Evidence of a clinically significant drug-drug interaction between cannabidiol and tacrolimus

Am J Transplant. 2019 Oct;19(10):2944-2948. doi: 10.1111/ajt.15398. Epub 2019 May 21.

Abstract

Cannabidiol (CBD), a major purified nonpsychoactive component of cannabis with anticonvulsant properties, was approved by the U.S. Food and Drug Administration (FDA) in June 2018 as an adjuvant treatment for refractory epilepsy (Epidiolex; GW Pharmaceuticals). CBD is metabolized by cytochrome P450 (CYP)3A4 and CYP2C19 with a growing body of evidence suggesting it is also a potent inhibitor of these pathways. We report for the first time a significant drug-drug interaction between the purified CBD product and tacrolimus. A participant in a CBD clinical trial for epilepsy who was also receiving tacrolimus showed an approximately 3-fold increase in dose-normalized tacrolimus concentrations while receiving 2000-2900 mg/day of CBD. Our report delineates an important concern for the transplant community with the increasing legalization of cannabis and advent of an FDA-approved CBD product. Larger studies are needed to better understand the impact of this drug-drug interaction in solid organ transplant recipients.

Keywords: alternative and complementary medicine; clinical research/practice; drug interaction; immunosuppressant - calcineurin inhibitor: tacrolimus; immunosuppression/immune modulation; pharmacology.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Cannabidiol / metabolism*
  • Cannabidiol / therapeutic use
  • Drug Interactions
  • Epilepsy / complications
  • Epilepsy / drug therapy*
  • Epilepsy / metabolism
  • Epilepsy / pathology
  • Female
  • Humans
  • Immunosuppressive Agents / metabolism*
  • Immunosuppressive Agents / therapeutic use
  • Nephritis, Interstitial / complications
  • Nephritis, Interstitial / drug therapy*
  • Nephritis, Interstitial / metabolism
  • Nephritis, Interstitial / pathology
  • Prognosis
  • Tacrolimus / metabolism*
  • Tacrolimus / therapeutic use

Substances

  • Immunosuppressive Agents
  • Cannabidiol
  • Tacrolimus