Hartman Rebecca L, Brown Timothy L, Milavetz Gary, Spurgin Andrew, Gorelick David A, Gaffney Gary R, Huestis Marilyn A
Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, NIH, Baltimore, MD;
National Advanced Driving Simulator, University of Iowa, Iowa City, IA;
Clin Chem. 2016 Feb;62(2):367-77. doi: 10.1373/clinchem.2015.248492.
In driving-under-the-influence cases, blood typically is collected approximately 1.5-4 h after an incident, with unknown last intake time. This complicates blood Δ(9)-tetrahydrocannabinol (THC) interpretation, owing to rapidly decreasing concentrations immediately after inhalation. We evaluated how decreases in blood THC concentration before collection may affect interpretation of toxicological results.
Adult cannabis smokers (≥1×/3 months, ≤3 days/week) drank placebo or low-dose alcohol (approximately 0.065% peak breath alcohol concentration) 10 min before inhaling 500 mg placebo, 2.9%, or 6.7% vaporized THC (within-individuals), then took simulated drives 0.5-1.3 h postdose. Blood THC concentrations were determined before and up to 8.3 h postdose (limit of quantification 1 μg/L).
In 18 participants, observed Cmax (at 0.17 h) for active (2.9 or 6.7% THC) cannabis were [median (range)] 38.2 μg/L (11.4-137) without alcohol and 47.9 μg/L (13.0-210) with alcohol. THC Cmax concentration decreased 73.5% (3.3%-89.5%) without alcohol and 75.1% (11.5%-85.4%) with alcohol in the first half-hour after active cannabis and 90.3% (76.1%-100%) and 91.3% (53.8%-97.0%), respectively, by 1.4 h postdose. When residual THC (from previous self-administration) was present, concentrations rapidly decreased to preinhalation baselines and fluctuated around them. During-drive THC concentrations previously associated with impairment (≥8.2 μg/L) decreased to median <5 μg/L by 3.3 h postdose and <2 μg/L by 4.8 h postdose; only 1 participant had THC ≥5 μg/L after 3.3 h.
Forensic blood THC concentrations may be lower than common per se cutoffs despite greatly exceeding them while driving. Concentrations during driving cannot be back-extrapolated because of unknown time after intake and interindividual variability in rates of decrease.
在酒驾案件中,血液通常在事件发生后约1.5 - 4小时采集,末次摄入时间未知。由于吸入后浓度迅速下降,这使得血液中Δ⁹ - 四氢大麻酚(THC)的解读变得复杂。我们评估了采集前血液中THC浓度的下降如何影响毒理学结果的解读。
成年大麻吸烟者(≥每月1次,≤每周3天)在吸入500毫克安慰剂、2.9%或6.7%的雾化THC(个体内)前10分钟饮用安慰剂或低剂量酒精(呼气酒精浓度峰值约为0.065%),然后在给药后0.5 - 1.3小时进行模拟驾驶。在给药前及给药后长达8.3小时测定血液THC浓度(定量限为1微克/升)。
在18名参与者中,活性(2.9%或6.7% THC)大麻的观察到的Cmax(在0.17小时)[中位数(范围)]在未饮酒时为38.2微克/升(11.4 - 137),饮酒时为47.9微克/升(13.0 - 210)。活性大麻摄入后的前半小时内,THC Cmax浓度在未饮酒时下降了73.5%(3.3% - 89.5%),饮酒时下降了75.1%(11.5% - 85.4%),给药后1.4小时分别下降了90.3%(76.1% - 100%)和91.3%(53.8% - 97.0%)。当存在残留THC(来自先前的自我给药)时,浓度迅速降至吸入前基线并在其周围波动。先前与损伤相关的驾驶期间THC浓度(≥8.2微克/升)在给药后3.3小时降至中位数<5微克/升,在4.8小时降至<2微克/升;只有1名参与者在3.3小时后THC≥5微克/升。
尽管在驾驶时法医血液THC浓度可能大大超过常见的自身临界值,但实际浓度可能较低。由于摄入后时间未知以及个体间下降速率的差异,驾驶期间的浓度无法回溯推断。