Does CBD Cause Live Function Abnormalities?

By Gregory L. Smith, MD, MPH

A Forbes magazine article in the June 18, 2019 issue was headlined “Marijuana Study Finds CBD Can Cause Liver Damage.” The article correctly notes that CBD is non-psychoactive, “highly revered as an alternative treatment for a variety of common ailments,” and that “CBD is becoming more popular than sliced bread,” referring to the exponential growth in sales of artisanal cannabidiol (CBD) extracts and products. However, after these positive, evidence-based opening comments, the science becomes subjective and hyperbolic—a confusing choice in what is typically a very prestigious and influential magazine.

The essence of the story is that the author of the Forbes article reviewed a piece recently published in the peer-reviewed journal Molecules, entitled “Hepatotoxicity of a Cannabidiol-Rich Cannabis Extract in the Mouse Model.”[1] This article provides an analysis of liver damage from astronomical doses of CBD (doses of up to one-quarter of the mice’s weight in CBD) ingested through the stomach. The study performed was to investigate the possible adverse effects of CBD on the liver.

The extensive trials of Epidiolex®, which is a 99.5% pure isolate of CBD, revealed that as the dose of oral CBD went up, so did an increase in liver enzyme elevations and liver damage. This new mice study confirms that several days of excessively high oral doses of CBD isolate can damage the liver.

Epidiolex® is an FDA-approved cannabis extract that is 99.5% pure CBD. The drug originally studied was by administering oral doses to humans. When CBD is swallowed and ingested, it is processed by the liver and metabolized. Roughly 90% of the CBD is turned into different metabolites by a process in the liver known as the ‘first-pass effect.’ Scientists know little to nothing about what these metabolites do, and most are thought to be inactive [2]. Only a tiny fraction (estimates of 6-10%) of the oral dose of CBD eventually becomes bioavailable in the blood to trigger therapeutic effects [3]. For an average-sized adult, the recommended maintenance dose of Epidiolex® is a whopping 1600mg/day. By comparison, for a typical artisanal CBD extract taken under the tongue, not orally, the usual dose is a much smaller fraction of this, roughly 25-100mg/day. By taking the dose under the tongue, the CBD is absorbed in the mouth and the CBD misses the intense metabolism of the ‘first-pass effect.’

This Forbes article misses the mark by a long shot. The fact that very large oral doses of Epidiolex® cause liver enzyme elevations have been well established in recent years. However, the exponential increase in the U.S. has not been in the use of the oral CBD drug Epidiolex®. G.W. Pharma reports only 7,600 patients have received Epidiolex® prescriptions during the first quarter of 2019[4]. The average cost, according to G.W. Pharma reports, is $32,500 a year.

The use of artisanal CBD extracts has grown exponentially in recent years. Artisinal CBD typically comes in dropper bottles, and the recommended directions are to swish the dose under the tongue for 1-2 minutes. Many of these artisanal CBD products are broad-spectrum extracts filled with minor cannabinoids and terpenes from the hemp oil. These other components of raw hemp oil are purported to improve the dose-response [5] compared to a 99.5% pure CBD isolate, such as Epidiolex®. This synergistic effect from broad-spectrum extracts is widely known as the “entourage effect.” [6, 7] The cost for a high-quality, broad-spectrum CBD extract made in an FDA OTC-certified facility with independent lab testing and certified good manufacturing practices (cGMP) is about $1,200 a year.

These artisanal CBD extracts are absorbed sublingually into the bloodstream through the mouth, therefore bypassing the metabolic process that occurs in the liver, or the ‘first-pass effect.’ The result is that much fewer milligrams are needed to achieve the same bioavailability and 90% of the CBD is not turned into a stew of metabolites, much of which scientists still know very little about (such as their hepatotoxicity).

Finally, total consumer sales of these CBD extracts have gone from $108.1 million in 2014 to an estimated $813.2 million in sales for 2019 [8]. A survey of 2,500 adults in January 2019 revealed that nearly 6.9% of Americans currently use CBD and that 44% of people use CBD extracts [9]. Despite years of extensive use of artisanal CBD extracts, there has not been a single report of elevated liver enzymes or liver damage in persons using these products. In fact, the only reported animal or human evidence of liver damage from CBD has been when accompanied with oral doses of the CBD isolate required by the FDA-approved Epidiolex®.

Both medical professionals and the public must exercise extreme caution as to where they get their scientific information. Non-peer reviewed sources such as Forbes and websites that spread disinformation to promote their own products or agendas are very poor sources of evidence-based medical information.

Citations

  1. Hepatotoxicity of a Cannabidiol-Rich Cannabis Extract in the Mouse Model. Molecules
  2. Metabolites of cannabidiol identified in human urine.
  3. Human Metabolites of Cannabidiol
  4. US Quarterly Sales
  5. Pharmacology & Pharmacy
  6. Some of the Parts
  7. Taming THC
  8. Total CBD consumer sales U.S. 2014-2022
  9. Collective View of CBD