ARTICLE IN BRIEF
✓ A Food and Drug Administration announcement in April that “no sound scientific studies” support the medical use of marijuana has fired up the debate among neurologists and other physicians on potential benefits for symptom relief for epilepsy, multiple sclerosis, and amyotrophic lateral sclerosis.
According to Gregory T. Carter, MD, most of what we've been told about marijuana – that it causes brain damage and lung cancer at a rate higher than tobacco, and that it is a dangerous, addictive drug – is simply not true.
“The government has done a good job convincing the public that marijuana is a dangerous substance with a lot of horrible side effects,” he said in a phone interview with Neurology Today.
Dr. Carter, Clinical Professor of Rehabilitation Medicine at the University of Washington School of Medicine in Seattle, is one of several scientists trying to elevate the drug from its underground status into the realms of modern medicine.
“A large body of evidence shows the medical and neurological benefits of cannabinoids [the active ingredients in marijuana],” he said. Dr. Carter was the senior author of a study published in the American Journal of Hospice and Palliative Medicine (2004;21(2):95–104), reporting that cannabis can be moderately effective in reducing symptoms of appetite loss, depression, pain, spasticity, and drooling in patients with amyotrophic lateral sclerosis (ALS).
While cannabis has existed across diverse cultures for hundreds of thousands of years, its therapeutic potential continues to be a controversial topic. A Food and Drug Administration (FDA) announcement in April that “no sound scientific studies” support the medical use of marijuana seems to have only fired up that debate. The FDA vaguely described the basis of its conclusion, saying it is the result of “past review by federal drug enforcement, regulatory, and research agencies.” That review also found that “currently sound evidence” shows that smoked marijuana is harmful.
POLITICS OR SCIENCE?
FDA spokesperson Kathleen Quinn said the agency announcement was prompted by inquiries from individuals and members of Congress regarding recent reports that marijuana may offer pain relief for some conditions.
But in a Medscape editorial, Dr. Carter and Bruce Mirken, Communications Director for the Marijuana Policy Project, wrote: “The FDA's announcement is puzzling at many levels. It makes no mention of any recent FDA analysis or investigation, regulatory filing, or any other activity within normal scope of the agency's work that led to this policy change.” The authors contend that US Rep. Mark Souder (R-IN) had been demanding for months that the FDA issue such a statement. In a January 18, 2006, letter to acting FDA Commissioner Andrew C. von Eschenbach, Dr. Souder wrote, “I am exasperated at the FDA's failure to act against the fraudulent claims about ‘medical’ marijuana.”
The Medscape editorialists noted that contrary to the FDA's statement, hundreds of peer-reviewed scientific articles document the benefits of marijuana. They also refer to a 1999 Institute of Medicine report, Marijuana and Medicine: Assessing the Science Base, which declared that marijuana can mitigate nausea, appetite loss, pain, and anxiety in disease-afflicted patients. The report recommended that clinical trials of marijuana continue under the following conditions: they should involve only short-term marijuana use (less than six months), be conducted in patients with conditions for which there is reasonable expectation of efficacy, be approved by institutional review boards, and collect data about efficacy.
“Rational, apolitical minds need to take over the debate on marijuana, separating myth from fact, right from wrong, and responsible, medical use from other, less compelling usages,” Dr. Carter and Mirken wrote. “The scientific process continues to document the therapeutic effects of marijuana through ongoing research and assessment of available data.”
Joseph I. Sirven, MD, Associate Professor of Neurology at the Mayo Clinic in Scottsdale, AZ, said he is uncertain whether the FDA was correct in taking a stand against medical marijuana. While marijuana has shown promise in the areas of pain and appetite loss in general, and also for spasticity in multiple sclerosis (MS), more studies are needed before it can be recommended to patients, he said.
“Is there evidence to say that you should use it right now for that? No, there has been no randomized trial,” he said. “So in that regard, it should be treated like any other drug that is up for approval.”
Dr. Sirven co-authored an editorial in Neurology (2004;62:1924–1925) that called for more relaxed federal laws toward medical use of marijuana so that more randomized, controlled trials of the drug can take place.
IS THERE THERAPEUTIC EVIDENCE FOR EFFICACY?
The 2004 study co-authored by Dr. Carter claimed to be the first to survey people with ALS about their use of cannabis. Of 131 anonymous respondents, 13 had used cannabis in the last 12 months, and they reported that marijuana moderately helped relieve appetite loss, depression, spasticity, drooling, and pain.
The level was reported on a five-point scale ranging from (0) “not at all” to (4) “completely relieves the symptom.” On average, the cannabis users reported a level of relief of 2.13 for appetite loss and depression, 1.86 for spasticity, 1.75 for drooling, and 1.67 for pain.
A study published in the April 3 issue of Brain (2006;129(5):1096–1112) concluded that marijuana does indeed affect the brain, but whether this is harmful or beneficial is still unclear and will require further research, lead author Linda Chang, MD, told Neurology Today.
Dr. Chang, a Professor in the Department of Medicine (Neurology) at the University of Hawaii, and colleagues used blood oxygenation-level dependent fMRI to study the brain activity of 24 chronic marijuana users and 19 controls as they completed a set of visual-attention tasks with graded levels of difficulty. Of the 24 marijuana users, 12 had abstained from marijuana between .5 and 156 months before the test and the other 12 had used marijuana between 4 and 24 hours before their fMRI scans as indicated by positive urine tests and self report. Active and abstinent users had both smoked about the same number of days per month, but the active group had done so more recently before their fMRI tests.
Despite task and cognitive test performance similar to that of control subjects, active and abstinent marijuana users showed less activation in the normal attention network, particularly the right prefrontal, medial and dorsal parietal, occipital and medial cerebellar regions. In addition, active marijuana users showed greater activation in the frontal and medial cerebellar regions than abstinent users and greater usage of the reserve network, areas that activate more with the more difficult tasks in the control subjects, such as the precuneus. The decreased medial cerebellar activation in the marijuana users was greater in those with greater marijuana usage, but normalized with longer duration of abstinence. This suggests that the altered brain network or activation might become normal again after long periods of abstinence, Dr. Chang said.
But a 2002 study led by neuropsychologist Karen Bolla, PhD, found that heavy marijuana use, smoking between 78 and 117 joints a week, is associated with persistent decline in neurocognitive performance even after 28 days of abstinence (Neurology 59:1337–1343).
Despite these conflicting results, studies also show that people with neurological disorders are using marijuana for symptom relief. A survey of epilepsy patients In Canada found that 21 percent had used marijuana in the past year, with 68 percent reporting beneficial effects on seizure severity and 54 percent reporting decreased seizure frequency (Neurology 2004; 62:2095–2097). Another paper reported that 14 percent of MS patients surveyed were using marijuana for symptomatic management of stress, sleep, mood, spasticity, and pain (Neurology 2004;62:2098–2100). No serious adverse effects were reported in either study.
FINDING THE “TRUTH”
The experts interviewed by Neurology Today all agreed that more studies are needed to put this debate to rest. “It should be researched for the sake of seeking the truth,” Dr. Sirven said. “Either we're going to find out that there is some kernel of something positive – that this is useful – or we can at least finally dispel the myth.”
Dr. Carter and colleagues at the University of Washington are currently investigating whether marijuana's reported neuroprotective qualities might be beneficial in slowing the progression of ALS. He said that marijuana's effectiveness in treating clinical symptoms coupled with the fact that it does not suppress breathing, like opioid derivatives do, makes it especially attractive for patients with breathing problems associated with neuromuscular disorders.
Dr. Chang said the federal government should continue to support research to determine how marijuana affects the brain because it is one of the most commonly abused drugs. She said investigators in her lab are currently researching how marijuana might affect brain development in adolescents. Her research is currently supported by the National Institute on Drug Abuse.
While more studies are always a good thing, Dr. Sirven said the federal government will need to decide whether marijuana research is worth funding over other types of research at a time when the NIH is experiencing budget cuts. “I guess it's a question of prioritization,” he said.
FDA QUESTIONS MEDICINAL VALUE OF MARIJUANA – IS THE AGENCY RIGHT?
An FDA decision that there are “no scientific studies” to support the medical use of marijuana has inspired debate among investigators who have researched the compound's use and potential for symptomatic relief for epilepsy, multiple sclerosis, and other neurological conditions. Story on page 8.
• Antmann D, Weydt P, Johnson KL, Jensen, MP, Carter GT. Survey of cannabis use in patients with amyotrophic lateral sclerosis. Am J Hosp Palliat Care
• Carter GT, Mirken B. Medical Marijuana: Politics trumps science at the FDA. Medscape General Medicine
• Sirven JI, Berg AT. Marijuana as a treatment for epilepsy and multiple sclerosis?:A grass roots movement. Neurology
• Chang L, Yakupov R, Cloak C, Ernst T. Marijuana use is associated with a reorganized visual-attention network and cerebellar hypoactivation. Brain
• Bolla KI, Brown K, Eldreth D, Tate K, Cadet JL. Dose-related neurocognitive effects of marijuana use. Neurology
• Gross DW, Hamm J. Ashworth NL, Quigley D. Marijuana use and epilepsy: Prevalence in patients of a tertiary care epilepsy center. Neurology
©2006 American Academy of Neurology
• Clark AJ, Ware MA, Yazer E, Murray TJ, Lynch ME. Patterns of cannabis use among patients with multiple sclerosis. Neurology
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