Vol. 304, Issue 3, 1010-1015, March 2003

Antinociceptive Synergy between ⁹-Tetrahydrocannabinol and Opioids after Oral Administration

Diana L. Cichewicz and Erin A. McCarthy

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

The analgesic effects of opioids, such as morphine and codeine, in mice are enhanced by oral administration of the cannabinoid ⁹-tetrahydrocannabinol (⁹-THC). However, isobolographic analysis has never been done to confirm a synergy between ⁹-THC and morphine or codeine via oral routes of administration. To determine the nature of the interaction between these drugs for pain relief and extend previous experimental results, we performed an isobolographic analysis to evaluate for additivity or synergy in the tail-flick test. Fixed-ratio combinations of ⁹-THC with either morphine or codeine were tested for antinociceptive effects. The experimentally derived ED₅₀ for each combination was compared with the theoretical additive ED₅₀, using an isobolographic analysis. All of the fixed-ratio combinations tested produced greater antinociception (synergy) than predicted from simple additivity. These findings suggest that the use of a low-dose combination of analgesics is a valid and effective approach for the treatment of pain and necessitates further study.