Marihuana is the most common street drug of abuse in the United States. Delta- 9-tetrahydrocannabinol (Delta-9-THC) is the major psychoactive component of marihuana and accounts for the majority of its immunosuppressive properties. The widespread use of marihuana has occurred at a time of the pandemic spread of sexually-transmitted viruses in the human population. The goal of this research is to define the effect of Delta-9-THC on T- lymphocyte functional competence to heroes simplex virus type 2 (HSV2). The B6C3F1 mouse will be employed for in vivo studies and as a source of splenocytes and T-lymphocytes. During the first phase of the study, the T-lymphocyte functional subset targeted by Delta-9-THC will be defined. A 3H-thymidine proliferative assay and a plaquing assay employing HSV2 antigen will be used to assess the effect of in vivo Delta-9-THC exposure on T-helper and T-suppressor cell activity. Reconstitution studies, using anti-L3T4 or anti-Lyt2 antibodies for selection for T-helper or T-suppressor cells, also, will be performed. Cytotoxic T-cell activity will be assessed by 51Cr-release from HSV2-infected mouse embryo fibroblast targets. In the second phase, the effect of the drug on early events of T-lymphocyte activation, as mediated by the inositol phosphate system, will be defined. In the third phase, the effect of the drug on T-lymphocyte: target cell adhesion will be determined using a LFA-1-dependent lymphocyte homotypic cluster assay, Nomarski microscopy, and scanning electron microscopy. In addition, immunochemical staining and transmission electron microscopy will be used to examine the effect of the drug on the lymphocyte cytoskeleton. The effect of the cannabinoid on macromolecular synthesis will be determined. A proliferative assay using IL-2-dependent CTLL-A2 cells will be used to assess interleukin 2 (IL-2) secretion. Monoclonal antibody to the IL-2 receptor will be used for immunofluorescence and flow cytofluorometry to define its cell-surface expression. The effect of Delta-9-THC on IFN-gamma will be assessed using a vesicular stomatitis virus plaque assay.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA003647-05
Application #
3208209
Study Section
Sociobehavioral Subcommittee (DAAR)
Project Start
1984-09-01
Project End
1991-11-30
Budget Start
1990-01-01
Budget End
1990-11-30
Support Year
5
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Virginia Commonwealth University
Department
Type
Schools of Medicine
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) 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; 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; 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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