Cross-tolerance development to the prolongation of pentobarbitone-induced sleep by delta 8-tetrahydrocannabinol and 11-hydroxy-delta 8-tetrahydrocannabinol in mice.

Abstract

Repeated administration (5 mg kg-1 day-1 i.v.) of delta 8-tetrahydrocannabinol and its active metabolite, 11-hydroxy-delta 8-tetrahydrocannabinol caused tolerance to develop to their prolonging effect on pentobarbitone-induced sleep in mice. Reciprocal cross-tolerance also developed after seven daily doses of these cannabinoids. The magnitude of the tolerance developed by the metabolite was greater than that by delta 8-tetrahydrocannabinol. The results suggest that 11-hydroxy-delta 8-tetrahydrocannabinol plays an important role both in the sleep-prolonging effect of delta 8-tetrahydrocannabinol and its tolerance development.