There is no clinical evidence of liver toxicity in patients ingesting CBD products, show the initial findings from the industry-sponsored, decentralized human safety study of hemp-derived CBD products.
Between August 2020 and February 2021, 839 consumers completed the study led by 12 companies, commissioned and designed in response to the FDA’s requests.
After seven months of clinical investigation, the study shows no evidence of liver disease in the 839 participants and no increase in the prevalence of elevated liver function tests when compared to a population with a similar incidence of medical conditions.
Clinically insignificant elevations
“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. Three of the 839 participants had 3x normal levels of the liver enzyme ALT. These three consumers are taking prescription medications that are known to elevate liver enzymes, and we are investigating whether prescribed medications or other factors contribute to these outliers,” said co-investigator Jeff Lombardo PharmD, BCOP.
Almost 70% of study participants reported having a medical condition and taking medications for those conditions, without an increase in reporting of adverse events. Studies of similar populations demonstrate an 11% elevation in liver function tests, while this research demonstrated ~9% elevation.
“This unexpected, positive finding makes the data even more compelling and provides significant data to consider secondary safety measurements in the general population,” said Keith Aqua, MD, co-principal investigator of this IRB-approved study.
“We are encouraged by these findings and hopeful this study provides FDA with sufficient science-based data to determine and take action on a safe regulatory path forward,” said Dr. Aqua. “We will continue to analyze these real-world data and are adding a second cohort to this study to increase statistical certainty for liver safety and secondary measures across diverse populations and consumers with various medical conditions.”
Principal investigators met with FDA on March 15 and reviewed preliminary liver safety study results in the form of an abstract. The parties also discussed establishing a direct communication feed to FDA so it can receive raw, blinded, aggregate data for its analysis.
These are only preliminary findings published by ValidCare. Considering the study has not been published yet, the detailed results and the dosage observed remain unknown.
CBD and liver toxicity: The risks of high dosage
Previously to these findings, there were concerns about potential liver toxicity caused by CBD. A paper published in Clinical Pharmacology & Therapeutics in October 2020, presenting results from a randomized controlled trial of CBD on healthy adults, showed that the administration of 1500 mg of CBD per day for 3,5 weeks is causing liver damage. Five out of 16 participants in the study met the international consensus criteria for drug-induced liver injury, and some had symptoms consistent with hepatitis or hypersensitivity. In the same trial, the peak serum alanine aminotransferase values were above the upper limit of normal in 7 (44%) participants.
There were treatment‐emergent adverse events (AEs) in 14 (88%) of the 16 participants. The most common were gastrointestinal disorders, including diarrhea in eight (50%) participants and abdominal discomfort in five (31%) participants. Most of these adverse events were first experienced during the CBD titration phase. They were generally mild (31%) or moderate (50%) in severity.
However, the dose given to the participants in this trial exceeded the maximum recommended dosage (70 mg of CBD daily) by more than 20 times, which needs to be taken into account when speaking about the adverse effects and possible liver damage due to consuming CBD.
CBD helps patients with chronic liver disorders
When taken in recommended doses, CBD can help patients with chronic liver disorders, such as autoimmune hepatitis (AIH). A study on CBD consumption impact on 371 patients with autoimmune hepatitis (AIH) shows that 25% of patients with AIH used CBD for pain, poor sleep, and fatigue. More than 18% of patients who were using CBD were able to stop using other medications, and just over 3% reported side effects.
The most frequent AIH symptoms treated by participants with CBD were poor sleep (66.7%), pain (66.7%), fatigue (44.1%), “liver inflammation” (29%), and itch (10.8%). Survey participants reported CBD used resulted in significant improvement in sleep (54/59, 93%), pain (55/63, 87.3%), fatigue (25/38, 65.8%), “liver inflammation” (27/32, 84.4%), and itch (7/8, 87.5%). Seventeen (18.3%) ever CBD users reported they were able to stop or reduce a prescription medication because of CBD use. Drug classes reduced or stopped included pain (11/17; 5 narcotics, 4 NSAIDs, two other), immunosuppressants (4/17; 3 steroids, 1 AZA), anxiolytics (3/17; 2 lorazepam, one diazepam), antidepressants (1/17; sertraline), and sedatives (1/17; zolpidem).
The median dose was 20 mg and the median duration of CBD use among current CBD users was 3.5 months, significantly more than prior CBD users (1 month).
CBD was administered most frequently via sublingual drops (55.9%), oral capsule (32.3%), inhalation (28%), and topically (12.9%).
The most common cause for stopping CBD was cost (50%), worry about positive drug test (10.5%), side effects (10.5%), ineffective (7.9%), the doctor advised against CBD (7.9%), and change in the law (7.1%).
Serious side effects attributed to CBD therapy were reported by three participants (3.2%) and included: hunger (1), dry mouth (1), red eyes (1), euphoria (1), and itchiness (1).