There’s at least one study that shows CBD may be associated with liver damage.
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 as to what potential risks using CBD may pose for the liver.
Let’s get started.
Table of contents:
Why CBD May Cause Liver Damage
CBD gets metabolized by the liver in two phases (1):
- In phase 1, the cytochrome P450 enzyme system starts breaking down the CBD into different metabolites like 7-COOH-CBD;
- In phase 2, these metabolites are combined with glucuronic acid to form more water-soluble compounds which 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, this metabolization process of compounds by the liver can cause damage to the liver.
The exact mechanism responsible for this liver damage varies per compound.
The metabolization process can create oxidative stress damaging liver tissue.
Two key markers that indicate potential liver damage are:
- Elevated alanine aminotransferase (ALT) levels (an enzyme found in the cells of the liver and kidneys), and;
- Elevated aspartate transaminase (AST) levels (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 are correlated with elevated ALT and AST levels without being correlated with any liver damage.
There have been at least three studies that found elevated levels of ALT and AST in the blood after CBD consumption.
Which we will talk about next.
Study 1: CBD and Abnormal Liver Chemistries in Healthy Adults
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.
Seven participants (44%) were tested with ALT levels that were 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’.
In total, six participants stopped the trial before completion because of negative side effects.
Three participants out of sixteen stopped participation because of elevated ALT and AST levels.
Three participants out of sixteen stopped participation because of various side effects like nausea and abdominal discomfort.
RELATED: Side Effects of CBD
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 (20mg/kg/day or 1500mg) causes liver damage.
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.
CBD may be correlated with elevated ALT and ALS levels, without being correlated to liver damage.
Although the study found ALT levels meet the criteria of ‘drug-induced liver injury’ in 5 participants, the study didn’t examine whether there was any damaged liver tissue.
The doses taken in this study (20mg/kg/day) are also way above an average dose that you would take with a commercially produced and sold 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 a commercially produced and sold CBD product hovers between 20mg and 50mg of CBD.
That’s 30-times less than the amount of CBD used in this study.
Study 2: Abrupt Withdrawal of CBD
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.
Two out of thirty participants stopped the trial because of elevated ALT levels.
Eighteen out of thirty participants had elevated ALT levels more than 3-times the ‘upper limit of normal’ (60%).
Twelve out of thirty participants had ALT levels less than 3-times the ‘upper limit of normal’.
Again, although the study found elevated ALT levels, there was no indication of actual damage to the liver tissue.
Also, the doses were again significantly higher than the average dose you would take an over-the-counter CBD product (30-times higher on average).
That being said, these study results should be taken seriously and it's a bit alarming that 60% of study participants had such elevated ALT levels.
Further studies should show whether CBD taken in these doses is associated with actual liver damage.
Study 3: Dose-Ranging Effect of Oral CBD vs Placebo on Convulsive Seizure Frequency
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.
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 and has been shown to cause various degrees of liver damage (5).
This study shows that elevated liver transaminase levels (ALT and AST) within the context of CBD 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 a much lower prevalence of elevated liver transaminase levels than the previous two studies that looked at the effects of CBD in healthy adults (12% vs 44% and 12% vs 60%).
Study 4: Hepatotoxicity of a CBD-Rich Cannabis Extract in the Mouse Model
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) or daily doses of 0, 61.5, 184.5, or 615 mg/kg to test sub-acute toxicity (10 days).
The part of the study that looked at acute toxicity found that 2460 mg/kg dose resulted in significant 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’.
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.
While allometrically scaling has its use, there’s no evidence that allometric scaling works when it comes to cannabinoids like CBD.
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, which is a known toxin.
There are at least 4 studies that found CBD may have damaging effects on the liver evidenced by the correlation of CBD consumption with elevated liver transaminase enzyme levels (which in turn, may be an early sign of liver damage).
The doses used in human studies were all 1500mg CBD or 20mg/kg/day.
Whether these effects were dose-dependent is unclear.
ALSO READ: Guide to CBD Dosages
One study found that elevated liver transaminase enzyme levels were only observed in study participants that took the anti-epileptic drug valproate sodium. Valproate sodium is 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
This is a review study that reviewed study results of several CBD-liver-related studies (7).
Both human and animal studies were part of the review study. By comparing study methodologies and results, the authors formulate their ideas about the current state of CBD-liver-related research.
The authors identified 5 human studies that found CBD may increase liver transaminase enzyme levels (ALT and AST).
In all of these studies, participants took high doses of CBD together with at least one anti-epileptic medication, the most common one being valproic acid.
Earlier, we already learned that valproic acid is associated with various degrees of liver damage.
Although all 5 studies did find CBD was associated with increased ALT and AST levels, 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 indicate that CBD is associated with liver damage.
However, in some of these studies, products with CBD percentages ranging from 25% to 58% were used.
Since it’s unclear what the other compounds inside the products were, the authors argue that the effects can’t be attributed to CBD, and more research is needed whether these effects were caused by:
- An interaction of CBD with these other compounds, or,
- By these other compounds themselves.
In at least one animal study (this is study 4 in the paragraph “Why CBD May Cause Liver Damage”) that found CBD to be toxic to the liver of mice, the authors state that the doses used are not representative of even high doses of CBD in humans.
The authors further identified several animal studies that found CBD may have protective effects against bile duct ligation, alcohol-, cocaine- d-amphetamine-, and ketamine-induced liver damage.
The doses used in these studies were significantly lower than those used in previous animal studies, indicating 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 intraperitoneal injection can result in a 6.45-times higher CBD concentration in the blood than oral consumption (with the same dose).
The authors emphasize that it’s highly important to understand the effects of CBD on the human liver with regular doses of CBD (both therapeutic and non-therapeutic).
According to the authors, for seizures, the therapeutic dose is 20mg/kg/day or around 1200mg. And for non-therapeutic purposes like pain relief and headaches, this dose is between 25-100 mg/day.
In all animal studies that they reviewed, the doses used were not representative of even high doses of CBD regularly given to humans.
And in the human studies that they reviewed, all study participants were at taking at least one anti-epileptic medication that may be associated with liver damage.
Study 2: No Evidence of Liver Toxicity in 839 Adults Consuming Oral CBD
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.
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.
While these initial findings seem to indicate that regular human doses of CBD don’t affect the liver, these are preliminary findings and 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 looked at whether CBD can protect the liver from various forms of drug-induced liver damage.
For example, a 2019 review study found that there’s evidence suggesting that CBD reduces alcohol-induced liver damage through various mechanisms (9).
First, CBD may reduce liver fibrosis through its effects on the immune system and antioxidant properties.
Secondly, CBD may trigger the death of activated cells involved in liver fibrosis, stimulate the removal of these dead cells, and 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 whether even small amounts of CBD are completely safe for the liver.
But based on these studies, we can cautiously say it's likely that the average dose recommended in over-the-counter CBD products doesn't cause irreversible liver damage (20-50mg CBD) in healthy adults that don't take any prescription medicines.
However, 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.
If you plan on using CBD products for general health or non-therapeutic purposes like pain relief or anxiety relief, it’s especially important to consult with your doctor when you’re already using prescription medicines.
These and various other studies suggest that CBD may interact with most prescription drugs. Therefore, you must consult with your physician before you take even small doses of CBD.
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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