Clinical trial NCT05277636: Acute Effects of R- and S-MDMA in Healthy Subjects
Official title: Acute Effects of R- and S-MDMA in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
First posted: 2022-03-14
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: 5-period random order, placebo-controlled, double-blind cross-over study with four active substance conditions and placebo:

1. MDMA (125 mg), 2. S-MDMA (125 mg), 3. R-MDMA (125 mg), 4. R-MDMA (250 mg), 5. Placebo
Primary purpose: BASIC_SCIENCE

Brief summary: Racemic ±3,4-methylenedioxymethamphetamine (MDMA) is a psychoactive substance and prototypical empathogen acutely inducing feelings of heightened mood, empathy, trust and closeness to others. These acute subjective effects of MDMA may be helpful to assist psychotherapy and MDMA is currently investigated in phase 3 trials as a possible treatment in post-traumatic stress disorder.

Detailed description: MDMA is a racemic substance containing equal amounts of the enantiomers S(+)- and R(-)-MDMA. Preclinical research indicates that S-MDMA mainly releases dopamine, norepinephrine, serotonin, and oxytocin while R-MDMA may act more directly on 5-HT2A receptors and release prolactin. Animal studies also indicate that the two enantiomers act synergistically to produce the subjective effects of MDMA and that S-MDMA is mainly responsible for psychostimulation while R-MDMA may have fewer adverse effects and have greater prosocial effects. However, acute effects of S- and R-MDMA have never been validly examined in a human study. Therefore, the present study compares acute responses to R-MDMA, S-MDMA, MDMA, and placebo in a cross-over study in healthy subjects.

Eligibility criteria: Inclusion Criteria:

1. Age between 18 and 65 years.
2. Understanding of the German language.
3. Understanding the procedures and the risks that are associated with the study.
4. Participants must be willing to adhere to the protocol and sign the consent form.
5. Participants must be willing to refrain from taking illicit psychoactive substances during the study.
6. Participants must be willing to drink only alcohol-free liquids and no coffee, black or green tea, or energy drink after midnight of the evening before the study session, as well as during the study day.
7. Participants must be willing not to drive a traffic vehicle or to operate machines within 48 h after substance administration.
8. Willing to use double-barrier birth control throughout study participation.
9. Body mass index between 18-29 kg/m2.

Exclusion Criteria:

1. Chronic or acute medical condition
2. Current or previous major psychiatric disorder
3. Psychotic disorder in first-degree relatives, not including psychotic disorders secondary to an apparent medical reason, e.g. brain injury, dementia, or lesions of the brain.
4. Hypertension (SBP\>140/90 mmHg) or hypotension (SBP\<85 mmHg)
5. Illicit substance use (not including cannabis) more than 20 times or any time within the previous month
6. Pregnant or nursing women.
7. Participation in another clinical trial (currently or within the last 30 days).
8. Use of medications that may interfere with the effects of the study medications.
9. Tobacco smoking (\>10 cigarettes/day).
10. Consumption of alcoholic drinks (\>15 drinks/week).

Primary outcomes:
measure: Subjective effects I
timeFrame: 18 months
measure: Subjective effects II
timeFrame: 18 months
Secondary outcomes:
measure: Autonomic effects I
timeFrame: 18 months
measure: Autonomic effects II
timeFrame: 18 months
measure: Autonomic effects III
timeFrame: 18 months
measure: Adverse effects
timeFrame: 18 months
measure: Mood after study day I
timeFrame: 18 months
measure: Mood after study day II
timeFrame: 18 months
measure: Mood after study day III
timeFrame: 18 months
measure: Mood after study day IV
timeFrame: 18 months
measure: Plasma levels of cortisol
timeFrame: 18 months
measure: Plasma levels of prolactin
timeFrame: 18 months
measure: Plasma levels of oxytocin
timeFrame: 18 months
measure: Plasma levels of vasopressin
timeFrame: 18 months
measure: Plasma levels of S-MDMA
timeFrame: 18 months
measure: Plasma levels of R-MDMA
timeFrame: 18 months
measure: Plasma levels of S-MDA
timeFrame: 18 months
measure: Plasma levels of R-MDA
timeFrame: 18 months
measure: Additional subjective effects I
timeFrame: 18 months
measure: Additional subjective effects II
timeFrame: 18 months
measure: States of Consciousness Questionnaire
timeFrame: 18 months
measure: Spiritual Realms Questionnaire
timeFrame: 18 months
measure: Psychological Insight Questionnaire
timeFrame: 18 months
measure: NEO-Five-Factor-Inventory (NEO-FFI)
timeFrame: Baseline
measure: Freiburger Personality Inventory (FPI-R)
timeFrame: Baseline
measure: Saarbrücker Personality Questionnaire (SPF)
timeFrame: Baseline
measure: HEXACO personality inventory
timeFrame: Baseline
measure: Defense Style Questionnaire (DSQ-40)
timeFrame: Baseline
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: University Hospital Basel
Study officials:
affiliation: University Hospital Basel, Basel, Switzerland
name: Matthias E Liechti, MD
role: PRINCIPAL_INVESTIGATOR
References: