Tetrahydrocannabinol (THC) is the primary psychoactive cannabinoid found in marijuana. Cannabidiol (CBD) is also found in high concentrations in marijuana but is not psychoactive; it has an antagonistic effect at the cannabinoid receptors and appears to block some of the effects of THC.Cannabinol (CBN) is a relatively weak psychoactive cannabinoid existing in very small quantities within the marijuana plant but is one of the primary metabolites of THC. The marijuana plant contains more than 50 other cannabinoids, but synthetic medications approved by the US Food and Drug Administration (eg, dronabinol and nabilone) contain only THC without any CBD. The pharmacologic effect of these products may differ from that of natural cannabis.
Data are limited regarding the potential drug interactions associated with marijuana use; however, unstudied interactions can be theorized based on the metabolism of the primary cannabinoids in marijuana.
CYP450 Enzymes
Cytochrome P450 (CYP450) enzymes are responsible for the metabolism of most chemicals and medications that enter the human body. Humans have roughly 60 CYP genes. CYP450 enzymes occur primarily in liver cells where drug metabolism occurs.
Chemicals or drugs may be substrates, inhibitors, or inducers of CYP450 enzymes. Substrates are substances that are metabolized by the enzyme. Inhibitors reduce the activity of the enzyme, preventing the metabolism of its substrates and thus increasing the substrate concentration and effect. Inducers, on the other hand, increase the activity of the enzyme, enhancing the metabolism of its substrates and thus decreasing the substrate concentration and effect.
The CYP1A2, CYP3A4, CYP2C9, and CYP2C19 enzymes are known to be affected by marijuana use.
CYP1A2
Smoking marijuana regularly is believed to cause induction of the CYP1A2 enzyme, which may decrease serum concentrations of 1A2 substrates. One study reported that theophylline clearance was 48% greater in individuals who smoked more than 2 joints weekly. Marijuana would be expected to have a similar effect on other 1A2 substrates.
credit:medscape.com
