RT Journal Article SR Electronic T1 Decrease in Efficacy and Potency of Nonsteroidal Anti-Inflammatory Drugs by Chronic Δ9-Tetrahydrocannabinol Administration JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 340 OP 346 DO 10.1124/jpet.303.1.340 VO 303 IS 1 A1 Rene Anikwue A1 John W. Huffman A1 Zachary L. Martin A1 Sandra P. Welch YR 2002 UL http://jpet.aspetjournals.org/content/303/1/340.abstract AB Cannabinoids have been shown to increase the release of arachadonic acid, whereas nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to decrease the analgesic effects of cannabinoids. We evaluated the antinociceptive effects of chronic administration of Δ9-tetrahydrocannabinol (Δ9-THC), anandamide (an endogenous cannabinoid), arachadonic acid, ethanolamine, and methanandamide on several NSAIDs via p.o. and/or i.p. routes of administration using the mouse p-phenylquinone (PPQ) test, a test for visceral nociception. Our studies with a cannabinoid receptor (CB1) antagonist [N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboximide hydrochloride (SR141716A)], a CB2 antagonist [N-((1S)-endo-1,3,3-trimethyl-bicyclo-heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyrazole-3-carboxamide) (SR144528)], and an another CB2 agonist [1,1-dimethylbutyl-1-deoxy-Δ9-THC (JWH-133)] were performed to better characterize PPQ interactions with cannabinoid receptors. The acute affects of Δ9-THC were blocked by SR141716A (i.p.) and partially blocked by SR144528 (i.p.). When NSAIDs (p.o.) were administered, the ED50 values were as follows: 23 mg/kg aspirin, 3 mg/kg indomethacin, 5 mg/kg celecoxib, 3 mg/kg ketorolac, 57 mg/kg acetaminophen (32.3–99.8), and 0.8 mg/kg diclofenac (0.1–4.9). In animals given chronic Δ9-THC, only diclofenac and acetaminophen were active. Conversely, chronic methanandamide (i.p.) did not alter the antinociceptive effects of the NSAIDs. Neither the CB1 or CB2 antagonist blocked the effects of the NSAIDs. The effects of chronic arachadonic acid, ethanolamine, and anandamide could not be evaluated. In summary, our data indicate that chronic Δ9-THC alters the cyclooxygenase system. Alternatively, the data suggest that this alteration is not due to chronic endogenous cannabinoid release. Based upon these data, we hypothesize that human subjects who are chronic users of Δ9-THC may not respond to analgesic treatment with the above NSAIDs. The American Society for Pharmacology and Experimental Therapeutics