Conditioned taste aversion elicited by synthetic cannabinoid JWH‐018 in mice is attenuated by pretreatment with phytocannabinoid Δ 9 ‐THC

Aminoalkylindole cannabinioids have recently emerged as drugs of abuse in the US and worldwide. Perhaps the most common such compound present in commercial K2/Spice blends is JWH‐018. The effects of these smoking blends are often more intense than those of marijuana, likely because the aminoalkylindoles have higher affinity for and efficacy at CB1 cannabinoid receptors. Indeed, adverse reactions including agitation, paranoia, tachycardia, seizure, and even death have been reported following exposure to K2 products containing JWH‐018. To model the aversive effects of JWH‐018, we used a conditioned taste aversion procedure in mice. Briefly, mice were trained to emit an operant response (nose‐poke) reinforced with evaporated milk under a fixed‐ratio 5 (FR5) schedule. When responding became regular and reliable, the evaporated milk was replaced with a strawberry‐flavored milk solution; immediately after this session, mice were injected with 3 mg/kg JWH‐018. At least three evaporated milk recovery sessions occurred between strawberry‐flavored milk exposures. Separate groups of animals were treated with the phytocannabinoid Δ 9 ‐THC prior to the first strawberry‐flavored milk exposure. In mice lacking a Δ 9 ‐THC history, JWH‐018 elicited a robust and persistent taste aversion to the strawberry‐flavored milk which was apparent after a single pairing. Interestingly, mice pretreated with Δ 9 ‐THC developed a less intense and shorter‐lived taste aversion following exposure to JWH‐018. These studies suggest that JWH‐018 has pronounced aversive effects, and that these effects may be more prominent in users who have no previous history of marijuana use. This work was supported by US PHS Grant RR020146, and by National Center for Research Resources grant 1UL1RR029884.