Tolerance

Tolerance is a reduced response to a substance after repeated exposure, so that the same amount produces a smaller effect than it did at first.

The phenomenon arises through several mechanisms: receptors may become less numerous or less sensitive, the liver may speed up metabolism, or the nervous system may adapt in other ways. Tolerance is common with opioids, benzodiazepines, caffeine, and alcohol, and it can develop to some effects of a substance but not others. It is distinct from dependence, which concerns withdrawal on stopping, though the two often occur together. Clinicians assess tolerance by observing whether effect declines over time at a stable amount.

Regular THC use produces well-documented tolerance through downregulation of cannabinoid receptors. Whether cannabidiol produces tolerance is much less clear; some preclinical work and clinical experience with prescription CBD have not shown clear tolerance to its main effects, but data from long-term consumer use are lacking. Claims that tolerance never develops, or that a break resets it, are not well supported either way. Readers meet the concept in discussions of long-term use.