Preclinical evidence of cannabis-induced oxidative stress: A systematic review and meta-analysis

Although cannabis exposure is linked to oxidative stress, no systematic analysis has evaluated its effects on ROS production, lipid peroxidation, and antioxidant defenses. We conducted a systematic review and meta-analysis of recent in vivo and in vitro studies. Of 9,775 records identified across six databases, 51 met inclusion criteria and 49 were quantitatively analyzed (23 in vitro , 26 in vivo ). In vitro studies exposed cell lines to phytocannabinoids and measured ROS, MDA, and GSH. In vivo studies included 1,258 animals, mainly rats (52.7%) and mice (27%), treated with THC, CBD, THC+CBD, crude extracts, or synthetic cannabinoids via intraperitoneal, oral, or aqueous routes. Assessed biomarkers included MDA/TBARS, CAT, SOD, GSH, and GPx. Meta-analyses showed cannabis exposure was associated with ROS production in vitro (SMD = 0.04, 95% CI 0.02–0.06), a small, context-dependent effect, and in vivo (SMD = 0.93, 95% CI 0.10–1.75), along with increased lipid peroxidation in both systems. Cannabis reduced GSH and antioxidant enzymes, decreasing GR and CAT in vitro and SOD and GPx in vivo. Overall, cannabinoid exposure was associated with changes in oxidative stress markers in preclinical models. These findings suggest a possible biological pathway but do not provide definitive evidence of a consistent effect. • •Cannabis exposure increases ROS in vitro and in vivo models • •Lipid peroxidation is elevated following cannabis or cannabinoid treatment • •Cannabis reduces glutathione and disrupts redox homeostasis • •Antioxidant enzymes (GR, CAT, SOD, GPx) are inhibited by cannabis • •Effects vary by cannabinoid type, dose, treatment duration, and route