Box 3.1 Definitions Addiction. Substance dependence. Craving refers to the intense desire for a drug and is the most difficult aspect of addiction to overcome. Physiological dependence is diagnosed when there is evidence of either tolerance or withdrawal; it is sometimes, but not always, manifested in substance dependence. Reinforcement. A drug--or any other stimulus--is referred to as a reinforcer if exposure to it is followed by an increase in frequency of drug-seeking behavior. The taste of chocolate is a reinforcer for biting into a chocolate bar. Likewise, for many people the sensation experienced after drinking alcohol or smoking marijuana is a reinforcer. Substance dependence is a cluster of cognitive, behavioral, and physiological symptoms indicating that a person continues use of the substance despite significant substance-related problems. Tolerance is the most common response to repetitive use of a drug and can be defined as the reduction in responses to the drug after repeated administrations. Withdrawal. The collective symptoms that occur when a drug is abruptly withdrawn are known as withdrawal syndrome and are often the only evidence of physical dependence.