11-OH-THC in hair as marker of active cannabis consumption: estimating a reliable cut-off by evaluation of 672 cannabis users

Discrimination of cannabis active use from passive consumption by hair analysis may fail when performed by the sole detection of compounds present in plant material as well as in cannabis smoke such as 06\u20109\u2010tetrahydrocannabinol (THC), cannabidiol (CBD), and cannabinol (CBN). For this reason, the determination of THC metabolite 11\u2010nor\u20109\u2010carboxy\u2010 06-9-tetrahydrocannabinol (THC\u2010COOH) has been proposed by the Society of Hair Testing (SoHT)1 in order to prove active cannabis consumption. THC\u2010COOH is formed from THC via 11\u2010hydroxy\u2010 06\u20109-tetrahydrocannabinol (11-OH-THC) by cytochrome P450 enzymes. The identification of THC-COOH in hair is still challenging due to its acidic nature and the its critical low concentration, since the incorporation into hair shaft appears to be preferential for basic compounds. Alternatively, 11-OH-THC may be considered as a complementary marker for THC administration. Our recent study reported an accurate validated procedure for THC, CBD, CBN and 11-OH-THC in hair, based on a GC/MS-MS method in electron ionization mode2. However, unlike THC-COOH, a cut-off level for 11-OH-THC in hair has not been fixed yet. Therefore, the aim of this study is to propose a concentration value for 11-OH-THC in hair analysis in order to discriminate between chronic and occasional use. Receiver operating characteristics (ROC) analysis was applied for cut\u2010off evaluation after 11-OH-THC quantification (n = 672). Considering the experimental data collected in our laboratory, we propose a cut-off level of 0.48 pg/mg, as indicative of cannabis active consumption. The ROC curve AUCs for 11-OH-THC were 0.874 and 0.879 for 590 hair and 82 body hair samples, respectively. The comparison of the results for THC-COOH (control method) and 11-OH-THC (test method) was also made by means of the Cohen\u2019s kappa statistics providing a good agreement according to both Landis & Koch and Fleiss scales. Additionally, we suggest that the quantification of either THC-COOH or 11-OH-THC should be mandatory in order to prove active intake and exclude false positive result from external contamination