title: Characteristics of the designer drug and synthetic cannabinoid receptor agonist AM-2201 regarding its chemistry and metabolism.
abstract: Aminoalkylindoles, a subclass of synthetic cannabinoid receptor agonists, show an extensive and complex metabolism in vivo, and due to their structural similarity, they can be challenging in terms of unambiguous assignment of metabolic patterns in urine samples to consumed substances. The situation may even be more complicated as these drugs are usually smoked, and the high temperature exposure may lead to formation of artifacts. Typical metabolites of JWH-018 (Naphthalen-1-yl(1-pentyl-1H-indol-3-yl)methanone) were reportedly detected not only in urine samples collected after consumption of JWH-018 but also after AM-2201 (1-(5-fluoropentyl-1H-indol-3-yl)-(naphthalene-1-yl)methanone) use. The aim of the presented study was to evaluate if typical JWH-018 metabolites can be formed metabolically in humans and if JWH-018 may be formed artifactually during smoking of AM-2201. Therefore, one of the authors ingested 5 mg of pure AM-2201, and serum as well as urine samples were analyzed subsequently. Additionally, the smoke condensate from a cigarette laced with pure AM-2201 was investigated. In addition, urine samples of patients after known consumption of AM-2201 or JWH-018 were evaluated. The results of the study prove that typical metabolites of JWH-018 and JWH-073 are built in humans after ingestion of AM-2201. However, the N-(4-hydroxypentyl) metabolite of JWH-018, which is the major metabolite after JWH-018 use, was not detected after the self-experiment. In the smoke condensate, small amounts of JWH-018 and JWH-022 (Naphthalen-1-yl[1-(pent-4-en-1-yl)-1H-indol-3-yl]methanone) were detected. Nevertheless, the results of our study suggest that the amounts absorbed by smoking do not significantly influence the metabolic pattern in urine samples. Therefore, the N-(4-hydroxypentyl) metabolite of JWH-018 can serve as a valuable marker to distinguish consume of products containing AM-2201 from JWH-018 use.
authors.affiliation: Institute of Forensic Medicine, Forensic Toxicology, University Medical Center Freiburg, Albertstr. 9, 79104, Freiburg, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Hutter
authors.forename: Bjoern
authors.initials: B
authors.lastname: Moosmann
authors.forename: Stefan
authors.initials: S
authors.lastname: Kneisel
authors.forename: Volker
authors.initials: V
authors.lastname: Auwärter
mesh_terms: D000328:Adult; D063386:Cannabinoid Receptor Agonists / Q000097:blood / Q000737:chemistry* / Q000378:metabolism* / Q000652:urine; D002853:Chromatography, Liquid; D015198:Designer Drugs / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007211:Indoles / Q000032:analysis / Q000737:chemistry* / Q000378:metabolism* / Q000652:urine; D008297:Male; D009281:Naphthalenes / Q000378:metabolism; D012906:Smoke / Q000032:analysis; D053719:Tandem Mass Spectrometry
chemical_list: C582337:1-(5-fluoropentyl)-3-(1-naphthoyl)indole; D063386:Cannabinoid Receptor Agonists; D015198:Designer Drugs; D007211:Indoles; D009281:Naphthalenes; D012906:Smoke; C552597:1-pentyl-3-(1-naphthoyl)indole
keywords: AM-2201; JWH-018; JWH-022; Spice; metabolism; smoke condensate; synthetic cannabinoid