ABSTRACT Psychedelics such as psilocybin and lysergic acid diethylamide (LSD) exert hallucinogenic effects through stimulation of serotonin 5-HT2A receptors (5-HT2ARs) in the cerebral cortex. In recent years, numerous reports have demonstrated that psychedelics are effective in treating various psychiatric disorders such as major depressive disorder (MDD), t...
A Phase 1 trial comprising 15 patients has found that repeated high-dose administration of psilocybin was more effective than low-dose psilocybin or placebo in reducing symptoms of obsessive-compulsive disorder (OCD). Psilocybin was generally well-tolerated, with no reports of serious adverse events.
Naturally derived psilocybin is widely used, yet its therapeutic potential, pharmacological distinctiveness and regulatory feasibility remain understudied. This review evaluates the potential of naturally derived psilocybin using a six-criterion framework to evaluate: (1) therapeutic benefit, (2) safety and tolerability, (3) pharmacological uniqueness vs. sy...
Abstract Despite growing interest in psychedelic-assisted psychotherapy, research investigating the psychotherapeutic components is lacking. This leaves unanswered questions regarding the psychotherapy's necessity and form. This observational study addresses this gap by measuring the outcomes of a psilocybin truffle retreat, followed by the outcomes of two p...
Psilocybin-producing mushrooms exhibit considerable biochemical diversity, yet the extent of variability among strains within a single species under standardized conditions remains insufficiently characterized. In this study, we quantified psilocybin, psilocin, baeocystin, norbaeocystin, aeruginascin, and norpsilocin in the fruiting bodies of 14 distinct str...
ObjectiveEating disorders (EDs) are characterized by high rates of psychiatric comorbidity and suboptimal treatment outcomes. There remain critical gaps in research, including the exploration of effective transdiagnostic interventions. This forum article examines the potential of psilocybin treatment (PT) as a transdiagnostic intervention for EDs and common ...
Abstract Purpose Lifetime MDMA/ecstasy and psilocybin use have been associated with lower odds of psychological distress, suicidality, and depressive episodes, but these associations may vary by marginalized identity. Building on minorities' diminished psychedelic returns (MDPR) framework and extending Jones and Nock's race/ethnicity moderation work, this st...
This study is exploring how psilocybin (a psychedelic drug) may improve mood and wellbeing. Many people report feeling better after taking psilocybin, but it is not clear why. The CoPEWell study will test whether these improvements come from the psychedelic experience itself (the "trip") or from direct effects on the brain. To study this, up to 120 participa...
The fungivore-deterrence hypothesis, that psilocybin evolved as a chemical defence against arthropod fungivores via 5-HT receptor agonism, has become the working consensus in fungal chemical ecology, despite resting on a phylogenomic pattern of horizontal gene transfer among saprotrophs and remarkably little direct experimental evidence. Recent biochemistry ...
Interest has grown in the effects of psilocybin on mental health, but little is known about its naturalistic use alongside alcohol and its relationship to depression and/or anxiety symptoms. Data from the nationally-representative 2024 National Survey Investigating Hallucinogenic Trends of participants who did ( n = 1234) or did not ( n = 1607) report past-y...
RationaleInterest in psychedelic drugs has increased rapidly because of their potential therapeutic role in psychiatric disorders. Impairments in the sociocognitive skills needed to build and maintain social relationships are prominent features of many psychiatric and neurodevelopmental disorders. Emerging evidence suggests that compounds such as 3,4-methyle...
Up to 40% of individuals with alcohol use disorder (AUD) experience depression, which increases the risk of early relapse. Depression can cause relapse to occur 3 times faster in individuals with AUD who experience depressive symptoms at discharge. No treatments have been approved for individuals with both AUD and depression. Psilocybin, a psychedelic, shows...
A Phase 2, Open-Label Study to explore the efficacy, safety, and tolerability of psilocybin-assisted therapy in women with sexual assault-related Posttraumatic Stress Disorder (PTSD).
Psilocybin has been shown to induce fast and sustained symptoms improvements across various psychiatric conditions, yet its long-term mechanisms of action are not fully understood. Initial evidence suggests that longitudinal functional and structural brain changes implicate fronto-striatal-thalamic (FST) circuitry, a broad system involved in goal-directed be...
While the adoption of psilocybin-assisted therapy for existential distress offers promising support for patients with life-threatening illnesses, implementing this intervention into palliative care settings presents significant real-world challenges. To examine palliative care stakeholders' knowledge and attitudes regarding psilocybin-assisted therapy, and i...
Psilocybin is a serotonergic 5-HT2A R agonist that causes psychedelic and anxiolytic effects in human users. To delineate conservation of psilocybin pharmacology, we investigated behavioral effects of psilocybin in planarians ( Dugesia dorotocephala ), the simplest living animal with cephalization that also has a well defined serotonin (5-hydroxytryptamine [...
Mental disorders represent a major global health problem, with depression being one of the most prevalent and disabling conditions worldwide. Growing evidence suggests that the serotonergic system, particularly the 5-HT2A receptor, plays an important role in modulating mood and cognitive processes, constituting a key pharmacological target for several psycho...
This brief review highlights some of the structure-activity relationships of classic serotonergic psychedelics. In particular, we discuss structural features of three chemotypes: phenethylamines, ergolines and certain tryptamines, which possess psychedelic activity in humans. Where they are known, we point out the underlying molecular mechanisms utilized by ...
