Archive for the ‘NEJM’ Category

Medical Marijuana: Politics versus Science

Wednesday, November 27th, 2013
Marijuana in its raw form.

Marijuana in its raw form.

I recently read a New York Times article by Jane Brody titled "Tapping Medical Marijuana's Potential" in which she notes the long history of medical, spiritual and recreational use of the drug and mentions it contains  a multitude of chemicals (400 plus) in its raw form.  She confirmed my thought that if people are to use the drug for medical reasons, a joint or a pipe certainly isn't the optimal modality for administering it, When smoked, the number of compounds released multiplies by a factor of five (over 2,000 chemicals) and some are felt to lead to risks similar to those of tobacco.

As of November, 2013, twenty states and the District of Columbia have medical marijuana clinics; two states have even legalized its recreational use and a Gallup poll in October reported fifty-eight percent of Americans support legalizing marijuana for non-medical purposes. That's way up from the 12% in 1969 and roughly a third at the start of the 2000s who favored changing the laws concerning marijuana. Subgroups in this survey that still opposed legalization were those sixty-five and older and those who identified themselves as Republicans ( 62% of Democrats and 65% of Independents {up 12% since 2011} favored the change). Even the over sixty-five group had a considerable (+14%) increase in the last two years of those who are in favor of loosening the laws on the drug.

I'm going to stick to comments on medical marijuana, and not get into a discussion of recreational use.

Cornell University Law School's Legal Information Institute website details 21 USC § 812 Schedules of Controlled Substances. There are five levels of these drugs (or substances) and the most tightly controlled is Schedule I, drugs/substances (D/S) with a high potential for abuse and no currently accepted medical use in treatment in the United States. Additionally there is a lack of accepted safety for those D/S even if they are given under medical supervision. There's a long list of  Schedule I drugs including heroin, LSD, mescaline and GHB (the date rape drug). But marijuana is right alongside those, mostly for political, as opposed to scientific reasons.

Schedule II D/S  have a high potential for abuse, but do have a currently accepted  medical use in this country, some with and others without severe restrictions. Abuse can lead to severe psychological or physical dependence. Opium and cocaine are in Schedule II. Schedule III D/Ss have less potential for abuse, a currently accepted medical use and abuse can lead to moderate or low dependence. Amphetamine and its derivatives are in Schedule III. As you would expect, Schedule IV and V D/S have lower potential for abuse and habituation.

In 2005, the U.S. Supreme Court, discussing California's medical marijuana regulation (voted in under the 1996 Proposition 215) in  a case titled Gonzales v. Raich, issued a majority opinion that Congress had the power to prohibit local cultivation and use of marijuana in that state. They did so by case precedent under the Commerce Clause referring back to a 1942 decision about wheat farming. Justice O'Connor, Chief Justice Rehnquist and Justice Thomas dissented with Justice O'Connor writing that the Court's decision was sweeping overreach. She noted the two women who had sued the US Attorney General and the DEA were, in one case, raising a very small number of marijuana plants and, in the other case, relying on locally grown plants. Neither one was engaged in interstate commerce nor even conceivably had enough of the drug to substantially affect such. Both were acting in accordance with California law.

In 2008, an article in CMAJ, the Canadian equivalent of JAMA, reviewed safety studies on marijuana used medically and noted that short-term usage of the then existing forms of medical cannabinoids "appeared to increase the risk of non-serious adverse effects (the most common being dizziness), but not serious ones. The problem was the risks in longer-term use weren't well defined, even in that country which had been the pioneer in 2001 by legalizing medical usage of the drug.

2009 Department of Justice memorandum, directed at "Selected United States Attorneys," discussed "Investigations and Prosecutions in States Authorizing the Medical Use Of Marijuana." It firmly held to the DOJ being committed to enforcing the Controlled Substances Act (CSA) in all states, saying Congress still felt marijuana was a dangerous drug; its illegal distribution and sale was a serious crime and its sale provided gangs and cartels with oodles of money. While adhering to the CSA was still a clear priority, DOJ felt federal resources should not be expended in the pursuit of individuals who use marijuana medically in compliance of state laws.

An April, 2010 article in NEJM, written by two attorneys from the University of Maryland School of Law, mentions that the American Medical Association had recently voted for reviewing marijuana's status as a Schedule I drug. At that time, fourteen states had passed laws to allow the medical uses of the drug and over a dozen more were considering the idea. But there was very little if anything being done to "advance the development of standards" concerning dosing, packaging, potency, quality or purity issues. Experts in this country had urged reclassification to Schedule II as a means to allow rigorous testing of possible benefits, dosing and delivery means.

In early 2012, Mayo Clinic Proceedings published two articles and an editorial on Cannabis. The first article reported a case series of 98 patients with "Cannabinoid Hyperemesis." The first term meant chemicals found in marijuana and the second implies severe, persistent vomiting. The more common use of the medical term refers to the one to two percent of women who have continued, severe, nausea and vomiting during pregnancy…a condition termed hyperemesis gravidarum (gravid means pregnant).

How much THC is in this joint? Who knows?

How much THC is in this joint? Who knows?

A superb, long and detailed review by J. Michael Bostwick, MD of Mayo's Department of Psychiatry and Psychology has the intriguing title, "Blurred Boundaries: The Therapeutics and Politics of Medical Marijuana." and is available on an NIH website. It is well balanced and covers many facets of the history and pharmacology of the drug with caveats on its use in young individuals, an association with psychosis (marijuana may or may not be causative, but its use appears to have a distinctly negative effect on those already psychotic), the pros and cons of using it medically, and the currently available pharmaceutical cannabinoids.

The New York Daily News, on January 22, 2012, had an article titled "Marijuana-based drug Sativex may get FDA approval." A followup published August 14, 2013 in an industry online news source, Fierce Pharma, said the European pharmaceutical firm GW now had an American partner company working with the FDA on a Phase III trial for the drug in treating cancer pain and spasticity in multiple sclerosis patients. The oral spray has already been approved for patient use in the U.K., Canada, Denmark, Poland, Austria and Sweden. It has a mixture of THC, the psychoactive component, and cannabidiol, a non-psychoactive cannabinoid that can lessen the negative effects of THC while, potentially, offering reduced anxiety and anti-seizure effects of its own.

An October 3, 2013 article in Time Magazine's World section was titled "Canada Rolls Out a '$1 Billion" Privatized Medical Marijuana Industry." Medical marijuana has been legal in Canada for more than a decade but was strictly regulated. In a country whose population as of July, 2013, was estimated to be just over thirty-five million (versus the United States's November, 2013 estimate of 317 million), there are almost 40,000 registered medical marijuana users. The Canadian government thinks that there will be over eleven times that number by 2024 and has recently voted to shift to private companies, as opposed to Health Canada, controlling the drug's distribution by mail-order, but still under tight restrictions.

What next in the sweeping changes concerning marijuana? I'd like to see well-controlled prospective medical studies, but those can't happen until (and unless) it becomes a Schedule II drug.





Marijuana controversies: Part 1, background and medical use

Friday, March 1st, 2013
Now physicians can prescribe marijuana in some states

Now physicians can prescribe marijuana in some states

Last evening I glanced at the table of contents of the New England Journal of Medicine and was somewhat surprised to find there was an article online on medical marijuana.It discussed a hypothetical patient with metastatic breast cancer who had considerable pain issues and had asked her primary care physician if she could use pot to relieve her pain, nausea and fatigue. There were pro and con discussants with a psychiatrist from the Mayo Clinic in favor of "thoughtful prescription of medicinal marijuana,"  but wanting those to occur within established doctor-patient relationships.

That latter comment made sense to me; if medical marijuana (AKA Cannabis) is recommended by a physician, it should be by a doctor who knows that particular patient well, not someone who writes Rx's for dozens of people a day in a "pain mill."

On the other side of the issue were a Clinical Professor of Psychiatry at Georgetown University (a former White House Drug Czar) teamed with the Chief of the Pain Management Services at a Florida University. They noted that most of the research efforts have focused on specific chemicals from the marijuana plant and that there is limited, but high-quality, data supporting relief of some kinds of pain by smoking pot, but not the type of pain the patient being discussed had. They mentioned two prescription "cannabinoids" that are currently FDA-approved as oral agents specifically for the treatment of nausea/vomiting secondary to chemotherapy.

There have been over a hundred comments to date in the online discussion of the article. One was from a Colorado anesthesiologist/acute pain specialist who commented that patients who use marijuana on a daily basis may become cross-tolerant to opiate drugs, therefore requiring much higher and more dangerous doses of them to have a desired effect in pain control.

A major issue remains the 1970 classification of marijuana as a Controlled Substance Schedule 1 drug, therefore, putting it into the company of heroin, LSD and mescaline, chemicals that have a high potential for abuse and a lack of any medical value.

To date eighteen states have legalized physicians to prescribe the drug, but Federal policy lags far behind and, in theory, docs who write Rx's for marijuana could face legal action. In Israel, on the other hand, over 10,000 patients use marijuana under government license  according to a July, 2012 NPR article.

I found an online article titled "How Marijuana Works." This comes from one of the HowStuffWorks websites, not a medical publication, but seems fairly well balanced. It mentions that cultivation of marijuana is not at all new, with written reports in China dating back over 2,000 years. The plant apparently came from India where it can grow to heights over 13 feet. It contains an enormous number of chemicals, over 400 of them with 60 falling into the cannabinoid group. The National Cancer Institute's webpage on Cannabis and Cannabinoids define these as chemicals that activate specific receptors found throughout the body to produce drug-like effects.

So what's a receptor? I read a superb analogy in Discover magazine with science writer Gary Taubes comparing them to miniature locks on the surface of cells, locks that can only be opened with the correct chemical key.

Cells, including those involved in immunity and the central nervous system, have receptors that bind with substances such as hormones, antigens, drugs, or neurotransmitters (brain chemicals that communicate information from nerve cells). Two different kinds of receptors, termed CB1 and CB2, bind with cannabinoids. The CB1 receptor, when triggered, causes the drug high; THC (the full chemical name is delta-9-tetrahydrocannabinol) is primarily the cannabinoid that leads to this effect. A March, 2012 study from the Mount Sinai School of Medicine focused on the CB2 receptor after research showed that a medication that triggered only CB2 might prove a significant adjunctive treatment to standard anti HIV therapy in late-stage disease.

Other articles in the medical literature discuss the use of marijuana versus cannabinoids in glaucoma therapy. Smoking marijuana lowers intraocular pressure in roughly two-thirds of glaucoma patients. One issue, however, is smoking marijuana is smoking and in end-of-life care probably poses acceptable risks, but done in other situations it may cause a host of problems. Other means of administration include drinking raw cannabis juice, the use of inhalers or administering only specific active cannabinnoids.

In my state, Colorado, there's an organization, headed by an attorney and calling itself Sensible Colorado, that has advocated for medial marijuana. One of their websites outlines the "History of Colorado's Medical Marijuana Laws." Over thirteen years ago our voters passed Amendment 20 to the state constitution, legalizing limited amounts of marijuana for patients and their primary caregivers.

Checking for high intraocular pressure, a precursor of glaucoma

Checking for high intraocular pressure, a precursor of glaucoma

The statute listed the diseases for which a person could be prescribed marijuana/cannabinoids. The first group included cancer, HIV/AIDS and Glaucoma. As I read background articles I could see some reason behind those choices. I'm less impressed with data on most of the other reasons to give the drug  to patients.

In 2000, Colorado voters support the legalization of medical marijuana. In our city and around the state there followed a proliferation of "pot shops," without a great deal of unified regulation. Some cities were stricter in their approach toward the sale of marijuana than others.

All this may have been overcome by events; I'll write about the recent changes in the law in my next post.