The Acute and Chronic Pharmacokinetics and Pharmacodynamics of Oral Cannabidiol (CBD) With and Without Low Doses of Delta-9-Tetrahydrocannabinol (Δ9-THC).

IF 2.6 3区 医学 Q3 CHEMISTRY, ANALYTICAL
David Wolinsky, C Austin Zamarripa, Tory R Spindle, McKenna Klausner, Edward J Cone, Ruth E Winecker, Svante Vikingsson, Ronald R Flegel, Eugene D Hayes, Lisa S Davis, David Kuntz, Marcel Bonn-Miller, George E Bigelow, Ryan Vandrey
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引用次数: 0

Abstract

Introduction: Hemp products (cannabis with ≤0.3% Δ9-tetrahydrocannabinol (Δ9-THC)) are federally legal, but few controlled experiments have explored drug test results, pharmacokinetics, or pharmacodynamics.

Methods: Healthy adults (n = 60) self-administered 1.5 mL medium-chain triglyceride (MCT) oil containing 100 mg cannabidiol (CBD) and either 0 mg, 0.5 mg, 1 mg, 2 mg, 2.8 mg or 3.7 mg Δ9-THC (n = 10 per group). The study included an 8-hour acute dose laboratory session (Phase 1), a 14-day outpatient drug exposure period with twice daily dosing (Phase 2) and a 7-day washout period (Phase 3). Measures including urine, blood, subjective drug effects, and cognitive and psychomotor performance were assessed repeatedly throughout the experiment.

Results: At least one participant receiving Δ9-THC doses of 1.0 mg or greater had at least 1 positive urine drug test (Δ9-THC-COOH immunoassay screen ≥50ng/mL and LC-MS/MS confirmation ≥15ng/mL) during Phase 1 and the number of positive urine samples increased with Δ9-THC dose. Positive urine drug tests were observed during the Phase 2 outpatient drug exposure period from at least one participant in each dose condition that contained any amount of Δ9-THC. One urine specimen in the CBD only dose condition tested positive during Phase 2. Two positive urine samples were observed after the 1-week washout (Day 21). Blood concentrations of Δ9-THC were very low in all dose conditions, and there were no significant differences between the CBD only dose group and Δ9-THC-containing dose groups on any pharmacodynamic outcome.

Conclusions: Individuals subject to drug testing should recognize that hemp products contain detectable amounts of Δ9-THC. Conventional drug testing cannot reliably distinguish between illicit cannabis and legal hemp-derived product use, and a positive urine Δ9-THC test may result from low doses that do not produce intoxication or impairment.

低剂量δ -9-四氢大麻酚口服大麻二酚(CBD)的急性和慢性药代动力学和药效学(Δ9-THC)。
大麻产品(含≤0.3% Δ9-tetrahydrocannabinol (Δ9-THC)的大麻)在联邦法律上是合法的,但很少有对照实验探索药物测试结果、药代动力学或药效学。方法:健康成人(n = 60)自我给予1.5 mL中链甘油三酯(MCT)油,其中含有100 mg大麻二酚(CBD)和0 mg, 0.5 mg, 1 mg, 2 mg, 2.8 mg或3.7 mg Δ9-THC(每组n = 10)。该研究包括8小时的急性剂量实验室阶段(第一阶段),14天的门诊药物暴露期,每天两次给药(第二阶段)和7天的洗脱期(第三阶段)。在整个实验过程中,反复评估尿、血、主观药物效应、认知和精神运动表现等指标。结果:至少有一名接受Δ9-THC剂量1.0 mg或更高剂量的参与者在1期期间至少有1次尿药检阳性(Δ9-THC-COOH免疫分析筛查≥50ng/mL, LC-MS/MS确认≥15ng/mL),阳性尿样数量随着Δ9-THC剂量的增加而增加。在第二阶段门诊药物暴露期间,至少有一名参与者在含有任意量Δ9-THC的每种剂量条件下进行尿检。在第二阶段,只有CBD剂量条件下的一个尿液样本检测呈阳性。洗脱期1周(第21天)后,有2例尿样呈阳性。在所有剂量条件下,Δ9-THC的血药浓度都很低,并且CBD单独剂量组和Δ9-THC-containing剂量组在任何药效学结果上没有显著差异。结论:接受药物测试的个人应该认识到大麻产品含有可检测量的Δ9-THC。常规药物测试无法可靠地区分非法大麻和合法大麻衍生产品的使用,尿液Δ9-THC测试结果可能是阳性,因为低剂量不会产生中毒或损害。
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来源期刊
CiteScore
5.10
自引率
20.00%
发文量
92
审稿时长
6-12 weeks
期刊介绍: The Journal of Analytical Toxicology (JAT) is an international toxicology journal devoted to the timely dissemination of scientific communications concerning potentially toxic substances and drug identification, isolation, and quantitation. Since its inception in 1977, the Journal of Analytical Toxicology has striven to present state-of-the-art techniques used in toxicology labs. The peer-review process provided by the distinguished members of the Editorial Advisory Board ensures the high-quality and integrity of articles published in the Journal of Analytical Toxicology. Timely presentation of the latest toxicology developments is ensured through Technical Notes, Case Reports, and Letters to the Editor.
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