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Cannabis Users May Risk Harmful Drug Interactions

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A recent survey found that nearly half of American adults (49%), have tried marijuana, a figure that has risen steadily in recent years as more states legalize medical and recreational cannabis. While the Gallup poll didn’t ask why people use marijuana, it’s fair to say many are experimenting with cannabis products – and cannabidiol (CBD) in particular – as alternatives to mainstream medical treatment.

And that could be a problem for people with chronic pain and other illnesses, according to researchers at Washington State University, who found that CBD interferes with two families of enzymes that help metabolize pain relievers and other drugs prescribed for a variety of medical conditions. As a result, the medications’ positive effects might decrease or the drugs could build up in the body and become toxic.

“Physicians need to be aware of the possibility of toxicity or lack of response when patients are using cannabinoids,” said Philip Lazarus, PhD, a professor of pharmaceutical sciences and senior author of two new studies appearing in in the journal Drug Metabolism and Disposition.

“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.”

One study focused on enzymes known as cytochrome P450s (CYPs), while the second study looked at enyzymes called UDP-glucuronosyltransferases (UGTs). Together, the two enzyme families help metabolize and eliminate more than 70 percent of the most commonly used drugs from the body.

The WSU studies are among the first to look at the interaction between three of the most abundant cannabinoids — tetrahydrocannabinol (THC), cannabidiol (CBD) and cannabinol (CBN) -- and how they interact with CYP and UGT enzymes. Of particular interest to the researchers are the metabolites produced by cannabinoids as they break down in the body.     

“Cannabinoids stay in your body only for about 30 minutes before they are rapidly broken down,” said first author Shamema Nasrin, a graduate student in the WSU College of Pharmacy and Pharmaceutical Sciences. “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.”

The researchers found that cannabinoids and the major THC metabolites strongly inhibit several key CYP enzymes in the liver that play a role in metabolizing anti-cancer drugs, non-steroidal anti-inflammatory agents, antibiotics, anti-epileptics and other medications.

They also discovered that cannabinoids inhibit two of the primary UGT enzymes in the liver. CBD also blocks three enzymes that account for about 95 percent of kidney UGT metabolism, which helps clear toxins and certain drugs from the body. Atlhough the liver is considered the most important organ for the metabolism of drugs, kidneys also play a vital role.

“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,” Lazarus said.

The interactions between CBD and UGT enzymes could be especially risky for patients with acute kidney disease, kidney cancer or HIV, who may be using CBD to treat pain or to try to reduce the side effects from anti-cancer drugs.

“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,” Nasrin said.

“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.”

More research is needed to fully understand the drug-drug interactions that cannabis may have. Drugs.com has a list of 387 drugs that are known to interact with cannabis, with 26 categorized as major interactions and 361 described as moderate.

Medications known to have major interactions with cannabis include several opioids, such as codeine, fentanyl, buprenorphine, hydrocodone, methadone, morphine and oxycodone.

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