Published on December 4, 2021 by Kristina Willis
It’s official—cannabidiol has gone mainstream. In January 2019, a Consumer Reports nationally representative survey of more than 4,000 Americans found that 64 million people reported having tried CBD, with around 14% using it daily. However, despite the recent enthusiasm for CBD products, questions regarding liver complications have remained a prominent concern.
At high doses, CBD has the potential to cause liver problems, and when administered frequently in excess amounts, the damage can be severe. Moreover, CBD may attenuate the effects of other drugs known for stressing the liver, such as valproic acid. However, standard dosing under the commonly recommended maximum of 20 mg/kg a day does not harm the liver and is considered safe for healthy adults who do not already suffer from liver complications.
Over the past decade, the non-psychoactive cannabinoid has been promoted as a safer alternative to standard drugs with undesirable side effects and a valid therapeutic treatment for a handful of conditions. This article explores clinical evidence discussing CBD’s impact on the liver and what doses are considered safe.
The potential adverse side effects of CBD on the liver are a hotly contested issue. According to the FDA, CBD causes liver injury. Moreover, safety information for Epidiolex, an FDA-approved drug containing pure CBD, cites liver problems among other concerns. According to their website, an increase in liver enzymes is one of the most common side effects.
Such findings are understandable, considering that CBD is metabolized by the liver. A 2019 study on abnormal liver chemistries from CBD in healthy adults found that administering 1,500 mg daily (around 20 mg/kg) elevated serum alanine aminotransferase (ALT) levels consistent with drug-induced liver injury (DILI). On the other hand, conflicting studies suggest that CBD does not, in fact, damage the liver. There is even evidence that CBD may be useful for treating certain liver diseases, including alcohol-induced liver injuries.
A 2018 study of the long-term safety and treatment of effects of CBD on people with treatment-resistant epilepsies reported that 10% of patients experienced abnormal liver side effects. However, 75% of those patients were also taking valproic acid, which is already associated with acute and chronic liver injury. To put it succinctly, 2.47% of 607 patients experienced liver abnormalities that could not be attributed to valproate.
Likewise, a 2017 study on CBD for drug-resistant Dravet syndrome concluded that CBD was associated with elevated liver enzyme levels. However, all patients with high aminotransferase levels were taking a form of valproate, which could explain the results. Nevertheless, it is worth noting that 12 of those 13 patients were in the experimental group and only one in the control group. That may suggest that while CBD does not harm the liver on its own, it may still amplify the adverse effects of other drugs or consumables that stress the liver.
According to human studies, there are no adverse effects associated with CBD below the maximum daily dose of 20 mg/kg. In isolation—with no other medications or lifestyle factors to consider—a healthy adult would likely have to take an unrealistic amount of CBD to cause any sort of liver damage. Of course, that does not mean you can down a bottle of CBD and expect nothing bad to happen. You should always consult with a doctor or conduct comprehensive research on what you are attempting to treat to get an informed idea of a beneficial and safe dose.
At the request of congressional leadership, ValidCare conducted a 7-month clinical investigation to collect safety data for the FDA. Upon conclusion, investigators found no evidence of liver toxicity in 839 adults taking oral CBD. Unfortunately, the study has not yet been published, so the specific doses considered for the study are currently unknown.
“Our primary endpoint in this study is to observe potential liver effects in adults ingesting oral forms of hemp derived CBD for a minimum of 60 days. What we observed to date is no clinical evidence of liver disease in any participants. We observed slight, clinically insignificant elevations of liver function tests in less than ten percent of consumers irrespective of age, product composition and form and the amount consumed.”—Jeff Lombardo, PharmD, BCOP, co-investigator of Validcare study
“Our primary endpoint in this study is to observe potential liver effects in adults ingesting oral forms of hemp derived CBD for a minimum of 60 days. What we observed to date is no clinical evidence of liver disease in any participants. We observed slight, clinically insignificant elevations of liver function tests in less than ten percent of consumers irrespective of age, product composition and form and the amount consumed.”
Previously, a widely circulated 2019 study posited that CBD poses a risk for liver injury based on results from high dosage gavaging of mice to investigate CBD hepatotoxicity. However, while the study might have successfully demonstrated that excess amounts of CBD can be harmful, it also showed that CBD taken at the recommended dose likely does not impede liver function. Project CBD wrote a particularly reproachful article on the study, condemning the authors’ apparent bias against CBD as well as inconsistencies and inaccuracies.
“Although 2460 mg/kg (MED of 200 mg/kg CBD) 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 sub-chronic and chronic toxicity studies.”—Ewing et al. in Hepatotoxicity of a Cannabidiol-Rich Cannabis Extract in the Mouse Model
“Although 2460 mg/kg (MED of 200 mg/kg CBD) 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 sub-chronic and chronic toxicity studies.”
All things considered, it is arguable that erring on the side of caution is the best way to approach this particular issue. There is evidence both for and against liver damage from CBD, and other factors must also be considered.
For example, over-the-counter (OTC) pain relievers like Tylenol can cause severe liver damage when taken in excess. So, even if you use both CBD and OTCs in moderation, intaking multiple constituents that stress the liver could be harmful, which is why it is always important to be extra-diligent when using drug cocktails.
That said, recent studies strongly suggest that taking CBD in isolation does not cause liver damage at a reasonable dose. The bottom line is that CBD has a remarkably good safety profile especially compared to other drug therapies.
Most people can safely consume moderate amounts of CBD without having to worry in the slightest about how it might impact their liver. However, if you already have impaired liver function or are taking other medications with liver concerns, you should undoubtedly consult a doctor before adding CBD into the mix.
Preview image ‘Liver Disease’ by Nick Youngson licensed under CC BY-SA 3.0 on Pix4free.