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

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Am J Physiol Lung Cell Mol Physiol. 2006 Jun;290(6):L1202-9. Epub 2006 Jan

13.

Inhaled marijuana smoke disrupts mitochondrial energetics in pulmonary

epithelial cells in vivo.

Division of Pulmonary and Critical Care, Department of Medicine,

Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1690, USA.

tsarafian@...

Habitual marijuana smoking is associated with inflammation and atypia of

airway epithelium accompanied by symptoms of chronic bronchitis. We

hypothesized that Delta(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.

PMID: 16414979

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