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

Healthy Clinical Trial

— R-S-MDMA  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05277636
• Other study ID #: BASEC 2021-02386
• Status: Completed
• Phase: Phase 1
• Start date: October 1, 2022
• Est. completion date: January 13, 2024

Study information

• Verified date: November 2022
• Source: University Hospital, Basel, Switzerland
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: January 13, 2024
• Est. primary completion date: January 13, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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).

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• 3,4-methylenedioxymethamphetamine
A dose of 125 mg racemic MDMA will be administered.
• S-3,4-methylenedioxymethamphetamine
A dose of 125 mg enantiomeric S-MDMA will be administered.
• R-3,4-methylenedioxymethamphetamine (125 mg)
A dose of 125 mg enantiomeric R-MDMA will be administered.
• R-3,4-methylenedioxymethamphetamine (250 mg)
A dose of 250 mg enantiomeric R-MDMA will be administered.

Other:
• Placebo
Placebo (Mannitol)

Locations

Country	Name	City	State
Switzerland	University Hospital Basel	Basel

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Basel, Switzerland

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Autonomic effects I	Assessed 18 times on each study day via systolic and diastolic blood pressure	18 months
Secondary	Autonomic effects II	Assessed 18 times on each study day via heart rate	18 months
Secondary	Autonomic effects III	Assessed 18 times on each study day via tympanic body temperature	18 months
Secondary	Adverse effects	Assessed 3 times on each study day with the list of complaints (LC)	18 months
Secondary	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
Secondary	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
Secondary	Mood after study day III	Assessed once 3 days after administration via list of complaints (LC)	18 months
Secondary	Mood after study day IV	Assessed once 3 days after administration via adjective mood rating scale (AMRS)	18 months
Secondary	Plasma levels of cortisol	Assessed 3 times on each study day	18 months
Secondary	Plasma levels of prolactin	Assessed 3 times on each study day	18 months
Secondary	Plasma levels of oxytocin	Assessed 4 times on each study day	18 months
Secondary	Plasma levels of vasopressin	Assessed 4 times on each study day	18 months
Secondary	Plasma levels of S-MDMA	Assessed 17 times on each study day	18 months
Secondary	Plasma levels of R-MDMA	Assessed 17 times on each study day	18 months
Secondary	Plasma levels of S-MDA	Assessed 17 times on each study day	18 months
Secondary	Plasma levels of R-MDA	Assessed 17 times on each study day	18 months
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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