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According to the National Center on Addiction and Substance Abuse at Columbia University (CASAColumbia), 40 million people in the United States have a substance use disorder.1 Another 80 million (32% of the U.S. population) exhibit behaviors that put them at risk for becoming a substance abuser. For perspective, 19 million Americans have cancer, and 26 million have diabetes.


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The National Survey on Drug Use and Health (NSDUH), conducted by the Substance Abuse and Mental Health Services Administration (SAMHSA), revealed that 22.6 million Americans (8.9% of the U.S. population) older than age 12 years currently use illicit drugs.2 The NSDUH also showed that the use of illicit drugs among persons aged 18 to 25 years increased from 19.6% in 2008 to 21.5% in 2010.2

Annual U.S. expenses related to addictive disorders amount to hundreds of billions of dollars.3 One-third of all inpatient hospital costs are related to addiction, and in 2010, $28 billion was spent to treat 40 million individuals with this disease.1

Deaths caused by accidental overdose of prescription drugs are a growing problem. In 2009, more than 475,000 emergency department (ED) visits were related to abuse of prescription opioids, and this number has almost doubled in the intervening years.4 According to the CDC, for every death caused by accidental overdose of opioids in 2010, there were 35 ED visits for nonfatal overdoses.5

To illustrate the magnitude of the rise in accidental overdose deaths since 1970, consider that the U.S. population increased by approximately 50% to 306 million during that period.6 By contrast, the number of accidental overdose deaths increased more than tenfold during the same interval.5,7 A study in 2012 showed that almost half of the accidental deaths in four counties in southern California were caused by prescription drugs.8

The first of a two-part series, this article will explain the importance of recognizing addiction as a brain disease, understanding the underlying physiology and pathophysiology of addiction, and diagnosing substance use disorders.


Addiction as a brain disease


There is a lack of understanding about addiction as a brain disease and a subsequent minimization of the consequences of addiction among health-care providers. This is particularly noticeable in the realm of pain management. In general, clinicians receive minimal training in the area of addiction. 


Because addiction is a disease of the brain, health-care providers must have a basic understanding of the areas of the brain involved. Research using functional MRI and positron emission tomography (PET) scans has demonstrated that the brain’s survival and pleasure centers are the same areas affected by addiction.9 This part of the brain inspires such primitive and instinctive responses as hunger and thirst and is virtually identical in humans and other animals. 


A review of the underlying anatomy and physiology of the brain and how this organ normally functions will help the clinician understand addiction as a brain disease. 


Brain anatomy


The human brain consists of three major structures: the cerebrum, the cerebellum, and the brainstem. The cerebrum is the largest structure and is divided into right and left hemispheres. Each hemisphere consists of a frontal lobe, a parietal lobe, a temporal lobe, and an occipital lobe.

The frontal lobe controls problem-solving, judgment, mood, emotions, and skilled muscle movements. The parietal lobe contains the sensory cortex and receives and processes information pertaining to temperature, pain, touch, and taste. The temporal lobe contains the hippocampus and is involved in memory, language comprehension, and hearing. The main function of the occipital lobe is vision and discerning color and movement. The cerebrum’s outer covering is referred to as the cerebral cortex, which contains gray matter and unmyelinated neurons.


The cerebellum governs coordination, voluntary movement, balance, and muscle tone. The brainstem connects the brain to the spinal cord and consists of three structures (the midbrain, pons, and medulla oblongata). The brainstem controls autonomic functions that are necessary for survival (e.g., breathing, heart rate, sleep, digestion). Situated between the cerebral cortex and the midbrain, the thalamus is considered the major relay center of the brain and transmits information between the senses and the cortex. 


It is important to understand the limbic system of the brain as well when treating addiction. The limbic system regulates emotion and memory and is a complex set of structures located on both sides of the thalamus underneath the cerebrum. The hypothalamus, hippocampus, and amygdala are the three major structures of the limbic system.


The physiology of addiction


To function properly, the brain depends on neurons to transmit electrochemical signals effectively between brain cells. The electrical properties of neurons are controlled by biochemical and metabolic processes that take place among neurotransmitters and receptors.

Neurotransmitters in the brain are chemicals that enable the transport of information from one neuron to another across synapses in the synaptic cleft. Neurotransmitters are used in specific areas of the brain and have specialized functions. Some of the most common neurotransmitters of the brain are glutamate, gamma-aminobutyric acid (GABA), serotonin, acetylcholine, norepinephrine, and dopamine.


Neurotransmitters are commonly classified as excitatory or inhibitory. Glutamate, epinephrine, and norepinephrine are typically considered excitatory neurotransmitters, and serotonin and GABA are considered inhibitory neurotransmitters. Some neurotransmitters, such as acetylcholine and dopamine, may have both excitatory and inhibitory effects. 


A number of psychoactive drugs including antidepressants, nicotine, alcohol, marijuana, heroin, and cocaine exhibit their effects through the alteration of the expression of these neurotransmitters. The effect of the neurotransmitter serotonin is the primary target for some antidepressant medications. Acetylcholine and dopamine are involved in several areas of the brain; however, they are not as widely distributed as glutamate and GABA.


Addictive substances and the reward pathway 


The 1990s were often referred to as the decade of the brain. Research led to a better understanding of the reward circuitry of the brain, with increased insight into the nature of addiction as it related to specific parts of this organ. The neurotransmitter dopamine was noted to have an integral role in the process of addiction, specifically in the activation of the brain’s reward pathway. 


The reward pathway is made up of brain structures that regulate behavior by producing pleasurable responses. The major structures of the reward pathway are the ventral tegmental area (VTA), the nucleus accumbens, and the prefrontal cortex (Figure 1). The neurons of the VTA trigger the release of dopamine in the nucleus accumbens and the prefrontal cortex. When dopamine is released, a person feels pleasure. 


Figure 1. Major structures of the brain’s reward pathway

In 1954, Olds and Milner demonstrated that rats would press a lever to stimulate electrodes placed directly into the nucleus accumbens.10 Similar experiments in the 1960s demonstrated that rats would press a lever to self-administer injections of heroin.11–13 The rats kept pressing the bar to get more heroin because it is pleasurable. The heroin is positively reinforcing and serves as a reward. When the injection needle was placed in an area outside the nucleus accumbens, the rats would not self-administer the heroin.

PET scans have revealed that dopamine release is increased within the reward pathway of rats self-administering heroin, resulting in activation of the reward pathway.14 In many cases, the rats would ignore hunger or thirst to stimulate their nucleus accumbens by electrode or by self-administration of heroin.