Cross-tolerance development to the prolongation of pentobarbitone-induced sleep by delta 8-tetrahydrocannabinol and 11-hydroxy-delta 8-tetrahydrocannabinol in mice.
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.
D000818:Animals; D013759:Dronabinol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004361:Drug Tolerance; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010424:Pentobarbital / Q000494:pharmacology*; D012890:Sleep / Q000187:drug effects*
C020367:11-hydroxy-delta(8)-tetrahydrocannabinol; D013759:Dronabinol; D010424:Pentobarbital