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Many countries were the first to offer synthetic cannabinoids JWH-018 and JWH-250 in ‘herbal incense,’ commonly known as’spice.’ Several synthetic cannabinoids with comparable chemical structures appeared at the same time. There is currently insufficient information on their negative effects, including neurotoxicity. Only anecdotal evidence suggests that they are toxic. Using experimental mice at various doses (0.1, 1, 5 mg/kg), we assessed the neurotoxicity of two synthetic cannabinoids (JWH-081 and JWH-210) by observing numerous behavioral changes and analyzing histological abnormalities.


Animals given 5 mg/kg of JWH-081 or JWH-210 demonstrated traction and tremor in a functional observation battery (FOB) test. Their locomotor activity and rotarod retention time were both considerably reduced (p0.05). However, there was no discernible difference in learning or memory performance.
Histopathological study of brain cells from mice given a high dose (5 mg/kg) of JWH-081 or JWH-210 revealed deformed nuclei and nucleus membranes in the nucleus accumbens core shell, indicating neurotoxicity. Our findings imply that JWH-081 and JWH-210 are neurotoxic chemicals that cause neuronal cell destruction, particularly in the nucleus accumbens core shell. Future research will be required to confirm our findings.

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Many researchers have researched some well-known synthetic cannabinoids, such as JWH-018. In many nations, the majority of them are regulated. Many novel synthetic cannabinoids with chemical structures comparable to those of ‘conventional’ cannabinoids have appeared to satisfy the needs of users who are ready to seek substitutes. The absence of information on the hazards of these novel synthetic cannabinoids, such as toxicity, dependence liability, and acceptable doses, is worrisome. Only anecdotal reports can help one realize their risks.

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