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Interactions between Δ9-tetrahydrocannabinol and μ opioid receptor agonists in rhesus monkeys: discrimination and antinociception

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Abstract

Rationale

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 μ opioid receptor agonists and Δ9-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 μ receptor agonists did not alter the discriminative stimulus effects of THC, THC altered the effects of μ receptor agonists in a context-dependent manner.

Conclusion

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.

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Acknowledgements

The authors thank Christopher Cruz, Blake Harrington, Brandi Taylor, Armando Hernandez, and Ashley Varnon for expert technical assistance.

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Authors and Affiliations

  1. Department of Pharmacology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX, 78229-3900, USA

    Jun-Xu Li, Lance R. McMahon, Lisa R. Gerak, Ginger L. Becker & Charles P. France

  2. Department of Psychiatry, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA

    Charles P. France

Authors
  1. Jun-Xu Li
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  2. Lance R. McMahon
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  3. Lisa R. Gerak
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  4. Ginger L. Becker
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  5. Charles P. France
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Corresponding author

Correspondence to Charles P. France.

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Miscellaneous

This work was supported by USPHS Grants DA05018 (CPF), DA09157 (CPF), DA15468 (LRM), and DA19222 (LRM); CPF is supported by a Senior Scientist Award (DA17918). The authors have no other financial relationships with any organization that is relevant to the results presented in this manuscript.

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Li, JX., McMahon, L.R., Gerak, L.R. et al. Interactions between Δ9-tetrahydrocannabinol and μ opioid receptor agonists in rhesus monkeys: discrimination and antinociception. Psychopharmacology 199, 199–208 (2008). https://doi.org/10.1007/s00213-008-1157-0

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