Abstract

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, AB-PINACA, and FUBIMINA, with the hypothesis that these compounds, like those before them, would be highly susceptible to abuse. Cannabinoids were examined in vitro for binding and activation of CB₁ receptors, and in vivo for pharmacological effects in mice and in Δ⁹-THC discrimination. AB-CHMINACA, AB-PINACA and FUBIMINA bound to and activated CB₁ and CB₂ receptors, and produced locomotor suppression, antinociception, hypothermia, and catalepsy. Further, these compounds, along with JWH-018, CP47,497, and WIN55,212-2, substituted for Δ⁹-THC in Δ⁹-THC discrimination. Rank order of potency correlated with CB₁ receptor binding affinity, and all three compounds were full agonists in [³⁵S]GTPγS binding, as compared to the partial agonist Δ⁹-THC. Indeed, AB-CHMINACA and AB-PINACA exhibited higher efficacy than most known full agonists of the CB₁ receptor. Preliminary analysis of urinary metabolites of the compounds revealed the expected hydroxylation. AB-PINACA and AB-CHMINACA are of potential interest as research tools due to their unique chemical structures and high CB₁ receptor efficacies. Further studies on these chemicals is likely to include research on understanding cannabinoid receptors and other components of the endocannabinoid system that underlie the abuse of synthetic cannabinoids.