Researchers’ direst warnings on oral CBD should be taken with a lethal dose of salt

Researchers at the US Food and Drug Administration (FDA) recently published a review on the toxicity of orally-consumed CBD. The report largely echoes worries outlined in other safety reviews, such as by the European Food Safety Authority (Efsa) and the UK’s Food Standards Agency (FSA).

Like these earlier reports, the FDA review should be taken seriously and raises important considerations for future research and even use today. However, the extent of the identified risks is limited.

The findings arise mainly from animal models and/or reflect unrealistic use conditions that have yet to present as serious health risks in otherwise healthy individuals taking CBD in a responsible and moderated manner.

Drawing from studies using animal and cellular models, CBD was linked to developmental and reproductive toxicity (17 studies), liver toxicity (eight studies), immunotoxicity (four studies), and genotoxicity (four studies). One of the key pathways identified as a potential cause of this toxicity is CBD’s inhibition of certain enzymes that play a role in drug metabolism, further raising the risk that CBD could cause interactions with other drugs.

The studies do demonstrate that CBD can pose a threat, but the circumstances in which these harms manifest are difficult to extrapolate to population level health. Questions remain, too, over whether the results from the studies are really applicable to humans.

Most of the dosages considered throughout the review are unrealistically high. In one particularly egregious case, the amount of CBD used mirrored the lethal dose of table salt.

While several studies acknowledged that the doses were high, many did not, making dangerous generalisations about human use.


A question of exposure

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    Consider the study from Ewing et al cited in regards to potential liver toxicity. The authors claim the lowest dose they used in mice corresponded to the “human CBD dose of 5 mg/kg BW, the recommended daily starting dosage of Epidiolex” yet that calculation was arrived at quite informally, using a conversion scale which inadequately accounts for the specific pharmacokinetics of CBD.

    Overall, the studies provide grounds for caution and future research, but proposed parallels to human health may be overstated.

    Within the context of risk identification, excessive dosing is understandable and even desirable, as one wants to cast a broad net that captures any and all potential harms. But these studies must be understood as representing more extreme circumstances.

    As a review of those studies, the FDA report says itself it “is not a risk assessment and does not seek to identify levels of exposure that may result in adverse effects”. Unfortunately, the authors’ primary conclusion attempts to do just that, claiming “CBD raises safety concerns, especially for long term consumption by the general population”.

    Safety concerns arising from long-term consumption are fundamentally questions of exposure –in this case repeated exposure. The primary justification given for the claim is a reference to CBD’s long half-life following chronic exposure, but without concrete figures on a dose-response relationship in humans, the conclusion is nothing more than conjecture.

    As a review of the literature, the FDA’s report makes a solid case that CBD may have potential health harms that require follow-up, more active surveillance, and even may prompt caution for users with a history of liver impairment or fertility concerns.

    That said, the review oversteps its scope by trying to attribute such risks to an ultimately unsubstantiated compounding risk over time. Evidence regarding the health consequences of long-term CBD use is largely absent, and until such evidence is available, known risks should to be understood in the context of the existing evidence showing that short-term moderate CBD use is safe.

    – CannIntelligence

    Photo: Marek Kupiec

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    This article was written by one of CannIntelligence’s international correspondents. We currently employ more than 40 reporters around the world to cover individual cannabis and cannabinoid markets. For a full list, please see our Who We Are page.