CANBiome: Pilot-Study for the Comparison of Biomarkers Between Regular Cannabis Users and Non-Users
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- Quantification of phytochemicals in cannabis sativa (e.g. cannabinoids and flavonoids) and their metabolites in human whole blood samples.
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
Cannabis group
干预措施: Participants will prepare their cannabis product ad libitum and inhale the prepared product as usual for a maximum of 15 minutes. (Drug)
结局指标
主要结局
Quantification of phytochemicals in cannabis sativa (e.g. cannabinoids and flavonoids) and their metabolites in human whole blood samples.
时间窗: 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.
次要结局
- 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)
- 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)
- Targeted and untargeted analysis of endogenous biomarkers (e.g. endocannabinoids) using e.g. high-resolution mass-spectrometry(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)