A randomized, controlled pilot study of MDMA (±3,4-Methylenedioxymethamphetamine)-assisted psychotherapy for treatment of resistant, chronic Post-Traumatic Stress Disorder (PTSD)

Abstract

Psychiatrists and psychotherapists in the US (1970s to 1985 and Switzerland (1988Switzerland ( -1993 used MDMA legally as a prescription drug, to enhance the effectiveness of psychotherapy. Early reports suggest that it is useful in treating trauma-related disorders. Recently, the first completed pilot study of MDMA-assisted psychotherapy for PTSD yielded encouraging results. Designed to test the safety and efficacy of MDMA-assisted psychotherapy in patients with treatment-resistant PTSD; our randomized, double-blind, active-placebo controlled trial enrolled 12 patients for treatment with either low-dose (25 mg, plus 12.5 mg supplemental dose) or full-dose MDMA (125 mg, plus 62.5 mg supplemental dose). MDMA was administered during three experimental sessions, interspersed with weekly non-drug-based psychotherapy sessions. Outcome measures used were the Clinician-Administered PTSD Scale (CAPS) and the Posttraumatic Diagnostic Scale (PDS). Patients were assessed at baseline, three weeks after the second and third MDMA session (end of treatment), and at the 2-month and 1-year follow-ups. We found that MDMA-assisted psychotherapy can be safely administered in a clinical setting. No drug-related serious adverse events occurred. We did not see statistically significant reductions in CAPS scores (p = 0.066), although there was clinically and statistically significant self-reported (PDS) improvement (p = 0.014). CAPS scores improved further at the 1-year follow-up. In addition, three MDMA sessions were more effective than two (p = 0.016).

Altered Insula Connectivity under MDMA

“…Furthermore, propranolol-another pharmacological agent investigated as an adjunct for PTSD therapy (Brunet et al, 2008, but see Wood et al, 2015;Steenen et al, 2016)-decreases connectivity within the salience network (Hermans et al, 2011). Thus, it is worth considering whether action at the salience network might be an important component of the mechanism by which MDMA operates in MDMA-assisted psychotherapy for PTSD (Mithoefer et al, 2011;Mithoefer et al, 2012;Oehen et al, 2013).…”

“…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).…”

Psychedelic medicine: a re-emerging therapeutic paradigm

“…[3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] We will focus on two classes of psychedelics: classic psychedelics and "entactogens. "…”

“…The participants were randomly assigned to either the treatment group (receiving 200 µg LSD [n = 8]) or the active control group (20 µg LSD [n = 4], with an open-label crossover to 200 µg LSD after the initial blinding was unmasked). At two months' follow-up, the State-Trait Anxiety Inventory (STAI) showed nonsignificant reductions in [16][17][18] Note: DMT = dimethyltryptamine, LSD = lysergic acid diethylamide, MDMA = methylenedioxymethamphetamine, PTSD = posttraumatic stress disorder. *Potential harms identified here are associated with illicit and unsupervised nonmedical uses of psychedelic substances (often in the context of polysubstance use); current clinical studies on psychedelic agents have not reported such chronic adverse sequelae.…”

“…17 An additional small (n = 12) randomized controlled trial investigating MDMA-assisted psychotherapy for PTSD was recently completed in Switzerland. 18 This study compared three fulldose MDMA-assisted sessions per patient (with non-drug-assisted therapy before and after) with low-dose active placebo in a crossover design. Participants had no serious drug-related adverse events, and although reductions in CAPS scores were not statistically significant, self-assessment of PTSD symptoms as measured by the Posttraumatic Diagnostic Scale questionnaire was significantly reduced.…”