Increasing the selectivity of the discriminative stimulus effects of Δ 9-tetrahydrocannabinol: complete substitution with methanandamide

In an attempt to increase the selectivity of the discriminative stimulus effects of Δ 9-tetrahydrocannabinol (THC), rats were trained to discriminate 3.2 mg/kg of this compound from a group of “other” drugs consisting of morphine (3.2 mg/kg), PCP (2.5 mg/kg), and vehicle. Acquisition of the Δ 9-THC-other discrimination was rapid (38 days) and did not differ significantly from that of a group of “control” animals trained to discriminate Δ 9-THC (3.2 mg/kg) from its vehicle (33 days). In substitution (generalization) tests, a high dose of anandamide, which also severely decreased response rate, substituted partially in both the control and the Δ 9-THC-other group; ( R)-methanandamide, an analog of anandamide which is metabolized more slowly, substituted completely for Δ 9-THC in the control, and partially in the Δ 9-THC-other group; neither pentobarbital nor diazepam substituted completely for Δ 9-THC under any experimental condition. Regardless of the level of Δ 9-THC lever responding, all drugs except diazepam substituted less in the Δ 9-THC-other than in the control group. For this reason, the Δ 9-THC-other training procedure might be described as being more selective than the commonly used drug–no drug procedure.