ElSohly M A, deWit H, Wachtel S R, Feng S, Murphy T P
ElSohly Laboratories, Incorporated, Oxford, Mississippi 38655, USA.
J Anal Toxicol. 2001 Oct;25(7):565-71. doi: 10.1093/jat/25.7.565.
Delta9-tetrahydrocannabinol (THC), the main psychologically active ingredient of the cannabis plant (marijuana), has been prepared synthetically and used as the bulk active ingredient of Marinol, which was approved by the FDA for the control of nausea and vomiting in cancer patients receiving chemotherapy and as an appetite stimulant for AIDS patients. Because the natural and the synthetic THC are identical in all respects, it is impossible to determine the source of the urinary metabolite of THC, 11-nor-delta9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH), in a urine specimen provided in a drug-testing program. Over the last few years there has been a need to determine whether a marijuana positive drug test is the result of the ingestion of marijuana (or a related product) or whether it results from the sole use of Marinol. We have previously proposed the use of delta9-tetrahydrocannabivarin (THCV, the C3 homologue of THC) as a marker for the ingestion of marijuana (or a related product) because THCV is a natural component of most cannabis products along with THC and does not exist in Marinol. We have also reported that THCV is metabolized by human hepatocytes to 11-nor-delta9-tetrahydrocannabivarin-9-carboxylic acid (THCV-COOH); therefore, the presence of the latter in a urine specimen would indicate that the donor must have used marijuana or a related product (with or without Marinol). In this study, we provide clinical data showing that THCV-COOH is detected in urine specimens collected from human subjects only after the ingestion of marijuana and not after the ingestion of Marinol (whether the latter is ingested orally or by smoking). Four subjects (male and female) participated in the study in a three-session, within-subject, crossover design. The sessions were conducted at one-week intervals. Each subject received, in separate sessions and in randomized order, an oral dose of Marinol (15 mg), a smoked dose of THC (16.88 mg) in a placebo marijuana cigarette, or a smoked dose of marijuana (2.11% THC and 0.12% THCV). Urine samples were collected and vital signs were monitored every 2 h for a 6-h period following drug administration. Subjects were then transported home, were given sample collection containers and logbooks, and were instructed to record at home the volume and time of every urine collection for 24 h, and once a day for the remainder of a week (6 days). Subjects were also instructed to freeze the urine samples until the next session. All urine samples were analyzed by GC-MS for THC-COOH and THCV-COOH using solid-phase extraction and derivatization procedure on RapidTrace and TBDMS as the derivative. The method had a limit of detection of 1.0 ng/mL and 1.0 ng/mL for THCV-COOH and THC-COOH, respectively.
Δ9-四氢大麻酚（THC）是大麻植物（大麻）主要的具有心理活性的成分，已被人工合成并用作屈大麻酚的主要活性成分，屈大麻酚经美国食品药品监督管理局批准，用于控制接受化疗的癌症患者的恶心和呕吐，并作为艾滋病患者的食欲刺激剂。由于天然和合成的THC在各方面都相同，因此在药物检测程序提供的尿液样本中，无法确定THC的尿液代谢物11-去甲-Δ9-四氢大麻酚-9-羧酸（THC-COOH）的来源。在过去几年中，有必要确定大麻药物检测呈阳性是摄入大麻（或相关产品）的结果，还是仅使用屈大麻酚的结果。我们之前曾提议使用Δ9-四氢大麻萜酚（THCV，THC的C3同系物）作为摄入大麻（或相关产品）的标志物，因为THCV是大多数大麻产品与THC一起的天然成分，而不存在于屈大麻酚中。我们还报告称，THCV被人肝细胞代谢为11-去甲-Δ9-四氢大麻萜酚-9-羧酸（THCV-COOH）；因此，尿液样本中后者的存在表明供体一定使用过大麻或相关产品（无论是否使用屈大麻酚）。在本研究中，我们提供的临床数据表明，仅在摄入大麻后，而非摄入屈大麻酚后（无论后者是口服还是通过吸烟摄入），从人类受试者收集的尿液样本中可检测到THCV-COOH。四名受试者（男性和女性）以三阶段、受试者内交叉设计参与了该研究。各阶段间隔一周进行。每位受试者在不同阶段以随机顺序分别接受口服剂量的屈大麻酚（15毫克）、在安慰剂大麻香烟中吸入剂量的THC（16.88毫克）或吸入剂量的大麻（2.11% THC和0.12% THCV）。给药后6小时内，每2小时收集一次尿液样本并监测生命体征。然后将受试者送回家，给他们样本收集容器和日志，并指示他们在家记录24小时内每次尿液收集的量和时间，并在接下来一周（6天）每天记录一次。还指示受试者将尿液样本冷冻至下一次实验。所有尿液样本均通过气相色谱-质谱联用仪，采用固相萃取和衍生化程序，以RapidTrace和TBDMS作为衍生物，分析THC-COOH和THCV-COOH。该方法对THCV-COOH和THC-COOH的检测限分别为1.0纳克/毫升和1.0纳克/毫升。
