oxidase A. It undergoes further hepatic biotransformation into 4-hydroxyindole-3-acetic acid and 4-hydroxytryptophol. Elimination half-life varied across studies, ranging from 1.5 to 4 h. Conclusions: Psilocybin pharmacokinetics demonstrate significant variability based on dosage, route, and species. CYP enzymes play a critical role in its metabolism, highlighting the potential for drug-drug interactions. These findings underscore the importance of further research to elucidate psilocybin's pharmacokinetic profile, which is assessed in vivo by its active metabolite psilocin.

raw_json:
{"europe_pmc_id":"40284409","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2025-03-24
doi: 10.1038/s41398-025-03308-4
pubmed_id: 40128190
source_url: https://doi.org/10.1038/s41398-025-03308-4
substance_tags: psilocybin
topic_tags: Consciousness,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
title:
Intravenous psilocybin induces dose-dependent changes in functional network organization in rat cortex.

authors:
Silverstein BH, Kolbman N, Nelson A, Liu T, Guzzo P, Gilligan J, Lee U, Mashour GA, Vanini G, Pal D.

abstract:
Psilocybin produces an altered state of consciousness in humans and is associated with complex spatiotemporal changes in cortical networks. Given the emphasis on rodent models for mechanistic studies, there is a need for characterization of the effect of psilocybin on cortex-wide network dynamics. Previous electroencephalographic studies of psychedelics in rodents have primarily used sparse electrode arrays with limited spatial resolution, precluding network level analysis, and have been restricted to lower gamma frequencies. Therefore, in this study, we used electroencephalographic recordings from 27 sites/electrodes across rat cortex (n = 6 male, 6 female) to characterize the effect of psilocybin (0.1, 1, and 10 mg/kg delivered over an hour) on brain network organization as inferred through changes in node degree (an index of network density) and connection strength (via weighted phase-lag index). The removal of aperiodic component from the electroencephalogram localized the primary oscillatory changes to theta (4-10 Hz), medium gamma (70-110 Hz), and high gamma (110-150 Hz) bands, which were used for the network analysis. Additionally, we determined the concurrent changes in theta-gamma phase-amplitude coupling. We report that psilocybin, in a dose-dependent manner, 1) disrupted theta-gamma coupling [p

keywords:
Cerebral Cortex, Nerve Net, Animals, Rats, Rats, Sprague-Dawley, Hallucinogens, Electroencephalography, Dose-Response Relationship, Drug, Female, Male, Psilocybin

raw_json:
{"europe_pmc_id":"40128190","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Is there room for ethics of authenticity in psilocybin research?
authors: Jerotic S.
publication_date: 2025-03-23
doi: 10.1016/j.nsa.2025.105519
pubmed_id: 40654595
source_url: https://doi.org/10.1016/j.nsa.2025.105519
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 11:22:02
raw_json:
{"europe_pmc_id":"40654595","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: LPS-Induced Liver Inflammation Is Inhibited by Psilocybin and Eugenol in Mice.
publication_date: 2025-03-22
doi: 10.3390/ph18040451
pubmed_id: 40283890
source_url: https://doi.org/10.3390/ph18040451
substance_tags: psilocybin
topic_tags: Mechanism of Action,Receptor Pharmacology,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
authors:
Robinson GI, Gerasymchuk M, Zanikov T, Gojani EG, Asghari S, Groves A, Haselhorst L, Nandakumar S, Stahl C, Cruz C, Cameron M, Zahoruiko Y, Li D, Rodriguez-Juarez R, Snelling A, Hudson D, Fiselier A, Kovalchuk O, Kovalchuk I.

abstract:
Background/Objectives: Liver inflammatory diseases are a major global health burden and are often exacerbated by inflammation driven by lipopolysaccharides (LPS) through toll-like receptor 4 signaling. This study evaluates the anti-inflammatory effects of psilocybin and eugenol in an LPS-induced liver inflammation model in C57BL/6J mice. Methods: Mice were treated with psilocybin (0.88 mg/kg) and/or eugenol (17.59 mg/kg) either before (pre-treatment) or after (post-treatment) LPS injection. Results: Psilocybin and eugenol, individually and in combination, significantly reduced the LPS-induced mRNA levels of pro-inflammatory cytokines, with post-treatment administration exhibiting stronger effects than pre-treatment. Psilocybin alone displayed the most pronounced anti-inflammatory response, especially for IL-1β, IL-6, and MCP-1, while its combination with eugenol in 1:50 ratio demonstrated similar results, with strongly reduced COX-2 and TNF-α. Histological analysis revealed improved nuclear circularity and reduced inflammatory infiltration in the treatment groups. Eugenol alone showed potential adverse effects, including increased MCP-1 and GM-CSF, but this was mitigated by the co-administration of psilocybin. Conclusions: These findings highlight psilocybin and its combination with eugenol as promising therapies for hepatic inflammation, suggesting their application in treating acute and chronic liver diseases. Future research should explore their long-term effects, the mechanisms underlying their anti-inflammatory actions, and their therapeutic efficacy in humans.

raw_json:
{"europe_pmc_id":"40283890","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Anhedonia: Current and future treatments.
authors: Serretti A.
publication_date: 2025-03-22
doi: 10.1002/pcn5.70088
pubmed_id: 40129874
source_url: https://doi.org/10.1002/pcn5.70088
substance_tags: psilocybin
topic_tags: Receptor Pharmacology,Review Article
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:04
abstract:
Anhedonia is a transdiagnostic domain that leads to poor disorder outcome and low remission rates. This narrative review describes a broad range of interventions targeting anhedonia, including pharmacological, neuromodulatory, behavioral, and lifestyle-based approaches. Drugs such as vortioxetine, agomelatine, bupropion, ketamine, and brexpiprazole show promising anti-anhedonic effects, while traditional antidepressants, such as serotonin-norepinephrine reuptake inhibitors (SNRIs) and, even more so, selective serotonin reuptake inhibitors (SSRIs), are less effective. Neuromodulation techniques, including repetitive transcranial magnetic stimulation, transcranial direct current stimulation, and transcutaneous auricular vagus nerve stimulation, proved effective at improving anhedonia, particularly when used in targeted areas. Psychotherapeutic interventions, including behavioral activation, mindfulness-based strategies, and savoring techniques, also help re-engage patients with pleasurable activities and enhance positive affect. Innovative treatments, such as aticaprant and psilocybin, showed promising results. Substantial evidence suggests that improving anhedonia leads to better psychosocial functioning, quality of life, and sustained remission. Although most data come from short-term studies, several long-term analyses suggest that maintaining hedonic improvements is feasible and beneficial. The reviewed evidence underscores the importance of routine assessment of anhedonia and the integration of symptom-specific strategies. Tailoring interventions to address individual patterns of reward disruption may optimize outcomes for patients with anhedonia.

raw_json:
{"europe_pmc_id":"40129874","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Structural basis for psilocybin biosynthesis.
authors: Meng C, Guo W, Xiao C, Wen Y, Zhu X, Zhang Q, Liang Y, Li H, Xu S, Qiu Y, Chen H, Lin WJ, Wu B.
publication_date: 2025-03-21
doi: 10.1038/s41467-025-58239-x
pubmed_id: 40121242
source_url: https://doi.org/10.1038/s41467-025-58239-x
substance_tags: psilocybin
topic_tags: Depression,Mechanism of Action,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
abstract:
Psilocybin shows significant therapeutic potential for psilocybin-assisted psychotherapy in addressing various psychiatric conditions. The biosynthetic approach promises rapid and efficient production of psilocybin. Understanding the enzymes that contribute to the biosynthesis of psilocybin can enhance its production process. In this study, we elucidate the crystal structures of L-tryptophan-specific decarboxylase PsiD in both its apo and tryptamine-bound states, the 4-hydroxytryptamine kinase PsiK bound to its substrate, and several forms of the methyltransferase PsiM in either apo or substrate-bound forms derived from the psychedelic mushroom. Structure-based evaluations reveal the mechanisms of self-cleavage and self-inhibition in PsiD, along with the sequential catalytic steps from 4-hydroxytryptamine to the final compound, psilocybin. Additionally, we showcase the antidepressant properties of biosynthetic intermediates of psilocybin on female mice experiencing depression-like behaviors induced by sub-chronic variable stress. Our studies establish a structural basis for the future biosynthetic production of psilocybin using these enzymes and emphasize the clinical potential of norbaeocystin.

keywords:
Animals, Humans, Mice, Agaricales, Aromatic-L-Amino-Acid Decarboxylases, Methyltransferases, Hallucinogens, Antidepressive Agents, Crystallography, X-Ray, Depression, Models, Molecular, Female, Psilocybin

raw_json:
{"europe_pmc_id":"40121242","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Is there a place for psychedelics in sports practice?
authors: Portes MAM, Werle I, Bertoglio LJ.
publication_date: 2025-03-20
doi: 10.1017/neu.2025.13
pubmed_id: 40116762
source_url: https://doi.org/10.1017/neu.2025.13
substance_tags: psilocybin,psilocin
topic_tags: Depression,Anxiety,PTSD,Addiction,Pharmacology,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 11:22:01
abstract:
Growing evidence suggests that psychedelic-assisted therapies can alleviate depression, anxiety, posttraumatic stress, and substance use disorder, offering relatively safe profiles, enhanced efficacy, and lasting effects after a few applications. Athletes often experience high levels of stress and pressure, making them susceptible to these psychiatric conditions. However, the effects of psychedelic substances on athletic performance remain largely unknown. Before potential acceptance, evaluating their impact on physical and physiological measures beyond mental health outcomes is crucial. Here, we aim to explore this topic and highlight research directions to advance our understanding. Preclinical studies suggest that psilocybin/psilocin, lysergic acid diethylamide (LSD), N,N-dimethyltryptamine (DMT), and ayahuasca possess anti-inflammatory and anti-nociceptive properties. Studies investigating the effects of classical psychedelics or 3,4-methylenedioxymethamphetamine (MDMA) on factors such as muscle strength, motor coordination, locomotion, endurance, fluid and electrolyte balance, hormonal regulation, and metabolism are still scarce. While adhering to regulatory frameworks, further research in animal models, athletes, and non-athletes is needed to address these gaps, compare psychedelics with commonly used psychoactive drugs, and explore the potential prophylactic and regenerative benefits of specific interventions.

keywords:
Animals, Humans, Lysergic Acid Diethylamide, Hallucinogens, Sports, Athletic Performance, Athletes, Psilocybin

raw_json:
{"europe_pmc_id":"40116762","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Romeo B, Kervadec E, Fauvel B, Strika-Bruneau L, Amirouche A, Verroust V, Piolino P, Benyamina A.
publication_date: 2025-02-23
doi: 10.1016/j.pnpbp.2025.111300
pubmed_id: 40010428
source_url: https://doi.org/10.1016/j.pnpbp.2025.111300
substance_tags: psilocybin
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:
Exploring factors associated with the intensity of a mystical experience following naturalistic psychedelic use: A retrospective survey.

abstract:
IntroductionThe intensity of the psychedelic experience has been hypothesized as the main predictor of response to a psychedelic treatment. This study aimed to investigate factors that may be associated with the intensity of mystical experiences during naturalistic psychedelic use.MethodsThe data of this comprehensive sample were aggregated from four previous retrospective surveys, where mystical experience intensity was assessed using the mystical experience questionnaire (MEQ-30). Additional collected data included psychological flexibility levels, intentions regarding psychedelic use, substance used, subjective dosage levels, and socio-demographic information. ANOVA and linear regression were performed to identify predictors of MEQ-30 scores.ResultsA total of 1657 participants were included in this study. The significant predictors of the total MEQ score were: the main motive for the psychedelic experience (with a greater impact of spiritual/religious, therapeutic, and self-exploration, compared to recreational), the type of substance used (with a greater impact for Ayahuasca and lysergic acid diethylamide than for psilocybin), the subjective dosage (greater impact of very high, high, and moderate doses, compared to a very low dose), the number of psychedelic sessions, the time elapsed since the experience, and concomitant alcohol use.ConclusionThis large sample study highlights significant associations between the intensity of mystical experiences during naturalistic psychedelic use and several key factors: the type of the psychedelic substance used, dosage, and set, particularly participants' intentions. Moreover, results show that concomitant alcohol use is associated with less intense psychedelic experiences, emphasizing the relevance of screening participants for substance use in research settings.

keywords:
Humans, Banisteriopsis, Lysergic Acid Diethylamide, Hallucinogens, Retrospective Studies, Mysticism, Adolescent, Adult, Middle Aged, Female, Male, Young Adult, Surveys and Questionnaires, Psilocybin

topic_tags:
Addiction,Spirituality,Mystical Experience,Psychological Flexibility,Observational Study,Adolescents

raw_json:
{"europe_pmc_id":"40010428","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psychedelics in neuroinflammation: Mechanisms and therapeutic potential.
authors: de Deus JL, Maia JM, Soriano RN, Amorim MR, Branco LGS.
publication_date: 2025-01-30
doi: 10.1016/j.pnpbp.2025.111278
pubmed_id: 39892847
source_url: https://doi.org/10.1016/j.pnpbp.2025.111278
keywords: Animals, Humans, Hallucinogens, Signal Transduction, Neuroinflammatory Diseases
substance_tags: psilocybin
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:04
abstract:
Neuroinflammation is a critical factor in the pathogenesis of various neurodegenerative and psychiatric disorders, including Alzheimer's disease, Parkinson's disease, and major depressive disorder. Psychedelics, such as psilocybin, lysergic acid diethylamide (LSD), and dimethyltryptamine (DMT), have demonstrated promising therapeutic effects on neuroinflammation, primarily through interactions with serotonin (5-HT) receptors, particularly the 5-HT2A receptor. Activation of these receptors by psychedelics modulates the production of pro-inflammatory cytokines, regulates microglial activity, and shifts the balance between neurotoxic and neuroprotective metabolites. Additionally, psychedelics affect critical signaling pathways, including the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt), and mechanistic target of rapamycin (mTOR) pathways, promoting neuroplasticity and exerting anti-inflammatory effects. Beyond the serotonergic system, other neurotransmitter systems-including the glutamatergic, dopaminergic, noradrenergic, gamma-aminobutyric acid (GABAergic), and cholinergic systems-also play significant roles in mediating the effects of psychedelics. This review examines the intricate mechanisms by which psychedelics modulate neuroinflammation and underscores their potential as innovative therapeutic agents for treating neuroinflammatory and neuropsychiatric disorders.

topic_tags:
Depression,Neuroplasticity,Mechanism of Action,Receptor Pharmacology,Review Article,Drug Interactions,Inflammation

raw_json:
{"europe_pmc_id":"39892847","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


journal: PsyArXiv
publication_date: 2024-11-03
source_url: https://osf.io/preprints/psyarxiv/j8zb5_v1
keywords: Psychiatry, Social and Behavioral Sciences, Life Sciences
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: PsyArXiv
publication_status: preprint
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:30
raw_json: {"osf_id":"j8zb5_v1","version":1,"reviews_state":"accepted"}
title:
Preliminary safety and effectiveness of psilocybin-assisted therapy in adults with fibromyalgia: An open-label, pilot clinical trial

abstract:
Fibromyalgia (FM) is the prototypical nociplastic pain condition, characterized by widespread pain and issues with cognition, mood, and sleep. Currently, there are limited treatment options available that effectively treat FM symptoms. Psilocybin-assisted therapy (PAT) is an emerging combined drug-therapy intervention, but no studies to-date have investigated PAT for FM. Here, we report findings from an open-label, proof-of-concept trial of PAT for FM (N=5; NCT05128162). In conjunction with psychotherapy (two preparatory, four integration sessions), participants received two doses of oral psilocybin (15mg and 25mg) delivered two weeks apart. Regarding safety (primary outcome), there were transient elevations of blood pressure or heart rate during dosing which normalized by the end of treatment, with no serious adverse events. Four of five participants reported transient headaches following dosing. Compared to baseline, participants reported clinically meaningful improvements in the following secondary outcomes one month following their second psilocybin dose (reported as Cohen’s d): pain severity (d=-2.1, 95% CI[-3.7 to -0.49]), pain interference (d=-1.8, 95% CI [-3.27 to -0.24]), and sleep disturbance (d=-2.5, 95% CI [-4.21 to -0.75]). Using the Patient Global Impression of Change, one participant reported their symptoms “very much improved,” two reported “much improved,” and two reported “minimally improved.” Compared to baseline, there were improvements in the following exploratory outcomes after the intervention: FM symptoms, anxiety, and fatigue. This small open-label trial preliminarily supports that PAT is well-tolerated by people with FM, establishing a basis for larger randomized controlled trials.

topic_tags:
Anxiety,Chronic Pain,Headache / Migraine,Clinical Trial,Randomized Controlled Trial,Safety,Adverse Events


authors: Harari R, Getselter D, Elliott E.
publication_date: 2025-03-17
doi: 10.1186/s13041-025-01191-0
pubmed_id: 40102929
source_url: https://doi.org/10.1186/s13041-025-01191-0
substance_tags: psilocybin
topic_tags: Neuroplasticity,Mechanism of Action,Epigenetics,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
title:
The psychedelic psilocybin and light exposure have similar and synergistic effects on gene expression patterns in the visual cortex.

abstract:
Psilocybin, a psychedelic compound found in specific hallucinogenic mushrooms, is known to induce changes in visual perception and experience in humans. However, there is little knowledge of the molecular mechanisms through which psilocybin affects vision-associated regions in the brain, such as the visual cortex. The current study determined both psilocybin-induced and experience-dependent changes (exposure to light) in visual cortex gene expression in mice. Of great interest, psilocybin induced robust gene expression changes in the visual cortex that closely mirror light-induced gene expression changes, even when the mice are kept in the dark. These gene expression changes correspond to specific molecular pathways, including synaptic functioning, and represent genes expressed in specific subtypes of neurons. In addition, exposure to both psilocybin and light induced synergetic changes in genes involved in epigenetic programming. Overall, the study determined that psilocybin induces robust changes in gene expression in the visual cortex that may have functional consequences in visual perception both in the absence and in synergy with visual experience.

keywords:
Visual Cortex, Animals, Mice, Inbred C57BL, Mice, Hallucinogens, Visual Perception, Gene Expression Regulation, Epigenesis, Genetic, Light, Male, Psilocybin

raw_json:
{"europe_pmc_id":"40102929","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Dino F.
publication_date: 2025-03-16
doi: 10.7759/cureus.80707
pubmed_id: 40242672
source_url: https://doi.org/10.7759/cureus.80707
substance_tags: psilocybin
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:01
title:
A Modern Overview of the Potential Therapeutic Effects of Psilocybin in the Treatment of Depressive Disorders, Treatment-Resistant Depression, and End-of-Life Distress.

abstract:
The purpose of this review is to provide a comprehensive overview of the current findings and data on the therapeutic effects of psilocybin, a naturally occurring psychedelic alkaloid primarily found in Psilocybe mushrooms. This review covers psilocybin's efficacy and safety profile, therapeutic effects, proposed indications and contraindications, drug-drug interactions, adverse reactions, pharmacokinetics, pharmacodynamics, and dosing regimens as treatment guidelines. The goal is to offer a consolidated resource containing the essential pharmaceutical information on psilocybin currently available.

topic_tags:
Depression,End-of-Life Distress,Pharmacology,Review Article,Treatment-Resistant Depression,Safety,Drug Interactions,Contraindications

raw_json:
{"europe_pmc_id":"40242672","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Mice lacking the serotonin transporter do not respond to the behavioural effects of psilocybin.
authors: Gattuso JJ, Wilson C, Li S, Hannan AJ, Renoir T.
publication_date: 2025-01-26
doi: 10.1016/j.ejphar.2025.177304
pubmed_id: 39864573
source_url: https://doi.org/10.1016/j.ejphar.2025.177304
substance_tags: psilocybin
topic_tags: Depression,Anxiety,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
abstract:
Background and purposePsilocybin is a serotonergic psychedelic with therapeutic potential for several neuropsychiatric disorders, including depression and anxiety disorders. Serotonin transporter (5-HTT) knockout mice (KO) are a well-validated mouse model of anxiety/depression and are relevant to both chronic treatment with serotonin transporter reuptake inhibitors (SSRIs) and polymorphisms in the serotonin transporter-linked polymorphic region (5-HTTLPR) associated with depression/anxiety and resistance to classic antidepressant treatments. However, there is yet to be a study assessing the effect of psilocybin in 5-HTT KO mice.Experimental approachWe investigated the effects of a single dose of psilocybin (1 mg/kg) on locomotor activity and the head-twitch response as well as anxiety- and depressive-like behaviour in KO versus wild-type (WT) mice using the light-dark box and Porsolt swim test respectively.Key resultsWe found that both the psilocybin-induced head-twitch and hyperlocomotor responses observed in WT mice were completely absent in KO animals. In female WT mice only, psilocybin was also able to block the weight loss observed one day after intraperitoneal injection. While psilocybin did not alter anxiety- and depression-like behaviours for both genotypes, we revealed a genotype-specific trend for a main effect of treatment for WT females (p = 0.054) in the Porsolt swim test. Finally, we found that only female KO mice exhibit anhedonia-like behaviour in the saccharin-preference test.Conclusion and implicationsOur findings highlight the complexity of psilocybin's effects and suggest that functional integrity of 5-HTT is essential for psilocybin's acute behavioural effects. This could also have implications for pharmacogenetics, including individuals with polymorphisms or mutations in 5-HTT.

keywords:
Animals, Mice, Inbred C57BL, Mice, Knockout, Mice, Hallucinogens, Behavior, Animal, Depression, Anxiety, Locomotion, Female, Male, Serotonin Plasma Membrane Transport Proteins, Psilocybin

raw_json:
{"europe_pmc_id":"39864573","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Farinha-Ferreira M, Miranda-Lourenço C, Galipeau C, Lenkei Z, Sebastião AM.
publication_date: 2024-12-23
doi: 10.1016/j.neuropharm.2024.110280
pubmed_id: 39725123
source_url: https://doi.org/10.1016/j.neuropharm.2024.110280
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Observational Study,Animal Study,Drug Interactions
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Concurrent stress modulates the acute and post-acute effects of psilocybin in a sex-dependent manner.

abstract:
There is renewed interest in psychedelics, such as psilocybin, as therapies for multiple difficult-to-treat psychiatric disorders. Even though psychedelics can induce highly pleasant or aversive experiences, depending on multiple personal and environmental factors, there is little research into how such experiences impact post-acute mood-altering actions. Here we aimed at offsetting this gap. First, we tested whether acute psilocybin effects differed between sexes. Adult male and female C57BL/6J mice received saline or psilocybin (5 mg/kg; i.p.), and head-twitch response (HTR) frequency was quantified. Notably, while psilocybin increased HTR frequency in both sexes, the effect was greater in females. We then tested if stress exposure during acute drug effects impacted post-acute psilocybin actions. Following drug treatment, mice were returned to their homecage or restrained for 1 h. Anxiety- and depression-like behaviors were assessed starting 24 h following drug administration, using the marble burying, novelty-suppressed feeding, and splash tests. Psilocybin induced anxiolytic-, but not antidepressant-like, which were fully blocked by stress in males, but only partially so in females. Lastly, we assessed the acute stress-psilocybin interaction on plasma corticosterone levels in a separate cohort of mice, treated as above. Both stress and psilocybin independently increased corticosterone levels, without additive or interactive effects being observed for either sex. Our data reveals the role of sex and peri-acute negative experiences in the acute and post-acute actions of psilocybin. These findings underline the importance of non-pharmacological factors, such as the quality of the psychedelic experience, in the mood-altering effects of psychedelics, holding significant for both their therapeutic and recreational use.

keywords:
Animals, Mice, Inbred C57BL, Mice, Hallucinogens, Depression, Stress, Psychological, Anxiety, Sex Characteristics, Female, Male, Psilocybin

raw_json:
{"europe_pmc_id":"39725123","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Meyer TD, Ibrahim M, Vale LN, Soares JC.
publication_date: 2024-12-12
doi: 10.1016/j.jad.2024.12.044
pubmed_id: 39675677
source_url: https://doi.org/10.1016/j.jad.2024.12.044
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Addiction,Clinical Trial,Randomized Controlled Trial
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 11:22:04
title:
Psychedelic use and bipolar disorder - An investigation of recreational use and its impact on mental health.

abstract:
Psychedelic substances such as psilocybin have recently gained attention for their potential therapeutic benefits in treating depression and other mental health problems. However, individuals with bipolar disorder (BD) have been excluded from most clinical trials due to concerns about manic switches or psychosis. This study aimed to systematically examine the effects of recreational psychedelic use in individuals with BD. Using the Timeline Followback (TLFB) method, we assessed mood symptoms, substance use, and other mental health-related variables in the month before and three months following participants' most recent psychedelic experience. Results showed a significant reduction in depressive symptoms and cannabis use, an increase in the number of days without mental health symptoms, and an increase in the number of days with hallucinogen use. Importantly, no significant changes in (hypo)manic, psychotic, or anxiety symptoms were observed. These findings suggest that psychedelics may hold potential as a safe and effective treatment for BD, though further research, including randomized controlled trials, is needed.

keywords:
Humans, Hallucinogens, Mental Health, Bipolar Disorder, Adult, Middle Aged, Female, Male, Young Adult, Psilocybin, Recreational Drug Use

raw_json:
{"europe_pmc_id":"39675677","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psychedelics and Pro-Social Behaviors: A Perspective on Autism Spectrum Disorders.
authors: Wang X, Lin C, Wang X.
publication_date: 2025-02-09
doi: 10.1021/acsptsci.5c00034
pubmed_id: 40109751
source_url: https://doi.org/10.1021/acsptsci.5c00034
substance_tags: psilocybin
topic_tags: Mechanism of Action,Drug Interactions
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:
Autism Spectrum Disorders (ASD) are complex neurodevelopmental conditions characterized by deficits in social interaction, communication, and repetitive behaviors. This viewpoint explores the potential mechanisms through which psychedelics such as lysergic acid diethylamide (LSD), psilocybin, and 3,4-methylenedioxymethamphetamine (MDMA) may positively influence pro-social behaviors, focusing on their implications for individuals with ASD.

raw_json:
{"europe_pmc_id":"40109751","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Bobak L, Dorney I, Kovacevich A, Barnett BS.
publication_date: 2025-03-13
doi: 10.1080/02791072.2025.2478097
pubmed_id: 40084630
source_url: https://doi.org/10.1080/02791072.2025.2478097
substance_tags: psilocybin
topic_tags: Depression,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 11:22:00
title:
Therapeutic Potential of Psilocybin for Treating Neuropsychiatric Long COVID Symptoms: A Reddit Investigation.

abstract:
Long COVID lacks effective pharmaceutical treatment options. Psychedelic treatment for long COVID has received attention given anecdotal reports of neuropsychiatric symptom improvement. This study investigates the use of psilocybin for neuropsychiatric long COVID symptoms, examining online accounts of individuals with reported long COVID using psilocybin. We searched the Reddit communities, "r/LongCovid," and "r/covidlonghaulers" for terms, "psilocybin," "shrooms," and "magic mushrooms." Posts were included if they self-reported (1) neuropsychiatric symptoms of long COVID, (2) use of psilocybin, and (3) descriptions of the perceived effect or lack thereof on long COVID symptoms. Posts were manually coded to identify the nature of psilocybin ingestion, long COVID symptoms, and post's author's perceived effect on symptoms. The most common symptoms identified were fatigue (47.3%, N = 52), cognitive impairment (46.4%, N = 51), and depression (30.0%, N = 33). Of 110 posts meeting criteria, 78.2% (N = 86) reported any improvement in long COVID symptoms, while 11.8% (N = 13) reported worsening. For those with improvement, 77.9% (N = 67) reported improvement lasting beyond their acute psychedelic experience, while 5.8% (N = 5) reported improvement only during the experience. Given these findings, studies employing comparison social media data for other long COVID self-treatments and/or prospective observational studies of individuals self-treating neuropsychiatric long COVID symptoms with psychedelics may be warranted.

raw_json:
{"europe_pmc_id":"40084630","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Lasting effect of psilocybin on sociability can be blocked by DNA methyltransferase inhibition
authors: Song C, Chang T, Buchborn T, Knöpfel T.
journal: bioRxiv
publication_date: 2025-03-10
doi: 10.1101/2025.03.10.642385
source_url: https://doi.org/10.1101/2025.03.10.642385
substance_tags: psilocybin
topic_tags: Epigenetics,Animal Study
study_type: Animal Study
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
abstract:
The recent renaissance in research on psychedelics such as psilocybin has highlighted their therapeutic potential including their lasting influences on brain function. Here we report that a single systemic administration of the serotonergic psychedelic psilocybin can durably promote social behaviour in the Cntnap2-knockout mouse model of autism. This effect can be blocked by pharmacological inhibition of DNA methyltransferase I, indicating an epigenetic mechanism underlying the long-lasting effect of psilocybin.

raw_json:
{"europe_pmc_id":"PPR987875","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


publication_date: 2025-03-06
doi: 10.3390/ph18030380
pubmed_id: 40143157
source_url: https://doi.org/10.3390/ph18030380
substance_tags: psilocybin,psilocin
topic_tags: Systematic Review,Review Article,Toxicity
study_type: Systematic Review
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Extraction Yields of Psilocybin and Psilocin: A Short Review of Current Methods and Their Implications.

authors:
Galdino TP, Oliveira LC, Luz MA, Jesus RA, Lima EPN, Torres MCM, Sivieri K, Afonso VI, Delgado JMPQ, Lima AGB, Silva SML, Fook MVL.

abstract:
The growing body of evidence supporting the therapeutic efficacy of psychoactive substances, like psilocybin, has driven significant interest in recent decades due to their low toxicity and potential applications in treating various mental health disorders. However, producing pharmaceutical-grade psilocybin remains challenging, with three primary approaches: chemical synthesis, biosynthesis, and extraction from Psilocybe mushroom fruiting bodies. This systematic review evaluates the extraction and quantification methods for psilocybin and psilocin, aiming to contribute to the development of standardized protocols that ensure compound quality and purity. A total of 25 relevant studies were selected from an initial pool of 9152 publications indexed in platforms such as Scopus, ScienceDirect, Web of Science, and PubMed. The findings indicate that both the extraction method and the choice of mushroom species significantly influence compound yields. Ultrasonic bath extraction was identified as the most efficient technique, particularly for species including Psilocybe cyanescens and Psilocybe cubensis. High-performance liquid chromatography (HPLC) was the most-used method for identifying and quantifying these compounds. Furthermore, polar solvents were critical for effective solubilization, with parameters such as temperature, solvent-to-material ratio, and extraction time playing key roles in optimizing yields. This review serves as a key scientific reference for advancing research, enhancing analytical precision, and ensuring reproducibility through the standardization of extraction and quantification protocols.

raw_json:
{"europe_pmc_id":"40143157","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Abramsky-Sze S, Marseille E, Matzopoulos R, Morlock R, Lerer L
journal: Frontiers in psychiatry
publication_date: 2024-12-31
doi: 10.3389/fpsyt.2025.1508811
pubmed_id: 40109441
source_url: https://pubmed.ncbi.nlm.nih.gov/40109441/
keywords: anxiety, depression, mental health, psilocybin, psychedelic mushroom, psychedelics
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Observational Study,Veterans
study_type: Observational Study
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:20:36
raw_json: {"pubmed_id":"40109441"}
title:
Characteristics and mental health of psychedelic mushroom and multi-psychedelic users relative to non-psychedelic users in American adults, 2020-2021.

abstract:
Few population-based studies have examined associations between psychedelic use and mental health outcomes. This work describes characteristics of exclusive psychedelic mushroom use (referred to as PM use), PMs in combination with other psychedelic substances (multi-psychedelic or MP) use, and non-psychedelic use and explores mental health ratings in non-clinical settings.
This work uses cross-sectional survey data from American adults collected by Acumen Health Research Institute, including demographic characteristics, general health-related quality of life (Veterans RAND derived mental and physical health composite scores), depression (PHQ9-item), anxiety (GAD7-item), comorbid conditions (CCI), health resource utilization, and perceptions, knowledge, and use of psychedelics. Multivariate and descriptive statistics were used to describe participant characteristics. Correlation analysis assessed anxiety and depression scores across groups. Mean anxiety and depression scores were compared using ANOVA and Tukey's HSD. A multivariate linear regression model controlling for past-year depression, past-year anxiety, age, region, ethnicity, sex, educational attainment, employment, and psychedelic use predicted mental health composite scores (MCS).
Of the 6,869 participants included in the dataset, 256 (3.7%) reported using psychedelics in the last 12 months. Of those using psychedelics, 122 (47.7%) reported PM use and 134 (52.3%) reported MP use. All psychedelic users reported lower MCS and higher levels of anxiety and depression relative to non-users (those who said they had not used psychedelics in the past year). The lowest mental health scores were reported in the MP users followed by the PM users (higher MCS corresponded to better mental health). When controlling for confounding characteristics including past-year anxiety and depression, disparities in mental health scores persisted between those with any psychedelic use and the non-psychedelic group (p
This paper extends previous work describing the association between psychedelic use and mental health, controlling for confounding mental health factors such as comorbid anxiety and depression. These results suggest psychedelic users may have poorer mental health than their non-using counterparts in certain contexts and emphasize the need for future research in this field. Both non-adjusted and adjusted analyses demonstrate lower mental health scores for PM and MP users relative to non-psychedelic users. These differential effects highlight the need for further detailed, population-based research on the use of exclusive psilocybin and on psychedelics in combination.


title: Vermont Primary Care Provider Perspectives on Psychedelics - A Cross-Sectional Study.
authors: Yalovitser J, Levine J, Zweber C, Tien L, Stultz M, Mitchell H, Cote E, MacLean CD.
publication_date: 2025-03-04
doi: 10.1080/02791072.2025.2474246
pubmed_id: 40045530
source_url: https://doi.org/10.1080/02791072.2025.2474246
substance_tags: psilocybin
topic_tags: Observational Study,Adolescents,Safety
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
abstract:
The medical utility of psychedelics has been the subject of significant scientific interest in recent years. While most of these substances remain Schedule I under the Controlled Substances Act, advancements in research have led states to consider expanding legal access, impacting primary care, where patients often seek mental health support and treatment. In July 2023 we conducted a cross-sectional survey of 770 Vermont primary care providers (PCPs) about their familiarity and concerns with psychedelics, as well as opinions on access and therapeutic value (response rate 17%). Two-thirds of respondents reported familiarity with psychedelics being used therapeutically, but less than half were aware of current regulatory statuses of LSD, psilocybin, and MDMA. Ninety-six percent were neutral or agreed that psychedelics have high therapeutic potential. The highest concerns were effects on youth, potential for psychosis, and traffic safety. Eighty-three percent were not at all or only slightly concerned about the inherent dangers of psychedelics. Seventy-seven percent were interested in further education. Overall, PCPs in Vermont, a state considering changes in access to psilocybin, are familiar with psychedelics, and cautiously optimistic about their therapeutic role. As research develops, it is important to incorporate resultant changes in policy and medicine into PCP continuing education.

raw_json:
{"europe_pmc_id":"40045530","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Further education in psychedelic-assisted therapy - experiences from Switzerland.
authors: Aicher HD, Müller F, Gasser P.
publication_date: 2025-03-04
doi: 10.1186/s12909-025-06871-y
pubmed_id: 40045361
source_url: https://doi.org/10.1186/s12909-025-06871-y
keywords: Humans, Hallucinogens, Mental Disorders, Psychology, Curriculum, Switzerland
substance_tags: psilocybin
topic_tags: Depression,Anxiety,PTSD,Consciousness,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 11:22:04
abstract:
The growing interest in psychedelic-assisted therapy (PAT) for treating psychiatric disorders such as treatment-resistant depression, PTSD, and anxiety has led to an increasing demand for specialized training. In Switzerland, MDMA, psilocybin, and LSD are applied in the framework of limited medical use as exceptional treatment options since 2014. The Swiss Medical Association for Psychedelic Therapy (SÄPT) has been a key player in addressing the need for education, offering a comprehensive, three-year training program for physicians and psychologists. This curriculum integrates theoretical knowledge with hands-on experience, emphasizing the therapeutic relationship, ethical considerations, and the management of altered states of consciousness induced by psychedelics. This article gives an overview of the structure and framework of the training and addresses topics covered by the program through theoretical teaching and retreats focusing on practical learning. However, the demand for these programs far exceeds supply. This gap is expected to widen as psychedelics potentially become regulated prescription medications. In response, several organizations have expanded their educational offerings, including further education trainings, workshops, conferences, and symposia. Overall, there is a need for more comprehensive and accessible training programs to meet the growing demand. The evolving landscape of psychedelic research, regulatory changes, and diverse patient populations require flexible and adaptive training models. As the field progresses, it is essential to establish certification standards and ensure the continued quality of training programs to ensure the safe and effective use of PAT in clinical trials and practice.

raw_json:
{"europe_pmc_id":"40045361","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Improved LC-MS Detection of Opioids, Amphetamines, and Psychedelics Using TrEnDi.
publication_date: 2025-02-02
doi: 10.1021/jasms.4c00382
pubmed_id: 39895518
source_url: https://doi.org/10.1021/jasms.4c00382
substance_tags: psilocybin
topic_tags: Addiction,Epigenetics
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:04
authors:
Rosales CA, Lepinsky NA, Gebeyehu W, Wasslen KV, Colquhoun F, Warnes BB, Chihabi J, Manthorpe JM, Smith JC.

abstract:
Substances of misuse are becoming increasingly difficult to analyze as unique methods of smuggling are adopted and due to the rapid emergence of new psychoactive substances, increasing the pool of compounds to characterize and identify. Technologies such as gas chromatography and liquid chromatography coupled to mass spectrometry (MS) represent the gold standard for accurate and robust analysis, with on-site ambient- and portable-MS systems providing rapid methods of drug screening and testing. For many samples containing residual analyte quantities, methods to improve sensitivity through chemical derivatization are critical for accurate determination. Herein, we demonstrate for the first time the use of trimethylation enhancement using diazomethane (TrEnDi) to improve the MS-based sensitivity of 13 different drugs of misuse. All analytes were successfully permethylated, with 11 demonstrating improved analytical characteristics from TrEnDi with MS sensitivity enhancements ranging from 1.2-fold to as high as 24.2-fold in the case of psilocybin, as well as increases in reversed-phase chromatographic retention for most species. Derivatization using 13C-isotopically labeled TrEnDi reagents were used to successfully resolve isobaric interference issues between three pairs of controlled substances. By using an unconventional aprotic solvent system for electrospray ionization, the benefit of a fixed-permanent positive charge was highlighted as TrEnDi-modified amphetamine was easily measured while unmodified was not detected. Finally, TrEnDi was employed to boost the sensitivity of morphine in a real urine matrix. Our results demonstrate a percent recovery of 103.1% and a sensitivity enhancement of 2.4-fold, demonstrating the versatility and applicability of TrEnDi to pre-existing analytical workflows for trace analysis.

keywords:
Humans, Amphetamines, Diazomethane, Analgesics, Opioid, Hallucinogens, Chromatography, Liquid, Substance Abuse Detection, Mass Spectrometry, Limit of Detection, Liquid Chromatography-Mass Spectrometry

raw_json:
{"europe_pmc_id":"39895518","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2025-03-02
doi: 10.4088/jcp.24m15449
pubmed_id: 40047545
source_url: https://doi.org/10.4088/jcp.24m15449
substance_tags: psilocybin
topic_tags: Depression,Mechanism of Action,Observational Study,Treatment-Resistant Depression,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 11:22:01
title:
Results From a Long-Term Observational Follow-Up Study of a Single Dose of Psilocybin for a Treatment-Resistant Episode of Major Depressive Disorder.

authors:
Goodwin GM, Nowakowska A, Atli M, Dunlop BW, Feifel D, Hellerstein DJ, Marwood L, Shabir Z, Mistry S, Stansfield SC, Teoh E, Tsai J, Young MB, Malievskaia E.

abstract:
Background: The largest randomized study of psilocybin to date demonstrated the efficacy of COMP360 25 mg (Compass Pathways' investigational proprietary pharmaceutical-grade synthesized psilocybin formulation) in participants with treatment-resistant depression (COMP001), compared with 10 mg and 1 mg doses. Here, we report findings from COMP004, a 52-week observational follow-up of patients from COMP001 and COMP003, a small open-label study of the coadministration of 25 mg COMP360 with continuing antidepressant treatment.Methods: Adverse events (AEs) were collected over the full 52-week period. The primary efficacy endpoint was time to a prespecified depressive event over the 52 weeks following COMP360 administration in COMP001 participants, presented as Kaplan-Meier estimates. A post hoc analysis included only participants that entered COMP004. Data were collected from July 2020 to July 2022.Results: Sixty-six participants entered COMP004 (COMP001, n = 58 [25 mg group n = 22, 10 mg group n = 19, 1 mg group n = 17]; COMP003, n = 8). Few AEs were reported post-entry into COMP004, with 1 AE of mild suicidal ideation in the 1 mg group deemed possibly related to study drug. For all COMP001 patients (n = 233), median time to depressive event was greater for the 25 mg group (92 days) compared to the 10 mg (83 days) and 1 mg (62 days) groups, with the majority of participants having had a depressive event by Week 12 (25 mg n = 37/75, 10 mg n = 38/79, 1 mg n = 44/75). The post hoc supplementary analysis of those who enrolled in COMP004 from COMP001 exhibited the difference between groups more strikingly (25 mg, 189 days; 10 mg, 43 days; 1 mg, 21 days); however, only 10 participants experienced a depressive event post-COMP004 enrollment (25 mg n = 6, 10 mg n = 3, 1 mg n = 1) from COMP001 and none from COMP003. At COMP004 entry, the 1 mg group had the highest number of participants on antidepressant medication (n = 10; 10 mg, n = 9; 25 mg, n = 6) and generally initiated treatment earlier.Conclusion: Over 52 weeks, a single administration of 25 mg psilocybin suggested longer maintenance of antidepressant effect than both 1 mg and 10 mg. Larger long-term studies are required to confirm these findings and provide clarity on the longer-term effects of psilocybin.Trial Registration: ClinicalTrials.gov identifier: NCT04519957.

keywords:
Humans, Hallucinogens, Antidepressive Agents, Treatment Outcome, Follow-Up Studies, Dose-Response Relationship, Drug, Adult, Middle Aged, Female, Male, Depressive Disorder, Treatment-Resistant, Psilocybin, Major Depressive Disorder

raw_json:
{"europe_pmc_id":"40047545","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Kepner W, Yang KH, Dionicio P, Bailey K, Satybaldiyeva N, Moore A, Han BH, Palamar JJ.
publication_date: 2025-03-02
doi: 10.1080/02791072.2025.2474243
pubmed_id: 40033160
source_url: https://doi.org/10.1080/02791072.2025.2474243
substance_tags: psilocybin
topic_tags: Addiction,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 11:22:04
title:
Prevalence and Correlates of Lifetime Ecstasy/MDMA Use Among Asian American and Pacific Islander Adult Populations in the United States, 2015-2020.

abstract:
Little is known about ecstasy/MDMA use among Asian American and Pacific Islander populations. Research is important because AAPIs face unique cultural factors that may influence use. We estimated the prevalence and correlates of lifetime ecstasy/MDMA use based on a representative sample of US AAPI adults aged ≥18 from the 2015-2020 National Survey on Drug Use and Health. An estimated 5.1% of AAPI adults used ecstasy in their lifetime. Compared to males, females had higher odds of use (aOR = 1.45, 95% CI: 1.08-1.98). Compared to those aged 18-25, those aged 26-34 were at increased odds for use (aOR = 1.99, 95% CI: 1.30-3.06), while those aged ≥50 were at lower odds for use. Lifetime use of other substances including cannabis (aOR = 28.4, 95% CI: 17.1-47.2), ketamine (aOR = 10.9, 95% CI: 1.63-73.4), LSD (aOR = 3.82, 95% CI: 1.98-7.37), cocaine (aOR = 3.77, 95% CI: 2.54-5.59), psilocybin (aOR = 3.29, 95% CI: 1.75-6.16), prescription opioids (aOR = 2.43, 95% CI: 1.44-4.09), and prescription stimulants (aOR = 1.96, 95% CI: 1.29-2.99) were associated with increased odds of ecstasy/MDMA use. We estimated that over 1 in 20 AAPI adults have ever used ecstasy/MDMA. Variations by age, sex, family income, substance type, and mental health service utilization emphasize the need for targeted public health strategies.

raw_json:
{"europe_pmc_id":"40033160","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psychedelic-assisted therapy: An overview for the internist.
authors: Barnett BS, Mauney EE, King F.
publication_date: 2025-03-02
doi: 10.3949/ccjm.92a.24032
pubmed_id: 40032306
source_url: https://doi.org/10.3949/ccjm.92a.24032
substance_tags: psilocybin
topic_tags: Depression,PTSD,Addiction,Healthcare Workers
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:
Preliminary evidence suggests that psychedelic-assisted therapy-the enhancement of psychotherapy with psychedelics such as 3,4-methylenedioxymethamphet-amine (MDMA) and psilocybin-may be efficacious for depression, posttraumatic stress disorder, substance use disorders, and other conditions. Therapeutic psychedelic research is advancing steadily, with psilocybin, MDMA, and lysergic acid diethylamide designated breakthrough therapies by the US Food and Drug Administration (FDA). However, in August 2024, the FDA declined to approve a New Drug Application for MDMA and asked its sponsor to conduct another phase 3 trial. Clinicians are urged to prepare for the possible return of psychedelics to medicine.

keywords:
Humans, N-Methyl-3,4-methylenedioxyamphetamine, Lysergic Acid Diethylamide, Hallucinogens, Psychotherapy, United States, Psilocybin

raw_json:
{"europe_pmc_id":"40032306","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2025-02-26
doi: 10.1089/psymed.2024.0019
pubmed_id: 40351554
source_url: https://doi.org/10.1089/psymed.2024.0019
substance_tags: psilocybin
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:01
title:
A Field-Wide Review and Analysis of Study Materials Used in Psilocybin Trials: Assessment of Two Decades of Research.

authors:
Yaden DB, Graziosi M, Owen AM, Agin-Liebes G, Aaronson ST, Allen KE, Barrett FS, Bogenschutz MP, Carhart-Harris R, Ching THW, Cosimano MP, Danforth A, Davis AK, Garcia-Romeu A, Griffiths R, Grob CS, Gründer G, Gukasyan N, Heinzerling KG, Hendricks PS, Holze F, Horton DM, Johnson MW, Kelmendi B, Knatz Peck S, Koslowski M, Liechti ME, Mertens LJ, Moreno FA, Nayak SM, Nicholas CR, Preller KH, Rieser NM, Ross S, Sergi K, Sloshower J, Smigielski L, Stenbæk DS, Vollenweider FX, Weiss B, Wolff M, Yaden ME.

abstract:
IntroductionSerotonergic psychedelics, serotonin 2A receptor agonists such as psilocybin that can result in substantially altered states of consciousness, are used in recreational and research settings. The safety of psychedelic experiences in research settings is supported by controlled physical environments, presence of clinical and medical staff to address emergent issues, screening for personal and family history of potential contraindications, and psychoeducational preparation with psychological support. Research settings typically provide psychoeducation to participants verbally and in writing (e.g., informed consent), and such documents and conversations can provide safety-related information-but may also introduce a wide range of expectancies. Such expectancies might involve the specific character of the acute subjective effects of psychedelics, possible side effects, and anticipated outcomes.MethodsTo better understand the content of this psychoeducation, we gathered study materials from many psilocybin studies conducted in the past two decades in healthy and therapeutic populations. We conducted a reflexive thematic analysis to better understand these documents.ResultsWhile these documents varied substantially between studies, we identified themes intended to lower levels of risk and optimize therapeutic effects from psychedelic treatments. The most frequently coded themes related to (1) biological and physical safety, (2) psychological safety and well-being, (3) aspects of setting, and (4) potential for expectancies. Prioritizing biological and psychological safety was evident in the materials from all sites. Furthermore, we identify potential contributors to expectancy unrelated to safety and suggest that these extrapharmacological elements be studied systematically in future research.ConclusionsIdeally, future research should strive to maximize safety while attempting to minimize extraneous expectancies.

topic_tags:
Receptor Pharmacology,Consciousness,Wellbeing,Review Article,Safety,Adverse Events,Contraindications

raw_json:
{"europe_pmc_id":"40351554","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin-Assisted Psychotherapy for Treatment-Resistant Depression in Bipolar II Disorder.
publication_date: 2025-02-26
doi: 10.1089/psymed.2024.0032
pubmed_id: 40337756
source_url: https://doi.org/10.1089/psymed.2024.0032
substance_tags: psilocybin
topic_tags: Depression,Treatment-Resistant Depression,Safety
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:
Meshkat S, Kaczmarek E, Doyle Z, Brudner RM, Gomes FA, Blainey MG, Weiglein G, McIntyre RS, Mansur RB, Rosenblat JD.

abstract:
BackgroundBipolar II disorder (BD-II) is often associated with chronic and treatment resistant major depressive episodes. Psilocybin has shown promise for its rapid-acting antidepressant effects, though its impact on bipolar depression remains unexplored. In the present subgroup analysis of an already published trial on treatment-resistant depression (TRD), we aimed to preliminarily evaluate the safety and efficacy of psilocybin in patients with BD-II.MethodsAdults with TRD associated with BD-II, excluding those with psychosis were included. Participants underwent one or two psilocybin sessions, each with a dose of 25 mg, along with preparatory and integrative psychotherapy sessions.ResultsA total of four participants with a mean age of 37.5 ± 4.15 years were included. At baseline, the mean Montgomery-Åsberg Depression Rating Scale (MADRS) score was 32.5 (95% CI: 26.3-38.7, SD = 3.87). By week 2 post-dose, mean MADRS decreased to 20.3, and 2 weeks after dose 2, it further dropped to 19. At the end of the 6-month study, the mean MADRS score was 21.3. Young Mania Rating Scale scores remained stable at a mean of one throughout the study with no evidence of treatment emergent mania, hypomania or psychosis observed in any participants.ConclusionsThese findings suggest potential improvement in depressive symptoms with psilocybin administration in BD-II. Future studies with larger sample size are required to replicate our results and further evaluate antidepressant effects of psilocybin in bipolar depression.

raw_json:
{"europe_pmc_id":"40337756","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Modlin NL, McPhee T, Zazon N, Sarang M, Hignett R, Pick S, Cleare A, Williamson V, Rucker J.
publication_date: 2025-02-26
doi: 10.1089/psymed.2024.0027
pubmed_id: 40337755
source_url: https://doi.org/10.1089/psymed.2024.0027
substance_tags: psilocybin
topic_tags: Aging,Clinical Trial,Observational Study,Safety
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:04
title:
Participants' Experience of Psychedelic Integration Groups and Processes: A Qualitative Thematic Analysis.

abstract:
BackgroundPsychedelics such as psilocybin, lysergic acid diethylamide, and 3,4-methylenedioxymethamphetamine are increasingly recognized for their potential therapeutic benefits in treating complex and chronic mental health conditions. Growing public interest in psychedelics may drive increased consumption outside of medically supervised clinical trials. Correspondingly, legality issues and potential risks of unregulated use underscore the need for structured aftercare support, including psychedelic integration groups, to reduce harm potential.MethodsThis study utilized a cross-sectional, observational, online, anonymous survey with 65 participants who used psychedelics and attended psychedelic integration groups. Participants provided qualitative data on their experiences via open-ended questions. Employing a deliberate analytic strategy, responses were subsequently analyzed using thematic analysis to identify key patterns and themes.ResultsThree primary themes and associated subthemes emerged from the data: (1) reasons for attending psychedelic integration groups, (2) utility of psychedelic integration groups, and (3) adverse factors influencing participants' experience of the group.DiscussionThe study underscores the therapeutic potential of psychedelic integration groups in providing essential community support and facilitating the processing of psychedelic experiences. However, it also highlights significant challenges, such as managing group dynamics and ensuring facilitators are adequately trained. These findings suggest that while integration groups can mitigate some risks associated with psychedelic use, research is needed to optimize their structure and effectiveness. Specifically, future studies should explore the development of standardized protocols and facilitator training programs to enhance the safety and efficacy of these groups. This research is crucial to inform policy and practice, ensuring that individuals seeking integration support and aftercare following psychedelic use have access to well-designed and delivered interventions.

raw_json:
{"europe_pmc_id":"40337755","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin-Assisted Therapy May Enhance Conservation Values in Patients with Alcohol Use Disorder.
authors: Gold ND, Pagni BA, Petridis PD, Bogenschutz MP.
publication_date: 2025-02-26
doi: 10.1089/psymed.2024.0030
pubmed_id: 40337752
source_url: https://doi.org/10.1089/psymed.2024.0030
substance_tags: psilocybin
topic_tags: Addiction,Consciousness,Personality Change,Mystical Experience,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 11:22:00
abstract:
BackgroundPsilocybin can produce long-term changes in personality, personal values, and behavior. Although psilocybin-assisted therapy (PAT) is being actively studied for various psychiatric conditions, its effects on personal values in patients with alcohol use disorder (AUD) remain unexplored. This study examined the effects of PAT on personal values in patients with AUD and assessed relationships between value changes, acute psilocybin experiences, and drinking outcomes.MethodsIn a phase II clinical trial (NCT02061293), 93 participants with AUD received 12 weeks of treatment, including manualized psychotherapy and two 8-h drug administration sessions with either psilocybin (n = 48) or active placebo (n = 45). Personal values were assessed before and after treatment using the Schwartz Value Survey (SVS), which includes 4 domain scores (Openness to Change, Self-Enhancement, Conservation, Self-Transcendence) and 10 subscales. The acute psychedelic experience was measured using the 30-item Mystical Experience Questionnaire (MEQ) and the 5-Dimensional Altered States of Consciousness Scale (5D-ASC). Treatment effects were assessed using univariate ANCOVAs, with baseline SVS values as covariates. Time effects within each group were evaluated using paired t-tests. Pearson correlations examined the relationship between value changes and acute effects, and also value changes and drinking outcomes.ResultsSignificant treatment effects were detected for the Conservation domain and its subscales "security" and "tradition." No other domains or subscales showed significant treatment effects. Within the psilocybin group, time effects were significant only for conservation, and its subscales "tradition," and "security". No significant time effects were detected in the placebo group. In the psilocybin group, the MEQ subscale Ineffability was significantly associated with increases in Conservation, "security," and "tradition" (r = 0.31-0.34). 5D-ASC subscale Vigilance Reduction was associated with Conservation (r = 0.31), but not its subscales. 5D-ASC subscale Dread of Ego Dissolution during the psilocybin sessions correlated with increases in "tradition" (r = 0.31). None of the value changes were significantly associated with drinking outcomes.ConclusionPAT may alter value structure in patients with AUD patients by increasing Conservation. Although some associations were found between acute psychedelic effects and changes in Conservation, these value changes were not related to drinking outcomes.

raw_json:
{"europe_pmc_id":"40337752","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Belitzky E, Ravani Carvalho LV, Taylor M, Ortiz CN, Baum L, Fiellin DA, Lustberg MB.
publication_date: 2025-02-28
doi: 10.1002/cam4.70586
pubmed_id: 40052631
source_url: https://doi.org/10.1002/cam4.70586
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Addiction,Chronic Pain,Clinical Trial,Review Article,Cancer Patients,Safety
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:04
title:
Psychedelics for Cancer Pain and Associated Psychological Distress: A Narrative Review of a Potential Strategy.

abstract:
PurposeTo evaluate the current level of evidence for the use of psychedelics for the management of cancer pain and associated psychological distress.ContentPain is a common symptom of cancer and treatment. However, there are high rates of undertreatment of cancer pain due to the complex underlying biology of the condition, and potentially due to a decrease in opioid prescribing in response to the opioid epidemic. A diagnosis of cancer and cancer-related pain can trigger high levels of psychological distress throughout cancer treatment. Cancer pain can also be exacerbated by anxiety, depression, quality of life challenges, and fear of death and dying, as well as by fear of recurrence or progression. Several pharmacologic and non-pharmacologic approaches have been utilized to mitigate pain and symptom burden with some success. However, there remains an unmet need for better management of cancer pain and associated symptoms. Psychedelics, such as lysergic acid diethylamide (LSD), psilocybin, mescaline, and N,N-dimethyltryptamine (DMT), are under consideration as new pharmacologic strategies for mitigating pain and the distress associated with cancer pain and associated symptom burden. Although published studies are limited, regulatory hurdles have decreased. Many clinical trials are underway to assess further the use of psychedelics and behavioral counseling for patients with cancer and comorbidities such as anxiety or depression. These studies examine both the feasibility and efficacy of psychedelics for pain and psychological distress. Early results are promising, and additional research is needed to understand efficacy and tolerability in broader cancer populations.ImplicationsThere is an unmet need to improve pain management in patients with cancer and to mitigate psychological distress. Further research is required to understand the efficacy of psychedelics for the treatment of cancer pain and distress. Recent regulatory changes have paved the way for increased research on the clinical efficacy of psychedelics in cancer.

keywords:
Humans, Neoplasms, Hallucinogens, Quality of Life, Pain Management, Cancer Pain, Psychological Distress

raw_json:
{"europe_pmc_id":"40052631","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Irremediable Psychiatric Suffering, a Potential Indication for Psilocybin Treatment.
authors: Somers M, Scheepers FE.
publication_date: 2025-02-28
doi: 10.1176/appi.ajp.20240121
pubmed_id: 40022534
source_url: https://doi.org/10.1176/appi.ajp.20240121
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":"40022534","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Therapeutic Potential of Psychedelics for Treating Anosmia: An Investigation of Online Accounts.
authors: Kovacevich A, Dorney I, Bobak L, Kaelber DC, Barnett BS.
publication_date: 2025-02-28
doi: 10.1080/02791072.2025.2474239
pubmed_id: 40022524
source_url: https://doi.org/10.1080/02791072.2025.2474239
substance_tags: psilocybin
topic_tags: Mechanism of Action,Case Report
study_type: Case Report
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
abstract:
Olfactory dysfunction (OD) has become increasingly prevalent since the COVID-19 pandemic, yet effective treatments remain limited. In recent years, anecdotal reports have emerged on the potential benefits of serotonergic psychedelics (lysergic acid diethylamide [LSD], psilocybin, etc.) in improving OD. To date, only one case series in the medical literature has documented this phenomenon. This study aimed to explore the potential therapeutic effects of psychedelics on OD by conducting a thematic analysis of online posts from people with self-reported OD discussing whether psychedelic use affected their OD. We analyzed 125 online posts, extracting key demographic data, anosmia cause, psychedelic type, psychedelic dosage, and reported impact on olfactory function. 108 posts (86.4%) reported improvements in smell following psychedelic use. Among those reporting improvement, 55 (50.1%) first noticed smell enhancement during their psychedelic experience, and 42 (38.8%) reported olfactory improvements persisting at least one day post-psychedelic use. No statistical relationship was identified between duration of benefit and dose for either psilocybin or LSD. These exploratory findings highlight the need for further research to determine whether serotonergic psychedelics could serve as a viable clinical treatment for OD or facilitate the development of new therapies, if the mechanisms behind these reported improvements can be elucidated.

raw_json:
{"europe_pmc_id":"40022524","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Serotonergic Psychedelics Rapidly Modulate Evoked Glutamate Release in Cultured Cortical Neurons.
publication_date: 2025-02-28
doi: 10.1111/jnc.70020
pubmed_id: 40022486
source_url: https://doi.org/10.1111/jnc.70020
substance_tags: psilocybin,psilocin
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:
Petrušková A, Guhathakurta D, Akdaş EY, Perelló-Amorós B, Frischknecht R, Weiss EM, Páleníček T, Fejtová A.

abstract:
The serotonergic psychedelics psilocybin, LSD and DMT hold great promise for the development of new treatments for psychiatric conditions such as major depressive disorder, addiction and end-of-life anxiety. Previous studies in both animals and humans have confirmed the effects of these drugs on neuronal activity and plasticity. However, the understanding of the mechanisms of action of these substances is limited. Here we show rapid effects of psychedelics on presynaptic properties, using live cell imaging at the level of single synapses in primary rat cortical neurons. Using the genetically encoded reporter of synaptic vesicle fusion synaptopHluorin, we detected a reduced fraction of synaptic vesicles that fused in response to mild or strong electrical stimulation 3-30 min after application of serotonergic psychedelics. These effects were transient and no longer present 24 h after treatment. While DMT only reduced the total recycling pool, LSD and psilocin also reduced the size of the readily releasable vesicle pool. Imaging with the sensors for glutamate, iGluSnFR, and presynaptic calcium, synGCaMP6, showed that while psilocin and DMT increased evoked glutamate release, LSD and psilocin reduced evoked presynaptic calcium levels. Interestingly, psilocin also affected short-term plasticity leading to a depression of responses to paired stimuli. The rapid and drug-specific modulation of glutamatergic neurotransmission described in this study may contribute to distinct anxiolytic and antidepressant properties of serotonergic psychedelics.

keywords:
Cerebral Cortex, Neurons, Synaptic Vesicles, Cells, Cultured, Animals, Rats, Rats, Sprague-Dawley, Serotonin, Lysergic Acid Diethylamide, Glutamic Acid, Hallucinogens, Psilocybin

topic_tags:
Depression,Anxiety,Addiction,End-of-Life Distress,Neuroplasticity,Brain Imaging,Mechanism of Action,Receptor Pharmacology,Aging,Animal Study

raw_json:
{"europe_pmc_id":"40022486","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Otto ME, van der Heijden KV, Schoones JW, van Esdonk MJ, Borghans LGJM, Jacobs GE, van Hasselt JGC.
publication_date: 2025-02-28
doi: 10.1007/s40262-025-01487-3
pubmed_id: 39982684
source_url: https://doi.org/10.1007/s40262-025-01487-3
substance_tags: psilocybin,psilocin
topic_tags: Pharmacology,Systematic Review,Review Article
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:
Correction: Clinical Pharmacokinetics of Psilocin After Psilocybin Administration: A Systematic Review and Post-Hoc Analysis.

raw_json:
{"europe_pmc_id":"39982684","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin-assisted psychotherapy for Parkinson's disease without depression: A case-report.
authors: Fleury V, Tomkova E, Catalano Chiuvé S, Penzenstadler L.
publication_date: 2025-02-01
doi: 10.1177/1877718x241312604
pubmed_id: 39973494
source_url: https://doi.org/10.1177/1877718x241312604
keywords: Humans, Parkinson Disease, Hallucinogens, Anxiety, Psychotherapy, Adult, Female, Psilocybin
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Wellbeing,Emotional Processing,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 11:22:01
abstract:
BackgroundPsychedelic assisted psychotherapy (PAP) can improve treatment-resistant depression. Its usefulness in Parkinson's disease (PD) is unknown. PD patients may have problems adjusting to their chronic progressive neurological disease. A change from emotional avoidance to acceptance has been reported following psilocybin administration in patients with treatment-resistant depression.ObjectiveTo report for the first time the effect of psilocybin in a PD patient.MethodsA non-depressed 43-year-old female with a 2-year history of PD presented with difficulty adjusting to PD, anxious ruminations and pessimism. The patient declined an increase in dopaminergic medication or the introduction of an anxiolytic. Therapeutic patient education was not beneficial. The patient received four sessions of high-dose PAP within one year. Neurological and psychiatric assessments were performed before and at one year follow-up using qualitative interviews and quantitative assessment of motor status, dispositional optimism, depression, anxiety, apathy, and well-being.ResultsPAP was well tolerated. It significantly improved the patient's overall pessimistic outlook on her future and decreased her anxious ruminations and worries about potential handicap due to PD. Her general well-being improved, as well as all psychometric scores except for the apathy scale. Motor status remained unchanged. Better acceptance of PD allowed her to accept pharmacological treatment adjustment.ConclusionsPAP could be a safe and useful treatment for PD patients with dispositional pessimism and difficulties accepting their disease by promoting profound decentration from habitual thoughts and emotions, improving mood and PD acceptance. Randomized, controlled studies are needed to confirm this result.

raw_json:
{"europe_pmc_id":"39973494","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: The Hallucinogen Rating Scale: Updated Factor Structure in a Large, Multistudy Sample.
authors: Calder AE, Qualls C, Hasler G, Elmiger D, Strassman R.
publication_date: 2024-12-18
doi: 10.1016/j.bpsgos.2024.100436
pubmed_id: 39926700
source_url: https://doi.org/10.1016/j.bpsgos.2024.100436
substance_tags: psilocybin
topic_tags: Consciousness
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:04
abstract:
BackgroundThe Hallucinogen Rating Scale (HRS) has been widely used to measure the subjective effects of psychedelics and other psychoactive substances. Its advantages include a basis in phenomenological interviews and clinical studies, straightforward items, and broad coverage of psychedelic effects. Previous studies have attempted to resolve its factor structure but were limited by small samples of participants who took only one substance.MethodsWe obtained 991 HRS questionnaires from the authors of 18 publications involving 13 psychoactive substances. Exploratory factor analysis was used to analyze its factor structure, and mixed-effects analyses of variance were used to compare HRS scores between drugs.ResultsThe HRS resolved into 8 factors with good to excellent internal consistency and that intuitively map onto the effects of psychedelics. The factor model also showed good measures of fit that were superior to previous proposed models. Model factors were able to show dose responses for most drugs. Additionally, patterns of responses on the 8 factors significantly differentiated classic psychedelics, such as psilocybin and DMT, from other substance classes, including dissociatives such as ketamine and salvinorin A, empathogens such as MDMA, stimulants such as methylphenidate and amphetamine, and Δ9-tetrahydrocannabinol. The factor of meaningfulness also uniquely differentiated psychedelics from all other substances.ConclusionsThese data show that the HRS is an intuitive and psychometrically sound tool for measuring the effects of psychedelic drugs, and it may also have utility for measuring the effects of other drugs and altered states of consciousness.

raw_json:
{"europe_pmc_id":"39926700","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Suicide of a patient shortly after psilocybin-assisted psychedelic therapy: A case report.
authors: Müller F, Sauer T, Hänny C, Mühlhauser M, Lang UE.
publication_date: 2025-01-28
doi: 10.1016/j.psychres.2025.116381
pubmed_id: 39889565
source_url: https://doi.org/10.1016/j.psychres.2025.116381
substance_tags: psilocybin
topic_tags: Case Report
study_type: Case Report
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":"39889565","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Viohl N, Hakami Zanjani AA, Khandelia H.
publication_date: 2025-01-25
doi: 10.1002/1873-3468.15099
pubmed_id: 39865564
source_url: https://doi.org/10.1002/1873-3468.15099
substance_tags: psilocybin,psilocin
topic_tags: Pharmacology,Receptor Pharmacology,Healthcare Workers,Drug Interactions
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
title:
Molecular insights into the modulation of the 5HT2A receptor by serotonin, psilocin, and the G protein subunit Gqα.

abstract:
5HT2AR is a G-protein-coupled receptor that drives many neuronal functions and is a target for psychedelic drugs. Understanding ligand interactions and conformational transitions is essential for developing effective pharmaceuticals, but mechanistic details of 5HT2AR activation remain poorly understood. We utilized all-atom molecular dynamics simulations and free-energy calculations to investigate 5HT2AR's conformational dynamics upon binding to serotonin and psilocin. We show that the active state of 5HT2AR collapses to a closed state in the absence of Gqα, underscoring the importance of G-protein coupling. We discover an intermediate "partially-open" receptor conformation. Both ligands have higher binding affinities for the orthosteric than the extended binding pocket. These findings enhance our understanding of 5HT2AR's activation and may aid in developing novel therapeutics. Impact statement This study sheds light on 5HT2AR activation, revealing intermediate conformations and ligand dynamics. These insights could enhance drug development for neurological and psychiatric disorders, benefiting researchers and clinicians in pharmacology and neuroscience.

keywords:
Humans, Serotonin, GTP-Binding Protein alpha Subunits, Gq-G11, Receptor, Serotonin, 5-HT2A, Ligands, Binding Sites, Protein Conformation, Protein Binding, Molecular Dynamics Simulation, Psilocybin

raw_json:
{"europe_pmc_id":"39865564","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: A systematic review of participant diversity in psychedelic-assisted psychotherapy trials.
authors: Haft SL, Downey AE, Raymond-Flesch M, Fernandes-Osterhold G, Bradley ER, O'Donovan A, Woolley J.
publication_date: 2025-01-09
doi: 10.1016/j.psychres.2025.116359
pubmed_id: 39823947
source_url: https://doi.org/10.1016/j.psychres.2025.116359
substance_tags: psilocybin
topic_tags: Clinical Trial,Randomized Controlled Trial,Systematic Review,Review Article
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
abstract:
A lack of diverse and representative participant samples in mental health intervention research perpetuates mental health disparities. This issue has become a salient concern in studies of psychedelic-assisted psychotherapy (PAT), which is emerging as a promising mental health intervention. This systematic review evaluates the reporting, representation, and analysis of participant sociodemographic characteristics in randomized controlled trials (RCTs) of PAT. A total of 21 RCTs of psilocybin- and 3,4-methylenedioxy methamphetamine (MDMA)-assisted therapies (N = 1034) are summarized. Participants' gender (100%) and race or ethnicity (76%) were frequently reported, with socioeconomic status (SES) sometimes (57%) reported using heterogeneous metrics. Sexual orientation (9.5%) and immigration status (4.8%) were rarely reported, and no studies reported gender identity. Compared to their representation in the US population and non-psychedelic clinical trials, Black/African-American participants (2.2%) and Hispanic/Latino participants (7.2%) were significantly underrepresented in PAT RCTs. MDMA trials enrolled more diverse participant samples than psilocybin trials. Analyses on treatment effects based on demographic variables were virtually nonexistent. These findings underscore the need for more inclusive recruitment strategies, along with more rigorous reporting, to improve the generalizability of PAT research.

keywords:
Humans, N-Methyl-3,4-methylenedioxyamphetamine, Hallucinogens, Psychotherapy, Randomized Controlled Trials as Topic, Psilocybin

raw_json:
{"europe_pmc_id":"39823947","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Elucidating the Phase I metabolism of psilocin in vitro.
authors: Chen J, Wang Z, Yong CY, Goh EML, Moy HY, Chan ECY.
publication_date: 2025-01-02
doi: 10.1007/s00204-024-03952-7
pubmed_id: 39751877
source_url: https://doi.org/10.1007/s00204-024-03952-7
substance_tags: psilocybin,psilocin
topic_tags: End-of-Life Distress,Pharmacology,Mechanism of Action,Clinical Trial,In Vitro 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 11:22:00
abstract:
Psilocin is a well-studied controlled substance with potential psychotherapeutic applications. However, research gaps remain regarding its metabolism. Our objective was to elucidate a comprehensive Phase I metabolic profile of psilocin to support its forensic management and clinical development. We utilized human enzymes from various sources to characterize the Phase I metabolism of psilocin and estimated its hepatic and extrahepatic clearances via in vitro to in vivo extrapolation. We identified 2-(4-hydroxy-1H-indol-3-yl)-acetaldehyde (4-HIA) as the Phase I intermediate metabolite for the first time. Psilocin was metabolized to 4-HIA by monoamine oxidase A (MAO-A), and further metabolized to the terminal metabolite 2-(4-hydroxy-1H-indol-3-yl)-acetic acid (4-HIAA) by cytosolic aldehyde oxidase (AO) and aldehyde dehydrogenases (ALDHs). MAO-A-mediated hepatic clearance of psilocin (CLH,MAO-A) was estimated to be 158.74 mL/min, accounting for 80.9% of the total hepatic metabolism of psilocin (CLH,all). MAO-A primarily contributed to the Phase I metabolism of psilocin. Total MAO-A-mediated organ clearance (CLall organs,MAO-A) was estimated to be 614.81 mL/min, with CLH,MAO-A accounting for 25.8%, indicating extensive MAO-A-mediated extrahepatic clearance of psilocin. Overall, our study sheds novel insights on Phase I metabolic pathway of psilocin and illuminated the importance of MAO-A-mediated hepatic and extrahepatic clearances of psilocin.

keywords:
Liver, Microsomes, Liver, Animals, Humans, Aldehyde Dehydrogenase, Aldehyde Oxidase, Monoamine Oxidase, Hallucinogens, Metabolic Detoxication, Phase I, Psilocybin

raw_json:
{"europe_pmc_id":"39751877","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: The role of the psychedelic experience in psilocybin treatment for treatment-resistant depression.
publication_date: 2024-12-17
doi: 10.1016/j.jad.2024.12.061
pubmed_id: 39706482
source_url: https://doi.org/10.1016/j.jad.2024.12.061
substance_tags: psilocybin
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:01
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.

abstract:
ObjectiveTo determine the relationships between psilocybin dose, psychedelic experiences, and therapeutic outcome in treatment-resistant depression.MethodsFor treatment-resistant depression, 233 participants received a single dose of 25, 10, or 1 mg of COMP360 psilocybin (a proprietary, pharmaceutical-grade synthesized psilocybin formulation, developed by the sponsor, Compass Pathfinder Ltd.) with psychological support. The resulting psychedelic experience (Five-Dimensional Altered States of Consciousness questionnaire [5D-ASC] and Emotional Breakthrough Inventory [EBI]) were measured. These proximal variables and outcome 3 weeks post-administration (change in Montgomery-Åsberg Depression Rating Scale [MADRS]) were explored using correlation analysis.ResultsThe mean intensity of psychedelic effects was dose-related, but distributions of scores for different doses overlapped considerably. Depression response correlated with select aspects of the psychedelic experience overall and for individual doses. At the 25 mg dose, 5D-ASC dimensions Oceanic Boundlessness (Pearson correlation coefficient r = -0.508) and Visual Restructuralization (r = -0.516), and EBI (r = -0·637) were the variables with the strongest correlation to the Week 3 change from Baseline in MADRS score.LimitationsThe existence of correlation does not establish causation and exploratory findings require further replication, preferably in larger independent samples.ConclusionsThe intensity of psychedelic experience overlaps widely across doses and mitigates the risk of unblinding to dose. Correlations between psychedelic experience and outcome suggest specificity in psilocybin's mechanism of action. Quality and intensity of psychedelic experience may be a measure of pharmacodynamic effect and reveal an effective dose response phenomenon for single oral doses.

keywords:
Humans, Hallucinogens, Treatment Outcome, Psychiatric Status Rating Scales, Dose-Response Relationship, Drug, Adult, Middle Aged, Female, Male, Depressive Disorder, Treatment-Resistant, Surveys and Questionnaires, Psilocybin, Major Depressive Disorder

topic_tags:
Depression,Pharmacology,Mechanism of Action,Consciousness,Emotional Processing,Observational Study,Treatment-Resistant Depression,Safety

raw_json:
{"europe_pmc_id":"39706482","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Treatment Expectancies and Psilocybin vs Escitalopram for Depression.
authors: Dutcher EG, Krystal AD.
publication_date: 2025-02-28
doi: 10.1001/jamapsychiatry.2024.4387
pubmed_id: 39653344
source_url: https://doi.org/10.1001/jamapsychiatry.2024.4387
substance_tags: psilocybin
topic_tags: 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
raw_json:
{"europe_pmc_id":"39653344","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2024-12-04
doi: 10.1192/bjp.2024.143
pubmed_id: 39632615
source_url: https://doi.org/10.1192/bjp.2024.143
substance_tags: psilocybin
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:
Consistent evidence that brain serotonin 2A receptor binding is positively associated with personality-based risk markers of depression.

authors:
Høgsted ES, Beliveau V, Ozenne B, Madsen MK, Svarer C, Dam VH, Johansen A, Fisher P, Knudsen GM, Frokjaer VG, Sankar A.

abstract:
BackgroundUsing [18F]altanserin, a serotonin 2A receptor (5-HT2AR) antagonist Positron Emission Tomography (PET) tracer, a positive association between cortical 5-HT2AR binding and the inward-directed facets of neuroticism has been demonstrated in healthy individuals. Psilocybin, a 5-HT2AR agonist, shows promise for the treatment of depression, reducing neuroticism and mood symptoms potentially via hypothalamic-pituitary-adrenal (HPA) modulation. 5-HT2AR and neuroticism are both modulated by HPA axis function.AimsIn this study, we examined whether the association between 5-HT2AR binding and the inward facets of neuroticism can be replicated in an independent healthy cohort using the new 5-HT2AR agonist tracer [11C]Cimbi-36, and if their association is moderated by cortisol awakening response (CAR), an index of HPA axis function. If so, this could advance mechanistic insights into interventions that target the 5-HT2AR and reduce neuroticism.MethodEighty healthy volunteers underwent [11C]Cimbi-36 PET scans and completed the NEO personality inventory (NEO-PI-R) for the assessment of neuroticism. Salivary samples were available for determination of CAR in 70 of the participants. Using linear latent variable models, we evaluated the association between 5-HT2AR binding and inward facets of neuroticism, namely depression, anxiety, self-consciousness and vulnerability to stress, and whether CAR moderated this association.ResultsThe study confirms the positive association between 5-HT2AR binding and the inward facets of neuroticism (β = 0.01, 95% CI = [0.0005: 0.02], P = 0.04), and this association is independent of CAR (P = 0.33).ConclusionsThe findings prompt consideration of whether novel interventions such as psilocybin that actively targets 5-HT2AR and causes changes in personality could be particularly beneficial if implemented as a targeted approach based on neuroticism profiles.

keywords:
Hypothalamo-Hypophyseal System, Brain, Saliva, Humans, Benzylamines, Phenethylamines, Ketanserin, Carbolines, Hydrocortisone, Receptor, Serotonin, 5-HT2A, Positron-Emission Tomography, Depression, Personality, Anxiety Disorders, Adult, Middle Aged, Female, Male, Young Adult, Serotonin 5-HT2 Receptor Agonists, Neuroticism

topic_tags:
Depression,Anxiety,Brain Imaging,Receptor Pharmacology,Consciousness,Biomarkers,Personality Change,Observational Study,Healthy Volunteers,Safety

raw_json:
{"europe_pmc_id":"39632615","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2024-11-26
doi: 10.1038/s41380-024-02800-5
pubmed_id: 39592825
source_url: https://doi.org/10.1038/s41380-024-02800-5
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 11:22:04
title:
Reconsidering evidence for psychedelic-induced psychosis: an overview of reviews, a systematic review, and meta-analysis of human studies.

authors:
Sabé M, Sulstarova A, Glangetas A, De Pieri M, Mallet L, Curtis L, Richard-Lepouriel H, Penzenstadler L, Seragnoli F, Thorens G, Zullino D, Preller K, Böge K, Leucht S, Correll CU, Solmi M, Kaiser S, Kirschner M.

abstract:
BackgroundPersons with schizophrenia are excluded from psychedelic-assisted therapy due to concerns about the risk of triggering or worsening psychosis. However, there is limited meta-analytic data on the risk of psychedelic-induced psychosis in individuals with pre-existing psychotic disorders.MethodsWe conducted a systematic review, meta-analysis, and overview of reviews to assess the incidence of psychedelic-induced psychosis and symptom exacerbation in schizophrenia. Our pre-registered protocol (CRD42023399591) covered: LSD, psilocybin, mescaline, DMT, and MDMA, using data from Embase, PubMed, PsyARTICLES, PsyINFO, and trial registries up to November 2023. A random-effects model was used to calculate psychosis incidence, with standardized assessments of study quality.ResultsFrom 131 publications, we analyzed 14 systematic reviews, 20 reviews, 35 randomized-controlled trials (RCTs), 10 case-control studies, 30 uncontrolled trials (UCTs), and 22 cohort studies, most of which were low quality. Meta-analysis of nine studies showed an incidence of psychedelic-induced psychosis at 0.002% in population studies, 0.2% in UCTs, and 0.6% in RCTs. In UCTs including individuals with schizophrenia, 3.8% developed long-lasting psychotic symptoms. Of those with psychedelic-induced psychosis, 13.1% later developed schizophrenia. Sensitivity analyses confirmed the results.ConclusionIn summary, the reviewed evidence suggests that schizophrenia might not be a definite exclusion criterion for clinical trials exploring safety and efficacy of psychedelics for treatment-resistant depression and negative symptoms. However, given the low quality and limited number of studies, more high-quality research is needed, and a conservative approach is recommended until further data is available.

keywords:
Humans, Psychoses, Substance-Induced, Lysergic Acid Diethylamide, Hallucinogens, Psychotic Disorders, Schizophrenia, Psilocybin

topic_tags:
Depression,Clinical Trial,Randomized Controlled Trial,Meta-Analysis,Systematic Review,Review Article,Observational Study,Treatment-Resistant Depression,Safety

raw_json:
{"europe_pmc_id":"39592825","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Brownstien M, Lazar M, Botvinnik A, Shevakh C, Blakolmer K, Lerer L, Lifschytz T, Lerer B.
journal: bioRxiv
publication_date: 2024-06-28
doi: 10.1101/2024.06.25.600634
source_url: https://doi.org/10.1101/2024.06.25.600634
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:01
title:
Striking Long Term Beneficial Effects of Single Dose Psilocybin and Psychedelic Mushroom Extract in the SAPAP3 Rodent Model of OCD-Like Excessive Self-Grooming

abstract:
Obsessive compulsive disorder (OCD) is a highly prevalent disorder that causes serious disability. Available treatments leave 40% or more of people with OCD significantly symptomatic. There is an urgent need for novel therapeutic approaches. Mice that carry a homozygous deletion of the SAPAP3 gene (SAPAP3 KO) manifest a phenotype of excessive self-grooming, tic-like head-body twitches and anxiety. These behaviors closely resemble pathological self-grooming behaviors observed in humans in conditions that overlap with OCD. Following a preliminary report that the tryptaminergic psychedelic, psilocybin, may reduce symptoms in patients with OCD, we undertook a randomized controlled trial of psilocybin in 50 SAPAP3 KO mice (28 male, 22 female). Mice that fulfilled inclusion criteria were randomly assigned to a single intraperitoneal injection of psilocybin (4.4 mg/kg), psychedelic mushroom extract (encompassing the same psilocybin dose) or vehicle control and were evaluated after 2, 4 and 21 days by a rater blind to treatment allocation for grooming characteristics, head-body twitches, anxiety and other behavioral features. Mice treated with vehicle (n=18) manifested a 118.71 + 95.96 % increase in total self-grooming (the primary outcome measure) over the 21-day observation period. In contrast, total self-grooming decreased by 14.60% + 17.90% in mice treated with psilocybin (n=16) and by 19.20 + 20.05% in mice treated with psychedelic mushroom extract (n=16) (p=.001 for effect of time; p=.0001 for time X treatment interaction). 5 mice were dropped from the vehicle group because they developed skin lesions; 4 from the psilocybin group and none from the psychedelic mushroom extract group. Secondary outcome measures such as head-body twitches and anxiety all showed a significant improvement over 21 days. Notably, in mice that responded to psilocybin (n=12) and psychedelic mushroom extract (n=13), the beneficial effect of a single treatment persisted up to 7 weeks. Mice initially treated with vehicle and non-responsive, showed a clear and lasting therapeutic response when treated with a single dose of psilocybin or psychedelic mushroom extract and followed for a further 3 weeks. While equivalent to psilocybin in overall effect on self-grooming, psychedelic mushroom extract showed superior effects in alleviating head-body twitches and anxiety. These findings strongly justify clinical trials of psilocybin in the treatment of OCD and further studies aimed at elucidating mechanisms that underlie the long-term effects to alleviate excessive self-grooming observed in this study. Graphical Abstract Prepared with BioRender ( https://www.biorender.com/ )

topic_tags:
Anxiety,OCD,Mechanism of Action,Clinical Trial,Randomized Controlled Trial,Animal Study,Drug Interactions

raw_json:
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authors: Junges LH, Müller-Santos M.
publication_date: 2024-10-03
doi: 10.1002/btpr.3513
pubmed_id: 39366919
source_url: https://doi.org/10.1002/btpr.3513
keywords: Humans, Tryptamines, Biocatalysis, Psilocybin
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Mechanism of Action,Aging,Review Article
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:01
title:
Exploring the biocatalysis of psilocybin and other tryptamines: Enzymatic pathways, synthetic strategies, and industrial implications.

abstract:
Tryptamines play diverse roles as neurotransmitters and psychoactive compounds found in various organisms. Psilocybin, a notable tryptamine, has garnered attention for its therapeutic potential in treating mental health disorders like depression and anxiety. Despite its promising applications, current extraction methods for psilocybin are labor-intensive and economically limiting. We suggest biocatalysis as a sustainable alternative, leveraging enzymes to synthesize psilocybin and other tryptamines efficiently. By elucidating psilocybin biosynthesis pathways, researchers aim to advance synthetic methodologies and industrial applications. This review underscores the transformative potential of biocatalysis in enhancing our understanding of tryptamine biosynthesis and facilitating the production of high-purity psilocybin and other tryptamines for therapeutic and research use.

raw_json:
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authors: Perna J, Trop J, Palitsky R, Bosshardt Z, Vantine H, Dunlop BW, Zarrabi AJ.
publication_date: 2025-02-27
doi: 10.1186/s12888-024-06303-z
pubmed_id: 40021999
source_url: https://doi.org/10.1186/s12888-024-06303-z
keywords: Humans, Hallucinogens, Electroconvulsive Therapy, Female, Suicidal Ideation, Psilocybin
substance_tags: psilocybin
topic_tags: Emotional Processing,Case Report,Healthcare Workers
study_type: Case Report
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:01
title:
Prolonged adverse effects from repeated psilocybin use in an underground psychedelic therapy training program: a case report.

abstract:
BackgroundPsychedelic-assisted therapy has gained growing interest to improve a range of mental health outcomes. In response, numerous training programs have formed to train the necessary workforce to deliver psychedelic therapy. These include both legal and 'underground' (i.e., unregulated) programs that use psychedelics as part of their training. Prolonged adverse experiences (PAEs) may arise from psychedelic use, though they are poorly characterized in the clinical literature. Thus, understanding the potential harms related to psychedelic use is critical as psychedelic therapy training programs consider strategies to potentially integrate psychedelic use into therapy training.Case presentationWe present the case of a psychologist who underwent psychedelic therapy training that involved repeated high doses of psilocybin-containing mushrooms and subsequently developed prolonged adverse effects including severe sleep impairment, anhedonia, and suicidal ideation requiring hospitalization. Despite worsening symptoms, her psychedelic therapy trainers advised her against seeking psychiatric support, delaying treatment. Ultimately, the patient's symptoms resolved after a course of electroconvulsive therapy (ECT).ConclusionsThis case highlights the tensions between legal and underground psychedelic use within psychedelic therapy training programs, psychiatry and neo-shamanism, and the use of psychiatric interventions (i.e., ECT) and energy medicine to address prolonged adverse effects from psychedelics. Clinicians should be aware of these potential conflicts between psychiatric conceptualizations of PAEs and frameworks maintained in psychedelic community practices and their impacts on patients' presenting symptoms, decision making, and emotional challenges.

raw_json:
{"europe_pmc_id":"40021999","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Silva F, Butlen-Ducuing F, Guizzaro L, Balabanov P.
publication_date: 2025-02-25
doi: 10.1016/j.nsa.2025.105516
pubmed_id: 40654583
source_url: https://doi.org/10.1016/j.nsa.2025.105516
substance_tags: psilocybin
topic_tags: Depression,Clinical Trial,Review Article,Treatment-Resistant Depression,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 11:22:04
title:
A review of psychedelics trials completed in depression, informed by European regulatory perspectives.

abstract:
There is a growing body of clinical research on the therapeutic potential of psychedelics for the treatment of mental health disorders, notably depression. Accordingly, the new revision of the European Medicines Agency guideline on the clinical investigation of products for depression will incorporate a section covering specific regulatory recommendations for the design of studies with psychedelics. The present review investigated the methodological approaches adopted in completed controlled trials of psychedelics for depression in light of initial considerations included in the draft guideline revision. A systematic search conducted on scientific databases (Embase and Medline) and clinical trial registries (clinicaltrials.gov and WHO ICTPR) identified 8 completed trials as of February 2024. The trials tested psilocybin, LSD, Ayahuasca, and DMT, for major depressive disorder or treatment-resistant depression, and were all pahse 2 or 1/2. Patterns in pre-defined methodological variables pertaining to trial design, population, interventions, outcome measures and safety assessments were analysed and collated against considerations on unblinding and expectancy, choice of comparator, the definition of treatment frameworks, the characterisation of the subjective psychedelic experience and the specification of adverse events in relation to subjective psychedelic effects. Areas for future research, including long-term efficacy and safety and the influence of inter-individual differences, can be investigated in larger studies, necessary for marketing authorisation applications. Ultimately, balancing the intricacies of conducting trials with psychedelics with ensuring adherence to regulatory requirements can be facilitated by early dialogue with medicines regulators, and will be essential for the medical development of psychedelics to address unmet patient needs.

raw_json:
{"europe_pmc_id":"40654583","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psychedelics and Suicide-Related Outcomes: A Systematic Review.
publication_date: 2025-02-19
doi: 10.3390/jcm14051416
pubmed_id: 40094838
source_url: https://doi.org/10.3390/jcm14051416
substance_tags: psilocybin
topic_tags: PTSD,Mechanism of Action,Randomized Controlled Trial,Systematic Review,Review Article,Safety
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
authors:
Meshkat S, Malik T, Zeifman R, Swainson J, Zhang Y, Burback L, Winkler O, Greenshaw AJ, Claire Reichelt A, Vermetten E, Erritzoe D, Jha MK, Dunn W, Jetly R, Husain MI, Bhat V.

abstract:
Background/Objectives: Suicide accounts for 1.4% of global deaths, and the slow-acting nature of traditional treatments for suicide risk underscores the need for alternatives. Psychedelic therapies may rapidly reduce suicide risk. This systematic review evaluates impact of psychedelic therapies on suicide-related outcomes. Methods: A systematic search of MEDLINE, Embase, PsycINFO, and ClinicalTrials.gov was conducted up to November 2024. Results: Four randomized controlled trials (RCTs) evaluated suicidality as a secondary outcome or safety measure, showing significant reductions in suicidal ideation with psilocybin (three studies) and MDMA-assisted therapy (MDMA-AT; one study). Effect sizes, measured by Cohen's d, ranged from =0.52 to 1.25 (p = 0.01 to 0.005), with no safety issues reported. Five additional RCTs assessed suicidality as a safety measure, showing reductions in suicidal ideation with psilocybin (two studies) and MDMA-AT (three studies; p = 0.02 to 0.04). Among 24 non-randomized and cross-sectional studies, results were mixed. Psilocybin (three studies) reduced suicidal ideation, with odds ratios (OR) of 0.40-0.75. MDMA-AT (five studies in PTSD patients) had a pooled effect size of d = 0.61 (95% CI: 0.32-0.89). LSD (six studies) showed increased odds of suicidality, with odds ratios ranging from 1.15 to 2.08. Studies involving DMT (two studies) and multiple psychedelics (three studies) showed mixed results, with DMT studies not showing significant effects on suicidality and studies involving multiple psychedelics showing varying outcomes, some reporting reductions in suicidal ideation and others showing no significant change. Conclusions: The effect of psychedelic therapies on suicide-related outcomes remains inconclusive, highlighting the need for further trials to clarify safety and therapeutic mechanisms.

raw_json:
{"europe_pmc_id":"40094838","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psychiatric Treatments with Short-Duration Psychedelics and AI-Driven Behavioral Monitoring.
authors: Kargbo RB.
publication_date: 2025-01-28
doi: 10.1021/acsmedchemlett.5c00031
pubmed_id: 39967620
source_url: https://doi.org/10.1021/acsmedchemlett.5c00031
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Receptor Pharmacology,Review Article,Animal Study,Treatment-Resistant Depression
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
abstract:
Integrating advanced pharmaceutical innovations and artificial intelligence (AI) offers transformative potential for psychiatric care. This Patent Highlight reviews novel therapeutic strategies, including the synergistic use of monoamine antidepressants and short-duration psychedelics, alongside AI-driven behavioral efficacy tracking. The combination of selective serotonin reuptake inhibitors (SSRIs) with short-acting psychedelics, such as N,N-dimethyltryptamine (DMT) and psilocybin, provides rapid and sustained improvements in treatment-resistant depression and anxiety. Meanwhile, AI-enhanced behavioral monitoring leverages motion tracking and machine learning to quantify treatment outcomes in animal models, accelerating drug development. Together, these approaches redefine therapeutic paradigms, offering personalized and effective treatments for psychiatric disorders.

raw_json:
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authors: Adamczyk S, Paczyńska M, Ruban A, Szczypiński J, Bola M, Orłowski P.
publication_date: 2025-02-12
doi: 10.1080/02791072.2025.2464797
pubmed_id: 39948726
source_url: https://doi.org/10.1080/02791072.2025.2464797
substance_tags: psilocybin
topic_tags: Emotional Processing,Spirituality,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 11:22:04
title:
Setting the Stage for the Inner Journey: Unraveling the Interplay of Contextual Factors and the Intensity of Psychedelic-Induced Ego Dissolution.

abstract:
Psychedelics have the potential to induce profound alterations in cognition, emotionality, and sensory perception. The quality and intensity of these subjective effects exhibit high intra- and inter-individual variability, which can potentially be accounted for by the variability in contexts in which psychedelics are used. Therefore, the aim of the present cross-sectional study was to investigate how internal and external contextual factors are related to the subjective intensity of psychedelic-induced ego dissolution experiences. Participants completed an online survey in which they reported their motivations for past use of psychedelic substances, and the frequency of use in different environments and social contexts. Additionally, participants completed the Ego Dissolution Inventory to evaluate the intensity of past ego dissolution experiences. Robust linear regression analysis was performed on data from 862 psychedelics users (701 had used LSD and 553 had used psilocybin mushrooms); this revealed that participants consuming psychedelics for spiritual or self-healing purposes reported more intense, while those motivated by curiosity reported less intense ego dissolution experiences. However, the social context and physical environment did not exhibit robust associations with the reported ego dissolution. Therefore, our study enhances understanding of how set and setting factors relate to psychedelic-induced ego dissolution experiences in naturalistic contexts.

raw_json:
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journal: bioRxiv
publication_date: 2024-05-25
doi: 10.1101/2024.05.23.590306
source_url: https://doi.org/10.1101/2024.05.23.590306
substance_tags: psilocybin
topic_tags: Neuroplasticity,Brain Imaging,Biomarkers,Aging,Animal Study
study_type: Animal Study
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
title:
Classification of psychedelics and psychoactive drugs based on brain-wide imaging of cellular c-Fos expression

authors:
Aboharb F, Davoudian PA, Shao L, Liao C, Rzepka GN, Wojtasiewicz C, Indajang J, Dibbs M, Rondeau J, Sherwood AM, Kaye AP, Kwan AC.

abstract:
Psilocybin, ketamine, and MDMA are psychoactive compounds that exert behavioral effects with distinguishable but also overlapping features. The growing interest in using these compounds as therapeutics necessitates preclinical assays that can accurately screen psychedelics and related analogs. We posit that a promising approach may be to measure drug action on markers of neural plasticity in native brain tissues. We therefore developed a pipeline for drug classification using light sheet fluorescence microscopy of immediate early gene expression at cellular resolution followed by machine learning. We tested male and female mice with a panel of drugs, including psilocybin, ketamine, 5-MeO-DMT, 6-fluoro-DET, MDMA, acute fluoxetine, chronic fluoxetine, and vehicle. In one-versus-rest classification, the exact drug was identified with 67% accuracy, significantly above the chance level of 12.5%. In one-versus-one classifications, psilocybin was discriminated from 5-MeO-DMT, ketamine, MDMA, or acute fluoxetine with >95% accuracy. We used Shapley additive explanation to pinpoint the brain regions driving the machine learning predictions. Our results support a novel approach for characterizing and validating psychoactive drugs with psychedelic properties.

raw_json:
{"europe_pmc_id":"PPR858281","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


journal: bioRxiv
publication_date: 2025-02-05
doi: 10.1101/2025.02.03.636248
source_url: https://doi.org/10.1101/2025.02.03.636248
substance_tags: psilocybin
topic_tags: Neuroplasticity,Mechanism of Action,Receptor Pharmacology,Safety,Inflammation
study_type: Other
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:01
title:
Psilocybin as a Treatment for Repetitive Mild Head Injury: Evidence from Neuroradiology and Molecular Biology

authors:
Brengel EK, Axe B, Maheswari A, Abeer MI, Ortiz RJ, Woodward TJ, Walhof R, Utama R, Sawada C, Balaji S, Kulkarni PP, Bradshaw HB, Gitcho MA, Ferris CF.

abstract:
Repetitive mild head injuries incurred while playing organized sports, during car accidents and falls, or in active military service are a major health problem. These head injuries induce cognitive, motor, and behavioral deficits that can last for months and even years with an increased risk of dementia, Parkinson’s disease, and chronic traumatic encephalopathy. There is no approved medical treatment for these types of head injuries. To this end, we tested the healing effects of the psychedelic psilocybin, as it is known to reduce neuroinflammation and enhance neuroplasticity. Using a model of mild repetitive head injury in adult female rats, we provide unprecedented data that psilocybin can reduce vasogenic edema, restore normal vascular reactivity and functional connectivity, reduce phosphorylated tau buildup, enhance levels of brain-derived neurotrophic factor and its receptor TrkB, and modulate lipid signaling molecules.

raw_json:
{"europe_pmc_id":"PPR975392","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


title: High-quality draft genomes of ecologically and geographically diverse Psilocybe species.
publication_date: 2024-12-26
doi: 10.1128/mra.00250-24
pubmed_id: 39727395
source_url: https://doi.org/10.1128/mra.00250-24
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 11:22:02
authors:
Bollinger IM, Singer H, Jacobs J, Tyler M, Scott K, Pauli CS, Miller DR, Barlow C, Rockefeller A, Slot JC, Angel-Mosti V.

abstract:
Psilocybe is a genus of mushroom-forming fungi with ecological, ethnomycological, and clinical importance due to psilocybin production by most species. We present five genomes that enable deeper discovery and analysis of the psilocybin gene cluster and increase taxonomic resolution within Psilocybe: Psilocybe semilanceata, Psilocybe gandalfiana nom. prov., Psilocybe caeruleorhiza, Psilocybe azurescens, and Psilocybe allenii.

raw_json:
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publication_date: 2025-02-09
doi: 10.1136/bmj.r111
pubmed_id: 39929528
source_url: https://doi.org/10.1136/bmj.r111
substance_tags: psilocybin
topic_tags: Depression,Meta-Analysis,Systematic Review,Review Article
study_type: Meta-Analysis
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
title:
CORRECTION: Efficacy of psilocybin for treating symptoms of depression: systematic review and meta-analysis.

raw_json:
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journal: PsyArXiv
publication_date: 2023-10-13
source_url: https://osf.io/preprints/psyarxiv/hm6jn_v1
substance_tags: psilocybin
topic_tags: Chronic Pain,Pharmacology,Wellbeing,Emotional Processing,Observational Study
study_type: Observational Study
source_name: PsyArXiv
publication_status: preprint
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:30
raw_json: {"osf_id":"hm6jn_v1","version":1,"reviews_state":"accepted"}
title:
Shame, guilt and psychedelic experience: Results from a prospective, longitudinal survey of real-world psilocybin use

abstract:
Introduction: The classic psychedelic psilocybin has attracted special interest across clinical and non-clinical settings as a potential tool for mental health. However, despite increasing attention to challenging psychedelic experiences, few studies have explored the relevance of emotionally painful, shame-related processes with psychedelic use. Methods: This prospective, longitudinal study involved sequential, automated, web-based surveys that collected data from 679 adults planning to use psilocybin in naturalistic settings at timepoints before and after psilocybin use. State and trait shame and feelings of guilt were collected using validated measures and assessed alongside other measurements of psychological health. Results: Participants were primarily college-educated, White individuals residing in the United States with a prior history of psilocybin use; mean age = 38.9-41 years. Most users (89.7%) described their experience of psilocybin as positive, though acute feelings of shame or guilt were commonly reported (i.e., 68.2% of users) and difficult to predict. Ratings of participant ability to constructively work through these feelings predicted wellbeing 2-4 weeks after psilocybin use. Psilocybin on average produced a small but significant decrease in trait shame that was maintained 2-3 months after use (Cohen’s dz = 0.37; adjusted p

keywords:
breakthrough, challenging, guilt, psilocybin, psychedelics, shame, therapy, Social and Behavioral Sciences, Clinical Psychology, Psychopharmacology


title: A qualitative analysis of the psychedelic mushroom come-up and come-down.
authors: Brouwer A, Brown JK, Erowid E, Erowid F, Thyssen S, Raison CL, Carhart-Harris RL.
publication_date: 2025-02-06
doi: 10.1038/s44184-024-00095-6
pubmed_id: 39915687
source_url: https://doi.org/10.1038/s44184-024-00095-6
substance_tags: psilocybin
topic_tags: Consciousness,Clinical Trial
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 therapy has the potential to become a revolutionary and transdiagnostic mental health treatment, yielding enduring benefits that are often attributed to the experiences that coincide with peak psychedelic effects. However, there may be an underrecognized temporal structure to this process that helps explain why psychedelic and related altered states of consciousness can have an initially distressing but ultimately distress-resolving effect. Here we present a qualitative analysis of the self-reported 'come-up' or onset phase, and 'come-down' or falling phase, of the psychedelic experience. Focusing on psilocybin or psilocybin-containing mushroom experience reports submitted to Erowid.org, we use phenomenological, thematic content and word frequency analysis to show that the come-up is more often characterized by negatively valenced feeling states that resemble an acute stress reaction, while the come-down phase is more often characterized by positively valenced feeling states of the sort often observed following recovery from illness or resolution of stress. The therapeutic and theoretical relevance of these findings are discussed.

raw_json:
{"europe_pmc_id":"39915687","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Hogea L, Tabugan DC, Costea I, Albai O, Nussbaum L, Cojocaru A, Corsaro L, Anghel T.
publication_date: 2025-02-05
doi: 10.3390/medicina61020278
pubmed_id: 40005395
source_url: https://doi.org/10.3390/medicina61020278
keywords: Humans, Substance-Related Disorders, Hallucinogens, Clinical Trials as Topic, 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 11:22:02
title:
The Therapeutic Potential of Psychedelics in Treating Substance Use Disorders: A Review of Clinical Trials.

abstract:
Background and Objectives: Substance use disorders (SUDs) affect millions worldwide. Despite increasing drug use, treatment options remain limited. Psychedelic-assisted therapy (PAT), integrating psychedelic substances with psychotherapy, offers a promising alternative by addressing underlying neural mechanisms. Materials and Methods: This review's purpose is to investigate the current understanding of psychedelic therapy for treating SUDs, including tobacco, alcohol, and drug addiction. The systematic review approach focused on clinical trials and randomized controlled trials conducted from 2013 to 2023. The search was performed using PubMed, Google Scholar, and Consensus AI, following PRISMA guidelines. Studies involving psychedelics like LSD, psilocybin, ibogaine, and ayahuasca for treating various addictions were included, excluding naturalistic studies and reviews. Results: Our results highlight the key findings from 16 clinical trials investigating psychedelic therapy for SUDs. Psychedelics like psilocybin and ayahuasca showed promise in reducing alcohol and tobacco dependence, with psilocybin being particularly effective in decreasing cravings and promoting long-term abstinence. The studies revealed significant improvements in substance use reduction, especially when combined with psychotherapy. However, the variability in dosages and study design calls for more standardized approaches. These findings emphasize the potential of psychedelics in SUD treatment, though further large-scale research is needed to validate these results and develop consistent protocols. Conclusions: This research reviewed the past decade's international experience, emphasizing the growing potential of psychedelic therapy in treating SUDs pertaining to alcohol, tobacco, and cocaine dependence. Psychedelics such as psilocybin and ketamine can reduce cravings and promote psychological well-being, especially when combined with psychotherapy. However, regulatory barriers and specialized clinical training are necessary to integrate these therapies into mainstream addiction treatment safely. Psychedelics offer a promising alternative for those unresponsive to conventional methods.

topic_tags:
Addiction,Mechanism of Action,Wellbeing,Clinical Trial,Randomized Controlled Trial,Systematic Review,Review Article

raw_json:
{"europe_pmc_id":"40005395","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Lucido MJ, Dunlop BW.
publication_date: 2025-02-05
doi: 10.3390/brainsci15020161
pubmed_id: 40002494
source_url: https://doi.org/10.3390/brainsci15020161
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 11:22:05
title:
Emerging Medications for Treatment-Resistant Depression: A Review with Perspective on Mechanisms and Challenges.

abstract:
Background/Objectives: Non-response to initial treatment options for major depressive disorder (MDD) is a common clinical challenge with profound deleterious impacts for affected patients. Few treatments have received regulatory approval for treatment-resistant depression (TRD). Methods: A systematic search of United States and European Union clinical trials registries was conducted to identify Phase II, III, or IV clinical trials, with a last update posted on or after 1 January 2020, that were evaluating medications for TRD. For both the US and EU registries, the condition term "treatment resistant depression" and associated lower-level terms (per registry search protocol) were used. For the US registry, a secondary search using the condition term "depressive disorders" and the modifying term "inadequate" was also performed to capture registrations not tagged as TRD. Two additional searches were also conducted in the US registry for the terms "suicide" and "anhedonia" as transdiagnostic targets of investigational medications. Trials were categorized based on the primary mechanism of action of the trial's investigational medication. Results: Fifty clinical trials for TRD, 20 for anhedonia, and 25 for suicide were identified. Glutamate system modulation was the mechanism currently with the most compounds in development, including antagonists and allosteric modulators of NMDA receptors, AMPA receptors, metabotropic type 2/3 glutamate receptors, and intracellular effector molecules downstream of glutamate signaling. Psychedelics have seen the greatest surge among mechanistic targets in the past 5 years, however, with psilocybin in particular garnering significant attention. Other mechanisms included GABA modulators, monoamine modulators, anti-inflammatory/immune-modulating agents, and an orexin type 2 receptor antagonist. Conclusions: These investigations offer substantial promise for more efficacious and potentially personalized medication approaches for TRD. Challenges for detecting efficacy in TRD include the heterogeneity within the TRD population stemming from the presumed variety of biological dysfunctions underlying the disorder, comorbid disorders, chronic psychosocial stressors, and enduring effects of prior serotonergic antidepressant medication treatments.

topic_tags:
Depression,Mechanism of Action,Receptor Pharmacology,Clinical Trial,Review Article,Treatment-Resistant Depression,Inflammation,Immune Function

raw_json:
{"europe_pmc_id":"40002494","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Zamaria JA, Fernandes-Osterhold G, Shedler J, Yehuda R
journal: Frontiers in psychology
publication_date: 2024-12-31
doi: 10.3389/fpsyg.2025.1505894
pubmed_id: 39973948
source_url: https://pubmed.ncbi.nlm.nih.gov/39973948/
substance_tags: psilocybin
topic_tags: 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 11:20:36
raw_json: {"pubmed_id":"39973948"}
title:
Psychedelics assisting therapy, or therapy assisting psychedelics? The importance of psychotherapy in psychedelic-assisted therapy.

keywords:
MDMA-assisted therapy, clinical trials, psilocybin-assisted therapy, psychedelic-assisted therapy, psychedelics, psychotherapy


authors: Bender DA, Nayak SM, Siegel JS, Hellerstein DJ, Ercal BC, Lenze EJ.
publication_date: 2025-02-04
doi: 10.4088/jcp.24m15521
pubmed_id: 39928849
source_url: https://doi.org/10.4088/jcp.24m15521
substance_tags: psilocybin
topic_tags: Emotional Processing,Spirituality,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 11:22:04
title:
Psychological Support Approaches in Psychedelic Therapy: Results From a Survey of Psychedelic Practitioners.

abstract:
Objective: To assess the viewpoints of psychedelic practitioners in research settings on approaches to psychological support for psychedelic treatments.Methods: An anonymous survey was distributed via email to contacts listed on ClinicalTrials.gov for clinical trials of psilocybin and LSD, personal contacts of authors, and through snowball sampling. The survey included Likert type, multiple choice, free response, and demographic items. Responses to survey items were coded to represent either emotive (emphasizing human and spiritual elements) or neuromodulatory (emphasizing biological drug effects) approaches to psychedelic treatment. Summative scores ("E-Scores") were determined to quantitatively represent preferences. Data were collected from March 2023 to July 2023.Results: Forty qualified respondents completed the survey. Respondents came from varying educational backgrounds (42.5% MD/DO and 57.5% other) and practiced in at least 4 countries, 11 U.S. states, and 16 institutions. Respondents had overseen a total of 1,656 psychedelic sessions (average = 41.4). There was a substantial range of response for many items (average range = 84.2% of maximum). Exploratory factor analysis identified 4 latent factors: The Importance of Trust, The Role of Spirituality, Creating an Emotional Setting, and Conceptualizing Negative Experiences. The average respondent held a slight preference for an emotive approach. Respondents who received training at the Multidisciplinary Association for Psychedelic Studies (MAPS) or the California Institute of Integral Studies (CIIS) had significantly greater emotive preference compared to other respondents (P <.05).Conclusions: Among psychedelic researchers, there is no consensus on certain psychological support strategies for psychedelic treatments. There is an aggregate preference for an emotive approach to psychological support, which is higher among individuals receiving training at certain institutions.

keywords:
Humans, Lysergic Acid Diethylamide, Hallucinogens, Attitude of Health Personnel, Adult, Middle Aged, Female, Male, Surveys and Questionnaires, Psilocybin

raw_json:
{"europe_pmc_id":"39928849","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Hallucinogen-Persisting Perception Disorder in a 16-Year-Old Adolescent.
authors: Mori-Kreiner A, Aggarwal A, Bordoloi M.
publication_date: 2025-01-31
doi: 10.64719/pb.4525
pubmed_id: 39935673
source_url: https://doi.org/10.64719/pb.4525
substance_tags: psilocybin
topic_tags: Depression,Addiction,Review Article,Case Report,Adolescents
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:04
abstract:
ObjectiveHallucinogen-persisting Perception Disorder (HPPD) is a rare condition characterized by the re-experiencing of one or more perceptual symptoms that an individual experienced while intoxicated with a hallucinogenic substance when the individual is sober. While there are several case reports of HPPD in adult patients, there is a scarcity of documented cases in children and adolescents. The purpose of this article is to highlight the presentation, diagnosis, and treatment of HPPD in a 16-year-old male patient.MethodsIn this case report, the patient is a 16-year-old male with a history of major depressive disorder (MDD) and polysubstance use using Lysergic acid diethylamide (LSD), 3,4-Methylenedioxymethamphetamine (MDMA), psilocybin, cannabis, and benzodiazepines. He endorsed having auditory hallucinations and a heightened sense of hearing in between usage of MDMA for the past eight months and described auditory and visual hallucinations during his 5-day admission at the inpatient child psychiatric unit. Aripiprazole 5 mg was used as treatment for HPPD.ResultsOn review of literature, the first-line treatment for HPPD with clonidine and benzodiazepine has been documented by few case reports. Second generation antipsychotics are documented to be less effective with the exception of aripiprazole. The authors witnessed gradual improvement in the patient's symptoms with the use of aripiprazole, although it was not completely resolved during his hospital course.ConclusionsThis case demonstrates the presentation of HPPD and efficacy of aripiprazole in an adolescent patient. The diagnosis was further complicated by the patient's history of polysubstance use, and determining a distinction from non-substance-induced psychotic disorders was paramount.

keywords:
Humans, Perceptual Disorders, Hallucinations, Antipsychotic Agents, Hallucinogens, Adolescent, Male, Aripiprazole, Major Depressive Disorder

raw_json:
{"europe_pmc_id":"39935673","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: de Miranda AS, C B Toscano E, Venna VR, Graeff FG, Teixeira AL.
publication_date: 2025-02-02
doi: 10.1080/17460441.2025.2460674
pubmed_id: 39885729
source_url: https://doi.org/10.1080/17460441.2025.2460674
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 11:22:04
title:
Investigating novel pharmacological strategies for treatment-resistant depression: focus on new mechanisms and approaches.

abstract:
IntroductionA substantial number of patients exhibit treatment-resistant depression (TRD), posing significant challenges to clinicians. The discovery of novel molecules or mechanisms that may underlie TRD pathogenesis and antidepressant actions is highly needed.Areas coveredUsing the PubMed database, the authors searched for emerging evidence of novel approaches for TRD based on experimental and human studies. Herein, the authors discuss the mechanisms underlying glutamatergic antagonists, modulators of the opioid system, and tryptamine-derivate psychedelics as well as the emerging platforms to investigate novel pharmacological targets for TRD. A search for clinical trials investigating novel agents and interventions for TRD was also conducted.Expert opinionThe understanding of the multiple pathophysiological mechanisms involved in TRD may add further value to the effective treatment, contributing to a more personalized approach. Esketamine was approved for the treatment of TRD and novel drugs with rapid antidepressant actions such as psilocybin and buprenorphine have also been investigated as potential therapeutic strategies. Over the past decades, technological advances such as omics approaches have broadened our knowledge regarding molecular and genetic underpinnings of complex conditions like TRD. Omics approaches could open new avenues for investigating glial-mediated mechanisms, including their crosstalk with neurons, as therapeutic targets in TRD.

topic_tags:
Depression,Addiction,Mechanism of Action,Clinical Trial,Treatment-Resistant Depression,Healthcare Workers

raw_json:
{"europe_pmc_id":"39885729","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Among Psychedelics, Only Psilocybin Has Demonstrated Benefit to Treat Depression.
authors: Shaughnessy AF.
publication_date: 2025-01-31
pubmed_id: 39964936
source_url: https://europepmc.org/article/MED/39964936
substance_tags: psilocybin
topic_tags: 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
raw_json:
{"europe_pmc_id":"39964936","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Louie E, Towers E, Morse AR, Watt J, Bryant Z, Haber P, Morley K.
publication_date: 2025-01-31
doi: 10.1111/inm.70010
pubmed_id: 39952893
source_url: https://doi.org/10.1111/inm.70010
substance_tags: psilocybin
topic_tags: Depression,PTSD,Observational Study,Treatment-Resistant Depression,Safety
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:
The Acceptability of Psychedelic-Assisted Therapy Amongst Mental Health Consumers: Utilising the Theory of Planned Behaviour.

abstract:
Australian government approval has been granted for 3,4-methylenedioxy-methamphetamine (MDMA) treatment of post-traumatic stress disorder and psilocybin for treatment-resistant depression, but the process of translating psychedelic-assisted therapies (PAT) into more widespread use is complex. Along with establishing the efficacy and feasibility of PATs, their acceptability amongst consumers is a crucial factor of successful implementation. This study utilised the Theory of Planned Behaviour to evaluate the acceptability of PATs amongst mental health consumers, identifying potential influences of these attitudes and predictors of PAT uptake. Participants completed an online survey between February and July 2023. Survey items evaluated consumer characteristics, acceptability of PAT (effectiveness, efficacy and social norms) and behavioural intentions to undertake PAT. The 254 participants had a mean age of 42.5 years (SD = 12.8) and 79.1% were female. Three quarters expressed a desire to access PAT. Acceptability scores indicated strong agreement regarding the effectiveness of PAT, social norms that moderately endorsed PAT and mixed feelings about its expected efficacy. Whilst univariate analyses indicated that previous psychedelic experience was associated with increased acceptability of PAT (ds = 0.63-0.80), multivariate analyses revealed that intentions to access PAT were associated with higher acceptability scores (ds = 0.37-1.32) and poorer experiences of conventional therapy (d = -0.31). Although a relatively large portion of participants had used psychedelics recreationally, the desire to access PATs was more strongly related to its acceptability, along with more negative experiences of conventional therapy. This implies that mental health consumers who are looking for alternatives to conventional therapy may view PATs as a desirable option, despite some safety reservations.

keywords:
Humans, Hallucinogens, Psychological Theory, Mental Disorders, Adult, Middle Aged, Patient Acceptance of Health Care, Australia, Female, Male, Young Adult, Surveys and Questionnaires

raw_json:
{"europe_pmc_id":"39952893","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Swieczkowski D, Kwaśny A, Pruc M, Gaca Z, Szarpak L, Cubała WJ.
publication_date: 2024-12-22
doi: 10.1016/j.psychres.2024.116337
pubmed_id: 39754904
source_url: https://doi.org/10.1016/j.psychres.2024.116337
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 11:22:01
title:
Efficacy and safety of psilocybin in the treatment of Major Depressive Disorder (MDD): A dose-response network meta-analysis of randomized placebo-controlled clinical trials.

abstract:
Selecting the optimal dose of psilocybin for treating Major Depressive Disorder (MDD) and Treatment-Resistant Depression (TRD) is crucial for clinical development and regulatory approval. This meta-analysis evaluates psilocybin's efficacy and safety in treating MDD to determine the optimal dose and timing for clinical trials. A systematic review and Dose-Response Network Meta-Analysis (NMA) of Randomized Placebo-Controlled Clinical Trials (RCTs) registered with PROSPERO was conducted. Databases searched included Embase, PubMed, Cochrane Library, Scopus, Web of Science, and Google Scholar, up to July 2024. The PICOS framework defined eligibility criteria: P: adult patients with MDD; I: psilocybin; C: placebo; O: changes in MADRS scores at Days 2, 8 and 15, and adverse events; S: RCT. Independent researchers performed data extraction and bias assessment. From 5419 search results, three RCTs involving 389 patients were included. Psilocybin significantly reduced symptoms compared to placebo at Day 8 (MD = -7.42; 95 % CI:10.07 to -4.78; p < 0.001) and Day 15 (MD = -9.55; 95 % CI:12.44 to -6.65; p < 0.001), without significant effects on Day 2. The NMA indicated that a 25 mg dose was the most effective, with a SUCRA value of 92.25 %, compared to doses of 0.215 mg/kg and 10 mg. However, psilocybin was associated with a higher risk of adverse events, particularly nausea (RR = 8.35; p < 0.001). This meta-analysis supports psilocybin's efficacy in treating MDD, particularly at a 25 mg dose, showing a time-dependent therapeutic effect. The recommended timing of efficacy evaluation by regulatory authorities is validated by this evidence, underscoring its importance in clinical trial design for psychedelic substances.

keywords:
Humans, Hallucinogens, Dose-Response Relationship, Drug, Adult, Randomized Controlled Trials as Topic, Depressive Disorder, Treatment-Resistant, Psilocybin, Outcome Assessment, Health Care, Major Depressive Disorder

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

raw_json:
{"europe_pmc_id":"39754904","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Ferreira AE, Reis-Pina P.
publication_date: 2024-12-16
doi: 10.1016/j.jpsychores.2024.112020
pubmed_id: 39705901
source_url: https://doi.org/10.1016/j.jpsychores.2024.112020
keywords: Humans, Hallucinogens, Spirituality, Mysticism
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 11:22:04
title:
Exploring the role of psychedelic-assisted therapy in enhancing spirituality and mystical experiences in patients with life-threatening illnesses: A systematic review.

abstract:
IntroductionPsychedelic-Assisted Therapy (PAT) is gaining traction as a novel approach to addressing the psychological and existential distress experienced by patients.ObjectivesThis systematic review aimed to investigate the impact of PAT on spirituality, mystical experiences, and spiritual well-being (SpWB) in patients with life-threatening, incurable, or terminal illnesses.MethodsA comprehensive search was conducted across PubMed, Web of Science, and Cochrane databases to identify relevant studies published between 2013 and 2023. The study population comprised patients diagnosed with life-threatening illnesses. Various forms of PAT, encompassing both typical and atypical psychedelic substances, were considered as interventions, with no specific comparators outlined. The primary outcomes of interest included spirituality, mystical experience, and SpWB. Risk of bias assessment was performed using Cochrane's tools.ResultsSix studies with a high risk of bias were included in the review, all conducted in the United States of America, involving 140 patients, the majority of whom had cancer (99 %). PAT, especially with psilocybin, demonstrated significant enhancements in spirituality, mystical experiences, and SpWB. Notably, SpWB showed improvements in all studies which assessed this spiritual outcome following PAT. Mystical experiences were correlated with improvements in spirituality in one study.ConclusionsThis systematic review underscores the potential of PAT to address unmet spiritual needs and enhance SpWB in patients with life-threatening illnesses. However, further research is needed to elucidate the mechanisms underlying these therapeutic effects. Rigorous evaluation of healthcare practitioners' role in guiding patients through PAT protocols is essential to ensure safe and effective implementation in palliative care settings.

topic_tags:
End-of-Life Distress,Mechanism of Action,Wellbeing,Spirituality,Mystical Experience,Systematic Review,Review Article,Safety

raw_json:
{"europe_pmc_id":"39705901","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Geller J, Whitney E.
publication_date: 2024-12-18
doi: 10.1007/s11920-024-01577-2
pubmed_id: 39699759
source_url: https://doi.org/10.1007/s11920-024-01577-2
substance_tags: psilocybin
topic_tags: Depression,PTSD,Aging,Clinical Trial,Review Article,Adolescents,Safety
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:
Therapeutic Potential of MDMA- and Psychedelic-Assisted Psychotherapy for Adolescent Depression and Trauma.

abstract:
Purpose of reviewThere is a mental health crisis affecting youth, and the utility of existing treatments is often limited by lack of effectiveness and tolerability. The aim of this review is to report on outcomes of clinical trials for psilocybin-assisted psychotherapy for adults with depression and MDMA-assisted psychotherapy for adults with post-traumatic stress disorder (PTSD) and discuss recommendations for exploring these treatments in adolescent populations.Recent findingsThere have been encouraging data supporting the use of psilocybin-assisted psychotherapy for depression, including previously treatment-resistant symptoms. MDMA-assisted psychotherapy is showing similar promise in treating PTSD, with excellent response and remission rates that appear durable. However, no studies have looked at the use of these treatments in younger patients. The safety and efficacy of psychedelic- and MDMA-assisted psychotherapies should be investigated in adolescents, especially considering the burden of untreated and undertreated psychiatric illness in youth, and the benefits of a potentially earlier, more effective, and more tolerable recovery process. Research and implementation should be tailored to the needs of this population, and equity and access should be considered at every stage. In this novel and rapidly evolving landscape, the psychiatric community is encouraged to advocate for safe, appropriate, and inclusive inquiry into, and application and scaling of these treatment models in adolescent patients.

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

raw_json:
{"europe_pmc_id":"39699759","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Evaluating the value and risks of psychedelics for psychiatric medicine: a clinical perspective.
authors: Marazziti D, Weiss F, Gurrieri R, Russomanno G, Gambini M, Magnesa A, Coccoglioniti A, Perugi G
journal: Expert review of neurotherapeutics
publication_date: 2025-01-31
doi: 10.1080/14737175.2024.2445016
pubmed_id: 39699299
source_url: https://pubmed.ncbi.nlm.nih.gov/39699299/
keywords: 5-HT2a agonist, DMT, LSD, Psychedelic, mescaline, psilocin, psilocybin, use in clinical psychiatry
substance_tags: psilocybin,psilocin
topic_tags: Receptor Pharmacology,Emotional Processing,Safety
study_type: Other
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:20:36
raw_json: {"pubmed_id":"39699299"}
abstract:
After a long period of obscurantism, a possible role of psychedelics in clinical practice has progressively become a tangible perspective during the last two decades. However, the resounding enthusiasm linked to such 'psychedelic renaissance' runs the risk to unduly minimize the possible hazards associated with these compounds, while expanding their alleged benefits to improbable panacea-like proportions. In order to avoid mystifying or demonizing the properties of 5-HT2a agonists on emotional grounds, this subject requires a strictly unprejudiced and cautious approach to the evidence.
In this article, the authors attempted to comprehensively analyze the available literature to provide a balanced overview of the possible benefits of psychedelics in healthcare, taking into account their potential risks.
To date, psychedelics have shown a therapeutic potential in a wide range of conditions, with a seemingly limited risk of inducing adverse reactions, including abuse and dependence, when administered in a controlled environment by specialized personnel. In any case, although several questions remain unanswered before drawing firm conclusions, further studies are needed to establish which conditions and subjects could benefit from psychedelics and which patients bear the greater risk of adversities.


title: The safety of psilocybin-assisted psychotherapy: A systematic review.
authors: Freitas RR, Gotsis ES, Gallo AT, Fitzgibbon BM, Bailey NW, Fitzgerald PB.
publication_date: 2024-12-12
doi: 10.1177/00048674241289024
pubmed_id: 39670342
source_url: https://doi.org/10.1177/00048674241289024
keywords: Humans, Hallucinogens, Psychotherapy, Depressive Disorder, Treatment-Resistant, Psilocybin
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 11:22:00
abstract:
IntroductionPsilocybin, a classical psychedelic, has been rescheduled for use in psilocybin-assisted psychotherapy for treatment-resistant depression in Australia. While evidence for its use is promising, understanding the associated risks is crucial. Accordingly, this review aims to collate adverse event data from psilocybin-assisted psychotherapy clinical trials and evaluate its definition, way of measurement and reporting.MethodsA systematic method was employed to identify clinical trials related to the use of psilocybin-assisted psychotherapy in clinical populations that reported on adverse events. The quality assessment focused on relevant criteria related to adverse event definition, monitoring and reporting methods.ResultsA total of 24 articles were included. The studies reported heterogeneous psilocybin doses, study designs and indications. Physical and psychological adverse events during and after psilocybin sessions were examined, revealing variations in measuring, reporting methods and occurrences. The most common adverse events during and after sessions included elevated blood pressure, headaches, nausea, vomiting, fatigue and anxiety. In addition, both suicidal ideation and behaviour were observed infrequently and mainly in participants with a history of suicidal ideation or suicide attempt(s).ConclusionThe review highlights the need to standardise the defintion of an adverse event, including how they are measured and reported, in psychedelic clinical trials to ensure consistent reporting across studies. In addition, screening participants for suicidality history and ongoing monitoring remains important, given the potential risk identified in the literature. However, based on the available data, the safety of psilocybin-assisted psychotherapy is generally supported, and no deaths were attributed to psilocybin. Nevertheless, cautious optimism is needed due to the preliminary nature and heterogeneity of the safety data.

topic_tags:
Depression,Anxiety,Headache / Migraine,Clinical Trial,Systematic Review,Review Article,Treatment-Resistant Depression,Safety,Adverse Events

raw_json:
{"europe_pmc_id":"39670342","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Calder AE, Hase A, Hasler G.
publication_date: 2024-11-28
doi: 10.1038/s41380-024-02830-z
pubmed_id: 39613915
source_url: https://doi.org/10.1038/s41380-024-02830-z
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 11:22:05
title:
Effects of psychoplastogens on blood levels of brain-derived neurotrophic factor (BDNF) in humans: a systematic review and meta-analysis.

abstract:
BackgroundPeripheral levels of brain-derived neurotrophic factor (BDNF) are often used as a biomarker for the rapid plasticity-promoting effects of ketamine, psychedelics, and other psychoplastogens in humans. However, studies analyzing peripheral BDNF after psychoplastogen exposure show mixed results. In this meta-analysis, we aimed to test whether the rapid upregulation of neuroplasticity seen in preclinical studies is detectable using peripheral BDNF in humans.MethodsThis analysis was pre-registered (PROSPERO ID: CRD42022333096) and funded by the University of Fribourg. We systematically searched PubMed, Web of Science, and PsycINFO to meta-analyze the effects of all available psychoplastogens on peripheral BDNF levels in humans, including ketamine, esketamine, LSD, psilocybin, ayahuasca, DMT, MDMA, scopolamine, and rapastinel. Risk of bias was assessed using Cochrane Risk of Bias Tools. Using meta-regressions and mixed effects models, we additionally analyzed the impact of several potential moderators.ResultsWe included 29 studies and found no evidence that psychoplastogens elevate peripheral BDNF levels in humans (SMD = 0.024, p = 0.64). This result was not affected by drug, dose, blood fraction, participant age, or psychiatric diagnoses. In general, studies with better-controlled designs and fewer missing values reported smaller effect sizes. Later measurement timepoints showed minimally larger effects on BDNF.ConclusionThese data suggest that peripheral BDNF levels do not change after psychoplastogen administration in humans. It is possible that peripheral BDNF is not an informative marker of rapid changes in neuroplasticity, or that preclinical findings on psychoplastogens and neuroplasticity may not translate to human subjects. Limitations of this analysis include the reliability and validity of BDNF measurement and low variation in some potential moderators. More precise methods of measuring rapid changes in neuroplasticity, including neuroimaging and stimulation-based methods, are recommended for future studies attempting to translate preclinical findings to humans.

keywords:
Humans, N-Methyl-3,4-methylenedioxyamphetamine, Ketamine, Lysergic Acid Diethylamide, Brain-Derived Neurotrophic Factor, Hallucinogens, Psychotropic Drugs, Neuronal Plasticity, Biomarkers, Psilocybin

topic_tags:
Neuroplasticity,Brain Imaging,Biomarkers,Aging,Meta-Analysis,Systematic Review,Review Article,Animal Study,Safety

raw_json:
{"europe_pmc_id":"39613915","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Substrate recognition by the 4-hydroxytryptamine kinase PsiK in psilocybin biosynthesis.
authors: Rogge K, Wagner TJ, Hoffmeister D, Rupp B, Werten S.
publication_date: 2024-10-23
doi: 10.1002/1873-3468.15042
pubmed_id: 39449146
source_url: https://doi.org/10.1002/1873-3468.15042
substance_tags: psilocybin
topic_tags: Depression
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
abstract:
Psilocybin, the natural hallucinogen from Psilocybe (magic) mushrooms, is a highly promising drug candidate for the treatment of depression and several other mental health conditions. Biosynthesis of psilocybin from the amino acid l-tryptophan involves four strictly sequential modifications. The third of these, ATP-dependent phosphorylation of the intermediate 4-hydroxytryptamine, is catalysed by PsiK. Here we present a crystallographic analysis and a structure-based mutagenesis study of this kinase, providing insight into its mode of substrate recognition. The results of our work will support future bioengineering efforts aimed at generating variants of psilocybin with enhanced therapeutic properties.

keywords:
Protein Kinases, Hallucinogens, Crystallography, X-Ray, Substrate Specificity, Phosphorylation, Models, Molecular, Psilocybe, Psilocybin

raw_json:
{"europe_pmc_id":"39449146","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Jones G, Lowe MX, Nayak S, Sepeda N, Kettner H, Carhart-Harris R, Jackson H, Garcia-Romeu A.
publication_date: 2024-10-21
doi: 10.1016/j.jad.2024.10.058
pubmed_id: 39447981
source_url: https://doi.org/10.1016/j.jad.2024.10.058
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Wellbeing,Emotional Processing,Spirituality,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 11:22:01
title:
Examining differences in the effects and contexts of naturalistic psilocybin use for White participants vs. Participants of Color: A longitudinal online survey study.

abstract:
BackgroundPsilocybin (a psychoactive compound found in "magic mushrooms" or "shrooms") has been gaining increased attention in research and popular culture as a number of clinical and observational studies have demonstrated that it may have potential for improving mental wellbeing. Relatedly, there has been a substantial uptick in naturalistic (e.g., real-world, non-clinical) psilocybin use in the United States. While a number of longitudinal studies have demonstrated that naturalistic psilocybin use is linked to positive mental health outcomes on average, few studies have examined how the effects of psilocybin and contexts for psilocybin use may differ for White populations compared to Populations of Color.ObjectiveTo examine differences in health outcomes, subjective effects, and contexts of naturalistic psilocybin use in White participants compared to Participants of Color.MethodsThis study used data from a large, online longitudinal study of individuals who planned to engage in naturalistic psilocybin use (N = 2833). We used mixed-effects models to assess whether race/ethnicity (White vs. Participant of Color) moderated associations between time (Time 2 [initial assessment point for longitudinal measures], Time 5 [2-4 weeks post-psilocybin experience, and Time 6 [2-3 months post-experience]) and outcomes related to mental health (depression, anxiety, spiritual wellbeing, cognitive flexibility, emotion regulation [expressive suppression + cognitive reappraisal]). We also used exploratory chi-squared tests to examine differences in contexts for psilocybin use as well as differences in subjective effects related to the psilocybin experience.ResultsRace/ethnicity moderated the associations between time for predicting spiritual wellbeing (beta = -1.8; 95 % CI [-3.4, -0.17]; p

keywords:
Humans, Hallucinogens, Longitudinal Studies, Mental Health, Adult, Middle Aged, United States, Female, Male, Young Adult, Surveys and Questionnaires, Psilocybin, Ethnicity, Racial Groups, White

raw_json:
{"europe_pmc_id":"39447981","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Bogenschutz MP
journal: Addiction (Abingdon, England)
publication_date: 2025-01-31
doi: 10.1111/add.16647
pubmed_id: 39129581
source_url: https://pubmed.ncbi.nlm.nih.gov/39129581/
keywords: MDMA, harm reduction, health policy, pharmacotherapy, psilocybin, psychedelics
substance_tags: psilocybin
topic_tags: General
study_type: Other
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:20:36
raw_json: {"pubmed_id":"39129581"}
title:
A clinical research perspective on the regulation of medical and non-medical use of psychedelic drugs.


authors: Andrews CM, Hall W, Humphreys K, Marsden J.
publication_date: 2024-06-05
doi: 10.1111/add.16575
pubmed_id: 38845381
source_url: https://doi.org/10.1111/add.16575
substance_tags: psilocybin
topic_tags: Addiction
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:04
title:
Crafting effective regulatory policies for psychedelics: What can be learned from the case of cannabis?

abstract:
The turn of the century brought a resurgence of interest in psychedelics as a treatment for addiction and other psychiatric conditions, accompanied by extensive positive media attention and private equity investment. Government regulatory bodies in Australia, Israel, Canada and the United States now permit use of psychedelics for medical purposes. In the United States, citizen action and corporate financing have led to petitions and ballot initiatives to legalize psilocybin and other psychedelics for medical and recreational use. Given this momentum, policymakers must grapple with important questions that define whether and how psychedelics are made available to the public, as well as how companies produce and promote them. The current push to broaden the production, sale, and use of psychedelics bears many parallels to the movement to legalize cannabis in the United States and other nations-most notably, the use of poorly-evidenced therapeutic claims to create a de facto recreational market via the health care system. Experience with cannabis highlights the value of debating the question of legalization for nonmedical use as such rather than misrepresenting it as a medical issue. The lessons of cannabis policy also suggest a need to challenge hyping of psychedelic research findings; to promote rigorous clinical research on dosing and potency; to minimize the influence of for-profit industry in shaping policies to their economic advantage; and to coordinate federal, state, and local governments to regulate the manufacture, sale and distribution of psychedelic drugs (regardless of whether they are legalized for medical and/or recreational use).

keywords:
Humans, Cannabis, Hallucinogens, Legislation, Drug, Drug and Narcotic Control, Health Policy, Canada, United States, Australia, Medical Marijuana, Psilocybin

raw_json:
{"europe_pmc_id":"38845381","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: A Systematic Review of Interventions for Demoralization in Patients with Chronic Diseases.
authors: Dong L, Li L, Wu Y, Zhao X, Zhong H, Cheng X, Liu L, Cheng C, Ouyang M, Tao L.
publication_date: 2024-02-04
doi: 10.1007/s12529-024-10262-w
pubmed_id: 38316668
source_url: https://doi.org/10.1007/s12529-024-10262-w
keywords: Humans, Chronic Disease, Psychotherapy, Quality of Life
substance_tags: psilocybin
topic_tags: Randomized Controlled Trial,Systematic Review,Review Article
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:05
abstract:
BackgroundDemoralization, a significant mental health concern in patients with chronic diseases, can have a large impact on physical symptom burden and quality of life. The present review aimed to evaluate the effectiveness of interventions for demoralization among patients with chronic diseases.MethodPubMed, Scopus, Embase, and Web of Science were systematically searched. Research on providing interventions to patients with chronic diseases that included quantitative data on demoralization was then systematically reviewed.ResultsFourteen studies were included, most of which considered demoralization as a secondary outcome. Interventions included evidence-based meaning-centered psychotherapy, dignity therapy, psilocybin-assisted psychotherapy, and others. Ten studies used randomized controlled designs. Six of these investigated evidence-based meaning-centered therapy, and four investigated dignity therapy, showing the best empirical support for these intervention types. Most studies showed significant impacts on demoralization in patients with chronic diseases.ConclusionThis systematic review provides insights into potential psychological interventions for reducing demoralization in patients with chronic diseases. Randomized controlled designs and adequately powered samples, with demoralization as the primary outcome, are needed to more clearly evaluate its effectiveness.

raw_json:
{"europe_pmc_id":"38316668","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


abstract: [This corrects the article DOI: 10.7759/cureus.78171.].
publication_date: 2025-01-29
doi: 10.7759/cureus.c209
pubmed_id: 39897296
source_url: https://doi.org/10.7759/cureus.c209
substance_tags: psilocybin
topic_tags: OCD,Receptor Pharmacology
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:04
title:
Correction: Study Protocol for 'PsilOCD: A Pharmacological Challenge Study Evaluating the Effects of the 5-HT2A Agonist Psilocybin on the Neurocognitive and Clinical Correlates of Compulsivity'.

authors:
O'Connor S, Godfrey K, Reed S, Peill J, Rohani-Shukla C, Healy M, Robbins T, Frota Lisboa Pereira de Souza A, Tyacke R, Papasyrou M, Stenbæk D, Castro-Rodrigues P, Chiera M, Lee H, Martell J, Carhart-Harris R, Pellegrini L, Fineberg NA, Nutt D, Erritzoe D.

raw_json:
{"europe_pmc_id":"39897296","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psychedelic-assisted treatment for substance use disorder: A narrative systematic review.
authors: Piper T, Small F, Brown S, Kelleher M, Mitcheson L, Rucker J, Young AH, Marsden J.
publication_date: 2025-01-29
doi: 10.1111/add.16762
pubmed_id: 39887551
source_url: https://doi.org/10.1111/add.16762
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 11:22:02
abstract:
Background and aimsThis is the first systematic review of the extant literature on all major psychedelic-assisted treatment for alcohol use disorder (AUD), tobacco use disorder (TUD) and other substance use disorders (SUD). We aimed to summarise the evidence for efficacy of psychedelic-assisted treatment for AUD, TUD, and SUD; to evaluate its quality; and to offer recommendations for research.MethodsThis was a prospectively registered narrative systematic review of open-label, randomised controlled trials (RCT), and observational studies of d-lysergic acid diethylamide (LSD), mescaline, psilocybin, ayahuasca, ketamine, ibogaine and 3,4-methylenedioxymethamphetamine (MDMA). Eligible studies had SUD outcome measures including craving, substance use, relapse, and remission. Study quality was evaluated using the Cochrane Collaboration Risk of Bias (RoB), and Cochrane Collaboration RoB in Non-randomised Studies of Interventions tool. Certainty of evidence for RCTs was judged using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) tool.Findings37 studies (2035 participants) were reviewed: LSD (14; n = 1047); mescaline (1; n = 7); psilocybin (4; n = 135); ayahuasca (3; n = 101); ketamine (10; n = 579); ibogaine (5; n = 166); and MDMA (1; n = 14). There were no serious adverse events reported in any study. A two-centre, placebo-controlled, phase 2 superiority RCT of psilocybin for AUD, and a two-centre, double-blind, four-arm, placebo-controlled phase 2 RCT of ketamine for AUD yielded the best evidence of efficacy. Progression support to a phase 3 trials was secured from an open-label phase 2 study of psilocybin for TUD and nine phase 2 RCTs of ketamine for AUD, cannabis use disorder, cocaine use disorder, and opioid use disorder (all nine with high-RoB and low-GRADE evidence certainty).ConclusionsPsilocybin-assisted treatment for alcohol use disorder appears to have the best evidence of efficacy among all major psychedelic-assisted treatments for alcohol, tobacco, and other substance use disorders. Future research of psychedelic-assisted treatment should report all safety events; screen for person-level characteristics indicating that psychedelic-assisted substance use disorders treatment is contraindicated; strive to mitigate blinding of participants to interventions; use factorial designs for drug and psychotherapy randomised controlled trials; and build consensus for a field-specific Core Outcome Set.

topic_tags:
Addiction,Clinical Trial,Randomized Controlled Trial,Systematic Review,Review Article,Observational Study,Safety,Adverse Events

raw_json:
{"europe_pmc_id":"39887551","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Kinderlehrer DA.
publication_date: 2025-01-28
doi: 10.2147/ndt.s500337
pubmed_id: 39897712
source_url: https://doi.org/10.2147/ndt.s500337
substance_tags: psilocybin,psilocin
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:
Mushrooms, Microdosing, and Mental Illness: The Effect of Psilocybin on Neurotransmitters, Neuroinflammation, and Neuroplasticity.

abstract:
The incidence of mental health disorders is increasing worldwide. While there are multiple factors contributing to this problem, neuroinflammation underlies a significant subset of psychiatric conditions, particularly major depressive and anxiety disorders. Anti-inflammatory interventions have demonstrated benefit in these conditions. Psilocin, the active ingredient of mushrooms in the Psilocybe genus, is both a potent serotonin agonist and anti-inflammatory agent, increases neuroplasticity, and decreases overactivity in the default mode network. Studies using hallucinogenic doses of psilocin under the supervision of a therapist/guide have consistently demonstrated benefits to individuals with depression and end-of-life anxiety. Microdosing psilocybin in sub-hallucinogenic doses has also demonstrated benefit in mood disorders, and may offer a safe, less expensive, and more available alternative to full doses of psilocybin for mood disorders, as well as for other medical conditions in which inflammation is the principal pathophysiology.

topic_tags:
Depression,Anxiety,End-of-Life Distress,Neuroplasticity,Receptor Pharmacology,Default Mode Network,Microdosing,Inflammation

raw_json:
{"europe_pmc_id":"39897712","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2025-01-28
doi: 10.7759/cureus.78171
pubmed_id: 39882198
source_url: https://doi.org/10.7759/cureus.78171
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 11:22:01
title:
Study Protocol for 'PsilOCD: A Pharmacological Challenge Study Evaluating the Effects of the 5-HT2A Agonist Psilocybin on the Neurocognitive and Clinical Correlates of Compulsivity'.

authors:
O'Connor S, Godfrey K, Reed S, Peill J, Rohani-Shukla C, Healy M, Robbins T, Frota Lisboa Pereira de Souza A, Tyacke R, Papasyrou M, Stenbæk D, Castro-Rodrigues P, Chiera M, Lee H, Martell J, Carhart-Harris R, Pellegrini L, Fineberg NA, Nutt D, Erritzoe D.

abstract:
BackgroundObsessive-compulsive disorder (OCD) is a complex condition marked by persistent distressing thoughts and repetitive behaviours. Despite its prevalence, the mechanisms behind OCD remain elusive, and current treatments are limited. This protocol outlines an investigative study for individuals with OCD, exploring the potential of psilocybin to improve key components of cognition implicated in the disorder. The PsilOCD study strives to assess the effects of low-moderate psilocybin treatment (10 mg) alongside non-interventional therapy on several facets of OCD. The main focus points of PsilOCD are cognitive flexibility, measured with cognitive tests, and neuroplasticity, assessed through electroencephalography (EEG).Methods20 blinded participants with OCD will complete two dosing sessions, separated by four weeks, where they will receive 1 mg of psilocybin on the first and 10 mg on the second. The first dose serves as an active placebo, and the latter is a low-moderate dose that induces relatively mild-moderate emotional and perceptual effects. Participants will be supported by trained psychedelic therapists, who will sit with them during each dosing session and provide virtual preparation and integration sessions over the 12-week study period. Therapeutic support will be the same for both the 1 mg and 10 mg sessions. PsilOCD's primary outcomes include scores in the intradimensional-extradimensional (ID-ED) shift task, which is an established measure of cognitive flexibility, and neuroplasticity as quantified by a visual long-term potentiation (vLTP) task. This task is delivered as part of an EEG paradigm and measures acute quantified changes in neuroplasticity in the brain's visual system. The ID-ED task will be conducted twice, two days after each dosing session, and the EEG recordings will also be taken twice, immediately after each session. Secondary outcome assessments will include OCD and affective symptom severity, as well as an array of patient-reported outcome measures (PROMs), in the form of questionnaires designed to assess well-being, dissociable and well-established mood-related (affective) measures, and participants' subjective experience of the psilocybin experience.DiscussionThis study's results are expected to offer critical insights into the neural mechanisms underlying the effects of psilocybin-assisted therapy in treating OCD, and whether these correlate with changes in the cognitive features of the condition. As a secondary aim, it will ascertain whether a low, tolerable dose is a feasible and efficacious clinical treatment, and will provide crucial data to guide the design of a potential follow-up randomised control trial (RCT).

topic_tags:
OCD,Neuroplasticity,Brain Imaging,Mechanism of Action,Receptor Pharmacology,Wellbeing,Emotional Processing,Randomized Controlled Trial

raw_json:
{"europe_pmc_id":"39882198","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2025-01-28
doi: 10.1080/02791072.2025.2454474
pubmed_id: 39881568
source_url: https://doi.org/10.1080/02791072.2025.2454474
substance_tags: psilocybin
topic_tags: Consciousness,Spirituality,Review Article,Observational Study
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
title:
Oregon's Emerging Psilocybin Services Workforce: A Survey of the First Legal Psilocybin Facilitators and Their Training Programs.

authors:
Luoma JB, Hoffman K, Wilson-Poe AR, Levander XA, Bazinet A, Cook RR, McCarty D, Pertl K, Bielavitz S, Gregoire D, Wolf RC, Des Jarlais DC, Harrison HV, Stauffer CS, Korthuis PT.

abstract:
New legal frameworks for supervised psychedelic services are emerging, with Oregon and Colorado implementing programs to train and license psilocybin facilitators. This study describes Oregon's early psilocybin facilitator workforce and assesses state-approved training programs. The Open Psychedelic Evaluation Nexus (OPEN) reviewed Oregon Health Authority-approved training programs and surveyed facilitators who had completed or were enrolled in these programs between July and November 2023. Data collection included a review of public listings, contact with training programs, and facilitator survey. Results indicated that in the 16 active training programs, the mean tuition was $9,359 and half offered diversity scholarships. Survey respondents (n = 106) were relatively diverse; many had an existing healthcare license. The majority reported that training expenses were a moderate-to-severe financial strain. Most were satisfied with training. The mean planned price for a session was $1,388 and the most common areas of specialization were trauma, mental disorders, consciousness exploration, and spirituality. Facilitators requested ongoing training opportunities. In conclusion, Oregon's emerging psilocybin facilitator workforce and training programs are in early development. These findings are crucial for informing future policy and training program development to support a diverse and effective workforce.

raw_json:
{"europe_pmc_id":"39881568","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: From relaxed beliefs under psychedelics (REBUS) to revised beliefs after psychedelics (REBAS).
authors: Zeifman RJ, Spriggs MJ, Kettner H, Lyons T, Rosas FE, Mediano PAM, Erritzoe D, Carhart-Harris RL.
publication_date: 2025-01-28
doi: 10.1038/s41598-023-28111-3
pubmed_id: 39881126
source_url: https://doi.org/10.1038/s41598-023-28111-3
keywords: Humans, Hallucinogens, Electroencephalography, Adult, Female, Male, Young Adult, Psilocybin
substance_tags: psilocybin
topic_tags: Brain Imaging,Wellbeing
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
abstract:
The Relaxed Beliefs Under pSychedelics (REBUS) model proposes that serotonergic psychedelics decrease the precision weighting of neurobiologically-encoded beliefs. We conducted a preliminary examination of two psychological assumptions of REBUS: (a) psychedelics foster acute relaxation and post-acute revision of confidence in mental-health-relevant beliefs; which (b) facilitate positive therapeutic outcomes and are associated with the entropy of EEG signals. Healthy individuals (N = 11) were administered 1 mg and 25 mg psilocybin 4-weeks apart. Confidence ratings for personally held beliefs were obtained before, during, and 4-weeks post-psilocybin. Acute entropy and subjective experiences were measured, as was well-being (before and 4-weeks post-psilocybin). Confidence in negative self-beliefs decreased following 25 mg psilocybin. Entropy and subjective effects under 25 mg psilocybin correlated with decreases in negative self-belief confidence (acutely and at 4-weeks). Particularly strong evidence was seen for a relationship between decreases in negative self-belief confidence and increases in well-being. We report the first empirical evidence that the relaxation and revision of negative self-belief confidence mediates psilocybin's positive psychological outcomes, and provide tentative evidence for a neuronal mechanism, namely, increased neuronal entropy. Replication within larger and clinical samples is necessary. We also introduce a new measure for examining the robustness of these preliminary findings and the utility of the REBUS model.

raw_json:
{"europe_pmc_id":"39881126","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Cuttler C, Stueber A, Simone J, Mayo LM.
publication_date: 2025-01-28
doi: 10.1080/02791072.2025.2452226
pubmed_id: 39878200
source_url: https://doi.org/10.1080/02791072.2025.2452226
substance_tags: psilocybin
topic_tags: Anxiety,Headache / Migraine,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 11:22:04
title:
Down the Rabbit Hole: A Large-Scale Survey of Psychedelic Users' Patterns of Use and Perceived Effects.

abstract:
The ever-changing landscape surrounding legality and accessibility of psychedelics and their increasing popularity make it imperative to better understand the nature of psychedelic use by the general population. To this end, 1,486 eligible respondents (Mage = 29.58, 67.1% male) residing in the United States completed an online survey designed to assess the types of psychedelics used, methods of administration and dosing, frequency of use, intentions for use, context/environments in which they are used, perceived acute effects, frequency of those effects and distress about them, and their perceived residual effects and distress about them. Respondents predominantly endorsed using MDMA, LSD, DMT, and psilocybin. The predominant methods of administration were oral. Most reported using psychedelics for recreational purposes. The most endorsed acute effects were hallucinations, increased heart rate, positive mood, and visual tracers, while the most endorsed residual effects were headaches/migraine, dry mouth, nausea, hallucinations, and anxiety. Participants were most distressed by negative mood states, vomiting, and nausea when under the acute effects of psychedelics, but mean distress ratings were low. These results can help inform clinical trials, reform policy regarding legal access to psychedelics, and track changes in these metrics as sociocultural and legal landscapes continue to shift.

raw_json:
{"europe_pmc_id":"39878200","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Kurzbaum E, Páleníček T, Shrchaton A, Azerrad S, Dekel Y.
publication_date: 2025-01-27
doi: 10.3390/jof11020099
pubmed_id: 39997393
source_url: https://doi.org/10.3390/jof11020099
substance_tags: psilocybin,psilocin
topic_tags: Review Article
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:01
title:
Exploring Psilocybe cubensis Strains: Cultivation Techniques, Psychoactive Compounds, Genetics and Research Gaps.

abstract:
Psilocybe cubensis, a widely recognized psychoactive mushroom species, has played a significant role in both historical and modern therapeutic practices. This review explores the complex interplay between genetic diversity, strain variability and environmental factors that shape the biosynthesis of key psychoactive compounds, including psilocybin and psilocin. With many strains exhibiting substantial variability in their phenotypic characteristics and biochemical content, understanding and documenting this diversity is crucial for optimizing therapeutic applications. The review also highlights advances in cultivation techniques, such as submerged fermentation of the mycelium, and innovative analytical methodologies that have improved the precision of compound quantification and extraction. Although there is limited scientific information on P. cubensis due to nearly four decades of regulatory restrictions on psychedelic research, recent developments in genetic and biochemical studies are beginning to provide valuable insights into its therapeutic potential. Furthermore, this review emphasizes key knowledge gaps and offers insights into future research directions to advance the cultivation, scientific documentation of strain diversity, regulatory considerations and therapeutic use of P. cubensis.

raw_json:
{"europe_pmc_id":"39997393","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: When death is desired: A case of MAiD & the CL psychiatrist.
authors: Ganguly A, James M, Alici Y
journal: Palliative & supportive care
publication_date: 2025-01-20
doi: 10.1017/s1478951524002037
pubmed_id: 39834190
source_url: https://pubmed.ncbi.nlm.nih.gov/39834190/
substance_tags: psilocybin
topic_tags: End-of-Life Distress,Review Article,Cancer Patients,Healthcare Workers
study_type: Review Article
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:20:36
raw_json: {"pubmed_id":"39834190"}
abstract:
Since physician-assisted dying (PAD) has become a part of the clinical dialogue in the United States (US) and other Western countries, it has spawned controversy in the moral, ethical, and legal realm, with significant cross-country variation. The phenomenon of PAD includes 2 practices: Euthanasia and medical aid in dying (MAiD). Although euthanasia has been allowed in different parts of the world, in the US it is illegal. MAiD has been enacted into law in some jurisdictions. As the practice involves people at the end of life (EOL), often with cancer, and sometimes struggling with psychiatric symptoms; they gain added salience in the field of Consultation-Liaison (CL) Psychiatry in general and Psycho-Oncology in particular.
The current paper reviews a case where a patient did request for MAiD and successfully carried it through, this case became more salient, as the CL Psychiatry department was intimately linked at various stages of care for the patient.
In describing the case several other aspects of EOL care issues were touched upon, and the various debates as well as treatment modalities, for an individual requesting for medical aid in dying were described.
MAiD will possibly remain a sensitive and controversial topic of discussion across the spectrum of healthcare, and as responsible and compassionate advocates for the patients, clinicians need to engage more with the debate surrounding it and facilitate informed decision making. We believe that the present case will throw light on to this enigmatic practice and help in furthering the dialogue surrounding MAiD.

keywords:
Consultation-Liaison Psychiatry, Euthanasia, Hospice care, Ketamine, Logotherapy, Meaning Centered Therapy, Medical Aid in dying, Palliative Medicine, Physician Assisted Dying, Psilocybin, PsychoOncology


title: Uncovering Psychedelics: From Neural Circuits to Therapeutic Applications.
authors: Melani A, Bonaso M, Biso L, Zucchini B, Conversano C, Scarselli M.
publication_date: 2025-01-18
doi: 10.3390/ph18010130
pubmed_id: 39861191
source_url: https://doi.org/10.3390/ph18010130
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 11:22:04
abstract:
Psychedelics, historically celebrated for their cultural and spiritual significance, have emerged as potential breakthrough therapeutic agents due to their profound effects on consciousness, emotional processing, mood, and neural plasticity. This review explores the mechanisms underlying psychedelics' effects, focusing on their ability to modulate brain connectivity and neural circuit activity, including the default mode network (DMN), cortico-striatal thalamo-cortical (CSTC) loops, and the relaxed beliefs under psychedelics (REBUS) model. Advanced neuroimaging techniques reveal psychedelics' capacity to enhance functional connectivity between sensory cerebral areas while reducing the connections between associative brain areas, decreasing the rigidity and rendering the brain more plastic and susceptible to external changings, offering insights into their therapeutic outcome. The most relevant clinical trials of 3,4-methylenedioxymethamphetamine (MDMA), psilocybin, and lysergic acid diethylamide (LSD) demonstrate significant efficacy in treating treatment-resistant psychiatric conditions such as post-traumatic stress disorder (PTSD), depression, and anxiety, with favorable safety profiles. Despite these advancements, critical gaps remain in linking psychedelics' molecular actions to their clinical efficacy. This review highlights the need for further research to integrate mechanistic insights and optimize psychedelics as tools for both therapy and understanding human cognition.

topic_tags:
Depression,Anxiety,PTSD,Neuroplasticity,Brain Imaging,Mechanism of Action,Default Mode Network,Consciousness,Aging,Emotional Processing,Spirituality,Clinical Trial,Review Article,Safety

raw_json:
{"europe_pmc_id":"39861191","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Meshkat S, J Zeifman R, Stewart K, Janssen-Aguilar R, Lou W, Jetly R, Monson CM, Bhat V.
publication_date: 2025-01-16
doi: 10.1371/journal.pone.0313741
pubmed_id: 39823496
source_url: https://doi.org/10.1371/journal.pone.0313741
substance_tags: psilocybin
topic_tags: PTSD,Mechanism of Action,Wellbeing,Clinical Trial,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 11:22:01
title:
Psilocybin-assisted massed cognitive processing therapy for chronic posttraumatic stress disorder: Protocol for an open-label pilot feasibility trial.

abstract:
BackgroundPosttraumatic stress disorder (PTSD) affects 3.9% of the general population. While massed cognitive processing therapy (CPT) has demonstrated efficacy in treating chronic PTSD, a substantial proportion of patients still continue to meet PTSD criteria after treatment, highlighting the need for novel therapeutic approaches. Preliminary evidence supports the potential therapeutic action of psilocybin to alleviate PTSD symptoms. This open-label pilot study aims to evaluate the feasibility, tolerability, and preliminary efficacy of a single dose 25 mg psilocybin in combination with one week of massed CPT in patients with chronic PTSD.MethodFifteen participants with chronic PTSD will undergo 12 CPT sessions, two psilocybin-related psychotherapy sessions, and one psilocybin dosing session over a 7-days period. The primary outcomes are feasibility and tolerability, which will be measured by recruitment rates, withdrawal, data completion, adherence, number and nature of adverse events. Secondary objectives include assessing the preliminary efficacy of psilocybin-assisted CPT in reducing PTSD severity, self-reported treatment outcomes and exploring putative mechanisms of change. Participants will be monitored weekly for 12 weeks post-treatment and passive data relevant to mental health and well-being will be collected using a wearable device.DiscussionThis trial will generate important preliminary data on the use of psilocybin-assisted CPT for treating PTSD. The findings will guide the design of a multi-site, large-scale randomized control trial to more rigorously assess the efficacy of this intervention. De-identified data from this study will be available upon request after publication of the results. This study represents a promising and innovative approach to PTSD treatment, potentially offering an alternative therapeutic option for individuals unresponsive to conventional therapies.Trial registrationClinicalTrials.gov NCT06386003.

keywords:
Humans, Chronic Disease, Hallucinogens, Treatment Outcome, Feasibility Studies, Pilot Projects, Stress Disorders, Post-Traumatic, Adult, Middle Aged, Female, Male, Clinical Trials, Phase II as Topic, Young Adult, Psilocybin, Cognitive Behavioral Therapy

raw_json:
{"europe_pmc_id":"39823496","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


journal: Addiction (Abingdon, England)
publication_date: 2025-01-15
doi: 10.1111/add.16767
pubmed_id: 39821493
source_url: https://pubmed.ncbi.nlm.nih.gov/39821493/
substance_tags: psilocybin
topic_tags: Addiction,Mechanism of Action,Wellbeing,Safety
study_type: Qualitative Study
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:20:36
raw_json: {"pubmed_id":"39821493"}
title:
Self-reported experiences and perspectives on using psychedelics to manage opioid use among participants of two Reddit communities.

authors:
Krawczyk N, Miller M, Gu EY, Irvine N, Ramirez E, Santaella-Tenorio J, Lippincott T, Bogenschutz M, Bunting AM, Meacham MC

abstract:
The opioid crisis continues to exert a tremendous toll in North America, with existing interventions often falling short of addressing ongoing needs. Psychedelics are emerging as a possible alternative therapy for mental health and substance use disorders. This study aimed to gather insights on how people use or are considering using psychedelics to manage opioid use disorder (OUD), how these experiences are perceived to impact opioid use and what these lessons imply for future research and practice.
We conducted a qualitative study using the Reddit online community platform. We extracted posts that contained key psychedelic terms from the two most subscribed-to subreddits dedicated to discussions of OUD treatment (r/OpiatesRecovery and r/Methadone) from 2018 to 2021. We thematically analyzed content from 151 relevant posts and their respective comments.
Two prominent themes identified in discussions were perspectives on the effectiveness of psychedelics in treating OUD, and mechanisms through which psychedelics were thought to impact use and desire to use opioids. For many, psychedelics were deemed to have a strong impact on opioid use via multiple mechanisms, including alleviating physical symptoms of dependence, shifting motivations around desire to use opioids and addressing underlying mental health problems and reasons for use. Others saw the potential promise around psychedelics as exaggerated, acknowledging many people eventually return to use, or even considered psychedelics dangerous.
There appear to be diverse perspectives on the effects of using psychedelics to treat opioid use disorder and an urgent need for controlled studies to better understand the impact of different psychedelics on opioid use, how they may be used in the context of existing treatments and what strategies they must be combined with to ensure safety and effectiveness. Integrating the experiences of people who use drugs will help guide psychedelics research toward effective person-centered interventions to enhance health and wellness.

keywords:
ibogaine, on‐line communities, opioid use disorder, opioids, peer support, psilocybin, psychedelics, psychedelics‐assisted recovery, reddit, treatment


authors: Henderson I, Elsaadany R, Chan G, Bajaj V, Duarte D, Goodman S, Grunstein M, Vadhan NP, Duarte RA.
publication_date: 2025-01-15
doi: 10.1007/s11916-024-01321-8
pubmed_id: 39820774
source_url: https://doi.org/10.1007/s11916-024-01321-8
substance_tags: psilocybin
topic_tags: Chronic Pain,Headache / Migraine,Mechanism of Action,Review Article,Safety
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
title:
Exploring the Potential of Psychedelics in the Treatment of Headache Disorders: Clinical Considerations and Exploratory Insights.

abstract:
Purpose of reviewExploration of the potential of serotonergic psychedelic drugs, such as psilocybin and LSD, as potential treatments for headache disorders. This review addresses the need for well-informed physician guidelines and discusses mechanisms, safety, and efficacy of these treatments. Further research, including the consideration of combination with psychotherapy, is needed.Recent findingsPsychedelics demonstrate promising outcomes as treatments for headache disorders. Recent findings indicated that some patients who underwent brief periods of treatment with psychedelics experienced a reduction in headache attack frequency, severity, or duration. When prescription medications are ineffective at treating headache disorders, or are habit-forming, patients often turn to alternative options. There is anecdotal evidence that psychedelic drugs like LSD and psilocybin can effectively treat and prevent pain in patients with headache disorders, such as migraine or cluster headache. It is vital that physicians treating patients who self-treat with psychedelics be well-informed about the mechanisms and their effects to best advise their patients and coordinate their care well. This is a review assessing the literature on the mechanisms, safety, and efficacy of psychedelic drugs as a headache management intervention. We believe there is evidence that may support further investigation into the clinical use of psychedelic medications to treat cluster headache and migraine, including the consideration of use in conjunction with other interventions like cognitive behavioral therapy or acceptance and commitment training.

keywords:
Humans, Headache Disorders, Lysergic Acid Diethylamide, Hallucinogens, Treatment Outcome, Psilocybin

raw_json:
{"europe_pmc_id":"39820774","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Li JR, Chiang KT, Kao YC, Yu CL, Yang FC, Liang CS, Hsu TW.
publication_date: 2024-10-08
doi: 10.1016/j.jad.2024.10.016
pubmed_id: 39389119
source_url: https://doi.org/10.1016/j.jad.2024.10.016
substance_tags: psilocybin
topic_tags: Depression,Meta-Analysis
study_type: Meta-Analysis
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
title:
The association between study design and antidepressant effects in psychedelic-assisted therapy: A meta-analysis.

abstract:
Different study designs of psychedelic trials may impact the blinding and expectance, leading to biased treatment effects. This study aimed to examine the association between antidepressant efficacy and study designs in psychedelic trials. Six databases were systematically searched. Eligible trials were required to investigate the efficacy of psychedelics (psilocybin, lysergic acid diethylamide [LSD], 3,4-Methylenedioxymethamphetamine [MDMA], and ayahuasca) in adult patients with depressive symptoms. We only considered oral psychedelic-assisted therapy without concomitant use of antidepressants. The primary outcome was the change in depressive symptoms. There were five study designs of psychedelic trials, including non-active-drug-as-placebo, active-drug-as-placebo, waitlist-as-control, fixed-order, and pre-post designs. In non-active-drug -as-placebo design, psilocybin (k = 4, Hedges' g [g] = 0.87, 95 % confidence intervals[CIs] = 0.58 to 1.16) and MDMA (k = 2, g = 0.65, 95%CIs = 0.26 to 1.05) were associated with large and medium effect sizes, respectively. In active-drug-as-placebo design, both psilocybin (k = 2, g = 0.71, 95%CIs = -0.01 to 1.43) and MDMA (k = 3, g = 0.53, 95%CIs = -0.23 to 1.28) were not statistically significant. In pre-post single-arm (k = 3, g = 2.51, 95%CIs = 1.00 to 4.02) and waitlist-as-control (k = 1, g = 2.88, 95%CIs = 1.75 to 4.00) designs, psilocybin showed a large effect size of antidepressant effect. Ayahuasca also showed a large effect size in both pre-post (k = 2, g = 1.88, 95%CIs = 1.18 to 2.57) and non-active-drug-as-placebo (k = 1, g = 1.60, 95%CIs = 0.84 to 2.36) designs. LSD was associated with a significant antidepressant effect only in non-active-drug-as-placebo design (k = 1, g = 1.49, 95%CIs = 0.80 to 2.17) but not in active-drug-as-placebo design (k = 1, g = 0.44, 95%CIs = -0.90 to 1.78). The antidepressant effects of psychedelics may be overestimated in studies with pre-post single-arm, non-active-drugs-as placebo, and waitlist-control designs. Restricted sample size, difficulty with establishing blinding for participants, and over expectancy limit the estimation of the antidepressant effect of psychedelic-assisted therapy.

keywords:
Humans, Banisteriopsis, N-Methyl-3,4-methylenedioxyamphetamine, Lysergic Acid Diethylamide, Hallucinogens, Treatment Outcome, Depression, Research Design, Adult, Psilocybin

raw_json:
{"europe_pmc_id":"39389119","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2024-09-26
doi: 10.1016/j.jad.2024.09.133
pubmed_id: 39343309
source_url: https://doi.org/10.1016/j.jad.2024.09.133
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 11:22:01
title:
Single-dose psilocybin for U.S. military Veterans with severe treatment-resistant depression - A first-in-kind open-label pilot study.

authors:
Ellis S, Bostian C, Feng W, Fischer E, Schwartz G, Eisen K, Lean M, Conlan E, Ostacher M, Aaronson S, Suppes T.

abstract:
BackgroundThe enduring and severe depression often suffered by Veterans causes immense suffering and is associated with high rates of suicide and disability. This is the first study to evaluate the efficacy and safety of psilocybin in Veterans with severe treatment-resistant depression (TRD).Methods15 Veterans with severe TRD (major depressive episode failing to respond to ≥5 treatments, or lasting >2 years) received 25 mg of psilocybin. Primary outcome was change in Montgomery-Åsberg Depression Rating scale (MADRS) at 3 weeks posttreatment. Response was defined s ≥ 50 % reduction in MADRS, and remission as ≤10 MADRS score. Psychedelic experience was assessed using the Five-Dimensional Altered States of Consciousness scale (5D-ASC). Safety measures included assessment of suicidality and adverse events. Participants on antidepressants were tapered to avoid drug interactions.ResultsOf 15 participants, 60 % met response and 53 % met remission criteria at Week 3. At 12 weeks, 47 % maintained response, and 40 % remission. Co-morbid PTSD did not significantly influence study outcomes. The psychedelic experience reported in 5D-ASC did not correlate with response. Participants judged to need antidepressants were restarted and considered non-responders from that timepoint (n = 4). No unexpected adverse events occurred.LimitationsLimitations include the small sample size, and the uncontrolled and unblinded nature of the study.ConclusionsIn this first study on psilocybin for Veterans with severe TRD, a surprising response and remission was seen. Many Veterans had PTSD though no moderating impact of response was observed. The degree of psychedelic experience did not correlate with depression changes. Further study is warranted.Trial registrationClinicalTrials.gov Identifier: NCT04433858.

keywords:
Humans, Hallucinogens, Antidepressive Agents, Treatment Outcome, Pilot Projects, Psychiatric Status Rating Scales, Adult, Middle Aged, Veterans, United States, Female, Male, Depressive Disorder, Treatment-Resistant, Psilocybin, Major Depressive Disorder

topic_tags:
Depression,PTSD,Consciousness,Treatment-Resistant Depression,Veterans,Safety,Adverse Events,Drug Interactions

raw_json:
{"europe_pmc_id":"39343309","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Social pain: A systematic review on interventions.
authors: Brooks BM, Cordero FJ, Alchermes SL, Brooks BM.
publication_date: 2025-01-09
doi: 10.12688/f1000research.159561.1
pubmed_id: 40144800
source_url: https://doi.org/10.12688/f1000research.159561.1
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 11:22:04
abstract:
Social pain is emotional distress caused by harm or threat to social connections that results in social exclusion, rejection, or loss. Social Pain is also a potentiator of physical pain. Supportive social relationships are widely recognized for their impact on maintaining health and well-being. The Passion of Jesus Christ serves as a quintessential example of social pain (i.e., desertion, betrayal, denial) potentiating physical pain (i.e., beatings, Crown of Thorns, crucifixion). Christ opts to forgive. Although forgiveness is one solution to reduce social pain, other interventions exist. This review seeks to identify and summarize interventions associated with reducing social pain. We conducted a systematic review using Medline (PubMed), Google Scholar, and Cochrane CENTRAL to identify relevant articles. Results: The database searches produced 548 articles. Fourteen randomized controlled trials (RCTs) were included in this systematic review. Acetaminophen, both deceptive and open-label placebos, mindfulness training, and psilocybin were found to reduce social pain. Of note, the combination of acetaminophen and forgiveness yielded superior results compared to either acetaminophen or forgiveness alone. Pharmacological interventions operate on the premise that the neural pathways responsible for physical pain also play a role in social pain. Both pharmacological and non-pharmacological interventions are available for reducing social pain.

keywords:
Humans, Acetaminophen, Randomized Controlled Trials as Topic, Forgiveness, Mindfulness, Psychological Distress

topic_tags:
Chronic Pain,Mechanism of Action,Wellbeing,Emotional Processing,Randomized Controlled Trial,Systematic Review,Review Article

raw_json:
{"europe_pmc_id":"40144800","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Use of psychedelic treatments in psychiatric clinical practice: an EPA policy paper.
authors: Destoop M, Mohr P, Butlen F, Kéri P, Samochowiec J, De Picker L, Fiorillo A, Kuypers KPC, Dom G.
publication_date: 2025-01-09
doi: 10.1192/j.eurpsy.2024.1806
pubmed_id: 39791347
source_url: https://doi.org/10.1192/j.eurpsy.2024.1806
keywords: Humans, Hallucinogens, Mental Disorders, Psychiatry, Europe, Psilocybin
substance_tags: psilocybin
topic_tags: Depression,Mechanism of Action
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:04
abstract:
BackgroundRecent years show an exponential increased interest ("renaissance") in the use of psychedelics for the treatment of mental disorders and broader. Some of these treatments, such as psilocybin for depression, are in the process of formal regulation by regulatory bodies in the US (FDA) and Europe (EMA), and as such on the brink of real-world implementation. In the slipstream of these developments increasing commercial initiatives are taking shape. The European Psychiatric Association (EPA) acknowledges both the therapeutic potential of psychedelic substances and the challenges for both research and clinical implementation. Steps need to be taken toward a well-balanced policy based upon sound scientific evidence and research, aiming at safe, ethical responsible integration of psychedelic therapy available for all patients who can potentially benefit.MethodsIn this EPA policy paper, we highlight the potential benefits, and also the challenges of psychedelic treatments, which can be relevant for the future real-world implementation of these treatments.ResultsIn addition to an overview of the current evidence and hypotheses of working mechanisms of psychedelic treatment, this policy paper specifically highlights the importance of the psychosocial components of the treatment as well as the ethical and professional aspects playing a role in real-world implementation.ConclusionsFour recommendations are formulated for further research and clinical implementation.

raw_json:
{"europe_pmc_id":"39791347","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Constantino JL, van Dalfsen JH, Massetti S, Kamphuis J, Schoevers RA.
publication_date: 2025-01-06
doi: 10.1016/j.pnpbp.2025.111251
pubmed_id: 39788410
source_url: https://doi.org/10.1016/j.pnpbp.2025.111251
keywords: Humans, Antidepressive Agents, Biomarkers, Psilocybin, Major Depressive Disorder
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:
Neurobiological mechanisms of antidepressant properties of psilocybin: A systematic review of blood biomarkers.

abstract:
Psilocybin represents a novel therapeutic approach for individuals with major depressive disorder (MDD) who do not respond to conventional antidepressant treatment. Investigating the influence of psilocybin on the pathophysiological processes involved in MDD could enhance our neurobiological understanding of the presumed antidepressant action mechanism. This systematic review aims to summarize the results of human studies investigating changes in blood-based biomarkers of MDD to guide future research on potentially relevant analytes that could be monitored in clinical trials. A systematic search was performed in MEDLINE, Embase, and Web of Science to retrieve studies investigating changes in serum and plasma levels of neurotrophic, immunologic, neuroendocrine, and metabolic markers. Nine studies were included, describing findings on 15 biomarkers, exclusively in healthy participants. Studies consistently reported a decrease in interleukin-6, C-reactive protein, and eosinophils, and an increase in cortisol, prolactin, oxytocin, thyroid-stimulating hormone, adrenocorticotropic hormone, brain-derived neurotrophic factor, and free fatty acids following psilocybin administration. Less consistent effects were observed on interleukin-1β, interleukin-8, tumour necrosis factor-alpha, soluble urokinase plasminogen activator receptor, and growth hormone. The results are in line with preclinical studies and provide initial support from human studies that psilocybin potentially leads to beneficial effects on biomarkers of MDD. However, given the limited number of studies, findings should be approached with caution prior to replication. Further research should include larger samples, clinical populations, longer-term assessment, rigorous experimental designs, and account for the potential confounding of psychological stress related to the psychedelic experience.

topic_tags:
Depression,Mechanism of Action,Receptor Pharmacology,Biomarkers,Clinical Trial,Systematic Review,Review Article,Animal Study,Healthy Volunteers

raw_json:
{"europe_pmc_id":"39788410","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Clinical and preclinical evidence of psilocybin as antidepressant. A narrative review.
authors: Erkizia-Santamaría I, Horrillo I, Meana JJ, Ortega JE.
publication_date: 2025-01-05
doi: 10.1016/j.pnpbp.2025.111249
pubmed_id: 39778644
source_url: https://doi.org/10.1016/j.pnpbp.2025.111249
substance_tags: psilocybin,psilocin
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:
In the rapidly growing field of psychedelic research, psilocybin (and active metabolite psilocin) has been proposed as a promising candidate in the search for novel treatments for neuropsychiatric disorders. Clinical trials have revealed that psilocybin has a large, rapid, and persistent effect in the improvement of symptoms of depression and anxiety. The safety profile is considered favourable, with low toxicity and good tolerance. Several preclinical studies have also been carried out to determine the long-term mechanism of action of this drug. In this sense, preclinical studies in naïve animals as well as in animal models of disease have shown somewhat discrepant results in conventional tests for assessment of depression- and anxiety-like phenotype in response to psilocybin, but overall suggest positive outcomes. Additionally, several valuable assays in rodent models have been developed over the years to elucidate the neurochemical correlates of serotonin 2A receptor (5HT2AR) activation in the brain, primary molecular target of psilocin. This review aims to provide a general overview of the current and most recent literature in the therapeutic potential of psilocybin through a description of clinical trials of psilocybin-assisted psychotherapy, and to showcase the scene in the up-to-date preclinical research. A detailed description of preclinical rodent models and experimental approaches that have been used to study the neurobiological and behavioural actions of psilocybin is provided, and potential therapeutic mechanisms of action are discussed.

keywords:
Animals, Humans, Disease Models, Animal, Hallucinogens, Antidepressive Agents, Drug Evaluation, Preclinical, Depression, Psilocybin

topic_tags:
Depression,Anxiety,Mechanism of Action,Receptor Pharmacology,Clinical Trial,Review Article,Animal Study,Safety,Toxicity

raw_json:
{"europe_pmc_id":"39778644","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Wang Z, Robbins B, Zhuang R, Sandini T, van Bruggen R, Li XM, Zhang Y.
publication_date: 2025-01-02
doi: 10.1016/j.pnpbp.2024.111243
pubmed_id: 39756636
source_url: https://doi.org/10.1016/j.pnpbp.2024.111243
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Biomarkers
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:01
title:
Early psilocybin intervention alleviates behavioral despair and cognitive impairment in stressed Wistar rats.

abstract:
Chronic stress exerts profound effects on mental health, contributing to disorders such as depression, anxiety, and cognitive impairment. This study examines the potential of psilocybin to alleviate behavioral despair and cognitive deficits in a rodent model of chronic stress, focusing on the interplay between the Hypothalamic-Pituitary-Adrenal (HPA) axis and the Endocannabinoid System (ECS). Twenty-two male Wistar rats were divided into control and stress groups. Animals within the stress group were exposed to predator odor and chronic social instability to induce chronic stress, and were either sham treated, or given psilocybin. Behavioral assessments were conducted using the Open Field Test, Sucrose Preference Test, Novel Object Recognition, Elevated Plus Maze, and Forced Swimming Test to evaluate locomotion, anhedonia, memory, anxiety, and behavioral despair, respectively. Blood and brain samples were analyzed for biochemical markers. Results indicated that psilocybin significantly reduced stress-induced behavioral despair and cognitive impairments, likely through ECS-mediated downregulation of the HPA axis. These findings suggest that early intervention with psilocybin has sustained beneficial effects on stress-related behavioral and cognitive disturbances, underscoring its potential as a novel therapeutic approach for stress-related mental health disorders.

keywords:
Pituitary-Adrenal System, Hypothalamo-Hypophyseal System, Animals, Rats, Rats, Wistar, Disease Models, Animal, Corticosterone, Behavior, Animal, Depression, Stress, Psychological, Male, Psilocybin, Cognitive Dysfunction

raw_json:
{"europe_pmc_id":"39756636","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


