Introduction: The analgesic effects of delta-9-tetrahydrocannabinol (THC), the primary psychoactive compound in cannabis, have been widely promoted. Unfortunately, animal research is limited by the use of high doses and pain-evoked tests. Motor and psychoactive effects of THC may suppress evoked responses in the absence of antinociceptive effects. Materials and Methods: This study overcomes these problems by assessing the antinociceptive effect of low doses of subcutaneous THC on depression of home cage wheel running caused by hindpaw inflammation. Female and male Long-Evans rats were individually housed in a cage with a running wheel. Results: Female rats ran significantly more than male rats. Administration of Complete Freund's Adjuvant into the right hindpaw produced inflammatory pain that significantly depressed wheel running in female and male rats. Administration of a low dose of THC (0.32, but not 0.56 or 1.0 mg/kg) restored wheel running in the hour after administration in female rats. Administration of these doses had no effect on pain-depressed wheel running in male rats. Conclusions: These data are consistent with previous studies showing greater antinociceptive effects of THC in female compared with male rats. These data extend previous findings by showing that low doses of THC can restore pain-depressed behaviors.
Keywords: analgesia; cannabis; pain-depressed behavior; sex difference; wheel running.