The middle stage of addiction is characterized by Physical Dependence, Craving, and Loss of Control: As physiological changes gradually occur, the penalties of using begin to outweigh the benefits. Pleasurable using for a “high,” a lift in feeling and performance from a relatively normal base, gives way to a more urgent “using for medicine” to “cure” the pain and misery caused by previous using. The basic cause of the increase in penalties is deterioration. Organs and systems that once welcomed the large doses of drugs and tolerated their toxic after effects are being damaged. Now when the addict stops using, his suffering is more severe and prolonged. Physical Dependence: As [the addict] uses more, and more often, to get the desired effect, the cells of his body are exposed to drugs for long periods of time. The cell membranes become increasingly resistant to drug’s effects, and the mitochondria within the cells increase in size and shift functions in order to accommodate the drug. With these changes, the adapted cells are able to live and thrive in an environment where drugs are continually present in large amounts. If the addict over-uses his tolerance, the brain cells will be overwhelmed, and he will get high. If he stops using, the addicted cells will suddenly be thrown into a state of acute distress. They have become unable to function normally without drug. The cells’ distress when drug is no longer present in the body, or when the BDL is falling, is evident in various symptoms known as “the withdrawal syndrome.” Withdrawal symptoms demonstrate that physical dependence exists; they are the visible signs of addiction. Craving: Craving is the overwhelming need for a use. Like everything else in addiction, craving is progressive. In the middle stages of the disease, craving becomes a need—the addict needs to use because his cells are physically dependent on drug. As tolerance increases and physical dependence sets in, the addict gradually loses psychological control over his physiological need for drug. Finally, will power, self-restraint, and the ability to say “no” have no power over addict craving. The physical need for drug overshadows everything else in the addict’s life. Loss of Control: As the addict progressively loses control over his using, he is no longer able to restrict it to socially and culturally accepted times and places. He often uses more than he intended, and the using continues despite extremely punishing consequences. He may use in the morning, at lunch, in the middle of the night; he may use in the car, the bathroom, the garage, or the closet as well as the tavern. His using behavior can no longer be disguised as normal or even heavy using. His inability to stop using—despite his firm resolution that he will stop after one or two—is striking confirmation that he is physically addicted to drug. The addict loses control over his using because his tolerance decreases and the withdrawal symptoms increase. The addict’s tolerance, which was so high in the early stages of the disease, begins to decrease because his cells have been damaged and can no longer tolerate large amounts of drug. While tolerance in lessening, the withdrawal symptoms are increasing in severity. The addict is now in the dangerous position of needing to use because he suffers terribly when he stops using but being unable to handle the high levels of drug needed to relieve the symptoms. He has also lost the ability to judge accurately how much drug his body can handle. As a result, he often over-medicates himself with drug, using to the point where he either loses consciousness or becomes so violently ill that he is forced to stop using.