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6.3: Substance Use and Addiction - Theories, Brain Mechanisms, and Treatment

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    Learning Objectives
    1. Define addiction (substance use disorder) in terms of changes in behavior, emotion, and cognition.
    2. Describe the neural mechanisms of addiction, including the role of key neurotransmitters (dopamine & endorphins), brain structures & circuits, and genetics.
    3. Differentiate the actions of drugs of abuse in terms of their neurotransmitter effects, neuroanatomy of action, and abuse potential

    Overview

    Many people don’t understand why or how other people become addicted to drugs. They may mistakenly think that those who use drugs lack moral principles or willpower and that they could stop their drug use simply by choosing to. In reality, drug addiction is a complex disease, and quitting usually takes more than good intentions or a strong will. Drugs change the brain in ways that make quitting very difficult, even for those who want to. Fortunately, researchers know more than ever about how drugs affect the brain and have found treatments that can help people recover from drug addiction and lead productive lives.

    What Is Addiction?

    According to the National Institute of Drug Abuse (NIDA), drug addiction is defined as the continued compulsive use of drugs despite adverse health or social consequences. People addicted to drugs have lost control of their drug use. Because of this they can become isolated from family or friends, have difficulty at work or school, engage in unhealthy behaviors, and may become involved with the criminal justice system. For a person addicted to drugs, continuing to take them becomes the primary focus in life.

    The Diagnostic and Statistical Manual, 5th edition (DSM V) from the American Psychological Association has reframed addiction as substance use disorder (Hasin, et al., 2013). This diagnostic category views substance use on a continuum with a range of severity from mild to severe based on the presence of 11 criteria. These criteria include some of the same factors noted by the NIDA definition stated above in addition to others, such as physiological effects (i.e. withdrawal & tolerance) and psychological problems related to drug use.

    Disagreements about the nature of addiction remain: namely, whether it reflects voluntary or involuntary behavior and whether it should be punished or treated as a health issue. Even though the first time a person takes a drug, it is often by choice—to achieve a pleasurable sensation or desired emotional state—we now know from a large body of research that this ability to choose can be affected by drugs. And when addiction takes hold in the brain, it disrupts a person’s ability to exert control over behavior— reflecting the compulsive nature of this disease.

    The human brain is an extraordinarily complex and fine-tuned communications network made up of billions of cells that govern our thoughts, emotions, perceptions, and drives. Our brains reward certain behaviors such as eating or procreating—registering these as pleasurable activities that we want to repeat. Drug addiction taps into these vital mechanisms geared for our survival. And although not a life necessity, to an addicted person, drugs become life itself, driving the compulsive use of drugs—even in the face of dire life consequences—that is the essence of addiction.

    How Does Addiction Take Hold in the Brain?

    Decades of research supported by NIDA has proven that addiction is a complex brain disease characterized by compulsive, at times uncontrollable, drug craving, seeking, and use that persist despite potentially devastating consequences. Although not the only factor, the powerful rewarding effects of most drugs of abuse play a major role in their continued use despite negative effects.

    The rewarding effects of most drugs of abuse come mainly from large and rapid upsurges in dopamine, a neurochemical critical to stimulating feelings of pleasure and to motivating behavior. Increased activity of endorphins, our natural opiate system can also play a role in these effects. The rapid dopamine “rush” from drugs of abuse mimics but greatly exceeds in intensity and duration the feelings that occur in response to such pleasurable stimuli as the sight or smell of food, for example. Repeated exposure to large, drug-induced dopamine surges has the insidious consequence of ultimately blunting the response of the dopamine system to everyday stimuli. Thus the drug disturbs a person’s normal hierarchy of needs and desires and substitutes new priorities concerned with procuring and using the drug.

    Figure \(\PageIndex{1}\): Dopamine Pathways. In the brain, dopamine plays an important role in the regulation of reward and movement. As part of the reward pathway, dopamine is manufactured in nerve cell bodies located within the ventral tegmental area (VTA) and is released in the nucleus accumbens and the prefrontal cortex. Its motor functions are linked to a separate pathway, with cell bodies in the substantia nigra that manufacture and release dopamine into the striatum. From: NIDA Research Report Series - Methamphetamine Abuse and Addiction (2006), PD US NIH, via Wikimedia Commons

    Drug abuse also disrupts the brain circuits involved in memory and control over behavior. Memories of the drug experience can trigger craving as can exposure to people, places, or things associated with former drug use. Stress is also a powerful trigger for craving. Control over behavior is compromised because the affected frontal brain regions are what a person needs to exert inhibitory control over desires and emotions. That is why addiction is a brain disease.

    As a person’s reward circuitry becomes increasingly dulled and desensitized by drugs, nothing else can compete with them—food, family, and friends lose their relative value, while the ability to curb the need to seek and use drugs evaporates. Ironically and cruelly, eventually even the drug loses its ability to reward, but the compromised brain leads addicted people to pursue it, anyway; the memory of the drug has become more powerful than the drug itself.

    Certain drugs, including opioids and alcohol, cause strong physical reactions in the body when drug use stops. When a person addicted to heroin stops taking heroin, they can experience a variety of symptoms ranging from watery eyes and a runny nose to irritability and loss of appetite and then diarrhea, shivering, sweating, abdominal cramps, increased sensitivity to pain, and sleep problems. In general, withdrawal from heroin makes people feel miserable. Withdrawal from alcohol can cause serious effects such as seizures and even death. Withdrawal from other drugs, such as cocaine and amphetamines, does not typically lead to strong physical reactions, but it may make the person feel depressed or lethargic. For most drugs, physical withdrawal symptoms can usually be controlled effectively with medications.

    Even though withdrawal from some drugs does not cause the person abusing them to have physical reactions, stopping drug use is difficult because of the changes the drugs have caused in the brain. Once the drugs stop, the person will have cravings, or intense desire for the drugs that may lead to relapse of drug taking. Craving arises from the brain’s need to maintain a state of homeostasis (balance) that now relies on the presence of the drug. A person may experience cravings at any stage of drug abuse or addiction, even early in the experimentation phase of drug abuse. Cravings have been shown to have a physical basis in the brain. Using PET imaging, scientists have shown that just seeing images of drug paraphernalia can stimulate the amygdala (part of the brain involved in emotional memory) in an addicted person.

    Drugs of abuse do not merely cause short-term changes in an individual’s cognitive skill and behavior. A drug “high” (i.e. euphoric state) typically lasts a short time, ranging from less than an hour to 12 hours, depending on the drug, dose, and route of administration. The changes in the brain that result from continued drug use, however, can last a long time. Scientists believe that some of these changes disappear when drug use stops; some disappear within a short time after drug use stops, and other changes are potentially permanent.

    One of the first changes in the brain that may occur in response to repeated drug abuse is tolerance. Tolerance develops when a person needs increasing doses of a drug to achieve the same high or “rush” that previously resulted from a lower dose of the drug. Two primary mechanisms underlie the development of tolerance. First, the body may become more efficient at metabolizing the drug, thereby reducing the amount that enters the brain. Second, the cells of the body and brain may become more resistant to the effect of the drug. For example, after continued cocaine use, neurons decrease the number of dopamine receptors, which results in decreasing cocaine’s stimulatory effect. Opioids, on the other hand, do not typically cause a change in the number of receptors. Instead the opioid receptors become less efficient in activating associated cellular processes, thus reducing the effects of the opioids.

    Why do some people become addicted to drugs while others don’t?

    No one factor can predict if a person will become addicted to drugs. A combination of factors influences risk for addiction. The more risk factors a person has, the greater the chance that taking drugs can lead to addiction. For example:

    • Biology. The genes that people are born with account for about half of a person’s risk for addiction. Gender, ethnicity, and the presence of other mental disorders may also influence risk for drug use and addiction.
    • Environment. A person’s environment includes many different influences, from family and friends to economic status and general quality of life. Factors such as peer pressure, physical and sexual abuse, early exposure to drugs, stress, and socioeconomic pressures can greatly affect a person’s likelihood of drug use and addiction.
    • Development. Genetic and environmental factors interact with critical developmental stages in a person’s life to affect addiction risk. Although taking drugs at any age can lead to addiction, the earlier that drug use begins, the more likely it will progress to addiction. This is particularly problematic for teens. Because areas in their brains that control decision-making, judgment, and self-control are still developing, teens may be especially prone to risky behaviors, including trying drugs.

    Can drug addiction be treated?

    As with most other chronic diseases, such as diabetes, asthma, or heart disease, treatment for drug addiction generally isn’t a cure. However, addiction is treatable and can be successfully managed. People who are recovering from an addiction will most likely be at risk for relapse for years and possibly their whole lives. Research shows that combining addiction treatment medicines with behavioral therapy ensures the best chance of success for most patients. Treatment approaches tailored to each patient’s drug use patterns and any co-occurring medical, mental, and social problems can lead to continued recovery.

    More good news is that drug use and addiction are preventable. Results from NIDA-funded research have shown that prevention programs involving families, schools, communities, and the media are effective for preventing or reducing drug use and addiction. Although personal events and cultural factors affect drug use trends, when young people view drug use as harmful, they tend to decrease their drug taking. Therefore, education and outreach are key in helping people understand the possible risks of drug use. Teachers, parents, and health care providers have crucial roles in educating young people and preventing drug use and addiction.

    Medications and Devices used in Drug Addiction Treatment

    Medications and devices can be used to manage withdrawal symptoms, prevent relapse, and treat co-occurring conditions.

    Withdrawal. Medications and devices can help suppress withdrawal symptoms during detoxification. Detoxification is not in itself "treatment," but only the first step in the process. Patients who do not receive any further treatment after detoxification usually resume their drug use. One study of treatment facilities found that medications were used in almost 80 percent of detoxifications (SAMHSA, 2014). In November 2017, the Food and Drug Administration (FDA) granted a new indication to an electronic stimulation device, NSS-2 Bridge, for use in helping reduce opioid withdrawal symptoms. This device is placed behind the ear and sends electrical pulses to stimulate certain brain nerves. Also, in May 2018, the FDA approved lofexidine, a non-opioid medicine designed to reduce opioid withdrawal symptoms.

    Relapse prevention. Patients can use medications to help re-establish normal brain function and decrease cravings. Medications are available for treatment of opioid (heroin, prescription pain relievers), tobacco (nicotine), and alcohol addiction. Scientists are developing other medications to treat stimulant (cocaine, methamphetamine) and cannabis (marijuana) addiction. People who use more than one drug, which is very common, need treatment for all of the substances they use.

    • Opioids: Methadone (Dolophine®, Methadose®), buprenorphine (Suboxone®, Subutex®, Probuphine® , Sublocade™), and naltrexone (Vivitrol®) are used to treat opioid addiction. Acting on the same targets in the brain as heroin and morphine, methadone and buprenorphine suppress withdrawal symptoms and relieve cravings. Naltrexone blocks the effects of opioids at their receptor sites in the brain and should be used only in patients who have already been detoxified. All medications help patients reduce drug seeking and related criminal behavior and help them become more open to behavioral treatments. A NIDA study found that once treatment is initiated, both a buprenorphine/naloxone combination and an extended release naltrexone formulation are similarly effective in treating opioid addiction. Because full detoxification is necessary for treatment with naloxone, initiating treatment among active users was difficult, but once detoxification was complete, both medications had similar effectiveness.
    • Tobacco: Nicotine replacement therapies have several forms, including the patch, spray, gum, and lozenges. These products are available over the counter. The U.S. Food and Drug Administration (FDA) has approved two prescription medications for nicotine addiction: bupropion (Zyban®) and varenicline (Chantix®). They work differently in the brain, but both help prevent relapse in people trying to quit. The medications are more effective when combined with behavioral treatments, such as group and individual therapy as well as telephone quitlines.
    • Alcohol: Three medications have been FDA-approved for treating alcohol addiction and a fourth, topiramate, has shown promise in clinical trials (large-scale studies with people). The three approved medications are as follows:
      • Naltrexone blocks opioid receptors that are involved in the rewarding effects of drinking and in the craving for alcohol. It reduces relapse to heavy drinking and is highly effective in some patients. Genetic differences may affect how well the drug works in certain patients.
      • Acamprosate (Campral®) may reduce symptoms of long-lasting withdrawal, such as insomnia, anxiety, restlessness, and dysphoria (generally feeling unwell or unhappy). It may be more effective in patients with severe addiction.
      • Disulfiram (Antabuse®) interferes with the breakdown of alcohol. Acetaldehyde builds up in the body, leading to unpleasant reactions that include flushing (warmth and redness in the face), nausea, and irregular heartbeat if the patient drinks alcohol. Compliance (taking the drug as prescribed) can be a problem, but it may help patients who are highly motivated to quit drinking.
    • Co-occuring conditions: Other medications are available to treat possible mental health conditions, such as depression or anxiety, that may be contributing to the person’s addiction.

    More details on the addictive potential for some of the specific drugs mentioned above and others are included in the next section.

    Summary

    Drug addiction (i.e. Substance Use Disorder) is clearly a chronic disease characterized by drug seeking and use that is compulsive, or difficult to control, despite harmful consequences. Brain changes that occur over time with drug use challenge an individual's self-control and interfere with their ability to resist intense urges to take drugs, thus relapse is common. Most drugs affect the brain’s reward circuit by flooding it with the chemical messenger dopamine. This causes the “high” that leads people to take a drug again. Over time, the brain adjusts to excess dopamine activity, which ultimately results in the effect known as tolerance, leading the user to take more of the drug in order to achieve the same high. Typically, a combination of genetic, environmental, and developmental factors influences risk for drug misuse. The more risk factors a person has, the greater the chance that taking drugs can lead to a substance use disorder. However, there is hope in that substance use disorder is both preventable and treatable.

    Attributions

    References

    • Hasin, D. S., O'Brien, C. P., Auriacombe, M., Borges, G., Bucholz, K., Budney, A., Compton, W. M., Crowley, T., Ling, W., Petry, N. M., Schuckit, M., & Grant, B. F. (2013). DSM-5 criteria for substance use disorders: recommendations and rationale. The American journal of psychiatry, 170(8), 834–851. https://doi.org/10.1176/appi.ajp.2013.12060782
     

    This page titled 6.3: Substance Use and Addiction - Theories, Brain Mechanisms, and Treatment is shared under a mixed license and was authored, remixed, and/or curated by Multiple Authors (ASCCC Open Educational Resources Initiative (OERI)) .