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Cbd oil for elevated liver enzymes

Does CBD Elevate Liver Enzymes?

I am someone who doesn’t trust anything until I have researched it myself. In fact, before I would give my pets full spectrum hemp extract (CBD), I got my certificate in the biology and therapeutic uses of medical cannabis from the University of Vermont Larner College of Medicine. I also made it my mission to share as much research and information with pet parents about cannabis and other holistic modalities as possible.

One of the questions my team and I are asked often is whether CBD is safe and if it has any negative effects on pets. Because of a recent study, a stern warning from the FDA, and negative coverage in mainstream media outlets, the question has been posed: “Does CBD elevate liver enzymes to dangerous levels?” To find out the truth, I consulted the country’s top holistic veterinarians and did a little digging to find the most current research and medical opinion.

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NEW! Study Reports No Evidence of Liver Toxicity Associated With CBD

A New study on the “Observed Impact of Long-term Consumption of Oral Cannabidiol on Liver Function in Healthy Adults” has reported no evidence of liver toxicity associated with CBD. “Observational data gathered from 839 participants — ages 18–75 from across the U.S. and known to be taking hemp-derived CBD products orally for a minimum of 30 days — showed that CBD at the doses consumed in the study is not associated with clinical liver toxicity. Previous studies have suggested that prescribed cannabidiol (CBD) products may cause elevations in liver tests (LT).”

“This study compared the prevalence of elevated LT in an adult population self-administering CBD with the normal and general adult population prevalences. A total of 28,121 individuals were invited to participate in this study, 1475 enrolled, and 839 (female: 65.3%, male: 34.7%) completed the study. Full-spectrum hemp oil was used by 55.7%, CBD-isolate by 40.5%, and broad spectrum by 3.8%. The mean – SD daily dose of CBD was 50.3 + 40.7 mg. The prevalence of elevated ALT was 9.1%, aspartate aminotransferase (AST) 4.0%, alkaline phosphatase 1.9%, total bilirubin 1.7%, with 85.5% of the ALT elevations < 2 · the upper limit of normal (ULN) with only 0.3% having ALT levels >3 · ULN. The prevalence of ALT and AST elevations (9.1% and 4.0%) were not significantly different from known adult general population prevalences (8.9% and 4.9%). There was no significant association between CBD dosage and LT values. Thirty-three individuals with elevated ALT levels had follow-up LT performed with 21 having normal LT, 8 having the same severity of ALT elevation, and 4 having an increase in severity, 1 of which ultimately became normal.”

The results of the study concluded “Self-medication of CBD does not appear to be associated with an increased prevalence of LT elevation and most of the LT elevations are likely due to the conditions/medications for which the individuals are taking CBD.”

What About The Study That Alleged CBD Was Unsafe for Dogs Because of Elevated Liver Enzymes?

The original study that alleged that CBD raised liver enzymes was published in a medical journal called Molecules, and was conducted by the University of Arkansas for Medical Sciences. Researchers looked at the effect of various dosage amounts on mice, using the recommended dosage amount for humans to scale. The study found that mice who received higher doses of CBD showed liver damage within 24 hours, with 75 percent on the brink of death in a matter of days. Scary stuff, right?

There is just one big problem with the study: it was conducted using Epidiolex, an FDA approved CBD isolate, and the dosage was astronomically high. Epidiolex is NOT a full spectrum hemp extract, which means that the entourage effect is not in place and the amounts given were purposefully misleading.

To conduct the experiment, scientists fed mice single doses of CBD ranging from “low” at 246 mg/kg up to a mega-dose of 2460 mg/kg CBD. To break it down, for every kilogram of body weight, they gave the mice about 2.5 grams of CBD. This dose is over ten times the normal dose – which is unreasonably high, and which caused the study to be skewed away from reasonable use from the start. The study’s abstract also presents math that is impossible. Since only 6 mice were studied, 75 percent of mice would have been 4.5, leaving only 1.5 mice to survive. Perhaps it is the animal lover in me, but I do hope that whichever mouse was able to survive in two halves is living a healthy life to this day, but something tells me that this figure is simply incorrect.

Why Would the Makers of Epidiolex Want Negative Results?

Epidiolex is made by a pharmaceutical company called GW Pharmaceuticals, who has taken great pains to corner the market on cannabis. In fact, they routinely lobby for stricter regulations that only they can meet. For example, they have pushed for legislation making it harder for medical cannabis companies to be marketed unless FDA approved. So, pushing researchers to find an issue with liver toxicity can only serve to benefit them by allowing them to be the only company able to provide a product that potentially will NOT elevate enzymes when used as directed. By raising consumer skepticism and fear of cannabis, they can effectively corner the market.

Do Vets Think CBD Is Safe For Dogs?

Dr. Gary Richter, a holistic veterinarian and owner and medical director of Holistic Veterinary Care in Oakland, CA, has been using medical cannabis in his practice for years. After years of research, Dr. Richter has spoken publicly about this study and shares that your pet cannot overdose on CBD, and elevated liver enzymes were reported incorrectly.

“Life-threatening risks for dogs from medical cannabis are exceedingly rare,” Richter says. “Toxicity more often occurs when a pet has eaten a product that contains chocolate, coffee, or raisins. Even if the THC toxicity is not excessive, they can sometimes have problems due to these other ingredients.”

Dr. Richter also notes that most medications, including Tylenol, raise liver enzymes, and when given extremely high doses of these common medications (or small doses over long periods of time) liver damage can occur. However, research has not shown that life-long use of cannabis has an adverse effect on the liver. In fact, it has shown the opposite, because elevated liver enzymes cease as soon as cannabis leaves the system (unlike dangerous pharmaceuticals) and CBD can be tolerated in dogs at very high dosages without fatal side effects.

“You always have to look at the clinical picture. Looking at one study’s research regarding elevated liver enzymes and focusing on it is a fear-based approach to medicine. And, it’s inhibiting our ability to understand this plant as a whole.”- Dr. Zac Pilossoph

Is CBD Safe For Dogs?

Studies have shown that CBD is actually safer for dogs than many widely used prescription medications. In a study conducted by Colorado State University, 10 mg/kg/day or 20mg/kg/day of CBD was administered to dogs for 6 days. CBD was well-tolerated in the study population. There was an elevation in serum ALP in 36 percent of patients, and all other blood parameters were normal – nothing more than a reaction to normal over the counter medications. Six of the 30 dogs had vomiting, and all had mild diarrhea. 11 of 30 dogs experienced erythema of pinna and 10 of 30 dogs experienced nasal and ocular discharge. These effects were significantly safer than many side effects of both over the counter and prescription medications.

CBD and Liver Damage: How Does It Affect Liver Functions?

As the use of CBD is booming across the United States, people have become more aware of its health benefits as well as potential risks associated with the consumption of CBD products.

One recent study has sparked concerns among CBD users when it comes to liver function. While the study did show that extremely large amounts of CBD can damage the liver, the news coverage that warned about the potential risk of taking CBD failed to put the study into context.

It goes without saying that CBD — like any supplement or medication — does have side effects, including dose-dependent danger to liver health. However, while users using the peak-tested dosages should have their liver enzymes in check, the vast majority of people can safely use CBD without worrying about a negative impact on their liver function.

In this article, we’ll explain the context of the said study and provide evidence supporting the health benefits of regular doses of CBD for liver health.

Let’s resolve the doubts surrounding the topic of CBD and liver function.

Is CBD Oil Bad for Your Liver?

CBD has a remarkably good safety profile. Researchers have tested the efficacy and safety of CBD in humans using doses as high as 1,500 mg – 3000 mg CBD daily.

With 1,500 mg of CBD taken for a six-week period, no dangerous side effects were observed (1).

However, the recent 2019 study on mice showed that high doses of CBD can damage the liver — causing widespread sensation all over the media.

The study has also garnered attention among CBD skeptics who have been trying to undermine the therapeutic potential of CBD looking for at least one serious side effect.

Now, we’re not saying CBD doesn’t have any side effects — it does, like any other health supplement — but should you actually worry about your liver when you use normal doses?

Let’s shed some light on the infamous study on mice.

The Study on CBD and the Liver of Mice

According to researchers from the University of Arkansas, who investigated the effects of treatments of various doses of CBD on a group of 8-week-old mice, the study addressed the problem of a “lack of comprehensive toxicological studies devoted to CBD safety that are critical for further marketing of CBD and CBD-containing products.” (2)

The majority of mice tolerated the CBD, but those administered the highest doses — an equivalent to 200 mg of CBD in humans — showed clear symptoms of liver toxicity, as reported by the researchers.

In addition, repeated doses of a smaller amount of CBD (50 mg) also showed signs of liver damage and swelling.

Here’s what the authors wrote at the end of the paper:

“Although (a dose of) 200 mg is not applicable to most real-life scenarios, it does provide critical information regarding the potential consequences of CBD overdose as well as for doses needed for further subchronic and chronic toxicity studies.”

However, one of the caveats of this study was that it tested the maximum recommended daily dosage for humans. While all mammals share the same endocannabinoid system, mice and humans are different physiologically. The size of the liver is just one of the many variables that should be taken into consideration when evaluating the safety of CBD in human subjects.

Experts Say It’s About the Dosage

Although the results of the above study sound potentially discouraging, most experts say there’s no need to freak out over the impact of CBD on the liver. While experts stress the importance of knowing the risks of taking health supplements, the amount of CBD the mice were exposed to is much higher than what most humans take.

According to Dr. Diana Martins-Welch, attending physician in palliative medicine at Northwell Health in New Hyde Park, New York, there are certain quantities in which CBD may not be safe for humans; CBD also isn’t always more effective in high doses.

“Many people know that taking too much ibuprofen or Tylenol can have detrimental consequences. CBD is no different. Generally speaking, therapeutic CBD doses range from 0.5 mg/kg/day to 20 mg/kg per day. This study in mice used significantly higher doses of CBD (in relation to their weight) than what is usually taken for therapeutic benefit in humans.” Martins-Welch explained.

Martins-Welch also said that therapeutic-range CBD is generally safe, and while toxicity at extremely high doses is a concern, it is no different than with other supplements or medicines.

Therefore, what the study essentially showed was how people need to be careful if they take high doses of CBD daily.

Human studies that have examined the safety of different doses of CBD have found no negative effects at the recommended maximum daily dosage of 20 mg/kg. This dosage was taken from the trial of Epidiolex, a CBD-based pharmaceutical for treatment-resistant seizures. To put that in context, an individual weighing 150 pounds would need to take over 1,300 mg of CBD per day, which is way above what most people take (10–80 mg daily).

Effects of CBD On the Liver

Okay, so now you know that extremely high doses of CBD may cause liver toxicity when taken regularly. You also know that it’s impossible to trigger toxicity with normal doses of CBD oil.

Now it’s time to ask a different question: what positive effects does CBD have on the liver?

There are plenty, to be honest.

In the next section, we elaborate on the potential therapeutic uses of CBD oil for liver function.

CBD Oil for Fatty Liver

The endocannabinoid system (ECS) is found in all mammals and consists of receptors (CB1 and CB2) endogenous cannabinoids, and enzymes that facilitate their production or break them down.

The ECS is responsible for regulating many of our homeostatic control processes. In other words, this network controls the balance of various systems and organs in the body, including the liver.

When the liver gets damaged, inflamed, or dysfunctional, the body starts to release more endocannabinoids to solve the problem. A healthy liver is correlated with a modest activity of the endocannabinoid system. In fact, this particular organ has a relatively low concentration of the ECS components.

However, inflammation in the liver causes the endocannabinoid to be very active in this area. Unfortunately, an overactive endocannabinoid system plays a role in the development of fatty liver disease (3).

CBD is the modulator of CB1 and CB2 receptors. In simple English, it keeps them from going crazy by stopping the compounds that make these receptors go haywire in the liver.

CBD ensures the proper functioning of a system that balances us. So while it won’t cure fatty liver disease, it can prevent its development. And should the disease occur, it may be able to reduce the inflammation in the organ, protecting it against further damage.

CBD Oil for Liver Cancer

To this day, studies on cannabinoids and their effect on liver cancer show that cannabinoids can both prevent the dividing of tumor cells and kill cancer cells while protecting the healthy ones. Besides stopping cancer proliferation, there are several mechanisms CBD uses to help tackle liver cancer.

First, it provides anti-metastatic actions, preventing distant tumor masses from forming in the liver.

Second, it prevents the formation of blood vessels that facilitate tumor growth.

And last but not least, CBD triggers apoptosis, which is programmed cell death. Researchers have found this ability during animal and laboratory models; these properties apply to both CBD and THC (4).

Although no study has yet analyzed the effects of CBD on liver cancer in humans, current research supports the use of cannabinoids as a complementary therapy as well as a means of reducing the side-effects of chemotherapy and radiation.

CBD Oil for Viral Hepatitis

Viral hepatitis is one of the most common infectious diseases characterized by inflammation. It is also a great contributor to many deaths globally. Hepatitis can lead to the formation of liver cancer and cirrhosis.

CBD has been shown to have therapeutic effects on the models of viral hepatitis, especially Hepatitis C. According to a study published in the journal Pharmacognosy Research, CBD was shown to inhibit the replication of hepatitis C virus by almost 90% (5).

The inhibitory effects on the virus were dose-dependent but showed little toxicity towards the cells. CBD was also found to induce death in the infected cells containing the hepatitis B virus, although it did not inhibit the virus itself.

Finally, the attenuation of the immune response through the interaction with the ECS in the immune cells may help in alleviating autoimmune hepatitis.

CBD Oil for Hepatic Ischemia

Ischemia is a very common injury that occurs as an aftermath of liver surgeries and liver transplantations. It involves major inflammation and is responsible for deaths in the case of transplants and rejections. Oxidative stress can worsen the condition.

CBD is known for its anti-inflammatory and antioxidative properties, so it could be useful in reducing the inflammatory response and protecting the liver against oxidative damage. In experimental models, CBD effectively reduced inflammation, oxidative stress, and promoted the death of malignant cells in the liver.

Other studies found that administration of CBD to the rats with ischemic liver injury resulted in a significant reduction of liver damage associated with the condition (6).

CBD Oil for Hepatic Encephalopathy

Hepatic encephalopathy is characterized by psychological changes resulting from the damage and failure of the liver. Some symptoms include altered personality, confusion, movement problems, etc. It can lead to a coma in severe cases.

Inflammation is one of the main causes of hepatic encephalopathy. A study conducted on mice models of hepatic encephalopathy reported positive effects. The research team observed that applying CBD to mice could restore the neurological functions and cognitive performance in the mice. CBD also reduced the levels of ammonia in the blood, helping restore liver function and normalize the number of liver enzymes (7).

CBD Oil for Autoimmune Hepatitis

Autoimmune hepatitis results from a weakened immune system that attacks the liver. Again, inflammation is the key player in the development of this disease. One study has reported that the activation of TRPV1 vanilloid receptor — part of the ECS — lowers inflammation by activating myeloid-derived suppressor cells (MDSCs). These cells, in turn, block inflammation and the development of autoimmune hepatitis.

CBD happens to activate the TRPV1 receptors, not only reducing the pain but also inhibiting the proliferation of T cells that trigger inflammation (8). Therefore, it’s within reason to assume that CBD could be used for the prevention and treatment of liver inflammation and autoimmune hepatitis.

CBD Oil for Alcohol-Induced Liver Injury

Liver fibrosis is a common result of chronic liver damage caused by binge drinking. It can lead to cirrhosis and liver failure.

CBD has been shown to have anti-fibrosis properties by eliminating cells that secrete collagen and cause fibrosis. It can also reverse alterations in the liver associated with alcohol-induced injury (9).

Does CBD Oil Increase Liver Enzymes?

The studies performed on how CBD affects liver function have brought conflicting results.

For example, one study found that 10% of the subjects had higher levels of liver enzymes and had to stop using CBD for this reason. Other studies suggest that CBD can improve liver function. Since CBD is metabolized by the liver — as shown by the studies done on Epidiolex — patients with liver diseases should limit over-the-counter (OTC) medications to avoid potential CBD-drug interactions and reduce the stress experienced by the liver.

Long story short, CBD is generally safe for your liver enzymes if you don’t exceed the dose of 20 mg CBD/kg/day.

CBD Dosage for Liver

If you’re looking to improve liver function with CBD oil, you’re probably wondering how much CBD is enough to provide relief from pain and inflammation and to keep this organ healthy.

Unfortunately, there are no official dosage recommendations when it comes to CBD and the liver. Most clinical trials that suggest specific dosages of CBD have been performed on anxiety, chronic disorder such as epilepsy, and multiple sclerosis models in humans. No clinical study has yet investigated the efficacy of different doses of CBD on the symptoms of liver disease.

The optimal amount of CBD for each individual depends on factors such as weight, metabolism, age, gender, the severity of symptoms, and previous history with CBD products.

The best approach you can take is to start low and gradually increase the dose until you experience the desired relief. We suggest that you start with 5–10 mg CBD and try it out for one week, monitoring the effects. If you deem the dose insufficient, add another 5 milligrams and continue for another week, reassessing the results.

We also encourage you to consult a doctor knowledgeable about CBD and cannabis in general. A qualified physician should help you avoid potential interactions with other medications and determine the right dosage range.

Side Effects of CBD

As mentioned earlier in the article, CBD has an excellent safety profile. People turn to CBD because it’s a low-risk alternative to conventional treatment options for liver disease. That being said, it has a few relatively mild effects when consumed in high doses, including:

  • Dry mouth
  • Changes in appetite
  • Dizziness
  • Sedation
  • Diarrhea

Some of these side effects may result from consuming a mislabeled product that has more than 0.3% THC, or one that has been sourced from poor-quality hemp or extracted with aggressive solvents. When you take high-quality CBD oil at regular doses, the above side effects are nearly non-existent.

However, there’s a risk of potential drug interactions, as CBD is metabolized by the same group of enzymes that process active ingredients in pharmaceuticals. As an inhibitor of those enzymes, CBD can lead to either subtherapeutic effects or substance toxicity when taken along with medications for liver function. That’s why we recommend consulting a doctor before adding CBD oil to your routine.

CBD Oil and Liver: Bottom Line

The liver is a fundamental detoxifying organ that performs many important functions to keep the body in the optimum state. It plays a role in digestion, detoxification, drug metabolism, and more.

There are many diseases affecting the liver as it is constantly exposed to environmental damage from pollutants, alcohol, drugs, medications, etc. It is also prone to autoimmune diseases.

CBD has been shown to have therapeutic effects in many major liver diseases, including viral hepatitis, fatty liver disease, ischemia-reperfusion injury, cirrhosis, fibrosis, and liver cancer.

High-quality full-spectrum CBD oil could be beneficial in a range of disorders that involve liver dysfunction and might help replace the long-term use of other medications.

Although extremely high doses of CBD taken daily have been associated with liver toxicity, so have other supplements and medications. Therefore, it’s best to keep your use of CBD within reason. Doses as high as 20 mg of CBD per kg don’t pose a threat to your liver’s health, as tested in the clinical trial of Epidiolex, a CBD-based anti-seizure medication.

Patients should seek medical consultation before incorporating CBD into their routine to discuss the dosage and establish the right time schedule to avoid potential interactions with other medications.

References:

  1. Iffland, Kerstin, and Franjo Grotenhermen. “An Update on Safety and Side Effects of Cannabidiol: A Review of Clinical Data and Relevant Animal Studies.” Cannabis and cannabinoid research vol. 2,1 139-154. 1 Jun. 2017, doi:10.1089/can.2016.0034
  2. Ewing, Laura E et al. “Hepatotoxicity of a Cannabidiol-Rich Cannabis Extract in the Mouse Model.” Molecules (Basel, Switzerland)vol. 24,9 1694. 30 Apr. 2019, doi:10.3390/molecules24091694
  3. Purohit, Vishnudutt et al. “Role of cannabinoids in the development of fatty liver (steatosis).” The AAPS journal vol. 12,2 (2010): 233-7. doi:10.1208/s12248-010-9178-0
  4. Vara, D et al. “Anti-tumoral action of cannabinoids on hepatocellular carcinoma: role of AMPK-dependent activation of autophagy.” Cell death and differentiation vol. 18,7 (2011): 1099-111. doi:10.1038/cdd.2011.32
  5. Lowe, Henry I C et al. “Potential of Cannabidiol for the Treatment of Viral Hepatitis.” Pharmacognosy research vol. 9,1 (2017): 116-118. doi:10.4103/0974-8490.199780
  6. Fouad, Amr A, and Iyad Jresat. “Therapeutic potential of cannabidiol against ischemia/reperfusion liver injury in rats.” European journal of pharmacology vol. 670,1 (2011): 216-23. doi:10.1016/j.ejphar.2011.08.048
  7. Avraham, Y et al. “Cannabidiol improves brain and liver function in a fulminant hepatic failure-induced model of hepatic encephalopathy in mice.” British journal of pharmacology vol. 162,7 (2011): 1650-8. doi:10.1111/j.1476-5381.2010.01179.x
  8. Muller, Chanté et al. “Cannabinoid Ligands Targeting TRP Channels.” Frontiers in molecular neuroscience vol. 11 487. 15 Jan. 2019, doi:10.3389/fnmol.2018.00487
  9. Zurier, Robert B, and Sumner H Burstein. “Cannabinoids, inflammation, and fibrosis.” FASEB journal : official publication of the Federation of American Societies for Experimental Biology vol. 30,11 (2016): 3682-3689. doi:10.1096/fj.201600646R
Livvy Ashton

Livvy is a registered nurse (RN) and board-certified nurse midwife (CNM) in the state of New Jersey. After giving birth to her newborn daughter, Livvy stepped down from her full-time position at the Children’s Hospital of New Jersey. This gave her the opportunity to spend more time writing articles on all topics related to pregnancy and prenatal care.

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Cbd oil for elevated liver enzymes

We support health writers who wish to spread their work to a wider audience. This article was submitted by Natalie Shae.

Note, the study cited in the article was very small with children under physician care but if you are a liver patient it is a cautionary note if you are considering CBD oil. We are not aware of any research that would suggest using it more broadly but consult your doctor.

Liver Damage and CBD Oil

June 4, 2019 by Natalie Shae

The FDA has approved a CBD-based drug named Epidiolex®. The drug was researched and made by Greenwich Biosciences, and the company’s vice-president of U.S. professional relations, Alice Mead, has stated to the FDA that CBD is “potentially” a liver toxin. She said this during the FDA’s first public hearing on CBD oil on May 31, 2019.

What is CBD oil?

Cannabidiol oil is extracted from the hemp plant, which is in the same family as marijuana. Unlike THC in marijuana, CBD does not cause a “high” or chemical dependence. CBD that is extracted from the hemp plant is legal, but individual states have laws to regulate it.

Because CBD oil is not considered a drug, it can be a common additive in many products. This includes e-cigarettes (vape oil), lotions and various herbal supplements. It has also been shown to relieve symptoms of different disorders like epilepsy, anxiety and multiple sclerosis.

How does it impact the liver?

The few studies performed on how CBD affects the liver are not clear.

In one study , 10% of the subjects developed high liver enzymes—they had to stop using CBD for this reason. Other research suggests that CBD can improve liver function.

As determined by the studies done on Epidiolex®, CBD is metabolized by the liver. People with nonalcoholic steatohepatitis (NASH) are encouraged to limit over-the-counter (OTC) medications to avoid stressing the liver.

How much CBD is too much?

To further complicate the question, products with CBD oil may not give the exact amount listed on the package . Depending on the brand, the consumer may be using much more or less than they think. This is especially true of OTC supplements and e-cigarettes.

Now that CBD oil is appearing in different products, anyone with liver damage needs to be alert to this. A doctor or specialist should be consulted before adding it to the diet.