NEUROLOGY 2007;68:515-521 © 2007 American
Academy of Neurology
Cannabis in painful HIV-associated sensory neuropathy A randomized placebo-controlled trial D. I. Abrams, MD, C. A. Jay, MD, S. B. Shade, MPH, H. Vizoso, RN, H. Reda, BA, S. Press, BS, M. E. Kelly, MPH, M. C. Rowbotham, MD and K. L. Petersen, MD From the Community Consortium, Positive Health Program (D.I.A., S.B.S., H.V., M.E.K.), Hematology-Oncology (D.I.A., M.E.K.), and Neurology (C.A.J.), Divisions at San Francisco General Hospital; and Departments of Medicine (D.I.A., S.B.S., H.V., M.E.K.) and Neurology (C.A.J., H.R., S.P., M.C.R., K.L.P.), and the UCSF Pain Clinical Research Center (H.R., S.P., M.C.R., K.L.P.), University of California San Francisco.
Address correspondence and reprint requests to Dr. Donald I. Abrams, San Francisco General Hospital, Ward 84, 995 Potrero Avenue, San Francisco, CA 94110; e-mail: firstname.lastname@example.org
Objective: To determine the effect of smoked cannabis on the neuropathic pain of HIV-associated sensory neuropathy and an experimental pain model.
Methods: Prospective randomized placebo-controlled trial conducted in the inpatient General Clinical Research Center between May 2003 and May 2005 involving adults with painful HIV-associated sensory neuropathy. Patients were randomly assigned to smoke either cannabis (3.56% tetrahydrocannabinol) or identical placebo cigarettes with the cannabinoids extracted three times daily for 5 days. Primary outcome measures included ratings of chronic pain and the percentage achieving >30% reduction in pain intensity. Acute analgesic and anti-hyperalgesic effects of smoked cannabis were assessed using a cutaneous heat stimulation procedure and the heat/capsaicin sensitization model.
Results: Fifty patients completed the entire trial. Smoked cannabis reduced daily pain by 34% (median reduction; IQR = –71, –16) vs 17% (IQR = –29, 8) with placebo (p = 0.03). Greater than 30% reduction in pain was reported by 52% in the cannabis group and by 24% in the placebo group (p = 0.04). The first cannabis cigarette reduced chronic pain by a median of 72% vs 15% with placebo (p < 0.001). Cannabis reduced experimentally induced hyperalgesia to both brush and von Frey hair stimuli (p 0.05) but appeared to have little effect on the painfulness of noxious heat stimulation. No serious adverse events were reported.
Conclusion: Smoked cannabis was well tolerated and effectively relieved chronic neuropathic pain from HIV-associated sensory neuropathy. The findings are comparable to oral drugs used for chronic neuropathic pain.
Pain Study Supports Medical Marijuana
(AIDSmeds.com) - A study conducted by veteran HIV researcher Donald Abrams, MD, and his colleagues at the University California, San Francisco (UCSF), suggests that smoking marijuana is safe and effective for the management of chronic pain associated with peripheral neuropathy in HIV-positive people. Based on these results, some HIV/AIDS groups and other healthcare advocacy organizations have begun calling for congressional hearings to push for national legalization of cannabis for medical purposes. The cannabis plant (marijuana) has been used throughout history by a variety of cultures around the world. Its use for medicinal purposes was permitted in the United States until 1937, when the Marijuana Tax Act made cannabis prescriptions illegal. Then, in 1970, it was classified as a Schedule I drug of the Controlled Substance Act, meaning that the federal government considered it to have "no accepted medical use" and illegal for any reason, with the notable exception of research specifically approved by the U.S. Food and Drug Administration (FDA).
While some states have passed legislation allowing the use of marijuana for medicinal purposes under certain circumstances, a central goal of several advocacy organizations is to petition Congress to remove marijuana from Schedule I so that it may be consistently prescribed and distributed for medicinal purposes. This requires the successful completion of FDA-sanctioned research confirming that medical marijuana has an accepted medical use with an accepted safety profile.
Advocacy groups, including the National Associated of People with AIDS (NAPWA) and Americans for Safe Access (ASA), believe that the long-awaited publication of the UCSF study results support marijuana's reclassification. "This study validates the experience people living with HIV/AIDS and their doctors have reported for years, [that] medical cannabis provides much-needed relief from pain and suffering," says NAPWA Executive Director Frank Oldham Jr. "That is why we are joining Americans for Safe Access to call on Congress to address cannabis for its medicinal value."
The pain associated with peripheral neuropathy, which can be caused by nucleoside reverse transcriptase inhibitors (NRTIs) and HIV itself, is often treated using anti-seizure medications such as Lamictal® (lamotrigine) and Neurontin® (gabapentin). However, some patients fail to respond or cannot tolerate these drugs. Other agents have been evaluated over the years, but have either been found to be no more effective than placebo in clinical trials or are associated with adverse drug interactions when combined with antiretroviral therapy. In turn, there has been heightened interest in evaluating smoked cannabis as a treatment for chronic neuropathic pain.
The encouraging results of a clinical trial evaluating smoked cannabis for chronic neuropathic pain – the first of its kind in the U.S. in nearly 20 years to indicate the medical efficacy of marijuana – were reported in the February 13 issue of the peer-reviewed medical journal Neurology. The study was a placebo-controlled evaluation that took place in the inpatient General Clinical Research Center at UCSF between May 2003 and May 2005 involving adults with painful HIV-associated peripheral neuropathy.
All patients enrolled in the study were required to have prior experience smoking marijuana – defined as six or more times in their lifetime – so that they would know how to inhale and would be familiar with the drug's neuropsychiatric effects. Current users were asked to discontinue any cannabis prior to study admission.
The National Institute on Drug Abuse – the source of controlled marijuana for all U.S. cannabis studies – provided identically appearing pre-rolled cannabis and placebo cigarettes. Active marijuana cigarettes contained 3.56% delta-9 THC, the primary active ingredient in cannabis, and identical-appearing placebo cigarettes containing no delta-9 THC.
The study volunteers were admitted to the research center and smoked marijuana or placebo cigarettes three times a day for a total of five days. There was also extensive pre- and post-cannabis use testing in the study.
The primary measurement was a pain diary kept by the study volunteers before, during, and after cannabis or placebo treatment. Before and after the first and last cigarettes smoked, the patients also underwent controlled pain testing involving the application of heat (long thermal stimulation) and stimulation (e.g., foam brush and "van Frey" hair) to a section of skin.
Fifty patients completed the entire study. Approximately 67% of patients in the cannabis group were receiving antiretroviral therapy, compared to 86% of those in the placebo group. The average duration of neuropathy, prior to entering the study, was seven years in both groups.
Over the five-day inpatient period, smoking marijuana cigarettes three times a day reduced the pain associated with peripheral neuropathy by 34%, significantly more than the 17% reduction with placebo cigarettes. Half (52%) of those randomized to cannabis experienced at least a 30% reduction in pain, while a quarter (24%) of those randomized to placebo experienced a similar reduction in pain. The first marijuana cigarette reduced chronic pain by an average of 72% vs. 15% with placebo. All of these differences were statistically significant, meaning that they were not likely due to chance.
As for the controlled pain testing, smoked marijuana reduced the pain associated with foam brush and hair stimulation. It did not, however, reduce the pain associated with heat application.
In terms of safety, no patients withdrew from the study because of adverse events. While side effects were low in both study groups, the severity of side effects were somewhat higher among patients in the cannabis group, notably reports of anxiety, sedation, disorientation, confusion, and dizziness. However, the researchers noted, the reported adverse events "do not represent any serious safety concerns in this short-term study."
Dr. Abrams and his colleagues hope that these study results will provide additional weight to a 1999 Institute of Medicine report (IOM), Marijuana and Medicine, Assessing the Science Base. "The Institute of Medicine report, along with other recent reviews, suggest that if cannabis compounds can be shown to have therapeutic value then the margin of safety is acceptable," they write. "An acceptable safety margin has been shown in the present study as well as in a previous study of cannabinoids in patients with HIV-1 infection."
"This study demonstrates the potential effectiveness of medical cannabis to treat the chronic pain of people living with HIV/AIDS," says Dr. Barbara T. Roberts, Director of Medical and Scientific Affairs for ASA and former Senior Policy Analyst at the White House Office of National Drug Control Policy. "In addition to people living with HIV/AIDS, there are thousands of vets returning from Iraq who will spend decades coping with neurological pain. By implementing the recommendations of the IOM report, the federal government would be exploring more options for their long-term treatment of neuropathic pain."
NAPWA, ASA, and other groups are calling on Congress to hold hearings on the IOM report to adopt its recommendations to allow patients and researchers to have access to medical cannabis.
"It's time for Washington to stop playing politics with patients' lives and advance this important scientific discovery," says Steph Sherer, Executive Director of ASA. "The study is a wake-up call for Congress to hold hearings to investigate therapeutic use and encourage research."
Source: Abrams DI, Jay CA, Shade SB, et al. Cannabis in painful HIV-associated sensory neuropathy. Neurology 68:515-21, 2007.
Ed note: Please also read: Long Term Exposure To Cannabis
*Industrial-Hemp has no psychoactive properties following definition of the European Economic Community (EEC); THC content is less than 0.3%. In general, low THC-seed varieties without psychoactive properties are those that have a THC content of less than 1%. (See also No-THC Hemp-seed.) THC= Delta-9 TetraHydroCannabinol.
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