The Disease of Addiction: What Goes Wrong When Drugs Enter the Brain

Posted: August 26, 2015
Brain Gears Drug Addiction

Based on a webinar offered by Dr. Nora Volkow on August 19, 2015, exclusively for the Foundation. 

By all accounts, drug addiction across America has reached epidemic proportions. More than 22 million people suffer from substance abuse problems, and in 2014, over 43,000 died from unintentional drug overdoses in the United States. Despite these tragic numbers, there are few effective treatments for recovery, and relapse rates are high.

Efforts to develop new and better therapies for addiction are stymied by persistent misconceptions and a lack of data. People with addictions are often seen as weak or lazy, but new research suggests something dramatically different: Addiction is a brain disorder, just as are illnesses like schizophrenia or depression, and scientists are now working to find effective treatments based on the neural changes that take place in the addicted brain. 

New research from Nora Volkow, M.D., Director of the National Institute on Drug Abuse at the NIH and a member of the BBRF’s Scientific Council, offers insights into how drugs alter neural pathways in the brain. Her research helps to define what drives addiction and provides possible new avenues for intervention.

At its most basic, addiction is characterized by a profound loss of control, even in the face of the most fervent desire to remain steadfast. For most people, neural circuitry in the brain maintains the delicate equilibrium between motivation and restraint. But in people with addictions, this balance is disrupted. Faulty neural circuits allow temptation to win out, despite the full knowledge of the harmful consequences by people who abuse drugs.

Restraint and motivation are balanced in the brain, in part, by a chemical messenger known as dopamine. Neurons release dopamine whenever we experience something positive, like eating a piece of cake or dancing at a concert. Dopamine release activates so-called “reward centers” in the brain, creating positive associations with experience. Addictive drugs, like amphetamines or alcohol, hijack this pathway, causing a tremendous spike in dopamine levels.

But why do some people suffer from addiction and not others? Dr. Volkow set out to define how the addicted brain is different from the brain of the average individual. She used advanced imaging technology known as PET scans of the brain to measure changes in addicted and recovering patients.

Dr. Volkow theorized that the amount of dopamine released in response to drugs might play a role in addiction. Perhaps a greater release of dopamine might feed addiction, she reasoned.

The data proved her idea entirely wrong. Surprisingly, addicts and recovering addicts released less dopamine than healthy individuals. Consistent with this, they also did not experience the same high associated with a drug. Despite this blunted response to the drug, people with addictions reported a more intense, almost insatiable desire for the drug.

Dr. Volkow then turned her attention to the brain circuits that regulate restraint, rather than motivation and desire. The nexus of self-control in the brain is a region known as the prefrontal cortex (PFC). Dr. Volkow and colleagues measured the number of dopamine receptors, or docking sites for the chemical messenger, in the brain.  She found that people who suffered from addiction had a lower number of dopamine receptors than their healthy counterparts and observed that this reduction was associated with decreased activity of the PFC.  Reduced activity in the PFC, which is necessary for judgement, planning, and self-regulation, could explain the poor decisions and impaired control that are typically observed in addicted individuals.

The implications of Dr. Volkow’s research are significant. With multiple neural circuits impaired, there are many potential targets in the search for new therapies to successfully treat addiction.

– Jaclyn Jansen, Ph.D., science writer