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Is CBD Oil Bad for Your Liver? Ask a Pharmacist

Posted by Dr. Leslie Mudd, PharmD on Oct 19th 2020

Is CBD Oil Bad for Your Liver? Ask a Pharmacist

Is CBD oil harmful to the liver?

Research from our pharmacist

As people learn more about cannabidiol (CBD) oil and its profound potential health benefits, they become more educated CBD consumers. That’s a good thing. One question advanced CBD users are asking now is: “Is CBD oil bad for your liver?” It’s a natural question for CBD users to ask because CBD is a compound that gets processed and digested in part by your liver.

If you’re a person who is taking CBD oil regularly, you may start to wonder if taking CBD oil will have any long term side effects. One possible long term side effect of CBD products involves your liver.

Concern for how CBD products may impact the liver has increased because a preliminary study on mice published in the summer of 2019 seemed to indicate that very high doses of CBD could affect the liver. Luckily, a human study on the effects of CBD on the liver was published in October 2020 to provide more context and better information.

This study shed new light on the effects of CBD oil on the liver. Here we will review the available literature on the impact of CBD products on the liver, and will look at these two studies from 2019 and 2020 to help CBD consumers better understand the science and the conclusions of these studies.

How is Something “Bad” for the Liver?

The liver is the largest solid organ in the body. It is classified as a gland and has many functions—nearly 500 of them. One of the liver’s main jobs is to filter the blood and break down nutrients and compounds. During this process, the liver metabolizes drugs into forms that are nontoxic and easier to use or excrete.

Certain substances can be harmful to the liver and result in inflammation. These substances can be anything—foods, pharmaceutical drugs, herbs, alcohol, chemicals, etc. This inflammation can occur soon after the exposure or develop over time. When drugs injure the liver and upset its normal function, certain blood tests—liver function tests—may be abnormal. This is because enzymes leak from a liver damage and are elevated in the blood. Other symptoms of liver inflammation might include a yellowing of the skin, abdominal pain, rash, or dark colored urine.

What is CBD?

Cannabidiol (CBD) is one the many cannabinoids found in the cannabis plant. Since becoming legal, hemp derived CBD oil has become a very popular wellness supplement in the past few years. This is because CBD shows remarkable potential to help with a wide range of health issues, according to anecdotal reports and pre-clinical data.

Currently, there is a drug approved by the US Food and Drug Administration that is isolated from single molecule CBD. This drug is administered in prescribed doses to children with certain types of seizure-inducing conditions. These prescription doses seem very high when compared to full spectrum CBD oil. Part of the FDA approval process examined how this drug affected liver function, and the FDA approved the drug with a warning in the label about the risk of liver damage. This risk is greater when used with other pharmaceutical drugs. The FDA states that liver damage was most likely related to high doses. 

The maximum recommended dosage for this FDA approved drug in patients with mild hepatic impairment is 20 mg per kilogram of body weight per day. To help with the math — an adult who weighs 200 pounds translates into 90 kg. So the maximum dose for this drug approved by the FDA is 1,800 mg per day for a 200-pound adult.1

Why is CBD and Liver Interaction Important?

The liver is the organ that digests and processes many medicines and other compounds that enter the body, especially through the digestive system. This includes CBD. What we know from preliminary research is that CBD impacts the function of the Cytochrome P 450 system of enzymes found in the lipid bi-layer of hepatocytes in the liver.

This same liver enzymes pathway is affected by grapefruit juice. So in an interesting twist, CBD seems to affect the metabolism of drugs that come with a “grapefruit juice warning.” This is especially true with certain blood thinner medications.2

That’s why this issue of CBD’s influence on liver function is so important for CBD users to properly understand. There have been at least two studies on CBD interactions with liver function. This post will look at both beginning with an animal study published in 2019 and a phase-1 clinical trial in humans published in October 2020.

The 2019 CBD-Liver Study from Arkansas

In April 2109, researchers from the University of Arkansas published a study in the journal Molecules that claimed to describe “hepatotoxicity,” or liver damage, in mice who had been taking CBD. The study used a full spectrum CBD extract made from government-supplied cannabis and using hexane as a solvent. While hexane is commonly used in food grade oil extraction, one would hope that it is all removed. Hexane is poisonous and a neurotoxin and adds to air pollution. 

The study initially used a dose of 246 mg/kg. This is the Mouse Equivalent Dose (MED) of the normal prescription human dose of 20 mg/kg. To evaluate liver toxicity, they then used 738 mg/kg, which is 3 times the normal dose, and 2460 mg/kg, which is 10 times the normal dose. The researchers observed “overt toxicity” of CBD in the liver of the mice in the study at the 2460 mg/kg. The authors said that this high dose of CBD is not applicable to normal conditions, but does indicate the potential consequences of a CBD overdose.3

This study began to get national attention after Forbes wrote about it in June 2019 with the headline “Marijuana Study Finds CBD Can Cause Liver Damage.” The author said, “People that use CBD are at an elevated risk for liver toxicity.”4

Questionable Findings in the Arkansas Study

Instantly, observers began to call the veracity of the Arkansas study into question. Leafly, the cannabis news site, called the Forbes story “clickbait media panic." Noting that the information is from mice—not people.5  

Project CBD, a California-based non-profit organization on a mission to educate the public about CBD, published a full rebuttal of the Arkansas study and the Forbes article, calling it “a single, flawed, preclinical study [that is] exaggerate[d] to the point of falsehood.”6 

The author of the Forbes piece had quipped in his conclusion, “It’s hard to argue with dead mice.” But the author at Project CBD had no problem doing so, calling the Forbes’ statement “Nonsense.” The Project CBD author goes on to say, “Even if we suspend our disbelief and look past every problem described thus far, a dead mouse... isnt proof of what happens to a human.” 

Animal Studies vs Human Studies

Educated consumers need not pay much attention to this study in mice — because it doesn’t directly translate to a drug’s effect in humans. In short, it is difficult to extrapolate findings from a study of small animals into an understanding on how that drug might affect humans. At best, these mice have given their all to show us potential toxicities at 10 times the normal prescription dose.

In clinical terms, this is a problem of allometric scaling. Allometry is the study of biological size relative to other organisms and how an organism’s size affects behavior, such as metabolism. Mice have far greater metabolisms than humans because of their smaller size.

This means that the Arkansas study does not mean much for humans because of the tremendously high dose. This study has caused confusion about the safety of CBD, just as people began to exhibit higher levels of interest in this cannabinoid. Project CBD called the Arkansas study “a hit piece against CBD, not legitimate scientific work.”

The October 2020 CBD-Liver Study

What had been missing from this conversation was a reputable study in humans of the effects of CBD on the liver. As of October 2020, we finally have one, published by the American Society for Clinical Pharmacology & Therapeutics.7

There have been studies on CBD-Liver interaction in mice, and in children as part of the FDA approval process for a CBD-based drug used to treat certain types of seizure-inducing diseases in children. However, until the study  (ASCPT) was published, there were only anecdotal reports of CBD-Liver inaction in healthy adult humans.

The study enrolled 16 health adults in a phase 1, open-label, fixed single-sequence drug-drug interaction trial to investigate the effects of CBD on the cytochrome P450 activity in the liver. Researchers administered CBD to each adult for 3.5 weeks at the rate of 1,500 mg of CBD per day.

For context, 1,500 mg of CBD per day is a normal prescription dose and far more realistic than the Arkansas study giving mice megadoses of CBD equal to a quarter of their body weight. As for dosing recommendations for CBD for wellness, 1,500 mg of CBD per day is 60 times the starting dose as recommended by Cornbread Hemp. Cornbread Hemp offers our USDA certified organic CBD oils in 1,500 mg per 1oz bottles, and we assume a customer will use that bottle for a month or two. The ASCPT study assumed healthy adults would be taking this much CBD every day.

Even despite this dramatic increase in suggested dosing, the study found that a majority of the healthy adult human subjects could tolerate this megadose of CBD for a period of 3.5 weeks. However, the study did find that 44 percent of subjects “experienced peak serum alanine aminotransferase (ALT) values greater than the upper limit of normal.” And a smaller number, 31 percent, met the criteria for drug-induced liver damage.

This human study is helpful because we now have some baseline other than the Arkansas mouse study to work with, but the high doses of CBD used in this study still remains 30 to 60 times higher than what CBD brands like Cornbread Hemp recommend for a daily dose of CBD.

Choose High Quality CBD

Cornbread Hemp is a family owned company that sources organic hemp from Kentucky. Only the flowering parts of the hemp plant are used for our extracts. This, coupled with our organic sugarcane ethanol extraction process, leaves the end product smooth and tasting great without the need for added flavors or sweeteners.

We are the first company in the region to attain a USDA organic certification on CBD oils. This official seal is indicative of a high quality CBD product by automatically ensuring that the products are free of any pesticides or toxins.

The safety and potency of all Cornbread Hemp CBD products are backed by third-party lab analysis, accessible via scannable QR code on each product's packaging. The COA tells you exactly how much CBD and THC are in every bottle.

Bottom Line: CBD's Effect on the Liver

If you suffer from fragile liver health due to a pre-existing condition, it is important to discuss using CBD with your doctor because, as these studies point out, high doses of CBD could interact with a key liver function controlled by cytochrome P450 liver enzymes.

In healthy adults, doses of CBD that are under 300 mg per day appear to be safe to use for general health and wellness. However, we still need more studies on adult humans at this dosage level to know for sure. More research is being done but results are not yet available.

If you take any medications that come with a “grapefruit juice warning,” be sure to ask your doctor of pharmacist before adding CBD to your routine. Otherwise, healthy adults can assume that CBD is safe in the range of 25 mg to 300 mg per day.

References

1.

EPIDIOLEX, Initial U.S. Approval. US Food and Drug Administration. June 2018. Accessed on 20 Oct., 2020: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210365lbl.pdf 

2.

Grinspoon, P. "Cannabidiol (CBD) -- What we know and what we don't." Harvard Health Blog. August 24, 2018. Accessed: 20 Oct., 2020: https://www.health.harvard.edu/blog/cannabidiol-cbd-what-we-know-and-what-we-dont-2018082414476

3.

Ewing, L. et al. "Hepatotoxicity of a Cannabidiol-Rich Cannabis Extract in the Mouse Model." Molecules. 11 April 2019. Accessed 20 Oct. 2020: https://www.mdpi.com/1420-3049/24/9/1694/htm

4.

Adams, M. "Marijuana Study Finds CBD Can Cause Liver Damage." Forbes. 18 June 2019. Accessed 20 Oct. 2020: https://www.forbes.com/sites/mikeadams/2019/06/18/marijuana-study-finds-cbd-can-cause-liver-damage/#5b2b8f0c43ff

5.

Bienenstock, D. "That alarming CBD liver damage study is bunk -- and the media should know better." Leafly. 12 July 2019. Accessed 20 Oct. 2020: https://www.leafly.com/news/industry/alarming-cbd-liver-damage-study-is-bunk

6.

Devitt-Lee, A. "Is CBD Toxic to the Liver?" Project CBD. 11 July 2019, updated 2 December 2019. Accessed 20 Oct. 2020: https://www.projectcbd.org/science/cbd-toxic-liver

7.

Watkins, P. et al. Cannabidiol and Abnormal Liver Chemistries in Healthy Adults: Results o a Phase 1 Clinical Trial. Clinial Pharmacology & Therapeutics. 06 Oct. 2020. Accessed 20 Oct. 2020: https://ascpt.onlinelibrary.wiley.com/doi/abs/10.1002/cpt.2071#.X3-OUr2cLu0.linkedin

All rights reserved. The statements made regarding cannabidiol (CBD) products have not been evaluated by the Food and Drug Administration. The efficacy of CBD products has not been confirmed by FDA-approved research. CBD products are not intended to diagnose, treat, cure or prevent any disease. All information presented here is not meant as a substitute for or alternative to information from health care practitioners. Please consult your health care professional about potential interactions or other possible complications before using any product.