If cannabis is your remedy for aches and pains, take note—new research shows its ingredients could potentially cause serious interactions with over-the-counter and prescription drugs.
Since Washington legalized medical marijuana in 1998, cannabinoids like tetrahydrocannabinol (THC) and cannabidiol (CBD) have been used to treat everything from sore joints and anxiety to migraines and the side effects of cancer treatments. But actual data on the effectiveness and long-term impact still lags behind.
Philip Lazarus, Boeing Distinguished Professor of Pharmaceutical Sciences, Washington State University Health Sciences Spokane, recently added clarity to the discussion with studies showing that several chemicals in cannabis interfere with the body’s most important enzyme systems in the liver and kidneys.
“Our primary focus is on the enzymes which metabolize everything we inhale, ingest, or absorb through our skin,” says Lazarus. “We’re most interested in the cytochrome P450s and UDP-glucuronosyltransferases (UGTs), which metabolize and excrete in urine or feces over 70 percent of the most commonly used drugs.”
Lazarus says occasional cannabis use in young people is typically not a concern, but for older people who are taking multiple medications, there could be problems.
His studies are based on 30 years of research examining nicotine addiction and the effects of tobacco on enzymes and human health. Four years ago, he extended those studies to cannabis.
His recent findings were published last winter in the journal Drug Metabolism and Disposition. They are the first studies to investigate the most abundant cannabinoids, their metabolites, and the way they interact with enzymes. Those cannabinoids include THC, CBD, and cannabinol (CBN).
College of Pharmacy and Pharmaceutical Sciences graduate student Shamema Nasrin was first author on the findings and explained in a press release that although the body breaks down cannabinoids within about 30 minutes, the metabolites can linger in the bloodstream at higher concentrations than the cannabinoids for days.
Lazarus says, “We’re showing that these metabolites are very inhibitory to the metabolism of a variety of compounds. For example, the breast cancer drug tamoxifen needs to be metabolized by cytochrome P450 enzymes into endoxifen, which is the main active compound. But the enzyme necessary for this metabolism is inhibited by cannabinoids.
“A lot of cancer patients are taking or being prescribed medical marijuana and it’s probably not a good idea for breast cancer patients,” he says. “The tamoxifen may not be as efficacious and hypothetically you might see a higher rate of secondary tumors. It has to be studied.”
Another example is ibuprofen. Lazarus says cannabis strongly inhibits both the P450 and UGT enzymes necessary to metabolize ibuprofen.
“If a person is taking cannabis and ibuprofen simultaneously and long-term, the concentrations of ibuprofen in the body will be higher than normal as it’s not getting metabolized and excreted as quickly. So, the toxic effects of ibuprofen on the kidney and GI tract may be stronger and could happen earlier.”
Lazarus also says many of the major UGT enzymes in the kidney are inhibited by cannabinoids, so people with kidney problems might have trouble metabolizing drugs they previously handled well.
“I think doctors and pharmacists need to be thinking about this, especially those with older patients who might be prescribed CBD or medical marijuana,” he says.
Despite the drawbacks, Lazarus says cannabis offers hope as a potential treatment for opioid and nicotine addictions.
“It’s something we want to study,” he says. “In our lab, we see there’s an interaction between cannabis and the metabolism of opioids like oxycodone and morphine. There are also interactions with benzodiazepines like valium.
“If we could inhibit an opioid user’s metabolism through cannabinoids, maybe they won’t need to take the opioid as much,” says Lazarus. “Maybe they could have less toxicity and addiction.”
The same holds for cigarette smokers who might not need to light up as often if nicotine levels stayed high in the body for longer periods of time. A smoker might be able to go from two packs a day to only a few cigarettes a day.
Lazarus makes it clear he is not advocating a ban on cannabis. Drug interactions are common for many medications, including statins whose metabolism is inhibited by grapefruit juice.
“Cannabis is useful,” he says. “Even though it inhibits enzymes, it’s not enough to cause problems for most people. It’s only when you introduce other drugs into the system that it’s a concern.”