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

Introduction

Psychiatric disorders remain prevalent worldwide and current first-line antidepressant treatments have limited and delayed efficacy, prompting interest in alternative pharmacological approaches. Psychedelic and psychoplastogenic drugs such as ketamine and psilocybin have emerged as promising candidates because they promote rapid neural plasticity and can produce marked changes in consciousness, perception, mood and cognition. Despite shared neurobiological actions, these compounds generate qualitatively different subjective experiences: ketamine typically produces short-lived dissociation, whereas psilocybin commonly evokes mystical-type and oceanic-boundlessness experiences. Dahan and colleagues set out to examine whether those subjective effects are quantitatively related to therapeutic benefit. Noting prior inconsistent findings and methodological concerns (timing of measures, measurement instruments, and dose–response issues), the study performs a systematic review and meta-correlation analysis focused on ketamine (including racemic ketamine and esketamine) and psilocybin for treatment of depression and substance use disorder (SUD). The principal research question was the magnitude of the correlation between drug‑induced subjective effects and clinical improvement, and whether this relationship differs between ketamine and psilocybin or between depression and SUD.