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

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, neuronal processing assessed by fMRI as well as D2-receptor availability assessed by [18F] desmethoxyfallypride.

Official Title
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Gene-Environment-Interaction: Influence of the COMT Genotype on the Effects of Different Cannabinoids on the Endocannabinoid System and Brain Function

Conditions
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Healthy Volunteers, 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) or contradiction for the PET-CT method and the radiopharmaceutical

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>* oral administration of delta-9-tetrahydrocannabinol<br>* Other names: Dronabinol;Drug: Placebo<br>* oral administration of placebo<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>* oral administration of cannabidiol<br>Drug: Placebo<br>* oral administration of placebo<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) | Drug: Delta-9-tetrahydrocannabinol<br>* oral administration of delta-9-tetrahydrocannabinol<br>* Other names: Dronabinol;Drug: Cannabidiol<br>* oral administration of cannabidiol<br>|
| Placebo Comparator: Placebo<br>Subjects receive corresponding delta-9-tetrahydrocannabinol and cannabidiol placebo capsules | Drug: Placebo<br>* oral administration of placebo<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 D2-receptor availability |  | up to 6 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in PANSS subscores and clusters (baseline to post drug intake) |  | up to 4 hours | 
| Change in Digit Symbol Coding |  | up to 6 hours | 
| Change in Letter-Number-Sequencing |  | up to 6 hours | 
| Change in emotional state (EWL, Eigenschaftswörterliste) |  | up to 6 hours | 
| Change in attentional state (d2-test of attention d2-R) |  | up to 6 hours | 
| Change in imagination (Bett's Questionaire upon Mental Imagery) |  | up to 6 hours | 
| Change in binocular depth inversion illusion (BDII) |  | up to 6 hours | 
| Change in Wisconsin Card Sorting Test Performance |  | up to 6 hours | 
| Assessment of hallucinogenic states scale (APZ) (post drug intake) | questionaire | 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 | 
| D2-receptor availability 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