Associate editor: G. Dusting
New horizons for therapeutics in drug and alcohol abuse

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Abstract

Alcohol, tobacco and illicit drug dependence represents a serious health and social issue within the community. As drug dependence has become more widely recognized as a clinical disorder and the severity of the problem been fully realized, options available for treatment have grown along with our understanding of the neurobiological mechanisms underlying the development and persistence of addiction. Treatment has progressed from purely social and behavioral approaches to now encompass pharmacotherapy to attempt to disrupt the mechanisms underlying these disorders. Despite these advances, many forms of addiction lack effective therapeutics and the prevalence of this disorder remains unacceptably high. As a result, a significant effort within the research community has been dedicated to the identification of novel targets for the development of therapeutics based upon our understanding of the pathological processes underlying addiction. The current review aims to provide an overview of existing and clinically trialed pharmacotherapies for alcohol, opiate, psychostimulant, nicotine, cannabis and inhalant addictions. Further, we discuss some of the potential targets that have been recently indentified from basic studies that may hold promise for the development of novel treatments.

Introduction

Drug addiction is typically characterized as a chronically relapsing disorder involving repeated bouts of compulsive drug seeking and use despite potential adverse consequences associated with this behavior (Koob & Le Moal, 1997). Addiction is increasingly clinically recognized as a neurobiological disease and it is believed that its manifestation and enduring nature is influenced by a combination of genetic, behavioral and psychosocial factors. Drug addiction is an insidious disorder, with the extent of worldwide drug use estimated to include 2 billion alcohol users, 1.3 billion smokers and 185 million illicit drug users (WHO, 2002). This use accounts for approximately 12.4% of all deaths worldwide each year (WHO, 2002). According to estimates, alcohol, tobacco and illicit drug addiction costs the United States over $500 billion each year in healthcare, criminal justice and lost productivity costs (Harwood, 2000), while in Europe each addict has been suggested to cost its nation between €4000–12000 each year (Andlin-Sobocki, 2004). In a social context, 63% of Americans say that addiction has had an impact on their lives (Hart & Tetter, 2004).

The use of pharmacological agents has become a standard approach to attempt 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. Further, there are addictions that at present have no therapeutics registered for treatment thereof. Given this, a significant amount of research has been dedicated to advancing the knowledge of the pathological process(es) of addiction to aid in the development of new therapeutics. The current review aims to discuss existing pharmacotherapies and those currently in clinical trials. In addition, we provide some foresight into potential targets for the development of novel treatments based upon recent basic findings. Whether the latter ultimately translate into useful therapeutic options will unfold over the coming years.

Section snippets

Neurobiology of addiction

Studies utilizing advances in technologies such as neuroimaging, molecular biological and neurochemical techniques and the development of animal models of drug-taking (use) and drug seeking (relapse) have contributed significantly to advances in recent years in the understanding of the biological basis of addiction. The complex series of molecular and cellular events that are responsible for the reinforcing effects of drugs of abuse and the adaptations that result from repeated use of these

Current pharmacotherapies

Historically, disulfiram was the first medication used to prevent relapse to alcohol consumption through aversion therapy. Its action was thought to be via inhibition of the metabolism of acetaldehyde, a byproduct of alcohol metabolism, resulting in accumulation of this metabolite which stimulates unpleasant symptoms such as flushing, palpitations, tachycardia, hypotension, headache, nausea and vomiting (Kitson, 1977). More recently however, it has been reported that disulfiram inhibits

Current pharmacotherapies

There are currently two general approaches to the treatment of opiate addiction, assisted detoxification followed by relapse prevention treatment and opiate maintenance therapy. Given the generally disappointing long term results of abstinence oriented approaches and increased risk of fatal intoxication upon relapse (Petrakis et al., 2000), opiate maintenance approaches have become the primary approach to treatment of opiate dependence in many countries (Kerr et al., 2005). Rather than

Pharmacotherapeutic approaches for the treatment of psychostimulant addiction

Despite the prevalence of psychostimulant addiction (i.e. cocaine or amphetamine dependence) within society there are currently no medically approved treatments for this type of addiction. While recent advances have been made in psychotherapeutic approaches for the treatment of this addiction, many patients are ineffectively managed and the rate of discontinuance is exceptionally high (Alterman et al., 1996). To help combat the relative lack of pharmacotherapeutic options for cocaine and

Current pharmacotherapies

Tobacco use is the main preventable cause of morbidity and premature death worldwide. Given this, effective treatment of this form of addiction is important to reduce the significant burden tobacco use places on the health system. A number of pharmacotherapies have been approved by the United States Food and Drug Administration (USFDA) for the treatment of nicotine addiction. Currently, the primary approach to the treatment of nicotine addiction is nicotine replacement therapy (NRT). Similar to

Cannabis

Marijuana remains the most widely used illicit drug in the United States, Europe and Australia (AIHW, 2005, SAMHSA, 2007, EMCDDA, 2008) and is associated with dependence and withdrawal (Budney & Hughes, 2006). Despite the prevalence of its use, no medically approved pharmacotherapeutics currently exist for this form of addiction. In spite of the distinct lack of therapies there are still only a few clinical trials and laboratory studies that have been conducted for this form of addiction,

Future directions in the identification and development of therapeutics for drugs of abuse

It is clear that a large volume of research has been dedicated to the development, preclinical and clinical testing of therapeutics for the treatment of addiction to drugs of abuse. Despite this effort, many forms of addiction still have no clinically indicated therapeutics and for those that do, many addicts are still ineffectively treated by these medications. While these limitations may arise due to limits that still exist in our understanding of the behavioral, molecular and cellular basis

Conclusions

Many therapeutics have been tested for their potential efficacy to treat substance use disorders and advances in our understanding of the behavioral, molecular and cellular basis of these very difficult to treat conditions has driven much of this research. The identification of novel targets through preclinical research and the continued review and evaluation of clinical and preclinical studies has proven vital for these advances. Despite this there is still a substantial lack of effective

Acknowledgments

This research was supported by The National Health & Medical Research Council of Australia (NHMRC) of which AJL is a Senior Fellow.

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