Effects of MDMA-like Substances in Healthy Subjects

  • STATUS
    Recruiting
  • End date
    Dec 31, 2023
  • participants needed
    24
  • sponsor
    University Hospital, Basel, Switzerland
Updated on 5 January 2022
Accepts healthy volunteers

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.

Details
Condition Healthy
Treatment Placebo, 3,4-methylenedioxymethamphetamine, 3,4-methylenedioxyamphetamine, lysine-3,4-methylenedioxymethamphetamine, lysine-3,4-methylenedioxyamphetamine
Clinical Study IdentifierNCT04847206
SponsorUniversity Hospital, Basel, Switzerland
Last Modified on5 January 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Age between 18 and 65 years old
Sufficient 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
Abstaining from xanthine-based liquids from the evenings prior to the study sessions to the end of the study days
Willing not to operate heavy machinery within 48 hours 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 or bipolar disorder in first-degree relatives
Hypertension (>140/90 mmHg) or hypotension (SBP<85 mmHg)
Hallucinogenic substance or MDMA use more than 20 times or use of any illicit substance within the previous two months (not including cannabis)
Pregnancy or current breastfeeding
Participation in another clinical trial (currently or within the last 30 days)
Use of medication that may interfere with the effects of the study medication
Tobacco smoking (>10 cigarettes/day)
Consumption of alcoholic beverages (>20 drinks/week)
Clear my responses

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