Pilot-Study for the Comparison of Biomarkers Between Regular Cannabis Users and Non-Users
- Conditions
- Driving Under the Influence of Cannabis
- Interventions
- Drug: Participants will prepare their cannabis product ad libitum and inhale the prepared product as usual for a maximum of 15 minutes.
- Registration Number
- NCT06975020
- Lead Sponsor
- University of Basel
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 120
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Cannabis group Participants will prepare their cannabis product ad libitum and inhale the prepared product as usual for a maximum of 15 minutes. -
- Primary Outcome Measures
Name Time Method Quantification of phytochemicals in cannabis sativa (e.g. cannabinoids and flavonoids) and their metabolites in human whole blood samples. 24 months 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.
- Secondary Outcome Measures
Name Time Method 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) 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 24 months Subjectively experienced effects of cannabis inhalation (e.g. subjective driving ability, psychological effects and well-being) assessed by questionnaires (e.g. VAS) 24 months The effects of cannabis inhalation on neurocognition by non-invasive, neurocognitive testing 24 months Self-reported mood as measured e.g. by the Bf-SR questionnaire. 24 months Usual reasons for cannabis use as measured e.g. by the Marijuana Motives Questionnaire (MMQ) 24 months Measurement of hormones and biomarkers involved in the regulation of fluid balance (e.g. plasma osmolality …) 24 months Measurement of hormones and biomarkers of the anterior and posterior pituitary gland (e.g., plasma oxytocin, neurophysin I, ACTH, TSH, prolactin …) 24 months Analysis of the protein-bound and free fractions of the different cannabinoids and their metabolites using e.g. equilibrium dialysis or ultracentrifugation 24 months Targeted and untargeted analysis of endogenous biomarkers (e.g. endocannabinoids) using e.g. high-resolution mass-spectrometry 24 months 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 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 24 months