Monday, November 19, 2007

2007 - Medical Cannabis in Oncology

"Medical Cannabis in Oncology"

I came across this article while I was searching on PubMed on the Brown University Library Website. It was published in the European Journal of Cancer on September 19, 2007. The content of this article has a great impact on the public perception of this technology. The use of medical marijuana (cannabis) for medical and social purposes has been debated for years. While interest in marijuana in the 1980s and 1990s focused on preventing its recreational use, attention is now being turned to its clinical and medicinal uses.

Patients and doctors have resorted to medical marijuana when conventional treatments were unsuccessful or deficient for the past four thousand years. Nonetheless, the safety and efficacy of cannabis remains controversial. The U.S. Food and Drug Administration (FDA) does not support the use of smoked marijuana for medical purposes on the ground that no sound scientific studies, animal, or human data support its safety or efficacy. However, a growing number of U.S. states have passed legislation making medical cannabis available upon doctor’s recommendations. Medical marijuana can be used to treat refractory neurological symptoms, pain associated with multiple sclerosis (MS) or spinal cord injury, chronic neuralgic pain, aids-related anorexia, HIV medication induced nausea and vomiting, Crohn’s disease, and Tourette syndrome. Other palliative effects include insomnia relief, mood elevation, appetite stimulation, and analgesia.

Cancer is the second leading cause of death in the United States, and one of the top ten leading causes of death in the world. Beneficial effects of marijuana have been reported for cancer-associated anorexia, delayed chemo or radiotherapy induced nausea, and vomiting. If there is a reason to approve the use of marijuana for medicinal purposes, in the public’s eye, there is not one better than for the treatment of cancer.

Much of the existing controversy surrounding the positive effects of medicinal marijuana is due to the lack of well-designed (randomized, double-blind, and placebo-controlled) and adequately powered clinical trials. The majority of clinical trials done so far have evaluated a wide range of different cannabis products, varying in dose, cannabinoid content, quality, and route of administration, in a heterogeneous patient population. Hence, the existing clinical data is inappropriate for comparison, thus making it unable to draw sound scientific conclusions.

One explanation the article gives for the lack of clinical trials is the fact that the current legal status of medicinal marijuana differs around the world and within the nation. In most countries, medicinal cannabis is illegal. As a result, registered standardized products are limited or unavailable. In the US, there are only two FDA-approved medicinal cannabis products available, Marinol and Cesamet. The Investigative New Drug Application of a third medicinal cannabis product, Sativex, was accepted in April 2006.

In the Netherlands, however, the policy surrounding the medicinal use of marijuana is quite disparate from that in the United States. Since September 2003, a legal medicinal cannabis product, constituting the whole range of cannabinoids and meeting pharmaceutical quality standards, has been available for pre-clinical and clinical research, drug formulation development, and on prescription for patients. This change in policy was expected to cause major changes leading to the general acceptance of marijuana for medicinal purposes, especially in treating cancer. However, four years of clinical experience with legal, standardized medicinal cannabis in the Netherlands has not led to the desired results.

A gap between the medicinal marijuana proponents and opponents still exists. Contrary to what was expected, only a minority of patients resorts to physician prescribed cannabis distributed by their community pharmacy. Preclinical research with crude cannabis varieties is ongoing in the Netherlands, but far fewer than expected. The Dutch Minister of Public Health, who was responsible for the initiated policy, decided to guarantee continued distribution and availability of legal medicinal cannabis until the end of 2007, but a renewed decision to keep medicinal marijuana legal in the Netherlands will depend on registration of the only one drug derived from cannabis varieties in the Netherlands. Thus, while many proponents of medical marijuana viewed the Netherlands as the leader in changes to medical marijuana policies, the efforts to make marijuana accepted in the medical community in Netherlands have been unsuccessful.

The percent of cancer patients that use legal cannabis fluctuates between 8% and 23%. According to the article, cancer-associated use of medicinal marijuana seems to be especially low. The majority of patients still acquire medicinal cannabis through illegal distributors, “coffee-shops”, or by growing at home despite its legalization. Thus, firm scientific evidence has not been found and the controversy around medicinal marijuana still carries on.


Sunday, November 18, 2007

2007 - Cannabis, Pain, and Sleep

“Cannabis, Pain, and Sleep: Lessons from Therapeutic Clinical Trials of Sativex, a Cannabis-Based Medicine.”

The article “Cannabis, Pain, and Sleep: Lessons from Therapeutic Clinical Trials of Sativex, a Cannabis-Based Medicine” was published in Chemistry & Biodiversity in 2007. I came across this article while searching on PubMed through the Brown University Website. The content of this article is instrumental in establishing marijuana’s use for medicinal purposes. In another article “Medicinal cannabis in oncology” written about earlier, the medicinal uses of marijuana for cancer did not have enough evidence in clinical trials. However, this article presents evidence supporting the medicinal uses of marijuana to treat pain and sleep disorders.

Sativex is the world's first pharmaceutical prescription medicine derived from the cannabis plant, which is a major step in pushing for the legalization of marijuana for medicinal purposes. Sativex, created by GW Pharmaceuticals and marketed in conjunction with Bayer, is a combination of plant-derived delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). While the article “Medicinal cannabis in oncology” argues that there is not enough clinical evidence to support the use of marijuana for medicinal purposes, experience to date with Sativex in a number of Phase I-III studies in 2000 subjects with 1000 patient years of exposure show marked improvement in subjective sleep parameters in patients with a wide variety of pain conditions indlucing multiple sclerosis, peripheral neuropathic pain, intractable cancer pain, and rheumatoid arthritis. Sativex patients and their caregivers have noted to their physicians how the medicine has changed their lives through its ability to allow them more restful sleep, increase their daytime level of function, and markedly improve their quality of life.

In 2005, Canada was the first country in the world to license Sativex, the first plant-based cannabinoid pharmaceutical medicine in the modern era. This approval has huge implications for the future of cannabis law in the US. The Canadian approval of Sativex is noteworthy because it was marijuana plants themselves, not a chemical factory that produced the THC and CBD in Sativex. Almost always, drugs based on primarily natural non-chemical plant derivates fail to get regulatory approval because regulators have an arbitrary source material standard that essentially excludes natural extracts. The pharmaceutical industry and regulatory agencies prefer machine-made drugs. The philosophical underpinnings of modern drug medicine protocols assume that natural substances are substandard, irregular, and hazardous.

In February 2007, GW and Otsuka Pharmaceutical announced an exclusive agreement to develop and market Sativex in the US. Sativex has received permission from the FDA to enter directly into late stage Phase III trials in the US. Approval of Sativex provides more credibility to the idea that cannabis is a legitimate medicine. If plant-based cannabinoids are medicine, this supports the argument that marijuana itself does not belong in Schedule One status, where all drugs are assumed to be without medical value. As Sativex has shown, marijuana clearly has remarkable medical value.


Monday, November 12, 2007

2005 - Marijuana as treatment for Alzheimer’s Disease

“Marijuana may block Alzheimer's”

This is a very interesting article that I found in the BBC News’ official website. It was first published in February 2005, and its importance for this blog not only lies in its relation to the use of marijuana as medicinal therapy. The article also touches specifically on cannabinoid’s effect on Alzheimer’s, a disease whose effects and impacts have been previously discussed in class.

A research study published in the Journal of Neuroscience, conducted by Madrid’s Complutense University and the Cajal Institute, suggests that a synthetic version of marijuana might halt the declining symptoms of Alzheimer’s disease. By studying brain cell receptors to which cannabinoids bind and the structure of microglia, the researchers were able to find that there is a clear dysfunction of cannabinoid receptors in the brain tissue of diseased Alzheimer patients. Patients suffering from this neurodegenerative disease become unable to experience the protective effects of cannabinoids.

When testing cannabinoid’s effect on rats, the researchers not only saw an improvement in their mental functioning, but also a decrease in their immune system’s inflammatory response caused by an inactivation of microglia. The study led to the conclusion that cannabinoids not only protect the brain but also prevent the normal inflammatory response caused by Alzheimer’s disease. After the discoveries made by their study, the aim of the researchers has shifted into developing a drug that acts only on the CR2 cannabinoid receptors, producing the positive effects of cannabinoids, without acting on the CR1 receptors, which produce the damaging and harmful effects of marijuana.

Even though the use of marijuana as medical therapy is extremely controversial nowadays, the introduction of research on its effect for patients with specifically Alzheimer’s disease is more than welcome. As we have learned during class, drugs currently used to treat Alzheimer’s disease have shown small results and have proven to be ineffective in stopping its natural progression. For a disease without a cure, one that affects 5 million Americans a year and is expected to affect up to 100 million worldwide by the middle of this century, the discovery of cannabinoid receptors as potential drug targets, controversial as it might be, is clearly progress.

The hope of developing new drug therapies based on cannabinoid’s healing effects is unfortunately contrasted by the knowledge of its adverse effects, the underdevelopment of its field of research, and the controversy surrounding its use as medical therapy.


Thursday, November 8, 2007

2000 - Pot Shrinks Tumors: Government Knew in '74

May 31, 2000
Raymond Cushing

Conspiracy theories are always entertaining, but this is a particularly convincing one. Published in AlterNet, an online news source, the writer, Raymond Cushing, alleges that the U.S. Government knew that medicinal marijuana had anti-cancer effects since 1974. The medical college of Virginia, funded by the National Institute of Health, found that THC, the active ingredient in marijuana, slowed the growth of lung cancer, breast cancer, and virus-induced leukemia. The DEA then shut down the research in 1976, and President Ford ended public research by granting rights to pharmaceutical companies in order to try to develop synthetic forms of THC without the high. A more recent study done by Madrid researchers in 2000 found that THC had beneficial effects on incurable brain tumors in rats. Most rats that were treated with THC lived longer, and some brain tumors went into remission. They also tested healthy rats for adverse side effects from THC, and found none. There was no water/food intake change, nor necrosis, edema, infection or trauma. The story of the Madrid findings ran on Feb. 29, 2000 in the March issue of “Nature Medicine,” but was ignored by mainstream press in America.

Is there really a giant governmental conspiracy to keep people from knowing about the beneficial effects of marijuana? Maybe, but this article doesn't prove it. The Madrid research was comparing rats with tumors given THC vs. rats that were given a similar, synthetic compound. There was no placebo trial of rats given a non-medicinal solution. Without a placebo, the results can't be compared, and by themselves, they don't mean much. This article also conflicts with the previous post about the 1978 program to start medicinal marijuana research. That program doesn't seem to fit with the idea of a government that's trying to cover up legitimate scientific research. Also, this article says that very little literature can be found about the 1974 Virginia study, since Reagan and Bush went on a crusade to destroy medicinal marijuana documents in 1983. However, the more likely explanation is that the Virginia study didn't happen—hence the lack of research articles...or is that what the government wants us to think?


Monday, November 5, 2007

1998 - Study Targets Stalemate Over Medicinal Use of Marijuana
San Jose Mercury News (CA)
July 19, 1998
Lisa M. Krieger

This is an older article discussing the first government-sanctioned marijuana research project since 1978. The researcher, Donald Abrams, underwent a rigorous process to get his proposal approved by the NIH on the affects of marijuana and HIV. About 60 volunteers were given marijuana three times a day for three weeks, all with HIV. This article was written during the time of the study, so the results hadn't been published yet. However, what was going on between 1978 and the year of the study, 1998? Marijuana was classified as a Schedule 1 controlled substance—on the same level as heroin and LSD. In 1978, the government started a program and distributed the drug under and Investigational New Drug procedure. However, the program was suspended in 1991 because there were too many requests for marijuana-related studies. Since then, the government made it's Schedule 1 ruling. What's interesting to note is that the government has a legal marijuana farm just outside the property of the University of Mississippi, which was originally created for the 1978 program. Under the jurisdiction of the Research Institute of Pharmaceutical Sciences, it's the only legal marijuana plantation in the United States.

However, between the years of 1978 and 1998, there seems to be a lack of conclusive evidence on the actual scientific affects of marijuana on various illnesses. Getting approval from the government for scientific studies involving marijuana is exceedingly difficult, and the researcher went through multiple submissions of his proposal before he was granted permission. Marijuana seemed (and seems?) to be such a controversial and taboo topic that automatically the government denies project proposals. Perhaps it's a backlash from the high numbers of marijuana project requests following the 1978 program commencement. In an effort to remedy the mistake of giving the public image for endorsing medicinal marijuana, the government wanted to convey the image that they are not promoting the drug for any purpose. The costs to create the image of an anti-drug government may have hurt the people in the long run—if more projects were approved, there would be more conclusive evidence on marijuana, either clinically supporting it or ending all rumors of a medical benefit. Although the government wouldn't have the same image, wouldn't it be worth the potential benefits? Also, I don't think its a coincidence that the first approved medicinal marijuana experiment was not on the illness that medicinal marijuana is most associated with—cancer. The widespread use of marijuana for cancer may be too controversial for the government to be ready to accept in 1998.
July 13, 2000
Alic Trinkl
“Marijuana does not appear to alter viral loads of HIV patients taking protease inhibitors”

What were the results of the mentioned study? All politics aside and two years later, it turns out that marijuana doesn't alter the viral loads of HIV patients that are taking protease inhibitors. There were no short term adverse virologic effects, which puts some worries to rest that patients who are smoking are doing more damage to themselves. The enzyme that breaks down marijuana is the same enzyme that breaks down the protease inhibitor drugs used to treat HIV, so there could have been possible side effects. The study was divided into three arms—smoking marijuana cigarettes, taking the drug orally, and a placebo. Although there was no change in HIV RNA, which was used to measure the amount of HIV in a patient, the patients given marijuana through both methods gained double the weight of the patients taking the placebos. Medicinal marijuana may still have a use in the treatment of HIV, since often patients with AIDS lose significant amounts of weight.


Thursday, November 1, 2007

1998 - Multiple Sclerosis, and Drug Rescheduling

Britain’s House of Lords’ Science and Technology Committee (HOLC)
Cannabis: The Scientific and Medical Evidence
November 1998

I found this article while browsing for definitive research supporting the use of marijuana for medical purposes. I chose to write about it specifically because it represents a variety of themes at once. It serves as an example of where the issue has gone in other countries, it addresses the need to rethink current policy regarding marijuana use, and most importantly it specifically cites the benefits of marijuana for patients suffering from Multiple Sclerosis.

Multiple sclerosis is an autoimmune disease where an individual’s immune system attacks the nervous system resulting in impaired mobility. It is characterized by muscular spasms, tremors, and acute or chronic pain. In the following passage, HOLC presents its recommendation for the use of cannabis by individuals with multiple sclerosis:

We have received enough evidence to convince us that cannabis almost certainly does have genuine medical applications, especially in treating the painful muscular spasms and other symptoms of MS and in the control of other forms of pain...”

The argument that marijuana works well for pain relief is one of the most commonly used in the debate. Almost every favorable report mentions it in one way or another. This is particularly confusing to me because I don’t know how pain relief can be a controversial point. I don’t think anyone can properly deny the therapeutic effects of marijuana for pain relief. How can research adequately disprove the anecdotal evidence of hundreds if not thousands of people with debilitating diseases?

I apparently share the same view as HOLC in that assertion. In their report, HOLC also said the following:

“We therefore recommend that the Government should take steps to transfer cannabis and cannabis resin from Schedule 1 of the Misuse of Drugs Regulations to Schedule 2, so as to allow doctors to prescribe an appropriate preparation of cannabis…”

The application for marijuana as pain relief contradicts its Schedule I categorization in the United Kingdom. Essentially, Schedule I drugs cannot have medical benefits and must have a high potential for abuse. I think rescheduling marijuana says a lot about current drug policy. For one, it makes me question the validity of government legislation in such matters. How can something be absolutely bad for you one day and then turn out to have been okay or “not so bad” the whole time? What does that say about how informed the original decision was in the first place?

The question of whether or not marijuana relieves pain for people with Multiple Sclerosis and whether or not is should be rescheduled is clearly a difficult one. At the very least, HOLC has contributed to an environment where one of our most basic assumptions about marijuana is challenged. The idea that marijuana has absolutely no benefit has existed for a long time in the United States. Currently, breaking past that concept and reevaluating ones stance regarding this controversial drug is proving to be very difficult. As this post has shown, it tends to create more questions than solve them.