Zenodo (CERN European Organization for Nuclear Research)
September 2, 2026
Andrea Vittorini
This hypothesis and perspective article proposes that uninterrupted daily low-dose psilocybin may constitute a pharmacologically distinct receptor-adaptation paradigm. Repeated 5-HT2A agonist pulses could progressively produce functional desensitization, internalization, and/or down-regulation; the fading of acute subjective effects may therefore mark the development of an adaptive state rather...
Neuropsychopharmacol Rep
September 1, 2026
Daisuke Ibi, Rika Takaba, Keisuke Yoshida et al.
Contribution of the Serotonin 5-HT2A Receptor to the Therapeutic Effect of Psilocin on Social Behavior Deficits in Mice Repeatedly Exposed to Social Defeat Stress.
Neuroscience
August 30, 2026
Yang Wang, Sinem Cetinkaya Karaca, Mille Deckmann Rasmussen et al.
Classical psychedelics exert therapeutic effects on affective disorders, with serotonin 5-HT2A receptor activation thought to play a central role. The cellular mechanisms by which 5-HT2A signaling modulates neural circuits remain incompletely understood and may differ across mood-regulating brain regions. While psychedelic actions have been extensively studied in the medial prefrontal cortex,...
Nursing Edição Brasileira
August 27, 2026
Ana Júlia Costa Matias Gomes, Jéssica Camilo Ramos Rodrigues, Valber Pinheiro Padilha Filho
Os psicodélicos clássicos, como a psilocibina, o LSD e a DMT, têm despertado crescente interesse na psiquiatria moderna devido ao seu potencial terapêutico em transtornos resistentes ao tratamento. O mecanismo de ação primário dessas substâncias envolve o agonismo dos receptores de serotonina 5-HT2A, localizados principalmente no córtex pré-frontal. Esta revisão sistemática analisou como a...
bioRxiv
August 19, 2026
D. Momi, Y. Nahas, D. Wyrick et al.
preprint
Psilocybin produces rapid and lasting therapeutic effects, yet how 5-HT2A receptor activation reshapes brain-wide circuit dynamics during acute drug administration remains poorly understood. Using simultaneous multi-region Neuropixels recordings of 46,360 single units from 35 mice, together with scalp electroencephalography (EEG), pupillometry, and locomotion monitoring, we provide a...
ACS Pharmacology & Translational Science
August 18, 2026
Richard A. Glennon, Maƚgorzata Dukat
Abstract Isotryptamines, or 2-(1-indolyl)ethylamines, are positional or geometric isomers of tryptamines where the aminoethyl substituent has been relocated from the indole 3-position to the N1-position. Early studies with these types of agents relied on peripheral tissue assays for examination of their serotonin (5-hydroxytryptamine; 5-HT) receptor affinities to investigate structure–affinity...
Nature Communications
August 3, 2026
Frederik Gudmundsen, Julia Czurylo, Daniel Ryskamp Rijsketic et al.
Serotonergic psychedelics show therapeutic potential across neuropsychiatric disorders despite transient acute effects. These compounds share serotonin 2 A receptor agonism but differ in broader pharmacology, motivating a systematic comparison of their neurobiological effects. Here, we use [18 F]FDG-PET in rats to assess acute and one-week effects of psilocybin, LSD, and 2C-B on brain metabolic...
TIPS - Trends in Pharmacological Sciences
August 1, 2026
S. Nasini, B. Barzon, A. Casile et al.
Classic serotonergic psychedelics act primarily via 5-HT2A receptor agonism, yet their therapeutic effects and biological responses are heterogeneous. Biological sex remains an underexamined source of this variability because many clinical and preclinical studies have not been designed to test sex-by-treatment effects. Recent preclinical findings, together with more limited human evidence,...
Cell
August 1, 2026
Yating Wen, Lingjie Tang, Wenwen Duan et al.
Cancer remains a leading cause of morbidity and mortality worldwide. While classical psychedelics have been used clinically to treat cancer-associated psychiatric disorders, their impact on tumor progression is unclear. Here, we show that by targeting the serotonin receptor 5-HT2AR, lysergic acid diethylamide (LSD) enhances CD8+ T cell-mediated antitumor immunity and suppresses colorectal...
Hearing research
August 1, 2026
Shuhan Lu, Zhixin Zhang, Xinmiao Xue et al.
Subjective tinnitus is a common auditory disorder characterised by the subjective perception of noise in the absence of external sound sources. Its prevalence has been rising annually due to noise exposure, medication misuse, and population ageing. Current tinnitus treatments employ antidepressants, anticonvulsants, and vasodilators, yet most demonstrate limited efficacy with significant side...
Science
February 16, 2023
Maxemiliano V. Vargas, Lee E. Dunlap, Chunyang Dong et al.
467 citations
Decreased dendritic spine density in the cortex is a hallmark of several neuropsychiatric diseases, and the ability to promote cortical neuron growth has been hypothesized to underlie the rapid and sustained therapeutic effects of psychedelics. Activation of 5-hydroxytryptamine (serotonin) 2A receptors (5-HT2ARs) is essential for psychedelic-induced cortical plasticity, but it is currently...
Neuron
July 5, 2021
Ling-Xiao Shao, Clara Liao, Ian Gregg et al.
589 citations
Summary Psilocybin is a serotonergic psychedelic with untapped therapeutic potential. There are hints that the use of psychedelics can produce neural adaptations, although the extent and time scale of the impact in a mammalian brain are unknown. In this study, we used chronic two-photon microscopy to image longitudinally the apical dendritic spines of layer 5 pyramidal neurons in the mouse...
Neuropsychopharmacology
January 26, 2019
M. Madsen, Patrick M. Fisher, Daniel Burmester et al.
505 citations
The main psychedelic component of magic mushrooms is psilocybin, which shows promise as a treatment for depression and other mental disorders. Psychedelic effects are believed to emerge through stimulation of serotonin 2A receptors (5-HT2ARs) by psilocybin's active metabolite, psilocin. We here report for the first time the relationship between intensity of psychedelic effects, cerebral 5-HT2AR...
Cell
January 26, 2017
Daniel Wacker, Sheng Wang, John D. Mccorvy et al.
466 citations
SUMMARY The prototypical hallucinogen LSD acts via serotonin receptors, and here we describe the crystal structure of LSD in complex with the human serotonin receptor 5-HT2B. The complex reveals conformational rearrangements to accommodate LSD, providing a structural explanation for the conformational selectivity of LSD’s key diethylamide moiety. LSD dissociates exceptionally slowly from both...
Journal of Psychopharmacology
September 11, 2014
Mary P Cosimano, Matthew W. Johnson, Albert Garcia‐romeu et al.
910 citations
Despite suggestive early findings on the therapeutic use of hallucinogens in the treatment of substance use disorders, rigorous follow-up has not been conducted. To determine the safety and feasibility of psilocybin as an adjunct to tobacco smoking cessation treatment we conducted an open-label pilot study administering moderate (20 mg/70 kg) and high (30 mg/70 kg) doses of psilocybin within a...
Science
March 22, 2013
Chong Wang, Yi Jiang, Jinming Ma et al.
522 citations
Dissecting Serotonin Receptors Serotonin receptors are the targets for many widely used drugs prescribed to treat ailments from depression to obesity and migraine headaches (see the Perspective by Palczewski and Kiser ). C. Wang et al. (p. 610 , published online 21 March) and Wacker et al. (p. 615 , published online 21 March) describe crystal structures of two members of the serotonin family of...
Science
March 21, 2013
Daniel Wacker, Chong Wang, Vsevolod Katritch et al.
689 citations
Dissecting Serotonin Receptors Serotonin receptors are the targets for many widely used drugs prescribed to treat ailments from depression to obesity and migraine headaches (see the Perspective by Palczewski and Kiser ). C. Wang et al. (p. 610 , published online 21 March) and Wacker et al. (p. 615 , published online 21 March) describe crystal structures of two members of the serotonin family of...
Synapse
2000
Richard B Rothman, Michael H. Baumann, Christina M Dersch et al.
933 citations
A large body of evidence supports the hypothesis that mesolimbic dopamine (DA) mediates, in animal models, the reinforcing effects of central nervous system stimulants such as cocaine and amphetamine. The role DA plays in mediating amphetamine-type subjective effects of stimulants in humans remains to be established. Both amphetamine and cocaine increase norepinephrine (NE) via stimulation of...
Neuroreport
December 1, 1998
Franz X. Vollenweider, M. F. I. Vollenweider-Scherpenhuyzen, Andreas Bäbler et al.
1,023 citations
Psilocybin, an indoleamine hallucinogen, produces a psychosis-like syndrome in humans that resembles first episodes of schizophrenia. In healthy human volunteers, the psychotomimetic effects of psilocybin were blocked dose-dependently by the serotonin-2A antagonist ketanserin or the atypical antipsychotic risperidone, but were increased by the dopamine antagonist and typical antipsychotic...
The Lancet
October 1, 1998
Ud Mccann, Zsolt Szabó, Ursula Scheffel et al.
664 citations
Quantitative PET studies with a ligand selective for 5-HT transporters can be used to assess the status of 5-HT neurons in the living human brain. We show direct evidence of a decrease in a structural component of brain 5-HT neurons in human MDMA users.
Journal of Neuroscience
April 15, 1997
Vidita A Vaidya, Gerard J. Marek, George K. Aghajanian et al.
482 citations
The influence of 5-HT receptor agonists on the expression of BDNF in brain was determined. Administration of a hallucinogenic 5-HT2A /2C receptor agonist, but not a 5-HT1A receptor agonist, resulted in a significant but differential regulation of BDNF mRNA levels in hippocampus and neocortex. In the hippocampus, the 5-HT2A /2C receptor agonist significantly decreased BDNF mRNA expression in the...
Proceedings of the National Academy of Sciences
March 1, 1992
Gary Rudnick, S C Wall
533 citations
MDMA ("ecstasy") has been widely reported as a drug of abuse and as a neurotoxin. This report describes the mechanism of MDMA action at serotonin transporters from plasma membranes and secretory vesicles. MDMA stimulates serotonin efflux from both types of membrane vesicle. In plasma membrane vesicles isolated from human platelets, MDMA inhibits serotonin transport and [3H]imipramine binding by...
Journal of Neuroscience
August 1, 1988
Elizabeth O’hearn, Giuseppe Battaglia, Eb de Souza et al.
546 citations
The psychotropic amphetamine derivatives 3,4-methylenedioxyamphetamine (MDA) and 3,4-methylenedioxymethamphetamine (MDMA) have been used for recreational and therapeutic purposes in man. In rats, these drugs cause large reductions in brain levels of serotonin (5-HT). This study employs immunocytochemistry to characterize the neurotoxic effects of these compounds upon monoaminergic neurons in...
Journal of Pharmacology and Experimental Therapeutics
1987
C J Schmidt
530 citations
The neurochemical effects of the unique psychedelic agent, methylenedioxymethamphetamine (MDMA), indicate it may be a serotonergic neurotoxin related to agents such as p-chloroamphetamine. MDMA had a biphasic effect on cortical serotonin concentrations beginning with an acute depletion of the transmitter which reached a maximum between 3 and 6 hr after drug administration. This early phase of...