Cannabis use could cause harmful and toxic drug interactions with prescription drugs

Consuming cannabis with other drugs can carry a significant risk of harmful drug interactions, new research from scientists at Washington State University suggests.

Researchers looked at cannabinoids – a group of substances found in the cannabis plant – and their main metabolites found in the blood of cannabis users and found that they interfere with two families of enzymes that help metabolize a wide range. drugs prescribed for various conditions. . As a result, either the positive effects of the drugs might decrease, or their negative effects might increase with too much accumulation in the body, causing unintended side effects such as toxicity or accidental overdose.

Although more research is needed, the authors said that one of the first lessons from these studies is that it is important to be careful when using cannabis with other prescription drugs.

“Physicians should be aware of the possibility of toxicity or a lack of response when patients use cannabinoids,” said Philip Lazarus, senior author of the papers and Boeing Distinguished Professor of Pharmaceutical Sciences. “It’s one thing if you’re young and healthy and smoke cannabis every now and then, but for older people who are on medication, taking CBD or medicinal marijuana can have a negative impact on their health. processing. “

The results were described in a pair of studies published in the journal Drug Metabolism and Disposition. One study focused on a family of enzymes known as cytochrome P450 (CYP), while the other looked at UDP-glucuronosyltransferases (UGT), another family of enzymes. Together, these two families of enzymes help metabolize and eliminate over 70 percent of the most commonly used drugs from the body.

Although there has been little previous research focusing on the potential drug interactions caused by cannabinoids, this new research provides the first known comprehensive overview of the interaction between three of the most abundant cannabinoids: tetrahydrocannabinol (THC), cannabidiol (CBD) and cannabinol (CBN) – and their metabolites and all major CYP enzymes. This is also the first known research to investigate the interactions between these cannabinoids and UGT enzymes, in particular.

“Cannabinoids only stay in your body for about 30 minutes before breaking down quickly,” said lead author Shamema Nasrin, a graduate student at WSU College of Pharmacy and Pharmaceutical Sciences. “The metabolites that result from this 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 we focus on those as well. “

The researchers used engineered human kidney cells that allowed them to examine only one enzyme at a time and validated their results in human liver and kidney samples in which many of these enzymes were present. They found that cannabinoids and the major metabolites of THC strongly inhibited several CYP enzymes. A key finding was that one of the most abundant THC metabolites, called THC-COO-Gluc – which had not previously been studied in this context – appears to play a major role in inhibiting several key enzymes in liver. Looking at the UGT family of enzymes, the researchers found that all three cannabinoids, but mostly CBD, inhibited two of the main UGT enzymes found in the liver. CBD has also been found to block three enzymes that make up about 95% of UGT’s kidney metabolism, which helps flush toxins and certain drugs from the body.

“If you have kidney disease or if you take one or more drugs that are mainly metabolized by the kidneys and you also smoke marijuana, you may be inhibiting normal kidney function and this may have long term effects on your kidneys. you, ”said Lazare.

Nasrin added that these interactions between the enzymes CBD and UGT could inhibit kidney function in patients with acute renal failure or kidney cancer, who could use CBD to treat pain or try to reduce the side effects of drugs. anticancer.

“Taking CBD or marijuana might ease your pain, but could make the other drug you’re taking more toxic, and this increase in toxicity may mean that you can’t keep taking this drug,” Nasrin said. “So there could be serious ramifications for anticancer drugs, and this is just one example of the many drugs that could potentially be affected by the cannabinoid-enzyme interactions that we are seeing.”

Reference: “Cannabinoid metabolites as inhibits of major hepatic CYP450 enzymes, with implications for cannabis-drug interactions” by Shamema Nasrin, Christy JW Watson, Yadira X Perez-Paramo and Philip Lazarus, December 2, 2021, Metabolism and elimination of drugs.
DOI: 10.1124 / dmd.121.000442

Other people who have worked with Nasrin and Lazarus on this research include Christy Watson, Yadira Perez-Paramo, Keti Bardhi, Gabriela Fort, and Gang Chen, all of whom are, or previously were, at the WSU College of Pharmacy and Pharmaceutical Sciences.

Funding for these studies came from the Spokane County Health Sciences and Services Authority and the Washington State Initiative Measure # 502, which funds the Alcohol and Drug Abuse Research Program. of the University.

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