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Clinical Studies of Cannabinoids

There have been three kinds of studies of the effects of cannabinoids on pain in human volunteers: studies of experimentally induced acute pain, studies of postsurgical acute pain, and studies of chronic pain. Overall, there have been very few studies—only one since 1981—and they have been inconclusive.

Experimentally Induced Acute Pain

Early studies of cannabinoids on volunteers did not demonstrate consistent analgesia when experimental pain models were used. In fact, three early volunteer studies of THC and experimental pain caused by a variety of pain modalities—electrical stimulation, tourniquet pain, and thermal pain—resulted in an increase in pain sensitivity (hyperalgesia).22^,84^,108

Other studies also failed to show an analgesic effect of THC, but they were not well designed. Raft and co-workers found no evidence of THC effect on pain thresholds and pain tolerance following electrical stimulation and noxious pressure.150 But their study suffers from two major methodological problems. First, they measured only the extremes of pain sensation—threshold (the lowest intensity at which a particular stimulus is perceived as painful) and tolerance (the maximum intensity of pain that a subject can withstand). However, most pain is experienced in an intermediate range, where effects on pain suppression are most detectable. Modern methods of pain assessment in humans typically use ratings of the intensity of the sensation of pain; those methods are superior to assessing the effects of a drug on the extremes of pain.192 Second, Raft and coworkers did not include a positive control; that is, they did not demonstrate the adequacy of their method by showing that an established analgesic, such as an opiate or narcotic, was effective under their study conditions.

Clark and co-workers22 tested the effect of smoked marijuana on thermal pain in volunteers and failed to observe an analgesic effect. However, because of the study design, the results are inconclusive. First, there was no positive control to demonstrate the adequacy of their methods; second, the study subjects were habitual marijuana users. During the study, they were hospitalized and allowed free access to marijuana cigarettes for a period of four weeks, consuming an average of four to 17 marijuana cigarettes per day. Pain was tested "approximately every one to two weeks." Thus, it is quite likely that the subjects were tolerant to THC at the time of testing.