In vitro elucidation of the metabolic profile of the synthetic cannabinoid receptor agonists JWH-175 and JWH-176

The continuing rise of synthetic cannabinoids consumption remains an analytical challenge. Proof of the intake of these substances is crucial when it comes to driving under the influence of illicit drugs, proof of abstinence after revocation of a driving license, mandatory workplace drug screenings, or judgement of legal culpability of a criminal suspect. Furthermore, in clinical cases of intoxication, the identification of the responsible substance is essential. Because of the short half-life time and the extensive metabolism of synthetic cannabinoids, blood is not the optimal matrix for the verification of elapsed consumption. The parent substance appears in urine only for a very short time period after intake. Therefore, it is crucial to include the metabolites of such substances in the analytical screening strategies. In this work we elucidated the in vitro metabolism of synthetic cannabinoids belonging to the naphthylmethylindole- and the naphthylmethylindene family. Low- and high-resolution mass spectrometry experiments have been performed to identify the formed metabolites. In total, 27 phase I metabolites of JWH-175 and eight of JWH-176 were identified. The obtained metabolic pattern of JWH-175 and JWH-176 can be used to supplement existing screening methods to be able to prove the intake of the investigated synthetic cannabinoids. To our knowledge this is the first report describing the metabolites of JWH-175 and JWH-176.