A comparison of MDMA-assisted psychotherapy to non-assisted psychotherapy in treatment-resistant PTSD: A systematic review and meta-analysis
Benjamin Illingworth, Declan J Lewis, Andrew T Lambarth, Kate Stocking, James Mn Duffy, Luke A. Jelen, James Rucker
Journal of Psychopharmacology December 20, 2020 DOI: 10.1177/0269881120965915 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review with meta-analysis Randomized Double-blind Peer reviewed |
|---|---|
| Population | Patients with treatment-resistant PTSD |
| Intervention | MDMA-assisted psychotherapy |
| Dose | 75 mg, 100 mg, 125 mg |
| Topics | MDMA Psychedelic-assisted therapy PTSD |
| Keywords | Placebo Meta-analysis Randomized controlled trial Adverse effect Mood Beck depression inventory |
| Citations | 47 |
| Key findings | MDMA-assisted psychotherapy at 75 mg and 125 mg doses significantly reduced PTSD symptoms compared to active placebo, but only the 75 mg dose significantly reduced depression scores. |
Abstract
Rationale: Novel, evidence-based treatments are required for treatment-resistant post-traumatic stress disorder (PTSD). 3,4-Methylenedioxymethamphetamine (MDMA) has beneficially augmented psychotherapy in several small clinical trials.
Objective: To review the use of MDMA-assisted psychotherapy in treatment-resistant PTSD.
Methods: Systematic searches of four databases were conducted from inception to February 2020. A meta-analysis was performed on trials which were double-blinded, randomised, and compared MDMA-assisted psychotherapy to psychotherapy and placebo. The primary outcomes were the differences in Clinician Administered PTSD Scale (CAPS-IV) score and Beck’s Depression Inventory (BDI). Secondary outcome measures included neurocognitive and physical adverse effects, at the time, and within 7 days of intervention.
Results: Four randomised controlled trials (RCTs) met inclusion criteria. When compared to active placebo, intervention groups taking 75 mg (MD −46.90; 95% (confidence intervals) CI −58.78, −35.02), 125 mg (MD −20.98; 95% CI −34.35, −7.61) but not 100 mg (MD −12.90; 95% CI −36.09, 10.29) of MDMA with psychotherapy, had significant decreases in CAPS-IV scores, as did the inactive placebo arm (MD −33.20; 95% CI −40.53, −25.87). A significant decrease in BDI when compared to active placebo (MD −10.80; 95% CI −20.39, −1.21) was only observed at 75 mg. Compared to placebo, participants reported significantly more episodes of low mood, nausea and jaw-clenching during sessions and lack of appetite after 7 days.
Conclusion: These results demonstrate potential therapeutic benefit with minimal physical and neurocognitive risk for the use of MDMA-assisted psychotherapy in TR-PTSD, despite little effect on Beck’s Depression Inventory. Better powered RCTs are required to investigate further. International Prospective Register of Systematic Reviews: CRD42019109132 available online at www.crd.york.ac.uk/prospero .
Comparable studies
Other systematic reviews and meta-analyses on MDMA and psychedelic-assisted therapy, most cited first.
Citations in the library
Cited by 38
- Treatment of Posttraumatic Stress Disorder: A State-of-the-art Review. Current Neuropharmacology 2024
- Models of Psychedelic-Assisted Psychotherapy: A Contemporary Assessment and an Introduction to EMBARK, a Transdiagnostic, Trans-Drug Model Frontiers in Psychology June 2, 2022
- Psilocybin and MDMA for the treatment of trauma-related psychopathology International Review of Psychiatry April 3, 2021
- Alleviating anxiety and taming trauma: Novel pharmacotherapeutics for anxiety disorders and posttraumatic stress disorder Neuropharmacology January 6, 2023
- MDMA and MDMA-Assisted Therapy. American Journal of Psychiatry 2025
and 33 more in the library
Cites 17
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- 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for post-traumatic stress disorder in military veterans, firefighters, and police officers: a randomised, double-blind, dose-response, phase 2 clinical trial. The Lancet Psychiatry May 1, 2018
- A randomized, controlled pilot study of MDMA (±3,4-Methylenedioxymethamphetamine)-assisted psychotherapy for treatment of resistant, chronic Post-Traumatic Stress Disorder (PTSD) Journal of Psychopharmacology October 31, 2012
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- MDMA-assisted psychotherapy for treatment of PTSD: study design and rationale for phase 3 trials based on pooled analysis of six phase 2 randomized controlled trials. Psychopharmacology September 1, 2019
and 12 more in the library