From the Guidelines
CBD can potentially cause liver injury (hepatotoxicity), particularly at doses above 300 mg/day, and clinicians should not recommend doses of 300 mg or more per day due to the risk of reversible liver enzyme abnormalities. The risk of CBD-related liver damage is relatively low in most users, but it increases with higher doses 1. Patients with pre-existing liver disease, those taking other hepatotoxic medications, or those using unregulated CBD products with unknown purity are at higher risk. Signs of CBD hepatotoxicity include elevated liver enzymes (ALT, AST), fatigue, abdominal pain, dark urine, and jaundice.
Some key points to consider when evaluating the risk of CBD hepatotoxicity include:
- The pooled proportion of elevated liver enzymes was 0.07 (95% CI, 0.05 to 0.12), whereas the pooled proportion of those with drug-induced liver injury was 0.03 (95% CI, 0.10 to 0.06) 1.
- No cases were reported in adults using a total CBD dose of <300 mg/day 1.
- The package insert for CBD, FDA-approved for pediatric epilepsy, describes dose-related, reversible transaminase elevations, typically occurring in the first 2 months after CBD initiation 1.
- Clinicians should monitor liver enzymes in patients using CBD, especially at high doses, and consider the possible effects of CBD in the setting of new or worsening hepatotoxicity 1.
For safety, patients should start with low CBD doses (5-10 mg twice daily) and gradually increase while monitoring for side effects 1. Those with liver conditions or taking other medications should consult healthcare providers before using CBD. Regular liver function tests are recommended for patients on high-dose CBD therapy. The mechanism of CBD hepatotoxicity likely involves inhibition of cytochrome P450 enzymes, which can affect drug metabolism and potentially cause drug interactions that stress the liver 1. CBD's direct effects on liver cells may also contribute to injury at high concentrations.
From the Research
CBD Hepatotoxicity Overview
- CBD use has been associated with clinically significant liver enzyme elevations and drug-induced liver injury (DILI) 2
- The proportion of liver enzyme elevations and DILI events reported in the literature meet the Council for International Organizations of Medical Sciences' (CIOMS) classification of a common adverse drug reaction 2
Animal Studies
- A study in mice found that CBD exhibited clear signs of hepatotoxicity, possibly of a cholestatic nature, with significant increases in liver-to-body weight ratios, plasma ALT, AST, and total bilirubin 3
- The study also found that CBD differentially regulated more than 50 genes, many of which were linked to oxidative stress responses, lipid metabolism pathways, and drug metabolizing enzymes 3
Human Studies
- A phase I clinical trial found that 44% of healthy adults who received therapeutic daily doses of CBD experienced peak serum alanine aminotransferase (ALT) values greater than the upper limit of normal (ULN) 4
- The trial also found that 31% of participants had ALT values that exceeded 5 × ULN, meeting the international consensus criteria for drug-induced liver injury 4
- A decentralized, observational study found that the prevalence of elevated ALT was 9.1%, which was not significantly different from known adult general population prevalences 5
- The study also found that there was no significant association between CBD dosage and liver test values 5
Metabolism and Liver Toxicity
- A review of human-derived data and animal studies found that CBD has been linked to a spectrum of toxicological effects, including changes in appetite, gastrointestinal discomfort, fatigue, and elevated liver aminotransferase enzymes 6
- The review also found that animal studies have reported changes in organ weight, reproduction, liver function, and the immune system 6
- CBD-drug interactions are also a concern, with the potential for CBD to interact with other medications and affect liver function 6