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.
From folk medicine and anecdotal reports it is known that Cannabis may reduce pain. In animal studies it has been shown that delta-9-tetrahydrocannabinol (THC) has antinociceptive effects or potentiates the antinociceptive effect of morphine. The aim of this study was to measure the analgesic effect of THC, morphine, and a THC-morphine combination (THC-morphine) in humans using experimental pain models. THC (20 mg), morphine (30 mg), THC-morphine (20 mg THC+30 mg morphine), or placebo were given orally and as single doses. Twelve healthy volunteers were included in the randomized, placebo-controlled, double-blinded, crossover study. The experimental pain tests (order randomized) were heat, cold, pressure, single and repeated transcutaneous electrical stimulation. Additionally, reaction time, side-effects (visual analog scales), and vital functions were monitored. For the pharmacokinetic profiling, blood samples were collected. THC did not significantly reduce pain. In the cold and heat tests it even produced hyperalgesia, which was completely neutralized by THC-morphine. A slight additive analgesic effect could be observed for THC-morphine in the electrical stimulation test. No analgesic effect resulted in the pressure and heat test, neither with THC nor THC-morphine. Psychotropic and somatic side-effects (sleepiness, euphoria, anxiety, confusion, nausea, dizziness, etc.) were common, but usually mild.