Jan/Feb 2008

The Brain, Drugs, and Behavior — The New Science of Addiction
Social Work Today
Vol. 8 No. 1 P. 12

Marianne Mallon, editor of Social Work Today, and John K. Smith, PhD, LCSW, had the privilege of interviewing Nora Volkow, MD, director of the National Institute on Drug Abuse (NIDA). Below is an introduction by Dr. Smith followed by Dr. Volkow’s responses. Many thanks to Dr. Volkow and the NIDA for their assistance with this article.

I am approaching nearly 30 years in the field of treating dually diagnosed individuals—those with both mental health conditions and substance use disorders.

I have seen the development of new methodologies for treatment and witnessed the development of new medications offering hope and recovery for those with the most severe disorders. While these advances have improved treatment outcomes for many, there are still unanswered questions about the causes of mental illness and addiction. As a result, stigma remains about those who suffer from mental illness and addiction.

Some still believe that addictions are a matter of moral weakness or lack of willpower. Despite the increasing evidence that addictions and mental illnesses are the result of brain dysfunction, some providers have been slow to recognize this and adopt prevention and treatment methodologies reflecting this knowledge. Treatment has primarily focused on the psychosocial aspects of recovery and relied on support-based programs, such as 12-step groups, as the foundation for recovery. This primary approach to addictions treatment has not changed substantially in many years. While the 12-step model of recovery consistently produces good outcomes, success rates remain low at roughly 20% for all forms of supportive and behavioral therapies.

Fortunately, new research on the “science” of addiction is producing important information that is helping scientists and practitioners understand the biopsychosocial aspects of addiction. Some of the most remarkable research on addiction is being done by the National Institute on Drug Abuse (NIDA).

— John K. Smith, PhD, LCSW, is a licensed psychotherapist with more than 25 years of experience in the mental health and chemical dependency fields and is program administrator for the Dual Diagnosis Day Treatment Program at Doctor’s Hospital of West Covina, CA. He is also a professor of alcohol and drug counseling at Mt. San Antonio College in Walnut, CA, and the author of the recently published book Co-occurring Substance Abuse and Mental Disorders: A Practitioner’s Guide.

SWT: What are the major neuroscientific discoveries that led to the revolution in thinking about addiction not as a moral failure but as a health problem?

Volkow: You are absolutely right that, in the past, addicted individuals were dismissed as moral failures or people with serious character flaws. We now understand that addiction is a disease of the brain that can be chronic and relapsing. While initial drug experimentation and occasional use may be largely voluntary, the results of neuroimaging and other types of studies have revolutionized our understanding of brain disorders in general and the disease of addiction in particular.

Modern scientific tools reveal that addicted individuals often display severely disrupted brain function in regions that are critical for the normal processes of motivation, reward, and behavior control, including those areas that enable us to exert willpower. This justifies the assertion that addiction is a bona fide disease, one accompanied by well-known maladaptive behaviors that are the result of discrete and definable brain alterations and dysfunctions.

SWT: How has information from research on brain changes due to substance abuse influenced prevention efforts and treatment program design?

Volkow: Now that we know addiction shares so many fundamental features with other chronic medical conditions, we must act accordingly to adapt or at least revisit our treatment strategies. Take the example of heart disease, which, like addiction, is influenced by multiple factors, including genetic vulnerability and harmful behaviors (e.g., poor diet, lack of exercise). Once a heart attack occurs, the heart tissue can be damaged requiring comprehensive medical treatment, which may include medications and changes in behavioral patterns to treat the disease.

However, one of the most insidious facets of addiction compared with heart disease is that the disease itself affects volitional control over behavior, thus requiring comprehensive and continuing care to address the many aspects of the disease. Thus, we support research that takes advantage of this new knowledge at the level of the whole person (e.g., psychosocial interventions) and at the neurochemical and neurocircuitry levels to identify molecular species that could be used as targets for novel medications.

Research to date indicates that addiction treatment benefits most from the combination of medications (when available) and scientifically validated behavioral interventions. Support programs such as Alcoholics Anonymous can also help former drug abusers remain abstinent and offer social reinforcement, as well as motivation for behavioral change.

Finally, another important lesson we have learned about chronic relapsing diseases (e.g., asthma, diabetes) is that there is a high likelihood that patients will experience a recurrence or setback. This triggers the need for treatment to be reinstated or modified. The same approach must be applied to the treatment of addiction rather than concluding that a given course of treatment has failed because a patient has relapsed.

Similarly, the implications of this new knowledge for prevention efforts are enormous. The fact that genes, environment, and developmental stage all interact to play important roles in the onset, establishment, and trajectory of abuse and addiction means that effective prevention hinges on a multipronged approach that considers the individual in context and as a whole.

On another level, the knowledge that a person’s ability to make sound decisions changes with age and becomes impaired by many drugs of abuse should play a central role in our strategies to develop public health messages and programs. Therefore, the NIDA is particularly eager and committed to using the latest scientific technologies to better understand decision making and ascertain the key features of effective messages for different populations.

SWT: Can you briefly explain how environment affects addiction-related gene expression and function?

Volkow: We have known for many years that factors from the outside world can modify genetic output. Our environment can affect gene expression and its functional consequences directly or indirectly. We can cite a growing number of examples in which specific types of environmental exposure can affect gene expression directly by causing epigenetic changes, which are defined as distinct chemical modification to the building blocks of the DNA without changing its sequence. This phenomenon has been studied most extensively in the context of cancer development, but it also impacts the function of every cell in the periphery and in the brain.

In the context of drug abuse, it has been found, for example, that chronic cocaine administration to rats can cause epigenetic modifications to genes that influence drug-seeking behaviors or prime the animal for developing exaggerated responses to chronic cocaine use. There appears to be a balance in the level of epigenetic modifications to target genes such that too much or too little can become the signal to transition from an acute adaptive response to a chronic psychiatric illness.

There are many other stimuli—some environmental and some biological—that can trigger epigenetic changes with the potential to influence addictive behaviors. These include prenatal exposure to drugs of abuse or neurotoxic compounds, rearing conditions, parenting style, chronic stress or physical abuse, age, and the co-occurrence of other mental disorders.

But the environment can also modulate the functional consequences of specific genes in more indirect ways. One example is the ability of stressful early environments to increase the risk of impulsivity and antisocial behaviors later in life in individuals that carry the low expressing form of the monoamine oxidase, a gene. Some of the brain circuitry in these individuals is likely to have developed in ways that render them more vulnerable to the deleterious effects of chronic or extreme psychosocial stress. This example is very relevant to your question because we know that impulsivity and antisocial behaviors are often observed in sensation seekers, risk takers, and substance abusers.

SWT: What are the most important scientific advances that have directly affected substance abuse treatment and recovery programs?

Volkow: One of the most important advances in this regard has (or should have) derived from the convergent evidence showing that addiction is a chronic and relapsing disease. This knowledge must be used to erase the practice of punishing and banishing individuals who “slip up” in the course of treatment. Similarly, it’s becoming increasingly clear that simply withdrawing an addicted person from the drug or subjecting him or her to a 30-day detoxification protocol may not be sufficient to achieve lasting results since the brain changes induced by chronic drug abuse are likely to persist, underlying the continuing risk of relapse. Somewhat related to the cyclic nature of addiction is the realization that, contrary to common wisdom, patients don’t have to “hit bottom” to become amenable to treatment. In fact—just like for any other chronic disease—the opposite is true, with the best prognoses correlating with early intervention.

I would next list the overwhelming epidemiological evidence demonstrating that addiction is a developmental disease in the sense that most individuals who become addicted to drugs started using them during their preadolescent or adolescent period, when the brain undergoes dramatic structural and functional development. Therefore, early intervention and treatment for young people should be a high priority if we are committed to protecting some of the most vulnerable populations.

In the medications development arena, the creation of buprenorphine is worth highlighting as an important milestone. Buprenorphine is a recent addition to the array of medications now available for treating addiction to heroin and other opiates. This medication is different from methadone in at least two important ways. First, because of its distinct pharmacology (i.e., a partial agonist of Mu-opiate receptors), buprenorphine affords a significantly lower risk of overdose or addiction. Second, a specific formulation with reduced potential for diversion was developed that combines buprenorphine with a low dose of the opiate antagonist naloxone. When the medication is taken orally, as prescribed, the naloxone is without effect; however, if naloxone is injected, it can precipitate withdrawal symptoms, thus reducing its abuse liability. Indeed, unlike other opiates, the trendline for prevalence of buprenorphine abuse in the United States has remained essentially flat from the time it was introduced in 2002 to the present.

Finally, buprenorphine has one last but extremely important feature, which is that it can be prescribed in the privacy of a doctor’s office. This strategy appears to have paid off with a growing number of physicians becoming certified to prescribe it as a treatment for addiction.

SWT: What new medications are being developed to treat addictions, and how do they work?

Volkow: The NIDA uses a dual strategy to develop new drug abuse medications. The first, which relies on testing existing medications, is relatively less expensive because it focuses on compounds that have known safety profiles and are already FDA approved for other indications. For example, bupropion, a medication used for the treatment of depression and nicotine dependence, has been shown to inhibit the reuptake of monoamines (e.g., dopamine) and is now being evaluated as a treatment for methamphetamine addiction. Ondansetron, a serotonin receptor antagonist approved for reducing nausea, particularly in chemotherapy patients, is being tested in clinical trials as another possible medication to treat methamphetamine addiction. Another good example in this class is disulfiram, which produces an aversive reaction to alcohol but has also shown efficacy in several double-blind, placebo-controlled clinical trials exploring its possible use as a treatment for cocaine addiction.

The NIDA also implements a second, complementary strategy designed to translate scientific advances into better treatments by supporting researchers who investigate the therapeutic potential of totally new compounds and approaches. We have several examples in this category, such as compounds that act on the cannabinoid system that are being evaluated as possible treatments for marijuana addiction, vaccines and monoclonal antibodies developed to block the action of stimulants or nicotine even before they reach their targets in the brain, and promising novel compounds (heterodimeric opiate receptor protagonists) that target opiate receptors in a wholly different way, offering the possibility of better analgesia with reduced abuse liability.

SWT: How does this new scientific knowledge help us to treat those with co-occurring substance use and mental disorders?

Volkow: One fundamental principle that has emerged from the latest advances in addiction research is the need to treat comorbid drug addiction and other psychiatric disorders concurrently. Now, this can be challenging for several reasons:

• Different treatment systems address substance abuse and other mental illnesses separately. Whereas physicians are most often the front line of treatment for other mental disorders, drug abuse treatment is provided by a mix of healthcare professionals with different backgrounds and in assorted venues. Thus, neither system may be prepared to address the full range of problems presented by patients.

• There is a lingering bias in some substance abuse treatment centers against using any medications, including those necessary to treat other serious mental disorders such as depression.

In spite of these obstacles, steady progress has been made through evaluating how existing treatment options for either disorder fare when tested in comorbid populations. Also, several existing treatments have been modified for people with comorbid substance use and other mental disorders.

SWT: Is there resistance to this new information about addiction by the 12-step recovery community, treatment community, etc.?

Volkow: The drug abuse and addiction treatment community is very diverse; therefore, it would be impossible to provide an answer that applies to all situations. While some programs are embracing and utilizing the new information, others remain reluctant to implement or even experiment with changes to their protocols.

It follows that the NIDA is very interested in disseminating scientific information and educating the treatment community about its far-reaching therapeutic implications. Training community providers to deliver the research-based treatments is absolutely essential to their optimization and effective implementation. Efforts to systematically move science-based interventions and practices into community settings are occurring through the NIDA’s National Drug Abuse Treatment Clinical Trials Network, which involves practitioners from community treatment programs in formulating, adapting, and testing promising interventions. Moreover, this infrastructure is set up as an iterative process, in which information and results travel back and forth between research labs and treatment providers. The NIDA expects that this two-way communication pipeline will lead to more useful and widely accepted prevention and treatment strategies and better research questions.