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Striking long-term beneficial effects of single dose psilocybin and psychedelic mushroom extract in the SAPAP3 rodent model of OCD-like excessive self-grooming

Summary

Researchers tested whether psilocybin (the active compound in magic mushrooms) could treat obsessive-compulsive disorder using genetically modified mice that exhibit excessive grooming similar to OCD in humans. A single dose of psilocybin or psychedelic mushroom extract significantly reduced the excessive grooming behavior and anxiety in these mice, with benefits lasting up to six weeks. These findings suggest psilocybin may be a promising new treatment for OCD in humans, offering longer-lasting effects from a single dose compared to current medications.

Background

Obsessive compulsive disorder (OCD) is a highly prevalent disorder affecting 2-3% of the US population, with 40-60% of patients experiencing only partial recovery with current treatments. SAPAP3 knockout mice manifest excessive self-grooming, tics, and anxiety that closely resemble OCD pathology in humans. Recent preliminary reports suggest psilocybin may reduce OCD symptoms.

Objective

To evaluate the effects of a single dose of psilocybin or psychedelic mushroom extract on excessive self-grooming, tics, and anxiety in SAPAP3 knockout mice in a randomized controlled trial with extended follow-up.

Results

Vehicle-treated mice showed a 118.71% increase in total self-grooming over 21 days, while psilocybin-treated mice showed a 14.60% decrease and mushroom extract-treated mice showed a 19.20% decrease. Beneficial effects on grooming and head-body twitches persisted up to 6 weeks in responders, with mushroom extract showing superior effects on anxiety. Vehicle-treated non-responders showed lasting therapeutic response when subsequently treated with psilocybin or extract.

Conclusion

A single administration of psilocybin or psychedelic mushroom extract significantly attenuates excessive self-grooming and anxiety in SAPAP3 knockout mice with long-lasting effects extending up to 6 weeks. These findings provide strong translational support for clinical trials of psilocybin in OCD treatment.
  • Published in:Molecular Psychiatry,
  • Study Type:Randomized Controlled Trial,
  • Source: PMID: 39394457, DOI: 10.1038/s41380-024-02786-0
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