Progress in agonist therapy for substance use disorders: Lessons learned from methadone and buprenorphine.
Substance use disorders (SUD) are serious public health problems worldwide. Although significant progress has been made in understanding the neurobiology of drug reward and the transition to addiction, effective pharmacotherapies for SUD remain limited and a majority of drug users relapse even after a period of treatment. The United States Food and Drug Administration (FDA) has approved several medications for opioid, nicotine, and alcohol use disorders, whereas none are approved for the treatment of cocaine or other psychostimulant use disorders. The medications approved by the FDA for the treatment of SUD can be divided into two major classes - agonist replacement therapies, such as methadone and buprenorphine for opioid use disorders (OUD), nicotine replacement therapy (NRT) and varenicline for nicotine use disorders (NUD), and antagonist therapies, such as naloxone for opioid overdose and naltrexone for promoting abstinence. In the present review, we primarily focus on the pharmacological rationale of agonist replacement strategies in treatment of opioid dependence, and the potential translation of this rationale to new therapies for cocaine use disorders. We begin by describing the neural mechanisms underlying opioid reward, followed by preclinical and clinical findings supporting the utility of agonist therapies in the treatment of OUD. We then discuss recent progress of agonist therapies for cocaine use disorders based on lessons learned from methadone and buprenorphine. We contend that future studies should identify agonist pharmacotherapies that can facilitate abstinence in patients who are motivated to quit their illicit drug use. Focusing on those that are able to achieve abstinence from cocaine will provide a platform to broaden the effectiveness of medication and psychosocial treatment strategies for this underserved population. This article is part of the Special Issue entitled 'New Vistas in Opioid Pharmacology'.
['Jordan|Chloe J|CJ|', 'Cao|Jianjing|J|', 'Newman|Amy Hauck|AH|', 'Xi|Zheng-Xiong|ZX|']
D000701:Analgesics, Opioid D002047:Buprenorphine D000697:Central Nervous System Stimulants D019970:Cocaine-Related Disorders D003913:Dextroamphetamine D050483:Dopamine Plasma Membrane Transport Proteins D018765:Dopamine Uptake Inhibitors D000076722:Drug Development D006801:Humans D008691:Methadone D008774:Methylphenidate D000077408:Modafinil D018722:Nicotinic Agonists D058850:Opiate Substitution Treatment D009293:Opioid-Related Disorders D010070:Oxalates D010879:Piperazines D017450:Receptors, Opioid, mu D014029:Tobacco Use Disorder D014326:Tropanes D000068580:Varenicline
Substance use disorders Methadone Addiction Opioids Cocaine Agonist replacement therapy Atypical dopamine uptake inhibitor Dopamine transporter