Neurobiology of addiction
How drugs hijack the brain's reward system, the difference between tolerance, dependence and addiction, and the principles of treatment.
Addiction is a chronic, relapsing brain disorder: compulsive drug use continues despite harm. Addictive drugs share one action, a large surge of dopamine in the brain's reward circuit, and repeated use changes the circuits for reward, stress and self-control. Understanding these changes explains craving, relapse and why treatment combines medicines with psychosocial support.
The reward circuit
Natural rewards such as food and social contact release dopamine from neurons in the ventral tegmental area that project to the nucleus accumbens and the prefrontal cortex. Dopamine signals that something is worth repeating more than it creates pleasure itself. Drugs of abuse produce surges much larger and faster than natural rewards, so the brain learns to prioritise the drug.
How different drugs get there
- Opioids, cannabinoids and GHB act on receptors that remove inhibition from dopamine neurons.
- Nicotine, alcohol and benzodiazepines act on ion channels that change dopamine neuron firing.
- Cocaine and amphetamines act on the dopamine transporter, blocking reuptake or reversing it.
Tolerance, dependence and addiction
Tolerance is a reduced response with repeated exposure. Dependence (physical dependence) is shown by a withdrawal syndrome when the drug stops; it also occurs with medicines used correctly, such as opioids for pain. Addiction is different: loss of control and compulsive use despite harm. Tolerance to euphoria can grow faster than tolerance to respiratory depression, which is one reason opioid overdoses happen.
Why people relapse
The extended amygdala drives anxiety and irritability when the drug wears off, so the drug is taken to feel normal (negative reinforcement). The prefrontal cortex, which supports planning and self-control, works less well; it is also the last region to mature, which makes adolescents especially vulnerable. Places, people and objects linked to past use can trigger strong craving years later.
Principles of treatment
Substance use disorders are treatable chronic conditions. Medicines are combined with counselling and social support: methadone or buprenorphine (opioid agonist treatment) and naltrexone for opioid use disorder; naltrexone, acamprosate and disulfiram for alcohol; nicotine replacement, varenicline and cytisine for tobacco. WHO recommends that naloxone be available to people likely to witness an opioid overdose.
Test yourself
Think of the answer, then tap the question to see it.
Which pathway forms the core of the brain's reward circuit?
Dopamine neurons from the ventral tegmental area projecting to the nucleus accumbens (and the prefrontal cortex).
Is physical dependence the same as addiction?
No. Dependence means a withdrawal syndrome appears on stopping; addiction is compulsive use despite harm. A patient on long-term opioids for pain can be dependent without being addicted.
Why are adolescents especially vulnerable to addiction?
The prefrontal cortex, which supports self-control and planning, is the last brain region to mature.
Which two medicines are used as agonist treatment for opioid use disorder?
Methadone and buprenorphine (agonist treatment); naltrexone is an antagonist option.
Example drugs
- Methadone
- Buprenorphine
- Naltrexone
- Naloxone
- Acamprosate
- Disulfiram
- Nicotine (replacement therapy)
- Varenicline
- Cytisine
- Cocaine
- Amfetamine
Connections
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: Drugs, Brains, and Behavior: The Science of Addiction: Drugs and the Brain (National Institute on Drug Abuse (NIDA), NIH, 2026); Opioid overdose (World Health Organization, 2026); Alcohol (World Health Organization, 2026).
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Representative model, for educational purposes only.