Marijuana Could Disrupt Medication and Risk Harm, Doctors Say

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Many people turn to marijuana or cannabidiol to relieve and help their aching joints, but a new study suggests it could wreak havoc with any other medication they take.

Why? Because the body uses the same set of enzymes to process them all, scientists report.

The chemicals in marijuana – THC, cannabidiol or CBD, and cannabinol or CBN – are metabolized in the body by at least two families of enzymes that also help process and remove over 70% of drugs. most commonly used prescription drugs. the body, the researchers said.

This means that there is a risk that the pot will dangerously amplify the effects of certain prescription drugs, or that other drugs will spread through your system so quickly that they do you no good, said lead researcher Philip. Lazarus.

He is professor of pharmaceutical sciences at Washington State University in Spokane.

“We saw some significant inhibitions,” Lazarus said. “The concentrations that we see in the lab are probably an indicator that there is at least some inhibition of these enzymes in real time.”

Some drugs that could be affected by the use of the pot include warfarin, a breast cancer drug, tamoxifen, and pain relievers like acetaminophen, like Tylenol, or ibuprofen, like Motrin, Lazarus said and Ed Bednarczyk, Clinical Associate Professor of Pharmacy Practice. at the University of Buffalo, New York.

In two lab reports published in the December issue of the journal Drug Metabolism and Disposition, Lazarus was the lead author. One study looked at a family of enzymes known as cytochrome P450 (CYP), and the other looked at the UDP-glucuronosyltransferase (UGT) group of enzymes.

CYPs are involved in the early stages of THC and CBD metabolism, while UGTs are involved in the later stages.

THC and CBD only stay in your body for about 30 minutes before enzymes break them down, but the chemicals resulting from the process can linger in your body for up to two weeks, the study authors said in briefing notes.

In the lab, researchers tested how pot chemicals might interfere with the ability of these enzymes to break down other drugs, using cultured human kidney cells to test for one enzyme at a time.

Researchers found that the major metabolites of THC inhibited key CYP enzymes, including several that play key roles in the liver.

And all three chemicals in cannabis, but mostly CBD, inhibited two of the major UGT enzymes in the liver.

CBD has also been found to block three enzymes that make up about 95% of UGT metabolism in the kidney, which helps flush toxins and certain drugs from the body.

CBD, THC block enzymes

“It’s a very, very good reminder that these interactions are real,” Bednarczyk said. “It’s important that doctors and pharmacists who work with patients explore this.

This is the first research effort to demonstrate the potential effects of pot on UGT enzymes, the researchers said. The study also sheds more light on the effect of marijuana on CYP enzymes.

It has been known for some time that pot can interact with other drugs, said Paul Armentano, deputy director of NORML, a group that advocates for reform of marijuana laws.

The United States Food and Drug Administration’s labeling of a form of synthetic THC called dronabinol, which has been available as a prescription drug for over 30 years, indicates that it may influence CYP levels, noted Armentano.

And the agency’s warning for Epidiolex, a herbal prescription CBD drug, also addresses how the substance could affect the liver, he added.

But Armentano wondered how powerful these interactions could be, given how long marijuana has been used for recreational and medicinal purposes.

“Adults – and patients in particular – have been consuming cannabinoids for medical purposes for centuries, and the practice has become quite common over the past few decades,” Armentano said.

“Many of these patients are older and many of them may also be prescribed other drugs. If cannabinoids were significantly contraindicated in this population, one would assume that there would already be a lot of empirical evidence available. substantiating this concern, ”Armentano said.

The effect of pot on metabolism likely wouldn’t affect someone who takes a recreational puff or three on weekends, Lazarus said.

“While it probably inhibits these enzymes, it doesn’t inhibit them enough to interfere with your daily metabolism,” Lazarus admitted.

The problem arises when you mix regular weed use with other drugs, or if you take a marijuana derivative in addition to your prescription.

“Usually,” said Bednarczyk, “CBD is thought to inhibit metabolic pathways and THC to induce metabolic pathways. THC can lower your blood levels of other drugs and CBD can raise your blood levels.”

A dangerous combo

A well-known example is warfarin, “a very, very strong blood thinner,” Bednarczyk said.

A case study published a few years ago noted that a patient on warfarin “got the effects of this drug to the danger zone soon after starting CBD,” Bednarczyk said.

“That one, you’re not kidding. Effects at too high a level, even transiently for a few days, can be fatal,” he warned.

“It’s king of the hill for risk, because it’s all over the map in terms of patient-to-patient variability,” Bednarczyk said of warfarin and pot. “One patient may need a bucket of this stuff to have the same effect as another patient who receives the lowest manufactured dose.”

The reverse happens when you mix pot with tamoxifen, a hormone therapy drug used to treat breast cancer by blocking the effects of estrogen, Lazarus said.

In order for tamoxifen to work, he noted, it must be broken down by the body into another chemical called endoxifen, which is 100 times more active than tamoxifen.

If the pot interferes with tamoxifen treatment, it could cause the breast cancer patient to benefit little or no benefit from the drug, Lazarus explained.

Lazarus said he was also concerned about the potential interaction with over-the-counter pain relievers.

Ibuprofen “is toxic to your liver and kidneys anyway, but you start taking marijuana on top of that, then you’re going to see significant effects,” Lazarus said.

“It would probably cause toxicity because you slow down its metabolism, which means you don’t excrete the substance and you have more of it in your body,” Lazarus said.

However, all of these concerns are based on laboratory studies. What is needed now are clinical trials to establish the true effects of pot on other drugs, Lazarus noted.

“We have to do clinical studies to show in people that if you take a specific drug and also smoke a marijuana cigarette that morning, you see higher or lower levels of that drug in your body,” he said. Lazarus said.

In the meantime, people should discuss their use of the jarred products with their doctor and pharmacist to make sure they don’t put their health at risk, Lazarus and Bednarczyk said.

“It shouldn’t be a stand-alone process,” Bednarczyk said.

More information

The Mayo Clinic has more information on possible drug interactions with marijuana.

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