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Completed

NCT Number: NCT05277636

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

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.

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Key information

Conditions

Healthy

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

University Hospital Basel

Basel, Switzerland

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Age between 18 and 65 years.
  • Understanding of the German language.
  • Understanding the procedures and the risks that are associated with the study.
  • Participants must be willing to adhere to the protocol and sign the consent form.
  • Participants must be willing to refrain from taking illicit psychoactive substances during the study.
  • 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.
  • Participants must be willing not to drive a traffic vehicle or to operate machines within 48 h after substance administration.
  • Willing to use double-barrier birth control throughout study participation.
  • Body mass index between 18-29 kg/m2.

Exclusion criteria

  • Chronic or acute medical condition
  • Current or previous major psychiatric disorder
  • 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.
  • Hypertension (SBP>140/90 mmHg) or hypotension (SBP<85 mmHg)
  • Illicit substance use (not including cannabis) more than 20 times or any time within the previous month
  • Pregnant or nursing women.
  • Participation in another clinical trial (currently or within the last 30 days).
  • Use of medications that may interfere with the effects of the study medications.
  • Tobacco smoking (>10 cigarettes/day).
  • Consumption of alcoholic drinks (>15 drinks/week).

Treatment and study plan

3,4-methylenedioxymethamphetamine

Drug

A dose of 125 mg racemic MDMA will be administered.

Other names: MDMA

S-3,4-methylenedioxymethamphetamine

Drug

A dose of 125 mg enantiomeric S-MDMA will be administered.

Other names: S-MDMA

R-3,4-methylenedioxymethamphetamine (125 mg)

Drug

A dose of 125 mg enantiomeric R-MDMA will be administered.

Other names: R-MDMA

R-3,4-methylenedioxymethamphetamine (250 mg)

Drug

A dose of 250 mg enantiomeric R-MDMA will be administered.

Other names: R-MDMA

Placebo

Other

Placebo (Mannitol)

Primary outcomes

  1. Subjective effects I

    Time frame: 18 months

    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

  2. Subjective effects II

    Time frame: 18 months

    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

Secondary outcomes

  1. Autonomic effects I

    Time frame: 18 months

    Assessed 18 times on each study day via systolic and diastolic blood pressure

  2. Autonomic effects II

    Time frame: 18 months

    Assessed 18 times on each study day via heart rate

  3. Autonomic effects III

    Time frame: 18 months

    Assessed 18 times on each study day via tympanic body temperature

  4. Adverse effects

    Time frame: 18 months

    Assessed 3 times on each study day with the list of complaints (LC)

  5. Mood after study day I

    Time frame: 18 months

    Assessed once 3 days after administration via the Beck Depressionindex questionnaire (BDI) with low values indicating normal mood and high values indicating severe depression

  6. Mood after study day II

    Time frame: 18 months

    Assessed once 3 days after administration via Symptom checklist 90R (SCL-90R) to evaluate a number of different psychological symptoms.

  7. Mood after study day III

    Time frame: 18 months

    Assessed once 3 days after administration via list of complaints (LC)

  8. Mood after study day IV

    Time frame: 18 months

    Assessed once 3 days after administration via adjective mood rating scale (AMRS)

  9. Plasma levels of cortisol

    Time frame: 18 months

    Assessed 3 times on each study day

  10. Plasma levels of prolactin

    Time frame: 18 months

    Assessed 3 times on each study day

  11. Plasma levels of oxytocin

    Time frame: 18 months

    Assessed 4 times on each study day

  12. Plasma levels of vasopressin

    Time frame: 18 months

    Assessed 4 times on each study day

  13. Plasma levels of S-MDMA

    Time frame: 18 months

    Assessed 17 times on each study day

  14. Plasma levels of R-MDMA

    Time frame: 18 months

    Assessed 17 times on each study day

  15. Plasma levels of S-MDA

    Time frame: 18 months

    Assessed 17 times on each study day

  16. Plasma levels of R-MDA

    Time frame: 18 months

    Assessed 17 times on each study day

  17. Additional subjective effects I

    Time frame: 18 months

    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. Additional subjective effects II

    Time frame: 18 months

    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

  19. States of Consciousness Questionnaire

    Time frame: 18 months

    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

  20. Spiritual Realms Questionnaire

    Time frame: 18 months

    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

  21. Psychological Insight Questionnaire

    Time frame: 18 months

    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

  22. NEO-Five-Factor-Inventory (NEO-FFI)

    Time frame: Baseline

    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".

  23. Freiburger Personality Inventory (FPI-R)

    Time frame: Baseline

    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").

  24. Saarbrücker Personality Questionnaire (SPF)

    Time frame: Baseline

    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.

  25. HEXACO personality inventory

    Time frame: Baseline

    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.

  26. Defense Style Questionnaire (DSQ-40)

    Time frame: Baseline

    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".

Sponsors and collaborators

Lead sponsor

University Hospital, Basel, Switzerland

Other

Registry information

Acronym: R-S-MDMA

Important dates

Study start
2022
Primary completion
2024
Study completion
2024
First posted
Mar 14, 2022
Registry last updated
Jan 17, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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