Efficacy and Safety of Four Psychedelic-Assisted Therapies for Adults with Symptoms of Depression, Anxiety, and Posttraumatic Stress Disorder: A Systematic Review and Meta-Analysis

ABSTRACT

There has been a resurgence in psychedelic research for managing psychiatric conditions in recent years. This study aimed to present a comprehensive review of the current state of the field by applying a systematic search strategy for articles on the effectiveness and tolerability of four psychedelic-assisted therapies (psilocybin, lysergic acid diethylamide [LSD], 3,4-Methylenedioxymethamphetamine [MDMA], and ayahuasca) for adults with symptoms of depression, anxiety, and posttraumatic stress disorder (PTSD). Psychometric scores and adverse events were pooled using random-effects meta-analysis models with Hedges’ g bias-corrected standardized mean differences (g) and rate ratios (RR) with 95% confidence intervals (CI). Bias evaluation followed PRISMA and Cochrane guidelines. Eighteen studies were identified, which suggested that psychedelic therapies were well tolerated and presented a large effect size for the management of depression symptoms in a transdiagnostic population with psilocybin (g = -1.92, 95% CI, −2.73 to −1.11) and MDMA (g = -0.71; 95% CI, −1.39 to −0.03). These are promising results that complement the current literature. However, evidence certainty was low to very low due to methodological limitations, small sample size, blinding, study heterogeneity, and publication bias. These results also highlight the need for more adequately powered studies exploring these novel therapies.

KEYWORDS:

• Psychedelic-assisted therapies
• mood disorders
• anxiety disorders
• PTSD

Disclosure statement

Dr. Bahji receives a small honorarium for teaching undergraduate and postgraduate medical trainees in the Cumming School of Medicine at the University of Calgary. In addition, Dr. Bahji is an unpaid member of the Canadian Network for Mood and Anxiety Treatments (CANMAT) editorial committee, the International Society of Addiction Journal Editors (ISAJE), and the Section of Addiction Psychiatry of the Canadian Psychiatric Association (CPA). Dr. Bahji is also an unpaid associate editor of the Canadian Journal of Addiction (CJA) and a mental health educator for TED-Ed, where he receives a small honorarium for supporting online educational content. Finally, Dr. Bahji does not report any royalties, licenses, consulting fees, payment or honoraria for lectures or presentations, speaker’s bureaus, manuscript writing, expert testimony, patents, or participation on other boards.

Data availability statement

The data supporting this study’s findings are available from the corresponding author upon request.

Supplementary Material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/02791072.2023.2278586.

Notes

1. Note. BDI = Beck Depression Inventory; CAPS = Clinician-Administered PTSD Scale; DMT = N, N-dimethyltryptamine; HAMD = Hamilton Depression Rating Scale; LSD = Lysergic Acid Diethylamide; MADRS = Montgomery–Åsberg Depression Rating Scale; MDD = major depressive disorder; MDMA = 3,4-Methylenedioxymethamphetamine; PTSD = posttraumatic stress disorder; QIDS = Quick Inventory of Depression Self Report; RCT = randomized controlled trial; SD = standard deviation; SE = standard error; SEM = standard error of mean; STAI = State-Trait Anxiety Inventory; TRD = treatment-resistant depression.

2. Notes: MDMA = 3,4-Methylenedioxymethamphetamine. SMD=Standardized Mean Difference. RR=Rate Ratio. 95%-CI = 95% Confidence Interval. The (Goodwin et al. 2022) trial was split into two rows as there were three arms (25 mg, 10 mg, and 1 mg of psilocybin).

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.