MDMA-assisted Psychotherapy for Anxiety Associated With a Life-threatening Illness

IIndividuals facing, or who have faced, a life-threatening illness contend with more than
just the physical symptoms of their condition. Research suggests that diagnosis of, and
living with a life-threatening illness can result in symptoms similar to those seen in
Posttraumatic Stress Disorder (PTSD).

3,-4-methylenedioxymethamphetamine (MDMA) is a monoamine releaser with a unique
pharmacological profile that include decreased feelings of fear, increased positive mood and
increased interpersonal trust. Findings from clinical trials in people with PTSD and
anecdotal reports suggest that MDMA-assisted psychotherapy may assist people who are anxious
as a result of facing a life-threatening illness.

This randomized, placebo-controlled pilot study of MDMA-assisted psychotherapy in 18 people
with anxiety stemming from a life-threatening illness examines the safety and efficacy of
this treatment. This study will allow comparison between the impact of placebo and an active
dose of MDMA-assisted psychotherapy on anxiety, depression, sleep quality, global
functioning, attitudes toward death, posttraumatic growth, mindfulness, self-compassion, and
overall quality of life.

Participants must be people of either gender aged 18 years or older diagnosed with a
life-threatening cancer or non-dementing neurological illness and anxiety resulting from
confronting this illness. Eighteen participants will be enrolled in the study. Five of 18
participants will receive placebo and 13 will receive MDMA.

Therapy will be conducted by male/female teams, some of whom will be experienced therapists,
and the others will be intern therapists under supervision of the Principal Investigator.

In the first study segment, Stage 1, all participants will have two blinded experimental
sessions of MDMA-assisted psychotherapy scheduled at a two to four week interval, within a
moderate course of non-drug psychotherapy (preparatory and integrative sessions), after which
they will complete the primary endpoint assessment. After the primary endpoint assessment,
the subject and therapists will be unblinded and fully debriefed. Participants assigned to
receive active dose MDMA will then receive a third open-label experimental session with the
same active dose of MDMA, which will complete Stage 1. Participants assigned to receive
placebo will crossover, without completing Stage 1, to an open-label study segment following
similar procedures, referred to as Stage 2. Participants enrolled in this group will receive
the same dose of MDMA as the active dose in Stage 1, with an optional supplemental half dose,
at each of three experimental sessions at time points equivalent to those in Stage 1.

Anxiety, depression, sleep quality, attitudes toward death, posttraumatic growth,
mindfulness, self-compassion, and overall quality of life will be assessed by participants'
self-report at baseline, the primary endpoint, and one month after the third experimental
session in Stage 1, and at equivalent points in Stage 2. Additional assessments of depression
and overall psychological functioning will be made by a blinded Independent Rater at these
time points. A caregiver and individuals in close relationship to the study subject will also
provide ratings of the subject's posttraumatic growth and mood. Symptoms, long-term benefits,
and harms will be assessed again at 6 months and 12 months after the final experimental
session. This study will provide an estimate of effect size based on response of
psychological symptoms to MDMA-assisted psychotherapy.

Inclusion Criteria:

- Diagnosed with life-threatening cancer or non-dementing neurological illness, which
can be ongoing or in remission, but with a possibility of recurrence

- Prognosis of at least nine months life expectancy from the time of screening

- Have anxiety as a result of facing their illness

- Are at least 18 years old

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

- Are willing to commit to medication dosing, experimental sessions, follow-up sessions,
and to complete evaluation instruments

- Are willing to remain overnight at the study site after each experimental session
until after the integrative session occurring the next morning

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

- Are willing to select up to three observers who will complete observer measures of
subject attitudes and behavior

- Negative pregnancy test if able to bear children and agree to use effective birth
control

- Are proficient in speaking and reading English

- Agree to have all psychotherapy sessions recorded to audio/video.

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, 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