Methodology for controlled administration of smoked synthetic cannabinoids JWH-018 and JWH-073

NEUROPHARMACOLOGY

卷:134

Article

Cooper, Ziva D.^1,2  Poklis, Justin L.³  Liu, Fei⁴ 

[1] Columbia Univ, Med Ctr, New York State Psychiat Inst, Div Subst Abuse, 1051 Riverside Dr,Unit 120, New York, NY 10032 USA

[2] Columbia Univ, Med Ctr, Dept Psychiat, 1051 Riverside Dr,Unit 120, New York, NY 10032 USA

[3] Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA USA

[4] Vanderbilt Univ, Inst Imaging Sci, 221 Kirkland Hall, Nashville, TN 37235 USA

关键词: Synthetic cannabinoids;    Pharmacokinetics;    Cannabis;    JWH-018;    JWH-073;   

DOI  :  10.1016/j.neuropharm.2017.11.020

来源: Elsevier

【 摘 要 】

Synthetic cannabinoids (SCs) are a significant public health concern given their widespread use and severe effects associated with intoxication. However, there is a paucity of controlled human studies investigating the behavioral and physiological effects and pharmacokinetics of these compounds. Designing a reliable method to administer consistent, concentration-dependent synthetic cannabinoids is an integral component of controlled study of these compounds. Further, optimizing methods to assess the parent compounds and metabolites in plasma is critical in order to be able to establish their pharmacokinetics after administration. To develop a reliable method to administer smokable, concentration dependent SCs, cigarettes were prepared with plant matter adulterated with increasing concentrations of the first generation cannabinoids found in SC products, JWH-018 and JWH-073. Cigarettes were assessed 1-6 months after preparation using ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) to determine compound stability over time and concentration consistency throughout the cigarettes. Optimal conditions to detect metabolites in human plasma as a function of storage temperature (-4 degrees C to -80 degrees C) and time (24 h - 1 month) were also determined. Analyses verified that the method utilized to develop SC cigarettes yielded consistent, concentration-dependent products within 25% of the expected concentrations. JWH-018, JWH-073 and metabolites in spiked plasma were stable under the time and temperature conditions; concentrations were within +/- 20% of target values. These studies provide techniques and methods to conduct controlled investigations of the dose dependent effects of first generation SCs to begin understanding risks associated with use. This article is part of the Special Issue entitled 'Designer Drugs and Legal Highs.'

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