Separation of the discriminative stimulus effects of stereoisomers of delta 2- and delta 3-tetrahydrocannabinols in pigeons.

Pigeons, trained to discriminate between the presence or absence of delta 1-tetrahydrocannabinol (THC) (I) (0.56 mg/kg), were tested with (1S,4R)-delta 2-THC (II) (1-17.5 mg/kg), with the C-1 epimers of (4R)-delta 2-THC acetate, namely (1S,4R)-delta 2-THC acetate (IIIA) (3-17.5 mg/kg) and (1R,4R)-delta 2-THC acetate (IIIB) (1-17.5 mg/kg) and with the enantiomers of delta 3-THC acetate, namely (1S)-delta 3-THC acetate (IVA) (1-10 mg/kg) and (1R)-delta 3-THC acetate (IVB) (3-30 mg/kg). The results indicated that (I) was considerably more potent than any of the other compounds evaluated (ED50 of compound I = 0.18 and 0.25 mg/kg at the two post-injection intervals examined, 90 and 270 min, respectively). Furthermore, of the two delta 2-THC acetates, compound (IIIB) was active whereas compound (IIIA) was not in comparable doses. The parent phenol of compound (IIIA), namely (II), was also inactive. Comparison of the pair of enantiomers, (IVA) and (IVB), showed the former to be significantly more potent than the latter. We have thus shown that the delta 1-THC-like cue properties are separated in the stereoisomers of delta 2- and delta 3-THC.