Clinical trial NCT05809271: Acute Effects of 3,4-methylenedioxymethamphetamine (MDMA) With and Without a Booster Dose
Official title: Acute Effects of 3,4-methylenedioxymethamphetamine (MDMA) With and Without a Booster Dose (MDMA-booster Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
First posted: 2023-04-12
Enrollment: 25
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: 3-period, random order, placebo-controlled, double-blind cross-over study
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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).

Primary outcomes:
measure: Subjective effect duration for "any drug effect"
timeFrame: Every 15 minutes for 9 hours after substance administration
Secondary outcomes:
measure: Maximal subjective effects for "any drug effect"
timeFrame: Every 15 minutes for 9 hours after substance administration
measure: Total subjective effects for "any drug effect"
timeFrame: Every 15 minutes for 9 hours after substance administration
measure: Further acute subjective effects I duration
timeFrame: Every 30 minutes for 9 hours after substance administration
measure: Further acute subjective effects II maximal effects
timeFrame: Every 30 minutes for 9 hours after substance administration
measure: Further acute subjective effects III total effects
timeFrame: Every 30 minutes for 9 hours after substance administration
measure: Further acute subjective effects IV AMRS
timeFrame: 5 times during each study day: 30 minutes before as well as 2, 4, 6, and 9 hours after substance administration.
measure: Acute autonomic effects I (blood pressure)
timeFrame: 16 times during each study day: 30 minutes before as well as 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 9 hours after substance administration
measure: Acute autonomic effects II (heart rate)
timeFrame: 16 times during each study day: 30 minutes before as well as 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 9 hours after substance administration
measure: Acute autonomic effects III (body temperature)
timeFrame: 16 times during each study day: 30 minutes before as well as 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 9 hours after substance administration
measure: Adverse effects (acute and subacute)
timeFrame: Before each study day as baseline as well as 9 hours, 3 days and 7 days after substance administration
measure: Subacute effects on general and mental well-being I (WEMWBS)
timeFrame: Before each study day as baseline as well as 3 days and 7 days after substance administration
measure: Subacute effects on general and mental well-being II (GHQ-12)
timeFrame: Before each study day as baseline as well as 3 days and 7 days after substance administration
measure: Subacute effects on general and mental well-being III (SPANE)
timeFrame: Before each study day as baseline as well as 3 days and 7 days after substance administration
measure: Subacute effects on subjective sleep quality (ISI)
timeFrame: Before each study day as baseline as well as 3 days and 7 days after substance administration
measure: Plasma concentrations of MDMA
timeFrame: 16 times during each study day: 30 minutes before as well as 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 9 hours after substance administration
measure: Plasma concentrations of MDMA-metabolites
timeFrame: 16 times during each study day: 30 minutes before as well as 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 9 hours after substance administration
measure: Plasma concentrations of Plasma levels of oxytocin
timeFrame: 4 times during each study day: 30 minutes before as well as 2, 4 and 6 hours after substance administration
measure: Effects on life satisfaction, well-being and appreciation before and after study I (BFW/E)
timeFrame: Twice during study: at screening and at end of study 12-14 weeks later.
measure: Effects on life satisfaction, well-being and appreciation before and after study II (GLS)
timeFrame: Twice during study: at screening and at end of study 12-14 weeks later.
measure: Effect moderation by personality traits I (NEO-FFI)
timeFrame: Baseline
measure: Effect moderation by personality traits II (FPI-R)
timeFrame: Baseline
measure: Effect moderation by personality traits III (SPF)
timeFrame: Baseline
measure: Effect moderation by personality traits IV (HEXACO)
timeFrame: Baseline
measure: Effect moderation by personality traits V (DSQ-40)
timeFrame: Baseline
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: University Hospital
Study officials:
affiliation: University Hospital Basel, Basel, Switzerland
name: Matthias E Liechti, Prof. Dr. MD
role: PRINCIPAL_INVESTIGATOR
References: