Hostname: page-component-586b7cd67f-rcrh6 Total loading time: 0 Render date: 2024-11-24T03:41:25.117Z Has data issue: false hasContentIssue false
  • English
  • Français

Neuroinflammation as a possible link between cannabinoids and addiction

Published online by Cambridge University Press:  02 October 2013

Livia C.M. Rodrigues ,
Pedro H. Gobira ,
Antonio Carlos de Oliveira ,
Renan Pelição ,
Antonio Lucio Teixeira ,
Fabricio A. Moreira  and
Alline Cristina Campos
Livia C.M. Rodrigues
Affiliation:
Department of Physiological Sciences, Health Science Center, Universidade Federal do Espírito Santo, Vitoria, Brazil
Pedro H. Gobira
Affiliation:
Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
Antonio Carlos de Oliveira
Affiliation:
Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
Renan Pelição
Affiliation:
Department of Physiological Sciences, Health Science Center, Universidade Federal do Espírito Santo, Vitoria, Brazil
Antonio Lucio Teixeira
Affiliation:
Group of Neuroimmunology, Laboratory of Immunopharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil Infectious Diseases and Tropical Medicine Program, Medical School, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
Fabricio A. Moreira
Affiliation:
Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
Alline Cristina Campos*
Affiliation:
Group of Neuroimmunology, Laboratory of Immunopharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil Infectious Diseases and Tropical Medicine Program, Medical School, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
*
Alline Cristina de Campos, Interdisciplinary Laboratory of Medical Investigation, Department of Internal Medicine/Infectious Disease and Tropical Medicine Graduate Program, School of Medicine – Federal University of Minas Gerais, Av. Alfredo Balena, Belo Horizonte, MG, Brazil. Tel: +55 31 34098073; Fax: +55 31 34099640; E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

Objective

Substance dependence disorder is a chronically relapsing condition characterised by neurobiological changes leading to loss of control in restricting a substance intake, compulsion and withdrawal syndrome. In the past few years, (endo)cannabinoids have been raised as a possible target in the aetiology of drug addiction. On the other hand, although the exact mechanisms of the genesis of addiction remain poorly understood, it is possible that neuroinflammation might also play a role in the pathophysiology of this condition. Studies demonstrated that (endo)cannabinoids act as immunomodulators by inhibiting cytokines production and microglial cell activation. Thus, in the present review, we explore the possible role of neuroinflammation on the therapeutic effects of cannabinoids on drug addiction.

Methods

We conducted an evidence-based review of the literature in order to assess the role of cannabinoids on the neuroinflammatory hypothesis of addiction (terms: addiction, cannabinoids and inflammation). We searched PubMed and BioMedCentral databases up to April 2014 with no date restrictions.

Results

In all, 165 eligible articles were included in the present review. Existing evidence suggests that disruption in cannabinoid signalling during the drug addiction process leads to microglial activation and neuroinflammation.

Conclusion

The literature showed that inflammation and changes in endocannabinod signalling occur in drug abuse; however, it remains uncertain whether these changes are causally or coincidentally associated with addiction. Additional studies, therefore, are needed to elucidate the contribution of neuroinflammation on the behavioural and neuroprotective effects of cannabinoids on drug addiction.

Keywords

addictionalcoholcannabinoidscocaineneuroinflammation
Type
Review Article
Information
Acta Neuropsychiatrica , Volume 26 , Issue 6 , December 2014 , pp. 334 - 346
Copyright
© Scandinavian College of Neuropsychopharmacology 2014 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1.American Psychiatric Association. Diagnostic and statistical manual of mental disorders, text revision, 4th edn. Washington, DC: American Psychiatric Association, 2000.Google Scholar
2.Koob, GF, Volkow, ND. Neurocircuitry of addiction. Neuropsychopharmacology 2010;1:217–238.Google Scholar
3.UNODOC. World Drug Report. United Nations Publications. New York, 2013; Sales E13.XI.6.Google Scholar
4.Bloomfield, MA, Morgan, CJ, Egerton, A, Kapur, S, Curran, HV, Howes, OD. Dopaminergic function in cannabis users and its relationship to cannabis-induced psychotic symptoms. Biol Psychiatry 2013;5:470–478.Google Scholar
5.Iversen, L. Cannabis and the brain. Brain 2003;6:1252–1270.Google Scholar
6.Murray, RM, Morrison, PD, Henquet, C, Di Forti, M. Cannabis, the mind and society: the hash realities. Nat Rev Neurosci 2007;11:885–895.Google Scholar
7.Wiley, JL. 1999 Cannabis: discrimination of ‘internal bliss’? Pharmacol Biochem Behav 1999;64:257–260.CrossRefGoogle ScholarPubMed
8.Gardner, EL, Paredes, W, Smith, Det al. Facilitation of brain stimulation reward by delta 9-tetrahydrocannabinol. Psychopharmacology 1988;96:142–144.Google Scholar
9.Gardner, EL, Lowinson, JH. Marijuana's interaction with brain reward systems: update 1991. Pharmacol Biochem Behav 1991;40:571–580.Google Scholar
10.Chen, JP, Paredes, W, Li, J, Smith, D, Lowinson, J, Gardner, EL. Delta 9-tetrahydrocannabinol produces naloxone-blockable enhancement of presynaptic basal dopamine efflux in nucleus accumbens of conscious, freely-moving rats as measured by intracerebral microdialysis. Psychopharmacology 1990;102:156–162.CrossRefGoogle ScholarPubMed
11.Xi, ZX, Gilbert, J, Campos, ACet al. Blockade of mesolimbic dopamine D3 receptors inhibits stress-induced reinstatement of cocaine-seeking in rats. Psychopharmacology 2004;176:57–65.CrossRefGoogle ScholarPubMed
12.Hillard, CJ, Bloom, AS, Houslay, MD. Effects of delta 9-tetrahydrocannabinol on glucagon receptor coupling to adenylate cyclase in rat liver plasma membranes. Biochem Pharmacol 1986;35:2797–2803.Google Scholar
13.Devane, WA, Dysarz, FA 3rd, Johnson, MR, Melvin, LS, Howlett, AC. Determination and characterization of a cannabinoid receptor in rat brain. Mol Pharmacol 1988;34:605–613.Google Scholar
14.Matsuda, LA, Lolait, SJ, Brownstein, MJ, Young, AC, Bonner, TI. Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature 1990;346:561–564.CrossRefGoogle ScholarPubMed
15.Mechoulam, R, Hanus, L. A historical overview of chemical research on cannabinoids. Chem Phys Lipids 2000;108:1–13.Google Scholar
16.Freund, TF, Katona, I, Piomelli, D. Role of endogenous cannabinoids in synaptic signaling. Physiol Rev 2003;83:1017–1066.Google Scholar
17.Katona, I, Freund, TF. Endocannabinoid signaling as a synaptic circuit breaker in neurological disease. Nat Med 2008;14:923–930.CrossRefGoogle ScholarPubMed
18.DI Marzo, V, Bifulco, M, De Petrocellis, L. The endocannabinoid system and its therapeutic exploitation. Nat Rev Drug Discov 2004;3:771–784.Google Scholar
19.Onaivi, ES. An endocannabinoid hypothesis of drug reward and drug addiction. Ann N Y Acad Sci 2008;1139:412–421.Google Scholar
20.Gardner, EL, Vorel, SR. Cannabinoid transmission and reward-related events. Neurobiol Dis 1998;5:502–533.Google Scholar
21.Serrano, A, Parsons, LH. Endocannabinoid influence in drug reinforcement, dependence and addiction-related behaviors. Pharmacol Ther 2011;132:215–241.CrossRefGoogle ScholarPubMed
22.Maldonado, R, Valverde, O, Berrendero, F. Involvement of the endocannabinoid system in drug addiction. Trends Neurosci 2006;29:225–232.Google Scholar
23.Herkenham, M, Lynn, AB, Johnson, MR, Melvin, LS, De Costa, BR, Rice, KC. Characterization and localization of cannabinoid receptors in rat brain: a quantitative in vitro autoradiographic study. J Neurosci 1999;11:563–583.Google Scholar
24.Ueda, N, Goparaju, SK, Katayama, K, Kurahashi, Y, Suzuki, H, Yamamoto, S. A hydrolase enzyme inactivating endogenous ligands for cannabinoid receptors. J Med Invest 1998;45:27–36.Google Scholar
25.Atwood, BK, Mackie, K. CB2: a cannabinoid receptor with an identity crisis. Br J Pharmacol 2010;160:467–479.Google Scholar
26.Hermann, H, Marsicano, G, Lutz, B. Coexpression of the cannabinoid receptor type 1 with dopamine and serotonin receptors in distinct neuronal subpopulations of the adult mouse forebrain. Neuroscience 2002;109:451–460.Google Scholar
27.Tanda, G, Munzar, P, Goldberg, SR. Self-administration behavior is maintained by the psychoactive ingredient of marijuana in squirrel monkeys. Nat Neurosci 2000;3:1073–1074.Google Scholar
28.Onaivi, ES. Commentary: functional neuronal CB2 cannabinoid receptors in the CNS. Curr Neuropharmacol 2011;9:205–208.CrossRefGoogle ScholarPubMed
29.Mansbach, RS, Nicholson, KL, Martin, BR, Balster, RL. Failure of delta(9)-tetrahydrocannabinol and CP 55,940 to maintain intravenous self-administration under a fixed-interval schedule in rhesus monkeys. Behav Pharmacol 1994;5:219–225.Google Scholar
30.Tanda, G, Pontieri, FE, Di Chiara, G. Cannabinoid and heroin activation of mesolimbic dopamine transmission by a common mu1 opioid receptor mechanism. Science 1997;276:2048–2050.Google Scholar
31.Justinova, Z, Solinas, M, Tanda, G, Redhi, GH, Goldberg, SR. The endogenous cannabinoid anandamide and its synthetic analog R(+)-methanandamide are intravenously self-administered by squirrel monkeys. J Neurosci 2005;25:5645–5650.CrossRefGoogle ScholarPubMed
32.Justinová, Z, Yasar, S, Redhi, GH, Goldberg, SR. The endogenous cannabinoid 2-arachidonoylglycerol is intravenously self-administered by squirrel monkeys. J Neurosci 2011;31:7043–7048.Google Scholar
33.Tanda, G, Goldberg, SR. Cannabinoids: reward, dependence, and underlying neurochemical mechanisms – a review of recent preclinical data. Psychopharmacology 2003;169:115–134.Google Scholar
34.Justinova, Z, Tanda, G, Redhi, GH, Goldberg, SR. Self-administration of delta 9-tetrahydrocannabinol (THC) by drug naive squirrel monkeys. Psychopharmacology 2003;169:135–140.Google Scholar
35.Solinas, M, Yasar, S, Goldberg, SR. Endocannabinoid system involvement in brain reward processes related to drug abuse. Pharmacol Res 2007;56:393–405.Google Scholar
36.Schlosburg, JE, Carlson, BLA, Ramesh, Det al. Inhibitors of endocannabinoid-metabolizing enzymes reduce precipitated withdrawal responses in THC-dependent mice. AAPS J 2009;11:342–352.CrossRefGoogle ScholarPubMed
37.Pava, MJ, Woodward, JJ. A review of the interactions between alcohol and the endocannabinoid system: implications for alcohol dependence and future directions for research. Alcohol 2012;46:185–204.Google Scholar
38.Colombo, G, Orrù, A, Lai, Pet al. The cannabinoid CB1 receptor antagonist, rimonabant, as a promising pharmacotherapy for alcohol dependence: preclinical evidence. Mol Neurobiol 2007;36:102–112.Google Scholar
39.Gonzalez, S, Fernandez-Ruiz, J, Sparpaglione, V, Parolaro, D, Ramos, JA. Chronic exposure to morphine, cocaine or ethanol in rats produced different effects in brain cannabinoid CB(1) receptor binding and mRNA levels. Drug Alcohol Depend 2002;66:77–84.Google Scholar
40.Caille, S, Alvarez-Jaimes, L, Polis, I, Stouffer, DG, Parsons, LH. Specific alterations of extracellular endocannabinoid levels in the nucleus accumbens by ethanol, heroin, and cocaine self-administration. J Neurosci 2007;27:3695–3702.Google Scholar
41.Gonzalez, S, Valenti, M, De Miguel, Ret al. Changes in endocannabinoid contents in reward-related brain regions of alcohol-exposed rats, and their possible relevance to alcohol relapse. Br J Pharmacol 2004;143:455–464.Google Scholar
42.Basavarajappa, BS, Yalamanchili, R, Cravatt, BF, Cooper, TB, Hungund, BL. Increased ethanol consumption and preference and decreased ethanol sensitivity in female FAAH knockout mice. Neuropharmacology 2006;50:834–844.Google Scholar
43.Gallate, JE, Saharov, T, Mallet, PE, Mcgregor, IS. Increased motivation for beer in rats following administration of a cannabinoid CB1 receptor agonist. Eur J Pharmacol 1999;370:233–240.Google Scholar
44.Hungund, BL, Szakall, I, Adam, A, Basavarajappa, BS, Vadasz, C. Cannabinoid CB1 receptor knockout mice exhibit markedly reduced voluntary alcohol consumption and lack alcohol-induced dopamine release in the nucleus accumbens. J Neurochem 2003;84:698–704.Google Scholar
45.Thanos, PK, Dimitrakakis, ES, Rice, O, Gifford, A, Volkow, ND. Ethanol self-administration and ethanol conditioned place preference are reduced in mice lacking cannabinoid CB1 receptors. Behav Brain Res 2005;164:206–213.Google Scholar
46.Serra, S, Carai, MA, Brunetti, Get al. The cannabinoid receptor antagonist SR 141716 prevents acquisition of drinking behavior in alcohol-preferring rats. Eur J Pharmacol 2001;430:369–371.CrossRefGoogle ScholarPubMed
47.Gessa, GL, Serra, S, Vacca, G, Carai, MA, Colombo, G. Suppressing effect of the cannabinoid CB1 receptor antagonist, SR147778, on alcohol intake and motivational properties of alcohol in alcohol-preferring sP rats. Alcohol Alcohol 2005;40:46–53.CrossRefGoogle ScholarPubMed
48.Soyka, M, Koller, G, Schmidt, Pet al. Cannabinoid receptor 1 blocker rimonabant (SR 141716) for treatment of alcohol dependence: results from a placebo-controlled, double-blind trial. J Clin Psychopharmacol 2008;28:317–324.Google Scholar
49.George, DT, Herion, DW, Jones, CLet al. Rimonabant (SR141716) has no effect on alcohol self-administration or endocrine measures in nontreatment-seeking heavy alcohol drinkers. Psychopharmacology 2010;208:37–44.Google Scholar
50.Ortega-Álvaro, A, Ternianov, A, Aracil-Fernández, A, Navarrete, F, García-Gutiérrez, MS, Manzanares, J. Role of cannabinoid CB(2) receptor in the reinforcing actions of ethanol. Addict Biol 2013; doi:10.1111/adb.12076.Google Scholar
51.Arnold, JC. The role of endocannabinoid transmission in cocaine addiction. Pharmacol Biochem Behav 2005;81:396–406.Google Scholar
52.Wiskerke, J, Pattij, T, Schoffelmeer, AN, De Vries, TJ. The role of CB1 receptors in psychostimulant addiction. Addict Biol 2008;13:225–238.Google Scholar
53.De Vries, TJ, Schoffelmeer, AN. receptors control conditioned drug seeking. Trends Pharmacol Sci 2005;26:420–426.Google Scholar
54.Fitzgerald, ML, Shobin, E, Pickel, VM. Cannabinoid modulation of the dopaminergic circuitry: implications for limbic and striatal output. Prog Neuropsychopharmacol Biol Psychiatry 2012;38:21–29.Google Scholar
55.Solinas, M, Justinova, Z, Goldberg, SR, Tanda, G. Anandamide administration alone and after inhibition of fatty acid amide hydrolase (FAAH) increases dopamine levels in the nucleus accumbens shell in rats. J Neurochem 2006;98:408–419.Google Scholar
56.Sanchis-Segura, C, Spanagel, R. Behavioural assessment of drug reinforcement and addictive features in rodents: an overview. Addict Biol 2006;11:2–38.Google Scholar
57.Corbille, AG, Valjent, E, Marsicano, Get al. Role of cannabinoid type 1 receptors in locomotor activity and striatal signaling in response to psychostimulants. J Neurosci 2007;27:6937–6947.Google Scholar
58.Filip, M, Golda, A, Zaniewska, Met al. Involvement of cannabinoid CB1 receptors in drug addiction: effects of rimonabant on behavioral responses induced by cocaine. Pharmacol Rep 2006;58:806–819.Google Scholar
59.Soria, G, Mendizabal, V, Tourino, Cet al. Lack of CB1 cannabinoid receptor impairs cocaine self-administration. Neuropsychopharmacology 2005;30:1670–1680.CrossRefGoogle ScholarPubMed
60.Xi, ZX, Spiller, K, Pak, ACet al. Cannabinoid CB1 receptor antagonists attenuate cocaine's rewarding effects: experiments with self-administration and brain-stimulation reward in rats. Neuropsychopharmacology 2008;33:1735–1745.Google Scholar
61.Vaughn, LK, Mantsch, JR, Vranjkovic, Oet al. Cannabinoid receptor involvement in stress-induced cocaine reinstatement: potential interaction with noradrenergic pathways. Neuroscience 2012;204:117–124.Google Scholar
62.Alvaro-Bartolome, M, Garcia-Sevilla, JÁ. Dysregulation of cannabinoid CB receptor and associated signaling networks in brains of cocaine addicts and cocaine-treated rodents. Neuroscience 2013;247C:294–308.Google Scholar
63.Aracil-Fernandez, A, Trigo, JM, Garcia-Gutierrez, MSet al. Decreased cocaine motor sensitization and self-administration in mice overexpressing cannabinoid CB(2) receptors. Neuropsychopharmacology 2012;37:1749–1763.Google Scholar
64.Xi, ZX, Peng, XQ, Li, Xet al. Brain cannabinoid CB(2) receptors modulate cocaine's actions in mice. Nat Neurosci 2011;14:1160–1166.Google Scholar
65.Centoze, D, Battista, N, Rossi, Set al. A critical interaction between dopamine D2 receptors and endocannabinoids mediates the effects of cocaine on striatal gabaergic transmission. Neuropsychopharmacology 2004;29:1488–1497.Google Scholar
66.Callie, S, Alvarez-Jaimes, L, Polis, I, Stouffer, DG, Parsons, LH. Specific alterations of extracellular endocannabinoid levels in the nucleus accumbens by ethanol, heroin, and cocaine self-administration. J Neurosci 2007;27:3695–3702.CrossRefGoogle Scholar
67.Justinova, Z, Panlilio, LV, Goldberg, SR. Drug addiction. Curr Top Behav Neurosci 2009;1:309–346.Google Scholar
68.Adamczyk, P, Mccreary, AC, Przegalinski, E, Mierzejewski, P, Bienkowski, P, Filip, M. The effects of fatty acid amide hydrolase inhibitors on maintenance of cocaine and food self-administration and on reinstatement of cocaine-seeking and food-taking behavior in rats. J Physiol Pharmacol 2009;60:119–125.Google ScholarPubMed
69.Vinklerova, J, Novakova, J, Sulcova, A. Inhibition of methamphetamine self-administration in rats by cannabinoid receptor antagonist AM 251 J Psychopharmacol 2002;16:139–143.CrossRefGoogle ScholarPubMed
70.Anggadiredja, K, Nakamichi, M, Hiranita, Tet al.Endocannabinoid system modulates relapse to methamphetamine seeking: possible mediation by the arachidonic acid cascade. Neuropsychopharmacology 2004;29:1470–1478.Google Scholar
71.Thiemann, G, van der Stelt, M, Petrosino, S, Molleman, A, Di Marzo, V, Hasenohrl, RU. The role of the CB1 cannabinoid receptor and its endogenous ligands, anandamide and 2-arachidonoylglycerol, in amphetamine-induced behavioural sensitization. Behav Brain Res 2008;187:289–296.Google Scholar
72.Runkorg, K, Orav, L, Koks, S, Matsui, T, Volke, V, Vasar, E. Rimonabant attenuates amphetamine sensitisation in a CCK2 receptor-dependent manner. Behav Brain Res 2012;226:335–339.Google Scholar
73.Gutierrez-Lopez, MD, Llopis, N, Feng, S, Barrett, DA, O'Shea, E, Colado, MI. Involvement of 2-arachidonoyl glycerol in the increased consumption of and preference for ethanol of mice treated with neurotoxic doses of methamphetamine. Br J Pharmacol 2010;160:772–783.Google Scholar
74.Eisenstein, SA, Holmes, PV, Hohmann, AG. Endocannabinoid modulation of amphetamine sensitization is disrupted in a rodent model of lesion-induced dopamine dysregulation. Synapse 2009;63:941–950.Google Scholar
75.Scavone, JL, Sterling, RC, Van Bockstaele, EJ. Cannabinoid and opioid interactions: implications for opiate dependence and withdrawal. Neuroscience 2013;248:637–654.Google Scholar
76.Tucci, S. Addiction and pain: cannabinoid and opioid interactions. Curr Drug Targets 2010;11:392.Google Scholar
77.Solinas, M, Zangen, A, Thiriet, N, Goldberg, SR. Beta-endorphin elevations in the ventral tegmental area regulate the discriminative effects of delta-9-tetrahydrocannabinol. Eur J Neurosci 2004;19:3183–3192.Google Scholar
78.Chaperon, F, Soubrie, P, Puech, AJ, Thiebot, MH. Involvement of central cannabinoid (CB1) receptors in the establishment of place conditioning in rats. Psychopharmacology 1998;135:324–332.CrossRefGoogle ScholarPubMed
79.Navarro, M, Carrera, MR, Fratta, Wet al. Functional interaction between opioid and cannabinoid receptors in drug self-administration. J Neurosci 2001;21:5344–5350.Google Scholar
80.Fattore, L, Spano, MS, Cossu, G, Deiana, S, Fratta, W. Cannabinoid mechanism in reinstatement of heroin-seeking after a long period of abstinence in rats. Eur J Neurosci 2003;17:1723–1726.CrossRefGoogle ScholarPubMed
81.Cossu, G, Ledent, C, Fattore, Let al. Cannabinoid CB1 receptor knockout mice fail to self-administer morphine but not other drugs of abuse. Behav Brain Res 2001;118:61–65.Google Scholar
82.Ledent, C, Valverde, O, Cossu, Get al. Unresponsiveness to cannabinoids and reduced addictive effects of opiates in CB1 receptor knockout mice. Science 1999;283:401–404.Google Scholar
83.Ramesh, D, Haney, M, Cooper, ZD. Dual inhibition of endocannabinoid catabolic enzymes produces enhanced antiwithdrawal effects in morphine-dependent mice. Neuropsychopharmacology 2013;38:1039–1049.Google Scholar
84.Raby, WN, Carpenter, KM, Rothenberg, Jet al.Intermittent marijuana use is associated with improved retention in naltrexone treatment for opiate-dependence. Am J Addict 2009;18:301–308.Google Scholar
85.Xi, ZX, Spiller, K, Gardner, EL. Mechanism-based medication development for the treatment of nicotine dependence. Acta Pharmacol Sin 2009;30:723–739.Google Scholar
86.Peters, EN, Schwartz, RP, Wang, S, O'Grady, KE, Blanco, C. Psychiatric, psychosocial, and physical health correlates of co-occurring cannabis use disorders and nicotine dependence. Drug Alcohol Depend 2014;134:228–234.CrossRefGoogle ScholarPubMed
87.Valjent, E, Mitchell, JM, Besson, MJ, Caboche, J, Maldonado, R. Behavioural and biochemical evidence for interactions between delta 9-tetrahydrocannabinol and nicotine. Br J Pharmacol 2002;135:564–578.CrossRefGoogle ScholarPubMed
88.Cohen, C, Perrault, G, Voltz, C, Steinberg, R, Soubrie, P. SR141716, a central cannabinoid (CB(1)) receptor antagonist, blocks the motivational and dopamine-releasing effects of nicotine in rats. Behav Pharmacol 2002;13:451–463.Google Scholar
89.Foll, LE, Goldberg, B, Rimonabant, SR. A CB1 antagonist, blocks nicotine-conditioned place preferences. Neuroreport 2004;15:2139–2143.Google Scholar
90.Cohen, C, Kodas, E, Griebel, G. CB1 receptor antagonists for the treatment of nicotine addiction. Pharmacol Biochem Behav 2005;81:387–395.Google Scholar
91.Castane, A. Lack of CB1 cannabinoid receptors modifies nicotine behavioural responses, but not nicotine abstinence. Neuropharmacology 2002;43:857–867.Google Scholar
92.Ignatowska-Jankowska, BMet al. The cannabinoid CB2 receptor is necessary for nicotine-conditioned place preference, but not other behavioral effects of nicotine in mice. Psychopharmacology 2013;229:591–601.Google Scholar
93.Gelfand, EV, Cannon, CP. Rimonabant: a selective blocker of the cannabinoid CB1 receptors for the management of obesity, smoking cessation and cardiometabolic risk factors. Expert Opin Investig Drugs 2006;15:307–315.Google Scholar
94.Rigotti, NA, Gonzales, D, Dale, LC, Lawrence, D, Chang, Y, Group, CS. A randomized controlled trial of adding the nicotine patch to rimonabant for smoking cessation: efficacy, safety and weight gain. Addiction 2009;104:266–276.Google Scholar
95.Muldoon, PP, Lichtman, AH, Parsons, LH, Damaj, MI. The role of fatty acid amide hydrolase inhibition in nicotine reward and dependence. Life Sci 2013;92:458–462.Google Scholar
96.Luque-Rojas, MJ, Galeano, P, Suarez, Jet al. Hyperactivity induced by the dopamine D2/D3 receptor agonist quinpirole is attenuated by inhibitors of endocannabinoid degradation in mice. Int J Neuropsychopharmacol 2013;16:661–676.Google Scholar
97.Clark, KH, Wiley, CA, Bradberry, CW. Psychostimulant abuse and neuroinflammation: emerging evidence of their interconnection. Neurotox Res 2013;23:174–188.Google Scholar
98.Sadasivan, S, Pond, BB, Pani, AK, Qu, C, Jiao, Y, Smeyne, RJ. Methylphenidate exposure induces dopamine neuron loss and activation of microglia in the basal ganglia of mice. PLoS One 2012;7:e33693.Google Scholar
99.Ramamoorthy, S, Ramamoorthy, JD, Prasad, PDet al. Regulation of the human serotonin transporter by interleukin-1 beta. Biochem Biophys Res Commun 1995;216:560–567.Google Scholar
100.Zalcman, S, Savina, I, Wise, RA. Interleukin-6 increases sensitivity to the locomotor-stimulating effects of amphetamine in rats. Brain Res 1999;847:276–283.Google Scholar
101.Zalcman, SS. Interleukin-2 potentiates novelty- and GBR 12909-induced exploratory activity. Brain Res 2001;899:1–9.Google Scholar
102.Ho, BT, Lu, JG, Huo, YYet al. Neurochemical basis of interleukin 2-modified discrimination behaviour. Cytokine 1994;6:365–367.Google Scholar
103.Nakajima, A, Yamada, K, Nagai, Tet al. Role of tumor necrosis factor-alpha in methamphetamine-induced drug dependence and neurotoxicity. J Neurosci 2004;24:2212–2225.Google Scholar
104.Yamada, K, Nabeshima, T. Pro- and anti-addictive neurotrophic factors and cytokines in psychostimulant addiction: mini review. Ann N Y Acad Sci 2004;1025:198–204.Google Scholar
105.Gan, X, Zhang, L, Newton, Tet al. Cocaine infusion increases interferon-gamma and decreases interleukin-10 in cocaine-dependent subjects. Clin Immunol Immunopathol 1998;89:181–190.Google Scholar
106.Avila, AH, Morgan, CA, Bayer, BM. Stress-induced suppression of the immune system after withdrawal from chronic cocaine. J Pharmacol Exp Ther 2003;305:290–297.Google Scholar
107.Llorente-Garcia, E, Abreu-Gonzalez, P, Gonzalez-Hernandez, MC. Hematological, immunological and neurochemical effects of chronic amphetamine treatment in male rats. J Physiol Biochem 2009;65:61–69.CrossRefGoogle ScholarPubMed
108.Lee, YW, Hennig, B, Yao, J, Toborek, M. Methamphetamine induces AP-1 and NF-kappaB binding and transactivation in human brain endothelial cells. J Neurosci Res 2001;66:583–591.Google Scholar
109.Bogdal, J, Cichecka, K, Kirchmayer, S, Mika, M, Tarnawski, A. Immunoglobulins in chronic alcoholics: relation to liver histology and effect of 2-month abstinence therapy. Arch Immunol Ther Exp 1976;24:799–805.Google Scholar
110.Redwine, L, Dang, J, Hall, M, Irwin, M. Disordered sleep, nocturnal cytokines, and immunity in alcoholics. Psychosom Med 2003;65:75–85.Google Scholar
111.Blank, SE, Duncan, DA, Meadows, GG. Suppression of natural killer cell activity by ethanol consumption and food restriction. Alcohol Clin Exp Res 1991;15:16–22.Google Scholar
112.Cohen, PR, Hebert, AA, Adler-Storthz, K. Focal epithelial hyperplasia: Heck disease. Pediatr Dermatol 1993;10:245–251.Google Scholar
113.Schleifer, SJ, Keller, SE, Czaja, S. Major depression and immunity in alcohol-dependent persons. Brain Behav Immun 2006;20:80–91.Google Scholar
114.Pettinati, HM, O'brien, CP, Dundon, WD. Current status of co-occurring mood and substance use disorders: a new therapeutic target. Am J Psychiatry 2013;170:23–30.Google Scholar
115.Szabo, G, Mandrekar, P, Petrasek, J, Catalano, D. The unfolding web of innate immune dysregulation in alcoholic liver injury. Alcohol Clin Exp Res 2011;35:782–786.Google Scholar
116.Khoruts, A, Stahnke, L, Mcclain, CJ, Logan, G, Allen, JI. Circulating tumor necrosis factor, interleukin-1 and interleukin-6 concentrations in chronic alcoholic patients. Hepatology 1991;13:267–276.Google Scholar
117.Nicolaou, C, Chatzipanagiotou, S, Tzivos, D, Tzavellas, EO, Boufidou, F, Liappas, IA. Serum cytokine concentrations in alcohol-dependent individuals without liver disease. Alcohol 2004;32:243–247.Google Scholar
118.Chiva-Blanch, G, Urpi-Sarda, M, Llorach, Ret al. Differential effects of polyphenols and alcohol of red wine on the expression of adhesion molecules and inflammatory cytokines related to atherosclerosis: a randomized clinical trial. Am J Clin Nutr 2012;95:326–334.Google Scholar
119.Cook, RT. Cytoplasmic cytokines in the T cells of chronic alcoholics. Alcohol Clin Exp Res 2000;24:241–243.Google Scholar
120.Mandrekar, P, Bellerose, G, Szabo, G. Inhibition of NF-kappa B binding correlates with increased nuclear glucocorticoid receptor levels in acute alcohol-treated human monocytes. Alcohol Clin Exp Res 2002;26:1872–1879.Google Scholar
121.Zhao, YN, Wang, F, Fan, YX, Ping, GF, Yang, JY, Wu, CF. Activated microglia are implicated in cognitive deficits, neuronal death, and successful recovery following intermittent ethanol exposure. Behav Brain Res 2013;236:270–282.Google Scholar
122.Pascual, M, Fernandez-Lizarbe, S, Guerri, C. Role of TLR4 in ethanol effects on innate and adaptive immune responses in peritoneal macrophages. Immunol Cell Biol 2011;89:716–727.Google Scholar
123.Szabo, G, Mandrekar, P, Oak, S, Mayerle, J. Effect of ethanol on inflammatory responses. Implications for pancreatitis. Pancreatology 2007;7:115–123.Google Scholar
124.Fang, H, Wang, PF, Zhou, Y, Wang, YC, Yang, QW. Toll-like receptor 4 signaling in intracerebral hemorrhage-induced inflammation and injury. J Neuroinflammation 2013;10:27.CrossRefGoogle ScholarPubMed
125.Agrawal, RG, Hewetson, A, George, CM, Syapin, PJ, Bergeson, SE. Minocycline reduces ethanol drinking. Brain Behav Immun 2001;25(Suppl. 1):S165–S169.CrossRefGoogle Scholar
126.Hutchinson, MR, Northcutt, AL, Chao, LWet al. Minocycline suppresses morphine-induced respiratory depression, suppresses morphine-induced reward, and enhances systemic morphine-induced analgesia. Brain Behav Immun 2008;22:1248–1256.Google Scholar
127.Kovacs, KJ. Microglia and drug-induced plasticity in reward-related neuronal circuits. Front Mol Neurosci 2012;5:74.Google Scholar
128.Thomas, DM, Francescutti-Verbeem, DM, Kuhn, DM. Methamphetamine-induced neurotoxicity and microglial activation are not mediated by fractalkine receptor signaling. Journal Neurochem 2008;106:696–705.Google Scholar
129.Espinosa-Oliva, AM, De Pablos, RM, Sarmiento, Met al. Role of dopamine in the recruitment of immune cells to the nigro-striatal dopaminergic structures. Neurotoxicology 2014;41:89–101.CrossRefGoogle Scholar
130.Shah, A, Silverstein, PS, Singh, DP, Kumar, A. Involvement of metabotropic glutamate receptor 5, AKT/PI3K signaling and NF-kappaB pathway in methamphetamine-mediated increase in IL-6 and IL-8 expression in astrocytes. J Neuroinflammation 2012;9:52.Google Scholar
131.Galiegue, S, Mary, S, Marchand, J, Dussossoy, D, Carriere, D. Expression of central and peripheral cannabinoid receptors in human immune tissues and leukocyte subpopulations. Eur J Biochem 1995;232:54–61.Google Scholar
132.Kerr, DM, Harhen, B, Okine, BNet al. The monoacylglycerol lipase inhibitor JZL184 attenuates LPS-induced increases in cytokine expression in the rat frontal cortex and plasma: differential mechanisms of action. Br J Pharmacol 2013;169:808–819.Google Scholar
133.Klein, TW, Friedman, H, Specter, S. Marijuana, immunity and infection. J Neuroimmunol 1998;83:102–115.Google Scholar
134.Klein, TW, Newton, C, Larsen, Ket al. The cannabinoid system and immune modulation. J Leukoc Biol 2003;74:486–496.Google Scholar
135.Zhang, J, Chen, C. Endocannabinoid 2-arachidonoylglycerol protects neurons by limiting COX-2 elevation. J Biol Chem 2008;283:22601–22611.Google Scholar
136.Sancho, R, Calzado, MA, Di Marzo, V, Appendino, G, Munoz, E. Anandamide inhibits nuclear factor-kappaB activation through a cannabinoid receptor-independent pathway. Mol Pharmacol 2003;63:429–438.Google Scholar
137.Navarrete, CM, Fiebich, BL, De Vinuesa, AGet al. Opposite effects of anandamide and N-arachidonoyl dopamine in the regulation of prostaglandin E and 8-iso-PGF formation in primary glial cells. J Neurochem 2009;109:452–464.Google Scholar
138.Nomura, DK, Morrison, BE, Blankman, JLet al. Endocannabinoid hydrolysis generates brain prostaglandins that promote neuroinflammation. Science 2011;334:809–813.Google Scholar
139.Shi, J, Johansson, J, Woodling, NS, Wang, Q, Montine, TJ, Andreasson, K. The prostaglandin E2 E-prostanoid 4 receptor exerts anti-inflammatory effects in brain innate immunity. J Immunol 2010;184:7207–7218.Google Scholar
140.Croxford, JL, Miller, SD. Immunoregulation of a viral model of multiple sclerosis using the synthetic cannabinoid R+WIN55,212. J Clin Invest 2003;111:1231–1240.Google Scholar
141.Eljaschewitsch, E, Witting, A, Mawrin, Cet al. The endocannabinoid anandamide protects neurons during CNS inflammation by induction of MKP-1 in microglial cells. Neuron 2006;49:67–79.Google Scholar
142.Mestre, L, Correa, F, Arevalo-Martin, Aet al. Pharmacological modulation of the endocannabinoid system in a viral model of multiple sclerosis. J Neurochem 2005;92:1327–1339.Google Scholar
143.Ortega-Gutierrez, S. Therapeutic perspectives of inhibitors of endocannabinoid degradation. Curr Drug Targets CNS Neurol Disord 2005;4:697–707.Google Scholar
144.Sun, Y, Bennet, A. Cannabinoids: a new group of agonists of PPARs. PPAR Res 2007;23513:49–55.Google Scholar
145.Stahel, PF, Smith, WR, Bruchis, J, Rabb, CH. Peroxisome proliferator-activated receptors: ‘key’ regulators of neuroinflammation after traumatic brain injury. PPAR Res 2008;2008:538141.Google Scholar
146.O’Sullivan, S, Bennet, A, Kendal, D, Randall, M. Cannabinoids and peroxisome proliferator-activated receptor gamma (PPARγ). Proceedings of the International Cannabinoid Research Society (ICRS’06), Tihany, Hungary, 2006; 59.Google Scholar
147.Enayatfard, L, Rostami, F, Nasoohi, S, Oryan, S, Ahmadiani, A, Dargahi, L. Dual role of PPAR-gamma in induction and expression of behavioral sensitization to cannabinoid receptor agonist WIN55,212-2. Neuromolecular Med 2013;15:523–535.Google Scholar
148.Liu, PC, Huber, R, Stow, MDet al. Induction of endogenous genes by peroxisome proliferator activated receptor alpha ligands in a human kidney cell line and in vivo. J Steroid Biochem Mol Biol 2003;85:71–79.Google Scholar
149.Rockwell, CE, Kaminski, NE. A cyclooxygenase metabolite of anandamide causes inhibition of interleukin-2 secretion in murine splenocytes. J Pharmacol Exp Ther 2004;311:683–690.Google Scholar
150.Rockwell, CE, Snider, NT, Thompson, JT, Vanden Heuvel, JP, Kaminski, NE. Interleukin-2 suppression by 2-arachidonyl glycerol is mediated through peroxisome proliferator-activated receptor gamma independently of cannabinoid receptors 1 and 2. Mol Pharmacol 2006;70:101–111.Google Scholar
151.Combs, CK, Johonson, DE, Karlo, JC, Cannady, SB, Landreth, GE. Inflammatory mechanism in Alzheimer’s disease: inhibition of beta-amyloid-stimulated pro-inflammatoryresponse and neurotoxicity by PPARγ. J Neurosci 2000;20:558–567.Google Scholar
152.Colino, M, Aragno, M, Mastrocola, Ret al. Modulation of the oxidative stress and inflammatory response by PPAR-γ agonists in the hippocampus of rats exposed to cerebral ischemia-reperfusion. Eur J Pharmacol 2006;530:70–80.Google Scholar
153.Rockwell, CEet al. Interleukin-2 supression by 2-arachidonyl glycerol is mediated through peroxisome proliferator-activated receptor gamma independently of cannabinoid receptors 1 and 2. Mol Pharmacol 2006;70:101–111.Google Scholar
154.Le Foll, B, Di Ciano, P, Panlilio, LV, Goldberg, SR, Ciccocioppo, R. Peroxisome proliferator-activated receptor (PPAR) agonsts as promising new medications for drug addiction: preclinical evidence. Curr Drug Targets 2013;14:768–776.Google Scholar
155.Matute, C, Alberdi, E, Ibarretxe, G, Sanchez-Gomez, MV. Excitotoxicity in glial cells. Eur J Pharmacol 2002;447:239–246.Google Scholar
156.Ehrhart, J, Obregon, D, Mori, Tet al. Stimulation of cannabinoid receptor 2 (CB2) suppresses microglial activation. J Neuroinflammation 2005;2:29.Google Scholar
157.Albayram, O, Alferink, J, Pitsch, Jet al. Role of CB1 cannabinoid receptors on GABAergic neurons in brain aging. Proc Natl Acad Sci U S A 2011;108:11256–11261.Google Scholar
158.Mnich, SJ, Hiebsch, RR, Huff, RM, Muthian, S. Anti-inflammatory properties of CB1-receptor antagonist involves beta2 adrenoceptors. J Pharmacol Exp Ther 2010;333:445–453.Google Scholar
159.Correa, F, Mestre, L, Docagne, F, Guaza, C. Activation of cannabinoid CB2 receptor negatively regulates IL-12p40 production in murine macrophages: role of IL-10 and ERK1/2 kinase signaling. Br J Pharmacol 2005;145:441–448.Google Scholar
160.Ashton, JC. Cannabinoids for the treatment of inflammation. Curr Opin Investig Drugs 2007;8:373–384.Google Scholar
161.Merighi, S, Gessi, S, Varani, Ket al. Cannabinoid CB(2) receptors modulate ERK-1/2 kinase signalling and NO release in microglial cells stimulated with bacterial lipopolysaccharide. Br J Pharmacol 2012;165:1773–1788.Google Scholar
162.Morales, M, Bonci, A. Getting to the ore of addiction: hooking CB2 receptor into drug abuse? Nat Med 2012;18:504–505.Google Scholar
163.Merighi, S, Gessi, S, Varani, K, Fazzi, D, Mirandola, P, Borea, PA. Cannabinoid CB(2) receptor attenuates morphine-induced inflammatory responses in activated microglial cells. Br J Pharmacol 2012;166:2371–2385.Google Scholar
164.Xi, ZX, Peng, XQ, Li, Xet al. Brain cannabinoid CB2 receptors modulate cocaine’s actions in mice. Nat Neurosci 2011;14:1100–1102.Google Scholar