Antisense oligodeoxynucleotides to the kappa-1 receptor block the antinociceptive effects of delta 9-THC in the spinal cord.

Intrathecal pretreatment of mice with an antisense oligodeoxynucleotide directed against the kappa-1 receptor significantly reduced the antinociceptive effects of the kappa receptor agonist U50,488 as well as delta 9-THC, the major psychoactive ingredient found in cannabis. A mismatched oligodeoxynucleotide which contained four switched bases did not block the antinociception produced by U50,488 or delta 9-THC. Furthermore, kappa-1 antisense did not alter the antinociceptive effects of either the mu receptor-selective opioid DAMGO, or the delta receptor-selective opioid DPDPE. By using kappa-1 antisense, we were able to demonstrate that an interaction occurs between the cannabinoids and opioids in the spinal cord.