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PsilOCD: A Pharmacological Challenge Study Evaluating the Effects of the 5-HT2A Agonist Psilocybin on the Neurocognitive and Clinical Correlates of Compulsivity

Summary

This study is investigating whether psilocybin (an active compound in magic mushrooms) can help people with obsessive-compulsive disorder (OCD) by improving their mental flexibility and brain plasticity. Participants will receive two doses of psilocybin—a low test dose and a slightly higher therapeutic dose—four weeks apart, while receiving professional psychological support. Researchers will measure changes in cognitive abilities and brain activity to understand how psilocybin might help reduce OCD symptoms like intrusive thoughts and repetitive behaviors.

Background

Obsessive-compulsive disorder (OCD) is a complex psychiatric condition characterized by persistent intrusive thoughts and repetitive behaviors, with current treatments having limited efficacy. Cognitive inflexibility and altered neuroplasticity are hallmark features implicated in OCD pathophysiology. Psilocybin, a 5-HT2A receptor agonist, has shown promise in modulating cognition and neuroplasticity in other psychiatric conditions.

Objective

This study protocol describes PsilOCD, an investigation of psilocybin’s effects on cognitive flexibility and neuroplasticity in individuals with OCD. The primary aims are to assess whether low-moderate psilocybin (10 mg) improves cognitive flexibility on the ID-ED task and enhances neuroplasticity measured by visual long-term potentiation EEG paradigm.

Results

This is a study protocol paper describing planned methodology; results are not yet available as the study is prospective in design.

Conclusion

The PsilOCD protocol represents a mechanistic investigation into psilocybin-assisted therapy for OCD targeting cognitive and neurobiological mechanisms. The study aims to provide critical data on whether low-dose psilocybin can improve cognitive flexibility and neuroplasticity in OCD patients, potentially guiding future randomized controlled trials.
  • Published in:Cureus,
  • Study Type:Clinical Trial Protocol,
  • Source: PMID: 39882198
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