International journal of toxicology
January 31, 2026
Amir Lotfi, Samantha Sparapani, Mylène Pouliot et al.
5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a serotonin receptor agonist, in clinical development for the treatment of major depression and other psychiatric disorders. A critical safety concern for serotonergic compounds is their potential to induce seizures, as a severe manifestation of serotonin toxicity. The objective of this study was to evaluate the seizure liability of 5-MeO-DMT in a...
Nature
January 28, 2026
Zheng Xu, Hongshuang Wang, Jingjing Yu et al.
5 citations
Psychedelics are undergoing a renaissance as potential therapy for psychiatric disorders, with more than 200 clinical trials being studied across several countries1-3. However, the precise mechanisms by which these drugs bring about benefits and the potential clinical risks are not yet fully understood. The serotonin 2A receptor (5-HT2AR) was reported to be a Gq-coupled receptor and the primary...
Neuropharmacology
January 21, 2026
Ana Domi, Erika Lucente, Davide Cadeddu et al.
1 citation
Psilocybin is a naturally occurring psychedelic compound with potential antidepressant effects. Although it has long been used by humans, primarily for recreational purposes, the molecular mechanisms underlying its actions remain incompletely understood. Here, we examined the acute effects of psilocin, the active metabolite of psilocybin, on excitatory neurotransmission in the prefrontal cortex...
Psychedelic Medicine
January 7, 2026
Carter J. Richardson, Alice J. McQueney, Thomas Stevens et al.
Introduction: Oxycodone is a necessary analgesic medication but carries abuse potential. There is an urgent need to develop therapeutics to reduce abuse potential. Psychedelic compounds may be a viable option, but the behavioral and pharmacological mechanism of action is undefined. Methods: Male and female Sprague–Dawley rats were implanted with indwelling jugular catheters and allowed to...
Journal of Psychopharmacology
January 6, 2026
Connor J. Maltby, Adam K. Klein, Enya Paschen et al.
3 citations
Background: Psilocybin has shown rapid and sustained antidepressant effects in patients with major depressive disorder, yet the neurobiological mechanisms underlying these outcomes remain unclear. Aims: This study aimed to bridge clinical and preclinical findings by investigating the relationships between 5-HT 2A receptor occupancy (RO) achieved after administration of psilocybin and its...
ACS Chemical Neuroscience
January 2, 2026
Mario de la Fuente Revenga, Javier González-Maeso
1 citation
The distinct subjective effects that define psychedelics such as lysergic acid diethylamide (LSD), psilocybin, or 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) as drug class are causally linked to the activation of the serotonin 2A receptor (5-HT 2A R). However, some aspects of 5-HT 2A R pharmacology remain elusive, such as what molecular drivers differentiate psychedelic from...
Frontiers in Pharmacology
2026
Camila Estay-Olmos, Koyam Morales-Weil, Juan Ahumada et al.
The serotonin 2A receptor (5-HT2A) is a Gq/11-coupled receptor implicated in reward processing, neuropsychiatric disorders, and the actions of serotonergic psychedelics. Although 5-HT2A activation has been shown to engage endocannabinoid (eCB) signaling in several brain regions, its role in inhibitory synaptic plasticity within the nucleus accumbens (NAc) remains poorly understood. Here, we...
Aggression and violent behavior
2026
Simona Scheggi, Giulia Braccagni, Caterina Branca et al.
Aggression, anger, and irritability emerge from dysregulated interactions between prefrontal and limbic circuits, with serotonin (5-HT) exerting a central regulatory influence. Among serotonergic targets, the 5-HT2A receptor has emerged as a key modulator of aggressive behavior. Convergent neuroimaging, postmortem, and preclinical studies consistently implicate heightened prefrontal 5-HT2A...
Neuroscience Applied
2026
CA Madsen, M. Navarro, E. Kolesnik et al.
Background: Serotonergic psychedelics induce their psychoactive effects by stimulating the brain’s serotonin 2A receptor (5-HT2AR). In humans, a cerebral 5-HT2AR occupancy of ≥60% is required to elicit a profound psychedelic experience with psilocybin [1] and for pigs, a dose corresponding to ∼65% 5-HT2AR occupancy elicits headshakes [2]. We posit that in order to assess biochemical and...
SSRN Electronic Journal
2026
Dennis Parker Kelley, Gabriel Sturm, Katy Venable et al.
preprint
Serotonergic psychedelics produce therapeutic effects in clinical trials of diverse neuropsychiatric disorders, and preclinical models of inflammatory, cardiometabolic, and neuropsychiatric diseases. These effects appear largely mediated by the serotonin 5-HT2A receptor (5-HT2AR). How could psychedelics elicit transdiagnostic therapeutic effects through a single receptor across tissues as...