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HLT 214 - Substance Use and Abuse - Textbook

Chapter 4 : Understanding the Science of Addiction - Behavioral Neuropharmacology 

Chapter Objectives

At the conclusion of the chapter, students will be able to:

    1. Understand the neurobehavioral mechanisms underlying addiction.
    2. Discuss the effect of psychoactive drugs on the brain.
    3. Explain why adolescence is a critical “at-risk period” for substance use and abuse.
    4. Discuss protective and risk factors for drug addiction in the youth.
    5. Understand the schedule of drugs and its implications.


Behavioral neuropharmacology focuses on the study of how drugs affect human behavior (neuropsychopharmacology), including the study of how drug dependence and addiction affect the human brain.  All psychoactive drugs act centrally (i.e. on the brain). Drugs affect neurotransmission in diverse ways. The vast majority of drug actions take place through direct effects on neurotransmission. Substance use disorders result from changes in the brain that can occur as a consequence of  repeated use of alcohol and/or other  drugs. WHO defines addiction to drug or alcohol as repeated use of a psychoactive substance(s)1 to the extent that the user (referred to as an addict,  or preferably person who uses a substance ) has the following manifestations:

  1. Understand the neurobehavioral mechanisms underlying addiction.
  2. Discuss the effect of psychoactive drugs on the brain.
  3. Explain why adolescence is a critical “at-risk period” for substance use and abuse.
  4. Discuss protective and risk factors for drug addiction in the youth.
  5. Understand the schedule of drugs and its implications.
  6. Periodically or chronically intoxicated, shows a compulsion a craving to take the preferred substance(s),
  7. Has great difficulty in voluntarily quitting or modifying substance use, and
  8.  exhibits determination to obtain the drug by almost any means.
  9.  Defined in other words,  drug addiction constitutes a chronic  central nervous system disorder,  characterized by recurrent episodes of  relapse in which individuals resume  drug-seeking and drug-taking  behavior, even in the face of adverse  consequences and diminishing reward.

    Note that addiction is “a behavioral pattern of drug use, characterized by

  10. overwhelming involvement with the use of a drug  (compulsive use)
  11. the securing of its supply (compulsive drug-seeking),  &
  12. a high tendency to relapse after withdrawal”
  13. This is known as tolerance, and it reflects the way that the brain maintains balance and adjusts to a “new normal”—the frequent presence of the substance.

    Tolerance is defined as a person’s diminished response to a drug that is the result of repeated use  People can develop tolerance to both illicit drugs and prescription medications.  Tolerance is a physical effect of repeated use of a drug, not necessarily a sign of addiction. For example, patients with chronic pain frequently develop tolerance to some effects of prescription pain medications without developing an addiction to them.3
  15. Tolerance happens when a person no longer responds to a drug in the way they did at first. So it takes a higher dose of the drug to achieve the same effect as when the person first used it. This is why people with substance use disorders use more and more of a drug to get the “high” they seek.  These same circuits control our ability to take pleasure from ordinary rewards like food, sex, and social interaction, and when they are disrupted by substance use, the rest of life can feel less and less enjoyable to the user when they are not using the substance.
  17. Repeated use of a substance “trains” the brain to associate the rewarding high with other cues in the person’s life, such as friends they drink or do drugs with, places where they use substances, and paraphernalia that accompany substance-taking. As these cues become increasingly associated with the substance, the person may find it more and more difficult not to think about using, because so many things in life are reminders of the substance.
  19. Addiction is associated with changes in the function of brain circuits involved in pleasure (the reward system), learning, stress, decision making, and self-control. Every substance has different effects on the brain, but all addictive substances, including alcohol, opioids, and cocaine, produce a pleasurable surge of the neurotransmitter dopamine in a region of the brain called the basal ganglia. The mesolimbic area of the brain is primarily concerned with basic survival. Within the mesolimbic pathway is an area called the ventral tegmental area. The ventral tegmental area projects to the nucleus accumbens (the reward center). This area of the brain is responsible for controlling reward and our ability to learn based on rewards. 3

    The neurotransmitter most commonly linked with the mesolimbic system is dopamine. As substance use increases, these circuits adapt, leading to a down regulation of receptors. Down regulation is a decrease in the number of receptors on the surface of target cells, making the cells less sensitive to a hormone or a neurotransmitter. The receptors scale back their sensitivity to dopamine, leading to a reduction in a substance’s ability to produce euphoria or the “high” that comes from using it.

Figure 2: Probability of becoming dependent when you have tried a substance at least once.

Changes to two other brain areas, the extended amygdala and the prefrontal cortex, help explain why stopping use can be so difficult for someone with a severe substance use disorder. The extended amygdala controls our responses to stress. If dopamine bursts in the reward circuitry in the basal ganglia are like a carrot that lures the brain toward rewards, bursts of stress neurotransmitters in the extended amygdala are like a painful stick that pushes the brain to escape unpleasant situations. Together, they control the spontaneous drives to seek pleasure and avoid pain and compel a person to action.

              In substance use disorders, however, the balance between these drives shifts over time. Increasingly, people feel emotional or physical distress whenever they are not taking the substance. This distress, known as withdrawal, can become hard to bear, motivating users to escape it at all costs. Withdrawal symptoms are symptoms that can occur after long-term use of a drug is reduced or stopped; these symptoms occur if tolerance to a substance has occurred and vary according to substance.  Note that many non-addictive drugs can cause tolerance,  sensitization, or dependence.  Therefore, tolerance, per se define addiction. Rather, addiction is caused by drug-induced changes in reward or reinforcement. 

            As a substance use disorder deepens in intensity, substance use is the only thing that produces relief from the bad feelings associated with withdrawal. And like a vicious cycle, relief is purchased at the cost of a deepening disorder and increased distress when not using. The person no longer takes the substance to “get high” but instead to avoid feeling low. Other priorities, including job, family, and hobbies that once produced pleasure have trouble competing with this cycle.3

             Healthy adults are usually able to control their impulses when necessary, because these impulses are balanced by the judgment and decision-making circuits of the prefrontal cortex. Unfortunately, these prefrontal circuits are also disrupted in substance use disorders. The result is a reduced ability to control the powerful impulses toward alcohol or drug use despite awareness that stopping is in the person’s best long-term interest.

           This explains why substance use disorders are said to involve compromised self-control. It is not a complete loss of autonomy—addicted individuals are still accountable for their actions—but they are much less able to override the powerful drive to seek relief from withdrawal provided by alcohol or drugs. At every turn, people with addictions who try to quit find their resolve challenged. Even if they can resist drug or alcohol use for a while, at some point the constant craving triggered by the many cues in their life may erode their resolve, resulting in a return to substance use, or relapse. 3

In summary,

  • addiction to alcohol or drugs is a chronic brain disease that has potential for recurrence and recovery.
  • addiction process involves a three-stage cycle: binge/intoxication, withdrawal/negative affect, and preoccupation/anticipation. This cycle becomes more severe as a person continues substance use and it produces dramatic changes in brain function that reduce a person’s ability to control their substance use.
  • disruptions in three areas of the brain are particularly important in the onset, development, and maintenance of substance use disorders: the basal ganglia, the extended amygdala, and the prefrontal cortex. These disruptions:
    1. enable substance-associated cues to trigger substance seeking (i.e., they increase incentive salience)
    2. reduce sensitivity of brain systems involved in the experience of pleasure or reward, and heighten activation of brain stress systems
    3. reduce functioning of brain executive control systems, which are involved in the ability to make decisions and regulate one’s actions, emotions, and impulses
  •  these changes in the brain persist long after substance use stops. It is not yet known how much these changes may be reversed or how long that process may take .
  •  adolescence is a critical “at-risk period” for substance use and addiction. All addictive drugs, including alcohol and marijuana, have especially harmful effects on the adolescent brain, which is still undergoing significant development.

Why do people take drugs? There are different “reasons”  why people take drugs, although there should be no reason at all for people to take drugs that cause addiction unless  prescribed for medical indications.  Figure 2 outlines the protective factors as well as the risk factors for drug abuse and addiction. Buy why do people take drugs?

  • To feel high- most abused drugs produce intense feelings of pleasure
  • To feel better- people who have social anxiety, stress-related disorders, and depression may begin abusing drugs in an attempt to lessen feelings of distress.
  • To do better- Some people who feel pressure may use drugs to enhance or improve their cognitive or athletic performance
  1. Curiosity and peer pressure- adolescents often start experimenting use of drugs lured by the strong influence of peer pressure.

Assessing the risk and protective factors that contribute to substance use disorders helps practitioners select appropriate interventions.

Many factors influence a person’s chance of developing a mental and/or substance use disorder. Effective prevention focuses on reducing those risk factors, and strengthening protective factors, that are most closely related to the problem being addressed.

Risk factors are characteristics at the biological, psychological, family, community, or cultural level that precede and are associated with a higher likelihood of negative outcomes.1

Protective factors are characteristics associated with a lower likelihood of negative outcomes or that reduce a risk factor’s impact. Protective factors may be seen as positive countering events.

Some risk and protective factors are non-modifiable (fixed): they don’t change over time. Other risk and protective factors are considered variable and can change over time. Modifiable risk factors (variable) include income level, peer group, adverse childhood experiences and employment status.

Individual-level risk factors may include a person’s genetic predisposition to addiction or exposure to alcohol prenatally.  Individual-level protective factors might include positive self-image, self-control, or social competence. Figure 3 depicts some of the risk and protective Factors for drug abuse and addiction.


Figure 3Risk and protective factors for drug abuse and Addiction

 Figure 3.   Risk and protective factors for drug abuse and Addiction  Source: NIH. (2020). Drugs, brains, and behavior: the science of addiction (link here).

Key Features of Risk and Protective Factors

Prevention professionals should consider these key features of risk and protective factors when designing and evaluating prevention interventions. Then, prioritize the risk and protective factors that most impact your community. All people have biological and psychological characteristics that make them vulnerable to, or resilient in the face of, potential behavioral health issues. Because people have relationships within their communities and larger society, each person’s biological and psychological characteristics exist in multiple contexts.

A variety of risk and protective factors operate within each of these contexts. These factors also influence one another. Contributions to the disease of addiction are 50% genetic and 50% environmental, both of which act together to produce the addiction.  Risk factors for addiction include the agent, the environment, and the host (See Figure 4). Substantial evidence suggests both environmental and social factors can influence the. development of drug addiction.  

Figure 4

Figure 4: Genetic and Environmental Risk Factors for Addiction

Source: NIH. (2020). Drugs, brains, and behavior: the science of addiction (link here).

Targeting only one context when addressing a person’s risk or protective factors is unlikely to be successful, because people don’t exist in isolation. For example:

  • In relationships, risk factors include parents who use drugs and alcohol or who suffer from mental illness, child abuse and maltreatment, and inadequate supervision. In this context, parental involvement is an example of a protective factor.
  • In communities, risk factors include neighborhood poverty and violence. Here, protective factors could include the availability of faith-based resources and after-school activities.
  • In society, risk factors can include norms and laws favorable to substance use, as well as racism and a lack of economic opportunity. Protective factors in this context would include hate crime laws or policies limiting the availability of alcohol.

Risk factors tend to be positively correlated with one another and negatively correlated to protective factors. In other words, people with some risk factors have a greater chance of experiencing even more risk factors, and they are less likely to have protective factors.

Risk and protective factors also tend to have a cumulative effect on the development—or reduced development—of behavioral health issues. Young people with multiple risk factors have a greater likelihood of developing a condition that impacts their physical or mental health; young people with multiple protective factors are at a reduced risk. These correlations underscore the importance of early intervention and  interventions that target multiple, not single, factors.4

Drug Schedules

The Controlled Substances Act (CSA) of 1970 places all substances which were in some manner regulated under existing federal law into one of five schedules.  This placement is based upon the substance’s medical use, potential for abuse, and safety or dependence liability. Schedule I drugs have the highest abuse potential and schedule V drugs represents the least potential for abuse (Drug Enforcement Administration.5

Schedule I

Schedule I drugs, substances, or chemicals are defined as drugs with no currently accepted medical use and a high potential for abuse. Some examples of Schedule I drugs are: heroin, lysergic acid diethylamide (LSD), marijuana (cannabis),  and ecstasy.

Schedule II

Schedule II drugs, substances, or chemicals are defined as drugs with a high potential for abuse, with use potentially leading to severe psychological or physical dependence. These drugs are also considered dangerous. Some examples of Schedule II drugs are cocaine, methamphetamine, methadone, oxycodone, fentanyl, and Ritalin

Schedule III

Schedule III drugs, substances, or chemicals are defined as drugs with a moderate to low potential for physical and psychological dependence. Schedule III drugs abuse potential is less than Schedule I and Schedule II drugs but more than Schedule IV. Some examples of Schedule III drugs are ketamine, anabolic steroids, testosterone

Schedule IV

Schedule IV drugs, substances, or chemicals are defined as drugs with a low potential for abuse and low risk of dependence. Some examples of Schedule IV drugs are Xanax, Valium, Ambien, and Tramadol

Schedule V

Schedule V drugs, substances, or chemicals are defined as drugs with lower potential for abuse than Schedule IV and consist of preparations containing limited quantities of certain narcotics. Schedule V drugs are generally used for antidiarrheal, antitussive, and analgesic purposes.  Examples of Schedule V drugs are: Lomotil and Lyrica.

Chapter Review and Discussion Questions

    1. Define the terms addiction, tolerance, dependence, and withdrawal.
    2. Why do people take drugs? Explain.
    3. Why is it so difficult to educate a person out of addiction.
    4. Outline the schedule of drugs., giving at least one example for each.
    5. Describe risk and protective factors for substance use and abuse.