Comparative Acute Effects of R-MDMA and S-MDMA in Healthy Participants (R-S-)

University Hospital Basel

Status and phase: Not yet enrolling; Phase 1

Conditions: Healthy

Treatments: Drug: R-3,4-methylenedioxymethamphetamine; Drug: S-3,4-methylenedioxymethamphetamine; Other: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT06905652

BASEC 2024-01835

Details and patient eligibility

About

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.

Full 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.

Enrollment: 24 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

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)

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

---

24 participants in 3 patient groups, including a placebo group

300mg R-MDMA

Experimental group

Description:

R-MDMA (300mg)

Treatment:

Drug: R-3,4-methylenedioxymethamphetamine

100mg S-MDMA

Experimental group

Description:

S-MDMA (100mg)

Treatment:

Drug: S-3,4-methylenedioxymethamphetamine

Placebo

Placebo Comparator group

Description:

Placebo

Treatment:

Other: Placebo