Clinical trial NCT02487381: Gene-Environment-Interaction: Influence of the COMT Genotype on the Effects of Different Cannabinoids
Official title: Gene-Environment-Interaction: Influence of the COMT Genotype on the Effects of Different Cannabinoids on the Endocannabinoid System, Cognition and Neuronal Oscillations
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Modeling Psychosis
Keywords: delta-9-tetrahydrocannabinol
cannabidiol
COMT
Volunteers
Lead sponsor: Central Institute of Mental Health, Mannheim
Sponsor class: OTHER
First posted: 2015-07-01
Enrollment: 60
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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, neural synchrony and neuronal processing assessed by EEG and fMRI.


Eligibility criteria: 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)

Primary outcomes:
measure: 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.
timeFrame: up to 4 hours
Secondary outcomes:
measure: Change in Positive and Negative Syndrome Scale (PANSS) subscores and clusters (baseline to post drug intake)
timeFrame: up to 4 hours
measure: Change in neuropsychological parameters
timeFrame: up to 6 hours
measure: Assessment of hallucinogen states (APZ) (post drug intake)
timeFrame: 1 day
measure: 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
timeFrame: 1 day
measure: Metabolic markers post drug intake (blood)
timeFrame: up to 4 hours
measure: Metabolic markers post drug intake (cerebrospinal fluid)
timeFrame: up to 4 hours
measure: Neural synchrony and event-related potentials post drug intake
timeFrame: up to 5 hours
Other outcomes:
measure: Assessment of biomarker profiles in serum and cerebrospinal fluid of subjects.
timeFrame: 1 day
Locations:
city: Mannheim
country: Germany
facility: Central Institute of Mental Health
state: BW
Study officials:
References:
citation: 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.