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...
Quality in Sport
January 31, 2026
Anna Maria Komarczewska, Filip Matusiak, Klaudia Brzoza et al.
Psilocybin-assisted interventions have shown rapid reductions in depressive symptoms in controlled clinical settings, raising questions about biological mechanisms supporting durability beyond the acute drug effect. [5,7] Mechanistic accounts increasingly focus on neuroplasticity as a candidate pathway linking transient serotonergic receptor activation to longer-lasting psychological and...
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...
Journal of Medicinal Chemistry
January 26, 2026
Marco Banzato, Martina Colognesi, Lorena Lucatello et al.
Psilocybin, the phosphorylated prodrug of psilocin, holds therapeutic promise across a range of neuropsychiatric conditions, yet its clinical utility is constrained by acute psychoactive effects. Here, we report the rational design, synthesis, and evaluation of a focused library of fluorinated reversible N-alkyl carbamate derivatives of psilocin aimed at reducing acute psilocin exposure and...
International Journal of Innovative Technologies in Social Science
January 23, 2026
Jakub Klepacz, Radosław Swędrak, Marzena Swojnóg et al.
The escalating global burden of mental health disorders, coupled with the stagnation of innovation in traditional monoaminergic pharmacotherapy (e.g., SSRIs), has precipitated a critical need for novel therapeutic paradigms. This article presents a comprehensive systematic review of the so-called "Psychedelic Renaissance," focusing on the clinical resurgence of classical serotonergic...
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...
Pharmacological Reports
January 20, 2026
Piotr Olejnik, Katarzyna Kamińska, Krystyna Gołembiowska et al.
INTRODUCTION: Psilocybin, a classic serotonergic psychedelic, has antidepressant, anxiolytic, anti-inflammatory, and analgesic properties. However, the immunomodulatory effects of psilocybin within the central nervous system, particularly on microglial activation, remain poorly understood. Therefore, this study aimed to investigate the effects of psilocybin on microglial activation markers and...
bioRxiv (Cold Spring Harbor Laboratory)
January 15, 2026
Justyna K. Hinchcliffe, Christopher W. Thomas, Gary Gilmour et al.
preprint
Abstract The serotonergic psychedelic, psilocybin, shows potential for rapid and sustained antidepressant effects but the underlying mechanisms remain unknown. Using a chronic interferon-alpha–induced rat model of depression, we show acute psilocybin (0.3 mg/kg) reverses impaired reward-induced biases within 24hrs, with effects enduring for at least 7 days. This suggests psilocybin can restore...
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...
Molecular Pharmacology
2026
Lindsay P. Cameron, Alaina M Jaster, Raul A Ramos et al.
3 citations
2,5-dimethoxy-4-iodoamphetamine (DOI) is a phenethylamine psychedelic with high affinity for 5-HT2 receptors. In 2022 and 2023, the US Drug Enforcement Administration proposed to place DOI, along with a similar compound, 2,5-dimethoxy-4-chloroamphetamine, in Schedule I of the Controlled Substances Act based on their psychoactivity and alleged abuse potential. Here, we describe the history of...
Frontiers in Pharmacology
2026
Patricio Sáez-briones, Amanda Silva-Rodríguez, Michelle Morales-Vidal et al.
In humans, empathy is expressed through various prosocial behaviours between individuals that may be enhanced after intake of the synthetic entactogen MDMA (3,4-methylenedioxymethamphetamine, "Ecstasy") as the behavioural expression of the so-called entactogenic syndrome. Rodents may also exhibit empathy-like behaviours, such as social interaction and helping behaviour. In this regard, while...
Frontiers in Pharmacology
2026
Joseph Geraci, Erik Viirre, Bessi Qorri et al.
Classical serotonergic psychedelics (e.g., LSD, psilocybin, DMT) alter perception and neuroplasticity primarily via 5-HT2A receptor activation and downstream Ca2+-dependent signaling cascades. Here we propose a speculative yet falsifiable pharmacological hypothesis that these drug-induced biochemical cascades might interface with quantum-mechanical processes in the brain. We focus on nuclear...
Psychopharmakotherapie
2026
Antonia Bendau, Felix Betzler, Twyla Michnevich et al.
1 citation
Party drugs encompass a broad spectrum of legal and illegal psychoactive substances used in party settings such as clubs, festivals, raves or private gatherings to modulate mood, perception, social interaction and bodily states. Most commonly, alcohol and cannabis are consumed, followed by amphetamine, MDMA (“ecstasy”), cocaine and ketamine. Synthetic cathinones, GHB/GBL (“liquid ecstasy”),...
OPUS FAU - Online publication system of Friedrich-Alexander-Universität Erlangen-Nürnberg
2026
Aneta Petrušková
INTRODUCTION: Sertonergic psychedelics LSD, psilocin and DMT, have been shown to hold a great potential for treatment of various neuropsychiatric conditions, such as major depressive disorder, addiction, and end-of-life anxiety. Effects of these substances on neuronal activity and plasticity have been demonstrated, however, better understanding of their mechanism of action is crucial for...