Interactions between Delta(9)-tetrahydrocannabinol and mu opioid receptor agonists in rhesus monkeys: discrimination and antinociception.
Jun-Xu Li, Lance R Mcmahon, Lisa R Gerak, Ginger L Becker, Charles P France
Psychopharmacology August 2008 DOI: 10.1007/s00213-008-1157-0 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational study Peer reviewed |
|---|---|
| Population | Rhesus monkeys |
| Interventions | Delta(9)-tetrahydrocannabinol (THC) heroin morphine naltrexone midazolam |
| Dose | 0.1 mg/kg THC i.v.; 1.78 mg/kg morphine s.c.; 5.6 mg/kg/12 h morphine; 0.0178 mg/kg naltrexone s.c.; 0.32 mg/kg midazolam s.c. |
| Topics | Cannabis |
| Key findings | THC attenuated the discriminative stimulus effects of morphine and heroin in nondependent monkeys but not in morphine-dependent monkeys, and the same THC doses enhanced morphine's antinociceptive effects. The authors suggest that attenuation of morphine by THC may result from perceptual masking rather than common pharmacodynamic or pharmacokinetic interactions. |
Abstract
Opioid receptor agonists can enhance some effects of cannabinoid receptor agonists, and cannabinoid receptor agonists can enhance some effects of opioid receptor agonists; however, the generality of these interactions is not established. This study examined interactions between the discriminative stimulus and antinociceptive effects of mu opioid receptor agonists and Delta(9)-tetrahydrocannabinol (THC) in rhesus monkeys. Neither heroin nor morphine (intravenous (i.v.) or subcutaneous (s.c.)) altered the discriminative stimulus effects of THC in monkeys (n = 5) discriminating 0.1 mg/kg THC i.v. In contrast, THC (s.c.) markedly attenuated the discriminative stimulus effect of morphine and heroin in nondependent monkeys (n = 4) discriminating 1.78 mg/kg morphine s.c. Doses of THC that attenuated the discriminative stimulus effects of morphine in nondependent monkeys failed to modify the discriminative stimulus effects of morphine in morphine-dependent (5.6 mg/kg/12 h) monkeys (n = 4) discriminating 0.0178 mg/kg naltrexone s.c. THC also failed to modify the discriminative stimulus effects of naltrexone in morphine-dependent monkeys or the effects of midazolam in monkeys (n = 4) discriminating 0.32 mg/kg midazolam s.c. Doses of THC (s.c.) that attenuated the discriminative stimulus effects of morphine in nondependent monkeys enhanced the antinociceptive effects of morphine (s.c.) in nondependent monkeys. While mu receptor agonists did not alter the discriminative stimulus effects of THC, THC altered the effects of mu receptor agonists in a context-dependent manner. That the same doses of THC enhance, attenuate, or do not affect morphine, depending on the condition, suggests that attenuation of morphine by THC can result from perceptual masking rather than common pharmacodynamic mechanisms or pharmacokinetic interactions.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cited by 6
- Differential effects of serotonin 5-HT1A receptor agonists on the discriminative stimulus effects of the 5-HT2A receptor agonist 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane in rats and rhesus monkeys. Journal of Pharmacology and Experimental Therapeutics April 1, 2010
- Discriminative Stimulus Effects of Hallucinogenic Drugs: a Possible Relation to Reinforcing and Aversive Effects Journal of Pharmacological Sciences June 12, 2019
- Δ9-tetrahydrocannabinol attenuates oxycodone self-administration under extended access conditions. Neuropharmacology June 1, 2019
- Naltrexone does not attenuate the effects of intravenous Δ9-tetrahydrocannabinol in healthy humans. The International Journal of Neuropsychopharmacology October 2012
- Opioid antagonism enhances marijuana's effects in heavy marijuana smokers. Psychopharmacology August 2010
and 1 more in the library
Cites 4
- Opioid antagonism of cannabinoid effects: differences between marijuana smokers and nonmarijuana smokers. Neuropsychopharmacology June 2007
- Involvement of mu-, delta- and kappa-opioid receptor subtypes in the discriminative-stimulus effects of delta-9-tetrahydrocannabinol (THC) in rats. Psychopharmacology June 2005
- Interaction between naltrexone and oral THC in heavy marijuana smokers. Psychopharmacology February 2003
- Cannabis: discrimination of "internal bliss"? Pharmacology, Biochemistry, and Behavior October 1999