Marijuana Use May Cause Harmful Drug Interactions

Elderly adults on multiple medications are particularly at risk for negative health consequences.

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When cannabinoids are processed in the body, the resulting metabolites can interfere with two families of enzymes that help metabolize a wide range of drugs used for pain or for treating conditions such as cancer.Anna Efetova/Getty Images; Everyday Health

Using marijuana with common medications, including blood thinners and drugs used to treat cancer and HIV, may cause significant drug interactions and lead to a potentially harmful buildup in the system, according to two new research studies.

When cannabinoids (a group of substances found in the cannabis plant) are processed in the body, the resulting metabolites can linger in the body for as long as two weeks and interfere with two families of enzymes that help metabolize a wide range of drugs used for pain or for treating conditions such as cancer, according to the authors.

“Physicians need to be aware of the possibility of toxicity or lack of response when patients are using cannabinoids,” said senior author Philip Lazarus, PhD, professor of pharmaceutical sciences at Washington State University in Pullman, in a university release. “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.”

Marijuana Use in Older Adults Has Risen by 75 Percent

There are 36 states and four U.S. territories that allow for the medical use of marijuana and 18 states and two territories that allow the recreation use of the drug, according to the National Conference of State Legislatures (NCSL).

The increased availability and decreased social stigma — former Presidents Barack Obama, George W. Bush, and Bill Clinton all acknowledged smoking marijuana, according to High Times — means more widespread use among all adults, even older ones.

It’s estimated that between 2015 and 2018, cannabis use in adults aged 65 and older increased from 2.4 percent to 4.2 percent, an increase of 75 percent, per a study published in February 2020 in JAMA Internal Medicine.

First Study to Examine Interaction Between Liver and Kidney CYP Enzyme and 3 Most Abundant Cannabinoids — THC, CBD, and CBN

It’s important to look at the impact of marijuana on enzymes because of their important role in our health, says Klarissa Jackson, PhD, assistant professor at the UNC Eshelman School of Pharmacy in Chapel Hill, North Carolina, and was not involved in the study. “Enzymes help us process or metabolize chemicals and get rid of what our body doesn’t use, which is a protective measure that keeps chemicals from building up in the system. Drug metabolism occurs in many sites in the body, but primarily in the liver, kidneys, and lungs,” she says.

The research papers, published December 2021 in Drug Metabolism and Disposition, are the first to comprehensively study the interaction between three of the most abundant cannabinoids — tetrahydrocannabinol (THC), cannabidiol (CBD), and cannabinol (CBN) — and their metabolites and all of the major CYP enzymes.

Investigators found that each of these compounds inhibit several enzymes important for metabolizing drugs. All three cannabinoids, but especially CBD, inhibited two of the primary UGT enzymes present in the liver. CBD was also found to block three enzymes that account for about 95 percent of kidney UGT metabolism, which helps clear toxins and certain drugs from the body.

“While it should be noted that these are in vitro results obtained from kidney cells rather than humans in clinical studies, it does suggest that these cannabinoids interact with other drugs metabolized by the same enzymes,” says Jessica Beers, PharmD, graduate student in pharmacotherapy and experimental therapeutics at the UNC Eshelman School of Pharmacy, who was not involved in the research. In vitro experiments are routinely performed during drug development before testing a new drug in humans to determine the potential for causing interactions, she notes.

“These results align with other in vitro studies, as well as case reports of drug interactions between cannabinoids and other drugs metabolized through these pathways,” says Dr. Beers.

Cannabis Use May Cause Dangerous Drug Buildups in Older Adults

If a cannabinoid blocks the enzymes that process these drugs, that can result in having too much of the drug in the body, says Dr. Jackson. “This is concerning, especially for elderly patients who may be taking multiple drugs that are metabolized or processed by these same enzymes — the buildup could be dangerous.”

The authors cite the anticoagulant, warfarin, as an example of a medication where it’s important to be exact in dosing for both safety and efficacy reasons. “If there’s too much warfarin in the body, it can cause bleeding, and if there’s not enough, the patient can be at risk for blood clotting,” says Jackson.

It’s been shown that when a person consumes CBD with warfarin in clinical studies, it increases the concentration of warfarin in the body and that puts the patient at risk for bleeding, she says. “That’s a serious drug interaction that we want to avoid,” she says.

How Marijuana Impacts Other Medications Depends on How You Use It

“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," Dr. Lazarus said.

And it’s not just smoking that interferes with how drugs are processed in the body — marijuana has to be metabolized no matter how you ingest it, and what form you choose can impact that, notes Beers. “An edible, for example, will likely result in greater exposure to the GI tract compared to an inhaled dose, which would have greater lung exposure,” she says.

There are other limitations that can make it challenging to draw conclusions from this type of research, says Beers. “Since cannabis products on the market vary widely by strength, strain, and formulation, it can be difficult to extrapolate results to different forms of cannabis that may have different amounts of cannabinoids,” she says.

Use Marijuana? You May Want to Let Your Doctor or Pharmacist Know

Although it can be hard to know whether a specific cannabis product will interact with a drug in a single patient, studies like this can be useful in making predictions and providing recommendations based on a patient’s health status, cannabis use, and medications, says Beers. “We know from the available clinical data that cannabis can cause drug interactions, and patients should be made aware of this risk by their doctor or pharmacist,” says Beers.

If you use a cannabis product, Beers recommends talking with your doctor or pharmacist. “Since different cannabinoids carry different risks for interactions, care should be taken to identify the ingredients and doses of cannabinoids present if possible,” she adds.