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 ...
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...
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...
BackgroundAnorexia nervosa (AN) is a severe psychiatric disorder with high morbidity, mortality, and relapse rates, most commonly emerging during adolescence. Despite specialized psychological and nutritional treatments, outcomes remain suboptimal, with high rates of relapse and chronicity. Psilocybin has been investigated with preliminary efficacy in other ...
BackgroundPosttraumatic stress disorder (PTSD) and major depressive disorder are often comorbid in humans. Psilocybin reportedly has beneficial therapeutic effects on depression, possibly by promoting neuroplasticity. PTSD is associated with the dysregulation of neuroplasticity in the hippocampus and medial prefrontal cortex (mPFC). We hypothesized that psil...
The PEARL-C1 trial is a phase II open-label trial. Participants will receive a single high-dose (25 mg) of psilocybin in the context of Psilocybin-assisted Existential, Attachment and RelationaL (PEARL) therapy. Caregivers of patients with advanced cancer often experience high levels of distress but there is currently little evidence-based guidance on how to...
BACKGROUND: Major depressive disorder is one of the most debilitating psychiatric disorders worldwide. First-line treatments such as selective serotonin reuptake inhibitors have significant limitations, including delayed onset of therapeutic effects and treatment resistance in about 30% of patients. Increasing evidence suggests that acute administration of s...
The PEARL Pilot is a phase II open-label trial. Participants will receive a single high-dose (25 mg) of psilocybin in the context of Psilocybin-assisted Existential, Attachment and RelationaL (PEARL) therapy. Individuals with advanced cancer often experience high levels of distress due to physical suffering, difficult treatment decisions, social isolation, a...
Treatment-resistant depression (TRD) remains a major clinical challenge and is typically defined as the persistence of depressive symptoms despite at least two adequate antidepressant trials. Individuals with TRD experience substantial morbidity, impaired functioning, and elevated suicide risk, highlighting the need for therapeutic strategies beyond incremen...
Psilocybin, a psychedelic drug with reported anxiolytic and antidepressant potential, is rapidly metabolized to its active metabolite psilocin. However, a lack of adequate toxicity studies and tissue distribution studies currently restricts its development and application. This study combined behavioral assays in zebrafish with desorption electrospray ioniza...
