Psilocybin is a serotonergic psychedelic with growing evidence for efficacy in mood disorders, and its therapeutic potential in obsessive-compulsive disorder (OCD) and related conditions is increasingly recognised but remains understudied. We systematically evaluated clinical and preclinical evidence on psilocybin's effects on obsessive and compulsive behavi...
Provided herein are novel psilocin derivatives as serotonergic psychedelic agents, pharmaceutical compositions, use of such compounds in treating central nervous system (CNS) disorders, and processes for preparing such compounds.
Psychedelic clinical research is expanding rapidly. This review analyses the state and trends in psychedelic clinical trial registrations. A systematic search of ClinicalTrials.Gov was conducted on 11 November 2024, to identify registered interventional trials investigating (therapeutic) effects of serotonergic psychedelics (e.g. lysergic acid diethylamide [...
Serotonergic psychedelics, such as LSD, psilocybin, and DMT, have strong effects on human brain activity, yet their mechanisms of action at the whole-brain level are only partially understood. Here, we present a biophysically-based mean-field model that integrates cellular and network-level details to simulate the effects of these compounds at different spat...
BackgroundResults from contemporary clinical trials of serotonergic psychedelic therapies have led to an increasing focus on their potential clinical use across mental disorders. However, studies examining mechanisms of clinical response to psychedelic therapy in psychiatric populations are limited. This review aimed to synthesize evidence from studies exami...
Background and Purpose Given the increase in recreational psychedelic use and ongoing efforts to explore psychedelics as therapeutic agents for mental health disorders, there is an urgent need to understand the effect of psychedelics such as psilocybin and N,N-dimethyltryptamine (DMT) on sleep-wake states, which share a bidirectional relationship with mental...
A crystalline cocrystal of psilocin and psilocybin enhances exposure, neuroplasticity biomarkers, and functional activity, while adjunctive atypical antipsychotics modulate serotonergic signaling to mitigate 5-HT2B-linked safety concerns. Together, these inventions advance formulation, mechanistic selectivity, and translational biomarkersoffering a chemistr...
Abstract Classic serotonergic psychedelics engage 5-HT receptors throughout the nervous system, but how maternal exposure intersects with embryonic brain interfaces is poorly defined. Here we tested in mice whether maternally administered lysergic acid diethylamide (LSD) accesses embryonic cerebrospinal fluid (CSF) and whether embryonic choroid plexus (ChP) ...
Based on promising preliminary results from clinical trials, it seems likely that psychedelic substances (classic serotonergic psychedelics, such as psilocybin, and entactogens, such as MDMA) will be introduced into psychiatry as psychedelic-assisted therapy. This also raises a range of ethical questions that urgently need to be addressed before widespread r...
Rationale: Recent evidence shows that Lysergic Acid Diethylamide (LSD), even when administered in low, non-hallucinogenic doses, can produce analgesic effects and improve pain tolerance in a sample of healthy volunteers. Such results complement what was already observed with other serotonergic psychedelics such as psilocybin: survey studies and case series i...
Psilocybin, a serotonergic psychedelic, is gaining attention for its rapid and sustained therapeutic effects in depression and other hard-to-treat neuropsychiatric conditions, potentially through its capacity to enhance neuronal plasticity. While its neuroplastic and therapeutic effects are commonly attributed to serotonin 2A (5-HT2A) receptor activation, em...
The serotonin 2C receptor (5-HT2C) is a G protein-coupled receptor implicated in multiple physiological and psychological processes and has been investigated as a therapeutic target for neuropsychiatric conditions such as obesity, drug abuse, and depression. With renewed interest in serotonergic psychedelics for treating depression, 5-HT2C may contribute to ...
Serotonergic psychedelics have shown promise in clinical trials for treating an array of mental health disorders, including depression, anxiety, and post-traumatic stress disorder. Despite these findings, our understanding of how these drugs mechanistically exert their therapeutic effects remains incomplete. While researchers have regularly employed rodent p...
This randomized controlled clinical trial evaluates the effectiveness of psilocybin and psilocybin-assisted cognitive behavioral therapy (CBT) in the management of Major Depressive Disorder (MDD). The study aims to compare the effects of psilocybin-only therapy, CBT, and psilocybin-assisted CBT on depression symptoms, neurochemical markers, inflammatory mark...
Psilocybin, a serotonergic psychedelic, has emerged as a promising treatment for a range of mental health conditions, including anorexia nervosa. Recent insights from animal models and human imaging studies suggest psilocybin enhances cognitive flexibility and modifies reward processing - two core processes disrupted in anorexia nervosa. Both cognitive flexi...
Serotonergic psychedelics, including the recreationally used psilocybin and LSD, have become promising therapeutic agents for the treatment of treatment-resistant depression. While it is generally agreed that they exhibit their antidepressant effects by inducing rapid and sustained neuroplasticity, the molecular mechanisms responsible are widely debated. In ...
Recent advances in psychedelic research have renewed interest in their therapeutic potential for psychiatric disorders characterized by cognitive and behavioral rigidity. This review examines the rationale for using serotonergic psychedelics-particularly 5-HT2A receptor agonists such as psilocybin-in the treatment of eating disorders (EDs), including anorexi...
Psilocybin, a serotonergic compound that produces psychedelic effects primarily through activation of the 5-HT2A receptor, has shown promise in treating neuropsychiatric conditions, including obsessive-compulsive disorder (OCD). However, the effects of chronic psilocybin administration on gut function, microbiota, and behavioural phenotypes remain understudi...
Through its widespread reciprocal connections with the cerebral cortex, the claustrum is implicated in sleep and waking cortical network states. Yet, basic knowledge of neuromodulation in this structure is lacking. The claustrum is richly innervated by serotonergic fibers, expresses serotonin receptors, and is suggested to play a role in the ability of psilo...
