251
Views
1
CrossRef citations to date
0
Altmetric
Review

The role of the D3 dopamine receptor and its partial agonist cariprazine in patients with schizophrenia and substance use disorder

ORCID Icon
Pages 1985-1992 | Received 29 Aug 2023, Accepted 29 Sep 2023, Published online: 10 Oct 2023

References

  • Swofford CD, Scheller-Gilkey G, Miller AH, et al. Double jeopardy: schizophrenia and substance use. Am J Drug Alcohol Abuse. 2000;26(3):343–353. doi: 10.1081/ADA-100100248
  • Volkow ND. Substance use disorders in schizophrenia–clinical implications of comorbidity. Schizophr Bull. 2009;35:469–472. doi: 10.1093/schbul/sbp016
  • Regier DA, Farmer ME, Rae DS, et al. Comorbidity of mental disorders with alcohol and other drug abuse. JAMA. 1990;264:2511–2518. doi: 10.1001/jama.1990.03450190043026
  • Swofford CD, Kasckow JW, Scheller-Gilkey G, et al. Substance use: a powerful predictor of relapse in schizophrenia. Schizophr Res. 1996;20(1–2):145–151. doi: 10.1016/0920-9964(95)00068-2
  • Rezvani AH, Levin ED. Cognitive effects of nicotine. Biol Psychiatry. 2001;49(3):258–267. doi: 10.1016/S0006-3223(00)01094-5
  • Green AI, Drake RE, Brunette MF, et al. Schizophrenia and co-occurring substance use disorder. Am J Psychiatry. 2007;164(3):402–408. doi: 10.1176/ajp.2007.164.3.402
  • Khantzian EJ. The self-medication hypothesis of addictive disorders: focus on heroin and cocaine dependence. Am J Psychiatry. 1985;142:1259–1264.
  • Blanchard JJ, Squires D, Henry T, et al. Examining an affect regulation model of substance abuse in schizophrenia: the role of traits and coping. J Nerv Ment Dis. 1999;187(2):72–79. doi: 10.1097/00005053-199902000-00002
  • Green AI, Zimmets SV, Strous RD, et al. Clozapine for comorbid substance use disorder and schizophrenia: do patients have a reward-deficiency syndrome that can be ameliorated by clozapine? Harv Rev Psychiatry. 1999;6:287–296. doi: 10.3109/10673229909017206
  • Azorin JM, Simon N, Adida M, et al. Pharmacological treatment of schizophrenia with comorbid substance use disorder. Expert Opin Pharmacother. 2016;17:231–253. doi: 10.1517/14656566.2016.1114101
  • Citrome L. Cariprazine for the treatment of schizophrenia: a review of this dopamine D3-preferring D3/D2 receptor partial agonist. Clin Schizophr Relat Psychoses. 2016;10(2):109–119. doi: 10.3371/1935-1232-10.2.109
  • Patel A, Patel A, Patel D, et al. Mini review on cariprazine: a promising antipsychotic agent. CNS Neurol Disord Drug Targets. 2023;22(2):226–236. doi: 10.2174/1871527321666220324121935
  • Stahl SM. Mechanism of action of cariprazine. CNS Spectr. 2016;21(2):123–127. doi: 10.1017/S1092852916000043
  • Sokoloff P, Diaz J, Le Foll B, et al. The dopamine D3 receptor: a therapeutic target for the treatment of neuropsychiatric disorders. CNS Neurol Disord Drug Targets. 2006;5(1):25–43. doi: 10.2174/187152706784111551
  • Fleischhacker W, Galderisi S, Laszlovszky I, et al. The efficacy of cariprazine in negative symptoms of schizophrenia: post hoc analyses of PANSS individual items and PANSS-derived factors. Eur Psychiatry. 2019;58:1–9. doi: 10.1016/j.eurpsy.2019.01.015
  • Rodriguez Cruz J, Sahlsten Schölin J, Hjorth S. Case report: cariprazine in a patient with schizophrenia, substance abuse, and cognitive dysfunction. Front Psychiatry. 2021;12:727666. doi: 10.3389/fpsyt.2021.727666
  • Montes JM, Montes P, Hernández-Huerta D. Cariprazine in three acute patients with schizophrenia: a real-world experience. Neuropsychiatr Dis Treat. 2021;17:291–296. doi: 10.2147/NDT.S298005
  • Ross S, Peselow E. Co-occurring psychotic and addictive disorders: neurobiology and diagnosis. Clin Neuropharmacol. 2012;35(5):235–243. doi: 10.1097/WNF.0b013e318261e193
  • Baler RD, Volkow ND. Drug addiction: the neurobiology of disrupted self-control. Trends Mol Med. 2006;12(12):559–566. doi: 10.1016/j.molmed.2006.10.005
  • Payer DE, Behzadi A, Kish SJ, et al. Heightened D3 dopamine receptor levels in cocaine dependence and contributions to the addiction behavioral phenotype: a positron emission tomography study with [11C]-±PHNO. Neuropsychopharmacology. 2014;39:311–318. doi: 10.1038/npp.2013.192
  • Martinez D, Gil R, Slifstein M, et al. Alcohol dependence is associated with blunted dopamine transmission in the ventral striatum. Biol Psychiatry. 2005;58(10):779–786. doi: 10.1016/j.biopsych.2005.04.044
  • Volkow ND, Chang L, Wang GJ, et al. Low level of brain dopamine D2 receptors in methamphetamine abusers: association with metabolism in the orbitofrontal cortex. Am J Psychiatry. 2001;158(12):2015–2021. doi: 10.1176/appi.ajp.158.12.2015
  • Boileau I, Nakajima S, Payer D. Imaging the D3 dopamine receptor across behavioral and drug addictions: positron emission tomography studies with [(11)C]-(+)-PHNO. Eur Neuropsychopharmacol. 2015;25:1410–1420. doi: 10.1016/j.euroneuro.2015.06.002
  • Caravaggio F, Plitman E, Chung JK, et al. Trait impulsiveness is related to smaller post-commissural putamen volumes in males but not females. Eur J Neurosci. 2017;46:2253–2264. doi: 10.1111/ejn.13661
  • Ghahremani DG, Tabibnia G, Monterosso J, et al. Effect of modafinil on learning and task-related brain activity in methamphetamine-dependent and healthy individuals. Neuropsychopharmacology. 2011;36(5):950–959. doi: 10.1038/npp.2010.233
  • Wang GJ, Smith L, Volkow ND, et al. Decreased dopamine activity predicts relapse in methamphetamine abusers. Mol Psychiatry. 2012;17(9):918–925. doi: 10.1038/mp.2011.86
  • Martinez D, Broft A, Foltin RW, et al. Cocaine dependence and d2 receptor availability in the functional subdivisions of the striatum: relationship with cocaine-seeking behavior. Neuropsychopharmacology. 2004;29(6):1190–1202. doi: 10.1038/sj.npp.1300420
  • Grunze H, Csehi R, Born C, et al. Reducing addiction in bipolar disorder via hacking the dopaminergic system. Front Psychiatry. 2021;12:803208. doi: 10.3389/fpsyt.2021.803208
  • Staley JK, Mash DC. Adaptive increase in D3 dopamine receptors in the brain reward circuits of human cocaine fatalities. J Neurosci. 1996;16(19):6100–6106. doi: 10.1523/jneurosci.16-19-06100.1996
  • Neisewander JL, Fuchs RA, Tran-Nguyen LT, et al. Increases in dopamine D3 receptor binding in rats receiving a cocaine challenge at various time points after cocaine self-administration: implications for cocaine-seeking behavior. Neuropsychopharmacology. 2004;29:1479–1487. doi: 10.1038/sj.npp.1300456
  • Boileau I, Payer D, Houle S, et al. Higher binding of the dopamine D3 receptor-preferring ligand [11C]-(+)-propyl-hexahydro-naphtho-oxazin in methamphetamine polydrug users: a positron emission tomography study. J Neurosci. 2012;32(4):1353–1359. doi: 10.1523/jneurosci.4371-11.2012
  • Nakajima S, Gerretson P, Tekeuchi H, et al. The potential role of dopamine D3 receptor neurotransmission in cognition. Eur Neuropsychopharmacol. 2013;23(8):799–813. doi: 10.1016/j.euroneuro.2013.05.006
  • Volkow ND, Baler RD. NOW vs LATER brain circuits: implications for obesity and addiction. Trends Neurosci. 2015;38(6):345–352. doi: 10.1016/j.tins.2015.04.002
  • Francis TC, Lobo MK. Emerging role for nucleus accumbens medium spiny neuron subtypes in depression. Biol Psychiatry. 2017;81(8):645–653. doi: 10.1016/j.biopsych.2016.09.007
  • Cools R, D’Esposito M. Inverted-U-shaped dopamine actions on human working memory and cognitive control. Biol Psychiatry. 2011;69(12):e113–e125. doi: 10.1016/j.biopsych.2011.03.028
  • Nestler EJ, Carlezon WA Jr. The mesolimbic dopamine reward circuit in depression. Biological Psychiatry. 2006;59(12):1151–1159. doi: 10.1016/j.biopsych.2005.09.018
  • Leggio GM, Bucolo C, Platania CB, et al. Current drug treatments targeting dopamine D3 receptor. Pharmacol Ther. 2016;165:164–177.
  • Sokoloff P, Le Foll B, Herman J. The dopamine D3 receptor, a quarter century later. Eur J Neurosci. 2017;45(1):2–19. doi: 10.1111/ejn.13390
  • Gurevich EV, Joyce JN. Distribution of dopamine D3 receptor expressing neurons in the human forebrain: comparison with D2 receptor expressing neurons. Neuropsychopharmacology. 1999;20(1):60–80. doi: 10.1016/S0893-133X(98)00066-9
  • Khan ZU, Gutierrez A, Martin R, et al. Differential regional and cellular distribution of dopamine D2-like receptors: an immunocytochemical study of subtype-specific antibodies in rat and human brain. J Comp Neurol. 1998;402(3):353–371. doi: 10.1002/(SICI)1096-9861(19981221)402:3<353:AID-CNE5>3.0.CO;2-4
  • Lévesque D, Diaz J, Pilon C, et al. Identification, characterization, and localization of the dopamine D3 receptor in rat brain using 7-[3H]hydroxy-N,N-di-n-propyl-2-aminotetralin. Proc Natl Acad Sci, USA. 1992;89(17):8155–8159. doi: 10.1073/pnas.89.17.8155
  • Sokoloff P, Giros B, Martres MP, et al. Localization and function of the D3 dopamine receptor. Arzneimittelforschung. 1992;42(2A):224–230.
  • Richtand NM. Behavioral sensitization, alternative splicing, and d3 dopamine receptor-mediated inhibitory function. Neuropsycho-pharmacology. 2006;31(11):2368–2375. doi: 10.1038/sj.npp.1301163
  • Stahl SM. Stahl’s essential psychopharmacology. 4th ed. Cambridge (UK): Cambridge University Press; 2013.
  • Stahl SM. Dazzled by the dominions of dopamine: clinical roles of D3, D2, and D1 receptors. CNS Spectr. 2017;22(4):305–311. doi: 10.1017/S1092852917000426
  • Crow TJ, Deakin JF, Longden A. The nucleus accumbens–possible site of antipsychotic action of neuroleptic drugs? Psychol Med. 1977;7(2):213–221. doi: 10.1017/s0033291700029287
  • Lieberman JA, Kinon BJ, Loebel AD. Dopaminergic mechanisms in idiopathic and drug-induced psychoses. Schizophr Bull. 1990;16(1):97–110. doi: 10.1093/schbul/16.1.97
  • Sinha R, Catapano D, O’Malley S. Stress-induced craving and stress response in cocaine dependent individuals. Psychopharmacol (Berl). 1999;142(4):343–351. doi: 10.1007/s002130050898
  • Walker EF, Diforio D. Schizophrenia: a neural diathesis-stress model. Psychol Rev. 1997;104(4):667–685. doi: 10.1037/0033-295x.104.4.667
  • Chambers RA, Krystal JH, Self DW. A neurobiological basis for substance abuse comorbidity in schizophrenia. Biol Psychiatry. 2001;50(2):71–83. doi: 10.1016/s0006-3223(01)01134-9
  • Bunney WE, Bunney BG. Evidence for a compromised dorsolateral prefrontal cortical parallel circuit in schizophrenia. Brain Res Brain Res Rev. 2000;31(2–3):138–146. doi: 10.1016/s0165-0173(99)00031-4
  • Selemon LD, Goldman-Rakic PS. The reduced neuropil hypothesis: a circuit based model of schizophrenia. Biol Psychiatry. 1999;45(1):17–25. doi: 10.1016/s0006-3223(98)00281-9
  • Weinberger DR, Aloia MS, Goldberg TE, et al. The frontal lobes and schizophrenia. J Neuropsychiatry Clin Neurosci. 1994;6(4):419–427. doi: 10.1176/jnp.6.4.419
  • Weinberger DR, Lipska BK. Cortical maldevelopment, anti-psychotic drugs, and schizophrenia: a search for common ground. Schizophr Res. 1995;16(2):87–110. doi: 10.1016/0920-9964(95)00013-c
  • Schaub CL, Schmelzeis MC, Mittleman G. The effects of limbic lesions on locomotion and stereotypy elicited by dopamine agonists in the rat. Behav Brain Res. 1997;84(1–2):129–143. doi: 10.1016/s0166-4328(96)00142-8
  • O’Donnell P, Greene J, Pabello N, et al. Modulation of cell firing in the nucleus accumbens. Ann NY Acad Sci. 1999;877:157–175. doi: 10.1111/j.1749-6632.1999.tb09267.x
  • Jay TM, Glowinski J, Thierry AM. Inhibition of hippocampoprefrontal cortex excitatory responses by the mesocortical DA system. Neuroreport. 1995;6(14):1845–1848. doi: 10.1097/00001756-199510020-00006
  • Kiss B, Horvath A, Nemethy Z, et al. Cariprazine (RGH-188), a dopamine D(3) receptor-preferring, D(3)/D(2) dopamine receptor antagonist-partial agonist antipsychotic candidate: in vitro and neurochemical profile. J Pharmacol Exp Ther. 2010;333(1):328–340. doi: 10.1124/jpet.109.160432
  • Elsworth JD, Roth RH. Dopamine autoreceptor pharmacology and function. In: Neve R, editor. I: dopamine receptors. Totowa (NJ USA): Humana Press; 1997. p. 232–265. doi: 10.1007/978-1-4757-2635-0_8
  • Bolonna AA, Kerwin RW. Partial agonism and schizophrenia. Br J Psychiatry. 2005;186:7–10. doi: 10.1192/bjp.186.1.7
  • Hernández-Huerta D, Morillo-González J. Dopamine D3 partial agonists in the treatment of psychosis and substance use disorder comorbidity: a pharmacological alternative to consider? CNS Spectr. 2021;26:444–445. doi: 10.1017/S1092852920001510
  • Volkow ND, Wang G-J, Fowler JS, et al. Relationship between blockade of dopamine transporters by oral methylphenidate and the increases in extracellular dopamine: therapeutic implications. The Synapse. 2002;43(3):181–187. doi: 10.1002/syn.10038
  • Abi-Dargham A, Gil G, Krystal J, et al. Increased striatal dopamine transmission in schizophrenia: confirmation in a second cohort. Am J Psychiatry. 1998;155(6):761–767. doi: 10.1176/ajp.155.6.761
  • Breier A, Su T-P, Saunders R, et al. Schizophrenia is associated with elevated amphetamine-induced synaptic dopamine concentrations: evidence from a novel positron emission tomography method. Proc Natl Acad Sci, USA. 1997;94(6):2569–2574. doi: 10.1073/pnas.94.6.2569
  • Farde L, Nordstrom A-L, Wiesel F-A, et al. Positron emission tomographic analysis of central D1 and D2 dopamine receptor occupancy in patients treated with classical neuroleptics and clozapine: relation to extrapyramidal side effects. Arch Gen Psychiatry. 1992;49(7):538–544. doi: 10.1001/archpsyc.1992.01820070032005
  • Gross G, Drescher K. The role of dopamine D3 receptors in antipsychotic activity and cognitive functions. Handb Exp Pharmacol. 2012;213:167–210.
  • Sautel F, Griffon N, Levesque D, et al. A functional test identifies dopamine agonists selective for D3 versus D2 receptors. Neuroreport. 1995;6(2):329–332. doi: 10.1097/00001756-199501000-00026
  • Freedman SB, Patel S, Marwood R, et al. Expression and pharmacological characterization of the human D3 receptor. J Pharmacol Exp Ther. 1994;268(1):417–426.
  • Gobert A, Rivet JM, Audinot V, et al. Functional correlates of dopamine D3 receptor activation in the rat in vivo and their modulation by the selective antagonist, (+)-S 14297: II. Both D2 and “silent” D3 auto-receptors control synthesis and release in mesolimbic, mesocortical and nigrostriatal pathways. J Pharmacol Exp Ther. 1995;275:899–913.
  • Lacroix LP, Ceolin L, Zocchi A, et al. Selective dopamine D3 receptor antagonists enhance cortical acetylcholine levels measured with high-performance liquid chromatography/tandem mass spectrometry without anti-cholinesterases. J Neurosci Methods. 2006;157(1):25–31. doi: 10.1016/j.jneumeth.2006.03.017
  • Németh G, Laszlovsky I, Czobor P, et al. Cariprazine versus risperidone monotherapy for treatment of predominant negative symptoms in patients with schizophrenia: a randomized, double-blind, controlled trial. Lancet. 2017;389(10074):1103–1113. doi: 10.1016/S0140-6736(17)30060-0
  • Frankel JS, Schwartz TL. Brexpiprazole and cariprazine: distinguishing two new atypical antipsychotics from the original dopamine stabilizer aripiprazole. Ther Adv Psychopharmacol. 2017;7(1):29–41. doi: 10.1177/2045125316672136
  • Greenberg WM, Citrome L. Pharmacokinetics and pharmacodynamics of lurasidone hydrochloride, a second-generation antipsychotic: a systematic review of the published literature. Clin Pharmacokinet. 2017;56(5):493–503. doi: 10.1007/s40262-016-0465-5
  • Tenjin T, Miyamoto S, Nonmiya Y, et al. Profile of blonanserin for the treatment of schizophrenia. Neuropsychiatr Dis Treat. 2013;9:587–594. doi: 10.2147/NDT.S34433
  • Laszlovszky I, Barabássy Á, Németh G. Cariprazine, a broad-spectrum antipsychotic for the treatment of schizophrenia: pharmacology, efficacy, and safety. Adv Ther. 2021;38(7):3652–3673. doi: 10.1007/s12325-021-01797-5
  • Citrome L. A review of the pharmacology, efficacy and tolerability of recently approved and upcoming oral antipsychotics: an evidence-based medicine approach. CNS Drugs. 2013;27(11):879–911. doi: 10.1007/s40263-013-0105-7
  • Tóth M, Varrone A, Steiger C, et al. Brain uptake and distribution of the dopamine D3/D2 receptor partial agonist [11 C]cariprazine: an in vivo positron emission tomography study in nonhuman primates. The Synapse. 2013;67(5):258–264. doi: 10.1002/syn.21631
  • Caccia S. Pharmacokinetics and metabolism update for some recent antipsychotics. Expert Opin Drug Metab Toxicol. 2011;7(7):829–846. doi: 10.1517/17425255.2011.575061
  • Zhou SF, Yang LP, Zhou ZW, et al. Insights into the substrate specificity, inhibitors, regulation, and polymorphisms and the clinical impact of human cytochrome P450 1A2. AAPS J. 2009;11(3):481–494. doi: 10.1208/s12248-009-9127-y
  • Reagila S. Reagila [summary of product characteristics]. [cited 2018 Jun 25]. Available from: https://www.ema.europa.eu/en/documents/product-information/reagila-epar-product-information_en.pdf.
  • Citrome L. The ABC’s of dopamine receptor partial agonists: aripiprazole, brexpiprazole and cariprazine: the 15-min challenge to sort these agents out. Int J Clin Pract. 2015;69(11):1211–1220. doi: 10.1111/ijcp.12752
  • Hernández-Huerta D, Morillo-González J. Dopamine D3 partial agonists in the treatment of psychosis and substance use disorder comorbidity: a pharmacological alternative to consider? CNS Spectr. 2021;26(5):444–445. doi: 10.1017/S1092852920001510
  • Martinotti G, Chiappini S, Mosca A, et al. Atypical antipsychotic drugs in dual disorders: Current evidence for clinical practice. Curr Pharm Des. 2022;28(27):2241–2259. doi: 10.2174/1381612828666220623092853
  • Beresford T, Buchanan J, Thumm EB, et al. Late reduction of cocaine cravings in a randomized, double-blind trial of aripiprazole vs perphenazine in schizophrenia and comorbid cocaine dependence. J Clin Psychopharmacol. 2017;37(6):657–663. doi: 10.1097/JCP.0000000000000789
  • Szerman N, Basurte-Villamor I, Vega P, et al. Once-monthly long-acting injectable aripiprazole for the treatment of patients with schizophrenia and co-occurring substance use disorders: a multicentre, observational study. Drugs Real World Outcomes. 2020;7(1):75–83. doi: 10.1007/s40801-020-00178-8
  • Román V, Gyertyán I, Sághy K, et al. Cariprazine (RGH-188), a D₃-preferring dopamine D₃/D₂ receptor partial agonist antipsychotic candidate demonstrates anti-abuse potential in rats. Psychopharmacol (Berl). 2013;226(2):285–293. doi: 10.1007/s00213-012-2906-7
  • Gentile A, Marini S, Matarazzo I, et al. Cariprazine in the treatment of psychosis with comorbid cannabis use: a case report. Psychiatry Res Commun. 2022;2(2):100048. doi: 10.1016/j.psycom.2022.100048
  • Sanders LO, Miller JJ. Cariprazine may decrease substance abuse in patients with bipolar I disorder. Psychiatr Times. 2019;36:10–13.
  • Truong TT, Li B. Case series: cariprazine for treatment of methamphetamine use disorder. Am J Addict. 2022;31(1):85–88. doi: 10.1111/ajad.13241
  • Rafizadeh R, Danilewitz M, Bousman CA, et al. Effects of clozapine treatment on the improvement of substance use disorders other than nicotine in individuals with schizophrenia spectrum disorders: a systematic review and meta-analysis. J Psychopharmacol. 2023;37(2):135–143. doi: 10.1177/02698811221142575
  • Brunette MF, Dawson R, O’Keefe CD, et al. A randomized trial of clozapine vs. other antipsychotics for cannabis use disorder in patients with schizophrenia. J Dual Diagn. 2011;7(1–2):50–63. doi: 10.1080/15504263.2011.570118
  • Khokhar JY, Henricks AM, Sullivan EDK, et al. Unique effects of clozapine: a pharmacological perspective. Adv Pharmacol. 2018;82:137–162. doi: 10.1016/bs.apha.2017.09.009
  • Warsi M, Sattar SP, Bhatia SC, et al. Aripiprazole reduces alcohol use. Can J Psychiatry. 2005;50(4):244. doi: 10.1177/070674370505000415
  • Martinotti G, Di Nicola M, Di Giannantonio M, et al. Aripiprazole in the treatment of patients with alcohol dependence: a double-blind, comparison trial vs. naltrexone. J Psychopharmacol. 2009;23(2):123–129. doi: 10.1177/0269881108089596
  • Janiri L, Martinotti G, Di Nicola M. Aripiprazole for relapse prevention and craving in alcohol-dependent subjects: results from a pilot study. J Clin Psychopharmacol. 2007;27(5):519–520. doi: 10.1097/JCP.0b013e318150c841
  • Cuomo I, Kotzalidis GD, Persis SD, et al. Head-to-head comparison of 1-year aripiprazole long-acting injectable (LAI) versus paliperidone LAI in comorbid psychosis and substance use disorder: impact on clinical status, substance craving, and quality of life. Neuropsychiatr Dis Treat. 2018;14:1645–1656. doi: 10.2147/NDT.S171002
  • Temmingh HS, Williams T, Siegfried N, et al. Risperidone versus other antipsychotics for people with severe mental illness and co-occurring substance misuse. Cochrane Database Syst Rev. 2018;1(1):CD011057. doi: 10.1002/14651858.CD011057.pub2
  • Beresford TP, Clapp L, Martin B, et al. Aripiprazole in schizophrenia with cocaine dependence: a pilot study. J Clin Psychopharmacol. 2005;25(4):363–366. doi: 10.1097/01.jcp.0000169419.38899.5b
  • Smith RC, Lindenmayer JP, Davis JM, et al. Cognitive and antismoking effects of varenicline in patients with schizophrenia or schizoaffective disorder. Schizophr Res. 2009;110(1–3):149–155. doi: 10.1016/j.schres.2009.02.001
  • Meszaros ZS, Abdul-Malak Y, Dimmock JA, et al. Varenicline treatment of concurrent alcohol and nicotine dependence in schizophrenia: a randomized, placebo-controlled pilot trial. J Clin Psychopharmacol. 2013;33(2):243–247. doi: 10.1097/JCP.0b013e3182870551
  • Petrakis IL, O’Malley S, Rounsaville B, et al. Naltrexone augmentation of neuroleptic treatment in alcohol abusing patients with schizophrenia. Psychopharmacol (Berl). 2004;172(3):291–297. doi: 10.1007/s00213-003-1658-9
  • Chou S, Fish KN, Lewis DA, et al. Terminal type-specific cannabinoid CB1 receptor alterations in patients with schizophrenia: a pilot study. Neurobiol Dis. 2023;14:106262. doi: 10.1016/j.nbd.2023.106262
  • Coyle JT. Substance use disorders and schizophrenia: a question of shared glutamatergic mechanisms. Neurotox Res. 2006;10(3–4):221–233. doi: 10.1007/BF03033359
  • Bradlow RCJ, Berk M, Kalivas PW, et al. The potential of N-acetyl-L-cysteine (NAC) in the treatment of psychiatric disorders. CNS Drugs. 2022;36(5):451–482. doi: 10.1007/s40263-022-00907-3

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.