Respiratory and immunologic consequences of marijuana smoking

Habitual smoking of marijuana has a number of effects on the respiratory and immune systems that may be clinically relevant. These include alterations in lung function ranging from no to mild airflow obstruction without evidence of diffusion impairment, an increased prevalence of acute and chronic bronchitis, striking endoscopic findings of airway injury (erythema, edema, and increased secretions) that correlate with histopathological alterations in bronchial biopsies, and dysregulated growth of the bronchial epithelium associated with altered expression of nuclear and cytoplasmic proteins involved in the pathogenesis of bronchogenic carcinoma. Other consequences of regular marijuana use include ultrastructual abnormalities in human alveolar macrophages along with impairment of their cytokine production, antimicrobial activity, and tumoricidal function. Cannabinoid receptor expression is altered in leukocytes collected from the blood of chronic smokers, and experimental models support a role for Delta(9)-tetrahydrocannabinol in suppressing T cell function and cell-mediated immunity. The potential for marijuana smoking to predispose to the development of respiratory malignancy is suggested by several lines of evidence, including the presence of potent carcinogens in marijuana smoke and their resulting deposition in the lung, the occurrence of premalignant changes in bronchial biopsies obtained from smokers of marijuana in the absence of tobacco, impairment of antitumor immune defenses by Delta(9)-tetrahydrocannabinol, and several clinical case series in which marijuana smokers were disproportionately overrepresented among young individuals who developed upper or lower respiratory tract cancer. Additional well-designed epidemiological and immune monitoring studies are required to determine the potential causal relationship between marijuana use and the development of respiratory infection and/or cancer. Journal of Clinical Pharmacology, 2002.