Inhaled marijuana smoke disrupts mitochondrial energetics in pulmonary epithelial cells in vivo

1 Division of Pulmonary and Critical Care and 2 Center for Human Nutrition, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles; and 3 Department of Community and Environmental Medicine, University of California, Irvine, California Submitted 24 August 2005 ; accepted in final form 6 January 2006 Habitual marijuana smoking is associated with inflammation and atypia of airway epithelium accompanied by symptoms of chronic bronchitis. We hypothesized that 9 -tetrahydrocannabinol (THC), the primary psychoactive component of marijuana, might contribute to these findings by impairing cellular energetics and mitochondrial function. To test this hypothesis, we examined particulate smoke extracts from marijuana cigarettes, tobacco cigarettes, and placebo marijuana (0% THC) cigarettes for their effects on the mitochondrial function of A549 cells in vitro. Only extracts prepared from marijuana cigarettes altered mitochondrial staining by the potentiometric probe JC-1. With the use of a cross-flow, nose-only inhalation system, rats were then exposed for 20 min to whole marijuana smoke and examined for its effects on airway epithelial cells. Inhalation of marijuana smoke produced lung tissue concentrations of THC that were 8–10 times higher than those measured in blood (75 ± 38 ng/g wet wt tissue vs. 9.2 ± 2.0 ng/ml), suggesting high local exposure. Intratracheal infusion of JC-1 immediately following marijuana smoke exposure revealed a diffuse decrease in lung cell JC-1 red fluorescence compared with tissue from unexposed or placebo smoke-exposed rats. Exposure to marijuana smoke in vivo also decreased JC-1 red fluorescence (54% decrease, P < 0.01) and ATP levels (75% decrease, P < 0.01) in single-cell preparations of tracheal epithelial cells. These results suggest that inhalation of marijuana smoke has deleterious effects on airway epithelial cell energetics that may contribute to the adverse pulmonary consequences of marijuana smoking. 9 -tetrahydrocannabinol; JC-1; A549; adenosine 5'-triphosphate Address for reprint requests and other correspondence: T. Sarafian, 37-131 Center for Health Sciences, Division of Pulmonary and Critical Care, Dept. of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1690 (e-mail: tsarafian{at}mednet.ucla.edu )