Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Dependence Potential of the Synthetic Cannabinoids JWH-073, JWH-081, and JWH-210: In Vivo and In Vitro Approaches

  • Cha, Hye Jin (Pharmacological Research Division, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety) ;
  • Lee, Kwang-Wook (Pharmacological Research Division, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety) ;
  • Song, Min-Ji (Pharmacological Research Division, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety) ;
  • Hyeon, Yang-Jin (Pharmacological Research Division, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety) ;
  • Hwang, Ji-Young (School of Pharmacy, Sungkyunkwan University) ;
  • Jang, Choon-Gon (School of Pharmacy, Sungkyunkwan University) ;
  • Ahn, Joon-Ik (Pharmacological Research Division, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety) ;
  • Jeon, Seol-Hee (Pharmacological Research Division, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety) ;
  • Kim, Hyun-Uk (Pharmacological Research Division, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety) ;
  • Kim, Young-Hoon (Pharmacological Research Division, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety) ;
  • Seong, Won-Keun (Pharmacological Research Division, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety) ;
  • Kang, Hoil (Pharmacological Research Division, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety) ;
  • Yoo, Han Sang (Department of Infectious Diseases, College of Veterinary Medicine, Seoul National University) ;
  • Jeong, Ho-Sang (Pharmacological Research Division, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety)
  • Received : 2014.04.01
  • Accepted : 2014.06.02
  • Published : 2014.07.31
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Abstract

Synthetic cannabinoids (CBs) such as the JWH series have caused social problems concerning their abuse liability. Because the JWH series produces euphoric and hallucinogenic effects, they have been distributed illegally under street names such as "Spice" and "Smoke". Many countries including Korea have started to schedule some of the JWH series compounds as controlled substances, but there are a number of JWH series chemicals that remain uncontrolled by law. In this study, three synthetic CBs with different binding affinities to the $CB_1$ receptor (JWH-073, 081, and 210) and ${\Delta}^9$-tetrahydrocannabinol (${\Delta}^9$-THC) were evaluated for their potential for psychological dependence. The conditioned place preference test (unbiased method) and self-administration test (fixed ratio of 1) using rodents were conducted. $K_i$ values of the three synthetic cannabinoids were calculated as supplementary data using a receptor binding assay and overexpressed $CB_1$ protein membranes to compare dependence potential with $CB_1$ receptor binding affinity. All mice administered JWH-073, 081, or 210 showed significantly increased time spent at unpreferred space in a dose-dependence manner in the conditioned place preference test. In contrast, all tested substances except ${\Delta}^9$-THC showed aversion phenomenon at high doses in the conditioned place preference test. The order of affinity to the $CB_1$ receptor in the receptor binding assay was JWH-210 > JWH-081 >> JWH-073, which was in agreement with the results from the conditioned place preference test. However, no change in self-administration was observed. These findings suggest the possibility to predict dependence potential of synthetic CBs through a receptor binding assay at the screening level.

Keywords

References

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