The cannabis extract cannabidiol (CBD) has become a popular and viable medical treatment strategy in children and adults. Anecdotal accounts of successful CBD treatment of childhood epilepsy, and CBD’s strong safety profile have lent momentum to the cannabis legalization movement and expanded the scope of medicinal uses for cannabis.
However, some are skeptical of cannabidiol's medicinal value because they believe CBD could convert to THC in the patient's stomach. But should you buy into the fear?
CBD vs. THC
CBD’s feasibility as a medical treatment for individuals of all ages hinges on its safety profile, known as the therapeutic index. The therapeutic index is the range between the effective dose (the one that is used to treat an ailment) and the toxic dose (the one that has an adverse effect). The greater the difference between effective dose and toxic dose, the greater the therapeutic index and the better the safety profile.
Δ9-THC, the primary psychoactive ingredient in cannabis that gets you stoned, has a particularly low therapeutic index throughout age demographics where the brain is still developing (i.e. from birth until around 21 to 25 years). THC exposure during early stages of development is thought to disrupt the neuronal connections between the brain’s primary relay center and its cortical targets, which may underlie the increased propensity of schizophrenia in children exposed to THC.
Heavy marijuana use, which results in greater THC exposure, is also associated with fewer connections between the left and right sides of the brain. But once the brain is more fully developed in adulthood, the therapeutic index of THC increases.
CBD has a higher therapeutic index - not only in adulthood, but in childhood as well. A number of studies have found that heavy CBD use has no substantial side effects of heavy CBD use even after doses as high as 600 mg/kg - which is well-beyond the effective dose in laboratory animals and humans.
However, if CBD is indeed metabolized into THC, as a recent report published in 'Cannabis and Cannabinoid Research' claims, the overall safety profile of CBD could be in jeopardy.
In the 'Cannabis and Cannabinoid Research' report, scientists with ties to Zynerba Pharmaceuticals tested the effect of the stomach’s acidic environment on CBD stability by simulating our gastric fluids in a glass dish. They found that CBD converted to Δ8-THC and Δ9-THC in the simulated gastric fluid, but that conversion did not occur when CBD was tested in a non-gastric physiological solution. That means if this conversion is likely to occur in the human body, it would take place in the stomach.
This unsettling finding comes at a crucial moment since CBD has been gaining greater acceptance among the public and physicians. If the study is accurate, then its finding could upend the progress scientists have made toward demonstrating CBD’s strong potential as a treatment with a low-side effect profile in the laboratory and in human clinical trials.
But should we believe it? Or could this be a case of misinterpretation and overgeneralization motivated by the financial interests of the company backing the study?
The case for CBD
Rebuttals to the original publication came quickly. And the criticisms landed several blows that severely undercut the conclusions drawn in the study. Here are the four main counterarguments:
- Simulated gastric fluid is a far deviation from an individual’s stomach conditions. It’s hard to mimic one’s stomach outside of the body, and small differences in the gastric juice “recipe” can impact how CBD gets converted. Using a different gastric fluid recipe, an earlier study found that while some CBD gets converted to THC in a simulated stomach environment, it’s far less than that demonstrated in the current study. Were the scientists just “lucky” to land on their chosen gastric fluid recipe which led to an exaggerated effect?
- If CBD gets converted to THC in people, then THC should be present in the urine of individuals given high doses of CBD. But THC is largely absent in the urine of subjects administered CBD (trace amounts of THC were detected, but since THC metabolites were absent, it was proposed that THC formed after samples were collected).
- If CBD converts to THC in people, then they should experience effects typical of THC. But they don’t. Individuals administered CBD at levels well beyond therapeutic doses don’t experience side-effects or behavioral symptoms typical of THC.
- Lastly, it’s hard not to acknowledge the study's ties to Zynerba Pharmaceuticals, which funded the project. Several of the study’s authors have director or managerial roles within the company. That does not necessarily mean that the researchers have nefarious intentions. But Zynerba does have a large financial stake in the conclusions of this study. They have developed a transdermal cannabinoid administration method that would allow patients to use CBD in a treatment that would bypass the stomach. So showing that CBD converts to THC in the stomach could convince many patients (including children, adolescents, and adults looking to avoid THC’s effects) to use a transdermal treatment method. Again, that doesn't mean the researchers meddled with their results. But it does mean there’s a financial benefit for them to amplify their own conclusions, overstate those by other researchers, and generalize their findings for human patients.
In general, individuals who consume large amounts of CBD don’t get high or experience THC-like effects. Further, the available research suggests that even if CBD does convert to THC, the amount of THC would be so minimal that it would be below physiological or behavioral consequence.
But this debate does raise an important point: the method of cannabis consumption matters. Whether it’s smoked, vaped, eaten, or applied to the skin, it’s going to lead to different responses among individuals. Given the large number of cannabinoid receptors in the digestive tract, many individuals may indeed find more effective treatment with fewer side effects with a transdermal administration of cannabis that bypasses the gut.
So Zynerba Pharmaceuticals may indeed have an important product, but not because of their claim that CBD converts to THC in the stomach. Spewing this idea only hurts public opinion and impedes the progression of pro-medicinal cannabis public policy initiatives. In the end, it hurts those who, out of fear or restricted access, fail to obtain relief from CBD’s wide medicinal scope and high therapeutic index.