Cannabis reduces pain only within a narrow dose range

Although smoking "moderate" doses of cannabis helps reduce pain in healthy research volunteers, pain is actually increased at high doses.

The November issue of the journal Anesthesiology features a study showing that marijuana, or cannabis, reduces pain only within a narrow dose range. "Our study suggests that there is a therapeutic window for analgesia, with low doses being ineffective, medium doses resulting in pain relief, and high doses increasing pain," comments lead author Dr. Mark S. Wallace of University of California, San Diego.

Dr. Wallace and colleagues evaluated the effects of smoking cannabis on pain responses in 15 healthy volunteers. On different days, the research subjects smoked low, medium, or high doses of cannabis (based on the content of 9-delta-tetrahydrocannabinol [THC], the main active chemical in cannabis), or an inactive placebo. Pain was induced by injecting capsaicin, the "hot" chemical found in chili peppers, into the skin. Capsaicin injection is a standard technique used in pain studies.

Five minutes after smoking, none of the three doses of cannabis had any effect on pain responses to capsaicin. However, 45 minutes after smoking the moderate dose of cannabis, pain was significantly reduced—approximately six points lower on a 100-point scale, compared with the inactive placebo.

In contrast, 45 minutes after smoking the high dose of cannabis, pain scores were increased—about eight points higher than with placebo.

The low dose of cannabis had no effect on pain scores. None of the three doses affected the extent of secondary hyperalgesia—that is, the spread of pain beyond the area injected with capsaicin.

Levels of THC measured in the blood were significantly related to reduced pain scores at the moderate dose of cannabis, but not to the increase in pain with high-dose cannabis. The volunteers' sense of feeling "high" increased with each dose of cannabis, even though the pain-relieving effects did not.

Research has suggested that the active components of cannabis might have pain-reducing effects, but few studies have actually looked at how cannabis affects pain in humans. "With several states having passed laws legalizing the medical use of cannabis, there has been a call for more research on medicinal cannabis," says Dr. Wallace. "The Center for Medicinal Cannabis Research received a large grant from the State of California to investigate the medicinal use of cannabis, and this is one of the many studies that were funded through the Center. The research arising from the Center can provide an evidence basis for deciding the appropriate use of cannabis and related compounds as medicines."

The results are an important addition to research on the pain-relieving potential of cannabis. "This is the first study using different doses of cannabis and a tightly controlled pain stimulus that suggests that cannabis has a therapeutic window of pain relief," adds Dr. Wallace. Although the researchers were surprised at the delayed analgesic effect of cannabis, the increase in pain with high-dose cannabis is consistent with earlier studies.

Dr. Wallace and colleagues call for further research, including studies of the clinical value of the pain-reducing effects. Pending more information on this and other issues, including the potential for abuse and safety issues of inhaled cannabis, the researchers conclude, "We cannot recommend advocate a place for using cannabis in the treatment armamentarium at this time."

For additional information on this study, go to http://www.anesthesiology.org

Founded in 1905, the American Society of Anesthesiologists is an educational, research and scientific association with 41,000 members organized to raise and maintain the standards of the medical practice of anesthesiology and improve the care of the patient.

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