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Drug Dependence

by Patrick G. O’Connor, MD, MPH

People usually progress from experimentation to occasional use and then to dependence. This progression is complex and only partially understood. The process depends on interaction between the drug, user, and setting.


Commonly used psychoactive drugs vary in their potential for creating dependence.


The user’s predisposing physical characteristics (probably including genetic predisposition), personal characteristics, and circumstances (eg, coexistence of other disorders) influence whether drug dependence develops. For example, sadness, emotional distress that is symptomatically relieved by the drug, and a sense of social alienation may lead to increased use and dependence or addiction. Psychiatric disorders increase the risk of becoming drug dependent.

Patients with chronic pain (eg, back pain, pain due to sickle cell disease, neuropathic pain, fibromyalgia) often require narcotics for relief; many subsequently become dependent, and a few become addicted. However, in many of these patients, nonnarcotic drugs and other treatments (see Chronic Pain) are not adequate to relieve pain and suffering.

Few differences exist between the biochemical, drug dispositional, and physical responsiveness of people who become addicted or dependent and those who do not, although such differences have been vigorously sought. However, exceptions exist; nonalcoholic relatives of alcoholics have a diminished physical response to alcohol. Consequently, they need to drink more to get the desired effect.

A neural substrate for reinforcement (the tendency to seek more drugs and other stimuli) has been identified in animal models. In these studies, self-administration of such drugs as opioids, cocaine, amphetamine, nicotine, and benzodiazepines is associated with enhanced dopaminergic transmission in specific midbrain and cortical circuits. This finding suggests the existence of a brain reward pathway involving dopamine in the mammalian brain. However, evidence that hallucinogens and cannabinoids activate this system is insufficient, and not everyone who experiences these rewards becomes dependent or addicted.

An addictive personality has been described variously by behavioral scientists, but little scientific evidence backs this concept.


Cultural and social factors include peer or group pressure and environmental stress (particularly if accompanied by feelings of impotence to effect change or to accomplish goals).

Physicians may inadvertently contribute to harmful use of psychoactive drugs by overzealously prescribing them to patients for stress relief or may be manipulated by patients to overprescribe the drugs. Many social factors and the mass media may contribute to the expectation that drugs can safely relieve all distress and gratify all needs.

Drugs Mentioned In This Article

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