Liver safety concerns were raised in randomized controlled trials of cannabidiol (CBD) in patients with Lennox-Gastaut and Dravet syndromes but the relevance of these concerns to healthy adults consuming CBD is unclear. The objective of this manuscript is to report on liver safety findings from healthy adults who received therapeutic daily doses of CBD for ~3.5 weeks and to investigate any correlation between transaminase elevations and baseline characteristics, pharmacogenetic, and pharmacokinetic data. Sixteen healthy adults were enrolled in a phase 1, open-label, fixed single-sequence drug-drug interaction trial to investigate the effect of repeated dose administration of CBD (1500 mg/day) on cytochrome P450 (CYP) 1A2 activity. Seven (44%) participants experienced peak serum alanine aminotransferase (ALT) values greater than the upper limit of normal (ULN). For 5 (31%) participants, the value exceeded 5× ULN, therefore meeting the international consensus criteria for drug-induced liver injury. There was no correlation between transaminase elevations and baseline characteristics, CYP2C19 genotype, or CBD plasma concentrations. All ALT elevations above the ULN began within 2-4 weeks of initial exposure to CBD. Among the 6 participants with ALT elevations who were discontinued from the protocol, some had symptoms consistent with hepatitis or hypersensitivity. We conclude that healthy adults consuming CBD may experience elevations in serum ALT consistent with drug-induced liver injury. Given the demonstrated inter-individual variation in susceptibility, clinicians should be alert to this potential effect from CBD, which is increasingly available in various non-prescription forms and doses to consumers.This article is protected by copyright. All rights reserved.