Medicinal Marijuana Effective For Neuropathic Pain In HIV
In a double-blind, placebo-controlled clinical trial to assess the impact of smoked medical cannabis, or marijuana, on the neuropathic pain associated with HIV, researchers at the University of California, San Diego School of Medicine found that reported pain relief was greater with cannabis than with a placebo.
The study, sponsored by the University of California Center for Medical Cannabis Research (CMCR) based at UC San Diego, will be published on line, August 6 in the journal Neuropsychopharmacology.
Led by Ronald J. Ellis, M.D., Ph.D., associate professor of neurosciences at UCSD School of Medicine, the study looked at 28 HIV patients with neuropathic pain not adequately controlled by other pain-relievers, including opiates. They took part in the controlled study as outpatients at the UCSD Medical Center. The proportion of subjects achieving pain reduction of 30 percent or more was greater for those smoking cannabis than those smoking the placebo.
“Neuropathy is a chronic and significant problem in HIV patients as there are few existing treatments that offer adequate pain management to sufferers,” Ellis said. “We found that smoked cannabis was generally well-tolerated and effective when added to the patient’s existing pain medication, resulting in increased pain relief.”
Each trial participant participated in five study phases over seven weeks. During two five-day phases, randomly selected participants smoked either cannabis or placebo cigarettes made from whole plant material with cannabinoids (the psychoactive compound found in marijuana) removed, both provided by the National Institute on Drug Abuse. Outcome was tested by standardized tests measuring analgesia (lessened pain sensation), improvement in function and relief of pain-associated emotional distress.
Using verbal descriptors of pain magnitude, cannabis was associated with an average reduction of pain intensity from ‘strong’ ‘to mild-to-moderate’ in cannabis smokers, according to Ellis. Also, cannabis was associated with a sizeable (46% versus 18% for placebo) proportion of patients reporting clinically meaningful pain relief.
The study’s findings are consistent with and extend other recent research supporting the short-term efficacy of cannabis for neuropathic pain, also sponsored by the CMCR.
“This study adds to a growing body of evidence that indicates that cannabis is effective, in the short-term at least, in the management of neuropathic pain,” commented Igor Grant, M.D., professor of psychiatry and director of the CMCR.
Grant noted that this is the fourth CMCR sponsored study to provide convergent evidence that cannabis can help in relieving these types of pain. The previous studies were conducted with CMCR support by Donald I. Abrams, M.D., Professor of Clinical Medicine at UCSF, who reported efficacy in short-term treatment of HIV neuropathy (Neurology, 2007, 68:515-521); by Mark Wallace, M.D., Program Director for the UCSD Center for Pain Medicine, who found that normal volunteers subjected to chemically induced pain which mimics neuropathy also responded to medium doses of cannabis (Anesthesiology, 2007, 107(5):785-796); and by Barth Wilsey, M.D., Director of the UC Davis Analgesic Research Center, who also reported benefit from smoked cannabis in a group of patients with neuropathy of multiple origins (Journal of Pain, 2008 Jun;9(6):506-21).
Neuropsychopharmacology advance online publication, August 6, 2008; doi:10.1038/npp.2008.120
Smoked Medicinal Cannabis for Neuropathic Pain in HIV: A Randomized, Crossover Clinical Trial
Ronald J Ellis, Will Toperoff, Florin Vaida, Geoffrey van den Brande, James Gonzales, Ben Gouaux, Heather Bentley and J Hampton Atkinson
Despite management with opioids and other pain modifying therapies, neuropathic pain continues to reduce the quality of life and daily functioning in HIV-infected individuals. Cannabinoid receptors in the central and peripheral nervous systems have been shown to modulate pain perception. We conducted a clinical trial to assess the impact of smoked cannabis on neuropathic pain in HIV. This was a phase II, double-blind, placebo-controlled, crossover trial of analgesia with smoked cannabis in HIV-associated distal sensory predominant polyneuropathy (DSPN). Eligible subjects had neuropathic pain refractory to at least two previous analgesic classes; they continued on their prestudy analgesic regimens throughout the trial. Regulatory considerations dictated that subjects smoke under direct observation in a hospital setting. Treatments were placebo and active cannabis ranging in potency between 1 and 8% Delta-9-tetrahydrocannabinol, four times daily for 5 consecutive days during each of 2 treatment weeks, separated by a 2-week washout. The primary outcome was change in pain intensity as measured by the Descriptor Differential Scale (DDS) from a pretreatment baseline to the end of each treatment week. Secondary measures included assessments of mood and daily functioning. Of 127 volunteers screened, 34 eligible subjects enrolled and 28 completed both cannabis and placebo treatments. Among the completers, pain relief was greater with cannabis than placebo (median difference in DDS pain intensity change, 3.3 points, effect size=0.60; p=0.016). The proportions of subjects achieving at least 30% pain relief with cannabis versus placebo were 0.46 (95%CI 0.28, 0.65) and 0.18 (0.03, 0.32). Mood and daily functioning improved to a similar extent during both treatment periods. Although most side effects were mild and self-limited, two subjects experienced treatment-limiting toxicities. Smoked cannabis was generally well tolerated and effective when added to concomitant analgesic therapy in patients with medically refractory pain due to HIV DSPN.