Traumatic brain injury (TBI) causes persistent neurobehavioral deficits and increases the risk of psychiatric disorders, including depression, anxiety, and cognitive dysfunction linked to disrupted neuroplasticity, neuroinflammation, and serotonergic (5-HT) signaling. No effective pharmacotherapies exist for chronic TBI. Psilocybin, a psychedelic 5-HT2A receptor agonist, shows promise due to...
NeuropharmacologyJune 11, 2026Vincenzo Crunelli, Tatiana P Morais, William M Connelly et al.
Renewed interest in psychedelic therapeutics has brought serotonin 5-HT2A receptors (5-HT2ARs) back into focus. Given the role of the thalamus in sensory integration and network synchronization, we examined the expression, developmental regulation, and functional impact of thalamic 5-HT2ARs, with particular emphasis on their interaction with extrasynaptic GABAA receptors and the generation of...
Provided herein are novel 5,6-bicyclic compounds as 5-HT2A receptor agonists, pharmaceutical compositions, use of such compounds in treating depression, anxiety, substance abuse and headaches, and processes for preparing such compounds.
New psychoactive substances (NPS) are a heterogeneous group of recreational drugs that mimic the actions and psychoactive effects of existing pharmaceutical products or recreational drugs. As NPS can be highly potent, even exceeding their template compound's potency, there are frequent reports of non-fatal and fatal intoxications. One principal target for hallucinogenic and psychedelic drugs,...
Dextromethorphan (DM) is an FDA-approved treatment for major depressive disorder when combined with bupropion. DM functions as an inhibitor for 5-HT membrane transporters and antagonist for sigma-1 receptors (S1Rs) and NMDA receptors, which are pharmacological actions potentially therapeutically relevant for obsessive-compulsive disorder (OCD). The present study examined DM and compounds...
Psilocybin has emerged as a transformative, rapid-acting, and long-lasting therapeutic for treatment-resistant depression, with its efficacy rooted in the induction of sustained structural and functional remodeling of mood-regulating neural circuits 1 , 2 . However, the field faces a fundamental mechanistic paradox that defies linear signaling models: psilocin, the bioactive metabolite of...
Despite renewed investigations into classical psychedelic compounds, their pharmacokinetic profiles remain incompletely understood. This systematic review collated data from healthy adult volunteers on the pharmacokinetic properties of lysergic acid diethylamide (LSD), psilocybin, dimethyltryptamine (DMT), mescaline, and 5-methoxy-N,N-dimethyltryptamine (5-MEO-DMT). We identified 32 eligible...
Major depressive disorder (MDD) and treatment-resistant depression (TRD) remain leading causes of disability, providing the impetus for receptor-level treatment strategies beyond monoamine reuptake. The serotonin 5-HT2B receptor (5-HT2BR) is uniquely positioned at the interface of central-antidepressant mechanisms and peripheral cardiac risks. Herein, we reviewed preclinical, translational and...
High Resolution Image Download MS PowerPoint Slide Tryptamine psychedelics induce psychoactive effects via agonist actions at serotonin 2A receptors (5-HT 2A ), but the compounds are generally nonselective. 4-Methoxy- N -methyl- N -isopropyltryptamine (4-MeO-MiPT) is a 5-HT 2A agonist which also blocks the 5-HT transporter (SERT) and has blunted visual and other psychedelic effects in humans....
Background and objective: Anxiety disorders are among the most prevalent psychiatric disorders worldwide and affect all age groups. Current pharmacological treatments, such as selective serotonergic reuptake inhibitors (SSRI’s) and benzodiazepines, have limitations in terms of adverse effects and efficacy, which highlights the need for alternative therapies. Serotonergic psychedelics have...