Psychedelic therapy without durable effects: A review and re-evaluation of controlled studies between 1965 and 1977.

Abstract

Common wisdom in the psychedelic literature suggests that early controlled trials of psychedelic therapy were methodologically flawed. In this review we challenge this view and discuss 11 controlled studies that were conducted in the United States and Canada between 1965 and 1977 to evaluate psychedelic (peak) therapy for individuals suffering from alcohol and opioid use disorder and psychoneuroses. We provide a narrative review of the designs, methods, settings, treatment issues and results and show that these studies already adhered quite well to the regulatory and evidentiary standards of their time. These early psychedelic trials tried to effectively address common methodological problems that still threaten the validity of contemporary psychedelic clinical trials (e.g., regarding blinding and active control conditions). Our review indicates that despite a significant heterogeneity in the methods and research designs, most early controlled studies converge on the same conclusion: there are no durable improvements in the condition of patients treated with psychedelic therapy beyond a few weeks. We discuss implications for contemporary psychedelic science in terms of (a) patient selection (i.e., better prospects for non-chronic conditions), (b) the problems with a single-sided focus on mystical experiences as the primary mechanism of action, (c) the positive afterglow as a therapeutic window of opportunity and (d) the need for a strong psychotherapeutic framework to induce sustained therapeutic effects.

In the evidence

This study is part of the evidence base for 2 syntheses in the library. Here is how each one recorded it.

• State of the evidence: Addiction ↓Opposes

  Argues that early controlled psychedelic trials (1965-1977) were methodologically sound for their era and that most found no durable patient improvements beyond a few weeks.

  Synthesized September 20, 2026

• State of the evidence: Psychedelic-assisted therapy ↓Opposes

  Argues that early controlled psychedelic trials (1965-1977) were methodologically sound for their era and most found no durable patient improvements beyond a few weeks.

  Synthesized September 20, 2026

Comparable studies

Other narrative reviews on psychedelic-assisted therapy, most cited first.