Hyponatremic Cognitive Dysfunction Resulting from Drug-Drug-Gene Interaction between Sertraline and Cannabidiol in an Intermediate CYP2C19 Metabolizer Patient

  • Jade Nanan Mayo Clinic Florida
  • Sheena Crosby Mayo Clinic Florida
  • Michael J. Schuh Mayo School of Health Related Sciences
Keywords: CYP2C19, Hyponatremia, Drug-drug-gene interaction, pharmacogenomics, cannabidiol, PGx


Background: Pharmacogenomics (PGx) can provide more precision in determining causation of adverse drug reactions (ADRs) from drug-drug-gene interaction clinical application.

Case Summary: Patient was an intermediate CYP2C19 metabolizer on stable therapy taking a low but therapeutic dose of sertraline for depression and anxiety over a period of 20 years. The patient then became hyponatremic and cognitively impaired after addition of cannabidiol (CBD) to this sertraline regimen. The proposed mechanism was drug-drug-gene interaction of CBD further inhibiting the CYP2C19 metabolism of sertraline and increasing drug exposure to produce moderate to severe hyponatremia and subsequent cognitive dysfunction.

Practice Implications: Pharmacogenomics (PGx) testing may assist in etiology of patient symptoms from adverse drug reactions (ADRs) or drug-drug interactions by combining these with detection and application of drug-gene interactions. This case shows inhibition of CYP2C19 by CBD to further increase sertraline exposure, producing hyponatremia and subsequent cognitive dysfunction through CYP2C19 phenoconversion by CBD.


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Received 2022-05-27
Accepted 2022-08-04
Published 2022-09-23
Pharmacy Practice & Practice-Based Research