Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, NIH, Baltimore, MD 21224, USA.
Drug Alcohol Depend. 2013 Jun 1;130(1-3):68-76. doi: 10.1016/j.drugalcdep.2012.10.011. Epub 2012 Nov 10.
We characterize cannabinoid disposition in oral fluid (OF) after dronabinol, synthetic oral Δ(9)-tetrahydrocannabinol (THC), and Sativex, a cannabis-extract oromucosal spray, and evaluate whether smoked cannabis relapse or Sativex compliance can be identified with OF cannabinoid monitoring.
5 and 15 mg synthetic oral THC, low (5.4 mg THC, 5.0 mg cannabidiol (CBD)) and high (16.2 mg THC, 15.0 mg CBD) dose Sativex, and placebo were administered in random order (n=14). Oral fluid specimens were collected for 10.5 h after dosing and analyzed for THC, CBD, cannabinol (CBN), and 11-nor-9-carboxy-THC (THCCOOH).
After oral THC, OF THC concentrations decreased over time from baseline, reflecting residual THC excretion from previously self-administered smoked cannabis. CBD and CBN also were rarely detected. After Sativex, THC, CBD and CBN increased greatly, peaking at 0.25-1 h. Median CBD/THC and CBN/THC ratios were 0.82-1.34 and 0.04-0.06, respectively, reflecting cannabinoids' composition in Sativex. THCCOOH/THC ratios within 4.5 h post Sativex were ≤ 1.6 pg/ng, always lower than after oral THC and placebo. THCCOOH/THC ratios increased throughout each dosing session.
Lack of measurable THC, CBD and CBN in OF following oral THC, and high OF CBD/THC ratios after Sativex distinguish oral and sublingual drug delivery routes from cannabis smoking. Low THCCOOH/THC ratios suggest recent Sativex and smoked cannabis exposure. These data indicate that OF cannabinoid monitoring can document compliance with Sativex pharmacotherapy, and identify relapse to smoked cannabis during oral THC medication but not Sativex treatment, unless samples were collected shortly after smoking.
我们描述了大麻二酚在口服液(OF)中的分布情况,包括大麻二酚(THC)、合成口服 Δ(9)-四氢大麻酚(THC)和大麻素提取物口腔黏膜喷雾 Sativex,以及评估 OF 大麻素监测是否可识别吸食大麻的复吸或 Sativex 依从性。
14 名参与者随机接受 5mg 和 15mg 合成口服 THC、低剂量(5.4mg THC,5.0mg 大麻二酚(CBD))和高剂量(16.2mg THC,15.0mg CBD)Sativex 和安慰剂。在给药后 10.5 小时内采集口服液样本,并分析 THC、CBD、大麻酚(CBN)和 11-去甲-9-羧基-THC(THCCOOH)的含量。
口服 THC 后,OF THC 浓度随时间从基线下降,反映了之前自行吸食大麻后 THC 的残留排泄。CBD 和 CBN 也很少被检测到。Sativex 给药后,THC、CBD 和 CBN 迅速增加,在 0.25-1 小时达到峰值。中位 CBD/THC 和 CBN/THC 比值分别为 0.82-1.34 和 0.04-0.06,反映了 Sativex 中大麻素的组成。Sativex 给药后 4.5 小时内的 THCCOOH/THC 比值均≤1.6pg/ng,始终低于口服 THC 和安慰剂。THCCOOH/THC 比值在每个给药周期内均升高。
口服 THC 后 OF 中无法检测到可测量的 THC、CBD 和 CBN,而 Sativex 后 OF 中 CBD/THC 比值较高,这表明口服和舌下药物递送途径与吸食大麻不同。低 THCCOOH/THC 比值提示近期使用 Sativex 和吸食大麻。这些数据表明,OF 大麻素监测可以证明 Sativex 药物治疗的依从性,并在口服 THC 药物治疗期间识别吸食大麻的复吸,但在 Sativex 治疗期间不会识别,除非在吸烟后不久采集样本。