CBD levels in commercially available products vary widely. The FDA has issued warning letters every year since 2015 to companies marketing unapproved new drugs that allegedly contain CBD. 8,10-13 As part of these warnings, the FDA tests the chemical content of CBD compounds, and it has found that many products do not contain the claimed level of CBD. Commercially available products have been assessed in laboratories, whose findings support the FDA’s concerns about product inconsistency and mislabeling. A laboratory assessment of OTC CBD products sold in the U.S. demonstrated that only 26 of 84 (31%) products tested were accurately labeled. 14 Not only was the amount of CBD in products overlabeled or underlabeled, but 21% of products contained THC even though it was not listed in the product information. In addition, the FDA has cited concerns regarding reports of contaminants such as pesticides and heavy metals. 8
Commercially available CBD products may not contain the CBD concentrations claimed on the label, and the FDA warns consumers to be aware of this inconsistency when using such products. 13 Of particular concern is the THC component in mislabeled CBD products. Older adults may be predisposed to adverse effects caused by the psychoactive properties of THC. The use of marijuana in older adults has been associated with increased risk of injury and adverse events. 34
Administration and Absorption
Cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC) are among the many cannabinoids, or components, of the Cannabis sativa plant. CBD is nonpsychoactive, whereas THC has psychoactive properties such as euphoria and psychosis. Two common strains of Cannabis sativa are marijuana and hemp. 1 CBD may be derived from either marijuana (which often contains more than 15% THC) or hemp (having a THC concentration of no more than 0.3%). 2 In addition, CBD may be extracted from Cannabis indica and hybrid plants, which may have higher concentrations of CBD than THC. A recent survey revealed that one in seven Americans uses CBD products, with the most common reasons for its use being pain, anxiety, poor sleep, and arthritis. 3
Absorption of CBD may also be altered by food intake. In clinical trials, coadministration of Epidiolex with a high-fat, high-calorie meal increased plasma levels of CBD fourfold to fivefold compared with administration on an empty stomach. 7 In one study using a purified (99%) CBD capsule, coadministration with food resulted in a maximum concentration and AUC of 14-fold and fourfold higher, respectively, compared with administration on an empty stomach. 22 CBD inhalation in humans has an average bioavailability of approximately 31%, with the use of one type of metered-dose inhaler demonstrating bioavailability of more than 65%. 18,23 Transdermal absorption of CBD is variable in animal studies and has yet to be fully elucidated in humans. 4
CBD absorption depends on the product formulation. In animal and human studies, CBD administered orally has been shown to be poorly absorbed, with bioavailability of 13% to 19%. 19,20 CBD’s bioavailability is believed to be reduced by first-pass metabolism. Poor bioavailability can be avoided with the use of alternative formulations. There is an emerging market for novel delivery methods to increase CBD’s oral bioavailability. 21
The researchers further warned that while the list may be used as a starting point to identify potential drug interactions with marijuana or CBD oil, plant-derived cannabinoid products may deliver highly variable cannabinoid concentrations (unlike the FDA-regulated prescription cannabinoid medications previously mentioned), and may contain many other compounds that can increase the risk of unintended drug interactions.
Researchers from Penn State College of Medicine evaluated existing information on five prescription CBD and delta-9-tetrahydrocannabinol (THC) cannabinoid medications: antinausea medications used during cancer treatment (Marinol, Syndros, Cesamet); a medication used primarily for muscle spasms in multiple sclerosis (Sativex, which is not currently available in the US, but available in other countries); and an antiseizure medication (Epidiolex). Overall, the researchers identified 139 medications that may be affected by cannabinoids. This list was further narrowed to 57 medications, for which altered concentration can be dangerous. The list contains a variety of drugs from heart medications to antibiotics, although not all the drugs on the list may be affected by CBD-only products (some are only affected by THC). Potentially serious drug interactions with CBD included
While generally considered safe, CBD may cause drowsiness, lightheadedness, nausea, diarrhea, dry mouth, and, in rare instances, damage to the liver. Taking CBD with other medications that have similar side effects may increase the risk of unwanted symptoms or toxicity. In other words, taking CBD at the same time with OTC or prescription medications and substances that cause sleepiness, such as opioids, benzodiazepines (such as Xanax or Ativan), antipsychotics, antidepressants, antihistamines (such as Benadryl), or alcohol may lead to increased sleepiness, fatigue, and possibly accidental falls and accidents when driving. Increased sedation and tiredness may also happen when using certain herbal supplements, such as kava, melatonin, and St. John’s wort. Taking CBD with stimulants (such as Adderall) may lead to decreased appetite, while taking it with the diabetes drug metformin or certain heartburn drugs (such as Prilosec) may increase the risk of diarrhea.
Does the form of CBD matter?
CBD has the potential to interact with many other products, including over-the-counter medications, herbal products, and prescription medications. Some medications should never be taken with CBD; the use of other medications may need to be modified or reduced to prevent serious issues. The consequences of drug interactions also depend on many other factors, including the dose of CBD, the dose of another medication, and a person’s underlying health condition. Older adults are more susceptible to drug interactions because they often take multiple medications, and because of age-related physiological changes that affect how our bodies process medications.
Absolutely. Inhaled CBD gets into the blood the fastest, reaching high concentration within 30 minutes and increasing the risk of acute side effects. Edibles require longer time to absorb and are less likely to produce a high concentration peak, although they may eventually reach high enough levels to cause an issue or interact with other medications. Topical formulations, such as creams and lotions, may not absorb and get into the blood in sufficient amount to interact with other medications, although there is very little information on how much of CBD gets into the blood eventually. All of this is further complicated by the fact that none of these products are regulated or checked for purity, concentration, or safety.
People considering or taking CBD products should always mention their use to their doctor, particularly if they are taking other medications or have underlying medical conditions, such as liver disease, kidney disease, epilepsy, heart issues, a weakened immune system, or are on medications that can weaken the immune system (such as cancer medications). A pharmacist is a great resource to help you learn about a potential interaction with a supplement, an herbal product (many of which have their own drug interactions), or an over-the-counter or prescription medication. Don’t assume that just because something is natural, it is safe and trying it won’t hurt. It very well might.
Products containing cannabidiol (CBD) seem to be all the rage these days, promising relief from a wide range of maladies, from insomnia and hot flashes to chronic pain and seizures. Some of these claims have merit to them, while some of them are just hype. But it won’t hurt to try, right? Well, not so fast. CBD is a biologically active compound, and as such, it may also have unintended consequences. These include known side effects of CBD, but also unintended interactions with supplements, herbal products, and over-the-counter (OTC) and prescription medications.
Most importantly, CBD can interact with other important medications like blood thinners, heart medications, and immunosuppressants (medications given after organ transplantation), potentially changing the levels of these important medications in the blood and leading to catastrophic results, including death. Also, more information needs to be gathered about its safety in special populations such as the elderly, children, those who are immunocompromised, and pregnant and breastfeeding women.
Given the rapid change in the legality of cannabis coupled with the increased appetite for something new, and driven by unprecedented profit margins, the advertising for cannabinoids in general and CBD in particular has gone wild. The FDA is very clear that it is illegal to market CBD by adding it to a food or labeling it as a dietary supplement. And it warns the public about its potential side effects, as it’s often advertised in a way that may lead people to mistakenly believe using CBD “can’t hurt.” CBD can cause liver injury, and can affect the male reproductive system (as demonstrated in laboratory animal studies).
Cannabis (most commonly obtained from the Cannabis indica and Cannabis sativa plants) has three major components: cannabinoids, terpenoids, and flavonoids. While there are over a hundred different cannabinoids, the two major components are tetrahydrocannabional (THC) and cannabidiol (CBD). Historically more attention has been paid to the psychoactive (euphoric “getting high”) component of the cannabis plant, THC; there have been fewer scientific studies on the medical use of CBD, a non-psychoactive component of the plant.
Many of the CBD products on the market are unregulated
If you or someone close to you is considering trying CBD, I would recommend Dr. Robert Shmerling’s advice about the dos and don’ts in choosing an appropriate product. Until there is high-quality scientific evidence in humans, it is difficult to make a recommendation for the regular use of CBD in chronic pain management.
So far, pharmaceutical CBD is only approved by the FDA as adjunct therapy for the treatment of a special and rare form of epilepsy. Currently, CBD alone is not approved for treatment of pain in the United States. But a combination medication (that contains both THC and CBD in a 1:1 ratio) was approved by Health Canada for prescription for certain types of pain, specifically central neuropathic pain in multiple sclerosis, and the treatment of cancer pain unresponsive to optimized opioid therapy. There is currently no high-quality research study that supports the use of CBD alone for the treatment of pain.
Finally, there is anecdotal wisdom, when experiences by patients and health professionals have positive results. While the experience or medication could be beneficial, that doesn’t mean it is going to work for everyone. That’s because each and every person is unique, and what works perfectly for one patient could have no effect on another patient. This is especially true for pain, where many other factors (our mood and stress level, our environment and other medical conditions, and our previous experiences) can affect the perception of pain. Please be careful, and keep in mind that some of these incredible-sounding testimonials are merely marketing materials meant to lure consumers to buy more products, as the CBD market is expected to hit $20 billion by 2024.
If you ask health care providers about the most challenging condition to treat, chronic pain is mentioned frequently. By its nature, chronic pain is a complex and multidimensional experience. Pain perception is affected by our unique biology, our mood, our social environment, and past experiences. If you or a loved one is suffering from chronic pain, you already know the heavy burden.