On its own—at least in the short-to-medium term—cannabidiol (CBD) is thought to be largely safe. Sure, a few people who use this non-inebriating weed compound for recreation or for its potential medical benefits may experience mild tiredness, appetite changes, or an occasional case of diarrhea. For most, though, these rare side effects are worth withstanding if CBD can help them with inflammation issues, anxiety, and more. This is one of the reasons why the stuff has grown so popular of late.
But just because CBD is fairly benign on its own doesn’t mean that it will be as benign when mixed with other drugs. Any time we put two or more substances inside our bodies, there’s always a chance that they will interact with each other in new ways. Even foods as simple as black pepper can have an impact on the absorption of other drugs, says Donald Abrams, a professor in the department of medicine at the University of California, San Francisco, who specializes in medicinal cannabis treatments. CBD, it turns out, could potentially react with numerous other substances, though no one is sure about the specific drugs or dosage levels at which this might start to pose serious issues.
No one has systematically studied CBD’s interactions with other drugs. The only clear documentation of interactions comes from studies on Epidiolex, a federally approved treatment for a few rare forms of epilepsy made primarily of concentrated CBD. Those studies found that particularly high CBD doses could, in some patients, increase blood levels of other antiepileptics they were taking, such as clobazam, eslicarbazepine, rufinamide, topiramate, valproate, and zonisamide. With clobazam, this led to increased sedative side effects. And with valproate, it led to increased liver functioning that could become toxic over time. One case study also found that using the CBD drug led a patient on the blood thinner warfarin to have even thinner than expected blood. These documented interactions are pretty isolated, though, so at this point, they seem minor.
We do, however, know a good amount about how CBD interacts with our bodies as we process it. Namely, we know that CBD interacts with an enzyme system in the liver particularly potently. To put it very simply, CBD could potentially prevent other drugs from accessing these enzymes, causing some of them to build up in our bloodstream. Recent research from Carola Rong, a scientist from the University of Toronto, builds on the idea that when that happens, many of these other drugs can become more potent. This effect could also prevent some types of drugs from having a timely effect.
It would be one thing if this liver enzyme group only interacted with a few types of drugs. Instead, it's involved in processing about 60 percent of all pharmaceuticals on the market, including common psych drugs like Klonapin, Valium, Xanax, and a whole host of antihistamines, antiretrovirals, and steroids, to name a few, Rong says.
Fortunately, the mere presence of CBD doesn’t mean that the enzyme system will be affected to the point that it changes the way these drugs work. But unfortunately, Rong explains, we don’t know the exact doses of CBD that would result in something clinically significant for any given drug—even those we know can be affected by the extract at certain high dosages. Nor do we know how long any given dose of CBD would exert an effect on these enzymes, another factor in assessing the risks, adds Adrian Devitt-Lee, a cannabinoid researcher working on the Project CBD research initiative. However, as a rule of thumb (and a very rough estimate), he thinks that anyone taking a gram or more of CBD in a day should be prepared for an interaction of some kind, although interactions could occur at lower doses as well. (A gram is well above the 30 mg or so dosage that show up on the most popular CBD brands, like Lord Jones and Charlotte's Web, but as noted below, CBD isn't regulated and therefore one cannot trust the the content per dose listed on every product on the market without testing it.)
Dave Bearman, a California-based primary care physician who has worked with medical marijuana for almost two decades and seen over 3,000 patients, notes that he rarely hears complaints that would point to interactions with drugs. Devitt-Lee adds that he’s only aware of a few reports of cannabis interacting with blood thinners. And most CBD products often contain far lower levels of the extract than the doses of Epidiolex that have led to issues, says Timothy Welty, a pharmacologist at Drake University in Iowa.
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Still, the more CBD you have, the more likely it is to interfere with other drugs metabolized by these liver enzymes. “With people taking highly concentrated tinctures and oils containing CBD, I am concerned that there may be some potential interactions with pharmaceuticals,” Abrams says. While there is no specific definition of “highly concentrated,” the doses on the market now are higher than they’ve ever been before. The fact that these concentrates are growing more common, and that some contain higher doses than they advertise, increases the risk. A lack of federal regulation (for now at least) of the CBD space enables such false advertising—and also makes it difficult to know what other substances might be in any given CBD product. Each additional unknown substance could raise its own drug-drug interaction concerns.
Experts like Sarah Melton, a clinical pharmacist and professor of pharmacy practice at the East Tennessee State University, have publicly worried that people taking regular, high doses of over-the-counter CBD could run a higher risk of accidentally overdosing on, say, sedatives. Devitt-Lee notes that most medications are safe enough that, even if they built up in our bloodstream, they’d still provide their intended benefits and, at worst, possibly risk a few more benign side effects than usual. The real concern, he explains, is drugs that are only useful in narrow dosages, below which they have no real effect and above which they may be toxic, and drugs that are already administered at high doses. In theory, some of those drugs could flip from therapeutic to toxic if CBD caused them to build up.
The fact that we don’t know which drugs CBD could interact with most potently is a major issue, especially given its frequent popular use in conjunction with other medications. If CBD turns out to delay metabolism of chemotherapy drugs, for instance, Devitt-Lee says that could be a major issue: Doctors try to give the maximal tolerable dose to start with, so an unforeseen buildup could easily cause toxic effects.
There is no good way to systematically study which drugs might pose a serious interaction risk with CBD either. That is partly thanks to limited access and funding surrounding cannabis-related research. But it is also in part a practical constraint as well. As Abrams notes, “you’re not going to give everybody getting hundreds of different kinds of chemotherapy increasing doses of CBD to get the kind of data you’re looking for.”
Even if we could gather that data, it might not be the greatest risk predictor. Rong notes that we know different people, for a number of reasons, metabolize via the same enzyme pathways at different rates. But we do not know what those differences translate to in terms of drug tolerances or interactions.
Much of the work on this issue, Welty says, will involve more case studies and observations as individuals see what happens when CBD is combined with other drugs. That may sound risky, but watchful doctors can spot concerning symptoms suggesting an adverse interaction with CBD and simply step back the dosage of one substance or another to find a sweet spot that offers help and avoids harm. That’s how Epidiolex researchers resolved the issues they came up against, Devitt-Lee says, and concluded that despite the negative interactions they witnessed between CBD and some antiepileptic meds, it was essentially safe.
For now, caution is the watchword for anyone taking significant doses of CBD and other drugs simultaneously. Devitt-Lee notes that people on chemotherapy drugs and warfarin blood thinners should be especially cautious, given how easily an increased blood concentration of either could lead to some serious negative side effects. And Rong urges physicians to be conscientious when prescribing medications to patients who have a history of using CBD or products containing it.
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