FASEB J. 2022 May;36 Suppl 1. doi: 10.1096/fasebj.2022.36.S1.R3008.
The antinociceptive effects of major cannabinoids such as ∆9-tetrahydrocannabinol (THC) and cannabidiol (CBD) have been extensively studied in rats. These studies have led to formulations of THC and CBD for human use; however, humans use different strains of Cannabis that contain several hundred different compounds. The contribution of these compounds to pain relief produced by Cannabis is unclear. ß-caryophyllene (BCP) is one compound found in the essential oils of Cannabis. Despite some early studies, the extent to which these compounds produce pain relief in assays of pain-evoked behaviors (i.e., von Frey and Hargreaves tests) and pain-depressed behaviors (i.e., home cage wheel running) is unclear. We hypothesized that BCP would inhibit mechanical allodynia and thermal hyperalgesia as well as restore depressed wheel running activity in male Sprague-Dawley rats with inflammatory pain. Three different doses of BCP (10, 30, and 100 mg/kg) or vehicle were administered to rats via an intraperitoneal injection after hindpaw inflammation induced by an intraplantar injection of Complete Freund’s Adjuvant (CFA). Neither the low dose (10 mg/kg) nor the medium dose (30 mg/kg) of BCP reversed mechanical allodynia of the inflamed hindpaw after intraperitoneal injection. However, a high dose of BCP (100 mg/kg) reversed mechanical allodynia on the von Frey test; however, this dose did not reverse thermal hyperalgesia. A hindpaw injection of 0.1 mL CFA decreased wheel running activity as is consistent with a painful stimulus. However, neither 30 mg/kg BCP nor 100 mg/kg BCP restored pain-depressed wheel running in injured rats. These same doses of BCP did not affect wheel running in uninjured control rats. Therefore, a high dose BCP produces pain relief, although it only does so against mechanical allodynia. BCP does not restore normal activity. This suggests that although pain may be eliminated following BCP administration, a return to normal levels of activity may not be possible which raises questions about the utility of BCP to treat pain. Future studies of the pain-relieving effects of Cannabis constituents must include tests of many pain-related behaviors to understand dose-response relationships and their therapeutic potential.