EDITORIAL
Up in Smoke: A Neurologist’s Approach to “Medical Marijuana”
A
s physicians, we treat our patients with a wide range of therapies, only some of which have been approved by the US Food and Drug Administration (FDA). Because FDA approval generally requires multiple randomized, placebo-controlled trials, the process is expensive and most manufacturers will only seek FDA approval for a single indication (usually the most common one). At the same time, everyone understands that once a drug has been approved for one indication, it can be prescribed by physicians for other indications, at their discretion. As academic clinicians, we generally try to adhere to evidence-based rules for using these drugs for off-label indications. The best evidence is level I, which requires a well-constructed, randomized, placebo-controlled trial. However, if we limited our treatments to those supported by level I evidence, we would have a very small armamentarium and would be sending many of our patients home disappointed. Therefore, we often prescribe drugs based on level II evidence, that is, a well-designed controlled trial, but which may lack randomization or a placebo control. Few would argue with these applications. We also understand that many drugs have unexpected effects (eg, excess hair growth in early minoxidil trials, or penile erections in sildenafil trials) that may initially be viewed as annoying side effects, but may ultimately become the most common indication for prescribing the drug. Other drugs, once they are in common use, are observed to have useful side effects, such as pain relief with gabapentin or weight loss with topiramate, to name just a few. Clinicians often prescribe these drugs based on level III evidence, that is, anecdotal reports or uncontrolled case series. Medicine has generally moved away from the use of nonstandardized biological preparations as treatments. Where once we prescribed foxglove leaf, we now prescribe digoxin; thyroid sicca has given way to thyroxine. In medicine, there is a strong tendency to break down a useful plant product into its component parts, to purify them, and then to standardize treatment based on providing purified chemicals. Level I or II evidence relies upon such standardization, because without it, there is no control of dosage, and one cannot really design a proper clinical trial. Against this background, several states have passed laws in the past few years permitting “medical
marijuana.” These are states in which the production, sale, or consumption of marijuana for recreational purposes remains illegal, but may be permissible if there is a prescription by a physician recommending it. Even in states where “medical marijuana” is legal, that status does not extend to federal law, and the legal status of those who distribute it or abet its distribution is far from settled. For example, few if any banks will handle the financial transactions of “medical marijuana” distributors, because they do not want to run afoul of the federal government regulation of interstate banking. It is not yet clear whether the federal government will take an interest in physicians who write large numbers of prescriptions for “medical marijuana,” and if so, what their threshold will be. Hence, it is worthwhile analyzing the rationale for the participation of physicians in an activity whose legal basis remains at best murky. What then is the evidence supporting the use of “medical marijuana”? First, it is important to know that, like other botanical preparations, marijuana has been resolved into its component substances. The main active ingredient is delta-9-tetrahyrdrocannibinol (THC). Thus, it is worthwhile to look first at the evidence for medical use of THC. The case for prescribing “medical marijuana” would be limited to indications where smoking or ingesting the leaf could be shown to be superior to taking the purified drug. THC is available as an FDA-approved formulation (dronabinol), which is approved for treating nausea and vomiting in patients receiving chemotherapy or for weight loss in patients with acquired immunodeficiency syndrome. It is available in 5mg pills. There have been many studies exploring off-label indications for dronabinol. These include recent randomized, placebo-controlled (level I) trials showing efficacy for improving such things as causing weight gain in anorexia nervosa1 and reducing pain.2,3 It is not the purpose of this editorial to provide a systematic review of the data on usage of dronabinol; suffice it to say that evidence is available to support its use in many different conditions, and its off-label use in those conditions is up to the individual practitioner. Because this drug is FDA approved, in most cases would be covered by prescription insurance, and is sold through a rigorously controlled system that insures potency and safety, it would make sense for physicians to prescribe
C 2014 American Neurological Association V 13
ANNALS
of Neurology
dronabinol for indications for which cannabinoids may be beneficial. Conversely, prescription of marijuana leaf should be reserved for situations where there is clear evidence that this form is superior to taking THC. Given the paucity of such evidence, there should be little if any need for “medical marijuana.” One might wonder, therefore, why states would be passing laws to authorize physicians to provide prescriptions for a drug whose sale technically violates federal law, and for which a superior substitute is already available and FDA approved. The answer, of course, is that marijuana is widely smoked or ingested as a recreational drug, but there is not yet a consensus in most states or in the federal government to permit it to be sold legally. Some legislators worry about the health risks of marijuana, although it is relatively harmless compared to the 2 most commonly used, legal mind-altering substances, tobacco and alcohol, both of which are clearly lethal in large numbers of users. Other lawmakers worry that marijuana is a portal to other illegal drugs. But our past experience with prohibition of alcohol shows that making a commonly used intoxicant illegal generates widespread contempt for the law and makes the drug profitable for criminal enterprises. In states where marijuana is sold only by criminals, the recreational user is driven into the hands of unscrupulous people who would like to sell him or her other, more profitable and more highly addicting drugs. States that are unable to pass a law decriminalizing marijuana instead turn to “medical marijuana” as a pretext for bypassing the state and federal legal systems. A walk down the boardwalk at Venice Beach in California, where there are numerous sites offering medical prescrip-
14
tions for marijuana, would convince anyone that the supposed medical nature of this access is not being taken seriously. “Medical marijuana” is simply a way for timid legislators to dump the problem of recreational marijuana access onto the medical community. But just as criminalizing a widely used intoxicant undermines respect for the law, medicalizing the use of that intoxicant degrades respect for the medical profession. Providing access to recreational marijuana is not, fundamentally, a medical issue. The doctor–patient relationship should not be burdened with having to provide a fix for the failure of our legislators.
Potential Conflicts of Interest Nothing to report. Clifford B. Saper, MD, PhD Editor-in-Chief
References 1.
Andries A, Frystyk J, Flyvbjerg A, et al. Dronabinol in severe, enduring anorexia nervosa: a randomized controlled trial. Int J Eat Disord 2014;47:18–23.
2.
Cooper ZD, Comer SD, Haney M. Comparison of the analgesic effects of dronabinol and smoked marijuana in daily marijuana smokers. Neuropsychopharmacology 2013;38:1984–1992.
3.
Issa MA, Narang S, Jamison RN, et al. The subjective psychoactive effects of oral dronabinol studied in a randomized, controlled crossover clinical trial for pain. Clin J Pain 2014;30:472–478.
DOI: 10.1002/ana.24327
Volume 77, No. 1
Up in Smoke: A Neurologist’s Approach to “Medical Marijuana”
A
s physicians, we treat our patients with a wide range of therapies, only some of which have been approved by the US Food and Drug Administration (FDA). Because FDA approval generally requires multiple randomized, placebo-controlled trials, the process is expensive and most manufacturers will only seek FDA approval for a single indication (usually the most common one). At the same time, everyone understands that once a drug has been approved for one indication, it can be prescribed by physicians for other indications, at their discretion. As academic clinicians, we generally try to adhere to evidence-based rules for using these drugs for off-label indications. The best evidence is level I, which requires a well-constructed, randomized, placebo-controlled trial. However, if we limited our treatments to those supported by level I evidence, we would have a very small armamentarium and would be sending many of our patients home disappointed. Therefore, we often prescribe drugs based on level II evidence, that is, a well-designed controlled trial, but which may lack randomization or a placebo control. Few would argue with these applications. We also understand that many drugs have unexpected effects (eg, excess hair growth in early minoxidil trials, or penile erections in sildenafil trials) that may initially be viewed as annoying side effects, but may ultimately become the most common indication for prescribing the drug. Other drugs, once they are in common use, are observed to have useful side effects, such as pain relief with gabapentin or weight loss with topiramate, to name just a few. Clinicians often prescribe these drugs based on level III evidence, that is, anecdotal reports or uncontrolled case series. Medicine has generally moved away from the use of nonstandardized biological preparations as treatments. Where once we prescribed foxglove leaf, we now prescribe digoxin; thyroid sicca has given way to thyroxine. In medicine, there is a strong tendency to break down a useful plant product into its component parts, to purify them, and then to standardize treatment based on providing purified chemicals. Level I or II evidence relies upon such standardization, because without it, there is no control of dosage, and one cannot really design a proper clinical trial. Against this background, several states have passed laws in the past few years permitting “medical
marijuana.” These are states in which the production, sale, or consumption of marijuana for recreational purposes remains illegal, but may be permissible if there is a prescription by a physician recommending it. Even in states where “medical marijuana” is legal, that status does not extend to federal law, and the legal status of those who distribute it or abet its distribution is far from settled. For example, few if any banks will handle the financial transactions of “medical marijuana” distributors, because they do not want to run afoul of the federal government regulation of interstate banking. It is not yet clear whether the federal government will take an interest in physicians who write large numbers of prescriptions for “medical marijuana,” and if so, what their threshold will be. Hence, it is worthwhile analyzing the rationale for the participation of physicians in an activity whose legal basis remains at best murky. What then is the evidence supporting the use of “medical marijuana”? First, it is important to know that, like other botanical preparations, marijuana has been resolved into its component substances. The main active ingredient is delta-9-tetrahyrdrocannibinol (THC). Thus, it is worthwhile to look first at the evidence for medical use of THC. The case for prescribing “medical marijuana” would be limited to indications where smoking or ingesting the leaf could be shown to be superior to taking the purified drug. THC is available as an FDA-approved formulation (dronabinol), which is approved for treating nausea and vomiting in patients receiving chemotherapy or for weight loss in patients with acquired immunodeficiency syndrome. It is available in 5mg pills. There have been many studies exploring off-label indications for dronabinol. These include recent randomized, placebo-controlled (level I) trials showing efficacy for improving such things as causing weight gain in anorexia nervosa1 and reducing pain.2,3 It is not the purpose of this editorial to provide a systematic review of the data on usage of dronabinol; suffice it to say that evidence is available to support its use in many different conditions, and its off-label use in those conditions is up to the individual practitioner. Because this drug is FDA approved, in most cases would be covered by prescription insurance, and is sold through a rigorously controlled system that insures potency and safety, it would make sense for physicians to prescribe
C 2014 American Neurological Association V 13
ANNALS
of Neurology
dronabinol for indications for which cannabinoids may be beneficial. Conversely, prescription of marijuana leaf should be reserved for situations where there is clear evidence that this form is superior to taking THC. Given the paucity of such evidence, there should be little if any need for “medical marijuana.” One might wonder, therefore, why states would be passing laws to authorize physicians to provide prescriptions for a drug whose sale technically violates federal law, and for which a superior substitute is already available and FDA approved. The answer, of course, is that marijuana is widely smoked or ingested as a recreational drug, but there is not yet a consensus in most states or in the federal government to permit it to be sold legally. Some legislators worry about the health risks of marijuana, although it is relatively harmless compared to the 2 most commonly used, legal mind-altering substances, tobacco and alcohol, both of which are clearly lethal in large numbers of users. Other lawmakers worry that marijuana is a portal to other illegal drugs. But our past experience with prohibition of alcohol shows that making a commonly used intoxicant illegal generates widespread contempt for the law and makes the drug profitable for criminal enterprises. In states where marijuana is sold only by criminals, the recreational user is driven into the hands of unscrupulous people who would like to sell him or her other, more profitable and more highly addicting drugs. States that are unable to pass a law decriminalizing marijuana instead turn to “medical marijuana” as a pretext for bypassing the state and federal legal systems. A walk down the boardwalk at Venice Beach in California, where there are numerous sites offering medical prescrip-
14
tions for marijuana, would convince anyone that the supposed medical nature of this access is not being taken seriously. “Medical marijuana” is simply a way for timid legislators to dump the problem of recreational marijuana access onto the medical community. But just as criminalizing a widely used intoxicant undermines respect for the law, medicalizing the use of that intoxicant degrades respect for the medical profession. Providing access to recreational marijuana is not, fundamentally, a medical issue. The doctor–patient relationship should not be burdened with having to provide a fix for the failure of our legislators.
Potential Conflicts of Interest Nothing to report. Clifford B. Saper, MD, PhD Editor-in-Chief
References 1.
Andries A, Frystyk J, Flyvbjerg A, et al. Dronabinol in severe, enduring anorexia nervosa: a randomized controlled trial. Int J Eat Disord 2014;47:18–23.
2.
Cooper ZD, Comer SD, Haney M. Comparison of the analgesic effects of dronabinol and smoked marijuana in daily marijuana smokers. Neuropsychopharmacology 2013;38:1984–1992.
3.
Issa MA, Narang S, Jamison RN, et al. The subjective psychoactive effects of oral dronabinol studied in a randomized, controlled crossover clinical trial for pain. Clin J Pain 2014;30:472–478.
DOI: 10.1002/ana.24327
Volume 77, No. 1
