The analgesic effect of oral thc alone or in combination with morphine in healthy subjects under experimental pain conditions

From folk medicine and andecdotal reports it is known that Cannabis may reduce pain. It has been shown in different animal studies 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 potency of orally administered THC and THC in combination with morphine under controlled clinical conditions. THC (20 mg), morphine (30 mg), the combination of the two (20 mg THC + 30 mg morphine) or placebo were given orally as single doses. Twelve healthy volunteers were included in the randomized, placebo controlled, double-blind, crossover study. The experimental pain tests (order randomized) were: single and repeated transcutaneous electrical stimulation, mechanical pressure, heat stimulation and ice water. Additionally, reaction time, side effects (visual analog scales) and vital functions (blood pressure, heart rate and blood oxygen saturation) were monitored. Each test session was started with training phase and baseline determination, followed by administration of the drugs and pain tests every hour up to 8 hours post drug. For the pharmacokinetic profiling, blood samples were collected at defined intervals up to 8 hours. THC alone did not significantly reduce pain. In the ice water and heat test it even produced hyperalgesia which was completely neutralized by the combination with morphine. A slight additive analgesia could be observed after electrical stimulation when combining THC and morphine. No analgesic effect resulted in the pressure and heat pain test, neither with THC nor the combination. The following, usually mild, side-effects of THC were monitored: sleepiness, euphoria (reduced in combination with morphine), feelings of anxiety and aggression, confusion, changing of perception, hallucinations (reduced in combination with morphine), nausea, vomiting, dizziness, headache, difficulties in breathing, heart flutter, digestive problems and dry mouth. In conclusion, this study shows that oral THC does not significantly reduce pain in healthy subjects under experimental conditions. Some analgesic effects were only observed in combination with morphine. Psychotropic and somatic side-effects were common, but not severe. If the analgesic potency of THC could be increased by using alternative application forms, e.g. pulmonal aerosols, resulting in reduced first-pass effect and better bioavailability, will show ongoing studies.