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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Other: Placebo; Drug: 3,4-methylenedioxymethamphetamine; Drug: S-3,4-methylenedioxymethamphetamine; Drug: R-3,4-methylenedioxymethamphetamine (125 mg); Drug: R-3,4-methylenedioxymethamphetamine (250 mg)

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, 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.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Matthias E Liechti, MD; Phone Number: +41 61 328 68 68; Email: matthias.liechti@usb.ch
• Study Contact Backup: Name: Isabelle Straumann, MSc; Phone Number: +41 61 328 43 68; Email: isabelle.straumann@usb.ch

Study Locations

• Switzerland
  • Basel, Switzerland
    • University Hospital Basel

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Other: Placebo; Placebo (Mannitol)
Experimental: 125 mg MDMA; MDMA (125 mg)	Drug: 3,4-methylenedioxymethamphetamine; A dose of 125 mg racemic MDMA will be administered.; Other Names: MDMA
Experimental: 125 mg S-MDMA; S-MDMA (125 mg)	Drug: S-3,4-methylenedioxymethamphetamine; A dose of 125 mg enantiomeric S-MDMA will be administered.; Other Names: S-MDMA
Experimental: 125 mg R-MDMA; R-MDMA (125 mg)	Drug: R-3,4-methylenedioxymethamphetamine (125 mg); A dose of 125 mg enantiomeric R-MDMA will be administered.; Other Names: R-MDMA
Experimental: 250 mg R-MDMA; R-MDMA (250 mg)	Drug: R-3,4-methylenedioxymethamphetamine (250 mg); A dose of 250 mg enantiomeric R-MDMA will be administered.; Other Names: R-MDMA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subjective effects I	5 Dimensions of Altered States of Consciousness (5D-ASC) consisting of 94 items to be rated on a visual analog scale (0-100 mm), with higher values indicating stronger effects with higher scores representing more intense effects. Assessed once on each study day	18 months
Subjective effects II	Stimulation on the Visual Analog Scales (VAS) assessing the intensity and duration of the stimulant effect on a scale from 0 - 100 percent with higher scores representing more intense effects. Assessed 18 times on each study day	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
NEO-Five-Factor-Inventory (NEO-FFI)	The NEO-FFI is a self-description questionnaire with 60 items for the measurement of the "big five": neuroticism, extraversion, openness, agreeableness, and consciousness. It uses a 5-point Likert scale ranging from "completely disagree" to "fully agree".	Baseline
Freiburger Personality Inventory (FPI-R)	The FPI-R version comprises 138 items and covers 12 dimensions of personality: life satisfaction, social orientation, performance orientation, inhibition, excitability, aggressiveness, stress, physical complaints, health concerns, openness, as well as the secondary factors according to Eysenck's Extraversion and Emotionality (Neuroticism). It uses a 2-point scale ("true" and "not true").	Baseline
Saarbrücker Personality Questionnaire (SPF)	The SPF defines empathy as the "reactions of one individual to the observed experiences of another." It assesses 28-items on a 5-point Likert scale ranging from "Does not describe me well" to "Describes me very well". The measure has 4 subscales (Perspective Taking, Fantasy, Empathic Concern, Personal Distress) each made up of 7 different items.	Baseline
Defense Style Questionnaire (DSQ-40)	The DSQ-40 can provide scores for 20 individual defenses, and scores for the three factors "mature", "neurotic", and "immature". Each item is evaluated on a scale from 1 to 9, where "1" indicates "completely disagree" and "9" indicates "fully agree".	Baseline
HEXACO personality inventory	The HEXACO personality inventory is a six-dimensional model of human personality with 100 items.The six factors are: Honesty-Humility, Emotionality, Extraversion, Agreeableness, Conscientiousness and Openness to Experience.	Baseline
Autonomic effects I	Assessed 18 times on each study day via systolic and diastolic blood pressure	18 months
Autonomic effects II	Assessed 18 times on each study day via heart rate	18 months
Autonomic effects III	Assessed 18 times on each study day via tympanic body temperature	18 months
Adverse effects	Assessed 3 times on each study day with the list of complaints (LC)	18 months
Mood after study day I	Assessed once 3 days after administration via the Beck Depressionindex questionnaire (BDI) with low values indicating normal mood and high values indicating severe depression	18 months
Mood after study day II	Assessed once 3 days after administration via Symptom checklist 90R (SCL-90R) to evaluate a number of different psychological symptoms.	18 months
Mood after study day III	Assessed once 3 days after administration via list of complaints (LC)	18 months
Mood after study day IV	Assessed once 3 days after administration via adjective mood rating scale (AMRS)	18 months
Plasma levels of cortisol	Assessed 3 times on each study day	18 months
Plasma levels of prolactin	Assessed 3 times on each study day	18 months
Plasma levels of oxytocin	Assessed 4 times on each study day	18 months
Plasma levels of vasopressin	Assessed 4 times on each study day	18 months
Plasma levels of S-MDMA	Assessed 17 times on each study day	18 months
Plasma levels of R-MDMA	Assessed 17 times on each study day	18 months
Plasma levels of S-MDA	Assessed 17 times on each study day	18 months
Plasma levels of R-MDA	Assessed 17 times on each study day	18 months
Additional subjective effects I	Visual Analog Scales (VAS) assessing the intensity and duration of subjective effects on a scale from 0 - 100 percent with higher scores representing more intense effects. Assessed 18 times on each study day	18 months
Additional subjective effects II	Adjective Mood Rating Scale (AMRS) assesses the occurrence and intensity of 60 moods on a 4-point Likert scale ranging from "not at all" to "extremely" assessed 4 times on each study day	18 months
States of Consciousness Questionnaire	Assesses the emergence and intensity of phenomenons occurring in altered states of consciousness on a 6-point Likert scale ranging from 0 ("not at all") to 5 ("extremely") once on each study day	18 months
Spiritual Realms Questionnaire	Assesses the spiritual phenomenons elicited by psychedelic substances through 11 main questions to be answered on a total of 65 sub-ordered 100mm visual analog scales once on each study day	18 months
Psychological Insight Questionnaire	Assesses the degree of psychological insight caused by a psychedelic experience through 14-items to be answered on a 6-point Likert scale ranging from 0 ("not at all") to 5 ("extremely") once on each study day	18 months

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland
• Investigators: Principal Investigator: Matthias E Liechti, MD, University Hospital Basel, Basel, Switzerland

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2022
• Primary Completion (Actual): January 13, 2024
• Study Completion (Actual): January 13, 2024

Study Registration Dates

• First Submitted: March 3, 2022
• First Submitted That Met QC Criteria: March 3, 2022
• First Posted (Actual): March 14, 2022

Study Record Updates

• Last Update Posted (Actual): January 17, 2024
• Last Update Submitted That Met QC Criteria: January 15, 2024
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Hallucinogens; Adrenergic Uptake Inhibitors; N-Methyl-3,4-methylenedioxyamphetamine
• Other Study ID Numbers: BASEC 2021-02386

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No