Cross‐tolerance development to the prolongation of pentobarbitone‐induced sleep by Δ⁸‐tetrahydrocannabinol and 11‐hydroxy‐Δ⁸‐tetrahydrocannabinol in mice

Repeated administration (5 mg kg⁻¹ day⁻¹ i.v.) of Δ⁸‐tetrahydrocannabinol and its active metabolite, 11‐hydroxy‐Δ⁸‐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 Δ⁸‐tetrahydrocannabinol. The results suggest that 11‐hydroxy‐Δ⁸‐tetrahydrocannabinol plays an important role both in the sleep‐prolonging effect of Δ⁸‐tetrahydrocannabinol and its tolerance development. 1987 Royal Pharmaceutical Society of Great Britain