Psilocybin modulates social behaviour in male and female mice in a time-dependent manner.

Sheida Shadani; Kaspar McCoy; Lina Ong; Erika Greaves; Kyna Conn; Zane B. Andrews; Claire J. Foldi

doi:10.1038/s41386-026-02450-x

Psilocybin modulates social behaviour in male and female mice in a time-dependent manner.

Sheida Shadani, Kaspar McCoy, Lina Ong, Erika Greaves, Kyna Conn, Zane B. Andrews, Claire J. Foldi

Neuropsychopharmacology May 25, 2026 DOI: 10.1038/s41386-026-02450-x (opens in new tab)

Read Full Text

Relevant Not relevant

Study at a glance

AI-extracted from the abstract

Characteristics	Preclinical experimental study Peer reviewed
Population	C57BL/6 J mice
Intervention	Psilocybin
Dose	1.5 mg/kg
Duration	7 days post-administration
Topics	Psilocybin
Key findings	Psilocybin induces temporally dynamic, sex-differentiated patterns of social behavior and dopaminergic modulation in mice, with females showing acute and post-acute prosocial effects and males showing delayed sociability and altered dopamine responses.

Abstract

With the resurgence of psychedelic research and growing evidence of their therapeutic potential, there is an urgent need to understand how these compounds act across biological sexes. Despite widespread interest in their use for conditions marked by social impairments, including depression, anxiety, and anorexia nervosa, the influence of sex as a biological variable on the prosocial effects of psychedelics remains poorly understood. Indeed, enhanced connectedness, sociability and empathy are common outcomes of psychedelic use and these have shaped human social structures for millennia. Here, we investigated the sex-specific effects of a single dose of psilocybin (1.5 mg/kg) in C57BL/6 J mice across multiple aspects of social behaviour. Psilocybin acutely enhanced huddling and induced hypothermia selectively in female mice and post-acutely (4 h) enhanced novelty-seeking and grooming in females, with no comparable effects in males. By 24 h, psilocybin-treated males showed reduced grooming and rearing alongside increased sociability directed toward a cage-mate. This was accompanied by blunted novelty-evoked nucleus accumbens dopamine responses that persisted to 7 days post-administration. At 7 days, psilocybin shifted female social preference toward familiarity over novelty, associated with prolonged nucleus accumbens dopamine release during familiar conspecific interactions, while males exhibited increased grooming, opposing the effect observed at 24 h. Both 5-HT1AR and 5-HT2AR contributed to psilocybin's behavioural effects in sex-specific ways. These findings reveal temporally dynamic, sex-differentiated patterns of social behaviour and dopaminergic modulation following psilocybin, underscoring the importance of sex-informed approaches in preclinical research and clinical application of psychedelic compounds.

Comparable studies

Other preclinical and animal studies on psilocybin, most cited first.

Study	Year	Design
Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Mice	2021	Observational cohort
Harnessing psilocybin: antidepressant-like behavioral and synaptic actions of psilocybin are independent of 5-HT2R activation in mice Mice	2021	Experimental study
Psychedelics reopen the social reward learning critical period Mice	2023	Experimental study in mice
Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species. C57BL/6J mice	2020	Experimental study with dose-response experiments
Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning Mice	2013	Experimental study

Citations in the library

Cited by 1

Psilocybin produces amplified acute responses and sex-specific long-term increases in sensorimotor gating in the mGlu5 knockout mouse model of schizophrenia Neuropsychopharmacology July 18, 2026

Cites 48

and 43 more in the library