Effects of Delta 9‐Tetrahydrocannabinol in Assays of Pain‐Stimulated and Pain‐Depressed Behavior in Rats

Δ9‐tetrahydrocannabinol (THC), the primary active constituent of marijuana, produces reliable antinociception in many preclinical assays but inconsistent analgesic efficacy in humans. This disparity suggests that preclinical antinociception may result from motor impairment or other non‐selective effects rather than from decreased sensitivity to pain. To evaluate this possibility, the present study compared THC's effects in assays of pain‐stimulated and pain‐depressed behavior. Intraperitoneal (IP) injection of dilute lactic acid (1.8% in 1 ml/kg) stimulated a stretching response or depressed intracranial self‐stimulation (ICSS) in separate groups of male Sprague‐Dawley rats. THC (1–10 mg/kg, IP, 30 min pretreatment) dose‐dependently blocked acid‐stimulated stretching but only exacerbated acid‐induced depression of ICSS. THC doses that decreased stretching and acid‐induced depression of ICSS also decreased control ICSS in the absence of a noxious stimulus. Thus, these findings suggest that preclinical antinociceptive effects of acute THC in assays of pain‐stimulated behavior can be attributed to non‐selective motor impairment rather than to a decreased sensitivity to pain. Further studies will need to be conducted to determine if THC can produce antinociception in assays of pain‐depressed behavior under other conditions.