MDMA-assisted psychotherapy using low doses in a small sample of women with chronic posttraumatic stress disorder

This small double-blind placebo-controlled study (n=6) studied the safety (psychological & physiological) of a low dose of MDMA (50-75mg) in women with chronic PTSD and found no adverse effects.

Abstract

“The purpose of this study was to investigate the safety of different doses of MDMA-assisted psychotherapy administered in a psychotherapeutic setting to women with chronic PTSD secondary to a sexual assault, and also to obtain preliminary data regarding efficacy. Although this study was originally planned to include 29 subjects, political pressures led to the closing of the study before it could be finished, at which time only six subjects had been treated. Preliminary results from those six subjects are presented here. We found that low doses of MDMA (between 50 and 75 mg) were both psychologically and physiologically safe for all the subjects. Future studies in larger samples and using larger doses are needed in order to further clarify the safety and efficacy of MDMA in the clinical setting in subjects with PTSD.”

Authors: José C. Bouso, Rick Doblin, Magí Farré, Miguel A. Alcázar & Gregorio Gómez-Jarabo

Notes

Many studies (and now Phase III clinical trials) followed this initial study. Notable are the first two by Mithoefer et al. (2010) and Oehen et al. (2012).

This study was supported by MAPS.

“As the objective of this study was to assess the safety of MDMA in a chronic PTSD population, a wide range of psychopathological scales was used in order to measure not only PTSD symptoms, but also its associated comorbidities, such as anxiety, depression, phobias, maladjustment and damaged self-esteem. Neither of the two doses of MDMA increased symptomatology in any of the psychopathological scales in any of the subjects treated, thus demonstrating that the doses administered in this trial were psychologically safe for all the subjects. Blood pressure, heart rate and other somatic side effects were also assessed and showed no significant elevation, again suggesting that the doses administered were physiologically safe.”

Following years of research only into the dangers of MDMA, this was a good sign and confirmation (from millions of ‘ecstasy’ dosages sold on the street without many adverse events) that MDMA is safe to use in a therapeutic/clinical setting.

See Ecstasy by Julie Holland for more research about the safety or Drugs: Without The Hot Air by David Nutt for a broader perspective.

Summary

MDMA-Assisted Psychotherapy Using Low Doses in a Small Sample of Women with Chronic Posttraumatic Stress Disorder†

3,4-Methylenedioxymethamphetamine (MDMA) is a ring-substituted phenethylamine with a chemical structure related both to mescaline and methamphetamine. It has a distinctive and unique psychological profile characterized by a specificity to act over the human emotional sphere.

MDMA was first synthesized by Merck in 1912, but was not tested in humans or animals until the 1950s. It was found being used on the street in the 1970s, but the first scientific references regarding its pharmacological profile appeared at the end of the decade.

MDMA was widely used as an adjunct to the psychotherapeutic process from its rediscovery until its prohibition in the U.S. in 1985, although no formal controlled studies were undertaken.

The inclusion of MDMA in the list of Schedule I controlled substances shut down all legal use, though recent studies have shown that MDMA may be useful in the treatment of psychological disorders and physical pain associated with cancer.

In 80 patients, Greer and Tolbert found that 90% reported positive experiences with lasting beneficial effects that remained at the one-year follow-up. In 171 patients, Gasser found that 65% reported “good improvement” and 26% “slight improvement” after a course of LSD or MDMA-assisted psychotherapy.

MDMA has the potential to reduce anxiety and fear, thus helping subjects access their emotions and internal conflicts without the overwhelming fear normally associated with these emotions and memories. This article presents preliminary data from the first government-approved clinical trial designed to assess the safety and efficacy of MDMA in the treatment of PTSD.

Sample

Six women with chronic, treatment-resistant PTSD were recruited through women’s associations in the city of Madrid. They had to be in good physical health and be free of medications for one month prior to the drug administration session.

Study Design

A study was originally designed to assess the safety of a single dose of MDMA in women with chronic PTSD secondary to a sexual assault. The study design was a double-blind, ascending-dose study, randomized and placebo-controlled within each dose condition, with six subjects treated: two received placebo, three received MDMA 50 mg, four received MDMA 75 mg, and five received MDMA 150 mg.

All subjects had six nondrug psychotherapy sessions with two therapists, three before and three after the experimental session.

The experimental session consisted of discussing the events and material from the experimental session with subjects. Blood pressure and heart rate were measured every 30 minutes during the first six hours of the experimental session. Subjects filled out a questionnaire after each session, and again 24 hours and five to seven days after the experimental session. They also underwent psychological tests at the beginning and end of the treatment.

Psychological Approach

The psychological approach involved three 90-minute psychotherapeutic sessions before and after an eight-hour experimental session. The therapists discussed the nature of the MDMA experience, stressed its potential lasting benefits, and trained the subject in some relaxation techniques that could be helpful during the experience.

The experimental session was intended to offer subjects a deep psychological experience where they could reexperience the traumatic event without being emotionally overwhelmed, and where they would perceive emotional control as internally rather than externally situated. After two hours of therapy, the subject was invited to sit in a chair and share her experience with the therapists. The two hours of therapy ended with a meal and the subject was driven home by a friend or significant other.

The integration session occurred one day after the MDMA/placebo experience. The therapists helped the subject work through the emotions arising in response to recalling and confronting difficult areas of the experimental session.

Psychological Assessment

We used a wide range of psychological tests to assess the safety of MDMA in patients with chronic PTSD.

The Severity of Symptoms Scale for Post-traumatic Stress Disorder (SSSPTSD) is an Spanish adaptation of the PTSD Symptom Scale and contains 17 items, 5 for re-experiencing symptoms, 7 for avoidance symptoms, 5 for increased arousal symptoms, and 13 for somatic symptoms related to anxiety.

The State-Trait Anxiety Inventory, State Version (STAIS) is comprised of two separate self-report scales that measure two independent concepts of anxiety, state (S) and trait (T).

The Beck Depression Inventory is a 21-item measure of depression that gives greatest importance to cognitive symptoms.

The Hamilton Rating Scale (HAM-D) measures behavioral and physiological symptoms of depression and is a good complement to the BDI scale.

The Modified Fear Scale (MFS III) is a self-report measure based on the Fear Questionnaire with 42 items related to issues specific to sexual assault.

The Maladjustment Scale is composed of six items, and responses are made on a Likert-type scale from 1 to 6.

The Rosenberg Self-Esteem scale is a self-report measure that evaluates self-acceptance and self-esteem in a general sense.

The Hallucinogen Rating Scale consists of 100 items, with each item assessing one of six factors: somaesthesia, affect, volition, cognition, perception, and intensity.

The UKU Scale of Secondary Effects measures 43 symptoms of psychoactive medication use. It is divided into four groups: psychological, neurological, anatomical and others.

The Penn Helping Alliance Questionnaire (HAq) measures the patient’s experience of the helping alliance and contains 11 items that the subject responds to using a scale ranging from +3 to -3.

Demographic Data

Six women were interviewed, ranging from 29 to 49 years old. Two out of six suffered anal rape, another two vaginal rape and the other two body touching and other kinds of sexual aggression.

Psychological Assessment

Six subjects were treated in a clinical trial. Table 2 shows the direct scores obtained by each subject in each outcome psychopathological scale and subscale at the pretreatment stage, at post-treatment, and at follow-ups.

Subject 5 (75 mg) improved in almost all outcome scales more than the other subjects (50 mg group improved 4.5 points more than the placebo group, who improved 4.5 points), and subject 5 improved 16 points overall.

Subject 5 showed greater improvement than the 50 mg group and the placebo group on the first and second follow-ups in the STAI/S, and attained lower scores than the 50 mg group and the placebo group on post-treatment and follow-up measures on both depression scales.

Side-Effects Assessment

Subjects 1 and 5 reported very mild side effects, and blood pressure and heart rate did not increase during the experimental session.

Other Assessments

Table 8 shows the doses of MDMA received by each subject, and Table 9 shows their beliefs regarding the dose administered.

DISCUSSION

This report is about the world’s first fully approved, controlled study to investigate the safety of administering MDMA to a patient population. Two other clinical trials have been approved in the U.S., one with PTSD patients and the other with advanced-stage cancer patients.

A study reported on in this article used a double-blind, ascending-dose, placebo controlled design.

The subject who received 75 mg of MDMA experienced the greatest reduction in almost all the outcome scales employed, including the PTSD scale. The 50 mg group improved more than the placebo group, suggesting that greater efficacy as doses increase, at least within the range studied here. Given these findings, more studies should be done on higher doses of MDMA to see what dose exhibits the best outcomes with the fewest side effects.

A study of MDMA-assisted therapy with 125 mg MDMA for people with PTSD has produced encouraging preliminary findings and no drug-related serious adverse events. The study now includes the possibility of administering a supplemental dose of 62.5 mg MDMA or placebo.

This study assessed the safety of MDMA in a chronic PTSD population by measuring PTSD symptoms and its associated comorbidities. The doses administered were psychologically safe and did not increase blood pressure or heart rate.

The double-blind approach is effective in MDMA/PTSD research, at least for low doses. Subject 4 met criteria for tachycardia and hypertension at some points during the MDMA session, but her scores can be considered between the range of safety.

Low doses of MDMA administered as an adjunct to psychotherapy were found to be safe for six subjects with chronic PTSD. There were promising signs of efficacy.