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Mini-Reviews in Medicinal Chemistry


ISSN (Print): 1389-5575
ISSN (Online): 1875-5607

Review Article

The Role of the Cannabinoid System in Opioid Analgesia and Tolerance

Author(s): Ercan Ozdemir*

Volume 20, Issue 10, 2020

Page: [875 - 885] Pages: 11

DOI: 10.2174/1389557520666200313120835

Price: $65


Opioid receptor agonist drugs, such as morphine, are very effective for treating chronic and severe pain; but, tolerance can develop with long-term use. Although there is a lot of information about the pathophysiological mechanisms of opioid tolerance, it is still not fully clarified. Suggested mechanisms for opioid tolerance include opioid receptor desensitisation, reduction of sensitivity G-proteins, activation of Mitogen-Activated Protein Kinase (MAPK), altered intracellular signaling pathway including nitric oxide, and activation of mammalian Target of Rapamycin (mTOR). One way to reduce opioid tolerance and increase the analgesic potential is to use low doses. Combination of cannabinoids with opioids has been shown to manifest the reduction of the opioid dose. Experimental studies revealed an interaction of the endocannabinoid system and opioid antinociception. Cannabinoid and opioid receptor systems use common pathways in the formation of analgesic effect and demonstrate their activity via G Protein Coupled Receptors (GPCR). Cannabinoid drugs modulate opioid analgesic activity at a number of distinct levels within the cell, ranging from direct receptor associations to post-receptor interactions through shared signal transduction pathways. This review summarizes the data indicating that with combining cannabinoids and opioids drugs may be able to produce long-term analgesic effects, while preventing the opioid analgesic tolerance.

Keywords: Cannabinoids, cannabinoid receptors, cannabinoid analgesia, opioid analgesia, opioid tolerance, analgesic.

Graphical Abstract
Chen, Y.; Sommer, C. The role of mitogen-activated protein kinase (MAPK) in morphine tolerance and dependence. Mol. Neurobiol., 2009, 40(2), 101-107.
[] [PMID: 19468867]
Harrison, L.M.; Kastin, A.J.; Zadina, J.E. Opiate tolerance and dependence: receptors, G-proteins, and antiopiates. Peptides, 1998, 19(9), 1603-1630.
[] [PMID: 9864069]
Christie, M.J. Cellular neuroadaptations to chronic opioids: tolerance, withdrawal and addiction. Br. J. Pharmacol., 2008, 154(2), 384-396.
[] [PMID: 18414400]
Liu, W.; Wang, C.H.; Cui, Y.; Mo, L.Q.; Zhi, J.L.; Sun, S.N.; Wang, Y.L.; Yu, H.M.; Zhao, C.M.; Feng, J.Q.; Chen, P.X. Inhibition of neuronal nitric oxide synthase antagonizes morphine antinociceptive tolerance by decreasing activation of p38 MAPK in the spinal microglia. Neurosci. Lett., 2006, 410(3), 174-177.
[] [PMID: 17101217]
Ozdemir, E.; Bagcivan, I.; Durmus, N.; Altun, A.; Gursoy, S. The nitric oxide-cGMP signaling pathway plays a significant role in tolerance to the analgesic effect of morphine. Can. J. Physiol. Pharmacol., 2011, 89(2), 89-95.
[] [PMID: 21326339]
Gursoy, S.; Ozdemir, E.; Bagcivan, I.; Altun, A.; Durmus, N. Effects of alpha 2-adrenoceptor agonists dexmedetomidine and guanfacine on morphine analgesia and tolerance in rats. Ups. J. Med. Sci., 2011, 116(4), 238-246.
[] [PMID: 21919812]
Sim-Selley, L.J.; Scoggins, K.L.; Cassidy, M.P.; Smith, L.A.; Dewey, W.L.; Smith, F.L.; Selley, D.E. Region-dependent attenuation of mu opioid receptor-mediated G-protein activation in mouse CNS as a function of morphine tolerance. Br. J. Pharmacol., 2007, 151(8), 1324-1333.
[] [PMID: 17572699]
Cichewicz, D.L. Synergistic interactions between cannabinoid and opioid analgesics. Life Sci., 2004, 74(11), 1317-1324.
[] [PMID: 14706563]
Smith, F.L.; Cichewicz, D.; Martin, Z.L.; Welch, S.P. The enhancement of morphine antinociception in mice by delta9-tetrahydrocannabinol. Pharmacol. Biochem. Behav., 1998, 60(2), 559-566.
[] [PMID: 9632241]
Frank, B.; Serpell, M.G.; Hughes, J.; Matthews, J.N.; Kapur, D. Comparison of analgesic effects and patient tolerability of nabilone and dihydrocodeine for chronic neuropathic pain: randomised, crossover, double blind study. BMJ, 2008, 336(7637), 199-201.
[] [PMID: 18182416]
Pickel, V.M.; Chan, J.; Kash, T.L.; Rodríguez, J.J.; MacKie, K. Compartment-specific localization of cannabinoid 1 (CB1) and mu-opioid receptors in rat nucleus accumbens. Neuroscience, 2004, 127(1), 101-112.
[] [PMID: 15219673]
Battista, N.; Fezza, F.; Finazzi-Agrò, A.; Maccarrone, M. The endocannabinoid system in neurodegeneration. Ital. J. Biochem., 2006, 55(3-4), 283-289.
[PMID: 17274532]
Lynch, M.E. Cannabinoids in the management of chronic pain: a front line clinical perspective. J. Basic Clin. Physiol. Pharmacol., 2016, 27(3), 189-191.
[] [PMID: 26581068]
Wilson, R.I.; Nicoll, R.A. Endogenous cannabinoids mediate retrograde signalling at hippocampal synapses. Nature, 2001, 410(6828), 588-592.
[] [PMID: 11279497]
Bacci, A.; Huguenard, J.R.; Prince, D.A. Long-lasting self-inhibition of neocortical interneurons mediated by endocannabinoids. Nature, 2004, 431(7006), 312-316.
[] [PMID: 15372034]
Mechoulam, R.; Ben-Shabat, S.; Hanus, L.; Ligumsky, M.; Kaminski, N.E.; Schatz, A.R.; Gopher, A.; Almog, S.; Martin, B.R.; Compton, D.R. Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochem. Pharmacol., 1995, 50(1), 83-90.
[] [PMID: 7605349]
Devane, W.A.; Hanus, L.; Breuer, A.; Pertwee, R.G.; Stevenson, L.A.; Griffin, G.; Gibson, D.; Mandelbaum, A.; Etinger, A.; Mechoulam, R. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science, 1992, 258(5090), 1946-1949.
[] [PMID: 1470919]
Wang, J.; Ueda, N. Biology of endocannabinoid synthesis system. Prostaglandins Other Lipid Mediat., 2009, 89(3-4), 112-119.
[] [PMID: 19126434]
Kondo, S.; Kondo, H.; Nakane, S.; Kodaka, T.; Tokumura, A.; Waku, K.; Sugiura, T. 2-Arachidonoylglycerol, an endogenous cannabinoid receptor agonist: identification as one of the major species of monoacylglycerols in various rat tissues, and evidence for its generation through CA2+-dependent and -independent mechanisms. FEBS Lett., 1998, 429(2), 152-156.
[] [PMID: 9650580]
Szaflarski, J.P.; Bebin, E.M. Cannabis, cannabidiol, and epilepsy--from receptors to clinical response. Epilepsy Behav., 2014, 41, 277-282.
[] [PMID: 25282526]
Grant, I.; Atkinson, J.H.; Gouaux, B.; Wilsey, B. Medical marijuana: clearing away the smoke. Open Neurol. J., 2012, 6, 18-25.
[] [PMID: 22629287]
Piomelli, D. More surprises lying ahead. The endocannabinoids keep us guessing. Neuropharmacology, 2014, 76(Pt B), 228-234.
[] [PMID: 23954677]
Kenakin, T. New concepts in pharmacological efficacy at 7TM receptors: IUPHAR review 2. Br. J. Pharmacol., 2013, 168(3), 554-575.
[] [PMID: 22994528]
Vasileiou, I.; Fotopoulou, G.; Matzourani, M.; Patsouris, E.; Theocharis, S. Evidence for the involvement of cannabinoid receptors’ polymorphisms in the pathophysiology of human diseases. Expert Opin. Ther. Targets, 2013, 17(4), 363-377.
[] [PMID: 23293857]
Ryberg, E.; Larsson, N.; Sjögren, S.; Hjorth, S.; Hermansson, N.O.; Leonova, J.; Elebring, T.; Nilsson, K.; Drmota, T.; Greasley, P.J. The orphan receptor GPR55 is a novel cannabinoid receptor. Br. J. Pharmacol., 2007, 152(7), 1092-1101.
[] [PMID: 17876302]
Rahn, E.J.; Hohmann, A.G. Cannabinoids as pharmacotherapies for neuropathic pain: from the bench to the bedside. Neurotherapeutics, 2009, 6(4), 713-737.
[] [PMID: 19789075]
Beltramo, M.; Bernardini, N.; Bertorelli, R.; Campanella, M.; Nicolussi, E.; Fredduzzi, S.; Reggiani, A. CB2 receptor-mediated antihyperalgesia: possible direct involvement of neural mechanisms. Eur. J. Neurosci., 2006, 23(6), 1530-1538.
[] [PMID: 16553616]
Laprairie, R.B.; Kelly, M.E.; Denovan-Wright, E.M. The dynamic nature of type 1 cannabinoid receptor (CB(1) ) gene transcription. Br. J. Pharmacol., 2012, 167(8), 1583-1595.
[] [PMID: 22924606]
Seely, K.A.; Brents, L.K.; Franks, L.N.; Rajasekaran, M.; Zimmerman, S.M.; Fantegrossi, W.E.; Prather, P.L. AM-251 and rimonabant act as direct antagonists at mu-opioid receptors: implications for opioid/cannabinoid interaction studies. Neuropharmacology, 2012, 63(5), 905-915.
[] [PMID: 22771770]
Rahn, E.J.; Zvonok, A.M.; Thakur, G.A.; Khanolkar, A.D.; Makriyannis, A.; Hohmann, A.G. Selective activation of cannabinoid CB2 receptors suppresses neuropathic nociception induced by treatment with the chemotherapeutic agent paclitaxel in rats. J. Pharmacol. Exp. Ther., 2008, 327(2), 584-591.
[] [PMID: 18664590]
den Boon, F.S.; Chameau, P.; Schaafsma-Zhao, Q.; van Aken, W.; Bari, M.; Oddi, S.; Kruse, C.G.; Maccarrone, M.; Wadman, W.J.; Werkman, T.R. Excitability of prefrontal cortical pyramidal neurons is modulated by activation of intracellular type-2 cannabinoid receptors. Proc. Natl. Acad. Sci. USA, 2012, 109(9), 3534-3539.
[] [PMID: 22331871]
Callén, L.; Moreno, E.; Barroso-Chinea, P.; Moreno-Delgado, D.; Cortés, A.; Mallol, J.; Casadó, V.; Lanciego, J.L.; Franco, R.; Lluis, C.; Canela, E.I.; McCormick, P.J. Cannabinoid receptors CB1 and CB2 form functional heteromers in brain. J. Biol. Chem., 2012, 287(25), 20851-20865.
[] [PMID: 22532560]
McHugh, D.; Page, J.; Dunn, E.; Bradshaw, H.B.Δ. Δ(9) -Tetrahydrocannabinol and N-arachidonyl glycine are full agonists at GPR18 receptors and induce migration in human endometrial HEC-1B cells. Br. J. Pharmacol., 2012, 165(8), 2414-2424.
[] [PMID: 21595653]
Schuelert, N.; McDougall, J.J. The abnormal cannabidiol analogue O-1602 reduces nociception in a rat model of acute arthritis via the putative cannabinoid receptor GPR55. Neurosci. Lett., 2011, 500(1), 72-76.
[] [PMID: 21683763]
Eldeeb, K.; Leone-Kabler, S.; Howlett, A.C. CB1 cannabinoid receptor-mediated increases in cyclic AMP accumulation are correlated with reduced Gi/o function. J. Basic Clin. Physiol. Pharmacol., 2016, 27(3), 311-322.
[] [PMID: 27089415]
Demuth, D.G.; Molleman, A. Cannabinoid signalling. Life Sci., 2006, 78(6), 549-563.
[] [PMID: 16109430]
Rhee, M.H.; Bayewitch, M.; Avidor-Reiss, T.; Levy, R.; Vogel, Z. Cannabinoid receptor activation differentially regulates the various adenylyl cyclase isozymes. J. Neurochem., 1998, 71(4), 1525-1534.
[] [PMID: 9751186]
Maneuf, Y.P.; Brotchie, J.M. Paradoxical action of the cannabinoid WIN 55,212-2 in stimulated and basal cyclic AMP accumulation in rat globus pallidus slices. Br. J. Pharmacol., 1997, 120(8), 1397-1398.
[] [PMID: 9113356]
Lauckner, J.E.; Hille, B.; Mackie, K. The cannabinoid agonist WIN55,212-2 increases intracellular calcium via CB1 receptor coupling to Gq/11 G proteins. Proc. Natl. Acad. Sci. USA, 2005, 102(52), 19144-19149.
[] [PMID: 16365309]
Navarrete, M.; Araque, A. Endocannabinoids mediate neuron-astrocyte communication. Neuron, 2008, 57(6), 883-893.
[] [PMID: 18367089]
Brown, S.P.; Safo, P.K.; Regehr, W.G. Endocannabinoids inhibit transmission at granule cell to Purkinje cell synapses by modulating three types of presynaptic calcium channels. J. Neurosci., 2004, 24(24), 5623-5631.
[] [PMID: 15201335]
Szabó, G.G.; Lenkey, N.; Holderith, N.; Andrási, T.; Nusser, Z.; Hájos, N. Presynaptic calcium channel inhibition underlies CB1 cannabinoid receptor-mediated suppression of GABA release. J. Neurosci., 2014, 34(23), 7958-7963.
[] [PMID: 24899717]
Mackie, K.; Lai, Y.; Westenbroek, R.; Mitchell, R. Cannabinoids activate an inwardly rectifying potassium conductance and inhibit Q-type calcium currents in AtT20 cells transfected with rat brain cannabinoid receptor. J. Neurosci., 1995, 15(10), 6552-6561.
[] [PMID: 7472417]
Howlett, A.C.; Blume, L.C.; Dalton, G.D. CB(1) cannabinoid receptors and their associated proteins. Curr. Med. Chem., 2010, 17(14), 1382-1393.
[] [PMID: 20166926]
McCudden, C.R.; Hains, M.D.; Kimple, R.J.; Siderovski, D.P.; Willard, F.S. G-protein signaling: back to the future. Cell. Mol. Life Sci., 2005, 62(5), 551-577.
[] [PMID: 15747061]
Elmes, S.J.R.; Jhaveri, M.D.; Smart, D.; Kendall, D.A.; Chapman, V. Cannabinoid CB2 receptor activation inhibits mechanically evoked responses of wide dynamic range dorsal horn neurons in naïve rats and in rat models of inflammatory and neuropathic pain. Eur. J. Neurosci., 2004, 20(9), 2311-2320.
[] [PMID: 15525273]
Hasanein, P.; Parviz, M.; Keshavarz, M.; Javanmardi, K. CB1 receptor activation in the basolateral amygdala produces antinociception in animal models of acute and tonic nociception. Clin. Exp. Pharmacol. Physiol., 2007, 34(5-6), 439-449.
[] [PMID: 17439413]
Whiteside, G.T.; Gottshall, S.L.; Boulet, J.M.; Chaffer, S.M.; Harrison, J.E.; Pearson, M.S.; Turchin, P.I.; Mark, L.; Garrison, A.E.; Valenzano, K.J. A role for cannabinoid receptors, but not endogenous opioids, in the antinociceptive activity of the CB2-selective agonist, GW405833. Eur. J. Pharmacol., 2005, 528(1-3), 65-72.
[] [PMID: 16316650]
Lichtman, A.H.; Martin, B.R. The selective cannabinoid antagonist SR 141716A blocks cannabinoid-induced antinociception in rats. Pharmacol. Biochem. Behav., 1997, 57(1-2), 7-12.
[] [PMID: 9164547]
Hsieh, G.C.; Pai, M.; Chandran, P.; Hooker, B.A.; Zhu, C.Z.; Salyers, A.K.; Wensink, E.J.; Zhan, C.; Carroll, W.A.; Dart, M.J.; Yao, B.B.; Honore, P.; Meyer, M.D. Central and peripheral sites of action for CB2 receptor mediated analgesic activity in chronic inflammatory and neuropathic pain models in rats. Br. J. Pharmacol., 2011, 162(2), 428-440.
[] [PMID: 20880025]
Kinsey, S.G.; Mahadevan, A.; Zhao, B.; Sun, H.; Naidu, P.S.; Razdan, R.K.; Selley, D.E.; Imad Damaj, M.; Lichtman, A.H. The CB2 cannabinoid receptor-selective agonist O-3223 reduces pain and inflammation without apparent cannabinoid behavioral effects. Neuropharmacology, 2011, 60(2-3), 244-251.
[] [PMID: 20849866]
Ebrahimzadeh, M.; Haghparast, A. Analgesic effects of cannabinoid receptor agonist WIN55,212-2 in the nucleus cuneiformis in animal models of acute and inflammatory pain in rats. Brain Res., 2011, 1420, 19-28.
[] [PMID: 21911208]
Deng, L.; Guindon, J.; Cornett, B.L.; Makriyannis, A.; Mackie, K.; Hohmann, A.G. Chronic cannabinoid receptor 2 activation reverses paclitaxel neuropathy without tolerance or cannabinoid receptor 1-dependent withdrawal. Biol. Psychiatry, 2015, 77(5), 475-487.
[] [PMID: 24853387]
Ibrahim, M.M.; Porreca, F.; Lai, J.; Albrecht, P.J.; Rice, F.L.; Khodorova, A.; Davar, G.; Makriyannis, A.; Vanderah, T.W.; Mata, H.P.; Malan, T.P., Jr CB2 cannabinoid receptor activation produces antinociception by stimulating peripheral release of endogenous opioids. Proc. Natl. Acad. Sci. USA, 2005, 102(8), 3093-3098.
[] [PMID: 15705714]
Seltzman, H.H.; Shiner, C.; Hirt, E.E.; Gilliam, A.F.; Thomas, B.F.; Maitra, R.; Snyder, R.; Black, S.L.; Patel, P.R.; Mulpuri, Y.; Spigelman, I. Peripherally selective cannabinoid 1 receptor (CB1R) agonists for the treatment of neuropathic pain. J. Med. Chem., 2016, 59(16), 7525-7543.
[] [PMID: 27482723]
Wang, P.; Zheng, T.; Zhang, M.; Xu, B.; Zhang, R.; Zhang, T.; Zhao, W.; Shi, X.; Zhang, Q.; Fang, Q. Antinociceptive effects of the endogenous cannabinoid peptide agonist VD-hemopressin(β) in mice. Brain Res. Bull., 2018, 139, 48-55.
[] [PMID: 29425797]
Craft, R.M.; Greene, N.Z.; Wakley, A.A. Antinociceptive effects of JWH015 in female and male rats. Behav. Pharmacol., 2018, 29(2 and 3-Spec Issue), 280-289.
[PMID: 28914627]
Lin, X.; Dhopeshwarkar, A.S.; Huibregtse, M.; Mackie, K.; Hohmann, A.G. Slowly signaling G protein–biased CB2 cannabinoid receptor agonist LY2828360 suppresses neuropathic pain with sustained efficacy and attenuates morphine tolerance and dependence. Mol. Pharmacol., 2018, 93(2), 49-62.
[] [PMID: 29192123]
Pasternak, G.W. Molecular biology of opioid analgesia. J. Pain Symptom Manage., 2005, 29(5)(Suppl. 1), S2-S9.
[] [PMID: 15907642]
Massi, P.; Vaccani, A.; Romorini, S.; Parolaro, D. Comparative characterization in the rat of the interaction between cannabinoids and opiates for their immunosuppressive and analgesic effects. J. Neuroimmunol., 2001, 117(1-2), 116-124.
[] [PMID: 11431011]
Corchero, J.; Manzanares, J.; Fuentes, J.A. Cannabinoid/opioid crosstalk in the central nervous system. Crit. Rev. Neurobiol., 2004, 16(1-2), 159-172.
[] [PMID: 15581411]
Roberts, J.D.; Gennings, C.; Shih, M. Synergistic affective analgesic interaction between delta-9-tetrahydrocannabinol and morphine. Eur. J. Pharmacol., 2006, 530(1-2), 54-58.
[] [PMID: 16375890]
Parolaro, D.; Rubino, T.; Viganò, D.; Massi, P.; Guidali, C.; Realini, N. Cellular mechanisms underlying the interaction between cannabinoid and opioid system. Curr. Drug Targets, 2010, 11(4), 393-405.
[] [PMID: 20017730]
Nestler, E.J.; Alreja, M.; Aghajanian, G.K. Molecular control of locus coeruleus neurotransmission. Biol. Psychiatry, 1999, 46(9), 1131-1139.
[] [PMID: 10560020]
Salio, C.; Fischer, J.; Franzoni, M.F.; Mackie, K.; Kaneko, T.; Conrath, M. CB1-cannabinoid and mu-opioid receptor co-localization on postsynaptic target in the rat dorsal horn. Neuroreport, 2001, 12(17), 3689-3692.
[] [PMID: 11726775]
Rodriguez, J.J.; Mackie, K.; Pickel, V.M. Ultrastructural localization of the CB1 cannabinoid receptor in mu-opioid receptor patches of the rat Caudate putamen nucleus. J. Neurosci., 2001, 21(3), 823-833.
[] [PMID: 11157068]
Muntoni, A.L.; Pillolla, G.; Melis, M.; Perra, S.; Gessa, G.L.; Pistis, M. Cannabinoids modulate spontaneous neuronal activity and evoked inhibition of locus coeruleus noradrenergic neurons. Eur. J. Neurosci., 2006, 23(9), 2385-2394.
[] [PMID: 16706846]
Oropeza, V.C.; Mackie, K.; Van Bockstaele, E.J. Cannabinoid receptors are localized to noradrenergic axon terminals in the rat frontal cortex. Brain Res., 2007, 1127(1), 36-44.
[] [PMID: 17113043]
Reyes, B.A.; Rosario, J.C.; Piana, P.M.; Van Bockstaele, E.J. Cannabinoid modulation of cortical adrenergic receptors and transporters. J. Neurosci. Res., 2009, 87(16), 3671-3678.
[] [PMID: 19533736]
Scavone, J.L.; Mackie, K.; Van Bockstaele, E.J. Characterization of cannabinoid-1 receptors in the locus coeruleus: relationship with mu-opioid receptors. Brain Res., 2010, 1312, 18-31.
[] [PMID: 19931229]
Welch, S.P.; Stevens, D.L. Antinociceptive activity of intrathecally administered cannabinoids alone, and in combination with morphine, in mice. J. Pharmacol. Exp. Ther., 1992, 262(1), 10-18.
[PMID: 1320680]
Cox, M.L.; Haller, V.L.; Welch, S.P. Synergy between delta9-tetrahydrocannabinol and morphine in the arthritic rat. Eur. J. Pharmacol., 2007, 567(1-2), 125-130.
[] [PMID: 17498686]
Viganò, D.; Rubino, T.; Parolaro, D. Molecular and cellular basis of cannabinoid and opioid interactions. Pharmacol. Biochem. Behav., 2005, 81(2), 360-368.
[] [PMID: 15927245]
Rubino, T.; Massi, P.; Viganò, D.; Fuzio, D.; Parolaro, D. Long-term treatment with SR141716A, the CB1 receptor antagonist, influences morphine withdrawal syndrome. Life Sci., 2000, 66(22), 2213-2219.
[] [PMID: 10834304]
Cadoni, C.; Pisanu, A.; Solinas, M.; Acquas, E.; Di Chiara, G. Behavioural sensitization after repeated exposure to Delta 9-tetrahydrocannabinol and cross-sensitization with morphine. Psychopharmacology (Berl.), 2001, 158(3), 259-266.
[] [PMID: 11713615]
Goldberg, J.S. Chronic opioid therapy and opioid tolerance: a new hypothesis. Pain Res. Treat., 2013, 2013407504
[] [PMID: 23401765]
Allouche, S.; Noble, F.; Marie, N. Opioid receptor desensitization: mechanisms and its link to tolerance. Front. Pharmacol., 2014, 5(5), 280.
[] [PMID: 25566076]
Levitt, E.S.; Williams, J.T. Morphine desensitization and cellular tolerance are distinguished in rat locus ceruleus neurons. Mol. Pharmacol., 2012, 82(5), 983-992.
[] [PMID: 22914548]
Law, P.Y.; Hom, D.S.; Loh, H.H. Loss of opiate receptor activity in neuroblastoma X glioma NG108-15 hybrid cells after chronic opiate treatment. A multiple-step process. Mol. Pharmacol., 1982, 22(1), 1-4.
[PMID: 6126803]
Lu, L.; Su, W.J.; Yue, W.; Ge, X.; Su, F.; Pei, G.; Ma, L. Attenuation of morphine dependence and withdrawal in rats by venlafaxine, a serotonin and noradrenaline reuptake inhibitor. Life Sci., 2001, 69(1), 37-46.
[] [PMID: 11411809]
Lee, M.; Silverman, S.M.; Hansen, H.; Patel, V.B.; Manchikanti, L. A comprehensive review of opioid-induced hyperalgesia. Pain Physician, 2011, 14(2), 145-161.
[PMID: 21412369]
Hamidi, G.A.; Manaheji, H.; Janahmadi, M.; Noorbakhsh, S.M.; Salami, M. Co-administration of MK-801 and morphine attenuates neuropathic pain in rat. Physiol. Behav., 2006, 88(4-5), 628-635.
[] [PMID: 16815501]
Laulin, J.P.; Maurette, P.; Corcuff, J.B.; Rivat, C.; Chauvin, M.; Simonnet, G. The role of ketamine in preventing fentanyl-induced hyperalgesia and subsequent acute morphine tolerance. Anesth. Analg., 2002, 94(5), 1263-1269.
[] [PMID: 11973202]
Watanabe, M.; Maemura, K.; Kanbara, K.; Tamayama, T.; Hayasaki, H. GABA and GABA receptors in the central nervous system and other organs. Int. Rev. Cytol., 2002, 213, 1-47.
[] [PMID: 11837891]
Shokoofeh, S.; Homa, M.; Leila, D.; Samira, D. Expression of spinal cord GABA transporter 1 in morphine-tolerant male Wistar rats. Eur. J. Pharmacol., 2015, 767, 77-81.
[] [PMID: 26463038]
Riahi, E.; Mirzaii-Dizgah, I.; Karimian, S.M.; Sadeghipour, H.R.; Dehpour, A.R. Attenuation of morphine withdrawal signs by a GABAB receptor agonist in the locus coeruleus of rats. Behav. Brain Res., 2009, 196(1), 11-14.
[] [PMID: 18634832]
Acquas, E.; Di Chiara, G. Depression of mesolimbic dopamine transmission and sensitization to morphine during opiate abstinence. J. Neurochem., 1992, 58(5), 1620-1625.
[] [PMID: 1313849]
Johnson, D.W.; Glick, S.D. Dopamine release and metabolism in nucleus accumbens and striatum of morphine-tolerant and nontolerant rats. Pharmacol. Biochem. Behav., 1993, 46(2), 341-347.
[] [PMID: 8265688]
Zarrindast, M.R.; Moghaddampour, E. Opposing influences of D-1 and D-2 dopamine receptors activation on morphine-induced antinociception. Arch. Int. Pharmacodyn. Ther., 1989, 300, 37-50.
[PMID: 2619426]
Ozdemir, E.; Gursoy, S.; Bagcivan, I. The effects of serotonin/norepinephrine reuptake inhibitors and serotonin receptor agonist on morphine analgesia and tolerance in rats. J. Physiol. Sci., 2012, 62(4), 317-323.
[] [PMID: 22544464]
Arends, R.H.; Hayashi, T.G.; Luger, T.J.; Shen, D.D. Cotreatment with racemic fenfluramine inhibits the development of tolerance to morphine analgesia in rats. J. Pharmacol. Exp. Ther., 1998, 286(2), 585-592.
[PMID: 9694907]
Buckingham, J.C.; Cooper, T.A. Differences in hypothalamo-pituitary-adrenocortical activity in the rat after acute and prolonged treatment with morphine. Neuroendocrinology, 1984, 38(5), 411-417.
[] [PMID: 6328347]
Hendrie, C.A. ACTH: a single pretreatment enhances the analgesic efficacy of and prevents the development of tolerance to morphine. Physiol. Behav., 1988, 42(1), 41-45.
[] [PMID: 2838853]
Finn, D.P.; Beckett, S.R.; Roe, C.H.; Madjd, A.; Fone, K.C.; Kendall, D.A.; Marsden, C.A.; Chapman, V. Effects of coadministration of cannabinoids and morphine on nociceptive behaviour, brain monoamines and HPA axis activity in a rat model of persistent pain. Eur. J. Neurosci., 2004, 19(3), 678-686.
[] [PMID: 14984418]
Altun, A.; Yildirim, K.; Ozdemir, E.; Bagcivan, I.; Gursoy, S.; Durmus, N. Attenuation of morphine antinociceptive tolerance by cannabinoid CB1 and CB2 receptor antagonists. J. Physiol. Sci., 2015, 65(5), 407-415.
[] [PMID: 25894754]
Welch, S.P.; Thomas, C.; Patrick, G.S. Modulation of cannabinoid-induced antinociception after intracerebroventricular versus intrathecal administration to mice: possible mechanisms for interaction with morphine. J. Pharmacol. Exp. Ther., 1995, 272(1), 310-321.
[PMID: 7815346]
Li, J.X.; McMahon, L.R.; Gerak, L.R.; Becker, G.L.; France, C.P. Interactions between Delta(9)-tetrahydrocannabinol and mu opioid receptor agonists in rhesus monkeys: discrimination and antinociception. Psychopharmacology (Berl.), 2008, 199(2), 199-208.
[] [PMID: 18470505]
Maguire, D.R.; Yang, W.; France, C.P. Interactions between μ-opioid receptor agonists and cannabinoid receptor agonists in rhesus monkeys: antinociception, drug discrimination, and drug self-administration. J. Pharmacol. Exp. Ther., 2013, 345(3), 354-362.
[] [PMID: 23536317]
Welch, S.P.; Eads, M. Synergistic interactions of endogenous opioids and cannabinoid systems. Brain Res., 1999, 848(1-2), 183-190.
[] [PMID: 10612710]
Yesilyurt, O.; Dogrul, A.; Gul, H.; Seyrek, M.; Kusmez, O.; Ozkan, Y.; Yildiz, O. Topical cannabinoid enhances topical morphine antinociception. Pain, 2003, 105(1-2), 303-308.
[] [PMID: 14499448]
Tham, S.M.; Angus, J.A.; Tudor, E.M.; Wright, C.E. Synergistic and additive interactions of the cannabinoid agonist CP55,940 with mu opioid receptor and alpha2-adrenoceptor agonists in acute pain models in mice. Br. J. Pharmacol., 2005, 144(6), 875-884.
[] [PMID: 15778704]
Trang, T.; Sutak, M.; Jhamandas, K. Involvement of cannabinoid (CB1)-receptors in the development and maintenance of opioid tolerance. Neuroscience, 2007, 146(3), 1275-1288.
[] [PMID: 17395382]
Smith, P.A.; Selley, D.E.; Sim-Selley, L.J.; Welch, S.P. Low dose combination of morphine and delta9-tetrahydrocannabinol circumvents antinociceptive tolerance and apparent desensitization of receptors. Eur. J. Pharmacol., 2007, 571(2-3), 129-137.
[] [PMID: 17603035]
Wilson, A.R.; Maher, L.; Morgan, M.M. Repeated cannabinoid injections into the rat periaqueductal gray enhance subsequent morphine antinociception. Neuropharmacology, 2008, 55(7), 1219-1225.
[] [PMID: 18723035]
Fischer, B.D.; Ward, S.J.; Henry, F.E.; Dykstra, L.A. Attenuation of morphine antinociceptive tolerance by a CB(1) receptor agonist and an NMDA receptor antagonist: Interactive effects. Neuropharmacology, 2010, 58(2), 544-550.
[] [PMID: 19699755]
Maguire, D.R.; France, C.P. Impact of efficacy at the μ-opioid receptor on antinociceptive effects of combinations of μ-opioid receptor agonists and cannabinoid receptor agonists. J. Pharmacol. Exp. Ther., 2014, 351(2), 383-389.
[] [PMID: 25194020]
Altun, A.; Ozdemir, E.; Yildirim, K.; Gursoy, S.; Durmus, N.; Bagcivan, I. The effects of endocannabinoid receptor agonist anandamide and antagonist rimonabant on opioid analgesia and tolerance in rats. Gen. Physiol. Biophys., 2015, 34(4), 433-440.
[PMID: 26374993]
Zhang, M.; Wang, K.; Ma, M.; Tian, S.; Wei, N.; Wang, G. Low-dose cannabinoid type 2 receptor agonist attenuates tolerance to repeated morphine administration via regulating μ-opioid receptor expression in Walker 256 tumor-bearing rats. Anesth. Analg., 2016, 122(4), 1031-1037.
[] [PMID: 26720619]
Gerak, L.R.; France, C.P. Combined treatment with morphine and ∆9-tetrahydrocannabinol in rhesus monkeys: Antinociceptive tolerance and withdrawal. J. Pharmacol. Exp. Ther., 2016, 357(2), 357-366.
[] [PMID: 26937020]
Grenald, S.A.; Young, M.A.; Wang, Y.; Ossipov, M.H.; Ibrahim, M.M.; Largent-Milnes, T.M.; Vanderah, T.W. Synergistic attenuation of chronic pain using mu opioid and cannabinoid receptor 2 agonists. Neuropharmacology, 2017, 116, 59-70.
[] [PMID: 28007501]
Yuill, M.B.; Hale, D.E.; Guindon, J.; Morgan, D.J. Anti-nociceptive interactions between opioids and a cannabinoid receptor 2 agonist in inflammatory pain. Mol. Pain, 2017, 131744806917728227
[] [PMID: 28879802]
Desroches, J.; Bouchard, J-F.; Gendron, L.; Beaulieu, P. Involvement of cannabinoid receptors in peripheral and spinal morphine analgesia. Neuroscience, 2014, 261, 23-42.
[] [PMID: 24365460]
Zhang, M.; Chi, M.; Zou, H.; Tian, S.; Zhang, Z.; Wang, G. Effects of coadministration of low dose cannabinoid type 2 receptor agonist and morphine on vanilloid receptor 1 expression in a rat model of cancer pain. Mol. Med. Rep., 2017, 16(5), 7025-7031.
[] [PMID: 28901432]

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