Cannabinoids – a type of compounds found in cannabis plants – and their primary metabolites found in cannabis users’ blood were studied. The researchers discovered that these compounds interact with two enzyme families that assist to metabolize a wide range of medications prescribed for a variety of illnesses. The unfavorable effects might increase with too much building up in the body, resulting in unanticipated side effects such as toxicity or unintentional overdose.
While further research is needed, the study authors claim one initial insight from these trials is that cannabis should be used with caution when combined with other prescription medications.
“Physicians need to be aware of the possibility of toxicity or lack of response when patients are using cannabinoids. It’s one thing if you’re young and healthy and smoke cannabis once in a while, but for older people who are using medications, taking CBD or medicinal marijuana may negatively impact their treatment.” said study senior author Philip Lazarus, a distinguished professor of Pharmaceutical Sciences.
The findings from a pair of research works were published in the journal Drug Metabolism and Disposition. One study examined the cytochrome P450s (CYPs) enzyme family, while the other analyzed the UDP-glucuronosyltransferases (UGTs) enzyme family. These two enzyme families work together to help the body digest and remove more than 70 percent of the most widely used medicines.
While previous research on cannabinoids’ potential drug interactions has been limited, this new study is the first to look at the interaction between three of the most abundant cannabinoids – tetrahydrocannabinol (THC), cannabidiol (CBD), and cannabinol (CBN) – and their metabolites, as well as all of the major CYP enzymes. The study is also the first to examine explicitly for drug interactions between these cannabinoids and UGT enzymes.
“Cannabinoids stay in your body only for about 30 minutes before they are rapidly broken down. The metabolites that result from that process stay in your body for much longer – up to 14 days – and at higher concentrations than cannabinoids and have been overlooked in previous studies, which is why we thought we should focus on those as well.” explained first author Shamema Nasrin, a graduate student in the WSU College of Pharmacy and Pharmaceutical Sciences.
The researchers tested their findings in human liver and kidney tissues that contained many of these enzymes, using modified human kidney cells that enabled them to look at a single enzyme at a time. Several CYP enzymes were shown to be substantially inhibited by cannabis and the primary THC metabolites.
One important finding was that THC-COO-Gluc, one of the most abundant THC metabolites, appeared to have a large role in blocking numerous essential enzymes in the liver, which had never been studied before.
When the researchers looked at the UGT enzyme family, they discovered that all three cannabinoids, but notably CBD, blocked two of the liver’s key UGT enzymes. Cannabidiol was also discovered to suppress three enzymes that account for nearly 95 percent of kidney UGT metabolism, which aids in the elimination of toxins and some medications.
“If you have a kidney disease, or you are taking one, or more drugs that are metabolized primarily through the kidney, and you’re also smoking marijuana, you could be inhibiting normal kidney function, and it may have long-term effects for you,” said Professor Lazarus.
“Taking CBD or marijuana might help your pain but could be making the other drug you’re taking more toxic, and that increase in toxicity may mean that you can’t continue taking that drug,” said Nasrin. “So, there could be serious ramifications for anti-cancer drugs, and that’s only one example of the many drugs that could potentially be affected by the cannabinoid-enzyme interactions we’re seeing.”
The Health Sciences and Services Authority of Spokane County and the State of Washington’s Initiative Measure No. 502, which funds the university’s Alcohol and Drug Abuse Research Program, provided funding for these studies.