Cannabinoids

Effects on the Immune System 405

among men referred for possible AIDS in their analysis of responses to a lifestyle
questionnaire among 13 patients with Kaposi’s sarcoma and 18 with an op-
portunistic infection as compared with those of 29 symptom-free referred in-
dividuals. In addition, immuno-epidemiological studies using univariant and
multivariant analyses have indicated an association between marijuana use and
progression of HIV seropositivity to development of symptomatic AIDS (Tin-
dall et al. 1988). Whitfield et al. (1997) examined the impact of ethanol and
Marinol/marijuana on HIV+/AIDS patients undergoing azidothymidine (AZT),
azidothymidine/dideoxycytidine (AZT/DDC), or dideoxyinosine (DDI) therapy.
Marinol/marijuana was reported to be associated with declining health status in
boththeAZTandAZT/DDCgroups.However,inHIV+/AIDSpatientswiththelow-
est CD4+counts undergoing DDI monotherapy, utilization of Marinol/marijuana
did not seem to have a deleterious impact. Caiaffa et al. (1994) indicated that
smoking illicit drugs such as marijuana was one of several factors that increased
risk of bacterial pneumonia in HIV-seropositive drug users.

5

Distribution of Cannabinoid Receptors in the Immune System

5.1

Native Distribution

Two cannabinoid receptor types have been identified in various cells and tissues
of the immune system (Table 1). The first of these, the CB 1 receptor, was cloned
originally from a cDNA rat library by Matsuda et al. (1990). Munro et al. (1993)
reported on the cloning of the second receptor for cannabinoids, designated the
CB 2 receptor, which was not expressed in the brain but rather in the immune
system. Recent studies suggest the existence of a third cannabinoid receptor, ten-
tatively designated as non-CB 1 , non-CB 2 (Breivogel et al. 2001; Fride et al. 2003;
Wiley and Martin 2002). Cannabinoid receptor CB 1 mRNA is found primarily in
brain and neural tissue but can be found also at lower levels in peripheral tissues
including the adrenal gland, bone marrow, heart, lung, prostate, testis, thymus,
tonsils, and spleen (Bouaboula et al. 1993; Galiègue et al. 1995; Kaminski et al.
1992; Noe et al. 2000). Messenger RNA for the CB 1 receptor has been identified
also in microglia from the brain (Sinha et al. 1998; Waksman et al. 1999). Tran-
scripts (i.e., mRNAs) for the CB 2 receptor are abundant in spleen and tonsils
and are found at levels equivalent to those for CB 1 mRNA in the CNS (Galiègue
et al. 1995; Munro et al. 1993). However, in other tissues of the immune system
mRNA levels for the CB 2 receptor, while exceeding those for the CB 1 receptor
(Bouaboula et al. 1993; Galiègue et al. 1995), are relatively low. The distribution
pattern of CB 2 mRNA displays major variation in human blood cell populations
with a rank order of B lymphocytes>NK cells>>monocytes>polymorphonuclear
neutrophils>T8 lymphocytes>T4 lymphocytes (Bouaboula et al. 1993; Galiègue
et al. 1995). Lee et al. (2001b) reported a comparable pattern of distribution for
murine immune cells.