ABSTRACT

The role of marijuana, Cannabis sativa, in health and infectious disease has been examined for many years. In vivo and in vitro studies have demonstrated that THC is immunosuppressive and impairs cell-mediated immunity, humoral immunity, and cellular defenses against a variety of infectious agents (see the work of Cabral and Pettit? and Friedman and Klein14 for overviews). Two modes of action by which THC and other cannabinoids affect cell functions have been proposed. 13 THC may exert nonspecific effects by perturbing cellular membranes since it is a highly lipophilic molecule. This property of THC may account, in part, for its diverse array of immunosuppressive effects. Alternatively, THC may affect cell function by specific interaction with cannabinoid receptors (see Chapter 7). Two receptor subtypes, CB land CB2, have been identified in various cells and tissues of the immune system. The CBl' while preponderant in brain and neural tissue, is present at low levels in immune cells. Transcripts (i.e., mRNA) for the CB2 are abundant in spleen and tonsils and are found at levels equivalent to those for CB 1 mRNA in the central nervous system. l5,29 However, in other tissues of the immune system, mRNA levels for the CB2, while exceeding those for the CB l,3,29 are relatively low. The distribution pattern of CB2 mRNA displays major variation in human blood cell popUlations with a rank order of B lymphocytes> natural killer (NK) cells> monocytes > polymorphonuclear neutrophils > T8 lymphocytes> T4 lymphocytes.29 A rank order for levels of CB2 transcripts similar to that for primary human cell types has been recorded for human cell lines belonging to the myeloid, monocytic, and lymphoid lineages (see Table 25.1).29