390 G.A. Cabral and A. Staab
effects of drugs on infection and immunity due to their well-defined immune sys-
tems.Furthermore,useofanimalmodelshasallowedforthedefinitionoffactorsof
host resistance that are targeted by drugs under stringently controlled conditions.
As a result, acquisition of statistically significant data with minimal confound-
ing variables has been possible, a condition that is difficult to attain for human
populations as a result of potential environmental toxic exposures and multiple
drug use. The collective data that have been obtained through studies involving
experimental animals indicate that cannabinoids alter humoral and cellular im-
munity and can compromise resistance to a variety of infectious agents including
bacteria, protozoa, and viruses. Rosenkrantz et al. (1975) indicated that THC sup-
pressed the primary immune response in rats. Klykken et al. (1977) extended
these studies and demonstrated that 8,9-epoxyhexahydrocannabinol (EHHC) in-
hibited both humoral and cell-mediated immunity in BDG1 mice administered
Corynebacterium parvum (C.parvum). Zimmerman et al. (1977) compared the
effectsofTHC,CBD,andCBNontheimmuneresponseofimmaturemice.THC
elicited a dose-dependent depression of immune responsiveness. However, the im-
pairment of humoral immunity was specific to THC in that CBD or CBN did not
have an effect. These results served as an indicator that the effects of cannabinoids
on immune function were selective in that a psychotropic cannabinoid exerted an
immunomodulatory effect, while a non-psychotropic cannabinoid at comparable
doses did not. Baczynsky et al. (1983a) examined the effects of THC, CBD, and
CBN on the primary humoral immune response, the secondary humoral immune
response, and the memory aspect of humoral immunity following sheep red blood
cell immunization. Mice treated with THC during the primary immunization pe-
riod exhibited a suppression of the primary humoral immune response while those
treated during the secondary immunization period showed no measurable sup-
pression of the secondary humoral immune response. However, CBD and CBN had
no effect.
Studies using animal models have suggested also that cannabinoid immunolog-
ical tolerance differs from pharmacological tolerance. Luthra et al. (1980) adminis-
teredTHCorallytoFischerratsofbothsexesatdosesthatproducedpharmacologi-
cal tolerance. In order to assess for immunological tolerance, the primary immune
response was evaluated by determining splenic antibody-forming cells, hemag-
glutinin titers, and/or hemolysin titers. Modalities of action that were operative
in the establishment of pharmacological tolerance appeared to differ from those
associated with tolerance at the immunological level. The effects of cannabinoids
on immune function appear also to differ with age. Pross et al. (1990) examined
the suppression of murine lymphoid cell blastogenesis by marijuana components
in adult versus juvenile mice of various ages. Differences in susceptibility to THC-
and 11-OH-THC-induced suppression were observed for in vitro proliferative re-
sponses of murine lymphoid cells to the mitogens concanavalin A (ConA) and
PHA. Thymus cells from adults were suppressed more readily than splenocytes,
while splenocytes from mice under 2 weeks of age were suppressed much more
readily than those from older mice. Snella et al. (1995) evaluated the relationship
of aging and THC-mediated immunomodulation of murine lymphoid cells. Cells
from 2- and 18-month-old mice, in contrast to those from adult mice, were resis-