Healthy adults who took doses representative of consumer use of cannabidiol (CBD) daily for four weeks showed significant increases in liver enzymes—though no actual liver damage—in the first controlled trial to examine the cannabis compound’s effects on liver function, researchers reported in JAMA Internal Medicine.
CBD is a common chemical compound found in the cannabis plant, specifically in both hemp and marijuana. Unlike tetrahydrocannabinol (THC), another common cannabinoid, CBD does not produce a psychoactive effect, also called the “high.”
CBD is frequently marketed as a wellness product with research interest in its supposed benefits in treating conditions like chronic pain and anxiety.
“Just because it’s sold over the counter, sold under a health and wellness stamp, does not mean it is safe,” Dr. Diana Martins-Welch, a Northwell Health palliative medicine physician and cannabis clinician, and not involved in the trial, told The Epoch Times.
The Clinical Trial
The double-blinded, placebo-controlled clinical trial, recently published in JAMA Internal Medicine, involved 201 healthy adults randomly assigned to receive either 2.5 milligrams of CBD per kilogram of body weight (about 2.3 milligrams per pound) or a placebo twice daily for four weeks. The average age of participants was 36 and more than half were male.
Those who used CBD daily experienced significant increases in liver enzymes, specifically alanine aminotransferase, with levels rising more than three times the upper limit of normal. Women were most affected.
Seven participants met criteria to withdraw from the trial due to having high enough blood cell and liver enzymes levels to suggest potential drug-induced liver injury, though no participants experienced jaundice or clinical symptoms of impaired liver function.
“We selected a dose toward the upper end of reported consumer CBD use with sufficient dosing duration and monitoring to observe liver enzyme level elevations should they occur,” the study authors wrote.
No participants in the placebo group experienced these effects.
The researchers pointed to a systematic review showing that 25 percent of liver enzyme elevations from daily CBD treatment resolved spontaneously with continued use, suggesting the body may adapt to the compound over time.
While CBD is generally considered well tolerated, it can cause side effects such as dry mouth, diarrhea, and drowsiness.
What the Findings Mean for CBD Users
The trial found that people who had higher liver enzymes after taking CBD also tended to have higher levels of eosinophils, a type of white blood cell. Eosinophils are often released during liver injury, and their levels are commonly measured as a potential indicator of such injury.
Only one participant had symptoms potentially indicating liver problems, though that participant’s liver enzyme and eosinophil levels were not sufficient to meet withdrawal criteria.
“While it’s not necessarily showing you that your liver is inherently damaged,” Martins-Welch noted, “It means that you’re inching closer to doing damage to it. And if you keep it up you’re putting this undue stress on the liver.”
Elevated liver enzymes from CBD use are already known in clinical practice, particularly because users often take higher doses since CBD isn’t intoxicating like THC, Martins-Welch said.
While authors said the amount tested in participants were “doses representative of consumer use,” Avis Bulbulyan, chief executive officer of SIVA Enterprises, a full-service cannabis business development and solutions firm, said that the study’s findings may not reflect in typical CBD users.
“This study uses a pretty high dose and it’s not reflective of typical use and dosage,” Bulbulyan, told The Epoch Times.
“To subject a patient that doesn’t normally consume that sort of dosage, it shouldn’t be surprising when the liver shows signs of stress, which elevated enzymes is really more of an indication that the liver is under stress than anything else,” Bulbulyan continued.
Bulbulyan said that the study doesn’t prove that typical, consumer level CBD is dangerous, only that sudden high doses puts the liver under stress “without any indication of serious or long term damage.”
The Regulation Problem
The findings highlight ongoing concerns about the unregulated CBD market. While the 2018 Farm Bill legalized hemp-derived CBD, products remain largely unregulated, with varying levels of active compounds and no standardized dosing guidelines.
“If these are the results using clean CBD, imagine what’s out there in the unregulated market,” Bulbulyan said. “Which again goes back to the need for federal reform,” he added. “In fact, lack of reform and the drug laws on cannabis are more harmful and dangerous than cannabis itself.”
CBD products are currently popular for treating conditions including pain, anxiety, and depression, but there’s little guidance on safe usage. Data from the 2022 National Survey on Drug Use and Health indicate that 20.6 percent of U.S. adults reported using CBD in the prior year.
Since unregulated CBD products are increasing in popularity and because CBD can increase liver enzyme levels, the authors say that CBD should be included as part of medical screenings, especially in patients with existing liver conditions or those taking drugs that need to be broken down in the liver.
“Just because it’s sold over the counter, it’s sold under a health and wellness stamp, does not mean it is safe,” Martins-Welch said. “And I tell patients that about everything down to fish oil, [and] omega-3s—too much of anything is not good, so moderation is key.”