A recent clinical trial raises questions about the safety of widely consumed CBD capsules, gummies, edibles, oils and lotions that are omnipresent in the United States and many other countries. But pioneer cannabis clinician Bonni Goldstein, MD, cautions patients and physicians not to overstate the findings of the new FDA study, which was published in JAMA Internal Medicine. Below is a summary of the trial results followed by comments from Dr. Goldstein, the CEO and co-founder of GoldsteinWellness.com, a free medical cannabis educational platform for licensed healthcare clinicians, and Medical Director of Canna-Centers in California.
Last year, scientists from the FDA’s Division of Applied Regulatory Science carried out a randomized double-blind placebo-controlled trial to assess how “low-dose CBD” affects liver function in a group of healthy middle-aged men and women. The results of the trial were recently published by JAMA Internal Medicine.
Over the course of four weeks, 201 volunteers received either 5 mg per kilogram of body weight (approximately 2.3 mg per pound or the equivalent of 350 mg for a 154-pound individual) of oral CBD isolate, or a placebo for comparison. The CBD dose administered to participants is described in the report as “a typical amount that might be used by consumers.”
While the vast majority of people in the trial were unaffected, five percent showed greatly elevated levels of the liver enzyme aminotransferase, a known marker of liver cell damage or inflammation. Women appeared to be more vulnerable than men. Those who experienced the most serious liver problems also developed signs of an immune condition called eosinophilia, which occurs when the body produces an excess of a type of white blood cell called eosinophils. In all cases, the liver enzyme levels returned to normal within one or two weeks of stopping CBD.
Elevated levels of liver enzymes were among the leading causes of withdrawal of young epilepsy patients from previous clinical trials involving high doses of Epidiolex, a pharmaceutical CBD isolate. Raised liver enzymes were observed in 14% of participants, who were concurrently taking other anti-epileptic medications, which could have contributed to the adverse liver effects.
But the newest FDA findings are the first to suggest that even “low-dose CBD,” in the absence of other drugs, may pose a risk to liver health. This could have significant implications for numerous individuals who are consuming over-the-counter CBD supplements. According to various surveys in recent years, the majority of people in the U.S. have heard of CBD, and around 20% reported using CBD products in the past 12 months.
Dr. Bonni Goldstein replies:
I do not consider 350 mg CBD a low dose. It would be interesting to see how the researchers determined this particular dose as representative or typical, as this does not reflect what most adult CBD consumers/patients are using, at least in my experience. In fact, the majority of people that seek my advice about CBD are underdosing. Additionally, the cost of 350 mg of CBD per day ranges from about $7 – $40 per day, so we are talking about $210 per month up to $1200 per month. Moderately to severely ill pediatric and adult patients might pay this amount for relief, but for the general population using CBD to help with pain/sleep/anxiety, this cost may be prohibitive.
It should be noted that the drug administered in the study was an isolate (which typically requires a higher dose than a full spectrum CBD-rich product). Elevated liver enzymes are well-documented in the purified CBD (Epidiolex) studies, and in a few other reports as well, so this is nothing new.
In my practice, less than 10 patients in total have had elevated liver enzymes, all of whom were taking chemo or valproic acid concurrently (and I have a fair number of patients taking over 500 mg per day, all full spectrum). In all cases, labs normalized after CBD dosing was reduced or discontinued. I know of no instances where liver injury from CBD was irreversible.
The key take-away from this study is the importance of clinicians routinely asking about cannabinoid use during patient appointments, assessing dosing and checking liver function tests if indicated. Unfortunately, I think most clinicians do not have working knowledge of cannabinoid pharmacology, and if they see or hear about this report they will likely generalize and tell patients that CBD causes liver damage, missing the critical nuances of full spectrum vs. isolate, the importance of minimal effective dosing, and the advantages of the entourage effect, which allows for lower dosing.
Bonni Goldstein, MD is the CEO and co-founder of GoldsteinWellness.com, a free medical cannabis educational platform for licensed healthcare clinicians in the U.S. and Medical Director of Canna-Centers.
Source link