Drug assisted psychotherapy to treat posttraumatic stress disorder in war veterans, using 3,4-methylenedioxymethamphetamine (commonly known as MDMA).

This is a two arm, randomised, multi-dose study with an additional open label lead-in for two participants. The open label lead-in will involve two participants receiving two experimental drug-assisted psychotherapy sessions of approximately eight hours duration each, using the full dose of 125mg 3,4-methylenedioxymethamphetamine (MDMA) with an optional supplemental dose 2.5 hours later of 62.5mg MDMA (cumulative dose 187.5mg, administered as capsules). At the commencement of each experimental session the participant will undergo a urine drug screen and pregnancy test, a psychological assessment and then begin acclimatising to the environment. The MDMA will be administered soon afterwards, approximately 30-60 minutes after the session begins. The two drug-assisted psychotherapy sessions will be 3-5 weeks apart and form part of a 12 session treatment over six months, which includes 10 non-drug psychotherapy sessions of 90 minutes duration for preparatory, integrative and follow-up purposes. The session sequence will be as follows. Sessions 1,2,3: Non-drug preparatory psychotherapy. Session 4: Experimental drug-assisted psychotherapy. Sessions 5,6,7: Non-drug integrative psychotherapy. Session 8: Experimental drug-assisted psychotherapy. Sessions 9,10,11: Non-drug integrative psychotherapy. Session 12: Non-drug follow-up psychotherapy. The aim of the open label lead-in is to verify therapist adherence to the psychotherapy manual prior to proceeding with Stage 1. Stage 1 is double-blinded and will compare 125mg MDMA versus 30mg MDMA active placebo in the remaining 12 participants. The 30mg MDMA active placebo is not expected to provide therapeutic benefits and is aimed at ensuring an effective blind by producing some physiological effects. Those randomised to receive the full dose in Stage 1 will receive two drug-assisted psychotherapy sessions and 10 non-drug psychotherapy sessions of exactly the same duration and sequence as those in the lead-in. Those randomised to receive the active placebo in Stage 1 will receive two drug-assisted (active placebo) psychotherapy sessions using 30mg MDMA with an optional supplemental dose of 15mg MDMA (cumulative dose 45mg) and 10 non-drug psychotherapy sessions. The session duration and the sequence of the 12 sessions will be exactly the same as those in the lead-in. Stage 2 is an optional treatment for those participants (only) who received the active placebo in Stage 1. After unblinding at the end of Stage 1, eligible participants who choose to complete Stage 2 will undergo an open label full dose treatment involving two drug-assisted psychotherapy sessions and eight non-drug psychotherapy sessions. The session durations will be the same as for the lead-in. The session sequence for Stage 2 is as follows. Session 1: Non-drug preparatory psychotherapy. Session 2: Experimental drug-assisted psychotherapy. Sessions 3,4,5: Non-drug integrative psychotherapy. Session 6: Experimental drug-assisted psychotherapy. Sessions 7,8,9: Non-drug integrative psychotherapy. Session 10: Non-drug follow-up psychotherapy. All study participants will attend an additional long term follow-up session 12 months after their final experimental drug-assisted session.