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

Sponsor

Central Institute of Mental Health, Mannheim (Other)

Overall Status

Unknown status

CT.gov ID

NCT02492074

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

2.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers Modeling Psychosis	Drug: Delta-9-tetrahydrocannabinol Drug: Cannabidiol Drug: Placebo	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Basic Science

Official Title:

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

Anticipated Study Start Date :

Jun 1, 2020

Anticipated Primary Completion Date :

Apr 1, 2022

Anticipated Study Completion Date :

May 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: THC Subjects receive 20 mg delta-9-tetrahydrocannabinol (2 capsules containing 10 mg each) and corresponding cannabidiol placebo capsules.	Drug: Delta-9-tetrahydrocannabinol oral administration of delta-9-tetrahydrocannabinol Other Names: Dronabinol Drug: Placebo oral administration of placebo
Experimental: CBD Subjects receive 800 mg cannabidiol (4 capsules containing 200 mg each) and corresponding delta-9-tetrahydrocannabinol placebo capsules.	Drug: Cannabidiol oral administration of cannabidiol Drug: Placebo oral administration of placebo
Experimental: CBD+THC 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 oral administration of delta-9-tetrahydrocannabinol Other Names: Dronabinol Drug: Cannabidiol oral administration of cannabidiol
Placebo Comparator: Placebo Subjects receive corresponding delta-9-tetrahydrocannabinol and cannabidiol placebo capsules	Drug: Placebo oral administration of placebo

Outcome Measures

Primary Outcome Measures

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

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) [1 day]
questionaire
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]

Other Outcome Measures

Assessment of biomarker profiles in serum and cerebrospinal fluid of subjects [1 day]
Comparison of biomarker profiles in serum and cerebrospinal fluid after different treatments

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 45 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Yes

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