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

University Hospital Basel

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: R-3,4-methylenedioxymethamphetamine (125 mg); Drug: S-3,4-methylenedioxymethamphetamine; Drug: R-3,4-methylenedioxymethamphetamine (250 mg); Other: Placebo; Drug: 3,4-methylenedioxymethamphetamine

Study type: Interventional

Funder types: Other

Identifiers

NCT05277636

BASEC 2021-02386

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 is currently 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, 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.

Enrollment: 24 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

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).

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

---

24 participants in 5 patient groups, including a placebo group

125 mg MDMA

Experimental group

Description:

MDMA (125 mg)

Treatment:

Drug: 3,4-methylenedioxymethamphetamine

125 mg S-MDMA

Experimental group

Description:

S-MDMA (125 mg)

Treatment:

Drug: S-3,4-methylenedioxymethamphetamine

125 mg R-MDMA

Experimental group

Description:

R-MDMA (125 mg)

Treatment:

Drug: R-3,4-methylenedioxymethamphetamine (125 mg)

250 mg R-MDMA

Experimental group

Description:

R-MDMA (250 mg)

Treatment:

Drug: R-3,4-methylenedioxymethamphetamine (250 mg)

Placebo

Placebo Comparator group

Description:

Placebo

Treatment:

Other: Placebo