MDMA-assisted Therapy in People With Anxiety Related to Advanced Stage Cancer

People who learn they have cancer can feel frightened, upset and depressed, and a diagnosis
of advanced stage cancer can generate intense anxiety. People with advanced stage cancer may
be anxious about their deteriorating health and the nearness of death, disruption in their
close relationships caused by current or future changes in health, and grief for the life
planned and expected prior to learning they had advanced stage cancer. There are treatments
for reducing intense anxiety, such as Valium and related drugs, but these drugs have unwanted
side effects that may be especially distressing for people already taking medication for pain
control and seeking to remain clear-headed.

3,4-methylenedioxymethamphetamine (MDMA) is a drug that can produce effects uniquely suited
to reducing anxiety for people with anxiety arising from a cancer diagnosis. MDMA has been
hypothesized to belong to a class of drugs, called entactogens, that produce feelings of
closeness to others, empathy, wellbeing, and insightfulness. Currently, MDMA is scheduled
(illegal) and cannot be used outside of research studies like this one. However, prior to its
being made illegal, some psychotherapists treated people with cancer or other terminal
illnesses with MDMA-assisted psychotherapy, and they reported a reduction in anxiety and
improved quality of life.

This study will examine the effects of MDMA-assisted psychotherapy in 12 people aged 18 or
older who have received a diagnosis of advanced stage cancer (usually meaning inoperable and
with metastases) who have anxiety as a result of this diagnosis that is either not helped by
conventional anti-anxiety medication (such as Xanax or Valium), or who do not wish to take
these medications because of their side effects. In Stage 1, all study subjects will receive
an initial dose of MDMA followed by a second (supplemental) dose approximately two and a half
hours later if the initial dose does not produce any problems. Eight of twelve study subjects
will get 83.3 mg MDMA followed by 47.1 mg the first time, and 125 mg followed by 67.5 mg the
second time. Four of twelve study subjects will receive 25 mg followed by 12.5 mg MDMA.
Whether a person receives low doses or full doses of MDMA will be decided at random, as if by
coin toss, and none of the researchers will know which dose of MDMA a person will get in
Stage 1. The four subjects who received the lower doses of MDMA in Stage 1 may continue to
participate into Stage 2 in which they repeat the study except that they will receive
open-label 83.3 mg MDMA followed by 47.1 mg the first time, and 125 mg followed by 67.5 mg
the second time. The eight participants in Stage 1 who had MDMA-assisted psychotherapy
sessions at these higher dose strengths will not continue into Stage 2. The Stage 2 study
extension will provide potential additional data on the MDMA doses being evaluated without
having to recruit additional subjects.

For Stage 1, the study will last 14 weeks (about three and a half months). All study
participants will have six (6) hour-long psychotherapy sessions and two (2) MDMA-assisted
psychotherapy sessions lasting six to eight hours and requiring an overnight stay at the
treatment facilities. The ordinary and MDMA-assisted sessions will be conducted by the same
therapists. For the four subjects continuing into Stage 2, the study will last an additional
10 weeks (about two and a half months) with additional six (6) hour-long psychotherapy
sessions and two (2) MDMA-assisted psychotherapy sessions lasting six to eight hours and
requiring an overnight stay at the treatment facilities.

People enrolled in the study can continue taking anti-anxiety medications, but cannot take
any other psychiatric medications for the entire course of the study. They can take their
usual pain control medications, but if they take more pain control medications than usual on
the day of the MDMA-assisted session, they may have to delay or reschedule the session.
People enrolled in this study will complete questionnaires about their anxiety and quality of
life, and they will keep a daily diary where they write down how much anxiety and pain
control medication they are using, and a daily record of the amount of pain they experience.

Anxiety and quality of life will be measured at the start of the study, before each sessions
of MDMA-assisted therapy, one week after receiving MDMA-assisted therapy and once at the end
of the study, 84 days after a person started the study (approximately two months after the
second MDMA-assisted psychotherapy session; for Stages 1 and 2). All study subjects will also
receive a second medical examination 36 days after the study has begun (and again 36 days
after starting Stage 2). The medical examination will be performed at the Lahey Clinic
Medical Center's Medical Oncology department or at McLean Hospital.

Study participants will not be paid for taking part in the study. We will pay for all tests
and measures used to determine study eligibility. Transportation, if needed, will also be
paid for by the study. MDMA-assisted sessions require overnight stay at McLean Hospital: we
will provide overnight accommodations and all meals and snacks for the subject and a
significant support person of the subject's choosing on those days.

Inclusion Criteria:

- Diagnosis with advanced-stage cancer (usually meaning inoperable or incurable) with a
life expectancy of less than 12 months.

- Anxiety as a result of cancer diagnosis

- Failure to respond adequately or at all to medication intended to reduce anxiety, or
have refused to take anxiolytic medication.

- Completed or independently decided to end all direct cancer treatments, such as
chemotherapy and radiation, two weeks prior to the first experimental (MDMA) session.
If subjects wish to initiate or resume treatment for cancer at any point prior to the
second experimental (MDMA) session, then they will be withdrawn from the study and
will be asked to see the co-investigator oncologist for a final physical examination.
Participants will not be withdrawn from the study if they initiate or resume treatment
after the second experimental (MDMA) session. Those who are receiving cycles of cancer
treatments for only palliative purposes (no longer for any curative reasons or to
induce complete remission), may also be included in this study provided that they, as
well, have completed their last cycle of treatment at least two weeks prior to the
first experimental (MDMA) session and provided that they will not resume another cycle
of treatment until after completion of the second experimental (MDMA) session. If a
subject receiving palliative cancer treatment decides to receive a next cycle of this
cancer treatment prior to the second experimental session, then, again, they will be
withdrawn from the study. Participants will not be withdrawn from the study if they
initiate or resume palliative cancer treatments after the second experimental (MDMA)
session.

- Willing to commit to and follow all directions and restrictions relating to the study
period

- Must be willing and able to discontinue use of psychiatric medication except that
being used to treat anxiety. If still taking medication when enrolled to the study,
medication will be discontinued long enough before the first MDMA-assisted
psychotherapy session to avoid a drug-drug interaction

- Must be willing and able to stay overnight at the facility after each MDMA-assisted
session.

- If seeing another psychotherapist, participants must be willing to give the principal
investigator permission to communicate with him or her.

- Female participants of childbearing potential must have a negative pregnancy test and
must agree to use an effective form of birth control.

Exclusion Criteria:

- People with a life expectancy of longer than 12 months

- Women who are pregnant or nursing, or of child bearing potential and are not
practicing an effective means of birth control.

- People with any dissociative disorder, anorexia nervosa, bulimia nervosa, a primary
psychotic disorder or affective disorder other than anxiety related to advanced stage
cancer

- People diagnosed with abuse of or dependence on any substance (other than caffeine or
nicotine) in the past 60 days.

- People with known primary or metastatic cancer of the CNS

- People with significant, unstable hematological, endocrine, cerebrovascular,
cardiovascular, coronary, pulmonary, renal, gastrointestinal, immunocompromising, or
neurological disease, including seizure disorder, that in the clinical judgment of the
investigators poses too great a potential for side-effects.

- People with significant peripheral vascular disease, hepatic disease, renal
insufficiency, or preexisting or past evidence of hyponatremia.

- People diagnosed with hypertension, even if well-controlled with medication. A
systolic blood pressure of 140 or greater and/or a diastolic blood pressure of 90 or
greater will exclude the potential participant from this study.

- People with liver enzyme values indicative of severely compromised hepatic (liver)
function

- People who weigh less than 45 kg (98 lb)

- People reporting a history of use of "ecstasy" (illicit drug preparations purported to
contain MDMA) at any time within the previous 3 months.

- People reasonably judged to present a serious suicide risk or who are likely to
require psychiatric hospitalization during the course of the study

- People requiring psychotropic medication other than anxiolytic medication or for pain
control