THC and Epigenetic Changes in Blood Cells: Why Concentration and Recovery Matter
Repeated THC exposure altered epigenetic-regulatory measures in cultured human blood cells at the higher tested concentration. Several changes were absent at the lower concentration or returned toward control levels after incubation ended. The study does not establish permanent brain injury or diagnose cannabis use disorder.
Human cells, in-vitro exposure
Researchers isolated peripheral blood mononuclear cells from healthy male donors and exposed them to THC in culture. Experiments examined repeated incubation, a drug-free interval and an additional challenge. Measurements included gene expression, enzyme activity and DNA hydroxymethylation-related changes.
The culture medium is not a patient’s whole blood. Its stated THC concentration should not be converted directly into a threshold for a clinical or forensic diagnosis.
Preserve the concentration-dependent findings
At 50 ng/mL, the investigators did not detect significant changes in the examined DNMT, TET or cannabinoid-receptor expression measures. At 200 ng/mL, repeated incubation produced substantial changes in several of those endpoints.
Cytokine responses differed by marker, and some enzyme and receptor-expression measures returned to control levels after the final repeated incubation. An additional challenge produced another pattern. Calling every effect permanent would discard the time-course evidence.
A mechanism is not a behavioral diagnosis
Epigenetic regulation, gene expression and enzyme activity are related but distinct measurements. Their alteration in immune cells does not itself demonstrate the same change in brain tissue or establish its functional consequences.
The small, male-donor laboratory model did not measure drug-seeking, driving or clinical addiction outcomes. It provides a basis for further mechanistic investigation, with the concentration, sampling time and measured tissue kept explicit.
Related analysis
See our analysis of why a THC concentration does not independently establish impairment.
Primary research
Kerda Pulk and colleagues. Concentration-dependent effect of delta-9-tetrahydrocannabinol on epigenetic DNA modifiers in human peripheral blood mononuclear cells. Translational Psychiatry. DOI: 10.1038/s41398-025-03419-y.
