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

• ClinicalTrials.gov Identifier: NCT02427568
• Recruitment Status: Completed
• First Posted: April 28, 2015
• Last Update Posted: June 25, 2020
• Sponsor: Multidisciplinary Association for Psychedelic Studies
• Information provided by (Responsible Party): Multidisciplinary Association for Psychedelic Studies

Study Description

Brief Summary:

This small study is designed to provide information on whether MDMA-assisted psychotherapy is safe and helpful for people with anxiety related to a life-threatening cancer or neurological illness. The research is to see if psychotherapy combined with MDMA in a therapeutic setting can ease anxiety in the face of a life threatening illness. Once enrolled in the study, people will either receive two day-long psychotherapy sessions with MDMA or placebo, with five people getting placebo and 13 getting MDMA. Anxiety, depression, sleep quality, attitudes toward death, posttraumatic growth, mindfulness, self-compassion, and overall quality of life will be measured at the start of the study and after these two sessions. People close to the participant will also complete questionnaires about the participant during the study on their mood and behavior. Participants who received placebo can enroll in "Stage 2," during which they will receive three psychotherapy sessions with MDMA, and participants who received MDMA will have a third MDMA-assisted experimental session. Anxiety and other symptoms will be measured again six and 12 months after each participant's final experimental session.

Condition or disease	Intervention/treatment	Phase
Anxiety	Drug: MDMA; Drug: Placebo	Phase 2

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 18 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Randomized, Double-Blind, Placebo-Controlled Phase 2 Pilot Study of MDMA-Assisted Psychotherapy for Anxiety Associated With a Life-Threatening Illness
• Study Start Date: April 2015
• Actual Primary Completion Date: May 2018
• Actual Study Completion Date: July 2018

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Placebo; 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 supplement half the size of the initial dose.	Drug: Placebo; Subjects undergo two day-long experimental sessions of psychotherapy; Other Name: Inactive placebo
Active Comparator: MDMA; 125 mg 3,4-methylenedioxymethamphetamine (MDMA) administered on 2 blinded experimental sessions scheduled 2 to 4 weeks apart. Initial dose possibly followed 1.25 to 2.5 hours later by a supplemental dose of 62.5 mg MDMA.	Drug: MDMA; Subjects undergo two day-long experimental sessions of psychotherapy; Other Name: 3,4-methylenedioxymethamphetamine

Outcome Measures

Primary Outcome Measures :

1. Change in State Trait Anxiety Inventory (STAI) Trait Score - Primary Endpoint [ Time Frame: Baseline - 3 months from enrollment ]
   Measure of trait anxiety from self-report measure of anxiety
2. Change in STAi score Trait score - 6 month follow up [ Time Frame: Baseline - Up to 11 months from enrollment (9 or 11 months dependent upon subject enrolled in stage 2) ]
   Measure of trait anxiety from self-report measure of anxiety
3. Change in STAI score Trait (12 month follow up) [ Time Frame: Baseline - up to 18 months from enrollment (15 or 18 months dependent upon subject enrolled in stage 2) ]
   Measure of trait anxiety from self-report measure of anxiety

Secondary Outcome Measures :

1. Change in State Trait Anxiety Inventory (STAI) State score - Primary endpoint [ Time Frame: Baseline - 3 months from enrollment ]
   Measure of state anxiety from self-report measure of anxiety
2. Change in State Trait Anxiety Inventory (STAI) State score - 6 month follow up [ Time Frame: Baseline - up to 11 months from enrollment (9 or 11 months dependent upon subject enrolled in stage 2) ]
   Measure of state anxiety from self-report measure of anxiety
3. Change in State Trait Anxiety Inventory (STAI) State score - 12 month follow up [ Time Frame: Baseline - up to 18 months from enrollment (15 or 18 months dependent upon subject enrolled in stage 2) ]
   Measure of state anxiety from self-report measure of anxiety
4. Change in Beck Depression Inventory II score - 3rd Integration session [ Time Frame: Baseline - 1.5 months from enrollment ]
   Self-report measure of depression symptoms
5. Change in Beck Depression Inventory II score - Primary Endpoint [ Time Frame: Baseline - 3 months from enrollment ]
   Self-report measure of depression symptoms
6. Change in Beck Depression Inventory II score - 6 month follow up [ Time Frame: Baseline - Up to 11 months from enrollment (9 or 11 months dependent upon subject enrolled in stage 2) ]
   Self-report measure of depression symptoms
7. Change in Beck Depression Inventory II score - 12 month follow up [ Time Frame: Baseline - Up to18 months from enrollment (15 or 18 months dependent upon subject enrolled in stage 2) ]
   Self-report measure of depression symptoms
8. Change in Global Assessment of Functioning (GAF) score - Primary Endpoint [ Time Frame: Baseline - 3 months from enrollment ]
9. Change in Global Assessment of Functioning (GAF) score - 6 month follow up [ Time Frame: Baseline - Up to 11 months from enrollment (9 or 11 months dependent upon subject enrolled in stage 2) ]
10. Change in Global Assessment of Functioning (GAF) score - 12 month follow up [ Time Frame: Baseline - Up to 18 months from enrollment (15 or 18 months dependent upon subject enrolled in stage 2) ]
11. Columbia Suicide Severity Rating Scale (CSSRS) Baseline [ Time Frame: Baseline (screening / enrollment) ]
    Interviewer-administered measure of suicidal thinking (ideation) and behavior
12. Average Pre-treatment CSSRS [ Time Frame: Average of CSSRS scores collected from 1 week post enrollment to up to 3 weeks post-enrollment ]
    Interviewer-administered measure of suicidal thinking (ideation) and behavior
13. Average CSSRS - Experimental sessions [ Time Frame: (Average) of CSSRS scores collected from all experimental sessions 1 month from enrollment and 2 months from enrollment, with at least two scores recorded during each session ]
    Interviewer-administered measure of suicidal thinking (ideation) and behavior
14. Average Post-treatment CSSRS [ Time Frame: Average scores from 1 month+1 day from enrollment to 3 months from enrollment ]
    Interviewer-administered measure of suicidal thinking (ideation) and behavior
15. 6 month Follow up CSSRS [ Time Frame: Up to 11 months post day of drug administration 2 (9 or 11 months dependent upon subject enrolled in stage 2) ]
    Interviewer-administered measure of suicidal thinking (ideation) and behavior
16. 12 month Follow up CSSRS [ Time Frame: Up to 18 months post day of drug administration 2 (15 or 18 months dependent upon subject enrolled in stage 2) ]
    Interviewer-administered measure of suicidal thinking (ideation) and behavior
17. Change in MADRS score - Primary endpoint [ Time Frame: Baseline - 3 months from enrollment ]
    Montgomery Asberg Depression Scale; short interview measuring depression
18. Change in MADRS score - Six-month follow up [ Time Frame: Baseline - Up to 11 months from enrollment (9 or 11 months dependent upon subject enrolled in stage 2) ]
    Montgomery Asberg Depression Scale; short interview measuring depression
19. Change in MADRS score - 12-month follow up [ Time Frame: Baseline - Up to 18 months from enrollment (15 or 18 months dependent upon subject enrolled in stage 2) ]
    Montgomery Asberg Depression Scale; short interview measuring depression
20. Pittsburgh Sleep Quality Inventory (PSQI) - Primary Endpoint [ Time Frame: Baseline - 3 months from enrollment ]
    Self-report measure of sleep quality
21. Pittsburgh Sleep Quality Inventory (PSQI) - 6 month follow up [ Time Frame: Baseline - Up to 11 months from enrollment (9 or 11 months dependent upon subject enrolled in stage 2) ]
    Self-report measure of sleep quality
22. Pittsburgh Sleep Quality Inventory (PSQI) - 12 month follow up [ Time Frame: Baseline - Up to 18 months post day of drug administrastion 2 (15 or 18 months dependent upon subject enrolled in stage 2) ]
    Self-report measure of sleep quality
23. Change in Posttraumatic Growth Inventory (PTGI) - Primary Endpoint [ Time Frame: Baseline - 3 months from enrollment ]
    Self-report measure of post-traumatic growth
24. Change in Posttraumatic Growth Inventory (PTGI) - 6 month follow up [ Time Frame: Baseline - Up to 11 months from enrollment (9 or 11 months dependent upon subject enrolled in stage 2) ]
    Self-report measure of post-traumatic growth
25. Change in Posttraumatic Growth Inventory (PTGI) - 12 month follow up [ Time Frame: Baseline - Up to 18 months post day of drug administration 2 (15 or 18 months dependent upon subject enrolled in stage 2) ]
    Self-report measure of post-traumatic growth
26. Posttraumatic Growth Inventory, Caregiver form - Primary Endpoint [ Time Frame: Baseline - 3 months from enrollment ]
    Modified version of the PTGI completed by selected caregiver
27. Posttraumatic Growth Inventory, Caregiver form - 6 month follow up [ Time Frame: Baseline - Up to 11 months from enrollment (9 or 11 months dependent upon subject enrolled in stage 2) ]
    Modified version of the PTGI completed by selected caregiver
28. Posttraumatic Growth Inventory, Caregiver form - 12 month follow up [ Time Frame: Baseline - Up to 18 months from enrollment (15 or 18 months dependent upon subject enrolled in stage 2) ]
    Modified version of the PTGI completed by selected caregiver
29. Functional Assessment of Chronic Illness Therapy Scale (FACIT-Sp) - Primary Endpoint [ Time Frame: Baseline - 3 months from enrollment ]
    Self-report measure of quality of life designed for people with life-threatening illnesses
30. Functional Assessment of Chronic Illness Therapy Scale (FACIT-Sp) - 6 month follow up [ Time Frame: Baseline - Up to 11 months from enrollment (9 or 11 months dependent upon subject enrolled in stage 2) ]
    Self-report measure of quality of life designed for people with life-threatening illnesses
31. Functional Assessment of Chronic Illness Therapy Scale (FACIT-Sp) - 12 month follow up [ Time Frame: Baseline - Up to 18 months from enrollment (16 or 18 months dependent upon subject enrolled in stage 2) ]
    Self-report measure of quality of life designed for people with life-threatening illnesses
32. Change in Death Attitude Profile (DAP) - Primary Endpoint [ Time Frame: Baseline -3 months from enrollment ]
    Self-report measure of attitudes concerning death
33. Change in Death Attitude Profile (DAP) - 6 Month Follow up [ Time Frame: Baseline - Up to 11 months from enrollment (9 or 11 months dependent upon subject enrolled in stage 2) ]
    Self-report measure of attitudes concerning death
34. Change in Death Attitude Profile (DAP) - 12 Month Follow up [ Time Frame: Baseline - Up to 18 months from enrollment (15 or 18 months dependent upon subject enrolled in stage 2) ]
    Self-report measure of attitudes concerning death
35. Change in Five-Factor Mindfulness Questionnaire (FFMQ) - Primary Endpoint [ Time Frame: Baseline - 3 months from enrollment ]
    Self-report questionnaire on mindfulness
36. Change in Five-Factor Mindfulness Questionnaire (FFMQ) - 6 Month follow up [ Time Frame: Baseline - Up to 11 months from enrollment (9 or 11 months dependent upon subject enrolled in stage 2) ]
    Self-report questionnaire on mindfulness
37. Change in Five-Factor Mindfulness Questionnaire (FFMQ) - 12 Month follow up [ Time Frame: Baseline - Up to 18 months from enrollment (15 or 18 months dependent upon subject enrolled in stage 2) ]
    Self-report questionnaire on mindfulness
38. Change in Self-Compassion Scale (SCS) - Primary Endpoint [ Time Frame: Baseline - 3 months from enrollment ]
    Self-report measure of self-compassion
39. Change in Self-Compassion Scale (SCS) - 6 Month follow up [ Time Frame: Baseline - Up to 11 months from enrollment (9 or 11 months dependent upon subject enrolled in stage 2) ]
    Self-report measure of self-compassion
40. Change in Self-Compassion Scale (SCS) - 12 Month follow up [ Time Frame: Baseline - Up to 18 months from enrollment (15 or 18 months dependent upon subject enrolled in stage 2) ]
    Self-report measure of self-compassion
41. Long Term Follow Up Questionnaire - 6 Month follow up [ Time Frame: 9 or 11 months from enrollment (dependent upon enrollment in stage 2) ]
42. Long Term Follow Up Questionnaire - 12 Month follow up [ Time Frame: 15 or 18 months from enrollment (depending upon enrollment in stage 2) ]
43. Observer Rating Form scores - Baseline [ Time Frame: Baseline ]
    Measure of participant mood, demeanor and behavior completed by up to 3 individuals selected by the participant
44. Observer Rating Form scores - Primary Endpoint [ Time Frame: 3 months from enrollment ]
    Measure of participant mood, demeanor and behavior completed by up to 3 individuals selected by the participant
45. Observer Rating Form scores - 6 Month follow up [ Time Frame: Up to 11 months day from enrollment (9 or 11 months dependent upon subject enrolled in stage 2) ]
    Measure of participant mood, demeanor and behavior completed by up to 3 individuals selected by the participant
46. Observer Rating Form scores - 12 Month follow up [ Time Frame: Up to 18 months from enrollment (15 or 18 months dependent upon subject enrolled in stage 2) ]
    Measure of participant mood, demeanor and behavior completed by up to 3 individuals selected by the participant
47. Brief Pain Inventory - Short Version (BPI-S) - Baseline [ Time Frame: Baseline value ]
    Self-report measure of pain symptoms
48. Average Brief Pain Inventory - Short Version (BPI-S) Score after drug [ Time Frame: 1 and 2 months from enrollment (averaged) ]
    Self-report measure of pain symptoms
49. Brief Pain Inventory - Short Version (BPI-S) Score - Primary Endpoint [ Time Frame: 3 months from enrollment ]
    Self-report measure of pain symptoms
50. Average pre-drug Systolic Blood Pressure (SBP) [ Time Frame: Averaged pre-drug SBP across readings on two separate drug administration days 1 month and 2 months from enrollment ]
    Single SBP value prior to drug administration, for comparison with maximum and final readings
51. Average peak Systolic Blood Pressure (SBP) [ Time Frame: Average peak SBP across two separate druga dministration days 1 month and 2 months from enrollment ]
    Highest SBP value recorded during 8 hours of experimental session
52. Average end of Session Systolic Blood Pressure (SBP) [ Time Frame: Average end of session SBP across two separate drug administration days 1 month and 2 months from enrollment ]
    Last SBP value recorded for experimental session
53. Average pre-drug diastolic blood pressure (DBP) [ Time Frame: Averaged pre-drug DBP across two separate drug administration days 1 month and 2 months from enrollment ]
    Single DBP value prior to drug administration, for comparison with peak and end of session readings.
54. Average peak diastolic blood pressure (DBP) [ Time Frame: Average peak DBP across two separate drug administration days 1 month and 2 months from enrollment ]
    Highest DBP value recorded during 8 hours of experimental session
55. Average end of session diastolic blood pressure (DBP) [ Time Frame: Average end of session DBP across two separate drug administration days 1 month and 2 months from enrollment ]
    Last DBP value recorded for experimental session
56. Average pre-drug heart rate (HR) [ Time Frame: Averaged pre-drug HR across two separate drug administration days 1 month and 2 months from enrollment ]
    Single HR value prior to drug administration, for comparison with peak and end of session readings.
57. Average peak heart rate (HR) [ Time Frame: Average peak HR across two separate drug administration days 1 month and 2 months from enrollment ]
    Highest heart rate value recorded during 8-hour experimental session
58. Average end of session heart rate (HR) [ Time Frame: Averaged end of session HR across two separate drug administration days 1 month and 2 months from enrollment ]
    Last heart rate value recorded for experimental session
59. Average pre-drug body temperature [ Time Frame: Averaged pre-drug body temperature (BT) across two separate drug administration days 1 month and 2 months from enrollment ]
    Single BT value prior to drug administration, for comparison with peak and end of session readings.
60. Average peak body temperature [ Time Frame: Average peak BT across two separate drug administration days 1 month and 2 months from enrollment ]
    Highest body temperature value recorded during 8-hour experimental session
61. Average end of session body temperature [ Time Frame: Average end of session BT across two separate drug administration days 1 month and 2 months from enrollment ]
    Last body temperature reading for experimental session
62. Average pre-drug Subjective Units of Distress (SUD) [ Time Frame: Averaged pre-drug SUD across drug administration 1, drug administration 2 ]
    Single SUD rating level of distress on 1-7 scale
63. Average peak Subjective Units of Distress (SUD) [ Time Frame: Average peak SUD across two separate drug administration days 1 month and 2 months from enrollment ]
    Highest rating level of distress on 1-7 scale during each 8-hour experimental session
64. Average end of session Subjective Units of Distress (SUD) [ Time Frame: Average end of session SUD across two separate drug administration days 1 month and 2 months from enrollment ]
    Last rating level of distress on 1-7 scale

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, California

Offices of Philip Wolfson MD

San Anselmo, California, United States, 94960

Sponsors and Collaborators

Multidisciplinary Association for Psychedelic Studies

Investigators

• Principal Investigator: Philip Wolfson, MD; Private Practice

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Wolfson PE, Andries J, Feduccia AA, Jerome L, Wang JB, Williams E, Carlin SC, Sola E, Hamilton S, Yazar-Klosinski B, Emerson A, Mithoefer MC, Doblin R. MDMA-assisted psychotherapy for treatment of anxiety and other psychological distress related to life-threatening illnesses: a randomized pilot study. Sci Rep. 2020 Nov 24;10(1):20442. doi: 10.1038/s41598-020-75706-1.

• Responsible Party: Multidisciplinary Association for Psychedelic Studies
• ClinicalTrials.gov Identifier: NCT02427568
• Other Study ID Numbers: MDA-1
• First Posted: April 28, 2015
• Last Update Posted: June 25, 2020
• Last Verified: December 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: We will share outcome data appearing in any published reports upon request.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF)
• Time Frame: Data and study-related documents will be available when all participants have completed the study, and when data has been quality checked and locked.
• Access Criteria: Interested persons should correspond with the central contact for the multisite study.

Keywords provided by Multidisciplinary Association for Psychedelic Studies:

Anxiety; MDMA; Life-threatening illness; psychotherapy

Additional relevant MeSH terms:

Anxiety Disorders; Mental Disorders; N-Methyl-3,4-methylenedioxyamphetamine; Hallucinogens; Physiological Effects of Drugs; Psychotropic Drugs; Serotonin Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Adrenergic Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Adrenergic Agents