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

Study Overview
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Brief Summary
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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.

Official Title
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Effect of MDMA (Serotonin Release) on Fear Extinction

Conditions
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Healthy

Intervention / Treatment
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* Drug: MDMA
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 |