Enzyme inhibition

Enzyme inhibition is the reduction of an enzyme's activity by a molecule that binds to it, and in pharmacology it is the main mechanism behind many drug interactions.

Enzymes are proteins that speed up chemical reactions, including the liver reactions that break down drugs. An inhibitor slows an enzyme either by occupying the site where its normal substrate binds, competitive inhibition, or by binding elsewhere and changing the enzyme's shape, non-competitive inhibition. Some inhibitors act only while present and are reversible; others chemically alter the enzyme and are effectively permanent until the body makes new enzyme.

When a substance inhibits a cytochrome P450 enzyme, other drugs cleared by that enzyme accumulate to higher blood levels. CBD is a notable inhibitor of CYP3A4, CYP2C19 and several other enzymes at the doses used in clinical trials, which explains its documented interactions with clobazam, valproate and warfarin and the familiar grapefruit comparison. The same principle underlies the action of some medicines that are designed as inhibitors, and it is also how cannabinoids are proposed to raise endocannabinoid levels by slowing FAAH, the enzyme that breaks down anandamide, an effect shown mainly in laboratory studies.