Psilocybin reduces grooming in the SAPAP3 knockout mouse model of compulsive behaviour.
James J Gattuso, Carey Wilson, Anthony J. Hannan, Thibault Renoir
Neuropharmacology 2025 DOI: 10.1016/j.neuropharm.2024.110202 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical animal study Peer reviewed |
|---|---|
| Population | Male and female SAPAP3 knockout and wild-type mice |
| Intervention | Psilocybin |
| Dose | 1 mg/kg, intraperitoneal |
| Duration | Assessments at 1, 3, and 8 days post-injection |
| Topics | Anxiety Psilocybin |
| Keywords | Psilocybin magic mushrooms Hallucinogens Psychedelics OCD Obsessive-Compulsive Disorder Compulsion Preclinical trials Sapap3 Compulsive behavior |
| Citations | 10 |
| Key points | Acute psilocybin administration led to enduring reductions in compulsive behavior in male SAPAP3 knockout mice and reduced grooming in female wild-type and knockout mice. |
Abstract
Psilocybin is a serotonergic psychedelic compound which shows promise for treating compulsive behaviours. This is particularly pertinent as compulsive disorders require research into new pharmacological treatment options as the current frontline treatments such as selective serotonin reuptake inhibitors, require chronic administration, have significant side effects, and leave almost half of the clinical population refractory to treatment. In this study, we investigated psilocybin administration in male and female SAPAP3 knockout (KO) mice, a well-validated mouse model of obsessive compulsive and related disorders. We assessed the effects of acute psilocybin (1 mg/kg, intraperitoneal) administration on head twitch and locomotor behaviour as well as anxiety- and compulsive-like behaviours at multiple time-points (1, 3 and 8 days post-injection). While psilocybin did not have any effect on anxiety-like behaviours, we revealed that acute psilocybin administration led to enduring reductions in compulsive behaviour in male SAPAP3 KO mice and reduced grooming behaviour in female wild-type (WT) and SAPAP3 KO mice. We also found that psilocybin increased locomotion in WT littermates but not in SAPAP3 KO mice, suggesting in vivo serotonergic dysfunctions in KO animals. On the other hand, the typical head-twitch response following acute psilocybin (confirming its hallucinogenic-like effect at this dose) was observed in both genotypes. Our novel findings suggest that acute psilocybin may have potential to reduce compulsive-like behaviours (up to 1 week after a single injection). Our study can inform future research directions as well as supporting the utility of psilocybin as a novel treatment option for compulsive disorders.
Comparable studies
Other preclinical and animal studies on psilocybin for anxiety, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psychedelics, but Not Ketamine, Produce Persistent Antidepressant-like Effects in a Rodent Experimental System for the Study of Depression Rats | 2020 | Preclinical study | |
| Psilocin and ketamine microdosing: effects of subchronic intermittent microdoses in the elevated plus-maze in male Wistar rats Wistar rats | 2018 | Experimental study | n = 40 |
| Striking long-term beneficial effects of single dose psilocybin and psychedelic mushroom extract in the SAPAP3 rodent model of OCD-like excessive self-grooming SAPAP3 knockout mice | 2024 | Randomized controlled trial | n = 50 |
| Psilocybe cubensis extract potently prevents fear memory recall and freezing behavior in short- but not long-term in a rat model of posttraumatic stress disorder. Male rats | 2024 | Preclinical study | |
| Psilocybin induces acute anxiety and changes in amygdalar phosphopeptides independently from the 5-HT2A receptor Mice | 2024 | Experimental study |
Citations in the library
Cited by 10
- Mice lacking the serotonin transporter do not respond to the behavioural effects of psilocybin. European Journal of Pharmacology March 15, 2025
- Chronic psilocybin administration increases sociability and alters the gut microbiome in male wild-type mice but not in a preclinical model of obsessive-compulsive disorder Neuropharmacology August 21, 2025
- Letter to the editor: Comments on ‘Striking long-term beneficial effects of single-dose psilocybin and psychedelic mushroom extract in the SAPAP3 rodent model of OCD-like excessive self-grooming’ by Brownstien et al. (2024) Molecular Psychiatry April 6, 2025
- Psilocybin's effects on obsessive-compulsive behaviors: A systematic review of preclinical and clinical evidence Psychedelics October 28, 2025
- Psilocybin restores social novelty investigation in male SAPAP3 knockout mice and engages prefrontal–hippocampal circuitry Molecular Psychiatry September 17, 2026
and 5 more in the library
Cites 38
- Safety, Tolerability, and Efficacy of Psilocybin in 9 Patients With Obsessive-Compulsive Disorder The Journal of Clinical Psychiatry November 15, 2006
- Long-term follow-up of psilocybin-facilitated smoking cessation The American Journal of Drug and Alcohol Abuse July 21, 2016
- Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Neuron July 5, 2021
- The Subjective Effects of Psychedelics Are Necessary for Their Enduring Therapeutic Effects. ACS Pharmacology & Translational Science December 10, 2020
- Psychedelics promote plasticity by directly binding to BDNF receptor TrkB Nature Neuroscience June 1, 2023
and 33 more in the library