Effect of Methylenedioxymethamphetamine (MDMA) (Serotonin Release) on Fear Extinction (MFE)

Effect of MDMA (Serotonin Release) on Fear Extinction

Serotonin and oxytocin play a role in fear conditioning and fear extinction learning, psychological processes that are critically involved in psychiatric disorders such as posttraumatic stress disorder (PTSD). Specifically, administration of oxytocin has been shown to facilitate fear extinction in humans. Similarly, substances that release serotonin and oxytocin such as MDMA have been shown to enhance the extinction of fear memory in animals. However, there are no data on the effects of MDMA on fear extinction in humans. Therefore, the primary aim of this study is to investigate the role of acute serotonin release in the effects of fear extinction. MDMA will be used as pharmacological tool to induce serotonin release in this study.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: MDMA; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• Switzerland
  • Basel, Switzerland, 4056
    • Clinical Pharmacology & Toxicology, University Hospital Basel

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 48 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Male
• Age between 18 and 50 years.
• Understanding of the German language.
• Understanding the procedures and the risks associated with the study.
• Participants must be willing to adhere to the protocol and sign the consent form.
• Participants must be willing to refrain from taking illicit psychoactive substances during the study.
• 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.
• Participants must be willing not to drive a traffic vehicle or to operate machines within 48 h after substance administration.
• Body mass index 18-29 kg/m2.

Exclusion Criteria:

• Chronic or acute medical condition
• Hypertension (>140/90 mmHg) or hypotension (SBP<85 mmHg)
• Current or previous major psychiatric disorder
• Psychotic disorder in first-degree relatives
• Illicit substance use (with the exception of cannabis) of more than 5 times or any time within the previous month.
• Participation in another clinical trial (currently or within the last 30 days)
• Use of medications that may interfere with the effects of the study medications (any psychiatric medications)
• Tobacco smoking (>10 cigarettes/day)
• Consumption of alcoholic standard drinks (>10/week or >120 g ethanol/week)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MDMA, Placebo; Cross-over within-subjects design with both treatment conditions, separated by a wash-out phase	Drug: MDMA; 125 mg MDMA per os, single dose; Other Names: 3,4-Methylenedioxymethamphetamine; Drug: Placebo; Capsules containing mannitol looking identical to the other drugs.
Experimental: Placebo, MDMA; Cross-over within-subjects design with both treatment conditions, separated by a wash-out phase	Drug: MDMA; 125 mg MDMA per os, single dose; Other Names: 3,4-Methylenedioxymethamphetamine; Drug: Placebo; Capsules containing mannitol looking identical to the other drugs.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fear extinction measured by Skin conductance response	a) Skin conductance response to conditioned stimuli	12 months
Fear extinction measured by Fear-potentiated startle	b) Fear-potentiated startle to conditioned stimuli	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma concentration of Oxytocin		12 months
Subjective effects measured by Visual analog scales	Visual analog scales, 0-100, 0 for 'not at all' and 100 for 'extremely'	12 months
Autonomic effects measured by Blood pressure	Autonomic effects measured by vital signs	12 months
Autonomic effects measured by Hearth rate	Autonomic effects measured by vital signs	12 months
Autonomic effects measured by Body temperature	Autonomic effects measured by vital signs	12 months
Subjective effects measured by State-trait anxiety inventory for state (STAI-S)		12 months
Plasma concentration of MDMA		12 months

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland
• Investigators: Principal Investigator: Matthias E Liechti, MD, MAS, University Hospital, Basel, Switzerland

Publications and helpful links

General Publications

• Vizeli P, Straumann I, Duthaler U, Varghese N, Eckert A, Paulus MP, Risbrough V, Liechti ME. Effects of 3,4-Methylenedioxymethamphetamine on Conditioned Fear Extinction and Retention in a Crossover Study in Healthy Subjects. Front Pharmacol. 2022 Jul 13;13:906639. doi: 10.3389/fphar.2022.906639. eCollection 2022.

Study record dates

Study Major Dates

• Study Start (Actual): October 18, 2019
• Primary Completion (Actual): December 10, 2020
• Study Completion (Actual): December 24, 2020

Study Registration Dates

• First Submitted: May 4, 2018
• First Submitted That Met QC Criteria: May 4, 2018
• First Posted (Actual): May 17, 2018

Study Record Updates

• Last Update Posted (Actual): January 19, 2022
• Last Update Submitted That Met QC Criteria: January 17, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Hallucinogens; Adrenergic Uptake Inhibitors; N-Methyl-3,4-methylenedioxyamphetamine
• Other Study ID Numbers: BASEC 2017-01947

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No