Huestis Marilyn A, Barnes Allan, Smith Michael L
Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA.
Clin Chem. 2005 Dec;51(12):2289-95. doi: 10.1373/clinchem.2005.056838. Epub 2005 Oct 13.
Knowing the time cannabis was last used is important for determining impairment in accident investigations and clinical evaluations. Two models for predicting time of last cannabis use from single plasma cannabinoid concentrations-model I, using Delta(9)-tetrahydrocannabinol (THC), and model II, using the concentration ratio of 11-nor-9-carboxy-THC (THCCOOH) to THC-were developed and validated from controlled drug administration studies. Objectives of the current study were to extend the validation by use of a large number of plasma samples collected after administration of single and multiple doses of THC and to examine the effectiveness of the models at low plasma cannabinoid concentrations.
Thirty-eight cannabis users each smoked a 2.64% THC cigarette in the morning, and 30 also smoked a second cigarette in the afternoon. Blood samples (n = 717) were collected at intervals after smoking, and plasma THC and THCCOOH concentrations measured by gas chromatography-mass spectrometry. Predicted times of cannabis smoking, based on each model, were compared with actual smoking times.
The most accurate approach applied a combination of models I and II. For all 717 plasma samples, 99% of predicted times of last use were within the 95% confidence interval, 0.9% were overestimated, and none were underestimated. For 289 plasma samples collected after multiple doses, 97% were correct with no underestimates. All time estimates were correct for 76 plasma samples with THC concentrations between 0.5 and 2 mug/L, a concentration range not previously examined.
This study extends the validation of the predictive models of time of last cannabis use to include multiple exposures and low THC concentrations. The models provide an objective and validated method for assessing the contribution of cannabis to accidents or clinical symptoms.
了解大麻最后一次使用时间对于事故调查和临床评估中确定损伤情况很重要。从受控药物给药研究中开发并验证了两种根据单一血浆大麻素浓度预测最后一次使用大麻时间的模型——模型I,使用Δ⁹-四氢大麻酚(THC);模型II,使用11-去甲-9-羧基-THC(THCCOOH)与THC的浓度比。本研究的目的是通过使用大量单次和多次给予THC后采集的血浆样本扩展验证,并检查模型在低血浆大麻素浓度下的有效性。
38名大麻使用者每人在早上吸食一支含2.64% THC的香烟,30人还在下午吸食了第二支香烟。吸烟后每隔一段时间采集血样(n = 717),并通过气相色谱-质谱法测量血浆THC和THCCOOH浓度。根据每个模型预测的大麻吸烟时间与实际吸烟时间进行比较。
最准确的方法是结合使用模型I和模型II。对于所有717份血浆样本,99%的最后使用时间预测值在95%置信区间内,0.9%被高估,无一被低估。对于多次给药后采集的289份血浆样本,97%正确且无低估情况。对于THC浓度在0.5至2μg/L之间的76份血浆样本,所有时间估计均正确,该浓度范围之前未进行过研究。
本研究将最后一次使用大麻时间预测模型的验证扩展到包括多次暴露和低THC浓度的情况。这些模型为评估大麻对事故或临床症状的影响提供了一种客观且经过验证的方法。