Study Comparing Three Doses of MDMA Along With Psychotherapy in Veterans With Posttraumatic Stress Disorder

Posttraumatic stress disorder (PTSD) is a debilitating mental disorder, that can develop
after service in the armed forces. Psychotherapy performed along with MDMA is an innovative
form of therapy for posttraumatic stress disorder. This study will follow on the findings of
an initial pilot study in a sample largely made up of people whose PTSD did not develop from
serving in the military. This study will investigate whether MDMA-assisted psychotherapy is
safe and efficacious in a sample of veterans and whether maintaining an effective
double-blind can be better addressed by performing a dose comparison study.

This study is a randomized, double-blind, dose comparison study with an open-label cross-over
segment that will assess the safety and efficacy of MDMA-assisted psychotherapy in veterans
with chronic posttraumatic stress disorder. Twelve of 24 participants will receive the full
dose of 125 mg, six will receive 75 mg and six will receive 30 mg (active placebo dose). An
independent rater blind to condition will assess symptoms of PTSD and depression, general
quality of life and posttraumatic growth prior to any psychotherapy sessions one month after
the second experimental session.

After undergoing three 90-minute non-drug introductory psychotherapy sessions with a
male/female co-therapist team, study participants will undergo two eight-hour long
experimental sessions scheduled three to five weeks apart, during which they will randomly
receive either 30, 75 or 125 mg MDMA on both occasions, followed by a supplemental dose of
half the initial dose. Participants will undergo integrative psychotherapy in between each
experimental session, including on the day after each session. Vital signs and psychological
distress will be measured throughout each experimental session, and suicidality will be
assessed throughout the course of the study. Spontaneously reported side effects will be
collected on the day of each experimental session, and for six days afterward. PTSD symptoms,
symptoms of depression, general psychological function, posttraumatic growth and quality of
sleep will be assessed one month after the second experimental session, and the blind will be
broken.

Participants who received 125 mg MDMA will continue to have a third experimental session, and
they will be assessed two months after the third experimental session.

Participants who received 30 or 75 mg MDMA may take part in an open-label crossover segment
that will follow nearly identical procedures, except that there will only be one introductory
session prior to the first experimental session. There will be three experimental sessions.
Symptoms of PTSD, depression and posttraumatic growth will be assessed at the start of the
study. They will also be assessed one month after the second and two months after the third
experimental session.

All participants will be assessed 12 months after their final experimental session. PTSD and
depression symptoms and posttraumatic growth will be assessed, and participants will complete
a questionnaire concerning the costs and benefits of being in the study.

Inclusion Criteria:

- Be diagnosed with chronic PTSD, duration of 6 months or longer resulting from
traumatic experience during military service;

- Have a CAPS score showing moderate to severe PTSD symptoms;

- Have had at least one unsuccessful attempt at treatment for PTSD either with talk
therapy or with drugs, or discontinuing treatment because of inability to tolerate
psychotherapy or drug therapy.

- Are at least 18 years old;

- Must be generally healthy;

- Must sign a medical release for the investigators to communicate directly with their
therapist and doctors;

- Are willing to refrain from taking any psychiatric medications during the study
period;

- Willing to follow restrictions and guidelines concerning consumption of food,
beverages, and nicotine the night before and just prior to each experimental session;

- Willing to remain overnight at the study site;

- Agree to have transportation other than driving themselves home or to where they are
staying after the integrative session on the day after the MDMA session;

- Are willing to be contacted via telephone for all necessary telephone contacts;

- Must have a negative pregnancy test if able to bear children, and agree to use an
effective form of birth control;

- Must provide a contact in the event of a participant becoming suicidal;

- Are proficient in speaking and reading English;

- Agree to have all clinic visit sessions recorded to audio and video

- Agree not to participate in any other interventional clinical trials during the
duration of this study.

Exclusion Criteria:

5.3.2 Exclusion Criteria:

- Are pregnant or nursing, or if a woman who can have children, those who are not
practicing an effective means of birth control;

- Weigh less than 48 kg;

- Are abusing illegal drugs;

- Are unable to give adequate informed consent;

- Upon review of past and current drugs/medication must not be on or have taken a
medication that is exclusionary.

- Upon review of medical or psychiatric history must not have any current or past
diagnosis that would be considered a risk to participation in the s