Using measured cannabidiol and tetrahydrocannabinol metabolites in urine to differentiate marijuana use from consumption of commercial cannabidiol products

Context: Detecting marijuana use is a component of most urine drug screens targeting a single Δ⁹-tetrahydrocannabinol metabolite. Recently, the non-intoxicating cannabinoid, cannabidiol (CBD), has gained popular acceptance for a myriad of reasons. Commercially available CBD products sold without purity regulations have become ubiquitous. Many products contain trace tetrahydrocannabinol. Long-term or high dose use of CBD products can result in tetrahydrocannabinol exposures, potentially producing a positive marijuana drug test. These results are not false positives since marijuana biomarkers are present, but inaccurately identify donors as marijuana users. Addressing this conundrum, we developed an assay discriminating marijuana use from the use of CBD contaminated with tetrahydrocannabinol.

Methods: Following the synthesis of a primary CBD metabolite, a LC-MS/MS assay was developed measuring the urinary metabolites tetrahydrocannabinol, 11-nor-carboxy-Δ⁹-tetrahydrocannabinol, CBD, and 7-carboxy-cannabidiol. The assay was utilized on 425 patients claiming CBD use, and sixteen samples from trusted users of commercial CBD products.

Results and discussion: Clear data clusters enabled metabolic cut-points assignments. Forty-three percent of samples contained CBD metabolites in ten-fold excess to tetrahydrocannabinol metabolites which was then used as a set point to classify donors as CBD users. An excess of tetrahydrocannabinol metabolites classify donors as marijuana users. Additionally, urine samples were procured from donors personally known to use commercial CBD ad libitum, yet abstain from tetrahydrocannabinol. Results from trusted users substantiated the use of the resulting metabolic ratios despite 11-carboxy-tetrahydrocannabinol measured in 75% of these samples.

Conclusion: A method has been developed and utilized to distinguish marijuana use from tetrahydrocannabinol exposure from contaminated CBD use.