Pilot-Study for the Comparison of Biomarkers Between Regular Cannabis Users and Non-Users

University of Basel120 enrolled

Overview

The relevance of driving under the influence of cannabis is becoming increasingly important in the context of legalization. However, the measurement of tetrahydrocannabinol (THC) blood concentration is an inadequate marker for assessing driving impairment. Currently, there is no reliable marker available for estimating the time of last cannabis inhalation, which would provide a promising tool for regulating driving under the influence of cannabis. This pilot study aims to explore potential biomarkers and factors that could approximate the timing of the last cannabis inhalation, with emphasis on the potential explanation of interindividual differences in THC pharmacokinetics and -dynamics. The results will assist future research aimed at improving the ability to distinguish between impaired and unimpaired cannabis users in road traffic. These findings are of significant importance for road safety and for society at large, as they may provide more objective markers for cannabis inhalation, thereby permitting a methodologically sound evaluation of driving under the influence of cannabis.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Enrollment

120

Conditions

Driving Under the Influence of Cannabis

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Experience of smoking cannabis products, on average once a week. This may be in combination with tobacco. * Age 18-65 years Possession of driving license in at least one of the categories A, B, A1; B1, F, G or M * Sufficient knowledge of German * No cannabis inhalation or nicotine consumption on study day * No alcohol consumption within the last 24 h Exclusion Criteria: * Participation in a trial with investigational drugs within 30 days * Current or previous major psychiatric disorder (e.g., major depression, schizophrenia spectrum disorder) * Pregnancy or breastfeeding * Intake of CYP2C9, CYP2C19, and CYP3A4-inducers in the last 4 weeks before the study visit, e.g. rifampicin (antibiotic), carbamazepine (anticonvulsant), phenobarbital (anticonvulsant), phenytoin (anticonvulsant) or inhibitors, such as amiodarone (class III antiarrhythmic medication), antifungal drugs such as fluconazole, miconazole, voriconazole and itraconazole, antibiotics such as clarithromycin and sulfamethoxazole, ritonavir (protease inhibitor) and grapefruit juice. * The following conditions: vasopressin deficiency, pituitary tumor, active malignancy, severe hyponatremia requiring treatment, congestive heart failure, liver cirrhosis.

Outcomes

Primary Outcomes

Quantification of phytochemicals in cannabis sativa (e.g. cannabinoids and flavonoids) and their metabolites in human whole blood samples.

Quantification of the blood concentration of cannabis sativa phytochemicals such as minor cannabinoids, cannabinoids, and flavonoids. Blood samples will be analyzed at baseline and several time-points (0, 10, 20, 60, 180) post consumption of cannabis. Concentrations will be reported as ng/mL whole blood.

Time frame: 24 months

Secondary Outcomes

Measurement of the expression levels of relevant genes e.g. cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2) in whole blood samples by e.g. RT-PCR to evaluate especially their correlation with cannabinoid plasma levels, metabolism, and ph

Time frame: 24 months

Assessment of selected genetic polymorphisms in the genes known to interact with cannabinoids (i.e. CYP2C9, CYP2C19) by e.g. RT-PCR to evaluate their influence on cannabinoid plasma levels and the ability to predict cannabinoid metabolism and pharmaco

Time frame: 24 months

Quantitation of biomarkers applicable to determine the activity of enzymes or transporters known to be involved in the handling of cannabinoids (e.g. 4-ß-hydroxycholesterol, Coproporphyrin I und Coproporphyrin III)

Time frame: 24 months

Comparison of DNA methylation profiles on blood-derived DNA samples between regular and non-cannabis users by evaluating key CpG sites (e.g., in the MCU gene) that interplay with risk factors and mental health by e.g. targeted Illumina DNA methylation

Time frame: 24 months

Analysis of the protein-bound and free fractions of the different cannabinoids and their metabolites using e.g. equilibrium dialysis or ultracentrifugation

Time frame: 24 months

Targeted and untargeted analysis of endogenous biomarkers (e.g. endocannabinoids) using e.g. high-resolution mass-spectrometry

Time frame: 24 months

Subjectively experienced effects of cannabis inhalation (e.g. subjective driving ability, psychological effects and well-being) assessed by questionnaires (e.g. VAS)

Time frame: 24 months

The effects of cannabis inhalation on neurocognition by non-invasive, neurocognitive testing

Time frame: 24 months

Self-reported mood as measured e.g. by the Bf-SR questionnaire.

Time frame: 24 months

Usual reasons for cannabis use as measured e.g. by the Marijuana Motives Questionnaire (MMQ)

Time frame: 24 months

Measurement of hormones and biomarkers involved in the regulation of fluid balance (e.g. plasma osmolality …)

Time frame: 24 months

Measurement of hormones and biomarkers of the anterior and posterior pituitary gland (e.g., plasma oxytocin, neurophysin I, ACTH, TSH, prolactin …)

Time frame: 24 months

Pilot-Study for the Comparison of Biomarkers Between Regular Cannabis Users and Non-Users

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts