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Interactions between Delta(9)-tetrahydrocannabinol and mu opioid receptor agonists in rhesus monkeys: discrimination and antinociception.
Psychopharmacology (Berl) 2008; 199(2):199-208P

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 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.

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.

Authors+Show Affiliations

Department of Pharmacology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

18470505

Citation

Li, Jun-Xu, et al. "Interactions Between Delta(9)-tetrahydrocannabinol and Mu Opioid Receptor Agonists in Rhesus Monkeys: Discrimination and Antinociception." Psychopharmacology, vol. 199, no. 2, 2008, pp. 199-208.
Li JX, McMahon LR, Gerak LR, et al. Interactions between Delta(9)-tetrahydrocannabinol and mu opioid receptor agonists in rhesus monkeys: discrimination and antinociception. Psychopharmacology (Berl). 2008;199(2):199-208.
Li, J. X., McMahon, L. R., Gerak, L. R., Becker, G. L., & France, C. P. (2008). Interactions between Delta(9)-tetrahydrocannabinol and mu opioid receptor agonists in rhesus monkeys: discrimination and antinociception. Psychopharmacology, 199(2), pp. 199-208. doi:10.1007/s00213-008-1157-0.
Li JX, et al. Interactions Between Delta(9)-tetrahydrocannabinol and Mu Opioid Receptor Agonists in Rhesus Monkeys: Discrimination and Antinociception. Psychopharmacology (Berl). 2008;199(2):199-208. PubMed PMID: 18470505.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Interactions between Delta(9)-tetrahydrocannabinol and mu opioid receptor agonists in rhesus monkeys: discrimination and antinociception. AU - Li,Jun-Xu, AU - McMahon,Lance R, AU - Gerak,Lisa R, AU - Becker,Ginger L, AU - France,Charles P, Y1 - 2008/05/10/ PY - 2007/11/30/received PY - 2008/04/03/accepted PY - 2008/5/13/pubmed PY - 2008/12/17/medline PY - 2008/5/13/entrez SP - 199 EP - 208 JF - Psychopharmacology JO - Psychopharmacology (Berl.) VL - 199 IS - 2 N2 - 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 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. 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. SN - 0033-3158 UR - https://www.unboundmedicine.com/medline/citation/18470505/Interactions_between_Delta_9__tetrahydrocannabinol_and_mu_opioid_receptor_agonists_in_rhesus_monkeys:_discrimination_and_antinociception_ L2 - https://dx.doi.org/10.1007/s00213-008-1157-0 DB - PRIME DP - Unbound Medicine ER -