Durability of improvement in post-traumatic stress disorder symptoms and absence of harmful effects or drug dependency after 3,4-methylenedioxymethamphetamine-assisted psychotherapy: a prospective long-term follow-up study

Abstract

We report follow-up data evaluating the long-term outcomes for the first completed trial of 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for chronic, treatment-resistant post-traumatic stress disorder (PTSD) (Mithoefer et al., 2011). All of the 19 subjects who received MDMA-assisted treatment in the original trial participated in the long-term follow-up (LTFU), with 16 out of 19 completing all of the long-term outcome measures, which were administered from 17 to 74 months after the original study’s final MDMA session (mean = 45.4; SD = 17.3). Our primary outcome measure used was the Clinician-Administered PTSD Scale (CAPS). Secondary outcome measures were the Impact of Events Scale-Revised (IES-R) and the Neuroticism Extroversion Oppenness Personality Inventory-Revised (NEO PI-R) Personality Inventory. We also collected a long-term follow-up questionnaire. Results for the 16 CAPS completers showed there were no statistical differences between mean CAPS score at LTFU (mean = 23.7; SD = 22.8) (tmatched = 0.1; df = 15, p = 0.91) and the mean CAPS score previously obtained at Study Exit (mean = 24.6, SD = 18.6). On average, subjects maintained statistically and clinically-significant gains in symptom relief, although two of these subjects did relapse. It was promising that we found the majority of these subjects with previously severe PTSD who were unresponsive to existing treatments had symptomatic relief provided by MDMA-assisted psychotherapy that persisted over time, with no subjects reporting harm from participation in the study.

Effects of MDMA and Intranasal Oxytocin on Social and Emotional Processing

“…This pattern of effects provides further evidence that the drug may be useful in the treatment of PTSD, by facilitating engagement with the therapist and increasing the client's ability to focus on negative emotions (Mithoefer et al, 2013). By contrast, intranasal oxytocin produced small increases in selected ratings of sociability and enhanced negative emotion recognition.…”

“…Nonetheless, the extent to which MDMA increases social behavior by decreasing sensitivity to negative expressions or increasing sensitivity to positive expressions remains to be resolved. In a recent study, patients receiving MDMAassisted treatment for PTSD (Mithoefer et al, 2013) reported an increased ability to focus on negative emotions. However, the nature of the MDMA effect remains unclear.…”

“…In light of these effects, it is also being tested as an adjunct to psychotherapy for post traumatic stress disorder (Mithoefer et al, 2013). Yet, the mechanisms by which MDMA produces its apparently unique empathogenic effects are not known.…”

Altered Insula Connectivity under MDMA

“…The first randomized controlled trials (RCTs) of MDMAassisted psychotherapy for treatment-resistant PTSD demonstrated decreases in both clinician-and participant-rated symptom severity (Mithoefer et al, 2011;Oehen et al, 2013). The efficacy of these interventions persisted at follow-up (Mithoefer et al, 2012), and effect sizes surpassed even those demonstrated by prolonged exposure therapy, the most widely accepted treatment for PTSD (Amoroso and Workman, 2016). Nonetheless, limitations pertaining to modest sample sizes and potential implicit biases warrant cautious interpretation of these preliminary, yet promising results.…”

Clinically Relevant Pharmacological Strategies That Reverse MDMA-Induced Brain Hyperthermia Potentiated by Social Interaction

“…Variability in temperature responses may explain the large individual differences in the emergence of adverse psychological and cognitive symptoms seen in some longterm MDMA users (for review, see Parrott, 2013b). Therefore, despite the modest hyperthermic responses to MDMA seen in humans under standard laboratory conditions (Freedman et al, 2005;Liechti, 2014), and its potential as a therapeutic agent for post-traumatic stress disorder (Mithoefer et al, 2011(Mithoefer et al, , 2013, our study underscores the possible dangers of 'recreational' MDMA use.…”