In 2006, substance dependence or abuse was diagnosed in about 22.6 million persons in the United States.¹ Addiction-related morbidity and mortality pose a major burden to society, costing our economy more than $500 billion annually: about $181 billion for illicit drugs,² $168 billion for tobacco,³ and $185 billion for alcohol.⁴ Loss of productivity, broken families, jail time, HIV infection, hepatitis C, and death are common sequelae of drug addiction.

In addition, population surveys show a high prevalence of comorbid drug abuse and other mental illnesses,⁵ such as mood and anxiety disorders (especially in women), antisocial personality disorder (particularly in men), and schizophrenia (highly comorbid with nicotine dependence). Compelling evidence shows that the disease of addiction arises through the complex interaction of genetic, behavioral, and environmental factors and that it is most effectively prevented and treated through research-based approaches.⁶

Investment in addiction research and treatment is opening up avenues that are profitable not only to persons who are addicted but also to their families, communities, and society at large. It is a good investment: estimates show that every dollar spent on addiction treatment programs yields a $4 to $7 reduction in the cost of drug-related crimes. With some outpatient programs, total savings can exceed costs by a ratio of 12:1.⁷

What do we know?
Over the past several decades, we have witnessed changing trends in the abuse of heroin, cocaine, methamphetamine and its derivative ecstasy (3,4-methylenedioxymethamphetamine), and other drugs of abuse. Influencing factors include the existence of purer and more potent formulations, which the illegal drug industry strives for and achieved with crack cocaine and heroin. Prepotent methamphetamine continues to afflict communities across the country, showing marked increases in abuse consequences and in treatment admissions over the past decade—from about 48,000 admissions a year in 1995 to more than 150,000 a year in 2005.⁸

Although cocaine use is viewed as having stabilized somewhat, there are still about 2.4 million current cocaine users aged 12 years and older in this country.¹ While marijuana use continues to decline among teenagers, it remains the most commonly used illicit drug.¹ Outside the illicit drug arena, prescription drug abuse continues to gather momentum; about 7 million US persons report current (in the past month) nonmedical use of prescription drugs, mostly pain relievers—more than the number of persons abusing cocaine, heroin, hallucinogens, and inhalants combined.¹

In the more than 30 years since the National Institute on Drug Abuse (NIDA) was established, major strides have been made in understanding addiction as a complex disease of the brain.⁶ Advances in molecular biology, genetics, and neuroimaging technologies have elucidated the complexity of the opioid, dopaminergic, and other systems, greatly improving our understanding of how the brain responds to and is altered by the acute and long-term use of illicit drugs. Imaging studies have shown that addicted persons have blood flow abnormalities in brain areas involved in impulse control, decision making, motivation, and reward mechanisms. These areas include the orbitofrontal cortex, amygdala, and ventral striatum.⁹

Hypotheses around these systems have helped explain some neurobiological underpinnings of addiction. Brain imaging studies by Volkow's group¹⁰ and others suggest that many types of addiction (including compulsive eating) share common neurobiological substrates and mechanisms. These findings center on the dopamine reward system and on dopamine D₂ receptor (DRD₂) density. Simply stated, the findings suggest an intrinsic diminished ability of some people to experience pleasure, which leads them to seek pleasurable experiences more reliably through the use of illicit substances that artificially reward them by powerfully stimulating the dopamine system.

Unfortunately, addictive drugs can be so reinforcing that no natural stimuli can compete with them. Common reinforcers—food, family, friends—lose their relative value as a person's reward circuitry becomes increasingly blunted and desensitized. Ironically and cruelly, even the drug eventually loses its ability to reward; continued use causes receptor down-regulation and neuronal depletion. Still, the compromised brain leads addicted persons to pursue the use of addictive drugs because by that point the memory of the drug has become more powerful than the drug itself. This compulsive craving, seeking, and use of drugs, even in the face of dire life consequences, is the essence of addiction —what addicts may describe as "chasing the high."

Attempts at quitting give way to withdrawal symptoms so severe, as in the case of opioids (eg, heroin) and nicotine, that they can lead patients to relapse. As with other chronic diseases, such as high blood pressure or diabetes mellitus, sustained positive health outcomes (in this case, abstinence) may require repeated treatment episodes to counter relapse triggers. In persons who are addicted, common daily life stressors and cues in their environment, such as the people, places, and things associated with their former drug abuse, can trigger a relapse.

New findings from animal models of addiction reveal a major role of the corticotropin-releasing factor (CRF) system in stress-induced relapse. This system belongs to a complex neural circuitry that regulates behavioral and autonomic responsiveness to stressful stimuli. Recent findings also suggest that manipulation of dopamine D₃ receptors can block cue-induced relapses.¹¹

Where has it led us?
Research discoveries that reveal the effects of drug abuse and addiction on the brain and body have led to major advances in our understanding of how to best prevent and treat this disease. The relatively recent FDA approval of the use of buprenorphine to treat her-oin and other opioid addiction has changed the way we treat addiction in this country and exemplifies how long-term investments in research can result in tangible products that have a dramatic effect on public health. In particular, approved physicians can now prescribe buprenorphine in office settings rather than in specialty clinics, which will result in greater access to and choices for people who are addicted to opiates. This, in turn, can bring different kinds of patients into care and can reach communities that previously did not have access to appropriate treatment. Given that most persons with substance abuse or dependence are not in treatment and are more likely to come into contact with general medicine or psychiatric services than with a specialty clinic,¹² this is a cultural change of great consequence.