Even Low Doses of Synthetic Cannabinoid JWH-018 Caused Lasting Heart Damage and Multi-Organ Injury in Rats

Repeated JWH-018 at 0.25 mg/kg for 14 days caused persistent hypothermia, increased blood pressure and heart rate throughout treatment. One day after stopping, cardiac lesions (vacuolization, waving, edema) were found. Seven days later, lung, kidney, and liver degeneration appeared. Heart mitochondria showed defective lipid oxidation, suggesting a mechanism for JWH-018's cardiac toxicity.

In silico toxicity screening of 36 synthetic cannabinoids, followed by 14-day repeated dosing of JWH-018 (0.25 mg/kg IP) in male rats, with cardiovascular monitoring during treatment and post-mortem tissue analysis at 1 and 7 days after discontinuation.

This study demonstrates that even low doses of a common synthetic cannabinoid can cause lasting organ damage, particularly to the heart. The finding that damage worsens after stopping the drug suggests ongoing pathological processes that outlast drug exposure.

Reports of sudden cardiac deaths among synthetic cannabinoid users have been increasing. This study provides a biological mechanism (mitochondrial dysfunction) and shows that damage can progress even after stopping use, which has important clinical implications.

Animal study with a single synthetic cannabinoid and dose level. IP injection does not mimic human smoking/vaping routes. Only male rats studied. Short treatment period relative to human use patterns.