The detection of cannabinoids via LC-MSMS to gauge impaired driving.
Recently, we’ve been touring the world of forensic cannabinoid detection, since there are exponentially more people using cannabis-derived products, some with loads of delta-9-tetrahydrocannabinol (THC), others with scarcely any, or those just flat-out labeled as “THC-free”. And given the propensity for strip mall cannabidiol (CBD) products to significantly differ from product labels, such as advocating THC-free products when in fact the molecule can be detected, understanding the efforts that go into developing new technology for forensic applications is a sobering topic.
Why? Drug tests scour one’s fluids and hair for miniscule amounts of THC metabolites. Efforts to assess impaired driving while using cannabis are on the rise, despite several studies arguing that cannabis doesn’t impair driving any more than perfectly legal and commonly used pharmaceuticals. [1,2]
Despite these past evaluations, there are always countercurrent claims. A recent study sought to evaluate the “impact of acute cannabis use on safety and driving performance.”  The authors cite a report by the National Roadside Study of Alcohol and Drug Use by Drivers (NRSADUD) indicating that THC was the most frequently detected drug in drivers , and provide the blanket statement that THC impairs learning and inhibits reaction time, despite literature to the contrary.  Interestingly, THC was found in roughly 9% of daytime drivers (n=1991) versus 13% of nighttime drivers (n=5907).  Comparably, opioids, benzodiazepines, or antidepressants were present in a combined 12% of daytime drivers and 8% of nighttime drivers.
The focus of the current research was to validate a liquid chromatography tandem mass spectrometry (LC-MSMS) method for the detection of cannabinoids in blood and breath.  Challenges regarding the detection of THC metabolites in the body include the time between ingestion, the traffic stop, and when a blood sample can be drawn. This means that once the blood has typically been tested, THC concentrations are not representative of a possible intoxicated state at the time of the citation. What’s more, unlike alcohol, THC concentrations in blood don’t correlate with changes in cognition, making the more invasive blood test less relevant than saliva or breath. 
The researchers evaluated their method for detection of THC, 11-hydroxy-THC (11-OH-THC), (±)-11-nor-9-carboxy-Δ9-THC (THCCOOH), (+)-11-nor-Δ9-THC-9-carboxylic acid glucuronide (THCCOOH-gluc), cannabidiol (CBD), cannabinol (CBN), cannabigerol (CBG), and tetrahydrocannabivarin (THCV) using a 5-minute analysis time. Whole blood and breath samples were used, the latter collected on pads designed to trap aerosol breath that contains eliminated drugs that have passed through the user’s lungs. The pads were put into SensAbues® devices that are used to measure non-volatile chemicals in exhaled breath.
The authors sought to validate their method, and you may recall method validation terms like limit of quantitation (LOQ), accuracy, and linearity. The authors were able to validate their method for the detection of eight cannabinoids in whole blood and THC in breath. The LOQ for THC in breath was 80 picograms per pad; those for the cannabinoids in whole blood ranged from 0.5 to 2 micrograms per liter.
Once the method was validated, the authors wanted to demonstrate proof of concept by measuring blood and breath concentrations in five volunteers before and after smoking a joint. As expected, prior to smoking the joint, blood and breath cannabinoid levels were below the LOQ, except for THCCOOH and THCCOOH-gluc. And 10 minutes after smoking the joint, breath THC ranged from 88,595–279,000 pg/pad, and blood THC ranged from 10.3–78.4 µg/L.
Regardless of where you fall when it comes to opining on cannabis and driving, there will be studies seeking to refine detection technology for law enforcement. Interestingly, though, in a technical report by the U.S. Department of Transportation, National Highway Traffic Safety Administration, a possible defense for a DUID (Driving Under the Influence of Drugs) in Delaware reads “No person shall be guilty … when the person has used or consumed the drug or drugs detected according to the directions and terms of a lawfully obtained prescription for such drug or drugs.” Other states have similar verbiage. Hopefully, this wording will apply to the millions of people who lawfully access medical cannabis and who consult with their recommending physician routinely.
- Robbe, H. W. J., & O’Hanlon, J. F. Marijuana and Actual Driving Performance. (Report No. DOT HS 808 078). Washington, DC: U.S. Department of Transportation, 1993. [cited by 44 (ResearchGate)]
- Young, A. “Marijuana Legalization and Road Safety: A Panel Study of US States.” Kansas State University, Masters’ Thesis, 2019.
- Hubbard, J. et al. “Validation of a Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS) Method to Detect Cannabinoids in Whole Blood and Breath.” Clin Chem Lab Med, 2019, ahead of print. [journal impact factor = 3.556; cited by N/A]
- Kelley-Baker, T. et al. “2013–2014 National Roadside Study of Alcohol and Drug Use by Drivers: Drug Results (Report No. DOT HS 812 411).” Washington, DC: National Highway Traffic Safety Administration, 2017.
- Bilkei-Gorzo, A. et al. “A Chronic Low Dose of Δ9-tetrahydrocannabinol (THC) Restores Cognitive Function in Old Mice.” Nature Medicine, vol.23, no.6, 2017, pp.782-787. [journal impact factor = 30.641; cited by 55 (ResearchGate)]
Image Credit: Air Honest