STEREOSPECIFICITY OF THE DISCRIMINATIVE STIMULUS FUNCTIONS OF THE DIMETHYLHEPTYL HOMOLOGS OF 11-HYDROXY-DELTA-8-TETRAHYDROCANNABINOL IN RATS AND PIGEONS

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  • 1 September 1989
    • journal article
    • research article
    • Vol. 250  (3) , 1000-1005
Abstract
Rats and pigeons were trained to discriminate between the presence and absence of the effects of (-)-.DELTA.9-tetrahydrocannibol (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-TCH in rats and pigeons, respectively). The enantiomer, (+)-11-OH-.DELTA.8-TCH-DMH, was inactive as at TCH-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.