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.

Comparison of the Neurotoxic and Seizure-Inducing Effects of Synthetic and Endogenous Cannabinoids with Δ9-Tetrahydrocannabinol

“…The lack of pathological changes from cannabinoids is consistent with other studies in which animals had minimal to no pathology or the pathological changes were associated with factors such as route of administration. [29][30][31][32][33][34] The chronic peritonitis observed in this study was attributed to the multiple IP injections.…”

Pharmaco‐toxicological effects of the novel third‐generation fluorinate synthetic cannabinoids, 5F‐ADBINACA, AB‐FUBINACA, and STS‐135 in mice. In vitro and in vivo studies

“…Those events have a considerable impact on cell viability. The present data are in agreement with recent studies showing the neurotoxicity of SCBs in mice (Cha et al ., ; Tomiyama & Funada, ). Although the three SCBs tested presented similar affinity for both murine CD‐1 and human CB 1 and CB 2 receptors, they have different neurotoxic properties.…”

Synthetic Cannabinoids: Psychopharmacology, Clinical Aspects, Psychotic Onset

“…SC can cause cell damaging through affecting lipid metabolism and inflammatory signalling [33]. Chronic systemic exposure can modify the structure of cortical and sub-cortical neurons [34], with effects on nuclei and nucleus membranes [35] and suppression of neuronal activity in the hippocampus [36][37]. Metabolites of SC also demonstrate neurotoxic effects decreasing cellular viability, apoptosis and necrosis [38][39] as well as DNA damaging and micronuclei aberration of chromosomes [40][41].…”