Beyond the CB1 Receptor: Is Cannabidiol the Answer for Disorders of Motivation?

Literature Cited

1. Adamczyk P, Miszkiel J, McCreary AC, Filip M, Papp M, Przegaliński E. 2012. The effects of cannabinoid CB1, CB2 and vanilloid TRPV1 receptor antagonists on cocaine addictive behavior in rats. Brain Res. 1444:45–54 [Google Scholar]
2. Ahrens J, Demir R, Leuwer M, de la Roche J, Krampfl K. et al. 2009. The nonpsychotropic cannabinoid cannabidiol modulates and directly activates alpha-1 and alpha-1-beta glycine receptor function. Pharmacology 83:4217–22 [Google Scholar]
3. Alex KD, Pehek EA. 2007. Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission. Pharmacol. Ther. 113:2296–320 [Google Scholar]
4. Alger BE. 2009. Endocannabinoid signaling in neural plasticity. Curr. Top. Behav. Neurosci. 1:141–72 [Google Scholar]
5. Alger BE, Kim J. 2011. Supply and demand for endocannabinoids. Trends Neurosci. 34:6304–15 [Google Scholar]
6. Anighoro A, Bajorath J, Rastelli G. 2014. Polypharmacology: challenges and opportunities in drug discovery. J. Med. Chem. 57:197874–87 [Google Scholar]
7. Barnes MP. 2006. Sativex: clinical efficacy and tolerability in the treatment of symptoms of multiple sclerosis and neuropathic pain. Expert Opin. Pharmacother. 7:5607–15 [Google Scholar]
8. Ben-Shabat S, Fride E, Sheskin T, Tamiri T, Rhee MH. et al. 1998. An entourage effect: Inactive endogenous fatty acid glycerol esters enhance 2-arachidonoyl-glycerol cannabinoid activity. Eur. J. Pharmacol. 353:123–31 [Google Scholar]
9. Bergamaschi MM, Queiroz RHC, Chagas MHN, de Oliveira DCG, De Martinis BS. et al. 2011. Cannabidiol reduces the anxiety induced by simulated public speaking in treatment-naïve social phobia patients. Neuropsychopharmacology 36:61219–26 [Google Scholar]
10. Bhargava HN. 1976. Effect of some cannabinoids on naloxone-precipitated abstinence in morphine-dependent mice. Psychopharmacology 49:3267–70 [Google Scholar]
11. Bidaut-Russell M, Devane WA, Howlett AC. 1990. Cannabinoid receptors and modulation of cyclic AMP accumulation in the rat brain. J. Neurochem. 55:121–26 [Google Scholar]
12. Bisogno T, Hanuš L, De Petrocellis L, Tchilibon S, Ponde DE. et al. 2001. Molecular targets for cannabidiol and its synthetic analogues: effect on vanilloid VR1 receptors and on the cellular uptake and enzymatic hydrolysis of anandamide. Br. J. Pharmacol. 134:4845–52 [Google Scholar]
13. Blanco E, Pavón FJ, Palomino A, Luque-Rojas MJ, Serrano A. et al. 2014. Cocaine-induced behavioral sensitization is associated with changes in the expression of endocannabinoid and glutamatergic signaling systems in the mouse prefrontal cortex. Int. J. Neuropsychopharmacol. 18:1pyu024 [Google Scholar]
14. Bloom AS, Hillard CJ. 1985. Cannabinoids, neurotransmitter receptors and brain membranes. Marihuana '84 Harvey DJ 217–31 Oxford, UK: IRL [Google Scholar]
15. Breivogel CS, Griffin G, Di Marzo V, Martin BR. 2001. Evidence for a new G protein-coupled cannabinoid receptor in mouse brain. Mol. Pharmacol. 60:1155–63 [Google Scholar]
16. Campos AC, Guimarães FS. 2008. Involvement of 5HT1A receptors in the anxiolytic-like effects of cannabidiol injected into the dorsolateral periaqueductal gray of rats. Psychopharmacology 199:2223–30 [Google Scholar]
17. Campos AC, Moreira FA, Gomes FV, Del Bel EA, Guimarães FS. 2012. Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders. Philos. Trans. R. Soc. B Biol. Sci. 367:16073364–78 [Google Scholar]
18. Campos AC, Ortega Z, Palazuelos J, Fogaça MV, Aguiar DC. et al. 2013. The anxiolytic effect of cannabidiol on chronically stressed mice depends on hippocampal neurogenesis: involvement of the endocannabinoid system. Int. J. Neuropsychopharmacol. 16:61407–19 [Google Scholar]
19. Capasso R, Borrelli F, Aviello G, Romano B, Scalisi C. et al. 2008. Cannabidiol, extracted from Cannabis sativa, selectively inhibits inflammatory hypermotility in mice. Br. J. Pharmacol. 154:51001–8 [Google Scholar]
20. Carrier EJ, Auchampach JA, Hillard CJ. 2006. Inhibition of an equilibrative nucleoside transporter by cannabidiol: a mechanism of cannabinoid immunosuppression. PNAS 103:207895–900 [Google Scholar]
21. Chauvet C, Nicolas C, Thiriet N, Lardeux MV, Duranti A, Solinas M. 2014. Chronic stimulation of the tone of endogenous anandamide reduces cue- and stress-induced relapse in rats. Int. J. Neuropsychopharmacol. 18:1pyu025 [Google Scholar]
22. Cheer JF, Kendall DA, Mason R, Marsden CA. 2003. Differential cannabinoid-induced electrophysiological effects in rat ventral tegmentum. Neuropharmacology 44:5633–41 [Google Scholar]
23. Cheer JF, Marsden CA, Kendall DA, Mason R. 2000. Lack of response suppression follows repeated ventral tegmental cannabinoid administration: an in vitro electrophysiological study. Neuroscience 99:4661–67 [Google Scholar]
24. Cheer JF, Wassum KM, Heien MLAV, Phillips PEM, Wightman RM. 2004. Cannabinoids enhance subsecond dopamine release in the nucleus accumbens of awake rats. J. Neurosci. 24:184393–400 [Google Scholar]
25. Cheer JF, Wassum KM, Sombers LA, Heien MLAV, Ariansen JL. et al. 2007. Phasic dopamine release evoked by abused substances requires cannabinoid receptor activation. J. Neurosci. 27:4791–95 [Google Scholar]
26. Chesher GB, Jackson DM. 1985. The quasi-morphine withdrawal syndrome: effect of cannabinol, cannabidiol and tetrahydrocannabinol. Pharmacol. Biochem. Behav. 23:113–15 [Google Scholar]
27. Christensen R, Kristensen PK, Bartels EM, Bliddal H, Astrup A. 2007. Efficacy and safety of the weight-loss drug rimonabant: a meta-analysis of randomised trials. Lancet 370:96001706–13 [Google Scholar]
28. Cilio MR, Thiele EA, Devinsky O. 2014. The case for assessing cannabidiol in epilepsy. Epilepsia 55:6787–90 [Google Scholar]
29. Cippitelli A, Astarita G, Duranti A, Caprioli G, Ubaldi M. et al. 2011. Endocannabinoid regulation of acute and protracted nicotine withdrawal: effect of FAAH inhibition. PLOS ONE 6:11e28142 [Google Scholar]
30. Cippitelli A, Bilbao A, Hansson AC, Del Arco I, Sommer W. et al. 2005. Cannabinoid CB1 receptor antagonism reduces conditioned reinstatement of ethanol-seeking behavior in rats. Eur. J. Neurosci. 21:82243–51 [Google Scholar]
31. Cohen C, Perrault G, Griebel G, Soubrié P. 2004. Nicotine-associated cues maintain nicotine-seeking behavior in rats several weeks after nicotine withdrawal: reversal by the cannabinoid (CB₁) receptor antagonist, rimonabant (SR141716). Neuropsychopharmacology 30:1145–55 [Google Scholar]
32. Conway KP, Compton W, Stinson FS, Grant BF. 2006. Lifetime comorbidity of DSM-IV mood and anxiety disorders and specific drug use disorders: results from the National Epidemiologic Survey on Alcohol and Related Conditions. J. Clin. Psychiatry 67:2247–57 [Google Scholar]
33. Costa B, Trovato AE, Comelli F, Giagnoni G, Colleoni M. 2007. The non-psychoactive cannabis constituent cannabidiol is an orally effective therapeutic agent in rat chronic inflammatory and neuropathic pain. Eur. J. Pharmacol. 556:1–375–83 [Google Scholar]
34. Crippa JAS, Zuardi AW, Garrido GEJ, Wichert-Ana L, Guarnieri R. et al. 2004. Effects of cannabidiol (CBD) on regional cerebral blood flow. Neuropsychopharmacology 29:2417–26 [Google Scholar]
35. Crippa JAS, Hallak JEC, Machado-de-Sousa JP, Queiroz RHC, Bergamaschi M. et al. 2013. Cannabidiol for the treatment of cannabis withdrawal syndrome: a case report. J. Clin. Pharm. Ther. 38:2162–64 [Google Scholar]
36. David DJ, Wang J, Samuels BA, Rainer Q, David I. et al. 2010. Implications of the functional integration of adult-born hippocampal neurons in anxiety-depression disorders. Neuroscientist 16:5578–91 [Google Scholar]
37. de Guglielmo G, Kallupi M, Scuppa G, Stopponi S, Demopulos G. et al. 2014. Analgesic tolerance to morphine is regulated by PPARγ. Br. J. Pharmacol. 171:235407–16 [Google Scholar]
38. de Meijer EPM, Bagatta M, Carboni A, Crucitti P, Moliterni VMC. et al. 2003. The inheritance of chemical phenotype in Cannabis sativa L. Genetics 163:1335–46 [Google Scholar]
39. de Paula Soares V, Campos AC, Camin de Bortoli V, Zangrossi H Jr, Guimarães FS, Zuardi AW. 2010. Intra-dorsal periaqueductal gray administration of cannabidiol blocks panic-like response by activating 5-HT1A receptors. Behav. Brain Res. 213:2225–29 [Google Scholar]
40. De Petrocellis L, Ligresti A, Moriello AS, Allarà M, Bisogno T. et al. 2011. Effects of cannabinoids and cannabinoid-enriched Cannabis extracts on TRP channels and endocannabinoid metabolic enzymes. Br. J. Pharmacol. 163:71479–94 [Google Scholar]
41. De Petrocellis L, Vellani V, Schiano-Moriello A, Marini P, Magherini PC. et al. 2008. Plant-derived cannabinoids modulate the activity of transient receptor potential channels of ankyrin type-1 and melastatin type-8. J. Pharmacol. Exp. Ther. 325:31007–15 [Google Scholar]
42. Devane WA, Dysarz FA, Johnson MR, Melvin LS, Howlett AC. 1988. Determination and characterization of a cannabinoid receptor in rat brain. Mol. Pharmacol. 34:5605–13 [Google Scholar]
43. Devane WA, Hanuš L, Breuer A, Pertwee RG, Stevenson LA. et al. 1992. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science 258:50901946–49 [Google Scholar]
44. Devinsky O, Cilio MR, Cross H, Fernandez-Ruiz J, French J. et al. 2014. Cannabidiol: pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders. Epilepsia 55:6791–802 [Google Scholar]
45. De Vries TJ, Shaham Y, Homberg JR, Crombag H, Schuurman K. et al. 2001. A cannabinoid mechanism in relapse to cocaine seeking. Nat. Med. 7:101151–54 [Google Scholar]
46. Diana M, Melis M, Gessa GL. 1998. Increase in meso-prefrontal dopaminergic activity after stimulation of CB1 receptors by cannabinoids. Eur. J. Neurosci. 10:92825–30 [Google Scholar]
47. Di Chiara G, Imperato A. 1988. Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats. PNAS 85:145274–78 [Google Scholar]
48. Di Marzo V, De Petrocellis L, Fezza F, Ligresti A, Bisogno T. 2002. Anandamide receptors. Prostaglandins Leukot. Essent. Fat. Acids 66:2–3377–91 [Google Scholar]
49. Di Marzo V, Matias I. 2005. Endocannabinoid control of food intake and energy balance. Nat. Neurosci. 8:5585–89 [Google Scholar]
50. Drysdale AJ, Ryan D, Pertwee RG, Platt B. 2006. Cannabidiol-induced intracellular Ca²⁺ elevations in hippocampal cells. Neuropharmacology 50:5621–31 [Google Scholar]
51. El-Alfy AT, Ivey K, Robinson K, Ahmed S, Radwan M. et al. 2010. Antidepressant-like effect of Δ⁹-tetrahydrocannabinol and other cannabinoids isolated from Cannabis sativa L. Pharmacol. Biochem. Behav. 95:4434–42 [Google Scholar]
52. Enayatfard L, Rostami F, Nasoohi S, Oryan S, Ahmadiani A, Dargahi L. 2013. Dual role of PPAR-γ in induction and expression of behavioral sensitization to cannabinoid receptor agonist WIN55,212–2. Neuromolecular Med. 15:3523–35 [Google Scholar]
53. Fattore L, Spano S, Cossu G, Deiana S, Fadda P, Fratta W. 2005. Cannabinoid CB₁ antagonist SR 141716A attenuates reinstatement of heroin self-administration in heroin-abstinent rats. Neuropharmacology 48:81097–104 [Google Scholar]
54. Fankhauser M. 2002. History of cannabis in Western Medicine. Cannabis and Cannabinoids F Grotenhermen, E Russo 37–51 New York: Haworth Integr. Heal. [Google Scholar]
55. Ferré S, Lluís C, Justinova Z, Quiroz C, Orru M. et al. 2010. Adenosine-cannabinoid receptor interactions: implications for striatal function. Br. J. Pharmacol. 160:3443–53 [Google Scholar]
56. Forget B, Coen KM, Le Foll B. 2009. Inhibition of fatty acid amide hydrolase reduces reinstatement of nicotine seeking but not break point for nicotine self-administration—comparison with CB₁ receptor blockade. Psychopharmacology 205:4613–24 [Google Scholar]
57. French ED, Dillon K, Wu X. 1997. Cannabinoids excite dopamine neurons in the ventral tegmentum and substantia nigra. NeuroReport 8:3649–52 [Google Scholar]
58. Freund TF, Katona I, Piomelli D. 2003. Role of endogenous cannabinoids in synaptic signaling. Physiol. Rev. 83:31017–66 [Google Scholar]
59. Fusar-Poli P, Allen P, Bhattacharyya S, Crippa JAS, Mechelli A. et al. 2010. Modulation of effective connectivity during emotional processing by Δ⁹-tetrahydrocannabinol and cannabidiol. Int. J. Neuropsychopharmacol. 13:4421–32 [Google Scholar]
60. Gamaleddin I, Guranda M, Goldberg SR, Le Foll B. 2011. The selective anandamide transport inhibitor VDM11 attenuates reinstatement of nicotine seeking behaviour, but does not affect nicotine intake. Br. J. Pharmacol. 164:61652–60 [Google Scholar]
61. Gaoni Y, Mechoulam R. 1964. Isolation, structure, and partial synthesis of an active constituent of hashish. J. Am. Chem. Soc. 86:81646–47 [Google Scholar]
62. Gelfand EV, Cannon CP. 2006. Rimonabant: a selective blocker of the cannabinoid CB1 receptors for the management of obesity, smoking cessation and cardiometabolic risk factors. Expert Opin. Investig. Drugs 15:3307–15 [Google Scholar]
63. Gomes FV, Reis DG, Alves FHF, Corrêa FMA, Guimarães FS, Resstel LBM. 2012. Cannabidiol injected into the bed nucleus of the stria terminalis reduces the expression of contextual fear conditioning via 5-HT_1A receptors. J. Psychopharmacol. 26:1104–13 [Google Scholar]
64. Gomes FV, Resstel LBM, Guimarães FS. 2010. The anxiolytic-like effects of cannabidiol injected into the bed nucleus of the stria terminalis are mediated by 5-HT1A receptors. Psychopharmacology 213:2–3465–73 [Google Scholar]
65. Granjeiro ÉM, Gomes FV, Guimarães FS, Corrêa FMA, Resstel LBM. 2011. Effects of intracisternal administration of cannabidiol on the cardiovascular and behavioral responses to acute restraint stress. Pharmacol. Biochem. Behav. 99:4743–48 [Google Scholar]
66. Grinspoon L, Bakalar JB. 1995. Marijuana as medicine: a plea for reconsideration. JAMA 273:231875–76 [Google Scholar]
67. Guimarães FS, Chiaretti TM, Graeff FG, Zuardi AW. 1990. Antianxiety effect of cannabidiol in the elevated plus-maze. Psychopharmacology 100:4558–59 [Google Scholar]
68. Heng L-J, Huang B, Guo H, Ma L-T, Yuan W-X. et al. 2014. Blocking TRPV1 in nucleus accumbens inhibits persistent morphine conditioned place preference expression in rats. PLOS ONE 9:8e104546 [Google Scholar]
69. Henry DJ, Chavkin C. 1995. Activation of inwardly rectifying potassium channels (GIRK1) by co-expressed rat brain cannabinoid receptors in Xenopus oocytes. Neurosci. Lett. 186:2–391–94 [Google Scholar]
70. Herkenham M, Lynn AB, Johnson MR, Melvin LS, de Costa BR, Rice KC. 1991. Characterization and localization of cannabinoid receptors in rat brain: a quantitative in vitro autoradiographic study. J. Neurosci. 11:2563–83 [Google Scholar]
71. Herkenham M, Lynn AB, Little MD, Johnson MR, Melvin LS. et al. 1990. Cannabinoid receptor localization in brain. PNAS 87:51932–36 [Google Scholar]
72. Hill AJ, Williams CM, Whalley BJ, Stephens GJ. 2012. Phytocannabinoids as novel therapeutic agents in CNS disorders. Pharmacol. Ther. 133:179–97 [Google Scholar]
73. Hill M, Miller G, Ho W-S, Gorzalka B, Hillard C. 2008. Serum endocannabinoid content is altered in females with depressive disorders: a preliminary report. Pharmacopsychiatry 41:248–53 [Google Scholar]
74. Hine B, Torrelio M, Gershon S. 1975a. Differential effect of cannabinol and cannabidiol on THC-induced responses during abstinence in morphine-dependent rats. Res. Commun. Chem. Pathol. Pharmacol. 12:1185–88 [Google Scholar]
75. Hine B, Torrelio M, Gershon S. 1975b. Interactions between cannabidiol and Δ⁹-THC during abstinence in morphine-dependent rats. Life Sci. 17:6851–57 [Google Scholar]
76. Hoffman AF, Lupica CR. 2000. Mechanisms of cannabinoid inhibition of GABA_A synaptic transmission in the hippocampus. J. Neurosci. 20:72470–79 [Google Scholar]
77. Hopkins AL. 2008. Network pharmacology: the next paradigm in drug discovery. Nat. Chem. Biol. 4:11682–90 [Google Scholar]
78. Hsiao Y-T, Yi P-L, Li C-L, Chang F-C. 2012. Effect of cannabidiol on sleep disruption induced by the repeated combination tests consisting of open field and elevated plus-maze in rats. Neuropharmacology 62:1373–84 [Google Scholar]
79. Huestis MA, Gorelick DA, Heishman SJ, Preston KL, Nelson RA. et al. 2001. Blockade of effects of smoked marijuana by the CB1-selective cannabinoid receptor antagonist SR141716. Arch. Gen. Psychiatry 58:4322–28 [Google Scholar]
80. Hurd YL, Yoon M, Manini AF, Hernandez S, Olmedo R. et al. 2015. Early phase in the development of cannabidiol as a treatment for addiction: opioid relapse takes initial center stage. Neurotherapeutics 12:4807–15 [Google Scholar]
81. Jenny M, Santer E, Pirich E, Schennach H, Fuchs D. 2009. Δ9-Tetrahydrocannabinol and cannabidiol modulate mitogen-induced tryptophan degradation and neopterin formation in peripheral blood mononuclear cells in vitro. J. Neuroimmunol. 207:1–275–82 [Google Scholar]
82. Jones NA, Hill AJ, Smith I, Bevan SA, Williams CM. et al. 2010. Cannabidiol displays antiepileptiform and antiseizure properties in vitro and in vivo. J. Pharmacol. Exp. Ther. 332:2569–77 [Google Scholar]
83. Julian MD, Martin AB, Cuellar B, Rodriguez De Fonseca F, Navarro M. et al. 2003. Neuroanatomical relationship between type 1 cannabinoid receptors and dopaminergic systems in the rat basal ganglia. Neuroscience 119:1309–18 [Google Scholar]
84. Justinova Z, Munzar P, Panlilio LV, Yasar S, Redhi GH. et al. 2008. Blockade of THC-seeking behavior and relapse in monkeys by the cannabinoid CB₁-receptor antagonist rimonabant. Neuropsychopharmacology 33:122870–77 [Google Scholar]
85. Kathmann M, Flau K, Redmer A, Tränkle C, Schlicker E. 2006. Cannabidiol is an allosteric modulator at mu- and delta-opioid receptors. Naunyn-Schmiedeberg's Arch. Pharmacol. 372:5354–61 [Google Scholar]
86. Katsidoni V, Anagnostou I, Panagis G. 2013. Cannabidiol inhibits the reward-facilitating effect of morphine: involvement of 5-HT_1A receptors in the dorsal raphe nucleus. Addict. Biol. 18:2286–96 [Google Scholar]
87. Kessler RC. 1997. The effects of stressful life events on depression. Annu. Rev. Psychol. 48:191–214 [Google Scholar]
88. Koob GF, Volkow ND. 2009. Neurocircuitry of addiction. Neuropsychopharmacology 35:1217–38 [Google Scholar]
89. Leweke FM, Piomelli D, Pahlisch F, Muhl D, Gerth CW. et al. 2012. Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia. Transl. Psychiatry 2:e94 [Google Scholar]
90. Li H-L. 1978. Hallucinogenic plants in Chinese herbals. J. Psychoact. Drugs 10:117–26 [Google Scholar]
91. Ligresti A, Moriello AS, Starowicz K, Matias I, Pisanti S. et al. 2006. Antitumor activity of plant cannabinoids with emphasis on the effect of cannabidiol on human breast carcinoma. J. Pharmacol. Exp. Ther. 318:31375–87 [Google Scholar]
92. Liou GI, Auchampach JA, Hillard CJ, Zhu G, Yousufzai B. et al. 2008. Mediation of cannabidiol anti-inflammation in the retina by equilibrative nucleoside transporter and A_2A adenosine receptor. Investig. Ophthalmol. Vis. Sci. 49:125526–31 [Google Scholar]
93. Long LE, Chesworth R, Huang X-F, Wong A, Spiro A. et al. 2012. Distinct neurobehavioural effects of cannabidiol in transmembrane domain neuregulin 1 mutant mice. PLOS ONE 7:4e34129 [Google Scholar]
94. Lupica CR, Riegel AC. 2005. Endocannabinoid release from midbrain dopamine neurons: a potential substrate for cannabinoid receptor antagonist treatment of addiction. Neuropharmacology 48:81105–16 [Google Scholar]
95. McPartland JM, Duncan M, Di Marzo V, Pertwee RG. 2015. Are cannabidiol and Δ⁹-tetrahydrocannabivarin negative modulators of the endocannabinoid system? A systematic review. Br. J. Pharmacol. 172:3737–53 [Google Scholar]
96. Mechoulam R, Ben-Shabat S. 1999. From gan-zi-gun-nu to anandamide and 2-arachidonoylglycerol: the ongoing story of cannabis. Nat. Prod. Rep. 16:2131–43 [Google Scholar]
97. Mechoulam R, Ben-Shabat S, Hanuš L, Ligumsky M, Kaminski NE. et al. 1995. Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochem. Pharmacol. 50:183–90 [Google Scholar]
98. Mechoulam R, Parker LA. 2013. The endocannabinoid system and the brain. Annu. Rev. Psychol. 64:21–47 [Google Scholar]
99. Mechoulam R, Shani A, Edery H, Grunfeld Y. 1970. Chemical basis of hashish activity. Science 169:3945611–12 [Google Scholar]
100. Mechoulam R, Shvo Y. 1963. Hashish—I: The structure of cannabidiol. Tetrahedron 19:122073–78 [Google Scholar]
101. Melis M, Pistis M, Perra S, Muntoni AL, Pillolla G, Gessa GL. 2004. Endocannabinoids mediate presynaptic inhibition of glutamatergic transmission in rat ventral tegmental area dopamine neurons through activation of CB1 receptors. J. Neurosci. 24:153–62 [Google Scholar]
102. Mencher SK, Wang LG. 2005. Promiscuous drugs compared to selective drugs (promiscuity can be a virtue). BMC Clin. Pharmacol. 5:3 [Google Scholar]
103. Moreira FA, Aguiar DC, Guimarães FS. 2006. Anxiolytic-like effect of cannabidiol in the rat Vogel conflict test. Prog. Neuropsychopharmacol. Biol. Psychiatry 30:81466–71 [Google Scholar]
104. Morgan CJA, Das RK, Joye A, Curran HV, Kamboj SK. 2013. Cannabidiol reduces cigarette consumption in tobacco smokers: preliminary findings. Addict. Behav. 38:92433–36 [Google Scholar]
105. Munro S, Thomas KL, Abu-Shaar M. 1993. Molecular characterization of a peripheral receptor for cannabinoids. Nature 365:644161–65 [Google Scholar]
106. Nestler EJ, Carlezon WA Jr. 2006. The mesolimbic dopamine reward circuit in depression. Biol. Psychiatry 59:121151–59 [Google Scholar]
107. Onaivi ES, Green MR, Martin BR. 1990. Pharmacological characterization of cannabinoids in the elevated plus maze. J. Pharmacol. Exp. Ther. 253:31002–9 [Google Scholar]
108. O'Sullivan SE, Sun Y, Bennett AJ, Randall MD, Kendall DA. 2009. Time-dependent vascular actions of cannabidiol in the rat aorta. Eur. J. Pharmacol. 612:1–361–68 [Google Scholar]
109. Pandolfo P, Silveirinha V, dos Santos-Rodrigues A, Venance L, Ledent C. et al. 2011. Cannabinoids inhibit the synaptic uptake of adenosine and dopamine in the rat and mouse striatum. Eur. J. Pharmacol. 655:1–338–45 [Google Scholar]
110. Panlilio LV, Justinova Z, Goldberg SR. 2013. Inhibition of FAAH and activation of PPAR: new approaches to the treatment of cognitive dysfunction and drug addiction. Pharmacol. Ther. 138:184–102 [Google Scholar]
111. Parker LA, Burton P, Sorge RE, Yakiwchuk C, Mechoulam R. 2004. Effect of low doses of Δ⁹-tetrahydrocannabinol and cannabidiol on the extinction of cocaine-induced and amphetamine-induced conditioned place preference learning in rats. Psychopharmacology 175:3360–66 [Google Scholar]
112. Perras C. 2005. Sativex for the management of multiple sclerosis symptoms. Issues Emerg. Health Technol. 72:1–4 [Google Scholar]
113. Pertwee RG. 2007. GPR55: a new member of the cannabinoid receptor clan?. Br. J. Pharmacol. 152:7984–86 [Google Scholar]
114. Pertwee RG. 2008. The diverse CB₁ and CB₂ receptor pharmacology of three plant cannabinoids: Δ⁹-tetrahydrocannabinol, cannabidiol and Δ⁹-tetrahydrocannabivarin. Br. J. Pharmacol. 153:2199–215 [Google Scholar]
115. Pertwee RG, Ross RA, Craib SJ, Thomas A. 2002. (−)-Cannabidiol antagonizes cannabinoid receptor agonists and noradrenaline in the mouse vas deferens. Eur. J. Pharmacol. 456:1–399–106 [Google Scholar]
116. Pompeiano M, Palacios JM, Mengod G. 1992. Distribution and cellular localization of mRNA coding for 5-HT_1A receptor in the rat brain: correlation with receptor binding. J. Neurosci. 12:2440–53 [Google Scholar]
117. Potenza MN, Sofuoglu M, Carroll KM, Rounsaville BJ. 2011. Neuroscience of behavioral and pharmacological treatments for addictions. Neuron 69:4695–712 [Google Scholar]
118. Qin N, Neeper MP, Liu Y, Hutchinson TL, Lubin ML, Flores CM. 2008. TRPV2 is activated by cannabidiol and mediates CGRP release in cultured rat dorsal root ganglion neurons. J. Neurosci. 28:246231–38 [Google Scholar]
119. Rahimi A, Hajizadeh Moghaddam A, Roohbakhsh A. 2015. Central administration of GPR55 receptor agonist and antagonist modulates anxiety-related behaviors in rats. Fundam. Clin. Pharmacol. 29:2185–90 [Google Scholar]
120. Rakhshan F, Day TA, Blakely RD, Barker EL. 2000. Carrier-mediated uptake of the endogenous cannabinoid anandamide in RBL-2H3 cells. J. Pharmacol. Exp. Ther. 292:3960–67 [Google Scholar]
121. Ren Y, Whittard J, Higuera-Matas A, Morris CV, Hurd YL. 2009. Cannabidiol, a nonpsychotropic component of cannabis, inhibits cue-induced heroin seeking and normalizes discrete mesolimbic neuronal disturbances. J. Neurosci. 29:4714764–69 [Google Scholar]
122. Resstel LBM, Joca SRL, Moreira FA, Corrêa FMA, Guimarães FS. 2006. Effects of cannabidiol and diazepam on behavioral and cardiovascular responses induced by contextual conditioned fear in rats. Behav. Brain Res. 172:2294–98 [Google Scholar]
123. Resstel LBM, Tavares RF, Lisboa SFS, Joca SRL, Corrêa FMA, Guimarães FS. 2009. 5-HT_1A receptors are involved in the cannabidiol-induced attenuation of behavioural and cardiovascular responses to acute restraint stress in rats. Br. J. Pharmacol. 156:1181–88 [Google Scholar]
124. Riedel G, Fadda P, McKillop-Smith S, Pertwee RG, Platt B, Robinson L. 2009. Synthetic and plant-derived cannabinoid receptor antagonists show hypophagic properties in fasted and non-fasted mice. Br. J. Pharmacol. 156:71154–66 [Google Scholar]
125. Riegel AC, Lupica CR. 2004. Independent presynaptic and postsynaptic mechanisms regulate endocannabinoid signaling at multiple synapses in the ventral tegmental area. J. Neurosci. 24:4911070–78 [Google Scholar]
126. Rinaldi-Carmona M, Barth F, Congy C, Martinez S, Oustric D. et al. 2004. SR147778 [5-(4-Bromophenyl)-1-(2,4-dichlorophenyl)-4-ethyl-N-(1-piperidinyl)-1H-pyrazole-3-carboxamide], a new potent and selective antagonist of the CB1 cannabinoid receptor: biochemical and pharmacological characterization. J. Pharmacol. Exp. Ther. 310:3905–14 [Google Scholar]
127. Robbe D, Kopf M, Remaury A, Bockaert J, Manzoni OJ. 2002. Endogenous cannabinoids mediate long-term synaptic depression in the nucleus accumbens. PNAS 99:128384–88 [Google Scholar]
128. Roberts DC, Corcoran ME, Fibiger HC. 1977. On the role of ascending catecholaminergic systems in intravenous self-administration of cocaine. Pharmacol. Biochem. Behav. 6:6615–20 [Google Scholar]
129. Robson P. 2011. Abuse potential and psychoactive effects of δ-9-tetrahydrocannabinol and cannabidiol oromucosal spray (Sativex), a new cannabinoid medicine. Expert Opin. Drug Saf. 10:5675–85 [Google Scholar]
130. Ross RA. 2009. The enigmatic pharmacology of GPR55. Trends Pharmacol. Sci. 30:3156–63 [Google Scholar]
131. Russo EB, Burnett A, Hall B, Parker KK. 2005. Agonistic properties of cannabidiol at 5-HT1a receptors. Neurochem. Res. 30:81037–43 [Google Scholar]
132. Russo EB, Guy GW. 2006. A tale of two cannabinoids: the therapeutic rationale for combining tetrahydrocannabinol and cannabidiol. Med. Hypotheses 66:2234–46 [Google Scholar]
133. Russo SJ, Nestler EJ. 2013. The brain reward circuitry in mood disorders. Nat. Rev. Neurosci. 14:9609–25 [Google Scholar]
134. Ryan D, Drysdale AJ, Pertwee RG, Platt B. 2006. Differential effects of cannabis extracts and pure plant cannabinoids on hippocampal neurones and glia. Neurosci. Lett. 408:3236–41 [Google Scholar]
135. Ryberg E, Larsson N, Sjögren S, Hjorth S, Hermansson N-O. et al. 2007. The orphan receptor GPR55 is a novel cannabinoid receptor. Br. J. Pharmacol. 152:71092–101 [Google Scholar]
136. Santos CJPA, Stern CAJ, Bertoglio LJ. 2008. Attenuation of anxiety-related behaviour after the antagonism of transient receptor potential vanilloid type 1 channels in the rat ventral hippocampus. Behav. Pharmacol. 19:4357–60 [Google Scholar]
137. Scherma M, Panlilio LV, Fadda P, Fattore L, Gamaleddin I. et al. 2008. Inhibition of anandamide hydrolysis by cyclohexyl carbamic acid 3′-carbamoyl-3-yl ester (URB597) reverses abuse-related behavioral and neurochemical effects of nicotine in rats. J. Pharmacol. Exp. Ther. 327:2482–90 [Google Scholar]
138. Schoedel KA, Chen N, Hilliard A, White L, Stott C. et al. 2011. A randomized, double-blind, placebo-controlled, crossover study to evaluate the subjective abuse potential and cognitive effects of nabiximols oromucosal spray in subjects with a history of recreational cannabis use. Hum. Psychopharmacol. 26:3224–36 [Google Scholar]
139. Sugiura T, Kondo S, Sukagawa A, Nakane S, Shinoda A. et al. 1995. 2-Arachidonoylglycerol: a possible endogenous cannabinoid receptor ligand in brain. Biochem. Biophys. Res. Commun. 215:189–97 [Google Scholar]
140. Terzian ALB, Aguiar DC, Guimarães FS, Moreira FA. 2009. Modulation of anxiety-like behaviour by Transient Receptor Potential Vanilloid Type 1 (TRPV1) channels located in the dorsolateral periaqueductal gray. Eur. Neuropsychopharmacol. 19:3188–95 [Google Scholar]
141. Thomas A, Baillie GL, Phillips AM, Razdan RK, Ross RA, Pertwee RG. 2007. Cannabidiol displays unexpectedly high potency as an antagonist of CB₁ and CB₂ receptor agonists in vitro. Br. J. Pharmacol. 150:5613–23 [Google Scholar]
142. Touw M. 1981. The religious and medicinal uses of cannabis in China, India and Tibet. J. Psychoact. Drugs 13:123–34 [Google Scholar]
143. Tudge L, Williams C, Cowen PJ, McCabe C. 2015. Neural effects of cannabinoid CB1 neutral antagonist tetrahydrocannabivarin on food reward and aversion in healthy volunteers. Int. J. Neuropsychopharmacol. 18:6pyu094 [Google Scholar]
144. Twitchell W, Brown S, Mackie K. 1997. Cannabinoids inhibit N- and P/Q-type calcium channels in cultured rat hippocampal neurons. J. Neurophysiol. 78:143–50 [Google Scholar]
145. Volkow ND, Morales M. 2015. The brain on drugs: from reward to addiction. Cell 162:4712–25 [Google Scholar]
146. Wade DT, Makela P, Robson P, House H, Bateman C. 2004. Do cannabis-based medicinal extracts have general or specific effects on symptoms in multiple sclerosis? A double-blind, randomized, placebo-controlled study on 160 patients. Mult. Scler. 10:4434–41 [Google Scholar]
147. Ward SJ, Raffa RB. 2011. Rimonabant redux and strategies to improve the future outlook of CB1 receptor neutral-antagonist/inverse-agonist therapies. Obesity 19:71325–34 [Google Scholar]
148. Wilson RI, Nicoll RA. 2001. Endogenous cannabinoids mediate retrograde signalling at hippocampal synapses. Nature 410:6828588–92 [Google Scholar]
149. Wise RA, Bozarth MA. 1985. Brain mechanisms of drug reward and euphoria. Psychiatr. Med. 3:4445–60 [Google Scholar]
150. Wolf SA, Bick-Sander A, Fabel K, Leal-Galicia P, Tauber S. et al. 2010. Cannabinoid receptor CB1 mediates baseline and activity-induced survival of new neurons in adult hippocampal neurogenesis. Cell Commun. Signal. CCS 8:12 [Google Scholar]
151. Xi Z-X, Peng X-Q, Li X, Song R, Zhang H. et al. 2011. Brain cannabinoid CB₂ receptors modulate cocaine's actions in mice. Nat. Neurosci. 14:91160–66 [Google Scholar]
152. Xiong W, Cui T, Cheng K, Yang F, Chen S-R. et al. 2012. Cannabinoids suppress inflammatory and neuropathic pain by targeting α3 glycine receptors. J. Exp. Med. 209:61121–34 [Google Scholar]
153. Yoshimoto K, McBride WJ. 1992. Regulation of nucleus accumbens dopamine release by the dorsal raphe nucleus in the rat. Neurochem. Res. 17:5401–7 [Google Scholar]
154. Zanelati TV, Biojone C, Moreira FA, Guimarães FS, Joca SRL. 2010. Antidepressant-like effects of cannabidiol in mice: possible involvement of 5-HT_1A receptors. Br. J. Pharmacol. 159:1122–28 [Google Scholar]
155. Zhang H-Y, Gao M, Liu Q-R, Bi G-H, Li X. et al. 2014. Cannabinoid CB₂ receptors modulate midbrain dopamine neuronal activity and dopamine-related behavior in mice. PNAS 111:46E5007–15 [Google Scholar]
156. Zuardi AW. 2006. History of cannabis as a medicine: a review. Rev. Bras. Psiquiatr. 28:2153–57 [Google Scholar]
157. Zuardi AW, Cosme RA, Graeff FG, Guimarães FS. 1993. Effects of ipsapirone and cannabidiol on human experimental anxiety. J. Psychopharmacol. 7:1 Suppl.82–88 [Google Scholar]
158. Zuardi AW, Shirakawa I, Finkelfarb E, Karniol IG. 1982. Action of cannabidiol on the anxiety and other effects produced by Δ⁹-THC in normal subjects. Psychopharmacology 76:3245–50 [Google Scholar]