A Double Blind, Active Placebo Controlled Crossover Trial of the Antinociceptive Effects of Smoked Marijuana on Subjects with Neuropathic Pain; Correlation with Changes in Mood, Cognition, and Psychomotor Performance
INVESTIGATOR: Barth Wilsey, M.D.
STUDY LOCATION: University of California, Davis
PROJECT TITLE: A Double Blind, Active Placebo Controlled Crossover Trial of the Antinociceptive Effects of Smoked Marijuana on Subjects with Neuropathic Pain; Correlation with Changes in Mood, Cognition, and Psychomotor Performance
PROJECT TYPE: Clinical Study
Thirty-eight patients with central and peripheral neuropathic pain underwent a standardized procedure for smoking either high-dose (7%), low-dose (3.5%) or placebo cannabis. In addition to the primary outcome of pain intensity, secondary outcome measures included evoked pain using heat-pain threshold, sensitivity to light touch, psychoactive side-effects, and neuropsychological performance. A mixed linear model demonstrated an analgesic response to smoking cannabis. No effect on evoked pain was seen. Psychoactive effects were minimal and well-tolerated, with some acute cognitive effects, particularly with memory, at higher doses.
The full results of this study have been published in the Journal of Pain.
The present study will be designed to evaluate the analgesic effects of inhaled marijuana in patients with neuropathic pain. A within-subject crossover study of the effects of marijuana versus active placebo (lorazepam) on spontaneous and evoked pain will be performed in subjects with complex regional pain syndrome. Spontaneous pain relief will be assessed using VAS scales. Both pain unpleasantness and pain intensity will be assessed to distinguish the effect of marijuana on the motivational-affective aspect of pain relative to the sensory-discriminative component. The degree of pain relief will also be assessed by a seven-point patient global impression of change (PGIC) category scale; i.e., (1) very much improved (2) much improved (3) minimally improved (4) no change (5) minimally worse (6) much worse (7) very much worse. Spontaneous pain relief will also be assessed using the neuropathic pain scale (Galer, 1997) to measure changes in the pain qualities associated with nerve injury pain. If present, areas of mechanical allodynia will be evaluated with repeated testing utilizing a foam paintbrush to determine the degree of the allodynia regression (if any) after smoking marijuana. Evoked pain will be studied using mild to moderately painful heat stimuli delivered to the painful area of the subject's body using the Medoc TSA 2001 quantitative sensory tester (http://www.medoc-web.com/fprod.htm), an electronically controlled Peltier contact thermode. The degree of antinociception in these various chronic pain states will then be compared with neuropsychological effects of marijuana for a correlation synopsis.
The study hypothesis will be that marijuana can induce dose dependent antinociceptive changes in spontaneous and evoked pain in human subjects with nerve injury pain. The second hypothesis will be that higher doses of inhaled marijuana induce greater degrees of antinociception that are not independent of differences in mood, cognition and psychomotor performance. It is furthermore hypothesized that a significantly higher number of neuropathic pain patients receiving "high doses" of marijuana (as compared to those receiving "low doses" or placebo) will not be able to tolerate the side effects. Finally, it is hypothesized that an interaction with time will occur such that antinociception will outlast changes in mood, cognitive impairment and psychomotor performance.