THURSDAY, December 16, 2021 (HealthDay News) – Many people are turning marijuana or cannabidiol to ease their sore joints and help them sleep, but a new study suggests it could wreak havoc with any other medications they take.
Why? Because the body uses the same set of enzymes to process them all, scientists report.
Chemicals in marijuana – THC, cannabidiol (CBD), cannabinol (CBN) – are metabolized in the body by at least two families of enzymes that also help process and eliminate more than 70% of the most commonly used prescription drugs from the body, the researchers said.
This means there is a risk that the pot could dangerously potentiate the effects of some prescription drugs or cause other drugs to pass 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, Spokane.
“We’ve seen some significant inhibitions,” Lazarus said. “The concentrations we see in the lab are probably an indication that there is at least some real-time inhibition of these enzymes.”
Some medications that may be affected by the use of the dish include blood thinner warfarin, the breast cancer drug tamoxifen, and painkillers like acetaminophen (Tylenol) or ibuprofen (Motrin), said Lazarus and Ed Bednarczyk, a clinical associate professor of pharmaceutical practice at Buffalo University in New York.
In two laboratory reports published in the December issue of the journal Metabolism and disposition of drugs, Lazarus was a senior author. One study studied a family of enzymes known as cytochrome P450 (CYP) and another analyzed a group of UDP-glucuronosyltransferase (UGT) enzymes.
CYPs are involved in the early stages of THC and CBD metabolism, while UGTs are involved in the later stages.
THC and CBD remain in your body for only about 30 minutes before they are broken down by enzymes, but the chemicals that result from this process can stay in your body for up to two weeks, the study authors said in notes.
In the lab, researchers tested how the chemicals in the vessel could interfere with the ability of these enzymes to break down other drugs, using cultured human kidney cells to test one enzyme at a time.
The researchers found that the major metabolites of THC inhibit key CYP enzymes, including several that play a key role in the liver.
And all three cannabis chemicals, but especially CBD, inhibit the two primary UGT enzymes in the liver.
CBD It has also been found to block three enzymes responsible for about 95% of UGT metabolism in the kidneys, which helps clear toxins and some drugs from the body.
CBD, THC block enzymes that break down other drugs
“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 investigate this.”
This is the first research attempt to demonstrate the potential effect of sweat 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 the pot could interact with other drugs, said Paul Armentano, deputy director of NORML, a group advocating for marijuana law reform.
Marking the form of synthetic THC by the US Food and Drug Administration so-called dronabinol, which has been available as a prescription drug for more than 30 years, suggests it could affect CYP levels, Armentano said. And the agency’s warning for Epidiolex, A CBD herbal prescription drug, also deals with how the substance could affect the liver, he added.
But Armentano questioned how powerful those interactions could be, given how long marijuana has been used both recreationally and medically.
“Adults – and especially patients – have been consuming cannabinoids medically for centuries, and this practice has become quite common over the last few decades,” Armentano said. “Many of these patients are older and many of them may be prescribed other drugs. If cannabinoids were significantly contraindicated among this population, it would be assumed that there would already be enough empirical evidence to support this concern.”
The pot effect on metabolism would probably not affect someone who recreationally drinks toke or three for the weekend, Lazarus said.
“While it probably inhibits those enzymes, it doesn’t inhibit them enough to interfere with your daily metabolism,” Lazarus admitted.
The problem arises when you mix regular use with other drugs or if you take a marijuana product with your prescription.
“In general,” Bednarczyk said, “CBD is thought to inhibit metabolic pathways, while THC induces metabolic pathways. THC can cause a drop in other drugs in the blood, and CBD can increase blood levels.”
Warfarin, CBD dangerous combination
One well-known example is warfarin, “a very, very powerful blood thinner,” Bednarczyk said.
A case study published several years ago noted one patient with warfarin in whom “the effects of this drug went far into the danger zone soon after the onset of CBD,” Bednarczyk said. “Oh, you don’t mess with it. The consequences of too high a level, even a few days, can be deadly,” he warned.
“It’s the biggest risk, because it’s everywhere on the map in terms of patient-to-patient variability,” Bednarczyk said of warfarin and the pot. “One patient may need a bucket of this thing to have the same effect as another patient using the lowest dose produced.”
The opposite happens when you mix a pot with tamoxifen, a hormone therapy drug used to treat breast cancer by blocking the effects of estrogen, Lazarus said.
For tamoxifen to work, he noted, the body must break it down into another chemical called endoxifene, which is 100 times more active than tamoxifen.
If the pot interferes with the processing of tamoxifen, it could cause a patient with breast cancer to get little or no benefit from the drug, Lazarus explained.
Lazarus said he is also concerned about the pot’s interaction with over-the-counter pain medications.
“Ibuprofen is toxic to your liver and kidneys anyway, but if you start taking marijuana on top of that, then you will see some significant effects,” Lazarus said. “It would probably cause toxicity because you’re slowing down his metabolism, so that means you’re not excreting substances and having more of them in your body.”
However, all of these concerns are based on laboratory studies. What is needed now are clinical trials to determine the true effects of the drug on other drugs, Lazarus noted.
“We need to do some clinical studies to show people that if you take a certain drug and then smoke a marijuana cigarette that morning, you see higher or lower levels of that drug in your body,” Lazarus said.
Meanwhile, people should discuss the use of pottery with their doctor and pharmacist to make sure they do not endanger their health, Lazarus and Bednarczyk said.
“This should not be a stand-alone process,” Bednarczyk said.
The Mayo Clinic has more on that possible drug interactions with marijuana.
SOURCES: Philip Lazarus, PhD, Professor, Pharmaceutical Sciences, Washington State University, Spokane, Wash .; Ed Bednarczyk, PharmD, Clinical Associate Professor, Pharmacy Practice, University of Buffalo, New York; Paul Armentano, Deputy Director, NORML, Washington, DC; Metabolism and disposition of drugs, December 13, 2021