1. the ability of one substance to prevent withdrawal symptoms from a different substance of the same class or with a similar effect. This is the pharmacological mechanism behind substitution pharmacotherapy: Cross-dependence allows the substitution of a less dangerous drug as treatment for substance dependence, as in the substitution of methadone for heroin.

2. the condition of becoming rapidly dependent on a substance that is related to one for which there is already dependence.

3. the condition of being simultaneously dependent on more than one substance. Also called cross-addiction. Compare cross-tolerance.