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That Alarming CBD Liver Damage Study Is Bunk—And the Media Should Know Better

July 12, 2019
(DrAfter123/iStock)
It’s 2019 and we still live in a world where one small study, on mice, with a highly questionable methodology, published in a marginal journal, with major flaws, leads to a clickbait media panic.

Recently, you may have seen a Forbes article headlined “Marijuana Study Finds CBD Can Cause Liver Damage” that reported on a study out of the University of Arkansas for Medical Sciences.

It’s scary stuff:

Shockingly, researchers discovered that the mice given higher doses of CBD showed signs of liver damage within 24 hours. To that end, 75 percent of these animals in the sub-acute phase had either died or were on the verge of death within a few days.

But this panic and misinformation is nothing new—back in 1974, a study conducted at Tulane University supposedly showed that “the active ingredient in marijuana [THC] impairs the brain circuitry,” leading the press to dutifully run articles claiming that pot causes brain damage without a trace of skepticism.

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The 1974 study was deeply flawed. In Smoke Signals: A Social History of Marijuana, author Martin Lee called out this exceedingly small study of rhesus monkeys as “a textbook case of scientific fraud”:

Shackled in air-tight gas masks, Heath’s monkeys were [regularly] forced to inhale the equivalent of 63 high-potency marijuana cigarettes in five minutes. Lo and behold, the primates suffered brain damage from suffocation and carbon monoxide poisoning, but Heath attributed the results to marijuana toxicity.

Lucky for us—if not Forbes readers—Project CBD, a non-profit dedicated to boosting science-based understanding of cannabidiol (CBD), have just released a detailed rebuttal to the Forbes article.

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The Rebuttal

Much has changed in the last forty-five years, but the National Institute on Drug Abuse (NIDA) still holds a monopoly on the sole supply of cannabis that can be used for federally-approved studies. And the research they approve remains laser-focused on finding harm—either that or trying to create a pathway to patenting synthetic THC as a prescription drug.

Regardless of your feelings on the CBD study, it is hard to argue with dead mice—even if you are an all-knowing marijuana expert.

Mike Adams, author of the Forbes, wrote another article in which he claims there’s no such thing as an expert in cannabis because not enough is known about the plant and its effects on human beings. That’s a highly questionable claim, and I suppose it explains why he didn’t quote anyone in his article who might have poured cold water on the study’s more alarming claims.

For example, Project CBD.

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In their rebuttal of the Forbes article, Project CBD says:

The breathless reporting in Forbes focuses on a single, flawed, preclinical study and exaggerates it to the point of falsehood… A close examination of the Molecules study reveals a Pandora’s box of strange statements, problematic publishing, and unreasonable experimental design. On the first page, the abstract makes a claim that is fundamentally impossible, stating that, with chronic administration of CBD, ‘75% of mice gavaged with 615 mg/kg developed a moribund condition.’ But there were only 6 animals that received this dose! One doesn’t need an advanced degree in science or math to recognize that something is amiss. Seventy-five percent of six equals 4.5.

Dead mice aside (or rather, dead half-mice), the biggest problem with the study, according to Project CBD, is that just like in the 1974 rhesus monkey study, the dosage administered was astronomically high.

Scientists force-fed mice a single dose of CBD, ranging from the supposedly ‘low’ dosage of 246 mg/kg up to a mega-dose of 2460 mg/kg CBD… The maximum human dosage recommended for the CBD-isolate Epidiolex is 20 mg/kg, which is over 100x less than what the Little Rock researchers force fed their experimental mice.

The researchers explain away this mega-dosing by pointing to something called allometric scaling, which is basically a set of guidelines for estimating an equally potent dose of a substance for humans and other animals based on body weight and body-mass index.

But Project CBD argues that allometric scaling is a rule of thumb at best, and cannabinoids in particular are a very poor fit for the model: “The ridiculously high doses in this study will saturate the body’s metabolic machinery, preventing relevant dose-extrapolations.”

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False Claims in a Sketchy Journal

In their critique of the study, Project CBD flatly charged the University of Arkansas researchers with producing “A hit piece against CBD, not legitimate scientific work.”

Specifically, the Project CBD article cites instances of cherry-picking previous research on CBD to downplay benefits and hype harms, which obscures how unreliable past studies on mice have been in predicting how humans will react to cannabinoids, and which also presents false or deliberately misleading information.

Project CBD points to the study’s claim that “numerous reports have demonstrated neurological, cardiovascular and reproductive toxicities subsequent to CBD use”—the researchers cited nine sources to back that claim, but the only one to actually involve humans did not show toxicity.

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In fact, when contacted by Project CBD, Saoirse O’Sullivan, that study’s lead author, said, “Our research showing that CBD causes a small reduction in resting and stress-induced blood pressure does not support the authors’ claim that we demonstrated cardiovascular toxicity of CBD. In fact, most of our work is about the potential protective effects of CBD in the cardiovascular system.”

Project CBD also called into question the credibility of Molecules, the journal that published the CBD liver study.

MDPI, which publishes the journal Molecules, has been called a predatory publisher. MDPI has been criticized for publishing unsound articles… Even if such allegations are true, it doesn’t mean that good work can’t end up in one of MDPI’s 213 journals. But it underscores the importance of checking scientific work, rather than diligently repeating and amplifying whatever claims are presented.

And that really gets to the heart of the issue.

Because it’s 2019, and we still live in a world where one small study, on mice, with highly questionable methodology, published in a marginal journal, with major flaws, can lead to articles like the one in Forbes.

Which get clicks for sounding the alarm—without a legitimate reason to do so—while simultaneously drowning out more reasoned discussions of CBD’s potential dangers, and how they can best be mitigated.

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A Final Thought Experiment

One thought experiment occurred to me while researching this article.

I came across this Leafly article describing a day of testimony this past May before the FDA. In particular, I was struck by the words of Alice Mead, on hand to represent the interests of GW Pharmaceuticals, which specializes in developing pharmaceutical drugs extracted from cannabis plants—including Epidiolex, the world’s first FDA-approved CBD drug.

Normally, when Big Pharma talks to the FDA about their products, they make every effort to present the rosiest picture possible. But Mead took pains to mention that CBD is “potentially toxic to the liver” and “has powerful drug-drug interactions.”

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But the real tell was when she argued for a “strong regulatory framework.”

Because what that really means is GW Pharmaceuticals wants a regulatory framework for CBD so strong that only they can surmount it. Leafly has been reporting on the company’s attempts to win temporary monopolies for its products in a number of US states since 2017, and there’s certainly no reason to believe GW wouldn’t prefer a blanket monopoly on the entire country.

And so here’s the thought experiment:

You’re GW Pharmaceuticals, and you’ve invested heavily in both time and money to create a patented CBD drug. Now you’re about to go to market, and want to make a huge return on that investment without having to compete with CBD hamburgers and truck stop snake oil.

So what’s the biggest threat to your bottom line—that people think CBD is too dangerous, or that people think CBD is too safe?

David Bienenstock's Bio Image

David Bienenstock

Veteran cannabis journalist David Bienenstock is the author of "How to Smoke Pot (Properly): A Highbrow Guide to Getting High" (2016 - Penguin/Random House), and the co-host and co-creator of the podcast "Great Moments in Weed History with Abdullah and Bean." Follow him on Twitter @pot_handbook.

View David Bienenstock's articles

  • Andrew Jackson

    Have you ever felt sick to your stomach after taking CBD oil?

    • 360dunk

      Nope. Then again, I use about 25-35 mg per dosage twice a day.

  • 360dunk

    I’ve been smoking cannabis since going to a Jimi Hendrix concert in 1969 and haven’t slowed down a bit. That’s a half century of enjoyment with no adverse health issues. Granted, I smoke just half a joint at night, take a 10 mg edible dose, and some CBD, but if there’s any brain damage, it’s certainly not apparent. I can still beat most people at Jeopardy and crossword puzzles at my advanced age.

    Brain damage? Please. Reducing inflammation in the brain is the end result of the cannabinoids that I take. If anything, lowering inflammation helps COMBAT brain disease. Those who don’t realize this are misinformed.

  • RealTalk

    !!CANNABIS IS NOT FOR EVERYONE!!
    I have been using cannabis for over twenty years.
    In the last 5 years I have had many blood test checking specifically my liver function, having used high doses of THC and CBD for this long of time, I never have had a negative result on my liver function. My DNA allows me to metabolize cannabis, Unfortunately not everyones does.

  • Red Starnes

    Amen….I agree Big Pharmacy will demonize weed until they can get their hooks in it.

  • Adam VanWert

    As a pharmacology professor I agree that the doses used in this study were astronomical. So called allometric scaling is very flawed. Rodents metabolize faster than humans on a body weight basis, but there is one problem with this allometric method. A big problem. If CBD produces toxicity through a metabolite rather than the CBD itself, such high dosing used in allometric scaling will actually overestimate the toxicity of CBD, because the rodents produce metabolite faster. In this case, they are producing the toxin faster, if in fact CBD must be metabolized to be toxic. That we actually do not know, but without knowledge one should not assume. This article appears to be your typical alarmist publication, and a cheap shot in order to garner attention. Again, as a pharmacologist, I am not happy with the panacea claims of CBD, but to say this study has any merit is absolutely foolish.

  • Concerned Scientist

    The risk of cannabidiol induced hepatotoxicity is actually very real. High quality clinical data was produced during Phase 2 trials of Epidiolex as to the specific CYP subtypes involved in metabolism of cannabidiol.

    Cannabidiol interacts in complex ways with other CYP metabolized drugs, food constituents, and dietary supplements. In the pediatric seizure population this manifested as changes in blood levels of anti-seizure compounds and liver function assay values.

    FDA judged the risk severe enough to warrant diagnostic blood testing for liver function before starting patients on Eipdiolex.

    This is the same reason that one should not consume alcohol in combination with acetaminophen. Other PK/PD interactions are well known including with grapefruit juice (CYP inhibitor) and St. Johns wort (MAO inhibitor).

    CBD is a CNS active drug, please differ to experts on matters of its saftey profile.

    Consider this, many in the CBD community contend that because CBD is a naturally occuring substance in Cannabis it shares the same saftey profile as vaporized/orally consumed Cannabis plant material.

    This is a false equivalence. At no time in human history have large doses of pure cannabidiol been consumed by people on a regular basis. Ingesting 100 mg/day of CBD is very different than smoking 1-2 grams of cannabis.

    This holds true for other cannabinoids that are being isolated by irresponsible garage chemists and introduced to the food supply.

    Caveat Emptor until some real federal regulations are in place.