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A pretty good review of two small studies among people with HIV.

M.

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http://scienceblogs.com/whitecoatunderground/2010/02/human_beings_are_fundamenta\

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http://tinyurl.com/ybeo3wx

Clinical Marijuana Research Update

Category: Medicine

Posted on: February 22, 2010 2:28 PM, by PalMD

Human beings are fundamentally narcissistic, and this narcissism can be

antithetical to good science and good medicine. We place far too much confidence

in our individual abilities to understand what happens to us, and we place far

too much importance on our own experiences, inappropriately generalizing them.

That's why science is so important in medicine---to avoid basing life-or-death

decisions on something some guy thinks he might have heard once.

In my recent piece on medical marijuana in Forbes, commenters took me to task

for what they perceived to be a host of errors in my reasoning. Some of these

deserve to be specifically addressed, but not before a summary of the topic.

Marijuana's legal status is a political issue, not a scientific one. I will

leave the politics to those cursed with such things. But I'm responsible for

medical decisions, and as much as is possible, I have to look at data

dispassionately. I have no doubt the individuals find marijuana beneficial for a

wide range of problems---this may be a basis for study, but is not adequate data

to prescribe a powerful pharmacologic agent.

In 2000, the University of California established the Center for Medicinal

Cannabis Research. This month, they released a summary of results to date.

The federal government has historically made it very difficult to study

marijuana. The state of California, though specific legislation, was able to

encourage a significant amount of research into the clinical use of marijuana,

and this month's report is a summary of their work to date. So far CMCR has

produced four published clinical studies and one poster/abstract.

The first study, by Abrams, et al, deals with painful HIV-associated sensory

neuropathy (HIV-SN). This is a painful condition that can be caused by HIV

infection or by certain treatments for HIV. This is a good place to start, as

current treatments are disappointing. The study enrolled 55 patients with

HIV-SN, and randomly assigned some to smoke real joints, and other to smoke

joints with the cannabanoids extracted. Fifty patients completed the five-day

study, with some encouraging results, but there are a few problems. First, it's

unlikely that patients remained truly blinded to their assignment (unless they

though the treatment group was given Grade F ditch weed). The authors recognized

that unblinding might have been a problem. The authors also made an attempt to

compare their data to studies of other drugs for this condition, but they did

not compare cannabis directly to any other drug, including opioids.

This is a small study, and since the number needed to treat (NNT) found in this

study and studies of other drugs was not dramatically different, head-to-head

studies of marijuana, opioids, and standard drugs for this condition would be

very useful. Given the benefits of opioids in a variety of pain conditions,

including neuropathic pain, it would be important to compare the benefits and

negative effects of opioids vs. marijuana. Finally, the authors concluded that

the drug was generally safe during the five day study, as there were no major

adverse events requiring subjects to drop out. I'm not certain this is a fair

interpretation:

No patient withdrew from the study because of adverse events. One episode of

grade 3 dizziness related to study medication occurred in the cannabis group.

One case of transient grade 3 anxiety possibly related to study medication was

reported in each group. Both patients received a one-time dose of lorazepam.

These patients required a second medication to treat the symptoms of the drug.

This may or may not be significant when compared to the level of pain relief or

when compared to other drugs, but it cannot be concluded that the drug was

entirely safe and well-tolerated, especially given what may be observed when

there is more than 125 person-days of exposure.

A second study by Ellis, et al, also looked at painful HIV-related neuropathy,

and addressed some of the issues with the Abrams study. This was also a small

pilot study, but used a crossover design. The authors actually surveyed the

subjects to see if they remained blinded, and by the end of the study, many

subjects " knew " which toke was placebo and which was the good stuff. They also

explicitly addressed one of the interesting questions that comes up in relation

to marijuana research.

Because of funding mandates, these studies used smoked marijuana. Given the

likely harm of long term smoking of anything, Ellis brought up the need to study

non-smoked cannabis. Boosters often promote smoked cannabis as having " special "

properties not available in extracts and derivatives, something these two

studies, which each contained de-THC'd fatties, argue against.

More important is that while these results are encouraging, they are not enough

to make a clear medical recommendation. Two small pilot studies are not

sufficient to make significant clinical recommendations. They may give us good

reason to study the use of marijuana or its derivatives for the treatment of

HIV-related painful sensory neuropathy. Hopefully future studies will include

comparisons to standard therapy, and clearer evaluation of long-term effects of

marijuana ingestion in these patients.

References

Abrams DI, Jay CA, Shade SB, Vizoso H, Reda H, Press S, ME, Rowbotham MC,

& sen KL (2007). Cannabis in painful HIV-associated sensory neuropathy: a

randomized placebo-controlled trial. Neurology, 68 (7), 515-21 PMID: 17296917

Ellis, R., Toperoff, W., Vaida, F., van den Brande, G., , J., Gouaux,

B., Bentley, H., & Atkinson, J. (2008). Smoked Medicinal Cannabis for

Neuropathic Pain in HIV: A Randomized, Crossover Clinical Trial

Neuropsychopharmacology, 34 (3), 672-680 DOI: 10.1038/npp.2008.120

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