I remain cautiously optimistic that cannabidiol will someday become another weapon in our arsenal of anti-seizure drugs, but we are not there yet.
As a follow-on from my previous post about alternative medicine, I want to discuss the current state of medical marijuana. This is one of the hottest and most contentious topics in alternative medicine at present, and efforts to bring it under the umbrella of mainstream medicine are active and quite promising. Marijuana plants contain two chemical compounds of particular interest, tetrahydrocannabinol (THC), and cannabidiol (CBD). THC is thought to be the cause of most of the harmful effects of marijuana use, including its addiction potential, and is probably responsible for the low educational achievement of adolescent marijuana users. Most of the current medical research is focused on the potential therapeutic effects of CBD, which seems to have little of the baggage that comes along with THC.
The term “medical marijuana” means different things to different people. For medical professionals it means medicines derived from marijuana compounds, properly vetted through pharmaceutical research trials. I think it is fair to say that most doctors are in favor of this, in the same way that we are also in favor of properly vetted medicines derived from literally anything else (cone snail venom, leeches, Clostridium botulinum, human blood, etc.). “Properly vetted” is the key phrase, and I spent some time elaborating on this in my previous post.
Before we get too deep into things, let me share an anecdote. About a year ago an older gentleman, who is a member of the LDS Church, sat in my clinic complaining of a hand tremor (which was caused by an albuterol inhaler). His son had given him a bottle of CBD oil, which he had been using to quiet down the tremor. While we talked the man pulled the bottle of oil out of his pocket and sprayed it under his tongue, then we watched as his tremor markedly reduced over the next minute. After this very interesting demonstration, the man turned to me and asked, “So, is this against the Word of Wisdom?”
I was surprised at such a direct theological question in my medical clinic, and I didn’t feel comfortable giving a definitive yes or no answer in that setting, so I told him to ask his bishop. People shouldn’t come to my clinic for religious advice. He wasn’t satisfied with that answer, so I offered him the following discussion, which I often share with patients who ask about medical marijuana. Again, please refer to my disclaimer to keep this post in context.
The Three Hurdles
Currently I see three major hurdles to widespread appropriate medical marijuana: 1) legal, 2) scientific, and 3) pharmacologic. I would like to see all three of them cleared before I will recommend its use to my patients.
I am not a lawyer, so my discussion of the legal aspects of medical marijuana should not be considered authoritative, but I will present the issues as I understand them. The United States Department of Justice includes the Drug Enforcement Administration, which is the primary enforcement agency for the Controlled Substances Act (CSA). The CSA categorizes controlled substances into a graded schedule, depending on their potential for abuse, accepted medical uses, and safety considerations. Here is a summary table:
|Schedule||Accepted Medical Uses||Potential for abuse, Psychological or Physical Dependence||Familiar Examples|
|I||No||Unacceptably high risk, lack of accepted safety||heroin, LSD, marijuana|
|II||Yes||Severe||amphetamines, cocaine, morphine, oxycodone|
|III||Yes||Moderate or low||ketamine, anabolic steroids, buprenorphine|
|IV||Yes||Lower than III||benzodiazepines, phenobarbital, modafinil, tramadol|
|V||Yes||Lower than IV||pregabalin, lacosamide, codeine-containing cough suppressant|
As you can see, marijuana is currently listed as a schedule I controlled substance, meaning that it has no accepted medical uses, high abuse potential, and a lack of accepted safety. I happen to disagree with this classification, as I will explain below, but the fact remains that as of this writing, use or possession of marijuana and all of its derivatives (including CBD oil derived from hemp) is illegal under federal law in all 50 states. Individual states which have “legalized” marijuana for medical or recreational use have done so in defiance of United States law, and federal law supersedes state law under the Constitution. The Obama Justice Department maintained a policy of non-enforcement of federal law in states which legalize marijuana, and this has more or less continued under the Trump administration, although the attorney general has threatened to alter this policy.
Every year we are learning more about the biology and pharmacologic properties of marijuana-derived compounds. Just a few years ago the level of evidence supporting medical marijuana was only slightly better than Joe the Pot Smoker saying to his buddies, “Hey, man. I haven’t had a seizure since I started smoking this!” But now we have a few well-designed and well-executed clinical trials showing that CBD oil is effective at lowering seizure frequency in devastating childhood epilepsy syndromes. We are also learning about the safety profile of these compounds, and there are definitely side effects which will complicate their usage in the clinic.
This evidence is promising, but it is not yet sufficient. The available data would not be enough to get FDA approval of an investigational new drug. As of today less than 500 patients have been reported in placebo-controlled trials, which is a very small number in this context. Also, we have no good data at this point to guide our use of this drug in people with milder forms of epilepsy, no information about long-term efficacy or long-term side effects, and very limited information about interactions with other drugs. I remain cautiously optimistic that CBD will someday become another weapon in our arsenal of anti-seizure drugs, but we are not there yet.
Proponents of medical marijuana have also advocated its use for tremors, multiple sclerosis, Alzheimer disease, and many others. The level of evidence for using marijuana to treat most of these other conditions is still near the “Joe the Pot Smoker” level, mainly anecdote, case series, and open-label studies. One exception is chronic pain, where a few small placebo-controlled studies of smoking marijuana have shown some benefit.
The third problem right now is the lack of regulation and pharmaceutical rigor among producers and distributors of marijuana products intended for medicinal use. Preparations are not consistent or reliable from manufacturer to manufacturer, or even sometimes from batch to batch. Some suppliers are better than others, and the higher quality trials have tended to use the better manufacturers. But currently I don’t have any kind of confidence that my patient would consistently get the dose I prescribe, and that is a big problem when you are treating epilepsy, where some patients will have a breakthrough seizure after missing a single dose of their medications.
This third obstacle is probably the least important for me, as I could see myself working with whatever is available on the market as long as the legal and scientific questions are satisfied. But I really want all three problems resolved. The preponderance of evidence suggests that marijuana, and at least CBD, should be moved out of the schedule I classification to a lower level. This will allow better research and development of the therapeutic uses. I disagree with making marijuana legal for recreational or indiscriminate use, as THC is clearly an addictive and damaging drug, and exacts a particular toll on adolescent users. (If there were a prescription drug with the side effects listed on that link, no one would ever take it.) In an ideal world I would like to write a prescription for a pharmacologic-grade CBD or a synthetic CBD analog, which my patients take to a pharmacy to fill like any other prescription drug.
Is there a specific Church teaching about medical marijuana? There are some guiding principles. The Word of Wisdom is generally considered to be a prohibition against using illicit addictive substances, including marijuana. But we are not really talking about recreational use here, and medications prescribed by doctors, if done responsibly and used as directed, are considered okay even if the illicit or addictive use of the same drugs would be considered wrong. I think a similar principle would apply to the medical use of marijuana under medical supervision, which would be analogous to an opioid prescription.
Latter-day Saints are law-abiding people, as declared in our 12th Article of Faith: “We believe in being subject to kings, presidents, rulers, and magistrates, and in obeying, honoring, and sustaining the law.” On the specific topic of health care the Church Handbook states, “Members should not use medical or health practices that are ethically or legally questionable” (Handbook 2, 21.3.6). I think it is fair to say that medical marijuana is legally questionable at this point in time. Of the three hurdles listed above, the legal problem is by far the most important one for me.
While I was working on an early draft of this post, the First Presidency of the Church issued a statement in response to a Utah Medical Association statement about medical marijuana. (Disclosure: I practice in Utah, but I am not a member of UMA.) There is currently a petition to place a statewide ballot initiative on the November election ballot to broaden the legality of medical marijuana in Utah, and the UMA is strongly against it for many reasons. Their statement aligns pretty well with the concerns I have laid out above, such as this statement, “Utah’s physician community is greatly interested in discovering the legitimate medical uses of cannabis‐based medicines, but the Utah initiative is not the way to do it. Real science takes time and careful, unbiased research.” There are already legal mechanisms to obtain CBD oil in Utah (legal at the state-level, anyway), so this proposed law is addressing a problem which already has an implemented solution.
The First Presidency statement commends the UMA, and includes this summary line: “The public interest is best served when all new drugs designed to relieve suffering and illness and the procedures by which they are made available to the public undergo the scrutiny of medical scientists and official approval bodies.” This is especially true when the new drugs are derived from a controlled substance.
Making Sense of the Clamor
Despite the reasoned and principled approach from the UMA and the First Presidency, this announcement was met with a sarcasm and scorn by many people. This debate illustrates the tension between mainstream medicine and alternative medicine, and understanding the difference between the two approaches helps us make sense of the cacophony. You can hear the tug-of-war in the Twitter responses to the First Presidency statement. Most of the strong advocates of medical marijuana are in the alternative medicine camp, and are already satisfied with the level of anecdotal evidence. They are ready to go large-scale with distribution and use of marijuana, even to treat conditions for which there is no good supporting evidence, with unfettered access like all of the other compounds at the herbalist shop. Among this group there are also some with less pure motives, who are more interested in legalizing and profiting from an addictive drug for recreational use than they are with advancing medicine. Mainstream medicine is approaching the subject with its typical scientific rigor, tempered by its characteristic legal caution, with a goal to produce a high quality product backed by high quality evidence, just like the other prescription-only medications at the pharmacy. The slow pace of scientific progress and the efforts to maintain control over the product is maddening to people in the alternative medicine camp.
The 2018 ballot initiative in Utah isn’t really for “medical marijuana” as I have defined it above. Its result would be closer to a naturopathic or herbalist approach to treating symptoms with marijuana, which is not appropriate when we are dealing with a controlled substance. Would we be comfortable letting an herbalist shop sell opium extracts? Or hallucinogenic mushrooms? That is why the UMA has rejected the marijuana ballot initiative, and why I will vote against it.
Back to the Patient
The patient I described in the opening anecdote, who had used the CBD oil in my clinic, listened while I discussed these three concerns, and then asked another pointed follow-up question to put me on the spot again. “Would you use it if you were me?”
I didn’t think it was my place to answer what I thought was essentially a personal moral question. Also, I figured that the 20 minutes I had just spent giving him all of the reasons why I thought medical marijuana wasn’t ready for prime time were probably enough of an answer. But saying that the scientific evidence is inadequate is not the same thing as saying I wouldn’t use it myself, and anyway he wouldn’t let me off the hook. So I looked him in the eyes and said, “No, I wouldn’t use it.”
Although maybe that’s not entirely accurate. Increasing evidence suggests that the experience known as the “runner’s high” is probably caused by endogenous cannabinoids such as anadamide, which increase in concentration in the bloodstream during exercise. That good feeling I get on a long run, and which I crave on days when I am not running, might just be my own natural and healthy endocannabinoid addiction. As with so many other things in life, the best approach to this controversy might be to stop worrying about it so much and just go running.
But in all seriousness, I think this is an important topic for Latter-day Saints. Our church president is a man with no shallow understanding of this issue, having been a medical doctor at the bleeding edge of medical technology during his career. Notice that neither the UMA nor First Presidency statements contain a condemnation of medical marijuana. They only argue against the slipshod approach of the 2018 ballot initiative. Competing interests here include advancing medical science, providing effective and safe treatments to patients, maintaining law and order, discouraging recreational use of harmful drugs, and community safety. The opinion of UMA and the First Presidency is that the 2018 ballot initiative does a poor job of balancing these, and I agree with that assessment. This is too important an issue to be so sloppy about it, and the stakes are too high to get this wrong.
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