Abstract N, N-dimethyltryptamine (DMT) and 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) are structurally related tryptamine psychedelics with emerging therapeutic potential, yet their comparative acute pharmacology and longer-term neuroplastic effects remain incompletely defined. Here we show that DMT produces a bell-shaped dose–response curve in the mouse head-twitch response (HTR) assay,...
ABSTRACT N,N -dimethyltryptamine (DMT) is an endogenous psychedelic tryptamine that has recently emerged as a promising therapeutic candidate for acute ischemic stroke. Although DMT consistently reduces infarct size, attenuates neuroinflammation, and improves functional outcome in experimental stroke, the cellular and receptor mechanisms underlying these effects remain poorly understood....
The precise neuromodulatory mechanisms underlying consciousness and its disorders, despite growing evidence in both animals and humans, remain poorly understood at the subcortical level. The basal ganglia, a key component of the cortico-basal ganglia-thalamo-cortical loop, are known to play a crucial role in mediating consciousness and behavioural responsiveness to the environment. Here, we...
A dependência da nicotina representa um dos principais desafios da saúde pública mundial, sendo responsável por elevadas taxas de morbimortalidade e associada ao desenvolvimento de doenças cardiovasculares, respiratórias e neoplásicas. Embora existam diferentes estratégias terapêuticas para a cessação do tabagismo, as elevadas taxas de recaída evidenciam a necessidade de novas abordagens...
Background and Purpose Serotonergic psychedelics affect behavior and physiology, but the relationships among these effects remain poorly understood. In rodents, the head-twitch response is used as a measure of psychedelic-like activity, yet it does not capture changes in physiological state or the performance of learned behaviors. Here, we investigated the acute effects of the 5-HT2A receptor...
Abstract Introduction Major depressive disorder (MDD) is characterized by dysfunction in higher-order cortical regions involved in emotional and cognitive processes; however, its neurobiological basis remains unclear. Pharmacological treatments, including esketamine and sertraline, produce rapid antidepressant effects. We investigated the local intrinsic neural dynamics underlying these...
To the Editor In JAMA Psychiatry, Cubała et al. report that inhaled mebufotenin (GH001) reduced depression severity by 15.5 points more than placebo on the Montgomery-Åsberg Depression Rating Scale (MADRS) at 1 week, with 57.5% of patients achieving remission vs 0% in the placebo group. The effect size (d = −2.0) overwhelmingly surpasses those of selective serotonin reuptake inhibitors,...
The psychiatric utility of ketamine is limited by its dissociative and systemic side effects. Recently, to enable precision ketamine pharmacotherapy, we introduced SonoKet, ketamine-loaded acoustically activatable liposomes that enable focused ultrasound (FUS)-targeted ketamine delivery to millimeter-sized brain regions. In initial studies, we observed that SonoKet uncaging targeted ketamine to...
Women experience a disproportionate burden of affective and stress-related disorders, with symptom variability shaped by endocrine transitions across the menstrual cycle, pregnancy, postpartum, and menopause. Although psychedelic-assisted therapies are increasingly investigated for these conditions, hormonal state represents a largely unaccounted determinant of variability in exposure,...