New FDA Clinical Trial Raises Concerns Over Potential Liver Risks From Even Low Doses of CBD
Despite Widespread Use, Scientific Evidence on CBD Safety Remains Limited
Cannabidiol (CBD), once a niche wellness product, has grown into a billion-dollar industry in the United States, with capsules, oils, edibles, and lotions lining shelves from pharmacies to grocery stores. Yet while consumer interest has surged, scientific data on its safety—particularly concerning liver health—remains limited and inconsistent. A newly published study from the U.S. Food and Drug Administration (FDA) aims to change that by closely examining the physiological effects of even low doses of CBD in healthy individuals.
Clinical Trial Finds Signs of Liver Stress in a Small but Notable Subset of Participants
In a randomized, double-blind, placebo-controlled trial conducted by the FDA’s Division of Applied Regulatory Science, researchers assessed how low-dose oral CBD impacts liver function in a diverse group of healthy, middle-aged adults. Over four weeks, 201 participants were given either a placebo or a daily CBD dose of 5 mg per kilogram of body weight—roughly equivalent to 350 mg for someone weighing 154 pounds.
While most participants tolerated the compound without notable issues, approximately 5% developed significantly elevated levels of the liver enzyme aminotransferase. This enzyme serves as a biomarker for liver cell stress or damage, indicating that CBD, even at moderate doses, may affect liver health in some individuals. Notably, the enzyme levels typically returned to normal within one to two weeks after discontinuing CBD.
Small Number of Withdrawals Due to Possible Drug-Induced Liver Injury Raises Red Flags
The study also documented seven withdrawals due to clinical indicators consistent with drug-induced liver injury (DILI). While no participant required hospitalization or experienced permanent damage, the findings suggest that even healthy individuals are not universally immune to the compound’s potential side effects. Women were more likely than men to experience elevated enzyme levels, though researchers caution that larger trials are needed to confirm this pattern.
These outcomes reinforce the need for broader population studies and enhanced consumer awareness about the risks associated with unregulated, over-the-counter CBD consumption.
Rapid Rise in CBD Use Has Outpaced Regulatory and Scientific Oversight
Between 2014 and 2022, U.S. sales of CBD products jumped from $108 million to $1.9 billion. Much of this growth followed the passage of the 2018 Farm Bill, which legalized the commercial sale of hemp-derived products containing less than 0.3% THC. As a result, CBD has become a household name, with approximately 20% of American adults reporting usage in the past year.
However, while the popularity of CBD continues to grow, public health guidance and rigorous regulatory standards have lagged behind. Many products are sold without clinical validation, dosage instructions, or safety warnings—leaving consumers largely in the dark about proper use and potential adverse effects.
Liver Injury Symptoms Often Go Unnoticed, Complicating Diagnosis and Treatment
Liver damage often manifests subtly, with symptoms such as fatigue, abdominal discomfort, and yellowing of the skin or eyes appearing only after significant injury has occurred. In the FDA trial, only one participant with elevated enzyme levels experienced symptoms within the four-week window.
This underscores a critical issue: many users may unknowingly experience liver stress without outward signs. Consequently, experts suggest incorporating CBD usage into routine medical screenings, especially for individuals presenting with unexplained liver enzyme abnormalities.
Prior Studies Have Also Linked CBD to Liver Risks in Specific Clinical Settings
Concerns over CBD’s potential impact on liver health are not new. Previous clinical trials, especially those focused on using CBD for epilepsy treatment in children, have shown liver enzyme elevations in as many as 14% of participants. However, in those cases, the participants were also taking anti-epileptic medications, making it difficult to isolate CBD as the cause.
This new FDA study differs by examining the effects of CBD in isolation, eliminating potential interactions with other drugs. The results, while not alarming in a general sense, highlight the need for caution—particularly for individuals with preexisting liver conditions or those combining CBD with other medications.
Similarities to Acetaminophen Highlight Potential Mechanism of Liver Stress
The mechanism through which CBD affects the liver remains under investigation. Research suggests that certain dosages may induce liver stress in a manner similar to acetaminophen (paracetamol), a widely used over-the-counter drug known to cause liver damage when taken in excess.
Acetaminophen is one of the leading causes of drug-induced liver injury in the United States. Though CBD is not yet in that category, the comparison raises important questions about the compound’s pharmacology and the potential for adverse reactions in vulnerable individuals.
High Doses Are Known to Pose Greater Risk, But Moderate Doses May Also Be Problematic
Most documented liver injuries from CBD have occurred at high oral doses exceeding 1000 mg per day. However, emerging reports suggest that even moderate intake levels—between 300 mg and 1000 mg—may pose risks for some users.
The reasons behind this variability remain unclear but could involve genetic predispositions, immune responses, or preexisting health conditions. In the FDA study, several participants with the most concerning liver enzyme elevations also showed signs of eosinophilia, an immune response characterized by an excess of white blood cells known as eosinophils. This may signal that certain individuals experience a heightened inflammatory reaction to CBD.
Enzyme Inhibition and Drug Interactions Add Complexity to CBD Use
CBD has been shown to inhibit several liver enzymes that are crucial for metabolizing pharmaceutical drugs. This property complicates its use for people taking prescription medications, increasing the risk of interactions that can alter drug effectiveness or amplify toxicity.
As CBD continues to be explored as a treatment for psychiatric conditions and substance use disorders, researchers and clinicians are urging more rigorous monitoring of liver enzyme levels in clinical trials. These precautions are essential to ensure that CBD’s therapeutic potential is not overshadowed by preventable safety concerns.
Experts Urge More Research but Emphasize CBD’s Overall Safety Profile for Most Users
While the trial’s findings raise important safety questions, medical experts involved in broader studies emphasize that CBD remains relatively safe for the majority of users. The liver is highly resilient and often adjusts to new compounds without lasting damage. Furthermore, the national drug injury surveillance network has yet to flag over-the-counter CBD as a major cause of liver toxicity.
However, as the industry becomes more competitive and potent formulations enter the market, concerns remain that vulnerable individuals may begin to experience negative effects, particularly if dosage guidelines remain unclear or nonexistent.
Consumers and Healthcare Providers Are Encouraged to Proceed with Caution
As the CBD market continues to expand, the findings from the FDA trial serve as a timely reminder that “natural” does not always mean risk-free. With more potent products hitting shelves and consumer demand surging, the need for clear, evidence-based usage guidelines is greater than ever.
Healthcare professionals are encouraged to discuss CBD use with their patients, particularly those with underlying health conditions or abnormal liver test results. Meanwhile, consumers are advised to start with low doses, monitor their reactions, and seek products from reputable sources that provide third-party lab testing and accurate dosing information.
Topic(s):
OG source Download Article 
