Tolerance to a drug can develop if a person uses it frequently. The first time a person uses a drug, they have a very low tolerance and are more likely to feel the effects very strongly, or overdose. The more often the drug is used, the less intense the effects will be. This results in the need to take larger amounts to get the desired effects. When you stop using a drug, or have a break of even a few days, tolerance will reduce.

This corresponds with the experience of withdrawal symptoms. After detoxification from heroin, tolerance drops considerably and the first use of heroin after detox is a high risk time for overdose. Release from prison is another example of a high risk time for heroin overdose due to the reduction of tolerance.

Tolerance often develops rapidly in people who have been tolerant to a substance in the past. The brain appears to have a memory of past drug use, although the process for this is not well understood. People with alcohol dependence, for example, often find that even after a break in alcohol consumption of months or years, tolerance can return in a couple of days. A tobacco smoking habit is quickly re-established even after years of not smoking.