Is CBD Bad for Your Liver? Review of 8 Studies

There’s at least one study that shows CBD may be associated with liver damage.

However:

Some studies show CBD doesn’t have any negative effects on the liver.

Which is true? Is CBD bad for your liver?

Today you’ll get a review of the studies that looked at the effects of CBD on the liver…

So you can make up your own mind on what potential risks using CBD may pose for the liver.

Let’s get started.

Table of contents:

Why CBD May Cause Liver Damage

Studies That Didn’t Find Negative Effects of CBD on the Liver

Why CBD May Protect the Liver

When to Be Careful with CBD

Why CBD May Cause Liver Damage

CBD gets metabolized by the liver in two phases (1):

1. In phase 1, the cytochrome P450 enzyme system starts breaking down the CBD into different metabolites like 7-COOH-CBD;
2. In phase 2, these metabolites are combined with glucuronic acid to form more water-soluble compounds. Water-soluble compounds enable fecal and urinary excretion by the kidneys.

Broadly speaking, the metabolization process of CBD doesn’t differ from other compounds that get metabolized by the liver.

In some cases, the metabolization process of compounds by the liver can cause damage to the liver.

The exact mechanism responsible for this liver damage varies per compound.

For example:

The metabolization process can create oxidative stress damaging liver tissue.

Two key markers that indicate potential liver damage are:

• Elevated alanine aminotransferase (ALT) levels. ALT is an enzyme found in the cells of the liver and kidneys, and;
• Elevated aspartate transaminase (AST) levels. AST is an enzyme found in cells throughout the body, but mostly in the liver and heart.

When liver cells are damaged, they release ALT and AST into the blood.

But elevated ALT and AST don’t always mean that there is liver damage. Some drugs cause elevated ALT and AST levels without causing any liver damage.

Now:

At least three studies found elevated levels of ALT and AST after CBD consumption.

Which we will talk about next.

Study 1: CBD and Abnormal Liver Chemistries in Healthy Adults

Study setup:

This study looked at the effects of daily CBD consumption on ALT and AST in healthy adults (2).

As explained, ALT and AST are two enzymes that get released in the blood when liver cells are damaged.

Sixteen healthy adults were given a daily dose of 1500mg CBD for 3.5 weeks.

The results:

Seven participants (44%) tested with ALT levels higher than the ‘upper limit of normal’. As explained elevated ALT levels may be early signs of liver damage.

Five of these participants had ALT levels that were higher than 5-times the upper limit of normal. According to international consensus, these levels meet the criteria of ‘drug-induced liver injury’.

Six participants stopped the trial before completion because of negative side effects.

Three participants out of sixteen stopped because of elevated ALT and AST levels.

Three participants out of sixteen stopped because of various side effects like:

• nausea, and,
• abdominal discomfort.

RELATED: Side Effects of CBD

Discussion:

First, it’s important to state that these study results should be taken seriously.

Elevated ALT and ALS levels in healthy adults may indicate that CBD taken at doses corresponding to those in this study causes liver damage. The doses used in this study are 20mg/kg/day or 1500mg.

Looking at the high dose used in this study, this may hold especially true for people that use pharmaceutical CBD products like Epidiolex, where daily doses are somewhat similar to those from this study.

But also keep in mind:

While these study results may look alarming on the surface, these study results don’t prove that CBD causes liver damage.

The study only shows that CBD taken at these doses is correlated with elevated ALT and ALS levels.

Like other compounds that cause elevated ALT and ALS levels without liver damage, CBD could be similar.

The study found ALT levels meet the criteria of ‘drug-induced liver injury’ in 5 participants. But the study didn’t examine whether there was any damaged liver tissue.

The doses taken in this study are also way above an average dose that you would take with an average CBD product.

Taking a CBD dose in line with this study would mean that a person that weighs 75kg takes 1500mg of CBD in a single day.

The average dose of an average CBD product hovers between 20mg and 100mg of CBD.

That’s 30- to 15-times less than the amount of CBD used in this study.

Study 2: Abrupt Withdrawal of CBD

Study setup:

This study looked at the effects of abrupt CBD withdrawal after 4-weeks of CBD administration (3).

Thirty healthy adult participants were given a daily dose of 1500mg CBD.

After 4 weeks, the participants got divided into two groups. The first group kept receiving 1500mg CBD, while the second group received a placebo.

The participants were then checked on various withdrawal symptoms, including liver enzyme levels.

The results:

Two out of thirty participants stopped the trial because of elevated ALT levels.

Eighteen out of thirty participants (60%) had elevated ALT levels more than 3-times the ‘upper limit of normal’.

Twelve out of thirty participants had ALT levels less than 3-times the ‘upper limit of normal’.

Discussion:

Although the study found elevated ALT levels, there was no sign of actual damage to the liver tissue.

Also, the doses were significantly higher than the average dose you would take with an over-the-counter CBD product. The dose was 15- to 30-times higher.

That said, these study results should be taken seriously. It’s alarming that 60% of study participants had such elevated ALT levels.

Further studies should show whether CBD taken in these doses causes liver damage. Or whether it only causes elevated liver enzymes.

Study 3: Dose-Ranging Effect of Oral CBD vs Placebo on Convulsive Seizure Frequency

Study setup:

This study looked at the potential of CBD as a treatment of seizures in patients with Dravet syndrome (4).

The researchers looked at both the safety and efficacy of 10mg/kg/day CBD and 20 mg/kg/day CBD for 14 weeks.

There were 199 participants.

The results:

What’s important for us are the results with regards to effects on the liver.

Elevated ALT and ALS levels were detected in 16 patients (12%). Out of those 16, 3 were in the group that took a dose of 10mg/kg/day CBD and 13 in the group that took a dose of 20 mg/kg/day CBD.

All participants that experienced elevated ALT and ALS levels were given valproate sodium as well during this trial.

Valproate sodium is a medicine used to treat epilepsy. It has been shown to cause various degrees of liver damage (5).

Discussion:

This study shows that elevated liver enzyme levels within the context of CBD use are correlated to:

• The dose taken (10mg/kg/day had a lower incidence of elevated liver transaminase levels than 20 mg/kg/day CBD), and;
• Possible interaction with other pharmaceutical drugs like valproate sodium.

Interestingly, this study found much lower levels of elevated liver enzyme levels than the previous two studies.

The two studies that looked at the effects of CBD on liver enzymes in healthy adults found 44% and 60% of participants had elevated liver enzymes.

This study, which combined valproate sodium with CBD, only found 12% of participants had elevated liver enzymes.

Why is this so interesting?

Because valproate sodium is known to cause liver damage. You would expect combining valproate sodium with CBD will lead to an even higher chance for elevated liver enzymes. Yet, this study found less participants with elevated liver enzymes.

Study 4: Hepatotoxicity of a CBD-Rich Cannabis Extract in the Mouse Model

Study setup:

This study looked at the potentially toxic effects of CBD on the liver of mice (6).

The mice were given 0, 246, 738, or 2460 mg/kg of CBD to test acute toxicity (24h). They were also given daily doses of 0, 61.5, 184.5, or 615 mg/kg to test sub-acute toxicity (10 days).

The results:

The part of the study that looked at acute toxicity found that 2460 mg/kg dose resulted in increases in:

• Liver-to-body weight (LBW) ratios;
• Plasma ALT and AST, and;
• Total bilirubin.

The part of the study that looked at sub-acute toxicity found that 615 mg/kg/day increased:

• Liver-to-body weight (LBW) ratios;
• Plasma ALT and AST, and;
• Total bilirubin.

75% of mice that were given 615 mg/kg/day also developed a condition that can be described as ‘at the point of death’.

Discussion:

To determine the doses, the researchers in this study made use of allometrically scaled mouse equivalent doses. Using this method, the researchers came to these doses of 615 mg/kg/day.

It’s highly questionable whether a dose of 615 mg/kg/day given to mice has any resemblance in terms of effects with a dose of 20mg/kg/day in humans. 20mg/kg/day is currently the maximum safe recommended CBD dose.

A dose of 615 mg/kg/day given to mice may be significantly higher than 20mg/kg/day when translated to human doses.

There’s no evidence that allometric scaling works when it comes to cannabinoids like CBD.

Also:

The extract used in this study was a hexane extract. Without a certificate of analysis, we can’t know whether the used extract wasn’t contaminated with hexane. Hexane is a known toxin.

Conclusion

There are at least 4 studies that found CBD may have damaging effects on the liver. The studies found high doses of CBD were correlated with elevated liver enzyme levels. Elevated liver enzyme levels, in turn, may be an early sign of liver damage.

The doses used in human studies were all 1500mg CBD or 20mg/kg/day.

The average dose of an over-the-counter CBD product is between 20mg and 100mg. For example, the average recommended dose of CBD oils we have reviewed never exceeded 85mg.

Whether these effects were dose-dependent is unclear.

ALSO READ: Guide to CBD Dosages

One study only found elevated liver enzyme levels in participants that combined CBD with valproate sodium. Valproate sodium is an anti-epileptic drug that’s associated with liver damage.

Although all 3 human studies found that CBD use was correlated with increased liver enzymes (ALT and AST), none of these studies examined whether there was damaged liver tissue in the study participants.

Studies That Didn’t Find Any Negative Effects of CBD on the Liver

Several studies looked at the effects of CBD on the liver and that didn’t find any negative effects.

Study 1: Is CBD Hepatotoxic or Hepatoprotective

Study setup:

This is a review study that looked at study results of several CBD-liver-related studies (7).

The researchers compared study methodologies and results. Based on this comparison, the authors formulate their ideas about CBD-liver-related research.

Results:

The authors identified 5 human studies that found CBD may increase liver enzyme levels (ALT and AST).

In all these studies, participants took high doses of CBD together with at least one anti-epileptic drug. The most common anti-epileptic drug was valproic acid.

Earlier, we already learned that valproic acid is associated with liver damage.

All 5 studies found CBD was associated with increased ALT and AST levels. But the effects were generally small (less than 3x increase).

In two of the five studies, ALT and AST levels returned to normal for some of the participants as the study proceeded.

One study explicitly stated that although ALT and AST levels were elevated, there was no liver damage.

With regards to the animal studies, the authors found several studies that may show CBD is associated with liver damage.

However, in some of these studies, products with CBD percentages ranging from 25% to 58% were used. The average over-the-counter CBD product has a CBD-percentage of 5%.

It’s unclear what other compounds were inside the CBD products used in the tests. The authors state that the liver effects can’t be fully attributed to CBD. They further state that more research is needed to look whether these effects were caused by:

• CBD,
• An interaction of CBD with these other compounds, or,
• By these other compounds themselves.

One of the animal studies they reviewed was study 4 in the paragraph “Why CBD May Cause Liver Damage”. In the discussion part, we already explained why the doses used in this study are unlikely to be representative of human doses. The authors of this review study agree. They state that the doses used are not representative of even high doses of CBD in humans.

The authors further found several animal studies that show CBD may be protective against:

• bile duct ligation,
• alcohol-,
• cocaine-,
• d-amphetamine-, and,
• ketamine-induced,
• liver damage.

The doses used in these studies were much lower than those used in previous animal studies. This shows that CBD has dose-dependent effects on the liver in mice.

The authors also note that CBD has different absorption rates based on the consumption method.

For example:

One study found that injection can result in 6.45-times higher levels of CBD in the blood than oral consumption. That’s with the same dose.

Discussion:

The authors state the importance of understanding the effects of regular doses of CBD on the liver. Both medical and non-medical doses should be researched.

According to the authors, for seizures, the therapeutic dose is 20mg/kg/day or around 1200mg. For non-medical purposes like pain relief and headaches, this dose is between 25-100 mg/day.

In all animal studies they reviewed, the doses used were not representative of even high doses of CBD given to humans.

In the human studies they reviewed, all study participants were taking at least one anti-epileptic drug. Some of these drugs are associated with liver damage.

Study 2: No Evidence of Liver Toxicity in 839 Adults Consuming Oral CBD

Study setup:

In this study, 839 participants that were taking oral forms of hemp-derived CBD were tested after 60 days on various liver functions (8).

Only the preliminary findings have been published so far. The exact setup of the study is unclear. How much CBD the participants took or how frequently is unknown.

Results:

According to the preliminary findings, there was no clinical evidence of liver disease in any participants.

9% of the participants had slightly elevated liver enzymes like ALT. 3 out of 839 participants had 3-times more ALT than the upper limit of normal. All 3 of these participants were taking prescription medications known to elevate liver enzymes.

Furthermore, when compared to a similar population, the CBD group had a lower incidence of elevated liver function tests.

Discussion:

These initial findings seem to indicate that regular human doses of CBD don’t affect the liver. But these are preliminary findings. We need to wait until the full study is published so we can scrutinize the methods used and results in a better way.

Why CBD May Protect the Liver

Several studies examined if CBD can protect the liver from drug-induced liver damage.

A 2019 review study found that CBD may reduce alcohol-induced liver damage. And it may do so through various mechanisms (9).

First, CBD may reduce liver fibrosis through its effects on the immune system. This includes its antioxidant properties.

Secondly, CBD may:

1. trigger the death of activated cells involved in liver fibrosis,
2. stimulate the removal of these dead cells, and,
3. reduce the accumulation of fatty acids in the liver.

RELATED: The Potential Benefits of CBD

How Much CBD Is Safe for the Liver

It’s currently unclear if even small amounts of CBD are completely safe for the liver.

But based on these studies, it’s unlikely that the average dose of CBD in most products doesn’t cause irreversible liver damage. The average dose of CBD for non-medical use hovers between 20 and 100mg CBD.

Everything changes though if you’re taking prescription drugs.

It may be that higher doses of CBD and/or taken together with prescription medicines may cause liver damage.

Based on these studies, we can’t give an exact number though.

When to Be Careful with CBD

If you plan on using CBD products medically, don’t do it before consulting with your doctor. Your doctor can provide a proper assessment of whether CBD can be useful for your specific medical condition.

In general:

If you’re using prescription drugs, always consult your doctor before using cannabinoids. It doesn’t matter if plan on using CBD for health purposes like pain relief or anxiety relief.

Various studies suggest that CBD may interact with most prescription drugs.

What’s Next…

Go  to our CBD Hub to learn more about CBD-related topics.

References

1. Lucas, C. J., Galettis, P., & Schneider, J. (2018b). The pharmacokinetics and the pharmacodynamics of cannabinoids. British Journal of Clinical Pharmacology, 84(11), 2477–2482. https://doi.org/10.1111/bcp.13710

2. Watkins, P. B., Church, R. J., Li, J., & Knappertz, V. (2020). Cannabidiol and Abnormal Liver Chemistries in Healthy Adults: Results of a Phase I Clinical Trial. Clinical Pharmacology & Therapeutics, 109(5), 1224–1231. https://doi.org/10.1002/cpt.2071

3. Taylor, L., Crockett, J., Tayo, B., Checketts, D., & Sommerville, K. (2020). Abrupt withdrawal of cannabidiol (CBD): A randomized trial. Epilepsy & Behavior, 104, 106938. https://doi.org/10.1016/j.yebeh.2020.106938

4. Miller, I., Scheffer, I. E., Gunning, B., Sanchez-Carpintero, R., Gil-Nagel, A., Perry, M. S., . . . Knappertz, V. (2020). Dose-Ranging Effect of Adjunctive Oral Cannabidiol vs Placebo on Convulsive Seizure Frequency in Dravet Syndrome. JAMA Neurology, 77(5), 613. https://doi.org/10.1001/jamaneurol.2020.0073

5. Abdel-Dayem, M. A., Elmarakby, A. A., Abdel-Aziz, A. A., Pye, C., Said, S. A., & El-Mowafy, A. M. (2014). Valproate-Induced Liver Injury: Modulation by the Omega-3 Fatty Acid DHA Proposes a Novel Anticonvulsant Regimen. Drugs in R&D, 14(2), 85–94. https://doi.org/10.1007/s40268-014-0042-z

6. Ewing, L. E., Skinner, C. M., Quick, C. M., Kennon-McGill, S., McGill, M. R., Walker, L. A., . . . Koturbash, I. (2019). Hepatotoxicity of a Cannabidiol-Rich Cannabis Extract in the Mouse Model. Molecules, 24(9), 1694. https://doi.org/10.3390/molecules24091694

7. Stohs, S., & Ray, S. (2020). Is cannabidiol hepatotoxic or hepatoprotective: A review. Toxicology Research and Application, 4, 239784732092294. https://doi.org/10.1177/2397847320922944

8. Clinical Study Reports Preliminary Results of Liver Safety. (2021). Retrieved 2021, from https://validcare.com/news/clinical-study-reports-cbd-liver-safety-results/

9. De Ternay, J., Naassila, M., Nourredine, M., Louvet, A., Bailly, F., Sescousse, G., . . . Rolland, B. (2019). Therapeutic Prospects of Cannabidiol for Alcohol Use Disorder and Alcohol-Related Damages on the Liver and the Brain. Frontiers in Pharmacology, 10. Published. https://doi.org/10.3389/fphar.2019.00627