Clinical trial NCT06905652: Comparative Acute Effects of R-MDMA and S-MDMA in Healthy Participants
Official title: Comparative Acute Effects of R-MDMA and S-MDMA in Healthy Participants
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Healthy
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
First posted: 2025-04-01
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: double-blind, placebo-controlled, 3-period cross-over design with two treatment conditions and placebo: 1. R-MDMA (300mg), 2. S-MDMA (100mg), 3. 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 has been 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 (DA), norepinephrine (NE), serotonin (5-HT), and oxytocin while R-MDMA may act more directly on 5-HT2A receptors and release prolactin (PRL). 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. A human study conducted between 10/2022 and 01/2024 by our team compared the effects of R-MDMA, S-MDMA, and racemic MDMA revealing that both enantiomers have generally similar effects. However, the study did not administer equivalent doses of R- and S-MDMA. In the present study a single dose of R-MDMA and a single dose of S-MDMA, now adjusted and presumed to be equivalent, will be compared.

Eligibility criteria: Inclusion Criteria:

1. Age between 18 and 65 years
2. Good understanding of the German language
3. Understanding of procedures and risks associated with the study
4. Willing to adhere to the protocol and signing of the consent form
5. Willing to refrain from the consumption of illicit psychoactive substances during the study
6. Willing not to operate heavy machinery within 48 h after administration of a study substance (including driving a car)
7. Willing to use effective birth-control throughout study participation.
8. Body mass index 18 - 34.9 kg/m2

Exclusion Criteria:

1. Relevant chronic or acute medical condition
2. Current or previous major psychiatric disorder (e.g. bipolar disorder, schizophrenia), current depression or anxiety disorder
3. Psychotic disorder or bipolar disorder in first-degree relatives
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. Pregnancy or current breastfeeding
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 medication
9. Tobacco smoking (\>10 cigarettes/day).
10. Excessive consumption of alcoholic beverages (\>15 drinks/week)

Primary outcomes:
measure: Subjective effects
timeFrame: through study completion, an average of 18 months.
Secondary outcomes:
measure: Autonomic effects I
timeFrame: Through study completion, an average of 18 months.
measure: Autonomic effects II
timeFrame: Through study completion, an average of 18 months.
measure: Autonomic effects III
timeFrame: through study completion, an average of 18 months.
measure: Plasma levels of oxytocin
timeFrame: Through study completion, an average of 18 months.
measure: Plasma levels of cortisol
timeFrame: Through study completion, an average of 18 months.
measure: Plasma levels of prolactin
timeFrame: Through study completion, an average of 18 months.
measure: Plasma levels of R-MDMA
timeFrame: Through study completion, an average of 18 months.
measure: Plasma levels of S-MDMA
timeFrame: Through study completion, an average of 18 months.
measure: Additional subjective effects I
timeFrame: Through study completion, an average of 18 months.
measure: Additional subjective effects II
timeFrame: Through study completion, an average of 18 months.
measure: Additional subjective effects III
timeFrame: Through study completion, an average of 18 months.
measure: NEO-Five-Factor-Inventory (NEO-FFI)
timeFrame: Baseline
measure: Freiburger Personality Inventory (FPI-R)
timeFrame: Baseline
measure: Saarbrücken Personality Questionnaire (SPF)
timeFrame: Baseline
measure: HEXACO personality inventory
timeFrame: Baseline
measure: Defense Style Questionnaire (DSQ-40)
timeFrame: Baseline
measure: Acute adverse effects
timeFrame: Through study completion, an average of 18 months.
measure: Subacute adverse effects I
timeFrame: Through study completion, an average of 18 months.
measure: Subacute adverse effects II
timeFrame: Through study completion, an average of 18 months.
measure: Dose equivalence I
timeFrame: Through study completion, an average of 18 months.
measure: Dose equivalence II
timeFrame: Through study completion, an average of 18 months.
measure: Life satisfaction and well-being I
timeFrame: Through study completion, an average of 18 months.
measure: Life satisfaction and well-being II
timeFrame: Through study completion, an average of 18 months.
measure: Life satisfaction and well-being III
timeFrame: Through study completion, an average of 18 months.
measure: Life satisfaction and well-being IV
timeFrame: Baseline/End of Study Visit
measure: Empathogenic effects I
timeFrame: Through study completion, an average of 18 months.
measure: Empathogenic effects II
timeFrame: Through study completion, an average of 18 months.
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: University Hospital Basel
state: Basel Stadt
Study officials:
affiliation: University Hospital, Basel, Switzerland
name: Matthias E Liechti, Prof. Dr. MD
role: PRINCIPAL_INVESTIGATOR
References: