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A historical perspective on clonidine as an alpha-2A receptor agonist in the treatment of addictive behaviors: Focus on opioid dependence

Mark S. Gold1 ,  Kenneth Blum2,3,4,5,6,7,8,9,10,11* ,  Abdalla Bowirrat5 ,  Albert Pinhasov5 ,  Debasis Bagchi12,13 ,  Catherine A. Dennen14 ,  Panayotis K. Thanos5,15,16 ,  Colin Hanna15,16 ,  Kai-Uwe Lewandrowski17,18,19 ,  Alireza Sharafshah20 ,  Igor Elman5,21 ,  Rajendra D. Badgaiyan22,23
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1 Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, United States of America
2 Division of Addiction Research and Education, Center for Sports, Exercise and Global Mental Health, Western University Health Sciences, Pomona, California, United States of America
3 The Kenneth Blum Behavioral and Neurogenetic Institute LLC, Austin, Texas, United States of America
4 Department of Psychology, Faculty of Education and Psychology, Institute of Psychology, Eötvös Loránd University Budapest, Budapest, Hungary
5 Department of Molecular Biology and Adelson School of Medicine, Ariel University, Ariel, Israel
6 Division of Personalized Medicine, Cross-Cultural Research and Educational Institute, San Clemente, California, United States of America
7 Centre for Genomics and Applied Gene Technology, Institute of Integrative Omics and Applied Biotechnology, Nonakuri, West Bengal, India
8 Department of Clinical Psychology and Addiction, Institute of Psychology, Faculty of Education and Psychology, Eötvös Loránd University, Budapest, Hungary
9 Department of Psychiatry, University of Vermont, Burlington, Vermont, United States of America
10 Department of Psychiatry, Wright University, Boonshoft School of Medicine, Dayton, Ohio, United States of America
11 Division of Personalized Medicine, Ketamine Infusion Clinic of South Florida, Pompano, Florida, United States of America
12 Department of Nutrigenomic Research, Victory Nutrition International, Inc., Bonita Springs, Florida, United States of America
13 Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Texas Southern University, Houston, Texas, United States of America
14 Department of Family Medicine, Jefferson Health Northeast, Philadelphia, Pennsylvania, United States of America
15 Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions, Clinical Research Institute on Addictions, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biosciences, State University of New York at Buffalo, Buffalo, New York, United States of America
16 Department of Psychology, State University of New York at Buffalo, Buffalo, New York, United States of America
17 Division of Personalized Pain Therapy Research, Center for Advanced Spine Care of Southern Arizona, Tucson, Arizona, United States of America
18 Department of Orthopaedics, Fundación Universitaria Sanitas, Bogotá, Colombia
19 Department of Orthopedics, Hospital Universitário Gaffree Guinle Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro, Brazil
20 Cellular and Molecular Research Center, School of Medicine, Guilan University of Medical Sciences, Rasht, Gilan, Iran
21 Department of Psychiatry, School of Medicine, Harvard University, Cambridge, Massachusetts, United States of America
22 Department of Psychiatry, Mt. Sinai School of Medicine, New York City, New York, United States of America
23 Department of Psychiatry, School of Medicine, Case Western Reserve University, Cleveland, Ohio, United States of America
INNOSC Theranostics and Pharmacological Sciences 2024, 7(3), 1918 https://doi.org/10.36922/itps.1918
Submitted: 26 September 2023 | Accepted: 27 March 2024 | Published: 29 July 2024
(This article belongs to the Special Issue Behavioral Addictions: From Bench to Bedside)
© 2024 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Clonidine operates through agonism at the alpha-2A receptor, a specific subtype of the alpha-2-adrenergic receptor located predominantly in the prefrontal cortex. By inhibiting the release of norepinephrine, which is responsible for withdrawal symptoms, clonidine effectively addresses withdrawal-related conditions such as anxiety, hypertension, and tachycardia. The groundbreaking work by Gold et al. demonstrated clonidine’s ability to counteract the effects of locus coeruleus stimulation, reshaping the understanding of opioid withdrawal within the field. In the 1980s, the efficacy of clonidine in facilitating the transition to long-acting injectable naltrexone was confirmed for individuals motivated to overcome opioid use disorders (OUDs), including physicians and executives. Despite challenges with compliance, naltrexone offers sustained blockade of opioid receptors, reducing the risk of overdose, intoxication, and relapse in motivated patients in recovery. The development of clonidine and naltrexone as treatment modalities for OUDs, and potentially other addictions, including behavioral ones, underscores the potential for translating neurobiological advancements from preclinical models (bench) to clinical practice (bedside), ushering in innovative approaches to addiction treatment.

Keywords
Behavioral addictions
Clonidine
Opioid use disorder
Substance use disorder
Naltrexone
Locus coeruleus
Funding
The study is supported by The Pharmacotherapies for Alcohol and Substance Abuse (PASA) Consortium (grant no.: AS170014-A6).
Conflict of interest
Dr. Blum is the inventor of GARS® and Pro-dopamine Regulation (KB220Z™). There are no other conflicts of interest.
References
  1. Neil MJ. Clonidine: Clinical pharmacology and therapeutic use in pain management. Curr Clin Pharmacol. 2011;6(4):280-287. doi: 10.2174/157488411798375886

 

  1. Clonidine Monograph for Professionals. Available from: https://www.drugs.com/monograph/clonidine.html [Last accessed on 2023 Sep 22].

 

  1. Yasaei R, Saadabadi A. Clonidine. Treasure Island, FL: StatPearls Publishing; 2023.

 

  1. Bolliger L, Stevens H. From opioid pain management to opioid crisis in the USA: How can public-private partnerships help? Front Med (Lausanne). 2019;6:106. doi: 10.3389/fmed.2019.00106

 

  1. Srivastava AB, Mariani JJ, Levin FR. New directions in the treatment of opioid withdrawal. Lancet. 2020;395(10241):1938-1948. doi: 10.1016/S0140-6736(20)30852-7

 

  1. Ziegenhorn AA, Roepke S, Schommer NC, et al. Clonidine improves hyperarousal in borderline personality disorder with or without comorbid posttraumatic stress disorder: A randomized, double-blind, placebo-controlled trial. J Clin Psychopharmacol. 2009;29(2):170-173. doi: 10.1097/JCP.0b013e31819a4bae

 

  1. Gold MS, Pottash AC, Extein IL, Kleber HD. Neuroanatomical sites of action of clonidine in opioid withdrawal: The locus coeruleus connection. Prog Clin Biol Res. 1981;71:285-298.

 

  1. Kane SP. Phar, BCPS. Clonidine. Available from: https:// clincalc.com/drugstats/drugs/clonidine [Last accessed on 2023 Sep 22].

 

  1. Khan ZP, Ferguson CN, Jones RM. Alpha-2 and imidazoline receptor agonists. Their pharmacology and therapeutic role. Anaesthesia. 1999;54(2):146-165. doi: 10.1046/j.1365-2044.1999.00659.xwsx

 

  1. Foye WO. Foye’s Principles of Medicinal Chemistry. Philadelphia, PA: Lippincott Williams & Wilkins; 2008.

 

  1. Pajouhesh H, Lenz GR. Medicinal chemical properties of successful central nervous system drugs. NeuroRx. 2005;2(4):541-553. doi: 10.1602/neurorx.2.4.541

 

  1. Fitzgerald PJ. Elevated norepinephrine may be a unifying etiological factor in the abuse of a broad range of substances: Alcohol, nicotine, marijuana, heroin, cocaine, and caffeine. Subst Abuse. 2013;7:171-183. doi: 10.4137/SART.S13019

 

  1. Glassman AH, Jackson WK, Walsh BT, Roose SP, Rosenfeld B. Cigarette craving, smoking withdrawal, and clonidine. Science. 1984;226(4676):864-866. doi: 10.1126/science.6387913

 

  1. Giannini AJ, Extein I, Gold MS, Pottash AL, Castellani S. Clonidine in mania. Drug Dev Res. 1983;3(1):101-103.

 

  1. Streetz VN, Gildon BL, Thompson DF. Role of clonidine in neonatal abstinence syndrome: A systematic review. Ann Pharmacother. 2016;50(4):301-310. doi: 10.1177/1060028015626438

 

  1. Disher T, Gullickson C, Singh B, et al. Pharmacological treatments for neonatal abstinence syndrome: A systematic review and network meta-analysis. JAMA Pediatr. 2019;173(3):234-243. doi: 10.1001/jamapediatrics.2018.5044

 

  1. Lester BM, Tronick EZ, LaGasse L, et al. The maternal lifestyle study: Effects of substance exposure during pregnancy on neurodevelopmental outcome in 1-month-old infants. Pediatrics. 2002;110(6):1182-1192. doi: 10.1542/peds.110.6.1182

 

  1. Oesterle TS, Thusius NJ, Rummans TA, Gold MS. Medication-assisted treatment for opioid-use disorder. Mayo Clin Proc. 2019;94(10):2072-2086. doi: 10.1016/j.mayocp.2019.03.029

 

  1. Rhee TG, Rosenheck RA. Use of drug treatment services among adults with opioid use disorder: Rates, patterns, and correlates. Psychiatr Serv. 2019;70(11):992-999. doi: 10.1176/appi.ps.201900163

 

  1. McLellan AT, Skipper GS, Campbell M, DuPont RL. Five year outcomes in a cohort study of physicians treated for substance use disorders in the United States. BMJ. 2008;337:a2038. doi: 10.1136/bmj.a2038

 

  1. DuPont RL, McLellan AT, White WL, Merlo LJ, Gold MS. Setting the standard for recovery: Physicians’ health programs. J Subst Abuse Treat. 2009;36(2):159-171. doi: 10.1016/j.jsat.2008.01.004

 

  1. Merlo LJ, Campbell MD, Skipper GE, Shea CL, DuPont RL. Outcomes for physicians with opioid dependence treated without agonist pharmacotherapy in physician health programs. J Subst Abuse Treat. 2016;64:47-54. doi: 10.1016/j.jsat.2016.02.004

 

  1. Buhl A, Oreskovich MR, Meredith CW, Campbell MD, Dupont RL. Prognosis for the recovery of surgeons from chemical dependency: A 5-year outcome study. Arch Surg. 2011;146(11):1286-1291. doi: 10.1001/archsurg.2011.271

 

  1. Bell J, Strang J. Medication treatment of opioid use disorder. Biol Psychiatry. 2020;87(1):82-88. doi: 10.1016/j.biopsych.2019.06.020

 

  1. Merlo LJ, Gold MS. Prescription opioid abuse and dependence among physicians: Hypotheses and treatment. Harv Rev Psychiatry. 2008;16(3):181-194. doi: 10.1080/10673220802160316

 

  1. Merlo LJ, Greene WM. Physician views regarding substance use-related participation in a state physician health program. Am J Addict. 2010;19(6):529-533. doi: 10.1111/j.1521-0391.2010.00088.x

 

  1. Merlo LJ, Greene WM, Pomm R. Mandatory naltrexone treatment prevents relapse among opioid-dependent anesthesiologists returning to practice. J Addict Med. 2011;5(4):279-283. doi: 10.1097/ADM.0b013e31821852a0

 

  1. Gold MS, Kleber HD. A rationale for opioid withdrawal symptomatology. Drug Alcohol Depend. 1979;4(5):419-424. doi: 10.1016/0376-8716(79)90074-7

 

  1. Roth RH, Elsworth JD, Redmond DE Jr. Clonidine suppression of noradrenergic hyperactivity during morphine withdrawal by clonidine: Biochemical studies in rodents and primates. J Clin Psychiatry. 1982;43(6 Pt 2):42-46.

 

  1. Gold MS, Pottash AC, Sweeney DR, Extein I, Annitto WJ. Opioid detoxification with lofexidine. Drug Alcohol Depend. 1981;8(4):307-315. doi: 10.1016/0376-8716(81)90040-5

 

  1. Pergolizzi JV Jr., Annabi H, Gharibo C, LeQuang JA. The role of lofexidine in management of opioid withdrawal. Pain Ther. 2019;8(1):67-78. doi: 10.1007/s40122-018-0108-7

 

  1. Kosten TR, O’Connor PG. Management of drug and alcohol withdrawal. N Engl J Med. 2003;348(18):1786-1795. doi: 10.1056/NEJMra020617

 

  1. Zornetzer SF, Gold MS. The locus coeruleus: Its possible role in memory consolidation. Physiol Behav. 1976;16(3):331-336. doi: 10.1016/0031-9384(76)90140-2

 

  1. Gold MS, Redmond DE Jr., Kleber HD. Clonidine blocks acute opioid-withdrawal symptoms. Lancet. 1978;2(8090):599-602. doi: 10.1016/s0140-6736(78)92823-4

 

  1. Gold MS, Dackis CA. The Discovery of Clonidine’s Action in Opioid Withdrawal. Munich: Catapressan, Arsneimittel- Forschung; 1983. p. 155-175.

 

  1. Gold MS. Opioid addiction and the locus coeruleus. The clinical utility of clonidine, naltrexone, methadone, and buprenorphine. Psychiatr Clin North Am. 1993;16(1):61-73.

 

  1. Kleber HD, Gold MS, Riordan CE. The use of clonidine in detoxification from opioids. Bull Narc. 1980;32(2):1-10.

 

  1. Gold MS, Roehrich H. Treatment of opioid withdrawal with clonidine. ISI Atlas of Science. Pharmacology. 1987;1741:29-32.

 

  1. Gold MS, De R. Pharmacological activation and inhibition of noradrenergic activity after specific behaviors in nonhuman primates. Soc Neurosci. 1977;3(783):250.

 

  1. De R, Hwang Y, Gold MS. Anxiety: The locus coeruleus connection. Soc Neurosci. 1977;3.

 

  1. Redmond DE, Gold MS, Huang YH. Enkephalin Acts to Inhibit Locus Coeruleus Mediated Behaviors. In: Society for Neuroscience Abstracts; 1978. p. 4.

 

  1. Gold MS, Redmond DE Jr., Kleber HD. Noradrenergic hyperactivity in opioid withdrawal supported by clonidine reversal of opioid withdrawal. Am J Psychiatry. 1979;136(1):100-102. doi: 10.1176/ajp.136.1.100

 

  1. Redmond DE Jr. Boehringer Ingelheim International GmbH, Assignee. Method of Eliminating Opioid Withdrawal Symptoms with Clonidine in Humans. United States Patent US 4,312,878; 1982.

 

  1. Blum K, Wallace JE. Effects of catecholamine synthesis inhibition on ethanol-induced withdrawal symptoms in mice. Br J Pharmacol. 1974;51(1):109-111. doi: 10.1111/j.1476-5381.1974.tb09640.x

 

  1. Blum K, Eubanks JD, Wallace JE, Schwertner H, Morgan WW. Possible role of tetrahydroisoquinoline alkaloids in postalcohol intoxication states. Ann N Y Acad Sci. 1976;273:234-246. doi: 10.1111/j.1749-6632.1976.tb52887.x

 

  1. Blum K, Eubanks JD, Wallace JE, Schwertner HA. Suppression of ethanol withdrawal by dopamine. Experientia. 1976;32(4):493-495. doi: 10.1007/BF01920816

 

  1. Blum K, Eubanks JD, Wiggins B, Wallace JE. Morphine withdrawal reactions in male and female mice. Am J Drug Alcohol Abuse. 1976;3(2):363-368. doi: 10.3109/00952997609077204

 

  1. Blum K, Wallace JE, Schwerter HA, Eubanks JD. Morphine suppression of ethanol withdrawal in mice. Experientia. 1976;32(1):79-82. doi: 10.1007/BF01932634

 

  1. Blum K, Wallace JE, Schwertner HA, Eubanks JD. Enhancement of ethanol-induced withdrawal convulsions by blockade of 5-hydroxytryptamine receptors. J Pharm Pharmacol. 1976;28(11):832-835. doi: 10.1111/j.2042-7158.1976.tb04066.x

 

  1. Blum K, Briggs AH, DeLallo L. Clonidine enhancement of ethanol withdrawal in mice. Subst Alcohol Actions Misuse. 1983;4(1):59-63.

 

  1. Gold MS, Pottash AC, Sweeney DR, Extein I, Annitto WJ. Lofexidine blocks acute opioid withdrawal. NIDA Res Monogr. 1982;41:264-268.

 

  1. Washton AM, Pottash AC, Gold MS. Naltrexone in addicted business executives and physicians. J Clin Psychiatry. 1984;45(9 Pt 2):39-41.

 

  1. Taylor JR, Elsworth JD, Garcia EJ, Grant SJ, Roth RH, Redmond DE Jr. Clonidine infusions into the locus coeruleus attenuate behavioral and neurochemical changes associated with naloxone-precipitated withdrawal. Psychopharmacology (Berl). 1988;96(1):121-134. doi: 10.1007/BF02431544

 

  1. Kimes AS, Bell JA, London ED. Clonidine attenuates increased brain glucose metabolism during naloxone-precipitated morphine withdrawal. Neuroscience. 1990;34(3):633-644. doi: 10.1016/0306-4522(90)90170-9

 

  1. Gold MS, Kleber HD. Clinical utility of clonidine in opioid withdrawal: A study of 100 patients. Prog Clin Biol Res. 1981;71:299-306.

 

  1. Washton AM, Resnick RB. Outpatient opioid detoxification with clonidine. J Clin Psychiatry. 1982;43(6 Pt 2):39-41.

 

  1. Sullivan M, Bisaga A, Pavlicova M, et al. Long-acting injectable naltrexone induction: A randomized trial of outpatient opioid detoxification with naltrexone versus buprenorphine. Am J Psychiatry. 2017;174(5):459-467. doi: 10.1176/appi.ajp.2016.16050548

 

  1. Gold MS, Dackis CA, Washton AM. The sequential use of clonidine and naltrexone in the treatment of opioid addicts. Adv Alcohol Subst Abuse. 1984;3(3):19-39. doi: 10.1300/J251v03n03_03

 

  1. Charney DS, Heninger GR, Kleber HD. The combined use of clonidine and naltrexone as a rapid, safe, and effective treatment of abrupt withdrawal from methadone. Am J Psychiatry. 1986;143(7):831-837. doi: 10.1176/ajp.143.7.831

 

  1. Gowing L, Farrell MF, Ali R, White JM. Alpha2-adrenergic agonists for the management of opioid withdrawal. Cochrane Database Syst Rev. 2014;(3):CD002024. doi: 10.1002/14651858.CD002024.pub4. Update in: Cochrane Database Syst Rev. 2016;(5):CD002024

 

  1. Kowalczyk WJ, Moran LM, Bertz JW, et al. Using ecological momentary assessment to examine the relationship between craving and affect with opioid use in a clinical trial of clonidine as an adjunct medication to buprenorphine treatment. Am J Drug Alcohol Abuse. 2018;44(5):502-511. doi: 10.1080/00952990.2018.1454933

 

  1. Kowalczyk WJ, Phillips KA, Jobes ML, et al. clonidine maintenance prolongs opioid abstinence and decouples stress from craving in daily life: A randomized controlled trial with ecological momentary assessment. Am J Psychiatry. 2015;172(8):760-767. doi: 10.1176/appi.ajp.2014.14081014

 

  1. Kosten TR, Baxter LE. Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. Am J Addict. 2019;28(2):55-62. doi: 10.1111/ajad.12862

 

  1. Rehman SU, Maqsood MH, Bajwa H, Tameez Ud Din A, Malik MN. Clinical efficacy and safety profile of lofexidine hydrochloride in treating opioid withdrawal symptoms: A review of literature. Cureus. 2019;11(6):e4827. doi: 10.7759/cureus.4827

 

  1. Blum K, Badgaiyan RD, Braverman ER, et al. Hypothesizing that, a pro-dopamine regulator (KB220Z) should optimize, but not hyper-activate the activity of trace amine-associated receptor 1 (TAAR-1) and induce anti-craving of psychostimulants in the long-term. J Reward Defic Syndr Addict Sci. 2016;2(1):14-21. doi: 10.17756/jrdsas.2016-023

 

  1. Febo M, Blum K, Badgaiyan RD, et al. Dopamine homeostasis: Brain functional connectivity in reward deficiency syndrome. Front Biosci (Landmark Ed). 2017;22(4):669-691. doi: 10.2741/4509

 

  1. Blum K, Liu Y, Wang W, et al. rsfMRI effects of KB220Z™ on neural pathways in reward circuitry of abstinent genotyped heroin addicts. Postgrad Med. 2015;127(2):232-241. doi: 10.1080/00325481.2015.994879

 

  1. Blum K, Baron D. Opioid substitution therapy: Achieving harm reduction while searching for a prophylactic solution. Curr Pharm Biotechnol. 2019;20(3):180-182. doi: 10.2174/138920102003190422150527

 

  1. Blum K, Baron D, Hauser M, et al. Americas’ opioid/ psychostimulant epidemic would benefit from general population early identification of genetic addiction risk especially in children of alcoholics (COAs). J Syst Integr Neurosci. 2019;5(2):1-3.

 

  1. Downs BW, Blum K, Baron D, et al. Death by opioids: Are there non-addictive scientific solutions? J Syst Integr Neurosci. 2019;5. doi: 10.15761/JSIN.1000211

 

  1. Blum K, Febo M, Badgaiyan RD, et al. Common neurogenetic diagnosis and meso-limbic manipulation of hypodopaminergic function in reward deficiency syndrome (RDS): Changing the recovery landscape. Curr Neuropharmacol. 2017;15(1):184-194. doi: 10.2174/1570159x13666160512150918

 

  1. Blum K, Febo M, Fried L, et al. Pro-dopamine regulator - (KB220) to balance brain reward circuitry in reward deficiency syndrome (RDS). J Reward Defic Syndr Addict Sci. 2017;3(1):3-13.

 

  1. Blum K, Gold MS, Jacobs W, et al. Neurogenetics of acute and chronic opioid/opioid abstinence: treating symptoms and the cause. Front Biosci (Landmark Ed). 2017;22(8):1247-1288. doi: 10.2741/4544

 

  1. Baron D, Blum K, Chen A, Gold M, Badgaiyan RD. Conceptualizing addiction from an osteopathic perspective: Dopamine homeostasis. J Am Osteopath Assoc. 2018;118(2):115-118. doi: 10.7556/jaoa.2018.026

 

  1. Febo M, Blum K, Badgaiyan RD, et al. Enhanced functional connectivity and volume between cognitive and reward centers of naïve rodent brain produced by pro-dopaminergic agent KB220Z. PLoS One. 2017;12(4):e0174774. doi: 10.1371/journal.pone.0174774

 

  1. Blum K, Chen ALC, Thanos PK, et al. Genetic addiction risk score (GARS)™, a predictor of vulnerability to opioid dependence. Front Biosci (Elite Ed). 2018;10(1):175-196. doi: 10.2741/e816

 

  1. Blum K, Gold M, Modestino EJ, et al. Would induction of dopamine homeostasis via coupling genetic addiction risk score (GARS®) and pro-dopamine regulation benefit benzodiazepine use disorder (BUD)? J Syst Integr Neurosci. 2018;4. doi: 10.15761/JSIN.1000196

 

  1. Blum K, Gondré-Lewis MC, Baron D, et al. Introducing precision addiction management of reward deficiency syndrome, the construct that underpins all addictive behaviors. Front Psychiatry. 2018;9:548. doi: 10.3389/fpsyt.2018.00548

 

  1. Blum K, Lott L, Siwicki D, et al. Genetic Addiction Risk Score (GARS™) as a predictor of substance use disorder: Identifying predisposition not diagnosis. Curr Trends Med Diagn Methods. 2018;1(1). doi: 10.29011/CTMDM-101.100001

 

  1. Blum K, Modestino EJ, Badgaiyan RD, et al. Analysis of evidence for the combination of pro-dopamine regulator (KB220PAM) and naltrexone to prevent opioid use disorder relapse. EC Psychol Psychiatr. 2018;7(8):564-579.

 

  1. Blum K, Modestino EJ, Gondre-Lewis M, et al. The benefits of genetic addiction risk score (GARS™) testing in substance use disorder (SUD). Int J Genom Data Min. 2018;2018(1):115. doi: 10.29014/IJGD-115.000015

 

  1. Blum K, Modestino EJ, Neary J, et al. Promoting precision addiction management (PAM) to combat the global opioid crisis. Biomed J Sci Tech Res. 2018;2(2):1-4. doi: 10.26717/BJSTR.2018.02.000738

 

  1. Blum K, Baron D, Lott L, et al. In search of reward deficiency syndrome (RDS)-free controls: The “Holy Grail” in genetic addiction risk testing. Curr Psychopharmacol. 2020;9(1):7-21.

 

  1. Blum K, Baron D, McLaughlin T, Gold MS. Molecular neurological correlates of endorphinergic/dopaminergic mechanisms in reward circuitry linked to endorphinergic deficiency syndrome (EDS). J Neurol Sci. 2020;411:116733. doi: 10.1016/j.jns.2020.116733

 

  1. Gold MS, Badgaiyan RD, Blum K. A shared molecular and genetic basis for food and drug addiction: Overcoming hypodopaminergic trait/state by incorporating dopamine agonistic therapy in psychiatry. Psychiatr Clin North Am. 2015;38(3):419-462. doi: 10.1016/j.psc.2015.05.011

 

  1. Blum K, Gold MS. Neuro-chemical activation of brain reward meso-limbic circuitry is associated with relapse prevention and drug hunger: A hypothesis. Med Hypotheses. 2011;76(4):576-584. doi: 10.1016/j.mehy.2011.01.005

 

  1. Blum K, Liu Y, Shriner R, Gold MS. Reward circuitry dopaminergic activation regulates food and drug craving behavior. Curr Pharm Des. 2011;17(12):1158-1167. doi: 10.2174/138161211795656819

 

  1. Blum K, Oscar-Berman M, Blum SH, et al. Can genetic testing coupled with enhanced dopaminergic activation reduce recidivism rates in the workers compensation legacy cases? J Alcohol Drug Depend. 2014;2(3):161. doi: 10.4172/2329-6488.1000161

 

  1. Blum K, Oscar-Berman M, Demetrovics Z, Barh D, Gold MS. Genetic addiction risk score (GARS): Molecular neurogenetic evidence for predisposition to Reward Deficiency Syndrome (RDS). Mol Neurobiol. 2014;50(3):765-796. doi: 10.1007/s12035-014-8726-5

 

  1. Blum K, Oscar-Berman M, Jacobs W, McLaughlin T, Gold MS. buprenorphine response as a function of neurogenetic polymorphic antecedents: Can dopamine genes affect clinical outcomes in reward deficiency syndrome (RDS)? J Addict Res Ther. 2014;5:1000185. doi: 10.4172/2155-6105.1000185

 

  1. Sibai M, Mishlen K, Nunes EV, Levin FR, Mariani JJ, Bisaga A. A week-long outpatient induction onto XR-naltrexone in patients with opioid use disorder. Am J Drug Alcohol Abuse. 2020;46(3):289-296. doi: 10.1080/00952990.2019.1700265

 

  1. Gowing L, Ali R, White JM, Mbewe D. Buprenorphine for managing opioid withdrawal. Cochrane Database Syst Rev. 2017;2(2):CD002025. doi: 10.1002/14651858.CD002025.pub5

 

  1. Makani R, Pradhan B, Shah U, Parikh T. Role of repetitive transcranial magnetic stimulation (rTMS) in treatment of addiction and related disorders: a systematic review. Curr Drug Abuse Rev. 2017;10(1):31-43. doi: 10.2174/1874473710666171129225914

 

  1. Dunlop K, Hanlon CA, Downar J. Noninvasive brain stimulation treatments for addiction and major depression. Ann N Y Acad Sci. 2017;1394(1):31-54. doi: 10.1111/nyas.12985

 

  1. Lefaucheur JP, André-Obadia N, Antal A, et al. Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS). Clin Neurophysiol. 2014;125(11):2150-2206. doi: 10.1016/j.clinph.2014.05.021

 

  1. Diana M, Raij T, Melis M, Nummenmaa A, Leggio L, Bonci A. Rehabilitating the addicted brain with transcranial magnetic stimulation. Nat Rev Neurosci. 2017;18(11):685-693. doi: 10.1038/nrn.2017.113

 

  1. Ekhtiari H, Tavakoli H, Addolorato G, et al. Transcranial electrical and magnetic stimulation (tES and TMS) for addiction medicine: A consensus paper on the present state of the science and the road ahead. Neurosci Biobehav Rev. 2019;104:118-140. doi: 10.1016/j.neubiorev.2019.06.007

 

  1. Zhang JJQ, Fong KNK, Ouyang RG, Siu AMH, Kranz GS. Effects of repetitive transcranial magnetic stimulation (rTMS) on craving and substance consumption in patients with substance dependence: A systematic review and meta-analysis. Addiction. 2019;114(12):2137-2149. doi: 10.1111/add.14753

 

  1. Coles AS, Kozak K, George TP. A review of brain stimulation methods to treat substance use disorders. Am J Addict. 2018;27(2):71-91. doi: 10.1111/ajad.12674

 

  1. Salling MC, Martinez D. Brain stimulation in addiction. Neuropsychopharmacology. 2016;41(12):2798-2809. doi: 10.1038/npp.2016.80.

 

  1. Song S, Zilverstand A, Gui W, Li HJ, Zhou X. Effects of single session versus multi-session non-invasive brain stimulation on craving and consumption in individuals with drug addiction, eating disorders or obesity: A meta-analysis. Brain Stimul. 2019;12(3):606-618. doi: 10.1016/j.brs.2018.12.975

 

  1. Robison LS, Alessi L, Thanos PK. Chronic forced exercise inhibits stress-induced reinstatement of cocaine conditioned place preference. Behav Brain Res. 2018;353:176-184. doi: 10.1016/j.bbr.2018.07.009

 

  1. Swenson S, Blum K, McLaughlin T, Gold MS, Thanos PK. The therapeutic potential of exercise for neuropsychiatric diseases: A review. J Neurol Sci. 2020;412:116763. doi: 10.1016/j.jns.2020.116763

 

  1. Swenson S, Hamilton J, Robison L, Thanos PK. Chronic aerobic exercise: Lack of effect on brain CB1 receptor levels in adult rats. Life Sci. 2019;230:84-88. doi: 10.1016/j.lfs.2019.05.058

 

  1. Thanos PK, Hamilton J, O’Rourke JR, et al. Dopamine D2 gene expression interacts with environmental enrichment to impact lifespan and behavior. Oncotarget. 2016;7(15):19111-19123. doi: 10.18632/oncotarget.8088

 

  1. Thanos PK, Stamos J, Robison LS, et al. Daily treadmill exercise attenuates cocaine cue-induced reinstatement and cocaine induced locomotor response but increases cocaine-primed reinstatement. Behav Brain Res. 2013;239:8-14. doi: 10.1016/j.bbr.2012.10.035

 

  1. Rahman N, Mihalkovic A, Geary O, Haffey R, Hamilton J, Thanos PK. Chronic aerobic exercise: Autoradiographic assessment of GABA(a) and mu-opioid receptor binding in adult rats. Pharmacol Biochem Behav. 2020;196:172980. doi: 10.1016/j.pbb.2020.172980

 

  1. Blum K, Oscar-Berman M, Dinubile N, et al. Coupling genetic addiction risk score (GARS) with electrotherapy: Fighting iatrogenic opioid dependence. J Addict Res Ther. 2013;4(163):1000163. doi: 10.4172/2155-6105.1000163

 

  1. Blum K, Oscar-Berman M, Femino J, et al. Withdrawal from buprenorphine/naloxone and maintenance with a natural dopaminergic agonist: A cautionary note. J Addict Res Ther. 2013;4(2). doi: 10.4172/2155-6105.1000146

 

  1. Blum K, Badgaiyan RD, Agan G, et al. Molecular genetic testing in reward deficiency syndrome (RDS): Facts and fiction. J Reward Defic Syndr. 2015;1(1):65-68. doi: 10.17756/jrds.2015-009

 

  1. Blum K, Thanos PK, Wang GJ, et al. The food and drug addiction epidemic: Targeting dopamine homeostasis. Curr Pharm Des. 2018;23(39):6050-6061. doi: 10.2174/1381612823666170823101713

 

  1. Blum K, Bowirrat A, Baron D, et al. Biotechnical development of genetic addiction risk score (GARS) and selective evidence for inclusion of polymorphic allelic risk in substance use disorder (SUD). J Syst Integr Neurosci. 2020;6(2). doi: 10.15761/JSIN.1000221

 

  1. Fried L, Modestino EJ, Siwicki D, et al. Hypodopaminergia and “precision behavioral management” (PBM): It is a generational family affair. Curr Pharm Biotechnol. 2020;21(6):528-541. doi: 10.2174/1389201021666191210112108

 

  1. McLaughlin T, Blum K, Steinberg B, et al. Pro-dopamine regulator, KB220Z, attenuates hoarding and shopping behavior in a female, diagnosed with SUD and ADHD. J Behav Addict. 2018;7(1):192-203. doi: 10.1556/2006.6.2017.081

 

  1. McLaughlin T, Febo M, Badgaiyan RD, et al. KB220Z™ a pro-dopamine regulator associated with the protracted, alleviation of terrifying lucid dreams. Can we infer neuroplasticity-induced changes in the reward circuit? J Reward Defic Syndr Addict Sci. 2016;2(1):3-13. doi: 10.17756/jrdsas.2016-022

 

  1. McLaughlin T, Han D, Nicholson J, et al. Improvement of long-term memory access with a pro-dopamine regulator in an elderly male: Are we targeting dopamine tone? J Syst Integr Neurosci. 2017;3(3). doi: 10.15761/JSIN.1000165

 

  1. Blum K, Gondré-Lewis MC, Modestino EJ, et al. Understanding the scientific basis of post-traumatic stress disorder (PTSD): Precision behavioral management overrides stigmatization. Mol Neurobiol. 2019;56(11):7836-7850. doi: 10.1007/s12035-019-1600-8

 

  1. Blum K, Marcelo F, Dushaj K, Fried L, Badgaiyan RD. “Pro-dopamine regulation (KB220Z™)” as a long-term therapeutic modality to overcome reduced resting state dopamine tone in opioid/opioid epidemic in America. J Syst Integr Neurosci. 2016;2(3):162-165. doi: 10.15761/JSIN.1000129

 

  1. Blum K, Downs BW, Dushaj K, et al. The benefits of customized dna directed nutrition to balance the brain reward circuitry and reduce addictive behaviors. Precis Med (Bangalore). 2016;1(1):18-33.

 

  1. Solanki N, Abijo T, Galvao C, Darius P, Blum K, Gondré- Lewis MC. Administration of a putative pro-dopamine regulator, a neuronutrient, mitigates alcohol intake in alcohol-preferring rats. Behav Brain Res. 2020;385:112563. doi: 10.1016/j.bbr.2020.112563

 

  1. Steinberg B, Blum K, McLaughlin T, et al. Low-resolution electromagnetic tomography (LORETA) of changed brain function provoked by pro-dopamine regulator (KB220z) in one adult ADHD case. Open J Clin Med Case Rep. 2016;2(11):1121.

 

  1. Bruijnzeel AW, Marcinkiewcz C, Isaac S, et al. The effects of buprenorphine on fentanyl withdrawal in rats. Psychopharmacology (Berl). 2007;191(4):931-941. doi: 10.1007/s00213-006-0670-2

 

  1. Dackis C, O’Brien C. Neurobiology of addiction: Treatment and public policy ramifications. Nat Neurosci. 2005;8(11):1431-1436. doi: 10.1038/nn1105-1431

 

  1. O’Brien CP. Anti-craving medications for relapse prevention: A possible new class of psychoactive medications. Am J Psychiatry. 2005;162(8):1423-1431. doi: 10.1176/appi.ajp.162.8.1423

 

  1. Heidbreder CA, Hagan JJ. Novel pharmacotherapeutic approaches for the treatment of drug addiction and craving. Curr Opin Pharmacol. 2005;5(1):107-118. doi: 10.1016/j.coph.2004.08.013

 

  1. Mei W, Zhang JX, Xiao Z. Acute effects of sublingual buprenorphine on brain responses to heroin-related cues in early-abstinent heroin addicts: An uncontrolled trial. Neuroscience. 2010;170(3):808-815. doi: 10.1016/j.neuroscience.2010.07.033

 

  1. Yücel M, Lubman DI, Harrison BJ, et al. A combined spectroscopic and functional MRI investigation of the dorsal anterior cingulate region in opioid addiction. Mol Psychiatry. 2007;12(7):611, 691-702. doi: 10.1038/sj.mp.4001955

 

  1. De Ridder D, Vanneste S, Kovacs S, Sunaert S, Dom G. Transient alcohol craving suppression by rTMS of dorsal anterior cingulate: An fMRI and LORETA EEG study. Neurosci Lett. 2011;496(1):5-10. doi: 10.1016/j.neulet.2011.03.074

 

  1. Lin C, Karim HT, Pecina M, et al. Low-dose augmentation with buprenorphine increases emotional reactivity but not reward activity in treatment resistant mid- and late-life depression. Neuroimage Clin. 2019;21:101679. doi: 10.1016/j.nicl.2019.101679

 

  1. Verdejo-García A, Lubman DI, Roffel K, et al. Cingulate biochemistry in heroin users on substitution pharmacotherapy. Aust N Z J Psychiatry. 2013;47(3):244-249. doi: 10.1177/0004867412463088

 

  1. Seah S, Asad AB, Baumgartner R, et al. Investigation of cross-species translatability of pharmacological MRI in awake nonhuman primate - a buprenorphine challenge study. PLoS One. 2014;9(10):e110432. doi: 10.1371/journal.pone.0110432

 

  1. Nestler EJ. Reinforcement and addictive disorders. In: Molecular Neuropharmacology: A Foundation for Clinical Neuroscience. United States: McGraw Hill; 2009.

 

  1. Hermann D, Frischknecht U, Heinrich M, et al. MR spectroscopy in opioid maintenance therapy: Association of glutamate with the number of previous withdrawals in the anterior cingulate cortex. Addict Biol. 2012;17(3):659-667. doi: 10.1111/j.1369-1600.2010.00290.x

 

  1. Edwards D, Roy AK 3rd, Boyett B, et al. Addiction by any other name is still addiction: Embracing molecular neurogenetic/epigenetic basis of reward deficiency. J Addict Sci. 2020;6(1):1-4.

 

  1. Blum K, Chen TJ, Bailey J, et al. Can the chronic administration of the combination of buprenorphine and naloxone block dopaminergic activity be causing anti-reward and relapse potential? Mol Neurobiol. 2011;44(3):250-268. doi: 10.1007/s12035-011-8206-0

 

  1. Hill E, Han D, Dumouchel P, et al. Long term Suboxone™ emotional reactivity as measured by automatic detection in speech. PLoS One. 2013;8(7):e69043. doi: 10.1371/journal.pone.0069043. Erratum in: PLoS One. 2013;8(8). doi: 10.1371/annotation/be0b3a26-c1bc-4d92-98c1-c516acc8dcf2

 

  1. Bisaga A, Mannelli P, Sullivan MA, et al. Antagonists in the medical management of opioid use disorders: Historical and existing treatment strategies. Am J Addict. 2018;27(3):177-187. doi: 10.1111/ajad.12711

 

  1. Chalhoub RM, Kalivas PW. Non-opioid treatments for opioid use disorder: Rationales and data to date. Drugs. 2020;80(15):1509-1524. doi: 10.1007/s40265-020-01373-1

 

  1. Walsh SL, Gilson SF, Jasinski DR, et al. Buprenorphine reduces cerebral glucose metabolism in polydrug abusers. Neuropsychopharmacology. 1994;10(3):157-170. doi: 10.1038/npp.1994.18

 

  1. Dahlstroem A, Fuxe K. Evidence for the existence of monoamine-containing neurons in the central nervous system. I. Demonstration of monoamines in the cell bodies of brain stem neurons. Acta Physiol Scand Suppl. 1964;Suppl 232:1-55.

 

  1. Poe GR, Foote S, Eschenko O, et al. Locus coeruleus: A new look at the blue spot. Nat Rev Neurosci. 2020;21(11):644-659. doi: 10.1038/s41583-020-0360-9

 

  1. Valentino RJ, Van Bockstaele E. Convergent regulation of locus coeruleus activity as an adaptive response to stress. Eur J Pharmacol. 2008;583(2-3):194-203. doi: 10.1016/j.ejphar.2007.11.062

 

  1. Chandler DJ, Waterhouse BD, Gao WJ. New perspectives on catecholaminergic regulation of executive circuits: Evidence for independent modulation of prefrontal functions by midbrain dopaminergic and noradrenergic neurons. Front Neural Circuits. 2014;8:53. doi: 10.3389/fncir.2014.00053

 

  1. Tjoumakaris SI, Rudoy C, Peoples J, Valentino RJ, Van Bockstaele EJ. Cellular interactions between axon terminals containing endogenous opioid peptides or corticotropin-releasing factor in the rat locus coeruleus and surrounding dorsal pontine tegmentum. J Comp Neurol. 2003;466(4):445-456. doi: 10.1002/cne.10893

 

  1. Valentino RJ, Wehby RG. Morphine effects on locus coeruleus neurons are dependent on the state of arousal and availability of external stimuli: Studies in anesthetized and unanesthetized rats. J Pharmacol Exp Ther. 1988;244(3):1178-1186.

 

  1. Curtis AL, Leiser SC, Snyder K, Valentino RJ. Predator stress engages corticotropin-releasing factor and opioid systems to alter the operating mode of locus coeruleus norepinephrine neurons. Neuropharmacology. 2012;62(4):1737-1745. doi: 10.1016/j.neuropharm.2011.11.020

 

  1. Guajardo HM, Snyder K, Ho A, Valentino RJ. Sex differences in μ-opioid receptor regulation of the rat locus coeruleus and their cognitive consequences. Neuropsychopharmacology. 2017;42(6):1295-1304. doi: 10.1038/npp.2016.252

 

  1. Brady KT, Randall CL. Gender differences in substance use disorders. Psychiatr Clin North Am. 1999;22(2):241-252. doi: 10.1016/s0193-953x(05)70074-5

 

  1. Srivastava AB, Gold MS. Naltrexone: A history and future directions. Cerebrum. 2018;2018:cer-13-18.

 

  1. Christie MJ. Cellular neuroadaptations to chronic opioids: Tolerance, withdrawal and addiction. Br J Pharmacol. 2008;154(2):384-396. doi: 10.1038/bjp.2008.100

 

  1. Gagne C, Moyse E, Kocher L, Bour H, Pujol JF. Light-microscopic localization of somatostatin binding sites in the locus coeruleus of the rat. Brain Res. 1990;530(2):196-204. doi: 10.1016/0006-8993(90)91283-m

 

  1. Williams JT, Christie MJ, Manzoni O. Cellular and synaptic adaptations mediating opioid dependence. Physiol Rev. 2001;81(1):299-343. doi: 10.1152/physrev.2001.81.1.299

 

  1. Lee JD, Nunes EV, Mpa PN, et al. NIDA clinical trials network CTN-0051, extended-release naltrexone vs. Buprenorphine for opioid treatment (X: BOT): Study design and rationale. Contemp Clin Trials. 2016;50:253-264. doi: 10.1016/j.cct.2016.08.004

 

  1. Patterson Silver Wolf DA, Gold M. Treatment resistant opioid use disorder (TROUD): Definition, rationale, and recommendations. J Neurol Sci. 2020;411:116718. doi: 10.1016/j.jns.2020.116718

 

  1. Doughty B, Morgenson D, Brooks T. Lofexidine: A newly FDA-approved, nonopioid treatment for opioid withdrawal. Ann Pharmacother. 2019;53(7):746-753. doi: 10.1177/1060028019828954

 

  1. Clemow DB, Bushe CJ. Atomoxetine in patients with ADHD: A clinical and pharmacological review of the onset, trajectory, duration of response and implications for patients. J Psychopharmacol. 2015;29(12):1221-1230. doi: 10.1177/0269881115602489

 

  1. Fukada K, Endo T, Yokoe M, Hamasaki T, Hazama T, Sakoda S. L-threo-3,4-dihydroxyphenylserine (L-DOPS) co-administered with entacapone improves freezing of gait in Parkinson’s disease. Med Hypotheses. 2013;80(2):209-212. doi: 10.1016/j.mehy.2012.11.031

 

  1. Vonck K, Raedt R, Naulaerts J, et al. Vagus nerve stimulation…25 years later! What do we know about the effects on cognition? Neurosci Biobehav Rev. 2014;45:63-71. doi: 10.1016/j.neubiorev.2014.05.005

 

  1. Berridge CW, Waterhouse BD. The locus coeruleus-noradrenergic system: Modulation of behavioral state and state-dependent cognitive processes. Brain Res Brain Res Rev. 2003;42(1):33-84. doi: 10.1016/s0165-0173(03)00143-7

 

  1. Kosten TA, Galloway MP, Duman RS, Russell DS, D’Sa C. Repeated unpredictable stress and antidepressants differentially regulate expression of the bcl-2 family of apoptotic genes in rat cortical, hippocampal, and limbic brain structures. Neuropsychopharmacology. 2008;33(7):1545-1558. doi: 10.1038/sj.npp.1301527

 

  1. Aston-Jones G, Chen S, Zhu Y, Oshinsky ML. A neural circuit for circadian regulation of arousal. Nat Neurosci. 2001;4(7):732-738. doi: 10.1038/89522

 

  1. Fang J, Rong P, Hong Y, et al. Transcutaneous vagus nerve stimulation modulates default mode network in major depressive disorder. Biol Psychiatry. 2016;79(4):266-273. doi: 10.1016/j.biopsych.2015.03.025

 

  1. Gold MS, Blum K, Febo M, et al. Molecular role of dopamine in anhedonia linked to reward deficiency syndrome (RDS) and anti- reward systems. Front Biosci (Schol Ed). 2018;10(2):309-325. doi: 10.2741/s518

 

  1. Pallanti S, Bernardi S, Allen A, et al. Noradrenergic function in pathological gambling: blunted growth hormone response to clonidine. J Psychopharmacol. 2010;24(6):847-853. doi: 10.1177/0269881108099419

 

  1. Saddichha S, Vibha P, Vishnuvardhan G. Sapophagia (Compulsive Soap Eating) and attention-deficit/ hyperactivity disorder in a child responsive to clonidine. J Clin Psychopharmacol. 2012;32(2):291. doi: 10.1097/JCP.0b013e3182499ad2

 

  1. Cazala P. Effect of clonidine and phentolamine on self-stimulation behavior in the dorsal and ventral regions of the lateral hypothalamus in mice. Psychopharmacology (Berl). 1980;68(2):173-177. doi: 10.1007/BF00432137

 

  1. Commissaris RL, Ellis DM, Hill TJ, Schefke DM, Becker CA, Fontana DJ. Chronic antidepressant and clonidine treatment effects on conflict behavior in the rat. Pharmacol Biochem Behav. 1990;37(1):167-176. doi: 10.1016/0091-3057(90)90058-p

 

  1. Geller I, Blum K. The effects of 5-HTP on para-chlorophenylalanine (p-CPA) attenuation of “conflict” behavior. Eur J Pharmacol. 1970;9(3):319-324. doi: 10.1016/0014-2999(70)90229-3

 

  1. Veilleux JC, Skinner KD. Smoking, food, and alcohol cues on subsequent behavior: A qualitative systematic review. Clin Psychol Rev. 2015;36:13-27. doi: 10.1016/j.cpr.2015.01.001

 

  1. Covey LS, Glassman AH. A meta-analysis of double-blind placebo-controlled trials of clonidine for smoking cessation. Br J Addict. 1991;86(8):991-998. doi: 10.1111/j.1360-0443.1991.tb01860.x

 

  1. Blum K, Whitney D, Fried L, et al. Hypothesizing that a pro-dopaminergic regulator (KB220z™ Liquid Variant) can Induce “dopamine homeostasis” and provide adjunctive detoxification benefits in opioid/opioid dependence. Clin Med Rev Case Rep. 2016;3(8):125. doi: 10.23937/2378-3656/1410125

 

  1. Blum K, Lott L, Baron D, Smith DE, Badgaiyan RD, Gold MS. Improving naltrexone compliance and outcomes with putative pro- dopamine regulator KB220, compared to treatment as usual. J Syst Integr Neurosci. 2020;7. doi: 10.15761/JSIN.1000229

 

  1. Christie MJ, Williams JT, Osborne PB, Bellchambers CE. Where is the locus in opioid withdrawal? Trends Pharmacol Sci. 1997;18(4):134-140. doi: 10.1016/s0165-6147(97)01045-6

 

  1. Christie MJ, Williams JT, North RA. Cellular mechanisms of opioid tolerance: Studies in single brain neurons. Mol Pharmacol. 1987;32(5):633-638.

 

  1. Colzato L, Elmers J, Xu X, Zhou Q, Hommel B, Beste C. Regaining control over opioid use? The potential application of auricular transcutaneous vagus nerve stimulation to improve opioid treatment in China. Addict Biol. 2023;28(11):e13343. doi: 10.1111/adb.13343
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INNOSC Theranostics and Pharmacological Sciences, Electronic ISSN: 2705-0823 Print ISSN: 2705-0734, Published by AccScience Publishing
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