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研究
A historical perspective on clonidine as an alpha-2A receptor agonist in the treatment of addictive behaviors: Focus on opioid dependence
Mark S. Gold
1
Kenneth Blum
2,3,4,5,6,7,8,9,10,11*
Abdalla Bowirrat
5
Albert Pinhasov
5
Debasis Bagchi
12,13
Catherine A. Dennen
14
Panayotis K. Thanos
5,15,16
Colin Hanna
15,16
Kai-Uwe Lewandrowski
17,18,19
Alireza Sharafshah
20
Igor Elman
5,21
Rajendra D. Badgaiyan
22,23

1 Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri

2 Division of Addiction Research and Education, Center for Sports, Exercise and Global Mental Health, Western University Health Sciences, Pomona, California

3 The Kenneth Blum Behavioral and Neurogenetic Institute LLC, Austin, Texas

4 Department of Psychology, Faculty of Education and Psychology, Institute of Psychology, Eötvös Loránd University Budapest, Budapest

5 Department of Molecular Biology and Adelson School of Medicine, Ariel University, Ariel

6 Division of Personalized Medicine, Cross-Cultural Research and Educational Institute, San Clemente, California

7 Centre for Genomics and Applied Gene Technology, Institute of Integrative Omics and Applied Biotechnology, Nonakuri, West Bengal

8 Department of Clinical Psychology and Addiction, Institute of Psychology, Faculty of Education and Psychology, Eötvös Loránd University, Budapest

9 Department of Psychiatry, University of Vermont, Burlington, Vermont

10 Department of Psychiatry, Wright University, Boonshoft School of Medicine, Dayton, Ohio

11 Division of Personalized Medicine, Ketamine Infusion Clinic of South Florida, Pompano, Florida

12 Department of Nutrigenomic Research, Victory Nutrition International, Inc., Bonita Springs, Florida

13 Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Texas Southern University, Houston, Texas

14 Department of Family Medicine, Jefferson Health Northeast, Philadelphia, Pennsylvania

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

16 Department of Psychology, State University of New York at Buffalo, Buffalo, New York

17 Division of Personalized Pain Therapy Research, Center for Advanced Spine Care of Southern Arizona, Tucson, Arizona

18 Department of Orthopaedics, Fundación Universitaria Sanitas, Bogotá

19 Department of Orthopedics, Hospital Universitário Gaffree Guinle Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro

20 Cellular and Molecular Research Center, School of Medicine, Guilan University of Medical Sciences, Rasht, Gilan

21 Department of Psychiatry, School of Medicine, Harvard University, Cambridge, Massachusetts

22 Department of Psychiatry, Mt. Sinai School of Medicine, New York City, New York

23 Department of Psychiatry, School of Medicine, Case Western Reserve University, Cleveland, Ohio



INNOSC Theranostics and Pharmacological Sciences 2024, 7(3)2024-07-29 23:59:59; https://doi.org/10.36922/itps.1918
Submitted26 Sept 2023
Revised01 Jan 0001
Accepted27 Mar 2024
Published29 Jul 2024
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Cite This Article
Mark S. Gold ,Kenneth Blum ,Abdalla Bowirrat ,Albert Pinhasov ,Debasis Bagchi ,Catherine A. Dennen ,Panayotis K. Thanos ,Colin Hanna ,Kai-Uwe Lewandrowski ,Alireza Sharafshah ,Igor Elman ,Rajendra D. Badgaiyan . (2024). A historical perspective on clonidine as an alpha-2A receptor agonist in the treatment of addictive behaviors: Focus on opioid dependence. INNOSC Theranostics and Pharmacological Sciences , 7(3), itps1918. https://doi.org/10.36922/itps.1918
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.

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