Substance Use
the Brain

Table of Contents

Drug addiction is a disease characterized by compulsively seeking and using drugs despite adverse consequences1. Addiction also includes a loss of control in limiting the intake of a drug and the onset of a negative emotional state when the addicted individual cannot access the drug2.

Addiction is considered a brain disorder, as it changes the brain circuits related to reward, stress, and self-control. These changes can last long after the drug use stops. Addiction is just like other diseases, such as heart disease.

Like any other disease, it disrupts how bodily organs function and has severe health effects that are preventable and treatable in most cases. Untreated addiction can last a lifetime and can even lead to death1.

How Does the Brain Work?

The brain contains billions of cells, called neurons, each of which controls the flow of information in the brain. Neurons are connected to each other in the brain in circuits and networks, and if one neuron receives enough signals from other neurons, it fires and sends signals to other neurons in a circuit3.

There are many interconnected circuits in the brain that work together for various functions. Neuron networks send signals back and forth in different parts of the brain, the spinal cord, and other body parts. This system is called the peripheral nervous system3.

When sending a message, a neuron releases a neurotransmitter into the space between itself and the next cell. This neurotransmitter then attaches to receptors located on the neuron receiving it, which causes changes in the receiving cell. Transporters then recycle neurotransmitters by bringing them back to the neuron that released them, which shuts off the signal between neurons3.

Biological Cause of Addiction

Addiction is caused by biological processes involving the reward pathways in the basal ganglia. When someone uses drugs or alcohol, these pathways rush positive feelings and feel-good chemicals to the individual. The areas in the brain associated with stress (extended amygdala) and self-control (prefrontal cortex) also experience changes during addiction, making it difficult to stop using the drug4.

Brain Areas Affected by Addiction

Drugs interfere with the way neurons process, send, and receive information. They can alter essential brain functions that are necessary to sustain life. Different parts of the brain affected by drug use include the basal ganglia, the extended amygdala, and the prefrontal cortex 3.

Basal Ganglia

This brain area plays an essential role in positive motivation and forming habits and routines. Positive forms of motivation include the pleasurable effects that occur as a result of activities like eating, socializing, and sex 3.

This part of the brain is where the reward circuit exists. Drugs can overactive this circuit, resulting in the euphoria associated with being high.

When the drug is repeatedly used, the circuit eventually adapts to the drug, diminishing its sensitivity. This diminished sensitivity of the reward circuit makes it challenging for the individual to feel pleasure from anything other than the drug 3.

Extended Amygdala

This brain area plays a role in feelings like anxiety and irritability. These feelings occur when an individual experiences withdrawal from a drug and their high goes away. These uncomfortable feelings often motivate the individual to use the drug again3.

The overuse of drugs can cause this part of the brain to become extremely sensitive. Eventually, someone with a drug addiction will use drugs only to relieve uncomfortable feelings rather than to get high as they once did 3.

Prefrontal Cortex

This brain area plays a role in an individual’s ability to think, plan, solve problems, make decisions, and control impulses. The prefrontal cortex is the last area of the brain to mature, making teens vulnerable to making poor decisions. Someone with a drug addiction may compulsively seek the drugs they use due to reduced impulse control 3.

Brain Pathways Affected by Addiction

A pathway in the brain is like a power line between regions in the brain. It consists of interconnected neurons that send signals from one area of the brain to another. Any drug of abuse interferes with neurotransmitter signaling in some way5.

Dopamine Pathway

Dopamine is the primary neurotransmitter involved in the brain’s reward system, made up of the mesolimbic and mesocortical pathways. Dopamine is also used in the nigrostriatal pathway and the tuberoinfundibular pathway in the brain. All drugs of abuse interfere with dopamine signaling in all of these pathways5.

The nigrostriatal pathway is associated with motor control and is linked to Parkinson’s Disease. The tuberoinfundibular pathway is associated with hormone regulation, nurturing behavior, pregnancy, and sensory processes.

The mesolimbic and mesocortical ways are associated with memory, motivation, emotion, reward, desire, and addictions. Disfunction in the mesolimbic and mesocortical pathways is connected to hallucinations and schizophrenia5.

Dopamine is used by a small number of neurons, each connected to thousands of other areas of the brain. Thus, dopamine exhibits a significant amount of influence over complex processes in the brain5.

Serotonin Pathway

Like dopamine, serotonin has a significant amount of influence over complex processes. Neurons that make serotonin send signals to most of the brain and the spinal cord. Unlike dopamine, only some drugs of abuse interfere with serotonin signaling. These drugs include cocaine, amphetamines, LSD, and alcohol5.

Serotonin is involved in body temperature regulation, sleep, mood, appetite, and pain. Issues with serotonin signaling are associated with obsessive-compulsive disorder, anxiety disorders, and depression5.

Glutamate and GABA Neurotransmitters

Glutamate and GABA are the most abundant neurotransmitters in the brain, and they work together to control many processes. Many drugs of abuse either decrease or increase glutamate or GABA.

Alcohol decreases glutamate activity and increases GABA activity, PCP increases glutamate activity, and tranquilizers increase GABA activity. Increasing GABA activity decreases brain activity, and increasing glutamate activity causes an energized state5.

Brain Alteration Impacts

Because of the alterations drugs of abuse causes in the brain’s pathways, using these drugs for a long time can cause changes that negatively impact judgment, decision-making, memory, and learning abilities6.

Drug addiction can also create anxiety and stress when an individual is not using their preferred substance because their danger-sensing circuits have been sent into overdrive. At this stage of addiction, the individual primarily uses substances to stop themselves from feeling bad, rather than for the pleasurable effects they used to feel7.

Repeatedly using drugs can also damage the brain’s prefrontal cortex, which is responsible for decision-making7. This results in a reduced ability to control alcohol and drug use impulses, even when the individual is aware that it is not in their best interest. The damage to the prefrontal cortex also reduces the ability to control other impulses8.

Cognitive functions, including learning, memory, and reasoning, are also impacted by drug addiction. These impacts can lead to an inability to remain abstinent from drugs of abuse. The developing brain is particularly susceptible to the effects of these drugs. Exposure during childhood and adolescence can create long-lasting cognitive changes9.

How the Reward System Works

A healthy brain rewards healthy behaviors like exercising. These behaviors are rewarded by turning on circuits in the brain that create those feel-good chemicals. These chemicals motivate the individual to repeat the behavior7.

A healthy brain reacts quickly and without fear to avoid harmful situations when in danger. Someone will avoid unhealthy behaviors like eating ice cream before dinner or spending money on unaffordable items when their prefrontal cortex works to contemplate the consequences of such actions7.

When someone is becoming addicted to a substance, drugs or alcohol can hijack the reward system in their brain, causing the individual to want more and more of that substance7. Drugs and alcohol flood the brain with dopamine which triggers a feeling of intense pleasure. An individual may then continue to use a substance to feel that intense pleasure again6.

Eventually, the brain gets used to the extra dopamine caused by using a substance. Addiction develops when the individual starts taking more and more of the drug to get the same good feeling and cannot stop despite adverse consequences. The use of that substance often becomes paramount to any other activity that was once enjoyed, as those activities begin to produce less pleasure6.

Withdrawal and the Brain

What happens in the extended amygdala and the prefrontal cortex explains why it is so difficult for someone with an addiction to stop using. The stress response in the extended amygdala motivates the brain to find a way to escape uncomfortable feelings, which occurs when someone is coming down from a substance. This response pushes the individual to use the drug again to avoid those feelings8. Over time, the individual will feel emotional or physical distress whenever they are not using the substance. This experience is known as withdrawal. The feelings of withdrawal are so intense that the individual will do anything to avoid it, including using a substance they no longer want to use. Eventually, using the substance becomes the only way to prevent these feelings8. This is why it is imperative to seek addiction treatment as soon as possible.

Addiction Symptoms

There are specific signs and symptoms that can help decipher whether you or someone you love is suffering from drug addiction. These signs and symptoms include: 10

Treatment for Addiction

If you or someone you love is experiencing any combination of the above symptoms, it is vital to seek treatment as soon as possible. Treatment options include: 11
Various treatment programs and follow-up therapies can lead to successful recovery for someone struggling with addiction. Treatment should include medical and mental health services for the most effective results 11.


  1. National Institute on Drug Abuse. (2020, July 13). Drug Misuse and Addiction. National Institute on Drug Abuse. Retrieved January 17, 2022, from
  2. Koob, G. F., Arends, M. A., & Le Moal, M. (2014). Drugs, Addiction, and the Brain. ScienceDirect. Retrieved January 17, 2022, from https://www.sciencedirect.com/book/9780123869371/drugs-addiction-and-the-brain#book-description
  3. National Institute on Drug Abuse. (2021, July 27). Drugs and the Brain. National Institute on Drug Abuse. Retrieved January 17, 2022, from https://www.drugabuse.gov/publications/drugs-brains-behavior-science-addiction/drugs-brain
  4. Legg, T. J. (2018). Addictive Disorders: Causes and Reasons They May Get Worse. Medical News Today. Retrieved January 17, 2022, from https://www.medicalnewstoday.com/articles/323483#why-does-addiction-occur
  5. Learn Genetics. (n.d.). Drugs Affect Many Brain Pathways. Learn Genetics. Retrieved January 17, 2022, from https://learn.genetics.utah.edu/content/addiction/brainpathways
  6. Wein, H. (2017, September 8). Biology of Addiction. National Institutes of Health. Retrieved January 17, 2022, from https://newsinhealth.nih.gov/2015/10/biology-addiction
  7. Surgeon General. (2016). The Neurobiology of Substance Use, Misuse, and Addiction. The Neurobiology of Substance Use, Misuse, and Addiction | Surgeon General’s Report on Alcohol, Drugs, and Health. Retrieved January 17, 2022, from https://addiction.surgeongeneral.gov/executive-summary/report/neurobiology-substance-use-misuse-and-addiction
  8. Gould, T. J. (2010, December). Addiction and Cognition. Addiction science & clinical practice. Retrieved January 17, 2022, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3120118/
  9. National Institute on Drug Abuse. (2021, September 3). Treatment Approaches for Drug Addiction DrugFacts. National Institute on Drug Abuse. Retrieved January 17, 2022, from https://www.drugabuse.gov/publications/drugfacts/treatment-approaches-drug-addiction