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Naturalistic psychedelic therapy: The role of relaxation and subjective drug effects in antidepressant response

Summary

Researchers studied how LSD and psilocybin work in real-world therapy settings in Switzerland. They found that these compounds effectively reduced depression symptoms in patients who hadn’t responded to other treatments. Surprisingly, the feeling of relaxation during the session was more important for improvement than having intense mystical experiences. The therapy was generally safe, with side effects that resolved quickly.

Background

Psychedelic-assisted therapy (PAT) with psilocybin and LSD has shown efficacy for treating depression and other neuropsychiatric conditions. There is debate about which acute psychedelic effects are important for therapeutic outcomes, particularly whether mystical experiences are essential. Real-world data from naturalistic PAT settings can provide insights into clinical practice outside controlled trials.

Objective

This study compared subjective effects of LSD and psilocybin between PAT patients and healthy volunteers, and investigated relationships between acute drug effects and antidepressant outcomes in patients undergoing naturalistic PAT in Switzerland.

Results

Patients showed lower ego dissolution but similar overall drug effects and mystical experiences compared to controls. Relaxation during PAT was the strongest predictor of antidepressant response, while mystical-type experiences did not predict depression improvement. Real-time effect ratings explained 29% of variance in MADRS improvement compared to 4% for MEQ scores. PAT produced a significant 29% reduction in MADRS scores immediately after treatment.

Conclusion

PAT with psilocybin and LSD effectively reduced depressive symptoms in treatment-resistant patients. Relaxation during sessions emerged as a key predictor of antidepressant response, suggesting that hourly real-time assessments may be more clinically useful than retrospective mystical experience measures. Further investigation of relaxation’s role in PAT is warranted.
  • Published in:Journal of Psychopharmacology,
  • Study Type:Clinical Trial,
  • Source: PMID: 39302087, DOI: 10.1177/02698811241278873
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