Absence of Increased Susceptibility to Acetaminophen-Induced Liver Injury in a Diet-Induced NAFLD Mouse Model.

Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease and its influence on drug-induced liver injury (DILI) is not fully understood. We investigated whether NAFLD can influence acetaminophen (APAP [N-acetyl-p-aminophenol])-induced hepatotoxicity in a diet-induced obese (DIO) mouse model of NAFLD. The male C57BL/6NTac DIO mice, fed a high-fat diet for more than 12 weeks, developed obesity, hyperinsulinemia, impaired glucose tolerance, and hepatomegaly with hepatic steatosis, similar to human NAFLD.

Thermolytic Degradation of Synthetic Cannabinoids: Chemical Exposures and Pharmacological Consequences.

Synthetic cannabinoids are manufactured clandestinely with little quality control and are distributed as herbal "spice" for smoking or as bulk compound for mixing with a solvent and inhalation via electronic vaporizers. Intoxication with synthetic cannabinoids has been associated with seizure, excited delirium, coma, kidney damage, and other disorders. The chemical alterations produced by heating these structurally novel compounds for consumption are largely unknown.

AB-CHMINACA, AB-PINACA, and FUBIMINA: Affinity and Potency of Novel Synthetic Cannabinoids in Producing Δ9-Tetrahydrocannabinol-Like Effects in Mice.

Diversion of synthetic cannabinoids for abuse began in the early 2000s. Despite legislation banning compounds currently on the drug market, illicit manufacturers continue to release new compounds for recreational use. This study examined new synthetic cannabinoids, AB-CHMINACA (N-[1-amino-3-methyl-oxobutan-2-yl]-1-[cyclohexylmethyl]-1H-indazole-3-carboxamide), AB-PINACA [N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-pentyl-1H-indazole-3-carboxamide], and FUBIMINA [(1-(5-fluoropentyl)-1H-benzo[d]imadazol-2-yl)(naphthalen-1-yl)methanone], with the hypothesis that these compounds, like those before them, would be highly susceptible to abuse.

Cross-substitution of Δ9-tetrahydrocannabinol and JWH-018 in drug discrimination in rats.

Synthetic indole-derived cannabinoids, originally developed to probe cannabinoid CB1 and CB2 receptors, have become widely abused for their marijuana-like intoxicating properties. The present study examined the effects of indole-derived cannabinoids in rats trained to discriminate Δ(9)-tetrahydrocannabinol (Δ(9)-THC) from vehicle. In addition, the effects of Δ(9)-THC in rats trained to discriminate JWH-018 from vehicle were assessed.