A comparison of THC, nantradol, nabilone, and morphine in the chronic spinal dog

Morphine and delta 9-tetrahydrocannabinol (THC) have been shown to have certain pharmacologic characteristics in common. Among these are antinociception, hypothermia, and the suppression of precipitated abstinence in morphine-dependent rats. In the present study the effects of morphine were compared with the effects of THC and two synthetic cannabinoids, nantradol and nabilone, in both nondependent and morphine-dependent chronic spinal dogs. Single doses of THC, nantradol, and nabilone depressed the flexor and skin twitch reflexes and had a calming effect after intravenous infusion. These effects are similar to those of morphine. Morphine, nantradol, and nabilone, but not THC, depressed rectal temperature. Unlike morphine, however, the cannabinoids produced mydriasis and an increased startle response, and these effects were not antagonized by naltrexone. THC, nantradol, and nabilone suppressed withdrawal abstinence in 40-hour and maximally abstinent morphine-dependent chronic spinal dogs. The results suggest that THC, nantradol, and nabilone share some properties with morphine since they increased the latency of the skin twitch reflex and suppressed withdrawal abstinence. It is doubtful, however, that these actions of the cannabinoids are mediated through opioid receptors since they were not antagonized by naltrexone.