Posttraumatic Growth After MDMA‐Assisted Psychotherapy for Posttraumatic Stress Disorder

This study on data from the Phase II clinical trials (n=60, by MAPS) of MDMA-assisted (75-125mg) psychotherapy for PTSD, found that it led to posttraumatic growth (PTGI).

Abstract

“3,4‐Methylenedioxymethamphetamine (MDMA)–assisted psychotherapy for posttraumatic stress disorder (PTSD) has been shown to significantly reduce clinical symptomatology, but posttraumatic growth (PTG), which consists of positive changes in self‐perception, interpersonal relationships, or philosophy of life, has not been studied with this treatment. Participant data (n = 60) were pooled from three Phase 2 clinical studies employing triple‐blind crossover designs. Participants were required to meet DSM‐IV‐R criteria for PTSD with a score higher than 50 on the Clinician‐Administered PTSD Scale (CAPS‐IV) as well as previous inadequate response to pharmacological and/or psychotherapeutic treatment. Data were aggregated into two groups: an active MDMA dose group (75–125 mg of MDMA; n = 45) or placebo/active control (0–40 mg of MDMA; n = 15). Measures included the Posttraumatic Growth Inventory (PTGI) and the CAPS‐IV, which were administered at baseline, primary endpoint, treatment exit, and 12‐month follow‐up. At primary endpoint, the MDMA group demonstrated more PTG, Hedges’ g = 1.14, 95% CI [0.49, 1.78], p < .001; and a larger reduction in PTSD symptom severity, Hedges’ g = 0.88, 95% CI [−0.28, 1.50], p < .001, relative to the control group. Relative to baseline, at the 12‐month follow‐up, within‐subject PTG was higher, p < .001; PTSD symptom severity scores were lower, p < .001; and two‐thirds of participants (67.2%) no longer met criteria for PTSD. MDMA‐assisted psychotherapy for PTSD resulted in PTG and clinical symptom reductions of large‐magnitude effect sizes. Results suggest that PTG may provide a new mechanism of action warranting further study.”

Authors: Ingmar Gorman, Alexander B. Belser, Lisa Jerome, Colin Hennigan, Ben Shechet, Scott Hamilton, Berra Yazar‐Klosinski, Amy Emerson & Allison A. Feduccia

Summary

MDMA-assisted psychotherapy produces significant reductions in PTSD symptoms and endures, and the treatment may have preliminary evidence demonstrating substantial improvement over existing therapies for PTSD. However, posttraumatic growth has not yet been studied as an independent outcome or a mechanism of symptom reduction with MDMA-assisted psychotherapy.

Given the high incidence and prevalence of PTSD, it is critical to pursue promising treatments and explore and model possible mechanisms of action. However, existing research has tended to focus on symptom severity as a primary outcome while neglecting positive life changes.

Posttraumatic growth (PTG) is a psychological construct that is based on positive psychological change experienced as a result of the struggle with highly challenging life circumstances. It has been theorized that psychotherapy may facilitate PTG and that this growth may contribute to PTSD symptom reduction.

Five studies found that a clinical intervention improved PTG, including group cognitive behavioral stress management, an online cognitive behavioral therapy intervention for PTSD symptoms, and written or spoken disclosure about adversity.

The peer-reviewed literature on the PTG construct is not without criticism. It has also been shown that high PTG prior to or soon after traumatic event exposure is associated with significantly higher levels of posttraumatic stress.

It is possible that MDMA-assisted psychotherapy may promote positive psychological changes among individuals with PTSD, such as improved self-reported well-being, enhanced interpersonal closeness, more empathy for self and others, reduced distress in response to social exclusion and prosociality, enhanced introspection and emotional openness, and enhanced sense of personal efficacy.

In this exploratory secondary analysis of three Phase 2 trials, MDMA-assisted psychotherapy was found to influence PTG positively while also reducing trauma symptoms.

Method

Participants

Of the six Phase 2 studies of MDMA-assisted psychotherapy for PTSD, three included the PTGI. The data were pooled from three Phase 2 clinical studies with similar study designs.

Participants were individuals 18 years of age and older with a PTSD diagnosis that persisted for over 6 months. Exclusion criteria included presence of major medical conditions, past or current psychotic disorder, pregnancy or lactation, and weight under 48 kg.

Procedure

Three studies tested different doses of MDMA (75 mg, 100 mg, n = 9; 125 mg, n = 29) compared to either active control doses of MDMA (30 mg, n = 7; 40 mg, n = 6) or placebo (0 mg, n = 2). Participants received 8 hours of manualized psychotherapy in two blinded experimental sessions.

After unblinding, all participants received three open-label sessions with active doses of MDMA in a crossover segment. All participants who completed the 12-month follow-up received MDMA-assisted Tpsychotherapy.

All measures were administered prior to the first session, 1 month after the second blinded MDMA or placebo session, and 2 months after the third open-label session. The long-term follow-up measures were administered 12 months after treatment concluded.

Measures

The PTGI is a 21-item, validated measure of perceived positive outcomes of a traumatic event. It includes five subscales: Personal Strength, Spiritual Change, Relating to Others, Appreciation of Life, and New Possibilities.

The CAPS-IV is regarded as the gold standard measure of PTSD symptomology and provides a total symptom severity rating, severity indices for each PTSD symptom cluster, and a diagnostic score.

Data Analysis

Analyses for this paper aggregated participants into two groups: an active MDMA dose group and a placebo/active control group. The change in PTGI and CAPS-IV total scores from baseline to the primary endpoint was analyzed using independent samples t tests.

Twelve-month follow-up outcomes were compared to scores at baseline and treatment exit, and a mixed-effect repeated measure model was used to analyze the data. Age, PTSD duration, sex, race, and prestudy self-reported “ecstasy” use were all significant covariates.

A secondary study aim was to evaluate whether changes in PTSD symptoms correlated with PTG. Pearson correlations were used to evaluate scores at baseline and change in CAPS-IV and PTGI scores from baseline to the primary endpoint.

Results

Sample Characteristics

The sample was nearly evenly split by gender and racial, with a mean participant age of 40 years and a mean CAPS-IV total score of 89.4 and PTGI total score of 37.8 respectively. There were no between-group differences for baseline CAPS-IV or PTGI total scores.

Primary Outcome

The active MDMA group exhibited the largest improvement in both the CAPS-IV and PTGI, and the difference in PTSD symptom scores between groups was large.

At baseline, there was no significant correlation between PTGI and CAPS-IV scores. However, the PTGI score decreased as PTG increased in the MDMA group, and there was no significant correlation between PTGI and CAPS-IV scores in the control group.

Treatment Exit and 12-Month Follow-up

At treatment exit, PTSD symptom severity and PTG were significantly improved compared to baseline on the CAPS-IV and PTGI, with positive gains sustained at the 12-month follow-up.

Discussion

The results from the current analyses confirm previous findings that MDMA-assisted psychotherapy reduces PTSD symptoms in individuals diagnosed with PTSD. Furthermore, the results demonstrate that MDMA-assisted psychotherapy facilitates self-reported improvements in interpersonal relationships, spirituality, sense of possibility, assessment of personal strengths, and appreciation of life.

There have been numerous studies published regarding the association between posttraumatic stress disorder (PTSD) symptom severity and posttraumatic growth hormone (PTG). The current analyses showed that posttraumatic growth hormone levels were correlated with PTSD symptom severity 1 month after treatment with MDMA.

MDMA may be used in combination with psychotherapy to promote PTG in people living with PTSD. The pharmacological effects of MDMA may be synergistic with the psychotherapeutic processing of trauma to reduce PTSD symptoms.

The impact of MDMA-assisted psychotherapy on the PTG may be explained by the nondirective approach, the release of oxytocin and serotonin, and the effect of MDMA on spirituality.

These novel findings should be qualified by the fact that they originate from three different trials with different study designs, tested doses, and sample sizes. Additionally, the sample size was relatively small and uneven between groups, but significant group differences were detected due to large treatment effects.

The current study found that the MDMA group experienced higher levels of PTG and larger reductions in PTSD symptom severity compared to the placebo group. These improvements were enduring at the 12-month follow-up.