The title of this chapter is a bit misleading, as it actually is a mistake to suggest that the brain becomes addicted. It is more accurate to say that the person becomes addicted. Addiction is a very serious problem worldwide. For example, it is estimated that in the United States, over 60 million people are addicted to nicotine, alcohol, or both. Many millions more people are addicted to other substances and even to certain activities, as the current conceptualization of addiction is not limited to substances and drugs alone.
Most people do not understand what really qualifies as an “addiction.” An addict may be someone who habitually uses drugs (or habitually engages in some other behavior); however, not all habitual drug users are addicts. The clinical differentiation between habitual users and addicts occurs when they continue to use the drug despite adverse affects on their social functioning, occupational functioning, or physical health, and repeatedly fail when they try to stop using the drug or engaging in the behavior.
The current diagnostic criteria for addiction, or as it is now termed “substance dependence,” does not necessarily include physical symptoms, such as withdrawal, tolerance, and physical dependence (although these certainly are signs of addiction). In fact, if addiction were purely a physical phenomenon, then hospitalizing an addict for a short period of time and waiting for withdrawal symptoms to stop would result in an effective treatment. However, the relapse rate for addicts who leave detoxification centers without other supports and treatments is extremely high (relapse rates are high even with treatment). Therefore, addiction or dependence is a complex behavior involving brain systems, motivation, and elements of volition and choice.
Tolerance refers to the notion that as a person uses a drug repeatedly, or engages in an activity repeatedly, it takes more and more of the drug or activity to produce the same effect that it initially produced. Tolerance is often thought to be a purely physical phenomenon, and tolerance to a particular drug certainly does represent a physical habituation to a substance; however, some studies have shown that there are psychological effects to a person’s tolerance for a drug. For example, some studies have administered liquids to participants who were told that the liquid contained alcohol, when in fact it did not, and in many of these studies, the participants began acting as if they were inebriated.
Withdrawal refers to physical and psychological symptoms, usually negative, that occur when the body eliminates the drug from its system after a person stops using it. In the case of some drugs, such as alcohol, the withdrawal process can be life threatening. Withdrawal is often thought to be purely physical, but there have been studies that indicate that drug-dependent subjects experienced different withdrawal severities in different contexts.
Exhibiting tolerance and withdrawal indicates a physical dependence on a substance. This physical addiction is mediated by changes in the body and the brain that make one “dependent” on using the substance in order to feel functional; however, neither are required for a formal diagnosis of addiction. Tolerance and withdrawal do not occur in all addictions.
The study and treatment of addiction goes back hundreds of years; however, the current conceptualizations concerning addictive behavior got their start in the 1950s. A seminal study by James Olds and Peter Milner in 1954 determined that rodents would learn to continuously press a lever in response to having a specific area of the brain electrically stimulated via electrodes implanted in the brain. However, the researchers found that the rats would only learn to press a lever in response to stimulation in an area known as the septal area of the brain; stimulation to other areas of the brain did not result in lever pressing.
The septal area is basically the gray matter structures of the thalamic area and the limbic system. These studies, and many others like them, have come to be known as intracranial self-stimulation studies, and the general areas involved in these types of studies are often referred to as the pleasure centers of the brain.
The early studies of intracranial self-stimulation were performed with the assumption that the learned lever-pressing behaviors in rats for self-stimulation were different than the lever-pressing behaviors for food rewards and other natural reinforcers. However, subsequent research has indicated that the two brain mechanisms are essentially the same for both. Current thought in addiction physiology has taken the stance that the reward system in the brain functions in addictive behavior in a very similar manner as in normal reinforcement behavior and that the brain mechanisms involved in these behaviors are essentially the same.
The major brain pathways of the reward system are the mesolimbic and mesocortical dopamine pathways. The mesolimbic pathway begins in the midbrain (in an area called the ventral tegmentum, abbreviated VTA), connects to the limbic system by way of the nucleus accumbens, the amygdala, and the hippocampus, and then projects to the prefrontal cortex. The mesocortical pathway connects the VTA of the midbrain to the cerebral cortex and has especially strong connections to the frontal lobes. These two pathways are two of the four brain pathways that use dopamine as their primary neurotransmitter.
The mesolimbic pathway is commonly believed to be the “reward” pathway (although this notion is certainly not unanimously accepted). The mesocortical pathway is believed to be involved in emotional responses and motivation. The VTA is the primary release site for dopamine in the brain.
The neurotransmitter dopamine was the first neurotransmitter implicated in addictive behaviors and most likely plays a role in all types of addictions due to its role in reinforcement. However, it is not the only neurotransmitter involved in addiction.
The two brain pathways implicated in the physiological mechanisms of addiction, the mesolimbic and mesocortical pathways, have extensive connections with areas of the brain that are important in memory (e.g., the hippocampus), emotion and motivation (e.g., the amygdala and the frontal cortex), and goal-directed behavior (e.g., the frontal cortex). Therefore, one could surmise that addiction recruits all of these brain pathways and results in compulsive behaviors that are goal-directed toward self-stimulation.
Several neurotransmitters have been identified as contributing to addiction. Some may play roles only in specific addictions, whereas others may have a general role. This section begins with dopamine and then looks at several different drugs and their associated neurotransmitters.
There are several lines of evidence to support the notion that dopamine is a primary neurotransmitter that is involved in nearly all forms of addictive behaviors. For instance, in studies of rodents given drugs that are dopamine antagonists (an antagonist blocks the action of a specific neurotransmitter), the animals stop the self-administration of different addictive drugs. The administration of these drugs also diminishes the reinforcing effects of the food pellets.
Several lines of evidence for the role of dopamine in addiction come from the nucleus accumbens, an important brain structure that is part of the dopamine pathway. The nucleus accumbens is a collection of neurons in the ventral striatum area that is part of the basal ganglia. Many neuroimaging studies have found increases in extracellular dopamine levels in the nucleus accumbens following either a natural reinforcer, such as food, electrical brain stimulation, or addictive drugs, such as cocaine. Other studies have also indicated that the increased dopamine levels in the nucleus accumbens are related to the experience of getting a reward as well as the expectation of getting a reward. More recent research has indicated that the dopaminergic neurons in the VTA fire in response to the perceived value of a reward, such that a greater than expected reward was associated with increased neural firing and a less than expected reward was associated with decreased neural firing. When the expected reward was received, there was no change in the firing rate of the dopaminergic neurons in the nucleus accumbens.
Studies indicate that normal dopamine functioning is diminished in chronic addicts; however, when the person uses drugs, these pathways become hyperactive. In animal studies, the animals will self-administer injections of addictive drugs directly into the nucleus accumbens, even though damage to the nucleus accumbens or the VTA blocks this behavior. Thus, dopamine appears to play an important function in both the receiving and the expectation of rewards and in mediating the effects of reinforcement.
Cocaine and other stimulants, such as caffeine and amphetamines, are drugs that directly affect the dopaminergic brain pathways and in some cases alter them. Other excitatory neurotransmitters, such as glutamate, are affected by stimulant abuse. The overuse of stimulants can lead to a type of drug-induced psychosis that resembles the psychiatric disorder paranoid schizophrenia. Early theories of schizophrenia suggested that this disorder was related to an overabundance of dopamine in the brain. The primary mechanisms by which cocaine and related drugs work are through their blocking of dopamine transporter molecules in the presynaptic membrane that function to remove dopamine from the synapse and transfer it back into the neurons after it has performed its functions. Other stimulants increase the release of other neurotransmitters in the synapses.
Alcohol is classified as a depressant drug not because it causes depressed mood, although it can do that in large doses, but because at moderate or high levels, alcohol results in inhibition of neural firing, whereas at low doses it may increase neural firing. This is why when one initially drinks alcohol, one may feel excited and uninhibited, but as one continues to drink alcohol, one experiences slowed reflexes, slurring of words, and other similar effects. Alcohol addiction or alcoholism often produces physical dependence such that the person will experience withdrawal symptoms. Like with any other abused drug, the neurotransmitter dopamine is involved in the reinforcing effects of drinking alcohol; however, a number of other neurotransmitters are also implicated in alcohol abuse. Alcohol appears to be an agonist (facilitates the action) for inhibitory neurotransmitters such as GABA and an antagonist (blocks the action) for excitatory neurotransmitters such as glutamate and serotonin. At moderate or high levels then, alcohol use results in decreased firing of excitatory neurotransmitters and increased firing of inhibitory neurotransmitters.
Opiates are drugs that are derived from opium, the dried sap taken from the seeds of the poppy plant. Opiates, like heroin and morphine, are associated with high physical dependence because the brain is already wired for them. Endorphins and enkephalins are neurotransmitters that have their own receptors in the brain, and these receptors also have a high affinity to opiate drugs because the structure of these substances is basically the same. Analgesic drugs are extremely effective in the treatment of pain and other symptoms, like diarrhea and persistent cough, but are highly physically addicting because tolerance to these drugs develops quickly and periods of non-use are likely to result in withdrawal symptoms. Moreover, because they inhibit physical functions, such as breathing and heart rate, they are easily overdosed.
Synthetic opiate analgesics, such as OxyContin, produce the same effect as heroin or morphine. Many long-term detrimental physical effects associated with the use of these drugs appear to be due to issues such as sharing needles or poor hygiene, and not directly to the actions of the drugs themselves.
Tobacco, while actually legal for adults, may be more addictive than heroin. Some estimates suggest that about 70 percent of all people who experiment with smoking cigarettes become addicted, whereas 10 to 30 percent addiction rates are reported for alcohol and heroin, respectively. Tobacco is also responsible for far more deaths than any other drug, although nicotine overdoses are rare.
The major psychoactive ingredient in tobacco is nicotine, although there are some 4,000 other chemicals in cigarettes. Nicotine, like heroin, has a ready-made neural receptor in the brain called the nicotinic cholinergic receptor. Tolerance develops quickly to nicotine, and heavy smokers are drug addicts in every sense of the word.
The psychoactive effects of marijuana are largely due to a substance called THC (delta-9-tetrahydrocannabinol). However, marijuana contains over eighty other chemicals called cannabinoids similar to THC that are probably also psychoactive. There has been quite some controversy lately as to whether or not marijuana is an addictive drug, and while there are a small group of people that do become addicted to marijuana, marijuana’s addiction potential is low compared to other drugs discussed in this section. Marijuana also has some medicinal uses.
There are two confirmed health hazards of marijuana use: Chronic users can develop respiratory problems, and high doses of marijuana can trigger heart attacks, especially in people who previously suffered a heart attack. Current evidence does not suggest that marijuana causes significant brain damage in adults, although this research is ongoing.
There are many biologically based theories and biological approaches to addiction. The early attempts to explain addiction related it to the physiological dependence on drugs such that the physical dependence traps the addicted person in a downward spiral of taking drugs to avoid withdrawal symptoms. This is the classic depiction often seen in the movies or media, where the addict is driven to take drugs to avoid withdrawal. The problem with this notion is that when addicts are detoxified and are no longer experiencing withdrawal effects, there is almost a 100 percent relapse rate if no other treatment is undertaken. A second problem with this notion is that many highly addictive drugs, such as cocaine, are not associated with severe withdrawal symptoms. Finally, the pattern of addiction displayed by many addicts involves alternating periods of drug binging followed by relatively lengthy periods of abstinence. The avoidance of withdrawal symptoms can be a motivator to take a drug, but it appears that this is not the primary motivator for drug abuse and addiction. As a result, other theories have been proposed that do not assume that physical addiction is the driving force in addiction.
One group of theories that has received some prominence focuses on the rewarding effects of the substance. These positive-incentive theories assume that craving for a substance is targeted for the expected pleasure-producing effects of the drug. The positive-incentive value refers to the anticipated pleasure associated with a particular action, such as drug taking. This expected value is different than the actual amount of pleasure that is experienced from an action (often referred to as the hedonic value of an action). However, an observation that addicts almost universally agree with is that, with time, the effects of the drug are not as pleasurable as they once were, and these positive-incentive theories cannot explain what causes a person to become an addict as opposed to just a user. The compulsive use exhibited by addicts cannot be explained by these theories. Two major theories have addressed these concerns.
One such theory is the incentive-sensitization theory that hypothesizes that it is not the pleasure of taking the drug that is the basis of the addiction; it is the anticipated pleasure of taking the drug that drives addiction. At first the drug’s positive-incentive value is associated with its pleasurable effects; however, as time goes on, tolerance develops, reducing the actual pleasure received from the drug, and the addict’s desire for the drug becomes sensitized. Addicts continue to seek the drug for the anticipated pleasure it may bring and not the actual pleasure itself. It is the wanting of the drug that drives addiction in this model, not the liking of the effects of the drug.
The other theory is based on a medical model of behavior and is often termed the disease model of addiction. In this model drugs, such as cocaine, when taken chronically, alter the structure of the brain and interfere with rational decision making in the addict. The alteration of the brain occurs in the reward systems of the brain discussed earlier and associated areas in the frontal cortex that control the ability to terminate a repetitive behavior. Addiction is therefore a physical disease, like cancer.
This particular model and its variations are quite popular in medical circles with psychiatrists, physicians, and many addiction treatment professionals. This model forwards the notion that addicts cannot stop using their own willpower, that they need assistance, and that drugs of addiction rob the addict of the power to choose to quit. This model relies on the high rate of relapse in nearly all addictions as evidence that it is a physical process, and not a cognitive one, that drives addiction. The notion of addiction as a disease will be addressed later in this chapter.
Relapse occurs when someone who has been abusing a substance or is addicted to a substance quits taking that substance for a period of time and then begins to take the drug again. One cannot relapse if one is not addicted to or abusing a substance. One of the puzzles in addiction treatment is the repeated observation that getting someone to stop using a drug or substance is not typically the problem; the main problem is preventing him from relapsing. Research has indicated that there are several conditions that will increase the probability that a person will relapse:
Priming occurs when an addict who has been abstinent for some time starts using the drug again in a smaller dose or with intentions to only “have a little.” Typically, the addict believes that he has control over his use and will only use again one time; however, often once he starts using again, even with the intent to use significantly less, he reverts back to his old ways. Many addicts will attest to the fact that the relapse behavior is often worse than the original addictive behavior. Drug priming is so prevalent in addiction that many treatment programs believe that only total abstinence from the drug can control relapse.
Related to drug priming is the notion that environmental cues contribute to relapse. Environmental cues are such things as places, people, or objects that were associated with drug use in the past. These cues are so strong that they often are themselves priming mechanisms that lead to relapse.
Unclear goals, or not having a clear understanding of the relapse process associated with priming and cues, can lead a person to think that all he needs to do is stop taking the drug and everything will be fine. Addicts can relapse by trying to use only once or by returning to environments associated with using.
Stress is another factor associated with relapse. This reinforces the view that substance usage and the development of addiction is an attempt to cope with stressful situations in one’s life. Stress often results in an addict returning to familiar escape patterns.
One thing that should be clear from the discussion of factors leading to relapse is that there is a strong association between environment and substance dependence, such that addiction may represent a form of classical conditioning. This suggests that cues in the environment strongly pull for an addict to engage in his addiction, and that the brain pathways developed in addiction are powerful.
There are a large number of different treatment programs, self-help books, and other potential solutions for treating addictions. Interestingly, the most studied forms of treatment have just about the same relapse rates over the long-term. Many programs, such as the Alcoholics Anonymous twelve-step program, purport a total lifestyle change for the addict, whereas other programs concentrate on just the addictive behavior itself. One of the observations regarding successful outcomes in addiction treatment is the motivation of the addict. A number of studies have suggested that most addicts, such as cigarette smokers, quit on their own. And while many have occasional relapses, over the long run, they are successful. Any treatment program or any behavioral modification program will not work if the person is not committed to the particular goal in mind.
Secondly, support from friends, family members, and even professional support, such as therapy or groups, can be successful in increasing an addict’s motivation to stop. Even twelve-step programs that support the medical model of addiction, but that offer no medical treatment, are successful in cases when the addict is motivated and is provided with education and support. One of the advantages to twelve-step programs is that they do not cost anything (they are funded by voluntary donations), they develop a sense of group unity, and one can attend any day of the week. The members in these programs will often go out of their way to help a suffering individual. Other intervention programs, such as residential programs, offer similar benefits, but are time-limited. Many ex-addicts believe that addiction recovery is a lifetime endeavor and requires some form of ongoing support for a longer time period.
People become committed to quitting substance abuse and addictive behaviors when these behaviors conflict with important goals in their lives or when certain life-changing events occur, such as having a child. Not everyone follows this pattern, but when an addict views his addiction as harmful or limiting his choices, he often takes positive steps. The problem is that most addicts consider their addictive behavior a positive choice.
There are some medications that have demonstrated some success in treating people with certain types of addictions. By far the most commonly used of these is a medication called Antabuse. Antabuse interferes with the breakdown of alcohol in the person’s system and results in the person becoming violently ill if she drinks alcohol while taking the drug. Other drugs, such as Revia or Suboxone, were designed to treat narcotic addictions, but have also been used to treat alcoholism and addictions to other drugs and to help eliminate cravings. Most studies have found that these drugs are only moderately effective because they can only work if the person takes them. Thus, any medications prescribed to halt addictive behaviors are only as good as the addict’s own commitment to quit.
There are several things that are clear regarding addictions in humans. First, addiction is a psychologically complex phenomenon. Second, there has been much evidence to support the notion that addiction is a disturbance of decision making and that addicts have poorer decision-making skills than do normal controls. Third, addiction is not limited to just drugs but includes many other behaviors, including gambling, shopping, eating, sexual activity, and many others. Fourth, addiction, like many behaviors, has a strong genetic component in that a person’s potential for becoming an addict is increased if first-degree relatives have had an addiction. Finally, the change from the initial use to compulsive addiction is associated with structural changes in the limbic system and frontal cortex and involves many neurotransmitters.
Those who support models of addiction as a disease point to the fact that these changes in brain structure of addicts are responsible for an individual’s inability to stop her addiction. The evidence that they bring to the table is quite impressive and convincing.
However, those who refute the notion of addiction as a disease point out successes of treatment programs, such as twelve-step programs, as evidence that addiction is not a disease. They ask, “If addiction is a physical disease like cancer or heart disease, then how can attending a group, following a set rules, and interacting with others who have the same disease cure the disease?” There are no twelve-step programs that cure cancer, diabetes, or other physical diseases. While addiction certainly has a physical component to it (as do all behaviors), this viewpoint supports the notion of addiction as a volitional behavior.
The answer to this question is not a simple one. If addiction is a brain disease, it certainly is not like other brain diseases, such as Alzheimer’s disease, Parkinson’s disease, and others, where behavior is not goal-directed but instead becomes erratic and disorganized. Moreover, the proposal that drug use changes the brain should not be all that shocking. The brain changes in response to its environment, whether it occurs due to drug use, learning to play the piano, reading, or any number of activities. The final answer depends on what one accepts as a definition of what constitutes a disease. If one accepts the notion of a disease as a social metaphor for dysfunctional behavior, then perhaps addiction is a disease; however, if one accepts the traditional notion of a disease, perhaps the criteria for a true disease are not fully met by addiction. Moreover, there is no evidence that labeling addiction as a disease or believing that it is a disease offers any advantages to recovering addicts. Addicts who believe that addiction is a disease relapse as often as those who do not.