This Phase 2 pilot study is a randomized, double-blind, placebo-controlled study in 18
participants comparing the effects of MDMA-assisted therapy vs. placebo with therapy.
Thirteen participants were randomized to the active dose condition of 125 mg of MDMA
(plus an optional supplemental dose of 62.5 mg MDMA) with therapy and five participants
were randomized to the placebo with therapy condition. The study will consist of two
blinded experimental sessions of MDMA-assisted therapy or placebo with therapy, each
session lasting six to eight hours and scheduled two to four weeks apart. Each
participant will be unblinded one month after their second experimental session in Stage
1. After unblinding, participants receiving placebo will have the opportunity to cross
over to open-label Stage 2 and receive active MDMA. Only subjects who receive active dose
MDMA will complete an optional third open-label experimental session.

MDMA-Assisted Psychotherapy for Anxiety Associated With a Life-Threatening Illness

Anxiety

Individuals facing, or who have faced, a life-threatening illness contend with more than
just the physical symptoms of their condition and may experience anxiety, depression,
anger, and despair that can exacerbate their distress. 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 have
anxiety related to having a life-threatening illness.

This Phase 2 pilot study is a randomized, double-blind, placebo-controlled study in 18
participants comparing the effects of MDMA-assisted therapy vs. placebo with therapy.
Thirteen participants were randomized to the active dose condition of 125 mg of MDMA
(plus an optional supplemental dose of 62.5 mg MDMA) with therapy and five participants
were randomized to the placebo with therapy condition. The study will consist of two
blinded experimental sessions of MDMA-assisted therapy or placebo with therapy, each
session lasting six to eight hours and scheduled two to four weeks apart. Each
participant will be unblinded one month after their second experimental session in Stage
1. After unblinding, participants receiving MDMA will complete a third open-label
experimental session of MDMA-assisted therapy and participants who originally received
placebo will have the opportunity to cross over to open-label Stage 2 and receive active
MDMA-assisted therapy in 3 sessions.

The primary objective of the study is to assess changes in trait anxiety in subjects
receiving active dose MDMA compared to those receiving placebo as measured by State-Trait
Anxiety Index (STAI) Trait scores from Baseline to the Primary Endpoint (one month after
the second experimental session).

MDMA (125 mg)

Placebo

Therapy

A Randomized, Double-Blind, Placebo-Controlled Phase 2 Pilot Study of MDMA-Assisted Psychotherapy for Anxiety Associated With a Life-Threatening Illness

The State-Trait Anxiety Inventory (STAI) is a 20-item self-report measure of intensity of
anxiety. Each item consists of a 4-point Likert rating scale ranging from 1 ('Not at
all') to 4 ('Very Much So'), with higher scores indicating greater anxiety. Items were
summed for a total score that ranged from 20 to 80.

The STAI differentiates between State Anxiety, defined as "anxiety experienced in
reaction to a specific environmental circumstance," and Trait Anxiety, defined as
"long-standing nervous affect or anxiety disorder." The use of the trait subscale as the
primary outcome measure was intended to target those anxiety symptoms that are chronic
and pervasive.

The State-Trait Anxiety Inventory (STAI) is a 20-item self-report measure of intensity of
anxiety. Each item consists of a 4-point Likert rating scale ranging from 1 ('Not at
all') to 4 ('Very Much So'), with higher scores indicating greater anxiety. Items were
summed for a total score that ranged from 20 to 80.

The STAI differentiates between State Anxiety, defined as "anxiety experienced in
reaction to a specific environmental circumstance," and Trait Anxiety, defined as
"long-standing nervous affect or anxiety disorder." The use of the trait subscale as the
primary outcome measure is intended to target those anxiety symptoms that are chronic and
pervasive.

The state subscale of the STAI (STAI-S) is a 20-item self-reported scale which assesses
subjects' levels of transient, situationally oriented, anxiety. Like the trait subscale,
participants respond to each item on the state subscale by selecting a response from a
4-point Likert scale ranging from 4 ("Not at all") to 1 ("Very much so"), with higher
scores indicating greater anxiety. Items were summed for a total score that ranged from
20 to 80.

The STAI differentiates between State Anxiety, defined as "anxiety experienced in
reaction to a specific environmental circumstance," and Trait Anxiety, defined as
"long-standing nervous affect or anxiety disorder." The use of the trait subscale as the
primary outcome measure is intended to target those anxiety symptoms that are chronic and
pervasive.

The Beck Depression Inventory-II (BDI-II) is a a 21-item self-reported measure of
depression according to Diagnostic and Statistical Manual IV (DSM-IV) criteria. Each item
is rated on a 4-point Likert scale ranging from 0 to 3. The total score is the sum of 21
items and range from 0 to 63. Score cutoffs indicate: 0-13 minimal depression, 14-19 mild
depression, 20-28 moderate depression, and 29-63 severe depression. Higher scores
indicate more severe depressive symptoms.

The Global Assessment of Function (GAF) is a measure of a person's global social
functioning made through clinical observation. The GAF consists of a single score, with
scores ranging from 0 to 100, with 100 reflecting superior function and zero reflecting
serious risk of causing harm to the self or others.

The Montgomery-Asberg Depression Rating Scale (MADRS) is a 10-item, clinician
administered questionnaire used to diagnose the severity of depressive episodes. Each
item has a score of 0 to 6. Overall scores are summed and range from 0 to 60. Score
cutoffs indicate: 0-6 normal/symptom absent, 7-19 mild depression, 20-34 moderate
depression, > 34 severe depression. Higher scores indicate greater severe depression.

The Pittsburgh Sleep Quality Index (PSQI) is a measure of self-reported sleep quality
over a one month period. It consists of 19 items with possible responses ranging from
zero to four on a five-point scale. The PSQI consists of seven sub-scales: sleep quality,
sleep latency, sleep duration, habitual sleep efficiency, sleep disturbance, use of
sleeping medications, and daytime dysfunction. These are all summed to produce a single
global scale. Global scores can range from 0 to 21, with higher scores reflecting poorer
sleep quality, and a score below 5 indicating good sleep quality.

The Posttraumatic Growth Inventory (PTGI) is a 21-item self-report measure of perceived
growth or benefits occurring after a traumatic event. It contains five subscales;
relationship to others, new possibilities, personal strength, spiritual change, and
appreciation of life. Questions are answered on a scale from 0 (I did not experience this
change) to 5 (I experienced this change to a great degree). Items are added to calculate
the total PTGI score which ranges from 0 to 105, with higher scores indicative of greater
growth.

The Functional Assessment of Chronic Illness Therapy Scale (FACIT-Sp) is a 27-item
self-report measure of quality of life issues specifically relevant to individuals with a
chronic or life-threatening illness or condition. The core questionnaire consists of four
subscales: Physical Well-being, Social/Family Well-being, Emotional Well-being, and
Functional Well-being. Responses range from 0 (not at all) to 4 (very much), with higher
scores indicating greater well-being. For each subscale, total scores were summed and
range from 0 to 16.

The Death Attitudes Profile (DAP) is a 32-item self-reported questionnaire that assesses
individual attitudes and beliefs about death and dying. Each item on the scale is rated
along a 7-point Likert scale ranging from "strongly disagree" (score of 1) to "strongly
agree" (score of 7), with higher scores indicating more positive attitudes toward death.

The DAP consists of 5 dimensions: fear of death (7 items summed with total scores ranging
from 7 to 49), death avoidance (5 items summed with total scores ranging from 5 to 35),
neutral acceptance (5 items summed with total scores ranging from 5 to 35), approach
acceptance (10 items summed with total scores ranging from 10 to 70), and escape
acceptance (5 items summed with total scores ranging from 5 to 35). For each dimension, a
mean scale score can be computed by dividing the total scale score by the number of items
forming each scale.

The Self-Compassion Scale (SCS) is a 26-item self-reported questionnaire that assesses
how respondents relate to themselves and treat themselves during difficult or painful
experiences. Items are scored along a 5-point Likert-type scale ranging from 1 "almost
never" to 5 "almost always." The SCS has six component (subscale) scores: self-kindness,
self-judgment, common humanity, isolation, mindfulness, and over-identification. Subscale
scores are calculated by computing the mean of subscale item responses.

A total self-compassion score is calculated by the sum of the subscale scores and range
from 24 to 120 with higher scores indicating greater self compassion. Higher scores have
been found to correlate with positive mental health outcomes, as well as decreased
depression and anxiety.

Inactive placebo administered on 2 blinded experimental sessions scheduled 2 to 4 weeks
apart. Initial dose possibly followed 1.5 to 2.5 hours later by (optional) inactive
placebo supplemental dose.

125 mg 3,4-methylenedioxymethamphetamine (MDMA) administered on 2 blinded experimental
sessions scheduled 2 to 4 weeks apart. Initial dose possibly followed 1.5 to 2.5 hours
later by a (optional) supplemental dose of 62.5 mg MDMA.

MDMA-Assisted Psychotherapy for Anxiety Associated With a Life-Threatening Illness

About this trial

Study ID

Status

Type

Phase

Placebo

Accepting

Not accepting

Trial Timing

What is this trial about?

What are the participation requirements?

Locations

Location

Status