414 G.A. Cabral and A. Staab
8
Summary and Conclusions
Marijuana and other exogenous cannabinoids, primarily those which possess psy-
chotropic activity, alter immune functionality and decrease host resistance to bac-
terial, protozoan, and viral infections in experimental animal models and in vitro
systems. The main substance in marijuana that exerts these immuno depressive
effects is∆^9 -tetrahydrocannabinol (THC). This cannabinoid alters the function
of an array of immune cells including lymphocytes, natural killer (NK) cells, and
macrophages, thereby affecting their capacity to exert anti-microbial activities.
Two modes of action by which THC and other cannabinoids affect immune re-
sponsiveness have been proposed. First, these compounds may signal transduce
through cannabinoid receptors CB 1 and CB 2. Second, at sites of direct exposure
to marijuana or high concentrations of cannabinoids, such as the lung, mem-
brane perturbation may be involved. In addition, endogenous cannabinoids or
endocannabinoids have been identified and have been proposed as native modula-
tors of immune functions through cannabinoid receptors. Exogenously introduced
cannabinoids may disturb this homoeostatic immune balance. A mode by which
cannabinoids may alter immune responsiveness is by driving the expression of
cytokines from a Th 1 pro-inflammatory pattern to that of a Th 2 anti-inflammatory
pattern. While marijuana and various cannabinoids have been documented to alter
immune functions in vitro and in experimental animals, no controlled longitu-
dinal epidemiological studies have yet definitively correlated immunosuppressive
effects with increased incidence of infections or immune disorders in different
segments of the human population. However, cannabinoids by virtue of their im-
munomodulatory properties have the potential to serve as therapeutic agents for
ablation of untoward immune responses.
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