Cannabidiol, a non-intoxicating phytocannabinoid, has potential therapeutic effects over a broad range of disorders. Recently, there has been increased interest in CBD, as several studies showed promising anticonvulsant efficacy with few side effects. In 2018, a CBD-based oral solution, Epidiolex®, was approved by the FDA to treat two severe forms of pediatric epilepsy, Dravet syndrome, and Lennox-Gastaut syndrome. Although only these two syndromes are recognized indications for CBD, it has been consumed in an unregulated fashion for a variety of indications including chronic pain, muscle stiffness, inflammation, anxiety, smoking cessation, and even cancer. While CBD legislation in the USA is confusing due to the differences in state and federal laws, CBD has proliferated in the US market in several forms such as CBD oil or capsules, hemp oil/extract, and also as an ingredient in several dietary supplements, syrups, teas, and creams. With the ever-increasing use of CBD and its widespread availability to the general public, it is important to examine and report on possible drug-drug interactions between CBD and other therapeutic agents as well as addictive substances such as alcohol and tobacco. A detailed literature search for CBD’s possible interactions was conducted using online databases. As expected, CBD has been reported to interact with anti-epileptic drugs, antidepressants, opioid analgesics, and THC, but surprisingly, it interacts with several other common medications, e.g. acetaminophen, and substances including alcohol. This review provides a comprehensive list of interacting drugs. The possible mechanisms for these drug-drug interactions are presented in table format. Given the growing popularity of CBD as a medication and the dearth of available information on CBD drug-drug interactions, it is critical to be aware of current drug-drug interactions and it will be important to investigate the impact of CBD upon concomitant medication use in future randomized, controlled trials.
Keywords: cannabidiol; cannabinoids; cytochrome P450; drug–drug interactions; mechanism.
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.
Doubling up on side effects
Many drugs are broken down by enzymes in the liver, and CBD may compete for or interfere with these enzymes, leading to too much or not enough of the drug in the body, called altered concentration. The altered concentration, in turn, may lead to the medication not working, or an increased risk of side effects. Such drug interactions are usually hard to predict but can cause unpleasant and sometimes serious problems.
CBD can alter the effects of other drugs
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.