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Effect of psilocybin on marble burying in ICR mice: role of 5-HT1A receptors and implications for the treatment of obsessive-compulsive disorder

Summary

Researchers tested whether psilocybin mushrooms could help treat obsessive-compulsive disorder (OCD) using mice. They found that psilocybin reduced compulsive burying behavior in mice, similar to how approved OCD medications work. The study revealed that this anti-compulsive effect works through different brain mechanisms than previously thought, and that combining psilocybin with another drug called buspirone might block psychedelic effects while keeping therapeutic benefits.

Background

Obsessive-compulsive disorder (OCD) affects 100-150 million people worldwide, with at least one-third of patients not responding to first-line treatments. Preliminary clinical findings and preclinical studies using the marble burying test suggest psilocybin may be effective for treating OCD. However, the specific receptor mechanisms involved in psilocybin’s anti-obsessional effects remain unclear.

Objective

This study aimed to explore the role of 5-HT2A and 5-HT1A receptors in psilocybin’s effect on marble burying behavior in mice, examine the effects of staggered versus bolus psilocybin administration, and investigate whether the 5-HT1A partial agonist buspirone affects both marble burying and the head twitch response (HTR) induced by psilocybin.

Results

Psilocybin significantly reduced marble burying by 32.84% compared to vehicle control. The 5-HT2A antagonist M100907 did not attenuate psilocybin’s effect on marble burying. The 5-HT1A agonist 8-OH-DPAT showed additive effects with psilocybin, while the 5-HT1A antagonist WAY100635 did not block psilocybin’s marble-burying effect. Buspirone co-administration blocked psilocybin-induced HTR without impeding its anti-obsessional effects.

Conclusion

Neither 5-HT2A nor 5-HT1A receptors appear to be pivotally involved in psilocybin’s anti-obsessional effects on marble burying in mice. Co-administration of buspirone with psilocybin may block psychedelic effects while preserving anti-obsessional properties, suggesting a potential therapeutic strategy for OCD treatment.
  • Published in:Translational Psychiatry,
  • Study Type:Preclinical Research Study,
  • Source: PMID: 37164956, DOI: 10.1038/s41398-023-02456-9
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