Neuro Primer: Addiction Basics

Spanish Translation also available here: Neuro Cartilla: Los principios básicos de la adicción 


From alcohol to opioids to cocaine, most of us are familiar with addictive substances. But how does someone develop a substance use disorder (SUD), the most severe category of which is addiction? How do these phenomena occur in the brain? And why do some people become addicted when others don’t?

Addiction Stages

Addiction follows a specific cycle. In the first stage, someone begins using a substance for recreation, social, or even medical (prescription) use. These substances are rewarding or intoxicating, leading to positive reinforcement and an escalation of use. However, over time, the person can develop a tolerance, the next stage in which the brain becomes accustomed to receiving a certain amount of the drug and thus requires a greater dose to create the desired “high” effect. Eventually, use of the substance can escalate so that the brain requires a baseline level of the drug to even function normally and has adverse side effects in the absence of the drug, a phenomenon known as withdrawal. These undesirable effects may, either directly or by interactions with triggers like stress or drug cues, cause craving and eventually relapse.

“These substances are rewarding or intoxicating, leading to positive reinforcement and an escalation of use”

Reward System

Our drive to seek reward is an important component of evolution that makes important survival activities like eating, reproduction, and social bonding feel good. The brain’s reward system is largely conserved across species, from rodents to humans. Neurons in the reward system communicate via the neurotransmitter dopamine, which is released in response to pleasurable experiences and helps tell your brain that this activity is something that you want to repeat (i.e., reinforcement). These neurons also communicate with other brain areas related to memory and behavior, and these connections ensure that you remember what behavior made you feel good.

Drugs function by essentially hijacking this natural reward system. Although different addictive substances act in different ways, all of them appear to result in increased dopamine levels in an important reward region called the nucleus accumbens. This artificial increase in dopamine causes an intense “high” or intoxicating pleasurable feeling far beyond the natural rewarding effects of food or bonding. Between the reinforcing effects of nucleus accumbens dopamine release and the reward circuit’s connection to memory and future planning regions like the hippocampus and prefrontal cortex, the brain remembers what caused this good feeling and wants more.

“Drugs function by essentially hijacking this natural reward system”


Tolerance can develop with continued exposure to a substance. The brain — and the body in general — is very adaptable and tends toward equilibrium, or homeostasis. In order to maintain its balance, the brain down-regulates the ability of the reward circuit to respond to these substances. When the brain senses that its dopamine receptors are being flooded, or stimulated more than usual, it will try to reach its normal levels by decreasing the amount of receptors that interact with the drug, effectively shutting down the drug’s ability to increase dopamine release. For example, receptors that interact with the drug might be inactivated or their numbers reduced. This means that future instances of substance use have less of an effect, so a greater dose of the drug is needed to induce the original “high.” Of course, with each increased dose, the brain continues its homeostasis, further reducing the ability of the reward system’s responsiveness, creating a cycle of continually requiring more and more of the substance.

Since the natural reward system uses the same dopamine signaling mechanism, as tolerance causes the brain to down-regulate the reward system, the pleasure gained from natural rewards can also be decreased. Therefore, the drug may become the primary functional source of pleasure.


The homeostasis process limits the reward system’s ability to respond to natural levels of dopamine. Therefore, in the absence of the drug, the reward system is essentially unable to produce pleasurable feelings. As you might guess, this can cause negative mood, anhedonia, and depression. Furthermore, the homeostasis process doesn’t just act on the reward system, but happens throughout the brain and body, anywhere the substance interacts. The nature of homeostasis is to calibrate the brain and body to function normally when the drug is in the system, so when the drug is not there, the opposite of the drug’s effects are seen. For example, taking opioids results in feelings of relaxation and pain relief, but during withdrawal from opioids, one may become extremely agitated, anxious, and more sensitive to pain.

Unfortunately, the only way for the body to recalibrate its homeostasis is to spend time without the drug in its system, but these negative withdrawal effects are often so intolerable that they lead to craving and relapse. In fact, withdrawal from certain substances, such as alcohol and benzodiazepines, can have extremely severe symptoms, in some cases leading to death.


“The nature of homeostasis is to calibrate the brain and body to function normally when the drug is in the system, so when the drug is not there, the opposite of the drug’s effects are seen”



But there’s more to the story. Out of the population of risky or hazardous substance users, only some of them develop an SUD. And of that group that develops an SUD, only some of those fall into the most severe category of addiction. Some people may drink a glass of wine with dinner every night without becoming addicted, while addiction happens easily to others. What makes a person more or less vulnerable to developing a substance use disorder?

There are both biological and behavioral factors that contribute to the risk of developing an SUD. SUD is known to have a genetic component – even anecdotally, people have known for centuries that addictions “run in the family.” More recently, scientists have found genes that are directly related to people being more likely to drink or smoke heavily.

Many people who use drugs are also diagnosed with neuropsychiatric diseases – over half of people with an SUD also have a mental illness, and over half of those with a mental illness also have an SUD. This relationship goes both ways: individuals with mental illnesses might use drugs to self-medicate, and using drugs can also heighten symptoms of mental illness. Behavioral personality traits, such as impulsivity, risk-taking, compulsivity, and the desire to seek out new and exciting experiences, have also been linked with SUD. These are certainly not inherently bad characteristics – indeed, adventurous, risk-taking people are often highly successful – but they can indicate an increased risk for the development of an SUD.

Addiction takes an incredible toll on individuals and global society as a whole. Collectively, substance use kills 11.8 million people every year worldwide – more than the number of deaths from all cancers combined. Substance use disorder is also very complex, with many biological and behavioral correlates, and is related to a wide range of societal issues, including the criminal justice and police systems, the housing and homelessness crisis, veterans’ affairs, and the legalization and decriminalization of drugs. Understanding the biological and psychological basis of substance use disorders can help us develop treatments and policies to combat one of the world’s leading causes of preventable death.


Written by Elizabeth Burnette.
Edited by Zoe Guttman and Holly Hake. Illustrated by Gil Torten.


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Kosten, T. R., & George, T. P. (2002). The neurobiology of opioid dependence: Implications for treatment. Science & Practice Perspectives, 1(1), 13–20.

NIDA. (2018). Comorbidity: Substance Use Disorders and Other Mental Illnesses. National Institute on Drug Abuse.

Nutt, D. J., Lingford-Hughes, A., Erritzoe, D., & Stokes, P. R. A. (2015). The dopamine theory of addiction: 40 years of highs and lows. Nature Reviews. Neuroscience, 16(5), 305–312.

Volkow, N. (2020). Drugs, Brains, and Behavior: The Science of Addiction. National Institute on Drug Abuse.


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Elizabeth Burnette

Elizabeth Burnette is pursuing a PhD in Neuroscience at UCLA, in the lab of Dr. Lara Ray. Her research uses neuroimaging and psychoneuroimmunology methods to study the neurobiology of addiction in clinical populations. Her dissertation project explores the role of neuroinflammation in alcohol use disorder. She received her BS in Neuroscience from Duke University in 2018. For more about Elizabeth's research and experience, please visit her full profile and website.