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Effects of Drugs on the Brain: Impact of Drugs on Neurotransmitters

For many people, addiction can be difficult to understand. Understanding how drugs affect the brain can help shed some light on how a person develops an addiction.

This article will discuss how various drugs affect the chemistry of the brain and lead to certain effects and addiction.

Drug Use & Neurotransmitters: The Messengers of the Brain

The brain is the most complex organ in the human body and has even been called “the most complex object in the known universe.”2,3 The brain has around 100 billion individual nerve cells, or neurons, which form a complex network that has over 100 trillion (100,000,000,000,000) connections, or synapses.2

Information travels around this network 24 hours a day, allowing the brain to direct all the conscious and unconscious activities in the body. Everything from composing a symphony to deciding what to eat for dinner requires complex calculations carried out in the brain.

The brain uses chemicals called neurotransmitters to carry information from one neuron to another at junction points known as synapses.2 Neurotransmitter signaling is a crucial part of all the brain’s functions, and changes in neurotransmitter signaling can alter the way people think, feel, or perceive the world around them. A few important neurotransmitters in the human brain include endorphins, serotonin, and dopamine.2

Messages in the brain usually travel from the presynaptic neuron to the postsynaptic neuron. This occurs when the presynaptic neuron releases neurotransmitters into the synapse, which then attach to special proteins on the surface of the postsynaptic neuron called receptors.2

Neurotransmitters and receptors fit together in specific combinations like a lock and key. Other specialized proteins, called transporters, move neurotransmitters from the synapse back inside the neuron to turn off signaling.2

Medications and illicit drugs that affect the brain alter neurotransmitter signaling in several different ways:

  • Imitating neurotransmitters—Drugs like opioids and marijuana have chemical structures that are similar to those of natural neurotransmitters. Since they fit into the receptors, these drugs act like neurotransmitter “imposters.”
  • Causing neurotransmitter release—Drugs like methamphetamine cause neurons to release neurotransmitters into synapses when they would normally be inactive.
  • Preventing neurotransmitter signals from switching off—Certain drugs, like cocaine and many antidepressants, block transporters so that neurotransmitters stay in the synapse and continue to activate receptors longer than normal.

The various ways drugs affect neurotransmitters can change the information being processed by the brain.2 Drugs prescribed by a doctor, such as prescription painkillers and antidepressants, can be used to adjust brain chemistry in an individual experiencing physical or emotional distress. On the other hand, those who misuse drugs are altering the way their brains work in ways that may be temporarily pleasurable, but potentially dangerous in both the short- and long-term.

Why Do Drugs Feel Good?

Most addictive drugs produce an intense, euphoric high that people often seek out. This is the result of drugs either directly or indirectly increasing dopamine signaling in the limbic system, which includes a part of the brain that is involved with reward and motivation—the nucleus accumbens. Behaviors like eating, having sex, and socializing with friends cause an increase in dopamine levels in this area. This increase in dopamine feels good and motivates people to repeat these actions.

Stimulants flood the whole brain with dopamine, including the nucleus accumbens, which causes intense pleasure in abusers and motivates them to repeat this behavior. Likewise, studies have shown that drugs that affect other neurotransmitter systems, such as alcohol, opioids, and cannabinoids, also cause dopamine levels to rise in regions of the brain involved in pleasure, especially the nucleus accumbens.8,9

How Drugs Affect Communication in the Brain

Misusing drugs can disrupt the balance of chemicals in the brain. Drugs can affect brain chemistry by flooding the brain’s natural circuitry, resulting in potentially adverse health effects and consequences.2 Several classes of drugs and the neurotransmitter systems they affect are described below.

Stimulants & the Brain

Central nervous system stimulants are drugs that increase the activity of a few specific neurotransmitters in the brain. There are illicit stimulant drugs—like cocaine—and prescription stimulant medications that are mainly used to treat attention-deficit/hyperactivity disorder (ADHD) and narcolepsy. They function similarly to one another, resulting in increased levels of the neurotransmitter dopamine in the brain. Stimulants are also sometimes referred to as “uppers,” and prescription stimulants like Ritalin are sometimes called “study drugs.”

Well-known prescription stimulants include:

Common illicit stimulants include:

In the brain, dopamine is involved in several important behaviors, including:

  • Arousal (the state of being awake or alert)—Boosting dopamine levels increases energy, wakefulness, and attention, while decreasing dopamine causes fatigue and drowsiness.
  • Motor (movement) control—The death of dopamine-producing neurons in patients with Parkinson’s disease causes symptoms such as shaking, stiffness, and difficulty walking.
  • Reward and motivation—Activities such as eating food, having sex, socializing with friends, and hugging a puppy all increase dopamine levels in the brain’s reward circuitry.2

Dopamine is an important neurotransmitter for keeping people awake, focused, motivated, and coordinated. However, when someone misuses stimulants, the elevated levels of dopamine in their brain can cause hyperactivity, insomnia, anxiety, increased risk-taking, and euphoria.

Since stimulant drugs activate the brain’s reward and motivation circuitry, they are often misused in a “binge” pattern. Binging is when a person uses large doses of stimulants in a short time frame.1 Since the brain’s reward center is more strongly activated by stimulants, the brain may prioritize drug use over other healthy behaviors.

Opioids & the Brain

Opioids are a group of natural and synthetic drugs that activate opioid receptors in the brain, spinal cord, and digestive tract. Opioid medications are also known as opiates or narcotics and are used as painkillers, cough suppressants, and anti-diarrhea medications. Well-known illicit and prescription opioids include:

Normally, opioid receptors are activated by chemicals called endorphins. Endorphins are produced naturally in the brain and pituitary gland when the body is exposed to pain or other stressors such as an injury, childbirth, or intense exercise (runner’s high). In the brain, endorphin signaling has several roles, including:

  • Altering pain perception—Opioid signaling reduces pain sensations, centrally mitigating pain signaling within the brain without affecting the injury itself. This is different from many over-the-counter pain relievers such as aspirin or ibuprofen, which reduce swelling and inflammation at the site of the injury to achieve their analgesic effects.
  • Producing feelings of well-being—Endorphins cause more dopamine to be released in the reward and motivation circuits of the brain, which produces positive feelings. Opioid drugs mimic these endorphins but cause more dopamine release in the reward pathways, creating a strong euphoric high.
  • Decreasing respiration—There are many opioid receptors in the areas of the brain stem that unconsciously control breathing. Endorphin signaling in these neurons helps to slow breathing in situations that might otherwise lead to hyperventilation—such as feeling pain or being under stress. Because opioids can activate these receptors more strongly than endorphins, individuals who overdose on opioids could stop breathing and die.

The brain’s system of endorphins and opioid receptors are survival tools that help people in dangerous situations from being overcome by pain or fatigue. Medically, opioids are an important treatment for people who have severe pain that cannot be controlled with other medications.

Individuals who misuse illicit or prescription opioids may do so because these drugs have unnaturally significant effects on the opioid system, including the reward pathway. Since opioid use can initiate much higher dopamine release in the nucleus accumbens than endorphins, they produce a euphoric high that is difficult to achieve through natural means.

By simply swallowing, snorting, or injecting these drugs, people can get all the desired effects of endorphins without having to break a bone or run a marathon. Also, since people who misuse opioids can control how much and how often they take the drug, they may get a more intense, longer-lasting “high” than is possible with natural endorphins.

Depressants & the Brain

Several types of legal and illegal drugs are classified as central nervous system depressants. Dependent on the specific type of depressant medication, the prescription pharmaceuticals in this broad class may also be referred to as sedatives, tranquilizers, and hypnotics.

Substances classified as depressants include:

  • Alcohol—Technically called ethyl alcohol or ethanol, this was the most widely used and misused recreational drug in the U.S. in 2014.4
  • Barbiturates—These drugs are used as surgical anesthetics and to treat seizures. Historically, they were used to manage anxiety and insomnia, though their use for these applications has been largely supplanted by newer, safer medications. Examples include:
    • Phenobarbital (Luminal, goofballs).
    • Amobarbital (blue devils).
    • Secobarbital (Seconal, red devils).
    • Tuinal (Secobarbital + Amobarbital, rainbows)
  • Benzodiazepines, also known as benzos, are used to treat anxiety and panic attacks, as well as to manage acute seizures in emergency situations. Examples include:
  • Non-benzodiazepine sedatives—Often referred to as “z-drugs” because many of the drug names begin with the letter “z,” these medications are considered to be safer (milder effects and lower addictive potential) than benzodiazepines and are used to treat insomnia. Examples include:
        • Zolpidem (Ambien).
        • Eszopiclone (Lunesta).
        • Zaleplon (Sonata).

Although these CNS depressants are very different chemically, they all ultimately increase the activity of a neurotransmitter known as gamma-aminobutyric acid (GABA). Alcohol, barbiturates, and benzodiazepines all bind at different sites on the surface of the GABA receptor to activate this type of inhibitory signaling.

Activated GABA receptors inhibit, or decrease the firing of individual neurons, and GABA signaling is critical to maintaining a healthy level of brain activity. Insufficient levels of GABA can cause restlessness, insomnia, anxiety, and seizures due to abnormally high levels of neural overactivity.

Many people misuse sedatives because they reduce anxiety, help them to relax, and, in some cases, help them sleep. These drugs can also indirectly affect the reward pathway and cause a euphoric high, especially when taken in high doses.

However, excessive GABA signaling from depressant misuse can cause problems if brain activity is reduced too much. These negative side effects include:

  • Difficulty breathing
  • Slurred speech.
  • Memory loss.

In extreme cases, critical functions such as breathing might stop, causing death.

Cannabinoids & the Brain

Cannabinoids are chemicals that bind with cannabinoid receptors in the brain. They are found naturally (in marijuana or cannabis), but may also be laboratory-made (synthetic cannabinoids, Spice/K2).

Although illegal in many parts of the country under federal law, cannabinoids are very popular recreational drugs that produce effects such as:

  • A euphoric high.
  • Distortion of perception.
  • Memory impairment.

Cannabinoid receptors were first discovered in the 1980s using tetrahydrocannabinol (THC) and other cannabinoids found in the marijuana plant. It took another decade of research before scientists discovered the natural brain chemical counterparts–called endocannabinoids–that naturally bind to these receptors. In 1992, researchers discovered the first endocannabinoid in the brains of pigs, which they called “anandamide”—from the Sanskrit word for bliss.5

Endocannabinoid signaling is complex and slightly unusual because these are retrograde neurotransmitters. That means endocannabinoids are released by the postsynaptic neuron and their receptors are on the presynaptic neuron, so they send information in the reverse direction of most neurotransmitters.

Although scientists are still learning precisely what these chemicals do, they are involved in many brain processes, including:6

  • Energy balance—Endocannabinoid signaling is important in brain pathways controlling hunger and energy metabolism in the body.
  • Sensory perception—Many brain cells in the areas of the cortex that process sight, sound, hearing, and touch have cannabinoid receptors.
  • Learning and memory—The hippocampus, an area involved in learning and forming short-term memories, has many cannabinoid receptors.
  • Coordination—Endocannabinoids are important for the function of the cerebellum and basal ganglia, areas of the brain involved in balance and motor control.

In the brain, endocannabinoids are created only in specific neurons where they are needed and only for the amount of time they are needed, which can be as short as a few minutes.7 In contrast, THC and other cannabinoid drugs are ingested in relatively large amounts and indiscriminately activate receptors all over the brain.

This is why natural endocannabinoids are essential for forming clear memories and maintaining a normal appetite.

How Drugs Change the Brain

The brain and its networks have the ability to change and adapt—a property called plasticity. Plasticity is important for normal brain development and learning, as well as for recovering from brain injuries and strokes. Plasticity is also the reason that long-term exposure to drugs produces abnormal changes in the brain.

The brain will attempt to correct network activity that is much higher or much lower than normal levels. If an individual is regularly flooding their brain with opioid or endocannabinoid signaling by abusing drugs, the brain makes attempts to counteract these changes and bring them back to natural levels. Like a thermostat in a house, which works to keep the temperature from getting too hot or cold, plasticity allows the brain to keep neurotransmitter signaling from getting far from normal levels.

This adaptation by the brain leads to 2 important consequences of drug abuse: tolerance and withdrawal.13


Individuals who misuse drugs often find that they need to take larger doses of a drug over time to feel the same high. This is known as tolerance, and it is the result of the brain adapting to counteract the effects of abnormal neurotransmitter signaling caused by the drug.


People who regularly misuse a drug or alcohol may find that they feel sick or experience other uncomfortable withdrawal symptoms when they stop using the substance suddenly. This phenomenon is referred to as withdrawal syndrome.

Development of Addiction

Drug-induced changes in the brain can eventually lead to addiction, also known as a substance use disorder. Individuals who have addictions may show several signs of substance misuse, but they all share the key feature of this condition, which is that they use their drug of choice compulsively despite experiencing serious negative consequences from doing so.

The avoidance of withdrawal symptoms can partially explain why it can be especially difficult for people to stop taking drugs on their own.

However, it is adaptations in the nucleus accumbens and the motivation circuits of the brain that are thought to play the biggest part in the development of addiction. Every time a person misuses substances, they bombard the neurons in the reward pathway with unnaturally high levels of dopamine. Just as in other brain regions, these neurons adapt to counteract repeated overstimulation.

Eventually, the brain adjusts to the intense rewards of drugs, and natural rewards such as food and friends no longer produce a pleasurable response in a person’s brain (a phenomenon referred to as “anhedonia”). The anticipation of obtaining and using drugs (wanting and craving) becomes the main source of excitement and produces a flow of dopamine that narrows that individual’s focus and excitement to drug use and little else.

Individuals who have reached this stage may also stop feeling good at all when taking drugs. Instead, they need a substance in order to feel “normal.”

Once this level of brain adaptation has been reached, taking drugs is no longer truly a choice. The person will be driven to continue their habit as if it is necessary for survival, and drugs will seem more important than almost anything else. The effects of pleasure and motivation, powerful tools to help human survival, are essentially hijacked and the person is only motivated to use the substance.

These physical changes in the brain support the idea that addiction is, in fact, a disease and not simply a moral failing. While using drugs may start out as a choice, physiologic changes in the brain caused by drug use make it difficult for someone to make rational decisions about their drug use.

Instead of stigmatizing addiction, it’s possible to move forward by increasing understanding of drug use on the brain and highlighting how addiction is treatable.

How to Treat Drug and Alcohol Addiction

Addiction is a treatable, yet chronic condition. Knowing how drugs affect the brain has provided healthcare professionals with tools that can help to break the hold of addiction, including treatment medication, behavioral therapy, and relapse prevention services.

Addiction treatment can start anyone battling a substance use problem on the path to a healthier and happier life. There are drug detoxification and rehabilitation programs available throughout the country to help people in need. American Addiction Centers (AAC) is a leading treatment provider and has trusted rehab facilities across the U.S. For helpful advice, information, or admissions, please contact a caring AAC representative free at .

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