Cross-tolerance refers to a pharmacological phenomenon, in which a patient being treated with a drug exhibits a physiological resistance to that medication as a result of tolerance to a pharmacologically similar drug. In other words, there is a decrease in response to one drug due to exposure to another drug. It is observed in treatment with antivirals, antibiotics, analgesics and many other medications.

Cross-tolerance is particularly frequent amongst users of illicit drugs. For example, users with a high tolerance to the stimulant amphetamine

Amphetamine

Amphetamine or amfetamine is a psychostimulant drug of the phenethylamine class which produces increased wakefulness and focus in association with decreased fatigue and appetite.Brand names of medications that contain, or metabolize into, amphetamine include Adderall, Dexedrine, Dextrostat,...

 may also exhibit a high tolerance to the structurally similar methamphetamine

Methamphetamine

Methamphetamine is a psychostimulant of the phenethylamine and amphetamine class of psychoactive drugs...

 or other amphetamine-like stimulant

Stimulant

Stimulants are psychoactive drugs which induce temporary improvements in either mental or physical function or both. Examples of these kinds of effects may include enhanced alertness, wakefulness, and locomotion, among others...

s. The phenomenon is also observed in cigarette

Cigarette

A cigarette is a small roll of finely cut tobacco leaves wrapped in a cylinder of thin paper for smoking. The cigarette is ignited at one end and allowed to smoulder; its smoke is inhaled from the other end, which is held in or to the mouth and in some cases a cigarette holder may be used as well...

 smokers, in whom there is a demonstrably lessened sensitivity to the effects of caffeine

Caffeine

Caffeine is a bitter, white crystalline xanthine alkaloid that acts as a stimulant drug. Caffeine is found in varying quantities in the seeds, leaves, and fruit of some plants, where it acts as a natural pesticide that paralyzes and kills certain insects feeding on the plants...

. Cross-tolerance is also frequent in response to use of hallucinogens. General tolerance to the effects of tryptamines such as psilocybin

Psilocybin

Psilocybin is a naturally occurring psychedelic prodrug, with mind-altering effects similar to those of LSD and mescaline, after it is converted to psilocin. The effects can include altered thinking processes, perceptual distortions, an altered sense of time, and spiritual experiences, as well as...

, may be dramatic in response to repeated use, and this often translates into a tolerance to effects of other drugs such as Mescaline

Mescaline

Mescaline or 3,4,5-trimethoxyphenethylamine is a naturally occurring psychedelic alkaloid of the phenethylamine class used mainly as an entheogen....

 or DMT

Dimethyltryptamine

N,N-Dimethyltryptamine is a naturally occurring psychedelic compound of the tryptamine family. DMT is found in several plants, and also in trace amounts in humans and other mammals, where it is originally derived from the essential amino acid tryptophan, and ultimately produced by the enzyme INMT...

. This is also true of benzodiazepines such as Xanax and Klonopin, even opiates as well.