Dr. Nora D. Volkow, M.D. has been the Director of the U.S. National Institute on Drug Abuse (NIDA) since May 2003. Previously, Dr. Volkow was at Brookhaven National Laboratory (BNL), where she served as Associate Director for Life Sciences, Director of Nuclear Medicine, and Director of NIDA and the Department of Energy’s Regional Neuroimaging Center. She was also a Professor of Psychiatry and Associate Dean for the Medical School at the State University of New York at Stony Brook. Volkow’s research pioneered the use of imaging to understand the neurochemical changes that result from drug addiction. Born and raised in Mexico, Dr. Volkow is the great-granddaughter of the Russian revolutionary Leon Trotsky, and she grew up near the house where Trotsky was killed. She has authored or coauthored more than 280 peer-reviewed publications, three books, and over fifty book chapters and manuscripts. Volkow is a member of the Institute of Medicine in the National Academy of Sciences and was named “Innovator of the Year” by U.S. News and World Report in 2000. In 2007, Volkow was named to the TIME 100 list of “People Who Shape Our World”.

Many in the general public believe that addictions, from illegal drug abuse to al coholism, are due to a lack of willpower, and the perception of programs like Alcoholics Anonymous as primary forms of treatment might appear to support this. Why do you believe we should look at addiction as a medical condition in stead?

Addictions have been traditionally viewed by many as a deficit of willpower in addicted individuals. While initial drug experimentation and occasional use may be voluntary, the results of neuroimaging and other types of studies offer a more enlight­ened picture of the complex phenomenon of addiction. Modern scientific tools have revealed that addicted individuals often display severely disrupted brain function in regions that are critical for the normal processes of motivation, reward, and con­trol over behavior, including those areas of the brain that enable us to exert willpower. So addiction is a disease in which the brain has been altered. The associated maladap­tive behaviors are the result of discrete and definable brain dysfunctions.

Addiction is similar to other chronic medical conditions, both in its complex eti­ology and in how it is treated. For example, cardiac disease, like addiction, is influ­enced by multiple factors including genetic vulnerability and harmful behaviors (such as poor diet and lack of exercise). Once a heart attack occurs, the heart tissue can be damaged, requiring comprehensive medical treatment, which may include medications (to lower cholesterol, for example) along with changes in behavioral patterns to treat the disease. Likewise, the treatment of ad­diction may in­clude medications (if available) and behavioral inter­ventions, includ­ing programs like Alcoholics Anon­ymous, which can help former drug abusers remain abstinent and of­fer social support as well as moti­vation for behav­ioral change.

The more insidious problem with addiction, as compared to heart disease, is that the disease itself affects volitional control over behavior, thus requiring com­prehensive and continuing care to address this and other aspects of the disease. Re­search is beginning to show that with con­tinued abstinence, there is some recovery in the changes in brain physiology and neu­rochemistry.

You’ve stated that behaviors besides drug abuse, such as compulsive eating that leads to pathological obesity, can follow the same addictive patterns. But given that all of us have particular pref­erences and desires that might cause us to act irrationally at times, at what point would you call a behavior an addiction – something to be looked at similarly to alcoholism, for example?

You’ve asked a rather difficult question about when something actually shifts into the realm of pathology vs. nor­mal, albeit erratic or irratio­nal, behavior. In practice, the question is answered through the use of diagnostic tools like the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), which includes substance use disorders. But the DSM is not a perfect tool, and it is continually being updated as clinical syndromes become better defined. The DSM criterion for addiction, which is termed “dependence,” is based on symp­toms that reflect persistent drug taking de­spite adverse consequences – occupational, social, or health effects. Dependence can also include the presence of withdrawal symptoms upon drug cessation and toler­ance (the need to increase the amount of drug taken to achieve a particular effect, for example).

However, such a definition has not been established for other com­pulsive behaviors. Thus, while they have commonalities in phenomenol­ogy with drug addiction, more work is required to determine the extent to which they represent overlapping dis­ease entities.

Drug addiction works on the brain’s reward system, which includes the following major structures: the ventral tegmental area (VTA), the nucleus accumbens and the prefrontal cortex. The information travels from the VTA to the nucleus accumbens and then up to the prefrontal cortex.

Addiction can clearly have very negative effects, and given that mind-altering substances have been around for a long time, why haven’t there been any evolutionary pres­sures allowing people to more ef­fectively differentiate between real stimuli and drug-induced ones?

I don’t think that people have any trouble differentiating between real (or better yet, natural) and drug-induced stimuli. The problem arises from the uncanny ability of drugs of abuse to subvert much of the same brain circuitry in charge of decision-mak­ing, memory, learning, and, in particular, reward processes. The intimate connec­tions that exist between addictive and evo­lutionarily preserved rewarding behaviors, such as those that compel us to seek food and sex, have profound implications. We must recognize that most, if not all, abus­able substances usurp the very neural mechanisms that underlie the most basic of survival-type behaviors.

I would look at why haven’t there been any evolutionary pressures for the emergence of a more robustly protective mechanism against drug-induced effects? It is reasonable to assume that the cata­strophic medical and social consequences of addiction we are familiar with today are just too recent to have been significantly impacted by evolutionary processes. It is possible, however, that the overall net effect of the genetic and developmental factors that contribute to addiction vulner­ability, combined with a sustained and dra­matically higher availability of abusable drugs, could translate into a measurable selective pressure that will eventually en­gender novel defense mechanisms.

In the 1980s, you were among the first to use brain imaging – PET scans – to look at chronic drug abusers, and you found lingering effects even after years of ab­stinence. What kinds of ef­fects have you observed, and can these effects be caused by other kinds of addictions as well?

We were able to docu­ment a broad range of effects in the brains of drug abusers using PET-based techniques. Both PET and SPECT, which can monitor and map the presence of specific molecules in the brain, proved to be invaluable drug abuse research tools because they can mea­sure extremely low concentrations of the molecules of interest. Much of this work has focused on the dopamine system, but researchers have been increasingly explor­ing the roles of other neurotransmitters in drug abuse, as well as drugs’ effects on cells’ energy consumption and health. The level of sensitivity afforded by these tools has really clarified for us the ways in which long-term drug abuse can affect the neu­rotransmitter systems that link and coordi­nate brain cells.

Just to give you some specific exam­ples of what these techniques have revealed about the lingering effects of addiction in the brain, let’s consider the following ob­servations made with PET. Cocaine and methamphetamine interfere with activity in the orbitofrontal cortex (OFC), a brain area needed to make strategic, rather than impulsive, decisions. Methamphetamine abusers show depressed metabolism in specific brain regions after quitting meth­amphetamine but partial recovery after protracted abstinence. Cocaine appears to deplete the body’s natural opioids, which the body may try to compensate for by in­creasing the number – or efficiency – of existing receptors. One or more compo­nents of tobacco smoke reduce the level of monoamine oxidase (MAO) in the brain and throughout the body. MAO is an en­zyme that breaks down neurotransmitters, and one consequence of MAO inhibition by tobacco smoke may be the exacerbation of the nicotine-induced dopamine dysregu­lation that reinforces the desire to smoke as well as to abuse other substances.

Imaging techniques like structural MRI, fMRI, and mag­netic resonance spectroscopy have revealed other important aspects, that chronic drug ex­posure can enlarge or shrink some regions of the brain; that regional brain activity patterns in response to taking a drug correlate with vulnerability to drug abuse, addictive symptoms and behaviors, and long-term cognitive capacity; and that drugs of abuse affect inflammation pro­cesses and energy metabolism in the brain, and thus general neuronal health.

The combined results to date firmly establish that drug addiction is a disease of the brain, causing important physical and functional deficits in many areas, including pathways affecting reward and cognition. These studies are ongoing and continue to broaden our understanding of the dynamics underlying the development, symptoms, and consequences of addiction, as well as the recovery process. Having given rise to several potential approaches to medica­tions development, imaging technologies are becoming, increasingly, an important source of clinical benefits.

To address the second part of your question, there are other brain disorders and psychiatric conditions that share some of the symptoms displayed by addictive dis­orders. But we are only beginning to apply these technologies to study the long-term consequences of other conditions, such as morbid obesity and pathological gambling. Hence, it is too early to present a detailed side-by side comparison of commonalities and differences.

In normal brain function, dopamine is removed from the synaptic cleft and is subsequently degraded by monoamine oxidase (MAO) in the nerve terminal. However, cocaine binds to dopamine re-uptake transporters on the pre-synaptic membranes of the dopaminergic neurons thereby inhibiting removal of dopamine and this increased activation of the dopaminergic reward pathway leads to the feelings of euphoria and the ‘high’ associated with cocaine use. (Click to enlarge)

Could the lingering effects of addiction be used to monitor former addicts to predict whether they will relapse?

It is very likely that imaging tech­niques, particularly when combined with increasingly available genetic information, will change clinical practice, including ad­diction medicine. For example, there is preliminary evidence suggesting that brain fMRI, performed during a psychological test, can predict whether an individual will relapse following treatment for metham­phetamine abuse.

What factors make some more vulner­able to addiction and relapse than oth­ers? Are there any ways to preemptively deal with these?

We have already identified many de­velopmental and environmental factors that either protect or put individuals at higher risk for abuse and addiction. Epidemio­logical studies have shown conclusively that adolescents are at increased risk of en­gaging in the kinds of risky behaviors that include experimenting with drugs, and that early onset of drug abuse puts individuals at much higher risk of later addiction.

We have also developed a long list of environmental factors that contribute significantly to addiction vulnerability – early physical or sexual abuse, low socio­economic status, and in utero exposure to certain drugs are just a few examples. The many known environmental and develop­mental modulators of addiction risk offer invaluable opportunities to cost-effectively prevent the cycle of drug abuse and addic­tion. In the next few years, we also expect that the results from genomic studies will have identified genetic variations associ­ated with addiction vulnerability.

Some studies have shown that people who don’t use drugs before age 21 are much less likely to get addicted later in life than those who did, so clearly, tack­ling teenage drug abuse could help re­duce drug addictions in the future. Do you think current anti-drug programs focusing on scaring teens with the nega­tive effects of drug use are effective?

The epidemiological data, as I men­tioned before, are quite clear about the fact that adolescents are at high risk. So the real question is how to devise effective strate­gies for reducing early onset of drug abuse. There is no doubt that we have made signif­icant inroads in this area in the past twenty years, but a lot more remains to be done.

There are data available from recent evaluation pro­grams to suggest that some of the current and broadly used anti-drug programs are not as effective as one might have thought. It behooves us to look into the current efforts and at­tempt to extract the right les­sons in order to move forward. We believe, for example, that it is very important to pay much closer attention to the impact of brain development processes upon the way a particular message is perceived by young people. In fact, brain immaturity may not only explain teen risk-taking behaviors but also why “scare tactics” can backfire in drug prevention. It is not unreasonable to hypothesize that such tactics may translate in the brain of many adolescents into an “I dare you” message, which is the last mes­sage we want to convey.

The emerging area of “social neuro­sciences” is a particularly promising field of research, in which NIDA is heavily in­vested, and which we believe will generate much needed information to fill gaps in our knowledge of how messages reach differ­ent audiences, in different social circum­stances, and their brain/behavioral effects.

Addicts often may feel stigmatized and become less likely to seek help, particu­larly those using illegal drugs (as there may be legal consequences). How signif­icant is this issue in dealing with addic­tion, and how can it be resolved?

The negative impact of stigma on the ability of an individual to seek help or treatment is huge, not only in the case of people who are addicted to drugs but also in the more general population that suffers from other types of psychiatric disorders. This point is particularly relevant because of the high degree of comorbidity between substance abuse disorders and other men­tal disorders. We believe that the answer here is knowledge (science) dissemination. That is, we need to accelerate our efforts to inform the public that addiction is a disease of the brain, and that doing away with the stigma associated with all mental disorders, including addiction, will go a long way to­wards reducing the unacceptable gap be­tween the number of people seeking and receiving appropriate treatment and those who need it.

Many private insurance companies pro­vide very limited coverage for addiction treatment. Why has there not been more pressure on the American healthcare sys­tem as a whole, to deal with addictions?

Multiple factors are likely to underlie this issue, including the lack of patient ad­vocacy groups for addiction.

Do you feel the political influence and advertising power of drug-supplying sec­tors such as the tobacco industry are still a hindrance to increasing public aware­ness of the effects of addiction?

There isn’t sufficient information to determine whether tobacco advertisement campaigns are hindering our efforts to raise awareness about the fact that addiction is a disease of the brain.

Several medical organizations have en­dorsed the use of “medical marijuana” as an antiemetic, such as the British Medi­cal Association and some HIV/AIDS and cancer societies. How do you feel about this issue?

The mission of our Institute is to produce the best possible science so that policy makers and public health officials can make sound and informed decisions. In the context of recent efforts to legalize the use of smoked marijuana for medical purposes, we concur with the conclusions of a recent IOM report that analyzed this is­sue and determined that smoked marijuana is a crude THC delivery system that also delivers harmful substances.

Considering that the medicinally-active ingredients in marijuana have been largely identified and can be readily puri­fied, it makes perfect scientific and public health sense to support re­search efforts designed to maximize the beneficial impact of those ingre­dients while avoiding the risks as­sociated with their traditional form of delivery.

The primary role of the National Institute on Drug Abuse is to sup­port research in areas relating to drug abuse, but as director, do you also find yourself in an advisory role for public policy, especially given the need to publicize the re­sults of some of the research?

VOLKOW: Our role is very clearly delineated by the Congres­sional mandate that calls upon us to conduct broad-based drug abuse research and to ensure the rapid and effective dissemination of its results in order to improve prevention and treat­ment, and inform policy as it relates to drug abuse and addiction. Therefore, we make a concerted effort so that the knowledge derived from research becomes public in a timely fashion. NIDA’s science-based materials are avidly consumed by various constituent groups that incorporate them in their publications and routinely used by other federal agencies to better pursue their specific missions. The testimonies we give at various Congressional hearings on dif­ferent drug abuse related topics are also examples of how NIDA’s work may shape public policy.

You have a very interesting background, growing up in Mexico City as the great-granddaughter of famous Russian revo­lutionary Leon Trotsky, near the very same house where Trotsky was assas­sinated by a Soviet agent in 1940. Did your family have any influence on your career path?

My parents brought me and my sis­ters up with the conviction that we had a responsibility to lead our lives in ways that would help other human beings.