Journal of Medicinal Chemistry
September 25, 2026
Icaro A Simon, Eline Pottie, Madeleine K. Jensen et al.
The serotonin 2A receptor is the most abundant excitatory serotonin receptor in the brain and the target for serotonergic psychedelics. Despite its importance, the mechanisms of action and structure−activity relationship of receptor agonists are not fully understood. Experimental 5-HT2AR structures have identified a hydrophobic tunnel lateral to the orthosteric site. Here, we have examined this...
Expert Opinion on Therapeutic Targets
September 21, 2026
Sixtine Fleury, Katherine M. Nautiyal
INTRODUCTION: Depressive and anxiety disorders impose a substantial public health burden, yet current serotonergic therapies are limited by delayed onset, modest remission rates, and adverse side effects. Here we put forward the serotonin 1B receptor (5-HT1BR) as an important therapeutic target for mood related pathology. AREAS COVERED: We synthesize converging evidence from human and...
Progress in Neuro-Psychopharmacology and Biological Psychiatry
September 18, 2026
Ewelina Cyrano, Joanna Gołębiowska, Piotr Popik et al.
Psychedelics and psychostimulants produce subjective and often positive affective effects in humans. In rats, positive affective states are often associated with frequency-modulated ultrasonic vocalizations (USVs). We examined whether the hallucinogenic 2,5-dimethoxy-4-iodoamphetamine (DOI; 1.25-2.5 mg/kg) and LSD (0.04-0.08 mg/kg), the non-hallucinogenic lisuride (0.03 or 0.3 mg/kg) and the...
Nature Communications
September 17, 2026
Lingjie Tang, Xin Ji, Yumeng Wang et al.
Selective 5-HT2AR agonism without 5-HT2BR activation is critical for safe psychedelic-inspired therapeutics. Here, we systematically probe the ligand-binding pockets of 5-HT2AR and 5-HT2BR and identify steric and conformational constraints at the side-extended pocket (SEP) and extended binding pocket (EBP) that dictate ligand orientation and receptor signaling. Guided by these insights, we...
Chinese medical journal
September 15, 2026
Yingjie Du, Xiangting Zhao, Quan Chen et al.
Psilocybin facilitates fear extinction in rodents, but its clinical utility is hampered by 5-hydroxytryptamine (5-HT) 2A-receptor-mediated hallucinogenic effects. This study aimed to explore whether 5-HT2A receptor is obligatory for psilocybin's fear extinction and neuroplasticity effect. Male C57BL/6J mice underwent auditory-cue fear conditioning. Ketanserin (5-HT2A/2C antagonist) or MDL100907...
Translational Psychiatry
September 14, 2026
Muhammad Asim, Julia A. Galiza Soares, Jason M Tucciarone
Serotonin (5-hydroxytryptamine; 5-HT) modulates a vast array of brain functions via its diverse receptor subtypes. Among these, the serotonin 5-HT2A receptor (5-HT2AR) has garnered intense recent interest for its pivotal role in mediating the effects of psychedelic compounds. Substantial evidence indicates that psychedelics act as agonists at the 5-HT2AR, triggering profound alterations in...
The Journal of Physical Chemistry B
September 12, 2026
Cong Zhang, Mingqi Li, Jing Ma et al.
Abstract Precise control over the thermodynamics and kinetics of receptor–ligand interactions is pivotal for manipulating physiological processes and developing targeted therapies. However, conventional pharmacological approaches often lack the spatiotemporal precision required for noninvasive in vivo modulation. Terahertz (THz) technology offers a promising alternative by using nonionizing...
The International Journal of Neuropsychopharmacology
September 9, 2026
B Richardson, S Socolow, Martha López-canul et al.
Abstract Background Recent clinical trials show that 5-MeO-DMT produces rapid antidepressant effects, yet the receptor mechanisms underlying these outcomes remain incompletely defined. Although 5-MeO-DMT is a high-affinity agonist at multiple serotonergic receptors, the relative contribution of 5-HT1A and 5-HT2A receptor signaling to its antidepressant-like actions has not been causally...
Progress in Neuro-Psychopharmacology and Biological Psychiatry
September 9, 2026
Alexandre Seillier, Ghinwa Ibrahim El Dannan, Lenka Seillier
Psilocybin, a tryptamine alkaloid found naturally in numerous Psilocybe mushroom species, is currently being investigated for its therapeutic potential in treating several neurobehavioral and psychiatric diseases. Our previous data showed that the 5-HT2B receptor (5-HT2BR) immobility and increases in climbing behavior in the forced swim test (FST), revealing that psilocybin's predictive...
The International Journal of Neuropsychopharmacology
September 9, 2026
R Freire, C Chaves, M Cabo et al.
Abstract Background Anxiety disorders are among the most prevalent psychiatric disorders worldwide, causing significant impacts on physical and emotional health and substantial functional impairment. Not only individuals with anxiety disorders have severe and debilitating anxiety symptoms; patients with PTSD, OCD and mood disorders often present with anxiety. The term classic psychedelics...