Study topic · about 6 minutes

How drugs affect the brain

Drugs change how neurons talk to each other at the synapse. Some copy a neurotransmitter, some block its receptors, and some keep it in the synapse longer. Almost every addictive drug raises dopamine in the brain's reward pathway, which runs from the ventral tegmental area to the nucleus accumbens. With repeated use the brain adapts, leading to tolerance, withdrawal and, in some people, addiction.

Key points

Agonists copy or boost a neurotransmitter, antagonists block its receptors, and reuptake inhibitors keep it in the synapse longer.
Dopamine neurons in the ventral tegmental area reach the nucleus accumbens and the prefrontal cortex, and almost every addictive drug raises dopamine there.
The main drug classes are stimulants, depressants, opioids, hallucinogens and cannabis, and each acts on different receptors.
Opioids can slow breathing until it stops, because they act on breathing centers in the medulla.
Addiction is a chronic, relapsing brain disorder that changes the circuits for reward, stress and self-control.
The prefrontal cortex, which handles self-control, keeps maturing into the mid-20s, so the teenage brain is more at risk.

How drugs act at the synapse

Neurons pass messages across a tiny gap called the synapse. The sending neuron releases a neurotransmitter, which fits into receptors on the next cell like a key in a lock. Then transporter proteins pull it back into the sending neuron, which is called reuptake. Drugs work by changing one of these steps.

Type	What it does	Examples
Agonist	Copies a neurotransmitter or boosts its effect, so the receptor switches on.	Morphine and heroin act on the receptors for endorphins, the body's own painkillers.
Antagonist	Sits in a receptor without switching it on, blocking the neurotransmitter.	Caffeine blocks adenosine receptors. Naloxone blocks opioid receptors.
Reuptake inhibitor	Blocks the transporter, so the neurotransmitter stays in the synapse longer.	SSRI antidepressants do this for serotonin. Cocaine does it for dopamine.
Releaser	Makes the sending neuron push out extra neurotransmitter.	Amphetamines release dopamine and noradrenaline (norepinephrine).

A 3D dopamine synapse: an axon terminal full of vesicles above the receptors of the next cell — A dopamine synapse in the 3D app. The axon terminal (blue) is packed with vesicles of dopamine, and receptors (purple) wait on the receiving cell (pink). Small reuptake transporters (light blue) at the edge pull dopamine back, and cocaine blocks them.

The reward pathway

The brain has a built-in system that makes you want to repeat things that help you survive, like eating and spending time with friends. Its core is the mesolimbic pathway. Dopamine neurons in the ventral tegmental area, or VTA, in the midbrain send their axons to the nucleus accumbens, deep in the front of the brain. A second branch, the mesocortical pathway, reaches the prefrontal cortex.

Dopamine bursts when something turns out better than expected. That signal teaches the brain what is worth going after. Scientists now think dopamine drives wanting and learning more than pleasure itself, which relies more on the brain's own opioids.

Almost every addictive drug raises dopamine in the nucleus accumbens, often far more than natural rewards do. The brain learns to want the drug above other goals. It also links the drug to places, people and objects, which can later set off cravings on their own.

The main drug classes

Psychoactive drugs change how you feel, think or perceive. AP Psychology groups them into classes by their main effect:

Class	How they act	Main effects
Stimulants	Caffeine blocks receptors for adenosine, a chemical that builds up while you are awake and makes you sleepy. Nicotine acts on acetylcholine receptors. Cocaine blocks dopamine reuptake. Amphetamines, including methamphetamine, make neurons release dopamine and noradrenaline.	More alertness and energy, a faster heart rate and less appetite, often followed by a crash.
Depressants	Alcohol boosts GABA, the brain's main "stop" signal, and blocks NMDA receptors for glutamate, its main "go" signal. Benzodiazepines and barbiturates also boost GABA.	Relaxation, lowered inhibitions, and poorer coordination and memory. High doses can slow breathing dangerously, especially when mixed with other depressants or opioids.
Opioids	Heroin, morphine and fentanyl act on opioid receptors, the same receptors the brain's own endorphins use.	Pain relief, euphoria, drowsiness and tiny pupils. An overdose can stop breathing.
Hallucinogens	LSD and psilocybin act on serotonin 5-HT2A receptors. MDMA (ecstasy), which is also a stimulant, releases serotonin, plus some dopamine and noradrenaline.	Changes in what you see and hear, in the sense of time and in the sense of self. MDMA also brings energy and feelings of closeness.
Cannabis	THC, its main active chemical, acts on cannabinoid CB1 receptors. These are dense in the hippocampus, cerebellum and basal ganglia.	Relaxation and a changed sense of time, with weaker short-term memory and coordination.

Opioid overdoses are deadly because opioids act on the breathing centers of the brainstem, mainly in the medulla. Too much slows breathing until it can stop. Fentanyl is so strong that a tiny amount can cause an overdose. Naloxone, an opioid antagonist, can reverse an opioid overdose by blocking opioid receptors. An overdose is always a medical emergency: call 911 in the United States.

The medulla lit up in green at the bottom of the brainstem, with nerve roots branching off, in a 3D brain — The medulla (green), the lowest part of the brainstem, just above the spinal cord. Its breathing centers are why an opioid overdose can stop breathing.

Tolerance, withdrawal and addiction

Term	Meaning
Tolerance	The brain adapts to a drug, for example by making fewer receptors, so the same amount has less effect and more is needed.
Withdrawal	Unpleasant symptoms when the drug is stopped, often the opposite of its effects: anxiety and shakiness after depressants, exhaustion and low mood after stimulants.
Dependence	The body has adapted so that it works normally only with the drug, and stopping causes withdrawal. It can happen even with medicines taken as prescribed.
Addiction	A chronic, relapsing brain disorder: compulsive drug seeking and use despite harmful consequences. In medical terms, it is a severe substance use disorder.

Addiction changes three brain systems. The reward circuit in the basal ganglia becomes less sensitive, so everyday pleasures feel flat and the person needs the drug just to feel normal. The extended amygdala, a stress circuit centered on the amygdala, becomes more sensitive. It drives the anxiety and irritability of withdrawal, and the craving to use again. Changes in the prefrontal cortex weaken self-control, so resisting urges gets harder.

No single cause decides who becomes addicted. Genes account for about 40 to 60 percent of the risk, and stress, family, friends and the age when drug use starts matter too. Addiction can be treated, but like other chronic diseases it can come back, which is called relapse.

Why the teenage brain is more at risk

The brain keeps maturing into the mid-20s. The prefrontal cortex, which handles planning, judgment and self-control, is one of the last parts to finish. The reward system, by contrast, is already very active in the teen years. Many scientists think this gap helps explain why teens take more risks, including trying drugs.

Drugs used while the brain is still wiring itself can have lasting effects. The earlier drug use begins, the more likely it is to lead to addiction. Regular, heavy cannabis use in the teen years, for example, is linked to poorer memory, slower thinking and lower school performance.

This page is for learning, not medical advice. Anyone who needs help with drug or alcohol use can call SAMHSA's National Helpline at 1-800-662-4357. It is free, confidential and open 24 hours a day, every day, in the United States.

Memory tricks

Benzodiazepines versus barbituratesFREnzodiazepines, barbiDURatesBoth boost GABA-A receptors, which are chloride channels. Benzodiazepines make the channel open more FREquently; barbiturates keep it open for a longer DURation.

Quick quiz

5 questions. Your answers are saved and come back in your daily review.

Cocaine raises dopamine in the synapse mainly by...
Show the answer
Blocking dopamine reuptake. Cocaine blocks the dopamine transporter, so dopamine builds up in the synapse and keeps stimulating the next cell.
The dopamine neurons of the reward pathway start in which area?
Show the answer
Ventral tegmental area. Dopamine neurons in the ventral tegmental area, in the midbrain, send their axons to the nucleus accumbens and the prefrontal cortex.
Why can an opioid overdose be fatal?
Show the answer
It slows breathing, which the medulla controls. Opioids act on breathing centers in the medulla. Naloxone, an opioid antagonist, can reverse an overdose.
Alcohol, benzodiazepines and barbiturates all boost the effect of which neurotransmitter?
Show the answer
GABA. These depressants boost GABA, the brain's main "stop" signal, which is why they slow the brain down.
Someone who drinks coffee every day finds that one cup no longer keeps them alert. What has developed?
Show the answer
Tolerance. With tolerance, the brain adapts to a drug, so the same amount has less effect and more is needed for the same result.

In these study guides

MCATSleep, drugs, memory, language and reward
AP Psychology1.3 The neuron and neural firing
Intro psychologySleep and drugs (sections 4.2 to 4.5)

Take it further in 3D

Emotion and rewardFear, drive and the value of things. A short guided lesson in the 3D app.

Sources

Drugs, Brains, and Behavior: The Science of Addiction: Drugs and the Brain, National Institute on Drug Abuse (NIDA)
Drugs, Brains, and Behavior: The Science of Addiction: Drug Misuse and Addiction, National Institute on Drug Abuse (NIDA)
Psychology 2e, 4.5 Substance Use and Abuse, OpenStax

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