Addressing Criticisms of the Disease Model

Volkow, Koob, and McLellan on the neurobiology of addiction.

The New England Journal of Medicine recently published a review article, “Neurobiologic Advances from the Brain Disease Model of Addiction,” authored by three prominent figures in the field of addiction research: Nora Volkow, the director of the National Institute of Drug Abuse (NIDA); George Koob, the director of the National Institute of Alcohol Abuse and Alcoholism (NIAAA); and Thomas McLellan, founder and chairman of the Treatment Research Institute in Philadelphia.  The article summarizes the research that has “increasingly supported the view that addiction is a disease of the brain,” and concludes that “neuroscience continues to support the brain disease model of addiction.”

The implications of this, say the authors, are straightforward: “As is the case in other medical conditions in which voluntary, unhealthful behaviors contribute to disease progression (e.g., heart disease, diabetes, chronic pain, and lung cancer), evidence-based interventions aimed at prevention, along with appropriate health policies, are the most effective ways of changing outcomes.”

And some of the implications are immediate: “A more comprehensive understanding of the brain disease model of addiction many help to moderate some of the moral judgement attached to addictive behaviors and foster more scientific and public health-oriented approaches to prevention and treatment.”

In a supplementary appendix, the authors address some of the common criticisms of the disease model of addiction, and offer counter-arguments. The quotes below are excerpted directly from the appendix.

—Most people with addiction recover without treatment, which is hard to reconcile with the concept of addiction as a chronic disease.

This reflects the fact that the severity of addiction varies, which is clinically significant for it will determine the type and intensity of the intervention. Individuals with a mild to moderate substance use disorder, which corresponds to the majority of cases, might benefit from a brief intervention or recover without treatment whereas most individuals with a severe disorder will require specialized treatment

—Addicted individuals respond to small financial rewards or incentives (contingency management), which is hard to reconcile with the notion that there is loss of control in addiction.

The demonstrated effectiveness of contingency management shows that financial cues and incentives can compete with drug cues and incentives – especially when those financial incentives are significant and relatively immediate; and when control has been simply eroded rather than lost. Contingency management is increasingly being utilized in the management of other medical disorders to incentivize behavioral changes (i.e., compliance with medications, diets, physical activity).

—Gene alleles associated with addiction only weakly predict risk for addiction, which is hard to reconcile with the importance of genetic vulnerabilities in the Brain Disease Model of Addiction.

This phenomenon is typical of complex medical diseases with high heritability rates for which risk alleles predict only a very small percentage of variance in contrast to a much greater influence of environmental factors (i.e., cirrhosis, diabetes, asthma, cardiovascular disease). This reflects, among other things, that the risk alleles mediate the response to the environment; in the case of addiction, the exposures to drugs and stressful environments.

Overlaps in brain abnormalities between people with addiction and control groups raises questions on the role that brain abnormalities have on addiction.

The overlap is likely to reflect the limitation of currently available brain imaging techniques (spatial and temporal resolutions, chemical sensitivity), our limited understanding of how the human brain works, the complexity of the neurobiological changes triggered by drugs and the heterogeneity of substance use disorders.

Treatment benefits associated with the Brain Disease Model of Addiction have not materialized.

Medications are among the most effective interventions for substance use disorders for which they are available (nicotine, alcohol and opiates). Moreover, progress in the approval of new medications for substance use disorders has been slowed by the reluctance of pharmaceutical companies to invest in drug development for addiction.

Benefits to policy have been minimal.

The Brain Disease Model of Addiction provided the basis for patients to be able to receive treatment for their addiction and for insurances to cover for it. This is a monumental advance in health policy. The Brain Disease Model of Addiction also provides key evidence-based science for retaining the drinking age at 21 years.

NIH Director Calls Off NIDA-NIAAA Merger

Nation’s addiction research institutes to remain separate but unequal.

Two years ago, the National Institutes of Health’s Scientific Management Review Board (SMRB) issued a report recommending that NIH move to establish a new institute focused on substance use, abuse, and addiction-related research to optimize NIH research in these areas. The idea was to combine the two existing addiction research agencies: the National Institute on Drug Abuse (NIDA) and the National Institute on Alcohol Abuse and Alcoholism (NIAAA). Skeptics like myself wondered if it would ever happen.And now we have our answer—no, it’s not going to happen. (NIH'S Collins)-->

Score one for the alcohol researchers, who mostly opposed the merger from the start, viewing it as more of a hostile takeover. 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 have represented a recognition that alcohol is just another drug, albeit a legal one.

It was an obvious thing to do. Former NIH director Harold Varmus had complained that the sprawl was hobbling NIH’s ability to “respond to new science.”

However, in a Science (sub req) interview that year,  Francis Collins, the current director of the NIH, said: “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.”

It did not take long for the fraternity of alcohol researchers to view the potential move with alarm. 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.

On Friday, the traditional time for troubling news announcements in the media world, the NIH released its statement  from Director Collins: “After rigorous review and extensive consultation with stakeholders, I have concluded that it is more appropriate for NIH to pursue functional integration, rather than major structural reorganization, to advance substance use, abuse, and addiction-related research.”

Collins added: “The time, energy, and resources required for a major structural reorganization are not warranted, especially given that functional integration promises to achieve equivalent scientific and public health objectives.”

 But the smooth and cost-effective advance of addiction science may have met a stumbling block in the director’s refusal to do the obvious, and streamline the crucial research on drugs and addiction performed by the nation’s premier medical research agency, the NIH. As one observer commented,  there are rumors that “the alcohol beverage industry is lobbying Kentucky politicians, including U.S. Rep. Hal Rogers, chairman of the House Appropriations Committee, to keep the institutes separate because it doesn’t want alcohol to be associated with cocaine.”

Alcohol Researchers Still Wary of Combined Addiction Institute

 
Why can’t we all just get along?

A long time ago, an intrepid institutional director named Francis Collins promised his minions (as former NIH director Harold Varmus had promised his) that he would unite the nation’s two mighty addiction research bodies, The National Institute on Drug Abuse (NIDA) and the National Institute on Alcohol Abuse and Alcoholism (NIAAA), for the greater good of the entire kingdom—researchers and taxpayers alike.

Hasn't happened yet. 

Existing within the large institutional framework of the National Institutes of Health (NIH), the two agencies overlap sufficiently to make them prime candidates for a 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.”

However, as I wrote in 2010, the NIAAA has a long list of reasons why the merger—which looks, from the NIAAA point of view, more like an acquisition—is a bad idea. Alcohol use disorders are different than other drug addictions, researchers at NIAAA commonly propose. The genetics of alcoholism differs from the genetics of drug addiction, they say, and most people with “alcohol use disorders” don’t abuse other drugs. Furthermore, alcohol damages the brain and other organs in a consistent pattern “best suited to a single alcohol institute,” according to the NIAAA’s acting director.

At this stage, NIAAA’s heel dragging is patently obvious. The agency 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.

In a recent issue of Addiction Professional, Alison Knopf writes that “the alcoholism research field, which believes it would lose out under such a definition, is still fighting the reorganization. And some openly question whether the ‘merger’ ever will come to pass at all.”

Among the many unanswered questions are these, says Knopf: "The current portfolios for AIDS, fetal alcohol syndrome (FAS), liver disease and smoking—where the most money is at the two institutes—may or may not stay within the new institute. Also unknown to many is whether the new institute will cover all addictions (including those such as food and gambling) or will be devoted to the health effects of alcohol and drugs only."

The dark mutterings among alcohol researchers get even more specific in Knopf’s article. In one scenario, Fetal Alcohol Syndrome (FAS) “would go to the National Institute of Child Health and Development, liver disease and the entire organ damage portfolio would go to the National Institute of Diabetes & Digestive & Kidney Diseases, and cancer-related research would go to the National Cancer Institute (NCI). What would happen to drunk driving research is still unknown.”

Furthermore, “NIDA is worried about losing its AIDS funding, because it represents one-third of the institute’s budget.”

The NIH Substance Use, Abuse, and Addiction (SUAA) task force continues to wrestle with the question, which was originally to be decided by the end of the year. In the end, Knopf writes, one persistent rumor has stayed alive: The notion that “the alcohol beverage industry is lobbying Kentucky politicians, including U.S. Rep. Hal Rogers, chairman of the House Appropriations Committee, to keep the institutes separate because it doesn’t want alcohol to be associated with cocaine.”

Graphics Credit: http://www.puzzlemachine.com

NIDA’s Volkow Defends New Medications for Addiction

On Big Data, Big Vaccines, and a Big New Agency.

In her Director’s Report to the 2011 meeting of the College on Problems of Drug Dependence in San Diego last week, Dr. Nora Volkow, director of the National Institute on Drug Abuse, sought to refute allegations that NIDA lately has been too focused on pharmacological approaches to treating addiction—“magic bullets” in the form of pills or vaccines. Dr. Volkow presented figures showing, as the CPDD Community Website reported, that “NIDA funding allocation for new medication development has remained stable at about 12% for some time, despite concerns expressed by some researchers that funding in other areas is being sacrificed to support the medication development portfolio.” Basic and clinical neuroscience research accounts for 45% of expenditures, she said.

In other news, Volkow expressed her avid interest in the possibilities presented by so-called “big dataset science”—the act of pooling together huge amounts of data in order to generate greater statistical power. She traced a set of disciplines—genetics, epigenetics, proteomics, brain imaging, clinical data, and systems biology—and said that the NIH’s Working Group on Data and Informatics  was seeking systematic ways of integrating and analyzing large biomedical datasets in these crucial areas.

As for treatment, the current emphasis is on stimulants. Volkow said that work continues on finding reliable antagonist drugs to combat the dopamine disruptions promoted by active drug abuse. She suggested that work on buspirone, the D3 receptor antagonist and partial serotonin 5HT agonist used to treat generalized anxiety disorder, has shown that it may reduce cocaine self-administration in rhesus monkeys. This would be of considerable clinical interest, since addiction medicine presently has no effective drug treatments to offer for stimulants like cocaine and methamphetamine. A large clinical study now underway is showing that buspirone blocked D3 receptors in monkey brains in a way that reduced their interest in cocaine.

And she referred to the failed promise of NicVax, the short-lived vaccine for cigarette addiction. The treatment “failed to meet the primary endpoint in Phase II trials.” In other words, it flunked out. Only 30% of addicted smokers developed sufficient antibodies from NicVax to do them any good. But she cited new research on an alternative approach to vaccines, including a new cocaine vaccine (dAd5GNE) shown to be effective in reducing cocaine addiction-related behaviors in rats through the long-term blockade of dopamine transporters.

In a related approach to producing a reliable anti-cocaine antibody, researchers in the Department of Genetic Medicine at Weill Cornell Medical College went to work on “an adeno-associated virus (AAV) gene transfer vector as the delivery vehicle to persistently express an anti-cocaine monoclonal antibody in vivo, which would sequester cocaine in the blood, preventing access to cognate receptors in the brain.” An AAV is a small virus that is infectious but not pathogenic in humans. You might have it right now, but wouldn’t know it, since AAV doesn’t cause disease. So, the researchers used an AAV to build a transporter mechanism for their monoclonal antibody, GNC92H2. In mice, the result was “persistent serum levels of high-affinity, cocaine-specific antibodies that sequestered intravenously administered cocaine in the blood.”

And finally, while the name is still up in the air, a new national institute combining the study of alcohol and the study of all other addictive drugs will follow after final recommendations submitted to NIH Director by year’s end. Volkow briefly laid out the timeline of the merger for the assembled scientists. Call it the Institute for Substance Use Disorders, or the Institute for Addiction Disorders, or the National Institute of Substance Abuse, but whatever the eventual name, it will be fully operational by late 2013, or at least that’s the plan—and Nora Volkow, the current director of the NIDA, which will merge with, or rather absorb, the National Institute on Alcohol Abuse and Alcoholism (NIAAA), won’t be its director (See "NIH Turf Wars"). Whether that’s good or bad is the subject of much debate, but the project marches on, and seems sensible in the end.

Random Notes from the College on Problems of Drug Dependence

Opening day addresses at the annual meeting.

(These are notes on research in progress, not findings written in stone).

--NIDA director Nora Volkow talked up buspirone (Buspar) as a treatment for cocaine addiction, and referred to favorable results on buspirone for cocaine self-administration in monkeys in a large clinical trial. Also, different vaccine strategies are in the works, including different pharmacological approaches to blocking specific dopamine transporter molecules.

--Edward Sellers of DL Global Partners, a drug research consulting firm, emphasized the importance of enzyme variations in smoking. Variants of the CYP2A6 enzyme of metabolization allow us to identify “slow metabolizers” who respond well to placebo or nicotine patch therapy, and other smokers who don’t.

--Sherry McKee of the Yale University School of Medicine reminded everyone that cigarette smokers—even very light smoking “chippers”— are far more likely to have concurrent drinking problems than non-smokers. Smoking helps drinkers drink more and longer. To demonstrate such “potentiated reinforcement,” she showed a delightful video of her child eating cookies, then craving a glass of milk, then succumbing to another round of cookie consumption…

--Jack Henningfield of Pinney Associates, and former NIDA research chief, said that the reason the National Institute on Alcohol Abuse and Alcoholism (NIAAA) became an agency focused on “one molecule” is because Senator Harold Hughes, recovering alcoholic from Iowa, and Bill W., co-founder of Alcoholics Anonymous, wanted it that way.

--David Penetar of Harvard Medical School and McLean Hospital added more evidence of the link between alcohol and cigarettes, noting that “90 per cent of smokers drink,” and that smokers are three times as likely to be alcoholics than non-smokers. He pointed to research documenting a disturbing “increased desire to drink” when wearing a nicotine patch. With a patch, subjects reported feeling the effects of alcohol sooner and longer.

Photo Credit: http://www.thejournalshop.com/

Bath Salts and the College on Problems of Drug Dependence

CPDD holds annual meeting.

I’ll be out of the office for a few days, attending the annual meeting of the College on Problems of Drug Dependence (CPDD), the oldest group in the United States dedicated to addressing problems of drug addiction. The organization functions as an independent body, and is affiliated with other scientific and professional societies involved in the study of drug dependence and abuse. The meeting dovetails with the 2012 NIDA International Forum. A broad selection of the nation’s top drug and addiction researchers will be there, along with Nora Volkow, Director of the National Institute of Drug Abuse (NIDA), and Drug Czar Gil Kerlikowske, director of the Office of National Drug Control Policy.

 I’m pleased to be the recipient of the organization’s 2012 CPDD/NIDA Media Award, which is given each year for “contributions through the media that have enhanced the public understanding of scientific issues concerning drug use disorders.” That’s pretty nice of them, and you can find an interview I did for their CPDD blog HERE.

While in attendance, your faithful correspondent will be attending what looks to be a massively interesting panel discussion called “A Stimulating Soak in “Bath Salts”: Investigating Cathinone Derivative Drugs.” Look for a blog post on that one.

I’m also planning to attend a symposium on “Exercise as a Treatment for Drug Dependence in Humans,” and plan to report back on that topic as well.

Drug Addiction in 10 Slides or Less

Dr. David Friedman explains it all.

Dr. David Friedman, a professor of physiology and pharmacology at Wake Forest University School of Medicine, is also the co-founder and director of the Addiction Studies Program, a workshop for science journalists in Washington, D. C., funded by the National Institute on Drug Abuse (NIDA).

Sometimes it helps to step back and attempt to make the scientific case for addictive disorders as simply as we are able. Herewith, some highlights from Dr. Friedman’s useful presentation at the recent Addiction Studies Program workshop. Slides reproduced with Dr. Friedman’s kind permission. The comments adjacent to the slides are my own, as are any errors of fact or interpretation.

 There are important distinctions to be made between drug abuse and drug addiction, as Dr. Friedman makes clear in the slide to the right and the slide below. Unfortunately, government agencies have tended to take the position that any drug use is ipso facto drug abuse; a political position not well supported by the relevant science

  As a chronic medical condition, or “brain disorder,” addiction has a fair amount in common with other diseases, like hypertension, asthmas and diabetes, Friedman said. Relapses and setbacks are frequent, but not found in every case. 

  The key questions, indeed: What is different about the brains or the genes or the nerve cells of those who become dangerously addicted, compared to those who can take it or leave it? Scientists have discovered various so-called “markers” over the years in the brains of the children of adult alcoholics, but none of these have been broad enough in scope to point toward anything like an effective near-term treatment. However, the recent shift from chasing genes to studying neurobiological brain processes is a hopeful turn of events.

Again, a crucial distinction must be made between a state of physical dependence (at right) and a state of withdrawal (below). Non-addicts can become physical dependent on a variety of prescription medications. Such physical dependence precedes a full-blown state of addiction, but is not to be confused with addiction itself.

 The symptoms and intensity of drug withdrawal can vary from horrifying to essentially non-existent. It depends upon the drug, the drug taker’s metabolism, the social setting, environment and expectations of the users, etc. Craving and withdrawal represent the basic mechanism responsible for relapse.

 Most people are familiar with the “rebound effect” sometimes produced by over-the-counter nose sprays. Whey you inhale these medications regularly enough, the result of going turkey is… a profoundly stuffed-up nose.

In an effort to expand on the “chronic disease of the brain” label affixed by former NIDA director Alan Leshner, Dr.Friedman directs our attention toward specific brain mechanisms: reward, motivation, and memory.

Addiction is a pediatric disorder, Friedman emphasizes. This is particularly true with marijuana abuse and addiction.  Lke sugar in your blood, you can choose to control the amount of drugs you take, but you cannot choose your reaction to them.

We know for certain these days that adolescent brains are not yet fully formed, and that adolescent brains react to drugs differently than adult brains. For example, recent studies show that the actual composition of adult nicotine receptors in the brain is affected by exposure to nicotine in adolescence.

The net result of all this? Things happen at the biochemical level that change how things play out at the behavioral level.







Photo Credit: http://www.wakehealth.edu/

Drug Fact Not Fiction

National Drug Facts Week is upon us.

Yes, kids, times does fly, and it’s time again to do a CyberShoutout for National Drug Facts Week, which kicks off on Monday, October 31, and runs through November 6. (Check the map for related events in your neck of the woods.)

Sponsored by the National Institute on Drug Abuse (NIDA), National Drug Facts Week is an official health observance designed to shatter myths and spread the facts about drug abuse and addiction. (Information booklet available here). And, okay, let’s face it: Most programs, textbooks, and videos that attempt to instill an anti-drug message in our nation’s youth are lame beyond belief. From “Reefer Madness” to “This is Your Brain on Drugs,” adults have managed to inculcate one overriding message in the nation’s young people: When it comes to drugs and alcohol, you can’t count on older people to tell you what you really need to know.

So, in honor of National Drug Facts Week, it is with pleasure that I point to the Sara Bellum Blog,  maintained by NIDA, and dedicated to the proposition that tweens and teens might just be as interested in straightforward drug facts as anybody else. Here you will find such goodies as Brain Games (my personal favorite), informative videos by actual scientists, and Peerx, a new section about prescription drugs. Not to mention the actual blog for underagers by Sara herself, which is refreshingly science-oriented for that sort of thing, covering everything from alcopops to nanotechnology.

Addiction Inbox is pleased to join the CyberShout again this year, because cigarette smoking among 12th graders reached it’s lowest point in history in 2010—and also because, in the same year, about 10% of high school seniors reported abusing Vicodin. Good things are happening, more truth is being told—but there is a lot of hard work yet to do.

NIDA on Drugs, Brain, and Behavior

How Science Has Revolutionized the Understanding of Drug Addiction.

Addiction to alcohol, nicotine, and other drugs costs Americans as much as half a trillion dollars a year, according to the National Institute on Drug Abuse. Since the 1930s, when the science of addiction got its start, scientists have consistently battled against a prevailing view of addicted individuals as morally flawed and lacking in willpower. In an effort to dispel myths and keep drug arguments on track, NIDA has released an updated 2010 version of its valuable publication, “The Science of Addiction.” The report is available as a PDF for download.

As a disease that affects both brain and behavior, addiction is indeed the “cunning, baffling and powerful” disease described by Bill W., the founder of AA. Dr. Nora Volkow, director of NIDA, said that despite the plethora of scientific advances being made in addiction medicine, “many people today do not understand why individuals become addicted to drugs or how drugs change the brain to foster compulsive drug abuse. This booklet aims to fill that knowledge gap by providing scientific information about the disease of drug addiction, including the many harmful consequences of drug abuse and the basic approaches that have been developed to prevent and treat the disease.”

Dr. Volkow exhorted Americans to “adopt science-based policies and programs that reduce drug abuse and addiction in their communities, and support scientific research that improves the Nation's well-being.”

Today, "thanks to science,” writes Volkow, “our views and our responses to drug abuse have changed dramatically. Groundbreaking discoveries about the brain have revolutionized our understanding of drug addiction, enabling us to respond effectively to the problem.”

Meet Sara Bellum

It’s National Drug Facts Week.

Let’s face it: Most groups, movements, associations, programs, textbooks, and videos that attempt to instill an anti-drug message in our nation’s youth are lame beyond belief. From “Reefer Madness” to “This is Your Brain on Drugs,” adults have managed to inculcate one overriding message in the nation’s young people: When it comes to drugs and alcohol, you can’t count on older people to tell you the truth.

So, in honor of National Drug Facts Week, it is with pleasure that I point to the Sara Bellum Blog, maintained by the National Institute on Drug Abuse (NIDA) and dedicated to the notion that tweens and teens might be as interested in straightforward drug facts as anybody else. Here is what the blog has to say about itself:

The Sara Bellum Blog is written by a team of NIDA scientists, science writers, and public health analysts of all ages. We connect you with the latest scientific research and news, so you can use that info to make healthy, smart decisions.

Sometimes it can be hard to know where to go for the truth about drugs. Here at NIDA, we learn from science—not from rumors or gossip. We have thousands of researchers around the world who study drug addiction and come up with ways to help people recover and live healthy lives. Every day, scientists and physicians discover more about how drugs affect your brain and body.

You owe it to yourself to ask the right questions, look for the facts, and think hard about what you find out and what it means for you. We’re here to help you do that.

The year-old blog has been recognized as one of the top government blogs, and is targeted primarily at 12 to 17 year-olds. There is an “Ask Dr. NIDA” feature, and a National Drug I.Q. Challenge, which you can take here.

I scored 18 out of 20. But I nailed the bonus round, 5 for 5.

Articles at the site include:

· How Does Cocaine Work? It's Partly In Your Genes

· NIDA News: NIDA's Chat Day, More Questions on Marijuana

· Real Teens Ask: Do Many Kids in High School Do Drugs?

· Real Teens Ask: Can inhaling Sharpie markers make you high?

· Binge Drinking Matters--To Your Brain

· NIDA News: Back to the Future?

· Meth Mouth and Crank Bugs: Meth-a-morphosis

· Real Life: Eminem and Elton John

· NIDA News: Who Gets Fooled by Flavors?

In addition, here are some comments made by the blog's editor, Jennifer Elcano, and posted at Sara Bellum:

We thought it would be a good strategy for conveying drug abuse facts and prevention messages to teens, because we could tweak a blog format to offer brief and regularly updated content and keep it current and interesting. And a lot of our other publications geared to teens were longer or in book or brochure format. The blog allowed us a way to post short and topical items of interest to teens and also to elicit their instant feedback on what they were reading about, what we were offering them, so we could continue to adjust it as time went on since it was such a new thing.

Sara Bellum has a long history at NIDA and has appeared in a lot of our print publications in prior years. If you Google her, you can see some of our past publications where she appears as a fictional NIDA adventurer, scientist, and explorer with a big looking glass. She would be investigating the science behind drugs and their effects on the brain and the body. So what we did with the blog is basically update this character to be more of a “chic geek” type.”

I am really proud of the fact that we took a risk as a federal government agency in allowing a blog where moderated comments were permitted. We have fairly liberal guidelines, so we will only not post comments if they contain profanity, denigrate people or groups of people, or contain spam or link to outside websites. They are very basic rules mainly to protect the site’s integrity and the commenters themselves, who sometimes disclose identifying information that should stay private. I am glad we have been able to do this in a climate that tends to be averse to taking these kinds of risks.

Photo Credit: http://teens.drugabuse.gov

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