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New Analysis Finds Psychedelic Therapy Matches Antidepressants for Major Depression

Researchers say unblinding in psychedelic trials inflates apparent benefits.

Overview

  • A JAMA Psychiatry study led by UCSF, UCLA, and Imperial College compared psychedelic-assisted therapy trials with open-label antidepressant trials and found no meaningful difference in depression outcomes.
  • Across 24 studies reviewed, traditional antidepressants outperformed psychedelic-assisted therapy by 0.3 points on a 52-point scale, a gap that was neither statistically nor clinically significant.
  • Both treatment types produced substantial improvements, reducing standard depression scores by about 12 points when the influence of patients knowing they received an active drug was balanced.
  • Only one direct head-to-head trial to date, pitting psilocybin against escitalopram, reported no significant difference in easing depression.
  • A companion JAMA Psychiatry trial using low-dose psilocybin as a control saw 86% of participants correctly guess their group, and a separate Lancet review found no evidence that cannabinoids treat depression, anxiety, or PTSD, prompting calls for larger, longer, and better-controlled comparative studies with strong psychotherapeutic support and safety oversight.