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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Healthy Volunteers; Modeling Psychosis
• Intervention / Treatment: Drug: Placebo; Drug: Delta-9-tetrahydrocannabinol; Drug: Cannabidiol

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: F. Markus Leweke, MD; Phone Number: +49 621 1703 2321; Email: leweke@cimh.de
• Study Contact Backup: Name: Cathrin Rohleder, PhD; Phone Number: +49 621 1703 2333; Email: rohleder@cimh.de

Study Locations

• Germany
  • BW
    • Mannheim, BW, Germany, 68159
      • Central Institute of Mental Health
      • Contact: F. Markus Leweke, MD; Email: leweke@cimh.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of biomarker profiles in serum and cerebrospinal fluid of subjects	Comparison of biomarker profiles in serum and cerebrospinal fluid after different treatments	1 day

Collaborators and Investigators

• Sponsor: Central Institute of Mental Health, Mannheim
• Investigators: Principal Investigator: F. Markus Leweke, MD, Central Institute of Mental Health

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2024
• Primary Completion (Estimated): April 1, 2025
• Study Completion (Estimated): May 1, 2025

Study Registration Dates

• First Submitted: July 3, 2015
• First Submitted That Met QC Criteria: July 3, 2015
• First Posted (Estimated): July 8, 2015

Study Record Updates

• Last Update Posted (Actual): January 24, 2024
• Last Update Submitted That Met QC Criteria: January 23, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: cannabidiol; delta-9-tetrahydrocannabinol; COMT
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Psychotic Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Psychotropic Drugs; Anticonvulsants; Hallucinogens; Cannabinoid Receptor Agonists; Cannabinoid Receptor Modulators; Dronabinol; Cannabidiol
• Other Study ID Numbers: GEI-TCP I

Drug and device information, study documents

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