Changes in the prevalence of synthetic cannabinoids and cathinone derivatives in Japan until early 2012

Several synthetic cannabinoids were found in 44 of 46 different kinds of herbal products that are currently distributed on the illegal drug market in Japan due to their expected narcotic effects. Gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) analyses indicated that most of the products contained two major synthetic cannabinoids: (1RS,3SR)-3-[2-hydroxy-4-(2-methylnonan-2-yl)phenyl]cyclohexan-1-ol, renamed cannabicyclohexanol with the agreement of Pfizer Inc., and/or 1-naphthalenyl(1-pentyl-1H-indol-3-yl)methanone, named JWH-018. Oleamide (cis-9,10-octadecenoamide), which is an endogenous cannabinoid, was also detected in 7 products. Additionally, two synthetic cannabinoids were identified as minor components in some products. One was (1RS,3SR)-3-[2-hydroxy-4-(2-methyloctan-2-yl)phenyl]cyclohexan-1-ol, which is named CP-47,497 and is a homolog of cannabicyclohexanol. The other was 1-naphthalenyl(1-butyl-1H-indol-3-yl)methanone, which is named JWH-073 and is a homolog of JWH-018. These compounds were reported as synthetic cannabinoids possessing pharmacological cannabimimetic activity. The concentrations of cannabicyclohexanol, JWH-018 and oleamide in the products ranged from 1.1 to 16.9mg/g, 2.0 to 35.9mg/g and 7.6 to 210.9mg/g, respectively, and showed considerable variation. In this study, details of the analysis and identification of these synthetic cannabinoids in herbal products being sold on the Japanese drug market are described.

URB-754 (6-methyl-2-[(4-methylphenyl)amino]-1-benzoxazin-4-one) was identified as a new type of designer drug in illegal products. Though many of the synthetic cannabinoids detected in illegal products are known to have affinities for cannabinoid CB1/CB2 receptors, URB-754 was reported to inhibit an endocannabinoid deactivating enzyme. Furthermore, an unknown compound (N,5-dimethyl-N-(1-oxo-1-(p-tolyl)butan-2-yl)-2-(N'-(p-tolyl)ureido)benzamide), which is deduced to be the product of a reaction between URB-754 and a cathinone derivative 4-methylbuphedrone (4-Me-MABP), was identified along with URB-754 and 4-Me-MABP in the same product. It is of interest that the product of a reaction between two different types of designer drugs, namely, a cannabinoid-related designer drug and a cathinone-type designer drug, was found in one illegal product. In addition, 12 cannabimimetic compounds, 5-fluoropentyl-3-pyridinoylindole, JWH-307, JWH-030, UR-144, 5FUR-144 (synonym: XLR11), (4-methylnaphtyl)-JWH-022 [synonym: N-(5-fluoropentyl)-JWH-122], AM-2232, (4-methylnaphtyl)-AM-2201 (MAM-2201), N-(4-pentenyl)-JWH-122, JWH-213, (4-ethylnaphtyl)-AM-2201 (EAM-2201) and AB-001, were also detected herein as newly distributed designer drugs in Japan. Furthermore, a tryptamine derivative, 4-hydroxy-diethyltryptamine (4-OH-DET), was detected together with a synthetic cannabinoid, APINACA, in the same product.