Can MDMA cure PTSD? A new review of the evidence says it’s too early to tell

A meta-analysis of studies exploring the efficacy of MDMA-assisted therapy in treating PTSD (posttraumatic stress disorder) found that these treatments are associated with reductions in symptom severity. They were also associated with improved functioning and reductions in dissociative symptoms. The paper was published in European Neuropsychopharmacology.

3,4-methylenedioxymethamphetamine, also known as MDMA, ecstasy, or molly, is a psychoactive drug that changes mood, perception, emotional openness, and social connectedness. It mainly affects brain chemicals such as serotonin, dopamine, and norepinephrine. MDMA is an illicit drug in many jurisdictions because its use may lead to high blood pressure, overheating, dehydration or overhydration, anxiety, panic, sleep problems, and mood crashes after use.

However, scientists also study its potential uses in the therapy of mental health disorders. One such potential use is MDMA-assisted therapy. MDMA-assisted therapy is a form of psychotherapy in which MDMA is given in a controlled clinical setting in the presence of trained therapists. The idea is that MDMA may reduce fear and defensiveness while increasing trust and emotional openness, making it easier for some people to process traumatic memories. It has been studied especially for treating post-traumatic stress disorder.

Study author Natalia E. Fares-Otero and her colleagues note that while many studies exploring the effects of MDMA-assisted therapy have been conducted, major regulatory and methodological challenges affecting psychedelic research threaten the validity of the conclusions derived from these studies. They conducted a meta-analysis aiming to address these limitations by focusing exclusively on randomized controlled trials of MDMA-assisted therapy.

The researchers looked at the therapy’s effects on both the symptoms of PTSD and the overall daily functioning of adults suffering from PTSD. They focused on randomized controlled trials because this category of study design applies the highest level of experimental control, making it the most likely that the findings are valid.

The study authors searched a set of databases of research publications that included Scopus, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE via PubMed, Web of Science Core Collection (WoS), ClinicalTrials.gov, PTSDpubs (PILOTS), PsycINFO, and CINHAL, looking for randomized controlled trials that addressed the topic they were interested in. This search resulted in 14 studies that contained what these authors were looking for.

Six of these studies were secondary analyses of clinical trials and their results were interpreted qualitatively, while eight studies contained enough data for quantitative analyses. These eight studies were conducted primarily in North America, with additional sites in Europe and Israel. The total number of participants in all eight studies was 387 (ranging between 2 and 104 per study). Sixty-seven percent of the participants were women, and the participants’ average age was 40 years.

The overall results showed that MDMA-assisted therapy was associated with reductions in PTSD symptom severity, but also with reductions in dissociative symptoms and improvements in overall functioning compared to control groups. There was no clear evidence of benefit for depressive symptoms.

“Current findings suggest that MDMA-AT [MDMA-assisted therapy] may warrant further investigation as a potential treatment for PTSD; however, larger, higher-quality RCTs [randomized controlled trials] with active controls and long-term follow-up are needed to determine its efficacy,” the study authors concluded.

The study contributes to the scientific understanding of the potential of MDMA-assisted therapy in treating PTSD. However, the study authors issued a major warning regarding the quality of the data: most of the studies they analyzed showed a high risk of bias in the measurement of the outcome, primarily due to failures in “blinding.” Because MDMA produces obvious psychoactive effects, both patients and therapists usually knew who received the real drug and who received a placebo, leading to massive expectancy biases that could artificially inflate the positive results.

Consequently, the overall certainty of evidence was rated as “very low.” Some of the studies also had very small sample sizes and almost none tracked patients’ long-term outcomes (a year or more after treatment), further limiting the strength of the scientific evidence they provided. The authors also noted that most studies were funded and conducted by a single research group, which increases the risk of publication bias.

The paper, “Efficacy of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for posttraumatic stress disorder: A systematic review and meta-analysis of clinical and functional outcomes,” was authored by Natalia E. Fares-Otero, Yuki Furukawa, Marit Sijbrandij, Stefan Leucht, Eduard Vieta, Pim Cuijpers, Mathias Harrer, and Soraya Seedat.