Cannabidiol and Abnormal Liver Chemistries in Healthy Adults: Results of a Phase 1 Clinical Trial
In Summary: Cannabidiol (CBD) is a major component of the plant cannabis and in 2018, the first cannabidiol drug - Epidiolex - was approved for the treatment of 2 epilepsy disorders. However, over the past few years, non-prescription CBD-containing products including food, beverage, and supplements have been increasingly widely marketed and touted to deliver various health benefits. After concerns over liver safety arose in clinical trials of Epidiolex in epilepsy patients, clinicians and researchers began suspecting that consumption of CBD, even at low, therapeutic doses daily may cause injuries to the livers of healthy adults.
To investigate this possibility, doctors at the Eshelman School of Pharmacy and Institute for Drug Safety Sciences, University of North Carolina at Chapel Hill (NC, USA) conducted a clinical study with sixteen healthy adults. In this study, participants received a repeated dose administration of CBD at 1500mg/day and were monitored with the alanine aminotransferase (ALT) test, a blood test that checks for liver damage. An increased level of serum ALT is associated with liver damage because ALT is an enzyme normally existing primarily in the liver and at a low level in the serum. The researchers found that seven (44%) participants experienced peak serum ALT values greater than the upper limit of normal (ULN). More alarmingly, for 5 (31%) participants, this value exceeded 5*ULN, meeting the international consensus criteria for drug-induced liver injury. In those patients, all ALT elevations began within 2–4 weeks of initial exposure to CBD. After detection of the abnormally high blood ALT, 6/7 patients were promptly discontinued from the protocol; nonetheless, some retained symptoms consistent with hepatitis or hypersensitivity.
Based on their findings, the researchers concluded that healthy adults consuming CBD may experience drug-induced liver injury, as demonstrated by elevation in serum ALT and warned that clinicians and patients alike should be alert to this potential effect of CBD prior to prescribing or using it.
#MDNote: The goal for publishing this blog is, in part, to raise awareness of poor study design, as it may reflect upon typical use of CBD in every day health and wellness. The doses used in this study were unrealistically high for general use, and the description of a presence of detectable liver enzymes as a marker of evidence of liver damage is a skewed (if not outright deceptive) indicator. For most typical use, one would have to consume more than a complete bottle of over-the-counter CBD product to achieve the levels of doses they were investigating here. Large doses may cause liver function adjustment to accommodate the increased blood levels, but this is not necessarily indicative of damage, per se, but rather increased, and expected, functioning.