medRxiv
August 12, 2026
Scott M. Thompson, Devin P. Effinger, Andrew M Novick et al.
preprint
Abstract Oregon (OR) and Colorado (CO) were the first states to enact regulations for provision of psilocybin with support of licensed ‘facilitators.’ As more states and countries adopt similar policies, informed public policy decisions require that client characteristics and rationale for using psilocybin, psilocybin dosing practices, mental health outcomes, and adverse events are understood....
Translational Psychiatry
June 13, 2026
Jillian L. King, Devin P. Effinger, Cameron Basquez-Pfeifer et al.
The head-twitch response (HTR) is widely used as a preclinical assay for the hallucinogenic potential of compounds, with its utility based on 5HT 2A R activation. Here, we examine how the polypharmacological agonists lisuride and lysergic acid diethylamide (LSD) influence behavioral and physiological outcomes in mice to test whether the HTR reliably reflects overall psychoactivity. Lisuride...
ACS Pharmacology & Translational Science
August 22, 2025
Devin P. Effinger, Serena S. Schalk, Jillian L. King et al.
3 citations
High Resolution Image Download MS PowerPoint Slide Microdosing, the prolonged ingestion of psychedelics at subhallucinogenic doses, has gained popularity for its perceived cognitive and emotional benefits. Psychedelics have high affinity for 5-HT 2B receptors, a receptor known to cause human heart disease with strong chronic activation. We investigated the effects of microdosed psychedelics on...
Cell Reports
May 21, 2025
Lace M Riggs, Sage Aronson, Ta-Chung M Mou et al.
2 citations
An acute increase in excitatory synaptic transmission contributes to the rapid antidepressant actions of neuroplastogens, including ketamine and its bioactive metabolite, (2R,6R)-hydroxynorketamine (HNK). It is hypothesized that drug-induced metaplastic changes in synaptic strength account for therapeutically relevant behavioral adaptations in vivo. Using the plasticity-deficient Wistar Kyoto...
Molecular Psychiatry
December 1, 2024
Chloe E Page, C Neill Epperson, Andrew M Novick et al.
54 citations
The serotonin deficit hypothesis explanation for major depressive disorder (MDD) has persisted among clinicians and the general public alike despite insufficient supporting evidence. To combat rising mental health crises and eroding public trust in science and medicine, researchers and clinicians must be able to communicate to patients and the public an updated framework of MDD: one that is (1)...
Neuropharmacology
March 13, 2023
Andreas B. Wulff, Charles D. Nichols, Scott M. Thompson
30 citations
Psychedelic compounds have shown extraordinary potential in treating a wide range of neuropsychiatric disorders. Psilocybin, for example, has now been shown in several clinical trials to induce a rapid (within days) and persistent (3-12 months) improvement in human treatment-resistant depression and other neuropsychiatric conditions. Here we review the preclinical models and experimental...
Journal of Neuroscience
January 3, 2023
Panos Zanos, Kyle A Brown, Polymnia Georgiou et al.
109 citations
Ketamine is a well-characterized NMDA receptor (NMDAR) antagonist, although the relevance of this pharmacology to its rapid (within hours of administration) antidepressant actions, which depend on mechanisms convergent with strengthening of excitatory synapses, is unclear. Activation of synaptic NMDARs is necessary for the induction of canonical long-term potentiation (LTP) leading to a...
Proceedings of the National Academy of Sciences
April 13, 2021
Natalie Hesselgrave, Timothy A. Troppoli, Andreas B. Wulff et al.
380 citations
Significance Psychedelic compounds, such as psilocybin, have beneficial actions in several psychiatric diseases. They also produce strong alterations of consciousness, which may be a barrier to their widespread use. We found that psilocybin has fast-acting antidepressant-like properties in mice. Using multiple assays of hedonic behavior and an antagonist of prohallucinatory 5-HT2A receptors, we...
British Journal of Pharmacology
July 1, 2019
Panos Zanos, Jaclyn N. Highland, Xin Liu et al.
(R)-Ketamine (arketamine) may have utility as a rapidly acting antidepressant. While (R)-ketamine has lower potency than (R,S)-ketamine to inhibit NMDA receptors in vitro, the extent to which (R)-ketamine shares the NMDA receptor-mediated adverse effects of (R,S)-ketamine in vivo has not been fully characterised. Furthermore, (R)-ketamine is metabolised to (2R,6R)-hydroxynorketamine (HNK),...
The Annual Review of Pharmacology and Toxicology
October 9, 2018
Todd D Gould, Carlos A. Zarate, Scott M. Thompson
132 citations
For decades, symptoms of depression have been treated primarily with medications that directly target the monoaminergic brain systems, which typically take weeks to exert measurable effects and months to exert remission of symptoms. Low, subanesthetic doses of ( R,S)-ketamine (ketamine) result in the rapid improvement of core depressive symptoms, including mood, anhedonia, and suicidal...