title: Neurotoxicity of Synthetic Cannabinoids JWH-081 and JWH-210.
abstract: Synthetic cannabinoids JWH-018 and JWH-250 in 'herbal incense' also called 'spice' were first introduced in many countries. Numerous synthetic cannabinoids with similar chemical structures emerged simultaneously and suddenly. Currently there are not sufficient data on their adverse effects including neurotoxicity. There are only anecdotal reports that suggest their toxicity. In the present study, we evaluated the neurotoxicity of two synthetic cannabinoids (JWH-081 and JWH-210) through observation of various behavioral changes and analysis of histopathological changes using experimental mice with various doses (0.1, 1, 5 mg/kg). In functional observation battery (FOB) test, animals treated with 5 mg/kg of JWH-081 or JWH-210 showed traction and tremor. Their locomotor activities and rotarod retention time were significantly (p<0.05) decreased. However, no significant change was observed in learning or memory function. In histopathological analysis, neural cells of the animals treated with the high dose (5 mg/kg) of JWH-081 or JWH-210 showed distorted nuclei and nucleus membranes in the core shell of nucleus accumbens, suggesting neurotoxicity. Our results suggest that JWH-081 and JWH-210 may be neurotoxic substances through changing neuronal cell damages, especially in the core shell part of nucleus accumbens. To confirm our findings, further studies are needed in the future.
authors.affiliation: Pharmacological Research Division, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Chungju 28159, Republic of Korea.
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Cha
authors.affiliation: Laboratory of Veterinary Pharmacology, College of Veterinary Medicine, Chungbuk National University, Chungju 28644, Republic of Korea.
authors.forename: Yeon-Hee
authors.initials: YH
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, Chungju 28159, Republic of Korea.
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, Chungju 28159, Republic of Korea.
authors.forename: Ho-Sang
authors.initials: HS
authors.lastname: Jeong
authors.affiliation: Pharmacological Research Division, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Chungju 28159, Republic of Korea.
authors.forename: Jisoon
authors.initials: J
authors.lastname: Shin
authors.affiliation: Pharmacological Research Division, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Chungju 28159, Republic of Korea.
authors.forename: Jaesuk
authors.initials: J
authors.lastname: Yun
authors.affiliation: Pharmacological Research Division, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Chungju 28159, Republic of Korea.
authors.forename: Kyoungmoon
authors.initials: K
authors.lastname: Han
authors.affiliation: Pharmacological Research Division, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Chungju 28159, Republic of Korea.
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, Chungju 28159, Republic of Korea.
authors.forename: Hoil
authors.initials: H
authors.lastname: Kang
authors.affiliation: Pharmacological Research Division, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Chungju 28159, Republic of Korea.
authors.forename: Hyoung Soo
authors.initials: HS
authors.lastname: Kim
keywords: Functional observation battery; Histopathology; Motor function; Neurotoxicity; Synthetic cannabinoid