3,4-Methylenedioxymethamphetamine-assisted psychotherapy for treatment of chronic posttraumatic stress disorder: A randomized phase 2 controlled trial

Abstract

Background:Posttraumatic stress disorder often does not resolve after conventional psychotherapies or pharmacotherapies. Pilot studies have reported that 3,4-methylenedioxymethamphetamine (MDMA) combined with psychotherapy reduces posttraumatic stress disorder symptoms.Aims:This pilot dose response trial assessed efficacy and safety of MDMA-assisted psychotherapy across multiple therapy teams.Methods:Twenty-eight people with chronic posttraumatic stress disorder were randomized in a double-blind dose response comparison of two active doses (100 and 125 mg) with a low dose (40 mg) of MDMA administered during eight-hour psychotherapy sessions. Change in the Clinician-Administered PTSD Scale total scores one month after two sessions of MDMA served as the primary outcome. Active dose groups had one additional open-label session; the low dose group crossed over for three open-label active dose sessions. A 12-month follow-up assessment occurred after the final MDMA session.Results:In the intent-to-treat set, the active groups had the largest reduction in Clinician-Administered PTSD Scale total scores at the primary endpoint, with mean (standard deviation) changes of −26.3 (29.5) for 125 mg, −24.4 (24.2) for 100 mg, and −11.5 (21.2) for 40 mg, though statistical significance was reached only in the per protocol set (p=0.03). Posttraumatic stress disorder symptoms remained lower than baseline at 12-month follow-up (p<0.001) with 76% (n=25) not meeting posttraumatic stress disorder criteria. There were no drug-related serious adverse events, and the treatment was well-tolerated.Conclusions:Our findings support previous investigations of MDMA-assisted psychotherapy as an innovative, efficacious treatment for posttraumatic stress disorder.

Emotional remodeling with oxytocin durably rescues trauma-induced behavioral and neuro-morphological changes in rats: a promising treatment for PTSD

“…This hypothesis is in good agreement with the positive effects obtained by injecting the anxiolytic drug propranolol in cocaine addicted 72 or PTSD 73 patients before their respective exposure to drug-craving stimuli or to PTSD cues. It is also consistent with the evaluation of the recent advancements in MDMA-assisted psychotherapy for PTSD 74,75 which points out that treatments that block pathological activation in brain regions implicated in the expression of fear during the memory malleability phase are likely to induce re-processing of traumatic memories. This new memory with a lower emotional component could therefore reduce the forthcoming impact of the trauma.…”

Posttraumatic Growth After MDMA‐Assisted Psychotherapy for Posttraumatic Stress Disorder

“…Results from these trials demonstrate that MDMA-assisted psychotherapy produces significant reductions in PTSD symptoms (Mithoefer et al, 2018; DOI: 10.1002/jts.22479 This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. 2011; Oehen, Traber, Widmer, & Schnyder, 2013;Ot'alora et al, 2018) and that these reductions endure (Mithoefer et al, 2013). Results of a pooled analysis of six Phase 2 studies (Mithoefer et al, 2019) demonstrated that two psychotherapy sessions with active doses of MDMA more than doubled PTSD symptom reduction compared to psychotherapy with placebo controls (estimated mean difference between groups = −22.0, SE = 5.17), d = 0.8.…”

Interactive Motion-Assisted Exposure Therapy for Veterans with Treatment-Resistant Posttraumatic Stress Disorder: A Randomized Controlled Trial

“…Studies that have considered the efficacy of psychotherapeutic interventions following unsuccessful evidencebased PTSD treatment for veterans and other TR-PTSD populations are very scarce [51]. Results of multiple trials with 3,4-methylenedioxymethamphetamine (MDMA)assisted psychotherapy for TR-PTSD were encouraging with large effect sizes [52][53][54][55], and deep brain stimulation shows promise as well, with two positive case reports [56]. Considering that the current trial recruited veterans with, on average, 4 prior unsuccessful treatments and demonstrated a large effect size, 3MDR could prove to be a useful non-invasive, non-pharmacological addition to the toolbox of clinicians working with veterans with TR-PTSD.…”