MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study

Summary & key facts

Researchers ran a carefully controlled trial with about 90 people who had severe post-traumatic stress disorder. People were randomly assigned to the same structured therapy but with either MDMA or an inactive placebo, and neither patients nor therapists knew who got which drug. The team measured PTSD symptoms and day-to-day functioning two months after the last drug session. On average, the MDMA group had much larger drops in PTSD symptoms and better functioning than the placebo group. The treatment was generally safe in this study and did not show signs of increased abuse risk or more suicidal thoughts. The authors say this could be an important new treatment idea, but more research is still needed to confirm long-term effects.

Key facts:

• This was a controlled trial of about 90 people with severe PTSD who stopped other psychiatric medicines before starting the study.
• Participants were randomly assigned to receive the same manualized psychotherapy with either MDMA or an inactive placebo, and neither patients nor therapists knew who got which drug.
• PTSD symptoms were measured with a standard clinician rating, and functioning was measured with a standard disability scale, both checked two months after the last experimental session.
• On average, PTSD symptom scores fell by about 24 points in the MDMA group and by about 14 points in the placebo group, showing a substantially larger improvement with MDMA.
• The MDMA group also had a statistically significant improvement in day-to-day functioning compared with placebo.
• In this trial, MDMA-assisted therapy did not produce signs of drug-abuse problems, did not increase suicidal thoughts, and did not cause a specific heart rhythm problem called QT prolongation; however, results reflect the short follow-up time of two months and the study size of about 90 people.

Abstract

Post-traumatic stress disorder (PTSD) presents a major public health problem for which currently available treatments are modestly effective. We report the findings of a randomized, double-blind, placebo-controlled, multi-site phase 3 clinical trial (NCT03537014) to test the efficacy and safety of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for the treatment of patients with severe PTSD, including those with common comorbidities such as dissociation, depression, a history of alcohol and substance use disorders, and childhood trauma. After psychiatric medication washout, participants (n = 90) were randomized 1:1 to receive manualized therapy with MDMA or with placebo, combined with three preparatory and nine integrative therapy sessions. PTSD symptoms, measured with the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5, the primary endpoint), and functional impairment, measured with the Sheehan Disability Scale (SDS, the secondary endpoint) were assessed at baseline and at 2 months after the last experimental session. Adverse events and suicidality were tracked throughout the study. MDMA was found to induce significant and robust attenuation in CAPS-5 score compared with placebo (P < 0.0001, d = 0.91) and to significantly decrease the SDS total score (P = 0.0116, d = 0.43). The mean change in CAPS-5 scores in participants completing treatment was -24.4 (s.d. 11.6) in the MDMA group and -13.9 (s.d. 11.5) in the placebo group. MDMA did not induce adverse events of abuse potential, suicidality or QT prolongation. These data indicate that, compared with manualized therapy with inactive placebo, MDMA-assisted therapy is highly efficacious in individuals with severe PTSD, and treatment is safe and well-tolerated, even in those with comorbidities. We conclude that MDMA-assisted therapy represents a potential breakthrough treatment that merits expedited clinical evaluation.

Topics

Cannabis and Cannabinoid Research Psychedelics and Drug Studies Sleep and Wakefulness Research

Categories

Clinical Psychology Psychology Social Sciences

Tags

Adverse effect Alternative medicine Clinical endpoint Internal medicine MDMA Medicine Pathology Placebo Psychiatry Psychology Randomized controlled trial

Substances

MDMA

Conditions & symptoms

Depression PTSD Substance abuse disorder Feeling disconnected from others Sadness or low mood