Marijuana and the Cannabinoids

Effects of Marijuana on Immune Defenses 259
Fig. 2. Habitual marijuana smoking is associated with abnormal expression of epidermal
growth factor receptor (EGFR), a growth factor receptor that promotes autonomous
cell growth. Airway mucosal biopsies were obtained from a cohort of nonsmokers and
smokers of marijuana alone, tobacco alone, or both marijuana and tobacco, and
evaluated for EGFR expression by immunohistology. Compared to the limited basal
staining present in normal epithelium (left panel), biopsies demonstrated diffuse and
dark staining of epithelial cells in 58% of marijuana smokers (right panel) and in 89%
of those who smoked both marijuana and tobacco (not shown).
Table 2
Effects of Marijuana on Human Alveolar Macrophages
• Increased number of alveolar macrophages recovered by bronchoalveolar lavage from
habitual marijuana smokers compared to nonsmokers (37,38)
• Increased size of intracytoplasmic inclusions (39)
• Impaired ability to kill Candida albicans (40) and Candida pseudotropicalis (41)
• Impaired phagocytosis and killing of Staphylococcus aureus (41,42)
• Decreased respiratory burst activity (superoxide anion production) under both basal and
stimulated conditions (40)
• Limited tumoricidal activity against tumor cell targets in vitro (41)
• Reduced production of proinflammatory cytokines (tumor necrosis factor-α, interleukin-6,
and granulocyte macrophage–colony-stimulating factor [GM-CSF]) when stimulated by
bacterial lipopolysaccharide (41)
• Inability to express inducible nitric acid synthase or produce nitric oxide upon exposure to
pathogenic bacteria, largely reversed by stimulation with proinflammatory cytokines such
as GM-CSF and interferon-γ (42)
recovered from MS revealed large irregular-shaped cytoplasmic inclusions that most
likely contain particulates from marijuana tar, possibly including metabolites of THC
and other cannabinoids (39). AM from TS also show abnormal cytosolic inclusion
bodies, and the number of these inclusions is dramatically increased in smokers of
both marijuana and tobacco (39). It seems plausible that the presence of a large number
of abnormal inclusion bodies within the cytoplasm of AM from smokers of marijuana
and/or tobacco might interfere with the function of these important immune
effector cells.