Classic psychedelics, including psilocybin, LSD, DMT, 5-MeO-DMT, mescaline, and phenethylamines such as DOI, exert their core effects through 5-HT2A receptor agonism, inducing widespread neurobiological and behavioral changes relevant to psychiatric research. Emerging evidence suggests that these effects are modulated by sex, yet this dimension remains underrepresented in studies. This review...
AbstractPsychedelic-assisted interventions are complex, context-sensitive interventions in which pharmacological, psychological, relational, environmental, cultural, and temporal processes interact. Trials of psilocybin and related compounds have reported promising but heterogeneous findings across psychiatric, substance-use, and existential indications, while also revealing challenges related...
Mindfulness-based interventions have demonstrated benefits for emotional regulation, psychological resilience, and well-being, yet the structural mechanisms through which mindfulness produces sustained transformation remain insufficiently articulated. Existing explanations—attention regulation, body awareness, decentring, emotion regulation, neuroplasticity—are typically presented as parallel...
The occupancy-driven pharmacology model in psychopharmacology has guided drug discovery and development for decades, whereby the goal is stable receptor occupancy over an extended period with a direct relationship of drug exposure to pharmacodynamic and therapeutic response. Event-driven pharmacology (EDP) is a concept where the acute pharmacodynamic actions of a plastogen, a transient binding...
Objective: Human thought and consciousness are core advanced cognitive functions of the human brain, whose material basis derives from electrochemical activities of neurons. To explore the transformation mechanism from neural electrical signals to subjective thoughts, this paper systematically sorts out the micro-transmission rules of neuronal electrical signals, the intermediate coding process...
European Journal of PharmacologyJuly 10, 2026Amanda Gollo Bertollo, Vinicius Alexandre Wippel, Maiqueli Eduarda Dama Mingoti et al.
Major Depressive Disorder (MDD) is a debilitating mental health condition that significantly impacts quality of life. Despite available pharmacological treatments, response rates remain suboptimal, with a considerable number of patients experiencing treatment-resistant depression (TRD). Indeed, classical antidepressants, primarily targeting monoaminergic systems, exhibit a therapeutic delay due...
Classic psychedelics such as lysergic acid diethylamide (LSD), psilocybin, N,N-dimethyltryptamine (DMT), and mescaline induce lasting changes in neuroplasticity and behavior that extend far beyond their acute pharmacological effects. Emerging evidence highlights that these enduring therapeutic benefits in neuropsychiatric conditions may be significantly mediated through complex epigenetic...
bioRxivJuly 9, 2026Christine Liu, Ellie M. Ho, Alexander S. Enos et al.
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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 models of cognitive inflexibility in...
Open Science FrameworkJuly 9, 2026Raul Edison Luna Lazo, Nicole Milagritos Cardoso Azorza, Jatziri Yanina Vilca Yanac et al.
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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 insufficient response, supporting the need for...
The serotonergic psychedelic N,N-dimethyltryptamine (DMT) produces rapid antidepressant effects in preclinical and early clinical studies. Therapeutic benefits have been linked to sustained neural plasticity, including adult neurogenesis in rodents. Whether brief DMT exposure engages proliferative responses in human neural stem cells (NSCs) remains unresolved. Using human iPSC-derived NSCs, we...