Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, NIH, Baltimore, MD;
Clin Chem. 2013 Dec;59(12):1770-9. doi: 10.1373/clinchem.2013.207316. Epub 2013 Aug 12.
Oral Δ(9)-tetrahydrocannabinol (THC) is effective for attenuating cannabis withdrawal and may benefit treatment of cannabis use disorders. Oral fluid (OF) cannabinoid testing, increasing in forensic and workplace settings, could be valuable for monitoring during cannabis treatment.
Eleven cannabis smokers resided on a closed research unit for 51 days and received daily 0, 30, 60, and 120 mg of oral THC in divided doses for 5 days. There was a 5-puff smoked cannabis challenge on the fifth day. Each medication session was separated by 9 days of ad libitum cannabis smoking. OF was collected the evening before and throughout oral THC sessions and analyzed by 2-dimensional GC-MS for THC, cannabidiol (CBD), cannabinol (CBN), 11-hydroxy-THC (11-OH-THC), and 11-nor-9-carboxy-THC (THCCOOH).
During all oral THC administrations, THC OF concentrations decreased to ≤ 78.2, 33.2, and 1.4 μg/L by 24, 48, and 72 h, respectively. CBN also decreased over time, with concentrations 10-fold lower than THC, with none detected beyond 69 h. CBD and 11-OH-THC were rarely detected, only within 19 and 1.6 h after smoking, respectively. THCCOOH OF concentrations were dose dependent and increased over time during 120-mg THC dosing. After cannabis smoking, THC, CBN, and THCCOOH concentrations showed a significant dose effect and decreased significantly over time.
Oral THC dosing significantly affected OF THCCOOH but minimally contributed to THC OF concentrations; prior ad libitum smoking was the primary source of THC, CBD, and CBN. Higher cannabinoid concentrations following active oral THC administrations vs placebo suggest a compensatory effect of THC tolerance on smoking topography.
口服 Δ(9)-四氢大麻酚(THC)可有效减轻大麻戒断症状,可能有助于治疗大麻使用障碍。在法医和工作场所中,越来越多地使用口服液(OF)进行大麻素检测,这对于大麻治疗期间的监测可能很有价值。
11 名大麻吸食者在一个封闭的研究单位居住 51 天,并在 5 天内每天分剂量接受 0、30、60 和 120mg 的口服 THC。第五天进行了 5 口吸烟大麻挑战。每次用药疗程之间间隔 9 天的自由吸食大麻。在口服 THC 期间以及前一天晚上采集 OF,并通过二维 GC-MS 分析 THC、大麻二酚(CBD)、大麻酚(CBN)、11-羟基-THC(11-OH-THC)和 11-去甲-9-羧酸-THC(THCCOOH)。
在所有口服 THC 给药期间,THC OF 浓度分别在 24、48 和 72 小时降至≤78.2、33.2 和 1.4μg/L。CBN 也随着时间的推移而减少,其浓度是 THC 的 10 倍,在 69 小时后未检测到。CBD 和 11-OH-THC 很少被检测到,仅在吸烟后 19 和 1.6 小时内被检测到。THCCOOH OF 浓度与剂量有关,在 120mg THC 给药期间随着时间的推移而增加。在吸烟大麻后,THC、CBN 和 THCCOOH 浓度显示出显著的剂量效应,并随着时间的推移显著降低。
口服 THC 给药显著影响 OF THCCOOH,但对 THC OF 浓度的影响很小;之前的自由吸烟是 THC、CBD 和 CBN 的主要来源。与安慰剂相比,在口服 THC 给药后,较高的大麻素浓度表明 THC 耐受性对吸烟模式具有代偿作用。