Addiction Research and Treatment
Addiction Research and Treatment
The nation's leading causes of death are related to alcohol and drug use, tobacco smoke exposure, and behavioral addictions. Each year, more than 400,000 Americans die as a result of smoking, overeating, substance use, and related accidents and suicide. In addition, the comorbidity of addictions and psychiatric illnesses (ie, dual diagnosis) is quite common. Approximately 29% of those with a psychiatric disorder and almost half of those with severe mental illness (eg, schizophrenia) have a lifetime history of addiction.1 As a result, addiction-related prevention, research, and treatment have remained important areas of concentration in the field of psychiatry.
There are significant individual differences in drug experimentation, drug(s) of choice, susceptibility to addiction, prognosis following intervention, and likelihood of relapse. Over the past few decades, there have been notable advances in the identification, prevention, and treatment of addiction disorders. For example, it was not until DSM-III-R that cocaine was listed as a potential substance of abuse, but this discovery expanded the focus of addiction research and treatment beyond specific physical withdrawal symptoms. More recently, animal models have improved and research is currently under way with addicted rats.2 In addition, advances in neurobiology and imaging, proteomics, nanotechnology, pharmacology, and behavioral research have impacted the addiction field. This article highlights many of the latest developments in addiction research and focuses on those with a clear application to psychiatric practice.
Influence of neurobiology and neurotransmitters
Several components of the neurological reward system (eg, the nucleus accumbens, the ventral tegmental area, and the neurotransmitters [particularly dopamine]) have been implicated in addiction. For example, release of dopamine in the nucleus accumbens is associated with craving for cocaine and drug-seeking behavior.3,4 Similarly, morphine, cannabis, nicotine, and ethanol administration result in increased dopamine release in the nucleus accumbens.5-7 They are also associated with molecular adaptations in dopamine transporters, as well as opioid, g-aminobutyric acid (GABA), and nicotinic cholinergic receptors throughout the brain.8-10 In addition, the brain's endogenous opioid and cannabinoid systems, within the pathway connecting the ventral tegmental area and the nucleus accumbens, are activated by several drugs of abuse.11 Increased glutamate release in the pathway connecting the prelimbic cortex to the accumbens is associated with drug-seeking behavior.12 With regard to tobacco, findings from recent research indicate that patients with damage to the insula (an area associated with consciously experiencing an urge) were able to immediately quit smoking, without the typical urges and relapses that usually characterize smoking cessation.13
Research findings indicate that individual differences in sensitivity to substances of abuse may be affected by genetic factors and early environmental factors, and strong interactions between the cannabinoid and opioid systems within the brain may produce cross-sensitization of neurons following exposure to substances of abuse.14,15 Several pharmacological interventions for the treatment of addiction and the prevention of relapse target these neurotransmitters and their receptors.
When considering the possibility that all addictions represent 1 disease, one would expect a common neurobiology, as well as transposable treatments that might work for multiple addictions. For example, naltrexone was used in the 1970s for opioid relapse prevention and has been subsequently used to treat alcohol dependence, gambling, compulsive eating, and other addictions. Drug self-administration represents an acquired drive that results in use despite pain and suffering; it appears to be caused, in part, by pathological learning and preoccupation with the substance. This may help to explain the mechanisms of action in complete blockers such as naltrexone, partial agonists such as buprenorphine, and agonists such as methadone. Research continues to identify brain events associated with pleasure, which may shape behavior and the development of addiction.
Neuroimaging with MRI, magnetic resonance spectroscopy, positron emission tomography (PET), single photon emission CT (SPECT), and functional MRI scanning has helped to confirm that addiction is a disease marked by changes in brain structure and functioning, as well as behavioral correlates. In their review of the literature, Fowler and colleagues16 noted that structural abnormalities in the frontal cortex, prefrontal cortex, basal ganglia, and amygdala have been associated with abuse of various substances. Similarly, they reviewed functional imaging studies, which have demonstrated that the caudate nucleus, cingulate, and prefrontal cortex become activated during a drug "rush," whereas the nucleus accumbens becomes activated during periods of craving. PET and SPECT studies have highlighted the role of striatal dopamine in drug-related reward and addiction.
The dopamine spike that causes the pleasurable drug-related "high" is believed to attenuate drug users' ability to experience pleasure in other activities.9 In addition, findings from recent studies indicate that drug effects are long-lasting and recovery is slow and difficult. Imaging may also be useful in determining the likelihood of relapse in patients, which may have implications for treatment recommendations.17
Risk factors for alcohol dependence have been well studied, and many scientists expect that genes for alcoholism risk will be identified in the near future. However, early alcohol exposure and binge drinking appear to play a critical role in the development of alcohol dependence. Similarly, early brain exposure to drugs of abuse (whether in utero or through secondhand exposure) may sensitize the brain, making abuse and dependence more likely. For example, parents who drink alcohol inadvertently teach their children to identify the smell of their favorite alcoholic beverage. Mothers who smoke frequently have children who smoke, which may be associated with early secondhand smoke exposure.