New Synthetic Cannabinoids Metabolism and Strategies to Best Identify Optimal Marker Metabolites

doi:10.3389/fchem.2019.00109

	New Synthetic Cannabinoids Metabolism and Strategies to Best Identify Optimal Marker Metabolites
	Diao, Xingxing 1; Huestis, Marilyn A.2
刊名	FRONTIERS IN CHEMISTRY
	2019-03-04
卷号	7 页码:15
关键词	novel psychoactive substances NPS synthetic cannabinoid SC metabolism urinary metabolites hepatocyte incubation
ISSN号	2296-2646
DOI	10.3389/fchem.2019.00109
通讯作者	Huestis, Marilyn A.(marilyn.huestis@gmail.com)
英文摘要	Synthetic cannabinoids (SCs) were initially developed as pharmacological tools to probe the endocannabinoid system and as novel pharmacotherapies, but are now highly abused. This is a serious public health and social problem throughout the world and it is highly challenging to identify which SC was consumed by the drug abusers, a necessary step to tie adverse health effects to the new drug's toxicity. Two intrinsic properties complicate SC identification, their often rapid and extensive metabolism, and their generally high potency relative to the natural psychoactive Delta(9)-tetrahydrocannabinol in cannabis. Additional challenges are the lack of reference standards for the major urinary metabolites needed for forensic verification, and the sometimes differing illicit and licit status and, in some cases, identical metabolites produced by closely related SC pairs, i.e., JWH-018/AM-2201, THJ-018/THJ-2201, and BB-22/MDMB-CHMICA/ADB-CHMICA.We review current SC prevalence, establish the necessity for SC metabolism investigation and contrast the advantages and disadvantages of multiple metabolic approaches. The human hepatocyte incubation model for determining a new SC's metabolism is highly recommended after comparison to human liver microsomes incubation, in silico prediction, rat in vivo, zebra fish, and fungus Cunninghamella elegans models. We evaluate SC metabolic patterns, and devise a practical strategy to select optimal urinary marker metabolites for SCs. New SCs are incubated first with human hepatocytes and major metabolites are then identified by high-resolution mass spectrometry. Although initially difficult to obtain, authentic human urine samples following the specified SC exposure are hydrolyzed and analyzed by high-resolution mass spectrometry to verify identified major metabolites. Since some SCs produce the same major urinary metabolites, documentation of the specific SC consumed may require identification of the SC parent itself in either blood or oral fluid. An encouraging trend is the recent reduction in the number of new SC introduced per year. With global collaboration and communication, we can improve education of the public about the toxicity of new SC and our response to their introduction.
WOS关键词	RESOLUTION MASS-SPECTROMETRY ; IN-VITRO METABOLISM ; 3-N-BUTYLPHTHALIDE NBP ; HUMAN HEPATOCYTE ; 5-FLUORO ANALOG ; HUMAN URINE ; PSYCHOACTIVE SUBSTANCES ; RECEPTOR AGONISTS ; LIVER-MICROSOMES ; DRUG-METABOLISM
WOS研究方向	Chemistry
语种	英语
出版者	FRONTIERS MEDIA SA
WOS记录号	WOS:000460330100001
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/290307]
专题	中国科学院上海药物研究所
通讯作者	Huestis, Marilyn A.
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai, Peoples R China 2.Thomas Jefferson Univ, Inst Emerging Hlth Profess, Lambert Ctr Study Med Cannabis & Hemp, Philadelphia, PA 19107 USA
推荐引用方式 GB/T 7714	Diao, Xingxing,Huestis, Marilyn A.. New Synthetic Cannabinoids Metabolism and Strategies to Best Identify Optimal Marker Metabolites[J]. FRONTIERS IN CHEMISTRY,2019,7:15.
APA	Diao, Xingxing,&Huestis, Marilyn A..(2019).New Synthetic Cannabinoids Metabolism and Strategies to Best Identify Optimal Marker Metabolites.FRONTIERS IN CHEMISTRY,7,15.
MLA	Diao, Xingxing,et al."New Synthetic Cannabinoids Metabolism and Strategies to Best Identify Optimal Marker Metabolites".FRONTIERS IN CHEMISTRY 7(2019):15.