Neurodynamics of Prosocial Emotional Processing Following Serotonergic Stimulation With N,N-Dimethyltryptamine (DMT) and Harmine in Healthy Subjects

The aim of the project is to assess brain network dynamics, self-referential information processing and prosociality and learning following the modulation of the serotonin-system by serotonergic-psychoactive compounds.

Study Overview

• Status: Completed
• Conditions: Emotions; Mood; Cognitive Function 1, Social; Empathy
• Intervention / Treatment: Drug: DMT; Drug: Harmine; Drug: Placebo (DMT); Drug: Placebo (Harmine)

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• Switzerland
  • Zürich, Switzerland, 8032
    • Psychiatric University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Willing and capable to give informed consent for the participation in the study after it has been thoroughly explained
• Little or no previous experiences with psychedelic substances
• Body mass index (BMI) between 18.5 and 25
• Willing to refrain from drinking caffeine 3 days and alcohol the day before testing session, from drinking alcohol and caffeinated drinks at the testing days and from consuming psychoactive substances or other medications for 2 weeks before testing days and for the duration of the study
• Able and willing to comply with all study requirements
• Informed consent form was signed
• Good knowledge of the German language

Exclusion Criteria:

• Previous significant adverse response to a hallucinogenic drug
• Participation in another study where pharmaceutical compounds will be given
• Self or first-degree relatives with present or antecedent psychiatric disorders
• History of head trauma or fainting
• Recent cardiac or brain surgery
• Current use of medication or psychotropic substances (including nicotine addiction)
• Presence of major internal or neurological disorders (including sepsis, pheochromocytoma, thyrotoxicosis, drug-induced fibrosis, familiar or basilar artery migraine)
• Cardiovascular disease (hypertonia, coronary artery disease, heart insufficiency, myocardial infarction, coronary spastic angina)
• Peripheral vascular disease (thromboangiitis obliterans, luetic arteritis, severe arteriosclerosis, thrombophlebitis, Raynaud's disease)
• Liver or renal disease

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Harmine + DMT	Drug: DMT; DMT; Drug: Harmine; Harmine
Experimental: Harmine + Placebo(DMT)	Drug: Harmine; Harmine; Drug: Placebo (DMT); Placebo for DMT
Placebo Comparator: Placebo(Harmin & Placebo)	Drug: Placebo (DMT); Placebo for DMT; Drug: Placebo (Harmine); Placebo for Harmine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Behavioral Outcome Measures (Social Value Orientation - SVO, Charity Donation Frank Task)	Social Cognition	Acute drug effects (240 minutes - Charity Donation Frank Task, 300 minutes - SVO)
Change in Behavioral Outcome Measures (Visuall Oddball, Karaoke Task)	Self-referential Processing	Acute drug effects (60 min - Visuall Oddball, 150 min - Karaoke Task)
Change in Pharmacological-EEG (Lagged Phase Synchronicity)	Functional brain connectivity	Baseline, Acute drug effects (30 minutes , 135 minutes, 195 minutes, 285 minutes)
Change in Pharmacological-EEG (Resting State)	Spectral Density	Baseline, Acute drug effects (30 minutes , 135 minutes, 195 minutes, 285 minutes)
Change in Pharmacological-EEG	Event-Related Potentials (ERP)	Acute drug effects (60 minutes, 240 minutes)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in biomarkers	Tryptophan catabolites (TRYCAT)	Baseline, Acute drug effects (0 minutes, 30 minutes, 60 minutes, 90 minutes, 120 minutes, 150 minutes, 180 minutes, 210 minutes, 240 minutes, 270 minutes, 300 minutes)
Change in biomarkers	Brain-derived Neurotrophic Factor (BDNF)	Baseline, Acute drug effects (30 minutes, 90 minutes, 150 minutes, 300 minutes)
Change in biomarkers	Hypothalamic-Pituitary-Adrenal Axis (HPA-A)	Baseline, Acute drug effects (0 minutes, 30 minutes, 60 minutes, 90 minutes, 120 minutes, 150 minutes, 180 minutes, 210 minutes, 240 minutes, 270 minutes, 300 minutes)
Change in biomarkers	API (DMT, Harmine)	Baseline, Acute drug effects (0 minutes, 30 minutes, 60 minutes, 90 minutes, 120 minutes, 150 minutes, 180 minutes, 210 minutes, 240 minutes, 270 minutes, 300 minutes)
Change in biomarkers	Neuroinflammation - Interleukines	Baseline, Acute drug effects (30 minutes, 90 minutes, 150 minutes, 300 minutes)
Change in biomarkers	Oxidative Stress Markers (Nitric Oxide Synthase)	Baseline, Acute drug effects (30 minutes, 90 minutes, 150 minutes, 300 minutes)
Psychometry	Cognitive Flexibility	Baseline, Acute, 1 day after, 1 week after, 1 month after and 4 month after intervention
Psychometry	MINDSENS	Baseline, Acute, 1 day after, 1 week after, 1 month after and 4 month after intervention
Psychometry	PANAS	Baseline, Acute, 1 day after, 1 week after, 1 month after and 4 month after intervention
Psychometry	CFI	Baseline, Acute, 1 day after, 1 week after, 1 month after and 4 month after intervention
Psychometry	SRQ	Baseline, Acute, 1 day after, 1 week after, 1 month after and 4 month after intervention
Psychometry	MBQ	Baseline, Acute, 1 day after, 1 week after, 1 month after and 4 month after intervention

Collaborators and Investigators

• Sponsor: Psychiatric University Hospital, Zurich
• Collaborators: University of Basel

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2020
• Primary Completion (Actual): July 19, 2021
• Study Completion (Actual): January 10, 2022

Study Registration Dates

• First Submitted: December 23, 2020
• First Submitted That Met QC Criteria: January 15, 2021
• First Posted (Actual): January 20, 2021

Study Record Updates

• Last Update Posted (Actual): October 4, 2022
• Last Update Submitted That Met QC Criteria: October 3, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Psychotropic Drugs; Monoamine Oxidase Inhibitors; Hallucinogens; Harmine
• Other Study ID Numbers: 2018-01385

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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