Cannabis Effectively Relieves HIV Sensory Neuropathy (Neurology. 2007;68:515-521)
Medscape Medical News (2/20/2007)
by: Caroline Cassels
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February 20, 2007 - Cannabis is effective for the treatment of HIV-related sensory neuropathy (HIV-SN), a condition that affects up to 30% of AIDS patients, making it the most common peripheral nerve disorder of HIV infection.
A new study published in the February 13 issue of Neurology shows cannabis offers significant pain relief from this intractable condition compared with placebo.
The randomized, placebo-controlled trial showed individuals who smoked marijuana reduced their daily nerve pain, which mainly affects the feet, by 35%, vs 17% for the placebo group.
The study also found the first marijuana cigarette reduced chronic pain by an average of 72%, vs 15% with placebo. Furthermore, half of the study subjects who smoked marijuana achieved the study's primary end point of a greater-than-30% reduction in pain compared with 24% of individuals in the placebo group.
"We clearly demonstrated that cannabis does have a significant effect in reducing pain in patients with HIV-related peripheral neuropathy," principal investigator Donald Abrams, MD, from San Francisco General Hospital, California, told Medscape.
Permanent Nerve Damage
HIV-SN can result from either HIV infection itself or from some of the antiretroviral medications, particularly dideoxynucleoside analogs, which can permanently damage peripheral nerves.
He noted that effect is also seen in cancer patients as a result of chemotherapy. However, he added, in cancer this is usually a transient effect, which most often resolves once therapy is complete. Unfortunately, this is not the case with HIV-SN.
Dr. Abrams added that the decision to study cannabis in HIV-SN was based on preclinical data as well as anecdotal evidence from HIV patients that suggested it may provide pain relief. In addition, he said, clinical studies in multiple sclerosis patients have shown it has an analgesic effect.
Individuals with painful HIV-SN were recruited for the trial between May 2003 and May 2005. Study subjects were randomly assigned to smoke either cannabis (3.56% tetrahydrocannabinol) or identical placebo cigarettes with the cannabinoids extracted 3 times daily for 5 days.
A total of 55 patients were enrolled in the study. Of these, 27 were randomized to cannabis cigarettes and 28 to placebo. A total of 5 patients withdrew from the trial, leaving a total of 25 patients in each group who completed the study. On average, subjects had HIV infection for 14 years and peripheral neuropathy for 7 years.
To assess the pain-relieving effects of smoked cannabis compared with placebo, patients were asked to rate their pain using a 100-point visual analog scale (VAS). At trial entry, the median pain score on VAS was 53.
Experimental Pain Model
In addition, an experimental pain model was used to objectively map and quantify patients' pain before and after using marijuana or placebo. A defined rectangular area of skin on the patient's forearm was heated and capsaicin cream applied.
In this model, investigators used a foam brush and a 26-g von Frey hair (to induce a pricking sensation) to stimulate the skin starting well outside the hyperalgesic area and continuing toward the treated skin area. To ensure this was a blinded experiment, patients were asked to look away while the skin was being stimulated.
The skin was then marked where patients reported a definite change in sensation, such as burning, tenderness, or more intense pricking. This was done at baseline before smoking and then 3 times after smoking.
"The experimental pain model gave us a much more objective anchor than the patient's actual description of what was going on with their neuropathic pain," said Dr. Abrams.
There was a median of a 34% reduction in area of discomfort in the cannabis group vs 11% in placebo subjects; investigators found cannabis reduced the area of discomfort to both the foam brush and von Frey hair stimuli.
Based on these results, cannabis may offer patients with HIV-SN an alternative treatment. While antiepileptic agents, including gabapentin and lamotrigine, have proven effective in some patients; others fail to respond or cannot tolerate these medications.
In addition, said Dr. Abrams, while opioids, including morphine, are often prescribed for this condition, they are not particularly effective. Tricyclic antidepressants have also been tried but have been shown to be no more effective than placebo.
Implications for Cancer Pain?
"At this point we can't make any generalizable statement with respect to dose or the extent of the utility of this intervention in other patient populations, but I think that should all be studied. However, in this patient population we definitely saw that smoked cannabis had significant benefit in both neuropathic pain and in the experimental pain model," he said.
The low-grade government marijuana used in the study was well-tolerated and allowed patients to function normally. However, said Dr. Abrams, he is investigating potentially safer ways of delivering the drug.
A study conducted by Dr. Abrams and his team, which is currently in review, compared smoked cannabis to vaporized cannabis in healthy individuals and found vaporization delivers similar amounts of THC into the bloodstream with fewer toxic inhalants.
Finally, Dr. Abrams said he is currently recruiting patients for a pharmacokinetic study in patients with cancer pain to determine whether cannabis has the ability to potentiate the analgesic effect of opioids.
"The thought here is that if cannabinoids augment the analgesic effect of opioids, then cancer patients may be able to get away with taking lower doses of opioids for longer periods of time," he said.
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