Text adapted in 2021 from The Fundamentals of Addiction in The Primary Care Addiction Toolkit (online only). A complete list of Toolkit authors, editors and contributors is available here.
Physical dependence
Physical dependence is an adaptive physiological state that occurs with regular drug use and results in a withdrawal syndrome when drug use is stopped. It is usually associated with increased tolerance. Physical dependence tends to be a characteristic of substance use disorders, but in itself does not imply addiction.
Tolerance
Tolerance is a condition in which higher doses of a drug are required to produce the same effect experienced during initial use. It can also mean that the same amount of a drug produces less effect than it has in the past. It is often associated with physical dependence.
In the therapeutic use of a drug with psychoactive effects, patients tend to become tolerant to the drugs’ psychoactive effects (e.g., euphoria, reduced anxiety, sleep inducement), but not as much to the therapeutic effects of pain relief.
For example, a patient who needs higher doses of morphine for chronic pain relief may be seeking the psychoactive effects of the drug to which tolerance has developed. Patients can develop tolerance to a drug without it causing harm or meaning that the person has a substance use disorder.
It is sometimes difficult to determine tolerance by a patient's history alone because initial sensitivity to a particular substance varies significantly between individuals.
Withdrawal
Withdrawal is a characteristic of most substance use disorders, but does not necessarily imply addiction.
With regular use of a substance, biochemical and structural adaptations take place in the brain. Withdrawal is the constellation of symptoms and signs that a person experiences when, after a period of regular use, the quantity of the substance in the brain is reduced. Upon abstinence, central nervous system receptors take days or weeks to normalize.
Symptoms and signs of withdrawal are opposite to the main effect of the drug. Here are specific examples:
- Sedative withdrawal creates autonomic hyperactivity with dangerous medical complications.
- Opioid withdrawal is accompanied by anxiety, powerful cravings and flu-like symptoms.
- Stimulant withdrawal consists of depression, insomnia and cravings.
The addictive potential of drugs
Drugs are potentially addicting to the extent that they produce a marked contrast between altered and drug-free psychic states.
A drug's addictive potential is determined by its ability to produce:
- a rapid onset of action
- a powerful euphoric effect
- a short duration of action
- tolerance and withdrawal.
The more that a drug has these features, the greater its addictive potential.
Examples:
- Smoked crack cocaine enters the central nervous system within seconds, has an explosive effect on dopamine concentrations and wears off within 20 minutes—making it extremely addicting.
- Benzodiazepines have a much lower misuse potential than crack because they have a slower onset of action, provide only mild anxiolytic properties and wear off gradually over several hours.
- Nicotine is delivered to the brain within five to seven seconds of inhaling cigarette smoke, and over several hours when it is absorbed through the skin via a patch. The short time to peak effect of cigarettes makes them a far more addictive delivery system than the patch, even though the drug is the same.
Tolerance and withdrawal increase the addictive potential of a drug by making it difficult for a person to stop using it without experiencing discomfort.
In Fundamentals of Addiction: