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...
Psychedelic drugs show remarkable potential for treating psychiatric disorders, but the mechanisms underlying their therapeutic effects remain relatively unknown. Here, we demonstrate that psilocybin can powerfully ameliorate deficits in cognitive flexibility, but this effect depends on the specific circuit-level cause of those deficits. Using optogenetic mo...
Obsessive-compulsive disorder (OCD) is a chronic neuropsychiatric condition characterized by intrusive thoughts and repetitive behaviors that cause distress and functional impairment worldwide. Although selective serotonin reuptake inhibitors and cognitive behavioral therapy are first-line treatments, a considerable proportion of patients show an insufficien...
It is unclear how serotonin 2A receptors (5-HT2ARs) in cortical layer 5 pyramidal neurons (L5 PyrNs) differentially contribute to psilocybin-induced hallucinations versus neuroplasticity. Here we show that psilocybin promotes synapse formation and maturation while accelerating the elimination of pre-existing synapses. Cell type-specific manipulation further ...
This study will examine the synaptotrophic effects of psilocybin among medically healthy, detoxified OUD subjects. Eligible OUD participants will undergo pre- and post- psilocybin administration PET scans with the \[11C\]-UCB-J radiotracer while inpatient. Participants will undergo screening as outpatients at the Clinical Neuroscience Research Unit (CNRU). O...
The Psilocybe cubensis mushroom is recognized as the primary source of psilocybin in the Americas, occurring naturally across various regions. This fungus has a long history of use in Mesoamerican rituals due to its capacity to induce altered states of consciousness. The defining characteristic of Psilocybe mushrooms is their psilocybin content. Following in...
A central challenge in neuroscience is understanding how the human brain is organised to support optimal functioning and adaptability. One approach to characterise complex brain dynamics is by artificially perturbing whole-brain models. Here, we asked whether whole-brain organisation under perturbation in major depressive disorder (MDD) changes after interve...
Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition characterized by persistent deficits in social communication and interaction, restricted and repetitive patterns of behavior, and sensory processing alterations, frequently accompanied by anxiety, emotional dysregulation, and other psychiatric comorbidities. Despite advances in be...
This protocol describes a systematic review and meta-analysis assessing the efficacy and safety of classic serotonergic psychedelics and related serotonergic ergoline or lysergamide compounds in cluster headache and migraine. The review will include clinical studies evaluating psilocybin, psilocin, LSD, LSA, DMT/ayahuasca, mescaline, BOL-148 / 2-bromo-LSD / ...
Psychedelics have re-emerged as promising therapeutics for neuropsychiatric disorders, including depression, anxiety, post-traumatic stress disorder, and substance use disorders. While their beneficial effects are largely attributed to serotonin 2A (5-HT2A) receptor activation, psychedelics exhibit substantial diversity in chemical structure, receptor bindin...
Interest in psychedelics has expanded beyond clinical treatment contexts, yet little empirical work has examined how users describe psychedelic use in relation to sport and physical activity. This study conducted a qualitative content analysis of Reddit discussions involving psychedelics and physical performance. A Reddit search for “sports psychedelics” ret...
Floatation-REST (Reduced Environmental Stimulation Therapy) systematically alters sensory and bodily input by combining neutral buoyancy, thermal and proprioceptive neutrality, attenuation of exteroceptive stimulation, and enhancement of cardiorespiratory signaling to the brain. Here we examined whether this non-pharmacological sensory perturbation induces a...
Attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental condition in which prenatal stress and long-lasting disruptions of excitatory-inhibitory (E/I) balance have been implicated as key vulnerability factors. Although established pharmacological and behavioral treatments are effective for many individuals, they are not universally ...
ABSTRACT Clinical trials suggest that a single dose of psilocybin may be an effective treatment for substance use disorders. Choice impulsivity is a value-based decision-making bias that predicts drug-intake escalation and is commonly associated with substance use disorders. The dorsomedial prefrontal cortex regulates choice impulsivity and is enriched with ...
BACKGROUND: Psilocybin is among the serotonergic psychedelics closest to potential FDA approval, with growing evidence of therapeutic benefit across psychiatric conditions. As clinical trials expand, systematic characterization of adverse events (AEs) remains essential. While transient hypertensive responses are well documented, hypotensive events such as ne...
Background: Advanced Alzheimer's disease (AD) is generally regarded as a stage of irreversible functional decline. Psilocybin is known to transiently alter large-scale brain network dynamics and to induce plasticity-related mechanisms in preclinical models, yet clinical data in advanced dementia remain lacking. Case presentation: We report the case of an oct...
ABSTRACT Treatment-resistant depression (TRD) is characterized by chronic symptoms, impaired functioning, and limited response to conventional antidepressant therapy. Contemporary reviews have highlighted increasing interest in psilocybin-assisted therapy as a mechanistically novel approach for depressive disorders, grounded in early feasibility work demonst...
Mescaline, a 5-HT2A agonist psychedelic used ceremonially for millennia, lacks neuroimaging characterization due to its Schedule 1 status. Using pharmacological and resting-state fMRI in awake rats, we report mescaline's first comprehensive neurobiological profile. Acutely, mescaline produced cerebellar-selective BOLD suppression, suggesting functional disco...
Background: Treatment-resistant depression (TRD) affects a significant proportion of individuals with major depressive disorder and remains difficult to manage with conventional treatments. Psychedelic-assisted therapies and neuromodulation have emerged as innovative interventions targeting neurobiological mechanisms beyond traditional antidepressant approac...
Non-human models, including fish, are increasingly important for investigating how pharmacological agents such as hallucinogens influence behavior, physiology, and cellular processes. These models help to reveal underlying mechanisms and to support assessments of toxicological impact, efficacy, and safety. In this study, we used isogenic lineages of the amph...
