Psilocybin enhances sociability only in altered behavioural state and does not need an awake experience to be effective
Chenchen Song, Tinya Chang, Tobias Buchborn, Thomas Knöpfel
Nature Communications August 27, 2026 DOI: 10.1038/s41467-026-77238-0 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study Peer reviewed |
|---|---|
| Population | Cntnap2-knockout mouse model of autism spectrum disorder and isogenic control mice |
| Intervention | Psilocybin |
| Topics | Psilocybin |
| Key findings | A single systemic administration of psilocybin durably promoted social behavior in Cntnap2-knockout mice, but not in isogenic controls. The effect was also present in anesthetized mice, showing that wakefulness is not required for these sociability-enhancing actions. |
Abstract
Psilocybin, a psychoactive compound contained in certain mushrooms, can provoke profound psychedelic experiences and also exerts established and controversial therapeutic efficacy in clinical depression and other neuropsychiatric conditions respectively. Here we report that a single systemic administration of the serotonergic psychedelic psilocybin can durably promote social behaviour in the Cntnap2-knockout mouse model of autism spectrum disorder (ASD), while no increase in sociability is observed in isogenic control mice. Addressing the concern that the therapeutic actions of psilocybin may involve potentially adverse psychedelic effects, we tested drug application in anesthetised mice and found that awake brain states are not required for psilocybin’s sociability enhancing actions in ASD mice. Psilocybin shows therapeutic effects in the treatment of neuropsychiatric conditions but it can also cause strong hallucinations. Here, the authors show that psilocybin can improve social symptoms in a mouse model of autism, an effect that does not depend on wakefulness during the acute drug effects, suggesting that it might be possible to develop treatments that keep the benefits while avoiding the mind-altering side effects.
Comparable studies
Other preclinical and animal studies on psilocybin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| 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 |