A new clinical trial conducted by scientists at the U.S. Food and Drug Administration (FDA) suggests that even low, consumer-typical doses of cannabidiol (CBD) may pose a risk of liver injury in some individuals. This finding, published in the esteemed journal JAMA Internal Medicine, adds a critical layer of caution to the booming, yet largely unregulated, market for over-the-counter CBD capsules, gummies, edibles, oils, and lotions that have become omnipresent in the United States in recent years.
Despite the widespread availability and popularity of CBD products for self-medicating conditions like pain, anxiety, and insomnia, there has been a significant lack of robust clinical evidence on how well they work and, crucially, clear guidance on how to use them safely. This new FDA trial directly addresses the safety question, providing valuable data for consumers, doctors, and regulators.
The FDA Clinical Trial: A Closer Look at Low-Dose CBD
The study, carried out by the FDA’s Division of Applied Regulatory Science, was a randomized, double-blind, placebo-controlled trial – the gold standard for clinical research. Over a four-week period, 201 healthy middle-aged men and women were given either a placebo or a daily oral dose of CBD at 5 milligrams per kilogram of body weight. This dose was chosen to reflect a typical amount a consumer might use, equivalent to about 350 mg per day for a 154-pound (70 kg) individual.
Participants underwent weekly laboratory assessments to monitor their liver function. The results were revealing: while the vast majority of participants in the trial were unaffected, a notable **5% of those taking CBD showed greatly elevated levels of the liver enzyme aminotransferase**. This enzyme is a well-known biomarker for liver cell damage or inflammation. The study also found that women appeared to be more vulnerable to these effects than men. Encouragingly, the elevated liver enzyme levels returned to normal within one or two weeks after the participants stopped taking CBD.
However, the effects were significant enough that seven participants had to withdraw from the trial because they exhibited clinical signs of potential drug-induced liver injury (DILI). This is a crucial finding, as it suggests that CBD itself, even at consumer-level doses and in the absence of other interacting medications, can pose a risk to liver health in a subset of the population.
Expert Reactions and Broader Context
The findings have drawn attention from experts in the field. Amir Englund, a researcher at King's College London who studies cannabinoid psychopharmacology and was not involved in the trial, called the result a "significant finding." He stated, "The results have important implications for individuals using over-the-counter CBD supplements. Many may be unaware of the potential for liver injury and assume that CBD is entirely benign."
This is not the first time concerns about CBD and liver health have been raised. Such risks were initially described following FDA reviews of clinical trial data for CBD-based prescription drugs used to treat childhood epilepsy (like Epidiolex). In those trials, elevated liver enzymes were observed in up to 14% of participants. However, as Englund noted, "those participants were concurrently taking other anti-epileptic medications, which could have contributed to the observed liver effects." The new FDA trial is important because it isolated CBD's effect in a group of healthy adults not taking other potentially liver-affecting drugs.
Paul Watkins, a professor of pharmacy at the University of North Carolina at Chapel Hill, who was also not involved in this specific trial, has previously researched why CBD can affect liver cells. He noted that certain doses of CBD seem to have an effect similar to acetaminophen (paracetamol), which, when taken in excess, is one of the most common causes of drug-induced liver injury in the U.S. "It’s interesting because it’s also been shown that healthy adults, when they get recurrent therapeutic doses of paracetamol, also have these liver chemistry abnormalities," Watkins said.
Implications for a Booming, Unregulated Market
The context for this research is a CBD market that has exploded since the 2018 Farm Bill passed by the Trump administration enabled the unrestricted sale of hemp-derived cannabis products containing less than 0.3% THC (the main psychoactive compound). CBD product sales in the U.S. skyrocketed from approximately $108 million in 2014 to $1.9 billion by 2022. Surveys indicate that a majority of Americans have now heard of CBD, and around 20% report having used a CBD product in the past year.
A key observation from the FDA trial was that only one of the participants with elevated liver enzymes actually noticed any symptoms (like abdominal discomfort or jaundice) within the four-week study period. This suggests that users of over-the-counter CBD products may not realize they are incurring potential liver harm. The study authors recommend that doctors should start asking about regular CBD use as part of routine medical screenings. "When doctors get liver chemistry results back and they’re out of whack, they should be aware to ask, ‘Were you taking CBD?’ Because a lot of people are," Watkins commented.
Understanding Susceptibility and Future Research
Relatively little is known about why some people are more susceptible to CBD-induced liver injury than others, but genetic factors are thought to play a role. According to Englund, CBD can also inhibit certain liver enzymes that are necessary for metabolizing other medications, which can lead to drug-drug interactions. Interestingly, the new FDA trial found that the majority of participants who experienced the most serious liver issues also developed signs of an immune condition called eosinophilia, where the body produces an excess of a specific type of white blood cell. This finding, Englund said, emphasizes the importance of tracking liver safety as a potential adverse effect in all future clinical trials of CBD.
Despite these findings, some experts maintain that CBD is relatively safe for most people. Watkins, who co-chairs the Drug-Induced Liver Injury Network (a research group backed by the NIH), noted that his network has not yet detected a case of serious liver injury attributed to over-the-counter CBD. "Overall, the liver is very good at adjusting to sources of drug stress," he said. However, he also cautioned, "There could be people out there whose liver doesn’t adjust very well, and as companies compete for market share, you might start getting more potent CBD which could push people into the ranges where they’re getting into trouble."
The new FDA study provides a crucial piece of evidence in the ongoing effort to understand the safety profile of CBD. It underscores that while these products are widely available and often marketed as natural wellness supplements, they are not without potential risks. For consumers, it highlights the importance of caution, awareness of potential side effects, and discussing CBD use with a healthcare professional, especially for those with pre-existing liver conditions or who are taking other medications.
