Interactions between Delta(9)-tetrahydrocannabinol and mu opioid receptor agonists in rhesus monkeys: discrimination and antinociception.
BACKGROUND
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.


OBJECTIVE
This study examined interactions between the discriminative stimulus and antinociceptive effects of mu opioid receptor agonists and Delta(9)-tetrahydrocannabinol (THC) in rhesus monkeys.


RESULTS
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.


CONCLUSIONS
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.
Li
Jun-Xu
JX
Department of Pharmacology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA.
McMahon
Lance R
LR
Gerak
Lisa R
LR
Becker
Ginger L
GL
France
Charles P
CP
D000700:Analgesics / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D003627:Data Interpretation, Statistical; D004192:Discrimination, Psychological / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000494:pharmacology*; D004347:Drug Interactions; D005260:Female; D003932:Heroin / Q000494:pharmacology; D006358:Hot Temperature; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D008253:Macaca mulatta; D008297:Male; D008874:Midazolam / Q000494:pharmacology; D009020:Morphine / Q000494:pharmacology; D009021:Morphine Dependence / Q000523:psychology; D009271:Naltrexone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects; D017450:Receptors, Opioid, mu / Q000819:agonists*; D013375:Substance Withdrawal Syndrome / Q000523:psychology
D000700:Analgesics; D000701:Analgesics, Opioid; D006993:Hypnotics and Sedatives; D009292:Narcotic Antagonists; D017450:Receptors, Opioid, mu; D009271:Naltrexone; D003932:Heroin; D009020:Morphine; D013759:Dronabinol; D008874:Midazolam