Rudd RA, Aleshire N, Zibbell JE, Gladden RM. Increases in drug and opioid overdose deaths–United States, 2000-2014. MMWR Morb Mortal Wkly Rep. 2016;64:1378–82.

Article  PubMed  Google Scholar 

Ahmad FB, Cisewski JA, Rossen LM, Sutton P. In Center for Disease Control and Prevention (2023).

Jordan CJ, Cao J, Newman AH, Xi ZX. Progress in agonist therapy for substance use disorders: lessons learned from methadone and buprenorphine. Neuropharmacology. 2019;158:107609.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Jordan CJ, Xi ZX. Discovery and development of varenicline for smoking cessation. Expert Opin Drug Discov. 2018;13:671–83.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Galaj E, Newman AH, Xi ZX. Dopamine D3 receptor-based medication development for the treatment of opioid use disorder: rationale, progress, and challenges. Neurosci Biobehav Rev. 2020;114:38–52.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Filip M, Frankowska M, Sadakierska-Chudy A, Suder A, Szumiec L, Mierzejewski P, et al. GABAB receptors as a therapeutic strategy in substance use disorders: focus on positive allosteric modulators. Neuropharmacology. 2015;88:36–47.

Article  CAS  PubMed  Google Scholar 

Kalivas PW, Volkow ND. New medications for drug addiction hiding in glutamatergic neuroplasticity. Mol Psychiatry. 2011;16:974–86.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Volkow ND, Jones EB, Einstein EB, Wargo EM. Prevention and treatment of opioid misuse and addiction: a review. JAMA Psychiatry. 2019;76:208–16.

Article  PubMed  Google Scholar 

Tanda G, Hersey M, Hempel B, Xi ZX, Newman AH. Modafinil and its structural analogs as atypical dopamine uptake inhibitors and potential medications for psychostimulant use disorder. Curr Opin Pharmacol. 2021;56:13–21.

Article  CAS  PubMed  Google Scholar 

Newman AH, Xi ZX, Heidbreder C. Current Perspectives on Selective Dopamine D(3) receptor antagonists/partial agonists as pharmacotherapeutics for opioid and psychostimulant use disorders. Curr Top Behav Neurosci. 2023;60:157–201.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Fratta W, Fattore L. Molecular mechanisms of cannabinoid addiction. Curr Opin Neurobiol. 2013;23:487–92.

Article  CAS  PubMed  Google Scholar 

Freund TF, Katona I, Piomelli D. Role of endogenous cannabinoids in synaptic signaling. Physiol Rev. 2003;83:1017–66.

Article  CAS  PubMed  Google Scholar 

Han X, He Y, Bi GH, Zhang HY, Song R, Liu QR, et al. CB1 receptor activation on VgluT2-expressing glutamatergic neurons underlies Delta(9)-tetrahydrocannabinol (Delta(9)-THC)-induced aversive effects in mice. Sci Rep. 2017;7:12315.

Article  PubMed  PubMed Central  Google Scholar 

Humburg BA, Jordan CJ, Zhang HY, Shen H, Han X, Bi GH, et al. Optogenetic brain-stimulation reward: a new procedure to re-evaluate the rewarding versus aversive effects of cannabinoids in dopamine transporter-Cre mice. Addict Biol. 2021;26:e13005.

Article  CAS  PubMed  Google Scholar 

Matyas F, Yanovsky Y, Mackie K, Kelsch W, Misgeld U, Freund TF. Subcellular localization of type 1 cannabinoid receptors in the rat basal ganglia. Neuroscience. 2006;137:337–61.

Article  CAS  PubMed  Google Scholar 

Le Foll B, Goldberg SR, Cannabinoid CB. 1 receptor antagonists as promising new medications for drug dependence. J Pharmacol Exp Ther. 2005;312:875–83.

Article  PubMed  Google Scholar 

Pacher P, Batkai S, Kunos G. The endocannabinoid system as an emerging target of pharmacotherapy. Pharmacol Rev. 2006;58:389–462.

Article  CAS  PubMed  Google Scholar 

Sloan ME, Gowin JL, Ramchandani VA, Hurd YL, Le Foll B. The endocannabinoid system as a target for addiction treatment: Trials and tribulations. Neuropharmacology. 2017;124:73–83.

Article  CAS  PubMed  Google Scholar 

Galaj E, Xi ZX. Potential of cannabinoid receptor ligands as treatment for substance use disorders. CNS Drugs. 2019;33:1001–30.

Article  PubMed  PubMed Central  Google Scholar 

Bluher M. Efficacy and safety of the weight-loss drug rimonabant. Lancet. 2008;371:555–6.

Article  PubMed  Google Scholar 

Rinaldi-Carmona M, Barth F, Heaulme M, Shire D, Calandra B, Congy C, et al. SR141716A, a potent and selective antagonist of the brain cannabinoid receptor. FEBS Lett. 1994;350:240–4.

Article  CAS  PubMed  Google Scholar 

Sam AH, Salem V, Ghatei MA. Rimonabant: from RIO to ban. J Obes. 2011;2011:432607.

Article  PubMed  PubMed Central  Google Scholar 

Christensen R, Kristensen PK, Bartels EM, Bliddal H, Astrup A. Efficacy and safety of the weight-loss drug rimonabant: a meta-analysis of randomised trials. Lancet. 2007;370:1706–13.

Article  CAS  PubMed  Google Scholar 

Di Marzo V, Despres JP. CB1 antagonists for obesity–what lessons have we learned from rimonabant? Nat Rev Endocrinol. 2009;5:633–8.

Article  PubMed  Google Scholar 

Soler-Cedeno O, Xi ZX. Neutral CB1 receptor antagonists as pharmacotherapies for substance use disorders: rationale, evidence, and challenge. Cells. 2022;11:3262.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Nguyen T, Thomas BF, Zhang Y. Overcoming the psychiatric side effects of the cannabinoid CB1 receptor antagonists: current approaches for therapeutics development. Curr Top Med Chem. 2019;19:1418–35.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Goonawardena AV, Plano A, Robinson L, Ross R, Greig I, Pertwee RG, et al. Modulation of food consumption and sleep-wake cycle in mice by the neutral CB1 antagonist ABD459. Behav Pharmacol. 2015;26:289–303.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ma H, Zhang G, Mou C, Fu X, Chen Y. Peripheral CB1 receptor neutral antagonist, AM6545, ameliorates hypometabolic obesity and improves adipokine secretion in monosodium glutamate induced obese mice. Front Pharmacol. 2018;9:156.

Article  PubMed  PubMed Central  Google Scholar 

Balla A, Dong B, Shilpa BM, Vemuri K, Makriyannis A, Pandey SC, et al. Cannabinoid-1 receptor neutral antagonist reduces binge-like alcohol consumption and alcohol-induced accumbal dopaminergic signaling. Neuropharmacology. 2018;131:200–08.

Article  CAS  PubMed  Google Scholar 

Cluny NL, Vemuri VK, Chambers AP, Limebeer CL, Bedard H, Wood JT, et al. A novel peripherally restricted cannabinoid receptor antagonist, AM6545, reduces food intake and body weight, but does not cause malaise, in rodents. Br J Pharmacol. 2010;161:629–42.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gueye AB, Pryslawsky Y, Trigo JM, Poulia N, Delis F, Antoniou K, et al. The CB1 neutral antagonist AM4113 retains the therapeutic efficacy of the inverse agonist rimonabant for nicotine dependence and weight loss with better psychiatric tolerability. Int J Neuropsychopharmacol. 2016;19:pyw068.

Article  PubMed  PubMed Central  Google Scholar 

He XH, Jordan CJ, Vemuri K, Bi GH, Zhan J, Gardner EL, et al. Cannabinoid CB(1) receptor neutral antagonist AM4113 inhibits heroin self-administration without depressive side effects in rats. Acta Pharmacol Sin. 2019;40:365–73.

Article  CAS  PubMed  Google Scholar 

Schindler CW, Redhi GH, Vemuri K, Makriyannis A, Le Foll B, Bergman J, et al. Blockade of nicotine and cannabinoid reinforcement and relapse by a cannabinoid CB1-receptor neutral antagonist AM4113 and inverse agonist rimonabant in squirrel monkeys. Neuropsychopharmacology. 2016;41:2283–93.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Jarbe TU, LeMay BJ, Olszewska T, Vemuri VK, Wood JT, Makriyannis A. Intrinsic effects of AM4113, a putative neutral CB1 receptor selective antagonist, on open-field behaviors in rats. Pharmacol Biochem Behav. 2008;91:84–90.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sink KS, McLaughlin PJ, Wood JA, Brown C, Fan P, Vemuri VK, et al. The novel cannabinoid CB1 receptor neutral antagonist AM4113 suppresses food intake and food-reinforced behavior but does not induce signs of nausea in rats. Neuropsychopharmacology. 2008;33:946–55.

Article  CAS  PubMed  Google Scholar 

Chambers AP, Vemuri VK, Peng Y, Wood JT, Olszewska T, Pittman QJ, et al. A neutral CB1 receptor antagonist reduces weight gain in rat. Am J Physiol Regul Integr Comp Physiol. 2007;293:R2185–93.

Article  CAS  PubMed