Role of Dopamine, Serotonin and 5-HT2A Receptors in Emotion Processing

Study Overview
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Brief Summary
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The study will test the effect of dopamine, serotonin, and direct 5-HT2A receptor stimulation on empathy, mood perception, and amygdala activity to fearful stimuli. In addition, we predict associations between subjective effects/alterations in emotion processing tests and functional imaging (fMRI) activity.

Official Title
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Role of Dopamine, Serotonin and 5-HT2A Receptors in Emotion Processing

Conditions
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Healthy

Intervention / Treatment
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* Drug: LSD
* Drug: MDMA
* Drug: Amphetamine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 25 and 50 years. Sufficient understanding of the German language Subjects understand 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. Women of childbearing potential must have a negative pregnancy test at the beginning of the study. Pregnancy tests are repeated before each study session. Women and men must agree to use an effective form of birth control (double-barrier method). 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) more than 10 times or any time within the previous two months. Pregnant or nursing women. 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). fMRI related criteria including: metal implants (clips from operations, cochlea, large red/yellow tattoos in the neck area) Tobacco smoking (>10 cigarettes/day) Consumption of alcoholic drinks (>10/week)

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

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 |
| --- | --- |
| Other: Placebo, LSD, d-Amphetamine, MDMA<br>Cross-over within-subjects design with all treatment conditions, arms starting with either Placebo, lysergic acid diethylamide (LSD), d-Amphetamine or methylenedioxymethamphetamine (MDMA) and followed by all other drugs each separated by a wash-out phase | Drug: LSD<br>* 100ug per os, single dose<br>* Other names: Lysergic Acid Diethylamide;Drug: MDMA<br>* 125mg per os, single dose<br>* Other names: 3,4-methylenedioxymethamphetamine;Drug: Amphetamine<br>* 40.3mg per os, single dose<br>* Other names: d-amphetamine sulfate;Drug: Placebo<br>* Capsules containing mannitol looking identical to the other drugs<br>|
| Other: LSD, d-Amphetamine, MDMA, Placebo<br>Cross-over within-subjects design with all treatment conditions, arms starting with either Placebo, LSD, d-Amphetamine or MDMA and followed by all other drugs each separated by a wash-out phase | Drug: LSD<br>* 100ug per os, single dose<br>* Other names: Lysergic Acid Diethylamide;Drug: MDMA<br>* 125mg per os, single dose<br>* Other names: 3,4-methylenedioxymethamphetamine;Drug: Amphetamine<br>* 40.3mg per os, single dose<br>* Other names: d-amphetamine sulfate;Drug: Placebo<br>* Capsules containing mannitol looking identical to the other drugs<br>|
| Other: d-Amphetamine, MDMA, LSD, Placebo<br>Cross-over within-subjects design with all treatment conditions, arms starting with either Placebo, LSD, d-Amphetamine or MDMA and followed by all other drugs each separated by a wash-out phase | Drug: LSD<br>* 100ug per os, single dose<br>* Other names: Lysergic Acid Diethylamide;Drug: MDMA<br>* 125mg per os, single dose<br>* Other names: 3,4-methylenedioxymethamphetamine;Drug: Amphetamine<br>* 40.3mg per os, single dose<br>* Other names: d-amphetamine sulfate;Drug: Placebo<br>* Capsules containing mannitol looking identical to the other drugs<br>|
| Other: MDMA, LSD, Placebo, d-Amphetamine,,<br>Cross-over within-subjects design with all treatment conditions, arms starting with either Placebo, LSD, d-Amphetamine or MDMA and followed by all other drugs each separated by a wash-out phase | Drug: LSD<br>* 100ug per os, single dose<br>* Other names: Lysergic Acid Diethylamide;Drug: MDMA<br>* 125mg per os, single dose<br>* Other names: 3,4-methylenedioxymethamphetamine;Drug: Amphetamine<br>* 40.3mg per os, single dose<br>* Other names: d-amphetamine sulfate;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 |
| --- | --- | --- |
| Emotional enhancement as determined by fMRI | Emotional enhancement (empathy, oxytocin, mood perception, fMRI amygdala blood oxygen level-dependent (BOLD) signal reactivity to fearful stimuli) | 12 hours | 
| fMRI brain activity | Associations between subjective effects/alterations in emotion processing with fMRI amygdala BOLD activity | 1 hour | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Resting State fMRI | Association between emotional enhancement and resting state fMRI neuronal activity | 1 hour | 
| Effect Modulation by personality traits (assessed with questionnaires), | Effect modulation by personality traits (assessed with questionnaires), baseline amygdala reactivity to fear in the fMRI, and genetic polymorphisms determined by genotyping of each subject | 12 hours | 
| Effect Modulation by amygdala reactivity to fear (assessed in the fMRI) | Effect modulation by personality traits (assessed with questionnaires), baseline amygdala reactivity to fear in the fMRI, and genetic polymorphisms determined by genotyping of each subject | 12 hours | 
| Effect Modulation by genetic polymorphisms (determined by genotyping of each subject) | Effect modulation by personality traits (assessed with questionnaires), baseline amygdala reactivity to fear in the fMRI, and genetic polymorphisms determined by genotyping of each subject | 12 hours |