Oxidative stress produced by Marijuana smoke - An adverse effect enhanced by cannabinoids

Marijuana (MJ) smoking produces inflammation, edema, and cell injury in the tracheobronchial mucosa of smokers and may be a risk factor for lung cance r. Because oxidative stress may mediate some of these effects, this study w as designed to test the hypothesis that cannabinoids in MJ smoke contribute to cellular oxidative stress. Oxidative stress was evaluated in an endothe lial cell line (ECV 304) following exposure to smoke produced from MJ cigar ettes containing either 0, 1.77, or 3.95% Delta(9)-tetrahydrocannabinol (De lta(9)-THC). Brief exposure to smoke from 3.95% MJ cigarettes stimulated th e formation of reactive oxygen species (ROS) by 80% over control levels and lowered intracellular glutathione levels by 81%. Smoke-induced ROS generat ion increased in a dose- and time-dependent manner. In contrast, exposure t o smoke from MJ containing 0% Delta(9)-THC produced no increase in ROS desp ite a 70% decline in glutathione levels. Smoke from MJ containing 1.77% Del ta(9)-THC stimulated intermediate levels of ROS. A brief, 30-min exposure t o MJ smoke, regardless of the Delta(9)-THC content, also induced necrotic c ell death that increased steadily up to 48 h of observation. MJ smoke passe d through a Cambridge filter that removed particulate matter was 3.4-fold m ore active in ROS production compared with unfiltered smoke, suggesting tha t most of the oxidative effects are produced by the gaseous phase. Alveolar macrophages obtained from habitual MJ smelters displayed low levels of glu tathione compared with macrophages from nonsmokers. We conclude that MJ smo ke containing Delta(9)-THC is a potent source of cellular oxidative stress that could contribute significantly to cell injury and dysfunction in the l ungs of smokers.