This study examined
cannabinoid-
opioid interactions within the same subjects on measures of discrimination, antinociception, horizontal locomotion, and
catalepsy. Male Sprague-Dawley rats were trained to discriminate Δ(9)-tetrahydrocannabinol (
THC, 3 mg/kg) from vehicle.
THC alone (0.32-10 mg/kg) dose-dependently increased
THC-appropriate lever responding and decreased response rate.
THC alone also produced paw pressure antinociception and decreased locomotor activity, but did not produce
catalepsy.
Methadone (0.32-5.6 mg/kg) and
naltrexone (0.32-3.2 mg/kg) alone produced low
THC-appropriate lever responding up to doses that decreased response rate. When combined with
THC,
methadone (1.0 mg/kg) flattened the
THC discrimination curve, but did not affect antinociceptive or motoric effects of
THC.
Naltrexone did not alter any effects of
THC. In rats that were not trained to discriminate
THC from vehicle, 1.0 mg/kg
methadone did enhance
THC antinociception. These results suggest that μ-
opioid receptor agonists can disrupt the discriminative stimulus effects of
cannabinoids while not significantly altering their antinociceptive or motoric effects, in chronically
drug-exposed subjects. Further research is required to determine whether
opioid enhancement of
cannabinoid antinociception is limited to acute exposure, or simply requires higher doses in chronically
drug-exposed subjects.