Effects on the Immune System 403marijuana was associated with risks of both fungal exposure and infection, as well
as the possible induction of a variety of immunologic lung disorders. Kusher et al.
(1994) demonstrated that THC suppressed the functional activities of human large
granular lymphocytes (LGL). Exposure of LGL to THC at physiologically relevant
concentrations resulted in down-regulation of TNF-αproduction and diminished
LGL cytolytic activity against K562 tumor cells. The investigators suggested that,
since the natural killer /polymorphonuclear neutrophil axis represents an impor-
tant early defense against the opportunistic fungusCandida albicans, repression
of this system could contribute to susceptibility to opportunistic infections.
In addition to effects on infectious agents, habitual marijuana use may elicit
histopathological alterations and anti-inflammatory processes in the lung and
respiratory tract. Guarisco et al. (1988) reported on the development of isolated
uvulitis secondary to heavy marijuana use in three individuals. Barsky et al. (1998)
examined bronchoscopy specimens from groups of smokers and nonsmokers and
assessed them for incidence of molecular markers that antedate the development of
lung cancer. It was found that smokers of marijuana, cocaine, or tobacco exhibited
more molecular and histopathological alterations than did nonsmokers. The in-
vestigators concluded that marijuana and cocaine smoking, comparable to tobacco
smoking, placed subjects at increased risk of developing lung cancer. Baldwin et al.
(1997) indicated that marijuana and cocaine impaired lung alveolar macrophage
function and cytokine production. Alveolar macrophages were deficient in their
ability to phagocytoseStaphylococcus aureusand severely limited in their ability
to kill both bacteria and tumor cells. Alveolar macrophages of marijuana smokers
were not able to use NO as an antibacterial effector molecule and produced less
than normal amounts of TNF-α, GM-CSF, and IL-6 when stimulated in culture with
LPS. Tashkin et al.(2002) extended these studies and indicated that regular use
of marijuana was associated with ultrastructural abnormalities in human alveolar
macrophages along with impairment of their cytokine production, antimicrobial
activity, and tumoricidal function.
4.2
Effects Related to Infection with Human Immunodeficiency Virus and AIDS
There have been a limited number of studies which have addressed the issue of
effects of marijuana or cannabinoids on HIV infection and the acquired immunod-
eficiency syndrome (AIDS). No conclusive data have been obtained as to potential
risks and/or hazards associated with HIV infection and the use of marijuana or
administration of cannabinoids in a therapeutic mode. Kaslow et al. (1989), in a re-
port from the Multicenter AIDS Cohort Study, indicated that there was no evidence
for a role of alcohol or other psychoactive drugs such as marijuana in accelerat-
ing immunodeficiency in HIV-1-positive individuals. Coates et al. (1990) analyzed
cofactors of disease progression in a cohort of 249 male sexual contacts of men
with AIDS or an AIDS-related condition. No significant association with risk of
progression to AIDS was noted for use of various recreational drugs, history of spe-
cific infections, age at enrollment, or smoking and drinking status at enrollment.