Beyond CBD: Here come the other cannabinoids, but where’s the evidence?
In the span of a few years, the component of cannabis called CBD (cannabidiol) went from being a relatively obscure molecule to a healthcare fad that has swept the world, spawning billions in sales, millions of users, CBD workout clothing, pillowcases, hamburgers, ice cream — you name it. The concerns of such a rapid adoption are that enthusiasm might be soaring high above the actual science, and that there are safety issues, such as drug interactions, that are given short shrift in the enthusiasm to treat chronic pain, insomnia, anxiety, and many of the other conditions that CBD is believed to help alleviate.
Cannabis, however, consists of about 600 different molecules, some 140 of which are called cannabinoids because they work on our body’s endocannabinoid system — a vast system of chemical messengers and receptors that help control many of our most critical bodily systems such as appetite, inflammation, temperature, emotional processing, memory, and learning. It was only a matter of time until new cannabinoids were discovered and commercialized.
What are some of these newer cannabinoids, and what is the evidence they may help us?
Unfortunately, much of the data for these newly discovered compounds comes from animal studies, so it is going to take some time — and high-quality research — to determine if the benefits that have been found in animals will apply to humans.
CBG, or cannabigerol, is a nonintoxicating cannabinoid that is being marketed for the alleviation of anxiety, pain, infection, inflammation, nausea, and even the treatment of cancer. It has a wide variety of potential medical uses, but virtually all of the studies that have been done on it have been done in animals, so it is difficult to fully extrapolate to humans. Experiments in mice have shown that it can decrease inflammation associated with inflammatory bowel disease, and that it can slow the growth of colorectal cancer. In cells, it inhibits glioblastoma multiforme cells (the type of brain cancer that Senator John McCain suffered from).
CBG has also been shown to act as an antimicrobial against many different agents, including the difficult-to-treat MRSA bug that causes so many hospital-acquired infections. Additionally, CBG is an appetite stimulant, and it may help treat bladder contractions. Currently, one main danger in its use lies in the lack of regulation and standardization that accompanies the entire supplement industry in this country, so it isn’t always guaranteed that you are getting what you think you are getting — and this is true for all of the substances discussed in this post.
THCV, or tetrahydrocannabivarin, is potentially exciting because it may support efforts to treat our obesity and diabetes epidemics. There is robust animal data that it lowers fasting insulin levels, facilitates weight loss, and improves glycemic control. In a 2016 study published in Diabetes Care, THCV was shown to significantly improve fasting glucose, pancreatic beta cell function (the cells that make insulin and that ultimately fail in diabetes), as well as several other hormones associated with diabetes. In both animals and humans, it has been well tolerated without significant side effects. In places like Israel, where the study of cannabinoids is far more advanced than the United States, strains with high levels of cannabinoids such as THCV (and low levels of THC) are being cultivated so that they can be studied.
The cannabinoid CBN, or cannabinol, is present in trace amounts in the cannabis plant, but is mainly a byproduct of the degradation of THC. Marijuana that has been sitting around for too long has a reputation for becoming “sleepy old marijuana” — purportedly because of higher CBN concentrations in it, though there are other plausible explanations for this phenomenon. CBN is widely marketed for its sedative and sleep-inducing qualities, but if you review the literature, it is interesting to note that there is virtually no scientific evidence that CBN makes you sleepy, except for one study of rats that were already on barbiturates, and who slept longer when CBN was added. This isn’t to say that CBN doesn’t make people sleepy — as many people claim — just that it hasn’t been scientifically established yet.
Usually with claims about cannabinoids, there is some evidence, at least in animal studies, to back them. CBN does, however, have potential (though only in animal studies so far) to act as an appetite stimulant and an anti-inflammatory agent — both extremely important medical uses, if they pan out in humans. One recent study from Israel in humans demonstrated that strains of cannabis higher in CBN were associated with better symptom control of ADHD. We need more human studies before marketing claims about the benefits of CBN are supported by science.
Delta-8-THC is found in trace quantities in cannabis, but can be distilled and synthesized from hemp. It is increasingly being marketed as medical marijuana with less of the high and less of the anxiety that can come with this high. Unlike the other compounds discussed here, Delta-8-THC is an intoxicating cannabinoid, but it has only a fraction of the high that THC causes — and much less of the accompanying anxiety and paranoia. It can alleviate many of the same symptoms that cannabis can, making it a potentially attractive medicine for people who want little to do with the high of cannabis. It is thought to be especially helpful for nausea and appetite stimulation. There is some evidence (albeit from a very small study of 10 children) that suggests delta-8-THC may be an effective option to prevent vomiting during chemotherapy treatments for cancer. While the claims for delta-8 are intriguing, there is a lack of good human studies to substantiate its efficacy or safety, so we need to take the marketing claims with a grain of salt.
There is renewed interest in cannabis research
As acceptance of medical cannabis is growing — currently, 94% of Americans support legal access to medical cannabis — the one thing that virtually everyone agrees on is the need for further research into cannabis and cannabinoids: their benefits, their harms, and the ways we can develop and safely use them to improve human health. We are in the midst of an incredibly exciting time, with new discoveries occurring daily in cannabinoid science, and I am eager to see what the future holds. However, just as we’ve learned from our experiences with CBD, we need to be patient and filter our enthusiasm through the calm lens of science. Most of all, we need to be smart consumers who can find the true benefits amidst the complexity of political agendas and marketing claims that seem to accompany all things related to cannabis.
There are few subjects that can stir up stronger emotions among doctors, scientists, researchers, policy makers, and the public than medical marijuana. Is it safe? Should it be legal? Decriminalized? Has its effectiveness been proven? What conditions is it useful for? Is it addictive? How do we keep it out of the hands of teenagers? Is it really the "wonder drug" that people claim it is? Is medical marijuana just a ploy to legalize marijuana in general?
These are just a few of the excellent questions around this subject, questions that I am going to studiously avoid so we can focus on two specific areas: why do patients find it useful, and how can they discuss it with their doctor?
Marijuana is currently legal, on the state level, in 29 states, and in Washington, DC. It is still illegal from the federal government’s perspective. The Obama administration did not make prosecuting medical marijuana even a minor priority. President Donald Trump promised not to interfere with people who use medical marijuana, though his administration is currently threatening to reverse this policy. About 85% of Americans support legalizing medical marijuana, and it is estimated that at least several million Americans currently use it.
Marijuana without the high
Least controversial is the extract from the hemp plant known as CBD (which stands for cannabidiol) because this component of marijuana has little, if any, intoxicating properties. Marijuana itself has more than 100 active components. THC (which stands for tetrahydrocannabinol) is the chemical that causes the "high" that goes along with marijuana consumption. CBD-dominant strains have little or no THC, so patients report very little if any alteration in consciousness.
Patients do, however, report many benefits of CBD, from relieving insomnia, anxiety, spasticity, and pain to treating potentially life-threatening conditions such as epilepsy. One particular form of childhood epilepsy called Dravet syndrome is almost impossible to control but responds dramatically to a CBD-dominant strain of marijuana called Charlotte’s Web. The videos of this are dramatic.
Uses of medical marijuana
The most common use for medical marijuana in the United States is for pain control. While marijuana isn’t strong enough for severe pain (for example, post-surgical pain or a broken bone), it is quite effective for the chronic pain that plagues millions of Americans, especially as they age. Part of its allure is that it is clearly safer than opiates (it is impossible to overdose on and far less addictive) and it can take the place of NSAIDs such as Advil or Aleve, if people can’t take them due to problems with their kidneys or ulcers or GERD.
In particular, marijuana appears to ease the pain of multiple sclerosis, and nerve pain in general. This is an area where few other options exist, and those that do, such as Neurontin, Lyrica, or opiates are highly sedating. Patients claim that marijuana allows them to resume their previous activities without feeling completely out of it and disengaged.
Along these lines, marijuana is said to be a fantastic muscle relaxant, and people swear by its ability to lessen tremors in Parkinson’s disease. I have also heard of its use quite successfully for fibromyalgia, endometriosis, interstitial cystitis, and most other conditions where the final common pathway is chronic pain.
Marijuana is also used to manage nausea and weight loss and can be used to treat glaucoma. A highly promising area of research is its use for PTSD in veterans who are returning from combat zones. Many veterans and their therapists report drastic improvement and clamor for more studies, and for a loosening of governmental restrictions on its study. Medical marijuana is also reported to help patients suffering from pain and wasting syndrome associated with HIV, as well as irritable bowel syndrome and Crohn’s disease.
This is not intended to be an inclusive list, but rather to give a brief survey of the types of conditions for which medical marijuana can provide relief. As with all remedies, claims of effectiveness should be critically evaluated and treated with caution.
Talking with your doctor
Many patients find themselves in the situation of wanting to learn more about medical marijuana, but feel embarrassed to bring this up with their doctor. This is in part because the medical community has been, as a whole, overly dismissive of this issue. Doctors are now playing catch-up and trying to keep ahead of their patients’ knowledge on this issue. Other patients are already using medical marijuana, but don’t know how to tell their doctors about this for fear of being chided or criticised.
My advice for patients is to be entirely open and honest with your physicians and to have high expectations of them. Tell them that you consider this to be part of your care and that you expect them to be educated about it, and to be able to at least point you in the direction of the information you need.
My advice for doctors is that whether you are pro, neutral, or against medical marijuana, patients are embracing it, and although we don’t have rigorous studies and "gold standard" proof of the benefits and risks of medical marijuana, we need to learn about it, be open-minded, and above all, be non-judgemental. Otherwise, our patients will seek out other, less reliable sources of information; they will continue to use it, they just won’t tell us, and there will be that much less trust and strength in our doctor-patient relationship. I often hear complaints from other doctors that there isn’t adequate evidence to recommend medical marijuana, but there is even less scientific evidence for sticking our heads in the sand.
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