Delta-9-tetrahydrocannabinol inhibits cell contact-dependent cytotoxicity of bacillus calmétte-guérin-activated macrophages

The effect of delta-9-tetrahydrocannabinol (delta-9-THC), the major psychoactive component of marijuana, on the capacity of Bacillus Calmétte-Guérin (BCG)-activated macrophages to lyse L929 tumor cells, Naegleria fowleri amoebae, and herpes simplex virus-infected cells was examined. Delta-9-THC inhibited tumoricidal and amoebicidal activity in a dose-related manner. Antiviral activity was decreased when mice received 25 and 50 mg/kg delta-9-THC. The cannabinoid did not directly suppress the activation of macrophages as determined by levels of 5′-nucleotidase activity and did not inhibit splenic T-lymphocytes of BCG-recipient mice from producing interferon gamma. Nomarski optics microscopy, scanning electron microscopy, and radiolabeling binding studies demonstrated that macrophages from delta-9-THC-treated mice retained their capacity to attach to their targets. These results suggest that delta-9-THC suppresses cell contact-dependent amoebicidal, tumoricidal, and antiviral activities of activated macrophages at a stage following effector cell — target cell conjugation.