Presentation and course
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• Addiction is a chronic relapsing-remitting illness marked by progressive dysfunction in psychological, interpersonal, social, and medical domains alternating with periods of improved function (“recovery”) of variable duration. |
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• The disease course is characterized by a change from voluntary, adaptive use to compulsive, maladaptive use that persists despite negative consequences. |
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• Evolutionarily conserved reward neurocircuitry puts all people at risk for compulsive overconsumption, but not everyone will progress to severe addiction. |
No matter the addiction, whether to a substance or behavior, the progression of addiction is phenomenologically similar. Addiction is a chronic relapsing-remitting illness marked by progressive dysfunction in psychological, interpersonal, social, and medical domains alternating with periods of improved function (“recovery”) of variable duration.
The disease course is characterized by a change from voluntary, adaptive use to compulsive, maladaptive use. At first, addictive behaviors may address a need or solve a problem (26; 14). For example, someone may drink to feel relaxed and at ease socially; use stimulants to feel less depressed or be more productive; or play multiplayer video games to feel socially connected. However, when susceptible individuals repeatedly engage in addiction-related behaviors, the behaviors can become increasingly less voluntary and continue despite worsening psychological, medical, and social consequences.
Because the reward neurocircuitry underlying addiction is shared by all human beings, all people are susceptible to compulsive overconsumption, especially in our modern ecosystem that provides easy access to novel, high-potency rewards, without the barriers to overconsumption that previously existed (26; 14). In the past, rewards were scarce and of relatively low potency (eg, unprocessed food that had to be hunted or gathered). Today, we have easy access to high-potency rewards that more strongly activate reward neurocircuitry (eg, highly processed food from the grocery store rather than homegrown and harvested or home cooked; distilled spirits rather than beer or wine; nicotine in vape cartridges rather than leaf tobacco; social media rather than planned in-person gatherings; streaming pornography rather than sex with a partner), without external barriers to overconsumption that limit use. So, today, whether it’s eating one more potato chip or streaming one more episode of a favorite show, most people find themselves overdoing it occasionally.
But not everyone will progress to severe addiction. Most people can modulate addictive behavior when it threatens to interfere with important parts of their lives. For example, someone might want to reduce cannabis use to be more present with their young child, and they can do so. But some people at higher risk develop severe addiction, and they find themselves unable to temper addictive behaviors despite devastating costs to relationships, jobs, health, and self-esteem.
Clinical manifestations of addiction can be conceived in terms of the “4Cs”: Craving, loss of Control over use, Compulsive use, and continued use despite negative Consequences.
Craving. Craving is a strong urge or desire to use a substance or engage in a behavioral addiction, accompanied by an intense mental preoccupation with the substance or behavior. Cravings are relieved by use of the substance or by engaging in the addictive behavior. Such relief, in which a person shifts from an uncomfortable state to a neutral or pleasurable state, negatively reinforces addictive use, increasing the probability that use will continue. For example, after recovering from the depressive “crash” that follows binge cocaine use, someone may find themselves with an intense urge to use cocaine and obsessive thoughts of using cocaine, accompanied by signs of physiologic arousal (increased heart rate, increased motor activity).
Loss of control over use. The addicted person finds themselves using more than they intend or plan to, or in situations when using is ill-advised. For example, someone with a video game addiction may intend to play for only an hour, or only on weekends, but despite their intention find themselves playing for 5 to 6 hours every day.
Compulsive use. The addicted person finds that they are unable to stop themselves from using even when they are aware of important reasons not to use or face high barriers to use. For example, someone with an opioid addiction may suspect that the only available supply is contaminated with fentanyl, and that using risks overdose, but nevertheless cannot stop themselves from using that supply.
Use despite negative consequences. A person continues to use even after having negative medical, social/relational, or legal consequences. For example, someone who drinks may find themselves continuing to drink even after being told that they have liver damage, or after having suffered the legal consequence of a DUI.
Physiologic dependence versus addiction. Continued use despite negative consequences is the hallmark of addiction and can occur with or without physiologic dependence on a substance or medication. Physical dependence is the physiologic adaptation to the presence of a drug, manifesting as tolerance, needing more of the drug over time to get the same effect, and/or withdrawal when ingestion ceases or the dose is decreased, which can occur with both addictive substances (eg, alcohol, benzodiazepines, or opioids) and non-addictive medications (eg, antidepressants), as well as addictive behaviors (eg, gambling, gaming, sex).
Tolerance. High-dose, high-frequency stimulation of the brain’s reward system results in tolerance to the rewarding effects of any addictive drug or behavior. The same dose at the same frequency does not produce the original effect, which now can be produced only with larger, more potent, and more frequent dosing. This occurs with behavioral addictions as well as with substance addictions. For example, the softcore porn that was once titillating now seems boring and tame, and more extreme images of sexual behavior are needed to produce the same level of arousal and excitement.
Withdrawal. Stopping addictive use of any substance or behavior can result in a set of withdrawal symptoms universal to addiction—irritability, anxiety, depression, insomnia —lasting days to months after last use. These symptoms of withdrawal from addictive use partially overlap but are distinct from withdrawal from specific substances or medications (eg, withdrawal from alcohol or opioids). Withdrawal from addictive use results from hypersensitivity of the brain’s stress response and “anti-reward” system that develops over time to counterbalance the hyper-activation of the reward circuitry during addictive use (20).
Table 1. Psychological and Behavioral Changes Over Time as Addiction Progresses
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Initial use |
With disease progression |
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How using feels |
Use results in feeling “good” or “high” or less bad. |
Using results in feeling marginally less bad. (“I don’t get high anymore. Now I use to feel normal.”) |
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Motivational drive from |
Positive reinforcement (using to feel good) |
Negative reinforcement (using to feel less bad) |
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Motivational importance of using |
Using does not seem more important than other rewarding activities like relationships or school. |
Using feels more important than almost anything else. |
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Tolerance |
The same dose of substance or behavior produces the same effect. |
Increasingly larger, more frequent doses are needed to produce an effect. |
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Craving |
Thoughts about using are not intrusive. |
Craving and preoccupation: thoughts of using are intrusive and compelling. |
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Emotional baseline |
Affective baseline is stable: affect returns to baseline shortly after use. |
Negative affect predominates: affective baseline becomes progressively more negative over time; the norm is to feel bad. |
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Compulsive use |
Using can be planned and may look different on different occasions. Consideration of risks and benefits can influence behavior. |
The drive to use cannot be interrupted, at least not for extended periods of time. Attempts to use persist despite knowledge of negative consequences or high barriers to use. |
Prognosis and complications
Complications. Complications include increased morbidity and mortality.
Morbidity. Untreated substance use disorders are associated with significant medical, psychiatric, social, and spiritual consequences.
Medical. Medical consequences include death by overdose (respiratory depression, or cardiovascular collapse); end organ damage (eg, cardiovascular disease, lung disease, Wernicke-Korsakoff syndrome, liver disease); cancers (eg, liver, breast, lung); sexual and blood-borne illnesses (HIV, hepatitis C); and traumatic injury.
Neuropsychiatric. Neuropsychiatric consequences include psychosis, cognitive impairment, depression/amotivation, anxiety, and panic.
Social. Social consequences include loss of relationships, employment, increased exposure to violent crime, financial ruin, and incarceration.
Spiritual. Spiritual consequences include loss of feelings of self-worth, loss of hope, and loss of meaning.
Mortality. In general, people with untreated substance use disorders have a mortality rate higher than people in the general population. For example, opioid users not in treatment have a mortality rate 13 to 14 times higher than the general population (05). People with untreated alcohol use disorder have a mortality rate about 3.4 times (men) and 4.6 times (women) higher than the general population (35). People who smoke tobacco have a mortality rate about three times higher than those who have never smoked (16).
Prognosis. Most people using substances or behaviors addictively will not progress to severe addiction, and most people previously meeting criteria for addiction will have some reduction in symptoms or achieve remission over time (17; 44). For example, data from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC-III) showed that only about 34% of people surveyed who met criteria for alcohol use disorder prior to the survey continued to meet criteria when the survey was conducted; of those who achieved reduction in symptoms, most did so without treatment (44).
Progression is influenced by multiple factors, including type of drug or behavior, route of administration of drug, family history, developmental history, co-occurring psychiatric and medical illness, and socioeconomic factors.
Factors predicting more severe addiction or more chronic illness. More severe and more persistent illness is seen in people with a family history of substance use disorders; a history of extreme childhood stress/adverse childhood experiences, like exposure to abuse or an unstable home environment; polysubstance use; co-occurring psychiatric conditions; lack of social support; unstable living environment; unemployment or lack of meaningful activities; and chronic pain or other medical conditions (04; 38).
Factors predicting more favorable outcomes. More favorable outcomes are seen with earlier intervention and treatment and longer treatment duration, as well as higher socioeconomic and educational levels; stable housing; strong social support; stable employment or involvement in meaningful activities, including spiritual or religious involvement; absence of co-occurring psychiatric illness; strong coping skills (40; 09; 04; 06; 30; 38).
Thus, in general, there is a greater likelihood of a more favorable outcome when someone has (1) greater access to “natural” rewards, like strong relationships and stable employment, which can compete with the rewards of addiction; (2) fewer chronic stressors (like co-occurring medical and psychiatric illness, or unstable housing); and (3) internal psychological resources and social support that allow better coping with stress.