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Drug Alcohol Depend. 1997 Apr 14;45(1-2):39-45.

Characterization of anandamide-induced tolerance: comparison to delta 9-THC-induced interactions with dynorphinergic systems.

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Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond 980613, USA.


The endogenous ligand for the cannabinoid receptor, arachidonylethanolamide (anandamide), has been shown to produce antinociception using the tail-flick test following intrathecal administration. Anandamide was administered i.p. (40 mg kg) to mice four times per day for 3 days. Tolerance developed to anandamide: the ED50 for anandamide (i.t.) was shifted from 40 (26-61) to 139 (79-248) micrograms/mouse. Anandamide-tolerant mice were cross-tolerant to delta 9-THC and CP55,940, but not cross-tolerant to mu-, delta- or kappa- opioids, including dynorphins. Conversely, delta 9-THC-tolerant mice are cross-tolerant to anandamide, CP55,940 and kappa agonists. Our data indicate that anandamide and delta 9-THC differ in the mechanisms by which they induce tolerance, in particular the interaction with endogenous dynorphinergic systems.

[Indexed for MEDLINE]

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