Hyporesponsiveness to the Immunosuppressant Effects of Delta-8-Tetrahydrocannabinol

Abstract

Delta-9-tetrahydrocannabinol (Δ⁹-THC) and Δ⁸-THC have previously been shown to suppress humoral immunity in mice. The purpose of these investigations was to determine whether a hyporesponsiveness develops to the immunosuppressive effect of Δ⁸-THC. BALB/c mice were administered 60 mg/kg Δ⁸-THC i.p. 2 days after an i.p. immunizing dose of sheep erythrocytes (sRBC). Significant inhibition of direct hemolytic plaqueforming cells (PFC)/spleen was observed on days 3–6, with peak day of inhibition occurring on day 4. The effective inhibiting dose 50 (ED₅₀) measured on peak day of response was 40 mg/kg for PFC/10⁶ spleen cells and 38 mg/kg for PFC/spleen. When mice were pretreated daily for 5 days with different doses of Δ⁸-THC, similar ED₅₀'s were detected. Under this pretreatment regimen, 5 or 10 mg/kg produced no immunosuppression. Daily treatment with 5 or 10 mg/kg Δ⁸-THC for 5 days prior to sRBC and varying doses of Δ⁸-THC administered 2 days after sRBC resulted in significantly higher ED₅₀'s and increased values for the slopes of the dose response curves. These results suggest that a hyporesponsiveness develops to the immunosuppressive activity of Δ⁸-THC.