Distorted Science: Does CBD Change to THC in the Stomach, and Who Benefits By Claiming It Does?

Photo Credit: Clarissa A. Leon, Photographer — Creative Commons

In 2016, a new journal Cannabis and Cannabinoid Research published a paper suggesting that non-psychoactive cannabidiol (CBD) converts to psychoactive tetrahydrocannabinol (THC) in the stomach. The controversial paper was coauthored by several scientists employed by Zynerba Pharmaceuticals in Devin, Pennsylvania. It was not the first time that researchers addressed this issue.

In considering whether CBD converts to THC in the stomach, there are three major kinds of data that scientists examine:

• The first involves blood samples and physiological tests of humans who have ingested CBD, which demonstrates if they are actually exposed to THC and if they experience THC-like effects after CBD administration.
• The second kind of data involves studies that examine excreted metabolites after ingestion of CBD. Excretion studies may not prove that a particular metabolite is physiologically relevant, but they could prove if these breakdown metabolites are formed.
• And the third and least significant type of data derives from experimental organ models — such as artificial gastric fluid or extracted liver microsomes — that might demonstrate the possibility of a CBD-to-THC conversion, but does not necessarily translate into human experience.

The recent article by John Merrick et. al. (2016) that sparked renewed interest in CBD’s potential conversion to THC falls into the third category. It raised concerns among patients, physicians and policymakers about possible adverse side effects that might limit CBD’s otherwise formidable therapeutic utility and market potential. Misinformation regarding the consequences of oral CBD administration could skew public policy and regulatory decisions at a time when cannabinoid therapies are gaining favor among health professionals and the general public.

Inconsistent findings

There have been extensive clinical trials demonstrating that ingested CBD – even doses above 600 mg – does not cause THC-like effects.1 The lack of THC-like effects was discussed in detail by Grotenhermen et. al. (2017) in a response to Merrick’s publication. The lack of such effects strongly suggests that CBD does not trigger significant CB1 receptor activity in the brain, which would cause a THC-like “high.” One clinical study examined the blood concentration of THC and its active metabolites after 16 men ingested 600 mg of CBD; the resulting change in the concentration of THC metabolites was statistically meaningless. To the extent that THC is formed from orally ingested CBD, it is physiologically insignificant.

There are a few human studies indicating that very small amounts of THC are excreted in urine after someone ingests CBD. Less than 1% of the total CBD is excreted as ∆9-THC, and between 1-2% is excreted as ∆8-THC. These studies demonstrate that a small amount of ingested CBD does isomerize to THC, but this in and of itself has no practical significance. The clinical evidence demonstrating that CBD does not cause THC-like effects subsumes any imagined physiological consequences associated with this data.

Two studies have explored the conversion of CBD to THC in artificial gastric fluid: One performed by Watanabe et. al. (2007) and the recent publication by Merrick and colleagues. Although Merrick cites Watanabe’s work to build the case for CBD-to-THC conversion in the stomach, Merrick’s experiment is strikingly inconsistent with Watanabe’s data. In Watanabe’s simulated gastric fluid study, 15.4% of the CBD was converted into four compounds: ∆9-THC, CBN,

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