Consider CBD-Drug Interaction Potential: An Expert Interview
Cannabis (Cannabis sativa) is “one of the most widely used and controversial substances worldwide.” The “vast majority” of cannabis use is recreational, although cannabis and cannabis-derived substances are increasingly being used for medical and complementary health purposes.
Increased access has included the expansion of medical marijuana programs in approximately two-thirds of US states as well as “broad consumer marketing” and use of cannabidiol (CBD) products. Indeed, retail sales of hemp-derived CBD products in the United States reached $170 million in 2016, and are projected to grow at a 55% compound annual growth rate over the next 5 years to reach over $1 billion. A variety of cannabis products are now available, including high-potency herbal cannabis, mass-produced cannabis “edibles,” and cannabis oils, concentrates, and topical preparations.
The increased use of CBD has created some significant challenges because of a variety of factors. One is that CBD is one of many compounds derived from cannabis, with another compound being Δ-tetrahydrocannabinol (THC), which is the psychoactive component. Another is a paucity of research; despite the increasing use of cannabis products—including CBD—and “rapid changes in the social, political, cultural and legal landscape…there is insufficient decision support provided by available evidence regarding CBD.” One reason for this is that potential researchers encounter a myriad of regulatory barriers, and practical obstacles that impede the research process. Clinicians “therefore face the challenge of keeping up with the evolving use of cannabis to better assess and treat use disorders and counsel patients who choose to use cannabis for medical or recreational purposes
Two of the many areas of unclarity and insufficient evidence are the potential adverse drug events (ADEs) of CBD and potential drug-drug interactions (DDIs) with other agents a patient may be taking.
To shed light on this complex subject, MPR interviewed Joshua D Brown, PharmD, PhD, Assistant Professor, Pharmaceutical Outcomes & Policy, University of Florida College of Pharmacy. Dr Brown is the coauthor of a recent review article, “Potential Adverse Drug Events and Drug-Drug Interactions with Medical and Consumer Cannabidiol (CBD) Use.”
What motivated you to write your article?
We wrote the article to meet the need for cannabis-related education in the current environment in which cannabis products – especially CBD – are so easily accessible. Almost any patient could be using it recreationally or chronically for some type of medical condition, such as pain or insomnia.
This is a major problem from a safety perspective because cannabis has been regarded as a benign agent, which is assumed from its history of recreational use. People say, “Marijuana never killed anyone and no one has ever overdosed on it.” But when we look at the history of recreational users, they have traditionally been younger adults who don’t have serious conditions and are not taking multiple medications. So I think that we need a paradigm shift in the way we think about CBD and cannabis as a whole, not as a recreational illicit substance but as a medication.
CBD, THC, and other cannabinoids have the potential to interact with commonly used medications – at least hypothetically. If I were to hazard a guess, I would say that CBD might interact with at least one-half if not three-quarters of all medications, given its role as a potential inhibitor of certain enzymes that play a role in metabolizing other drugs. This can lead to potential ADEs and DDIs. CBD not only inhibits these enzymes but it also is itself metabolized by the enzymes, so one might say it is both a “perpetrator” and a “victim” of DDIs.
The potential for both ADEs and DDIs is related to the pharmacologic targets of CBD, its pharmacodynamic effects, and its impact on the metabolism, absorption, and elimination of other medications.
Should You Try CBD or Cannabis Creams for Pain Relief?
Cannabis-infused sports creams claim to offer muscle relief. We spoke to experts to see if they’re worth a shot.
Chances are, you’re no stranger to muscle aches. Well, what if we told you that cannabis creams might help provide relief?
Yes, there’s a new(ish) type of topical ointment on the market, and it’s infused with cannabidiol (CBD) from marijuana. Manufacturers claim it can help alleviate acute pain and muscle soreness. CBD is similar to THC, except it’s non-psychoactive, meaning some researchers view it as the golden child of medicinal use.
Science has confirmed that cannabis is an effective pain reliever, reinforced in a massive new report from the National Academies of Sciences, Engineering, and Medicine. But there’s a big difference between ingesting cannabis or its individual chemicals orally and absorbing it through your skin. Here, the lowdown on this new crop (no pun intended) of pain relievers.
What Exactly Is a CBD-Infused Topical Cream?
The ointment is made from infusing high-quality cannabis flowers in some kind of quality oil-coconut or olive typically-which extracts the active compounds, either CBD, THC, or both depending on the type of hemp used. This oil is then blended with other therapeutic herbs, like arnica or lemongrass essential oils, that are well-known pain relievers.
If you read the ingredient list, often everything in the jar is straight from mother earth. As long as that’s indeed the case with the cream you have your eye on, the formula is immensely safe, chemically, says Gregory Gerdeman, Ph.D., neurophysiologist who researches cannabinoid biology and pharmacology at Eckerd College in Saint Petersburg, FL. And since they’re formulated to be topical (absorbing into the top layer of skin) and not transdermal (which would pass through the skin and into your bloodstream) there’s no risk of getting high, explains Gerdeman.
“When it comes to cannabis-based topicals for muscle soreness or other pain relief, there’s absolutely no reason why it should be a big deal to try,” he says.
They may be safe, but there’s one massive problem: There’s practically no scientific data to support the idea that a CBD-infused topical cream is any more effective than other topical pain relievers, like Tiger Balm, BenGay, or Icy Hot. Michelle Sexton, a San Diego-based naturopathic doctor and medical research director of the Center for the Study of Cannabis and Social Policy says that her patients do seem to have a great interest in CBD ointments, and roughly 40 percent of them have indeed tried one. However, these people are in her office now because the topicals didn’t work for them. “As a medical professional, my opinion is there’s little evidence to back up the claims being made—it’s all marketing for now,” she says.
How CBD and Cannabis Pain-Relief Creams Work
There is an argument to be made for the simple fact that science hasn’t caught up to the trend (and laws) of cannabis yet. (Here’s what research has to say about the potential benefits of CBD and cannabis so far.) And there are doubtlessly researchers testing the efficacy of CBD creams for pain relief as we speak.
The theoretical logic is there, Gerdeman says. What, exactly, is that thinking? Well, there are a few different ways CBD could help regulate pain—by increasing your natural endocannabinoids, decreasing your inflammatory response, and desensitizing your pain receptors (although it’s still unclear whether this stands when absorbed topically compared to orally).
Let’s start simple: Endocannabinoids are natural signals in your body that help maintain homeostasis by detecting and regulating hunger, pain, mood, and memory. (They’re actually part of your post-workout exercise high.) CBD helps elevate your natural levels of pain-relieving endocannabinoids by blocking metabolism as they’re moving around your body.
The second method of pain relief centers around the damage you do when you work out. When you strength train, you create micro-tears in your muscles, which is why you feel sore as you heal. Once your immune cells detect damage, they release inflammatory mediators in order to repair the tissue. CBD, though has the ability to limit the release of some proinflammatory signals, thereby helping with pain without thwarting the healing entirely, Gerdeman explains.
Finally, you have receptors called TrpV1 that detect and regulate your body temperature. When activated, they put out heat, soothing your pain receptors. Using this channel, CBD makes these pain receptors hyperactive for a period of time, causing them to get hot, desensitizing them and downregulating those pain-sensing nerve endings.
What Science Says About CBD Creams
Phew—enough of that biology lesson. The real problem here is that all of this has yet to be proven in scientific studies on humans.
A study analysis in Journal of Pain Research confirms that topical use of certain cannabinoid topicals can reduce pain in animals with inflammation or neuropathic pain. And science has found topical creams with THC and CBD help relieve pain for conditions like multiple sclerosis. But for the vast majority of chronic pain—and most certainly for acute pain like post-workout—the scientific jury is 100 percent still out. “There’s a little bit of data in support of CBD for pain relief, but to go from animal to human is a giant leap,” Sexton says.
“The pain and stiffness that comes post-workout or from overexertion certainly has a pro-inflammatory component to it, so it’s reasonable to think CBD or other cannabinoids might have benefits, but we have no research to support this yet,” Gerdeman adds.
The other issue? Topical CBD and cannabis creams will treat anatomical structures within 1 centimeter of the skin—and the muscle where your actual soreness is located is going to be deeper than that, explains Ricardo Colberg, M.D., a physician at Andrews Sports Medicine and Orthopaedic Center in Birmingham, AL. (The good news: Since it doesn’t need to be absorbed deeply, CBD and cannabis could do amazing things as a skincare ingredient.)
The fatty tissue can only hold so much oil, so, theoretically, if you apply enough of a CBD cream to your skin, it might leak down into your skeletal muscle just out of diffusion, Sexton adds. But there’s no study to show this, and that means you’re going to be rubbing on a whole lot of the stuff.
This takes us to the next problem: There is no regulation around how much active CBD or THC is in each cream or how much of the compound is needed to see relief. Read: “If you have three products that say 1 percent CBD infused in coconut oil, one could be great and the other two could be crap—that’s the reality of cannabis medicine right now,” Gerdeman says.
So… Should I Try It?
That’s not to say CBD creams definitely won’t reduce your acute pain or muscle soreness. That’s because pretty much all of these creams on the market right now have other scientifically-proven analgesic compounds, like menthol, camphor, and capsaicin which are also found in other, non-CBD topical pain relievers. “Any cream with a heating or cooling sensation desensitizes the nerves to pain by distracting them with stimuli on top,” Dr. Colberg explains. Plus you’re often massaging the area as you apply, which improves circulation and reduces muscle spasms, he adds.
So do you need the CBD? All our experts agree that until we have more peer-reviewed research, all claims are marketing hype and not evidence-based.
But there is an argument to be made for simply believing the CBD adds that special something. “Scientific literature says there’s a 33 percent chance of the placebo effect helping people, so for some, just using a cream they believe can help will provide some relief,” Dr. Colberg adds.
The short of it: Science hasn’t confirmed creams with CBD will have any greater benefit than those without, but there’s little-to-no risk in trying it out (other than wasting your money, of course). And if you believe in the power of CBD-infused creams, that may be enough to score some relief.
Want to give it a shot?
If your state has legalized both compounds, look for a cream with 1:1 CBD to THC as well as another cannabinoid BCP (beta-caryophyllene) if possible, which manufacturers have seen better results with, Gerdeman suggests. Try Apothecanna’s Extra Strength Relieving Creme or Whoopi & Maya’s Medical Cannabis Rub (
If you don’t live in a legalized state, you can typically still get CBD creams. Since there’s no regulation or standardized testing, your best bet is to find trustworthy brands that use creams free of toxins but with additional pain relievers like menthol, capsaicin, lemongrass, or camphor.