Effects of MDMA-like Substances in Healthy Subjects

NCT04847206 | Completed Phase 1

• 1 other identifier: BASEC 2021-00405
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Healthy

Outcome Measures

Primary Outcomes (3)

• 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

• Plasma levels of MDMA

  Assessed 18 times on each study day via blood samples

  18 months

• Plasma levels of MDA

  Assessed 18 times on each study day via blood samples

  18 months

Secondary Outcomes (17)

• Acute Subjective effects II

  18 months

• Acute Subjective effects III

  18 months

• States of Consciousness Questionnaire

  18 months

• Psychological Insight Questionnaire

  18 months

• Autonomic effects I

  18 months

Study Arms (5)

MDMA (100 mg MDMA-hydrochloride)

EXPERIMENTAL

MDMA (100 mg MDMA-hydrochloride; 84.1 mg MDMA free base)

Drug: 3,4-methylenedioxymethamphetamine

MDA (93.9 mg MDA-hydrochloride)

EXPERIMENTAL

MDA (93.9 mg MDA-hydrochloride; 78.0 mg MDA free base)

Drug: 3,4-methylenedioxyamphetamine

lysine-MDMA (171.7mg lysMDMA dihydrochloride

EXPERIMENTAL

lysine-MDMA (171.7mg lysMDMA dihydrochloride; 84.1 mg MDMA free base)

Drug: lysine-3,4-methylenedioxymethamphetamine

lysine-MDA (165.6 mg lysMDA dihydrochloride;

EXPERIMENTAL

lysine-MDA (165.6 mg lysMDA dihydrochloride; 78.0 mg MDA free base)

Drug: lysine-3,4-methylenedioxyamphetamine

Placebo

PLACEBO COMPARATOR

Placebo

Other: Placebo

Interventions

3,4-methylenedioxymethamphetamine DRUG

A moderate dose of 100 mg MDMA will be administered.

Also known as: MDMA

MDMA (100 mg MDMA-hydrochloride)

3,4-methylenedioxyamphetamine DRUG

A moderate dose of 93.9 mg MDA will be administered.

Also known as: MDA

MDA (93.9 mg MDA-hydrochloride)

lysine-3,4-methylenedioxymethamphetamine DRUG

A moderate dose of 171.7 mg lysine-MDMA will be administered.

Also known as: lysine-MDMA

lysine-MDMA (171.7mg lysMDMA dihydrochloride

lysine-3,4-methylenedioxyamphetamine DRUG

A moderate dose of 165.6 mg lysine-MDA will be administered.

Also known as: lysine-MDA

lysine-MDA (165.6 mg lysMDA dihydrochloride;

Placebo OTHER

Placebo (Mannitol)

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead

Study Sites (1)

University Hospital Basel, Clinical Trial Unit

Basel, Canton of Basel-City, 4056, Switzerland

Location

Related Publications (1)

• Straumann I, Vizeli P, Avedisian I, Erne L, Noorshams D, Vukalovic I, Eckert A, Luethi D, Rudin D, Liechti ME. Acute effects of MDMA, MDA, lysine-MDMA, and lysine-MDA in a randomized, double-blind, placebo-controlled, crossover trial in healthy participants. Neuropsychopharmacology. 2026 Jan;51(2):476-485. doi: 10.1038/s41386-025-02248-3. Epub 2025 Sep 25.

  PMID: 40999236 DERIVED

MeSH Terms

Interventions

N-Methyl-3,4-methylenedioxyamphetamine; 3,4-Methylenedioxyamphetamine; N(epsilon)-(malondialdehyde)lysine

Intervention Hierarchy (Ancestors)

Amphetamines; Phenethylamines; Ethylamines; Amines; Organic Chemicals

Study Officials

• Matthias E Liechti, Prof. Dr. MD

  University Hospital, Basel, Switzerland

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Double-blind, placebo-controlled, 5-period cross-over design with four active substance conditions (equimolar doses of psychoactive substance) and placebo: 1\. MDMA (100 mg MDMA-hydrochloride; 84.1 mg MDMA free base) 2) MDA (93.9 mg MDA-hydrochloride; 78.0 mg MDA free base) 3) lysMDMA (171.7mg lysMDMA dihydrochloride; 84.1 mg MDMA free base) 4) lysMDA (165.6 mg lysMDA dihydrochloride; 78.0 mg MDA free base) 5) Placebo

Study Record Dates

• First Submitted: April 1, 2021
• First Posted: April 19, 2021
• Study Start: December 1, 2021
• Primary Completion: June 18, 2024
• Study Completion: June 18, 2024
• Last Updated: August 14, 2024

Record last verified: 2024-08

Locations

CH (1)