The enzymes in the body that synthesize ingested drugs are in the CYP450 family. Cannabidiol (CBD) inhibits or slows the metabolism of the CYP1 family when given 20 minutes before the pharmaceutical. The timing of applying Delta-9-tetrahydrocannabinol (THC) and cannabinol does not slow its metabolism. High concentrations of CBD or THC can boost the production of those enzymes a day later.
The CYP2C enzymes metabolize many antiepileptic drugs, phytocannabinoids (including THC and CBD), and some endocannabinoids, as well as nonsteroidal anti-inflammatory drugs, warfarin, diazepam, and other pharmaceuticals. THC has a more varied effect on drugs metabolized by CYP2. People with certain genetic differences in CYP2C enzymes are likely to experience more significant cannabinoid-drug interactions and at lower doses. CBD isolates, like Epidiolex ® cannabidiol, have caused significant interactions with antiepileptic drugs, whereas whole-plant extracts generally have not.
How Cannabis Affects Body Systems
In the liver, CYP1 enzymes metabolize caffeine, melatonin, smoke, and several pharmaceuticals. Whether CBD is inhaled or ingested, drug interactions with CYP1 are less likely if it is administered after the other drug. A cannabis-infused edible may also slow drug metabolism, which in the case of THC could intensify and prolong the effect of melatonin.
When administered sublingually, cannabinoids aren’t immediately processed but neither do they go directly to the brain and heart—like inhaled drugs. Topical administration does not enter the blood stream therefore has no potential for drug interactions.
The mode of administration affects the amount of cannabinoids in the liver and how quickly they get there. Ingested cannabinoids are primarily absorbed through the intestines and processed by the liver before being distributed through the body. Cannabinoids are absorbed more if ingested on a full stomach, but the absorption is slower ranging from two to four hours. Ingested cannabinoids will also have higher peak liver concentrations than inhaled cannabinoids and thus more potent drug interactions.
“Because grapefruit is a commonly-encountered food that is famous as a CYP450 inhibitor, which should not be used with some medications, I often use it as a surrogate for CBD and THC to check for potential drug interactions,” says Wohlschlagel. ”Due to the historic lack of research on cannabis, we do not have a wealth of research on its potential drug-drug interactions. But when I educate patients, I tell them to check for grapefruit interactions on trustworthy pharmaceutical websites like WebMD. There, they will see that using tamoxifen with grapefruit—and, we must conclude, large doses of cannabinoids as well—could risk reducing the hormone-blocking effects of tamoxifen for breast cancer patients. This could be critical for their outcomes.”
This may be the case with cannabis and tamoxifen.
“How this is all interacting is a question that will take time to clarify,” she says, “and more research is urgently needed. Then there’s another factor: All tumors can mutate or change when it is treated or spreads, which can change the efficacy of all medications, even when they have been previously helpful. Close monitoring with scans or tumor markers of cancer status is very important, possibly including genomic reassessment of the tumors over time. We are thankfully getting much closer to precision or personalized therapies for many forms of cancer. Unfortunately not all patients and doctors realize how rapidly genomic testing is changing cancer therapy choices, potentially opening up treatment options customized to their unique needs.”
In fact, in addition to possibly interfering with hormone-suppressing activity of tamoxifen, larger doses of THC can also suppress the body’s T-cell proliferation, which is a part of the immune system that is critical for tumor cell growth suppression. In these cases, the use of high-THC forms of cannabis could theoretically not only not help, but could also make matters worse, allowing the tumor cells to grow more rapidly.
But especially in the case of breast cancer—or, more accurately, breast cancers—the therapeutic potential of cannabis also comes laden with the potential for harm, and, like all medications, patients need to understand that powerful drugs can create unanticipated interactions with other powerful drugs.