CBD & Metabolism

Cytochrome P450 System

The majority of drugs are broken down by what’s called Cytochrome P450 (CYP450) enzymes. There are over 50,000 distinct enzymes in this group that are found in tissues throughout your entire body.

The Cp3a enzymes

CYP3A, a subfamily of the CYP450 system, is involved in the metabolism of more than 50% of drugs clinically used. The human CYP3A subfamily expressed in the liver consists of at least three members: CYP3A4 (the most abundant), CYP3A5 and CYP3A7.

How CBD may be metabolized

In vitro data were identified that characterize CYP450 enzymes as potential significant contributors to the primary metabolism of CBD via the Cyp3A4 and CYP2c19 enzyme systems (1,4).

CYP3A4 inhibitors & Inducers

Various medications, as well as furanocoumarins (found in grapefruit) and CBD (found in hemp), can inhibit the action of the CYP3A4 enzymes. Various medications, as well as CBD, may induce the CYP3A4 enzymes (i.e amplify its ability to work). To put it simply, anything that can inhibit or induce the CYP3A system can effect how we clear other prescription medications from the body.

Medications that can effect how CBD functions.

Various drugs such as Ketoconazol, Itraconazol, Ritonavir, and Clarithromycin are strong inhibitors of CYP3A4 enzymes. This may lead to slower CBD degradation and can consequently lead to higher CBD doses that are longer pharmaceutically active. In contrast, Phenobarbital, Rifampicin, Carbamazepine, and Phenytoin induce the CYP3A4 system, causing reduced bio-availability (i.e. less CBD in the bloodstream) (5).

CBD inhibits the CP450 system

The exact mechanism of how CBD effects your body's metabolism of other medications is not yet fully understood. However, research has shown that CBD is a potent inhibitor against human CYP3A and other CYP450 enzymes (2). It was also found to interact with CYP1A2, CYP2C8, CYP2C9. CYP2C19 and UGT1a9, UGT2b7 substrates in vitro.

CBD could induce the CYP450 system

In 2015, at the International Cannabinoid Research Society meeting, Dr. Kazuhito Watanabe disclosed preliminary research evidence that CBD may induce some CYP450 enzymes (3).

More CBD Pharmacokinetics Research is needed.

Studies of CBD inhibition and induction of major human CYP450 enzymes generally reflect a low risk of clinically significant drug interactions with most use, but specific human data is still lacking (4). At current, research supports that CBD inhibits the CYP3A4, CYP3A5 and CYP2D6 enzymes (5), which could potentially cause higher than normal amounts of common prescription medications in your bloodstream when taken with CBD.

 Caution is also advised with concomitant use of CBD and substrates of UDP-glucuronosyltransferases UGT1A9 and UGT2B7, and other drugs metabolized by the CYP2C19 enzyme (5).

As a precaution, please always consult with a licensed health care provider before taking CBD with your prescription medication(s) as certain medications (some main ones listed above) may warrant medical supervision.

Source: 1, 2, 3, 4, 5, 6, 7, 8 ,9

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