Acute Effects of 3,4-methylenedioxymethamphetamine (MDMA) With and Without a Booster Dose

University Hospital Basel

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: Placebo; Drug: MDMA 120 mg + placebo; Drug: MDMA 120 mg + MDMA 60 mg

Study type: Interventional

Funder types: Other

Identifiers

NCT05809271

BASEC 2023-00167

Details and patient eligibility

About

3,4-methylenedioxymethamphetamine (MDMA) is a psychoactive substance and prototypical empathogen acutely inducing feelings of heightened mood, empathy, trust and closeness to others. The current study investigates differences in duration of acute effects and side effects after administration of a single dose of MDMA compared to a repeated administration.

Full description

MDMA is a psychoactive substance that primarily enhances serotonergic neurotransmission by releasing 5-HT through the SERT. It also releases dopamine and norepinephrine, although less potently, through the dopamine transporter and norepinephrine transporter, respectively. In addition to its use as a recreational drug, MDMA-assisted psychotherapy has been investigated in several phase 2 trials and one phase 3 trial for PTSD. Further indications for MDMA-assisted therapy being planned or ongoing are eating disorders, social anxiety, and alcohol use disorder.

The present study focuses on dosing aspects of MDMA used in clinical studies and recreational settings, specifically the benefits of a second administration (booster dose) given several hours after the initial dose. Most published studies of MDMA-assisted psychotherapy used a booster dose. A typical dosing regimen would be 80-120 mg of MDMA initially followed by half the initial dose after 1.5-2.5 hours. Although previous studies have found that a booster dose could prolong the acute effects of MDMA, others have shown an acute tolerance reflected in the finding that acute subjective effects return to baseline within 4-5 hours, while plasma concentrations are still close to peak levels.

These findings have led to controversy regarding how effective a booster dose would be in prolonging acute effects, as it has never been directly compared to placebo. Additionally, the higher total dose could lead to an increase in side effects.

Therefore, the present phase 1 study intends to compare the acute subjective, physiological, and endocrine effects of MDMA (120 mg + 60 mg after 2 hours), MDMA (120 mg + placebo after 2 hours), and (placebo + placebo after 2 hours) using a double-blind, random-order, crossover design in healthy subjects.

Enrollment: 25 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

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

Exclusion criteria

1. Relevant 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. Previous MDMA use 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

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25 participants in 3 patient groups, including a placebo group

MDMA with booster

Experimental group

Description:

MDMA followed by MDMA

Treatment:

Drug: MDMA 120 mg + MDMA 60 mg

MDMA without booster

Experimental group

Description:

MDMA followed by placebo

Treatment:

Drug: MDMA 120 mg + placebo

Placebo

Placebo Comparator group

Description:

Placebo followed by placebo

Treatment:

Drug: Placebo