Substance Use

Impact of Substances on the Brain

How do substances affect the brain?

Drugs and alcohol affect three primary areas of the brain: the brain stem, the limbic system, and the cerebral cortex. When substances enter the brain, they interfere with its normal processing and can eventually lead to dramatic changes in the neurons and brain circuits – changes that can still be present even after an individual has stopped taking drugs.

What parts of the brain do drugs affect?

  • Drugs affect three primary areas of the brain: the brain stem, the limbic system, and the cerebral cortex.

How do drugs affect the brain?

  • When drugs enter the brain, they interfere with its normal processing and can eventually lead to changes in how well it works.
  • There are at least two ways the drugs work in the brain:
    • They imitate the brain’s natural chemical messengers
    • They over-stimulate the brain’s “reward” circuit
    • Normally, the reward circuit responds to feelings of pleasure by releasing the neurotransmitter dopamine. Drugs take control of this system, causing large amounts of dopamine to flood the system. This flood of dopamine is what causes the “high” or intense excitement and happiness (sometimes called euphoria) linked with drug use.


  • Some drugs, like marijuana and heroin, have chemical structures that mimic those of a neurotransmitter that naturally occurs in our bodies. The drugs can deceive our brain’s receptors, lock onto them, and activate nerve cells. Because these drugs do not function like natural neurotransmitters, the neurons end up sending abnormal messages through the brain.
  • Other drugs, such as cocaine and methamphetamine, cause nerve cells to release too much dopamine, which is a natural neurotransmitter, or prevent the normal recycling of dopamine. This leads to exaggerated messages in the brain, causing problems with communication channels.
  • When some drugs of abuse are taken, they can release 2 to 10 times the amount of dopamine that natural rewards such as eating and sex do.

Long-Term Brain Changes

  • Drug use can eventually lead to dramatic changes in neurons and brain circuits. These changes can still be present even after the person has stopped taking drugs.
  • After repeated drug use, the brain starts to adjust to the surges of dopamine. As a result, dopamine’s impact on the reward circuit of the brain of someone who abuses drugs can become abnormally low, and that person’s ability to experience any pleasure is reduced.
  • Studies have shown some deterioration of the brain’s white matter due to heroin use, which may affect decision-making abilities, the ability to regulate behavior, and responses to stressful situations.
  • The relationship between opioid overdose and depressed respiration (slowed breathing) has been confirmed, and this can affect the amount of oxygen that reaches the brain, a condition called hypoxia. Hypoxia can have short- and long-term psychological and neurological effects, including coma and permanent brain damage.
  • Some drugs of abuse, such as inhalants, are toxic to nerve cells and may damage or destroy them either in the brain or the peripheral nervous system.

Adolescents and Teens

  • Introducing drugs during adolescence may cause brain changes that have profound and long-lasting consequences.
  • Using abusable substances during the teenage years can disrupt brain function in areas critical to motivation, memory, learning, judgment, and behavior control.
  • One of the brain areas still maturing during adolescence is the prefrontal cortex—the part of the brain that enables us to assess situations, make sound decisions, and keep our emotions and desires under control.
  • Findings indicate that even subtle binge drinking behaviors can have a substantial impact on tissue development. Teens with both an alcohol use disorder as well as less frequent or new-onset binge drinking habits were found to have altered white matter integrity. White matter affects how the brain learns and functions.
  • Study results suggest slightly poorer initial verbal learning, disadvantaged verbal processing, and decelerated learning for teens who engage in binge drinking compared to abstinent teens.
  • A study comparing alcohol dependent and healthy control teens found that drinkers recalled 10% less verbal and nonverbal information than controls, even after three weeks of monitored abstinence.
  • Teens who had a history of alcohol withdrawal symptoms (e.g., orthostatic hypotension, nausea, insomnia, or irritability) were the most likely to have decreases in performance scores, especially on tests of spatial functioning.
  • Observations of heavy drinking youth show greater brain activation while viewing alcohol advertisements than they do to non-alcohol beverage ads.
    • This substantially greater brain activation to alcoholic beverage pictures was observed throughout the brain, particularly in the prefrontal area, nucleus accumbens, hypothalamus, posterior cingulate, and temporal lobe.
    • This suggests that reward, visual attention limbic, appetitive, and episodic memory systems were preferentially invoked in response to alcohol ads relative to non-alcohol ads in heavy drinking teens.
    • Data suggest that even after four weeks of monitored abstinence, teens who regularly smoke marijuana performed poorer on performance tests of learning, cognitive flexibility, visual scanning, error commission, and working memory.


  • Brain imaging technology has demonstrated that addiction is a brain disease by delineating profound disruptions in the specific brain circuits affected by addiction. Repeated drug exposure “resets” these circuits toward compulsive behavior so that a person’s control over the desire to seek and use drugs is compromised, despite devastating consequences.
  • Changes from addiction go beyond the brain’s reward system to include regions involved in memory, learning, impulse control, stress reactivity, and more.
  • By causing abnormal regulation of key brain receptors (e.g., glutamate, dopamine), addictive drugs modify the strength of connections between neurons. This finding casts a new light on the phenomenon of drug addiction as a process of maladaptive learning that over time can become an automatic, compulsive behavior.
  • Genes account for about 50 percent of a person’s risk of becoming addicted, and environmental factors influence the effect of these genes.

Sources: NIDA, NIDA Teens, NIH, NCBI

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