THC-methadone and THC-naltrexone interactions on discrimination, antinociception, and locomotion in rats.
Alexa A Wakley, Rebecca M Craft
Behavioural Pharmacology September 2011 DOI: 10.1097/fbp.0b013e328348ed22 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational study Peer reviewed |
|---|---|
| Population | Male Sprague-Dawley rats |
| Interventions | THC Methadone Naltrexone |
| Dose | THC 3 mg/kg (training dose); THC 0.32-10 mg/kg; methadone 0.32-5.6 mg/kg; naltrexone 0.32-3.2 mg/kg; methadone 1.0 mg/kg in combination |
| Topics | Cannabis |
| Key findings | Methadone (1.0 mg/kg) flattened the THC discrimination curve without affecting THC's antinociceptive or motoric effects, while naltrexone did not alter any THC effects. In rats not trained to discriminate THC, methadone enhanced THC antinociception. The authors suggest mu-opioid agonists can disrupt cannabinoid discriminative stimulus effects in chronically drug-exposed subjects. |
Abstract
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.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cited by 3
- Repeated Tetrahydrocannabinol Injections Induce Tolerance but Do Not Disrupt Ongoing Behaviour Upon Withdrawal in Male and Female Rats With Inflammatory Pain. European Journal of Pain May 1, 2026
- Tolerance to hypothermic and antinoceptive effects of ∆9-tetrahydrocannabinol (THC) vapor inhalation in rats. Pharmacology, Biochemistry, and Behavior September 2018
- Naltrexone does not attenuate the effects of intravenous Δ9-tetrahydrocannabinol in healthy humans. The International Journal of Neuropsychopharmacology October 2012