Many people – including behavioral health experts – find addiction baffling. How is it that people suffering from addictive disorders continue to seek out their source of such behavior, even when they know it is destroying their personal, and often professional, lives?

The answer to addiction lies in its neurobiology. The disease develops as a dysregulation of the brain’s drive-reward system. This clinical primer provides a description of the neurobiological basis of addictive disorders – which include substance use disorders (including alcohol and sugar) as well as behavioral addictions (such as to sex or gambling) – that will hopefully shed some light for those aiming to monitor and treat these complex disorders.

Desire and the Triggers Behind Addictive Behavior: Distress and Reward


Human neurobiology drives people to do things that promotes their survival and propagate their DNA. These drives are experienced as motivations, compulsions, impulses, urges, desires, or cravings. Throughout this primer, the term “desire” refers to these drives.

Think of this component of neurobiology as being a part of the “ego,” a complex brain system involving both cortical (conscious) and subcortical (unconscious) parts. Desire drives the ego to compel individuals to act to insure their safety, to enhance their vitality, to experience pleasure, and to reproduce.

Desire is triggered by two forces:

  • distress
  • anticipation of reward, or pleasure

Humans experience desires essentially to “feel good” and to “not feel bad.” The brain has evolved to experience rewards for the fulfilment of desire. These rewards are relief of distress and pleasure. Relief can be from pain, anxiety, discomfort, or other forms of distress. Pleasure can include satisfaction or enjoyment. Often, actions generate both relief and pleasure, such as eating a good meal when hungry. Neurobiologically, pleasure and the relief of distress are closely coupled.

The experience of relief and pleasure is mediated by four main chemicals:

  • endorphins
  • dopamine
  • serotonin
  • oxytocin

Gamma-aminobutyric acid (GABA) and endocannabinoids may also be involved in the brain’s drive-reward system.1 This drive-reward system, and distress, are described as triggers of addictive behavior in more detail below.


Distress can trigger desire and comes in many forms:

  • biological distress
  • emotional distress
  • spiritual distress

Biological distress includes physical pain, hunger, and fatigue. This type of distress stimulates desires to do things to relieve the distress, such as eating when hungry, sleeping or resting when tired, defecating or urinating when the rectum or bladder are full, or removing a hand from a hot stove when sensing pain.

Biological distress can also trigger the use of a substance or engagement in a behavior that alleviates pain. If these substances or behaviors also induce pleasure or other positive emotional states, such as can happen with narcotics (including opioid use disorder, OUD), then addiction can develop in at-risk or genetically vulnerable individuals who use pleasure-inducing substances to alleviate biological distress. (More on these populations below.)

Emotional distress is experienced as negative emotional states, including:

  • fear
  • anxiety
  • depression
  • restlessness
  • irritability
  • anger
  • loneliness

Emotional distress motivates individuals to act to reduce this distress. Fear triggers a biological freeze, fight, or flee response through the extended amygdala deep within the brain. Individuals do what they can to neutralize or avoid the threat. Anxiety arises in anticipation of distress or danger. It motivates people to act in a variety of ways to avoid harm and secure safety and comfort. Thus, they lock their doors, wear their seatbelts, and look both ways when crossing the street. Fear of hunger and homelessness motivates people in part to work or to otherwise procure food and shelter.

Individuals reduce emotional distress in other ways as well. Humans are designed to make attachments to others, and use these attachments to help regulate negative emotional states, helping each other get through their days. Emotional support can help to relieve feelings of loneliness, hopelessness, helplessness, and depression.

There are various psychiatric treatments that alleviate emotional distress, such as various psychotherapies and pharmacotherapies, including antidepressants.

Human neurobiology also predisposes individuals to alleviate emotional distress with pleasurable substances and activities. Some of these activities can be healthy, such as exercise, practicing yoga, going on a walk, meditating, having fun with friends, or spending time in nature. Some people treat distress with sex, food, videogames, or addictive, pleasure-inducing substances. In at-risk individuals or those with a genetic predisposition,2 treating emotional distress with pleasure—including pleasure-inducing drugs and activities—can lead to addiction.

Spiritual distress can be experienced as a:

  • lack of a sense of reverence for existence
  • lack of higher meaning or purpose
  • lack of connectedness to something greater than ourselves

Rather than negative emotional states, spiritual distress can be thought of as the lack of positive emotions related to the experience of existence. Such emotions can be experienced as a lack of joy, passion, wonder, awe, reverence, gratitude, or a sense of being connected to and part of something greater than ourselves.

Over time, humans have discovered that this sort of distress can be alleviated through spiritual practices that entail solitude, silence, and stillness. They may seek practices of meditation, prayer, or reading spiritual literature. People also tend to alleviate spiritual distress by engaging in a spiritual community or by engaging in loving service and other life-promoting activities.

Some have discovered that certain psychoactive substances or entheogens, such as psilocybin, can induce spiritual experiences. Cannabis may also fall into this category for some people at times. Opioids can induce a feeling of euphoria or well-being as well. Again, the use of such pleasure-inducing substances to generate spiritual experiences can lead to addiction, although addiction to psychedelics is uncommon.3-5


The second trigger of desire is anticipation of reward, or pleasure. This drive includes the desire to engage in pleasurable activities such as having sex, playing, eating, and having fun. It includes the pleasure of socializing, as humans are an interdependent species that, as noted, rely on relationships for survival. Because of this interdependence, humans have evolved the capacity to experience the higher rewards of loving, creating, contributing, or otherwise nurturing life. These higher rewards are often experienced as more subtle manifestations of pleasure, including satisfaction and fulfillment, or a sense of wholeness.

Addiction can arise when pleasure is pursued for pleasure’s sake. However, it’s important to note that everyone does this – it is human nature to pursue pleasure for pleasure’s sake. In genetically vulnerable or disposed individuals, the experience of a pleasurable reward causes an excessive stimulation of the drive component of the brain’s drive-reward system, which can lead to an even stronger desire for the pleasure-inducing substance or behavior. With repetition, intense cravings and compulsions can arise. If the individual loses control and acts upon these compulsions, they have engaged in the process of addicting.

When Desire, Distress, and Reward Shape Addiction

For many, addiction develops because the altered state caused by the addictive object solves a problem. The problem may be loneliness, anxiety, insecurity, depression, some other negative emotional state, physical distress, or spiritual distress. For these individuals, distress (or pain) serves as a motivator for continuing to engage in potentially addictive behaviors or to use addictive substances. They discover that pleasure (reward) gives temporary relief from their pain.

If there is a genetic vulnerability, the brain’s drive-reward system becomes dysregulated, with the experience of excessive drive in the form of cravings and compulsions to addict.

The Neurobiology of Addiction: 3 Stages from a 10,000-Foot Perspective

There are three stages that generally take place in the cycle of addiction.6,7

The 3 Stages of Addiction

The first is called the binge/intoxication stage. In this stage, people use drugs or engage in addictive behaviors.  When they stop, they enter what is called the withdrawal/negative affect (emotion) stage. The pain of this stage drives further cravings and compulsions to addict. The preoccupation/anticipation stage comes next, where people who suffer from addiction ruminate about addicting again and experience cravings to addict. See Figure 1.

The binge/intoxication stage arises from the experience of a substance or behavior as being very important in providing either pleasure or relief of pain. It also involves compulsions to addict. These compulsions are mediated by the basal ganglia (this and other brain structures discussed below) with input from the frontal lobes, the anterior cingulate cortex, and the insula. During this stage, positive rewards decrease, resulting in increased stimulation (drugs, behavior) to trigger the brain drive-reward system. During this stage, addiction is motivated primarily by positive rewarding experiences or “positive reinforcement.”

Figure 1. The 3 Stages of Addiction and the Associated Brain Regions (Source: SAMHSA, full citation at end of article)


The Role of the Brain in Addiction

The withdrawal/negative affect stage is mediated largely by the amygdala and the habenula, which seems to be activated when we are missing rewards. The frontal lobes also interact with these structures to organize behavior to addict again. During this stage, the sufferer of addiction experiences pain (mainly in the form of withdrawal symptoms) Now the motivation to addict is driven primarily by the desire to avoid this pain, or “negative reinforcement.”

The preoccupation/anticipation stage is mediated by the medial, inferior, and lateral orbitofrontal cortices with input from the insula and the anterior cingulate gyrus. These structures get input from the structures that mediate the other stages of addiction. This is sometimes called the craving stage. In this third stage, the person with addiction experiences exaggerated desires and compulsions to addict. These are sometimes called “conditioned reinforcement,” because prior experience with the object of addiction (substance or behavior) created, or conditioned, these cravings.

Addiction is caused by damage to motivational circuitry.7 Victims of addiction experience increased drive, experienced as cravings for a substance or behavior along with compulsions to act to use a substance or engage in a behavior – called “incentive salience.” Victims of addiction then develop addiction-related habits in which addicting becomes routine and – to some degree – automatic. The reward, or pleasure experienced can then decrease over time, leading to a “wanting” of the object of the addiction (mediated by dopamine circuitry) but a decrease in “liking” of the object of the addiction.8 There is then compulsive addicting with less pleasure.

To make matters worse, addiction produces an increase in the experience of stress/distress, which then drives addicting to reduce this distress.9 Finally, the frontal lobes, which govern wise behavior, are impaired, resulting in an inability to resist the compulsions to addict.

As you can see, specific parts of the brain are associated with each stage of addiction. See Figure 2. Changes in brain structure and functioning, including changes in neurotransmitters, occur with addicting, better known as “neuroadaptation.”

Figure 2. Actions of Addictive Substances on the Brain (Source: SAMHSA, full citation at end of article)

The Neuroanatomy of the Brain’s Drive-Reward System

It is sometimes helpful to understand the anatomy and technical detail of a particular disorder and how it occurs in the brain when assessing and treating patients or clients. The following section describes the neuroanatomy behind addiction.

The Limbic System

In between the cerebral cortex and the midbrain is a middle group of structures – the limbic system – that play a key role in the brain’s drive-reward system. The limbic system mediates, along with other parts of the brain, emotion and drive, or motivation.

Limbic structures include a circular strip of deep cortex called the limbic lobe, which includes the cingulate gyrus. It also includes the orbitofrontal cortex (OFC), which rests just above the eyes; the amygdala, which is buried deep in the temporal lobes; and the nucleus accumbens (NAc), the hypothalamus, and the anterior nuclei of the thalamus. These structures work together with other parts of the brain to mediate motivations and emotions, including desire (including cravings) and pleasure.

The amygdala determines if an experience is painful or pleasurable. It directs the brain to either repeat or avoid the experience. A part of the amygdala called the extended amygdala is involved both in drug reward and in the negative experience produced by the stress of withdrawal that drives the compulsion to addict. It induces negative emotions such as unease, anxiety, and irritability during withdrawal. It interacts with the brain’s stress system through connections to the hypothalamus.

The hippocampus records memories, including memories of euphoria and associated details, such as where, when, and with whom a pleasurable experience occurred. These associations can trigger cravings.

The frontal lobes synthesize information to decide whether to act and what action to take. They act as a brake on dopamine-induced impulses to act in the NAc if they discern that an action is unwise. Impairment in frontal lobe functioning due to impairment caused by addictive substances contributes to the loss of control that characterizes addicting.10

 Those with an addiction tend to do what they feel urges to do regardless of what they know to be right. They have lost their “prefrontal brakes” so to speak.11 Part of treatment, thus, entails enhancing frontal lobe functioning so that the individual becomes more apt to do what is right regardless of urges to do otherwise.

Basal Ganglia

There are several nuclei at the base of the forebrain. Together, these “subcortical” nuclei are called the basal ganglia. The basal ganglia include two collections of nuclei, the ventral striatum and the dorsal striatum.

The dorsal striatum includes basal ganglia called the caudate nucleus, the globus pallidus, the thalamus, and the putamen. Drives in the form of habits are mediated by the dorsal striatum, including the routines involved in addicting. This region of the brain is involved in the binge-intoxication stage of addicting.

The ventral striatum includes the previously discussed NAc and the olfactory tubercle. It is part of the mesocorticolimbic drive-reward pathway which includes neurons that originate in the middle part of the front of the midbrain called the ventral tegmental area (VTA).

The VTA plays a key role in motivation, cognition, orgasm, and intense emotions such as feeling in love. The dopamine neurons from the VTA travel along the drive-reward pathway to the ventral striatum, where they mediate drives through the NAc to act to trigger behaviors anticipated to reduce distress or generate pleasure. This mesocorticolimbic pathway determines how rewarding an activity is to a particular individual. The pathway also mediates the pleasure of the binge–intoxication stage of the addiction cycle.12

Disordered regulation of dopamine output from the mesocorticolimbic drive-reward pathway also plays a key role in the development of addiction. The release of dopamine drives reward-seeking behavior.

Other chemicals involved in the experience of the rewarding effects of addictive substances and activities include: gamma-aminobutyric acid (GABA), opioid peptides, and endocannabinoids.1 Opioids stimulate the nucleus accumbens to release dopamine.13 Cocaine, amphetamine, and nicotine also stimulate the release of dopamine in the NAc.

Anterior Cingulate Cortex

The anterior cingulate cortex is involved in reward anticipation, decision-making, ethics and morality, impulse control, and emotion. It mediates anticipated reward-based decision-making. It may also play a key role in the capacity for free will and thus may be impaired in the loss of control that goes along with addiction.

The medial prefrontal cortex participates in decision-making based on memories of past experiences and emotions. Impairment may lead to reduced insight into the adverse consequences of addicting when experiencing cravings.

The orbitofrontal cortex (OFC) signals expected rewards or punishments of an action given the details of a situation. Thus, it helps to inhibit acting on cravings when adverse consequences are anticipated. It is part of the frontal lobe “brake” system. In those with addiction, impairment is seen in the striato-thalamo-orbitofrontal circuit of the OFC.

Impairment is associated with compulsive behavior, repetitive behavior, and increased motivation to addict. Individuals suffering from addiction show deficits in orbitofrontal, striatal, and thalamic regions. Studies have demonstrated decreased activity in the OFC in subjects withdrawing from cocaine and alcohol.14-16 It appears that the OFC is not only the target from the limbic system for reinforcing drug effects but also modulates responses of the limbic areas to drugs of abuse. Impairment appears to reduce the ability to resist cravings to addict.

See also, assessing for alcohol abuse and related dementia.

Risk Factors for Addiction and Addictive Behaviors

Several risk factors contribute to the development of addiction. As explained above, addictive substances and behaviors induce pleasure via the drive-reward system – and humans universally enjoy pleasurable experiences, except when neurological or psychiatric illnesses block the experience of pleasure.

Alcohol and certain drugs, for example, may be used to relieve pain, numb uneasiness, or quell distress. Addiction develops when an individual uses that substance as an experience of “pleasure” to manage their pain or emotional state.

Some people are genetically less risk-averse or harm-avoidant. Their DNA, so to speak, may increase their propensity to use addictive substances out of a decreased fear of the potential harmful consequences of use. In fact, most people who develop addictions do not use addictive substances with the thought that they will become addicted. Many people just assume, even though they know there may be a risk of addiction, that “It will never happen to me.” In either case, the memory of the intense pleasure of an addictive object (substance or behavior) can stimulate the desire to use again.

 Neurodevelopmental Disorders

Those who live with neurodevelopmental impairments that include impulsivity may be at higher risk for addiction. For instance, some people with attention deficit hyperactivity disorder (ADHD) experience a higher rate of addiction, likely due in part to their impulsivity. With reduced activity in the frontal lobes, including the cingulate cortex, they may utilize addictive substances without thought of the potential consequences. With repetition, the addictive object or behavior carves neural trails in their brain that lead to exaggerated drives experienced as cravings, compulsions to addict, and loss of control – all resulting in addiction.

Chronic Pain

Individuals living with pain, especially chronic pain, can also be at greater risk of addiction. Pain (represented as physical, emotional, or spiritual distress) motivates some people to treat – or over-treat – that pain with pleasure (reward), while others impulsively engage in excessive pleasure-inducing substances or behaviors simply because it feels good, without heeding the early signals of withdrawal and craving that begin to emerge with repeated use.

In fact, some individuals actually cultivate an addiction due to impulsivity alone – with no apparent life pain motivating their actions. For the latter group, an addictive substance or behavior does not necessarily ease a pain – it just feels good.

See also, our sister site, Practical Pain Management

Genetic Vulnerabilities

Finally, there are individuals with a genetic vulnerability to dysregulation of their drive-reward system that, when exposed to intensely-pleasurable substances or experiences, may develop addiction simply because of this genetic vulnerability.

In each of these vulnerable populations, the pleasure of the addictive object leaves a mark on the brain, resulting in cravings and a compulsion to addict that can be so powerful that some find they cannot resist. This can lead to a loss of control. Cravings, compulsion, and loss of control can last long after withdrawal ends. They can be triggered by emotional distress, by the addictive substance, or by environmental cues associated with prior addicting, sometimes years after the last use/behavior.

Impulsivity and Compulsivity

Impulsivity happens when people act on urges without reflection. The amygdala constantly scans our environment for threats as well as rewards. It signals the ventral striatum, including the nucleus accumbens, to take action through neurons that secrete dopamine. Dopamine is the primary neurotransmitter that drives motivation, or the urge to take action.

Sometimes, acting without reflecting is essential for survival – urging individuals to act immediately, or reflexively. The need for a quick response, however, means they do not have the luxury of extra time to process what is going on consciously in the gray-matter surface of the brain, the cerebral cortex.

Outside of life-threatening emergencies, individuals do well to process impulses from the amygdala and ventral striatum in the cerebral cortex before acting. The cerebral cortex generates the experience of conscious reflection while the hippocampus accesses relevant memories that aid decision-making. The dorsolateral prefrontal cortex accesses the rest of the cortex to weigh the pros and cons of taking a specific action, or not acting at all. Together, they serve as the brain’s executive decision-maker.

If one’s dorsolateral prefrontal cortex decides something is not a good idea, such as having a second drink before driving home, then the orbitofrontal cortex sends signals in part to the ventral striatum, thereby inhibiting action. The person resists acting on that impulse to have a second drink.

Some people are more impulsive than others. Those with impulse control difficulties may slip into the abyss of addiction because they do not think through the consequences of what they are doing. They are less cautious, possibly due to impaired connections between the dorsolateral prefrontal cortex, the orbito-frontal cortex (OFC), the cingulate cortex, the amygdala, and the ventral striatum. Impaired communication between the frontal cortex and the amygdala may lessen their experience of fear when experiencing desires that entail risks, thus making certain individuals more prone to trying addictive substances than other, more cautious people, who are more capable of processing desires.

Compulsivity is different from impulsivity. With impulsivity, there is little or no thought. With compulsivity, there is thought, but there is also a drive to act to reduce distress or experience a reward.

When one acts on compulsions despite a conscious desire not to do so, there is a loss of control. This loss of control can be called “addictivity. With repeated addicting, there is a weakening of connections between the prefrontal cortex and the nucleus accumbens. In a sense, addiction involves an impairment in the inhibition part of executive functioning, as people do what they feel an urge to do regardless of what is best for them or others. Imaging studies show reduced activity in the medial and ventromedial prefrontal cortex in those with addictions. These areas of the brain are active in both performance and inhibition of action.17


With repetition, reduced pleasure (reward) in the form of tolerance can develop. From there, continued use can lead to negative withdrawal states, where the person addicts less for pleasure and more to relieve the pain of withdrawal.

As addiction progresses, high concentrations of dopamine in the nucleus accumbens increase the production of cyclic adenosine monophosphate (cAMP). cAMP activates cyclic AMP response element binding protein (CREB). CREB acts to reduce the amount of dopamine released by the drive-reward pathway. This may indirectly result in  less pleasure with use. This is called tolerance, which is the brain’s way of attempting to normalize brain functioning in the presence of addictive substances.

CREB also activates an endogenous opioid called dynorphin, which further reduces dopamine by stimulating inhibitory neurons that loop back from the NAc to the VTA. As a result, increased drug use produces less euphoria.18

Increased Sensitivity

With cessation of addicting, cravings arise. Cravings occur, in part, due to decreased production of CREB, resulting in a decrease in tolerance and a corresponding increase in drug sensitivity.17,19

Cravings also occur because of enhanced activity of circuits between the amygdala, hippocampus, and nucleus accumbens.20 This circuitry is triggered by memories (people, places, sounds, smells, sights) associated with prior addicting and the mechanism is known as cue-induced relapse. Even without cues, just thinking about prior addicting can cause cravings.

The drive-reward pathway interacts with the anterior cingulate cortex, the medial prefrontal cortex, the orbitofrontal cortex, the basolateral nucleus of the amygdala, and the hippocampus to produce and mediate the experience of cravings.

The neurotransmitter glutamate mediates cravings in part. Glutamate interacts between the prefrontal cortex and the brain’s motivational circuitry – the basolateral amygdala, insula, and hippocampus to the extended amygdala and the NAc. Increased dopamine secretion in the NAc activates glutamate pathways, which leads to the encoding of pleasurable memories between the amygdala and the hippocampus, thereby assigning a high degree of importance to addiction-related behaviors and experiences.21

Re-Addiction or Relapse

Another molecule produced in the nucleus accumbens, Delta-FosB, may also be involved in the phenomenon of craving and relapse.22 Concentrations go down only after weeks of abstinence. Even then, structural changes in spiny neuron branches called dendrites in the NAc occur long after the cessation of drug use, likely due to elevated concentrations of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in the NAc because of the release of Delta-FosB.16 These changes in brain structure may set the stage for a full-blown readdiction even after years of abstinence.

There are three general triggers for re-addiction or relapse:23

  1. re-exposure to addictive substances or behaviors
  2. exposure to drug- or addiction-related stimuli, such as passing by a liquor store or, in the case of sex addiction, seeing sexually arousing materials
  3. stress

Vulnerability to re-addiction is due in part to alterations in the brain’s stress system caused by addiction. Chronic stress triggers dopamine release in the NAc; this sensitizes the drive-reward system, thus triggering readdiction. The hypothalamic-pituitary-adrenal (HPA) axis and the stress hormone corticotropin-releasing factor (CRF) are involved in acute withdrawal. There is increased activity of CRF in the HPA axis and the extended limbic system during withdrawal.

This activity stimulates the release of dynorphin, which then inhibits dopamine release in the nucleus accumbens – all promoting relapse by sensitizing the brain drive-reward system.24 Of note, the HPA axis and CRF pathway has been termed an “anti-reward pathway,”25 creating an experience that is the opposite of pleasure or euphoria (ie, dysphoria). The dysphoria of withdrawal and of stress trigger urges to re-addict.

The Two Pains of Addiction and Addiction Treatment – Withdrawal and Cravings

One can think of addictivity—or addiction—as pain management gone awry. For some, addiction starts as an attempt to manage pain with pleasure. This is certainly true once the addiction has begun, as victims experience two new types of distress:

  1. The first pain is the pain of withdrawal once the drink, drug, or addictive behaviors are gone.
  2. The second pain is one of intense desire, which they experience as intense cravings, mediated by the disordered interplay between the cerebral cortex and the brain’s drive-reward system.

When in a state of withdrawal or craving, discomfort urges the person to addict to ease their distress. So even if there was little or no pain before addicting, the act of addicting will ensure that pain will arise to further fuel the addicting behavior. It is a neurodynamic vicious cycle.

The Neurobiology of Withdrawal

Withdrawal from an addictive substance or behavior activates the brain’s stress system. The stress hormone CRF increases in certain brain regions during periods of withdrawal (ie, the central nucleus of the amygdala and the neurons exiting the amygdala, called the bed nucleus of the stria terminalis). Other stress molecules, dynorphins, increase in withdrawal as well, stimulating kappa opioid receptors to produce dysphoria. Reductions in dopamine and serotonin during withdrawal also produce dysphoria,26 while reductions in GABA during withdrawal can induce anxiety and panic attacks. Dysregulation of noradrenaline, vasopressin, orexin, and substance P also may play a role in withdrawal and addiction.27

As part of a stress response, withdrawal appears to increase levels of norepinephrine in the bed nucleus of the stria terminalis. Withdrawal further impairs the brain’s anti-stress system by decreasing levels of a neuropeptide called neuropeptide Y in the central and medial nuclei of the amygdala. Decreases in reward neurotransmitters, including dopamine and serotonin, likely contribute to the negative motivational state of withdrawal and to the vulnerability to readdiction.

Addictive substances or behaviors may also cause glutamate hyperactivity, which leads to hyperexcitability. Glutamate is the major workhorse neurotransmitter of the brain. Dopamine in the NAc activates glutamate pathways which create pleasurable memories of the use of addictive substances or engagement in addictive behaviors in the amygdala after the hippocampus assigns a positive value to the experience of addicting.21 Modulation of glutamate with medications such as acamprosates may help with withdrawal and craving.28

 See also, our primer on using medication-assisted treatment for Opioid Use Disorder.

 Compulsivity and Cravings

When people addict, they act compulsively, even though they know it’s not a good idea. The person experiences a partial loss of free will. A disconnection between the emotional limbic system and the inhibiting part of the cortex, the orbitofrontal cortex, may mediate this in part; otherwise, drives to act may be so powerful that the inhibiting function of the orbitofrontal cortex is overwhelmed.

 Together, the twin pains of addiction – cravings (desire) and withdrawal, drive compulsivity. Compulsive disturbances in the activity of the dorsal striatal circuits lead to the loss of control that is a hallmark of addiction.

Addiction Treatment: The Neurobiology Behind What Works

So how does the neurobiology of addiction inform treatment?

Prevention First

Clinicians must first consider prevention of the development of this brain disorder. Clinicians can do this through adequate assessment, risk identification, and follow-through – as well as patient education. All health professionals – including psychiatrists, social workers, and psychotherapists – need to identify and intervene with young people who are in distress/pain and who gravitate to substance-using peer groups because of low self-esteem or impaired relationship skills. Practitioners need to be especially vigilant when there is a family history of addiction and must carefully monitor children who have had adverse childhood experiences (ACEs), such as neglect or abuse.

Once clinicians have identified vulnerable children and teens, practitioners can help them to make healthy connections, heal from trauma, deal with disability, and develop self-compassion and self-worth. These interventions will reduce the pain that often drives relief and reward-seeking through pleasure.

Children and teens need to know what addiction is. They need to know that if their family has a history of addiction, they will be at increased risk of addiction. Health professionals and other adults need to help them “think through” the potential consequences of addicting. It is important to intervene early in individuals who exhibit impulsivity. Clinicians should identify and treat impulsivity with the aim of reducing the impulsive use of addictive substances. For example, it is known that treating ADHD reduces the use of addictive substances.29

It is important to ensure young people have natural ways of feeling pleasure that satisfy. This includes nurturing meaningful activities, fun, and loving connections that give adolescents and young adults a sense of value, meaning, and purpose.

Psychotherapy Approaches to Addiction

When treatment is necessary, clinicians must use evidence-based approaches. Such methods include helping patients and clients to stop addicting and learn to manage cravings. Cognitive, behavioral, and interpersonal therapies aimed at cultivating such capacities can be quite effective.

Those whose addiction has been initiated by pain (often the pain of trauma or neglect) may need help to heal that pain, following by teaching them more effective ways to manage distress in the future. Clinicians may guide them toward skillful or intelligent living, such as behavioral intelligence (self-care), emotional intelligence (healthy relationships), and spiritual intelligence (the capacity to act with compassion and wisdom with equanimity).

To put the DLPFC (dorsolateral prefrontal cortex) back in charge, those struggling with addiction need a life vision worth pursuing. Clinicians can help patients build motivation for delayed gratification over the “now” appeal. With purpose and a renewed network of loving connections, those with addiction can sustain the motivation needed to rewire their brains.

Psychiatric Approaches to Addiction

Healing the distress that drives addiction often also requires medical and psychiatric treatment. Medication-assisted treatment (MAT), in combination with psychotherapy, aims to reduce disability and optimize functioning so that patients may be empowered to live more skillfully. It also gives them the ability to manage their cravings. (The details of psychopharmacology for addiction are outside the scope of this primer.)


Professional Takeaways

Understanding the neurobiology and neuroanatomy of addiction and addictive behavior has already led to many medication-based treatments, especially in the area of opioid (OUD) and alcohol use disorder (AUD) where drugs like buprenorphine and naltrexone have saved many lives. It is hoped that further research will lead to other pharmacological and behavioral approaches that promote healing from addiction by reducing cravings and withdrawal symptoms, and by reducing the experience of reward when addicting.

By educating ourselves and our patients about addiction as a brain disorder, addictive behavior will become less an indictment of a person’s character and more objective as treatable and preventable. Since shame both perpetuates addiction and prevents people from seeking treatment, an understanding of the neurobiology of addiction can promote positive treatment outcomes by reducing shame and facilitating compassion for those who suffer from this disorder.

Last Updated: May 3, 2021