A study and associated article on the dangers of CBD for the liver was recently released. After significant review we have identified major problems with the study itself in the journal Molecules and the reporting on Forbes, needlessly creating fear about a tremendously safe compound. Below is our analysis.
The main criticism is the doses they use. They use a FDA recommended method to convert animal doses into human doses, and their starting point is the dosing used with Epidiolex for refractory epilepsy (20mg/Kg).
First, that dose of Epidiolex is extremely high. Although controlled clinical information is very limited, the experience of people dealing with epileptic kids shows positive results using much lower doses.
Second, that conversion may work for other herbal preparations or drugs in general, but it doesn’t seem to work for cannabis. For example, anticancer responses in mice have been reported with 45mg/Kg THC that, according to this conversion method, is 3.6g of THC daily in humans. Although results from controlled clinical studies are not available yet, the experience from groups guiding cancer patients in the medical use of cannabis suggests positive results with at least one order of magnitude less than that. That is clearly suggesting that this conversion doesn’t work for cannabis.
Third, the doses authors used in the study are unreasonably high. They even acknowledge it in the Discussion. There is a sentence where they literally say “Although 2460 mg/kg (MED of 200 mg/ kg CBD) is not applicable to most real-life scenarios, it does provide critical information regarding the potential consequences of CBD overdose”. 200mg/Kg for humans (2460mg/Kg in mice, the only dose that produced effects in the acute protocol) is 16g of CBD for an 80kg average man and 12g of CBD for a 60kg average woman. It is inconceivable that anybody is going to ever use that amount of CBD in a single dose. Even the 50mg/Kg for humans (615mg/Kg in mice in the sub-acute experiments, the only dose that produced effects) is not a “real-life scenario”: 4g for a 80Kg person and 3g for a 60Kg person, and taken several times. Who is going to do that???? This is also an example of a manuscript that has not been properly reviewed: the title of the article and the abstract are misleading. Authors should have mentioned that the doses used in the study are not “real-life” doses, and mention the word overdose as well. An objective reviewer shouldn’t have allowed those two concepts to be left in a short sentence in the Discussion (that very few people read).
Another criticism: The solvent. Although authors talk about CBD in the paper, they worked with a CBD extract, and they used hexane to produce it. They say that they analyzed the residual solvent, and that it was < 0.5%. That means that they may have up to 0.49% hexane in their preparations, which is not a minor amount, and that the higher doses would have more hexane than the lower doses. I would be interesting to analyze whether the effects that they observe are actually due to the CBD or to the residual hexane. I would be interesting to see the effect on the liver of sesame oil (what they used as vehicle) containing the exact same amount of hexane that their maximum doses of CBD had.
Another criticism: The results. The changes the authors observed (which were observed only at the highest doses) are just suggestive of minor liver changes, not of liver failure. An independent pathologist analyzed, for example, Figure 3, and she concluded the the images showed perfectly normal liver tissue in all cases.
Finally, a comment on the Forbes article: The journalist was not very precise in some of his statements. He says, for example, that CBD killed some of the animals, which is not true. He also references a few articles showing negative effects of CBD, but doesn’t mention the huge amount of papers pointing in the opposite direction. Apparently, when he did his research on the topic, he could only find one article showing positive effects of CBD on liver function, which he defines as controversial. It is extremely important to do exhaustive bibliographic searches when publishing articles like this one, to provide readers with complete information.