If you’ve spoken to a health professional, or Dr. Google, about CBD use, you might have heard that while it is generally safe, some people with known liver issues are told to avoid it. Additionally, someone may be advised to avoid CBD if they take other medications or supplements which can affect liver enzymes, such as blood thinners. Why is this? Does CBD cause liver issues or exacerbate liver damage? Do higher doses increase the risks of liver problems? How much research has been done on this topic so that we know the answers to these questions. Hopefully this article will answer all of these questions for you so you can make the best decision about the role of CBD in your health.
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First, it’s important to know where the idea that CBD may interfere with the liver comes from, so what evidence has been found for this? These concerns primarily come from a number of clinical trials in which CBD has been used to treat children and adults with seizure disorders, through a medication called Epidiolex. Although it has a branded name, Epidiolex is just high-dose CBD isolate oil. Thanks to the clinical trials for this medication, the safety of CBD, and its effect on the liver, are well understood. In fact, there is enough clinical data surrounding it that Epidiolex is FDA approved for use in adults and children with various seizure disorders. So, what do we know about its effect on the liver?
The Safety of Epidiolex
In some studies investigating Epidiolex, elevated liver enzymes (specifically AST) were noted as a possible adverse reaction in some participants. In these studies, about ten percent of study participants developed elevated AST levels. The likelihood of these AST changes was more likely at higher doses. Notably, all but a few of these cases resolved on their own, either spontaneously without any intervention, or after CBD doses (or doses of other medications the participant was taking) were lowered. The remaining few resolved when CBD was stopped. No participants experienced any symptoms of liver problems (such as abdominal pain, nausea, or excess fluid accumulation), nor any lasting enzyme elevation, nor any notable decline in liver function. In fact, each of these studies ends by noting that CBD can be a good option for treating seizure disorders in both adults and children, and has an acceptable side-affect profile.
So, will you have a ten percent chance of developing elevated ASTs if you take CBD? Actually, no! The rate is much lower than this for typical users of CBD, because normal users take much, much less CBD than is used in these clinical trials. In these studies, participants were taking 10-30 milligrams of CBD per kilogram of body weight per day. For example, this means a 200Ib man in this trial would be taking 900-2700 mg of CBD each day over the course of the trial! This is a good dose for treating moderate-severe seizure disorders but is much higher than an average over-the-counter CBD user will ever need or want to use. For a typical person looking to soothe anxiety, sleeplessness, or pain we recommended starting with as little as 5 mg twice a day, up to about 150 mg twice a day. This is clearly not the upper amount of CBD that is safe (based on how much the above studies use), it is simply the amount that we (and many other organizations) find can be helpful for addressing common concerns while managing the severity of side-effects such as drowsiness.
Not only do most typical people take much less CBD than was used in these clinical settings, but additionally, most participants in these studies were also taking one or multiple additional medications, especially valproic acid (Depakote) to treat their seizures. Valproic acid is known to cause acute liver toxicity on its own, and must be provided with lots of caution and frequent monitoring. As such, it is very hard to tell if CBD was truly the cause of any liver changes, if it was other medications interacting with the CBD, or if it is only at these very high doses of CBD. Either way, the FDA did approve this medication for prescription use, and no participants experienced any lasting liver changes after the studies.
CBD as an Antioxidant
These trials for Epidiolex, both from before it was approved and since it has been available generally, are one of the biggest sources of information on the safety of CBD. However, there is even more research into this topic than that. For example, multiple studies have found that CBD is at least somewhat protective from oxidative stress. Oxidative stress is when there are excess reactive molecules interfering with the ability of your cells to do their jobs. It is why so much of a point is made about antioxidants, which are opposing molecules that help reduce the amount of oxidative stress being experienced by the body. CBD is a very effective antioxidant and can tackle many different oxidative agents in the body at once. Oxidation is also closely tied to inflammation, because one of the biggest and most common sources of oxidative stress in the body is inflammation caused by the immune system being activated. Whether because of an acute illness, or a chronic health concern, immune-mediated inflammation is a large cause of excess oxidation in the body. Obviously, some amount of immune response is necessary to keep us healthy, but even necessary immune actions can lead to an increase in reactive oxidizers running-amok.
This inflammation caused by the immune system is especially noticeable to the liver because it is responsible for filtering out excess gunk that our bodies want to get rid of. As such, it is often a center of oxidative stress, especially when someone is healing from an injury or short-term illness. In this case, CBD may in fact be protective of the liver, because it helps counteract any reactive molecules which are present in excess. For example, one study, which was specifically investigating inflammation and injury due to different types of surgery on the liver itself found that administration of CBD “significantly reduced the extent of liver inflammation, oxidative/nitrative stress, and cell death.” Essentially, CBD helped participants of this study, which in this case were lab mice, recover better and faster from liver operations and transplants. Very similar results were found in another study which was looking into the effects of CBD on cardiomyopathy, using both mice and isolated human heart cells. Again, CBD reduced oxidative and nitrative stresses, cell fibrosis (scarring) and improved overall function. Since these were not people, more research needed to be done in this arena, and it was! Several years later another study was done observing human subjects who were receiving bone-marrow transplants, and found that CBD significantly reduced graft-versus-host-disease, which is a common type of transplant rejection, compared to previous patients. The authors posit that it was able to do this, again, because of its anti-inflammatory and immune modulating properties. This is still a growing field of research, but it really seems that CBD may be protective to many different types of cells when going through various kinds of stressful recovery.
CBD’s Possible Impact on the Absorption of Other Medications
All of this is pretty promising on the part of CBD, but there is one more reason why someone might avoid it based on its effects on the liver: it may change how some things are absorbed by the body. In this case, the concern is not what CBD might do to the liver, but what it might do to another medication that a person is taking. This is again most well-studied in the context of epilepsy, where it has been found to potentially increase the bioavailability of drugs like Clobazam. This is because CBD (and THC, and potentially other cannabinoids as well) affect some of the enzymes found normally in the liver and modify how they interact with other substances. In the case of some participants taking Clobezam, they experienced increased side-effects typical of Clobezam, such as sedation, and needed to have their doses lowered. Now, this could potentially be a benefit of CBD if it is planned for. Afterall, it is usually the recommendation of physicians to be on as low a possible dose of needed medications. However, if someone is not aware of this effect, and is suddenly getting a functionally higher dose of a medication than they were planning for, there could be problems. This may be one of the forces at play in individuals who experienced elevated liver enzymes when adding CBD to a seizure-control regimen. It is possible the CBD was not influencing their liver directly but was changing how much of an effective dose of their other medications they were receiving.
This effect has also been potentially observed regarding blood thinners. In that case, CBD may make it so that less of the medication is absorbed. This is why blood thinners are mentioned at the top of this article and are one of the biggest reasons why caution may be needed when adding CBD to a lifestyle. Blood thinners are serious drugs, which are needed to prevent things like strokes and heart attacks in vulnerable people. If CBD changes how they are absorbed, and it is not realized, an adverse event could happen if there is not close monitoring of blood-clotting factors.
This enzyme-modification is the biggest reason that physicians and others will recommend caution when adding CBD to a drug-regimen. This effect would not necessarily preclude someone from taking CBD, but it is a good reason to pay close attention to the usual side-effect profile and stay in close touch with a doctor in case any modifications need to be made.
The Bottom Line on CBD and the Liver
With all of that said, why would medical professionals potentially recommend avoiding CBD in the name of your liver? If it barely causes liver concerns even in very high doses, hardly has any adverse reactions in more typical doses, and has a “favorable safety profile” in literature reviews of studies done about it, what’s the concern? Well, qualified people giving medical advice always want to be as cautious as possible. After all, it’s your health on the line. So, even when something is proven to be generally safe, as CBD has been, it can be good to be cautious anyway. That said, the bottom line is that CBD has been repeatedly proven to be appropriate for use by many types of people with many other health issues and has never been found to cause any kind of clinically significant liver injury. If you are concerned about the wellbeing of your liver for any reason, such as a history of elevated liver enzymes, it is safest to ask your doctor about their opinion of CBD in the context of your personal health history. They may recommend that you don’t add CBD to your routine out of an abundance of caution, but they might find that you can be one of the many, many people who uses CBD to improve your health and wellbeing.
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