Clinical trial NCT03527316: Effect of Methylenedioxymethamphetamine (MDMA) (Serotonin Release) on Fear Extinction
Official title: Effect of MDMA (Serotonin Release) on Fear Extinction
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Healthy
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
First posted: 2018-05-17
Enrollment: 30
Sex: MALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: 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.


Eligibility criteria: 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)

Primary outcomes:
measure: Fear extinction measured by Skin conductance response
timeFrame: 12 months
measure: Fear extinction measured by Fear-potentiated startle
timeFrame: 12 months
Secondary outcomes:
measure: Plasma concentration of Oxytocin
timeFrame: 12 months
measure: Subjective effects measured by Visual analog scales
timeFrame: 12 months
measure: Autonomic effects measured by Blood pressure
timeFrame: 12 months
measure: Autonomic effects measured by Hearth rate
timeFrame: 12 months
measure: Autonomic effects measured by Body temperature
timeFrame: 12 months
measure: Subjective effects measured by State-trait anxiety inventory for state (STAI-S)
timeFrame: 12 months
measure: Plasma concentration of MDMA
timeFrame: 12 months
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: Clinical Pharmacology & Toxicology, University Hospital Basel
Study officials:
affiliation: University Hospital, Basel, Switzerland
name: Matthias E Liechti, MD, MAS
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.