Clinical trial NCT06975020: Pilot-Study for the Comparison of Biomarkers Between Regular Cannabis Users and Non-Users
Official title: CANBiome: Pilot-Study for the Comparison of Biomarkers Between Regular Cannabis Users and Non-Users
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Driving Under the Influence of Cannabis
Keywords: Cannabis
Driving
Biomarker
Lead sponsor: University of Basel
Sponsor class: OTHER
Collaborators: name: University Psychiatric Clinics Basel, University of Basel, Basel, Switzerland
name: Department of Endocrinology, Diabetology and Metabolism, University Hospital Basel, Basel, Switzerland
name: Biopharmacy, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland
name: Institute of Forensic Medicine, University of Basel, Basel, Switzerland
First posted: 2025-05-16
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Quantification of phytochemicals in cannabis sativa (e.g. cannabinoids and flavonoids) and their metabolites in human whole blood samples.
timeFrame: 24 months
Secondary outcomes:
measure: 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
timeFrame: 24 months
measure: 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
timeFrame: 24 months
measure: 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)
timeFrame: 24 months
measure: 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
timeFrame: 24 months
measure: Analysis of the protein-bound and free fractions of the different cannabinoids and their metabolites using e.g. equilibrium dialysis or ultracentrifugation
timeFrame: 24 months
measure: Targeted and untargeted analysis of endogenous biomarkers (e.g. endocannabinoids) using e.g. high-resolution mass-spectrometry
timeFrame: 24 months
measure: Subjectively experienced effects of cannabis inhalation (e.g. subjective driving ability, psychological effects and well-being) assessed by questionnaires (e.g. VAS)
timeFrame: 24 months
measure: The effects of cannabis inhalation on neurocognition by non-invasive, neurocognitive testing
timeFrame: 24 months
measure: Self-reported mood as measured e.g. by the Bf-SR questionnaire.
timeFrame: 24 months
measure: Usual reasons for cannabis use as measured e.g. by the Marijuana Motives Questionnaire (MMQ)
timeFrame: 24 months
measure: Measurement of hormones and biomarkers involved in the regulation of fluid balance (e.g. plasma osmolality …)
timeFrame: 24 months
measure: Measurement of hormones and biomarkers of the anterior and posterior pituitary gland (e.g., plasma oxytocin, neurophysin I, ACTH, TSH, prolactin …)
timeFrame: 24 months
Other outcomes:
Locations:
Study officials:
References:
citation: Kraemer M, Madea B, Hess C. Detectability of various cannabinoids in plasma samples of cannabis users: Indicators of recent cannabis use? Drug Test Anal. 2019 Oct;11(10):1498-1506. doi: 10.1002/dta.2682. Epub 2019 Sep 1.
citation: Berman P, Futoran K, Lewitus GM, Mukha D, Benami M, Shlomi T, Meiri D. A new ESI-LC/MS approach for comprehensive metabolic profiling of phytocannabinoids in Cannabis. Sci Rep. 2018 Sep 24;8(1):14280. doi: 10.1038/s41598-018-32651-4.
citation: Manthey J, Freeman TP, Kilian C, Lopez-Pelayo H, Rehm J. Public health monitoring of cannabis use in Europe: prevalence of use, cannabis potency, and treatment rates. Lancet Reg Health Eur. 2021 Sep 24;10:100227. doi: 10.1016/j.lanepe.2021.100227. eCollection 2021 Nov.
citation: Marcotte TD, Umlauf A, Grelotti DJ, Sones EG, Sobolesky PM, Smith BE, Hoffman MA, Hubbard JA, Severson J, Huestis MA, Grant I, Fitzgerald RL. Driving Performance and Cannabis Users' Perception of Safety: A Randomized Clinical Trial. JAMA Psychiatry. 2022 Mar 1;79(3):201-209. doi: 10.1001/jamapsychiatry.2021.4037.