Dr. Hill Publishes Comprehensive Review of CBD Drug-Drug Interactions

Cannabidiol (CBD) has seen a surge in popularity over the last ten years. Unlike tetrahydrocannabinol (THC), the other major phytocannabinoid found in cannabis, CBD does not induce intoxication, it has a very good safety profile, it has proven to be effective at treating certain forms of seizure disorders, and anecdotal evidence suggests that it could have dozens of therapeutic applications. While many herald it as a wonder drug, the sole FDA-approved formulation of CBD is Epidiolex®, which to date has only been indicated to treat Lennox-Gastaut syndrome, Dravet syndrome, and tuberous sclerosis complex. Other formulations that contain CBD are widely available without the need for prescription and are being used to enhance wellness and to treat a host of conditions without strong evidence of efficacy.


While CBD is well tolerated and adverse effects tend to be relatively minor, CBD is still a drug and it does interact with other medications. It acts through several different targets, including cannabinoid receptors 1 and 2 (CB1 and CB2), multiple G-protein-coupled receptors (GPRs), and several 5-hydroxytryptamine receptors (5-HT1A, 5-HT2A, and 5-HT3A), among others. While being metabolized by the liver, CBD can alter the function of certain enzymes found in that organ (known as cytochromes P450 (CYP450) enzymes). This can mean that both CBD and other drugs that are also metabolized by the same enzymes take longer to be broken down and can remain in the bloodstream for longer periods of time. Without taking into consideration how CBD affects hepatic functioning and specific CYP450 enzymes, this could confound efforts to prescribe correct dosages.


To better understand these interactions, Kevin Hill, MD, MHS, one of the writers of Medical Marijuana: A Clinical Handbook, published a review in the Journal of General Internal Medicine that provides a comprehensive list of drugs whose effects or metabolism can be affected when co-administered with CBD. In addition to describing how CBD interacts with antiepileptic drugs, antidepressants, opioids, THC, alcohol, and acetaminophen, he and coauthors Mahmoud Elsohly, PhD, and Premalatha Balachandran, PhD, map out how CBD interacts with drugs that target the following:

  • CB1

  • CB2

  • GPR12

  • 5-HT1A

  • 5-HT2A

  • 5-HT3A

  • Glycine receptor subunit alpha-3

  • Prostaglandin G/H synthase 1

  • Prostaglandin G/H synthase 2

  • CYP450 1B1

  • CYP450 3A5

  • CYP450 2D6

  • CYP450 3A7

  • CYP450 1A2

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