This systematic review and meta-analysis synthesized data from 13 clinical trials (n=606) evaluating psilocybin-assisted psychotherapy for major depressive disorder and treatment-resistant depression. Despite early enthusiasm, the pooled standardized mean difference (-0.79, 95% confidence interval: -3.98 to 2.40, p=0.63) revealed no statistically significant overall antidepressant effect, with...
Psilocybin-assisted therapy shows promise for depression, though current evidence relies on Phase 2 trials with notable methodological limitations. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating psilocybin-assisted therapy for major or treatment-resistant depression up to February 2024. We evaluated depressive symptom severity using...
Preprints.orgApril 20, 2026Octavian Victor Brinzei
preprint
In the past year, the medical regulation of psilocybin-assisted therapy has expanded across additional international jurisdictions, requiring an update to the original medico-legal synthesis. Newly established or clarified regulatory pathways in New Zealand, Germany, Switzerland, the Czech Republic, and at the United States federal level reflect continued evolution in therapeutic governance....
Psilocybin simultaneously holds six contradictory legal classifications across jurisdictions: Schedule I (US federal), Breakthrough Therapy (FDA), legal therapeutic use (Oregon, Colorado), Schedule 8 medical use (Australia), and pending rescheduling review (DEA/HHS). This regulatory fragmentation constitutes a classification cascade—a multi-stage disruption propagated through administrative,...
Background: Psilocybin, a key psychoactive compound found in Psilocybe mushrooms, has gained increasing attention due to its therapeutic potential in neuropsychiatric disorders [1]. However, comparative preclinical data between isolated psilocybin and whole mushroom extracts remain scarce, particularly regarding behavioural reinforcement and peripheral toxicity [2,3]. Objective: To compare the...
Background: Psilocybe cubensis mushrooms contain the tryptamines psilocybin and psilocin, which are recognized for their therapeutic potential in mental health [1]. Additionally, due to their psychedelic effects, these mushrooms are also used for religious and recreational purposes. The increasing use of these tryptamines and other psychoactive substances has led to regulatory measures,...
Background: Psilocybin, the main psychoactive compound found in Psilocybe mushrooms, has gained increasing attention due to its potential therapeutic effects in neuropsychiatric disorders [1]. Beyond its central effects, increasing evidence highlights the relevance of the gut–brain axis, suggesting that psychedelics may also influence intestinal microbiota composition. Whole mushroom extracts...
Background Psilocybin is a classic psychedelic that acutely alters brain functional connectivity. These changes are linked to therapeutic doses and subjective effects, with some evidence that changes persist beyond acute drug administration. However, the effects of lower doses on sustained connectivity changes remain unclear.
Psychedelics show therapeutic potential for treating psychiatric disorders. While studies have emphasized the roles of cortical pyramidal cells, GABAergic neurons also express serotonin receptors and are therefore likely targets of psychedelics. In this study, we determine the effect of psilocybin on the activity dynamics of major GABAergic cell types in the mouse medial frontal cortex....
Journal of Psychedelic StudiesApril 15, 2026Jean C. Vélez Rodríguez, Yanice Duquesne-Maldonado, Julián M. Hernández Torres et al.
Abstract Background and aims Psilocybin, a psychoactive compound found in fungi commonly referred to as “magic mushrooms,” is consumed for both spiritual and recreational purposes. However, psilocybin use in Puerto Rico remains understudied. This exploratory cross-sectional survey aimed to describe patterns of use, motivations for consumption, explanatory factors, personality traits, and...
Prolonged obesity induces enduring structural changes within neural circuits that contribute to maintaining the body at an elevated/obese body weight. These circuits regulate various mechanisms which can inhibit extreme or persistent weight loss. Therefore, a potential therapeutic strategy to facilitate weight loss is to promote structural plasticity within the brain. Psychedelic compounds,...
Introduction: Psilocybin therapy has demonstrated efficacy for cancer-related anxiety and depression, but resource-intensive individual treatment models raise important questions for psychedelic public health about equitable access and scalability. In our prior Phase 1/2 study of group retreat psilocybin therapy for patients with metastatic cancer, we observed partial responders who did not...
PsychoactivesApril 13, 2026J. Morgan Penberthy, Fatma Wise, Nicholas P. Cherup et al.
Prolonged grief disorder (PGD) affects approximately 10% of bereaved individuals and is now formally recognized in both the DSM-5-TR and ICD-11. Despite its prevalence, PGD often responds poorly to traditional therapeutic approaches. This manuscript outlines the protocol for an early-stage open-label feasibility trial investigating the use of psilocybin, a psychedelic compound, in treating PGD...
Abstract Psilocybin and other serotonergic drugs acutely alter human brain function and large-scale connectivity as measured with BOLD fMRI, but whether these effects are frequency-specific remains unknown. We applied multitaper spectral and cross-spectral analyses to resting-state fMRI data from 28 healthy volunteers scanned multiple times acutely following oral psilocybin administration (0.2...
Philosophical PsychologyApril 10, 2026Eric Rundquist, Diego Nicolás Monasterio López, Juan Jonathan Oyarzo Alvarado et al.
This article presents the results of a Cognitive Linguistic analysis of metaphors used in a series of interviews by a single healthy volunteer following four moderate-to-high dosing sessions with psilocybin. The interviews were conducted by members of a human psychedelic research lab in a deep-sampling fMRI and EEG brain imaging study, allowing the participant to recount experiences under the...
Psychedelics such as psilocybin are known for their hallucinogenic properties and have also been reported to produce long-lasting therapeutic effects in depression and possibly also other psychiatric disorders. Several lines of evidence suggest that psilocybin exerts its effects through activation of 5-HT2A receptors located postsynaptically to serotonergic neurons, for example, in the frontal...
The psychedelic psilocybin has shown therapeutic potential, yet underlying neural mechanisms remain poorly understood. We investigated the impact of psilocin-the active metabolite of psilocybin-on basal activity and reactivity within the paraventricular nucleus of the thalamus (PVT) and PVT projections to central amygdala (CeA) in rats. Psilocin administration increased PVT c-Fos expression and...
Major depression is a prevalent condition among patients with life-threatening illnesses, such as cancer, and recent findings suggest that psilocybin may hold promising treatment potential. Contemporary trials of psilocybin generally employ a model that includes psychotherapeutic support consisting of preparation and integration sessions surrounding the dosing. However, there is limited...
In this case report, we highlight a 28-year-old male patient with predominantly retarded type of catatonia following a single incidence of psilocybin ingestion. This patient presented with a history of six months of mutism and inability to feed himself after consuming psilocybin for the first time. He did not have any history of psychiatric illness or substance use. Imaging and laboratory...
This article proposes a research agenda for psilocybin-assisted therapy focusing on the correlation between neural entropy and long-term cognitive flexibility.