9-nor-9beta-hydroxyhexahydrocannabinol, a cannabinoid with potent antinociceptive activity: comparisons with morphine.

The effects of (+/-)9-nor-9beta-hydroxyhexahydrocannabinol (beta-HHC) on tail-flick test activity and the accumulation of newly synthesized dopamine and norepinephrine were studied in the male albino mouse. The same parameters were also studied in naloxone-pretreated and morphine-tolerant mice. beta-HHC was about equipotent with morphine in the mouse tail-flick (ED50 = 7.12 mg/kg). The cannabinoid also produced dose-dependent increases in the accumulation of newly synthesized DA and NE. Pretreatment with 2 mg/kg of naloxone antagonized both the tail-flick activity and blocked the increases in catecholamine synthesis produced by beta-HHC. Cross-tolerance between beta-HHC and morphine did not exist in regard to either tail-flick activity or increased catecholamine synthesis. These studies suggest that beta-HHC may share some properties with the narcotic analgesics but that significant differences exist. Furthermore, these studies offer further evidence for the involvement of catecholamine containing neurons in the central mediation of the tail-flick response.