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

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.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• Switzerland
  • Basel Stadt
    • Basel, Basel Stadt, Switzerland, 4031
      • University Hospital Basel

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 46 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Placebo, LSD, d-Amphetamine, 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	Drug: MDMA; 125mg per os, single dose; Other Names: 3,4-methylenedioxymethamphetamine; Drug: LSD; 100ug per os, single dose; Other Names: Lysergic Acid Diethylamide; Drug: Amphetamine; 40.3mg per os, single dose; Other Names: d-amphetamine sulfate; Drug: Placebo; Capsules containing mannitol looking identical to the other drugs
Other: LSD, d-Amphetamine, MDMA, 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	Drug: MDMA; 125mg per os, single dose; Other Names: 3,4-methylenedioxymethamphetamine; Drug: LSD; 100ug per os, single dose; Other Names: Lysergic Acid Diethylamide; Drug: Amphetamine; 40.3mg per os, single dose; Other Names: d-amphetamine sulfate; Drug: Placebo; Capsules containing mannitol looking identical to the other drugs
Other: d-Amphetamine, MDMA, LSD, 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	Drug: MDMA; 125mg per os, single dose; Other Names: 3,4-methylenedioxymethamphetamine; Drug: LSD; 100ug per os, single dose; Other Names: Lysergic Acid Diethylamide; Drug: Amphetamine; 40.3mg per os, single dose; Other Names: d-amphetamine sulfate; Drug: Placebo; Capsules containing mannitol looking identical to the other drugs
Other: MDMA, LSD, Placebo, d-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	Drug: MDMA; 125mg per os, single dose; Other Names: 3,4-methylenedioxymethamphetamine; Drug: LSD; 100ug per os, single dose; Other Names: Lysergic Acid Diethylamide; Drug: Amphetamine; 40.3mg per os, single dose; Other Names: d-amphetamine sulfate; 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
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

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2017
• Primary Completion (Actual): August 11, 2018
• Study Completion (Actual): September 4, 2018

Study Registration Dates

• First Submitted: December 22, 2016
• First Submitted That Met QC Criteria: January 10, 2017
• First Posted (Estimate): January 13, 2017

Study Record Updates

• Last Update Posted (Actual): October 15, 2018
• Last Update Submitted That Met QC Criteria: October 12, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Dopamine Agents; Serotonin Receptor Agonists; Serotonin Antagonists; Dopamine Uptake Inhibitors; Central Nervous System Stimulants; Sympathomimetics; Hallucinogens; Adrenergic Uptake Inhibitors; N-Methyl-3,4-methylenedioxyamphetamine; Amphetamine; Dextroamphetamine; Lysergic Acid Diethylamide
• Other Study ID Numbers: BASEC 2016-01827

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

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