Classical serotonergic psychedelics primarily exert their profound effects through agonism at the serotonin 2A (5-HT2A) receptor, which is abundantly expressed in many cortical regions, particularly in layer V pyramidal neurons of associative and visual areas. At the cellular level, these receptors are predominantly localized postsynaptically on the soma and apical dendrites. This review...
Fear-related psychiatric disorders such as phobias and anxiety are insufficiently treated by current therapies. Psychedelics targeting 5-HT₂A receptors show promise in modulating fear circuits, but their specific neurobiological substrates remain unclear. This study investigates the effects of 4-acetoxy-N,N-dimethyltryptamine (4-AcO-DMT), a psychedelic compound, on innate fear responses and...
Mental disorders represent a major global health problem, with depression being one of the most prevalent and disabling conditions worldwide. Growing evidence suggests that the serotonergic system, particularly the 5-HT2A receptor, plays an important role in modulating mood and cognitive processes, constituting a key pharmacological target for several psychoactive compounds. In this study, we...
PsychopharmacologyJuly 1, 2026Sarah Ann Smith, Haseeb Mohammad, Lik Hang N Lee et al.
Interest in psychedelic drugs has increased rapidly because of their potential therapeutic role in psychiatric disorders. Impairments in the sociocognitive skills needed to build and maintain social relationships are prominent features of many psychiatric and neurodevelopmental disorders. Emerging evidence suggests that compounds such as 3,4-methylenedioxymethamphetamine (MDMA), lysergic acid...
Abstract Activation of mGluR2 (metabotropic glutamate receptor 2), the primary presynaptic autoreceptor for glutamate in the brain, is well established to attenuate the psychedelics-mediated behavioral and electrophysiological effects. However, the mechanisms responsible for these actions are controversial. The two competing mechanistic hypotheses have been proposed to explain this phenomenon...
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 serotonergic psychedelics, such as...
Abstract Background Serotonin has been implicated in cognitive flexibility and pathological perseverative thinking (PT), including rumination, worry, and obsessions. However, evidence remains fragmented across pharmacological manipulations, clinical populations, and outcome measures. This multilevel meta-analysis examined whether serotonergic interventions influence PT and cognitive...
Serotonin (5-hydroxytryptamine; 5-HT) is a key neuromodulator involved in the regulation of mood, appetite, aggression, and impulse control. Dysregulation of central 5-HT function has been implicated in alcohol use disorder (AUD) and comorbid depression. This review summarizes clinical and preclinical evidence on the role of 5-HT in AUD development, heterogeneity, and treatment response....
Autism Spectrum Disorder (ASD) is characterized by persistent social-communication deficits, cognitive rigidity, and atypical sensory processing. Current pharmacological treatments, including risperidone and aripiprazole, provide only limited symptomatic relief and do not address the underlying neurobiological mechanisms. Converging evidence implicates dysregulated serotonergic signaling,...
The aim of this study was to investigate the effects of deuterium substitution on the in vitro pharmacology of the psychedelic drug 2-(4-bromo-2,5-dimethoxyphenyl)ethan-1-amine (2C-B). Two deuterated isotopologues of 2C-B, namely 2-(4-bromo-5-methoxy-2-(methoxy-d3)phenyl)ethan-1-amine (2CB-2OCD3) and 2-(4-bromo-2-methoxy-5-(methoxy-d3)phenyl)ethan-1-amine (2CB-5OCD3), were synthesized and...