1.American Psychiatric Association. Diagnostic and statistical manual of mental disorders, text revision, 4th edn. Washington, DC: American Psychiatric Association, 2000.
2.Koob, GF, Volkow, ND. Neurocircuitry of addiction. Neuropsychopharmacology 2010;1:217–238.
3.UNODOC. World Drug Report. United Nations Publications. New York, 2013; Sales E13.XI.6.
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.
5.Iversen, L. Cannabis and the brain. Brain 2003;6:1252–1270.
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.
7.Wiley, JL. 1999 Cannabis: discrimination of ‘internal bliss’? Pharmacol Biochem Behav 1999;64:257–260.
8.Gardner, EL, Paredes, W, Smith, Det al. Facilitation of brain stimulation reward by delta 9-tetrahydrocannabinol. Psychopharmacology 1988;96:142–144.
9.Gardner, EL, Lowinson, JH. Marijuana's interaction with brain reward systems: update 1991. Pharmacol Biochem Behav 1991;40:571–580.
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.
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.
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.
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.
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.
15.Mechoulam, R, Hanus, L. A historical overview of chemical research on cannabinoids. Chem Phys Lipids 2000;108:1–13.
16.Freund, TF, Katona, I, Piomelli, D. Role of endogenous cannabinoids in synaptic signaling. Physiol Rev 2003;83:1017–1066.
17.Katona, I, Freund, TF. Endocannabinoid signaling as a synaptic circuit breaker in neurological disease. Nat Med 2008;14:923–930.
18.DI Marzo, V, Bifulco, M, De Petrocellis, L. The endocannabinoid system and its therapeutic exploitation. Nat Rev Drug Discov 2004;3:771–784.
19.Onaivi, ES. An endocannabinoid hypothesis of drug reward and drug addiction. Ann N Y Acad Sci 2008;1139:412–421.
20.Gardner, EL, Vorel, SR. Cannabinoid transmission and reward-related events. Neurobiol Dis 1998;5:502–533.
21.Serrano, A, Parsons, LH. Endocannabinoid influence in drug reinforcement, dependence and addiction-related behaviors. Pharmacol Ther 2011;132:215–241.
22.Maldonado, R, Valverde, O, Berrendero, F. Involvement of the endocannabinoid system in drug addiction. Trends Neurosci 2006;29:225–232.
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.
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.
25.Atwood, BK, Mackie, K. CB2: a cannabinoid receptor with an identity crisis. Br J Pharmacol 2010;160:467–479.
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.
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.
28.Onaivi, ES. Commentary: functional neuronal CB2 cannabinoid receptors in the CNS. Curr Neuropharmacol 2011;9:205–208.
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.
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.
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.
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.
33.Tanda, G, Goldberg, SR. Cannabinoids: reward, dependence, and underlying neurochemical mechanisms – a review of recent preclinical data. Psychopharmacology 2003;169:115–134.
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.
35.Solinas, M, Yasar, S, Goldberg, SR. Endocannabinoid system involvement in brain reward processes related to drug abuse. Pharmacol Res 2007;56:393–405.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
51.Arnold, JC. The role of endocannabinoid transmission in cocaine addiction. Pharmacol Biochem Behav 2005;81:396–406.
52.Wiskerke, J, Pattij, T, Schoffelmeer, AN, De Vries, TJ. The role of CB1 receptors in psychostimulant addiction. Addict Biol 2008;13:225–238.
53.De Vries, TJ, Schoffelmeer, AN. receptors control conditioned drug seeking. Trends Pharmacol Sci 2005;26:420–426.
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.
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.
56.Sanchis-Segura, C, Spanagel, R. Behavioural assessment of drug reinforcement and addictive features in rodents: an overview. Addict Biol 2006;11:2–38.
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.
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.
59.Soria, G, Mendizabal, V, Tourino, Cet al. Lack of CB1 cannabinoid receptor impairs cocaine self-administration. Neuropsychopharmacology 2005;30:1670–1680.
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.
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.
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.
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.
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.
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.
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.
67.Justinova, Z, Panlilio, LV, Goldberg, SR. Drug addiction. Curr Top Behav Neurosci 2009;1:309–346.
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.
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.
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.
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.
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.
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.
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.
75.Scavone, JL, Sterling, RC, Van Bockstaele, EJ. Cannabinoid and opioid interactions: implications for opiate dependence and withdrawal. Neuroscience 2013;248:637–654.
76.Tucci, S. Addiction and pain: cannabinoid and opioid interactions. Curr Drug Targets 2010;11:392.
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.
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.
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.
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.
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.
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.
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.
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.
85.Xi, ZX, Spiller, K, Gardner, EL. Mechanism-based medication development for the treatment of nicotine dependence. Acta Pharmacol Sin 2009;30:723–739.
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.
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.
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.
89.Foll, LE, Goldberg, B, Rimonabant, SR. A CB1 antagonist, blocks nicotine-conditioned place preferences. Neuroreport 2004;15:2139–2143.
90.Cohen, C, Kodas, E, Griebel, G. CB1 receptor antagonists for the treatment of nicotine addiction. Pharmacol Biochem Behav 2005;81:387–395.
91.Castane, A. Lack of CB1 cannabinoid receptors modifies nicotine behavioural responses, but not nicotine abstinence. Neuropharmacology 2002;43:857–867.
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.
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.
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.
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.
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.
97.Clark, KH, Wiley, CA, Bradberry, CW. Psychostimulant abuse and neuroinflammation: emerging evidence of their interconnection. Neurotox Res 2013;23:174–188.
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.
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.
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.
101.Zalcman, SS. Interleukin-2 potentiates novelty- and GBR 12909-induced exploratory activity. Brain Res 2001;899:1–9.
102.Ho, BT, Lu, JG, Huo, YYet al. Neurochemical basis of interleukin 2-modified discrimination behaviour. Cytokine 1994;6:365–367.
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.
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.
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.
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.
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.
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.
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.
110.Redwine, L, Dang, J, Hall, M, Irwin, M. Disordered sleep, nocturnal cytokines, and immunity in alcoholics. Psychosom Med 2003;65:75–85.
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.
112.Cohen, PR, Hebert, AA, Adler-Storthz, K. Focal epithelial hyperplasia: Heck disease. Pediatr Dermatol 1993;10:245–251.
113.Schleifer, SJ, Keller, SE, Czaja, S. Major depression and immunity in alcohol-dependent persons. Brain Behav Immun 2006;20:80–91.
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.
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.
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.
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.
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.
119.Cook, RT. Cytoplasmic cytokines in the T cells of chronic alcoholics. Alcohol Clin Exp Res 2000;24:241–243.
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.
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.
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.
123.Szabo, G, Mandrekar, P, Oak, S, Mayerle, J. Effect of ethanol on inflammatory responses. Implications for pancreatitis. Pancreatology 2007;7:115–123.
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.
125.Agrawal, RG, Hewetson, A, George, CM, Syapin, PJ, Bergeson, SE. Minocycline reduces ethanol drinking. Brain Behav Immun 2001;25(Suppl. 1):S165–S169.
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.
127.Kovacs, KJ. Microglia and drug-induced plasticity in reward-related neuronal circuits. Front Mol Neurosci 2012;5:74.
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.
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.
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.
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.
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.
133.Klein, TW, Friedman, H, Specter, S. Marijuana, immunity and infection. J Neuroimmunol 1998;83:102–115.
134.Klein, TW, Newton, C, Larsen, Ket al. The cannabinoid system and immune modulation. J Leukoc Biol 2003;74:486–496.
135.Zhang, J, Chen, C. Endocannabinoid 2-arachidonoylglycerol protects neurons by limiting COX-2 elevation. J Biol Chem 2008;283:22601–22611.
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.
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.
138.Nomura, DK, Morrison, BE, Blankman, JLet al. Endocannabinoid hydrolysis generates brain prostaglandins that promote neuroinflammation. Science 2011;334:809–813.
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.
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.
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.
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.
143.Ortega-Gutierrez, S. Therapeutic perspectives of inhibitors of endocannabinoid degradation. Curr Drug Targets CNS Neurol Disord 2005;4:697–707.
144.Sun, Y, Bennet, A. Cannabinoids: a new group of agonists of PPARs. PPAR Res 2007;23513:49–55.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
155.Matute, C, Alberdi, E, Ibarretxe, G, Sanchez-Gomez, MV. Excitotoxicity in glial cells. Eur J Pharmacol 2002;447:239–246.
156.Ehrhart, J, Obregon, D, Mori, Tet al. Stimulation of cannabinoid receptor 2 (CB2) suppresses microglial activation. J Neuroinflammation 2005;2:29.
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.
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.
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.
160.Ashton, JC. Cannabinoids for the treatment of inflammation. Curr Opin Investig Drugs 2007;8:373–384.
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.
162.Morales, M, Bonci, A. Getting to the ore of addiction: hooking CB2 receptor into drug abuse? Nat Med 2012;18:504–505.
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.
164.Xi, ZX, Peng, XQ, Li, Xet al. Brain cannabinoid CB2 receptors modulate cocaine’s actions in mice. Nat Neurosci 2011;14:1100–1102.