Mol Psychiatry
July 7, 2026
Axel F. Rosado, Abigail L. Yu, Jen-Hau Yang et al.
Classic serotonergic psychedelics such as psilocybin act as agonists at cortical serotonin (5-HT) 2A receptors (5-HT 2A R), inducing psychedelic effects in humans and head-twitch responses (HTRs) in rodents. Another class of psychedelic drugs called entactogens, exemplified by MDMA, function primarily as monoamine releasers and typically evoke minimal HTR despite causing serotonin release. The...
bioRxiv (Cold Spring Harbor Laboratory)
March 10, 2026
Gabriele Floris, Sarah J. Jefferson, Jocelyne Rondeau et al.
Abstract New treatments for depression are needed that combine robust efficacy with improved scalability. Although psilocybin has demonstrated antidepressant effects in Phase 3 clinical trials, some of its psychedelic effects limit tolerability, necessitating administration in highly supervised clinical settings, and thus motivating development of serotonergic therapeutics that preserve...
bioRxiv (Cold Spring Harbor Laboratory)
March 8, 2026
Nitzan Geva, Sarah J. Jefferson, Emi Krishnamurthy et al.
Abstract Fear extinction requires dynamic updating of cortical representations, yet the neural mechanisms underlying successful extinction remain poorly understood. Some psychoactive substances induce structural plasticity in medial prefrontal cortex (mPFC), possibly underlying their therapeutic potential. Here we investigated whether MDMA, which enhances fear extinction, induces prefrontal...
Nature Communications
February 12, 2025
Farid Aboharb, Pasha A. Davoudian, Ling-Xiao Shao et al.
19 citations
Psilocybin, ketamine, and MDMA are psychoactive compounds that exert behavioral effects with distinguishable but also overlapping features. The growing interest in using these compounds as therapeutics necessitates preclinical assays that can accurately screen psychedelics and related analogs. We posit that a promising approach may be to measure drug action on markers of neural plasticity in...
bioRxiv
May 26, 2024
Farid Aboharb, Pasha A. Davoudian, Ling-Xiao Shao et al.
preprint
Psilocybin, ketamine, and MDMA are psychoactive compounds that exert behavioral effects with distinguishable but also overlapping features. The growing interest in using these compounds as therapeutics necessitates preclinical assays that can accurately screen psychedelics and related analogs. We posit that a promising approach may be to measure drug action on markers of neural plasticity in...
Proceedings of the National Academy of Sciences of the United States of America
November 27, 2023
John H. Krystal, Alfred P. Kaye, Sarah J. Jefferson et al.
66 citations
Ketamine has emerged as a transformative and mechanistically novel pharmacotherapy for depression. Its rapid onset of action, efficacy for treatment-resistant symptoms, and protection against relapse distinguish it from prior antidepressants. Its discovery emerged from a reconceptualization of the neurobiology of depression and, in turn, insights from the elaboration of its mechanisms of action...
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
August 1, 2023
Sarah J. Jefferson, Ian Gregg, Mark Dibbs et al.
57 citations
Serotonergic psychedelics are gaining increasing interest as potential therapeutics for a range of mental illnesses. Compounds with short-lived subjective effects may be clinically useful because dosing time would be reduced, which may improve patient access. One short-acting psychedelic is 5-MeO-DMT, which has been associated with improvement in depression and anxiety symptoms in early phase...
Frontiers in Psychiatry
June 26, 2023
Simon Zhornitsky, Henrique Nunes Pereira Oliva, Laura A. Jayne et al.
12 citations
Background Ketamine and psychedelics have abuse liability. They can also induce “transformative experiences” where individuals experience enhanced states of awareness. This enhanced awareness can lead to changes in preexisting behavioral patterns which could be beneficial in the treatment of substance use disorders (SUDs). Preclinical and clinical studies suggest that ketamine and psychedelics...
Curr Biol
2022
Benjamin Kelmendi, Alfred P. Kaye, Christopher Pittenger et al.
115 citations
Psychedelics are compounds that alter consciousness by acting on serotonin receptors in the brain. The term 'psychedelic', from the Greek for mind manifesting, refers to the drugs' subjective effects and was first proposed by Humphry Osmond in 1956. Other terms have been used to emphasize different aspects of the psychological experiences produced by various related compounds, including...