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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy; Modeling Psychosis
• Intervention / Treatment: Drug: Placebo; Drug: Cannabidiol; Drug: delta-9-tetrahydrocannabinol

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

Contacts and Locations

Study Locations

• Germany
  • BW
    • Mannheim, BW, Germany, 68159
      • Central Institute of Mental Health

Participation Criteria

Eligibility Criteria

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

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)

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; Drug: 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; Drug: Cannabidiol
Placebo Comparator: Placebo; Subjects receive corresponding delta-9-tetrahydrocannabinol and cannabidiol placebo capsules	Drug: 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) a	Drug: Cannabidiol; Drug: delta-9-tetrahydrocannabinol; Other Names: Dronabinol

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 neural synchrony.	up to 4 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
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
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
Neural synchrony and event-related potentials post drug intake	up to 5 hours

Other Outcome Measures

Outcome Measure	Time Frame
Assessment of biomarker profiles in serum and cerebrospinal fluid of subjects.	1 day

Collaborators and Investigators

• Sponsor: Central Institute of Mental Health, Mannheim

Publications and helpful links

General Publications

• Woelfl T, Rohleder C, Mueller JK, Lange B, Reuter A, Schmidt AM, Koethe D, Hellmich M, Leweke FM. Effects of Cannabidiol and Delta-9-Tetrahydrocannabinol on Emotion, Cognition, and Attention: A Double-Blind, Placebo-Controlled, Randomized Experimental Trial in Healthy Volunteers. Front Psychiatry. 2020 Nov 13;11:576877. doi: 10.3389/fpsyt.2020.576877. eCollection 2020.

Study record dates

Study Major Dates

• Study Start: April 1, 2015
• Primary Completion (Actual): July 1, 2015
• Study Completion (Actual): August 1, 2015

Study Registration Dates

• First Submitted: June 29, 2015
• First Submitted That Met QC Criteria: June 30, 2015
• First Posted (Estimate): July 1, 2015

Study Record Updates

• Last Update Posted (Estimate): August 17, 2015
• Last Update Submitted That Met QC Criteria: August 13, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Keywords: Volunteers; 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 II