Assignment
Part 1
The FDA's Opposition to Medical Marijuana Legalization Is Based on Politics
"Virtually no research on potential risks and benefits has been done, because the government has blocked such studies."
Sydney Spiesel is a pediatrician and a clinical professor of pediatrics at Yale University School of Medicine. In the following viewpoint, he reports that the Food and Drug Administration (FDA) has issued a statement declaring that marijuana has no safe medical uses. Spiesel says that this statement is not based on science. The best evidence, Spiesel argues, suggests that marijuana may have medical uses but that further study is needed. Spiesel contends, however, that the government has blocked marijuana research. He concludes that the FDA's statement is based on politics, and he calls into question the objectivity of government science.
As you read, consider the following questions:
1. What does Spiesel say the FDA's statement implies, and is this implication accurate?
2. What benefits did the IOM report suggest might result from medical marijuana use?
3. What other example of politics trumping science at the FDA does Spiesel provide?
The Food and Drug Administration (FDA) reported that it had definitively established that marijuana has no medical use or value. Definitively? Established? I don't think so.
The FDA's announcement begins by acknowledging the claim that smoked marijuana may be beneficial for some conditions. Then the agency points out that among drugs with a potential for abuse, marijuana is lumped in with the most dangerous drugs, the ones that have no potential medical benefits and the highest likelihood of misuse. The FDA next affirms that a collection of federal agencies have together concluded that marijuana is both dangerous and medically valueless, based on scientific studies in humans and animals. The announcement-actually, it's an "inter-agency advisory"-concludes by asserting, with a boldness that might belie a certain uneasiness, that it is the FDA's job to approve drugs. Take that, state legislatures and voters.
The FDA's statement implies that the agency reached its conclusion about marijuana after conducting a new serious analysis of the existing scientific literature on the drug. But of course no such analysis was reported in the medical literature and, in fact, no identifiable official at the FDA took responsibility for last week's advisory. It was just put out there as a statement of fact.
But it's not. In 1999, the Institute of Medicine [IOM], the medical arm of the National Academy of Sciences (an organization chartered by Congress to provide independent, nonpartisan scientific and technological advice) examined this same question in considerable depth and published a 288-page report of its findings. Put together by 11 distinguished scientists and physicians, the IOM report examined the known and potential harms of marijuana use and the known and potential medical benefits. The report is broad in its vision and thoughtful and cautious in its interpretations and recommendations. Its authors acknowledged that the medical uses of marijuana entail some risk of harm-for instance, it's pretty clear that inhaling marijuana smoke can't be good for the lungs, and who knows if there are significant psychological side effects for some users. But the authors concluded that these risks were not terribly high. They also found that other putative risks often attached to this drug-the potential for addiction, for instance, or for marijuana serving as a "gateway" to further drug abuse-were much overstated. The report urged further study to determine the real level of risk.
In examining the potential medical benefits of medical marijuana, the IOM report was equally cautious. It described relief from nausea associated with cancer chemotherapy, appetite stimulation for cancer and HIV patients, and treatment of muscle spasticity for patients with multiple sclerosis or spinal cord injury. Though these benefits seem real, the authors of the IOM report point out that we really don't know yet if they are significant or valuable enough to warrant the use of medical marijuana. Again, the report urged further study to determine the real level of benefit.
The Government Is Blocking Research
However, in the seven years since the IOM report was issued, virtually no research on potential risks and benefits has been done, because the government has blocked such studies. So, we know neither more nor less [in 2006] about medical marijuana than we did seven years ago, whatever the FDA says. Why would the agency inaccurately claim that the science is settled when it isn't? I hardly need to say it: This isn't a medical or scientific conclusion. It's a political one.
This is certainly not the first time that politics has trumped science at the FDA. Another recent example: the agency's decision to block over-the-counter availability for emergency contraceptives in the face of overwhelming evidence that the treatment is safe and effective, and support for over-the-counter availability by the FDA's own advisory committee. From my standpoint as a doctor, the question is this: What do you do when federal agencies become so politicized that their recommendations can't necessarily be trusted? Do you have to treat other things they say as suspect? I depend on good advice and honest information from government agencies in the daily conduct of my work. I need to know what epidemic illnesses are circulating in my neighborhood even if that information might put a government agency in a bad light. I need to be able to trust government-sponsored research (especially because, goodness knows, I have learned not to trust manufacturer-sponsored research). I need to know that the advice I glean from government-sponsored agency websites will lead to the best care for my patients.
Marijuana as a medicine-whatever its risks and benefits are eventually determined to be-may turn out to be much less important than the question of whether we can count on agencies like the FDA to be honest in their dealings.
Part 2
Marijuana Can Help in the Treatment of Pain
"Numerous studies have now established that cannabinoids help lessen pain and affect a wide range of symptoms and bodily functions."
Bill McCarberg is founder of the Chronic Pain Management Program for Kaiser Permanente. In the following viewpoint, he says that cannabinoids found in marijuana have been shown to be effective in reducing pain. He notes that much more clinical study is required and that it is difficult to balance the intoxicating and pain relieving effects of marijuana. Nonetheless, he concludes that cannabinoid pain relievers are very promising and hopes that they will soon become an important medical therapy for pain.
As you read, consider the following questions:
1. What are the three informal categories of cannabinoid, according to McCarberg?
2. What problems does McCarberg say arise when taking cannabinoids orally?
3. According to McCarberg, what problems are there with the quality of herbal cannabis sold through dispensaries?
Millions of people in the United States suffer from chronic pain, and much of that suffering cannot be relieved adequately by existing treatments. Patients are in desperate need of new pain management approaches. Cannabinoid medicines appear very promising, although the subject often is obscured by controversy, prejudice, and confusion in part because cannabinoids have some relation to the cannabis plant-also known by the slang term marijuana.
Do Cannabinoids Work?
What scientific reasons do doctors have to think that cannabinoids actually work? Do they provide genuine symptom improvement, or do patients become intoxicated and merely think that their symptoms are reduced?
Basic research conducted over the past 20 years provides us with many answers. In the early 1990s, researchers identified the cannabinoid receptor system. This system is found in some of the most primitive animal forms on earth-it is also the most widespread receptor system in the human body.
The cannabinoid receptor system has two types of receptors:
• CB1 receptors are found primarily in the brain, spinal cord, and periphery.
• CB2 receptors are on the immune tissues.
Specific molecules (called endocannabinoids) are produced by the body that interact with these CB1 and CB2 receptors, much like endorphins interact with the body's opioid receptor system. These findings initiated a new era of scientific interest and research in cannabinoids.
Numerous studies have now established that cannabinoids help lessen pain and affect a wide range of symptoms and bodily functions. Such research has also demonstrated that cannabinoids may work together with opioids to enhance their effectiveness and reduce tolerance.
This body of research has allowed cannabinoids to be informally classified into three types:
• endocannabinoids (produced by the body)
• phytocannabinoids (produced by the cannabis plant)
• synthetic cannabinoids (produced in the laboratory)
Each type is being studied aggressively, but because endocannabinoids are quickly metabolized and probably cannot be patented, they have not yet been researched in humans.
What progress is being made toward developing cannabinoids as prescription pain relievers? Some cannabinoids are unstable and many are insoluble in water, which makes them difficult to research and turn into modern medicines. Patients react very differently to cannabinoids. Data from recent clinical trials are encouraging, but somewhat mixed. Looking closely at the results suggests that composition and delivery route (i.e., how a medicine is administered) are extremely important to the viability of cannabinoid medicines.
The Delivery Route
When taken orally, cannabinoids are not very well absorbed and often have unpredictable effects. Patients often become sedated or have intoxication-like symptoms when tetrahydrocannabinol (THC-the primary psychoactive cannabinoid in cannabis) is metabolized by the liver. A small number of studies with Marinol (synthetic THC in sesame oil in a gelatin capsule) and Cesamet (synthetic THC analogue) have shown some effectiveness in pain relief, but optimal doses that relieve pain often cannot be achieved because of unpleasant psychologic side effects.
Inhaling cannabinoids, especially THC, also may cause problems for many patients. Blood levels rise suddenly and then drop off sharply. This rapid on-off effect may produce significant intoxication, particularly in patients who are new to cannabinoids. This may pose the risk of abuse potential. Smoking cannabis produces this effect, which is the very reason that recreational users prefer the inhaled route. Patients, however, generally wish to avoid psychologic effects, and it is unclear how difficult it might be to find a dosing pattern that enables them to have pain control without side effects.
A new product, called Sativex, was approved by Health Canada in June 2005 for marketing as an adjunctive medicine for central neuropathic pain in multiple sclerosis. Adjunctive therapy means taking two or more medications to help control pain.
Sativex has a different delivery system-an oromucosal/sublingual spray absorbed by the lining of the mouth-that, according to the manufacturer, generally allows patients to gradually work up to a stable dose at which they obtain therapeutic pain relief without unwanted psychologic effects.
In the United States, Sativex is being studied in large randomized trials in cancer pain that has not been adequately relieved by opioids. Three early and six pivotal controlled studies in the United Kingdom demonstrated positive results treating chronic pain of various origins including neurologic pain, various symptoms of multiple sclerosis, rheumatoid arthritis, and cancer pain. Initial results show improvement in pain for more than one year despite lack of effectiveness of the opioids. Common adverse effects of Savitex have included complaints of bad taste, stinging, dry mouth, dizziness, nausea or fatigue.
Additional research also may uncover other ways of avoiding the problems associated with oral or inhaled delivery. Ajulemic acid, a synthetic cannabinoid, binds to both the CB1 and CB2 receptors, and has shown benefit in a small neuropathic pain trial. It may have reduced psychologic effects and is being studied for the treatment of interstitial cystitis.
Research Is Promising
The use of herbal cannabis-usually smoked-has received considerable media attention since California and Arizona passed "medical marijuana" initiatives in 1996. Despite numerous anecdotal reports of effectiveness, very few controlled studies have been published in the pain area. Little is known about the number of patients who actually experience some degree of benefit or side effects.
Furthermore, herbal cannabis is neither standardized nor monitored for quality. The cannabinoid content can vary a great deal, and cannabis sold at dispensaries may be contaminated with pesticides or mold. Dosing is uncertain, depending on the preparation or method of use. So-called "vaporizers" do not eliminate all the contaminants. Without clinical trial data and an assurance of product quality, physicians lack the information necessary to assist patients in making informed therapeutic decisions. Both the FDA [US Food and Drug Administration] and Institute of Medicine have stated that there is no future for herbal cannabis as a prescription medicine.
Nevertheless, there may be some truth to the idea that there is pain relief potential in phytocannabinoids (plant-based cannabinoids) and that such potential may be affected by the interaction of THC with other botanical components, particularly with other cannabinoids. Modern strains of cannabis have been bred to maximize the THC at the expense of all other cannabinoids, most of which do not have psychologic effects. Some of those cannabinoids, such as cannabidiol (CBD), have been demonstrated to have important therapeutic value, particularly on pain and inflammation.
The possibilities for cannabinoid medicines are very promising, and much exciting research is proceeding at a rapid pace. As new FDA-approved cannabinoid products become available, physicians and patients will have a solid scientific foundation from which to assess their appropriateness. Hopefully, robust scientific data will soon allow cannabinoids to take their place-along with opiates and other pain relievers-in the modern medical supply for treating chronic pain.
Attachment:- Critical-Analysis-Form.rar