Prevalence of ∆8-tetrahydrocannabinol carboxylic acid in workplace drug testing

Abstract

Δ8-Tetrahydrocannabinol (Δ8-THC) recently became widely available as an alternative to cannabis. Δ8-THC is likely impairing and poses a threat to workplace and traffic safety. In the present study the prevalence of Δ8-THC in workplace drug testing was investigated by analyzing 1,504 urine specimens with a positive immunoassay cannabinoid initial test using an LC-MS-MS method quantifying 15 cannabinoid analytes after hydrolysis. Δ8-tetrahydrocannabinol-9-carboxylic acid (Δ8-THC-COOH) was detected in 378 urine specimens (15 ng/mL cutoff), compared to 1,144 specimens containing Δ9-THC-COOH. The data could be divided into three general groups. There were 964 (76%) Δ9-THC-COOH dominant (<10% Δ8-THC-COOH) and 139 (11%) Δ8-THC-COOH dominant (>90% Δ8-THC-COOH) specimens, with the remaining 164 (13%) specimens showing a mixture of both analytes (>90% Δ8-THC-COOH). Similar concentrations of Δ9-THC-COOH (median 187 ng/mL) and Δ8-THC-COOH (150 ng/mL) as the dominant species support the use of similar cutoffs and decision rules for both analytes. Apart from the carboxylic acid metabolites, 11-hydroxy-Δ9-tetrahydrocannabinol (11-OH-Δ9-THC, n = 1,282), Δ9-tetrahydrocannabivarin-9-carboxylic acid (Δ9-THCV-COOH, n = 1,058), Δ9-THC (n = 746) and 7-hydroxy-cannabidiol (7-OH-CBD, n = 506) were the most prevalent analytes. Two specimens (0.13%) contained ≥140 ng/mL Δ9-THC without Δ9-THC-COOH, which could be due to genetic variability in the drug metabolizing enzyme CYP2C9 or an adulterant targeting Δ9-THC-COOH. The cannabinoid immunoassay was repeated, and five specimens (0.33%) generated negative initial tests despite Δ9-THC-COOH concentrations of 54-1,000 ng/mL, potentially indicative of adulteration. The use of Δ8-THC is widespread in the US populations, and all forensic laboratories should consider adding Δ8-THC and/or Δ8-THC-COOH to their scope of testing. Similar urinary concentrations were observed for both analytes indicating that the decision rules used for Δ9-THC-COOH are appropriate also for Δ8-THC-COOH.