Emerging drugs in phase II and III clinical development for the treatment of alcohol use disorder

References

• Witkiewitz K, Litten RZ, Leggio L. Advances in the science and treatment of alcohol use disorder. Sci Adv. 2019 Sep;5(9):eaax4043. doi: 10.1126/sciadv.aax4043
   PubMed Web of Science ®Google Scholar
• Griswold MG, Fullman N, Hawley C. Alcohol use and burden for 195 countries and territories, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. The Lancet. 2018 Sep 22;392(10152):1015–1035.
   PubMed Web of Science ®Google Scholar
• Ray LAP, Bujarski SP, Grodin EP, et al. State-of-the-art behavioral and pharmacological treatments for alcohol use disorder. Am J Drug Alcohol Abuse. 2019;45(2):124–140. doi: 10.1080/00952990.2018.1528265
   PubMed Web of Science ®Google Scholar
• White AM, Castle I-J, Powell PA, et al. Alcohol-related deaths during the COVID-19 pandemic. JAMA. 2022;327(17):1704–1706. doi: 10.1001/jama.2022.4308
   PubMed Web of Science ®Google Scholar
• World Health O. Front Matter. Global status report on alcohol and health 2018: World Health Org; 2018. p. i–ii.
   Google Scholar
• Rehm J, Shield KD, Gmel G, et al. Modeling the impact of alcohol dependence on mortality burden and the effect of available treatment interventions in the European Union. Eur Neuropsychopharmacol. 2013 Feb;23(2):89–97.
   PubMed Web of Science ®Google Scholar
• Koob GF, Volkow ND. Neurobiology of addiction: a neurocircuitry analysis. Lancet Psychiatry. 2016 Aug;3(8):760–773. doi: 10.1016/S2215-0366(16)00104-8
   PubMed Web of Science ®Google Scholar
• Lüscher C, Robbins TW, Everitt BJ. The transition to compulsion in addiction. Nat Rev Neurosci. 2020 May;21(5):247–263. doi: 10.1038/s41583-020-0289-z
   PubMed Web of Science ®Google Scholar
• Mar Y, Kunins H New York State Department of Health AIDS Institute Clinical Guidelines. treatment of alcohol use disorder. baltimore (MD): johns hopkins university copyright © Johns Hopkins University HIV Clinical Guidelines Program 2000-2018; 2020.
   Google Scholar
• Haber PS, Riordan BC, Winter DT, et al. New Australian guidelines for the treatment of alcohol problems: an overview of recommendations. Med j Aust. 2021;215(S7):S3–S32. doi: 10.5694/mja2.51254
   PubMedGoogle Scholar
• Kiefer F, Batra A, Bischof G, et al. S3-Leitlinie „Screening, Diagnose und Behandlung alkoholbezogener Störungen“. SUCHT. 2021;67(2):77–103. doi: 10.1024/0939-5911/a000704
   Google Scholar
• National Collaborating Centre for Mental H. National Institute for Health and Care Excellence: guidelines. Alcohol-Use Disorders: diagnosis, assessment and management of harmful drinking and alcohol dependence. Leicester (UK): British Psychological Society (UK) Copyright © 2011, The British Psychological Society & The Royal College of Psychiatrists; 2011.
   Google Scholar
• Bahji A, Bach P, Danilewitz M, et al. Pharmacotherapies for adults with alcohol use disorders: a systematic review and network meta-analysis. J Addict Med. 2022 Nov 1;16(6):630–638. doi: 10.1097/ADM.0000000000000992
   PubMed Web of Science ®Google Scholar
• Stanciu C, Penders T, Wuensch K, et al. Underutilization of pharmacotherapy for treatment of alcohol use disorders part II-results from a survey of practices among North Carolina mental health providers and brief review of efficacy of available pharmacotherapies. J Alcohol Drug Depend. 2017;5(5):285. doi: 10.4172/2329-6488.1000285
   Google Scholar
• Rittenberg A, Hines AL, Alvanzo AAH, et al. Correlates of alcohol use disorder pharmacotherapy receipt in medically insured patients. Drug Alcohol Depend. 2020 Sep 1;214:108174.
   PubMed Web of Science ®Google Scholar
• Harris AHS, Ellerbe L, Reeder RN, et al. Pharmacotherapy for alcohol dependence: perceived treatment barriers and action strategies among veterans health administration service providers. Psychol Serv. 2013 Nov;10(4):410–419.
   PubMed Web of Science ®Google Scholar
• Donoghue K. The correlates and extent of prescribing of medications for alcohol relapse prevention in England. Addiction. 2021 Nov;116(11):3019–3026. doi: 10.1111/add.15502
   PubMed Web of Science ®Google Scholar
• Wallhed Finn S, Lundin A, Sjöqvist H, et al. Pharmacotherapy for alcohol use disorders - unequal provision across sociodemographic factors and co-morbid conditions. A cohort study of the total population in Sweden. Drug Alcohol Depend. 2021 Oct 1;227:108964.
   PubMed Web of Science ®Google Scholar
• Han B, Jones CM, Einstein EB, et al. Use of medications for alcohol use disorder in the US: results from the 2019 National Survey on Drug use and health. JAMA Psychiatry. 2021;78(8):922–924. doi: 10.1001/jamapsychiatry.2021.1271
   PubMed Web of Science ®Google Scholar
• Crozier ME, Farokhnia M, Persky S, et al. Relationship between self-stigma about alcohol dependence and severity of alcohol drinking and craving. BMJ Ment Health. 2023 Nov 22;26(1):e300852. doi: 10.1136/bmjment-2023-300852
   PubMedGoogle Scholar
• Finn SW, Mejldal A, Nielsen AS. Public stigma and treatment preferences for alcohol use disorders. BMC Health Serv Res. 2023 Jan 24;23(1):76.
   PubMed Web of Science ®Google Scholar
• Jonas DE, Amick HR, Feltner C, et al. Pharmacotherapy for adults with alcohol use disorders in outpatient settings: a systematic review and meta-analysis. JAMA. 2014 May 14;311(18):1889–1900. doi: 10.1001/jama.2014.3628
   PubMed Web of Science ®Google Scholar
• Palpacuer C, Duprez R, Huneau A, et al. Pharmacologically controlled drinking in the treatment of alcohol dependence or alcohol use disorders: a systematic review with direct and network meta-analyses on nalmefene, naltrexone, acamprosate, baclofen and topiramate. Addiction. 2018;113(2):220–237. doi: 10.1111/add.13974
   PubMed Web of Science ®Google Scholar
• Ramprashad A, Burnett GM, Welsh C. Harm reduction: not dirty words any more. Psychiatr Clin North Am. 2022 Sep;45(3):529–546. doi: 10.1016/j.psc.2022.04.005
   PubMed Web of Science ®Google Scholar
• Rösner S, Hackl‐Herrwerth A, Leucht S, et al. Opioid antagonists for alcohol dependence. Cochrane Database Syst Rev. 2010:12. doi: 10.1002/14651858.CD001867.pub3
   Web of Science ®Google Scholar
• European Medicines Agency. Guideline on the development of medicinal products for the treatment of alcohol dependence. EMEA/CHMP/EWP/20097/2008. 2010:8.
   Google Scholar
• Looking Back MB. Looking forward: current medications and innovative potential medications to treat alcohol use disorder. Alcohol Res. 2022;42(1):11. doi: 10.35946/arcr.v42.1.11
   PubMed Web of Science ®Google Scholar
• Srisurapanont M, Jarusuraisin N. Opioid antagonists for alcohol dependence. Cochrane Database Syst Rev. 2005 Jan;25(1):Cd001867.
   Google Scholar
• Heikkinen M, Taipale H, Tanskanen A, et al. Real-world effectiveness of pharmacological treatments of alcohol use disorders in a Swedish nation-wide cohort of 125 556 patients. Addiction. 2021 Aug;116(8):1990–1998.
   PubMed Web of Science ®Google Scholar
• Lohoff FW. Pharmacotherapies and personalized medicine for alcohol use disorder: a review. Pharmacogenomics. 2020 Oct;21(15):1117–1138. doi: 10.2217/pgs-2020-0079
   PubMed Web of Science ®Google Scholar
• Cheng HY, McGuinness LA, Elbers RG, et al. Treatment interventions to maintain abstinence from alcohol in primary care: systematic review and network meta-analysis. BMJ. 2020 Nov 25;371:m3934.
   PubMedGoogle Scholar
• Shen WW. Anticraving therapy for alcohol use disorder: a clinical review. Neuropsychopharmacol Rep. 2018 Sep;38(3):105–116. doi: 10.1002/npr2.12028
   PubMedGoogle Scholar
• LiverTox: Clinical and research information on drug-induced liver injury [Internet]; 2021. Available from: https://www.ncbi.nlm.nih.gov/books/NBK548103/.
   Google Scholar
• Skinner MD, Lahmek P, Pham H, et al. Disulfiram efficacy in the treatment of alcohol dependence: a meta-analysis. PLoS ONE. 2014;9(2):e87366. doi: 10.1371/journal.pone.0087366
   PubMed Web of Science ®Google Scholar
• Burnette EM, Nieto SJ, Grodin EN, et al. Novel agents for the pharmacological treatment of alcohol use disorder. Drugs. 2022 Feb;82(3):251–274. doi: 10.1007/s40265-021-01670-3
   PubMed Web of Science ®Google Scholar
• Kedia SK, Ahuja N, Dillon PJ, et al. Efficacy of extended-release injectable naltrexone on alcohol use disorder treatment: A systematic review. J Psychoactive Drugs. 2023 Apr;55(2):233–245.
   PubMed Web of Science ®Google Scholar
• Murphy CE, Wang RC, Montoy JC, et al. Effect of extended-release naltrexone on alcohol consumption: a systematic review and meta-analysis. Addiction. 2022 Feb;117(2):271–281.
   PubMed Web of Science ®Google Scholar
• Tigh J, Daniel K, Balasanova AA. Impact of hospital-administered extended-release naltrexone on readmission rates in patients with alcohol use disorder: a Pilot Study. Prim Care Companion CNS Disord. 2022 Oct 25;24(6). doi: 10.4088/PCC.22m03213
   PubMedGoogle Scholar
• Rose JH, Karkhanis AN, Steiniger-Brach B, et al. Distinct effects of nalmefene on dopamine uptake rates and Kappa Opioid receptor activity in the nucleus accumbens following chronic intermittent ethanol exposure. Int J Mol Sci. 2016 Jul 27;17(8):1216. doi: 10.3390/ijms17081216
   PubMed Web of Science ®Google Scholar
• Higuchi S, Takahashi M, Murai Y, et al. Long-term safety and efficacy of nalmefene in Japanese patients with alcohol dependence. Psychiatry Clin Neurosci. 2020 Aug;74(8):431–438.
   PubMed Web of Science ®Google Scholar
• Chick J, Andersohn F, Guillo S, et al. Safety and persistence of Nalmefene treatment for alcohol dependence. Results from two post-authorisation safety studies. Alcohol Alcohol. 2021 Aug 30;56(5):556–564. doi: 10.1093/alcalc/agab045
   PubMed Web of Science ®Google Scholar
• Castera P, Stewart E, Großkopf J, et al. Nalmefene, given as needed, in the routine treatment of patients with alcohol dependence: an interventional, open-label study in primary care. Eur Addict Res. 2018;24(6):293–303. doi: 10.1159/000494692
   PubMed Web of Science ®Google Scholar
• Collins GB, MS M, Adury K. Drug adjuncts for treating alcohol dependence. Cleve Clin J Med. 2006 Jul;73(7):641–644. passim. doi: 10.3949/ccjm.73.7.641
   PubMed Web of Science ®Google Scholar
• Rösner S, Hackl-Herrwerth A, Leucht S, et al. Acamprosate for alcohol dependence. Cochrane Database Syst Rev. 2010 Sep;8(9):Cd004332.
   Google Scholar
• McPheeters M, O’Connor EA, Riley S, et al. Pharmacotherapy for alcohol use disorder: a systematic review and meta-analysis. JAMA. 2023 Nov 7;330(17):1653–1665. doi: 10.1001/jama.2023.19761
   PubMed Web of Science ®Google Scholar
• Fischler PV, Soyka M, Seifritz E, et al. Off-label and investigational drugs in the treatment of alcohol use disorder: a critical review. Front Pharmacol. 2022;13:927703. doi: 10.3389/fphar.2022.927703
   PubMed Web of Science ®Google Scholar
• Agabio R, Saulle R, Rösner S, et al. Baclofen for alcohol use disorder. Cochrane Database Syst Rev. 2023;2023(1):1. doi: 10.1002/14651858.CD012557.pub3
   Google Scholar
• Müller CA, Geisel O, Pelz P, et al. High-dose baclofen for the treatment of alcohol dependence (BACLAD study): a randomized, placebo-controlled trial. Eur Neuropsychopharmacol. 2015 Aug;25(8):1167–1177.
   PubMed Web of Science ®Google Scholar
• Agabio R, Baldwin DS, Amaro H, et al. The influence of anxiety symptoms on clinical outcomes during baclofen treatment of alcohol use disorder: a systematic review and meta-analysis. Neurosci Biobehav Rev. 2021 Jun;125:296–313. doi: 10.1016/j.neubiorev.2020.12.030
   PubMed Web of Science ®Google Scholar
• Duan F, Zhai H, Liu C, et al. Systematic review and meta-analysis: efficacy and safety of baclofen in patients with alcohol use disorder co-morbid liver diseases. J Psychiatr Res. 2023 Aug;164:477–484. doi: 10.1016/j.jpsychires.2023.06.042
   PubMed Web of Science ®Google Scholar
• Crunelle CL, Jegham S, Vanderbruggen N, et al. Baclofen during alcohol detoxification reduces the need for additional diazepam: a randomized placebo-controlled trial. Alcohol Alcohol. 2023 Sep 9;58(5):565–569. doi: 10.1093/alcalc/agad050
   PubMed Web of Science ®Google Scholar
• Guiraud J, Addolorato G, Aubin HJ, et al. Sodium oxybate for alcohol dependence: a network meta-regression analysis considering population severity at baseline and treatment duration. Alcohol Alcohol. 2023 Mar 10;58(2):125–133. doi: 10.1093/alcalc/agac070
   PubMed Web of Science ®Google Scholar
• Mannucci C, Pichini S, Spagnolo EV, et al. Sodium oxybate therapy for alcohol withdrawal syndrome and keeping of alcohol abstinence. Curr Drug Metab. 2018;19(13):1056–1064. doi: 10.2174/1389200219666171207122227
   PubMed Web of Science ®Google Scholar
• Leone MA, Vigna‐Taglianti F, Avanzi G, et al. Gamma‐hydroxybutyrate (GHB) for treatment of alcohol withdrawal and prevention of relapses. Cochrane Database Syst Rev. 2010 2. doi: 10.1002/14651858.CD006266.pub2
   PubMed Web of Science ®Google Scholar
• Dominguez A, Soca Gallego L, Parmar, M. Sodium Oxybate. [Updated 2023 Jan 17]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024. p. 4.
   Google Scholar
• Addolorato G, Lesch O-M, Maremmani I, et al. Post-marketing and clinical safety experience with sodium oxybate for the treatment of alcohol withdrawal syndrome and maintenance of abstinence in alcohol-dependent subjects. Expert Opin Drug Saf. 2020 Feb 01;19(2):159–166. doi: 10.1080/14740338.2020.1709821
   PubMed Web of Science ®Google Scholar
• Simpson TL, Saxon AJ, Meredith CW, et al. A pilot trial of the alpha-1 adrenergic antagonist, prazosin, for alcohol dependence. Alcohol Clin Exp Res. 2009 Feb;33(2):255–263.
   PubMed Web of Science ®Google Scholar
• Leggio L, Kenna GA. Commentary: doxazosin for alcoholism. Alcohol Clin Exp Res. 2013 Feb;37(2):191–193. doi: 10.1111/acer.12064
   PubMed Web of Science ®Google Scholar
• University of Wisconsin M, National Institute on Alcohol A, Alcoholism. Testing Doxazosin to treat stress mechanisms in alcoholism. 2020.
   Google Scholar
• Nocente R, Vitali M, Balducci G, et al. Varenicline and neuronal nicotinic acetylcholine receptors: a new approach to the treatment of co-occurring alcohol and nicotine addiction? Am J Addict. 2013 Sep;22(5):453–459.
   PubMed Web of Science ®Google Scholar
• Phimarn W, Sakhancord R, Paitoon P, et al. Efficacy of Varenicline in the treatment of alcohol dependence: an updated meta-analysis and meta-regression. Int J Environ Res Public Health. 2023 Feb 24;20(5):4091. doi: 10.3390/ijerph20054091
   PubMedGoogle Scholar
• Donato S, Green R, Ray LA. Alcohol use disorder severity moderates clinical response to varenicline. Alcohol Clin Exp Res. 2021 Sep;45(9):1877–1887. doi: 10.1111/acer.14674
   PubMed Web of Science ®Google Scholar
• Arias AJ, Feinn R, Oncken C, et al. Placebo-controlled trial of zonisamide for the treatment of alcohol dependence. J Clin Psychopharmacol. 2010 Jun;30(3):318–322.
   PubMed Web of Science ®Google Scholar
• Virginia Commonwealth U, University of C, Yale U, et al. Zonisamide treatment of alcohol use disorder: an evaluation of efficacy and mechanism of action. 2021.
   Google Scholar
• Boston University Charles River C, McLean H, University of H. Interdisciplinary study of a novel anticonvulsant in alcoholism. 2022.
   Google Scholar
• Petrakis I, Ralevski E, Arias AJ, et al. Zonisamide as an adjunctive treatment to cognitive processing therapy for veterans with posttraumatic stress disorder and comorbid alcohol use disorder: a pilot study. Am J Addict. 2020 Nov;29(6):515–524.
   PubMed Web of Science ®Google Scholar
• National Library of Medicine (U.S.). Zonisamide outpatient study. 2019–2021. https://clinicaltrials.gov/study/NCT03376139
   Google Scholar
• Petrakis I. Zonisamide in addition to E-CPT-C for veterans with PTSD and comorbid alcohol dependence. 2013–2020. https://clinicaltrials.gov/study/NCT01847469
   Google Scholar
• Rubio G, López-Muñoz F, Ponce G, et al. Zonisamide versus diazepam in the treatment of alcohol withdrawal syndrome. Pharmacopsychiatry. 2010 Nov;43(7):257–262.
   PubMed Web of Science ®Google Scholar
• Washington State U The Zonisamide and Reinforcement for Reducing Alcohol Use (ZARRA) Study. 2025.
   Google Scholar
• Gidal BE, Resnick T, Smith MC, et al. Zonisamide: a comprehensive, updated review for the clinician. Neurol Clin Pract. 2024 Feb;14(1):e200210.
   PubMedGoogle Scholar
• Laska EM, Siegel CE, Lin Z, et al. Gabapentin Enacarbil extended-release versus placebo: a likely responder reanalysis of a randomized clinical trial. Alcohol Clin Exp Res. 2020 Sep;44(9):1875–1884.
   PubMedGoogle Scholar
• Blednov YA, Da Costa AJ, Tarbox T, et al. Apremilast alters behavioral responses to ethanol in mice: I. Reduced consumption and preference. Alcohol Clin Exp Res. 2018 May;42(5):926–938.
   PubMed Web of Science ®Google Scholar
• Grigsby K, Ledford C, Batish T, et al. Targeting the maladaptive effects of binge drinking on circadian gene expression. Int J Mol Sci. 2022 Sep 21;23(19):11084. doi: 10.3390/ijms231911084
   PubMed Web of Science ®Google Scholar
• Grigsby KB, Mangieri RA, Roberts AJ, et al. Preclinical and clinical evidence for suppression of alcohol intake by apremilast. J Clin Invest. 2023 Mar 15;133(6). doi: 10.1172/JCI159103
   Web of Science ®Google Scholar
• Blednov YA, Da Costa A, Mason S, et al. Apremilast-induced increases in acute ethanol intoxication and decreases in ethanol drinking in mice involve PKA phosphorylation of GABA(A) β3 subunits. Neuropharmacology. 2022 Dec 1;220:109255.
   PubMed Web of Science ®Google Scholar
• Ray LA, Bujarski S, Shoptaw S, et al. Development of the neuroimmune modulator Ibudilast for the treatment of alcoholism: a randomized, placebo-controlled, human laboratory trial. Neuropsychopharmacology. 2017 Aug;42(9):1776–1788.
   PubMed Web of Science ®Google Scholar
• Grodin EN, Burnette EM, Green R, et al. Combined varenicline and naltrexone attenuates alcohol cue-elicited activation in heavy drinking smokers. Drug Alcohol Depend. 2021 Aug 1;225:108825.
   PubMed Web of Science ®Google Scholar
• Grodin EN, Meredith LR, Burnette EM, et al. Baseline C-reactive protein levels are predictive of treatment response to a neuroimmune modulator in individuals with an alcohol use disorder: a preliminary study. Am J Drug Alcohol Abuse. 2023 May 4;49(3):333–344. doi: 10.1080/00952990.2022.2124918
   PubMed Web of Science ®Google Scholar
• Burnette EM, Ray LA, Irwin MR, et al. Ibudilast attenuates alcohol cue-elicited frontostriatal functional connectivity in alcohol use disorder. Alcohol Clin Exp Res. 2021 Oct;45(10):2017–2028.
   PubMedGoogle Scholar
• Yardley MM, Wyatt L, Khoja S, et al. Ivermectin reduces alcohol intake and preference in mice. Neuropharmacology. 2012 Aug;63(2):190–201.
   PubMed Web of Science ®Google Scholar
• Khoja S, Huynh N, Warnecke AMP, et al. Preclinical evaluation of avermectins as novel therapeutic agents for alcohol use disorders. Psychopharmacol (Berl). 2018 Jun;235(6):1697–1709.
   PubMed Web of Science ®Google Scholar
• Roche DJ, Yardley MM, Lunny KF, et al. A pilot study of the safety and initial efficacy of Ivermectin for the treatment of alcohol use disorder. Alcohol Clin Exp Res. 2016 Jun;40(6):1312–1320.
   PubMed Web of Science ®Google Scholar
• Silva J, Carry E, Xue C, et al. A novel dual drug approach that combines Ivermectin and Dihydromyricetin (DHM) to reduce alcohol drinking and preference in mice. Molecules. 2021 Mar 22;26(6):1791. doi: 10.3390/molecules26061791
   PubMed Web of Science ®Google Scholar
• Narendran R, Mason NS, Paris J, et al. Decreased prefrontal cortical dopamine transmission in alcoholism. Am J Psychiatry. 2014 Aug;171(8):881–888.
   PubMed Web of Science ®Google Scholar
• Doyle MR, Dirik S, Martinez AR, et al. Catechol-O-Methyltransferase inhibition and alcohol use disorder: Evaluating the efficacy of tolcapone in ethanol-dependent rats. Neuropharmacology. 2023 Oct;17:109770. doi: 10.1016/j.neuropharm.2023.109770
   Google Scholar
• McCane AM, Ahn S, Rubchinsky LL, et al. COMT inhibition alters cue-evoked oscillatory dynamics during alcohol drinking in the rat. eNeuro. 2018 Sep;5(5):ENEURO.0326–18.2018.
   PubMed Web of Science ®Google Scholar
• Coker AR, Weinstein DN, Vega TA, et al. The catechol-O-methyltransferase inhibitor tolcapone modulates alcohol consumption and impulsive choice in alcohol use disorder. Psychopharmacol (Berl). 2020 Oct;237(10):3139–3148.
   PubMed Web of Science ®Google Scholar
• Schacht JP, Yeongbin I, Hoffman M, et al. Effects of pharmacological and genetic regulation of COMT activity in alcohol use disorder: a randomized, placebo-controlled trial of tolcapone. Neuropsychopharmacology. 2022 Oct;47(11):1953–1960.
   PubMed Web of Science ®Google Scholar
• Vendruscolo LF, Estey D, Goodell V, et al. Glucocorticoid receptor antagonism decreases alcohol seeking in alcohol-dependent individuals. J Clin Invest. 2015 Aug 3;125(8):3193–3197. doi: 10.1172/JCI79828
   PubMed Web of Science ®Google Scholar
• Haass-Koffler CL, Magill M, Cannella N, et al. Mifepristone as a pharmacological intervention for stress-induced alcohol craving: A human laboratory study. Addict Biol. 2023 Jul;28(7):e13288.
   Web of Science ®Google Scholar
• Khom S, Rodriguez L, Gandhi P, et al. Alcohol dependence and withdrawal increase sensitivity of central amygdalar GABAergic synapses to the glucocorticoid receptor antagonist mifepristone in male rats. Neurobiol Dis. 2022 Mar;164:105610. doi: 10.1016/j.nbd.2022.105610
   PubMed Web of Science ®Google Scholar
• Campbell EJ, Hill MK, Maddern XJ, et al. Orexin-1 receptor signaling within the lateral hypothalamus, but not bed nucleus of the stria terminalis, mediates context-induced relapse to alcohol seeking. J Psychopharmacol. 2020 Nov;34(11):1261–1270.
   PubMed Web of Science ®Google Scholar
• Flores-Ramirez FJ, Illenberger JM, Pascasio GE, et al. Alternative use of suvorexant (Belsomra(®)) for the prevention of alcohol drinking and seeking in rats with a history of alcohol dependence. Front Behav Neurosci. 2022;16:1085882. doi: 10.3389/fnbeh.2022.1085882
   PubMed Web of Science ®Google Scholar
• Mason BJ. Medication Development in Alcoholism: Suvorexant Versus Placebo. 2021–2023. https://clinicaltrials.gov/study/NCT04229095
   Google Scholar
• Sun H, Yee KL, Gill S, et al. Psychomotor effects, pharmacokinetics and safety of the orexin receptor antagonist suvorexant administered in combination with alcohol in healthy subjects. J Psychopharmacol. 2015 Nov;29(11):1159–1169.
   PubMed Web of Science ®Google Scholar
• McAndrew A, Lawn W, Stevens T, et al. A proof-of-concept investigation into ketamine as a pharmacological treatment for alcohol dependence: study protocol for a randomised controlled trial. Trials. 2017 Apr 4;18(1):159. doi: 10.1186/s13063-017-1895-6
   PubMedGoogle Scholar
• Kelson M, Burnett JM, Matthews A, et al. Ketamine treatment for alcohol use disorder: a systematic review. Cureus. 2023 May;15(5):e38498.
   PubMed Web of Science ®Google Scholar
• Nopoulos P. Psilocybin-Assisted vs Ketamine-Assisted Psychotherapy for Alcohol Use Disorder. 2022–2024. https://clinicaltrials.gov/study/NCT05421065
   Google Scholar
• Mark N, National Institute of Mental H, University of I. Ketamine Alcohol (in Treatment-Resistant Depression). 2024.
   Google Scholar
• de Veen BT, Schellekens AF, Verheij MM, et al. Psilocybin for treating substance use disorders? Expert Rev Neurother. 2017 Feb;17(2):203–212.
   PubMed Web of Science ®Google Scholar
• Meinhardt MW, Pfarr S, Fouquet G, et al. Psilocybin targets a common molecular mechanism for cognitive impairment and increased craving in alcoholism. Sci Adv. 2021 Nov 19;7(47):eabh2399. doi: 10.1126/sciadv.abh2399
   PubMed Web of Science ®Google Scholar
• Bogenschutz MP, Ross S, Bhatt S, et al. Percentage of heavy drinking days following psilocybin-assisted psychotherapy vs placebo in the treatment of adult patients with alcohol use disorder: a randomized clinical trial. JAMA Psychiatry. 2022 Oct 1;79(10):953–962. doi: 10.1001/jamapsychiatry.2022.2096
   PubMed Web of Science ®Google Scholar
• van der Meer PB, Fuentes JJ, Kaptein AA, et al. Therapeutic effect of psilocybin in addiction: a systematic review. Front Psychiatry. 2023;14:1134454. doi: 10.3389/fpsyt.2023.1134454
   PubMed Web of Science ®Google Scholar
• Dos Santos RG, Bouso JC, Alcázar-Córcoles M, et al. Efficacy, tolerability, and safety of serotonergic psychedelics for the management of mood, anxiety, and substance-use disorders: a systematic review of systematic reviews. Expert Rev Clin Pharmacol. 2018 Sep;11(9):889–902.
   PubMed Web of Science ®Google Scholar
• MacCallum CA, Lo LA, Pistawka CA, et al. Therapeutic use of psilocybin: practical considerations for dosing and administration. Front Psychiatry. 2022;13:1040217. doi: 10.3389/fpsyt.2022.1040217
   PubMed Web of Science ®Google Scholar
• Herkenham K. A regulatory framework review of schedule I psychedelics in the United States. J Am Coll Clin Pharm. 2023;6(10):1117–1124. doi: 10.1002/jac5.1841
   Google Scholar
• Anders Fink-Jensen MDD, The Neurobiology Research Unit at Copenhagen University Hospital R, Psychiatric Centre R. Psilocybin-assisted Therapy for Treatment of Alcohol Use Disorder. 2024.
   Google Scholar
• Jensen ME, Stenbæk DS, Juul TS, et al. Psilocybin-assisted therapy for reducing alcohol intake in patients with alcohol use disorder: protocol for a randomised, double-blinded, placebo-controlled 12-week clinical trial (The QUANTUM Trip Trial). BMJ Open. 2022 Oct 14;12(10):e066019. doi: 10.1136/bmjopen-2022-066019
   PubMed Web of Science ®Google Scholar
• Marty VN, Farokhnia M, Munier JJ, et al. Long-acting glucagon-like peptide-1 receptor agonists suppress voluntary alcohol intake in male wistar rats. Front neurosci. 2020;14:599646. doi: 10.3389/fnins.2020.599646
   PubMed Web of Science ®Google Scholar
• Aranäs C, Edvardsson CE, Shevchouk OT, et al. Semaglutide reduces alcohol intake and relapse-like drinking in male and female rats. EBioMedicine. 2023;93:104642. doi: 10.1016/j.ebiom.2023.104642
   PubMed Web of Science ®Google Scholar
• Chuong V, Farokhnia M, Khom S, et al. The glucagon-like peptide-1 (GLP-1) analogue semaglutide reduces alcohol drinking and modulates central GABA neurotransmission. JCI Insight. 2023 Jun 22;8(12). doi: 10.1172/jci.insight.170671
   PubMed Web of Science ®Google Scholar
• Shirazi RH, Dickson SL, Skibicka KP, et al. Gut peptide GLP-1 and its analogue, Exendin-4, decrease alcohol intake and reward. PLoS ONE. 2013;8(4):e61965. doi: 10.1371/journal.pone.0061965
   PubMed Web of Science ®Google Scholar
• Vallöf D, Kalafateli AL, Jerlhag E. Long-term treatment with a glucagon-like peptide-1 receptor agonist reduces ethanol intake in male and female rats. Transl Psychiatry. 2020;10(1):238. doi: 10.1038/s41398-020-00923-1
   PubMed Web of Science ®Google Scholar
• Egecioglu E, Steensland P, Fredriksson I, et al. The glucagon-like peptide 1 analogue Exendin-4 attenuates alcohol mediated behaviors in rodents. Psychoneuroendocrinology. 2013;38(8):1259–1270. doi: 10.1016/j.psyneuen.2012.11.009
   PubMed Web of Science ®Google Scholar
• Vallöf D, Maccioni P, Colombo G, et al. The glucagon‐like peptide 1 receptor agonist liraglutide attenuates the reinforcing properties of alcohol in rodents. Addict Biol. 2016;21(2):422–437. doi: 10.1111/adb.12295
   PubMed Web of Science ®Google Scholar
• Klausen MK, Jensen ME, Møller M, et al. Exenatide once weekly for alcohol use disorder investigated in a randomized, placebo-controlled clinical trial. JCI Insight. 2022;7(19). doi: 10.1172/jci.insight.159863
   PubMed Web of Science ®Google Scholar
• King CE, Griffin WC, Luderman LN, et al. Oxytocin reduces ethanol Self‐Administration in mice. Alcohol Clin Exp Res. 2017;41(5):955–964. doi: 10.1111/acer.13359
   PubMed Web of Science ®Google Scholar
• Stevenson JR, Wenner SM, Freestone DM, et al. Oxytocin reduces alcohol consumption in prairie voles. Physiol Behav. 2017 Oct 01;179:411–421.
   PubMed Web of Science ®Google Scholar
• Bowen MT, Neumann ID. Rebalancing the addicted brain: Oxytocin interference with the neural substrates of addiction. Trends Neurosci. 2016;40(12):691–708. doi: 10.1016/j.tins.2017.10.003
   Web of Science ®Google Scholar
• Pedersen CA, Smedley KL, Leserman J, et al. Intranasal oxytocin blocks alcohol withdrawal in human subjects. Alcohol Clin Exp Res. 2013 Mar;37(3):484–489.
   PubMed Web of Science ®Google Scholar
• Melby K, Grawe RW, Aamo TO, et al. Effect of intranasal oxytocin on alcohol withdrawal syndrome: a randomized placebo-controlled double-blind clinical trial. Drug Alcohol Dependence. 2019 Feb 13;197:95–101.
   PubMed Web of Science ®Google Scholar
• Melby K, Gråwe RW, Aamo TO, et al. Efficacy of self-administered intranasal oxytocin on alcohol use and craving after detoxification in patients with alcohol dependence. A double-blind placebo-controlled trial. Alcohol Alcohol. 2021;56(5):565–572. doi: 10.1093/alcalc/agaa133
   PubMed Web of Science ®Google Scholar
• Mitchell JM, Arcuni PA, Weinstein D, et al. Intranasal oxytocin selectively modulates social perception, craving, and approach behavior in subjects with alcohol use disorder. J Addict Med. 2016 May;10(3):182–189.
   PubMed Web of Science ®Google Scholar
• Flanagan JC, Allan NP, Calhoun CD, et al. Effects of oxytocin on stress reactivity and craving in veterans with co-occurring PTSD and alcohol use disorder. Exp Clin Psychopharmacol. 2019;27(1):45. doi: 10.1037/pha0000232
   PubMed Web of Science ®Google Scholar
• Stauffer CS, Meinzer NK, Morrison T, et al. Effects of oxytocin administration on cue‐induced craving in co‐occurring alcohol use disorder and PTSD: a within‐participant randomized clinical trial. Alcohol Clin Exp Res. 2019;43(12):2627–2636. doi: 10.1111/acer.14217
   PubMedGoogle Scholar
• Mellentin AI, Finn SW, Skøt L, et al. The effectiveness of oxytocin for treating substance use disorders: a systematic review of randomized placebo-controlled trials. Neuroscience & Biobehavioral Reviews. 2023 Aug 01;151:105185.
   PubMed Web of Science ®Google Scholar
• Zimmermann S, Thomas BC, Krisam J, et al. ON-ICE trial: investigation of the combined effects of oxytocin and naltrexone on stress-induced and alcohol cue-induced craving in alcohol use disorder-Study protocol of a phase II randomised double-blind placebo-controlled parallel-group trial. BMJ Open. 2022 Apr 11;12(4):e059672. doi: 10.1136/bmjopen-2021-059672
   PubMedGoogle Scholar
• Morales P, Hurst DP, Reggio PH. Molecular targets of the phytocannabinoids: a complex picture. Phytocannabinoids: unraveling the complex chemistry and pharmacology of cannabis sativa. 2017;103:103–131.
   Google Scholar
• Schoedel KA, Szeto I, Setnik B, et al. Abuse potential assessment of cannabidiol (CBD) in recreational polydrug users: a randomized, double-blind, controlled trial. Epilepsy Behav. 2018;88:162–171. doi: 10.1016/j.yebeh.2018.07.027
   PubMed Web of Science ®Google Scholar
• Babalonis S, Haney M, Malcolm RJ, et al. Oral cannabidiol does not produce a signal for abuse liability in frequent marijuana smokers. Drug Alcohol Dependence. 2017;172:9–13. doi: 10.1016/j.drugalcdep.2016.11.030
   PubMed Web of Science ®Google Scholar
• Gonzalez-Cuevas G, Martin-Fardon R, Kerr TM, et al. Unique treatment potential of cannabidiol for the prevention of relapse to drug use: preclinical proof of principle. Neuropsychopharmacology. 2018 Sep;43(10):2036–2045.
   PubMed Web of Science ®Google Scholar
• Viudez-Martínez A, García-Gutiérrez MS, Navarrón CM, et al. Cannabidiol reduces ethanol consumption, motivation and relapse in mice. Addict Biol. 2018;23(1):154–164. doi: 10.1111/adb.12495
   PubMed Web of Science ®Google Scholar
• Viudez-Martínez A, García-Gutiérrez MS, Fraguas-Sánchez AI, et al. Effects of cannabidiol plus naltrexone on motivation and ethanol consumption. Br J Pharmacol. 2018;175(16):3369–3378. doi: 10.1111/bph.14380
   PubMed Web of Science ®Google Scholar
• Hurd YL, Sharron Spriggs MA, Julia Alishayev RPA, et al. Cannabidiol for the reduction of cue-induced craving and anxiety in drug-abstinent individuals with heroin use disorder: a double-blind randomized placebo-controlled trial. Am J Psychiatry. 2019;176(11):911–922. doi: 10.1176/appi.ajp.2019.18101191
   PubMed Web of Science ®Google Scholar
• Karoly HC, Mueller RL, Andrade CC, et al. THC and CBD effects on alcohol use among alcohol and cannabis co-users. Psychol Addict Behav. 2021 Sep;35(6):749–759.
   PubMed Web of Science ®Google Scholar
• Soyka M, Rösner S. Pharmakotherapie der Alkoholentwöhnung: Update und neue Entwicklungen. Nervenarzt. 2021 Jan 01;92(1):57–65.
   PubMedGoogle Scholar
• Falk DE, O’Malley SS, Witkiewitz K, et al. Evaluation of drinking risk levels as outcomes in alcohol pharmacotherapy trials: a secondary analysis of 3 randomized clinical trials. JAMA Psychiatry. 2019 Apr 1;76(4):374–381. doi: 10.1001/jamapsychiatry.2018.3079
   PubMed Web of Science ®Google Scholar
• Rösner S, Soyka M. Outcome assessment in trials of pharmacological treatments for alcohol use disorders: fair and strict testing. CNS Drugs. 2019 Jul;33(7):649–657. doi: 10.1007/s40263-019-00644-0
   PubMed Web of Science ®Google Scholar
• Litten RZ, Ryan ML, Falk DE, et al. Heterogeneity of alcohol use disorder: understanding mechanisms to advance personalized treatment. Alcohol Clin Exp Res. 2015;39(4):579–584. doi: 10.1111/acer.12669
   PubMed Web of Science ®Google Scholar
• Pushpakom S, Iorio F, Eyers PA, et al. Drug repurposing: progress, challenges and recommendations. Nat Rev Drug Discov. 2019 Jan 01;18(1):41–58. doi: 10.1038/nrd.2018.168
   PubMed Web of Science ®Google Scholar