Structural requirements for cannabinoid-induced antinociceptive activity in mice.

The antinociceptive activity of delta 9-THC was found to be 45 times greater after i.v. (ED50 = 1.0 mg/kg) than after s.c. administration while its ability to depress spontaneous activity was increased only 8 fold. Route of administration had less of an impact on the antinociceptive potency of hydroxylated metabolites and analogs of delta 9-THC. The structural requirements for antinociception and depression of spontaneous activity were found to be similar. Both routes of administration and structural alterations dramatically changed the antinociceptive potency of delta 9-THC.