The interactions between plant cannabinoids and a drug-metabolizing enzyme called carboxylesterase 1 (CES1) was recently published in Drug Metabolism and Distribution. Researchers at the Universities of Michigan and Florida showed that THC, CBD, and cannabinol (CBN) all inhibit CES1. CES1 is important for activating or inactivating drugs that regulate blood pressure, as well as the ADD drug Ritalin. The concentrations at which the cannabinoids inhibit CES1 are large, but the interaction with high-dose CBD could be problematic. Large doses of CBD (hundreds or thousands of miligrams) are sometimes necessary, especially when CBD is used as an isolate. According to this study, THC and CBN are more potent inhibitors of CES1 than CBD, but they are used at much lower doses. Thus it is unlikely that THC or CBN will cause problematic interactions with CES1, though THC could conceivably inhibit CES1 at the peak of a high in heavy cannabis users. THC’s metabolites were also assayed, but they did not strongly affect CES1. Finally, there was some evidence that taking THC or CBN half an hour before the other drugs led to a greater interaction than taking both at the same time, but this didn’t seem to be the case with CBD. (This could be an artifact of the experimental method, or could suggest the mechanism of inhibition.) There’s a significant question that the researchers didn’t answer: What about chronic cannabis consumption? Often times the body adapts to the drugs it encounters; if CBD is inhibiting the CES1 enzyme, the liver may produce more of the enzyme to maintain balance. Currently there is no data to answer this question. The potential for cannabinoid-drug interactions shouldn’t be used to dredge up fears about cannabis, but it highlights another class of drugs that should be monitored when taking large doses of CBD.
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