Can MDMA assist psychotherapy in resistant PTSD?:Jl of Psychopharm: Jan 2013


European PTSD studies show a lifetime prevalence of  1% .  US studies report prevalence up to 8%.Exposure based therapies ( CBT,EMDR etc) are effective in this disorder.Drop out rates from treatment are  high and a good proportion remain symptomatic after these treatments. SSRIs  show modest effects on symptoms.

MDMA (3,4-Methylenedioxymethamphetamine)-assisted psychotherapy is a novel approach to the treatment . Merck synthesised MDMA in 1912.  MDMA was used (legally) to assist psychotherapy in USA and switzerland . The trials by Bouso et al., 2008; Mithoefer, 2011 show that  MDMA-assisted psychotherapy  may be effective in PTSD.

Peter Oehen, Rafael Traber, Verena Widmer and Ulrich Schnyder  report the results of their RCT in this issue.It is thought that amygdala  is overactive to trauma specific cues in PTSD.Inhibition of amygdala by ventromedial prefrontal cortex (vmPFC) is deficient in PTSD. MDMA might increase VmPFC activity and thus decrease amygdala activity.Brain imaging studies have shown reduced amygdalar activity after MDMA administration.Healthy volunteers given MDMA were better able to spot positive facial expressions and found it harder to spot negative ones, when compared with placebo (Hysek et al., 2012). It can create a positively toned cognitive emotional state, with reduced fear, and better encoding of  positive emotional experiences.MDMA increase serotonin and oxytocin improving mood and affiliation. It can increase self-acceptance and   interpersonal trust. These properties help in catalyzing the effective processing of emotionally distressing material. Typical MDMA effects are expected only at doses over 80 mg.


12 subjects with PTSD who have previously undergone at least 6 months of psychotherapy and 3 months of treatment with an SSRI, participated in this study. The mean duration of PTSD symptoms at entry was 18 years. In stage 1, eight subjects were randomized in a double blind manner to the full dose (125 mg followed 2.5 hours later by 62.5 mg MDMA) and four to the “active placebo” condition (25 mg, followed 2.5 hours later by 12.5 mg MDMA),with their three doses of MDMA administered in three all-day-long MDMA-assisted psychotherapy sessions. Therapy focus on experiencing and is only to a lesser extent a verbal method  ( non directive,following and encouraging the MDMA-induced psychological process) . Sessions last approximately 8 hours.


Symptom scores decreased 15.6 points (23.5%) in the full-dose subjects but this did not reach statistical significance (p = 0.066). There were no serious drug-related adverse events and no medical intervention was  necessary.Patient reported outcome measures show significant benefit from this treatment.

Comment: This is a small  exploratory study that shows that MDMA assisted psychotherapy is safe and might help resistant chronic PTSD. Study lacked power to detect a significant effect on primary outcome measure.

In another article in this issue of the journal, Mithoefer et al, who  conducted the first RCT of MDMA assisted psychotherapy ( 2011),  report that patients  maintained the benefits over a period of 17-74 months.(Mithoefer et al 2013).

Summary of the article:

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