At consumer-relevant concentrations determined by modeling, CBD, CBN, and CBD-matched hemp extract did not significantly affect human liver cell viability, though hemp extract caused modest decreases in some liver function markers at the highest dose.
CBD consumers, supplement regulators, and hepatotoxicity researchers
No cell death at any consumer-relevant CBD, CBN, or hemp extract dose
What the researchers found
Cell viability was not significantly affected by CBD, CBN, or hemp extract at any concentration tested (10nM to 25uM) after 24 or 48 hours. Hemp extract at the highest concentration produced modest but statistically significant decreases in albumin secretion, urea secretion, and mitochondrial membrane potential. CBD only affected albumin secretion. CBN showed no significant effects.
Why it matters
CBD has been flagged for potential liver toxicity based on the prescription drug Epidiolex at high doses. This study examines whether consumer-level exposures (much lower than pharmaceutical doses) pose similar risks, finding minimal hepatotoxicity at relevant concentrations.
The numbers in context
Concentrations tested: 10nM to 25uM. CBD, CBN, and hemp extract tested at consumer-relevant doses. No effect on cell viability at any concentration. Hemp extract: modest decrease in albumin, urea, and mitochondrial membrane potential at highest dose. CBD: modest decrease in albumin only.
How the study worked
In vitro study using primary human hepatocytes exposed to CBD, CBN, or CBD-concentration-matched hemp extract at concentrations determined by in silico pharmacokinetic modeling to represent consumer-relevant exposures. Assessed lactate dehydrogenase release, apoptosis, albumin secretion, urea secretion, and mitochondrial membrane potential at 24 and 48 hours.
What this study cannot tell us
In vitro study does not capture the full complexity of liver metabolism in a living organism. Consumer-relevant concentrations were estimated by modeling, not measured from actual consumers. Primary human hepatocytes from different donors may respond differently. Only 48-hour exposure tested.
How to read the evidence
Well-designed in vitro study with consumer-relevant dosing, but laboratory cell results may not fully reflect in vivo liver effects.
When this study was published
2024 study
The bigger picture
The gap between pharmaceutical CBD doses (up to 20 mg/kg/day for epilepsy) and consumer supplement doses is enormous. This study suggests that at the lower consumer-relevant concentrations, liver toxicity concern may be overstated, though the modest hemp extract effects warrant continued monitoring.
Questions still open
- Would chronic exposure over weeks or months produce different results? Do the modest effects of hemp extract at high concentrations reflect a real safety signal or normal biological variability? How do these in vitro results compare to liver enzyme changes seen in clinical studies?
Common questions
Is CBD safe for the liver?
Is CBN safe for the liver?
Read the original research
Examining the hepatotoxic potential of cannabidiol, cannabidiol-containing hemp extract, and cannabinol at consumer-relevant exposure concentrations in primary human hepatocytes.
Journal of applied toxicology : JAT, 44(10), 1595-1605
Citation
Striz, Anneliese; Zhao, Yang; Sepehr, Estatira; Vaught, Cory; Eckstrum, Kirsten; Headrick, Kyra; Yourick, Jeffrey; Sprando, Robert. (2024). Examining the hepatotoxic potential of cannabidiol, cannabidiol-containing hemp extract, and cannabinol at consumer-relevant exposure concentrations in primary human hepatocytes.. Journal of applied toxicology : JAT, 44(10), 1595-1605. https://doi.org/10.1002/jat.4646
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