“Addiction is a primary, chronic disease of brain reward, motivation, memory and related circuitry. Dysfunction in these circuits leads to characteristic biological, psychological, social and spiritual manifestations. This is reflected in an individual pathologically pursuing reward and/or relief by substance use and other behaviors.”¹ Drug addiction as a brain disease is a concept that has emerged over the past 25 years owing to advances in the understanding of the brain reward circuitry. Use of euphorigenic substances such as alcohol, cocaine, heroin, methamphetamine, nicotine, and opioids can escalate to compulsive use that can result in progressive dysfunction in all areas of the individual’s life. The American Medical Association has defined several International Classification of Diseases, Revision 10 categories associated with substance use disorder. Once a substance use disorder is identified in an individual, formal treatment is indicated. With respect to the neurobiology of addiction, much of the neural circuitry involving memory, mood, perception, and emotional states that is modified by addictive substances has been elucidated.^2,3 Repeated exposure to drugs of abuse can result in chronic long-term changes to these neural circuits that can affect the individual long after the individual discontinues use of the drug.^4,5 Addiction is manifested through a series of neuroadaptations in different circuits in the brain.^6,7,8,9 The reward and reinforcement centers in the ventral tegmental region associated with survival behavior are significantly affected. For instance, the inability to discontinue behavior that is clearly harmful inevitably affects the individual’s marriage, children, family, career, health, and well-being of himself/herself or others. Distortions of cognitive and emotional functioning, which characterizes addiction, such as compulsion to use drugs, are the hallmarks of addiction. The drugs have usurped the brain’s natural motivational control circuits, and consequently, drug use becomes the exclusive motivational priority. Higher inhibitory centers of the brain that modulate impulsive behavior, including the prefrontal cortex, are suppressed, leading to progressive loss of behavioral self-control.

In the clinical setting, primary care physicians may decide to discontinue chronic opioid therapy for chronic nonmalignant pain because of limited therapeutic benefit. If the physician were to offer the following dialogue to the patient: “I’m concerned about the risk of the opioid medication. I think tapering off is the best thing for you at this time. What are your thoughts?” The patient may exhibit signs of fear, anxiety, and opposition. As a physician who has the understanding that addiction has “changed his or her brain” and that the patient is no longer thinking rationally, he or she should be able to provide compassionate care and appropriate treatment resources.

The limbic system contains the brain’s reward reinforcement circuitry. It links the structures of the brain that control and regulate the ability to feel pleasure. Feeling pleasure motivates individuals to repeat behaviors that are necessary for existence and survival. Therefore, the limbic system can be activated by healthy, life-sustaining
activities such as eating and socializing. It can also be activated by drugs of abuse, such as cocaine, heroin, or opioids. Because the limbic system allows an individual to perceive other emotions that can be either positive or negative, it may account for the perception of the full range of the mood-altering properties of many drugs.¹⁰

There are 2 components involved in the reward reinforcement system.^8,9,11,12 First, the ventral tegmental dopaminergic brain circuitry (reward-reinforcement) mediates survival behavior, such as feeding, reproduction, and social behaviors. As this circuitry is usurped by drugs of abuse, discontinuation of the drug is interpreted by the individual as a limbic threat to survival. This unconscious reaction leads to great resistance to any discussion of tapering the addictive drug (i.e., opioids). The second is the physical withdrawal component and the impact on the reward reinforcement system. Negative reinforcement can be more powerful than the positive reinforcement of euphoria, and some data suggest that the negative (and not positive) reinforcement of physical withdrawal predicts increased difficulties associated with substance abuse over a person’s lifetime. The strong negative reinforcement of physical withdrawal drives the individuals to attempt to avoid gaps in drug use. Given the patient’s fear of physical withdrawal, therapists may apply strategies such as response prevention, generating alternative activities, environmental interventions within the family and community, and emotion regulation and distress tolerance skills. The intensification of the withdrawal syndrome, which is the hypo-dopaminergic state in the reward and reinforcement center, is the limbic survival call to action. By its very nature, any threat to survival has evolved to be noxious to get our attention. The more quickly the concentration of a drug falls to its nadir in the person’s circulatory system, the more intense the withdrawal, the more miserable the person feels, and the greater this limbic call to action. From a societal standpoint, this manifests in many well-known behaviors such as stealing, armed robbery, and the taking of life, all of which are examples of the length individuals will go to escape withdrawal. The roller coaster rides of positive reinforcement (taking the drug for the euphoria) and negative reinforcement (taking the drug to avoid withdrawal) leads to behavior that appears to defy logic.¹³ Because addiction is primarily a limbic disorder, attempts at a rational discussion with the substance-abusing individual are frequently unsuccessful.

Recently, there has been debate about the addictiveness of opioids.^14,15 The literature that emerged in the late 1990s downplayed the risk of addiction. In the setting of pain, addiction was estimated to be less than 1% in small studies advocating for use of opioids given this low risk in the pain, which were clearly not substantiated. At the same time, empirical evidence suggests that not everyone who drinks alcohol becomes an alcoholic. The genetic contribution to alcoholism risk is 40% to 50%.¹⁶ Studies have assessed individuals who have experimented with a particular substance and examined the percentage of those individuals who eventually became users or addicts. Dependence among any time users for tobacco, heroin, alcohol, and illicit drugs are 31.9%, 23%, 15.4%, and 14.7%, respectively.¹⁷ Dependence on opioid medications may fall within the range of these other addictive substances.