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Meta-correlation of the effect of ketamine and psilocybin induced subjective effects on therapeutic outcome

Summary

This study examined whether the psychological experiences people have while taking ketamine or psilocybin—such as feeling disconnected or having spiritual insights—are actually responsible for their mental health improvements. Researchers analyzed 23 studies and found that these subjective experiences explain about 10% of ketamine’s benefits and 24% of psilocybin’s benefits. Psilocybin’s effects appear more connected to therapeutic outcomes than ketamine’s, and both drugs showed stronger connections between subjective effects and treatment success in substance use disorder compared to depression.

Background

Psychedelics like ketamine and psilocybin have demonstrated efficacy in treating psychiatric conditions including depression and substance use disorder. There is evidence suggesting that subjective effects of these compounds may be crucial for their therapeutic outcomes, though this relationship remains unclear and debated.

Objective

To conduct a meta-analysis and systematic review evaluating the correlation between ketamine and psilocybin-induced subjective effects and therapeutic improvements in patients with depression or substance use disorder, and to determine whether the magnitude of correlation differs between the two treatments.

Results

Pooled correlation coefficients were -0.310 for ketamine (R²=5-10%) and -0.495 for psilocybin (R²=24%), indicating a modest mediating effect of subjective effects on therapeutic outcomes. Psilocybin showed significantly greater correlation than ketamine, particularly for depression treatment. Substance use disorder showed higher correlation coefficients (R²=54-60%) compared to depression (R²=4-18%).

Conclusion

Subjective effects mediate a modest proportion of therapeutic outcomes for both ketamine and psilocybin, with psilocybin showing greater mediation than ketamine. The relationship is more pronounced in substance use disorder than depression. Further research with improved measurement tools and study designs is needed to establish causal mechanisms.
  • Published in:npj Mental Health Research,
  • Study Type:Meta-analysis and Systematic Review,
  • Source: PMID: 39369173, DOI: 10.1038/s44184-024-00091-w
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