Clinical Trial Experience with Cannabinoids

The identification of a peripheral cannabinoid receptor localized to the immune system around the gastrointestinal tract stimulated a clinical trial of oral cannabinoids in a patient with chronic pain and inflammation of gastrointestinal origin. The patient had the symptoms of familial Mediterranean fever and required oral opioids for pain control before the study. A long-term randomized double-blind placebo-controlled study with capsules containing oil of cannabis (active) and virgin olive oil (placebo) demonstrated significant opioid sparing, with morphine used as escape analgesia, during three weeks of active treatment while pain scores remained similar in the three placebo weeks. There were no changes in inflammatory markers measured. Compliance was demonstrated by urine analyses for cannabinoids. Difficulties during this prolonged study were encountered with a lack of effectiveness during the final two weeks, which may have been induced by tolerance, and with mood disorders during two consecutive placebo weeks, which suggested withdrawal symptoms. Central effects during the active weeks were avoided by choosing a suitable dosage of tetrahydrocannabinol and with the marked reduction in morphine requirements achieved with the cannabinoid preparation. In future studies it should be possible to define the active constituents of the natural preparation and their appropriate route, which can produce these desirable analgesic effects.