Legalization of cannabis for medicinal and/or recreational use is expanding globally. Although cannabis is being regulated country by country, an accurate recent use test with indisputable results correlated with impairment has yet to be discovered. In the present study, a new approach for determining recent cannabis use within the impairment window after smoking was developed by studying 74 subjects with a mean age of 25 years and average use history of 9 years. Horizontal gaze nystagmus was evaluated along with subject self-assessments of impairment, and blood and breath samples were collected before and after smoking cannabis. Breath and blood pharmacokinetic parameters and cannabinoid profiles determined recent use within the impairment window. No subjects were positive for recent use pre-smoking, although all subjects had detectable cannabinoids in breath samples. We describe an inhaled cannabis recent use test that correlates with impairment and helps protect against wrongful prosecution and workplace discrimination.

Background Cannabis legalization is expanding rapidly throughout the United States, but there is no reliable means of establishing recent use. Objective To develop and validate a bioanalytical method for determination of Δ9-tetrahydrocannabinol (Δ9-THC), cannabinol, 11-hydroxy-Δ9-THC, 11-nor-9-carboxy-Δ9-THC, and 8β,11-dihydroxy-Δ9-THC in whole blood microsamples by liquid chromatography high-resolution mass spectrometry (LC-HRMS). Methods Cannabinoid extraction from whole blood was performed using a mixture of n-hexane/ethyl acetate (90:10, v/v). Chromatographic separation was performed with a C18 column using a binary mobile phase gradient of water and acetonitrile, each with 0.1% formic acid. Detection was performed by positive ion mode heated electrospray ionization with full scan MS on an Orbitrap mass spectrometer. A clinical study was performed in 30 subjects to identify recent cannabis use based on analysis of cannabinoids in blood samples up to 200 min post-smoking. Results Acceptable linearity of all calibration curves was observed (r2>0.99) for all analytes over a 1–100 ng/mL concentration range, with acceptable accuracy. Limit of detection (LOD) was 0.5 ng/mL. Accuracy and precision met acceptance criteria for all analytes. Repeatability (CV) was <5% at low (3 ng/mL) and high (90 ng/mL) concentrations. In the clinical study, the ratios between 11-nor-9-carboxy-Δ9-THC and Δ9-THC fell immediately after smoking and returned to near baseline levels by 200 min post-smoking, which is consistent with recent use. Conclusions and Highlights The developed LC-HRMS bioanalytical method is suitable for quantification of five key cannabinoids in whole capillary blood microsamples and can be used in conjunction with a test for determining recent cannabis use.

Background As a result of the legalization of U.S. industrial hemp production in late 2018, products containing hemp-derived Δ8-tetrahydrocannabinol (Δ8-THC) are increasing in popularity. Little, however, is known regarding Δ8-THC’s impairment potential and the associated impacts on roadway and workplace safety, and testing for Δ8-THC is not yet common. The present study explored impairment patterns and cannabinoid kinetics associated with recent use of Δ8-THC. Methods Hemp-derived Δ8-THC concentrate was administered by vaporization ad libitum to three male frequent cannabis users aged 23–25 years. In addition to self-assessments of impairment using a 10-point scale, horizontal gaze nystagmus (HGN) was evaluated in each subject as a physical means of assessing impairment before and after vaporization. To examine cannabinoid kinetic patterns, exhaled breath and capillary blood samples were collected prior to vaporization up to 180 min post-vaporization and analyzed by liquid chromatography high-resolution mass spectrometry for cannabinoid content using validated methods. The impairment and cannabinoid kinetic results were then compared to analogous results obtained from the same three subjects after they had smoked a ∆9-THC cannabis cigarette ad libitum in a previous study to determine whether any similarities existed. Results Patterns of impairment after vaporizing Δ8-THC were similar to those observed after smoking cannabis, with self-assessed impairment peaking within the first hour after use, and then declining to zero by 3 h post-use. Likewise, HGN was observed only after vaporizing, and by 3 h post-vaporization, evidence of HGN had dissipated. Cannabinoid kinetic patterns observed after vaporizing Δ8-THC (short ∆8-THC half-lives of 5.2 to 11.2 min at 20 min post-vaporization, presence of key cannabinoids cannabichromene, cannabigerol, and tetrahydrocannabivarin, and breath/blood Δ8-THC ratios > 2 within the first hour post-vaporization) were also analogous to those observed for ∆9-THC and the same key cannabinoids within the first hour after the same subjects had smoked cannabis in the previous study. Conclusions Hemp-derived Δ8-THC and Δ9-THC from cannabis display similar impairment profiles, suggesting that recent use of Δ8-THC products may carry the same risks as cannabis products. Standard testing methods need to incorporate this emerging, hemp-derived cannabinoid.

Legalization of cannabis for medicinal and/or recreational use is expanding globally. Although cannabis is being regulated country by country, an accurate recent use test with indisputable results correlated with impairment has yet to be discovered. In the present study, a new approach for determining recent cannabis use within the impairment window after smoking was developed by studying 74 subjects with a mean age of 25 years and average use history of 9 years. Horizontal gaze nystagmus was evaluated along with subject self-assessments of impairment, and blood and breath samples were collected before and after smoking cannabis. Breath and blood pharmaco-kinetic parameters and cannabinoid profiles determined recent use within the impairment window. No subjects were positive for recent use pre-smoking, although all subjects had detectable cannabi-noids in breath samples. We describe an inhaled cannabis recent use test that correlates with impairment and helps protect against wrongful prosecution and workplace discrimination.