Existing Therapeutics for Drug Abuse & Withdrawal
The use of pharmacological agents is one of the standard approaches to ameliorate aspects of drug addiction in combination with social and behavioral treatment. While pharmacotherapy may be an effective approach to the treatment of drug addiction for individuals, the prevalence of this disorder remains unacceptably high. Treatment has progressed from purely social and behavioral approaches to encompass pharmacotherapy to attempt to disrupt the mechanisms underlying these disorders.
In case of opiate withdrawal, the pharmacotherapy of acute dependence and withdrawal has benefited from the use of clonidine, particularly in combination with antagonist-precipitated withdrawal. However, protracted abstinence and its associated risk of relapse to drug abuse has underscored the need for maintenance pharmacotherapies such as methadone and naltrexone. Methadone is more widely used than naltrexone, an oral, long-acting heroin blocker that can maintain drug abstinence after detoxification. A methadone derivative called levo-α-acetylmethadol, which has µ-opioid receptor agonistic activity, was reported to have a longer and more effective action compared with methadone in opiate abuse. On the other hand, buprenorphine, a mixed opioid receptor agonist–antagonist has an advantage over methadone and levo-α-acetylmethadol in that as a partial µ-agonist its maximal efficacy is less than that required for suppression of consciousness and respiration, reducing rates of death from overdose and reducing its abuse liability. However, its use as a maintenance therapy is not as successful as methadone.
Topiramate, an anticonvulsant used for certain symptoms of alcohol withdrawal, decreases alcohol craving by facilitating GABA release while simultaneously inhibiting glutamatergic neurotransmission. However, the side effects associated with topiramate use such as parasthesia, fatigue, somnolence, hypoesthesia and nausea have limited its widespread use. Recently acamprosate, acting as an NMDA receptor modulator, used as an oral tablet for alcohol dependence has shown a twofold increase in abstinence rates at 1 year. Varenicline, a partial agonist for α4β2 and full agonist for α7 nicotinic acetylcholine receptors showed two- to three-fold increase in the odds of quitting smoking at 6 months. Apart form the existing pharmacological targets for several types of addictive drugs, no therapeutics are still registered for treatment of cannabinoid and some inhalant addictions. Therefore, a significant amount of research has been dedicated to advancing the knowledge of the pathological processes of addiction to aid in the development of new therapeutics.
Although drugs of abuse have different sites of action, each addiction can result in common adaptations in neurons and neurotransmitter systems. Chronic use of most of the main drugs of abuse causes changes in adenosine-mediated signaling pathways in several brain structures linked to the etiology of addiction. A growing body of evidence indicates that adenosine is a crucial mediator in dependence and withdrawal and that manipulation of adenosine signaling pathways may offer novel therapeutic strategies for the management and treatment of addiction. It has also been suggested that the behavioral effects of addictive drugs such as alcohol, morphine and diazepam are mediated at least partially via adenosine-dependent mechanisms.