The unusual year of 2020 will likely have long lasting impacts, especially given the confluence of circumstances and ongoing conversations related to drug use, criminal justice reform, and health equity. The impacts of stay-at-home orders and other pandemic behavioral changes are already supporting what we empirically know, that the pandemic has disrupted many facets of daily life including substance use. The CDC’s National Center for Health Statistics provisional data on drug overdose deaths indicate an almost 30% increase in 2020 over 2019 numbers (Ahmad et al., 2021). The DOT’s National Highway Traffic Safety Administration examined the impact of the pandemic on driving behavior during 2020 and reported an increase in unsafe driving practices as identified during serious motor vehicle accidents and fatalities including increased prevalence of drug use (NHTSB, 2021). Our broader understanding of the changes in and from 2020 will likely take time to unfold. In the meantime, one constant is cannabis, as evidenced by NIDA’s Monitoring the Future study, which shows the continuing popularity of cannabis use for college students and their same aged peers (Schulenberg, 2021).
One challenge with cannabis relates to the measurement and interpretation of intoxication and recent use of cannabis and cannabinoids. These compounds are derived from the plant Cannabis sativa, where the bulk of the literature has primarily focused on two compounds, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Currently there are several FDA approved cannabinoid medications containing CBD or synthetic compounds specifically, dronabinol (Marinol™, synthetic THC) and nabilone (Cesamet™, a synthetic cannabinoid). There are 36 states that have passed legislation allowing for medical cannabis use and 18 states allowing adult recreational use, despite cannabis remaining a federal schedule I drug. As legalization has occurred, and continues to expand, one persistent public safety concern is the potential for driving under the influence of cannabis.
There is much ongoing work attempting to assess cannabis intoxication or recent use, both in and outside the USA. One recent example is a study out of California, which examined 10 cannabinoids after smoking cannabis at 2 THC concentrations in blood and oral fluid (Hoffman et al., 2021). They measured THC, CBD, several metabolites, and other phytocannabinoids for 6 hours after cannabis smoking in a placebo-controlled, double blinded randomized trial in 191 individuals. The resulting pharmacokinetic profiles suggested potential markers of recent use include the phytocannabinoid cannabinol (CBN) and underscored the utility of oral fluid as an important matrix due to its lower interindividual variability than blood. After comparing performance for detecting recent cannabis use in varied matrices in a different study, the authors concluded that oral fluid has the highest performance for detecting recent cannabis use (Hubbard et al., 2021). A recent study by Krämer et al examined CBN and 4 other minor cannabinoids showed that the metabolites could still be detected more than 24 hours after last use (Krämer et al., 2021). The authors caution the assumption of recent use solely on based on minor cannabinoid detection. Another recent study by Kroner et al examined if CBN and three other cannabinoids had cross-reactivity with commercially available THC immunoassays (Kroner et al., 2020). They found that CBN did cross-react and reiterated the important role of confirmation testing for this class of drugs. As additional resources, there are several excellent reviews describing the varied matrices and cannabinoids of potential use to meet the needs of the future and effectively interpret cannabis impairment or recent use (Karschner et al., 2020) (Huestis & Smith, 2018).
To improve on current practices for cannabis testing and allow appropriate interpretation, studies will need to account for the many cannabis use variables. One notable example is exposure route, which includes vaping, smoking, or edibles. As this limited review of recent studies exemplifies, there is a lot more work to do to understand the best biomarker to identify acute cannabis use or intoxication.
- Ahmad, F., Rossen, L., & Sutton, P. (2021). Provisional drug overdose death counts. https://www.cdc.gov/nchs/pressroom/nchs_press_releases/2021/20210714.htm
- Hoffman, M. A., Hubbard, J. A., Sobolesky, P. M., Smith, B. E., Suhandynata, R. T., Sanford, S., Sones, E. G., Ellis, S., Umlauf, A., Huestis, M. A., Grelotti, D. J., Grant, I., Marcotte, T. D., & Fitzgerald, R. L. (2021). Blood and Oral Fluid Cannabinoid Profiles of Frequent and Occasional Cannabis Smokers. Journal of Analytical Toxicology, 45(8). https://doi.org/10.1093/jat/bkab078
- Hubbard, J. A., Hoffman, M. A., Ellis, S. E., Sobolesky, P. M., Smith, B. E., Suhandynata, R. T., Sones, E. G., Sanford, S. K., Umlauf, A., Huestis, M. A., Grelotti, D. J., Grant, I., Marcotte, T. D., & Fitzgerald, R. L. (2021). Biomarkers of Recent Cannabis Use in Blood, Oral Fluid and Breath. Journal of Analytical Toxicology, 45(8). https://doi.org/10.1093/jat/bkab080
- Huestis, M. A., & Smith, M. L. (2018). Cannabinoid Markers in Biological Fluids and Tissues: Revealing Intake. Trends in Molecular Medicine, 24(2). https://doi.org/10.1016/j.molmed.2017.12.006
- Karschner, E. L., Swortwood-Gates, M. J., & Huestis, M. A. (2020). Identifying and Quantifying Cannabinoids in Biological Matrices in the Medical and Legal Cannabis Era. Clinical Chemistry, 66(7). https://doi.org/10.1093/clinchem/hvaa113
- Krämer, M., Schäper, M., Dücker, K., Philipsen, A., Losacker, M., Dreimüller, N., Engelmann, J., Madea, B., & Hess, C. (2021). Detectability of cannabinoids in the serum samples of cannabis users: Indicators of recent cannabis use? A follow-up study. Drug Testing and Analysis, 13(9). https://doi.org/10.1002/dta.3110
- Kroner, G. M., Johnson-Davis, K. L., Doyle, K., & McMillin, G. A. (2020). Cannabinol (CBN) Cross-Reacts with Two Urine Immunoassays Designed to Detect Tetrahydrocannabinol (THC) Metabolite. The Journal of Applied Laboratory Medicine, 5(3). https://doi.org/10.1093/jalm/jfaa020
- Schulenberg, J., & Patrick, M. (2021). Monitoring the Future national survey results on drug use, 1975–2020: Volume II, College students and adults ages 19–60. http://www.monitoringthefuture.org/pubs/monographs/mtf-vol2_2020.pdf
- Update to Special Reports on Traffic Safety During the COVID-19 Public Health Emergency: Fourth Quarter Data. National Transportation Highway Safety Board (2021). https://rosap.ntl.bts.gov/view/dot/56125