(R)-methanandamide, but not anadamide, substitutes for Δ–9-THC in a drug-discrimination procedure.

Fourteen male rats were trained to discriminate between injections of 2 mg/kg delta-9 tetrahydrocannabinol (Δ–9-THC) and vehicle in a 2-lever operant drug-discrimination paradigm. Following training, substitution tests using a cumulative dosing procedure revealed that anandamide (0.5-16 mg/kg ip), the putative endogenous cannabinoid receptor ligand, failed to generalize to the discriminative stimulus properties of the training dose of Δ–9-THC. However, dose-dependent generalization to the Δ–9-THC cue was observed following administration of both CP-55,940 (0.05-0.8 mg/kg ip), a synthetic cannabinoid, and (R)-methanandamide (0.5-8 mg/kg ip), a metabolically stable analog of anandamide. Collectively, these results demonstrate a cannabinoid-specific in vivo effect of an anandamide compound and suggest that the naturally occurring form of anandamide may be metabolized too rapidly to produce a cannabimimetic interoceptive state when administered peripherally. (PsycINFO Database Record (c) 2010 APA, all rights reserved)