The growing usage of synthetic cannabinoids (SCs) has become a critical public health issue. Aside from skin toxicity and hepatotoxicity, SCs has been linked to several life-threatening adverse effects, including cardiovascular, gastrointestinal, neurological, renal, metabolic, ophthalmologic, and pulmonary consequences. This study aimed to evaluate the effects of SCs usage on oxidative stress, cell proliferation, and apoptosis in a group of SCs users by measuring the plasma levels of 4-hydroxy-2-nonenal (4-HNE), malondialdehyde (MDA), and glutathione peroxidase (GPX), as well as the expression of phosphoinositol-3-kinase (PI3K)/AKT and Caspase-9. Also, to find any association between the duration and frequency of SCs usage and the measured parameters. This study comprised 30 SCs users (aged 18–38 years) from Kasr Alainy Psychiatry and Addiction outpatient clinics, Cairo University, and 30 age-matched healthy males as a control group.

The mean values of 4-HNE, MDA, and Caspase-9 were significantly higher (P˂0.001) in the SCs users’ group than in the control group, while the mean value of GPX was significantly lower (P˂0.001). The mean relative expression values of PI3K and AKT were significantly lower (P˂0.001) in the SCs users’ group than in the control group. Significant correlations were detected between the duration and frequency of SCs use and oxidative stress, cell proliferation, and apoptosis biomarkers.

SCs can cause an increase in oxidative stress and a decrease in the expression of the proliferative pathways, consequently promoting apoptosis.