title: Dependence Potential of the Synthetic Cannabinoids JWH-073, JWH-081, and JWH-210: In Vivo and In Vitro Approaches.
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 CB1 receptor (JWH-073, 081, and 210) and Δ(9)-tetrahydrocannabinol (Δ(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. Ki values of the three synthetic cannabinoids were calculated as supplementary data using a receptor binding assay and overexpressed CB1 protein membranes to compare dependence potential with CB1 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 Δ(9)-THC showed aversion phenomenon at high doses in the conditioned place preference test. The order of affinity to the CB1 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.
authors.affiliation: Pharmacological Research Division, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Cheongju 363-700 ; Department of Infectious Diseases, College of Veterinary Medicine, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Cha
authors.affiliation: Pharmacological Research Division, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Cheongju 363-700.
authors.forename: Kwang-Wook
authors.initials: KW
authors.lastname: Lee
authors.affiliation: Pharmacological Research Division, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Cheongju 363-700.
authors.forename: Min-Ji
authors.initials: MJ
authors.lastname: Song
authors.affiliation: Pharmacological Research Division, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Cheongju 363-700.
authors.forename: Yang-Jin
authors.initials: YJ
authors.lastname: Hyeon
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon 440-746.
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Hwang
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon 440-746.
authors.forename: Choon-Gon
authors.initials: CG
authors.lastname: Jang
authors.affiliation: Pharmacological Research Division, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Cheongju 363-700.
authors.forename: Joon-Ik
authors.initials: JI
authors.lastname: Ahn
authors.affiliation: Pharmacological Research Division, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Cheongju 363-700.
authors.forename: Seol-Hee
authors.initials: SH
authors.lastname: Jeon
authors.affiliation: Pharmacological Research Division, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Cheongju 363-700.
authors.forename: Hyun-Uk
authors.initials: HU
authors.lastname: Kim
authors.affiliation: Pharmacological Research Division, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Cheongju 363-700.
authors.forename: Young-Hoon
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Pharmacological Research Division, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Cheongju 363-700.
authors.forename: Won-Keun
authors.initials: WK
authors.lastname: Seong
authors.affiliation: Pharmacological Research Division, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Cheongju 363-700.
authors.forename: Hoil
authors.initials: H
authors.lastname: Kang
authors.affiliation: Department of Infectious Diseases, College of Veterinary Medicine, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Han Sang
authors.initials: HS
authors.lastname: Yoo
authors.affiliation: Pharmacological Research Division, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Cheongju 363-700.
authors.forename: Ho-Sang
authors.initials: HS
authors.lastname: Jeong
keywords: Binding affinity; CB1 receptor; Psychological dependence; Synthetic cannabinoid; Δ9-Tetrahydrocannabinol (Δ9-THC)