Psilocybin reduces grooming in the SAPAP3 knockout mouse model of compulsive behaviour.

A single injection of psilocybin reduced compulsive grooming in male SAPAP3 knockout mice—a model of obsessive-compulsive disorder—for up to one week, without affecting anxiety-like behaviors. The drug also decreased grooming in female knockout and wild-type mice and increased locomotion in wild-type but not knockout animals, indicating serotonergic dysfunction in the knockout mice. The typical head-twitch response confirmed psilocybin's hallucinogenic-like effect at the dose used. These findings suggest acute psilocybin may offer a novel treatment option for compulsive disorders, addressing the need for alternatives to current therapies that leave many patients unresponsive.

Study at a glance

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.