3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for victims of sexual abuse with severe post-traumatic stress disorder: an open label pilot study in Brazil

This open-label clinical pilot study (n=3) investigated the efficacy of MDMA-assisted psychotherapy (75 mg in the 1st session, 75 or 125 mg in the 2nd and 3rd sessions) for patients suffering from severe post-traumatic stress disorder due to sexual abuse. One showed small but clinically significant improvement, one showed moderate improvement, and one showed strong improvement, with regard to diagnostic symptoms for PTSD.

Abstract

“Objective: To conduct Brazil’s first clinical trial employing 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for post-traumatic stress disorder (PTSD), given its high prevalence resulting from epidemic violence.

Methods: Of 60 volunteers, four matched the inclusion & exclusion criteria. Three patients with PTSD secondary to sexual abuse (diagnosed by the Structured Clinical Interview for DSM-IV and the Clinician Administered PTSD Scale for DSMV-4 [CAPS 4]) completed enrollment and treatment, following a standardized Multidisciplinary Association for Psychedelic Studies protocol consisting of 15 weekly therapy sessions: three with orally administered MDMA with concurrent psychotherapy and music, spaced approximately 1 month apart. CAPS-4 scores two months after the final MDMA session were the primary outcome.

Results: No serious adverse events occurred. The most frequent adverse events were somatic pains and anguish. CAPS-4 reductions were always greater than 25 points. The final scores were 61, 27, and 8, down from baseline scores of 90, 78, and 72, respectively. All reductions were greater than 30%, which is indicative of clinically significant improvement. Secondary outcomes included lower Beck Depressive Inventory scores and higher Post-Traumatic Growth Inventory and Global Assessment of Functioning scores.

Conclusions: Considering the current limitations in safe and efficacious treatments for PTSD and recent studies abroad with larger patient samples, MDMA-assisted psychotherapy could become a viable treatment in Brazil.”

Authors: Alvaro V. Jardim, Dora V. Jardim, Bruno R. Chaves, Matheus Steglich, Marcela Ot’alora G., Michael C. Mithoefer, Dartiu X. da Silveira, Luís Fernando Tófoli, Sidarta Ribeiro, Rebecca Matthews, Rick Doblin & Eduardo E. Schenberg

Summary

Introduction

Brazil suffers from increasing rates of violence and associated mental health problems. MDMA-AP, a promising alternative under development abroad, has been granted a breakthrough therapy designation by the U.S. Food and Drug Administration after completing Phase 2 trials.

We conducted the first clinical trial of MDMA-AP in Brazil to determine whether the methods and premises would be efficacious in a Brazilian sample of PTSD patients.

Sample and procedures

Participants were recruited through social media, the Brazilian press, medical referrals, and word of mouth. They underwent three preparatory psychotherapy sessions followed by three monthly cycles of one MDMA-AP session followed by three integrative psychotherapy sessions.

The inclusion criteria were: DSM-IV PTSD diagnosis, CAPS-4 score 4 604-6, minimum 18 years of age, at least one previous treatment failure, willingness to abstain from psychiatric medications, herbal supplements, any non-prescribed medications, and any illicit drugs, negative pregnancy tests, fluency in Portuguese.

The exclusion criteria were pregnancy, a history of psychotic disorder, type 1 bipolar disorder or personality disorder, hepatic disease, hypertension, weight below 48 kg, a history of hyponatremia or hyperthermia, a serious suicide risk, and inability to provide informed consent.

Outcomes

The primary outcome was the CAPS-4 score, and the effect size was estimated using Rosenthal’s r12 in Stata® statistical package (v.12). Secondary outcomes included PTSD symptoms, suicidal ideation and behavior, depressive symptoms, sleep quality, and the DSM-IV Global Assessment of Functioning.

Ethics statement and controlled substances

The protocol for this study was approved by the National Research Ethics Commission and registered in the Brazilian Clinical Trials Registry. MDMA was supplied by the Multidisciplinary Association for Psychedelic Studies (MAPS).

Results

Although 60 volunteers expressed interest in participation, only 24 underwent the screening process. Of the nine volunteers who met the criteria for PTSD diagnosis, two were married, one was divorced, and one was single.

All participants opted for supplemental doses in all MDMA-AP sessions, and there were clear changes in emotion, cognition, blood pressure, heart rate and temperature. There were no serious adverse events.

All patients showed significant improvement in the primary outcome (CAPS-4) and secondary outcomes (PTSD Checklist – Civilian Version, Post-Traumatic Growth Inventory, Beck Depression Inventory-II, and Global Assessment of Functioning).

Discussion

Three participants suffered from sexual abuse and experienced severe PTSD. After receiving MDMA-AP treatment, two of the three patients showed small but clinically significant improvement in the primary outcome (a 29-point [32% reduction in CAPS-4 score], one showed moderate improvement (a 51-point [65% reduction]), and one showed strong improvement (a 64-point [89% reduction in CAPS-4 score).

Changes in depressive symptomatology were minimal in patients 1, 2, and 3, with final Beck Depression Inventory-II scores of 10 and 2, respectively. There were no serious adverse events, and an acceptable level of adverse events.

These results compare fairly well with previous Phase 2 MDMA-AP studies, and warrant further MDMA-AP studies in Brazil. Furthermore, a Phase 3 MDMA-AP for PTSD trial is now underway, with potential approval anticipated in a few years.

Acknowledgements

The authors would like to thank the entire MAPS staff, the MAPS Public Benefit Corporation, 407 donors and attorneys for their assistance with this study.