Medical Marijuana – Joint Controversy

As laws change in different jurisdictions, many questions arise. Is marijuana safe? If alcohol and cigarettes kill more people than marijuana does, why are the former legal and the latter generally illegal? Can a doctor legally grow marijuana and prescribe it medically in jurisdictions where both activities are legal?   As over 20 states now have laws referring to marijuana, it is worthwhile to review what we do and do not know about the risks and benefits of its use, as well as what ‘legalization’ and ‘medical marijuana’ actually mean.

The more I read on the subject, the more confusing certain issues become. I first became curious about this topic when I read articles in the popular press about how if a person was taking a flight from one place to another, where possession was legal in both, they could still get arrested in the airport which is under federal control. Federal law does not recognize it as legal.

In our area, the residents of the District of Columbia voted to de-criminalize the possession of small amounts of marijuana but as of yesterday, Congress has included in the spending bill a provision that, “…prohibits both federal and local funds from being used to implement” the referendum. Stay tuned to see how they work this out!

The topic becomes muddy when we realize that marijuana does not affect all age groups in the same way. There are many issues regarding use, addiction, effects on brain development, driver safety, medical benefits and product quality. I once heard an interview on NPR of someone who was a taste tester of various pot-containing products. He was asked how he acquired this job, and he said “I have lots of experience.” Followed by, “It’s a tough job but someone’s gotta do it.”

Although the Department of Justice could in theory try to arrest people in states where it has been legalized, its current priorities of Justice are as follows:

– preventing distribution of marijuana to minors,
– preventing revenue from going to a criminal enterprise,
– preventing trafficking of other illegal drugs,
– and preventing drugged driving.

At the moment, it is discouraging the DEA (Drug Enforcement Administration) from using funds to interfere with implementation of state laws where it is legal.

Doctors are authorized to prescribe controlled substances (narcotics, for example) through the DEA which is a division of the Department of Justice. It is a federal license. Obviously, it cannot be used to prescribe something that is illegal on the federal level. Therefore, in states where it is legal, it is not exactly prescribed. A doctor can fill out the patient’s application for marijuana and the patient then picks it up at a dispensary.

In the past, the DEA discouraged doctors from even discussing marijuana with their patients, as it would legitimize its use. After a lawsuit in California in 1996, it was ruled that DEA action against a physician was permissible only if there was substantial evidence that the physician helped their patient obtain the marijuana.

When Massachusetts recently prepared to implement its medical marijuana law, physicians with ties to marijuana dispensaries were told to either give up their DEA registration or sever their formal ties with proposed dispensaries, even if they were only involved as a board member, as they could not be both a prescriber and a seller. So discussion about its use is allowed, but involvement in obtaining it is not.

Since 2000, in Colorado, where marijuana is legal for both recreational and medical use, patients may use marijuana for 8 diagnoses: pain, cancer, glaucoma, HIV/AIDS, cachexia, persistent muscle spasms, seizures and severe nausea. In practice, 95% of the recommendations are for pain control. The amount allowed for any diagnosis is standard – 2 ounces or 6 plants. For non-medical use, residents may purchase up to 1 ounce; visitors to the state can purchase marijuana if they are 21 years old, but less than an ounce. Access to the medical marijuana program is only for state residents.

What is the concern about decriminalizing or legalizing the possession or use of small amounts of marijuana – whether for recreational or medical use?

The cannabis or marijuana plant contains over 60 cannabinoids, with THC (delta-9-tetrahydrocannabinol), also known as dronabinol, being the primary psychoactive one.

Over 20 states have passed laws related to marijuana, each one somewhat different in detail. One major concern is the use in adolescents. Currently, alcohol and tobacco cause the greatest burden of disease of all drugs, ‘not because they are more dangerous than illegal drugs but because their legal status allows for more widespread exposure.’ (Volkow)

Currently, marijuana is the most commonly used ‘illicit’ drug in the US, with high rates among young people – about 12% of people 12 and over have used it in the past year, most commonly by inhalation. Hashish, created from the resin of the flower, and the oil-based extract of the plant can also be mixed into food products.

There are very strong feelings on both sides of the issue of legalization. On one hand, there are arguments about the punishment outweighing the severity of the crime for possession and how this affects minority youth more than others, legalization potentially eliminating the black market for the drug, thereby improving its safety, very convincing anecdotal stories about its benefits and more.

On the other hand, there is concern about brain development in adolescents and how the legalization will decrease the perception of risk and therefore increase frequency and duration of use, and with it, the risk of ‘drugged driving’ and impact on IQ.

In truth, much of the information we have about the risks and benefits of marijuana use is subject to debate, as there are few long-term studies, many potential confounding factors, and little or no assessment of the ‘dose’ of marijuana test subjects received. In fact, the THC content in confiscated samples has increased substantially over the past decade, so past data may not even reflect the effect of current marijuana content. Emergency room visits related to marijuana have doubled since 2004, which may be from increased use and/or increased THC content.

The use of medical marijuana for cancer pain and post-chemo nausea and vomiting, although the most accepted of all uses, is still controversial. It has been used for pain relief for centuries. There are studies and anecdotes supporting many of the diagnoses noted above, but even among medical experts there is disagreement as to the reliability of the data.

A recent article in JAMA (Wilkinson) revealed that there are no clinical trials evaluating any benefit for some of the less common diagnoses that it is used for, such as post-traumatic stress disorder (PTSD), Alzheimer’s and Parkinson’s. In fact, some data suggest PTSD may be worsened by it.

A further concern is that cannabis contains over 100 compounds with varying concentrations, but our knowledge is limited to THC and cannabidiol. We don’t know what the optimal dose is, nor do we have experience with any other medications in which smoking is the delivery system. At this point, widespread use would allow for marked variability in dose and effect. Pills and a spray delivery system for THC and cannabidiol are discussed below.

Medical concerns about inhaled marijuana use include:

— Use in adolescents may interfere with brain development, particularly in those areas with high cannabinoid receptors – areas that take care of complex functions, such as alertness or executive function. Since decreased function occurs at the time of use and for a few days after, adolescents can have impaired learning during acute use, that then carries over for a few days, putting them at a disadvantage for keeping up in class in the following days, even without further use. There is an increased likelihood of dropping out of school.

–When use is started in adolescence, there is an associated lower IQ and higher risk of addiction to it as well as to other drugs. In rodents this reaction to marijuana, as well as to alcohol and nicotine, can affect the reward center and lead to greater drug use and likelihood of addiction. (Levine)

— There is a higher risk of auto accidents, including fatal ones, especially when drugged driving occurs in those under 21 years old. As well, there is altered judgment, increasing the risk of sexual behaviors that might increase the risk of sexually transmitted diseases.

— There is an increased risk and earlier onset of psychosis, including schizophrenia, especially in those with a genetic predisposition. The effect is greater when exposure starts at a younger age, and the quantity of exposure is greater. There is an increased risk of anxiety and depression in users, but it is not clear which came first – the smoking or the anxiety/depression.

— Symptoms of bronchitis – cough, wheezing and sputum production – and pneumonia, are more common in long-term marijuana smokers. There are inflammatory changes in the airways immediately after smoking, but it has NOT been shown to result in chronic changes equivalent to emphysema in tobacco cigarette smokers. Lung cancer and bladder cancer were more common in users, but those might have been more related to cigarette smoking, as use of both often occur in the same person. Users usually smoke far less cannabis than tobacco, but the hand-rolled smoke is generally not filtered and contains three times the amount of tar and 50 percent more carcinogens than tobacco cigarettes.

— After use, there can be an increase in the heart rate and eventually, with higher blood levels, a slowing. This may be significant in those with underlying heart disease.

— Although this was not thought to be the case in the past, it appears that addiction and withdrawal syndromes do occur with frequent use.

— Paradoxically, although marijuana is used for post-chemotherapy nausea, it can actually cause nausea and vomiting with repeated use.

And the potential benefits are:

— glaucoma – in general, the standard treatments are more effective. More research is needed.

— nausea – THC in pill form can be used to prevent vomiting after chemotherapy, but patients often state that inhaled marijuana is more effective in suppressing nausea.

— AIDS-associated wasting syndrome – it has not been proven that smoking improves the complication or death rate from AIDS. The pill form of THC is used as an appetite stimulant.

— chronic pain – both marijuana and dronabinol, a pill form of THC, decrease pain, but the latter may lead to longer-lasting reductions in pain sensitivity and lower ratings of rewarding effects than smoking and so may be safer to use.

— inflammation – THC and cannabidiol can decrease inflammation and may prove to be useful in rheumatoid arthritis or Crohn’s, neuropathic pain, disturbed sleep and spasticity in patients with MS. More research is needed.

— epilepsy – the evidence is mainly in animal models and many anecdotes. More research is needed.

Currently, when cancer pain is not responsive to narcotics, pill forms of cannabinoids can be prescribed, although they are only officially recommended for nausea. These are nabilone and dronabinol/THC (Cesamet and Marinol, respectively). The most common side effects are dizziness, somnolence and dry mouth.

An oral spray, nabiximols (Sativex), which contains THC plus cannabidiol, is approved in Canada and the Netherlands for treatment of pain in multiple sclerosis and advanced cancer. It is rapidly absorbed and can be titrated easily by the patient by adjusting the number of sprays. It is being studied here in the US.

So the bottom line is — more research is needed, the pill forms of cannabinoids are available, and because the research is difficult to do, we will be discussing this for years to come. The best we can do is to remain well-informed so we can participate knowledgeably in the discussion.

REFERENCES:

Volkow, N., et al., Adverse Health Effects of Marijuana Use. NEJM 370; 23, 2219-2227.

Annas, G. Medical Marijuana, Physicians and State Law. NEJM 371; 11, 983-985.

Map: The United States of Legal Weed

Hesketh, et al. Prevention and treatment of chemotherapy-induced nausea and vomiting. www.uptodate.com. Oct 20,2014.

Levine, A, et al, Molecular mechanism for a gateway drug: epigenetic changes initiated by nicotine prime gene expression by cocaine. SciTransl Med 2011;3:107ra109.

Teitelbaum, S. et al, Cannabis use disorder: Treatment , prognosis and long-term medical effects. www.uptodate.com, Sept 22, 2014

Wilkinson, S., D’Souza, D.Problems With the Medicalization of Marijuana. JAMA. 2014; 311(23):2377-2378, June 18, 2014.

Kuehn, B. Colorado Tackles Medical Implications of Marijuana. JAMA. 2014;311(20):2053-2054.

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