Plasma and urine profiles of Δ9-tetrahydrocannabinol and its metabolites 11-hydroxy-Δ9-tetrahydrocannabinol and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol after cannabis smoking by male volunteers to estimate recent consumption by athletes

Abstract

Since 2004, cannabis has been prohibited by the World Anti-Doping Agency for all sports competitions. In the years since then, about half of all positive doping cases in Switzerland have been related to cannabis consumption. In doping urine analysis, the target analyte is 11-nor-9-carboxy-Delta(9)-tetrahydrocannabinol (THC-COOH), the cutoff being 15 ng/mL. However, the wide urinary detection window of the long-term metabolite of Delta(9)-tetrahydrocannabinol (THC) does not allow a conclusion to be drawn regarding the time of consumption or the impact on the physical performance. The purpose of the present study on light cannabis smokers was to evaluate target analytes with shorter urinary excretion times. Twelve male volunteers smoked a cannabis cigarette standardized to 70 mg THC per cigarette. Plasma and urine were collected up to 8 h and 11 days, respectively. Total THC, 11-hydroxy-Delta(9)-tetrahydrocannabinol (THC-OH), and THC-COOH were determined after hydrolysis followed by solid-phase extraction and gas chromatography/mass spectrometry. The limits of quantitation were 0.1-1.0 ng/mL. Eight puffs delivered a mean THC dose of 45 mg. Plasma levels of total THC, THC-OH, and THC-COOH were measured in the ranges 0.2-59.1, 0.1-3.9, and 0.4-16.4 ng/mL, respectively. Peak concentrations were observed at 5, 5-20, and 20-180 min. Urine levels were measured in the ranges 0.1-1.3, 0.1-14.4, and 0.5-38.2 ng/mL, peaking at 2, 2, and 6-24 h, respectively. The times of the last detectable levels were 2-8, 6-96, and 48-120 h. Besides high to very high THC-COOH levels (245 +/- 1,111 ng/mL), THC (3 +/- 8 ng/mL) and THC-OH (51 +/- 246 ng/mL) were found in 65 and 98% of cannabis-positive athletes' urine samples, respectively. In conclusion, in addition to THC-COOH, the pharmacologically active THC and THC-OH should be used as target analytes for doping urine analysis. In the case of light cannabis use, this may allow the estimation of more recent consumption, probably influencing performance during competitions. However, it is not possible to discriminate the intention of cannabis use, i.e., for recreational or doping purposes. Additionally, pharmacokinetic data of female volunteers are needed to interpret cannabis-positive doping cases of female athletes.

Cannabis in the Arm: What Can we Learn from Intravenous Cannabinoid Studies?

“…In contrast, Brenneisen and colleagues [74] asked participants to smoke a cannabis cigarette containing 70mg 9 -THC, 25mg of which was estimated to have been inhaled. Mean plasma (SD) 9 -THC 5 minutes post inhalation was 20.9 (16.9) ng/ml.…”

“…plasma levels are 2-3 times that of inhaled 9 -THC. This is especially true if participants self-titrate until they have reach their desired level of "high" [34,38], or in studies where unpleasant reactions such as anxiety or dysphoria are not reported [74].…”

“…9 -THC. The inhalation studies included in Table 2 were chosen as the amount of 9 -THC smoked was known, and participants either stopped when desired level of "high" was achieved [34,38] or no increase in anxiety was reported [53,74].…”

Comparison of cannabinoid concentrations in oral fluid and whole blood between occasional and regular cannabis smokers prior to and after smoking a cannabis joint

“…On the other hand, OF THCCOOH could estimate plasma THCCOOH levels. Throughout the last decade, several studies have been carried out to determine PK parameters of cannabinoids in blood, plasma, or serum [16][17][18][19][20][21] in humans. Some other studies were performed with oral fluid only [22] or in tandem with serum [23] or plasma [11,24] with a limited number of ten participants in each study.…”

Evaluation of Non-Contact Sampling and Detection of Explosives using Receiver Operating Characteristic Curves

“…Profiling of illicit drugs has been performed for many target analytes which include cocaine [90], marijuana [91], heroin [92,93], and 3,4-methylenedioxy-N-methylamphetamine (MDMA) [94][95][96]. Therefore, the different impurities and intermediate chemicals can be identified and help understand the different synthetic routes in order to achieve a common source.…”