A Meta-Analysis of Placebo-Controlled Trials of Psychedelic-Assisted Therapy

Abstract

After a two-decade hiatus in which research on psychedelics was essentially halted, placebo-controlled clinical trials of psychedelic-assisted therapy for mental health conditions have begun to be published. We identified nine randomized, placebo-controlled clinical trials of psychedelic-assisted therapy published since 1994. Studies examined psilocybin, LSD (lysergic acid diethylamide), ayahuasca (which contains a combination of N,N-dimethyltryptamine and harmala monoamine oxidase inhibitor alkaloids), and MDMA (3,4methylenedioxymethamphetamine). We compared the standardized mean difference between the experimental and placebo control group at the primary endpoint. Results indicated a significant mean between-groups effect size of 1.21 (Hedges g), which is larger than the typical effect size found in trials of psychopharmacological or psychotherapy interventions. For the three studies that maintained a placebo control through a follow-up assessment, effects were generally maintained at follow-up. Overall, analyses support the efficacy of psychedelic-assisted therapy across four mental health conditions-post-traumatic stress disorder, anxiety/depression associated with a life-threatening illness, unipolar depression, and social anxiety among autistic adults. While study quality was high, we identify several areas for improvement regarding the conduct and reporting of trials. Larger trials with more diverse samples are needed to examine possible moderators and mediators of effects, and to establish whether effects are maintained over time.

Ethical and legal issues in psychedelic harm reduction and integration therapy

“…While psychedelic use has thrived for thousands of years in Indigenous cultures and for many decades in underground subcultures, psychedelics are increasingly being encountered in the mainstream in countries around the world, as evidenced by a surge of media attention on the therapeutic use of psychedelics, including popular books written on the topic [ 1 ]. The potential application of psychedelics in combination with therapy for the treatment of mental health difficulties has been studied in at least 10 published placebo-controlled, randomized trials to date, with early results appearing promising [ 2 ]. As a result of these and other events, many individuals suffering from mental health issues are now seeking to utilize psychedelics for healing, especially in cases where currently available psychotherapeutic or psychopharmacological treatments have failed.…”

“…However, advocates such as the Multidisciplinary Association for Psychedelic Studies (MAPS) persisted in efforts to obtain legal permission to conduct psychedelic research and there has been a recent resurgence of well-controlled clinical trials providing strong preliminary evidence for the use of some psychedelics for therapeutic purposes. A recent meta-analysis of nine rigorous placebo-controlled trials of psychedelic-assisted therapy was conducted and found a “very large” between-groups effect size of 1.21 (Hedges g ) which is notably larger than average effect sizes for standard treatments using psychotherapy or psychopharmacological medications [ 2 ]. While previous decades of psychedelic research have focused on a wide array of psychological problems using many different psychedelic substances, modern research has demonstrated the strongest evidence for psychedelic-assisted therapy in the treatment of post-traumatic stress disorder (PTSD) [ 18 ], depression [ 19 ], end-of-life distress [ 20 ], addiction [ 21 – 23 ], and social anxiety in adults with autism [ 24 ].…”

Ketamine-Assisted Psychotherapy for PTSD Related to Racial Discrimination

“…Over the last decade there has been a growing interest in psychedelic-assisted psychotherapy for the treatment of a variety of mental health conditions such as anxiety, depression, substance abuse, OCD, and posttraumatic stress disorder (PTSD; Luoma et al, 2020). Psychedelic-assisted psychotherapy refers to pairing psychedelic substances with psychotherapeutic interventions to maximize therapeutic outcomes.…”

The Psychological Processes of Classic Psychedelics in the Treatment of Depression: A Systematic Review Protocol

“…Psychedelic therapy offers several advantages over conventional anti-depressant treatment. Most notably, psychedelic therapy appears to produce greater reductions in depression symptoms when compared to typical pharmacological and psychological treatments (24). These symptom changes typically result from a short treatment program and usually occur immediately following treatment, unlike the weeks or months typically seen in current treatments (25).…”