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

Early Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: LSD; Drug: MDMA; Drug: Amphetamine; Drug: Placebo

• Registration Number: NCT03019822
• Lead Sponsor: University Hospital, Basel, Switzerland

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-12-22
• Study First Submitted QC: 2017-01-10
• Study First Posted: 2017-01-13
• Study Start: 2017-02-01
• Primary Completion: 2018-08-11
• Study Completion: 2018-09-04
• Status Verified: 2018-10
• Last Update Submitted: 2018-10-12
• Last Update Posted: 2018-10-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 28

Inclusion Criteria

1. Age between 25 and 50 years.
2. Sufficient understanding of the German language
3. Subjects understand the procedures and the risks associated with the study.
4. Participants must be willing to adhere to the protocol and sign the consent form.
5. Participants must be willing to refrain from taking illicit psychoactive substances during the study.
6. 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.
7. Participants must be willing not to drive a traffic vehicle or to operate machines within 48 h after substance administration.
8. 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).
9. Body mass index 18-29 kg/m2.

Exclusion Criteria

1. Chronic or acute medical condition
2. Hypertension (>140/90 mmHg) or Hypotension (SBP<85 mmHg)
3. Current or previous major psychiatric disorder
4. Psychotic disorder in first-degree relatives
5. Illicit substance use (with the exception of cannabis) more than 10 times or any time within the previous two months.
6. Pregnant or nursing women.
7. Participation in another clinical trial (currently or within the last 30 days)
8. Use of medications that may interfere with the effects of the study medications (any psychiatric medications).
9. fMRI related criteria including: metal implants (clips from operations, cochlea, large red/yellow tattoos in the neck area)
10. Tobacco smoking (>10 cigarettes/day)
11. Consumption of alcoholic drinks (>10/week)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
MDMA, LSD, Placebo, d-Amphetamine,,	MDMA	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
LSD, d-Amphetamine, MDMA, Placebo	Placebo	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
Placebo, LSD, d-Amphetamine, MDMA	MDMA	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
Placebo, LSD, d-Amphetamine, MDMA	Placebo	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
d-Amphetamine, MDMA, LSD, Placebo	Placebo	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
MDMA, LSD, Placebo, d-Amphetamine,,	Placebo	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
MDMA, LSD, Placebo, d-Amphetamine,,	Amphetamine	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
Placebo, LSD, d-Amphetamine, MDMA	LSD	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
LSD, d-Amphetamine, MDMA, Placebo	MDMA	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
Placebo, LSD, d-Amphetamine, MDMA	Amphetamine	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
LSD, d-Amphetamine, MDMA, Placebo	Amphetamine	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
d-Amphetamine, MDMA, LSD, Placebo	LSD	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
d-Amphetamine, MDMA, LSD, Placebo	MDMA	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
d-Amphetamine, MDMA, LSD, Placebo	Amphetamine	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
LSD, d-Amphetamine, MDMA, Placebo	LSD	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
MDMA, LSD, Placebo, d-Amphetamine,,	LSD	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

Primary Outcome Measures

Name	Time	Method
Emotional enhancement as determined by fMRI	12 hours	Emotional enhancement (empathy, oxytocin, mood perception, fMRI amygdala blood oxygen level-dependent (BOLD) signal reactivity to fearful stimuli)
fMRI brain activity	1 hour	Associations between subjective effects/alterations in emotion processing with fMRI amygdala BOLD activity

Secondary Outcome Measures

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

Trial Locations

Locations (1)

University Hospital Basel; 🇨🇭 Basel, Basel Stadt, Switzerland