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Completed

NCT Number: NCT06905652

Comparative Acute Effects of R-MDMA and S-MDMA in Healthy Participants

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 has been 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, Canton of Basel-City, 4031, 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 (DA), norepinephrine (NE), serotonin (5-HT), and oxytocin while R-MDMA may act more directly on 5-HT2A receptors and release prolactin (PRL). 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. A human study conducted between 10/2022 and 01/2024 by our team compared the effects of R-MDMA, S-MDMA, and racemic MDMA revealing that both enantiomers have generally similar effects. However, the study did not administer equivalent doses of R- and S-MDMA. In the present study a single dose of R-MDMA and a single dose of S-MDMA, now adjusted and presumed to be equivalent, will be compared.

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
  • Good understanding of the German language
  • Understanding of procedures and risks associated with the study
  • Willing to adhere to the protocol and signing of the consent form
  • Willing to refrain from the consumption of illicit psychoactive substances during the study
  • Willing not to operate heavy machinery within 48 h after administration of a study substance (including driving a car)
  • Willing to use effective birth-control throughout study participation.
  • Body mass index 18 - 34.9 kg/m2

Exclusion criteria

  • Relevant chronic or acute medical condition
  • Current or previous major psychiatric disorder (e.g. bipolar disorder, schizophrenia), current depression or anxiety disorder
  • Psychotic disorder or bipolar disorder in first-degree relatives
  • 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.
  • Pregnancy or current breastfeeding
  • Participation in another clinical trial (currently or within the last 30 days)
  • Use of medications that may interfere with the effects of the study medication
  • Tobacco smoking (>10 cigarettes/day).
  • Excessive consumption of alcoholic beverages (>15 drinks/week)

Treatment and study plan

R-3,4-methylenedioxymethamphetamine

Drug

A dose of 300mg enantiomeric R-MDMA will be administered.

Other names: R-MDMA

S-3,4-methylenedioxymethamphetamine

Drug

A dose of 100mg enantiomeric S-MDMA will be administered.

Other names: S-MDMA

Placebo

Other

Placebo (Mannitol)

Primary outcomes

  1. Subjective effects

    Time frame: through study completion, an average of 18 months.

    Any drug effect on the Visual Analog Scales (VAS) assessing the intensity and duration of the subjective effect on a scale from 0 - 100 percent with higher scores representing more intense effects 14 times each study day.

Secondary outcomes

  1. Autonomic effects I

    Time frame: Through study completion, an average of 18 months.

    Blood pressure (systolic and diastolic) will be measured with an automatic oscillometric device 14 times each study day.

  2. Autonomic effects II

    Time frame: Through study completion, an average of 18 months.

    Heart rate will be measured with an automatic oscillometric device. Assessed 14 times on each study day.

  3. Autonomic effects III

    Time frame: through study completion, an average of 18 months.

    Body temperature will be measured with an ear thermometer. Assessed 14 times each study day.

  4. Plasma levels of oxytocin

    Time frame: Through study completion, an average of 18 months.

    Assessed 3 times on each study day

  5. Plasma levels of cortisol

    Time frame: Through study completion, an average of 18 months.

    Assessed 3 times on each study day

  6. Plasma levels of prolactin

    Time frame: Through study completion, an average of 18 months.

    Assessed 3 times on each study day

  7. Plasma levels of R-MDMA

    Time frame: Through study completion, an average of 18 months.

    Assessed 13 times on each study day

  8. Plasma levels of S-MDMA

    Time frame: Through study completion, an average of 18 months.

    Assessed 13 times on each study day

  9. Additional subjective effects I

    Time frame: Through study completion, an average of 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 14 times on each study day

  10. Additional subjective effects II

    Time frame: Through study completion, an average of 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

  11. Additional subjective effects III

    Time frame: Through study completion, an average of 18 months.

    This world connectogen scale (TWCS) assessing the connectogenic properties of MDMA as a strong sense of connection with the here-and-now, the body, the world and spiritual principles. Assessed once each study day

  12. 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".

  13. 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").

  14. Saarbrücken Personality Questionnaire (SPF)

    Time frame: Baseline

    Personality traits are known to affect subjective responses to psychoactive substances and are assessed for explorative future analysis of pooled data. The Saarbrücker Persönlichkeitsfragebogen (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.

  15. HEXACO personality inventory

    Time frame: Baseline

    Personality traits are known to affect subjective responses to psychoactive substances and are assessed for explorative future analysis of pooled data. 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.

  16. Defense Style Questionnaire (DSQ-40)

    Time frame: Baseline

    Personality traits are known to affect subjective responses to psychoactive substances and are assessed for explorative future analysis of pooled data. The Defense Style Questionnaire (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".

  17. Acute adverse effects

    Time frame: Through study completion, an average of 18 months.

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

  18. Subacute adverse effects I

    Time frame: Through study completion, an average of 18 months.

    The List of complains is a list of 50 symptoms assessed on a 4-point Likert scale ranging from "not at all" to "extremely". Assessed twice (24 and 72h) after each study day.

  19. Subacute adverse effects II

    Time frame: Through study completion, an average of 18 months.

    The Beck Depressionindex questionnaire (BDI) is assessed once after each study day (72h) with low values indicating normal mood and high values indicating severe depression.

  20. Dose equivalence I

    Time frame: Through study completion, an average of 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

  21. Dose equivalence II

    Time frame: Through study completion, an average of 18 months.

    The State of Consciousness (SCQ) Questionaire 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

  22. Life satisfaction and well-being I

    Time frame: Through study completion, an average of 18 months.

    The Scale of positive and negative experience (SPANE) assesses 12 items of subject well-being on a 5-point-scale ranging from "very rarely" to "very often or always". Assessed once each study day and 72 h after administration.

  23. Life satisfaction and well-being II

    Time frame: Through study completion, an average of 18 months.

    The "positive attitude towards life" is an 8-item subscale of the Berner Subjective Well-Being Quetsionaire for adults (BFW/E) using a six-point rating scale from "strongly disagree" (1) to "strongly agree" (6) to rate the attitude towards life. Assessed once each study day.

  24. Life satisfaction and well-being III

    Time frame: Through study completion, an average of 18 months.

    The Global Life Satisfaction (GLS) assesses the overall satisfaction on a 11 point scale with 0 meaning "not at all satisfied" and 10 meaning "completely satisfied". Assessed once each study day as well as 72 h after each drug adminstration.

  25. Life satisfaction and well-being IV

    Time frame: Baseline/End of Study Visit

    The Appreciation Scale (AS) includes 57 items to measure eight aspects of appreciation. Subjects are asked to rate themselves on a scale from 1 to 7 in terms of either attitude intensity ('strongly disagree' to 'strongly agree') or frequency ('never' to 'more than once a day'). Assessed at screening and end of study visit.

  26. Empathogenic effects I

    Time frame: Through study completion, an average of 18 months.

    Multifaceted Empathy Test (MET), effects on empathy in computer tests, assessed one time during each study session.

  27. Empathogenic effects II

    Time frame: Through study completion, an average of 18 months.

    Facial expression recognition test (FERT), effects on empathy in computer tests, assessed one time during each study session.

Sponsors and collaborators

Lead sponsor

University Hospital, Basel, Switzerland

Other

Registry information

Acronym: R-S-

Important dates

Study start
2025
Primary completion
2026
Study completion
2026
First posted
Apr 1, 2025
Registry last updated
May 15, 2026

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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