Stereospecificity of the discriminative stimulus functions of the dimethylheptyl homologs of 11-hydroxy-delta 8-tetrahydrocannabinol in rats and pigeons.

Rats and pigeons were trained to discriminate between the presence and absence of the effects of (-)-delta 9-tetrahydrocannabinol (THC) at doses of 3 and 0.56 mg/kg, respectively; injections were i.p. and i.m., 0.5 and 1.5 hr before session onset for the two species, respectively. Tests with the 1,1 dimethylheptyl (DMH) homolog of (-)- delta 8-THC as well as its 11-hydroxylated (11-OH) derivative [(-)-11-OH-delta 8-THC-DMH], showed that both compounds were more potent than the training compound, especially so in the case of the 11-OH product (66 and 80 times more potent than delta 9-THC in rats and pigeons, respectively). The enantiomer, (+)-11-OH-delta 8-THC-DMH, was inactive as a THC-like psychotomimetic in doses even up to 10 mg/kg [ED50 of (-)-11-OH-delta 8-THC being 0.01 mg/kg and 0.002 mg/kg in rats and pigeons, respectively]. Hence, the typical THC-like effects in rats and pigeons (and by extrapolation possibly also the feeling of "high" in humans), reside exclusively in the levo [(-)]-enantiomers of THC-type cannabinoids (at least in the pair studied by us) as demonstrated clearly in this study. Both (-)-delta 8-THC-DMH and (-)-11-OH-delta 8-THC-DMH had a slow onset and a long duration of action.