# publications

title: Psychedelic-related deaths in England, Wales and Northern Ireland (1997-2022).
authors: Kopra EI, Penttinen J, Rucker JJ, Copeland CS.
publication_date: 2024-10-19
doi: 10.1016/j.pnpbp.2024.111177
pubmed_id: 39437962
source_url: https://doi.org/10.1016/j.pnpbp.2024.111177
substance_tags: psilocybin
topic_tags: Addiction,Adolescents,Safety
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:05
abstract:
BackgroundPsychedelic drugs are increasingly visible in society once more, but their risks and adverse effects have received less attention than perhaps they should. While fatalities associated with psychedelics appear rare, a systematic approach to characterising their aetiology is required to inform harm minimisation efforts.AimsThis study aimed to analyse prevalence and characteristics of psychedelic-related deaths in England, Wales, and Northern Ireland, between 1997 and 2022.MethodsWe analysed coroner reports submitted to the National Programme on Substance Use Mortality where psychedelic serotonergic agonist drugs were involved in the death, and conducted a thematic framework analysis to explore potential factors associated with their occurrence.ResultsWe identified 28 cases where psychedelics were implicated (75 %, N = 21) or potentially implicated (25 %, N = 7) in the death; 19 of these involving psychedelic tryptamines (LSD39 %, N = 11; Psilocybin 21 %, N = 6; DMT7 %, N = 2), and 9 psychedelic phenethylamines (incl. NBOMes 18 %, N = 5). Most deaths were deemed accidental by the coroner (86 %, N = 24), including both traumatic injuries and drug toxicities; most cases involved multiple implicated drugs (68 %, N = 19); and most of the deceased were under 30 years of age (82 %, N = 23). Thematic framework analysis identified nine themes in the deaths across three categories. 'Polysubstance use' was the most common theme (82 % of cases, N = 23/28), followed by a suboptimal 'physical environment' (70 % of cases where this information was available, N = 14/20).ConclusionsThe profound and often unpredictable effects of psychedelics pose a unique profile of risks and adverse reactions. Nevertheless, psychedelic-related deaths remain very rare in comparison to other recreational drugs, and frequently involve polydrug use. Implications for harm reduction and policy are discussed.

keywords:
Humans, Substance-Related Disorders, Tryptamines, Hallucinogens, Adolescent, Adult, Middle Aged, England, Northern Ireland, Wales, Female, Male, Young Adult

raw_json:
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publication_date: 2024-09-29
doi: 10.1016/j.pnpbp.2024.111155
pubmed_id: 39357666
source_url: https://doi.org/10.1016/j.pnpbp.2024.111155
keywords: Animals, Humans, Parkinson Disease, Dementia, Metformin, Neuroprotective Agents, 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 11:22:01
title:
Comparing psilocybin to metformin as neuroprotective agents against Parkinson's dementia: A systematic review of evidence and efficacy.

authors:
Ordovich-Clarkson RD, Jabbour M, Pelayo DA, Lara D, La Croix S, Mumman M, Stukas S, Anderson R, Meraz D, Bangura A, Anderson B, Bamrud L, Blake C.

abstract:
Background & aimTreatment of Parkinson's disease (PD) has remained largely unchanged and focuses primarily on symptomatic relief through activation of dopaminergic pathways. Currently, there are no proven prophylactic approaches to the prevention of PD. This systematic review seeks to compare two separate compounds, metformin (MTF) and psilocybin, as potential prophylactic therapeutics against the development of PD.MethodsThe authors conducted a systematic review focusing on primary studies that test these compounds on cell and animal models to determine if they might have any neuroprotective or neuroplastic effects.ResultsThe results of this review found that MTF may halt the progression of diseases such as PD through multiple mechanisms including reduced oxidative stress at the level of the mitochondria, thereby reducing α-synuclein related damage. Psilocybin, on the other hand, may increase repair of damaged neurons through psychoplastogenic activation of serotonergic pathways, particularly 5-HT2A receptor activation, ultimately increasing the release of brain derived neurotropic factor (BDNF) and the reduction of α-synuclein accumulation.ConclusionImplications of this study include a need for further research in off-label use of MTF as well as further research into serotonergic compounds such as psilocybin for the treatment and prevention of neurodegenerative diseases.

topic_tags:
Mechanism of Action,Receptor Pharmacology,Mitochondrial Function,Oxidative Stress,Systematic Review,Review Article,Animal Study

raw_json:
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title: The immunomodulatory effects of classical psychedelics: A systematic review of preclinical studies.
authors: Low ZXB, Ng WS, Lim ESY, Goh BH, Kumari Y.
publication_date: 2024-09-06
doi: 10.1016/j.pnpbp.2024.111139
pubmed_id: 39251080
source_url: https://doi.org/10.1016/j.pnpbp.2024.111139
substance_tags: psilocybin,psilocin
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:
Emerging evidence suggests that classical psychedelics possess immunomodulatory and anti-inflammatory properties; however, these effects are yet to be well-established. This systematic review aims to provide a timely and comprehensive overview of the immunomodulatory effects of classical psychedelics in preclinical studies. A systematic search was conducted on six databases, including CINAHL, EMBASE, MEDLINE, PsychINFO, Scopus, and Web of Science. Eligible studies targeting classical psychedelics for evaluation of their effects on inflammatory markers and immunomodulation have been included for analysis. Data was extracted from 40 out of 2822 eligible articles, and their risk of bias was assessed using the Systematic Review Center for Laboratory Animal Experimentation (SYRCLE) tool and Quality Assessment Tool for In Vitro Studies (QUIN). Studies examined 2,5-dimethoxy-4-iodoamphetamine (DOI; n = 18); psilocybin (4-PO-DMT; n = 9); N,N-dimethyltryptamine (DMT; n = 8); lysergic acid diethylamide (LSD; n = 6); 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT; n = 3); psilocin (4-HO-DMT; n = 3); and mescaline (n = 2). In 36 studies where inflammatory cytokine levels were measured following psychedelic administration, a decrease in at least one inflammatory cytokine was observed in 29 studies. Immune cell activity was assessed in 10 studies and findings were mixed, with an equal number of studies (n = 5 out of 10) reporting either an increase or decrease in immune cell activity. Classical psychedelics were found to alleviate pre-existing inflammation but promote inflammation when administered under normal physiological conditions. This information is anticipated to inform future clinical trials, exploring classical psychedelics' potential to alleviate inflammation in various pathologies.

keywords:
Animals, Humans, Hallucinogens, Immunologic Factors, Drug Evaluation, Preclinical, Immunomodulation, Immunomodulating Agents

topic_tags:
Biomarkers,Clinical Trial,Systematic Review,Review Article,Animal Study,In Vitro Study,Safety,Inflammation,Immune Function

raw_json:
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authors: Han XX, Phurbu D, Cao B, Li JX, Zhu XY, Liu LH, Thongklang N, Hyde KD, Zhao RL.
publication_date: 2025-01-06
doi: 10.3390/jof11010045
pubmed_id: 39852464
source_url: https://doi.org/10.3390/jof11010045
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 11:22:04
title:
Molecular Phylogeny and Morphology Reveal Four New Species of Conocybe (Bolbitiaceae, Agaricales) from the Qinghai-Xizang Plateau, China.

abstract:
The Qinghai-Xizang Plateau, known for its high altitude, geological history of plate collision, crustal uplift, and special ecology factors, provides an ideal environment for studying fungal biodiversity in extreme environmental conditions. Some species within the Conocybe, containing secondary metabolites such as psilocybin, phallotoxins, and amatoxins, have potential medicinal value for treating psychiatric disorders and for use in drug development. This study investigates Conocybe (Bolbitiaceae, Agaricales) on the Plateau, based on specimens collected over the past decade, using morphological and molecular phylogenetic analyses. Seven species were identified, including four new species: C. alticola, C. alticoprophila, C. versicolor, and C. yadongensis. Molecular analyses, utilizing multi-gene sequence data (ITS, nrLSU, and tef-1α), support the taxonomic position of these new species within this genus as new species. Detailed descriptions, illustrations, photographs, line drawings, and comparisons with related species are provided for the new taxa. This study enriches the species diversity of Conocybe on the Qinghai-Tibet Plateau, further enhancing our understanding of fungal biodiversity in this region.

raw_json:
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title: Pain and Perception: Exploring Psychedelics as Novel Therapeutic Agents in Chronic Pain Management.
publication_date: 2025-01-06
doi: 10.1007/s11916-024-01353-0
pubmed_id: 39775134
source_url: https://doi.org/10.1007/s11916-024-01353-0
keywords: Humans, Analgesics, Hallucinogens, Pain Perception, Pain Management, Chronic Pain
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
authors:
Strand NH, Whitney M, Johnson B, Dunn T, Attanti S, Maloney J, Misra L, Gomez D, Viswanath O, Emami E, Leathem J.

abstract:
Purpose of reviewChronic pain affects approximately 1.5 billion people worldwide, representing the leading cause of disability and a significant financial burden on healthcare systems. Conventional treatments, such as opioids and non-steroidal anti-inflammatory drugs, are frequently linked to adverse effects, including dependency and gastrointestinal issues, and often offer limited long-term relief. This review explores the potential of psychedelics, including psilocybin, LSD, and ketamine, as alternative therapeutic agents in chronic pain management.Recent findingsThese substances modulate pain perception through actions on serotonergic and glutamatergic systems and may promote neuroplasticity, offering novel pathways for pain relief. Specifically, the review details the pharmacologic actions of psychedelics, their effects on chronic pain syndromes such as cancer pain, migraines, and neuropathic pain, and their clinical implications. The safety profiles, patient responses, and analgesic properties of these compounds are examined, highlighting the need for further research to validate their efficacy and optimize their therapeutic use in pain management.

topic_tags:
Addiction,Chronic Pain,Headache / Migraine,Neuroplasticity,Mechanism of Action,Review Article,Safety,Inflammation

raw_json:
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title: A Psilocybin Experience Gone Wrong: The Importance of Psychedelic Assisted Psychotherapy.
authors: Espi Forcen F.
publication_date: 2025-01-06
doi: 10.1080/02791072.2025.2449918
pubmed_id: 39773417
source_url: https://doi.org/10.1080/02791072.2025.2449918
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 11:22:00
abstract:
As psilocybin awaits approval by the Food and Drug Administration (FDA), scholars debate whether psychedelic-assisted psychotherapy should be required when prescribing this medicine. Here, we report the case of a patient who underwent a psilocybin experience without psychedelic-assisted psychotherapy, resulting in inpatient psychiatric admission. This case underscores the importance of taking psilocybin in controlled clinical settings. Moreover, we discuss how psychedelic-assisted psychotherapy could have altered the outcome of her experience and the role of experiential learning in psychedelics for potential prescribers.

raw_json:
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authors: Zhang M, Yang Y, Yang Z, Wen X, Zhang C, Xiao P, Wang Y, Sun J, Wang H, Wang X.
publication_date: 2024-11-11
doi: 10.1016/j.ejmech.2024.117049
pubmed_id: 39541872
source_url: https://doi.org/10.1016/j.ejmech.2024.117049
substance_tags: psilocybin,psilocin
topic_tags: Depression,Receptor Pharmacology,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:
Structural insights into tryptamine psychedelics: The role of hydroxyl indole ring site in 5-HT2A receptor activation and psychedelic-like activity.

abstract:
Recent advancements in the study of mushroom-derived tryptamines, particularly psilocybin and its metabolite psilocin, highlight their unique psychedelic properties and potential therapeutic applications, especially for mental health conditions like depression. This study examines how the position of the hydroxyl group on the indole ring affects the 5-HT2A receptor activity and psychedelic-like effects of psilocin analogs. Chemically synthesized psilocin (1) and its analogs bufotenine (2), 6-OH-DMT (3), and 7-OH-DMT (4) were assessed for 5-HT2A receptor agonistic activity using the Gαq-Gγ dissociation bioluminescence resonance energy transfer (BRET) assay and for psychedelic-like effects through the head-twitch response assay. Results show that compounds with hydroxyl group at the 4th and 5th positions exhibit significantly higher 5-HT2A agonistic and psychedelic-like activities than those with hydroxyl group at the 6th and 7th positions. Funnel metadynamics simulations revealed that psilocin (1) and bufotenine (2) have lower binding free energies, correlating with experimental data. Analysis of the simulation trajectories reveals that the formation of a hydrogen bond with residue L229 is crucial for guiding psilocin (1) and bufotenine (2) into the 5-HT2AR binding site. In contrast, analogs 3 and 4, which lack this interaction, fail to be directed into the orthosteric site. Furthermore, psilocin (1) and bufotenine (2) establish a stable salt bridge and hydrogen bond with residue D155. These interactions are more stable compared to those formed by ligands 3 and 4, contributing to the latter's poor 5-HT2AR activities. These findings underscore the critical role of the hydroxyl group position on the indole ring in modulating 5-HT2A receptor activity and the corresponding psychedelic-like effects, offering valuable insights for the development of targeted therapeutics.

keywords:
Animals, Humans, Tryptamines, Indoles, Receptor, Serotonin, 5-HT2A, Hallucinogens, Molecular Structure, Structure-Activity Relationship, Dose-Response Relationship, Drug, HEK293 Cells, Serotonin 5-HT2 Receptor Agonists, Psilocybin

raw_json:
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authors: Liao C, O’Farrell E, Weiner AM, Qalieh Y, Savalia NK, Girgenti MJ, Kwan KY, Kwan AC.
journal: bioRxiv
publication_date: 2025-01-03
doi: 10.1101/2025.01.04.631335
source_url: https://doi.org/10.1101/2025.01.04.631335
substance_tags: psilocybin
study_type: Clinical Trial
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:01
title:
Single-nucleus transcriptomics reveals cell type-specific and time-dependent effects of psilocybin and ketamine on gene expression

abstract:
ABSTRACT There is growing interest to investigate classic psychedelics and ketamine as therapeutics for mental illnesses. Previous studies have demonstrated that one dose of psilocybin or ketamine leads to persisting neural and behavioral changes. The durability of these effects suggests that there are likely alterations in gene expression at the transcriptional level. In this study, we performed single-nucleus RNA sequencing of the dorsal medial frontal cortex of male and female mice. Samples were collected at 1, 2, 4, 24, or 72 hours after psilocybin or ketamine administration and from control animals. At baseline, major subtypes of excitatory and GABAergic neurons selectively express particular serotonin receptor transcripts. The psilocybin-evoked differentially expressed genes in excitatory neurons are involved in synaptic plasticity, distinct from genes enriched in GABAergic neurons, which contribute to mitochondrial function and cellular metabolism, and non-neuronal glial cells. The effect of psilocybin on gene expression is time-dependent, including an early phase at 1 hour followed by a late phase at 72 hours of transcriptional response after administration, and differs from the changes following ketamine administration, which peaks at 2 - 4 hours. Collectively, the results provide a resource for understanding the cell type-specific and time-dependent changes in gene expression induced by psilocybin and ketamine in the mouse medial frontal cortex, which may underpin the drug’s long-term effects on neural circuits and behavior.

topic_tags:
Neuroplasticity,Pharmacology,Receptor Pharmacology,Mitochondrial Function,Animal Study,Transcriptomics

raw_json:
{"europe_pmc_id":"PPR962750","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


title: Mushroom poisoning: An updated review.
authors: Tuğcan MO, Akpınar AA.
publication_date: 2025-01-01
doi: 10.4103/tjem.tjem_129_24
pubmed_id: 39882097
source_url: https://doi.org/10.4103/tjem.tjem_129_24
substance_tags: psilocybin
topic_tags: Mechanism of Action,Review Article,Toxicity
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:
Mushrooms have been consumed frequently worldwide since ancient times. In addition to edible and harmless species, there are also poisonous species that cause a wide range of clinical syndromes, from simple gastrointestinal (GI) irritation to death. However, it is not possible to distinguish the poisonous species from some edible species morphologically. Therefore, the unintentional consumption of mushrooms is an important public health problem. Mushrooms can be categorized according to their toxins, such as cyclopeptides, gyromitrin, muscarine, coprine, orellanine, psilocybin, and GI irritants. Mushrooms containing cyclopeptide-amatoxin are responsible for more than 90% of deaths due to mushroom poisoning. Amanita phalloides is responsible for many fatal cases because of the toxicity of this species. This article reviews the clinical syndromes that may develop after the consumption of various poisonous mushroom species, the mechanisms of action of their toxins, and the current treatments applied.

raw_json:
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title: Psilocybin alleviates high-glucose and high-lipid-induced skin aging in BJ5Ta fibroblasts.
publication_date: 2024-12-31
doi: 10.1139/bcb-2025-0250
pubmed_id: 41105970
source_url: https://doi.org/10.1139/bcb-2025-0250
substance_tags: psilocybin
topic_tags: Biomarkers,Aging,Cellular Senescence,Mitochondrial Function,Oxidative Stress,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
authors:
Norouzkhani F, Gojani E, Wang B, Li D, Shujat S, Shrestha A, Rodriguez-Juarez R, Kovalchuk O, Kovalchuk I.

abstract:
Cellular aging, driven by oxidative stress, mitochondrial dysfunction, and inflammation, is exacerbated by a high-glucose and high-lipid (HGHL) diet, leading to collagen degradation and skin aging. Psilocybin, a naturally occurring compound, has shown potential in reducing symptoms of aging. This study explores the protective effects of psilocybin on BJ-5ta fibroblasts exposed to HGHL, focusing on cellular viability, apoptosis, senescence, the inflammatory responses, and wound healing. First, fibroblasts were exposed to 25 mmol/L glucose and 400 µmol/L palmitic acid to establish cell aging. Then, psilocybin effects were tested in co- and post-treatment with HGHL. Post-treatment with psilocybin at 15 µmol/L (P15) and co-treatment with psilocybin at 10 µmol/L (P10) preserved cellular viability and decreased beta-galactosidase activity. P10 was most effective in reducing apoptosis and alleviating HGHL-induced S phase arrest. P15 also reduced senescence markers and decreased the expression of inflammatory cytokines IL-1β, IL-6, and COX-2. Additionally, psilocybin promoted nonsignificant fibroblast migration, and P10 co-treated with HGHL significantly upregulated elastin gene expression. These findings suggest that psilocybin's antioxidative, anti-inflammatory, and regenerative properties make it a promising natural compound for reducing skin aging, particularly under oxidative stress conditions. Further research is needed to explore its long-term effects, optimal dosages, and clinical applications.

keywords:
Cell Line, Fibroblasts, Humans, Glucose, Apoptosis, Cell Survival, Oxidative Stress, Skin Aging, Cellular Senescence

raw_json:
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authors: D M Schuman H, Barkova S, Mina R, Deleemans JM, Nguyen T, Carlson LE
journal: Integrative cancer therapies
publication_date: 2024-12-31
doi: 10.1177/15347354251370982
pubmed_id: 41013977
source_url: https://pubmed.ncbi.nlm.nih.gov/41013977/
keywords: cancer, existential distress, psilocybin, psychedelic-assisted therapy, psychosocial symptoms
substance_tags: psilocybin
topic_tags: Emotional Processing,Spirituality,Observational Study,Cancer Patients,Safety
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":"41013977"}
title:
"" A Qualitative Analysis of Patient Perspectives on Psychedelic-Assisted Therapy for Cancer-Related Psychosocial Symptoms.

abstract:
People living with cancer (PLWC) often face profound existential distress that is insufficiently addressed by conventional psychosocial supports. This qualitative study explored PLWC's attitudes, beliefs, and experiences regarding psychedelic-assisted therapy (PAT) as a novel approach to addressing psychosocial suffering, particularly existential distress. Fifteen participants with varying cancer types and stages were recruited from a national survey. Semi-structured interviews were analyzed using reflexive thematic analysis informed by the Theory of Planned Behavior. Four key themes were identified: (1) Cautious Optimism and Substance-Specific Attitudes Toward Psychedelics reflected varied knowledge, openness, and perceptions of specific agents; (2) Relational and Societal Influences: Stigma, Support, and Cultural Framing; (3) Structural and Systemic Barriers: Cost, Legality, Provider Attitudes, and Unequal Access; and (4) Cancer Context and Psychosocial Needs: Seeking Relief from Existential and Emotional Distress captured the emotional, spiritual, and existential dimensions of living with and beyond cancer. Participants expressed cautious optimism about PAT, driven by unmet needs in conventional care, particularly after active treatment and at advanced stages of cancer, where existential and spiritual concerns often go unaddressed. PAT was seen as a potential adjunct that could meaningfully engage with suffering beyond symptom management. However, concerns about safety, access, and stigma underscore the need for culturally responsive, patient-informed, and equity-focused implementation strategies. Integrating PAT into oncology will require dismantling structural barriers and shifting toward a model of care that embraces the full human experience of serious illness.


title: Psychedelic-assisted therapies for existential and spiritual suffering in palliative care.
authors: Garcia ACM, Maia LO.
publication_date: 2025-08-17
doi: 10.1016/bs.pbr.2025.07.002
pubmed_id: 40967680
source_url: https://doi.org/10.1016/bs.pbr.2025.07.002
keywords: Humans, Hallucinogens, Palliative Care, Stress, Psychological, Existentialism, Spirituality
substance_tags: psilocybin
topic_tags: End-of-Life Distress,Mechanism of Action,Spirituality,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 11:22:03
abstract:
Existential and spiritual suffering are frequently reported by individuals facing serious illnesses, particularly at the end of life, and are associated with diminished quality of life, increased psychological distress, and requests for hastened death. While Palliative Care (PC) aims to provide holistic support, existing therapeutic options often fail to adequately address the profound disruptions in meaning, connection, and dignity experienced by patients. Psychedelic-Assisted Therapies (PAT), notably those using psilocybin, have re-emerged as promising interventions capable of eliciting transformative experiences that may alleviate existential and spiritual distress. This chapter explores the potential role of PAT in PC, beginning with a historical and conceptual overview of PC and an analysis of existential and spiritual suffering in this context. It then reviews scientific evidence on the therapeutic applications of classical psychedelics, with a focus on existential and spiritual suffering. Practical, clinical, ethical, and legal considerations for the integration of PAT into PC are discussed, including the challenges of implementation and the need for spiritually and existentially informed treatment models. The chapter concludes by reinforcing the urgency of innovative and compassionate responses to existential suffering and highlighting PAT as an emerging pathway toward improving the quality of life-and death-of individuals with serious illnesses.

raw_json:
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title: Brain changes associated with depression treatment: a meta-analysis.
authors: Perez GM, Rosenberg BM, Xu W, Oathes DJ.
publication_date: 2025-08-27
doi: 10.1016/j.nicl.2025.103874
pubmed_id: 40886591
source_url: https://doi.org/10.1016/j.nicl.2025.103874
keywords: Brain, Humans, Antidepressive Agents, Magnetic Resonance Imaging, Depression, Neuroimaging
substance_tags: psilocybin
study_type: Meta-Analysis
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:04
abstract:
BackgroundUnderstanding changes in brain activity following treatment is critical to advancing the use of neuroimaging in psychiatric research. Previous work has focused on defining abnormalities (biomarkers) between patients and healthy controls but there has been less investigation of brain changes in depression patients following treatment. To boost sample size and explore the possibility of common treatment mechanisms, we considered results from standard and emerging forms of treatment. In order to investigate and synthesize findings of brain changes, we conducted a coordinate based meta-analysis of depression treatment studies reporting pre- and post-treatment task-based neuroimaging data to determine if there were common brain regions that changed with effective depression treatment across treatment types.MethodsActivation likelihood estimation was performed to synthesize the imaging results. The meta-analysis included data from 302 depressed subjects yielding 87 foci across 18 experiments. The studies examined various depression treatments including pharmacology, psychotherapy, electroconvulsive therapy, psilocybin, and ketamine with brain activity measures in response to emotion tasks in the scanner.ResultsAcross studies, the right amygdala (peak MNI coordinates [30, 2, -22]) was a region of convergence, reflecting a consistent change in activity following depression treatment. Follow-up analyses suggested that this finding was driven by right amygdala activity decreasing with treatment.ConclusionsOur result, focusing on within-patient changes associated with treatment, highlights the right amygdala as a brain area especially relevant to depression treatment measured with fMRI. This finding provides a lens to focus depression biomarker research based on imaging measures that track depression treatment effects.

topic_tags:
Depression,Brain Imaging,Pharmacology,Mechanism of Action,Biomarkers,Aging,Emotional Processing,Meta-Analysis

raw_json:
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authors: Godfrey K, Weiss B, Zhang X, Spriggs M, Peill J, Lyons T, Carhart-Harris R, Erritzoe D.
publication_date: 2024-12-01
doi: 10.1016/j.nsa.2024.104092
pubmed_id: 40654586
source_url: https://doi.org/10.1016/j.nsa.2024.104092
substance_tags: psilocybin
topic_tags: Consciousness,Personality Change,Healthy Volunteers
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:02
title:
An investigation of acute physiological and psychological moderators of psychedelic-induced personality change among healthy volunteers.

abstract:
This study investigated the effects of a single high-dose of psilocybin on personality traits in psychedelic-naïve healthy volunteers. These data originate from a larger within-subjects fixed-order design trial, where a single high dose of psilocybin (25 mg) was administered in a psychologically supportive setting and was compared against a (one-month) prior, 1 mg 'placebo' dose. Personality shifts were assessed by the Big Five Inventory and the Big Five Aspect Scale, while the Altered States of Consciousness questionnaire (5D-ASC) and the Psychological Insight Scale gauged the acute psychological effects of the substance. Electroencephalography provided neurophysiological insights, specifically examining alpha power and Lempel-Ziv complexity (LZc). Results indicated significant reductions in neuroticism one month after 25 mg psilocybin administration, a finding consistent with prior studies. Reductions in neuroticism were moderated by the subjective meaningfulness of the psychedelic experience, as well as by the dread of ego dissolution subscale of the 5D-ASC, suggesting a relationship between acute drug effects and enduring personality alterations. Thus, this study substantiates the role of acute psychedelic states in catalysing lasting personality transformations in a generally beneficial direction, with broader implications for therapeutic applications and understanding of personality dynamics.

raw_json:
{"europe_pmc_id":"40654586","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Behavioral Neurobiology of Alcohol Addiction: A Decade of Great Challenges, New Hopes, and Hypes.
authors: Sommer WH, Spanagel R
journal: Current topics in behavioral neurosciences
publication_date: 2024-12-31
doi: 10.1007/7854_2025_586
pubmed_id: 40646424
source_url: https://pubmed.ncbi.nlm.nih.gov/40646424/
substance_tags: psilocybin
topic_tags: Addiction,Chronic Pain,Animal Study,Inflammation,Immune Function
study_type: Animal 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":"40646424"}
abstract:
Over a decade after the first edition of "Behavioral Neurobiology of Alcohol Addiction," this chapter revisits the field at a critical juncture, marked by both persistent challenges and emerging opportunities. We reflect on the translational gap that has stalled the development of new treatments for alcohol use disorder (AUD), despite decades of promising preclinical findings. Particular attention is given to the replicability crisis in animal research, publication biases, and the limited predictive validity of existing models. At the same time, we highlight advances that offer renewed hope, including molecular and circuit-level technologies, AI-driven data analysis, real-world assessments, and new pharmacological candidates, such as GLP-1 agonists and psychedelics. These breakthroughs are considered alongside the increasing recognition of inflammation, pain, and neuroimmune factors as integral to AUD. However, we caution against exaggerated claims and urge the field to avoid oversimplified models, especially those that conflate habits and compulsions. Finally, we argue that neurobiological progress must be complemented by public health strategies aimed at reducing stigma and improving access to care. By fostering empirical rigor, embracing complexity, and maintaining critical self-reflection, addiction science can better align its innovations with real-world clinical and societal needs.

keywords:
Addiction theory, Alcohol use disorder, Animal models, DELPHI method, GLP-1 agonists, Just-in-time-Adaptive-Interventions (JITAIs), Psilocybin, Translation, Valley of death


title: Emerging Risks of Amanita Muscaria: Case Reports on Increasing Consumption and Health Risks.
authors: Savickaitė E, Laubner-Sakalauskienė G.
publication_date: 2025-02-17
doi: 10.15388/amed.2025.32.1.23
pubmed_id: 40641545
source_url: https://doi.org/10.15388/amed.2025.32.1.23
substance_tags: psilocybin
topic_tags: Case Report,Safety,Toxicity
study_type: Case Report
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:04
abstract:
IntroductionThe increasing popularity of Amanita muscaria, driven by its hallucinogenic properties, has raised significant public health concerns, particularly as it remains largely unregulated across most European Union countries. The mushroom contains muscimol, a compound that induces euphoria, altered perception, and hallucinations, and its precursor, ibotenic acid, converts to muscimol when dried or heated, reducing toxicity while preserving psychoactive effects. The growing trend in intentional consumption of A. muscaria reflects evolving patterns of intoxication despite its known toxicity risks. The European Food Safety Authority has flagged A. muscaria as an emerging risk, highlighting concerns over its increasing availability and potential for misuse.Materials and methodsFour cases of Amanita muscaria consumption and subsequent intoxication have been documented in Lithuania in 2023. To further investigate this topic, a systematic search was conducted using the PubMed database with the following keyword combinations: 'Amanita muscaria', 'Amanita muscaria toxicity', 'muscimol', 'ibotenic acid', 'psilocybin', and 'hallucinogenic fungi'. After screening for relevance and eligibility, a total of 27 publications met the inclusion criteria and were incorporated into the final analysis.Case reportsIn 2023, four cases of intentional A. muscaria poisoning were reported in Lithuania, linked to recreational consumption. Symptoms included tremors, respiratory failure, dizziness, and paranoia. All patients were male and required hospitalization, but all were discharged in stable condition.ConclusionThe unregulated status and increasing accessibility of A. muscaria pose significant public health concerns. While A. muscaria remains largely unstudied in medical contexts, its toxicity risks are well-documented. Misleading online information contributes to uninformed consumption, especially among younger individuals. Further research is needed to elucidate its chemical composition, therapeutic potential, and health effects to inform regulatory policies.

raw_json:
{"europe_pmc_id":"40641545","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Clinical pharmacology.
authors: Vogt SB, Liechti ME.
publication_date: 2025-05-22
doi: 10.1016/bs.irn.2025.02.003
pubmed_id: 40541320
source_url: https://doi.org/10.1016/bs.irn.2025.02.003
keywords: Animals, Humans, Hallucinogens, Pharmacology, Clinical, Clinical Trials as Topic
substance_tags: psilocybin
topic_tags: Pharmacology,Mechanism of Action,Receptor Pharmacology,Clinical Trial,Safety,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
abstract:
To design therapeutic trials and select the most appropriate substance and dose for an indication, a detailed understanding of clinical pharmacology is crucial. In recent years, several studies have explored the human pharmacology of different psychedelics and 3,4-methylendioxymethylamphetamin (MDMA). This chapter summarizes pharmacological characteristics of the serotonergic psychedelics psilocybin, lysergic acid diethylamide (LSD), mescaline, N,N-dimethyltryptamine (DMT), 5-methoxy-DMT (5-MeO-DMT), and MDMA. We summarize their mechanisms of action, pharmacokinetics, pharmacodynamics, metabolism, and safety, with a focus on human data from modern clinical trials. Additionally, we provide recommendations for dosing, dose adjustment, and interactions with other medications. We show that the different serotonergic psychedelics produce overall comparable acute subjective and somatic effects primarily through interactions with 5-HT2A receptors. However, the exact mechanisms of their potential therapeutic benefits in patients remain to be elucidated. Moreover, classic psychedelics differ substantially in their pharmacokinetics and metabolism, resulting mainly in different durations of action, which may influence their suitability for specific therapeutic uses and indications. In contrast, MDMA has a psychopharmacological profile that is distinct from serotonergic psychedelics, characterized by acute stimulant-like and empathogenic effects. In terms of pharmacokinetic-pharmacodynamic relationships, acute effects of the psychedelics mirror their plasma-concentration-time curves, whereas acute effects of MDMA are shorter-lasting than its presence in the body. Thus, MDMA, but not the psychedelics, exhibits marked acute pharmacological tolerance. A good understanding of the pharmacology of classic psychedelics and MDMA forms the basis for their clinical use and the design of clinical therapeutic trials.

raw_json:
{"europe_pmc_id":"40541320","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psychedelics for the treatment of end-of-life distress in patients with a life-threatening disease.
authors: Tap S, Bostoen T, Breeksema J, Schoevers R
journal: International review of neurobiology
publication_date: 2024-12-31
doi: 10.1016/bs.irn.2025.03.001
pubmed_id: 40541316
source_url: https://pubmed.ncbi.nlm.nih.gov/40541316/
substance_tags: psilocybin
topic_tags: Depression,Anxiety,End-of-Life Distress,Wellbeing,Emotional Processing,Spirituality
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":"40541316"}
abstract:
Patients with a life-threatening disease (LTD) sometimes suffer from end-of-life distress (EOLD) which refers to the physical, psychological, emotional, and spiritual suffering related to chronic illness and the possibility of death. Palliative care interventions seek to improve the quality of life of patients with EOLD and their significant others. Currently, a range of psychological and pharmacological palliative care interventions may be used to mitigate the various symptoms related to EOLD. However, the evidence for their efficacy is inconclusive with only short- to moderate effects. Another significant and relevant limitation in the context of LTDs is that palliative care interventions often require months to take effect. In the past decade, psychedelic-assisted therapy (PAT) has been increasingly investigated for its therapeutic potential in addressing EOLD in various LTDs characterized by highly significant and sometimes sustained decreases in symptoms of depression and (death) anxiety along with other EOLD-related improvements (e.g., meaning, spiritual well-being, optimism, life satisfaction, and change attitudes towards LTDs). The current chapter will provide a detailed description of the concept of EOLD followed by estimated prevalence rates in a range of LTDs. Next, the chapter provides a brief overview of palliative interventions and their limitations. The chapter then introduces a description of PAT, its evidence-base, and why it seems to work in particular for patients with EOLD. The chapter is concluded with future perspectives.

keywords:
Demoralization, End-of-life distress, Existential distress, LSD, Life-threatening disease, Palliative care, Psilocybin, Psychedelic-assisted therapy, Psychological distress


title: Post-traumatic stress disorder in psychedelic research.
authors: Bostoen T, Tap S, Breeksema J, Schoevers R
journal: International review of neurobiology
publication_date: 2024-12-31
doi: 10.1016/bs.irn.2025.02.004
pubmed_id: 40541315
source_url: https://pubmed.ncbi.nlm.nih.gov/40541315/
substance_tags: psilocybin
topic_tags: PTSD,Mechanism of Action,Clinical Trial
study_type: Clinical Trial
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:20:36
raw_json: {"pubmed_id":"40541315"}
abstract:
Post-Traumatic Stress Disorder (PTSD) is a severe psychiatric condition that develops after exposure to trauma such as combat, natural disasters, or assault. It is characterized by re-experiencing trauma, avoidance, hyperarousal, and negative alterations in cognition and mood. Since its formal inclusion in the Diagnostic and Statistical Manual of Mental Disorders (DSM)-III in 1980, PTSD has been extensively researched. Current guideline-recommended treatments include trauma-focused psychotherapies and medications. However, a significant proportion of patients show limited response to these treatments. Psychedelic-assisted therapies, particularly 3,4-Methylenedioxymethamphetamine (MDMA)-assisted therapy, offer an innovative approach for treating PTSD. Over the past two decades, MDMA-assisted therapy has emerged as one of the most promising psychedelic treatments, especially for patients resistant to conventional therapies. MDMA can enhance the processing of traumatic memories during psychotherapy and holds potential for other psychiatric disorders. Recent clinical trials highlight the effectiveness of MDMA-assisted therapy, demonstrating substantial and sustained reductions in PTSD symptoms. The FDA has designated MDMA-assisted therapy as a "breakthrough therapy" for PTSD in 2017. However, due to methodological concerns such as unblinding and potential expectancy effects, the FDA decided in 2024 not to approve MDMA- assisted therapy for clinical use, requiring additional research to address these issues. This chapter explores the clinical research on psychedelic-assisted therapies for PTSD, with a particular focus on MDMA-assisted therapy. It will examine the potential psychological and neurobiological mechanisms of action, as well as the methodological challenges and future directions in the field. The growing body of evidence supporting MDMA-assisted therapy for PTSD is promising, especially for individuals who have not responded to traditional treatments.

keywords:
Ketamine, MDMA, MDMA-assisted psychotherapy, Neurobiological mechanisms, Post-traumatic stress disorder (PTSD), Psilocybin, Psychedelic-assisted therapy, Trauma-focused therapy


title: Psychedelics and substance use disorder treatment.
authors: DuPont CM, Johnson MW.
publication_date: 2025-04-20
doi: 10.1016/bs.irn.2025.03.005
pubmed_id: 40541314
source_url: https://doi.org/10.1016/bs.irn.2025.03.005
keywords: Humans, Substance-Related Disorders, Hallucinogens
substance_tags: psilocybin
topic_tags: Addiction,Emotional Processing,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
abstract:
The current chapter presents the literature evaluating the effects of classic psychedelic treatments on five substance use disorders: alcohol, tobacco, opioid, stimulant, and cannabis. Most work on psychedelics and substance use disorders was conducted for alcohol use disorder. A range of classic psychedelics (LSD, psilocybin, and ayahuasca) appear to be beneficial for facilitating both reduced drinking and abstinence. Small clinical trials have also shown promising initial results for both tobacco and opioid use disorders. In contrast, no trials have yet been conducted for stimulant and cannabis use disorders. Furthermore, the majority of studies described are naturalistic observational studies or correlational survey data. However, if such observational studies reflect causal therapeutic potential, these studies, combined with clinical trials, suggest potential broad transdiagnostic efficacy of psychedelics across multiple addictive drugs. The transdiagnostic effects of psychedelics are likely due to a combination of biological and psychological factors. Biologically, psychedelics appear to ameliorate deficits in brain areas involved in reward and emotional processing, which may reduce the risk of relapse. Psychologically, the insights gained during a psychedelic experience may reinforce personal motivations for sobriety and support subsequent behavior change. Overall, more work is needed to better characterize the potential benefits and limitations of psychedelic treatment for substance use disorders.

raw_json:
{"europe_pmc_id":"40541314","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Serotonergic psychedelics for depression: A comprehensive overview.
authors: Wingert AM, Agnorelli C, Peill J, Reed S, Nutt DJ, Erritzoe D.
publication_date: 2025-05-13
doi: 10.1016/bs.irn.2025.04.009
pubmed_id: 40541312
source_url: https://doi.org/10.1016/bs.irn.2025.04.009
substance_tags: psilocybin
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:02
abstract:
Depressive disorders continue to pose a major clinical challenge worldwide, particularly given the high prevalence and increasing number of treatment-resistant cases. Over the past decade, advances in research have elucidated the antidepressant potential of psilocybin and other 5-HT₂A receptor agonists in patients with major depressive disorder (MDD) and treatment-resistant depression (TRD). Phase I and II clinical trials have consistently demonstrated that even a single administration can yield rapid and sustained symptom reduction. These effects compare favourably with conventional pharmacotherapies such as SSRIs and ketamine. The distinctive pharmacological profile and robust safety data associated with serotonergic psychedelics make them particularly promising candidates, especially for patients who do not respond to standard treatments. Nonetheless, several challenges impede their integration into routine clinical practice, including the resource-intensive nature of psychedelic-assisted therapy, which demands specialized training and controlled settings. Despite those limitations, some countries including Australia, Switzerland or Canada are paving the way by allowing the use of psilocybin in TRD cases. This chapter reviews the antidepressant potential of psilocybin, DMT, ayahuasca and 5-MeO-DMT based on modern clinical trial data, comparing effect sizes of psychedelics to conventional treatments like SSRIs and ketamine, and provides a brief overview of their potential neurobiological mechanisms.

keywords:
Animals, Humans, Hallucinogens, Antidepressive Agents, Depressive Disorder, Treatment-Resistant, Psilocybin, Major Depressive Disorder

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

raw_json:
{"europe_pmc_id":"40541312","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Totomanova I, Haijen ECHM, Hurks PPM, Ramaekers JG, Kuypers KPC.
publication_date: 2025-04-01
doi: 10.1016/bs.irn.2025.03.002
pubmed_id: 40541311
source_url: https://doi.org/10.1016/bs.irn.2025.03.002
keywords: Brain, Animals, Humans, Hallucinogens, Mental Disorders, Psilocybin
substance_tags: psilocybin
topic_tags: Depression,OCD,Chronic Pain,Pharmacology,Microdosing,Clinical Trial,Review Article,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:
Potential therapeutic effects of psychedelics in small doses: Is there a role for microdosing in psychiatry?

abstract:
Clinical trials using full doses of psychedelics have provided preliminary evidence supporting their safety and efficacy in treating a variety of physical and psychological conditions. Anecdotal reports indicate that even very small amounts of these substances may provide therapeutic benefits, though robust clinical studies are still needed. This chapter reviews the current experimental studies in humans using psychedelics in small doses to better understand their therapeutic potential. Research in both neurotypical individuals (n = 18 studies) and patients (n = 3) suggests that small doses of LSD and psilocybin produce subtle, acute, effects on neural connectivity, brain electrophysiology, blood pressure, sleep duration, pain perception, temporal processing, and mood; and show reductions in symptoms of depression and obsessive-compulsive behavior in patient samples. The chapter also discusses the influence of extra-pharmacological factors, such as the baseline subjective state, expectations, and individual differences in drug metabolism, on treatment outcomes. Overall, controlled microdosing studies suggest the potential therapeutic applications of small psychedelic doses, warranting further exploration through large-scale trials in clinical populations.

raw_json:
{"europe_pmc_id":"40541311","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Molecular brain imaging of psychedelic action.
authors: Cumming P, Egger K, Knudsen GM
journal: International review of neurobiology
publication_date: 2024-12-31
doi: 10.1016/bs.irn.2025.02.005
pubmed_id: 40541310
source_url: https://pubmed.ncbi.nlm.nih.gov/40541310/
substance_tags: psilocybin
topic_tags: Brain Imaging,Pharmacology,Receptor Pharmacology,Aging,Review Article,Drug Interactions
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":"40541310"}
abstract:
Molecular brain imaging by positron emission tomography (PET) and single photon emission computer-tomography (SPECT) entails the mapping of the cerebral distribution of radiopharmaceuticals that track physiological processes such as blood perfusion and glucose metabolism, or the abundance in brain of specific molecular targets such as neuroreceptors. PET and SPECT emerged as useful in vivo research technologies in the 1980s, finding early application in the study of psychostimulant drugs. The past decade has seen growing use of molecular imaging methods in the study of psychedelic action, although the published literature remains comparatively small. The preponderance of publications cited in this review are SPECT studies of cerebral perfusion and PET studies of metabolism and neuroreceptors, the latter mainly focusing on the 5-hydroxytryptamine (serotonin) 5-HT receptors, which are largely responsible for the psychedelic action of classical psychedelic substances. There is some documentation of interactions of psychedelics at dopamine Dreceptors in the striatum, but many other plausible molecular targets of psychedelic action await investigation by molecular brain imaging. The emerging role of psychedelics as treatments for neurological and psychiatric disorders calls for a broader and systematic investigation of their effects on brain function.

keywords:
Cerebral blood flow, LSD, Metabolism, Positron emission tomography (PET), Psilocybin, Psychedelics, Receptors, Single photon emission computer tomography (SPECT)


title: Effects of psychedelics on human oscillatory brain activity.
authors: Godfrey K, Luan LX, Timmermann C.
publication_date: 2025-04-20
doi: 10.1016/bs.irn.2025.04.012
pubmed_id: 40541309
source_url: https://doi.org/10.1016/bs.irn.2025.04.012
keywords: Brain, Humans, Hallucinogens, Electroencephalography, Magnetoencephalography, Brain Waves
substance_tags: psilocybin
topic_tags: Brain Imaging,Mechanism of Action,Biomarkers,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 11:22:04
abstract:
This chapter reviews the effects of classic psychedelics on human oscillatory brain activity, as measured by resting-state electroencephalography (EEG) and magnetoencephalography (MEG). Across moderate to high doses of LSD, psilocybin, ayahuasca, and DMT, a consistent reduction in alpha power (8-13 Hz) emerges, particularly in occipital regions. Below 30 Hz, desynchronization is typical, although DMT can preserve or even increase delta/theta activity, possibly reflecting its immersive, immersive visual phenomenology. Complementing these spectral findings, measures of signal diversity (e.g., Lempel-Ziv complexity) reliably increase during psychedelic states, indicating a more variable and unpredictable pattern of neural firing. Retrospective subjective ratings of the psychedelic experience often fail to align consistently with M/EEG changes, possibly because fleeting, key experiences are obscured by data averaging or recording short segments of a long experience. In contrast, real-time evaluations of subjective intensity and plasma levels robustly covary with changes in spectral power and complexity, highlighting the potential for objective, real-time EEG biomarkers of drug activity. Limited research on functional connectivity and cortical travelling waves suggest that directed, top-down control may decrease while bottom-up signaling increases, indicating a transient reversal of typical hierarchical organization, though replications are warrented. Future work should implement more unified methodological approaches, alongside high-resolution behavioral sampling, to further our understanding of how these altered brain dynamics give rise to the distinctive qualities of the psychedelic experience. Notably, EEG has yet to be evaluated in clinical studies, and future work should aim to explore the relationship between acute EEG changes and clinical responses to psychedelic therapy.

raw_json:
{"europe_pmc_id":"40541309","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Human neuroimaging: fMRI.
authors: Wall MB, Carhart-Harris RL.
publication_date: 2025-06-05
doi: 10.1016/bs.irn.2025.04.013
pubmed_id: 40541308
source_url: https://doi.org/10.1016/bs.irn.2025.04.013
keywords: Brain, Humans, Hallucinogens, Magnetic Resonance Imaging, Neuroimaging
substance_tags: psilocybin
topic_tags: Brain Imaging,Aging,Emotional Processing,Observational Study
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
abstract:
Human neuroimaging with functional Magnetic Resonance Imaging has been a key feature of the current wave of psychedelic research, in both healthy and clinical populations. The available data has suggested that classic psychedelics (psilocybin, LSD, DMT) have a characteristic effect of acutely and profoundly disrupting the normal pattern of resting-state connectivity in the human brain, and that this effect may be closely related to both the characteristic subjective phenomenology of psychedelics, and their more clinically-relevant longer-term effects on emotional brain systems. This chapter briefly outlines the basic methodological background of fMRI, and then provides an overview of the current state of knowledge of psychedelic drug action as revealed by task and resting-state fMRI, in both non-clinical and clinical cohorts. Current limitations of the field are largely addressable by ongoing and future work, particularly in terms of providing additional datasets, increased standardisation of data acquisition and analysis procedures, potential multi-modal imaging studies, and more open data-sharing. Neuroimaging with fMRI remains a central platform of modern psychedelic research, with implications for our mechanistic understanding of psychedelics, as well as a strong influence on the clinical development of psychedelic-based treatments.

raw_json:
{"europe_pmc_id":"40541308","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Won NY, Wang A, Athay R, Striley CW, Cottler LB.
publication_date: 2025-06-04
doi: 10.1080/10826084.2025.2511242
pubmed_id: 40474383
source_url: https://doi.org/10.1080/10826084.2025.2511242
substance_tags: psilocybin
topic_tags: Addiction,Aging,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 11:22:02
title:
Geographical Differences in Self-Reported Past 12-Month Drug Use: Results from the NDEWS Rapid Street Reporting, 2021-2023.

abstract:
BackgroundThe National Drug Early Warning System Rapid Street Reporting study monitors over 100 drugs to identify emerging use trends.ObjectivesThis analysis examined geographical differences in the past 12-month self-reported drug use across 20 US urban cities, identifying the three most prevalent drugs reported, excluding alcohol.MethodsAdults (age ≥18) were surveyed in public settings using venue-intercept sampling over a weekend in each city between January 2022 and November 2023 regarding past 12-month drug use. We focused on the three most commonly reported drugs in each region. The prevalence of reported drug use by region was compared using generalized linear models with Poisson and log-link functions, adjusting for participant characteristics, time of year, and location.ResultsAmong 6,039 participants, cannabis for recreational use (50.3%), psilocybin (13.7%), and cocaine (11.0%) were the most commonly reported drugs used. While there were no regional differences in the prevalence of recreational cannabis use, psilocybin, and cocaine use were more commonly reported by people in the West versus the Midwest (adjusted prevalence ratio [aPR]=1.58, 95% confidence interval [CI]: 1.23, 2.06; aPR=1.67, 95% CI: 1.26, 2.23, respectively). We also found a higher prevalence of cocaine use reported by participants in the Northeast compared to participants in the Midwest (aPR=1.37, 95% CI: 1.00, 1.91).ConclusionsVenue intercept survey method detected signals of recreational cannabis, psilocybin, and cocaine use in the 20 US urban cities visited over a weekend. Reported prevalence differed by region. This suggests that prevention messaging should be tailored to the specific US regions.

keywords:
Humans, Substance-Related Disorders, Cocaine, Prevalence, Cities, Adolescent, Adult, Middle Aged, Urban Population, United States, Female, Male, Young Adult, Self Report, Recreational Drug Use

raw_json:
{"europe_pmc_id":"40474383","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Zhu X, Zhang C, Hellerstein D, Feusner JD, Wheaton MG, Gomez GJ, Schneier F.
publication_date: 2024-09-23
doi: 10.61373/pp024r.0028
pubmed_id: 40458078
source_url: https://doi.org/10.61373/pp024r.0028
substance_tags: psilocybin
topic_tags: Depression,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 11:22:01
title:
Single-dose psilocybin alters resting state functional networks in patients with body dysmorphic disorder.

abstract:
Body dysmorphic disorder (BDD) is a severe psychiatric condition characterized by preoccupation with perceived flaws in one's appearance, which the individual views as defective or ugly. Psilocybin, a serotonin 2A receptor agonist with psychedelic properties, has emerged as a potential therapeutic agent for depression and other psychiatric disorders. This study aimed to identify subacute neural changes predicting symptomatic response to psilocybin treatment in adults with BDD. Eight adults with moderate-to-severe nondelusional BDD were administered a single oral 25 mg dose of psilocybin, accompanied by psychological support, and underwent resting state functional magnetic resonance imaging assessments 1 day before and 1 day after the dosing. Both a region of interest (ROI)-to-ROI analysis and multivariate pattern analysis (MVPA) were used to identify changes in resting state functional connectivity (rsFC) at day 1 after dosing that predicted treatment response at week 1, measured by change in Yale-Brown Obsessive Compulsive Disorder Scale Modified for BDD (BDDYBOCS) score. All participants completed the dosing and follow-up assessments over 12 weeks. BDD-YBOCS scores decreased at week 1 and week 12 after dosing (p

raw_json:
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authors: Bires J.
publication_date: 2025-03-25
doi: 10.1080/07347332.2025.2482917
pubmed_id: 40138527
source_url: https://doi.org/10.1080/07347332.2025.2482917
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
title:
Existing evidence for the use of psychedelics in patients with cancer and other serious illness: A narrative review.

abstract:
ObjectivesMood disorders and existential distress impact those with cancer or a serious illness at higher rates than the general population. There have been limited pharmacological advances in recent years, and available psychological interventions vary in degree of impact and durability as a treatment modality in this population. A recent renaissance in psychedelic research has suggested that this class of medications might offer an alternative treatment model for anxiety, depression, and existential and psychological distress that often accompanies the diagnosis of a serious illness.MethodsUtilizing a narrative review approach, EMBASE and PubMed databases were searched with no beginning date range through April 2024 to identify randomized controlled clinical trials (RCTs) on LSD, psilocybin and MDMA in palliative care or oncology and other life limiting illnesses.ResultsFive articles published between 2011 and 2020 met the inclusion criteria. Three studies utilized psilocybin and one study evaluated MDMA and LSD. The number of participants ranged from 12 to 56 with four studies that utilized a crossover design. Four of the five studies showed a significant decrease in anxiety during at least one time point in their study and three studies indicated a significant decrease in depression. None of the studies reported serious adverse events related to the experimental drug sessions.ConclusionsPsychedelic assisted therapy for the treatment of depression, anxiety and existential distress is a promising treatment modality as an addition or compliment to other available pharmacological and psychotherapeutic treatment modalities.

keywords:
Humans, Neoplasms, Critical Illness, N-Methyl-3,4-methylenedioxyamphetamine, Lysergic Acid Diethylamide, Hallucinogens, Psilocybin

topic_tags:
Depression,Anxiety,End-of-Life Distress,Clinical Trial,Randomized Controlled Trial,Review Article,Cancer Patients,Adverse Events

raw_json:
{"europe_pmc_id":"40138527","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Nogueira M, García-Hernández S, Roberto GS, Marques LZ.
publication_date: 2024-12-31
doi: 10.1615/intjmedmushrooms.2024057053
pubmed_id: 40096533
source_url: https://doi.org/10.1615/intjmedmushrooms.2024057053
substance_tags: psilocybin
topic_tags: Addiction,Adolescents,Safety,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
title:
Psilocybin Mushrooms and Public Health in Brazil: Insights from a Retrospective Analysis of Adverse Events and Their Implications for Regulatory Discussions.

abstract:
Current drug policy classifies psilocybin, a compound found in psychoactive mushrooms, as having high abuse potential while overlooking its therapeutic properties. We evaluated the risk of psilocybin mushrooms to Brazilian public health compared to other toxic agents and assessed the need for regulatory discussions. This retrospective cross-sectional study followed STROBE guidelines, using data from the Notifiable Diseases Information System (SINAN) on adverse events reported from 2007 to 2022. Participants were categorized into a general drug abuse group, which was further divided into psilocybin and unknown mushroom subgroups. Clinical outcomes included non-hospitalization, hospitalization, and death, with associations analyzed via the Chi-square test. Out of 112,451 individuals seeking medical attention for drug abuse-related events, men predominated (n = 79,514; 70.7%), with alcohol being the primary agent (n = 71,824; 49.2%). The psilocybin mushroom group included 13 participants, and the unknown mushroom group included 51. Hospitalization rates were 19.5% (n = 21,923) for drug abuse, 46.2% (n = 6) for psilocybin mushrooms (0.02% of all hospitalizations) (99% CI: 10.6%-81.6%), and 23.5% (n = 12) for unknown mushrooms (99% CI: 8.3%-38.7%). Mortality was 1.8% (n = 2035) for drug abuse group, with no fatal events in the psilocybin or unknown mushroom groups. Deaths were mainly linked to cocaine (33.3%). These findings suggest a low risk for psilocybin mushrooms, though underreporting may be a factor. This study underscores the need for evidence-based regulatory discussions to ensure safe access to psilocybin for clinical and ceremonial use.

keywords:
Humans, Agaricales, Substance-Related Disorders, Hallucinogens, Hospitalization, Retrospective Studies, Cross-Sectional Studies, Public Health, Adolescent, Adult, Middle Aged, Brazil, Female, Male, Young Adult, Psilocybin

raw_json:
{"europe_pmc_id":"40096533","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Wijesekara T, Xu B.
publication_date: 2024-12-31
doi: 10.1177/09603271251323134
pubmed_id: 40066831
source_url: https://doi.org/10.1177/09603271251323134
keywords: Animals, Humans, Agaricales, Mushroom Poisoning, Toxins, Biological
substance_tags: psilocybin
topic_tags: Pharmacology,Systematic Review,Review Article,Toxicity,Immune Function
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:
Insights into therapeutic potential and practical applications of natural toxins from poisonous mushrooms.

abstract:
IntroductionMushrooms, belonging to the phyla Ascomycota and Basidiomycota, comprise approximately 14,000 known species, among which a small fraction are toxic. While toxic mushrooms are primarily associated with adverse health effects, recent research highlights their potential as sources of bioactive compounds with promising therapeutic applications.MethodsA systematic review was conducted using four major electronic databases: Web of Science, Google Scholar, PubMed, and ScienceDirect. The literature search, completed on July 1, 2024, utilized keywords including "Poisonous mushrooms," "Mushroom toxins," "Mycotoxins," "Beta-glucans," "Psilocybin," and "Therapeutic applications." Articles were selected based on specific inclusion criteria, focusing on studies investigating the biochemical, toxicological, and pharmacological properties of toxic mushroom compounds. Studies unrelated to mushrooms, non-peer-reviewed sources, or those with outdated or incomplete data were excluded.ResultsThis review examines key toxic mushroom compounds such as amanitins, phallotoxins, ibotenic acid, muscimol, orellanine, and gyromitrin, emphasizing their biosynthesis, structural features, and health effects. Despite their toxicity, compounds like beta-glucans, polysaccharides, lectins, and psilocybin exhibit immune-modulating, anticancer, and neuroprotective properties. These bioactive compounds have shown promise in targeting cancer stem cells and enhancing neurotransmitter activity, positioning them as potential therapeutic agents.DiscussionUnderstanding the therapeutic potential of toxic mushroom-derived bioactive compounds bridges toxicology and pharmacology, offering novel avenues for drug discovery. Comparative analysis with existing treatments highlights their unique advantages in modern medicine.

raw_json:
{"europe_pmc_id":"40066831","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Evaluating the potential for psilocybin as a treatment for post-traumatic stress disorder.
authors: Miller CE, Zoladz PR.
publication_date: 2024-11-21
doi: 10.1124/jpet.124.002237
pubmed_id: 39893004
source_url: https://doi.org/10.1124/jpet.124.002237
keywords: Animals, Humans, Hallucinogens, Stress Disorders, Post-Traumatic, Psilocybin
substance_tags: psilocybin
topic_tags: Anxiety,PTSD,Mechanism of Action,Review Article,Animal 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 11:22:01
abstract:
Post-traumatic stress disorder (PTSD) is a debilitating psychiatric condition that develops following exposure to a traumatic event. Individuals with this condition experience numerous physiological and behavioral alterations, including intrusive memories, avoidance of trauma-related stimuli, heightened anxiety, hypervigilance, impaired cognition, elevated resting heart rate and blood pressure, and altered neuroendocrine function, to name a few. In most patients, currently available pharmacological and psychological treatments are insufficient to alleviate the array of symptoms associated with the disorder. Thus, novel treatment options that can more effectively target the core etiology of PTSD are desperately needed. Recent work demonstrating the psychoplastogenic effects of psychedelics has reinvigorated research to examine their therapeutic potential in psychiatric conditions. Psilocybin, a psychedelic found in the Psilocybe genus of mushrooms, has exhibited promising antidepressant and anxiolytic effects in preclinical and clinical studies. The purpose of this review is to summarize the existing research that has examined the behavioral effects of psilocybin and link it to potential efficacy in treating PTSD-related symptoms. The proposed mechanisms for psilocybin's effects are then explored, as are the benefits and drawbacks for the agent's therapeutic use. Finally, the challenges faced by investigators aiming to study psilocybin as a therapeutic aid in future studies are discussed in order to shed light on this budding area of research. SIGNIFICANCE STATEMENT: Current pharmacotherapy for post-traumatic stress disorder is insufficient. Traditional antidepressants and anxiolytics help reduce symptom severity, but nonresponse rates often reach levels greater than 50%, emphasizing the need for more effective treatment options. The goal of this review is to summarize the existing evidence for and the potential mechanisms of the antidepressant and anxiolytic effects of psilocybin, a psychedelic compound found in the Psilocybe genus of mushrooms. The observed effects are then related to psilocybin's potential use as a treatment for PTSD.

raw_json:
{"europe_pmc_id":"39893004","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: 2025-01-14
doi: 10.1007/s40262-024-01454-4
pubmed_id: 39812743
source_url: https://doi.org/10.1007/s40262-024-01454-4
keywords: Humans, Hallucinogens, Administration, Oral, Half-Life, Administration, Intravenous, Psilocybin
substance_tags: psilocybin,psilocin
topic_tags: End-of-Life Distress,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 11:22:00
title:
Clinical Pharmacokinetics of Psilocin After Psilocybin Administration: A Systematic Review and Post-Hoc Analysis.

abstract:
Background and objectivePsilocybin is currently being extensively studied as a potential therapeutic agent for multiple psychiatric disorders. Here, a systematic literature review of all published pharmacokinetic data on the pharmacologically active metabolite of psilocybin, psilocin, is presented.MethodsThe review includes clinical studies that reported pharmacokinetic data and/or parameters after psilocybin administration in humans. In addition, raw pharmacokinetic data from these studies was requested and/or extracted to further compare results across studies.ResultsIn total, 309 publications were identified, of which 19 publications were ultimately included, which covered 12 unique clinical datasets. Except for one study that investigated intravenous psilocybin, all included studies administered psilocybin orally. Psilocybin acts as a pro-drug and is rapidly absorbed and transformed to psilocin after oral administration. In the majority of studies, unconjugated psilocin was measured while some also measured conjugated and total concentrations. Psilocin's biphasic concentration-time profiles demonstrates fast and extensive disposition with an apparent distribution volume of 505-1267 L and a terminal half-life of 1.23-4.72 h. Only 1.5-3.4% of the dose is excreted as psilocin in urine. Psilocin is mainly transformed to 4-hydroxyindole-3-acetic acid and in less amounts to conjugated psilocin, where 4-hydroxyindole-3-acetic acid formation may occur prior to systemic psilocin absorption. Information on the absolute bioavailability of psilocin was limited, and estimated at 55% in one study. No covariates nor food effects have been reported, based on four studies with known fasting status.ConclusionsOverall, we found the pharmacokinetic parameters of psilocin to be consistent between studies. This review may guide the further clinical development of psilocybin-based therapies.

raw_json:
{"europe_pmc_id":"39812743","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psychedelic Medicine Exceptionalism.
authors: Cohen IG, Marks M
journal: The American journal of bioethics : AJOB
publication_date: 2024-12-31
doi: 10.1080/15265161.2025.2434398
pubmed_id: 39804318
source_url: https://pubmed.ncbi.nlm.nih.gov/39804318/
keywords: FDA, MDMA, Psychedelics, informed consent, psilocybin, psychotherapy
substance_tags: psilocybin
topic_tags: Healthcare Workers
study_type: Other
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:20:36
raw_json: {"pubmed_id":"39804318"}
abstract:
Research on psychedelic medicines is experiencing a revival. Some clinicians, scientists, and ethicists believe that psychedelics are so different from other treatments that they warrant special consideration in how they are researched, regulated, commercialized, and administered. Others argue that psychedelic medicines show clinical potential, but they should be treated like other medical interventions. In other words, identical standards should apply. This article analyzes whether psychedelic medicines warrant special consideration from a regulatory and ethical perspective.


authors: Lewis BR, Hendrick J, Byrne K, Odette M, Wu C, Garland EL.
journal: medRxiv
publication_date: 2024-12-31
doi: 10.1101/2024.12.31.24319806
source_url: https://doi.org/10.1101/2024.12.31.24319806
substance_tags: psilocybin
topic_tags: Depression,Clinical Trial,Randomized Controlled Trial,Observational Study,Safety,Adverse Events
study_type: Randomized Controlled Trial
source_name: medRxiv
publication_status: preprint
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:01
title:
Psilocybin-Assisted Group Psychotherapy + Mindfulness Based Stress Reduction (MBSR) for Frontline Healthcare Provider COVID-19 Related Depression and Burnout: A Randomized Clinical Trial

abstract:
Objective This clinical trial sought to evaluate the safety and preliminary efficacy of psilocybin and MBSR for frontline healthcare providers with symptoms of depression and burnout related to the COVID-19 pandemic. Methods This was a randomized controlled trial that enrolled physicians and nurses with frontline clinical work during the COVID-19 pandemic and symptoms of depression and burnout. Participants were randomized in a 1:1 ratio to either an 8-week MBSR curriculum alone or an 8-week MBSR curriculum plus group psilocybin-assisted psychotherapy (PAP) with 25mg psilocybin. Symptoms of depression and burnout were assessed at baseline, and 2-weeks and 6-months post intervention utilizing the Quick Inventory of Depressive Symptoms (QIDS-SR-16) and Maslach Burnout Inventory Human Services Survey for Medical Professionals (MBI-HSS-MP), respectively. Secondary outcome measures included the Demoralization Scale (DS-II) and the Watt’s Connectedness Scale (WCS). Adverse events and suicidality were assessed through 6-month follow-up. Results 25 participants were enrolled and randomized. There were 12 study-related AEs recorded that were Grade 1-2 and no serious AEs. There was larger decrease in QIDS score for the MBSR+PAP arm compared to MBSR-only from baseline to 2-weeks post-intervention and significant between-group differences favoring MBSR+PAP on subscales of the MBI-HSS-MP as well as the DS-II and WCS. Conclusions Group psilocybin-assisted therapy plus MBSR was associated with clinically significant improvement in depressive symptoms without serious adverse events and with greater reduction in symptoms than MBSR alone. Study findings suggest that integrating psilocybin with mindfulness training may represent a promising treatment for depression and burnout among physicians and nurses.

raw_json:
{"europe_pmc_id":"PPR961100","source":"PPR","pub_type":null,"publisher":"medRxiv","importer":"Europe PMC"}


publication_date: 2024-12-31
doi: 10.1097/wnf.0000000000000617
pubmed_id: 39787428
source_url: https://doi.org/10.1097/wnf.0000000000000617
keywords: Humans, Hallucinogens, Psilocybin
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
title:
Exploring Psychedelics Pharmacology: A Scoping Review Charting the Course of Psilocybin Pharmacokinetics.

authors:
Manzano-Nunez R, Gomez DA, Toledo-Mendoza C, Perez-Otero M, Matilla IL, Prats C, Perez-Lopez E, Pardo H, Díaz-Pellicer P, De La Torre-Fornell R, Aldea AM.

abstract:
ObjectivesThis scoping review aimed to synthesize the existing data about psilocybin pharmacokinetics to learn what has been described regarding body disposition and safety when psilocybin was used in controlled research settings.MethodsWe performed a scoping literature review following the framework proposed by the JBI manual for evidence synthesis. Controlled clinical trials reporting pharmacokinetic data of psilocybin were considered appropriate for inclusion. We extracted the data on psilocybin pharmacokinetics and summarized it from the available literature on this topic. We also performed an exploratory-descriptive analysis using study level data to examine the relationship between dose of psilocybin and maximum serum concentrations (Cmax).ResultsWe initially identified 850 articles, of which 5 were included. These trials included 112 healthy volunteers who received psilocybin in a controlled clinical setting. The peak concentration of psilocin in plasma (Cmax) ranged from 8.2 ng/mL to 37.2 ng/mL (median = 17, IQR = 11.9 to 23.5). The maximal concentrations (Cmax) of psilocin were reached (Tmax) around 2 hours, ranging from 1.7 hours to 2.2 hours (median = 2, IQR = 1.9 to 2.1) after psilocybin oral administration. Elimination half-life was between 1.2 hours and 3.3 hours (median = 2.0, IQR = 1.6 to 2.8). A strong positive relationship between dose and Cmax ( R2 = 0.95) was found. No serious adverse events were observed. We did not find studies reporting pharmacokinetic data from patients with depression or cancer patients transitioning to palliative care.ConclusionsIn summary, this review unveils oral psilocybin pharmacokinetics in healthy adults, revealing gaps in its application to target populations like those with depression or in palliative care.

topic_tags:
Depression,End-of-Life Distress,Pharmacology,Clinical Trial,Review Article,Healthy Volunteers,Cancer Patients,Safety,Adverse Events

raw_json:
{"europe_pmc_id":"39787428","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2024-12-31
doi: 10.1176/appi.ajp.20230887
pubmed_id: 39741446
source_url: https://doi.org/10.1176/appi.ajp.20230887
substance_tags: psilocybin
topic_tags: Depression,Addiction,Personality Change,Clinical Trial,Randomized Controlled Trial,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 11:22:01
title:
Multidimensional Personality Changes Following Psilocybin-Assisted Therapy in Patients With Alcohol Use Disorder: Results From a Double-Blind, Placebo-Controlled Clinical Trial.

authors:
Pagni BA, Zeifman RJ, Mennenga SE, Carrithers BM, Goldway N, Bhatt S, O'Donnell KC, Ross S, Bogenschutz MP.

abstract:
ObjectiveEvidence suggests that psilocybin-assisted therapy (PAT) leads to durable shifts in personality structure. However, such changes have yet to be characterized in disorders of addiction. In this secondary analysis from a randomized controlled trial, the authors examined the effect of PAT on personality dimensions in patients with alcohol use disorder (AUD), hypothesizing that PAT would attenuate personality abnormalities in AUD and that reductions in trait impulsiveness would be associated with lower drinking.MethodsEighty-four adults with AUD were randomized to two medication sessions of either psilocybin (N=44) or active placebo (diphenhydramine; N=40), received 12 weekly psychotherapy sessions, and completed follow-up for an additional 24 weeks. Changes in personality traits (week 36 vs. baseline) were assessed with the revised NEO Personality Inventory; daily alcohol consumption was quantified using the timeline followback.ResultsRelative to the placebo group, the psilocybin group showed significant reductions in neuroticism and increases in extraversion and openness. Secondary analyses showed that reductions in neuroticism were driven by decreases in the facets depression, impulsiveness, and vulnerability; increases in openness were driven by increases in the facets openness toward feelings and fantasy. Across all participants, decreases in impulsiveness were associated with lower posttreatment alcohol consumption, and an exploratory analysis revealed that these associations were strongest among psilocybin-treated participants who continued moderate- or high-risk drinking prior to the first medication session.ConclusionsPAT elicited durable shifts in personality, suggesting normalization of abnormal personality trait expression in AUD. Further study is needed to clarify whether PAT exerts its beneficial effects by reducing impulsiveness or whether impulsive individuals inherently respond better to PAT.

keywords:
Humans, Alcoholism, Hallucinogens, Treatment Outcome, Combined Modality Therapy, Double-Blind Method, Impulsive Behavior, Personality, Personality Inventory, Adult, Middle Aged, Female, Male, Psilocybin

raw_json:
{"europe_pmc_id":"39741446","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Research and Implementation of Psychedelic-Assisted Therapy in the Veterans Health Administration.
journal: The American journal of psychiatry
publication_date: 2024-12-31
doi: 10.1176/appi.ajp.20240751
pubmed_id: 39741441
source_url: https://pubmed.ncbi.nlm.nih.gov/39741441/
keywords: Depression, MDMA, PTSD, Psilocybin, Psychedelics, Veterans
substance_tags: psilocybin
topic_tags: Depression,PTSD,Veterans
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":"39741441"}
authors:
Wolfgang AS, McClair VL, Schnurr PP, Holtzheimer PE, Woolley JD, Stauffer CS, Wolf RC, States LJ, Benedek DM, Capaldi VF, Bradley J, Fuller MA, Smyth MJ, Hermes EDA, Tenhula W, Wiechers IR


title: Single-Dose Psilocybin for Depression With Severe Treatment Resistance: An Open-Label Trial.
publication_date: 2024-12-31
doi: 10.1176/appi.ajp.20231063
pubmed_id: 39741440
source_url: https://doi.org/10.1176/appi.ajp.20231063
substance_tags: psilocybin
topic_tags: Depression,PTSD,Treatment-Resistant Depression,Safety,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
authors:
Aaronson ST, van der Vaart A, Miller T, LaPratt J, Swartz K, Shoultz A, Lauterbach M, Suppes T, Sackeim HA.

abstract:
ObjectiveDepression varies along a difficulty-to-treat spectrum. Patients whose illness fails to respond to at least five treatments may be considered to have severely treatment-resistant depression (TRD). The objective of this study was to document the safety and efficacy of psilocybin in patients with severe TRD.MethodsThis was a 12-week, open-label trial conducted at Sheppard Pratt Hospital. Participants were 18-65 years of age, in a major depressive episode with documented insufficient benefit from at least five treatments during the current episode. A single dose of synthetic psilocybin (25 mg) was administered. Psychotropic medications were discontinued at least 2 weeks prior to dosing through at least 3 weeks post-dosing. Therapists met with patients for three sessions during pretreatment, during the 8-hour dosing day, and for three integration sessions posttreatment. The primary outcome measure was change in Montgomery-Åsberg Depression Rating scale (MADRS) at 3 weeks posttreatment. Secondary measures including MADRS scores up to 12 weeks posttreatment, and subject-rated scales capturing depression and level of function were completed at baseline and all subsequent visits.ResultsTwelve participants (six male, six female; mean age=40.6 years [SD=9.6]) with severe TRD were followed over the study period. Depressive symptoms were significantly decreased at week 3 (MADRS least-squares mean change=-15.8, 95% CI=-25.4 to -6.3) and Week 12 (MADRS least-squares mean change=-17.2, 95% CI=-25.2 to -9.1). In exploratory analyses, the Oceanic Boundlessness (OB) dimension of the psychedelic experience correlated with post-dosing antidepressant responses. Patients with comorbid PTSD (N=5) showed significantly less antidepressant effect of psilocybin.ConclusionsThis open-label study suggests efficacy and safety of psilocybin in severe TRD and supports further study of psychedelics in this population, including consideration of PTSD interaction effects.

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

raw_json:
{"europe_pmc_id":"39741440","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Benefits and Challenges of Ultra-Fast, Short-Acting Psychedelics in the Treatment of Depression.
authors: Ramaekers JG, Reckweg JT, Mason NL.
publication_date: 2024-12-31
doi: 10.1176/appi.ajp.20230890
pubmed_id: 39741439
source_url: https://doi.org/10.1176/appi.ajp.20230890
substance_tags: psilocybin
topic_tags: Depression,Pharmacology,Receptor Pharmacology,Clinical Trial,Review Article
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:
Unlike classical antidepressants, psychedelics such as psilocybin have been shown to induce a rapid antidepressant response. In the wake of this development, interest has emerged in ultra-fast, short-acting psychedelics such as 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and N,N-dimethyltryptamine (DMT) with the expectation that these can produce rapid antidepressant effects following an intense but brief psychedelic intervention. The current paper reviews the clinical pharmacology of 5-MeO-DMT and DMT and their potential benefits and challenges in the treatment of depression. Both compounds display affinities for a variety of monoamine receptors and transporters, but mostly so for serotonergic (5HT) receptors, including 5HT1A and 5HT2A. Early clinical trials in small samples have shown that short interventions (15-30 min) with 5-MeO-DMT and DMT are safe and well tolerated and can induce marked improvement in symptoms of depression within 24 hours that sustain for at least 1 week. Data on long-term efficacy are currently scarce but do suggest a prolongation of the treatment response. Potential benefits of these treatments include flexible, single day dosing regimens, achievement of treatment efficacy independent from integrative therapy, and ease of clinical implementation. Future challenges include establishing the duration of the antidepressant effect and strategies on how to sustain the antidepressant response, optimization of treatment delivery parameters, and a mechanistic understanding of the clinical response. Acceptance of ultra-fast, short-acting psychedelics will depend on future randomized, placebo-controlled trials with a focus on replication, duration and maintenance of antidepressant efficacy in large patient samples.

keywords:
Humans, N,N-Dimethyltryptamine, Methoxydimethyltryptamines, Hallucinogens, Antidepressive Agents, Treatment Outcome, Depressive Disorder

raw_json:
{"europe_pmc_id":"39741439","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin: From Psychiatric Pariah to Perceived Panacea.
publication_date: 2024-12-31
doi: 10.1176/appi.ajp.20230682
pubmed_id: 39741437
source_url: https://doi.org/10.1176/appi.ajp.20230682
keywords: Humans, Hallucinogens, Mental Disorders, Psilocybin, Major Depressive Disorder
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
authors:
Fonzo GA, Wolfgang AS, Barksdale BR, Krystal JH, Carpenter LL, Kraguljac NV, Grzenda A, McDonald WM, Widge AS, Rodriguez CI, Nemeroff CB.

abstract:
ObjectiveThe authors critically examine the evidence base for psilocybin administered with psychological support/therapy (PST) in the treatment of psychiatric disorders and offer practical recommendations to guide future research endeavors.MethodsPubMed was searched for English-language articles from January 1998 to November 2023, using the search term "psilocybin." A total of 1,449 articles were identified and screened through titles and abstracts. Of these, 21 unique open-label or randomized controlled trials (RCTs) were identified that examine psilocybin for the treatment of obsessive-compulsive and related disorders (N=2), anxiety/depression associated with a cancer diagnosis (N=5), major depressive disorder (MDD; N=8), substance use disorders (N=4), anorexia (N=1), and demoralization (i.e., hopelessness, helplessness, and poor coping) in AIDS survivors (N=1).ResultsThe most developed evidence base is for the treatment of MDD (three double-blind RCTs with positive signals spanning a range of severities). However, the evidence is tempered by threats to internal and external validity, including unsuccessful blinding, small samples, large variability in dosing and PST procedures, limited sample diversity, and possibly large expectancy effects. Knowledge of mechanisms of action and predictors of response is currently limited.ConclusionsThe evidence is currently insufficient to recommend psilocybin with PST as a psychiatric treatment. Additional rigorously designed clinical trials are needed to definitively establish efficacy in larger and more diverse samples, address dosing considerations, improve blinding, and provide information on mechanisms of action and moderators of clinical response. Head-to-head comparisons with other evidence-based treatments will better inform the potential future role of psilocybin with PST in the treatment of major psychiatric disorders.

topic_tags:
Depression,Anxiety,Addiction,OCD,Eating Disorders,Mechanism of Action,Clinical Trial,Randomized Controlled Trial

raw_json:
{"europe_pmc_id":"39741437","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2024-12-31
doi: 10.1176/appi.ajp.20230884
pubmed_id: 39741434
source_url: https://doi.org/10.1176/appi.ajp.20230884
substance_tags: psilocybin
topic_tags: Depression,Clinical Trial,Treatment-Resistant Depression
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
title:
Compass Psychological Support Model for COMP360 Psilocybin Treatment of Serious Mental Health Conditions.

authors:
Kirlić N, Lennard-Jones M, Atli M, Malievskaia E, Modlin NL, Peck SK, Gaillard A, Goodwin GM, Koelpin D.

abstract:
The psychedelic experience can be challenging. There is a need for a structured framework for providing psychological support to individuals with mental health conditions receiving investigational psilocybin treatment. The primary benefit of such a framework is to support a safe and meaningful psilocybin experience. It also enables future research on the facets of psychological support and/or psychotherapy that most optimally complement psilocybin treatment. The authors describe the Compass Psychological Support Model (CPSM), currently used to support participants with treatment-resistant depression in Compass-sponsored clinical trials of investigational COMP360 psilocybin treatment. The authors also outline the therapist training, mentoring, and fidelity assessment programs they have developed to ensure the quality and consistency of the CPSM delivery.

keywords:
Humans, Hallucinogens, Psychotherapy, Models, Psychological, Depressive Disorder, Treatment-Resistant, Psilocybin

raw_json:
{"europe_pmc_id":"39741434","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Katragunta K, Avula B, Chittiboyina AG, Lata H, Khan IA.
publication_date: 2024-12-31
doi: 10.1615/intjmedmushrooms.2024056373
pubmed_id: 39717916
source_url: https://doi.org/10.1615/intjmedmushrooms.2024056373
keywords: Amanita, Chromatography, Liquid, Mass Spectrometry, Psilocybe, Psilocybin
substance_tags: psilocybin,psilocin
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 11:22:00
title:
Quantitative LC-QToF-MS Analysis of Mycochemicals in Amanita muscaria, Psilocybe spp. (Agaricomycetes), and Consumer Products.

abstract:
The psychedelic mushroom market has expanded rapidly due to changing regulations and increasing consumer demand. Product diversity now extends beyond traditional capsules and tablets to include gummies, powders, and confectionery items, complicating quality control efforts. To assess the quality and potential adulteration of Amanita musca-ria and Psilocybe cubensis-based products, a validated LC-QToF-MS method was developed. This method focused on five characteristic compounds: ibotenic acid (IBA), muscimol (MUS), muscarine, psilocin, and psilocybin that are constituents of A. muscaria and P. cubensis mushrooms. Method validation demonstrated satisfactory linearity, precision, and recovery of all five analytes. Psilocin and psilocybin levels ranged from 0.001-1.6% and 9.9-19.3%, respectively, in five Psilocybe species samples, while IBA, MUS, and muscarine levels in two samples of Amanita muscaria were 0.03-0.04%, 0.01- 0.02%, and 0.01-0.02%, respectively. By comparing commercial products to authentic samples, we evaluated the overall quality of 27 across various formulations. Our analysis included 14 gummies, three chocolates, six capsules, one tablet, and three powders. Although 11 of 14 gummies claimed to contain Amanita mushroom extracts, only MUS and muscarine were detected, without IBA. Interestingly, one gummy product indicated the presence of psilocin and psilocybin despite the labeling that claimed, "no psilocybin." Eleven products contained psilocin and psilocybin as anticipated, but five products lacked all target compounds. These findings underscore the need for standardized product specifications. Nevertheless, the established LC-QToF-MS approach could serve as a valuable tool for evaluating the quality of magic mushroom-based consumer products.

raw_json:
{"europe_pmc_id":"39717916","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Quality of reporting on psychological interventions in psychedelic treatments: a systematic review.
publication_date: 2024-12-08
doi: 10.1016/s2215-0366(24)00333-x
pubmed_id: 39667373
source_url: https://doi.org/10.1016/s2215-0366(24)00333-x
substance_tags: psilocybin
topic_tags: 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 11:22:04
authors:
Seybert C, Schimmers N, Silva L, Breeksema JJ, Veraart J, Bessa BS, d'Orsi D, Schoevers RA, Oliveira-Maia AJ.

abstract:
Although studies of psychedelic-assisted psychotherapy are accumulating, there is no consensus regarding best practice of the psychotherapeutic component. In this systematic review, we summarised the quality of reporting on psychological interventions in research about psychedelic treatments. The design followed PRISMA guidelines and was preregistered in PROSPERO (CRD42022319221). We searched MEDLINE, PsycINFO, and Embase for original studies on psychedelic-assisted psychotherapy and included 45 studies assessing psilocybin, 3,4-methylenedioxymethamphetamine (MDMA), lysergic acid diethylamide (known as LSD), or ayahuasca, for the treatment of mental disorders. Psychological interventions were done heterogeneously across studies, and completeness of information reported about these interventions was mostly low, according to an adaptation of the Template for Intervention Description and Replication checklist. In studies including MDMA, psychotherapy was more homogeneous and more procedural details were provided. Improved reporting on psychological interventions of psychedelic treatments will support replicability, generalisability, and accurate interpretation of research, while enhancing feasibility and safety of future clinical research and real-world implementation of treatments.

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

raw_json:
{"europe_pmc_id":"39667373","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Practical considerations in the establishment of psychedelic research programs.
journal: Psychopharmacology
publication_date: 2024-12-31
doi: 10.1007/s00213-024-06722-6
pubmed_id: 39627438
source_url: https://pubmed.ncbi.nlm.nih.gov/39627438/
keywords: Clinical research, Clinical trials, LSD, Psilocybin, Psychedelics
substance_tags: psilocybin
topic_tags: Aging,Clinical Trial,Review Article
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":"39627438"}
authors:
Barnett BS, Vest MF, Delatte MS, King Iv F, Mauney EE, Coulson AJ, Nayak SM, Hendricks PS, Greer GR, Murnane KS

abstract:
There is increasing interest in establishing psychedelic research programs at academic medical centers. However, psychedelics are intensely psychoactive, carry considerable sociopolitical baggage, and most are Schedule I drugs, creating significant potential impediments to implementation. There is little formal guidance for investigators on navigating the complex on-the-ground obstacles associated with establishing psychedelic research programs.
This article provides recommendations that may be helpful to investigators seeking to work with psychedelics, with a focus on academic medical centers in the United States.
The academic literature on relevant matters is reviewed, and the authors provide observations from their experiences either working for relevant regulatory agencies or conducting basic science studies, investigator-initiated trials, or industry sponsored trials with psychedelics.
Investigators planning to conduct psychedelic research should cultivate broad institutional support early. Challenges related to securing funding, obtaining approval for an Investigational New Drug application from the Food and Drug Administration, clinical grade drug sourcing, obtaining a Schedule I researcher registration from the Drug Enforcement Administration and an equivalent state license (if required), preparing spaces for treatment and study drug storage, managing controlled substance inventory, engaging the local community, and other issues should be anticipated.
Investigators should anticipate several implementation challenges when planning to work with psychedelics. However, these are likely surmountable with planning, persistence, and assistance from colleagues and other experts.


authors: Zech JM, Yaden DB, Jones GM.
publication_date: 2024-11-13
doi: 10.1016/j.drugalcdep.2024.112502
pubmed_id: 39586127
source_url: https://doi.org/10.1016/j.drugalcdep.2024.112502
substance_tags: psilocybin
topic_tags: Addiction,Observational Study,Adolescents,Safety
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
title:
Associations between psychedelic use and cannabis use disorder in a nationally representative sample.

abstract:
BackgroundCannabis Use Disorder (CUD) is an increasingly prevalent disorder affecting millions of Americans each year. Psychedelic compounds have recently been investigated for their therapeutic potential in treating substance use disorders, yet no prior work has examined the relationship between naturalistic use of specific psychedelic compounds and rates of disordered cannabis use.MethodsUsing a nationally representative sample of U.S adults from the National Survey on Drug Use and Health (2015 - 2019, 2021 - 2022), we used a series of survey-weighted multivariable logistic regressions to examine the association between past year disordered cannabis use and use of several classic psychedelics (i.e., LSD, psilocybin, mescaline, peyote, DMT) and non-classic psychedelics (i.e., ketamine, MDMA).Resultslifetime psilocybin use as well as past year LSD use were both associated with higher rates of past year DSM-5 CUD (adjusted risk ratio [aRR] range: 1.89 - 2.04), controlling for a variety of sociodemographic factors. These associations remained significant in the case of moderate-to-severe past year CUD (aRR range: 1.65 - 2.07). Past year LSD use also predicted three of eleven CUD symptoms among individuals with past year cannabis use (aRR range: 1.45 - 1.73).DiscussionDespite preliminary findings regarding the potential for psychedelic substances to help treat substance use disorders, our findings suggest a relationship between psychedelic use and disordered cannabis use, suggesting that certain psychedelic substances used in certain naturalistic settings are an indicator of greater risk of maladaptive cannabis use. Future directions to further disentangle these relationships are discussed.

keywords:
Humans, Marijuana Abuse, Lysergic Acid Diethylamide, Hallucinogens, Health Surveys, Adolescent, Adult, Middle Aged, United States, Female, Male, Young Adult, Psilocybin

raw_json:
{"europe_pmc_id":"39586127","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Richardson E, Patterson R, Meltzer-Brody S, McClure R, Tow A.
publication_date: 2025-01-15
doi: 10.1146/annurev-med-050423-095712
pubmed_id: 39527720
source_url: https://doi.org/10.1146/annurev-med-050423-095712
substance_tags: psilocybin
topic_tags: Depression,Review Article,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
title:
Transformative Therapies for Depression: Postpartum Depression, Major Depressive Disorder, and Treatment-Resistant Depression.

abstract:
Depressive disorders present an enormous global public health burden. A notable treatment gap exists between the prevalence of depression and our ability to provide rapid-acting, effective treatment that achieves remission. Brexanolone and zuranolone, the first US Food and Drug Administration-approved drugs for postpartum depression, signify a critical advancement in addressing the unmet needs of a vulnerable patient population. Psilocybin shows promise for treatment-resistant depression and for those who have struggled to find relief with existing treatments. This review discusses transformative therapies that represent significant advancements in postpartum depression, major depressive disorder, and treatment-resistant depression.

keywords:
Humans, Depression, Postpartum, beta-Cyclodextrins, Pregnanolone, Antidepressive Agents, Drug Combinations, Female, Depressive Disorder, Treatment-Resistant, Major Depressive Disorder

raw_json:
{"europe_pmc_id":"39527720","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Negrine JJ, Puljević C, Ferris J, Liknaitzky P, Perlman C, Piatkowski T.
publication_date: 2024-11-04
doi: 10.1111/dar.13973
pubmed_id: 39499579
source_url: https://doi.org/10.1111/dar.13973
substance_tags: psilocybin
topic_tags: Depression,Observational Study,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:
Australian psychologists' attitudes towards psychedelic-assisted therapy and training following a world-first drug down-scheduling.

abstract:
IntroductionThis study explores the attitudes of psychologists towards psychedelics and psychedelic-assisted therapy (PAT) following the world-first regulatory changes in 2023 in Australia which permitted psilocybin and 3,4-methylenedioxy-methamphetamine (MDMA) to be used in clinical services.MethodsA purposive sample of 20 Australian psychologists was recruited using snowball sampling. Semi-structured interviews were conducted which explored participants' attitudes, knowledge and concerns about PAT. Data were coded and analysed to identify and develop theme categories.ResultsMost psychologists exhibited positive attitudes towards psychedelics and their therapeutic potential, viewing them as promising for addressing chronic mental health conditions like depression. However, there was a notable concern regarding the limited evidence on efficacy and potential adverse experiences, as well as the complexity of the individualised treatment protocol. Despite enthusiasm, many psychologists had limited detailed knowledge about the interventions themselves. The need for comprehensive education and training programs, including exposure to psychedelic experiences and credible higher education institutions, was emphasised to ensure competence in administering PAT.Discussion and conclusionsPsychologists displayed notably positive attitudes towards PAT, likely reflecting both shifting perceptions of psychedelics and self-selection bias within the sample. Despite this optimism, concerns were raised about psychiatric risks and the necessity for comprehensive and reputable training and supervision. The cohort showed openness to both novel treatments and innovative training methods, underscoring the importance of enhancing educational frameworks to ensure effective implementation of PAT.

keywords:
Humans, N-Methyl-3,4-methylenedioxyamphetamine, Hallucinogens, Attitude of Health Personnel, Health Knowledge, Attitudes, Practice, Psychology, Adult, Middle Aged, Australia, Female, Male, Psilocybin, Psychologists

raw_json:
{"europe_pmc_id":"39499579","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin reduces grooming in the SAPAP3 knockout mouse model of compulsive behaviour.
authors: Gattuso JJ, Wilson C, Hannan AJ, Renoir T.
publication_date: 2024-11-01
doi: 10.1016/j.neuropharm.2024.110202
pubmed_id: 39489287
source_url: https://doi.org/10.1016/j.neuropharm.2024.110202
substance_tags: psilocybin
topic_tags: Anxiety,Receptor Pharmacology,Animal Study,Adverse Events
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 is a serotonergic psychedelic compound which shows promise for treating compulsive behaviours. This is particularly pertinent as compulsive disorders require research into new pharmacological treatment options as the current frontline treatments such as selective serotonin reuptake inhibitors, require chronic administration, have significant side effects, and leave almost half of the clinical population refractory to treatment. In this study, we investigated psilocybin administration in male and female SAPAP3 knockout (KO) mice, a well-validated mouse model of obsessive compulsive and related disorders. We assessed the effects of acute psilocybin (1 mg/kg, intraperitoneal) administration on head twitch and locomotor behaviour as well as anxiety- and compulsive-like behaviours at multiple time-points (1, 3 and 8 days post-injection). While psilocybin did not have any effect on anxiety-like behaviours, we revealed that acute psilocybin administration led to enduring reductions in compulsive behaviour in male SAPAP3 KO mice and reduced grooming behaviour in female wild-type (WT) and SAPAP3 KO mice. We also found that psilocybin increased locomotion in WT littermates but not in SAPAP3 KO mice, suggesting in vivo serotonergic dysfunctions in KO animals. On the other hand, the typical head-twitch response following acute psilocybin (confirming its hallucinogenic-like effect at this dose) was observed in both genotypes. Our novel findings suggest that acute psilocybin may have potential to reduce compulsive-like behaviours (up to 1 week after a single injection). Our study can inform future research directions as well as supporting the utility of psilocybin as a novel treatment option for compulsive disorders.

keywords:
Animals, Mice, Inbred C57BL, Mice, Knockout, Mice, Disease Models, Animal, Amidohydrolases, Nerve Tissue Proteins, Hallucinogens, Grooming, Compulsive Behavior, Anxiety, Locomotion, Female, Male, Psilocybin

raw_json:
{"europe_pmc_id":"39489287","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Harnessing Pharmacogenomics in Clinical Research on Psychedelic-Assisted Therapy.
authors: Halman A, Conyers R, Moore C, Khatri D, Sarris J, Perkins D.
publication_date: 2024-09-29
doi: 10.1002/cpt.3459
pubmed_id: 39345195
source_url: https://doi.org/10.1002/cpt.3459
keywords: Humans, Hallucinogens, Mental Disorders, Pharmacogenetics, Precision Medicine
substance_tags: psilocybin
topic_tags: Pharmacology,Review Article,Animal Study,Safety,Genomics
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:
Psychedelics have recently re-emerged as potential treatments for various psychiatric conditions that impose major public health costs and for which current treatment options have limited efficacy. At the same time, personalized medicine is increasingly being implemented in psychiatry to provide individualized drug dosing recommendations based on genetics. This review brings together these topics to explore the utility of pharmacogenomics (a key component of personalized medicine) in psychedelic-assisted therapies. We summarized the literature and explored the potential implications of genetic variability on the pharmacodynamics and pharmacokinetics of psychedelic drugs including lysergic acid diethylamide (LSD), psilocybin, N,N-dimethyltryptamine (DMT), 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), ibogaine and 3,4-methylenedioxymethamphetamine (MDMA). Although existing evidence is limited, particularly concerning pharmacodynamics, studies investigating pharmacokinetics indicate that genetic variants in drug-metabolizing enzymes, such as cytochrome P450, impact the intensity of acute psychedelic effects for LSD and ibogaine, and that a dose reduction for CYP2D6 poor metabolizers may be appropriate. Furthermore, based on the preclinical evidence, it can be hypothesized that CYP2D6 metabolizer status might contribute to altered acute psychedelic experiences with 5-MeO-DMT and psilocybin when combined with monoamine oxidase inhibitors. In conclusion, considering early evidence that genetic factors can influence the effects of certain psychedelics, we suggest that pharmacogenomic testing should be further investigated in clinical research. This is necessary to evaluate its utility in improving the safety and therapeutic profile of psychedelic therapies and a potential future role in personalizing psychedelic-assisted therapies, should these treatments become available.

raw_json:
{"europe_pmc_id":"39345195","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Humphreys K, Todd Korthuis P, Stjepanović D, Hall W.
publication_date: 2024-12-02
doi: 10.1146/annurev-psych-020124-023532
pubmed_id: 39094057
source_url: https://doi.org/10.1146/annurev-psych-020124-023532
substance_tags: psilocybin
topic_tags: Depression,PTSD,Addiction,Mechanism of Action,Treatment-Resistant Depression,Safety,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 11:22:04
title:
Therapeutic Potential of Psychedelic Drugs: Navigating High Hopes, Strong Claims, Weak Evidence, and Big Money.

abstract:
Therapeutic claims about many psychedelic drugs have not been evaluated in any studies of even modest rigor. The science of psychedelic drugs is strengthening, however, making it easier to differentiate some promising findings amid the hype that suffuses this research area. Ketamine has risks of adverse side effects (e.g., addiction and cystitis), but multiple studies suggest it can benefit individuals with treatment-resistant depression. Other therapeutic signals from psychedelic drug research that merit rigorous replication studies include 3,4-Methylenedioxymethamphetamine (MDMA) for post-traumatic stress disorder (PTSD) and psilocybin for depression, end of life dysphoria, and alcohol use disorder. The precise mechanisms through which psychedelic drugs can produce benefit and harm are not fully understood. Rigorous research is the best path forward for evaluating the therapeutic potential and mechanisms of psychedelic drugs. Policies governing the clinical use of these drugs should be informed by evidence and prioritize the protection of public health over the profit motive.

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

raw_json:
{"europe_pmc_id":"39094057","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2024-01-14
doi: 10.1080/02791072.2024.2302186
pubmed_id: 38225795
source_url: https://doi.org/10.1080/02791072.2024.2302186
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:
Validation of the Danish Translation of the Revised Mystical Experience Questionnaire (MEQ30) and Possible Impact of Setting, Dose and Intention.

authors:
Hovmand OR, Ebbesen Jensen M, Søgaard Juul T, Korsbak Madsen M, MacDonald Fisher P, Siggaard Stenbæk D.

abstract:
Research suggests positive changes in both well-being and psychiatric symptoms following a psychedelic experience. One explanation may be the ability of psychedelic compounds to occasion mystical-type experiences. The Revised Mystical Experiences Questionnaire (MEQ30) is designed to assess the intensity and quality of such experiences. We examined the validity, reliability, and factor structure of a Danish translation of the MEQ30 in one sample of healthy volunteers receiving psilocybin in a laboratory setting (N = 47) and two samples of recreative users of psychedelics, in which MEQ30 was reported retrospectively through an online survey based on their most recent experience with psilocybin (N = 834) or their most memorable experience with any psychedelic (N = 500). We conducted a confirmatory factor analysis of the previously suggested factor structures, calculated alpha and omega, and tested the associations between MEQ30 total score and setting, intention and dose. We found excellent internal reliability estimates across all samples, and confirmatory factor analysis showed that a four-factor structure, had the best, fair fit to the data. We further found that the MEQ30 total score was correlated with dose and a spiritual/religious intention, but not with setting. The Danish MEQ30 seems to be a valid tool for accessing mystical-type experiences among Danish-speaking individuals.

keywords:
Humans, Hallucinogens, Factor Analysis, Statistical, Reproducibility of Results, Intention, Psychometrics, Mysticism, Translations, Adolescent, Adult, Middle Aged, Denmark, Female, Male, Young Adult, Surveys and Questionnaires, Psilocybin

topic_tags:
Wellbeing,Creativity,Spirituality,Mystical Experience,Observational Study,Healthy Volunteers,Adolescents

raw_json:
{"europe_pmc_id":"38225795","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Unveiling the Psychedelic Journey: An Appraisal of Psilocybin as a Profound Antidepressant Therapy.
authors: Shah FI, Shehzadi S, Akram F, Haq IU, Javed B, Sabir S, Kazim Y, Ashfaq S.
publication_date: 2023-12-19
doi: 10.1007/s12033-023-00994-7
pubmed_id: 38117395
source_url: https://doi.org/10.1007/s12033-023-00994-7
keywords: Animals, Humans, Agaricales, Hallucinogens, Antidepressive Agents, Depression, Psilocybin
substance_tags: psilocybin
topic_tags: Depression,Mechanism of Action,Receptor Pharmacology,Consciousness,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
abstract:
Depression, a global health concern with significant implications for suicide rates, remains challenging to treat effectively with conventional pharmacological options. The existing pharmaceutical interventions for these illnesses need daily dosing, are accompanied by various adverse effects, and may exhibit limited efficacy in certain cases. However, hope emerges from an unlikely source-Psilocybin, a natural hallucinogen found in certain mushrooms. Recently, this enigmatic compound has garnered attention for its potential therapeutic benefits in addressing various mental health issues, including depression. Psilocybin alters mood, cognition, and perception by acting on a particular subtype of serotonin receptors in the brain. It's feasible that these shifts in consciousness will promote healing development, offering a novel approach to depression management. This comprehensive review explores psilocybin, derived from specific mushrooms, and its implications in the treatment of depression. The study examines new perspectives and therapeutic possibilities surrounding psilocybin, addressing existing gaps in academic literature. It delves into its biosynthesis, unique mechanisms of action, therapeutic applications, and anti-depressive effects. By uncovering the potential of this mind-altering substance, the review aims to advance psychiatric care, offering hope to those globally affected by depression.

raw_json:
{"europe_pmc_id":"38117395","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Hadley M, Halliday A, Stone JM
journal: Journal of psychoactive drugs
publication_date: 2024-12-31
doi: 10.1080/02791072.2023.2287081
pubmed_id: 38009828
source_url: https://pubmed.ncbi.nlm.nih.gov/38009828/
keywords: HPPD, Hallucinogen persisting perception disorder, LSD, anxiety, neuroticism, psilocybin
substance_tags: psilocybin
topic_tags: Anxiety
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":"38009828"}
title:
Association of Hallucinogen Persisting Perception Disorder with Trait Neuroticism and Mental Health Symptoms.

abstract:
Hallucinogen Persisting Perception Disorder (HPPD) is considered rare in hallucinogen users although there are conflicting reports about its incidence and prevalence. HPPD may be more common in those with trait neuroticism. In this study, we invited hallucinogen and other drug users to complete an online questionnaire about their use of hallucinogens, their experience of HPPD symptoms, and their trait neuroticism and mental health symptoms. We received 802 responses with 415 of these containing adequate data for further analysis. 39.7% of responders reported symptoms corresponding to Type I HPPD, and 4.3% reported symptoms corresponding to Type II HPPD. We found no significant difference between neuroticism scores for participants with or without HPPD. Individuals with Type II HPPD were more likely to report mental health symptoms including anxiety, obsessional thoughts, paranoia, hypochondria and panic attacks (


authors: Bahji A, Lunsky I, Gutierrez G, Vazquez G.
publication_date: 2023-11-14
doi: 10.1080/02791072.2023.2278586
pubmed_id: 37968944
source_url: https://doi.org/10.1080/02791072.2023.2278586
substance_tags: psilocybin
topic_tags: Depression,Anxiety,PTSD,Aging,Meta-Analysis,Systematic Review,Review Article,Safety,Adverse Events
study_type: Meta-Analysis
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:04
title:
Efficacy and Safety of Four Psychedelic-Assisted Therapies for Adults with Symptoms of Depression, Anxiety, and Posttraumatic Stress Disorder: A Systematic Review and Meta-Analysis.

abstract:
There has been a resurgence in psychedelic research for managing psychiatric conditions in recent years. This study aimed to present a comprehensive review of the current state of the field by applying a systematic search strategy for articles on the effectiveness and tolerability of four psychedelic-assisted therapies (psilocybin, lysergic acid diethylamide [LSD], 3,4-Methylenedioxymethamphetamine [MDMA], and ayahuasca) for adults with symptoms of depression, anxiety, and posttraumatic stress disorder (PTSD). Psychometric scores and adverse events were pooled using random-effects meta-analysis models with Hedges' g bias-corrected standardized mean differences (g) and rate ratios (RR) with 95% confidence intervals (CI). Bias evaluation followed PRISMA and Cochrane guidelines. Eighteen studies were identified, which suggested that psychedelic therapies were well tolerated and presented a large effect size for the management of depression symptoms in a transdiagnostic population with psilocybin (g = -1.92, 95% CI, -2.73 to -1.11) and MDMA (g = -0.71; 95% CI, -1.39 to -0.03). These are promising results that complement the current literature. However, evidence certainty was low to very low due to methodological limitations, small sample size, blinding, study heterogeneity, and publication bias. These results also highlight the need for more adequately powered studies exploring these novel therapies.

keywords:
Humans, Banisteriopsis, N-Methyl-3,4-methylenedioxyamphetamine, Lysergic Acid Diethylamide, Hallucinogens, Treatment Outcome, Depression, Anxiety, Stress Disorders, Post-Traumatic, Adult, Psilocybin

raw_json:
{"europe_pmc_id":"37968944","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Leistenschneider G, Majić T, Reiche S, Riemer TG.
publication_date: 2024-12-30
doi: 10.1038/s41598-024-82216-x
pubmed_id: 39741155
source_url: https://doi.org/10.1038/s41598-024-82216-x
substance_tags: psilocybin
topic_tags: Toxicity
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:
Neuropsychological profiles of patients suffering from hallucinogen persisting perception disorder (HPPD): A comparative analysis with psychedelic-using and non-using controls.

abstract:
Classic psychedelics like LSD and psilocybin are showing promising effects in treating certain psychiatric disorders. Despite their low toxicity and lack of an addictive potential, in some individuals, psychedelics can be associated with persisting psychological harms. Hallucinogen Persisting Perception Disorder (HPPD) is one of those complications, a rare disorder characterized by enduring perceptual symptoms without impaired reality control. While the phenomenological aspects of HPPD have been characterized, the neuropsychological consequences have remained understudied. This study probes the neuropsychological profiles of eight individuals with HPPD, utilizing a comprehensive test battery. Performance is benchmarked against normative data and compared with two control groups, each comprising eight matched subjects-with and without prior psychedelic use. The assessment of individual performances revealed below average results in tests of visual memory and executive function in some subjects. No significant differences were observed in alpha-adjusted comparisons with controls, whereas unadjusted analyses were suggestive of impaired executive functions among HPPD patients. Together, these preliminary results underline the need for further focused research into the neuropsychological dimensions of HPPD.

keywords:
Humans, Perceptual Disorders, Hallucinogens, Case-Control Studies, Neuropsychological Tests, Adult, Middle Aged, Female, Male, Young Adult, Executive Function

raw_json:
{"europe_pmc_id":"39741155","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Koning E, Chaves C, Kirkpatrick RH, Brietzke E.
publication_date: 2024-12-26
doi: 10.1186/s40337-024-01185-8
pubmed_id: 39731144
source_url: https://doi.org/10.1186/s40337-024-01185-8
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:
Exploring the neurobiological correlates of psilocybin-assisted psychotherapy in eating disorders: a review of potential methodologies and implications for the psychedelic study design.

abstract:
Eating disorders (EDs) are a group of debilitating mental illnesses characterized by maladaptive eating behaviors and severe cognitive-emotional dysfunction, directly affecting 1-3% of the population. Standard treatments are not effective in approximately one third of ED cases, representing the need for scientific advancement. There is emerging evidence for the safety and efficacy of psilocybin-assisted psychotherapy (PAP) to improve treatment outcomes in individuals with EDs. However, the limited knowledge of the neurobiological mechanisms underlying the therapeutic effects of PAP restricts the ability to confirm its clinical utility. This narrative review presents an overview of methodologies used to elucidate the pathophysiological mechanisms of EDs or the effects of psilocybin that could be employed to probe the neurobiological correlates of PAP in EDs, including magnetic resonance imaging and molecular neuroimaging techniques, electrophysiological approaches, and neuroplasticity markers. Finally, the implications of these methodologies are described in relation to the unique features of the psychedelic study design, challenges, limitations, and future directions to advance the field. This paper represents a valuable resource for scientists during study conceptualization and design phases and stimulates advancement in the identification of effective therapeutic interventions for EDs.

topic_tags:
Eating Disorders,Neuroplasticity,Brain Imaging,Mechanism of Action,Biomarkers,Aging,Emotional Processing,Review Article,Safety

raw_json:
{"europe_pmc_id":"39731144","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin as a Disease-Modifying Drug-A Salutogenic Approach in Psychiatry.
authors: Spangemacher M, Mertens LJ, Färber LV, Jungaberle A, Jungaberle H, Gründer G.
publication_date: 2024-11-30
doi: 10.3238/arztebl.m2024.0224
pubmed_id: 39628414
source_url: https://doi.org/10.3238/arztebl.m2024.0224
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
abstract:
BackgroundTreatment with so-called psychedelic drugs, including psilocybin, lysergic acid diethylamide (LSD), and others, is among the most promising recent developments in psychiatry. This review focuses on psilocybin, a substance found in all mushrooms of the genus Psilocybe, because the largest amount of available evidence relates to this drug.MethodsThis review is based on pertinent publications (since 1969) that were retrieved by a selective search carried out in August 2024 in the PubMed and ScienceDirect databases employing the keywords "psilocybin" AND "long-term effects" AND "mental disorders", with an emphasis on randomized, controlled clinical trials (RCTs).ResultsThe available RCTs document the efficacy of psilocybin mainly against depression, including otherwise medically refratory depression. Most of the trials revealed a strong effect, with Cohen's d ranging from 0.67 to 2.6; they used a variety of depression scales and follow-up intervals. Evidence was also found for the efficacy of psilocybin against substance use disorders (alcohol in particular) and symptoms of anxiety accompanying life-threatening somatic illnesses, such as cancer. Initial uncontrolled studies have also shown significant improvement after the administration of psilocybin for other indications.ConclusionTreatment with psilocybin differs fundamentally from classic psychopharmacotherapy. Its potentially transdiagnostic, rapid, and sustainable efficacy and its positive effect on further dimensions of mental health beyond the patient's symptoms and psychopathology imply that it may have diseasemodifying and salutogenic mechanisms of action. Psychotherapy accompanied by the administration of psychedelic drugs may turn out to be the first disease-modifying treatment in the history of psychiatry.

keywords:
Humans, Hallucinogens, Treatment Outcome, Mental Disorders, Randomized Controlled Trials as Topic, Psilocybin

topic_tags:
Depression,Anxiety,Addiction,End-of-Life Distress,Mechanism of Action,Clinical Trial,Randomized Controlled Trial,Review Article

raw_json:
{"europe_pmc_id":"39628414","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Classic psychedelics and the treatment for alcoholism.
authors: Lodetti G, de Bitencourt RM, Rico EP.
publication_date: 2024-08-22
doi: 10.1016/j.pnpbp.2024.111129
pubmed_id: 39181308
source_url: https://doi.org/10.1016/j.pnpbp.2024.111129
keywords: Animals, Humans, Alcoholism, Lysergic Acid Diethylamide, Hallucinogens, Psilocybin
substance_tags: psilocybin
topic_tags: Addiction,Neuroplasticity,Aging,Clinical Trial,Review Article
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:
Alcohol is a harmful drug, and reducing its consumption is a significant challenge for users. Furthermore, alcohol dependence is often treatment-resistant, and no completely effective treatment model is available for chemical dependence. Classic psychedelics, such as LSD, psilocybin, and ayahuasca have been used in different clinical and pre-clinical trials, demonstrating promising pharmacotherapeutic effects in the treatment of treatment-resistant psychopathological conditions, such as addiction, especially related to alcohol dependence. In this work, we conducted a narrative review of the emerging research regarding the potential of psychedelics for alcohol use disorder treatment. Psychedelic substances have demonstrated potential for treating drug addiction, especially AUD, mostly by modulating neuroplasticity in the brain. Given that serotonergic psychedelics do not produce physical dependence or withdrawal symptoms with repeated use, they may be considered promising treatment options for managing drug use disorders. However, certain limitations could be found. Although many participants achieve positive results with only one treatment dose in clinical studies, great inter-individual variability exists in the duration of these effects. Therefore, further studies using different doses and experimental protocols should be conducted to enhance evidence about psychedelic substances.

raw_json:
{"europe_pmc_id":"39181308","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Advanced Delivery Systems and Novel Psilocin Derivatives for Enhanced Therapeutic Applications.
authors: Kargbo RB.
publication_date: 2024-11-10
doi: 10.1021/acsmedchemlett.4c00521
pubmed_id: 39691529
source_url: https://doi.org/10.1021/acsmedchemlett.4c00521
substance_tags: psilocybin,psilocin
topic_tags: Depression,Chronic Pain,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 11:22:00
abstract:
Psychedelic compounds, particularly psilocybin and psilocin, have shown significant therapeutic potential in treating neurological and psychiatric disorders. However, their bioavailability, rapid metabolism, and stability challenges have limited their clinical use. This Patent Highlight reviews recent innovations in psychedelic drug delivery systems and the development of psilocin analogs aimed at improving their pharmacokinetic and pharmacodynamic profiles. Three patents-focused on controlled-release delivery systems, ester analogs, and acetal/ketal derivatives-present novel approaches to enhancing the stability, bioavailability, and efficacy of psilocin and related compounds. These advancements promise more effective treatments for conditions such as depression, chronic pain, and neurodegenerative diseases.

raw_json:
{"europe_pmc_id":"39691529","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Kargbo RB.
publication_date: 2024-11-10
doi: 10.1021/acsmedchemlett.4c00519
pubmed_id: 39691516
source_url: https://doi.org/10.1021/acsmedchemlett.4c00519
substance_tags: psilocin
topic_tags: Depression,Anxiety,Addiction,Review Article,Animal 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 11:22:03
title:
Advances in Psychedelic Therapeutics: Novel Prodrugs and Derivatives for Enhanced Mental Health Treatment.

abstract:
Recent innovations in psychedelic research have led to the development of novel compounds designed to enhance the therapeutic potential of psilocin and related tryptamines. This Patent Highlight reviews three essential patents that focus on improving the stability, bioavailability, and efficacy of these compounds for treating mental health disorders such as depression, anxiety, and substance use disorders. The compounds-4-pivaloyloxy-N-methyltryptammonium chloride, alkyl quaternary ammonium tryptamines, and 4-pivaloyloxy-N-methyltryptammonium derivatives-represent significant advancements in the field of psychedelic-assisted therapy. These innovations offer new hope for more reliable and effective treatments, particularly in addressing the limitations associated with traditional psychedelics. The findings from preclinical studies support the potential of these compounds to play a vital role in the treatment of mental and neurological disorders.

raw_json:
{"europe_pmc_id":"39691516","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Legal and Ethics Concerns of Psilocybin as Medicine.
authors: Schonholz SM, Appel JM, Bursztajn HJ, Nair M, MacIntyre MR.
publication_date: 2024-12-11
doi: 10.29158/jaapl.240089-24
pubmed_id: 39562046
source_url: https://doi.org/10.29158/jaapl.240089-24
substance_tags: psilocybin
topic_tags: Review Article
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:00
abstract:
Preliminary research shows the psychedelic psilocybin to be a promising potential treatment for psychiatric illnesses. Recent U.S. government legislation and policy indicate that access to psilocybin, which remains illegal on the federal level despite increasing efforts to decriminalize it at the state and local levels, will be expanded to enable further research into its treatment potential. It remains unclear how psilocybin will be regulated and who will have access to this new treatment, raising important legal and ethics questions psychiatrists must consider. This article reviews the current legal regulation of psilocybin and matters related to standard of care, right to effective treatment, and the respectable minority doctrine. It concludes with a discussion of the ethics matters surrounding the use of psilocybin as medicine, including provider bias, the interpersonal dynamic between providers and patients, informed consent, and equity and access.

keywords:
Humans, Hallucinogens, Mental Disorders, Informed Consent, Health Services Accessibility, United States, Psilocybin

raw_json:
{"europe_pmc_id":"39562046","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Wahba M, Hayes C, Kletter M, McAllister-Williams RH.
publication_date: 2024-12-09
doi: 10.1192/bjo.2024.768
pubmed_id: 39654264
source_url: https://doi.org/10.1192/bjo.2024.768
substance_tags: psilocybin
topic_tags: Depression,Clinical Trial,Case Report,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:
Worsening suicidal ideation and prolonged adverse event following psilocybin administration in a clinical setting: case report and thematic analysis of one participant's experience.

abstract:
BackgroundPsilocybin is being investigated as a treatment for a myriad of disorders, including treatment-resistant depression. The main focus has been on positive effects, with little attention paid to negative outcomes, especially in clinical settings. Quantitative methodology limits further exploration of such events and can also miss improvements not captured on rating scales.AimsTo highlight potential adverse events of psilocybin and underline limits of quantitative methodology, calling for process evaluations alongside clinical trials.Case presentationThis is a case of a participant in a phase 2b clinical trial of psilocybin for treatment-resistant depression who presented with increased suicidal ideation and a prolonged period of severely restricted eating following administration, leading to a period of destabilisation and a need for support. Despite the difficulties encountered and the participant's limited improvement on rating scales, she found the experience to have been helpful and led her to make changes to her life which she found beneficial. She described her experience in a written account to the authors.MethodThe case was summarised and the written account was thematically analysed and synthesised into a logic model.ConclusionsPsilocybin could lead to temporary worsening of suicidal ideation and instigate prolonged adverse events that outlast its acute effects. Paradoxically, it could simultaneously lead to an improvement in functional outcomes which is not clear on depression rating scales. This calls for a qualitative exploration of serious adverse events and participant accounts to deepen our understanding of the psilocybin experience and its different outcomes.

raw_json:
{"europe_pmc_id":"39654264","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Brett J, Knock E, Watson K, Albert S, Siefried KJ, Guss J.
publication_date: 2024-12-05
doi: 10.3389/fpsyt.2024.1490907
pubmed_id: 39713770
source_url: https://doi.org/10.3389/fpsyt.2024.1490907
substance_tags: psilocybin
topic_tags: Addiction,Aging,Emotional Processing,Clinical Trial,Case Report,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 11:22:01
title:
Psilocybin-assisted psychotherapy for methamphetamine dependence: a case report involving daily methamphetamine use.

abstract:
Methamphetamine (MA) dependence leads to severe physical and psychological issues. Current treatments, including psychosocial therapies and residential rehabilitation, face limitations such as high relapse rates, cost, and accessibility issues. As a result, there is an urgent need for novel approaches to treat MA dependence that are effective, affordable, and accessible to patients. Psilocybin, the active component in numerous mushrooms of the Psilocybe genus, has shown potential for enhancing psychotherapy for various addiction and mental health issues due to its effects on perception, cognition, and affect. Psilocybin-assisted psychotherapy (PAT) has demonstrated initial safety and efficacy in treating alcohol, cocaine, and nicotine dependence. The case presented here describes a 36-year-old transwoman and daily MA user, who participated in a single-arm open-label clinical trial assessing feasibility and safety of PAT for MA dependence at St. Vincent's Hospital, Sydney. Following inpatient withdrawal management and one session of psilocybin-assisted therapy, she experienced significant cognitive and emotional shifts and sustained MA abstinence. She reported improved mental health over 3 months following treatment completion. She also noted increased self-esteem, mindfulness, and distress tolerance. This study suggests that PAT (following inpatient MA withdrawal management) may offer a scalable, safe, and effective approach for treating MA dependence. However, further research is required to confirm the generalisability and efficacy of PAT for broader populations of people using MA. It is encouraging that this participant, a daily MA user, showed improvements in mood and cognition, in addition to abstinence from MA.

raw_json:
{"europe_pmc_id":"39713770","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Noah S, Shen M, Erowid E, Erowid F, Silver M.
publication_date: 2024-12-05
doi: 10.3389/fpsyg.2024.1397064
pubmed_id: 39712538
source_url: https://doi.org/10.3389/fpsyg.2024.1397064
substance_tags: psilocybin
topic_tags: Aging,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:
A novel method for quantitative analysis of subjective experience reports: application to psychedelic visual experiences.

abstract:
IntroductionPsychedelic compounds such as LSD, psilocybin, mescaline, and DMT can dramatically alter visual perception. However, the extent to which visual effects of psychedelics consistently vary for different substances is an open question. The visual effects of a given psychedelic compound can range widely both across and within individuals, so datasets with large numbers of participants and descriptions of qualitative effects are required to adequately address this question with the necessary sensitivity.MethodsHere we present an observational study with narrative self-report texts, leveraging the massive scale of the Erowid experience report dataset. We analyzed reports associated with 103 different psychoactive substances, with a median of 217 reports per substance. Thirty of these substances are standardly characterized as psychedelics, while 73 substances served as comparison substances. To quantitatively analyze these semantic data, we associated each sentence in the self-report dataset with a vector representation using an embedding model from OpenAI, and then we trained a classifier to identify which sentences described visual effects, based on the sentences' embedding vectors.ResultsWe observed that the proportion of sentences describing visual effects varies significantly and consistently across substances, even within the group of psychedelics. We then analyzed the distributions of psychedelics' visual effect sentences across different categories of effects (for example, movement, color, or pattern), again finding significant and consistent variation.DiscussionOverall, our findings indicate reliable variation across psychedelic substances' propensities to affect vision and in their qualitative effects on visual perception.

raw_json:
{"europe_pmc_id":"39712538","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2024-12-04
doi: 10.1038/s41398-024-03189-z
pubmed_id: 39639028
source_url: https://doi.org/10.1038/s41398-024-03189-z
substance_tags: psilocybin
topic_tags: Addiction,Mechanism of Action,Receptor Pharmacology,Biomarkers,Animal Study
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:04
last_checked: 2026-07-01 11:22:03
title:
Prefrontal electrophysiological biomarkers and mechanism-based drug effects in a rat model of alcohol addiction.

authors:
Habelt B, Afanasenkau D, Schwarz C, Domanegg K, Kuchar M, Werner C, Minev IR, Spanagel R, Meinhardt MW, Bernhardt N.

abstract:
Patients with alcohol use disorder (AUD) who seek treatment show highly variable outcomes. A precision medicine approach with biomarkers responsive to new treatments is warranted to overcome this limitation. Promising biomarkers relate to prefrontal control mechanisms that are severely disturbed in AUD. This results in reduced inhibitory control of compulsive behavior and, eventually, relapse. We reasoned here that prefrontal dysfunction, which underlies vulnerability to relapse, is evidenced by altered neuroelectric signatures and should be restored by pharmacological interventions that specifically target prefrontal dysfunction. To test this, we applied our recently developed biocompatible neuroprosthesis to measure prefrontal neural function in a well-established rat model of alcohol addiction and relapse. We monitored neural oscillations and event-related potentials in awake alcohol-dependent rats during abstinence and following treatment with psilocybin or LY379268, agonists of the serotonin 2A receptor (5-HT2AR), and the metabotropic glutamate receptor 2 (mGluR2), that are known to reduce prefrontal dysfunction and relapse. Electrophysiological impairments in alcohol-dependent rats are reduced amplitudes of P1N1 and N1P2 components and attenuated event-related oscillatory activity. Psilocybin and LY379268 were able to restore these impairments. Furthermore, alcohol-dependent animals displayed a dominance in higher beta frequencies indicative of a state of hyperarousal that is prone to relapse, which particularly psilocybin was able to counteract. In summary, we provide prefrontal markers indicative of relapse and treatment response, especially for psychedelic drugs.

keywords:
Prefrontal Cortex, Animals, Rats, Alcoholism, Disease Models, Animal, Amino Acids, Receptors, Metabotropic Glutamate, Evoked Potentials, Male, Biomarkers, Bridged Bicyclo Compounds, Heterocyclic, Psilocybin

raw_json:
{"europe_pmc_id":"39639028","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Terao I, Kodama W.
publication_date: 2024-12-03
doi: 10.1002/pcn5.70042
pubmed_id: 39641126
source_url: https://doi.org/10.1002/pcn5.70042
substance_tags: psilocybin
topic_tags: Depression,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 11:22:01
title:
Comparative antidepressant effects and safety of intravenous racemic ketamine, psilocybin and theta burst stimulation for major depressive disorder: A systematic review and network meta-analyses of randomized controlled trials.

abstract:
The individual efficacy and safety of intravenous racemic (IV) ketamine, psilocybin, and theta burst stimulation (TBS) for major depressive disorder have been demonstrated through meta-analyses of randomized controlled trials (RCTs), but the comparative usefulness of these novel treatments has not yet been fully examined. We systematically searched the CENTRAL, Medline, CINHAL, and ClinicalTrials.gov databases for randomized controlled trials up to July 4, 2024. Random-effects network meta-analyses were conducted to compare the Comparative antidepressant effects and safety of intravenous racemic ketamine, psilocybin and theta burst stimulation for major depressive disorderantidepressant efficacy, tolerability, and acceptability of IV ketamine, psilocybin, and TBS. Twenty-eight RCTs were included. All treatments were superior to placebo, with IV ketamine and psilocybin showing significantly greater antidepressant efficacy than TBS. No significant differences were detected between all treatments and placebo in tolerability and acceptability. In a subgroup analysis focusing on short periods of 1 week or less, only IV ketamine was significantly more effective than placebo. In another subgroup analysis focusing on periods of 4 weeks or longer, IV ketamine and psilocybin showed significantly better antidepressant effects than placebo. The confidence in the evidence ranged from very low to moderate. Specifically, there is a scarcity of studies on psilocybin and a lack of direct comparison trials. The findings suggest that IV ketamine and psilocybin may be more effective treatments compared to TBS. Additionally, IV ketamine may have an advantage in terms of rapid onset of action. The number of included studies is limited, especially for psilocybin, and therefore the current findings are preliminary, necessitating further accumulation of direct-comparison RCTs.

raw_json:
{"europe_pmc_id":"39641126","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Shinozuka K, Jerotic K, Mediano P, Zhao AT, Preller KH, Carhart-Harris R, Kringelbach ML.
publication_date: 2024-12-03
doi: 10.1038/s41398-024-03187-1
pubmed_id: 39632810
source_url: https://doi.org/10.1038/s41398-024-03187-1
substance_tags: psilocybin,psilocin
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:
Synergistic, multi-level understanding of psychedelics: three systematic reviews and meta-analyses of their pharmacology, neuroimaging and phenomenology.

abstract:
Serotonergic psychedelics induce altered states of consciousness and have shown potential for treating a variety of neuropsychiatric disorders, including depression and addiction. Yet their modes of action are not fully understood. Here, we provide a novel, synergistic understanding of psychedelics arising from systematic reviews and meta-analyses of three hierarchical levels of analysis: (1) subjective experience (phenomenology), (2) neuroimaging and (3) molecular pharmacology. Phenomenologically, medium and high doses of LSD yield significantly higher ratings of visionary restructuralisation than psilocybin on the 5-dimensional Altered States of Consciousness Scale. Our neuroimaging results reveal that, in general, psychedelics significantly strengthen between-network functional connectivity (FC) while significantly diminishing within-network FC. Pharmacologically, LSD induces significantly more inositol phosphate formation at the 5-HT2A receptor than DMT and psilocin, yet there are no significant between-drug differences in the selectivity of psychedelics for the 5-HT2A, 5-HT2C, or D2 receptors, relative to the 5-HT1A receptor. Our meta-analyses link DMT, LSD, and psilocybin to specific neural fingerprints at each level of analysis. The results show a highly non-linear relationship between these fingerprints. Overall, our analysis highlighted the high heterogeneity and risk of bias in the literature. This suggests an urgent need for standardising experimental procedures and analysis techniques, as well as for more research on the emergence between different levels of psychedelic effects.

keywords:
Brain, Humans, Dimethoxyphenylethylamine, Lysergic Acid Diethylamide, Hallucinogens, Neuroimaging, Psilocybin

topic_tags:
Depression,Addiction,Brain Imaging,Pharmacology,Receptor Pharmacology,Consciousness,Aging,Systematic Review,Review Article,Safety

raw_json:
{"europe_pmc_id":"39632810","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Protective Behavioral Strategies for Psychedelic Use: A Mini Review of the Evidence.
authors: Piercey CJ, Gray B, Sung A, Henry D, Karoly HC.
publication_date: 2024-12-01
doi: 10.1089/psymed.2023.0052
pubmed_id: 40051484
source_url: https://doi.org/10.1089/psymed.2023.0052
substance_tags: psilocybin
topic_tags: 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:
BackgroundApproximately 8.5 million Americans over the age of 12 endorsed past year psychedelic use in 2022, with 1.4 million individuals initiating use during this time. Although emerging evidence indicates there may be beneficial aspects of psychedelic use, there is a need to understand how individuals might mitigate potential risks within nonclinical contexts, such as through the use of protective behavioral strategies (PBS).MethodPubMed and Google Scholar databases were searched to identify articles reporting on PBS (i.e., harm reduction strategies implemented at the individual level) for psychedelic use within nonclinical contexts. We include articles pertaining to both classical serotonergic psychedelics (e.g., lysergic acid diethylamide [LSD], psilocybin) and nonclassical psychedelics (e.g., 3,4-methylenedioxymethamphetamine [MDMA], ketamine).ResultsAlthough research on psychedelic PBS use is limited, evidence suggests a culture of harm reduction present within psychedelic communities. Psychedelic PBS identified in the literature include strategies related to drug acquisition, dosing, set and setting, bodily nourishment, planning for and working through challenging experiences, and integration of psychedelic experiences. Few studies have examined the relationship between psychedelic PBS use and outcomes, but emerging evidence suggests that psychedelic PBS use may be associated with decreased consequences.ConclusionThere is a need to continue developing and validating measures of psychedelic PBS and outcomes for use within research and intervention settings. Additional research examining associations between psychedelic PBS use and outcomes is also critical to best serving the needs of individuals who use psychedelics within nonclinical contexts.

raw_json:
{"europe_pmc_id":"40051484","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Back A, Myers S, Guy J, Perez J, Lazar Thorn L, McGregor B.
publication_date: 2024-12-01
doi: 10.1089/psymed.2023.0069
pubmed_id: 40051480
source_url: https://doi.org/10.1089/psymed.2023.0069
substance_tags: psilocybin
topic_tags: 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 11:22:01
title:
Evolving Guidelines for the Use of Touch During a Clinical Trial of Group Psilocybin-Assisted Therapy.

abstract:
For a new clinical trial testing a group retreat-based format of psilocybin-assisted therapy, our research team created an initial set of practice guidelines that aimed to describe facilitator use of touch in a way that is ethical, supportive, and minimizes harm. In our first three retreats, however, we had two unexpected experiences with touch that led us to iterate our initial guidelines into a new version of guidelines. In this Technical Report, we describe our evolving guidelines specifying acceptable practices for facilitator use of touch to ensure a safe, supportive, and therapeutic participant experience. Our primary goal with these guidelines is to create a haptic experience during the psilocybin session that reinforces the participants' sense of safety and supports their own experience during the psilocybin session. Our secondary goal is to allow the facilitator team to notice and maintain therapeutic boundaries and to respond to participant experiences with empathy and openness in the context of those boundaries (Clinical Trials No: NCT05847686).

raw_json:
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abstract: [This corrects the article DOI: 10.1089/psymed.2022.0002.].
publication_date: 2024-12-01
doi: 10.1089/psymed.2022.0002.correx
pubmed_id: 40045987
source_url: https://doi.org/10.1089/psymed.2022.0002.correx
substance_tags: psilocybin
topic_tags: Depression
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
title:
Correction to: A Bayesian Reanalysis of a Trial of Psilocybin Versus Escitalopram for Depression by Nayak, et al. Psychedelic Med 2023;1(1):18-26; doi: 10.1089/psymed.2022.0002.

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publication_date: 2024-12-01
doi: 10.1001/jamanetworkopen.2024.49026
pubmed_id: 39636638
source_url: https://doi.org/10.1001/jamanetworkopen.2024.49026
substance_tags: psilocybin
topic_tags: Depression,PTSD,Clinical Trial,Healthcare Workers
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Psilocybin Therapy for Clinicians With Symptoms of Depression From Frontline Care During the COVID-19 Pandemic: A Randomized Clinical Trial.

authors:
Back AL, Freeman-Young TK, Morgan L, Sethi T, Baker KK, Myers S, McGregor BA, Harvey K, Tai M, Kollefrath A, Thomas BJ, Sorta D, Kaelen M, Kelmendi B, Gooley TA.

abstract:
ImportanceThe psychological morbidity experienced by physicians, advanced practice practitioners (APPs), and nurses from working during the COVID-19 pandemic includes burnout, depression, and posttraumatic stress disorder (PTSD).ObjectiveTo investigate whether psilocybin therapy could improve symptoms of depression, burnout, and PTSD in US clinicians who developed these symptoms from frontline clinical work during the pandemic.Design, setting, and participantsThis double-blind randomized clinical trial enrolled participants from February to December 2022. Participants included physicians, APPs, and nurses who provided frontline care for more than 1 month during the pandemic and had no prepandemic mental health diagnoses but had moderate or severe symptoms of depression at enrollment. Participants were randomly assigned to either the psilocybin or niacin arm. Data analysis was conducted between December 2023 and May 2024 and was based on the intention-to-treat principle.InterventionOne intervention episode consisted of 2 preparation visits, 1 medication session, and 3 integration visits. At the medication session, participants received psilocybin, 25 mg, or niacin, 100 mg, orally.Main outcome and measuresThe primary outcome was a change from baseline (preparation 1 session) to day 28 (after medication administration) in symptoms of depression as measured by the clinician-administered Montgomery-Asberg Depression Rating Scale (MADRS) used by blinded raters. The secondary outcomes were a change in symptoms of burnout (measured with the Stanford Professional Fulfillment Index [SPFI]) and symptoms of PTSD (measured with the Posttraumatic Stress Disorder Checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition [PCL-5]).ResultsA total of 30 clinicians (15 females [50%]; mean [range] age, 38 [29-60] years) participated, of whom 15 were randomly assigned to receive psilocybin and 15 to receive niacin. The mean change in symptoms of depression (MADRS scores) from preparation 1 session to day 28 was -21.33 (7.84) in the psilocybin arm compared with -9.33 (7.32) in the niacin arm, with a mean difference between arms of -12.00 (95% CI, -17.67 to -6.33; P

keywords:
Humans, Hallucinogens, Treatment Outcome, Double-Blind Method, Depression, Burnout, Professional, Stress Disorders, Post-Traumatic, Adult, Middle Aged, Female, Male, Pandemics, Psilocybin, COVID-19

raw_json:
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authors: Enriquez-Geppert S, Krc J, O'Higgins FJ, Lietz M.
publication_date: 2024-10-20
doi: 10.1098/rstb.2023.0095
pubmed_id: 39428872
source_url: https://doi.org/10.1098/rstb.2023.0095
substance_tags: psilocybin
topic_tags: Neuroplasticity,Mechanism of Action,Aging,Microdosing
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Psilocybin-assisted neurofeedback for the improvement of executive functions: a randomized semi-naturalistic-lab feasibility study.

abstract:
Executive function deficits, common in psychiatric disorders, hinder daily activities and may be linked to diminished neural plasticity, affecting treatment and training responsiveness. In this pioneering study, we evaluated the feasibility and preliminary efficacy of psilocybin-assisted frontal-midline theta neurofeedback (NF), a neuromodulation technique leveraging neuroplasticity, to improve executive functions (EFs). Thirty-seven eligible participants were randomized into an experimental group (n = 18) and a passive control group (n = 19). The experimental group underwent three microdose sessions and then three psilocybin-assisted NF sessions, without requiring psychological support, demonstrating the approach's feasibility. NF learning showed a statistical trend for increases in frontal-midline theta from session to session with a large effect size and non-significant but medium effect size dynamical changes within sessions. Placebo effects were consistent across groups, with no tasks-based EF improvements, but significant self-reported gains in daily EFs-working memory, shifting, monitoring and inhibition-showing medium and high effect sizes. The experimental group's significant gains in their key training goals underscored the approach's external relevance. A thorough study with regular sessions and an active control group is crucial to evaluate EFs improvement and their specificity in future. Psilocybin-enhanced NF could offer significant, lasting benefits across diagnoses, improving daily functioning. This article is part of the theme issue 'Neurofeedback: new territories and neurocognitive mechanisms of endogenous neuromodulation'.

keywords:
Humans, Feasibility Studies, Adult, Female, Male, Young Adult, Executive Function, Neurofeedback, Psilocybin

raw_json:
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authors: Hudspeth J, Rogge K, Wagner T, Müll M, Hoffmeister D, Rupp B, Werten S.
publication_date: 2024-11-08
doi: 10.1002/cbic.202400497
pubmed_id: 39413044
source_url: https://doi.org/10.1002/cbic.202400497
substance_tags: psilocybin
topic_tags: Epigenetics
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
title:
The Second Methylation in Psilocybin Biosynthesis Is Enabled by a Hydrogen Bonding Network Extending into the Secondary Sphere Surrounding the Methyltransferase Active Site.

abstract:
The Psilocybe cubensis SAM-dependent methyltransferase, PsiM, catalyzes the last step in the biosynthesis of psilocybin. Likely evolved from monomethylating RNA methyltransferases, PsiM acquired a key amino acid exchange in the secondary sphere of the active site, M247 N, which is responsible for its capacity to dimethylate. Two variants, PsiMN247M and PsiMN247A, were generated to further examine the role of Asn247 for mono- and dimethylation in PsiM. Herein, we present the kinetic profiles of both variants and crystal structures at resolutions between 0.9 and 1.0 Å. Each variant was crystallized as a ternary complex with the non-methylated acceptor substrate, norbaeocystin and S-adenosyl-l-homocysteine, and in a second complex with the cofactor analog, sinefungin, and the monomethylated substrate, baeocystin. Consistent with the inability of the variants to catalyze a second methyl transfer, these structures reveal catalytically non-productive conformations and a high level of disorder of the methylamine group of baeocystin. Additionally, both variants exhibit destabilization in the β5-β7 sheets and a conserved β-turn of the core Rossmann fold, causing 20-fold reduced substrate binding and 2-fold lower catalytic efficiency even with norbaeocystin. Our structural and kinetic analyses of the variants suggest that Asn247 is essential to allow enough space in the active site for multiple methylations while also participating in a network of hydrogen bonds that stabilizes secondary structure elements in the immediate vicinity of the active site for optimal methylation of norbaeocystin.

keywords:
Methyltransferases, Crystallography, X-Ray, Catalytic Domain, Methylation, Kinetics, Hydrogen Bonding, Models, Molecular, Psilocybe, Psilocybin

raw_json:
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title: Narrative review of the potential for psychedelics to treat Prolonged Grief Disorder.
authors: Ehrenkranz R, Agrawal M, Penberthy JK, Yaden DB.
publication_date: 2024-05-22
doi: 10.1080/09540261.2024.2357668
pubmed_id: 39980217
source_url: https://doi.org/10.1080/09540261.2024.2357668
keywords: Humans, Hallucinogens, Grief, Stress Disorders, Post-Traumatic, Psilocybin
substance_tags: psilocybin
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:03
abstract:
Prolonged Grief Disorder (PGD) is distinct from yet related to non-pathologic grief, depression, addiction, and Post-Traumatic Stress Disorder (PTSD) with a prevalence of up to 10% in bereaved populations. Hallmarks of PGD include functional impairment a year or more post-bereavement and intense yearning for the deceased. Current treatments for PGD are typically psychological rather than psychopharmacological, and more treatment options are needed. Psychedelics such as psilocybin and MDMA may be a promising treatment avenue for PGD. Randomized clinical trials demonstrated the efficacy of psilocybin in reducing symptom severity in depression and MDMA in reducing PTSD symptomatology. Furthermore, psychedelics often produce subjective effects (such as transcendence, mystical experiences, and a sense of oneness) that may be uniquely relevant to the existential distress experienced in PGD. No randomized clinical trials have thus far been conducted on the safety and efficacy of psychedelics for PGD. Initial research, including survey-based studies and an open-label trial, has begun to shed light on the possible benefits of psychedelics in the alleviation of grief. While the evidence from these studies is preliminary, it suggests a consistent trend towards the effectiveness of psychedelics in grief reduction. Conducting a randomized clinical trial would be an appropriate next step to explore the potential efficacy of using psychedelics to treat PGD.

topic_tags:
Depression,PTSD,Addiction,Mystical Experience,Clinical Trial,Review Article,Observational Study,Safety

raw_json:
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title: Wood-loving magic mushrooms from Australia are saprotrophic invaders in the Northern Hemisphere.
publication_date: 2024-07-18
doi: 10.3114/fuse.2024.14.14
pubmed_id: 39830294
source_url: https://doi.org/10.3114/fuse.2024.14.14
substance_tags: psilocybin
topic_tags: Neuroplasticity,Genomics
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:03
authors:
McTaggart AR, Scarlett K, Slot JC, Barlow C, Appleyard C, Gardiner DM, Fechner N, Tilden J, Hass D, Voogelbreinder S, Lording WJ, Lloyd RA, Shuey LS, Drenth A, James TY.

abstract:
Magic mushrooms are fungi that produce psilocybin, an entheogen with long-term cultural use and a breakthrough compound for treatment of mental health disorders. Fungal populations separated by geography are candidates for allopatric speciation, yet species connectivity typically persists because there is minimal divergence at functional parts of mating compatibility genes. We studied whether connectivity is maintained across populations of a widespread species complex of magic mushrooms that has infiltrated the Northern Hemisphere from a hypothesised centre of origin in Australasia. We analysed 89 genomes of magic mushrooms to examine erosion of species connectivity in disparate populations with support from gene flow, kinship, structure, allelic diversity, and mating compatibility. We used comparative genomics and synteny to test whether the genes that produce psilocybin are under selection in natural populations of magic mushrooms. Despite phenotypic plasticity and intercontinental distribution, sexual compatibility is maintained across geographically isolated populations of magic mushrooms. Psilocybin loci have high allelic diversity and evidence of balancing selection. Australasia is the centre of origin of wood-degrading magic mushrooms and geographically separated populations are fully sexually compatible, despite minimal gene flow since differentiation from a shared ancestor. Movement of woodchips, mulch, or plants has most likely facilitated invasion of these mushrooms in the Northern Hemisphere. Citation: McTaggart AR, Scarlett K, Slot JC, Barlow C, Appleyard C, Gardiner DM, Fechner N, Tilden J, Hass D, Voogelbreinder S, Lording WJ, Lloyd RA, Shuey LS, Drenth A, James TY (2024). Wood-loving magic mushrooms from Australia are saprotrophic invaders in the Northern Hemisphere. Fungal Systematics and Evolution 14: 209-217. doi: 10.3114/fuse.2024.14.14.

raw_json:
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title: Psilocybin and hallucinogenic mushrooms.
authors: Fradet M, Kelly CM, Donnelly AJ, Suppes T.
publication_date: 2024-11-30
doi: 10.1017/s1092852924002487
pubmed_id: 39789676
source_url: https://doi.org/10.1017/s1092852924002487
keywords: Humans, Agaricales, Hallucinogens, Psilocybin
substance_tags: psilocybin
topic_tags: Depression,Pharmacology,Aging,Safety
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:00
abstract:
Psilocybin therapy has recently emerged as a promising new treatment for depression and other mental health disorders. This chapter summarizes the most recent data on its safety and efficacy. The delivery of psilocybin therapy and its subjective effects are also presented. Furthermore, this chapter outlines our current understanding of psilocybin's pharmacology and neurobiological effects. Other similar psychedelic substances with encouraging therapeutic potential are briefly presented.

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publication_date: 2024-12-09
doi: 10.1017/s1092852924002268
pubmed_id: 39655426
source_url: https://doi.org/10.1017/s1092852924002268
keywords: Humans, Hallucinogens, Anxiety Disorders, Psychotherapy, Psilocybin
substance_tags: psilocybin
topic_tags: Depression,Anxiety,PTSD,Addiction,OCD,Review Article,Safety
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
The revival of psilocybin between scientific excitement, evidence of efficacy, and real-world challenges.

authors:
Scala M, Fabbri C, Fusar-Poli P, Di Lorenzo G, Ferrara M, Amerio A, Fusar-Poli L, Pichiecchio A, Asteggiano C, Menchetti M, De Ronchi D, MNESYS - Mood and Psychosis Sub-Project (Spoke 5), Fanelli G, Serretti A.

abstract:
The revival of psilocybin in psychopharmacological research heralds a potential paradigm shift for treating mood and anxiety disorders, and other psychiatric conditions beyond the psychotic spectrum. This critical review evaluates current evidence on psilocybin's efficacy, juxtaposing potential benefits with the practical aspects of psychedelic-assisted psychotherapy (PAP) and the methodological constraints of existing research.An electronic literature search was conducted using PubMed/MEDLINE, selecting studies published up to December 2023 that explored the clinical use of psilocybin in mood and anxiety disorders, obsessive-compulsive disorder, post-traumatic stress disorder, and substance use disorder. Despite promising preliminary results suggesting psilocybin's efficacy in alleviating depression and anxiety, as well as obsessions, compulsions, and addictive behaviors, significant evidence gaps persist. These include evaluating the efficacy of psilocybin compared to standard antidepressants or anxiolytic molecules and identifying patient subpopulations that might benefit most from PAP. Concerns about psilocybin's safety, long-term efficacy, and optimal dosage remain unclear due to previous trials' limitations. Real-world implementation faces challenges, including infrastructural requirements, personnel training, and unresolved legal and ethical issues. This paper argues for further research to substantiate the evidence base, emphasizing the need for larger studies that overcome current methodological limitations and explore psilocybin's full therapeutic potential. While psilocybin holds promise for psychiatry, its successful translation from research to clinical practice demands more robust evidence on efficacy, safety, and methodological rigor. In addition, other factors, such as cultural stigma and legal/ethical issues, need to be successfully addressed to facilitate psilocybin's implementation in healthcare systems.

raw_json:
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authors: de Jonge D, van der Meer PB, Kramers C, Schellekens A.
publication_date: 2024-11-28
doi: 10.1007/s11920-024-01567-4
pubmed_id: 39612154
source_url: https://doi.org/10.1007/s11920-024-01567-4
substance_tags: psilocybin
topic_tags: Depression,Addiction,Meta-Analysis,Review Article
study_type: Meta-Analysis
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
title:
Psychedelic Research for Alcohol Use Disorder with Comorbid Major Depressive Disorder: An Unmet Need.

abstract:
Purpose of reviewIn this narrative review, we discuss evidence for psilocybin- and LSD-assisted treatment of alcohol use disorder (AUD) and major depressive disorder (MDD). We describe limitations of psychedelic research and posit methodological considerations when designing a trial in patients with both disorders.Recent findingsIn AUD, a growing evidence base for psilocybin treatment shows a promising beneficial and sustained effect on measures of drinking frequency. In MDD, a recent meta-analysis has demonstrated that psilocybin therapy provides a large and consistent reduction in depressive symptoms compared to no treatment. Co-occurrence of MDD and AUD is quite prevalent, and this comorbidity exacerbates symptomatology of the two individual disorders and complicates their treatment. Theoretically, patients presenting with both AUD and MDD would benefit from an integrated therapy that could treat MDD and AUD simultaneously. We believe that more research into the efficacy of psilocybin in patients with both AUD and MDD is warranted and justified.

keywords:
Humans, Alcoholism, Lysergic Acid Diethylamide, Hallucinogens, Comorbidity, Psilocybin, Major Depressive Disorder

raw_json:
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title: Psychedelics for the Treatment of Obsessive-Compulsive Disorder: Efficacy and Proposed Mechanisms.
authors: Collins HM.
publication_date: 2024-11-30
doi: 10.1093/ijnp/pyae057
pubmed_id: 39611453
source_url: https://doi.org/10.1093/ijnp/pyae057
keywords: Animals, Humans, Hallucinogens, Treatment Outcome, Obsessive-Compulsive Disorder, Psilocybin
substance_tags: psilocybin
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
abstract:
Psychedelics are emerging as potential treatments for a range of mental health conditions, including anxiety and depression, treatment-resistant depression, and substance use disorders. Recent studies have also suggested that the psychedelic psilocybin may be able to treat obsessive-compulsive disorder (OCD). Since the 1960s, case studies have reported improvements to obsessive and compulsive behaviors in patients taking psychedelics recreationally. The effects of psilocybin were then systematically assessed in a small, open-label trial in 2006, which found that psilocybin significantly reduced the symptoms of OCD. Reduced compulsive behaviors have also been seen in rodent models of OCD after administration of psilocybin. Nonetheless, the mechanisms underlying the effects of psychedelics for OCD are unclear, with hypotheses including their acute pharmacological effects, changes in neuroplasticity and resting state neural networks, and their psychological effects. This review will evaluate the evidence supporting the theory that psychedelics can be used for the treatment of OCD, as well as the data regarding claims about their mechanisms. It will also discuss issues with the current evidence and the ongoing trials of psilocybin that aim to address these knowledge gaps.

topic_tags:
Depression,Anxiety,Addiction,OCD,Neuroplasticity,Mechanism of Action,Review Article,Treatment-Resistant Depression

raw_json:
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authors: Marwood L, Croal M, Mistry S, Simmons H, Tsai J, Young MB, Goodwin GM.
publication_date: 2024-10-10
doi: 10.1016/j.jpsychires.2024.10.009
pubmed_id: 39427449
source_url: https://doi.org/10.1016/j.jpsychires.2024.10.009
substance_tags: psilocybin
topic_tags: Depression,Clinical Trial,Randomized Controlled Trial,Treatment-Resistant Depression
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:00
title:
The impact of antidepressant discontinuation prior to treatment with psilocybin for treatment-resistant depression.

abstract:
It has been suggested that the recent use and discontinuation of antidepressant drugs compromises the action of psilocybin. As evidence is only available from small or uncontrolled samples, this post hoc analysis investigated this using data from the largest, phase II, randomized controlled trial of psilocybin treatment to date. Data from 233 participants with treatment-resistant depression (TRD) who received 25 mg, 10 mg, or 1 mg of investigational drug COMP360 psilocybin (a proprietary, pharmaceutical-grade synthetic psilocybin formulation, developed by the sponsor, Compass Pathfinder Ltd.), administered with psychological support, were compared for groups of participants who either discontinued one or more antidepressant drugs during screening or entered the trial antidepressant drug free. Measures of depression symptom severity change during the antidepressant drug discontinuation period, baseline suicidality, acute subjective psychedelic effects, and the study's primary endpoint (change in depression symptom severity between Baseline and Week 3) are described for both groups. Antidepressant drug discontinuation was not related to worsening of depression severity before Baseline. Suicidality was comparable between groups at Baseline. Psilocybin treatment efficacy and the subjective psychedelic experience did not appear to be compromised by antidepressant drug discontinuation. Thus, it does not limit the feasibility of psilocybin treatment for the future. These findings also support the overall homogeneity of our findings with psilocybin treatment as a monotherapy for TRD. The prior contradictory reports may come to appear misleading.

keywords:
Humans, Hallucinogens, Antidepressive Agents, Treatment Outcome, Double-Blind Method, Psychiatric Status Rating Scales, Dose-Response Relationship, Drug, Adult, Middle Aged, Female, Male, Suicidal Ideation, Depressive Disorder, Treatment-Resistant, Psilocybin

raw_json:
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authors: Szpręgiel I, Bysiek A.
publication_date: 2024-10-15
doi: 10.1007/s43440-024-00660-y
pubmed_id: 39412581
source_url: https://doi.org/10.1007/s43440-024-00660-y
substance_tags: psilocybin
topic_tags: Depression,Neuroplasticity,Mechanism of Action,Receptor Pharmacology,Review Article,Animal Study
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:00
title:
Psilocybin and the glutamatergic pathway: implications for the treatment of neuropsychiatric diseases.

abstract:
In recent decades, psilocybin has gained attention as a potential drug for several mental disorders. Clinical and preclinical studies have provided evidence that psilocybin can be used as a fast-acting antidepressant. However, the exact mechanisms of action of psilocybin have not been clearly defined. Data show that psilocybin as an agonist of 5-HT2A receptors located in cortical pyramidal cells exerted a significant effect on glutamate (GLU) extracellular levels in both the frontal cortex and hippocampus. Increased GLU release from pyramidal cells in the prefrontal cortex results in increased activity of γ-aminobutyric acid (GABA)ergic interneurons and, consequently, increased release of the GABA neurotransmitter. It seems that this mechanism appears to promote the antidepressant effects of psilocybin. By interacting with the glutamatergic pathway, psilocybin seems to participate also in the process of neuroplasticity. Therefore, the aim of this mini-review is to discuss the available literature data indicating the impact of psilocybin on glutamatergic neurotransmission and its therapeutic effects in the treatment of depression and other diseases of the nervous system.

keywords:
Animals, Humans, Glutamic Acid, Hallucinogens, Antidepressive Agents, Mental Disorders, Synaptic Transmission, Neuronal Plasticity, Psilocybin

raw_json:
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title: Impact of psilocybin on cognitive function: A systematic review.
publication_date: 2024-09-30
doi: 10.1111/pcn.13741
pubmed_id: 39354706
source_url: https://doi.org/10.1111/pcn.13741
substance_tags: psilocybin
study_type: Systematic Review
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
authors:
Meshkat S, Tello-Gerez TJ, Gholaminezhad F, Dunkley BT, Reichelt AC, Erritzoe D, Vermetten E, Zhang Y, Greenshaw A, Burback L, Winkler O, Jetly R, Mayo LM, Bhat V.

abstract:
Psilocybin is a classic psychedelic with demonstrated preliminary clinical efficacy in a range of psychiatric disorders. Evaluating the impact of psilocybin on cognitive function is essential to unravel its potential benefits and risks. In this systematic review, we assessed psilocybin's effect on cognitive function through a comprehensive search of electronic databases from inception to January 2024, identifying 20 articles involving 2,959 participants. While 85% of studies were conducted in healthy volunteers, most of these studies (85%) used macrodoses, ranging from 45 μg/kg to 30 mg/70 kg. Various cognitive aspects were evaluated and yielded mixed results. Global cognitive function, and processing speed remained mostly unchanged in healthy individuals; However, a limited number of studies reported improvements in certain areas such as sustained attention, working memory, and executive function especially in patients with treatment-resistant depression (TRD). Emotional processing was positively modified, particularly in TRD patients. Psilocybin was observed to enhance emotional empathy without significantly altering cognitive empathy and social cognition. Cognitive flexibility and creative cognition were noted to initially decline but could potentially improve over time. Additionally, with respect to learning and memory skills, psilocybin showed promise in improving specific memory types such as semantic associations and associative learning, while its effects on episodic and verbal memory have been less pronounced compared to other cognitive enhancers. The observed mixed findings underscore the complexity of psilocybin's cognitive influence. Further research is essential to provide a clearer understanding of psilocybin's impact on cognitive domains and to guide the development of safe and effective interventions.

keywords:
Humans, Hallucinogens, Cognition, Executive Function, Depressive Disorder, Treatment-Resistant, Psilocybin, Cognitive Dysfunction

topic_tags:
Depression,Emotional Processing,Creativity,Systematic Review,Review Article,Healthy Volunteers,Treatment-Resistant Depression,Safety

raw_json:
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authors: Werle I, Bertoglio LJ.
publication_date: 2024-09-18
doi: 10.1016/j.neubiorev.2024.105899
pubmed_id: 39305969
source_url: https://doi.org/10.1016/j.neubiorev.2024.105899
keywords: Animals, Rodentia, Hallucinogens, Anxiety, Fear, Mental Recall, Extinction, Psychological
substance_tags: psilocybin,psilocin
topic_tags: Anxiety,Receptor Pharmacology,Review Article
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Psychedelics: A review of their effects on recalled aversive memories and fear/anxiety expression in rodents.

abstract:
Threatening events and stressful experiences can lead to maladaptive memories and related behaviors. Existing treatments often fail to address these issues linked to anxiety/stress-related disorders effectively. This review identifies dose ranges associated with specific actions across various psychedelics. We examined psilocybin/psilocin, lysergic acid diethylamide (LSD), N,N-dimethyltryptamine (DMT), mescaline, 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), serotonin 2 A/2 C agonists (e.g., DOI) and 3,4-methylenedioxymethamphetamine (MDMA) on aversive memory extinction and reconsolidation, learned fear, anxiety, and locomotion in rodents. Nearly 400 studies published since 1957 were reviewed. Psychedelics often show biphasic effects on locomotion at doses that enhance extinction learning/retention, impair memory reconsolidation, or reduce learned fear and anxiety. Emerging evidence suggests a dissociation between their prospective benefits and locomotor effects. Under-explored aspects include sex differences, susceptibility to interference as memories age and generalize, repeated treatments, and immediate vs. delayed changes. Validating findings in traumatic-like memory and maladaptive fear/anxiety models is essential. Understanding how psychedelics modulate threat responses and post-retrieval memory processes in rodents may inform drug development and human studies, improving therapeutic approaches for related psychiatric conditions.

raw_json:
{"europe_pmc_id":"39305969","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Exploring the regulatory framework of psychedelics in the US & Europe.
publication_date: 2024-09-16
doi: 10.1016/j.ajp.2024.104242
pubmed_id: 39305768
source_url: https://doi.org/10.1016/j.ajp.2024.104242
substance_tags: psilocybin
topic_tags: Depression,Anxiety,PTSD,Mechanism of Action,Safety
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
authors:
Behera HK, Joga R, Yerram S, Karnati P, Mergu T, Gandhi K, M S, Nathiya D, Singh RP, Srivastava S, Kumar S.

abstract:
Psychedelic drug therapy has gained prominence for its potential in treating various mental health conditions, including depression, post-traumatic stress disorder (PTSD), and anxiety. Psychedelic treatment differs from conventional psychiatric approaches in mode of action, legal status, and treatment approach. This work delves into the therapeutic potential, mechanisms, and regulatory approvals of key psychedelic substances like psilocybin, 3,4-Methyl enedioxy methamphetamine (MDMA), mescaline, ketamine, and Lysergic acid diethylamide (LSD). It also provides an overview of legal aspects, and regulations surrounding psychedelics in the US & Europe, emphasizing their Schedule I classification due to potential misuse. The United States Food & Drug Administration (USFDA) closely monitors psychedelics, employing expedited pathways for evaluation. Further, recent guidance from the FDA on considerations for clinical Investigations supports the safe development of psychedelics for human welfare. European Medicines Agency (EMA) regulators focus on atypical psychedelics, addressing challenges in safety and efficacy. Marketed products, such as Spravato nasal spray, face limited distribution due to safety concerns. The call for careful regulation and legislation is essential for harnessing psychedelics' potential for therapeutic benefits and human welfare.

keywords:
Humans, Hallucinogens, Drug Approval, United States Food and Drug Administration, United States, Europe

raw_json:
{"europe_pmc_id":"39305768","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: New frontiers in the biosynthesis of psychoactive specialized metabolites.
authors: Li G, Facchini PJ.
publication_date: 2024-09-15
doi: 10.1016/j.pbi.2024.102626
pubmed_id: 39288539
source_url: https://doi.org/10.1016/j.pbi.2024.102626
keywords: Animals, Fungi, Plants, Hallucinogens, Biosynthetic Pathways
substance_tags: psilocybin
topic_tags: Depression,Anxiety,PTSD,Mechanism of Action,Clinical Trial,Review Article
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:03
abstract:
The recent relaxation of psychedelic drug regulations has prompted extensive clinical investigation into their potential use to treat diverse mental health conditions including anxiety, depression, post-traumatic stress, and substance-abuse disorders. Most clinical trials have relied on a small number of known molecules found in nature, such as psilocybin, or long-known synthetic analogs of natural metabolites, including lysergic acid diethylamide (LSD). Elucidation of biosynthetic pathways leading to several psychedelic compounds has established an opportunity to use synthetic biology as a complement to synthetic chemistry for the preparation of novel derivatives with potentially superior pharmacological properties compared with known drugs. Herein we review the metabolic biochemistry of pathways from plants, fungi and animals that yield the medicinally important hallucinogenic specialized metabolites ibogaine, mescaline, psilocybin, lysergic acid, and N,N-dimethyltryptamine (DMT). We also summarize the reconstitution of these pathways in microorganisms and comment on the integration of native and non-native enzymes to prepare novel derivatives.

raw_json:
{"europe_pmc_id":"39288539","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Adverse Events in Studies of Classic Psychedelics: A Systematic Review and Meta-Analysis.
authors: Hinkle JT, Graziosi M, Nayak SM, Yaden DB.
publication_date: 2024-11-30
doi: 10.1001/jamapsychiatry.2024.2546
pubmed_id: 39230883
source_url: https://doi.org/10.1001/jamapsychiatry.2024.2546
keywords: Humans, N,N-Dimethyltryptamine, Lysergic Acid Diethylamide, Hallucinogens, Psilocybin
substance_tags: psilocybin
study_type: Meta-Analysis
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
abstract:
ImportanceA clear and comprehensive understanding of risks associated with psychedelic-assisted therapy is necessary as investigators extend its application to new populations and indications.ObjectiveTo assess adverse events (AEs) associated with classic psychedelics, particularly serious AEs (SAEs) and nonserious AEs (NSAEs) requiring medical or psychiatric evaluation.Data sourcesThe search for potentially eligible studies was conducted in the Scopus, MEDLINE, PsycINFO, and Web of Science databases from inception through February 8, 2024.Study selectionTwo independent reviewers screened articles of classic psychedelics (lysergic acid diethylamide [LSD], psilocybin, dimethyltryptamine [DMT], and 5-methoxy-N,N-dimethyltryptamine [5-MeO-DMT]) involving administration in clinical or research contexts.Data extraction and synthesisAE data were extracted and synthesized by 2 reviewers and were used for random-effects meta-analysis of AE frequency and heterogeneity. Risk of bias assessment focused on AE ascertainment (eg, systematic assessment and quality of follow-up).Main outcomes and measuresA hybrid approach was used for capture of all reported AEs following high-dose classic psychedelic exposure and confirmatory capture of AEs of special interest, including suicidality, psychotic disorder, manic symptoms, cardiovascular events, and hallucinogen persisting perception disorder. AEs were stratified by timescale and study population type. Forest plots of common AEs were generated, and the proportions of participants affected by SAEs or NSAEs requiring medical intervention were summarized descriptively.ResultsA total of 214 unique studies were included, of which 114 (53.3%) reported analyzable AE data for 3504 total participants. SAEs were reported for no healthy participants and for approximately 4% of participants with preexisting neuropsychiatric disorders; among these SAEs were worsening depression, suicidal behavior, psychosis, and convulsive episodes. NSAEs requiring medical intervention (eg, paranoia, headache) were similarly rare. In contemporary research settings, there were no reports of deaths by suicide, persistent psychotic disorders, or hallucinogen persisting perception disorders following administration of high-dose classic psychedelics. However, there was significant heterogeneity in the quality of AE monitoring and reporting. Of 68 analyzed studies published since 2005, only 16 (23.5%) described systematic approaches to AE assessment, and 20 studies (29.4%) reported all AEs, as opposed to only adverse drug reactions. Meta-analyses of prevalence for common AEs (eg, headache, anxiety, nausea, fatigue, and dizziness) yielded comparable results for psilocybin and LSD.Conclusions and relevanceIn this systematic review and meta-analysis, classic psychedelics were generally well tolerated in clinical or research settings according to the existing literature, although SAEs did occur. These results provide estimates of common AE frequencies and indicate that certain catastrophic events reported in recreational or nonclinical contexts have yet to be reported in contemporary trial participants. Careful, ongoing, and improved pharmacovigilance is required to understand the risk and benefit profiles of these substances and to communicate such risks to prospective study participants and the public.

topic_tags:
Depression,Anxiety,Headache / Migraine,Meta-Analysis,Systematic Review,Review Article,Healthy Volunteers,Safety,Adverse Events

raw_json:
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authors: Jeffrey JK, Weintraub MJ, Grob CS.
publication_date: 2024-05-08
doi: 10.1016/j.jaac.2024.03.021
pubmed_id: 38734406
source_url: https://doi.org/10.1016/j.jaac.2024.03.021
substance_tags: psilocybin
topic_tags: Depression,PTSD,Addiction,Clinical Trial,Adolescents,Safety
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:03
title:
Clinical Research Trials of Psychedelic-Assisted Therapy in Adolescents Aged 16 to 17 Years: Rationale Balanced With Caution.

abstract:
Youth today are burdened by significant mental health challenges. In 2022, 25% of adolescents aged 12 to 17 years experienced a mental illness, with 20% experiencing a depressive episode, 12.5% reporting serious thoughts of suicide, and 17% meeting criteria for a substance use disorder.1 Close to 5% of adolescents experience posttraumatic stress disorder.2 Impairing psychiatric symptoms remain present in upwards of 40% of adolescents after receiving existing mental health services,3 so it is necessary to identify additional and more effective treatment options. We propose there is an acceptable benefit-to-risk calculation that supports trialing classic serotonergic psychedelics (eg, psilocybin) and phenethylamine compounds with empathogenic and entactogenic range of effects (eg, 3,4-methylenedioxymethamphetamine [MDMA]) in combination with psychotherapy among select adolescents aged 16 to 17 years. Specifically, we propose testing these treatments among adolescents aged 16 to 17 years who are experiencing treatment-resistant manifestations of psychiatric disorders (ie, multiple failed trials of current evidence-based treatments) or psychiatric disorders that are in line with the current evidence base for adults as determined, for example, by the breakthrough designation of the US Food and Drug Administration for a particular psychedelic medicine (eg, psilocybin for major depressive disorder, MDMA for posttraumatic stress disorder).

keywords:
Humans, N-Methyl-3,4-methylenedioxyamphetamine, Hallucinogens, Combined Modality Therapy, Psychotherapy, Adolescent, Clinical Trials as Topic, Psilocybin

raw_json:
{"europe_pmc_id":"38734406","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: A Case Report of Psilocybin-induced Psychosis in a Predisposed Patient.
authors: Morris SL.
publication_date: 2024-05-20
doi: 10.9758/cpn.24.1180
pubmed_id: 39420616
source_url: https://doi.org/10.9758/cpn.24.1180
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Personality Change,Review Article,Case Report,Safety
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
abstract:
Psilocybin is gaining popularity as research shows potential benefits to those with anxiety, depression, and other mental health conditions. Individuals with risk factors for psychosis are typically excluded from such studies, limiting the empiric research of the risks and benefits in vulnerable populations. In the real-world setting, many individuals who seek treatment with psilocybin will have comorbid psychiatric conditions and other factors that predispose them to psychosis. We report a case of a patient with multiple predisposing risk factors, including a history of depression, personality disorder traits, and cannabis use, who experienced a psychotic episode with catatonic features and suicidality after several months of heavy psilocybin use. A review of similar previously published case reports demonstrates a pattern of psilocybin-induced psychosis occurring primarily in individuals with predisposing factors who have consumed either high or repeated doses of the drug. This case report furthers this pattern, which serves as both a warning that psilocybin use is not without risks and reassurance for researchers using much lower doses to treat mental illness.

raw_json:
{"europe_pmc_id":"39420616","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Adams DR, Allen H, Nicol GE, Cabassa LJ.
publication_date: 2024-10-31
doi: 10.1093/tbm/ibae053
pubmed_id: 39419768
source_url: https://doi.org/10.1093/tbm/ibae053
substance_tags: psilocybin
topic_tags: Depression,PTSD,Addiction,Mechanism of Action,Clinical Trial,Veterans,Safety
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:03
title:
Moving psychedelic-assisted therapies from promising research into routine clinical practice: Lessons from the field of implementation science.

abstract:
Psychedelics (e.g., 3,4-Methylenedioxymethamphetamine [MDMA], lysergic acid diethylamide [LSD], psilocybin) are molecules that have the potential to produce rapid therapeutic effects when paired with psychotherapy. Randomized clinical trials of psychedelic-assisted psychotherapy (PAT) have shown promising results for post-traumatic stress disorder (PTSD), depression, and substance use disorders. The U.S. Food and Drug Administration has acknowledged the promise of PAT, signaling potential approval of psilocybin-assisted therapy for depression by 2026. Given this timeline, implementation scientists must engage with PAT researchers, policymakers, and practitioners to think critically about bringing these promising new treatments into routine practice settings while maintaining quality and safety. This commentary aims to initiate a dialogue between implementation scientists and PAT researchers and practitioners on addressing these questions with a lens toward equity. Specifically, we discuss how the field of implementation science can support PAT stakeholders to accelerate the translational process from research into practice, focusing specifically on safety-net settings (i.e., Federally Qualified Health Centers and Veterans Affairs health systems) that serve historically marginalized populations. We use the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) Framework to illustrate five critical areas where implementation science can help move PAT from research into real-world practice. For each RE-AIM dimension, we highlight ways the field of implementation science can contribute tools (e.g., implementation strategies), methodologies (e.g., pragmatic hybrid implementation-effectiveness trials), and approaches (community-based participatory research) for establishing the safety, effectiveness, and accessibility of PAT for historically underserved communities.

keywords:
Humans, Substance-Related Disorders, Hallucinogens, Depression, Stress Disorders, Post-Traumatic, Psychotherapy, United States, Psilocybin, Implementation Science

raw_json:
{"europe_pmc_id":"39419768","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Strategies for resolving challenging psychedelic experiences: insights from a mixed-methods study.
authors: Wood MJ, McAlpine RG, Kamboj SK.
publication_date: 2024-11-20
doi: 10.1038/s41598-024-79931-w
pubmed_id: 39572645
source_url: https://doi.org/10.1038/s41598-024-79931-w
substance_tags: psilocybin
topic_tags: Mechanism of Action,Emotional Processing,Observational Study,Safety,Drug Interactions
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
abstract:
Psychedelic substances are garnering renewed interest for their potential therapeutic applications, yet the mechanisms by which challenging experiences during psychedelic use contribute to positive outcomes remains poorly understood. Here we present a mixed-methods investigation into the strategies individuals employ to navigate difficult psychedelic experiences and their relationship to emotional breakthrough. Qualitative analysis of accounts from psilocybin retreat participants (n = 16) informed the development of the Responses to Challenging Psychedelic Experiences Inventory (ReCiPE). In a subsequent online survey (n = 529), exploratory factor analysis of the ReCiPE revealed three primary response strategies: Acceptance and Reappraisal, Sensory Regulation and Physical Interaction, and Social Support and Disclosure. Exploratory correlation and multiple regression analyses demonstrated significant relationships between different types of challenges, response strategies and emotional breakthrough. Notably, Acceptance and Reappraisal, and Social Support and Disclosure strategies were positively associated with greater emotional breakthrough. Fear-related challenges were negatively associated with emotional breakthrough and involved fewer adaptive coping strategies. These findings elucidate the complex interplay between challenging experiences and adaptive responses in psychedelic contexts, offering insights for optimising therapeutic protocols and enhancing safety in both clinical and non-clinical settings.

keywords:
Humans, Hallucinogens, Adaptation, Psychological, Emotions, Social Support, Adult, Middle Aged, Female, Male, Young Adult, Surveys and Questionnaires, Psilocybin

raw_json:
{"europe_pmc_id":"39572645","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


journal: PsyArXiv
publication_date: 2024-06-06
source_url: https://osf.io/preprints/psyarxiv/um2cy_v1
substance_tags: psilocybin
topic_tags: Safety,Adverse Events
study_type: Other
source_name: PsyArXiv
publication_status: preprint
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:30
raw_json: {"osf_id":"um2cy_v1","version":1,"reviews_state":"accepted"}
title:
Validation of the Swiss Psychedelic Side Effects Inventory: Standardized assessment of adverse effects in studies of psychedelics and MDMA

abstract:
Introduction: Studies of psychedelic-assisted therapy with LSD, psilocybin, MDMA, and related substances show clinical promise but inadequately assess side effects. Measuring side effects is challenging because they are not always easily differentiated from treatment effects or disease symptoms and show high heterogeneity, variable duration and impact, and sensitivity to context. A systematic questionnaire describing important characteristics of side effects of psychedelics and MDMA would greatly improve on previous methods. We aimed to create a standardized tool for recording clinically relevant side effects of psychedelics and MDMA, including their severity, duration, impact, and treatment-relatedness. Methods: We constructed the Swiss Psychedelic Side Effects Inventory (SPSI) based on insights from previous research. It was pilot tested in 145 participants from three studies. Structured feedback from an expert panel was used to improve validity and feasibility. Results: The final SPSI contains 32 side effects and standardized follow-up questions about their severity, impact, treatment-relatedness, and duration. It is compatible with any study design and can be administered as an interview or self-report at any timepoint after treatment with psychedelics or MDMA. Limitations: The SPSI omits relatively unimportant side effects for brevity’s sake, though space for additional symptoms is given. Future studies are needed to confirm its validity in different contexts. Conclusions: The SPSI is available in English and German for collecting systematic data on side effects from psychedelics and MDMA. This information is vital for improving clinical decisions, informed consent, and patient safety.

keywords:
adverse effects, MDMA, psychedelics, safety, side effects, Swiss Psychedelic Side Effects Inventory (SPSI), Psychiatry, Social and Behavioral Sciences, Clinical Psychology


title: Expanding the Therapeutic Horizons of Psilocybin in Mental Health.
authors: Kargbo RB.
publication_date: 2024-10-14
doi: 10.1021/acsmedchemlett.4c00488
pubmed_id: 39563826
source_url: https://doi.org/10.1021/acsmedchemlett.4c00488
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Wellbeing,Clinical Trial
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:00
abstract:
Psilocybin, a naturally occurring psychedelic compound, has recently emerged as a promising therapeutic agent for mental health. This Patent Highlight explores the innovative approaches to harnessing psilocybin's potential across various contexts. These include clinical trials targeting severe psychiatric conditions, the integration of low-dose psilocybin into dietary products to promote general mental well-being, and the personalization of psilocybin dosing for optimal treatment of depression and anxiety. These advancements demonstrate psilocybin's versatility and potential to reshape conventional mental health treatment paradigms, mainly through personalized medicine and accessible wellness applications.

raw_json:
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authors: Wang E, Mathai DS, Gukasyan N, Nayak S, Garcia-Romeu A.
publication_date: 2024-11-13
doi: 10.1038/s41598-024-78736-1
pubmed_id: 39543323
source_url: https://doi.org/10.1038/s41598-024-78736-1
substance_tags: psilocybin
topic_tags: Depression,PTSD,Pharmacology,Observational Study,Safety,Contraindications
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Knowledge, attitudes, and concerns about psilocybin and MDMA as novel therapies among U.S. healthcare professionals.

abstract:
Psychedelic-assisted therapy (PAT) with substances like psilocybin and MDMA has shown promise for conditions including depression and post-traumatic stress disorder. Psilocybin and MDMA may become approved medicines in the coming decade. This study assessed knowledge and attitudes regarding PAT among 879 U.S. healthcare professionals via anonymous online survey. Multivariable linear regression was used to identify predictors of openness to clinical use. Most participants (71.2%) were female and White (85.8%), with a mean (SD) age of 45.5 (12.7) years. Registered nurses (25.4%) and physicians (17.7%) comprised the largest professional groups. Respondents endorsed strong belief in therapeutic promise, and moderate openness to clinical use and support for legal access to both substances, with higher overall ratings for psilocybin compared to MDMA. Objective knowledge items revealed low knowledge of therapeutic uses, risks, and pharmacology. Primary concerns were lack of trained providers, financial cost, and potential contraindications. Prior psychedelic use, self-rated knowledge, younger age, and professional role predicted openness to clinical use of psilocybin and MDMA, with physicians reporting lower openness. As psychedelics continue to garner popular and scientific interest, results indicate a pressing need for additional formal training to provide balanced, evidence-based information from trusted sources.

keywords:
Humans, N-Methyl-3,4-methylenedioxyamphetamine, Hallucinogens, Attitude of Health Personnel, Health Knowledge, Attitudes, Practice, Adult, Middle Aged, Health Personnel, United States, Female, Male, Surveys and Questionnaires, Psilocybin

raw_json:
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title: Psychedelic 5-HT2A receptor agonism: neuronal signatures and altered neurovascular coupling.
journal: bioRxiv
publication_date: 2023-09-23
doi: 10.1101/2023.09.23.559145
source_url: https://doi.org/10.1101/2023.09.23.559145
substance_tags: psilocybin
topic_tags: Brain Imaging,Receptor Pharmacology,Aging,Animal Study
study_type: Animal Study
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
authors:
Padawer-Curry JA, Krentzman OJ, Kuo C, Wang X, Bice AR, Nicol GE, Snyder AZ, Siegel JS, McCall JG, Bauer AQ.

abstract:
Psychedelics hold therapeutic promise for mood disorders due to rapid, sustained results. Human neuroimaging studies have reported dramatic serotonin-2A receptor-(5-HT2AR)-dependent changes in functional brain reorganization that presumably reflect neuromodulation. However, the potent vasoactive effects of serotonin have been overlooked. We found psilocybin-mediated alterations to fMRI-HRFs in humans, suggesting potentially altered NVC. To assess the neuronal, hemodynamic, and neurovascular coupling (NVC) effects of the psychedelic 5-HT2AR agonist, 2,5-Dimethoxy-4-iodoamphetamine (DOI), wide-field optical imaging (WFOI) was used in awake Thy1-jRGECO1a mice during stimulus-evoked and resting-state conditions. While DOI partially altered tasked-based NVC, more pronounced NVC alterations occurred under resting-state conditions and were strongest in association regions. Further, calcium and hemodynamic activity reported different accounts of RSFC changes under DOI. Co-administration of DOI and the 5-HT2AR antagonist, MDL100907, reversed many of these effects. Dissociation between neuronal and hemodynamic signals emphasizes a need to consider neurovascular effects of psychedelics when interpreting blood-oxygenation-dependent neuroimaging measures.

raw_json:
{"europe_pmc_id":"PPR730039","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


publication_date: 2024-11-07
doi: 10.1080/24740527.2024.2406285
pubmed_id: 39529994
source_url: https://doi.org/10.1080/24740527.2024.2406285
substance_tags: psilocybin
topic_tags: Chronic Pain,Aging,Randomized Controlled Trial,Observational Study,Safety,Adverse Events
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Prospective Preference Assessment for the Psilocybin for Enhanced Analgesia in Chronic nEuropathic PAIN (PEACE-PAIN) Trial.

authors:
Lee J, Philip K, Wijeysundera DN, Clarke H, Pritlove C, Katz J, Ritvo P, Goel A, Husain MI, Ladha KS.

abstract:
BackgroundNegative perceptions of psilocybin and challenges of participant enrollment may represent barriers to conducting a randomized controlled trial examining psilocybin for chronic neuropathic pain.AimPrior to trial initiation, we aimed to examine patient attitudes toward the trial via a prospective preference assessment.MethodsTwenty-six patients with chronic neuropathic pain participated in a prospective preference assessment comprising quantitative (survey) and qualitative (interview) components. Content analysis was used to inductively and deductively identify factors that would motivate or discourage participation in the proposed trial. Demographics, clinical characteristics, and perceptions of psilocybin were collected to explore differences in characteristics between patients who were willing and unwilling to participate.ResultsSurvey results showed that most participants (76.9%) were willing to participate in the PEACE-PAIN trial. "Willing" participants reported higher prior psychedelic use (75%) as compared to the "maybe willing" (0%) and "not willing" participants (0%). Interviews indicated that the top two factors that motivated participation included the need for new treatment options (31.7%) and benefits to personal pain management (31.7%). The top two discouraging factors included practical difficulties of research participation (16.7%), and adverse events associated with psilocybin (16.7%).ConclusionsThe PEACE-PAIN trial study design is supported by patient survey responses but may benefit from modifications, namely incorporating thorough discussions of the current evidence for efficacy, safety, tolerability, and approaches to address adverse effects of psilocybin. Additionally, the interest in participation by individuals with prior psychedelic use holds important methodological implications for the inclusion/exclusion criteria of the trial.

raw_json:
{"europe_pmc_id":"39529994","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Amid magic and menace: psychiatrists' attitudes to psilocybin therapy.
publication_date: 2024-11-06
doi: 10.1017/ipm.2024.49
pubmed_id: 39506378
source_url: https://doi.org/10.1017/ipm.2024.49
substance_tags: psilocybin
topic_tags: Depression,Personality Change,Emotional Processing
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:00
authors:
Gribben A, Burke T, Harrington C, Husein A, Murnane KS, Hendricks PS, Tobin K, Ivers JH, Thuery G, Harkin A, Kelly JR.

abstract:
ObjectivesUnderstanding variations in knowledge and attitudes of psychiatrists to psilocybin therapy is important for the collective discourse about the potential impact on clinical practice and public health in Ireland.MethodsA 28-item questionnaire was designed based on previous studies and distributed to psychiatrists in Ireland via online mailing lists and at in-person academic events.Results151 psychiatrists completed the questionnaire (73.3% were under 40 years of age, 76.0% were trainees, and 49.0% were female). In the total sample, 81.5% agreed that psilocybin therapy shows promise in the treatment of psychiatric disorders and 86.8% supported funding research, 86.8% would be willing to refer a patient if it was licensed and indicated, and 78.1% would consider the treatment for themselves, if indicated. Conversely, 6.6% agreed that psilocybin therapy was unsafe even under medical supervision, and 21.9% thought it was potentially addictive. 15.9% of the total sample reported at least one concern including, lack of robust evidence, long-term effectiveness, superiority to current interventions, potential harmful effects, cost and accessibility, and impartiality. Less than half of respondents felt knowledgeable (40.0%) and 9.9% felt adequately prepared to participate in psilocybin therapy. Consultant psychiatrists trended towards less optimism for a potential role in bipolar depression and emotionally unstable personality disorder compared to trainee psychiatrists.ConclusionOverall psychiatrists in Ireland held positive attitudes towards psilocybin therapy. However, there was a lack of knowledge evident. Addressing the knowledge gap and aligning with the best available evidence will be key if psychedelic therapy is to prevail in a clinical setting.

raw_json:
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title: Therapeutic Potential of Psychedelic Compounds for Substance Use Disorders.
authors: Valdez T, Patel V, Senesombath N, Hatahet-Donovan Z, Hornick M.
publication_date: 2024-11-04
doi: 10.3390/ph17111484
pubmed_id: 39598395
source_url: https://doi.org/10.3390/ph17111484
substance_tags: psilocybin
topic_tags: Addiction,Review Article
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
abstract:
Psychedelics have recently (re)emerged as therapeutics of high potential for multiple mental health conditions, including substance use disorders (SUDs). Despite early mid-20th century anecdotal reports and pilot studies demonstrating the possibility of these substances in efficaciously treating conditions such as alcohol and opioid use disorders, legal restrictions and social stigma have historically hindered further research into this area. Nevertheless, concurrent with the rise in SUDs and other mental health conditions, researchers have again turned their attention to these compounds, searching for differing pharmacological targets as well as more holistic treatments that might increase patient adherence and efficacy. The aim of this review is to examine the emerging evidence-based data with regards to the therapeutic treatment of SUDs with the psychedelic compounds psilocybin, ketamine, lysergic acid diethylamide (LSD), 3,4-methylenedioxymethamphetamine (MDMA), ayahuasca, ibogaine and peyote.

raw_json:
{"europe_pmc_id":"39598395","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Holikulov U, Kazachenko AS, Issaoui N, Kazachenko AS, Raja M, Al-Dossary OM, Xiang Z.
publication_date: 2024-06-03
doi: 10.1016/j.saa.2024.124600
pubmed_id: 38852303
source_url: https://doi.org/10.1016/j.saa.2024.124600
substance_tags: psilocin
topic_tags: Drug Interactions
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:00
title:
The molecular structure, vibrational spectra, solvation effect, non-covalent interactions investigations of psilocin.

abstract:
Psilocin, or 4-HO-DMT (or 3-(2-dimethylaminoethyl)-1H-indol-4-ol), is a psychoactive alkaloid substance from the tryptamine family, isolated from Psilocybe mushrooms. This substance is being studied by various research groups because it has a clear therapeutic effect in certain dosages. In this work, the study of the structure and properties of psilocin was carried using theoretical methods: the effects of polar solvents (acetonitrile, dimethylsulfoxide, water, and tetrahydrofuran) on the structural parameters, spectroscopic properties (Raman, IR, and UV-Vis), frontier molecular orbital (FMO), molecular electrostatic potential (MEP) surface, and nonlinear optical parameters (NLO). Theoretical calculations were performed at the B3LYP/6-311++G(d,p) level by the density functional theory (DFT) method. IEFPCM was used to account for solvent effects. The types and nature of non-covalent interactions (NCI) between psilocin and solvent molecules were determined using Atoms in Molecules (AIM), the reduced density gradient method (RDG), the electron localization function (ELF), and the localization orbital locator (LOL). Experimental and calculated FT-IR, FT-Raman, and UV-Vis spectra were compared and found to be in good agreement.

raw_json:
{"europe_pmc_id":"38852303","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Swanson LR, Jungers S, Varghese R, Cullen KR, Evans MD, Nielson JL, Schallmo MP.
publication_date: 2024-10-31
doi: 10.1167/jov.24.12.5
pubmed_id: 39499526
source_url: https://doi.org/10.1167/jov.24.12.5
substance_tags: psilocybin
topic_tags: Depression,Mechanism of Action,Randomized Controlled Trial,Adverse Events
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Enhanced visual contrast suppression during peak psilocybin effects: Psychophysical results from a pilot randomized controlled trial.

abstract:
In visual perception, an effect known as surround suppression occurs wherein the apparent contrast of a center stimulus is reduced when it is presented within a higher-contrast surrounding stimulus. Many key aspects of visual perception involve surround suppression, yet the neuromodulatory processes involved remain unclear. Psilocybin is a serotonergic psychedelic compound known for its robust effects on visual perception, particularly texture, color, object, and motion perception. We asked whether surround suppression is altered under peak effects of psilocybin. Using a contrast-matching task with different center-surround stimulus configurations, we measured surround suppression after 25 mg of psilocybin compared with placebo (100 mg niacin). Data on harms were collected, and no serious adverse events were reported. After taking psilocybin, participants (n = 6) reported stronger surround suppression of perceived contrast compared to placebo. Furthermore, we found that the intensity of subjective psychedelic visuals induced by psilocybin correlated positively with the magnitude of surround suppression. We note the potential relevance of our findings for the field of psychiatry, given that studies have demonstrated weakened visual surround suppression in both major depressive disorder and schizophrenia. Our findings are thus relevant to understanding the visual effects of psilocybin, and the potential mechanisms of visual disruption in mental health disorders.

keywords:
Humans, Hallucinogens, Pilot Projects, Double-Blind Method, Photic Stimulation, Visual Perception, Contrast Sensitivity, Psychophysics, Adult, Female, Male, Young Adult, Psilocybin

raw_json:
{"europe_pmc_id":"39499526","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Jeanblanc J, Bordy R, Fouquet G, Jeanblanc V, Naassila M.
publication_date: 2024-10-31
doi: 10.1093/brain/awae136
pubmed_id: 38703387
source_url: https://doi.org/10.1093/brain/awae136
substance_tags: psilocybin
topic_tags: Addiction,Mechanism of Action,Receptor Pharmacology
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Psilocybin reduces alcohol self-administration via selective left nucleus accumbens activation in rats.

abstract:
The use of psilocybin to treat alcohol use disorder is very promising, but its mechanisms of action remain poorly understood. We combined behavioural, pharmacological and gene expression analyses to decipher the mechanisms of action of psilocybin, for the first time, when injected into the brain. Male Long Evans rats underwent chronic operant ethanol self-administration before testing the effect of intraperitoneal psilocybin or directly within the nucleus accumbens core or the ventral tegmental area. Transcripts from the dopaminergic system were quantified in the nucleus accumbens and prefrontal cortex. Psilocybin significantly reduced (by 50%) ethanol self-administration when injected 4 h before the session either intraperitoneally (1 mg/kg) or directly within the left nucleus accumbens (0.15 μg) but not the right nucleus accumbens or the left ventral tegmental area. The effect of intraperitoneal injection of psilocybin was prevented by intra-left nucleus accumbens injection of 0.3 μg of the 5-HT2A receptor antagonist ketanserin. In rats that self-administered ethanol but not in those self-administering saccharin, dopamine D2 receptor (D2R) mRNA was increased in both the nucleus accumbens and the prefrontal cortex by psilocybin, while dopamine D1 receptor mRNA was increased only in the prefrontal cortex. As in humans, psilocybin reduced ethanol self-administration in rats through the 5-HT2A receptor within the left nucleus accumbens, possibly through increased D2R expression. Our results open unexpected perspectives regarding the hemispheric lateralization of psychedelic effects.

keywords:
Nucleus Accumbens, Prefrontal Cortex, Animals, Rats, Rats, Long-Evans, Ethanol, Receptors, Dopamine D1, Receptors, Dopamine D2, Hallucinogens, Self Administration, Alcohol Drinking, Conditioning, Operant, Male, Functional Laterality, Psilocybin

raw_json:
{"europe_pmc_id":"38703387","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Pyramidal cell types and 5-HT2A receptors are essential for psilocybin’s lasting drug action
journal: bioRxiv
publication_date: 2024-11-02
doi: 10.1101/2024.11.02.621692
source_url: https://doi.org/10.1101/2024.11.02.621692
substance_tags: psilocybin
topic_tags: Neuroplasticity,Brain Imaging,Receptor Pharmacology,Aging,Animal Study
study_type: Animal Study
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
authors:
Shao L, Liao C, Davoudian PA, Savalia NK, Jiang Q, Wojtasiewicz C, Tan D, Nothnagel JD, Liu R, Woodburn SC, Bilash OM, Kim H, Che A, Kwan AC.

abstract:
Psilocybin is a serotonergic psychedelic with therapeutic potential for treating mental illnesses 1-4. At the cellular level, psychedelics induce structural neural plasticity 5,6, exemplified by the drug-evoked growth and remodeling of dendritic spines in cortical pyramidal cells 7-9. A key question is how these cellular modifications map onto cell type-specific circuits to produce psychedelics’ behavioral actions 10. Here, we use in vivo optical imaging, chemogenetic perturbation, and cell type-specific electrophysiology to investigate the impact of psilocybin on the two main types of pyramidal cells in the mouse medial frontal cortex. We find that a single dose of psilocybin increased the density of dendritic spines in both the subcortical-projecting, pyramidal tract (PT) and intratelencephalic (IT) cell types. Behaviorally, silencing the PT neurons eliminates psilocybin’s ability to ameliorate stress-related phenotypes, whereas silencing IT neurons has no detectable effect. In PT neurons only, psilocybin boosts synaptic calcium transients and elevates firing rates acutely after administration. Targeted knockout of 5-HT2A receptors abolishes psilocybin’s effects on stress-related behavior and structural plasticity. Collectively these results identify a pyramidal cell type and the 5-HT2A receptor in the medial frontal cortex as playing essential roles for psilocybin’s long-term drug action.

raw_json:
{"europe_pmc_id":"PPR934425","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


publication_date: 2024-10-06
doi: 10.1038/s44220-024-00331-0
pubmed_id: 41969367
source_url: https://doi.org/10.1038/s44220-024-00331-0
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Clinical Trial,Cancer Patients
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Psilocybin-assisted psychotherapy improves psychiatric symptoms across multiple dimensions in patients with cancer.

authors:
Petridis PD, Grinband J, Agin-Liebes G, Kinslow CJ, Zeifman RJ, Bogenschutz MP, Griffiths RR, Ross S.

abstract:
Psilocybin-assisted psychotherapy (PAP) has shown promise in treating mood and anxiety disorders in patients with cancer. However, patients with cancer often suffer from more than just depression and anxiety, and so far, PAP's effect on other psychiatric symptoms remains largely unknown. To address this gap, we pooled previously unpublished data from two phase II, randomized, placebo-controlled crossover trials involving 79 participants with cancer-related distress and analyzed PAP's effect on 9 psychiatric symptom dimensions: anxiety, depression, interpersonal sensitivity, hostility, obsession-compulsion, somatization, phobia, paranoia and psychosis. PAP significantly improved anxiety, depression, interpersonal sensitivity, hostility, obsession-compulsion and somatization without inducing any lasting phobia, paranoia or psychosis. Clinical improvements were consistent between trials. Together, our findings suggest that PAP has the potential to be a comprehensive mental health treatment for patients with cancer.

raw_json:
{"europe_pmc_id":"41969367","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Forte V, Shaughnessy AF, Kurotschka PK.
publication_date: 2024-10-31
doi: 10.1701/4365.43590
pubmed_id: 39550651
source_url: https://doi.org/10.1701/4365.43590
substance_tags: psilocybin
topic_tags: Depression
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
title:
[Depression and effectiveness of psychedelics: high-dose psilocybin has shown benefits in improving symptoms.]

raw_json:
{"europe_pmc_id":"39550651","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Reid MJ, Kettner H, Blanken TF, Weiss B, Carhart-Harris R.
publication_date: 2024-11-12
doi: 10.1007/s11920-024-01539-8
pubmed_id: 39532819
source_url: https://doi.org/10.1007/s11920-024-01539-8
substance_tags: psilocybin
topic_tags: Depression,Mechanism of Action,Clinical Trial,Drug Interactions
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:00
title:
Preliminary Evidence of Sleep Improvements Following Psilocybin Administration, and their Involvement in Antidepressant Therapeutic Action.

abstract:
Purpose of the studyPsilocybin is a rapidly-emerging treatment for depression, yet its impact on sleep is not well understood. We sought to explore the literature on sleep and psilocybin use, and explore the topic using our own primary data.FindingsWhilst clinical trials demonstrate large depressive symptom improvements, the impact of psilocybin on sleep quality or insomnia symptoms, has not been directly studied. Using our own preliminary-data we demonstrated that both depressive-symptoms and sleep-disturbances decreased significantly following psilocybin use, though sleep improvements were smaller compared to depressive symptoms. More severe sleep-disturbances at baseline were linked to lower probability of depression remission, underscoring a potential interaction between sleep and psilocybin's efficacy. Addressing sleep disturbances could enhance therapeutic outcomes in psilocybin-assisted therapy and could lead to more effective, personalized treatment-strategies. Future research should focus on populations with sleep disorders, and on examining causal-pathways of sleep physiology's impact on psilocybin efficacy.

keywords:
Humans, Sleep Initiation and Maintenance Disorders, Hallucinogens, Antidepressive Agents, Depressive Disorder, Adult, Female, Male, Sleep Wake Disorders, Psilocybin

raw_json:
{"europe_pmc_id":"39532819","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Optimized psilocybin production in tryptophan catabolism-repressed fungi.
publication_date: 2024-10-31
doi: 10.1111/1751-7915.70039
pubmed_id: 39487767
source_url: https://doi.org/10.1111/1751-7915.70039
substance_tags: psilocybin,psilocin
topic_tags: Depression,Addiction,Eating Disorders,Mechanism of Action,Genomics
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:00
authors:
Janevska S, Weiser S, Huang Y, Lin J, Hoefgen S, Jojić K, Barber AE, Schäfer T, Fricke J, Hoffmeister D, Regestein L, Valiante V, Kufs JE.

abstract:
The high therapeutic potential of psilocybin, a prodrug of the psychotropic psilocin, holds great promise for the treatment of mental disorders such as therapy-refractory depression, alcohol use disorder and anorexia nervosa. Psilocybin has been designated a 'Breakthrough Therapy' by the US Food and Drug Administration, and therefore a sustainable production process must be established to meet future market demands. Here, we present the development of an in vivo psilocybin production chassis based on repression of l-tryptophan catabolism. We demonstrate the proof of principle in Saccharomyces cerevisiae expressing the psilocybin biosynthetic genes. Deletion of the two aminotransferase genes ARO8/9 and the indoleamine 2,3-dioxygenase gene BNA2 yielded a fivefold increase of psilocybin titre. We transferred this knowledge to the filamentous fungus Aspergillus nidulans and identified functional ARO8/9 orthologs involved in fungal l-tryptophan catabolism by genome mining and cross-complementation. The double deletion mutant of A. nidulans resulted in a 10-fold increased psilocybin production. Process optimization based on respiratory activity measurements led to a final psilocybin titre of 267 mg/L in batch cultures with a space-time-yield of 3.7 mg/L/h. These results demonstrate the suitability of our engineered A. nidulans to serve as a production strain for psilocybin and other tryptamine-derived pharmaceuticals.

keywords:
Saccharomyces cerevisiae, Aspergillus nidulans, Transaminases, Tryptophan, Gene Deletion, Indoleamine-Pyrrole 2,3,-Dioxygenase, Metabolic Networks and Pathways, Metabolic Engineering, Psilocybin

raw_json:
{"europe_pmc_id":"39487767","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Imperio CG, Levin FR, Martinez D.
publication_date: 2024-10-08
doi: 10.1176/appi.ajp.20231023
pubmed_id: 39380375
source_url: https://doi.org/10.1176/appi.ajp.20231023
substance_tags: psilocybin
topic_tags: Addiction,Neuroplasticity,Wellbeing,Review Article
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:03
title:
The Neurocircuitry of Substance Use Disorder, Treatment, and Change: A Resource for Clinical Psychiatrists.

abstract:
Substance use disorder (SUD) is common in psychiatric patients and has a negative impact on health and well-being. However, SUD often goes untreated, and there is a need for psychiatrists, of all specialties, to address this pervasive clinical problem. In this review, the authors' goal is to provide a resource that describes treatments for SUD, using neuroscience as a framework. They discuss the effect of pharmacotherapy on craving, intoxication, and withdrawal and its ability to interrupt the cycle of substance use in SUD. The neuroscience of stress is reviewed, including medications targeting neurotransmitter systems activated by alarm and fear. Neuroplasticity and promising treatments that use this mechanism, including ketamine, psilocybin, and transcranial magnetic stimulation (TMS), are discussed. The authors conclude by listing resources and practice guidelines for physicians interested in learning more about treatments for SUD.

keywords:
Brain, Humans, Substance-Related Disorders, Psychiatry, Neuronal Plasticity, Transcranial Magnetic Stimulation, Psychiatrists

raw_json:
{"europe_pmc_id":"39380375","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Ivan VE, Tomàs-Cuesta DP, Esteves IM, Luczak A, Mohajerani M, McNaughton BL, Gruber AJ.
publication_date: 2024-10-03
doi: 10.1111/ejn.16558
pubmed_id: 39364682
source_url: https://doi.org/10.1111/ejn.16558
substance_tags: psilocybin
topic_tags: Mechanism of Action,Receptor Pharmacology,Animal Study
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Psilocybin reduces functional correlation and the encoding of spatial information by neurons in mouse retrosplenial cortex.

abstract:
Psychedelic drugs have profound effects on perception, cognition and mood. How psychedelics affect neural signaling to produce these effects remains poorly understood. We investigated the effect of the classic psychedelic psilocybin on neural activity patterns and spatial encoding in the retrosplenial cortex of head-fixed mice navigating on a treadmill. The place specificity of neurons to distinct locations along the belt was reduced by psilocybin. Moreover, the stability of place-related activity across trials decreased. Psilocybin also reduced the functional correlation among simultaneously recorded neurons. The 5-HT2AR (serotonin 2A receptor) antagonist ketanserin blocked these effects. These data are consistent with proposals that psychedelics increase the entropy of neural signaling and provide a potential neural mechanism contributing to disorientation frequently reported by humans after taking psychedelics.

keywords:
Gyrus Cinguli, Neurons, Animals, Mice, Inbred C57BL, Mice, Ketanserin, Hallucinogens, Space Perception, Male, Serotonin 5-HT2 Receptor Antagonists, Psilocybin

raw_json:
{"europe_pmc_id":"39364682","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2024-09-19
doi: 10.1111/head.14837
pubmed_id: 39301810
source_url: https://doi.org/10.1111/head.14837
substance_tags: psilocybin
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Low-dose psilocybin in short-lasting unilateral neuralgiform headache attacks: results from an open-label phase Ib ascending dose study.

authors:
Rucker J, Butler M, Hambleton S, Bird C, Seynaeve M, Cheema S, Campbell-Coker K, Maggio C, Dunbar F, Lambru G, Matharu M.

abstract:
BackgroundShort-lasting unilateral neuralgiform headache attacks (SUNHA) are trigeminal autonomic cephalalgias that feature intense and recurrent paroxysms of pain and autonomic symptoms. Many patients are left with debilitating symptoms despite best-available treatment. Psychedelics, such as the serotonin 2A partial agonist psilocybin, have shown promise in related disorders such as migraine and cluster headache. In this open-label phase Ib ascending dose study, we aimed to assess the effects of low-dose oral psilocybin with psychological support in six to 12 patients with chronic SUNHA. Study objectives were to determine effects on cognition, as well as safety, tolerability, and effects on headache severity and frequency.MethodsOral psilocybin in ascending doses of 5, 7.5, and 10 mg (one dose per session; three dosing sessions in total) were administered. Cognition was assessed via the Cambridge Neuropsychological Tests Automated Battery. Headache attacks were assessed via headache diaries and the six-item Headache Impact Test (HIT-6). Subjective dose intensity was assessed via the five-Dimensional Altered States of Consciousness Questionnaire (5D-ASC). The study was terminated early due to recruitment difficulties; four patients were enrolled, three of whom were study completers. Post hoc, we undertook a thematic analysis of the applicable free-text clinical trial notes from the dosing and subsequent visits (n = 22). An inductive method was employed to establish emergent themes.ResultsNo significant adverse events were recorded. We were unable to collect data as planned on cognitive function during the acute experience due to high ratings of subjective dose intensity (mean 5D-ASC scores 37.8-45.7). The impact of the headaches remained severe throughout the duration of the trial (HIT-6 mean scores 64.3-65.7). There were limited effects on headache duration and severity based on the diaries; however, mean daily attack frequency decreased by >50% in two participants at final follow-up (22.9 to 11.0 and 56.4 to 28.0, respectively). Completing participants and their clinicians recorded "much" (two participants) or "minimal" improvements (one participant) at final follow-up via the Clinical Global Impression rating scale. Thematic analysis indicated that psychological insights were key features of participants' experience; these insights included re-configured relationships to their headache pain.ConclusionThe study met with recruitment difficulties and cognition could not be assessed during the acute experience due to subjective dose intensity, likely mediated in part by expectancy effects. The clinical results provide no conclusive evidence for the use of psilocybin in SUNHA. We suggest that accounting for psychological factors in chronic SUNHA may be an important facet of treatment.

keywords:
Humans, Hallucinogens, Neuropsychological Tests, Dose-Response Relationship, Drug, Adult, Middle Aged, Female, Male, Trigeminal Autonomic Cephalalgias, Young Adult, Psilocybin

topic_tags:
Chronic Pain,Headache / Migraine,Receptor Pharmacology,Consciousness,Clinical Trial,Healthcare Workers,Safety,Adverse Events

raw_json:
{"europe_pmc_id":"39301810","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psychedelic mushroom-containing chocolate exposures: Case series.
authors: Gartner HT, Wan HZ, Simmons RE, Sollee DR, Sheikh S.
publication_date: 2024-09-13
doi: 10.1016/j.ajem.2024.09.038
pubmed_id: 39288500
source_url: https://doi.org/10.1016/j.ajem.2024.09.038
substance_tags: psilocybin,psilocin
topic_tags: Case Report,Observational Study,Adolescents
study_type: Case Report
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
abstract:
IntroductionThe recreational use of psilocybin or psilocin-containing products, a chemical found naturally in certain mushroom species, is on the rise across the United States. Several cases of serious clinical effects related to mushroom-containing products have recently been reported to the Food and Drug Administration (FDA). The emergence of these new products and their health consequences are not yet well understood. This case series aims to characterize exposures to mushroom-containing chocolate products, including patient characteristics, clinical effects, treatment(s), and clinical outcome severity, reported to a poison center network.Material and methodsThis was a retrospective case series conducted in patients exposed to mushroom-containing chocolate products across three poison centers between January 2023 to August 2024. Patients were identified via a database search of ToxSentry®. Patients were included if they were exposed to a mushroom-containing chocolate product. Patients were excluded if they ingested an unrelated product or if there was insufficient information documented within ToxSentry®. The primary endpoint was to describe clinical outcome severity after exposure to mushroom-containing chocolate products.ResultsA query of ToxSentry® identified 164 cases; 36 cases met study criteria. The median age of patients in this case series was 17 years old. For most patients (23, 64 %), the reason for the exposure was intentional, with 20 reporting intentional abuse or misuse of the product. Common clinical effects reported included mental status changes (26, 76 %), paranoia/hallucinations (10, 28 %), dysrhythmias (7, 19 %) and gastrointestinal discomfort (6, 17 %). There was one report of seizure. Most clinical effects lasted between 3 and 24 h after ingestion (29, 81 %). Intravenous fluids (18, 50 %) and benzodiazepines (7, 19 %) were the most common treatments given. No fatalities were reported.DiscussionWhile most patients in this series experienced minor clinical effects, some developed serious effects after ingestion of a mushroom-containing chocolate product. Findings from this study further characterize the limited patient demographics, clinical effects, and outcomes published thus far. Further characterization in a larger cohort of patients could expand on our initial findings and is needed to better identify factors that may influence clinical outcomes.

keywords:
Humans, Agaricales, Mushroom Poisoning, Hallucinogens, Retrospective Studies, Adolescent, Adult, Middle Aged, Child, Poison Control Centers, United States, Female, Male, Young Adult, Psilocybin, Chocolate

raw_json:
{"europe_pmc_id":"39288500","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Woollacott M, Riddle J, Hermansson N, Sacchet MD, Ingram DM.
publication_date: 2024-09-01
doi: 10.1016/j.explore.2024.103056
pubmed_id: 39244904
source_url: https://doi.org/10.1016/j.explore.2024.103056
substance_tags: psilocybin
topic_tags: Spirituality,Mystical Experience,Observational Study
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
title:
Fire Kasina advanced meditation produces experiences comparable to psychedelic and near-death experiences: A pilot study.

abstract:
Psychedelic-assisted therapy studies suggest that the induction of "mystical experiences" combined with psycho-therapy is a possible intervention for psychiatric illness. Advanced meditation may induce powerful experiences comparable to psychedelics. We investigated effects of an intensive meditation practice called Fire Kasina. Six individuals completed a retreat, and participated in an interview in which they described their experiences. They also completed the Revised Mystical Experience Questionnaire (MEQ), Hood Mystical Experience Scale (HME), and Cole's Spiritual Transformation Scale. Mean MEQ scores were 85 %, similar to prior observations of high-dose psilocybin and were stronger than moderate-dose psilocybin (t(5) = 4.41, p = 0.007, d = 1.80; W(5) = 21, p = 0.031). Mean HME scores were 93 %, exceeding levels reported for NDEs (mean 74 %) and high-dose psilocybin (mean 77 %). In qualitative analysis, experiences were described as the most intense of the individual's life, while subsequent transformational effects included substantial shifts in worldview.

keywords:
Humans, Death, Hallucinogens, Meditation, Pilot Projects, Spirituality, Mysticism, Adult, Middle Aged, Female, Male, Surveys and Questionnaires, Psilocybin

raw_json:
{"europe_pmc_id":"39244904","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psychoactive substances for the treatment of neuropsychiatric disorders.
authors: Zhen Z, Sun X, Yuan S, Zhang J.
publication_date: 2024-09-02
doi: 10.1016/j.ajp.2024.104193
pubmed_id: 39243659
source_url: https://doi.org/10.1016/j.ajp.2024.104193
substance_tags: psilocybin
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
abstract:
In the contemporary landscape of psychiatric medicine, critical advancements have been noted in the utilization of psychoactive substances such as hallucinogens, 3,4-methylenedioxymethamphetamine (MDMA), and ketamine for the treatment of severe mental health disorders. This review provides a detailed evaluation of these substances, focusing on their mechanisms of action and the profound clinical outcomes observed in controlled environments. Hallucinogens like lysergic acid diethylamide and psilocybin primarily target the 5-HT2A receptor agonist-2 (5-HT2AR), inducing substantial perceptual and cognitive shifts that facilitate deep psychological introspection and significant therapeutic advances, particularly in patients suffering from depression and anxiety disorders. MDMA, influencing multiple neurotransmitter systems including 5-Hydroxytryptamine (5-HT), dopamine, and norepinephrine, has been demonstrated to effectively alleviate symptoms of post-traumatic stress disorder, enhancing patients' emotional engagement and resilience during psychotherapy. Meanwhile, ketamine, a glutamate receptor antagonist, rapidly alleviates depressive symptoms, offering a lifeline for individuals with treatment-resistant depression through its fast-acting antidepressant properties. The integration of these substances into psychiatric practice has shown promising results, fundamentally changing the therapeutic landscape for patients unresponsive to traditional treatment modalities. However, the potent effects of these agents also necessitate a cautious approach in clinical application, ensuring careful dosage control, monitoring, and risk management to prevent potential abuse and mitigate adverse effects.

keywords:
Humans, N-Methyl-3,4-methylenedioxyamphetamine, Ketamine, Hallucinogens, Psychotropic Drugs, Mental Disorders

topic_tags:
Depression,Anxiety,PTSD,Mechanism of Action,Receptor Pharmacology,Resilience,Emotional Processing,Review Article,Treatment-Resistant Depression,Safety

raw_json:
{"europe_pmc_id":"39243659","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Anderson K, Elf P, Isham A.
publication_date: 2024-09-04
doi: 10.1016/j.drugpo.2024.104571
pubmed_id: 39241438
source_url: https://doi.org/10.1016/j.drugpo.2024.104571
substance_tags: psilocybin
topic_tags: General
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
title:
Psychedelics as a tool for a more connected and sustainable world? Considering the importance of rituals, boundaries, and commitment.

abstract:
Despite the surge of interest in psychedelic research in the past decade, largely due to the promise of psychedelics for improving mental health outcomes, there has been comparatively little discussion about the social and environmental consequences of psychedelic drug use. While there is growing evidence to suggest psychedelics could foster a greater connection to the natural world and improve social relationships, such positive repercussions are far from guaranteed. In this commentary, we focus on LSD, psilocybin and especially MDMA, and outline three insights we came to see as crucial to creating beneficial outcomes: 1) the importance of setting and rituals, 2) the establishment of boundaries, and 3) understanding the long-term commitment required. These insights are grounded in the history of psychedelics, which is intimately intertwined with ritualised use, yet the process of commercialisation of these substances threatens to strip away important contextual factors. Creating boundaries around when, how and with whom psychedelics are used have been found to protect recreational users from harm and could also be instrumental in steering commercial interests to align with socio-environmental goals. Finally, far from being a 'quick fix' for social or environmental problems, the use of psychedelics requires sustained engagement to integrate the insights obtained. Whereas we remain optimistic about the transformative potential of psychedelics for social relationships and the environment, we also emphasise the need for a more cautious, considered approach if we are to harness the benefits and minimise the challenges of psychedelic drug use.

keywords:
Humans, N-Methyl-3,4-methylenedioxyamphetamine, Lysergic Acid Diethylamide, Hallucinogens, Ceremonial Behavior, Psilocybin, Recreational Drug Use

raw_json:
{"europe_pmc_id":"39241438","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Pohořalá V, Kuchař M, Spanagel R, Bernardi RE.
publication_date: 2024-09-02
doi: 10.1016/j.neuroscience.2024.09.006
pubmed_id: 39236802
source_url: https://doi.org/10.1016/j.neuroscience.2024.09.006
substance_tags: psilocybin
topic_tags: Addiction,Animal Study
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Psilocybin administered following extinction sessions does not affect subsequent cocaine cue reinstatement in male and female rats and mice.

abstract:
There are currently no pharmacological treatments for cocaine use disorder. Recently there has been a great deal of interest in the potential of psychedelic drugs such as psilocybin to treat psychiatric disorders. Human studies have indicated that a single administration of psilocybin can have long-lasting effects. Few preclinical studies have examined a role for psilocybin in addiction models. The goal of the current study was to determine whether psilocybin would enhance extinction following cocaine self-administration in male and female mice and rats and thus result in an attenuation of cue-induced drug-seeking. In experiments in mice, 16 female and 19 male mice underwent 8d of cocaine self-administration (0.5 mg/kg/infusion) and extinction training. Immediately following extinction trials, mice were injected with vehicle or 1.0 mg/kg psilocybin. Following the conclusion of extinction training, mice were tested for cue-induced reinstatement. In experiments in rats, 24 female and 23 male rats underwent 15d of cocaine self-administration (0.8 mg/kg/infusion) and extinction training. Immediately following extinction trials, rats were injected with vehicle, 1.0 mg/kg psilocybin, or 2.5 mg/kg psilocybin. Following the conclusion of extinction training, rats were tested for cue-induced reinstatement. Psilocybin administered following extinction trials had no effect, as both female and male mice and rats demonstrated significant cue-induced reinstatement. These data suggest that psilocybin is ineffective at altering cocaine-seeking behavior in the paradigm and doses used in the current study. It remains to be seen whether treatment with psilocybin under different conditions may be useful in the long-standing goal of finding pharmacotherapies to treat CUD.

keywords:
Animals, Mice, Inbred C57BL, Mice, Rats, Rats, Sprague-Dawley, Cocaine-Related Disorders, Cocaine, Dopamine Uptake Inhibitors, Hallucinogens, Self Administration, Conditioning, Operant, Cues, Sex Characteristics, Female, Male, Extinction, Psychological, Drug-Seeking Behavior, Psilocybin

raw_json:
{"europe_pmc_id":"39236802","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Kim A, Halton B, Shah A, Seecof OM, Ross S.
publication_date: 2024-08-15
doi: 10.21037/apm-24-35
pubmed_id: 39168642
source_url: https://doi.org/10.21037/apm-24-35
substance_tags: psilocybin
topic_tags: Depression,Anxiety,End-of-Life Distress,Pharmacology,Clinical Trial,Review Article
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Psilocybin-assisted psychotherapy for existential distress: practical considerations for therapeutic application-a review.

abstract:
Existential distress is commonly experienced by patients diagnosed with a life-threatening illness. This condition has been shown to adversely impact quality of life and is correlated with increased suicidal ideation and requests for hastened death. While palliative care teams are experienced in treating depression and anxiety, existential distress is a distinct clinical condition for which traditional medications and psychotherapy approaches demonstrate limited efficacy or duration of effect. Psychedelic drugs, including psilocybin and lysergic acid diethylamide (LSD), in conjunction with psychotherapy have been shown to produce rapid and sustained reductions in existential and psychiatric distress and may be a promising treatment for patients facing existential distress in palliative care settings. In this narrative review article, we describe the history of psychedelic medicine including early studies and the modern wave of research over the past 20 years, which includes high quality clinical trial data. This review outlines specific considerations for therapeutic application of psilocybin including pharmacokinetics, patient selection, dosing, protocol designs, and safeguards to reduce potential adverse effects to help guide future psychedelic practitioners. With growing public interest and evolving state level policy reforms allowing access to psychedelic treatments, it is critical for palliative care providers to gain familiarity with the current state of science and the potential of psilocybin assisted psychotherapy in the treatment of existential distress.

keywords:
Humans, Hallucinogens, Palliative Care, Stress, Psychological, Existentialism, Psychotherapy, Psilocybin

raw_json:
{"europe_pmc_id":"39168642","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Evaluation of TrpM and PsiD substrate promiscuity reveals new biocatalytic capabilities.
authors: Kanis FC, Broude CN, Hellwarth EB, Gibbons WJ, Sen AK, Adams AM, Wang X, Jones JA.
publication_date: 2024-06-17
doi: 10.1002/btpr.3492
pubmed_id: 38888046
source_url: https://doi.org/10.1002/btpr.3492
substance_tags: psilocybin
topic_tags: Mechanism of Action
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
abstract:
N-methylated tryptamines, such as the hallucinogenic natural products, psilocybin and N,N-dimethyltryptamine (DMT), are gaining interest from the medical community due to their potential as next generation treatments for mental health disorders. The clinical relevance of these compounds has driven scientists to develop biosynthetic production routes to a number of tryptamine drug candidates, and efforts are ongoing to expand and further develop these biosynthetic capabilities. To that end, we have further characterized the substrate preferences of two enzymes involved in tryptamine biosynthesis: TrpM, a tryptophan N-methyltransferase from Psilocybe serbica, and PsiD, the gateway decarboxylase of the psilocybin biosynthesis pathway. Here, we show that TrpM can N-methylate the non-native amino acid substrate, 4-hydroxytryptophan, a key intermediate in the Escherichia coli-based recombinant psilocybin biosynthesis pathway. However, the ability to incorporate TrpM into a functional psilocybin biosynthesis pathway was thwarted by PsiD's inability to use N,N-dimethyl-4-hydroxytryptophan as substrate, under the culturing conditions tested, despite demonstrating activity on N-methylated and 4-hydroxylated tryptophan derivatives individually. Taken together, this work expands upon the known substrates for TrpM and PsiD, further increasing the diversity of tryptamine biosynthetic products.

keywords:
Escherichia coli, Tryptamines, Aromatic-L-Amino-Acid Decarboxylases, Methyltransferases, Substrate Specificity, Biocatalysis, Psilocybe, Psilocybin

raw_json:
{"europe_pmc_id":"38888046","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Trips Through the Skin: Reviewing Cutaneous Drug Reactions to Psychedelics and Hallucinogens.
authors: Rahman SM, Salem Y, Hussain A.
publication_date: 2024-04-16
doi: 10.1089/derm.2023.0292
pubmed_id: 38634840
source_url: https://doi.org/10.1089/derm.2023.0292
keywords: Skin, Humans, Drug Eruptions, Ketamine, Hallucinogens
substance_tags: psilocybin
topic_tags: Review Article
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:03
abstract:
Although psychedelic and hallucinogenic substances have gained popularity for therapeutic use, their dermatologic adverse effects are poorly characterized. This review characterizes the cutaneous reactions associated with psychedelic and hallucinogenic drugs. A review of PubMed and Scopus was conducted from the inception of databases to August 31, 2023. Search terms included drug names and classes (cannabis, MDMA, ecstasy, 3,4-methylenedioxymethamphetamine, psychedelics, hallucinogens, peyote, marijuana, lysergic acid diethylamide, LSD, ketamine, dimethyltryptamine, DMT, phencyclidine, PCP, dextromethorphan, psilocybin, and ayahuasca), and dermatosis terms (dermatitis, contact dermatitis, drug eruption, skin reaction, and urticaria). Studies were included if there was an association with a psychedelic or hallucinogenic and any cutaneous reaction; studies without both components were excluded. Twenty-two studies met inclusion criteria, describing reactions to cannabis (10 studies), MDMA (5 studies), ketamine (4 studies), and psilocybin (3 studies). Forty total patients were included. Among cannabis-related reactions, the most common reaction was type I hypersensitivity by topical exposure (n = 21). Three patients reported type IV hypersensitivity reactions to contact with cannabis or cannabis-derived oils, all of whom experienced vesicular contact dermatitis. Two additional patients presented with an erythema-multiforme-like reaction and acute generalized exanthematous pustulosis after systemic administration, respectively. MDMA was associated with acneiform eruptions (2 cases), an urticarial eruption, a guttate psoriasis-like reaction, a fixed drug eruption, and Stevens-Johnson syndrome (1 case). Four patients reported type I hypersensitivity reactions to ketamine. Four patients reported vesicular eruptions, cyanosis, or widespread jaundice to psilocybin. Of the cases, 8 patients had cutaneous reactions that resolved with drug cessation, 10 resolved with cessation plus treatment, and resolution in 7 cases was not reported. Zero studies were found describing other psychedelic or hallucinogenic compounds. Further research is required to characterize reactions and treatments linked to the variety of extant psychedelics and hallucinogens.

raw_json:
{"europe_pmc_id":"38634840","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Žuljević MF, Mijatović A, Marušić SL, Kudrjavets G, Buljan I, Hren D.
publication_date: 2023-11-02
doi: 10.1080/02791072.2023.2274382
pubmed_id: 37921118
source_url: https://doi.org/10.1080/02791072.2023.2274382
substance_tags: psilocybin
topic_tags: Mystical Experience
study_type: Qualitative Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
title:
Mystical and Affective Aspects of Psychedelic Use in a Naturalistic Setting: A Linguistic Analysis of Online Experience Reports.

abstract:
Analyzing online retrospective experience reports of psychedelic use can provide valuable insight into their acute subjective effects. Such reports are unexplored in relation to mystical states, which are thought to be a therapeutic mechanism within psychedelic-assisted psychotherapy. We created a set of words that, when encountered in an experience report, indicate the occurrence of mystical elements within the experience. We used the Shroomery.org website to retrieve 7317 publicly available retrospective psychedelic experience reports of psychedelic use, primarily of psilocybin, and have a designated experience intensity level self-assessed by the text authors during submission of the report. We counted the mystical language words using Linguistic Inquiry and Word Count (LIWC) software and additionally performed sentiment analysis of all reports. We found that the occurrence of mystical language grew with increased self-reported experience intensity. We also found that negative sentiment increased, and positive sentiment decreased as self-reported psychedelic experience intensity increased. These two findings raise the question of whether mystical experiences can co-exist with challenging elements within the psychedelic experience, a consideration for future qualitative studies. We present a new mystical language dictionary measure for further use and expansion, with some suggestions on how it can be used in future studies.

keywords:
Humans, Hallucinogens, Retrospective Studies, Affect, Mysticism, Linguistics, Internet, Self Report, Psilocybin

raw_json:
{"europe_pmc_id":"37921118","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Novel treatments for anorexia nervosa: Insights from neuroplasticity research.
authors: Keeler JL, Kan C, Treasure J, Himmerich H.
publication_date: 2023-10-11
doi: 10.1002/erv.3039
pubmed_id: 37823233
source_url: https://doi.org/10.1002/erv.3039
keywords: Humans, Anorexia Nervosa, Psychotherapy, Neuronal Plasticity
substance_tags: psilocybin
topic_tags: Eating Disorders,Neuroplasticity,Brain Imaging,Aging,Inflammation
study_type: Qualitative Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
abstract:
ObjectiveTreatment for anorexia nervosa (AN) remains challenging; there are no approved psychopharmacological interventions and psychotherapeutic strategies have variable efficacy. The investigation of evidence-based treatments has so far been compounded by an underdeveloped understanding into the neurobiological changes associated with the acute stages of AN. There is converging evidence of deficiencies in neuroplasticity in AN.MethodThis paper provides an overview of neuroimaging, neuropsychological, molecular and qualitative findings relating to neuroplasticity in AN, translating these findings to the identification of novel biological and psychotherapeutic strategies.ResultsNovel psychopharmacological approaches that may ameliorate deficiencies in neuroplasticity include medications such as ketamine, psilocybin and human recombinant leptin. Anti-inflammatory medications and brain-derived neurotrophic factor mimetics may emerge as potential treatments following further research. Psychotherapeutic strategies that may target neuroplastic deficiencies, as well as having wider effects on identity, include imagery rescripting, memory specificity training, cognitive remediation therapy, exposure therapies, narrative therapies, cultural interventions (e.g. music and arts therapies) and yoga/mindfulness-based interventions.ConclusionsTreatments specifically targeted towards mitigating the neurobiological sequalae of AN are warranted, and emerging neurobiological and neuropsychological research utilising longitudinal designs and large sample sizes, as well as initial feasibility studies, are necessitated to bolster translational efforts.

raw_json:
{"europe_pmc_id":"37823233","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Card KG, Grewal A, Closson K, Martin G, Baracaldo L, Allison S, Kruger DJ, Walsh Z.
publication_date: 2023-10-09
doi: 10.1080/02791072.2023.2268640
pubmed_id: 37815125
source_url: https://doi.org/10.1080/02791072.2023.2268640
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 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Therapeutic Potential of Psilocybin for Treating Psychological Distress among Survivors of Adverse Childhood Experiences: Evidence on Acceptability and Potential Efficacy of Psilocybin Use.

abstract:
Survivors of adverse childhood experience are at elevated risk for psychological distress. In recent years, renewed interest in psychedelic medicine has highlighted the therapeutic potential of psilocybin for those who have experienced childhood adversity. However, recreational psilocybin use remains illegal and access to approved therapies is difficult. Such use provides an opportunity to explore the therapeutic potential of psilocybin for psychological distress among people with adverse childhood experiences. Therefore, we conducted an online survey to assess interest in, acceptability of, and experiences with psilocybin. We further explored whether the association between Adverse Childhood Experiences Questionnaire (ACEQ) scores and psychological distress was lower among those who had used psilocybin in the past three months. Results showed high levels of interest in and acceptability of psilocybin that did not differ across ACEQ scores. Results also showed that the effect of adverse childhood experiences on psychological distress was lower for people who had recently used psilocybin (p =.019). Taken together, these findings suggest that psilocybin therapy may be potentially acceptable and may feasibly help in supporting survivors of adverse childhood experiences with particularly strong benefits to those with more severe childhood adversity.

keywords:
Humans, Hallucinogens, Stress, Psychological, Adolescent, Adult, Middle Aged, Patient Acceptance of Health Care, Female, Male, Young Adult, Surveys and Questionnaires, Psilocybin, Adverse Childhood Experiences, Psychological Distress

raw_json:
{"europe_pmc_id":"37815125","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: A narrative exploration of psilocybin's potential in mental health.
authors: Min H, Park SY, Park J, Na S, Lee HS, Kim T, Ham J, Park YT.
publication_date: 2024-10-29
doi: 10.3389/fpsyt.2024.1429373
pubmed_id: 39540010
source_url: https://doi.org/10.3389/fpsyt.2024.1429373
substance_tags: psilocybin
topic_tags: Mechanism of Action,Clinical Trial,Review Article,Safety,Adverse Events
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
abstract:
Psilocybin, a psychoactive substance, has recently garnered attention for its high therapeutic potential in psychiatry. In this study, we investigated the multifaceted aspects of psilocybin, highlighting its chemical properties, mechanisms of action, and burgeoning role in psychiatric treatment. Furthermore, we examined the clinical applications and potential therapeutic benefits of psilocybin in the treatment of various mental health disorders, supported by accumulating clinical evidence. This review aims to deepen our understanding of the clinical impact of psilocybin, elucidate its therapeutic value, and propose directions for future research, thereby paving the way for its integration into mainstream psychiatric treatments. Psilocybin has been shown to be safe in clinical trials with manageable side effects. However, additional safety measures are required after this discussion, including dosing protocols, patient monitoring, and distress management strategies.

raw_json:
{"europe_pmc_id":"39540010","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Wiens KR, Brooks NAH, Riar I, Greuel BK, Lindhout IA, Klegeris A.
publication_date: 2024-10-27
doi: 10.3390/molecules29215084
pubmed_id: 39519725
source_url: https://doi.org/10.3390/molecules29215084
substance_tags: psilocybin,psilocin
topic_tags: Receptor Pharmacology,Oxidative Stress,Animal Study,Inflammation,Immune Function
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:00
title:
Psilocin, the Psychoactive Metabolite of Psilocybin, Modulates Select Neuroimmune Functions of Microglial Cells in a 5-HT2 Receptor-Dependent Manner.

abstract:
Neuroinflammation that is caused by microglia, the main immune cells of the brain, contributes to neurodegenerative diseases. Psychedelics, including psilocybin and lysergic acid diethylamide (LSD), possess certain anti-inflammatory properties and, therefore, should be considered as drug candidates for treating neuroinflammatory pathologies. When ingested, psilocybin is rapidly dephosphorylated to yield psilocin, which crosses the blood-brain barrier and exerts psychotropic activity by interacting with the 5-hydroxytryptamine 2A receptors (5-HT2ARs) on neurons. Since microglia express all three 5-HT2R isoforms, we hypothesized that, by interacting with these receptors, psilocin beneficially modulates select neuroimmune functions of microglia. We used microglia-like cell lines to demonstrate that psilocin, at non-toxic concentrations, did not affect the secretion of tumor necrosis factor (TNF) by immune-stimulated microglial cells, but significantly inhibited their phagocytic activity, the release of reactive oxygen species (ROS), and nitric oxide (NO) production. The inhibitory activity of psilocin on the latter two functions was similar to that of two selective 5-HT2R agonists, namely, 25I-NBOH and Ro60-0175. The role of this subfamily of receptors was further demonstrated by the application of 5-HT2R antagonists cyproheptadine and risperidone. Psilocin should be considered a novel drug candidate that might be effective in treating neuroimmune disorders, such as neurodegenerative diseases, where reactive microglia are significant contributors.

keywords:
Microglia, Cell Line, Animals, Humans, Mice, Nitric Oxide, Reactive Oxygen Species, Tumor Necrosis Factor-alpha, Receptors, Serotonin, 5-HT2, Hallucinogens, Phagocytosis, Psilocybin

raw_json:
{"europe_pmc_id":"39519725","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Kim K, Yusuf A, Sud A, Persaud N, Kirubarajan A, Moller M, Lloyd T, O'Neill B.
publication_date: 2024-10-23
doi: 10.1371/journal.pone.0309911
pubmed_id: 39446753
source_url: https://doi.org/10.1371/journal.pone.0309911
keywords: Humans, Hallucinogens, Evidence-Based Medicine, Internet, Ontario
substance_tags: psilocybin
topic_tags: Depression,Healthcare Workers,Safety
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
title:
Critical appraisal of evidence supporting prescription of psychedelics from clinic websites in Ontario, Canada.

abstract:
Psychedelics, including ketamine, 3,4-Methyl enedioxy methamphetamine (MDMA), and psilocybin, have gained attention for their potential therapeutic role in mental health treatment. While recreational use is prohibited in Canada, medicinal exemptions can be granted. There are several psychedelic clinics in Ontario, Canada, promoting the use of psychedelics for a variety of medical indications. Our objective was to identify the indications for which psychedelics are being prescribed in Ontario clinics and assess the quality of evidence used to support these claims. Internet searches were conducted using Google and Bing to identify psychedelic clinics in Ontario. Inclusion criteria was as follow: clinics were physically located in Ontario, had a functioning website link, and demonstrated involvement of a licensed physician or nurse practitioner. Identified clinics were evaluated for their claims of effectiveness, the quality of evidence used to support these claims, and statements on psychedelic-related harms. The cited studies were appraised for quality using Oxford Centre for Evidence-Based Medicine Levels of Evidence, "level 5" being the lowest quality and "level 1" being the highest quality. Out of 200 search results, 10 psychedelic clinic websites met our inclusion criteria. These clinics advertised psychedelics for 47 medical conditions, most commonly for depression. Only 2 out of 10 clinics described potential risks associated with psychedelic use. There were 29 studies cited by these websites, majority coming from "level 4" evidence consisting of case-series and case-control studies. Overall, the cited evidence quality was low to moderate. Psychedelic clinics in Ontario promote a wide range of medical indications for psychedelics using primarily low to moderate "level 4" evidence. There is limited information shared on the potential adverse effects of psychedelics. Our study emphasizes the importance of using transparent and high-quality evidence by clinics and clinicians to ensure safe and effective use of psychedelics in mental health treatments.

raw_json:
{"europe_pmc_id":"39446753","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Expert recommendations for Germany's integration of psychedelic-assisted therapy.
authors: Perez Rosal SR, La Torre JT, Birnkammer S, Chernoloz O, Williams MT, Faber SC.
publication_date: 2024-10-23
doi: 10.1186/s12909-024-06141-3
pubmed_id: 39443907
source_url: https://doi.org/10.1186/s12909-024-06141-3
keywords: Humans, Hallucinogens, Germany
substance_tags: psilocybin
topic_tags: PTSD,Mechanism of Action,Clinical Trial
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
abstract:
As clinical trials for psychedelics move into phase III in the USA, Europe must address its lag in integrating professional education around psychedelic-assisted therapy (PAT) and supporting psychedelic drug research. This paper evaluates the necessary frameworks for implementing PAT in Germany, emphasizing the nation's potential leadership role within the European Union. With Australia having already approved MDMA and psilocybin for mental health indications, the Ukrainian government exploring MDMA treatment for war-related PTSD, and initial clinical trials involving MDMA and LSD with patients in Switzerland which restarted the restricted medical use of these substances around 2014, the medical authorization of psychedelics in these countries establishes precedent showcasing both the promise and challenges of researching and implementing PAT in nations where the substances were formally scheduled as illicit substances. Key challenges include establishing rigorous standards for practitioner training, accessibility, and defining regulatory oversight. This paper focuses on the development of robust infrastructure in Germany, which will support the roll out of PAT, and details ethical considerations, training protocols, and governmental roles in the formulation of treatment frameworks. This approach aims not only to guide Germany in adopting PAT but also to influence broader European policy, ensuring that patients receive ethically sound and proficient care. The findings suggest pathways for Europe to reclaim its historical lead in psychiatric and therapeutic innovation.

raw_json:
{"europe_pmc_id":"39443907","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Olami A, Peled-Avron L.
publication_date: 2024-10-17
doi: 10.1038/s41598-024-74810-w
pubmed_id: 39424835
source_url: https://doi.org/10.1038/s41598-024-74810-w
keywords: Humans, Lysergic Acid Diethylamide, Hallucinogens, Emotions, Empathy, Cognition, Psilocybin
substance_tags: psilocybin
topic_tags: Emotional Processing,Meta-Analysis,Review Article,Drug Interactions
study_type: Meta-Analysis
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:03
title:
Effects of classical psychedelics on implicit and explicit emotional empathy and cognitive empathy: a meta-analysis of MET task.

abstract:
This meta-analysis investigates the effect of classic psychedelic drugs on empathy and focuses on cognitive and emotional empathy measured using the Multifaceted Empathy Test (MET). Empathy entails the ability to understand and share the feelings of another and is a significant component of social interaction. Several studies have examined the effects of psychedelic drugs such as LSD, psilocybin and ayahuasca on empathy, yet their overall effect has not been studied so far. In this meta-analysis, we reviewed data from studies up to November 2023 with the aim of examining the effects of various psychedelic drugs on empathic abilities broadly. Our findings suggest that classical psychedelics significantly enhance explicit and implicit emotional empathy without affecting measures of cognitive empathy. The results emphasize the need to continue testing the therapeutic potential of classic psychedelic drugs.

raw_json:
{"europe_pmc_id":"39424835","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Lee J, Tantillo DJ, Wang LP, Fiehn O.
publication_date: 2024-09-26
doi: 10.1021/acs.jcim.4c00761
pubmed_id: 39329341
source_url: https://doi.org/10.1021/acs.jcim.4c00761
keywords: Protons, Quantum Theory, Models, Chemical, Tandem Mass Spectrometry, Molecular Dynamics Simulation
substance_tags: psilocin
topic_tags: Mechanism of Action
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
title:
Impact of Protonation Sites on Collision-Induced Dissociation-MS/MS Using CIDMD Quantum Chemistry Modeling.

abstract:
Protonation is the most frequent adduct found in positive electrospray ionization collision-induced mass spectra (CID-MS/MS). In a parallel report Lee, J. J. Chem. Inf. Model. 2024, 10.1021/acs.jcim.4c00760, we developed a quantum chemistry framework to predict mass spectra by collision-induced dissociation molecular dynamics (CIDMD). As different protonation sites affect fragmentation pathways of a given molecule, the accuracy of predicting tandem mass spectra by CIDMD ultimately depends on the choice of its protomers. To investigate the impact of molecular protonation sites on MS/MS spectra, we compared CIDMD-predicted spectra to all available experimental MS/MS spectra by similarity matching. We probed 10 molecules with a total of 43 protomers, the largest study to date, including organic acids (sorbic acid, citramalic acid, itaconic acid, mesaconic acid, citraconic acid, and taurine) as well as aromatic amines including uracil, aniline, bufotenine, and psilocin. We demonstrated how different protomers can converge different fragmentation pathways to the same fragment ions but also may explain the presence of different fragment ions in experimental MS/MS spectra. For the first time, we used in silico MS/MS predictions to test the impact of solvents on proton affinities, comparing the gas phase and a mixture of acetonitrile/water (1:1). We also extended applications of in silico MS/MS predictions to investigate the impact of protonation sites on the energy barriers of isomerization between protomers via proton transfer. Despite our initial hypothesis that the thermodynamically most stable protomer should give the best match to the experiment, we found only weak inverse relationships between the calculated proton affinities and corresponding entropy similarities of experimental and CIDMD-predicted MS/MS spectra. CIDMD-predicted mechanistic details of fragmentation reaction pathways revealed a clear preference for specific protomer forms for several molecules. Overall, however, proton affinity was not a good predictor corresponding to the predicted CIDMD spectra. For example, for uracil, only one protomer predicted all experimental MS/MS fragment ions, but this protomer had neither the highest proton affinity nor the best MS/MS match score. Instead of proton affinity, the transfer of protons during the electrospray process from the initial protonation site (i.e., mobile proton model) better explains the differences between the thermodynamic rationale and experimental data. Protomers that undergo fragmentation with lower energy barriers have greater contributions to experimental MS/MS spectra than their thermodynamic Boltzmann populations would suggest. Hence, in silico predictions still need to calculate MS/MS spectra for multiple protomers, as the extent of distributions cannot be readily predicted.

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{"europe_pmc_id":"39329341","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Latin American adults who regularly use macrodoses of psychedelics: a cross-sectional study.
authors: Véliz-García O, Domic-Siede M.
publication_date: 2024-10-12
doi: 10.1038/s41598-024-74590-3
pubmed_id: 39397094
source_url: https://doi.org/10.1038/s41598-024-74590-3
substance_tags: psilocybin
topic_tags: Wellbeing,Spirituality,Observational Study,Adolescents
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
abstract:
Psychedelics have a complex history marked by traditional use among indigenous cultures, early scientific interest, and subsequent prohibition. Despite their classification as controlled substances, recent decades have witnessed a resurgence of research into their therapeutic potential for various mental health conditions. However, most studies have focused on controlled clinical settings, leaving a significant gap in understanding how these substances are used in naturalistic contexts, particularly in Latin America. This study investigates the regular use of macrodoses of psychedelics among Latin American adults. We aimed to characterize the sociodemographic profiles, consumption practices, and subjective effects experienced by individuals who use psychedelics regularly. Data were collected via an online survey from 4,270 participants across several Latin American countries. Results indicated a diverse user base with varied motivations, predominantly psychological and spiritual well-being. The most frequently used substance was psilocybin mushrooms, with significant associations found between demographic variables and specific psychedelics used. The study provides new insights into the naturalistic use of psychedelics in Latin America, highlighting the need for informed, safe, and legal use frameworks.

keywords:
Humans, Hallucinogens, Cross-Sectional Studies, Adolescent, Adult, Middle Aged, Latin America, Female, Male, Young Adult, Surveys and Questionnaires, Psilocybin

raw_json:
{"europe_pmc_id":"39397094","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Snapshot of 5-HT2A receptor activation in the mouse brain via IP1 detection
authors: de la Fuente Revenga M, González-Maeso J.
journal: bioRxiv
publication_date: 2024-10-11
doi: 10.1101/2024.10.11.617861
source_url: https://doi.org/10.1101/2024.10.11.617861
substance_tags: psilocybin
study_type: Animal Study
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
abstract:
The distinct subjective effects that define psychedelics such as LSD, psilocybin or DOI as drug class are causally linked to activation of the serotonin 2A receptor (5-HT2A R). However, some aspects of 5-HT2A R pharmacology remain elusive, such as what molecular drivers differentiate psychedelic from non-psychedelic 5-HT2A R agonists. We developed an ex vivo platform to obtain snapshots of drug-mediated 5-HT2A R engagement of the canonical G q/11 pathway in native tissue. This non-radioactive methodology captures the pharmacokinetic and pharmacodynamic events leading up to changes in inositol monophosphate (IP1 ) in the mouse brain. The specificity of this method was assessed by comparing IP1 levels in homogenates from the frontal cortex in DOI-treated wild-type and 5-HT2A R-KO animals compared to other brain regions, namely striatum and cerebellum. Furthermore, we encountered that head-twitch response (HTR) counts and IP1 in the frontal cortex were correlated. We observed that IP1 levels in frontal cortex homogenates from mice treated with LSD and lisuride vary in magnitude, consistent with LSD’s 5-HT2A R agonism and psychedelic nature, and lisuride’s lack thereof. MDMA evoked an increase of IP1 signal in the frontal cortex that were not matched by the serotonin precursor 5-HTP or the serotonin reuptake inhibitor fluoxetine. We attribute differences in the readout primarily to the indirect stimulation of 5-HT2A R by MDMA via serotonin release from its presynaptic terminals. This methodology enables capturing a snapshot of IP1 turnover in the mouse brain that can provide mechanistic insights in the study of psychedelics and other serotonergic agents pharmacodynamics.

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

raw_json:
{"europe_pmc_id":"PPR923549","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


title: Neuroprotective effects of psilocybin in a rat model of stroke.
authors: Yu SJ, Wu KJ, Wang YS, Bae E, Chianelli F, Bambakidis N, Wang Y.
publication_date: 2024-10-07
doi: 10.1186/s12868-024-00903-x
pubmed_id: 39379834
source_url: https://doi.org/10.1186/s12868-024-00903-x
substance_tags: psilocybin
topic_tags: Mechanism of Action,Receptor Pharmacology,Randomized Controlled Trial,Animal Study
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:00
abstract:
BackgroundPsilocybin is a psychedelic 5HT2A receptor agonist found in "magic mushrooms". Recent studies have indicated that 5HT2A agonists, such as dimethyltryptamine, given before middle cerebral artery occlusion (MCAo), improve staircase behavior, increased BDNF expression, and reduce brain infarction in stroke rats. The objective of this study is to determine the protective effect of psilocybin in cellular and animal models of stroke.MethodsAdult male and timed-pregnant Sprague-Dawley rats were used for this study. The neural protective effects of psilocybin were determined in primary rat cortical neurons and adult rats. Rats were subjected to a 60-min middle cerebral artery occlusion. Brain tissues were collected for histological and qRTPCR analysis.ResultsPsilocybin reduced glutamate-mediated neuronal loss in rat primary cortical neuronal cultures. Psilocybin-mediated protection in culture was antagonized by the BDNF inhibitor ANA12. Pretreatment with psilocybin reduced brain infarction and neurological deficits in stroke rats. Early post-treatment with psilocybin improved locomotor behavior, upregulated the expression of MAP2 and synaptophysin, and down-regulated the expression of IBA1 in the stroke brain. ANA12 significantly attenuated psilocybin-mediated reduction in brain infarction and improvements in locomotor behavior.ConclusionsPsilocybin reduced brain infarction and improved locomotor behavior in stroke rats; the protective mechanisms involve regulating BDNF expression. Our data support a novel therapeutic approach of psilocybin in stroke.

keywords:
Cerebral Cortex, Neurons, Cells, Cultured, Animals, Rats, Rats, Sprague-Dawley, Infarction, Middle Cerebral Artery, Disease Models, Animal, Brain-Derived Neurotrophic Factor, Microtubule-Associated Proteins, Synaptophysin, Neuroprotective Agents, Female, Male, Stroke, Psilocybin

raw_json:
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authors: Dahan JDC, Dadiomov D, Bostoen T, Dahan A.
publication_date: 2024-10-05
doi: 10.1038/s44184-024-00091-w
pubmed_id: 39369173
source_url: https://doi.org/10.1038/s44184-024-00091-w
substance_tags: psilocybin
topic_tags: Depression,Addiction,Meta-Analysis,Systematic Review,Review Article
study_type: Meta-Analysis
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Meta-correlation of the effect of ketamine and psilocybin induced subjective effects on therapeutic outcome.

abstract:
There is some evidence that the subjective effects of ketamine and other psychedelics like psilocybin are crucial for their therapeutic outcomes, such as treatment of depression or substance use disorder (SUD). We performed a meta-analysis and systematic review on the correlation of subjective symptoms and dissociation versus ketamine-induced therapeutic outcomes in patients with depression or SUD. A similar analysis was conducted for psilocybin-induced therapeutic improvement. We retrieved 23 papers studying ketamine (21 on depression, 2 on SUD) in 471 patients and 8 papers studying psilocybin (6 on depression, 2 on SUD) in 183 patients. Our study demonstrated a modest role for subjective effects mediating therapeutic outcomes, with R2-values ranging from 5-10% for ketamine and for psilocybine the R2 was 24%. A greater mediating effect for psilocybin compared to ketamine was detected, particularly when restricting the analysis to depression. Additionally there is a greater mediating effect in SUD than depression, irrespective of treatment.

raw_json:
{"europe_pmc_id":"39369173","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: What should constitute a control condition in psychedelic drug trials?
authors: Colloca L, Fava M.
publication_date: 2024-09-29
doi: 10.1038/s44220-024-00321-2
pubmed_id: 39781538
source_url: https://doi.org/10.1038/s44220-024-00321-2
substance_tags: psilocybin
topic_tags: General
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
abstract:
Over the past decade there has been a surge in interest in placebo-controlled trials using non-classical 3,4-methylenedioxymethamphetamine (MDMA) and classical psychedelics such as psilocybin, lysergic acid diethylamide (LSD) and N,N-dimethyltryptamine (DMT) to treat neuropsychiatric disorders. However, the success and reliability of these trials depend on the design of the trials, the choice of control conditions, and the ability to blind both participants and researchers. When appropriate control conditions are lacking, it becomes difficult to disentangle placebo and expectation effects from medication effects. Here we explore the neurobiology of placebo and expectation effects, alongside the methodological considerations for selecting suitable control conditions in psychedelic trials. This includes examining the advantages and disadvantages of various control conditions and proposing new directions to enhance the validity of these trials and their regulatory science. By addressing these factors, we aim to improve the reliability of psychedelic research in uncovering the therapeutic benefits of psychedelics beyond placebo and expectation effects.

raw_json:
{"europe_pmc_id":"39781538","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2024-09-20
doi: 10.1016/j.eclinm.2024.102799
pubmed_id: 39764567
source_url: https://doi.org/10.1016/j.eclinm.2024.102799
substance_tags: psilocybin
topic_tags: Depression,Receptor Pharmacology,Clinical Trial,Observational Study,Safety,Contraindications
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Effect of psilocybin versus escitalopram on depression symptom severity in patients with moderate-to-severe major depressive disorder: observational 6-month follow-up of a phase 2, double-blind, randomised, controlled trial.

authors:
Erritzoe D, Barba T, Greenway KT, Murphy R, Martell J, Giribaldi B, Timmermann C, Murphy-Beiner A, Jones MB, Nutt D, Weiss B, Carhart-Harris R.

abstract:
BackgroundPsilocybin therapy (PT) produces rapid and persistent antidepressant effects in major depressive disorder (MDD). However, the long-term effects of PT have never been compared with gold-standard treatments for MDD such as pharmacotherapy or psychotherapy alone or in combination.MethodsThis is a 6-month follow-up study of a phase 2, double-blind, randomised, controlled trial involving patients with moderate-to-severe MDD. Participants were recruited from a hospital in the UK. Male or female patients with major depressive disorder (DSM-IV), moderate to severe depression (HAM-D ≥17), no MRI or SSRI contraindications, confirmed diagnosis by a GP or mental healthcare professional, aged 18-80, and competent in English were eligible. Patients were randomly assigned (1:1) to receive either two 25 mg doses of the psychedelic drug psilocybin administered orally combined with psychological support ('psilocybin therapy' or PT) and book-ended by further support or a 6-week course of the selective serotonin reuptake inhibitor (SSRI) escitalopram (administered daily at 10 mg for three weeks and 20 mg for the subsequent three weeks) plus matched psychological support ('escitalopram treatment' or ET). The primary outcome measure was change from baseline in the score on the 16-item Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR-16) at week 6, which has been reported previously. Herein, we present results at the 6-month follow-up time point. Measures of social functioning, connectedness, and meaning in life constituted the study's secondary outcomes during follow-up. Safety in the follow-up period was not assessed. This trial is registered at ClinicalTrials.gov, NCT03429075.FindingsBetween January 15th, 2019 and March 20th, 2020, 59 patients were enrolled and 30 (11 females [37%] and 19 males [63%]) were assigned to the psilocybin group and 29 (9 females [31%] and 20 males [69%]) to the escitalopram group. 25 participants in the PT group and 21 in the ET group completed the 6-month follow-up. At the 6-month follow-up, both PT and ET conditions yielded sustained improvements in depressive symptom severity. The mean between-condition difference in QIDS-SR-16 scores at 6-months was 1.51 (95% CI: -1.35, 4.38; p = 0.311). Secondary outcomes demonstrated that PT had greater mean between-condition differences in functioning (WSAS: -7.46; 95% CI: -12.4, -2.47; p

raw_json:
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publication_date: 2024-09-30
doi: 10.1017/s1478951524001494
pubmed_id: 39379285
source_url: https://doi.org/10.1017/s1478951524001494
substance_tags: psilocybin
topic_tags: End-of-Life Distress
study_type: Qualitative Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
What do health professionals think about implementing psilocybin-assisted therapy in palliative care for existential distress? A World Café qualitative study.

authors:
Masse-Grenier M, Chang SL, Bélanger A, Stephan JF, Hébert J, Deschamps P, Plourde L, Provost F, Farzin H, Fallu JS, Dorval M, P3A Research Group.

abstract:
ObjectivesPromising studies show that psilocybin-assisted therapy relieves existential distress in patients with serious illnesses, a difficult condition to treat with current treatment options. There is growing interest in this therapy in palliative care. Canada recently amended its laws to allow physicians to request psilocybin for end-of-life distress. However, barriers to access remain. Since implementing psilocybin-assisted therapy within palliative care depends on the attitudes of healthcare providers willing to recommend it, they should be actively engaged in the broader discussion about this treatment option. We aimed (1) to identify issues and concerns regarding the acceptability of this therapy among palliative care professionals and to discuss ways of remedying them and (2) to identify factors that may facilitate access.MethodsA qualitative study design and World Café methodology were adopted to collect data. The event was held on April 24, 2023, with 16 palliative care professionals. The data was analyzed following an inductive approach.ResultsAlthough participants were interested in psilocybin-assisted therapy, several concerns and needs were identified. Educational and certified training needs, medical legalization of psilocybin, more research, refinement of therapy protocols, reflections on the type of professionals dispensing the therapy, the treatment venue, and eligibility criteria for treatment were discussed.Significance of resultsPalliative care professionals consider psilocybin-assisted therapy a treatment of interest, but it generates several concerns. According to our results, the acceptability of the therapy and the expansion of its access seem interrelated. The development of guidelines will be essential to encourage wider therapy deployment.

keywords:
Humans, Palliative Care, Attitude of Health Personnel, Existentialism, Qualitative Research, Adult, Middle Aged, Health Personnel, Canada, Female, Male, Psilocybin, Psychological Distress

raw_json:
{"europe_pmc_id":"39379285","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2024-09-26
doi: 10.1177/02698811241282637
pubmed_id: 39340164
source_url: https://doi.org/10.1177/02698811241282637
substance_tags: psilocybin
topic_tags: Wellbeing,Emotional Processing,Spirituality,Mystical Experience
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
title:
Meditating on psychedelics. A randomized placebo-controlled study of DMT and harmine in a mindfulness retreat.

authors:
Meling D, Egger K, Aicher HD, Jareño Redondo J, Mueller J, Dornbierer J, Temperli E, Vasella EA, Caflisch L, Pfeiffer DJ, Schlomberg JT, Smallridge JW, Dornbierer DA, Scheidegger M.

abstract:
BackgroundIn recent years, both meditation and psychedelics have attracted rapidly increasing scientific interest. While the current state of evidence suggests the promising potential of psychedelics, such as psilocybin, to enhance meditative training, it remains equivocal whether these effects are specifically bound to psilocybin or if other classical psychedelics might show synergistic effects with meditation practice. One particularly promising candidate is N,N-dimethyltryptamine (DMT), an active ingredient of ayahuasca.AimThis study aims to investigate the effect of the psychedelic substance DMT, combined with the monoamine oxidase inhibitor harmine (DMT-harmine), on meditative states, compared to meditation with a placebo.MethodForty experienced meditators (18 females and 22 males) participated in a double-blind, placebo-controlled study over a 3-day meditation retreat, receiving either placebo or DMT-harmine. Participants' levels of mindfulness, compassion, insight, and transcendence were assessed before, during, and after the meditation group retreat, using psychometric questionnaires.ResultsCompared to meditation with a placebo, meditators who received DMT and harmine self-attributed greater levels of mystical-type experiences, non-dual awareness, and emotional breakthrough during the acute substance effects and, when corrected for baseline differences, greater psychological insight 1 day later. Mindfulness and compassion were not significantly different in the DMT-harmine group compared to placebo. At 1-month follow-up, the meditators who received DMT and harmine rated their experience as significantly more personally meaningful, spiritually significant, and well-being-enhancing than the meditators who received placebo.ConclusionInvestigating the impact of DMT-harmine on meditators in a naturalistic mindfulness group retreat, this placebo-controlled study highlights the specific effects of psychedelics during meditation.Trial registrationClinicalTrials.gov identifier NCT05780216.

keywords:
Humans, Banisteriopsis, N,N-Dimethyltryptamine, Harmine, Hallucinogens, Monoamine Oxidase Inhibitors, Meditation, Double-Blind Method, Adult, Middle Aged, Female, Male, Young Adult, Mindfulness

raw_json:
{"europe_pmc_id":"39340164","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Artificial intelligence and psychedelic medicine.
authors: Sarris J, Halman A, Urokohara A, Lehrner M, Perkins D
journal: Annals of the New York Academy of Sciences
publication_date: 2024-09-30
doi: 10.1111/nyas.15229
pubmed_id: 39308441
source_url: https://pubmed.ncbi.nlm.nih.gov/39308441/
substance_tags: psilocybin
topic_tags: Pharmacology,Clinical Trial,Review Article
study_type: Clinical Trial
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:36
raw_json: {"pubmed_id":"39308441"}
abstract:
Artificial intelligence (AI) and psychedelic medicines are among the most high-profile evolving disruptive innovations within mental healthcare in recent years. Although AI and psychedelics may not have historically shared any common ground, there exists the potential for these subjects to combine in generating innovative mental health treatment approaches. In order to inform our perspective, we conducted a scoping review of relevant literature up to late August 2024 via PubMed intersecting AI with psychomedical use of psychedelics. Our perspective covers the potential application of AI in psychedelic medicine for: drug discovery and clinical trial optimization (including pharmacodynamics); study design; understanding psychedelic experiences; personalization of treatments; clinical screening, delivery, and follow-up (potentially delivered via chatbots/apps); application of psychological preparation, integration, and general mental health support; its role in enhancing treatment via brain modulatory devices (including virtual reality and haptic suits); and the consideration of ethical and security safeguards. Challenges include the need for sufficient data protection and security, and a range of necessary ethical protections. Future avenues of exploration could involve directly administering psychedelics (or providing algorithm-generated effects) to inorganic AI-interfaced neural networks that may exceed human brain activity (i.e., cognitive capacity) and intelligence.

keywords:
AI, DMT, computational psychiatry, disruptive innovation, machine learning, natural language processing, psilocybin, virtual reality


authors: Calder AE, Rausch B, Liechti ME, Holze F, Hasler G.
publication_date: 2024-09-19
doi: 10.1177/02698811241278873
pubmed_id: 39302087
source_url: https://doi.org/10.1177/02698811241278873
substance_tags: psilocybin
topic_tags: Depression,Mystical Experience,Healthy Volunteers
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
title:
Naturalistic psychedelic therapy: The role of relaxation and subjective drug effects in antidepressant response.

abstract:
BackgroundPsychedelic-assisted therapy (PAT) is permitted in Switzerland under its limited medical use program. Data from patients in this program represent a unique opportunity to analyze the real-world practice of PAT.AimsThis study compared the subjective effects of lysergic acid diethylamide (LSD) and psilocybin between patients undergoing PAT and healthy volunteers. For the patients, it also investigated the relationship between antidepressant effects and six measures of acute drug effects.MethodsWe compared data on acute psychedelic drug effects between 28 PAT patients with data from 28 healthy participants who participated in a randomized, double-blind crossover trial. All participants received varying doses of psilocybin and LSD. Subjective effects were assessed on an hourly basis during the acute drug effects, and the Mystical Experience Questionnaire (MEQ) was completed retrospectively. For patients, depressive symptoms were assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS).ResultsRatings of overall drug effect and mystical experience were similar across groups. Compared with healthy controls, patients reported lower ratings of ego dissolution. Patients showed a significant decrease in MADRS scores, and the greatest predictor of antidepressant outcome was relaxation during the PAT session. We did not observe a relationship between mystical-type experiences and antidepressant effects. Most patients experienced mild adverse effects which resolved within 48 h.ConclusionPAT reduced depressive symptoms in this heterogeneous patient group. Patients may experience more challenging psychedelic effects and reduced ego dissolution. Hourly assessment of drug effects may predict clinical outcomes better than retrospectively assessed mystical experiences, and the impact of relaxation during PAT should be investigated further.

keywords:
Humans, Lysergic Acid Diethylamide, Hallucinogens, Antidepressive Agents, Treatment Outcome, Relaxation, Cross-Over Studies, Double-Blind Method, Depression, Psychiatric Status Rating Scales, Mysticism, Adult, Middle Aged, Switzerland, Female, Male, Young Adult, Psilocybin

raw_json:
{"europe_pmc_id":"39302087","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Less is more? A review of psilocybin microdosing.
authors: Savides IA, Outhoff K.
publication_date: 2024-09-15
doi: 10.1177/02698811241278769
pubmed_id: 39282928
source_url: https://doi.org/10.1177/02698811241278769
keywords: Animals, Humans, Hallucinogens, Dose-Response Relationship, Drug, Psilocybin
substance_tags: psilocybin
topic_tags: Microdosing,Personality Change,Systematic Review,Review Article,Observational Study,Animal Study
study_type: Systematic Review
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
abstract:
BackgroundThe applications of psilocybin, derived from 'magic mushrooms,' are vast, including a burgeoning practice known as microdosing, which refers to the administration of sub-hallucinogenic doses of psychedelic substances to obtain benefits without experiencing significant cognitive and perceptual distortion. However, current research is fairly new with several limitations and gaps that hinder adequate conclusions on its efficacy.AimsThis semi-structured review aimed to identify and highlight research gaps in the field of psilocybin microdosing for future research.MethodsA Preferred Reporting Items for Systematic Reviews and Meta-Analyses based strategy was employed, utilizing a chain of keywords and key phrases across multiple databases, augmented by a cross-sectional Google search for relevant grey literature in the form of the top 10 search results. A total of 40 studies and 8 unique websites were identified, summarized and tabulated into four distinct categories, namely non-clinical, clinical, observational and anecdotal evidence.ResultsThe majority of available evidence originates from observational studies, while non-clinical and clinical study findings remain comparatively sparse and inconsistent. Web-based findings were consistent with current research findings. Key research gaps were highlighted: the imperative for more randomized placebo-controlled trials, exploration of dose-response ranges, psychological and personality testing of participants, utilization of active placebos, greater diversity in study populations, an increase in psilocybin-exclusive microdosing studies and the refinement of animal models.ConclusionDefinitive conclusions regarding the efficacy of psilocybin microdosing remain elusive, emphasizing the need for further study. Numerous research gaps necessitate consideration for future investigations.

raw_json:
{"europe_pmc_id":"39282928","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: The role of psilocybin in depressive disorders.
authors: Najib J.
publication_date: 2024-08-27
doi: 10.1080/03007995.2024.2396536
pubmed_id: 39177339
source_url: https://doi.org/10.1080/03007995.2024.2396536
substance_tags: psilocybin
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:00
abstract:
Depression is a serious psychiatric disorder with a high incidence of morbidity and mortality and psilocybin with psychotherapy has emerged as a promising potential in the treatment of depressive disorders. A review of psilocybin use in patients with depressive disorders is presented.A search was conducted investigating the use of psilocybin in patients with depressive disorders and treatment resistant depression via PubMed/MEDLINE, EMBASE, and Google Scholar in October 2023; all publication types were permitted and limited for English-language. Keyword search terms included: "psilocybin" or "psychedelics" and "depression", or "major depressive disorder", or "treatment-resistant depression". Controlled and uncontrolled clinical trials utilizing psilocybin with psychological support for major depressive disorder and treatment-resistant depression, as well as in patients with depression and cancer related anxiety have demonstrated immediate and sustained antidepressant and anxiolytic effects. Psilocybin has a favorable safety profile and was well-tolerated in clinical trials. Psilocybin's abuse potential is low and clinical research suggests the potential of psilocybin to produce rapid and lasting antidepressant effects up to 12 months post-treatment. Psilocybin may offer a valuable contribution as an option to the currently available pharmacological and psychotherapeutic agents for patients with major depressive disorders, treatment-resistant depression as well as for patients with depression and comorbid terminal cancer. Future studies are needed to demonstrate these findings and any synergistic interaction between psilocybin and the psychological support offered to patients during sessions.

keywords:
Humans, Hallucinogens, Antidepressive Agents, Depressive Disorder, Psychotherapy, Psilocybin, Major Depressive Disorder

topic_tags:
Depression,Anxiety,End-of-Life Distress,Clinical Trial,Review Article,Treatment-Resistant Depression,Safety,Drug Interactions

raw_json:
{"europe_pmc_id":"39177339","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Yang X, Kuang W.
publication_date: 2024-08-07
doi: 10.1016/j.psychres.2024.116136
pubmed_id: 39141970
source_url: https://doi.org/10.1016/j.psychres.2024.116136
keywords: Humans, Depression, Meta-Analysis as Topic
substance_tags: psilocybin
topic_tags: Depression,Meta-Analysis,Systematic Review,Review Article
study_type: Meta-Analysis
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
title:
Letter to editor regarding "Psilocybin-assisted therapy for depression: A systematic review and meta-analysis".

raw_json:
{"europe_pmc_id":"39141970","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Hovmand OR, Madsen MK, Fisher PM, Stenbæk DS.
publication_date: 2024-08-12
doi: 10.1177/02698811241269669
pubmed_id: 39135498
source_url: https://doi.org/10.1177/02698811241269669
substance_tags: psilocybin
topic_tags: Consciousness,Creativity,Observational Study,Healthy Volunteers,Adolescents
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:02
title:
Altered states of consciousness in Danish healthy volunteers and recreational users of psilocybin and the possible impact of setting and intention: Danish validation of the five-dimensional altered states of consciousness questionnaire.

abstract:
BackgroundPsychedelic substances reliably induce marked altered states of consciousness (ASC), which may be important for lasting effects and clinical outcomes of psychedelic intervention. Several instruments are available to measure the acute psychedelic experience, of which the Five Dimensional Altered States of Consciousness Questionnaire (5D-ASC) is commonly used. The questionnaire can be scored and analyzed as having five dimensions or 11 subscales, but the two have not been evaluated with comparable factor analysis methods.MethodsThe Danish translation of the 5D-ASC was completed by one sample of healthy volunteers receiving psilocybin in a laboratory setting (N = 47) and one sample of recreative users5D-ASC of psychedelics (N = 550), who reported retrospectively through an online survey based on their most recent experience with psilocybin. We calculated internal consistency measures of Cronbach's alpha and McDonald's omega, conducted a confirmatory factor analysis of the previously suggested factor structures, and tested for possible associations between the 5D-ASC total scores and dose, setting, and intention. For the 11 subscales, we reported omega-sem (composite reliability) using the parameters of the fitted confirmatory factor analyses model.ResultsConfirmatory factor analysis showed that the 11 subscales had a good fit to data and showed a better fit compared to the originally proposed five-dimensional solution and good internal consistencies. We further found that the 5D-ASC total scores correlated positively with the dose in the recreative sample. We found no correlations between 5D-ASC total scores and intention or setting.DiscussionWe find the Danish 5D-ASC to be a valid tool for measuring ASC among Danish-speaking individuals.

keywords:
Humans, Consciousness Disorders, Hallucinogens, Factor Analysis, Statistical, Retrospective Studies, Reproducibility of Results, Intention, Consciousness, Adolescent, Adult, Middle Aged, Denmark, Female, Male, Young Adult, Healthy Volunteers, Surveys and Questionnaires, Psilocybin, Recreational Drug Use

raw_json:
{"europe_pmc_id":"39135498","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin for clinical indications: A scoping review.
authors: Madden K, Flood B, Young Shing D, Ade-Conde M, Kashir I, Mark M, MacKillop J, Bhandari M, Adili A.
publication_date: 2024-08-12
doi: 10.1177/02698811241269751
pubmed_id: 39135496
source_url: https://doi.org/10.1177/02698811241269751
keywords: Humans, Hallucinogens, Mental Disorders, Psilocybin
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
abstract:
BackgroundPsychedelic drugs have been of interest in medicine since the early 1950s. There has recently been a resurgence of interest in psychedelics.AimsThe objective of this study is to determine the extent of the available literature on psilocybin for medical indications including the designs used, study characteristics, indications studied, doses, and authors' conclusions. We identify areas for further study where there are research gaps.MethodsWe conducted a systematic scoping review of clinical indications for psilocybin, encompassing psychiatric and medical conditions. We systematically searched Medline and Embase using keywords related to psilocybin. We reviewed titles and texts in duplicate using Covidence software. We extracted data individually in duplicate using Covidence software and a senior reviewer resolved all author conflicts. We analyzed data descriptively.ResultsWe included 193 published and 80 ongoing studies. Thirty-seven percent of included studies were systematic reviews. Only 12% of included studies were randomized controlled trials. The median number of participants was 22 with a median of 18 participants who had taken psilocybin. Thirty-eight percent of studies reported at least one potential conflict of interest. The most common indication was depression (28%). Also commonly studied were substance use (14%), mental health in life-threatening illness (9%), headaches (6%), depression and anxiety (6%), obsessive-compulsive disorder (3%), and anxiety disorders (3%).ConclusionsMost studies involving the administration of psilocybin have small sample sizes and the most common focus has been psychiatric disorders. There is a need for high-quality randomized trials on psilocybin and to expand consideration to other promising indications, such as chronic pain.

topic_tags:
Depression,Anxiety,Addiction,OCD,End-of-Life Distress,Chronic Pain,Headache / Migraine,Randomized Controlled Trial,Systematic Review,Review Article

raw_json:
{"europe_pmc_id":"39135496","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin in pharmacotherapy of obsessive-compulsive disorder.
authors: Owe-Larsson M, Kamińska K, Buchalska B, Mirowska-Guzel D, Cudnoch-Jędrzejewska A.
publication_date: 2024-07-31
doi: 10.1007/s43440-024-00633-1
pubmed_id: 39088105
source_url: https://doi.org/10.1007/s43440-024-00633-1
substance_tags: psilocybin
topic_tags: OCD,Receptor Pharmacology,Aging
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
abstract:
Obsessive-compulsive disorder (OCD) is a chronic mental disease that affects approximately 2% of the population. Obsessions and compulsions are troublesome for patients and may disturb their everyday activities. The pathogenesis of this disease is still not fully elucidated, but dysfunctions of serotonin-, dopamine- and glutamate-mediated neurotransmission together with early maladaptive schemas seem of importance. Pharmacological treatment includes drugs affecting the serotoninergic, dopaminergic, and glutamatergic systems, such as selective serotonin reuptake inhibitors (SSRIs). Providing that up to 40% of patients with OCD are resistant to the currently available medications, there is a need for novel and effective therapies. Recent discoveries suggest that psilocybin, a non-physically addictive psychoactive substance, may ameliorate disease symptoms. When used in appropriate doses and under strict clinical control, psilocybin appears as a valuable treatment for OCD. This narrative article provides a thorough overview of OCD's etiology, current treatment options, and the emerging evidence supporting psilocybin's efficacy in managing OCD symptoms.

keywords:
Animals, Humans, Hallucinogens, Obsessive-Compulsive Disorder, Psilocybin, Selective Serotonin Reuptake Inhibitors

raw_json:
{"europe_pmc_id":"39088105","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2024-07-19
doi: 10.1007/s40263-024-01101-3
pubmed_id: 39033264
source_url: https://doi.org/10.1007/s40263-024-01101-3
keywords: Humans, Substance-Related Disorders, Hallucinogens, Biomedical Research
substance_tags: psilocybin
topic_tags: Depression,PTSD,Addiction,Review Article,Safety
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
title:
Current Perspectives on the Clinical Research and Medicalization of Psychedelic Drugs for Addiction Treatments: Safety, Efficacy, Limitations and Challenges.

authors:
Gomez-Escolar A, Folch-Sanchez D, Stefaniuk J, Swithenbank Z, Nisa A, Braddick F, Idrees Chaudhary N, van der Meer PB, Batalla A.

abstract:
Mental health disorders and substance use disorders (SUDs) in particular, contribute greatly to the global burden of disease. Psychedelics, including entactogens and dissociative substances, are currently being explored for the treatment of SUDs, yet with less empirical clinical evidence than for other mental health disorders, such as depression or post-traumatic stress disorder (PTSD). In this narrative review, we discuss the current clinical research evidence, therapeutic potential and safety of psilocybin, lysergic acid diethylamide (LSD), ketamine, 3,4-methylenedioxymethamphetamine (MDMA) and ibogaine, particularly in the context of the SUD treatment. Our aim was to provide a balanced overview of the current research and findings on potential benefits and harms of psychedelics in clinical settings for SUD treatment. We highlight the need for more clinical research in this particular treatment area and point out some limitations and challenges to be addressed in future research.

raw_json:
{"europe_pmc_id":"39033264","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Effects of psilocybin on body weight, body composition, and metabolites in male and female mice.
publication_date: 2024-07-01
doi: 10.1016/j.physbeh.2024.114627
pubmed_id: 38964565
source_url: https://doi.org/10.1016/j.physbeh.2024.114627
substance_tags: psilocybin
topic_tags: Eating Disorders,Pharmacology,Mechanism of Action,Receptor Pharmacology,Wellbeing,Animal Study
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
authors:
Shakir J, Pedicini M, Bullock BC, Hoen PW, Macias LK, Freiman J, Pletnikov MV, Tamashiro KLK, Cordner ZA.

abstract:
There is growing interest in the therapeutic potential of psilocybin for the treatment of a wide variety of medical problems, and even for the promotion of wellbeing among healthy individuals. Interestingly, among the many proposed indications, both obesity and anorexia nervosa (AN) have been discussed. However, the effect of psilocybin on appetitive behavior and metabolism is not well known. Here, we report the effects of psilocybin on body weight, intake and output, body composition, and metabolic function among lean male and female wild-type mice. In the days immediately following treatment, both male and female mice receiving a single intraperitoneal dose of psilocybin were consistently heavier than saline controls, with no effect of psilocybin on intake or output. Co-administration of the 5-HT2A/2C receptor antagonist ketanserin had no effect on this outcome. Body composition analysis revealed that psilocybin significantly increased lean and water mass among males, with a similar trend among females. A metabolic panel revealed increased creatine kinase (CK), aspartate aminotransferase (AST), and chloride among male and female psilocybin treated mice. Together, these findings begin to investigate the potential mechanisms of psilocybin's effects on body weight and metabolic measures. Such understanding will be critical for the safe, efficacious, and well-informed use of psilocybin in clinical and non-clinical settings.

keywords:
Animals, Mice, Inbred C57BL, Mice, Body Weight, Ketanserin, Hallucinogens, Body Composition, Sex Characteristics, Eating, Female, Male, Psilocybin

raw_json:
{"europe_pmc_id":"38964565","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Psilocybin and 2C-B at Encoding Distort Episodic Familiarity.
authors: Doss MK, Mallaroni P, Mason NL, Ramaekers JG.
publication_date: 2024-06-25
doi: 10.1016/j.bpsc.2024.06.008
pubmed_id: 38942147
source_url: https://doi.org/10.1016/j.bpsc.2024.06.008
substance_tags: psilocybin
topic_tags: Pharmacology,Receptor Pharmacology,Emotional Processing,Adolescents
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
abstract:
BackgroundAs research on psychedelics (hallucinogenic serotonin receptor 2A agonists) progresses, it is important to delineate the reliability of supposedly unique effects across this drug class. One such effect is how psychedelics impair the formation (i.e., encoding) of hippocampal-dependent recollections (retrieval of specific details) while potentially enhancing the encoding of cortical-dependent familiarity (a feeling of knowing that a stimulus has been previously experienced).MethodsIn a double-blind, placebo-controlled, within-participants study (N = 20), we tested the acute effects of 2 distinct psychedelics, psilocybin and 2C-B, on the encoding of emotional episodic memories. During acute drug effects, participants viewed negative, neutral, and positive pictures. The following day (while sober), participants completed 2 separate memory tests for these pictures.ResultsUsing computational models of memory confidence, we found trends for psilocybin and 2C-B at encoding to impair estimates of recollection that were supported by other measures/analyses. Surprisingly, psilocybin and 2C-B at encoding impaired estimates of familiarity, but these impairments were likely due to a misattribution of heightened familiarity, because both drugs at encoding selectively increased familiarity-based false alarms, especially for negative and positive stimuli. Psilocybin and 2C-B at encoding also tended to impair estimates of metamemory (understanding one's own memory) for negative and neutral memories but enhanced estimates of metamemory for positive memories, although these effects were less reliable in additional analyses.ConclusionsDespite differences in their chemistry, pharmacology, and subjective effects, both psilocybin and 2C-B distorted episodic familiarity, suggesting a common neurocognitive mechanism across psychedelics that may drive other phenomena.

keywords:
Humans, Hallucinogens, Double-Blind Method, Emotions, Mental Recall, Adolescent, Adult, Female, Male, Young Adult, Memory, Episodic, Psilocybin, Recognition, Psychology

raw_json:
{"europe_pmc_id":"38942147","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Nadeem Z, Parker S, McGovern H, Oestreich LK
journal: The Australian and New Zealand journal of psychiatry
publication_date: 2024-09-30
doi: 10.1177/00048674241261779
pubmed_id: 38907608
source_url: https://pubmed.ncbi.nlm.nih.gov/38907608/
keywords: MDMA, Psilocybin, psychedelic-assisted therapy, psychedelics, treatment-resistant depression
substance_tags: psilocybin
topic_tags: Depression,Observational Study,Treatment-Resistant Depression,Safety
study_type: Observational Study
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:36
raw_json: {"pubmed_id":"38907608"}
title:
Attitudes toward psychedelics and psychedelic-assisted therapy among potential mental health service users and the general population in Australia.

abstract:
Despite rapid advances in psychedelic sciences and the increasing number of countries legalizing psychedelics for the treatment of mental illnesses, the attitudes, knowledge and readiness of both mental health consumers and the general population remain largely unknown.
A cross-sectional survey was conducted among Australians, targeting individuals with mental illness as potential mental health service users. A sub-sample of individuals free of mental illness was also surveyed to assess attitudes in the general population. Participants completed the Attitudes on Psychedelics Questionnaire, the Basic Knowledge of Psychedelics Test and a questionnaire by Corrigan et al. to capture attitudes toward psychedelic therapy by mental health service users.
Of the 502 respondents, 64.5% self-identified as having a mental illness. A significant proportion favored legalizing psychedelics for medical use (43%) and were open to their use (52.4%), yet fewer viewed their effects positively (24%) or considered them safe (33%). Most participants reported to be psychedelic naive (61%). Participants with mental illness had significantly more experience with psychedelics than participant free of mental illness (44.1% vs 29.7%). Experience, perceived knowledge and actual knowledge significantly predicted attitudes toward legalization, effects, risks and openness to psychedelics.
While a large proportion of Australians are in favor of legalizing psychedelics for medical purposes, concerns about safety remain. People with self-identified mental illness, those with previous recreational psychedelic experience and those with greater knowledge of psychedelics were more likely to have positive attitudes toward psychedelics and psychedelic-assisted therapy.


title: Pharmacological and behavioural effects of tryptamines present in psilocybin-containing mushrooms.
publication_date: 2024-06-01
doi: 10.1111/bph.16466
pubmed_id: 38825326
source_url: https://doi.org/10.1111/bph.16466
substance_tags: psilocybin,psilocin
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:00
authors:
Rakoczy RJ, Runge GN, Sen AK, Sandoval O, Wells HG, Nguyen Q, Roberts BR, Sciortino JH, Gibbons WJ, Friedberg LM, Jones JA, McMurray MS.

abstract:
Background and purposeDemand for new antidepressants has resulted in a re-evaluation of the therapeutic potential of psychedelic drugs. Several tryptamines found in psilocybin-containing "magic" mushrooms share chemical similarities with psilocybin. Early work suggests they may share biological targets. However, few studies have explored their pharmacological and behavioural effects.Experimental approachWe compared baeocystin, norbaeocystin and aeruginascin with psilocybin to determine if they are metabolized by the same enzymes, similarly penetrate the blood-brain barrier, serve as ligands for similar receptors and modulate behaviour in rodents similarly. We also assessed the stability and optimal storage and handling conditions for each compound.Key resultsIn vitro enzyme kinetics assays found that all compounds had nearly identical rates of dephosphorylation via alkaline phosphatase and metabolism by monoamine oxidase. Further, we found that only the dephosphorylated products of baeocystin and norbaeocystin crossed a blood-brain barrier mimetic to a similar degree as the dephosphorylated form of psilocybin, psilocin. The dephosphorylated form of norbaeocystin was found to activate the 5-HT2A receptor with similar efficacy to psilocin and norpsilocin in in vitro cell imaging assays. Behaviourally, only psilocybin induced head twitch responses in rats, a marker of 5-HT2A-mediated psychedelic effects and hallucinogenic potential. However, like psilocybin, norbaeocystin improved outcomes in the forced swim test. All compounds caused minimal changes to metrics of renal and hepatic health, suggesting innocuous safety profiles.Conclusions and implicationsCollectively, this work suggests that other naturally occurring tryptamines, especially norbaeocystin, may share overlapping therapeutic potential with psilocybin, but without causing hallucinations.

keywords:
Blood-Brain Barrier, Animals, Humans, Mice, Rats, Rats, Sprague-Dawley, Agaricales, Tryptamines, Receptor, Serotonin, 5-HT2A, Hallucinogens, Behavior, Animal, Male, Psilocybin

topic_tags:
Brain Imaging,Pharmacology,Receptor Pharmacology,Biomarkers,Aging,Animal Study,In Vitro Study,Safety

raw_json:
{"europe_pmc_id":"38825326","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


publication_date: 2024-04-26
doi: 10.1038/s41380-024-02575-9
pubmed_id: 38678087
source_url: https://doi.org/10.1038/s41380-024-02575-9
substance_tags: psilocybin
topic_tags: Depression,Eating Disorders,Mechanism of Action,Receptor Pharmacology,Clinical Trial,Animal Study
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Psilocybin restrains activity-based anorexia in female rats by enhancing cognitive flexibility: contributions from 5-HT1A and 5-HT2A receptor mechanisms.

authors:
Conn K, Milton LK, Huang K, Munguba H, Ruuska J, Lemus MB, Greaves E, Homman-Ludiye J, Oldfield BJ, Foldi CJ.

abstract:
Psilocybin has shown promise for alleviating symptoms of depression and is currently in clinical trials for the treatment of anorexia nervosa (AN), a condition that is characterised by persistent cognitive inflexibility. Considering that enhanced cognitive flexibility after psilocybin treatment is reported to occur in individuals with depression, it is plausible that psilocybin could improve symptoms of AN by breaking down cognitive inflexibility. A mechanistic understanding of the actions of psilocybin is required to tailor the clinical application of psilocybin to individuals most likely to respond with positive outcomes. This can only be achieved using incisive neurobiological approaches in animal models. Here, we use the activity-based anorexia (ABA) rat model and comprehensively assess aspects of reinforcement learning to show that psilocybin (post-acutely) improves body weight maintenance in female rats and facilitates cognitive flexibility, specifically via improved adaptation to the initial reversal of reward contingencies. Further, we reveal the involvement of signalling through the serotonin (5-HT) 1 A and 5-HT2A receptor subtypes in specific aspects of learning, demonstrating that 5-HT1A antagonism negates the cognitive enhancing effects of psilocybin. Moreover, we show that psilocybin elicits a transient increase and decrease in cortical transcription of these receptors (Htr2a and Htr1a, respectively), and a further reduction in the abundance of Htr2a transcripts in rats exposed to the ABA model. Together, these findings support the hypothesis that psilocybin could ameliorate cognitive inflexibility in the context of AN and highlight a need to better understand the therapeutic mechanisms independent of 5-HT2A receptor binding.

keywords:
Animals, Rats, Rats, Sprague-Dawley, Disease Models, Animal, Body Weight, Anorexia, Receptor, Serotonin, 5-HT1A, Receptor, Serotonin, 5-HT2A, Hallucinogens, Cognition, Reward, Anorexia Nervosa, Female, Psilocybin

raw_json:
{"europe_pmc_id":"38678087","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Mamat R, Rashid RA, Shin SM, Ibrahim B, Wahab S, Ahmad A.
publication_date: 2023-08-03
doi: 10.1080/10550887.2023.2240932
pubmed_id: 37540000
source_url: https://doi.org/10.1080/10550887.2023.2240932
substance_tags: psilocybin
topic_tags: Addiction,Observational Study,Adolescents,Safety
study_type: Observational Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Prevalence of psilocybin use in vaping and associated factors: a study among amphetamine-type stimulants (ATS) use disorder in Malaysia.

abstract:
BackgroundThe emergence of New Psychoactive Substances (NPS), including synthetic psilocybin, has raised concern among health experts due to the numerous health and socioeconomic consequences. The current trend is shifting to the hazardous use of synthetic psilocybin in vaping, and little is known about the prevalence of use, specifically among amphetamine-type stimulants (ATS) users.MethodsInterviewer-administered questionnaires were conducted in drug detention centers between March and October 2022. The study was conducted using ASSIST 3.0 and obtained information on the respondents' socio-demographic characteristics and clinical profiles. N = 355 ATS users were enrolled in this study.ResultsThe results show a high prevalence of psilocybin vaping among ATS users (182/355, 53.1%). Most of the respondents were males (85.1%) and unmarried (69.3%), with a mean age of 29.2 (SD = 7.3). Across all respondents, five factors were associated with psilocybin vaping: tobacco smoking, aOR =5.790 (95% CI: 1.723, 8.183); cannabis uses, aOR= 9.152 (95% CI: 2.693, 10.396); and alcohol use, aOR= 3.137 (95% CI: 1.461, 5.817). Respondents of the Malay race had higher odds of being involved in psilocybin vaping compared to other races, with aOR= 1.638 (0.043, 2.459). Meanwhile, a reduction in age by 1.9 will increase the likelihood of involvement in psilocybin vaping with aOR = 1.897 (95% CI: 0.857, 1.938).ConclusionPsilocybin in vaping is growing among ATS users and across all populations. Unfortunately, knowledge regarding the long-term effects on health is limited. Further studies should highlight the harmful effects of psilocybin and the potential risk of psilocybin vaping among the younger population.

keywords:
Humans, Amphetamine-Related Disorders, Hallucinogens, Prevalence, Cross-Sectional Studies, Adolescent, Adult, Middle Aged, Malaysia, Female, Male, Young Adult, Surveys and Questionnaires, Psilocybin, Vaping

raw_json:
{"europe_pmc_id":"37540000","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Beyond the numbers: reimagining healing with psychedelics for eating disorders.
authors: Lafrance A, Spriggs MJ, Gukasyan N, Peck SK
journal: Journal of eating disorders
publication_date: 2024-09-29
doi: 10.1186/s40337-024-01111-y
pubmed_id: 39350242
source_url: https://pubmed.ncbi.nlm.nih.gov/39350242/
keywords: Anorexia nervosa, Eating disorders, Psilocybin treatment, Psychedelics
substance_tags: psilocybin
topic_tags: Eating Disorders,Safety
study_type: Other
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:36
raw_json: {"pubmed_id":"39350242"}
abstract:
Psychedelic medicine is currently being evaluated for numerous mental health indications, and there is significant interest in applying these models of care to eating disorders (EDs) given the limited efficacy of available treatment models, especially for those living with anorexia nervosa. Preliminary findings across a number of studies suggest promise. In this commentary, researchers with experience in psychedelics and EDs present a rationale and considerations for the application of psychedelic medicine, including psychedelic-assisted therapy (PAT) for EDs. These contributions are informed by those with lived experience as well as the authors' experiences in the field. By addressing underlying psychological and transpersonal factors and improving treatment engagement, psychedelic medicine, though not without risks, may offer a valuable adjunct to existing treatments, enhancing overall outcomes for some living with an ED. This commentary also aims to provide a multi-dimensional perspective to inform the field, including with respect to the etiology of these illnesses, as psychedelic medicine becomes more accessible in naturalistic, research and clinical settings.


title: Psilocybin increases optimistic engagement over time: computational modelling of behaviour in rats.
authors: Fisher EL, Smith R, Conn K, Corcoran AW, Milton LK, Hohwy J, Foldi CJ.
publication_date: 2024-09-29
doi: 10.1038/s41398-024-03103-7
pubmed_id: 39349428
source_url: https://doi.org/10.1038/s41398-024-03103-7
substance_tags: psilocybin
topic_tags: Depression,Mechanism of Action,Clinical Trial
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:00
abstract:
Psilocybin has shown promise as a novel pharmacological intervention for treatment of depression, where post-acute effects of psilocybin treatment have been associated with increased positive mood and decreased pessimism. Although psilocybin is proving to be effective in clinical trials for treatment of psychiatric disorders, the information processing mechanisms affected by psilocybin are not well understood. Here, we fit active inference and reinforcement learning computational models to a novel two-armed bandit reversal learning task capable of capturing engagement behaviour in rats. The model revealed that after receiving psilocybin, rats achieve more rewards through increased task engagement, mediated by modification of forgetting rates and reduced loss aversion. These findings suggest that psilocybin may afford an optimism bias that arises through altered belief updating, with translational potential for clinical populations characterised by lack of optimism.

keywords:
Animals, Rats, Hallucinogens, Behavior, Animal, Reward, Reversal Learning, Computer Simulation, Male, Optimism, Psilocybin, Reinforcement, Psychology

raw_json:
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title: Psilocybin for major depressive disorder: a systematic review of randomized controlled studies.
authors: Li LJ, Mo Y, Shi ZM, Huang XB, Ning YP, Wu HW, Yang XH, Zheng W.
publication_date: 2024-09-22
doi: 10.3389/fpsyt.2024.1416420
pubmed_id: 39376971
source_url: https://doi.org/10.3389/fpsyt.2024.1416420
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:00
abstract:
ObjectivesThe purpose of this systematic review of randomized controlled trials (RCTs) was to evaluate the effectiveness, safety, and tolerability of psilocybin in adult patients with major depressive disorder (MDD).MethodsA systematic search (up to September 14, 2023) was conducted for RCTs that examined the efficacy, safety, and tolerability of psilocybin in physically healthy adult patients with MDD. Three independent researchers extracted data from publications where the primary outcome was a change in depressive symptoms, and key secondary outcomes were changes in anxiety symptoms and suicidal ideation, discontinuation rates for any reason, and adverse drug reactions (ADRs).ResultsFive RCTs with 472 adult patients with MDD on psilocybin (n = 274) and controls (n = 198) were included. Two of the five RCTs (40%) reported mixed results, while the other three (60%) found that psilocybin had a beneficial effect on MDD treatment. Four RCTs (80%) assessing the anxiolytic effects of psilocybin for treating MDD found that psilocybin was significantly more effective than the control group in improving anxiety symptoms. Psilocybin was more effective than the control group in improving suicidal ideation in one out of five RCTs. Discontinuation rates were similar for any reason between the psilocybin group (2-13%) and the control group (4-21%) (P > 0.05). Four RCTs (80%) reported ADRs in detail. The most common ADR in both groups was headache.ConclusionPsilocybin was effective in improving depressive symptoms in over half of the included studies and reduced anxiety symptoms in patients with MDD. The long-term efficacy and safety of psilocybin for MDD treatment needs to be further investigated in large RCTs.

topic_tags:
Depression,Anxiety,Headache / Migraine,Randomized Controlled Trial,Systematic Review,Review Article,Safety

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title: Psychedelic research at a crossroads.
authors: Armstrong SB, Davis AK.
publication_date: 2024-09-18
doi: 10.1126/science.adt1024
pubmed_id: 39298596
source_url: https://doi.org/10.1126/science.adt1024
substance_tags: psilocybin
topic_tags: Depression,PTSD,Consciousness,Clinical Trial,Safety
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
abstract:
There is an urgent need to develop better treatments for mental health conditions that affect one in every eight people in the world. To combat this concern, psychedelic drugs have been combined with psychotherapy and studied in clinical trials in the United States and Europe. Psychedelics are hallucinogenic drugs that alter brain activity and facilitate altered states of consciousness. The proposed benefits of psychedelic-assisted therapy (PAT) include relatively short treatment times and stronger effects compared to other treatments. Although results of trials using MDMA for trauma or psilocybin for depression are promising, PAT is controversial because many questions about its safety and effectiveness are unanswered. This is evident in the recent ruling by the US Food and Drug Administration against the approval of MDMA therapy for post-traumatic stress disorder and the retraction of several papers about MDMA trials owing to unethical conduct by study therapists and data integrity, among other concerns. This field is at a crossroads, and the research community must address several obstacles to transition from exploratory trials to established, evidence-based treatments while avoiding pitfalls that can hinder advancement.

keywords:
Humans, N-Methyl-3,4-methylenedioxyamphetamine, Hallucinogens, Drug Approval, Mental Disorders, Psychotherapy, United States Food and Drug Administration, United States, Clinical Trials as Topic, Psilocybin

raw_json:
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authors: Gobbi G.
publication_date: 2024-09-18
doi: 10.1503/jpn.240037
pubmed_id: 39299781
source_url: https://doi.org/10.1503/jpn.240037
keywords: Brain, Humans, Hallucinogens, Spirituality, Mental Disorders, Psychopharmacology, Awards and Prizes
substance_tags: psilocybin
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
title:
CCNP Innovations in Neuropsychopharmacology Award: The psychopharmacology of psychedelics: where the brain meets spirituality.

abstract:
For 3000 years, psychedelics have been used in religious contexts to enhance spiritual thinking, well-being, and a sense of community. In the last few years, a renaissance in the use of psychedelic drugs for mental disorders has occurred in Western society; consequently, a pressing scientific need to elucidate the intricate mechanisms underlying their actions has arisen. Psychedelics mainly bind to serotonin (5-HT) receptors, particularly 5-HT2A receptors, but may also bind to other receptors. Unlike conventional psychotropic drugs used in psychiatry, psychedelics introduce a distinctive complexity. They not only engage in receptor activation, but also exert influence over specific neural circuits, thereby facilitating transformative cognitive experiences and fostering what many have identified as a spiritual contemplation or mystical experience. This comprehensive review describes clinical studies that have examined the propensity of psychedelics to enhance spiritual, mystical, and transcendent cognitive states. This multifaceted nature, encompassing diverse components and paradigms, necessitates careful consideration during the investigation of psychedelic mechanisms of action to avoid oversimplification. The present review endeavours to elucidate the mechanisms underlying the actions of 2 principal psychedelic substances, psilocybin and lysergic acid diethylamide (LSD), with a focus on monoamine and glutamate receptor mechanisms; molecular aspects, such as neuroplasticity and epigenetics; as well as the impact of psychedelics on brain circuits, including the default mode network and the cortico-striato-thalamo-cortical network. Given their distinctive and intricate mechanisms of action, psychedelics necessitate a novel conceptual framework in psychiatry, offering insight into the treatment of mental health disorders and facilitating the integration of the realms of brain, mind, and spirituality.

topic_tags:
Neuroplasticity,Pharmacology,Mechanism of Action,Receptor Pharmacology,Default Mode Network,Epigenetics,Wellbeing,Spirituality,Mystical Experience,Review Article

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title: Psychedelics as a potential treatment for tobacco use disorder: a systematic review.
authors: Spoelstra SK, Schoevers RA, Venema SD, Knegtering H.
publication_date: 2024-09-16
doi: 10.1007/s44192-024-00095-0
pubmed_id: 39289250
source_url: https://doi.org/10.1007/s44192-024-00095-0
substance_tags: psilocybin
topic_tags: Addiction,Systematic Review,Review Article,Safety
study_type: Systematic Review
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:03
abstract:
IntroductionDespite considerable efforts, tobacco use disorder persists as a significant public health issue. The effectiveness of current smoking cessation therapies is limited, leading to a growing interest in alternative treatment approaches such as psychedelics.AimThe aim of this review is to evaluate the scientific evidence regarding the role of psychedelics in smoking cessation.MethodsTo identify relevant literature on psychedelics and smoking cessation, a search was conducted in four academic literature databases PubMed, MEDLINE, PsycINFO, and Embase. Databases were searched from their inception up to March 24, 2024.ResultsOut of the 1073 articles identified in databases, 8 publications (both clinical and non-clinical studies) met the inclusion criteria, of which a total of 4 publications originated from a single study. The majority of the studies focused on psilocybin (n = 7), for which supportive evidence was suggested for the treatment of tobacco use disorder. Additionally, research was conducted with other psychedelics for smoking cessation, such as ayahuasca, mescaline, peyote, lysergic acid diethylamide (LSD), lysergic acid amide (LSA) and (dimethyltryptamine (DMT), but the evidence base for these psychedelics is too small to draw definitive conclusions.ConclusionsThere is, although limited, evidence that psychedelics, in particular psilocybin, may offer a potential avenue for combating tobacco use disorder, though more research is needed to understand their effectiveness and safety fully.

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authors: Kargbo RB.
publication_date: 2024-08-20
doi: 10.1021/acsmedchemlett.4c00414
pubmed_id: 39291015
source_url: https://doi.org/10.1021/acsmedchemlett.4c00414
substance_tags: psilocybin
topic_tags: Eating Disorders,Mechanism of Action,Emotional Processing,Clinical Trial
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Current Trends in Psychedelic Science: Integrating Modified Lysergic Acid Derivatives and Psilocybin in Modern Medicine.

abstract:
This article explores groundbreaking advancements in psychedelic research, highlighting the development of novel lysergic acid derivatives with modified LSD-like actions and innovative dosing methods based on ABCF1 gene expression for psilocybin. It also examines new strategies for treating binge eating disorder using psychedelics and techniques for neuroenhancement to enhance emotional responses. These developments offer fresh insights into the therapeutic potential of psychedelics, underscoring their significance in personalized medicine and mental health treatment. The article delves into the implications of these novel approaches, signaling a transformative phase in the application of psychedelics in clinical settings.

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authors: Kargbo RB.
publication_date: 2024-08-20
doi: 10.1021/acsmedchemlett.4c00412
pubmed_id: 39291007
source_url: https://doi.org/10.1021/acsmedchemlett.4c00412
substance_tags: psilocybin
topic_tags: Mechanism of Action,Resilience
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:03
title:
Exploring the Therapeutic Potential of Entheogens in Postoperative Cognitive Decline and Psychological Resilience.

abstract:
Recent advancements in medical research have focused on the utilization of entheogens, particularly psilocybin and its related compounds, as therapeutic agents in mitigating cognitive decline and enhancing psychological resilience in patients undergoing anesthesia and sedation. This Patent Highlight integrates findings from three patent applications, each contributing unique insights into the potential applications of these substances in medical settings. The article examines the therapeutic mechanisms, proposed treatment methods, and potential clinical outcomes, offering an overview of this innovative approach to postoperative care.

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title: Refractory CRPS pain treated with psilocybin: A case report.
authors: Jevotovsky DS, Chopra H, Wing C, Spotswood CJ, Castellanos J.
publication_date: 2024-09-11
doi: 10.1002/ccr3.9421
pubmed_id: 39281029
source_url: https://doi.org/10.1002/ccr3.9421
substance_tags: psilocybin
topic_tags: Chronic Pain,Case Report
study_type: Case Report
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
abstract:
Psilocybin shows promise as a treatment for CRPS, offering significant pain relief and functional improvement in a patient with refractory symptoms. This case highlights the need for further research into psilocybin's efficacy and optimal dosing for chronic pain management.

raw_json:
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publication_date: 2024-09-11
doi: 10.1038/s41398-024-03059-8
pubmed_id: 39266503
source_url: https://doi.org/10.1038/s41398-024-03059-8
keywords: Humans, Midazolam, Hallucinogens, Memory, Adult, Female, Male, Young Adult, Psilocybin
substance_tags: psilocybin
topic_tags: Neuroplasticity,Wellbeing,Healthy Volunteers
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:01
title:
Co-administration of midazolam and psilocybin: differential effects on subjective quality versus memory of the psychedelic experience.

authors:
Nicholas CR, Banks MI, Lennertz RC, Wenthur CJ, Krause BM, Riedner BA, Smith RF, Hutson PR, Sauder CJ, Dunne JD, Roseman L, Raison CL.

abstract:
Aspects of the acute experience induced by the serotonergic psychedelic psilocybin predict symptomatic relief in multiple psychiatric disorders and improved well-being in healthy participants, but whether these therapeutic effects are immediate or are based on memories of the experience is unclear. To examine this, we co-administered psilocybin (25 mg) with the amnestic benzodiazepine midazolam in 8 healthy participants and assayed the subjective quality of, and memory for, the dosing-day experience. We identified a midazolam dose that allowed a conscious psychedelic experience to occur while partially impairing memory for the experience. Furthermore, midazolam dose and memory impairment tended to associate inversely with salience, insight, and well-being induced by psilocybin. These data suggest a role for memory in therapeutically relevant behavioral effects occasioned by psilocybin. Because midazolam blocks memory by blocking cortical neural plasticity, it may also be useful for evaluating the contribution of the pro-neuroplastic properties of psychedelics to their therapeutic activity.

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authors: Schipper S, Nigam K, Schmid Y, Piechotta V, Ljuslin M, Beaussant Y, Schwarzer G, Boehlke C.
publication_date: 2024-09-11
doi: 10.1002/14651858.cd015383.pub2
pubmed_id: 39260823
source_url: https://doi.org/10.1002/14651858.cd015383.pub2
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
title:
Psychedelic-assisted therapy for treating anxiety, depression, and existential distress in people with life-threatening diseases.

abstract:
BackgroundPsychedelic-assisted therapy refers to a group of therapeutic practices involving psychedelics taken under therapeutic supervision from physicians, psychologists, and others. It has been hypothesised that psychedelic-assisted therapy may reduce symptoms of anxiety, depression, and existential distress in patients facing life-threatening diseases (e.g. cancer). However, these substances are illegal in most countries and have been associated with potential risks.ObjectivesTo assess the benefits and harms of psychedelic-assisted therapy compared to placebo or active comparators (e.g. antidepressants) for treatment of anxiety, depression, and existential distress in people with life-threatening diseases.Search methodsWe searched CENTRAL, MEDLINE, Embase, and two trial registers on 30 March 2024. In addition, we undertook reference checking, citation searching, and contact with study authors to identify additional studies. We used no language or date restrictions.Selection criteriaWe included randomised controlled trials (RCTs), with no restrictions regarding comorbidity, sex, or ethnicity. Interventions comprised a substance-induced psychedelic experience preceded by preparatory therapeutic sessions and followed by integrative therapeutic sessions.Data collection and analysisWe used the standard methodological procedures expected by Cochrane.Main resultsWe included six studies in the review, which evaluated two different interventions: psychedelic-assisted therapy with classical psychedelics (psilocybin ('magic mushrooms') and lysergic acid diethylamide (LSD)), and psychedelic-assisted therapy with 3,4-methylenedioxymethamphetamine (MDMA or 'Ecstasy'). The studies randomised 149 participants with life-threatening diseases and analysed data for 140 of them. The age range of participants was 36 to 64 years. The studies lasted between 6 and 12 months, and were conducted in outpatient settings in the USA and in Switzerland. Drug companies were not involved in study funding, but funding was provided by organisations that promote psychedelic-assisted therapy. Primary outcomes (at 1 to 12 weeks) Anxiety Psychedelic-assisted therapy using classical psychedelics (psilocybin, LSD) may result in a reduction in anxiety when compared to active placebo (or low-dose psychedelic): State Trait Anxiety Inventory (STAI-Trait, scale 20 to 80) mean difference (MD) -8.41, 95% CI -12.92 to -3.89; STAI-State (scale 20 to 80) MD -9.04, 95% CI -13.87 to -4.21; 5 studies, 122 participants; low-certainty evidence. The effect of psychedelic-assisted therapy using MDMA on anxiety, compared to placebo, is very uncertain: STAI-T MD -14.70, 95% CI -29.45 to 0.05; STAI-S MD -16.10, 95% CI -33.03 to 0.83; 1 study, 18 participants; very low certainty evidence. Depression Psychedelic-assisted therapy using classical psychedelics (psilocybin, LSD) may result in a reduction in depression when compared to active placebo (or low-dose psychedelic): Beck Depression Inventory (BDI, scale 0 to 63) MD -4.92, 95% CI -8.97 to -0.87; 4 studies, 112 participants; standardised mean difference (SMD) -0.43, 95% CI -0.79 to -0.06; 5 studies, 122 participants; low-certainty evidence. The effect of psychedelic-assisted therapy using MDMA on depression, compared to placebo, is very uncertain: BDI-II (scale: 0 to 63) MD -6.30, 95% CI -16.93 to 4.33; 1 study, 18 participants; very low certainty evidence. Existential distress Psychedelic-assisted therapy using classical psychedelics (psilocybin, LSD) compared to active placebo (or low-dose psychedelic) may result in a reduction in demoralisation, one of the most common measures of existential distress, but the evidence is very uncertain (Demoralisation Scale, 1 study, 28 participants): post treatment scores, placebo group 39.6 (SEM3.4), psilocybin group 18.8 (3.6), P ≤ 0.01). Evidence from other measures of existential distress was mixed. Existential distress was not measured in people receiving psychedelic-assisted therapy with MDMA. Secondary outcomes (at 1 to 12 weeks) Quality of life When classical psychedelics were used, one study had inconclusive results and two reported improved quality of life, but the evidence is very uncertain. MDMA did not improve quality of life measures, but the evidence is also very uncertain. Spirituality Participants receiving psychedelic-assisted therapy with classical psychedelics rated their experience as being spiritually significant (2 studies), but the evidence is very uncertain. Spirituality was not assessed in participants receiving MDMA. Adverse events No treatment-related serious adverse events or adverse events grade 3/4 were reported. Common minor to moderate adverse events for classical psychedelics were elevated blood pressure, nausea, anxiety, emotional distress, and psychotic-like symptoms (e.g. pseudo-hallucination where the participant is aware they are hallucinating); for MDMA, common minor to moderate adverse events were anxiety, dry mouth, jaw clenching, and headaches. Symptoms subsided when drug effects wore off or up to one week later. Certainty of the evidence Although all six studies had intended to blind participants, personnel, and assessors, blinding could not be achieved as this is very difficult in studies investigating psychedelics. Using GRADE criteria, we judged the certainty of evidence to be low to very low, mainly due to high risk of bias and imprecision (small sample size).Authors' conclusionsImplications for practice Psychedelic-assisted therapy with classical psychedelics (psilocybin, LSD) may be effective for treating anxiety, depression, and possibly existential distress, in people facing a life-threatening disease. Psychedelic-assisted therapy seemed to be well tolerated, with no treatment-emergent serious adverse events reported in the studies included in this review. However, the certainty of evidence is low to very low, which means that we cannot be sure about these results, and they might be changed by future research. At the time of this review (2024), psychedelic drugs are illegal in many countries. Implications for research The risk of bias due to 'unblinding' (participants being aware of which intervention they are receiving) could be reduced by measuring expectation bias, checking blinding has been maintained before cross-over, and using active placebos. More studies with larger sample sizes are needed to reduce imprecision. As the US Drug Enforcement Administration (DEA) currently classifies psychedelics as Schedule I substances (i.e. having no accepted medical use and a high potential for abuse), research involving these drugs is restricted, but is steadily increasing.

keywords:
Humans, Neoplasms, Lysergic Acid Diethylamide, Hallucinogens, Antidepressive Agents, Placebos, Combined Modality Therapy, Depression, Anxiety, Existentialism, Psychotherapy, Randomized Controlled Trials as Topic, Psilocybin, Bias, Psychological Distress

topic_tags:
Depression,Anxiety,End-of-Life Distress,Headache / Migraine,Emotional Processing,Spirituality,Randomized Controlled Trial,Review Article,Safety,Adverse Events

raw_json:
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authors: Smith CL, Sackett N, Stark BC, Dinh V, Romesburg EW, Roll J
journal: Psychedelic medicine (New Rochelle, N.Y.)
publication_date: 2024-08-31
doi: 10.1089/psymed.2023.0074
pubmed_id: 40051684
source_url: https://pubmed.ncbi.nlm.nih.gov/40051684/
keywords: LSD, MDMA, empathogen, psilocybin, psychedelic facilitators
substance_tags: psilocybin
topic_tags: Clinical Trial,Observational Study,Safety
study_type: Clinical Trial
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:36
raw_json: {"pubmed_id":"40051684"}
title:
Understanding Psychedelic-Assisted Psychotherapy Providers' Perspective and Insights: A Qualitative Analysis.

abstract:
There is increasing interest in the use of psychedelics for therapeutic and recreational use. Research has been hindered by federal prohibition, put in place in 1970. Despite the regulatory difficulty, research has rapidly expanded in the past decade. Multiple states and cities have drafted their own policies regarding the use of psychedelics. Assuming interest in psychedelics continues to expand; every opportunity should be explored to better understand how psychedelics may be helping or harming people.
This study examined underground psychedelic-assisted psychotherapy providers' protocols and perspectives, to better inform policy and public health, as psychedelics increasingly are used in the United States.
Transcripts of interviews were examined through qualitative content analysis.
The following four themes were identified: (1) personal experiences and self-healing motivated sharing and promotion of the positive effects of psychedelics as an expression of altruism, (2) guides articulated consistent, yet flexible processes, (3) guides believed that the client benefit was actualized through their own intrinsic ability to heal themselves, and (4) guides expressed an overwhelming sense of dissonance regarding psychedelic legalization, not only desiring increased access and decreased risk but also expressing concern about potential negative impacts on provider flexibility, and depersonalization that could come with standardizing this field of practice.
In order for current research and policy to be best informed, information must be gathered from both clinical trials and observational studies of current practice. This study identified themes within the latter to provide perspectives, practices, and insights of current underground practice, so it can be used to inform research and policy moving forward.


authors: Loizaga-Velder A, Loizaga Pazzi A.
publication_date: 2024-08-31
doi: 10.15288/jsad.23-00011
pubmed_id: 39400118
source_url: https://doi.org/10.15288/jsad.23-00011
substance_tags: psilocybin
topic_tags: Addiction,Mechanism of Action,Consciousness,Review Article,Observational Study,Safety
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
title:
Traditional Medicine, Culture, and Psychedelic Science: New Pathways for Recovery From Substance Use Disorders.

abstract:
ObjectiveThis article provides an intercultural transdisciplinary perspective on the Indigenous roots of the resurging field of psychedelic science in the management of substance use disorders (SUDs). Ritual uses of entheogens (i.e., psychedelics of natural origin) are elaborate technologies for navigating, containing, and therapeutically directing non-ordinary states of consciousness induced by these compounds.MethodA narrative review of the literature on the therapeutic potential of ayahuasca, peyote, psilocybin-containing mushrooms, Incilius alvarius-derived 5-MeO-DMT (5-methoxy-N,N-dimethyltryptamine), and iboga for the treatment of SUDs was conducted. This article also describes the application of some of these entheogens within a pilot intercultural clinical program implemented by the Yaqui tribe in Sonora, Mexico, for the treatment of SUDs and other mental health challenges.ResultsObservational research and preliminary clinical studies indicate the therapeutic potential and relative safety of these compounds in appropriate contexts, including the use of careful screening practices and complementary psychotherapeutic interventions.ConclusionsPreliminary research points to the potential therapeutic value of integrating entheogenic plant and fungi medicine with culturally attuned therapeutic strategies. Respectful intercultural dialogue across worldviews and scientific paradigms allows for the further development of new perspectives at the intersection of entheogens, addiction treatment, mental health, and traditional medicine. More interdisciplinary research is necessary in this field.

keywords:
Humans, Substance-Related Disorders, Hallucinogens, Medicine, Traditional, Culture, Mexico, Psilocybin

raw_json:
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title: Rapidly Trading Down Depression's 3 Pillars to 5HT3-Receptors Through ECT or Psilocybin?
authors: Treviranus GRS.
publication_date: 2024-08-31
pubmed_id: 39378462
source_url: https://europepmc.org/article/MED/39378462
substance_tags: psilocybin,psilocin
topic_tags: Depression,Neuroplasticity,Receptor Pharmacology,Mitochondrial Function
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:00
abstract:
Depression astonishingly can be stopped instantly by electrotherapies or through some psychedelics like psilocybin. In explaining this, the traditional approaches to their antidepressant effects via "reset" models and orthosteric serotonin receptors has neglected the only serotonin channel 5HT3, which e.g. has emerged as being helpful for the neurotrophic translation for all anti-depressants and final synaptic effects. Psychedelics here are confronted with a panorama of also anti-depressant 5HT3-channels and a search for their part e.g. in the "3 pillars" reigning depression. Of these M1) mitochondria, parasitic organelles from a fusion between some proto-bacteria and archae, founding eukaryotes, also through 5HT3 in depression determine much of its somatic crises. Two further pillars, "pushback" and "shame-link", are clarified by the parasympathetic (PS-) conspiciously 5HT3-rich "nasal" pterygo-palatine ganglion (PPG): PPG-1.) Intramural "pushbacks" intoxicating brain's tissues, show up on MRI e.g. along branches of the peri-/subcallosal artery. The brain-draining circular chambers, by CIMURAF, are plausibly driven by the PPG (and other PS-ganglia) through their dense nitrergic grid, causing loose wrung areas creating hyperboloid stenoses where they delimit contracted sliding segments PPG-2.) Existential conflicts trigger last-resort attacks, whereby the subduing are stopped into submissive shame. This plausibly occurs via the antidromic "Suzuki-link" from preparatory attack-biting (V3) via the trigeminal ggl. V3-V2-crosstalk onto the PPG, which, blushing via PACAP, maybe via MCs opens the BBB causing foggy confusion. Mushrooms may have acquired psilocybin to similarly stop feeding moves of worms (C. elegans) via the >100 5HT3-like ion channels. While on MOD-1 serotonin elicits "dwelling", collective feeding on just one fungus, psilocin could on promote audacious "roaming" (protecting fungi) - channel LGC-50 learning from this. The biphasic and pervasive H2S, being a dipole, might be flushed by ECT and on the 5HT3-receptors might get worms (and us) to move.

keywords:
Humans, Receptors, Serotonin, 5-HT3, Hallucinogens, Depressive Disorder, Electroconvulsive Therapy, Psilocybin

raw_json:
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title: Psychedelic-assisted therapy for palliative care within a home treatment setting: A case report.
publication_date: 2024-08-29
doi: 10.1002/ccr3.9305
pubmed_id: 39219779
source_url: https://doi.org/10.1002/ccr3.9305
substance_tags: psilocybin
topic_tags: Depression,Anxiety,End-of-Life Distress,Case Report,Safety
study_type: Case Report
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
authors:
Federico S, Geo M, Entela M, Bachmann S, Elisa R, Silvio C, Zoë D, Louise P, Gabriel T, Joël B, Daniele Z.

abstract:
Key clinical messageThis case study describes the feasibility and safety of psychedelic-assisted therapy (PAT) as a home-based intervention for a patient with throat cancer experiencing significant existential distress. The patient tolerated the intervention well. This case supports the feasibility and safety of PAT for patients with life-threatening conditions in a home setting.AbstractPsychedelic-assisted therapy (PAT), as it is practiced today, merges traditional psychotherapeutic techniques with the use of psychedelics such as LSD, psilocybin, or MDMA with the aim of unlocking deeper insights in patients and treating mental conditions that are resistant to other forms of therapy. The present case study describes the safety of PAT as a home-based intervention for a patient with throat cancer experiencing significant existential distress. The patient tolerated the intervention well and was asked to report on measures of anxiety, depression, and distress related to his somatic condition. The observations provided by this clinical case report align with previous findings, suggesting that PAT can be safely applied to potentially provide relief from existential distress in patients with life-threatening conditions. As this is a single-case study, generalizations should be made cautiously. Moreover, placebo effects, expectancy effects, and the natural course of the disease may influence outcomes. Future research should consider controlled trials to ascertain the efficacy and safety of such interventions in diverse settings.

raw_json:
{"europe_pmc_id":"39219779","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: [Psychedelic and dissociative agents in psychiatry: challenges in the treatment].
authors: Jungwirth J, Bavato F, Quednow BB.
publication_date: 2024-08-27
doi: 10.1007/s00115-024-01727-0
pubmed_id: 39196383
source_url: https://doi.org/10.1007/s00115-024-01727-0
substance_tags: psilocybin
topic_tags: Depression,Review Article,Treatment-Resistant Depression,Healthcare Workers,Safety
study_type: Review Article
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:03
abstract:
With the discovery of the antidepressive effects of ketamine and the increasing withdrawal of the pharmaceutical industry from the development of new psychotropic drugs, the psychiatric research into the clinical application of hallucinogens in psychiatry has literally blossomed in the last two decades. Promising results for various treatment approaches with psychedelic agents, such lysergic acid diethylamide (LSD) and psilocybin, and dissociative agents, such as ketamine and esketamine, have raised great hopes among researchers, clinicians and patients in recent years, so that there was already talk of a new era in psychiatry. As one of the first of these substances, in December 2019 intranasal esketamine was approved in the USA and the EU for the treatment of treatment-resistant depression and Switzerland followed in 2020. Recently, psilocybin was approved in Australia, Canada and Switzerland for compassionate use in exceptional cases for the treatment of depression, while large approval studies with various psychedelic agents are currently ongoing worldwide. The medical application of psychedelic agents and ketamine/esketamine is considered to be safe; however, as with all new forms of treatment it is of crucial importance that, in addition to the hopes, the specific challenges of these new treatment approaches must also be carefully considered and assessed. Excessive expectations and an insufficient risk-benefit estimation are detrimental to the patients and the reputation of the treating physician. Although a possible paradigm shift in the care of mental health is already being discussed, this review article consciously concentrates on the possible risks of treatment and the methodological weaknesses of the studies carried out so far.

keywords:
Humans, Ketamine, Lysergic Acid Diethylamide, Hallucinogens, Treatment Outcome, Mental Disorders, Psychiatry, Psilocybin

raw_json:
{"europe_pmc_id":"39196383","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Mind over matter: the microbial mindscapes of psychedelics and the gut-brain axis.
authors: Caspani G, Ruffell SGD, Tsang W, Netzband N, Rohani-Shukla C, Swann JR, Jefferies WA
journal: Pharmacological research
publication_date: 2024-08-31
doi: 10.1016/j.phrs.2024.107338
pubmed_id: 39111558
source_url: https://pubmed.ncbi.nlm.nih.gov/39111558/
substance_tags: psilocybin,psilocin
topic_tags: Neuroplasticity,Pharmacology,Mechanism of Action,Receptor Pharmacology,Review Article,Microbiome
study_type: Review Article
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:36
raw_json: {"pubmed_id":"39111558"}
abstract:
Psychedelics have emerged as promising therapeutics for several psychiatric disorders. Hypotheses around their mechanisms have revolved around their partial agonism at the serotonin 2 A receptor, leading to enhanced neuroplasticity and brain connectivity changes that underlie positive mindset shifts. However, these accounts fail to recognise that the gut microbiota, acting via the gut-brain axis, may also have a role in mediating the positive effects of psychedelics on behaviour. In this review, we present existing evidence that the composition of the gut microbiota may be responsive to psychedelic drugs, and in turn, that the effect of psychedelics could be modulated by microbial metabolism. We discuss various alternative mechanistic models and emphasize the importance of incorporating hypotheses that address the contributions of the microbiome in future research. Awareness of the microbial contribution to psychedelic action has the potential to significantly shape clinical practice, for example, by allowing personalised psychedelic therapies based on the heterogeneity of the gut microbiota.

keywords:
2, 3, 4-Methyl enedioxy methamphetamine (MDMA), 5-dimethoxy-4-iodoamphetamine (DOI), 5-methoxy-N, DMT, Dimethyltryptamine (DMT), Gut microbiota, Gut-brain axis, Ketamine, Lysergic acid diethylamide (LSD), N-dimethyltryptamine (5-MeO-DMT), Personalised medicine, Precision medicine, Psilocin, Psilocybin, Psychedelics, Serotonin, ayahuasca


title: Rapid, biochemical tagging of cellular activity history in vivo
authors: Zhang R, Anguiano M, Aarrestad IK, Lin S, Chandra J, Vadde SS, Olson DE, Kim CK.
journal: bioRxiv
publication_date: 2023-09-07
doi: 10.1101/2023.09.06.556431
source_url: https://doi.org/10.1101/2023.09.06.556431
substance_tags: psilocybin
topic_tags: Mechanism of Action,Animal Study
study_type: Animal Study
source_name: bioRxiv
publication_status: preprint
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
abstract:
ABSTRACT Intracellular calcium (Ca 2+ ) is ubiquitous to cell signaling across all biology. While existing fluorescent sensors and reporters can detect activated cells with elevated Ca 2+ levels, these approaches require implants to deliver light to deep tissue, precluding their noninvasive use in freely-behaving animals. Here we engineered an enzyme-catalyzed approach that rapidly and biochemically tags cells with elevated Ca 2+ in vivo. Ca 2+ -activated Split-TurboID (CaST) labels activated cells within 10 minutes with an exogenously-delivered biotin molecule. The enzymatic signal increases with Ca 2+ concentration and biotin labeling time, demonstrating that CaST is a time-gated integrator of total Ca 2+ activity. Furthermore, the CaST read-out can be performed immediately after activity labeling, in contrast to transcriptional reporters that require hours to produce signal. These capabilities allowed us to apply CaST to tag prefrontal cortex neurons activated by psilocybin, and to correlate the CaST signal with psilocybin-induced head-twitch responses in untethered mice.

raw_json:
{"europe_pmc_id":"PPR721525","source":"PPR","pub_type":null,"publisher":"bioRxiv","importer":"Europe PMC"}


title: Psilocybin desynchronization persists in the human brain.
authors: Rogers J.
publication_date: 2024-08-31
doi: 10.1038/s41583-024-00854-6
pubmed_id: 39085513
source_url: https://doi.org/10.1038/s41583-024-00854-6
keywords: Brain, Humans, Hallucinogens, Electroencephalography, Cortical Synchronization, Psilocybin
substance_tags: psilocybin
topic_tags: General
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:03
raw_json:
{"europe_pmc_id":"39085513","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Guo Q, Guo L, Wang Y, Shang S.
publication_date: 2024-06-19
doi: 10.1016/j.psychres.2024.116018
pubmed_id: 38924903
source_url: https://doi.org/10.1016/j.psychres.2024.116018
substance_tags: psilocybin
study_type: Randomized Controlled Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:03
title:
Efficacy and safety of eight enhanced therapies for treatment-resistant depression: A systematic review and network meta-analysis of RCTs.

abstract:
BackgroundTreatment-Resistant Depression (TRD) challenges psychiatric treatment, with existing guidelines covering only a subset of augmentation strategies.MethodsA network meta-analysis following PRISMA guidelines examined the efficacy and safety of TRD treatments, analyzing 72 randomized controlled trials from eight databases, assessing response and remission rates, tolerability, and safety through the Cochrane Risk of Bias Tool and CINeMA framework.FindingsIncluding 12,105 participants, the analysis highlighted ECT, Ketamine, Esketamine, and Psilocybin as superior first-line treatments due to their optimal balance between effectiveness and tolerability. Brexpiprazole and Quetiapine showed no significant efficacy over placebo in response rates, while Esketamine and Psilocybin exhibited lower tolerability.InterpretationThe results advocate for ECT, Ketamine, Esketamine, and Psilocybin as preferred treatments for TRD, guiding clinical practice with evidence-based recommendations for enhancing treatment outcomes. This study underscores the importance of considering both efficacy and safety in selecting augmentation strategies for TRD.

keywords:
Humans, Ketamine, Antidepressive Agents, Electroconvulsive Therapy, Randomized Controlled Trials as Topic, Depressive Disorder, Treatment-Resistant, Psilocybin, Outcome Assessment, Health Care

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

raw_json:
{"europe_pmc_id":"38924903","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Clark MP.
publication_date: 2024-06-24
doi: 10.1089/jpm.2024.0066
pubmed_id: 38916613
source_url: https://doi.org/10.1089/jpm.2024.0066
keywords: Humans, Neoplasms, Hospice Care, Spirituality, Hospice and Palliative Care Nursing, Psilocybin
substance_tags: psilocybin
topic_tags: End-of-Life Distress,Chronic Pain,Emotional Processing,Spirituality
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:04
title:
Psilocybin: Medicine for My Soul. Relief from Emotional and Spiritual Pain as a Hospice Nurse Diagnosed with Cancer.

raw_json:
{"europe_pmc_id":"38916613","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Effects of psilocybin on uncertain punishment learning.
authors: Jacobs DS, Bogachuk AP, Le Moing CL, Moghaddam B.
publication_date: 2024-06-21
doi: 10.1016/j.nlm.2024.107954
pubmed_id: 38909970
source_url: https://doi.org/10.1016/j.nlm.2024.107954
substance_tags: psilocybin
topic_tags: Depression,Anxiety,Mechanism of Action,Animal Study,Safety
study_type: Animal Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:00
abstract:
Psilocybin may provide a useful treatment for mood disorders including anxiety and depression but its mechanisms of action for these effects are not well understood. While recent preclinical work has begun to assess psilocybin's role in affective behaviors through innate anxiety or fear conditioning, there is scant evidence for its role in conflict between reward and punishment. The current study was designed to determine the impact of psilocybin on the learning of reward-punishment conflict associations, as well as its effects after learning, in male and female rats. We utilized a chained schedule of reinforcement that involved execution of safe and risky reward-guided actions under uncertain punishment. Different patterns of behavioral suppression by psilocybin emerged during learning versus after learning of risky action-reward associations. Psilocybin increased behavioral suppression in female rats as punishment associations were learned. After learning, psilocybin decreased behavioral suppression in both sexes. Thus, psilocybin produces divergent effects on action suppression during approach-avoidance conflict depending on when the conflict is experienced. This observation may have implications for its therapeutic mechanism of action.

keywords:
Animals, Rats, Rats, Sprague-Dawley, Hallucinogens, Uncertainty, Punishment, Reward, Female, Male, Psilocybin

raw_json:
{"europe_pmc_id":"38909970","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Commentary on Darke et al.: Expanded psychedelic access requires new safety monitoring systems.
authors: Korthuis PT, Wilson-Poe AR, Black JC, Monte A
journal: Addiction (Abingdon, England)
publication_date: 2024-08-31
doi: 10.1111/add.16589
pubmed_id: 38881433
source_url: https://pubmed.ncbi.nlm.nih.gov/38881433/
substance_tags: psilocybin
topic_tags: Safety,Toxicity
study_type: Other
source_name: PubMed
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:20:36
raw_json: {"pubmed_id":"38881433"}
keywords:
death, harm reduction, lysergic acid diethylamide (LSD), psilocybin, psychedelic epidemiology, psychedelic toxicity


title: Stutterers' experiences on classic psychedelics: A preliminary self-report study.
authors: Jackson ES, Goldway N, Gerlach-Houck H, Gold ND.
publication_date: 2024-05-18
doi: 10.1016/j.jfludis.2024.106062
pubmed_id: 38833909
source_url: https://doi.org/10.1016/j.jfludis.2024.106062
substance_tags: psilocybin
topic_tags: Depression,Anxiety,PTSD,Eating Disorders,Aging,Emotional Processing
study_type: Qualitative Study
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
abstract:
Stuttering poses challenges to social, occupational, and educational aspects of life. Traditional behavioral therapies can be helpful but effects are often limited. Pharmaceutical treatments have been explored but there are no FDA-approved treatments for stuttering. Interest has grown in the potential use of classic psychedelics, including psilocybin and LSD, which have shown effectiveness in treating disorders with similar symptoms (e.g., anxiety, depression, PTSD). The potential effects of psychedelics on stuttering have not been explored. We conducted a preliminary investigation of self-identified stutterers who report their experiences taking classic psychedelics on the online messaging forum, Reddit. We qualitatively analyzed 114 publicly available posts, extracting meaningful units and assigning descriptor codes inductively. We then deductively organized responses into an established framework of psychedelics which includes behavioral, emotional, cognitive, belief-based, and social effects. These effects were subsequently grouped under organizing themes (positive, negative, neutral). Descriptive statistics revealed that the majority of users (74.0%) reported positive overall short-term effects particularly related to behavioral and emotional change (e.g., reduced stuttering and anxiety), but negative (9.6%), mixed (positive and negative; 4.8%), and neutral overall experiences (11.6%) were also reported. The results support the possibility that psychedelics may impact stuttering, but caution must be applied in their interpretation given the entirely uncontrolled research setting and potential adverse health effects of psychedelics as reported elsewhere. While these results do not encourage the use of psychedelics by stutterers, they suggest that future work could examine the impact of psychedelics on stuttering under supervised and in clinically controlled settings.

keywords:
Humans, Stuttering, Lysergic Acid Diethylamide, Hallucinogens, Adult, Female, Male, Self Report, Psilocybin

raw_json:
{"europe_pmc_id":"38833909","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


authors: Darke S, Duflou J, Peacock A, Farrell M, Hall W, Lappin J.
publication_date: 2024-05-20
doi: 10.1111/add.16518
pubmed_id: 38771189
source_url: https://doi.org/10.1111/add.16518
substance_tags: psilocybin,psilocin
topic_tags: Adolescents,Toxicity
study_type: Other
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:00
title:
A retrospective study of the characteristics and toxicology of cases of lysergic acid diethylamide (LSD)- and psilocybin-related death in Australia.

abstract:
Background and aimsLysergic acid diethylamide (LSD) and psilocybin are used as recreational drugs, and there is renewed interest in their clinical use. The current study aimed to (1) determine the circumstances of death and case characteristics of LSD- and psilocybin-related death in Australia, 2000-23; and (2) determine the toxicological profile and major autopsy findings of these cases.MethodsThis was a retrospective exploratory study of all cases of LSD- and psilocybin-related death in Australia, 2000-23, retrieved from the National Coronial Information System.ResultsA total of 43 cases were identified: 33 LSD and 10 psilocybin. The median ages were 24 years [interquartile range (IQR) = 13, range = 16-53] (LSD) and 26 years (IQR = 18.5, range = 20-58) (psilocybin), and fewer than five cases were female. The most common circumstance of death among both groups was traumatic accident (LSD36.4%, psilocybin 40.0%). There were 12 cases of self-harm, all of which involved LSD, all by physical means. In a fifth, death was attributed to multiple drug toxicity (LSD18.2%, psilocybin 20.0%). In one case, death was attributed solely to LSD toxicity, while in a further two cases death was attributed to a cardiovascular event following LSD consumption (one LSD only, one multiple drug toxicity). In four psilocybin cases, the cause of death was undetermined. The most common clinical presentation was severe agitation (LSD27.3%, psilocybin 20.0%). Median blood concentrations were LSD0.8 μg/l (IQR = 1.7, range = 0.1-3), psilocin 20 μg/l (IQR = 53.5, range = 6-83). LSD was the only drug present in 25.0% of LSD cases and psilocybin in 20.0% of psilocybin cases. Pre-existing organ pathology was uncommon.ConclusionsLysergic acid diethylamide (LSD)- and psilocybin-related death in Australia from 2000 to 2023 was primarily due to traumatic injury, whether through accident or self-harm. Cases of acute toxic reactions that were attributed solely to LSD were rare.

keywords:
Humans, Substance-Related Disorders, Lysergic Acid Diethylamide, Hallucinogens, Cause of Death, Retrospective Studies, Adolescent, Adult, Middle Aged, Australia, Female, Male, Young Adult, Psilocybin

raw_json:
{"europe_pmc_id":"38771189","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


title: Emerging drugs in phase II and III clinical development for the treatment of alcohol use disorder.
authors: Köhne S, Hillemacher T, Glahn A, Bach P.
publication_date: 2024-04-17
doi: 10.1080/14728214.2024.2342951
pubmed_id: 38606899
source_url: https://doi.org/10.1080/14728214.2024.2342951
substance_tags: psilocybin
topic_tags: Addiction,Clinical Trial,Review Article
study_type: Clinical Trial
source_name: Europe PMC
publication_status: published
date_added: 2026-07-01 06:48:05
last_checked: 2026-07-01 11:22:05
abstract:
IntroductionAlcohol Use Disorder (AUD) poses an ongoing significant global health burden. AUD is highly prevalent and affects not only the individuals with AUD, but also their communities and society at large. Even though pharmacotherapy is an integral part of AUD treatment, the few available substances show limited efficacy and limited clinical impact. Thus, there is a need for new innovative pharmacotherapeutic approaches.Areas coveredThis paper provides a comprehensive review of drugs approved for the treatment of AUD as well as those currently in phase II and III development. Data from recent clinical trials has been reviewed and supplemented by additional literature based on a systematic search of the PubMed database and clinical trials registries. Compounds discussed include disulfiram, naltrexone, nalmefene, acamprosat, baclofen, sodium oxybate, doxazosin, varenicline, zonisamide, gabapentin, apremilast, ibudilast, ivermectin, tolcapone, mifepristone, suvorexant, ketamine, psilocybin, semaglutide, oxytocin and cannabidiol.Expert opinionEven though the majority of the discussed compounds lack sufficient evidence to support their efficacy, multiple promising new treatment options are currently under investigation. Future research has to consider specific phenotypes and subgroups of AUD as well as a possible enhancement of the effects of psychotherapy through combination with pharmacotherapy. Practitioners should be encouraged to use available compounds to support existing therapeutic regimens.

keywords:
Animals, Humans, Alcoholism, Alcohol Deterrents, Clinical Trials, Phase II as Topic, Clinical Trials, Phase III as Topic, Drug Development

raw_json:
{"europe_pmc_id":"38606899","source":"MED","pub_type":null,"publisher":null,"importer":"Europe PMC"}


