Delta 9-tetrahydrocannabinol (Delta 9-THC) is the major psychoactive component of marihuana. This drug has been shown to inhibit cellular macromolecular synthesis and to have suppressive effects on the host immune system. It has been shown, also, to decrease host resistance to Herpes simplex virus types 2 (HSV2) in the mouse. The increased use of marihuana among individuals who may be at risk of developing herpes genitalis, presents the hazard of decreased host resistance to this venereal disease. The goal of this research is to define the process by which Delta 9-THC induces decreased resistance of HSV2 genital infection in the guinea pig. The guinea pig has been selected as the animal of choice for these studies since HSV2 induces a spectrum of clinical disease similar to that seen in humans. It is proposed to determine the dose response curve for Delta 9-THC for decreased resistance to HSV2 using expression of lesions, virus shedding, and mortality as the response. The interval of susceptibility for decreased resistance will be established. Using a Delta 9-THC dose which produces a 50-80% increase in susceptibility to HSV2 genital infection, guinea pig serum will be tested for deficiency in ability to abrogate HSV2 infection in terms of interferon induction, virus-specific IgM and IgG responses, and complement levels. Host immunocompetent cells, such as peripheral blood lymphocytes, spleen cells, and peritoneal exudate cells will be tested for deficiency in B-cell, T-cell, and macrophage response to HSV2. Cells which function in nonspecific host resistance will also be examined. The direct effect of Delta 9-THC on virus protein synthesis, DNA synthesis, and replication will be assessed. In addition, a guinea pig model of HSV2 latent infection will be developed to allow for studies on the effect of Delta 9-THC on recurrent infection.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA003647-02
Application #
3208207
Study Section
(DABA)
Project Start
1984-09-01
Project End
1987-08-31
Budget Start
1985-09-01
Budget End
1986-08-31
Support Year
2
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Virginia Commonwealth University
Department
Type
Overall Medical
DUNS #
City
Richmond
State
VA
Country
United States
Zip Code
23298
Cabral, G A; Vasquez, R (1992) delta 9-Tetrahydrocannabinol suppresses macrophage extrinsic antiherpesvirus activity. Proc Soc Exp Biol Med 199:255-63
Fischer-Stenger, K; Updegrove, A W; Cabral, G A (1992) Delta 9-tetrahydrocannabinol decreases cytotoxic T lymphocyte activity to herpes simplex virus type 1-infected cells. Proc Soc Exp Biol Med 200:422-30
Cabral, G A; Vasquez, R (1991) Effects of marijuana on macrophage function. Adv Exp Med Biol 288:93-105
Cabral, G A; Stinnett, A L; Bailey, J et al. (1991) Chronic marijuana smoke alters alveolar macrophage morphology and protein expression. Pharmacol Biochem Behav 40:643-9
Cabral, G A; Mishkin, E M (1989) Delta-9-tetrahydrocannabinol inhibits macrophage protein expression in response to bacterial immunomodulators. J Toxicol Environ Health 26:175-82
Cabral, G A; McNerney, P J; Mishkin, E M (1987) Effect of micromolar concentrations of delta-9-tetrahydrocannabinol on herpes simplex virus type 2 replication in vitro. J Toxicol Environ Health 21:277-93
Cabral, G A; McNerney, P J; Mishkin, E M (1987) Delta-9-tetrahydrocannabinol inhibits the splenocyte proliferative response to herpes simplex virus type 2. Immunopharmacol Immunotoxicol 9:361-70
Cabral, G A; McNerney, P J; Mishkin, E M (1987) Interaction of delta-9-tetrahydrocannabinol with rat B103 neuroblastoma cells. Arch Toxicol 60:438-49
Mishkin, E M; Cabral, G A (1987) Inhibition of cell-associated herpes simplex virus type 2 glycoproteins by delta 9-tetrahydrocannabinol. Proc Soc Exp Biol Med 185:41-8
Cabral, G A; Lockmuller, J C; Mishkin, E M (1986) Delta 9-tetrahydrocannabinol decreases alpha/beta interferon response to herpes simplex virus type 2 in the B6C3F1 mouse. Proc Soc Exp Biol Med 181:305-11

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