Drug interactions are an important consideration in medicine. Although they are rarely so dangerous as to entirely preclude the use of a medication, they can have serious impacts on a patient’s treatment and wellbeing.
There are three main ways by which two drugs can interact:
- Metabolic interactions. One drug can affect the metabolism of another drug, thereby prolonging or reducing the activity, intensity, and side effects of the latter.
- Drug distribution. A drug can change how a second drug is absorbed and distributed throughout the body.
- Convergent pathways. Two drugs may work through convergent or similar biological pathways, which could lead to antagonistic or synergistic effects. In order to predict convergent drug interactions both drugs need to be well studied.
Some drug interactions can be understood by looking at the properties of a single compound. For example, if we know how cannabidiol (CBD), a non-intoxicating component of cannabis, inhibits drug-metabolizing enzymes, then we can foresee certain interactions.
When cannabinoids are added to someone’s existing medications, what actually happens?
At first, cannabinoids interact with some CYPs*. (Cytochromes P450 (CYPs) are a superfamily of enzymes. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various compounds, as well as for hormone synthesis and breakdown.)
The immediate interaction usually decreases drug metabolism via CYP inhibition, but in some cases it may increase metabolism. Moreover, metabolism may be an integral step in activating the drug if the medications are prodrugs.
Over the course of a day to a few weeks, some of the inhibited CYPs may become overexpressed in an attempt to restore homeostasis and normal baseline activity.
- Cannabinoids will likely reduce inflammation, which can increase the activity of some CYP enzymes.12
- CBD, which regulates the expression of at least 1200 genes, may modify the expression of certain CYPs.
The way cannabis is consumed adds another layer to the complexity of drug interactions. Cannabinoids can be smoked, vaporized, eaten, rubbed on skin, absorbed under the tongue, etc.
Ingested cannabinoids are primarily absorbed through the intestines (where CYP3A is present) and then are 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 in this case.
Sometimes a blood test may be necessary to see how the concentration of a drug changes—and if a change of dosage is required—when a patent begins taking CBD. This might be the case with chemotherapy, for example, since oncologists often utilize the maximum non-lethal dose to kill cancer cells. If CBD delays the metabolism of a chemotherapy agent, this could result in dangerous levels of a highly toxic drug.
Preclinical research indicates that administering CBD and/or THC in conjunction with first-line chemotherapy drugs could potentiate the latter, thereby reducing the dosage of chemo necessary to treat the cancer. If this indeed translates to human experience, it would be a huge benefit.
There is much more we need to learn about cannabinoid-drug interactions to avoid adverse reactions and harness potential synergies.