An abuser’s drug metabolism, the processes by which a drug is transformed to a different chemical state within the body, affects the impact of the drug. Most chemical drug transformations occur in the liver, stomach, kidneys, lungs, blood, and the brain. During drug metabolism, the fat-soluble amphetamine molecule is changed progressively through a sequence of reactions to a water-soluble product, which is then excreted. Because water-soluble substances are more easily excreted, a drug’s ability to enter the brain is diminished during drug metabolism.

Drugs are chemically transformed with the aid of enzymes; specialized protein molecules that act as catalysts. As drug exposure is repeated, the number of drug enzymes increases thereby increasing the speed at which drugs can be transformed in water soluble substances and then excreted. The abuser may develop a metabolic tolerance to the drug, a decrease in response to a drug dose that occurs with continued abuse, so that increased drug doses are required to achieve the effects originally produced at lower doses. Metabolic tolerance decreases when exposure to the drug is stopped. Furthermore, the enzymes used to transform one drug may also be used to transform another, so if a drug tolerance resulted from one drug in the amphetamine group then it may exist for another drug even if the second drug was never used. This can be dangerous for an unaware user.