Neuropsychopharmacology
July 10, 2026
Christopher W. Thomas, Kayleigh S. Lamalfa, Tobias P. Whelan et al.
Anhedonia, the blunted responsiveness to previously rewarding stimuli, is a core symptom of several psychiatric disorders. Ketamine and psilocybin have shown promising evidence in ameliorating anhedonic symptoms in clinical trials. The Probabilistic Reward Task (PRT) was developed to objectively quantify reward responsiveness in clinical populations and laboratory animals. Here, the PRT was...
Communications Biology
April 24, 2026
Tatum Askey, Daniel Allen-Ross, Daniil Luzyanin et al.
Chronic pain states remain challenging to control with current drug therapies. Here, we demonstrate that a single dose of psilocybin produces a sustained anti-nociceptive effect in chronic neuropathic pain models in male and female mice, mediated primarily by 5-HT2A receptors. Critically, psilocybin significantly potentiates the analgesic efficacy of gabapentin, a standard-of-care treatment,...
bioRxiv (Cold Spring Harbor Laboratory)
March 4, 2026
Matthew D. B. Claydon, Justyna K. Hinchcliffe, Julia M. Bartlett et al.
Abstract Psilocybin, a serotonergic psychedelic, can produce rapid and enduring antidepressant effects in patients with major depressive disorder (MDD)[1, 2], yet the neural mechanisms underlying these effects remain unclear. Negative affective biases are an important neuropsychological mechanism central to the development and perpetuation of MDD[3]. Using a translational rodent model, we...
bioRxiv (Cold Spring Harbor Laboratory)
January 15, 2026
Justyna K. Hinchcliffe, Christopher W. Thomas, Gary Gilmour et al.
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...
British Journal of Pharmacology
June 22, 2025
Aurelija Ippolito, Sridhar Vasudevan, Shaun Hurley et al.
9 citations
Serotonergic psychedelic drugs are under investigation as therapies for various psychiatric disorders, including major depression. Although serotonergic psychedelic drugs are 5-HT2A receptor agonists, some such agonists are not psychedelic, potentially due to differences in 5-HT2A receptor ligand bias or signalling efficacy. Here, we investigated 5-HT2A receptor signalling properties of...
Research Square
September 19, 2024
Maria Maiarù, Tatum Askey, Daniel Allen-Ross et al.
2 citations
Abstract Chronic pain states are challenging to control with current drug therapies. Here, we demonstrate that a single dose of psilocybin can produce a sustained anti-nociceptive effect in a mouse model of chronic neuropathic pain. Beyond this, the single dose of psilocybin caused a dramatic increase in the anti-nociceptive potential of gabapentin, a widely used treatment for neuropathic pain,...
bioRxiv (Cold Spring Harbor Laboratory)
June 16, 2024
Aurelija Ippolito, Sridhar Vasudevan, Shaun Hurley et al.
1 citation
preprint
ABSTRACT Background and Purpose Serotonergic psychedelic drugs are under renewed investigation for the potential treatment of several psychiatric disorders. While all serotonergic psychedelics have 5-HT 2A receptor activity, the explanation for why some 5-HT 2A receptor agonists are not psychedelic is unknown. To address this question, we investigated the 5-HT 2A receptor signalling bias and...
Science Translational Medicine
January 10, 2024
Katie Kamenish, Roberto Arban, Aslihan Selimbeyoglu et al.
26 citations
How rapid-acting antidepressants (RAADs), such as ketamine, induce immediate and sustained improvements in mood in patients with major depressive disorder (MDD) is poorly understood. A core feature of MDD is the prevalence of cognitive processing biases associated with negative affective states, and the alleviation of negative affective biases may be an index of response to drug treatment....