Uncovering the neural basis of psychedelics’ potent effects on brain activity and conscious experience has great potential for understanding their therapeutic effects. Numerous studies using functional magnetic resonance imaging (fMRI) uncovered a strong effect of psychedelics on global properties of fMRI signal, but how they map to underlying neural phenomena remains to be further explored. In...
Major depressive disorder is a highly prevalent psychiatric condition that can affect individuals across the lifespan, yet its pathophysiology remains incompletely understood. Classical hypotheses, informed by preclinical and clinical studies, emphasized dysregulated monoaminergic neurotransmission and guided the development of widely prescribed antidepressants, including selective serotonin...
Psilocybin, N,N-dimethyltryptamine (DMT), lysergic acid diethylamide (LSD), and 3,4-methylenedioxymethamphetamine (MDMA) are psychedelic compounds with therapeutic potential for depression, anxiety, and post-traumatic stress. However, their relevance to endurance athletes, who face particular psychological and physical stressors, remains underexplored. This study combines a conceptual overview...
Selective serotonin reuptake inhibitors (SSRIs) are widely prescribed for mood and anxiety disorders, the same conditions under which psychedelic-assisted therapies are gaining renewed interest. However, it remains unclear how SSRI treatment may influence sensitivity to psychedelics, particularly through the shared engagement of serotonergic pathways. Here, we used the head-twitch response...
Abstract New treatments for depression are needed that combine robust efficacy with improved scalability. Although psilocybin has demonstrated antidepressant effects in Phase 3 clinical trials, some of its psychedelic effects limit tolerability, necessitating administration in highly supervised clinical settings, and thus motivating development of serotonergic therapeutics that preserve...
Abstract Psilocybin, a serotonergic psychedelic, can produce rapid and enduring antidepressant effects in patients with major depressive disorder (MDD)[1, 2], yet the neural mechanisms underlying these effects remain unclear. Negative affective biases are an important neuropsychological mechanism central to the development and perpetuation of MDD[3]. Using a translational rodent model, we...
To support ongoing clinical trials, the major human metabolites of psilocybin were synthesized on a preparative scale, specifically psilocin-O-glucuronide and 4-hydroxyindole-3-acetic acid (4-HIAA), along with putative minor metabolites and several deuterium-labeled derivatives. Psilocybin, psilocin, psilocin-O-glucuronide, and 4-HIAA were assayed for engagement at seven serotonin receptor...
Abstract Repeated mild traumatic brain injury (RmTBI) can produce lasting cognitive, emotional, and social deficits (e.g., persistent post-concussion symptoms; PPCS). Despite the prevalence of RmTBI in sports, military, and domestic violence settings, effective treatments to alleviate the neurological consequences of RmTBI remain limited. Psilocybin, a serotonergic psychedelic, can enhance...
The findings suggest a clinically relevant interaction between ayahuasca and SSRIs, as even modest increases in DMT exposure may intensify serotonergic effects in individuals receiving antidepressant therapy. This study provides a mechanistic and quantitative framework for assessing interaction risks between ayahuasca alkaloids and SSRIs, supporting clinical decision-making and harm-reduction...
MDMA-assisted psychotherapy has emerged as a promising treatment for post-traumatic stress disorder (PTSD), particularly in individuals unresponsive to conventional interventions such as SSRIs and trauma-focused cognitive behavioral therapy. As recent clinical trials report durable symptom remission, ongoing debate surrounds the mechanisms underlying its therapeutic effects. This review...