Strategies for Success, New Pathways to Drug Abuse Prevention
Issue 1 • Volume 1
Fall/Winter 2006

The Biology of Drug Addiction

By Bertha K. Madras, Ph.D.
Deputy Director
Demand Reduction, Office of National Drug Control Policy

No one starts using drugs with the intention of becoming addicted. However, even first exposure can trigger changes in the brain.

This is the first in a series of articles on how drugs affect the brain and body. Specific drugs and their effects will be addressed in future articles.

The Magnitude of the Problem
Drug abuse and addiction account for thousands of deaths in the United States each year. In 2002, for example, more than 26,000 people died as a direct result of drug use, a figure that does not include those killed as an indirect consequence of drug-using behavior. Substance abuse and addiction are also the costliest and most prevalent of brain disorders, surpassing Alzheimer’s disease, depression, spinal cord injury, developmental disorders, and other devastating maladies of the brain and nervous system. Yet addictive disorders rank among the most preventable diseases in our Nation.

Substance abuse places an enormous burden on society, causing or contributing to a host of medical, social, and criminal justice problems and can affect people at all stages of life. Prenatal exposure to drugs is linked to low birth weight and has been associated with developmental disorders. In adolescence and young adulthood, drug use can be associated with poor school performance, accidents, unplanned sexual activity and pregnancy, violence, and criminal activity. The work performance of illicit drug users is characterized by absenteeism, illness, injuries, low productivity, and job turnover. Older persons do not escape the long-term effects of drugs; addiction, compromised health, and interrupted educational and social development are issues in this population.

Drug use, abuse, addiction
The environment is a major influence on whether a youth or adult will experiment with drugs. For instance, parents’ indifference or acceptance of drug use, access to drugs, peer pressure, and the media all play a role in a person’s attitude and behavior toward drugs.

A number of personal factors also can promote drug abuse problems. Examples include psychiatric conditions, personality disorders, poor school performance, inappropriate school behavior, and early drug use. There is also growing evidence that genetics may contribute approximately 50 percent of susceptibility to addiction, depending on the type of drug and the particular environment. It has been proposed that drug use and addiction are forms of self-medication, with users seeking to relieve depression, anxiety, grief, or severe psychiatric problems.

Drug-related risks
Drugs can exert powerful effects on the brain, but the exact response is determined by various factors, such as the chemistry of the drug, the dose, and the manner in which it is taken (injected, smoked, swallowed). A drug’s biological imprint in the brain can be as hard to predict as a New England storm. It might come and go with little trace of passage—or leave a trail of destruction that seriously impacts brain function, biology, personality, and behavior.

What is certain is that drug abuse can have different and more profound effects on a young person than an older person. According to Dr. Jean Lud Cadet of the Molecular Neuropsychiatry Branch at the National Institute on Drug Abuse and Dr. Mark S. Gold of the Department of Psychiatry, Neuroscience, Anesthesiology, and Community Health and Family Medicine at the University of Florida, the human brain takes at least 21 years to fully develop. Because the brain is still maturing during adolescence and young adulthood, and because drugs can change the programming responsible for the normal development of the brain, this population is particularly vulnerable to drug addiction.

The Cycle of Addiction
No one starts using drugs with the intention of becoming addicted. However, even a first exposure to a drug can trigger biochemical and cellular changes in the brain, often within hours or even minutes.While the majority of changes at this early stage are reversible, some may be permanent. After repeated use, susceptible people—approximately 8 percent to 32 percent of users—may transition from controlled use to addiction, depending on the drug. At this stage, the brain evidences many changes, the most obvious of which are reflected in altered behavior and judgment. The user is driven to take the drug regardless of the consequences. If he or she suddenly cannot obtain or otherwise stops using the drug, psychological and/or physical withdrawal symptoms emerge. Even after a long period of abstinence from the drug, the addicted brain can generate intensive drug-craving and compulsive drug-seeking. If not addressed, this craving can lead to relapse, possibly causing the addict to spin through the cycle of compulsive use, withdrawal, and relapse over and over again.

How do drugs affect the brain?
Over the past decade, astounding progress has been made in explaining how the brain is affected by drugs. The details are complex, but the key lies in understanding how the brain communicates. The human brain manufactures more than a hundred different chemicals that it uses for conveying important information. These chemical messages are exquisitely controlled, for the work they do is essential for survival.

Drugs resemble, but are not identical to, the chemical messages produced by the brain. The “imposters” cocaine, amphetamine, and Ecstasy, for example, are similar to the brain chemicals dopamine, serotonin, and norepinephrine; THC (9-tetrahydrocannabinol), an active ingredient in the marijuana plant, resembles anandamide and 2-arachidonylglycerol, produced by the brain.

But because drugs do not precisely duplicate brain chemicals, the brain cannot control drug messages the same way it controls its own. The results, as the brain tries to process these “false” messages, are euphoria, delusions, hallucinations, anger, and a host of other strange sensations or behaviors.

With repeated frequent drug use, the brain can adapt to and compensate for abnormal signals, and it is not clear to what extent this adaptation is reversible. Drugs can change cell structure, metabolism, signaling, and networks. And some drugs, such as amphetamines, alcohol, and inhalants, are quite toxic to the brain. Long-term users of specific drugs may experience durable changes in brain function and behavior. Withdrawal from drugs can lead people to feel their brain is no longer normal unless they consume more drugs. During withdrawal, a variety of problems can emerge, including anxiety, irritability, misery, stress, and other psychological or physical discomfits, such as tremors or flu-like symptoms. Drug addiction can be viewed as a chronic, relapsing disease characterized by compulsive, uncontrollable use despite adverse consequences. At the same time, it is important to recognize the role of personal responsibility in determining whether the addictive behavior stops or continues. Drug-addicted patients, like patients with other diseases, are urged to assume responsibility for compliance with treatment.

Prevention, intervention, and treatment of addiction
The goal of prevention is to keep people from initiating drug use. Intervention and treatment aim to prevent drug use from progressing to addiction, or to reverse the behavioral patterns of the addicted state. We must protect our young people from the threat of drugs using every means available. Student drug testing may help stop drug use among this highly vulnerable population and keep children from getting trapped in the devastating cycle of addiction.

Cocaine Decreases Blood Supply to the Brain

Cocaine use causes decreased blood flow to the brain, particularly in the frontal cortex, which is involved in important cognitive functions, including judgment and memory.

Graphic: Radioactive chemical illustrates strong blood flow to the brain of the control subject, particularly in the frontal cortex, which is marked with a yellow circle.
Radioactive chemical illustrates strong blood flow to the brain of the control subject, particularly in the frontal cortex, which is marked with a yellow circle.
Graphic: Radioactive chemical illustrates poor blood flow
in many areas of the brain of a chronic cocaine user (who also abuses other drugs), particularly in the
frontal cortex, which is marked with a yellow circle.
Radioactive chemical illustrates poor blood flow in many areas of the brain of a chronic cocaine user (who also abuses other drugs), particularly in the frontal cortex, which is marked with a yellow circle.

Credits: Composite courtesy of B.K. Madras and B.L. Holman

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