Effects of cannabinoids on host resistance to Listeria monocytogenes and herpes simplex virus

Abstract

Previous investigations from our laboratories have demonstrated that cannabinoids possess immunosuppressive properties. The present studies were designed to determine whether these agents decrease host resistance to infections with Listeria monocytogenes and herpes simplex virus type 2. Host resistance was measured by changes in the 50% lethal dose of the pathogen in cannabinoidtreated and control mice. The effect of cannabinoids on resistance to L. monocytogens was dose dependent. Delta-9-tetrahydrocannabinol at doses of 38, 75, and 150 mg/kg suppressed resistance to infection by 10-, 17-, and 657-fold, respectively. Marijuana extract was less active but significantly reduced resistance to L. moncytogenes at all tested doses. Resistance to systemic herpes simplex virus type 2 infection was decreased 96-fold by delta-9-tetrahydrocannabinol, although marijuana extract was inactive. The doses and regimen of treatment with cannabinoids that produced significant decreases in host resistance were similar to those which caused suppression of delayed-type hypersensitivity to sheep erythrocytes. The possible mechanisms and public health aspects of the decreased host resistance produced by marijuana extract and its cannabinoids are discussed.

Reduced endocannabinoid immune modulation by a common cannabinoid 2 (CB2) receptor gene polymorphism: possible risk for autoimmune disorders

“…These ECS components include several endogenously synthesized and degraded cannabinoid-like fatty acid amides and n-arachidonyl amino acids together with their receptors and primary inactivating enzyme FAAH. Earlier studies of exogenous cannabinoids such as ⌬ 9 -tetrahydrocannabinol and se- lected endogenous cannabinoids have demonstrated immune suppression with effects ranging from loss of resistance to infection [23,24] to inhibition of lymphocyte proliferation [20]. More recent studies of endocannabinoids in mammals have shown a complex range of immunomodulatory effects, primarily suppressive effects on leukocytes and immune functions [5], including modulation of Th cell development, chemotaxis, and cytokine secretion.…”

Addictive drugs and their relationship with infectious diseases

“…Although the molecular and cellular mechanisms for these effects are not completely defined, it is believed that both receptor and non-receptor mechanisms are involved. Two major cannabinoid receptors have been extensively studied (Mechoulam et al, 1969;Morahan et al, 1979;Mishkin & Cabral, 1985;Ashfaq et al, 1987;Matsuda et al, 1990;Specter et al, 1991;Munro et al, 1993;Paradise & Friedman, 1993;Klein et al, 1993Klein et al, , 2000Newton et al, 1994). The receptors CB1 and CB2 have been purified and shown to be G-protein-coupled 7-transmembrane molecules.…”

“…Various studies during the last decades have shown that cannabinoids have marked effects on resistance to infectious diseases, both intracellular opportunistic bacteria and a wide variety of viruses (Morahan et al, 1979;Mishkin & Cabral, 1985;Ashfaq et al, 1987;Specter et al, 1991;Paradise & Friedman, 1993;Klein et al, 1993Klein et al, , 2000Newton et al, 1994Newton et al, , 1998. For example, laboratory studies with rodents have shown that specific cannabinoids alter susceptibility to intracellular bacteria such as Listeria, Legionella, and even Treponema pallidum, the etiologic cause of syphilis, as well as to the herpes simplex virus, and, although still controversial, they may contribute to the more rapid progression of HIV-infected individuals to clinical AIDS and to increased susceptibility to opportunistic microbial infection (Table 3).…”

Direct suppression of autoreactive lymphocytes in the central nervous system via the CB2 receptor

“…Some of these immunological defects are likely due to disruptions in T-cell interactions with antigen-presenting cells (Berdyshev, 2000). In addition to these in vitro effects, it has been shown that administration of high-dose THC in mice resulted in decreased resistance to Listeria monocytogenes or Herpes simplex virus (Morahan et al, 1979). Although the list of possible immunological perturbations by the endocannabinoid system is extensive, regulation of any specific immune response that results in autoimmunity or protective immunity are not well studied or understood.…”