2007 - Medical Cannabis in Oncology

"Medical Cannabis in Oncology"
http://www.sciencedirect.com.revproxy.brown.edu/science?_ob=ArticleURL&_udi=B6T68-4R1FS78-2&_user=489286&_coverDate=10%2F31%2F2007&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000022678&_version=1&_urlVersion=0&_userid=489286&md5=b5a111c7cc600d0fb13fe0221af224cd

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.

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2007 - Cannabis, Pain, and Sleep

“Cannabis, Pain, and Sleep: Lessons from Therapeutic Clinical Trials of Sativex, a Cannabis-Based Medicine.”
http://www3.interscience.wiley.com/cgi-bin/abstract/115806134/ABSTRACT

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.

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2005 - Marijuana as treatment for Alzheimer’s Disease

“Marijuana may block Alzheimer's”
http://news.bbc.co.uk/2/hi/health/4286435.stm

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.

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