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(R)-methanandamide, but not anandamide, substitutes for delta 9-THC in a drug-discrimination procedure.

R T Burkey, J R Nation

Experimental and Clinical Psychopharmacology August 1997 DOI: 10.1037//1064-1297.5.3.195 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Drug discrimination study in rats Peer reviewed
Sample size 14
Population Male rats
Interventions delta-9-tetrahydrocannabinol (delta 9-THC) anandamide CP-55 940 (R)-methanandamide
Dose 2 mg/kg delta-9-THC; anandamide 0.5-16 mg/kg ip; CP-55,940 0.05-0.8 mg/kg ip; (R)-methanandamide 0.5-8 mg/kg ip
Topics Cannabis
Key points Anandamide did not generalize to the discriminative stimulus effects of delta-9-THC, whereas the synthetic cannabinoid CP-55,940 and the metabolically stable anandamide analog (R)-methanandamide produced dose-dependent generalization. The authors suggest that naturally occurring anandamide may be metabolized too rapidly after peripheral administration to produce a cannabimimetic interoceptive state.

Abstract

Fourteen male rats were trained to discriminate between injections of 2 mg/kg delta-9-tetrahydrocannabinol (delta 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 camabinoid receptor ligand, failed to generalize to the discriminative stimulus properties of the training dose of delta 9-THC. However, dose-dependent generalization to the delta 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 intercceptive state when administered peripherally.

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