Psychological Effects of Methylenedioxymethamphetamine (MDMA) When Administered to Healthy Volunteers

Study Overview
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Brief Summary
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This study will compare the effects of methylenedioxymethamphetamine (MDMA) and placebo on mood and psychological experience in people trained to practice MDMA-assistant psychotherapy in a therapy-like setting. Study participants will prepare for the experience with the investigators. After preparation, they will have two day-long sessions, one with placebo and one with MDMA, with the second session happening two days after the first. Order of session will be assigned randomly and the study will be double-blind. Subjects will complete measures and talk about the experience on the day after each session. Mood, psychological symptoms, and interpersonal closeness will be measured before and after each session. The investigators will speak with subjects again one and two months after the second experimental session, and subjects will complete a personality questionnaire two months after the second experimental session.

Detailed Description
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3,4-methylenedioxymethamphetamine (MDMA) produces changes in feelings and thoughts. It appears to have a unique pharmacological profile distinct from psychostimulants and classical hallucinogenic (psychedelic) compounds. Its unique properties have led to interest in using it in combination with psychotherapy. So far, studies in healthy volunteers have examined the effects of MDMA in a laboratory setting rather than a psychotherapeutic setting. This study is a Phase 1 study for up to a hundred people, The information gathered during this study may help us better understand the psychological effects produced by MDMA and how those effects can more effectively be used within a therapeutic context, as with people with PTSD. Participants will be healthy volunteers who have completed a program training them in conducting MDMA-assisted psychotherapy. In this randomized, double blind study, subjects will receive placebo and MDMA during two sessions scheduled at least two days apart in a psychotherapy setting. Mood, self-reported interpersonal closeness, psychological symptoms, blood pressure, heart rate and body temperature will be measured, and personality will be measured prior to the first therapy-like session and two months after the second session. The study will follow a cross-over design, meaning that all participants will receive both MDMA and placebo, with order of session randomly assigned. Study participants will have a preparatory session prior to each experimental session and an integrative session after each session. The researchers will contact them via telephone one and two months after the second experimental session. By comparing changes in mood, feelings of emotional closeness to the self and others and psychological symptoms after placebo and after MDMA, the investigators hope to learn something about the effects of MDMA on mood, subjective experience and the way we think and feel about others.

Official Title
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A Phase 1 Placebo-Controlled, Double-Blind Crossover Study to Assess Psychological Effects of MDMA When Administered to Healthy Volunteers

Conditions
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Psychological Effects of Study Drug

Intervention / Treatment
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* Drug: Lactose (inactive placebo)
* Drug: 3,4-methylenedioxymethamphetamine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: have successfully completed a sponsor-supported program for training therapists to perform MDMA-assisted psychotherapy research; are at least 21 years old; Are willing to follow all rules and restrictions related to study participation, including restrictions on medication use for a week prior to experimental sessions and restrictions on food and alcohol consumption on the day prior to each experimental session. are willing to remain overnight at the study site; agree to have transportation other than driving themselves after the integrative session on the day after each experimental session; are willing to be contacted via telephone for all necessary telephone contacts; if a woman of childbearing potential, must have a negative pregnancy test and agree to use an effective form of birth control; are proficient in speaking and reading English; agree to have all clinic visit sessions recorded to audio and video Exclusion Criteria: are pregnant or nursing, or are women of child bearing potential who are not practicing an effective means of birth control; weigh less than 48 kg; have used ecstasy (material represented as containing MDMA) within 6 months of the MDMA session; require ongoing therapy with a psychotropic drug; Are abusing illegal drugs 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.

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Lactose (Inactive Placebo)<br>Participant receives inactive placebo during day-long experimental session. Mood, interpersonal closeness, psychological symptoms are measured before, during and after the session, and vital signs (blood pressure, heart rate, body temperature) are measured during the session. | Drug: Lactose (inactive placebo)<br>* Placebo in an equivalent weight to MDMA will be administered in identical appearing capsules during one of two experimental sessions. An equivalent to the initial and supplemental dose will exist.<br>|
| Active Comparator: 3,4-methylenedioxymethamphetamine<br>Participant receives 120 mg MDMA possibly followed by 40 mg MDMA during a day-long experimental session. Mood, interpersonal closeness, psychological symptoms are measured before, during and after the session, and vital signs (blood pressure, heart rate, body temperature) are measured during the session. | Drug: 3,4-methylenedioxymethamphetamine<br>* 120 mg MDMA will be administered in opaque capsules at the outside of one of two experimental sessions, and upon mutual agreement between the investigator and participant, 60 mg may be administered 1.5 to 2.5 hours later.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Profile of Mood States (POMS) | Assesses current mood state | Experimental session approximately six hours after drug administration | 
| Profile of Mood States (POMS) | Assesses current mood state | Day prior to each experimental session | 
| Profile of Mood States (POMS) | Assesses current mood state | Day after each experimental session | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Interpersonal closeness measure | Visual analog scale assessing emotional closeness to self and four other targets | Day prior to experimental session | 
| Interpersonal closeness measure | Visual analog scale assessing emotional closeness to self and four other targets | Day of experimental session approximately six hours post-drug administration | 
| Interpersonal closeness measure | Visual analog scale assessing emotional closeness to self and four other targets | Day after each experimental session | 
| Brief Symptom Inventory (BSI) | Self-report measure assessing psychiatric symptoms | Day prior to each experimental session | 
| Brief Symptom Inventory (BSI) | Self-report measure assessing psychiatric symptoms | Day of experimental session prior to drug administration | 
| Brief Symptom Inventory (BSI) | Self-report measure assessing psychiatric symptoms | Day of experimental session approximately five to six hours after drug administration | 
| Brief Symptom Inventory (BSI) | Self-report measure assessing psychiatric symptoms | Day after each experimental session | 
| Columbia Suicide Severity Rating Scale (adapted C-SSRS) | Clinician-administered measure of suicide risk | Day prior to each experimental session | 
| Neuroticism Extroversion Openness Personality Inventory | Self-report measure of five personality factors; Neuroticism, extroversion, openness to experience, conscientiousness and agreeableness | At baseline | 
| Neuroticism Extroversion Openness Personality Inventory | Self-report measure of five personality factors; Neuroticism, extroversion, openness to experience, conscientiousness and agreeableness | Two months after the second experimental session | 
| Columbia Suicide Severity Rating Scale (adapted C-SSRS) | Clinician-administered measure of suicide risk | Day after each experimental session | 
| Columbia Suicide Severity Rating Scale (adapted C-SSRS) | Clinician-administered measure of suicide risk | One month after the second experimental session | 
| Columbia Suicide Severity Rating Scale (adapted C-SSRS) | Clinician-administered measure of suicide risk | Two months after the second experimental session | 
| Columbia Suicide Severity Rating Scale (adapted C-SSRS) | Clinician-administered measure of suicide risk | Day six and 12 of telephone contact after second experimental session | 
| Columbia Suicide Severity Rating Scale (adapted C-SSRS) | Clinician-administered measure of suicide risk | Day of each experimental session prior to drug administration | 
| Columbia Suicide Severity Rating Scale (adapted C-SSRS) | Clinician-administered measure of suicide risk | Day of each experimental session approximately five to six hours after drug administration | 
| Blood pressure (SBP/DBP) | Periodic assessment of participant blood pressure during both experimental sessions. | Throughout each experimental session, every 15 minutes for 6 hours, then every 30 minutes for 2 hours | 
| Heart rate (pulse) | Periodic assessment of participant pulse during both experimental sessions. | Throughout each experimental session, every 15 minutes for 6 hours, then every 30 minutes for 2 hours | 
| Body temperature | Periodic assessment of participant body temperature during both experimental sessions. | Approximately every 60 minutes for each experimental session | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MDMA, mood, subjective effects, interpersonal closeness