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

Study Overview
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Brief Summary
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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.

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

Conditions
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Emotions, Mood, Cognitive Function 1, Social, Empathy

Intervention / Treatment
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* Drug: DMT
* Drug: Harmine
* Drug: Placebo (Harmine)
* Drug: Placebo (DMT)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 40 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: Harmine + DMT<br> | Drug: DMT<br>* DMT<br>Drug: Harmine<br>* Harmine<br>|
| Experimental: Harmine + Placebo(DMT)<br> | Drug: Harmine<br>* Harmine<br>Drug: Placebo (DMT)<br>* Placebo for DMT<br>|
| Placebo Comparator: Placebo(Harmin & Placebo)<br> | Drug: Placebo (Harmine)<br>* Placebo for Harmine<br>Drug: Placebo (DMT)<br>* Placebo for DMT<br>|

What is the study measuring?
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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 |