Effects of chronic delta 9-tetrahydrocannabinol administration on schedule-controlled behavior of pigeons: cross-tolerance to pentobarbital and barbital.

Pigeons responding under a variable-interval (VI) 75-s schedule of food presentation were used to study cross-tolerance from delta 9-tetrahydrocannabinol (delta 9-THC) to pentobarbital and barbital. After initial dose-effect functions for pentobarbital and barbital were determined, the birds received delta 9-THC injections for 6 weeks. This chronic administration regimen resulted in a greater than 100-fold tolerance to delta 9-THC. Redetermination of the pentobarbital and barbital dose-effect functions during the chronic delta 9-THC regimen revealed statistically significant shifts to the right for the pentobarbital (0.191 log unit) and barbital (0.078 log unit) dose-effect curves. All six birds showed tolerance to pentobarbital, while four of the six showed tolerance to barbital. Blood barbital levels before and after chronic delta 9-THC was more prolonged and of much greater magnitude than the cross-tolerance to pentobarbital or barbital. The results demonstrate that cross-tolerance can develop from delta 9-THC to a barbiturate that normally undergoes little metabolism.