How is CBD metabolized?

CBD is very much in the news at the moment, but while the science community have been studying the cannabinoid since the 1960s, there is still comparatively little known about its mechanisms of action compared to THC.

A consensus certainly exists about the cannabinoid’s multiple molecular pathways, namely its binding affinity with non-endocannabinoid receptors such as 5-HT1A serotonin and TRPV-1.

But an area that remains much hypothesized about but largely unexplored, is what happens to CBD when it passes through the body, and could this metabolization contribute to the cannabinoid’s reported effects?

The importance of understanding CBD’s metabolism in the body

So why should we care so much about how CBD is metabolized? Well, if the cannabinoid is to be taken seriously as a drug for certain pathologies, how it is broken down in the body is almost as important as the drug itself.

According to scientist Ujváry István, “Whenever a new synthetic drug is found to have some activity, the first thing you do is look into how it is metabolized, how other drugs influence its metabolism, and how the drug influences the metabolism of other drugs.”

So what do we mean exactly by drug metabolism?

This relates to how drugs are broken down in the body to aid the elimination process. As most medication is taken orally, we will talk in terms of what happens after a drug has gone through the ‘first-pass effect’, in which the drug is absorbed by the digestive system, entering the hepatic portal system. It is then carried through the portal vein into the liver before it reaches the rest of the body.

The majority of the metabolic processes occur in the liver and while this greatly reduces the bioavailability of the drug, in some cases the resulting metabolites (products of metabolism) are also considered to have a pharmacological effect. Certain drugs such as codeine and tramadol have metabolites (morphine and O-desmethyltramadol respectively) that are stronger than the parent drug itself.

Could CBD metabolites also have therapeutic potential?

In the case of CBD, the most abundantly found metabolites are hydroxylated 7-COOH derivatives. While there is comparatively little known about CBD’s metabolites compared to THC, GW Pharma, the British biopharmaceutical company specialising in cannabis plant derivatives, does hold a patent on the CBD metabolite  7-hydroxy cannabidiol (7-OH-CBD) for use in the treatment of non-alcoholic fatty liver disease. This would suggest that not only are GW Pharma researching the therapeutic effects of the cannabinoid itself, but also its metabolites.

According to the scientific paper ‘Human Metabolites of Cannabidiol: A Review on Their Formation, Biological Activity, and Relevance in Therapy,’ another CBD metabolite that may hold promise is a 7-COOH-CBD derivative called D2 (E) Valproate, which “unlike the parent saturated acid, its anticonvulsant properties are not compromised by hepatotoxicity and teratogenicity, and is well tolerated in humans.” The paper hypothesizes whether this “metabolite species” might also be involved in the antiepileptic activity of CBD.

But so far, any research into CBD’s metabolites has only taken place at the preclinical level. But this does not mean the results can be extended out to human beings. Case in point being the recent assertion that CBD turns into THC in the human gut.

Does CBD convert into THC in humans?

Based on the findings outlined in the research paper ‘Identification of Psychoactive Degradants of Cannabidiol in Simulated Gastric and Physiological Fluid,’ in which it demonstrated that CBD could be converted into THC after prolonged exposure to ‘simulated’ gastric acid, it was assumed that these in vitro results could be applied to the human consumption of CBD.

However, it has since been refuted by neurologist and psychopharmacology researcher, Dr Ethan Russo who in a recent article suggested there is “no compelling evidence that that CBD undergoes cyclization or bioconversion to THC in humans.”

What effect could CBD have on other medication?

But it’s not just how CBD breaks down in the body that scientists are interested in when researching its pharmacological potential. A crucial question to understand is how CBD interacts with other drugs.

In an article published on Project CBD Adrian Devitt-Lee describes how “CBD and other plant cannabinoids can potentially interact with many pharmaceuticals by inhibiting the activity of cytochrome P450, a family of liver enzymes. This key enzyme group metabolizes most of the drugs we consume, including more than 60 percent of marketed meds.”

He goes on, “By occupying the site of enzymatic activity, CBD displaces its chemical competitors and prevents cytochrome P450 from metabolizing other compounds.”

What this means in effect is that if someone is taking other pharmaceutical medication alongside CBD, this blocking action may impede the prescription drug’s metabolism, resulting in higher levels in the bloodstream and possibly toxicity.

This was found to be the case in a small clinical study at Massachusetts General Hospital involving children with refractory epilepsy who took CBD alongside the anticonvulsant medication, clobazam.

Scientists discovered that CBD increased the concentration of clobazam in the blood, which required a reduction in dose as a result.

It would be prudent therefore if you are taking CBD alongside certain other prescribed drugs, to inform your doctor so they can look out for any changes in the levels of medication in your blood, as an adjustment in dosing regime might be necessary.

For more information about drugs that are metabolized by P-450 enzymes that could potentially interact with CBD, please see this table from the Indiana University Department of Medicine.

It’s clear then to see that CBD’s multiple molecular action is even more complex than originally thought, and that a crucial area of exploration should be into the cannabinoid’s interaction with other prescription medication. However, it remains hypothetical whether CBD’s metabolites contribute significantly to its observed therapeutic effect.