What is This Thing Called Neuroplasticity?

And how does it impact addiction and recovery?

Bielefeld, Germany—

The first in an irregular series of posts about a recent conference, Neuroplasticity in Substance Addiction and Recovery: From Genes to Culture and Back Again. The conference, held at the Center for Interdisciplinary Research (ZiF) at Bielefeld University, drew neuroscientists, historians, psychologists, philosophers, and even a freelance science journalist or two, coming in from Germany, the U.S., The Netherlands, the UK, Finland, France, Italy, Australia, and elsewhere. The organizing idea was to focus on how changes in the brain impact addiction and recovery, and what that says about the interaction of genes and culture. The conference co-organizers were Jason Clark and Saskia Nagel of the Institute of Cognitive Science at the University of Osnabrück, Germany.

One of the stated missions of the conference at Bielefeld’s Center for Interdisciplinary Research was to confront the leaky battleship called the disease model of addiction. Is it the name that needs changing, or the entire concept? Is addiction “hardwired,” or do things like learning and memory and choice and environmental circumstance play commanding roles that have been lost in the excitement over the latest fMRI scan?

What exactly is this neuroplasticity the conference was investigating? From a technical point of view, it refers to the brain’s ability to form new neural connections in response to illness, injury, or new environmental situations, just to name three. Nerve cells engage in a bit of conjuring known as “axonal sprouting,” which can include rerouting new connections around damaged axons. Alternatively, connections are pruned or reduced. Neuroplasticity is not an unmitigated blessing. Consider intrusive tinnitus, a loud and continuous ringing or hissing in the ears, which is thought to be the result of the rewiring of brain cells involved in the processing of sound, rather than the sole result of injury to cochlear hair cells.

The fact that the brain is malleable is not a new idea, to be sure. Psychologist Vaughn Bell, writing at Mind Hacks, has listed a number of scientific papers, from as early as 1896, which discuss the possibility of neural regeneration. But there is a problem with neuroplasticity, writes Bell, and it is that “there is no accepted scientific definition for the term, and, in its broad sense, it means nothing more than ‘something in the brain has changed.’” Bell quotes the introduction to the science text, Toward a Theory of Neuroplasticity: “While many scientists use the word neuroplasticity as an umbrella term, it means different things to different researchers in different subfields… In brief, a mutually agreed upon framework does not appear to exist.”

So the conference was dealing with two very slippery semantic concepts when it linked neuroplasticity and addiction. There were discussions of the epistemology of addiction, and at least one reference to Foucault, and plenty of arguments about dopamine, to keep things properly interdisciplinary. “Talking about ‘neuroscience,’” said Robert Malenka of Stanford University’s Institute for Neuro-Innovation and Translational Neurosciences, “is like talking about ‘art.’”

What do we really know about synaptic restructuring, or “brains in the wild,” as anthropologist Daniel Lende of the University of South Florida characterized it during his presentation? Lende, who called for using both neurobiology and ethnography in investigative research, said that more empirical work was needed if we are to better understand addiction “outside of clinical and laboratory settings.” Indeed, the prevailing conference notion was to open this discussion outwards, to include plasticity in all its ramifications—neural, medical psychological, sociological, and legal—including, as well, the ethical issues surrounding addiction.

Among the addiction treatment modalities discussed in conference presentations were optogenetics, deep brain stimulation, psychedelic drugs, moderation, and cognitive therapies modeled after systems used to treat various obsessive-compulsive disorders. Some treatment approaches, such as optogenetics and deep brain stimulation, “have the potential to challenge previous notions of permanence and changeability, with enormous implications for legal strategies, treatment, stigmatization, and addicts’ conceptions of themselves,” in the words of Clark and Nagel.

Interestingly, there was little discussion of anti-craving medications, like naltrexone for alcohol and methadone for heroin. Nor was the standard “Minnesota Model” of 12 Step treatment much in evidence during the presentations oriented toward treatment. The emphasis was on future treatments, which was understandable, given that almost no one is satisfied with treatment as it is now generally offered. (There was also a running discussion of the extent to which America’s botched health care system and associated insurance companies have screwed up the addiction treatment landscape for everybody.)

It sometimes seems as if the more we study addiction, the farther it slips from our grasp, receding as we advance. Certainly health workers of every stripe, in every field from cancer to infectious diseases to mental health disorders, have despaired about their understanding of the terrain of the disorder they were studying. But even the term addiction is now officially under fire. The DSM5 has banished the word from its pages, for starters.

Developmental psychologist Reinout Wiers of the University of Amsterdam used a common metaphor, the rider on an unruly horse, to stand in for the bewildering clash of top-down and bottom-up neural processes that underlie addictive behaviors. The impulsive horse and the reflective rider must come to terms, without entering into a mutually destructive spiral of negative behavior patterns. Not an easy task.

Interview with Howard Shaffer of the Division on Addiction at Cambridge Health Alliance

Defining addiction, making research more transparent, and dealing with the DSM-V

(The “Five-Question Interview” series.)

Like many incredibly busy people, Dr. Howard J. Shaffer, associate professor of psychology at Harvard Medical School, is generous with his time. This paradox works to the advantage of Addiction Inbox readers, as Dr. Shaffer, the director of the Division on Addiction at the Cambridge Health Alliance, a Harvard Medical School teaching affiliate, has graciously consented to be the next participant in our “Five-Question Interview” series. In addition to maintaining a private practice, Dr. Shaffer has been a principal or co-principal investigator on a wide variety of research projects related to addiction, including the Harvard Project on Gambling and Health, and a federal research project focusing on psychiatric co-morbidity among multiple DUI offenders. He is the past editor of the Journal of Gambling Studies and the Psychology of Addictive Behaviors.


1. Addiction is not like most medical/mental disorders. If you have cancer or schizophrenia, for example, you can’t recover by abstaining from certain things. What’s your response to those who say that the disease model of addiction is misleading?

We should remember that the concept of disease is difficult to define. This makes deciding whether addiction is a disease most difficult. However, I think most people accept the idea that addiction reflects a kind of dis-ease. Whenever people get into this disease model debate, it’s useful to remember that most models of addiction are misleading, and the disease model is no exception. The map is not the territory, the menu is not the meal, and the diagnosis is not the disorder.

Scientific models are simplified representations of complex phenomena. Models of addiction focus our attention to certain features of addiction and blind us to other potentially important aspects of the disorder.1 For example, the moral model of addiction suggested that bad judgment was the cause and piety was the solution. Some neurobiological models of addiction suggest that molecular activity is the cause and medication is the solution. Both of these views are simplifications.

Rather than trying to fit addiction into a particular box, I prefer to think of addiction as a complex multidimensional syndrome – with interactive biological, psychological, and social causes. In this way addiction is similar to other medical, mental and behavioral disorders than we previously have considered. My colleagues and I have been developing a syndrome model of addiction 2-4 that suggests people are vulnerable because of biological, psychological and social influences. When vulnerable people are exposed to a social context that reliably and robustly shifts their subjective state in a desirable direction, they are at the highest risk for developing addiction. What I like about this kind of model is that it holds the potential to help us determine who is at most risk so that we can predict the development of addiction – just like we can predict who is at risk for cardiovascular and other diseases. This kind of etiological model will help us establish primary and secondary prevention programs that can reduce the onset of addiction.

2. You have a book coming out soon about problem gambling and how it can be managed. Is gambling a legitimate addiction?

Gambling, as well as most other behavior patterns, can become excessive, lead to adverse consequences, and squeeze out many previously important and healthy behavior patterns. 5,6 Some behavior patterns like eating broccoli rarely lead to addiction, but other improbable behaviors like listening to music, or playing video games might.

I don’t think about the idea of a “legitimate” addiction anymore, though I used to. Now I think about addiction as a unitary disorder that has a variety of expressions. For example, AIDS is a syndrome with many different expressions. Syndromes like AIDS and addiction are complex because not all of the signs and symptoms associated with the disorder are present all of the time. Gambling addiction is more rare than alcohol dependence. However, the characteristics of different expressions of addiction and the sequelae across sufferers are more similar than different. Further, the treatments – including the medications – that are effective with one expression of addiction often work with another expression. Scientific evidence suggests that behaviors, such as excessive gambling, and substance use, such as cocaine, have similar effects on the neurocircuitry of reward – how the brain processes information to produce the experience of pleasure.

For a pattern of behavior, whether substance involved or not, to be considered as an addiction, it must reliably and robustly shift subjective experience in a desirable direction, lead to adverse consequences, and be associated with identifiable underlying biological and psychological features, for example, genetic influences and trauma.

3. You host the Transparency Project. What is it and why did you create it?

The Transparency Project is the world’s first data repository for addiction-related industry-funded research. Most people don’t realize that private industry funds the majority of scientific research. This particular funding stream is important. However, tobacco industry funded research properly encouraged people to worry that private funding can adversely influence research. In fact, I think observers should worry about the potential bias that might accompany any research, including research supported by public funding sources. There is no warranty that can assure unbiased research, except sound methods and careful data analysis reflecting sound scientific principles. Furthermore, critics shouldn’t presume that research is biased just because it has a particular kind of funding source. We are encouraging scientists who have received industry funding to send their data to the Transparency Project so that others can download and use their data. This should magnify the value of the data by having others analyze it similarly or differently from the original research. This strategy also should help observers both confirm and question findings, thereby leading to important dialogues about the central issues that are so very important to the advance of scientific knowledge.

4. What’s going on right now at the Division on Addiction that you are particularly excited about?

During 2012, we are celebrating our 20th anniversary at the Division on Addiction. The syndrome model is emerging as an important conceptual guide to our work going forward; we are very excited to see that others are similarly interested in this perspective. Very soon, for example, the American Psychological Association will be releasing another of our new books, the APA Addiction Syndrome Handbook. I am also very excited about our DUI research 7-11 as well as our efforts to develop new technology that will help lay interviewers—those often staffing DUI treatment programs—to assess complex psychiatric disorders and triage patients into the care they so desperately need. This is our Computer Assessment and Referral System or CARS project. Lots of people around the world are expressing interest in coming to the Division to study and conduct research focusing on addiction. For me, it is very satisfying to see young people come to the field of addiction with a sense of curiosity, wonder and scientific rigor that have not always been present in this area of interest.


5. How do you feel about the proposed DSM-V changes regarding addiction?

By now, most people interested in addiction are aware that the American Psychiatric Association has expressed some interest in moving Pathological Gambling from the impulse control disorder category to a new Addiction and Related Disorders category. This would represent the first time that the term “addiction” appears in the DSM. If this happens, it is a big deal and, in my opinion, represents a step forward. In many ways it reflects a syndrome model perspective toward addiction. Although pathological gambling has clinical, epidemiological, etiological, physiological, and treatment commonalities with substance use disorders, my colleague Ryan Martin and I have noted that these similarities also exist among the substance use disorders and a variety of other behavioral expressions of addiction (e.g., excessive shopping). A relatively large literature evidences these commonalities. Consequently, we think that the DSM-V work group should avoid creating a long list of addictions and related disorders/diagnoses organized by the objects of addiction. Instead, the syndrome model of addiction encourages an addiction diagnosis that is independent of the objects of addiction, other than as a clinical feature. Diagnostic systems need to identify the core features of addiction and then illustrate these with substance-related and behavioral expressions of this diagnostic class. Conceptualizing addiction this way avoids the incorrect view that the object causes the addiction and shifts the diagnostic focus more sharply toward patient needs.

References

1. Kuhn TS. The structure of scientific revolutions. Second ed. Chicago: University of Chicago Press; 1970.
2. Shaffer HJ, LaPlante DA, LaBrie RA, Kidman RC, Donato AN, Stanton MV. Toward a syndrome model of addiction: multiple expressions, common etiology. Harvard Review of Psychiatry 2004;12:367-74.
3. Shaffer HJ, LaPlante DA, Nelson SE, eds. The APA Addiction Syndrome Handbook. Washington, D.C.: American Psychological Association Press; in press.
4. Shaffer HJ, LaPlante DA, Nelson SE, eds. The APA Addiction Syndrome Handbook. Washington, D.C.: American Psychological Association Press; in press.
5. Shaffer HJ, Martin R. Disordered Gambling: Etiology, Trajectory, and Clinical Considerations. Annual Review of Clinical Psychology 2011;7:483-510.
6. Shaffer HJ, Korn DA. Gambling and related mental disorders: a public health analysis. In: Fielding JE, Brownson RC, Starfield B, eds. Annual Review of Public Health. Palo Alto: Annual Reviews, Inc.; 2002:171-212.
7. Albanese MJ, Nelson SE, Peller AJ, Shaffer HJ. Bipolar disorder as a risk factor for repeat DUI behavior. Journal of Affective Disorders in press.
8. LaPlante DA, Nelson SE, Odegaard SS, LaBrie RA, Shaffer HJ. Substance and psychiatric disorders among men and women repeat driving under the influence: offenders who accept a treatment-sentencing option. Journal of Studies on Alcohol and Drugs 2008;69:209-17.
9. Nelson SE, Laplante DA, Peller A, Labrie RA, Caro G, Shaffer HJ. Implementation of a Computerized Psychiatric Assessment Tool at a DUI Treatment Facility: A Case Example. Administration and Policy in Mental Health and Mental Health Services Research 2007;34:489-93.
10. Peller AJ, Najavits LM, Nelson SE, LaBrie RA, Shaffer HJ. PTSD Among a Treatment Sample of Repeat DUI Offenders. Journal of Traumatic Stress in press.
11. Shaffer HJ, Nelson SE, Laplante DA, Labrie RA, Albanese M, Caro G. The epidemiology of psychiatric disorders among repeat DUI offenders accepting a treatment-sentencing option. Journal of Clinical and Consulting Psychology 2007;75:795-804.

Essay: The Genuine Drug War is in Biomedicine

Knowledge, not firepower, is the key to the future.

In modern American society, heart disease, cancer, HIV\AIDS, diabetes, alcoholism, and cigarette addiction account for millions of deaths. They are all disease entities with strong psychological and behavioral components—complicated, multicellular, multi-organ disorders. But they have all been associated, at one time or another, with negative personality traits and moral flaws. The less we know about the mechanics of a human disorder, the more likely we are to view its external symptoms as signs of laziness, or neuralgia of the spirit, or as a form of damage caused by specific kinds of thoughts and emotions. Without a doubt, all kinds of flaws are sometimes expressed in the behavior of people who have these disorders. Yet none of these flaws can be considered the root cause of the diseases.

Addiction is being added to the roster of physical disorders once thought to be symptoms of insanity, but which are now seen to be disease entities with strong mental components, like most diseases. As Professor Felton J. Earls of the Harvard School of Public Health argued almost twenty years ago: “Until we have an Institute of Addictive Behaviors, we are not going to get very far on the public-policy issues because we will not have our science-policy issues properly aggregated and organized in order to move forward on the issues in any meaningful way.”  Witness the tangle over merging NIDA and the NIAAA, and you’ll have a good idea of how far we still have to go in this respect.

The genuine drug war is being fought in the arena of biomedicine. The New York State Division of Substance Abuse Services in Albany  estimated several years ago that the annual bill for successfully treating a single drug addict is $3,850, compared with $14,000 in estimated annual expenses— health, welfare and law enforcement costs—associated with one untreated addict. The real crisis is the indisputable fact that there exists today an appalling shortage of funds for biomedical research—ironically one of the fields of scientific endeavor in which the U.S. holds a clear lead.

The cause of the dilemma is a fundamental misunderstanding among politicians and the public about how diseases can be understood and conquered. Cross-fertilization among scientific disciplines yields unexpected results. Targeted research, such as the much-ballyhooed war on cancer, or the crash program to find a cure for A.I.D.S., is not necessarily the most desirable way to proceed. Insights come from unexpected places, in serendipitous ways. As the scientific understanding of cells and receptors deepens, diseases and disorders once thought to have unrelated causes are seen to have common and entirely unanticipated origins. Research into the viral mechanisms of the common cold may ultimately yield more insights into AIDS then all of the directed research now underway. In biomedicine, there is no guarantee that goals can be reached through the front door, by a systematic assault akin to an engineering project. We cannot, for example, hope to cure addiction, or even the common cold, by means of the same methods we used to put a man on the moon.

There are, however, certain things we can begin to do immediately, if, as a nation, we are serious about drug abuse. As a society, Americans have not done a very good job of laying the groundwork for an objective look at addiction and recovery. To begin with, we must attend to the staggering number of drug-related deaths, injuries, and hospitalizations caused by the abuse of prescription medications. The government itself has proven the case for this contention in numerous reports issued by the National Institute on Drug Abuse and other official bodies. According to the U.S. Department of Health and Human Services, “Older Americans account for more than half of all deaths from drug reactions,” leading one to suspect that the majority of drug fatalities stem from accidentally fatal overdoses by heavily medicated senior citizens. Our national fixation on illegal drugs has blinded us to certain verifiable facts about prescription drug abuse.

We also need to recognize the problem of underprescribing opiates and other addictive painkillers for children and adults in hospital settings. If we continue to stringently prohibit the use and sale of synthetic and designer drugs like methadone, morphine, amphetamines, and barbiturates, we will have to make one important exception: pain abatement in medical applications. One of the great scandals to come out of the drug war is the growing understanding that potent painkillers are not being offered in sufficient amounts to patients suffering intractable and agonizing pain.

“There’s a certain amount of hysteria about narcotics among doctors,” maintains one researcher. At least half of all cancer patients seen in routine practice report inadequate pain relief, according to the American College of Physicians. For cancer patients in pain, adequate relief is quite literally a flip of the coin.

At least 6 million cancer and AIDS patients currently receive no appropriate pain treatment of any kind. In addition, WHO estimates that four out of five patients dying of cancer are also suffering severe pain. The numbers of untreated patients suffering intractable, unrelieved pain from nerve damage, burns, gunshots, sickle cell anemia, and a host of other medical conditions can only be guessed at.

Figures gathered by a different U.N. agency, the International Narcotics Control Board, make clear that “citizens of rich nations suffer less.” To put it starkly, the use of morphine per person in the United States is 17,000 times higher than per person usage in Sierra Leone. Doctors in Africa paint a grim picture of patients hanging themselves or throwing themselves in front of trucks as an alternative to life without pain relief. The U.S., Canada, Britain, France, Germany, and Australia together account for roughly 80 per cent of the world’s medicinal morphine use. Other countries, particularly the poor and undeveloped nations, scramble for what’s left.

In many cases, pain relief is the one thing doctors can offer their patients, and the one thing they withhold.

--Adapted from The Chemical Carousel, by Dirk Hanson

Photo Credit: http://www.eurac.edu 

Who Controls Addiction Research?

The ongoing merger wars at the NIH.

As researchers await the National Institute of Health director’s decision on the matter of merging the nation’s two major addiction research agencies, interested parties to the dispute continued to wonder whether the alcoholic beverage industry will weigh in on the matter—with cash.

The National Institute on Drug Abuse (NIDA) and the National Institute on Alcohol Abuse and Alcoholism (NIAAA) exist within the large institutional framework of the National Institutes of Health (NIH), and operate under mandates that overlap enough to make them prime candidates for a cost-saving consolidation. Advocates of the merger, most of them advocates for NIDA, also suggest that the research itself will improve as a result of a decrease in “overlapping missions.” (See my earlier post.)

Recently, Nature News suggested the possibility of efforts against the merger from another interested party: “Although the alcohol industry is unlikely to relish its legal product being lumped in for study with street drugs such as cocaine and heroin, it has so far remained silent. US Trade groups including the Beer Institute, the Wine Institute, the American Beverage Institute and the Distilled Spirits Council of the United States all declined to comment for this article.”

DrugMonkey, an anonymous NIH-funded researcher, has noted on his blog: “I’m still betting [the beverage industry’s] entire strategy (if they actually care about this, which I suspect they do) is going to be by trying to get a pet Congress Critter or two to oppose the plan. Spirited opposition can probably block the whole plan.”

 DrugMonkey even notes that by one common yardstick—recent success rates for grant applicants—NIAAA has actually put up better numbers than its larger cousin, NIDA, “something that NIAAA people have been quietly bragging about for the past several years.”

There have been other rumblings. Behind the scenes, some NIAAA proponents have criticized NIDA’s Nora Volkow for what they see as a heavy-handed attempt on her part to steamroll any opposition to the merger.  The battle lines were clearly drawn earlier this year when Volkow testified before the Scientific Management Review Board. Quoted in the NIH Record, a National Institutes of Health publication, Volkow said that “all psychiatric disorders have similar roots involving combinations of genes and environment…. it is a serious problem, a devastating problem, whether you are talking about alcohol or drugs.”  The NIDA director also said she was “impatient” with progress on the matter, arguing that the separation of resources had already resulted in missed research opportunities. “Why put roadblocks in the way of treatment and prevention?”

At the same meeting, acting NIAAA director Dr. Kenneth Warren offered up what has come to be seen as the basic counter-argument: “The best way forward is a structure that increases collaboration all across NIH… nothing is gained by structural merger.” Warren said he favored “a separate, but equal” pair of agencies. “Alcoholism is a much broader issue than simply addiction.”

Here is where it starts to get tricky. The assertion that alcoholism is not simply an addiction distills the disagreement down to its essence, which can be found not so much within the arena of science as within the arenas of morality, ethics, and the law. NIH Director Francis Collins told Science (sub. required): “Alcohol is after all a legal substance and 90% of us at some point in our lives are comfortable with taking it in while the drug abuse institute is largely focused on drugs that are not legal.”

As Maia Szalavitz wrote at TIME Healthland:

There's another, somewhat moralistic argument for keeping the institutes separate. As Dr. Deborah Hasin argued at a February national advisory meeting on the question, “[There is] a need for a public health message more nuanced for alcohol than for drugs, including nicotine. In contrast with drugs, light drinking is not “bad.'’ It was a curious statement from a scientist who is supposedly charged with studying the effects of psychoactive substances objectively.

Does the NIAAA really have any solid, science-based arguments against the creation of a combined research agency?

Just ask them. Officially, the NIAAA has a very long list of reasons why they are just saying no to the merger—which looks, from the NIAAA point of view, more like an acquisition, anyway. Here are some of acting director Warren’s arguments, taken from an appendix to the minutes of the February 3-4 meeting of the National Advisory Council to the NIAAA, over which Warren presided:

--Alcohol use disorders are different than drug addiction. "The genetics of alcoholism differs from the genetics of drug addiction. Prospective studies have shown that the sons of alcoholics are at greater risk for alcoholism than for drug dependence.”

--The existence of certain commonalities in the brain pathways that mediate the rewarding effects of alcohol and other drugs of abuse does not justify the merger of NIAAA and NIDA. "The fact that dopamine is an important neurotransmitter in signaling reward associated with motivational stimuli does not provide a strong rationale for merging institutes.”

 --Most people with AUDs (alcohol use disorders) do not abuse other drugs.  “The large size of the population with AUDs who don’t abuse other drugs and the enormous public health burden of their illness justify NIAAA’s focused approach to research on AUDs, separate from drug dependence.”

--Alcohol differs from other drugs of abuse in the degree to which heavy use damages the brain and other organs. "Alcohol damages multiple organ systems through common mechanisms of toxicity, including oxidative stress, the disruption of critical cell signaling systems, and the generation of toxic metabolites, cytokines, and chemokines. The coordinated study of these multiple organ toxicities is best suited to a single alcohol Institute.”

--The systems approach is essential to the study of alcohol beneficial and adverse effects. "The merger of NIAAA with NIDA to form a new Institute focused on addiction would orphan and dissociate critical programs focused on alcohol and cardiovascular health, liver disease, pancreatitis, fetal alcohol spectrum disorders, immune disorders, myopathy, neuropathy, and brain disorders.”

Almost all of these contentions are open to debate. I believe some of them are just plain wrong. Nonetheless, the notion that a merger of two or more sprawling federal agencies will automatically streamline and strengthen government operations is equally open to question (See Department of Homeland Security). 

But the greater weight of logic, it seems, continues to tip the argument in the direction of a merger. Legal or illegal should have very little to do with it. David Rosenbloom, director of Join Together, said in an excellent article by Bob Curley that a single NIH addiction institute could “yield important science and public health benefits.”

Rosenbloom added that “many individuals with addiction use alcohol and tobacco and drugs at the same time. A broad addiction institute may be better able to design and sponsor clinical, basic, and health services research that matches this real-world reality instead of focusing on just one substance at a time.”

NIH Turf Wars

Combining Addiction Agencies.

For nearly a decade, the idea of combining the federal government’s two primary addiction research institutes has made good sense. Recently, an independent panel officially recommended a merger—but alcohol researchers opposed the notion, as they have in the past.

The National Institutes of Health, the nation’s premier biological research institution, is composed of 27 separate medical institutes, each fighting for its share of funding and recognition under the larger umbrella of the parent organization. If this seems like an unwieldy arrangement, that’s because it is. Duplication and overlap is inevitable in as vast an enterprise as the NIH. Yet the arrangement has produced some of the best medical and biological research in the world.

Former NIH director Harold Varmus complained, according to ScienceInsider (Sub req) “that the sprawl hobbles NIH’s ability to respond to new science.” The most obvious case for streamlining and cost-savings has always been the National Institute on Drug Abuse (NIDA) on the one hand, and the clumsily named National Institute on Alcohol Abuse and Alcoholism (NIAAA) on the other.

In 2006, Congress told the NIH to create the Scientific Management Review Board to recommend ways of overhauling the NIH structure. The obvious place to start was with the two overlapping addiction institutes.

It was not a new idea. In 2003, the National Academy of Sciences (NAS) recommended merging the agencies due to “overlapping missions.” Enoch Gordis, then director of the NIAAA, was adamantly opposed to the idea, and the undertaking fell away.

Recently, the Scientific Management Review Board of the NIH voted 12-3 in favor of the merger, and sent the proposal to the desk of NIH director Francis Collins. However, the board also recommended an outside search for a director, thereby eliminating current NIDA director Norah Volkow from consideration. Dr. Volkow has been an active and public advocate for addiction awareness. An obvious choice to head the combined institute, provisionally known as the National Institute on Addiction, she would be a significant loss to the NIH. A spokesperson for Dr. Volkow would only offer NIDA’s official stance on the matter: “NIDA’s position has always been that we should create an organizational structure that best serves the science of addiction. We appreciate the thoughtful process that preceded the Board’s recommendation, and we look forward to hearing about a final decision soon.”

For years, NIAAA supporters had a ready answer when asked what made their agency different from NIDA: the liver. NIAAA did research on the liver and other organs and metabolic processes involved in metabolizing alcohol. But over the past two decades, the meaningful research coming out of NIDA has been the primary focus for most addiction researchers. NIDA’s forceful and forward-thinking director, Norah Volkow, followed an equally outspoken director, Alan Leshner. At NIAAA, the most recent director, Dr. T.K. Li, came to the institute after a distinguished career as an alcohol researcher at the University of Indiana. Dr. Li recently retired and the position is being filled on an interim basis by acting director Kenneth Warren.

NIAAA has always been the weaker sister in the addiction research family. With only half of NIDA’s billion-dollar budget, NIAAA deals strictly with alcohol research, even if the NIAAA has at times seemed unsure of what constitutes its main area of study—alcohol the addictive drug, or alcohol the healthy beverage. The merger would represent a recognition that alcohol is just another drug, albeit a legal one.

However, in a Science (sub req) interview, Francis Collins, the current director of the NIH, noted that the advisory board was “not able to come to a consensus” on the NIDA-NIAAA merger. “I guess most people would have said, ‘Well yeah, of course.’ But when you look at the details…. and you consider that alcohol is after all a legal substance and 90% of us at some point in our lives are comfortable with taking it in while the drug abuse institute is largely focused on drugs that are not legal. So there's a personality of the institute issue here that people thought might be important to preserve, others thought would be good not to preserve.”

The director’s remarks reflect the turf protection responses that this seemingly straightforward move invokes. An article by Bob Curley at Join Together notes that last year, the advisory board “voted unanimously in favor of studying the merger despite the fact that every group and individual testifying live at the hearing opposed combining the two agencies.”

Every group and individual? Curley quotes Lawrence Tabak, former acting deputy director of NIH, who minimized the likelihood of significant cost savings, and said, “there are also some issues that NIAAA deals with that are not ‘addictive’ in nature, such as binge drinking.” Representatives from the Research Society on Alcoholism and the American Association for the Study of Liver Diseases said that NIAAA’s harm reduction approach to alcohol use was “fundamentally at odds with NIDA’s focus on illegal drugs.” The National Association of Addiction Treatment Providers also opposed the merger, citing fears of a “loss of focus” on the problems unique to alcohol.

Beyond the official testimony, many prominent drug addiction experts feel differently. “The basic biology of drug abuse and addiction are highly overlapping for all drugs of abuse,” according to Eric Nestler of the department of neuroscience at the Mount Sinai School of Medicine. “There’s a huge confusion—not only among the lay public but among some treatment providers too—that alcohol is ‘not a drug,’” he said in the Join Together article. “This is absurd, yet the current separation of alcohol into a separate institute provides credence to that notion.”

According to noted addiction researcher Charles O’Brien of the University of Pennsylvania’s department of psychiatry, “There’s no scientific rationale to have a separate institute for a single drug. Ethanol activates the reward system similar to opioids and other abused drugs using different mechanisms to act on the same structures.” In addition, O’Brien notes that most addicts use more than one drug, but that NIAAA funding limit researchers to projects for “pure alcoholics, despite the reality of the clinical populations.”

The dual agencies, by their very existence, imply that addiction to alcohol and addiction to other drugs are wholly separate spheres of inquiry and investigation—a notion damaging to scientific research and public health. The primary hurdle to the merger is political, not scientific.

On the face of it, the merger makes sense, and in fact is long overdue. To keep these agencies separate means continuing to perpetuate the myth that there is something crucial that separates alcoholism from drug addiction. And there isn’t. Treating alcoholism and alcohol abuse as a syndrome somehow apart from drug abuse and addiction is outdated and unwarranted. We know too much now about both conditions to maintain the pretense.

As DrugMonkey, a pseudonymous science blogger funded by the NIH, summed it up: “If Institutes are to be merged than NIDA/NIAAA is at the very top of the list. If these cannot be merged then I do not see how any other mergers can be accomplished.”

Graphics Credit: http://www.hbcprotocols.com/nihfunds.html

Drug Research and the Recovery Act of 2009

What's in the budget for addiction scientists?

Scientists were among the likely beneficiaries of President Obama’s American Recovery and Reinvestment Act of 2009.

The National Institutes of Health (NIH) is slated to receive $10 billion for use over the next two years. A yet-to-be-determined portion of the grant will end up with the National Institute on Drug Abuse (NIDA).

Here is a sampling of NIDA’s wish, or “Challenge Topics” for which the agency is seeking grant proposals. The application due date is April 27, 2009.

--Dietary treatment of substance disorders.
“There is abundant preclinical and clinical evidence that suggest dietary therapies and behavioral interventions can promote neurogenesis, diminish susceptibility to metabolic and excitotoxic injury (e.g., diets rich in antioxidants), and/or counteract stress responses within the brain. Dietary regimens or supplements can be evaluated as individual treatments or as adjuncts to FDA-approved medications.”

--Drug genetics and informed consent.
“Address ethical issues related to access to broad sharing and use of new genetic information and technologies for addiction research to improve treatment and prevention options for addicts.”

--Addiction drugs combined in treatment.
“Network biological analysis predicts that modification of a single target by a drug is not nearly as likely to affect disease outcome as would rational combinations of drugs that target multiple, complementary mechanisms. Applications will focus on combination of medication strategies for the treatment of substance use disorders.”

--Neurobiology of opioid addiction.
“There is an urgent need for research that will more thoroughly delineate the neurobiological implications of long-term opioid use. This knowledge gap is of particular concern when it comes to the developing brain - and the urgency is underscored by the fact that increasing numbers of adolescents and young adults are using opioid medications, prescribed and otherwise.”

--Research on addiction drugs for pregnant women.
“Substance abuse during pregnancy often occurs in the context of complex environmental factors and poly-drug exposure, as well as medical conditions which are associated with adverse neonatal consequences. Much is known in regard to the negative effects of substances of abuse on the pregnant/post partum women and their substance exposed neonates but relatively little is known in regard to medication treatment strategies and research methodology.”

--Internet-based prevention and treatment in rural locations.
“Many persons living in remote or rural locations have limited opportunities to obtain drug abuse treatment services, due to a lack of available service settings, the barrier of traveling long distances, and/or the perceived lack of private and confidential treatment options. This program seeks to develop web-based drug abuse treatment interventions that do not necessitate frequent in-person visits to a central facility.”

--Finding new molecular targets for addiction treatment drugs.
“Projects may utilize techniques ranging from gene knockout technologies, behavioral evaluations, assay development, and targeted library synthesis and screening that could lead to the development of medications for drug addiction treatment. The focus may be on the identification of new molecular targets, and/or the discovery of small molecule selective ligands for previously identified targets, such as muscarinic M5 antagonists, neuropeptide Y antagonists, and neurotensin agonists.”

For general information on the National Institute on Drug Abuse implementation of NIH Challenge Grants, contact:

Christine Colvis, Ph.D.
NIDA Challenge Grant Program Coordinator
National Institute on Drug Abuse
National Institutes of Health
Phone 301-443-6480
Email ccolvis@nida.nih.gov


Photo Credit:www.ecampusnews.com

addictiondrugs

Addiction Research Highlights

Clinical studies in 2008.

Alcohol, Other Drugs, and Health: Current Evidence—a free online newsletter from the Boston Medical Center—offers summaries of relevant clinical research on drugs of abuse and related drug issues.

In the November-December 2008 issue, the editors present “a comprehensive guide to all the clinically relevant research articles published by the newsletter in 2008.”

Herewith, a brief sampling:

Topiramate Reduces Drinking in Adults With Alcohol Dependence

“Topiramate may decrease alcohol consumption among people with alcohol dependence by reducing the release of dopamine.”

Treatment for Alcohol Withdrawal Is Poor Despite Proven Therapies

“Evidence-based practice guidelines are clear that patients at risk for alcohol withdrawal should be monitored and treated with benzodiazepines if the risk is high enough or symptoms are substantial.”

Oral Naltrexone Decreases Use and Extends Time to Relapse in Amphetamine Dependent Patients

“Currently, no medications are FDA-approved to treat amphetamine dependence. Naltrexone, an opioid antagonist, has shown efficacy in reducing relapse among subjects with opioid or alcohol dependence.”

Alcohol Counseling Can Reduce Blood Pressure

“Unhealthy alcohol use is associated with hypertension. Two recent articles examined whether reductions in drinking can decrease blood pressure among hypertensive heavy drinkers.”

Levetiracetam (Keppra) Shows Promise in Treating Alcohol Dependence

“Anticonvulsants have shown promise as pharmacologic agents in the treatment of alcohol dependence, although none are yet approved by the Food and Drug Administration for this indication.”

Are Myocardial Infarction Survivors Who Smoke Marijuana at Higher Risk of Death?

“Although a previous study demonstrated an increased risk of myocardial infarction (MI) within 1hour of smoking marijuana compared with periods of nonuse, the net impact of marijuana use on mortality has not been established.”

American Heart Association Releases Guidelines on Treatment of Cocaine-Associated Chest Pain

“There are approximately 500,000 cocaine-associated emergency department visits annually, and it is estimated that 40% involve chest pain.”

Opioid Maintenance Therapy Saves Lives

“Opioid-dependent patients are 13 times more likely to die than their age- and sex-matched peers in the general population.”

Bupropion Added to Nicotine Replacement for Patients in Alcohol Treatment

“The effectiveness of bupropion, an antidepressant approved for smoking cessation in the general population, has not been studied in people being treated for alcoholism.”


Photo Credit: Brief-TSF.com