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

Healthy Volunteers Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02492074
• Other study ID #: GEI-TCP I
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: December 2024
• Est. completion date: May 2025

Study information

• Verified date: January 2024
• Source: Central Institute of Mental Health, Mannheim
• Contact: F. Markus Leweke, MD
• Phone: +49 621 1703 2321
• Email: leweke[@]cimh.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 60
• Est. completion date: May 2025
• Est. primary completion date: April 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy Volunteers
• Modeling Psychosis
• Psychotic Disorders

Intervention

Drug:
• Delta-9-tetrahydrocannabinol
oral administration of delta-9-tetrahydrocannabinol
• Cannabidiol
oral administration of cannabidiol
• Placebo
oral administration of placebo

Locations

Country	Name	City	State
Germany	Central Institute of Mental Health	Mannheim	BW

Sponsors (1)

Lead Sponsor	Collaborator
Central Institute of Mental Health, Mannheim

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Primary	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	Change in PANSS subscores and clusters (baseline to post drug intake)		up to 4 hours
Secondary	Change in Digit Symbol Coding		up to 6 hours
Secondary	Change in Letter-Number-Sequencing		up to 6 hours
Secondary	Change in emotional state (EWL, "Eigenschaftswörterliste")		up to 6 hours
Secondary	Change in attentional state (d2-test of attention d2-R)		up to 6 hours
Secondary	Change in imagination (Bett's Questionaire upon Mental Imagery)		up to 6 hours
Secondary	Change in binocular depth inversion illusion (BDII)		up to 6 hours
Secondary	Change in Wisconsin Card Sorting Test Performance		up to 6 hours
Secondary	Assessment of hallucinogenic states scale (APZ) (post drug intake)	questionaire	1 day
Secondary	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
Secondary	Metabolic markers post drug intake (blood)		up to 4 hours
Secondary	Metabolic markers post drug intake (cerebrospinal fluid)		up to 4 hours
Secondary	D2-receptor availability post drug intake		up to 5 hours