Marijuana Legalization


In June, a good high school friend, Walt Kubilius from Aiken, SC, attended the 14th annual Symposium on the Cannabinoids, in Paestum Italy, sponsored by the International Cannabinoid Research Society. Walt's summary of the proceedings posed a question concerning marijuana legalization that I heard none of the 2003 California gubernatorial candidates address, which can be summarized as:

• the medical marijuana movement, without saying so explicitly, proposes to give the role of determining the safety and effectiveness of new drugs to legislatures and public referenda, rather than to medical professionals or the FDA, and that may be a problem.

Does anyone want to address that particular question? It's thought-provoking! Here's Walt's write-up:
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I recently attended a research conference on cannabinoids, a group of compounds one member of which is active ingredient in marijuana. I learned a lot at that conference, and I’ll share that here.

Cannabinoids are a group of chemicals, some natural and some synthetic, which share the property of being able to either increase or decrease the concentration of a neurotransmitter, glutamate, in brain cells. Modulation of glutamate levels in the human or animal brain affects/controls mental status. It’s a natural process - every minute, every day, operation of higher brain functions are associated with transient increases and decreases of cannabinoid concentrations, and therefore glutamate concentrations, in the brain.

Cannabinoids which occur naturally in humans are "endocannabinoids", and the molecules with which they interact are "cannabinoid receptors". In order to control glutamate concentrations on a time scale of minutes or seconds, both positive and negative feedback must operate. Cannabinoids which promote glutamate formation - which "activate" the receptors, are "agonists". Those with the opposite effect are "antagonists". Two endocannabinoid agonists are known. There also must be endocannabinoid antagonists as well, but none have yet been identified.

Endocannabinoids and cannabinoid receptors participate in higher brain functions: learning, memory, attention, and planning. Plants and lower animals do not have endocannabinoid systems; vertebrates do. A strain of mutant laboratory mice has been developed which lacks one of the three cannabinoid receptors. They look just like normal mice, but they are learning-disabled. Unlike insulin and vitamins, cannabinoids are not necessary for life, but they are necessary for learning and memory formation.

THC is not normally present in the human body, but it affects brain function because the molecule’s shape is similar to the shape of anandamide, one of the endocannabinoid agonists. The marijuana plant does not produce THC for its own use; plants cannot learn or form memories. It is thought that the marijuana plant evolved THC production in order to either be attractive to certain animals (like flowers are attractive to bees), or to be unattractive to certain animals (like toads taste bad). Its not yet known which way it goes.

There are definitely legitimate medical uses for cannabinoids. Its been known for over 20 years that marijuana can reduce nausea, enhance appetite, reduce intraocular pressure in glaucoma patients, and relieve muscle spasms in MS patients. However, recent research has found additional possible applications for cannabinoids. Probably the most important one is that cannabinoids facilitate early death of some kinds of cancer cells; they show promise as a chemotherapy. Endocannabinoids may also have a role in regulating bone mass. In addition, they may serve an antioxidant role in cell metabolism.

These known and possible medical applications form the basis for the medical marijuana movement. However, it is not clear that cannabinoids found in marijuana - THC, cannabinol, and cannabidiol-are the best choices for treatment. Marijuana has side effects known to every college student: intoxication and lethargy which make driving safely, operating machinery safely, or any mental work impossible. The trick is to find a compound with maximum benefit, and minimum side effects. Since endocannabinoids occur naturally in the brain, they might serve better. Drug companies and academic researchers are experimenting with synthetic cannabinoids, which exist neither in the animal kingdom, nor in the plant kingdom. It remains to be seen which compound is best for which medical condition.

Medical marijuana activists point to the known effectiveness of marijuana in managing MS, glaucoma, and nausea, and advocate legalization for medical purposes. I can’t blame people for wanting it. If I had glaucoma or MS, I’d obtain marijuana, illegally if necessary, to see for myself whether it could help. Marijuana advocates insist it is safe, and like to point out that nobody ever died of a marijuana overdose. That may be true, but acute nonlethality does not preclude chronic lethality. Nobody ever died of an acute tobacco overdose, and yet tobacco kills hundreds of thousands per year due to chronic effects. Medical marijuana advocates seem to be unaware of the possibilities. Here are some things I learned at the ICRS conference:

• In contrast to the common wisdom of the 1970s, marijuana is addictive. Researchers in Baltimore interviewed 20-year heavy-use pot smokers. They each reported an average of 5 unsuccessful attempts to quit. Reasons for failure were psychological withdrawal symptoms, including craving for marijuana.
• Long term frequent marijuana use causes enduring cognitive impairment. Researchers in Australia measured test performances of three groups of subjects: long-term heavy users, long-term light users, and non-users. Long-term heavy users performed worst in tasks related to learning, memory, attention, and planning. In addition, long-term users showed reduced MRI activity in the prefrontal lobe and hippocampus. Since Alzheimer’s disease affects the same brain functions, it is possible that persons destined to develop Alzheimer’s may show symptoms earlier if they are also long-term pot smokers.
• There is a "Fetal Cannabinoid Syndrome" observable in rats, analogous to Fetal Alcohol Syndrome. Progeny of female rats dosed with cannabinoids while pregnant showed hyperactive behavior while juveniles, and learning/memory deficits in adulthood.
• Marijuana causes the HIV virus to replicate faster. Scientists at UCLA dosed HIV-infected human white blood cells with THC, and subsequently found viral loads 50-60 times higher in the dosed cells as compared with un-exposed HIV-infected cells.
  

Several effects listed above are quite serious. Despite the claims of some, medical marijuana use will carry significant risk for some patients.

Debate on medical marijuana touches cultural battlefields. First, is the conflict between local vs. federal power. Efforts to make it accessible are made locally, it cities and states. It is the federal government which resists. Second, is the libertarian or counter-culture argument that there’s nothing wrong with using it if we want to. I believe that this is the major motivation of medical marijuana advocates; a desire to promote alternative lifestyles, more than a desire to treat patients. Centers of the movement are the centers of alternative lifestyles, and centers of medical expertise are not highly involved in the movement.

What has not received enough attention is the "Trojan Horse" of the medical marijuana movement. Without saying so explicitly, it proposes to give the role of determining the safety and effectiveness of new drugs to legislatures and public referenda, rather than to medical professionals or the FDA. There’s nothing special about marijuana. If it can be approved for medical use without the sanction of the FDA, then so can any number of treatments. For example, cancer sufferers who don’t want to undergo surgery will be encouraged to try various speculative and perhaps unsafe or ineffective remedies. The patent cure-all medicine days may return. Thalidomide-type tragedies may be repeated.

If the medical marijuana advocates want to make cannabinoids available for safe and effective medical use, they have already won. Pharmaceutical companies are developing and testing cannabinoids, including THC, cannabidiol, endocannabinoids, and synthetic compounds. They are going through the process, and may be in drugstores in several years if they are found to be safe and effective. The advocates don’t mention this much.

I don’t actually care whether marijuana is legalized or decriminalized for recreational use. It’s not morally wrong. It is no more dangerous than alcohol, and perhaps less so. However, long-term use is self-destructive. I do not wish to assign the FDA’s technical evaluation responsibilities to city councils without first clearly talking about the medical consequences down the road. I haven’t heard much of that talk yet.