Effects of MDMA-like Substances in Healthy Subjects

Healthy Clinical Trial

— MDMA-like  

Official title:

Effects of MDMA-like Substances in Healthy Subjects

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04847206
• Other study ID #: BASEC 2021-00405
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: December 1, 2021
• Est. completion date: May 31, 2024

Study information

• Verified date: February 2024
• Source: University Hospital, Basel, Switzerland
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The serotonin (5-HT) and oxytocin releaser and so-called "empathogen" 3,4-methylenedioxymethamphetamine (MDMA) acutely produces positive feelings, empathy, and trust. MDMA is used recreationally (ecstasy), as research tool to study 5-HT and oxytocin function, and is investigated for MDMA-assisted psychotherapy.

MDMA is metabolized in part (10%) to the psychoactive metabolite 3,4-methylenedioxyamphetamine (MDA) which itself is also a recreational substance and has also been used to assist psychotherapy in the past. The present study aims to describe and directly compare for the first time the effects of MDMA and MDA in the same healthy volunteers and using modern psychological and psychometric tests.

Additionally, although amphetamines including MDMA and MDA induce mainly positive subjective effects they may also produce negative subjective drug effects including anxiety in particular at the onset of the subjective response and the rapid onset of euphoria may increase the risk of abuse. Additionally, blood pressure may increase rapidly at drug onset. A possible solution to mitigate anxiety, abuse-related rapid euphoria increases and/or rapid blood pressure changes at onset consist of slowing the onset of the drug effect by using a slow-release formulation of MDMA. In the present study, the investigators will characterize the effects of lysine-MDMA and lysine-MDA and compare their effects with MDMA/MDA to test the concept of attenuated effects across both substances.

Description:

3,4-methylenedioxymethamphetamine (MDMA) is used as recreational substance (Ecstasy), research tool to stimulate serotonin (5-HT) and oxytocin release and study associated mood states, and as a potential therapeutic substance to enhance psychotherapy for post-traumatic stress disorder. MDMA is an amphetamine derivative which, unlike prototypical amphetamines, predominantly enhances serotonergic neurotransmission via release of 5-HT through the SERT and it less potently also releases dopamine and norepinephrine through the DA transporter and NE transporter, respectively. Furthermore, MDMA is known to trigger oxytocin release which may contribute to its effects to increase trust, prosociality, and enhance empathy. MDMA is therefore referred to as an "entactogen" or "empathogen". MDMA is currently the only empathogen investigated in substance-assisted psychotherapy but other substances including the MDMA-metabolite 3,4-methylenedioxyamphetamine (MDA) have been used in the past or may be used in the future.

Aim 1: MDA may exert greater perceptual psychedelic-like effects due to a more potent binding to the serotonin 5-HT2A receptor, and it may also act longer than MDMA partly due to a longer plasma half-life. However, effects of MDMA and MDA have never been compared directly in the same study in humans and there is only one modern study that characterized MDA in humans. Therefore, the present study aims to describe and directly compare for the first time the effects of MDMA and MDA in the same healthy volunteers using modern and sensitive psychological and psychometric tests.

Aim 2: Additionally, although amphetamines including MDMA and MDA induce mainly positive subjective effects they may also produce negative subjective drug effects including anxiety in particular at the onset of the subjective response and the rapid onset of euphoria may increase abuse liability. Additionally, blood pressure may increase rapidly at drug onset. A possible solution to mitigate anxiety, abuse-related rapid euphoria increases and/or rapid blood pressure changes at onset consist of slowing the onset of the drug effect by using a slow-release formulation of MDMA/MDA. Alternatively, amphetamines can be linked to the endogenous amino acid lysine forming inactive lysine-amphetamine which then liberates the active amphetamine slowly in the circulation via plasma peptidases. This approach has been implemented with the medication Lisdexamfetamine, which combines lysine with d-amphetamine. In the present study, the investigators will similarly characterize the effects of lysine-MDMA and lysine-MDA to test for attenuated effects across both substances in comparison with MDMA/MDA.

Using a two-factorial study design with four active substance conditions (MDMA vs. MDA and lysine-MDMA vs. lysine-MDA) the investigators will be able to test differences between MDMA and MDA (with and without lysine) as well as between lysinated a non-lysinated substance (regardless of active substance) in the same study and with high statistical power and within one study addressing two aims.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 24
• Est. completion date: May 31, 2024
• Est. primary completion date: May 31, 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 old

2. Sufficient understanding of the German language

3. Understanding of procedures and risks associated with the study

4. Willing to adhere to the protocol and signing of the consent form

5. Willing to refrain from the consumption of illicit psychoactive substances during the study

6. Abstaining from xanthine-based liquids from the evenings prior to the study sessions to the end of the study days

7. Willing not to operate heavy machinery within 48 hours 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 or bipolar disorder in first-degree relatives

4. Hypertension (>140/90 mmHg) or hypotension (SBP<85 mmHg)

5. Hallucinogenic substance or MDMA use more than 20 times or use of any illicit substance within the previous two months (not including cannabis)

6. Pregnancy or current breastfeeding

7. Participation in another clinical trial (currently or within the last 30 days)

8. Use of medication that may interfere with the effects of the study medication

9. Tobacco smoking (>10 cigarettes/day)

10. Consumption of alcoholic beverages (>20 drinks/week)

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• 3,4-methylenedioxymethamphetamine
A moderate dose of 100 mg MDMA will be administered.
• 3,4-methylenedioxyamphetamine
A moderate dose of 93.9 mg MDA will be administered.
• lysine-3,4-methylenedioxymethamphetamine
A moderate dose of 171.7 mg lysine-MDMA will be administered.
• lysine-3,4-methylenedioxyamphetamine
A moderate dose of 165.6 mg lysine-MDA will be administered.

Other:
• Placebo
Placebo (Mannitol)

Locations

Country	Name	City	State
Switzerland	University Hospital Basel, Clinical Trial Unit	Basel	BS

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	Acute 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	18 months
Primary	Plasma levels of MDMA	Assessed 18 times on each study day via blood samples	18 months
Primary	Plasma levels of MDA	Assessed 18 times on each study day via blood samples	18 months
Secondary	Acute 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"	18 months
Secondary	Acute Subjective effects III	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	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")	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")	18 months
Secondary	Autonomic effects I	Assessed 20 times on each study day via systolic and diastolic blood pressure	18 months
Secondary	Autonomic effects II	Assessed 20 times on each study day via heart rate	18 months
Secondary	Autonomic effects III	Assessed 20 times on each study day via tympanic body temperature	18 months
Secondary	Autonomic effects IV	Assessed 7 times on each study day via pupil diameter	18 months
Secondary	Autonomic effects V	Assessed one time on each study day via ECG (QT-time)	18 months
Secondary	Plasma levels of oxytocin	Assessed 5 times on each study day via blood samples	18 months
Secondary	Emotion processing I	Assessed one time on each study day via Face Emotion Recognition Task (FERT).	18 months
Secondary	Emotion processing II	Assessed one time on each study day via Multifaceted Empathy Test (MET).	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. The HEXACO uses a 5-point Likert scale ranging from "completely disagree" to "fully agree".	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