Gene-Environment-Interaction: Influence of the COMT Genotype on the Effects of Different Cannabinoids

Study Overview
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Brief Summary
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The study evaluates the gene-environment interaction of the COMT-genotype on the effects of the phytocannabinoids delta-9-tetrahydrocannabinol, cannabidiol or a combination of both on induction of psychotic symptoms, endocannabinoid levels in human body fluids, neuronal processing, and neural oscillations. In addition the effects of the phytocannabinoids on lipid levels in serum and cerebrospinal fluid, cognition, neural synchrony and neuronal processing assessed by EEG and fMRI.

Official Title
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Gene-Environment-Interaction: Influence of the COMT Genotype on the Effects of Different Cannabinoids on the Endocannabinoid System, Cognition and Neuronal Oscillations

Conditions
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Healthy, Modeling Psychosis

Intervention / Treatment
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* Drug: delta-9-tetrahydrocannabinol
* Drug: Cannabidiol
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent given by the subject Healthy young man (age between 18 and 45) insightful to the study (WST> 95) Right handedness At least one time consumption of Cannabis but less than 10 times/ per lifetime, no consumption of other psychotropic agents (despite coffee or nicotine), no alcohol abuse Negative drug-screening at the time of screening Body Mass Index between 18 and 30 Exclusion Criteria: Lack of accountability Participation in other interventional trials Severe medical or neurological illness, especially cardiovascular, renal, advanced respiratory, hematological or endocrinological failures or infectious diseases (acute hepatitis A, B or C or HIV) assessed at the time of the screening by the subject's history, clinical examination and laboratory testing, at the discretion of the investigator Any known psychiatric illness in the participant's history Known family history concerning psychiatric disorders Cannabis consumption within the last six months Consumption of any illegal drugs (except cannabis in history, see above) Intake of interfering medication, at the discretion of the investigator High intracranial pressure Any disorders in stereoscopic vision (measured by the TNO-Test, Lamerics, Utrecht) or hearing deficits Contraindications due to the Investigators Brochure Contraindication for Magnetic Resonance Imaging (e.g. cardiac pacemaker, claustrophobia, attached brace, in body metal, tattoos) or lumbar puncture (e.g. local or systemic infection, disturbance of blood coagulation, medication with anticoagulants like Phenprocoumon)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: THC<br>Subjects receive 20 mg delta-9-tetrahydrocannabinol (2 capsules containing 10 mg each) and corresponding cannabidiol placebo capsules. | Drug: delta-9-tetrahydrocannabinol<br> <br> * Other names: Dronabinol;Drug: Placebo<br> <br> |
| Experimental: CBD<br>Subjects receive 800 mg cannabidiol (4 capsules containing 200 mg each) and corresponding delta-9-tetrahydrocannabinol placebo capsules. | Drug: Cannabidiol<br> <br> Drug: Placebo<br> <br> |
| Experimental: CBD+THC<br>Subjects receive 800 mg cannabidiol (4 capsules containing 200 mg each) and 20 mg delta-9-tetrahydrocannabinol (2 capsules containing 10 mg each) a | Drug: delta-9-tetrahydrocannabinol<br> <br> * Other names: Dronabinol;Drug: Cannabidiol<br> <br> |
| Placebo Comparator: Placebo<br>Subjects receive corresponding delta-9-tetrahydrocannabinol and cannabidiol placebo capsules | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Positive and Negative Syndrome Scale total score (PANSS T) from baseline to post drug intake of both on induction of psychotic symptoms, endocannabinoid levels in human body fluids, neuronal processing, and neural synchrony. |  | up to 4 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Positive and Negative Syndrome Scale (PANSS) subscores and clusters (baseline to post drug intake) |  | up to 4 hours | 
| Change in neuropsychological parameters |  | up to 6 hours | 
| Assessment of hallucinogen states (APZ) (post drug intake) |  | 1 day | 
| Safety and tolerability assessments including (S)AEs, physical examination, vital signs (including heart rate and systolic and diastolic blood pressure in both supine and standing positions), and detailed laboratory assessments |  | 1 day | 
| Metabolic markers post drug intake (blood) |  | up to 4 hours | 
| Metabolic markers post drug intake (cerebrospinal fluid) |  | up to 4 hours | 
| Neural synchrony and event-related potentials post drug intake |  | up to 5 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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delta-9-tetrahydrocannabinol, cannabidiol, COMT, Volunteers