A Test of MDMA-Assisted Psychotherapy in People With Posttraumatic Stress Disorder

Posttraumatic stress disorder (PTSD) occurs in response to a traumatic event or events. It
is most likely to occur following an event involving perceived personal threat, such as rape
or physical assault. PTSD is clearly a public health problem that causes a great deal of
suffering and accounts for a significant portion of health care costs. This study will
examine whether two sessions of methylenedioxymethamphetamine (MDMA)-assisted psychotherapy
can be safely administered to participants with PTSD, and whether MDMA-assisted
psychotherapy, when compared with placebo-assisted therapy, will reduce PTSD symptoms after
each session and two months after the second session.

MDMA is a substance possessing unique effects that make it well suited to intensive
psychotherapy. MDMA has been hypothesized to represent a new class of drugs, called
entactogens, that produce feelings of closeness to others, empathy, well being, and
insightfulness. Currently, MDMA is scheduled (illegal) and cannot be used outside of
research studies like this one. Anecdotal reports of therapy conducted before MDMA was made
illegal suggest that MDMA-assisted psychotherapy may benefit people with PTSD.

This study will examine MDMA-assisted psychotherapy in twenty people ages 18 to 70 with PTSD
either related to crime victimization or combat, when combat-related PTSD lasts no longer
than five years, and that has not gotten better after psychotherapy and treatment with an
SSRI (selective serotonin uptake inhibitor, such as Paxil).

This study lasts three to four months. Participants attend up to fourteen (14) ordinary
(non-drug) psychotherapy sessions with the investigators as well as two eight hour long
experimental (MDMA or placebo) sessions and one MDMA session. People taking part in this
study cannot take any psychiatric medication during the study period. People will either get
125 mg MDMA or placebo "by chance," as by coin-toss, with twelve of twenty (60%) getting
MDMA during each experimental session, and eight of twenty (40%) getting placebo. Two to two
and a half hours later, if you and the investigators agree it is alright, you will take a
second supplemental, dose of MDMA or placebo. The supplemental dose will be half the size of
the first dose. The same investigators conducting non-drug therapy sessions conduct the
experimental sessions. All participants are required to stay the night at the clinic after
each experimental session. Participants meet with the investigators for a non-drug assisted
therapy session the day after each experimental session. A third MDMA session in this
placebo-controlled stage of the study will only be for people who received MDMA in the first
two sessions.

PTSD symptoms are measured at the start of the study, four days after each experimental
session, and finally two months after the second experimental session. People are tested on
memory and problem solving when they first enter the study and again two months after the
second experimental session. PTSD symptoms are measured to see whether there are any changes
in symptoms during the study, and tests of thinking, memory and problem-solving are meant to
spot any changes that could be due to MDMA or MDMA-assisted therapy.

Participants who recieved MDMA who complete the final evaluation, and upon discussion with
the investigators, will undergo a third MDMA session. The third session will happen
approximately two months after the second experimental session This session is "open label,"
meaning that they and the investigators will both know they are receiving MDMA. It will be
followed by one psychotherapy session a day after this session and two additional
psychotherapy sessions in the following weeks. PTSD symptoms will be measured again two
months after the third MDMA session.

Participants who received placebo and complete the final evaluation two months after the
second experimental procedure will be given an opportunity to take part in an open-label
continuation of the study where they will receive an initial dose of 125 mg MDMA and a
supplemental dose of 62.5 mg MDMA in up to three experimental sessions scheduled three to
five weeks apart. Participants in this open-label continuation will act as their own
controls. The open-label continuation lasts three months and will involve nine more visits
with the investigators, including the two experimental sessions.

Inclusion Criteria:

- Be diagnosed with chronic PTSD, duration of 5 years or longer resulting from
traumatic experience during military service or a victim of crime;

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

1. 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.

2. 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:

- 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 50 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 study