Smoking and Sadness

The chemistry of sorrow during nicotine withdrawal.

When you smoke a cigarette, nicotine pops into acetylcholine receptors in the brain, the adrenal glands, and the skeletal muscles, and you get a nicotine rush. Just like alcohol, a cigarette alters the transmission of several important chemical messengers in the brain. “These are not trivial responses,” said Professor Ovide Pomerleau of the University of Michigan Medical School. “It’s like lighting a match in a gasoline factory.”

Experiments at NIDA’s Addiction Research Center in Baltimore have confirmed that nicotine withdrawal not only makes people irritable, but also impairs intellectual performance. Logical reasoning and rapid decision-making both suffer during nicotine withdrawal. Acetylcholine appears to enhance memory, which may help explain a common lament voiced by many smokers during early withdrawal. As summarized by one ex-smoker, “I cannot think, cannot remember, cannot concentrate.”

But there is another, less widely discussed aspect of nicotine withdrawal: profound sadness. Profound enough, in many cases, to be diagnosed as clinical unipolar depression.

 Of course, people detoxing from addictive drugs like nicotine are rarely known to be happy campers. But quitting smoking, for all its other withdrawal effects, reliably evokes a sense of acute nostalgia, like saying goodbye to a lifelong friend. The very act of abstinence produces sadness, joylessness, dysphoria, melancholia—all emotional states associated with unipolar depression.

Work undertaken by Dr. Alexander Glassman and his associates at the New York State Psychiatric Institute has nailed down an unexpectedly strong relationship between prior depression and cigarette smoking, and the findings have been confirmed in other work. This sheds important light on the question of why some smokers repeatedly fail to stop smoking, regardless of the method or the motivation.  The problem, as Glassman sees it, is “an associated vulnerability between affective [mood] disorders and nicotine.”

A group of Canadian researchers, working out of the Centre of Addiction and Mental Health (CAMH), and the Department of Psychiatry at the University of Toronto, believe they have isolated the specific neuronal mechanisms responsible for the profound sadness of the abstinent smoker.

Writing in the Archives of General Psychiatry, the investigators, who had access to what the CAMH proudly calls the only PET scanner in the world dedicated to mental health and addiction research, gave PET scans to 24 healthy smokers and 24 healthy non-smokers. Non-smokers were scanned once, while heavy and moderate cigarette smokers were scanned after smoking a cigarette, and also after a period of acute withdrawal. Earlier research of this kind had focused on nicotine’s effect on dopamine release. But Ingrid Bacher and her coworkers in Toronto were measuring MAO-A levels in the prefrontal and anterior cingulate regions, two areas known to be involved in “affect,” or emotional responses. When patients suffering from major depressive disorders get scanned, they tend to show elevated levels of MAO-A. The so-called MAO-A inhibitors Marplan, Nardil, Emsam, and Parnate are still in use as antidepressant medications. In general, the higher the levels of MAO-A, the lower the levels of various neurotransmitters crucial to pleasure and reward. A high level of MAO-A would suggest that the enzyme was significantly altering the activity of serotonin, dopamine, and norepinephrine in brain regions involved in mood.

The researchers found that smokers in withdrawal had 25-35% more MAO-A binding activity than non-smoking controls. “This finding may explain why heavy smokers are at high risk for clinical depression," says Dr. Anthony Phillips, Scientific Director of the Canadian Institutes of Health Research's (CIHR's) Institute of Neurosciences, Mental Health and Addiction, which funded this study.

Although researchers involved in these kinds of drug studies almost always claim that the work is likely to lead to new pharmacological therapies, the plain truth is that such immediate spinouts are rare. But in this case, it does seem like the study provides a clear incentive to investigate the clinical standing of MAO-A inhibitors as an adjunct therapy in stop-smoking programs. “Understanding sadness during cigarette withdrawal is important because this sad mood makes it hard for people to quit, especially in the first few days,” said Dr. Jeffrey Meyer, one of the study authors.

As one addiction researcher noted, an associated vulnerability to depression “isn’t going to cover everybody’s problem, and it doesn’t mean that if you give up smoking, you’re automatically going to plunge into a suicidal depression. However, for people who have some problems along those lines, giving up smoking definitely complicates their lives.”

Bacher, I., Houle, S., Xu, X., Zawertailo, L., Soliman, A., Wilson, A., Selby, P., George, T., Sacher, J., Miler, L., Kish, S., Rusjan, P., & Meyer, J. (2011). Monoamine Oxidase A Binding in the Prefrontal and Anterior Cingulate Cortices During Acute Withdrawal From Heavy Cigarette Smoking Archives of General Psychiatry, 68 (8), 817-826 DOI: 10.1001/archgenpsychiatry.2011.82

(First published 8-4-11).

Big Tobacco Hasn't Given Up On Smoking. Have You?

World No Smoking Day.

Cigarettes: Should the FDA Mandate a National Taper?

Addiction expert calls for reduced-nicotine tobacco.

For years now, nicotine researcher Neal Benowitz has been a man on a mission. Dr. Benowitz, a professor of medicine at the University of California in San Francisco, has been pushing a Big Idea about how to eliminate cigarette smoking in America: Reduce the amount of nicotine in cigarettes.

In essence, Benowitz is calling for a national nicotine taper. Whether the FDA is interested remains an open question. But the result, several years down the road, would be a nation of teenagers confronted with only weakly addictive tobacco products.

It is an old idea, often viewed with great suspicion because of the failure of “light” and “low-tar” cigarettes to reduce nicotine intake, and in fact causing smokers to smoke harder. But Benowitz, one of the nation’s premier tobacco scientists, believes that when it comes to the roughly one out of five Americans who still smoke, a new generation of so-called “low-nicotine delivery” cigarettes is the answer. 

In a controlled study of 135 smokers of various ages, participants smoked cigarettes with progressively lower nicotine over a two-year period, and did so “without evidence of compensation”—meaning that they did not smoke more cigarettes or smoke differently when using the low-nicotine offerings. This varies dramatically from the behavior associated with light cigarettes and special filters—innovations that were marketed as “safer” cigarettes—that simply increase ventilation. The light cigarettes themselves contain the same amount of nicotine as a “regular” cigarette. And smokers quickly learn to puff harder, or cover small holes in the filter paper with their fingers, in order to extract more nicotine from each cigarette.

But with low-nicotine delivery cigarettes, you can’t get more nicotine, no matter what kind of smoker’s gyrations you perform. And the result, according to a paper by Benowitz and coworkers in Cancer, Epidemiology, Biomarkers and Prevention, is that “when the nicotine content of cigarettes is progressively decreased at monthly intervals over 6 months there is a progressive decline in nicotine intake by smokers, with only a small degree of compensation at the lowest nicotine content levels.”

The two-year study was randomized but unblinded, in order to simulate situations in which smokers are fully aware of using cigarettes with progressively less nicotine. A control group smoked their usual brands of cigarettes throughout the study. Benowitz, who led the studied, said in prepared remarks that the U.S. Food and Drug Administration (FDA) now has the authority to regulate the nicotine content of cigarettes sold in the U.S. (Benowitz is a member of the FDA’s Tobacco Products Scientific Advisory Committee.) “The idea is to reduce people’s nicotine intake, so that they get used to the lower levels, and eventually get to the point where smoking is no longer satisfying.”

The study was small, and there were dropouts. As always, further long-term study will be needed to track smokers during this kind of long-term nicotine taper. Traditionally, tapering has not been an effective method of breaking a nicotine addiction. But the reason for that may have to do with the easy availability of full-strength cigarettes in every store and gas station. The obvious goal for Benowitz is the reduction of nicotine in cigarettes to the point where they are no longer addictive. But would a robust black market in strong cigarettes leap up if nicotine reduction were a federally mandated program?

“Progressive reduction of the nicotine content of cigarettes as a national regulatory policy might have important potential benefits for the population,” the authors write, adding that “some people who had no intention of quitting upon entry into the study had… either quit spontaneously or were thinking about quitting in the near future after smoking reduced-nicotine content cigarettes.” Low-nicotine cigarettes could be produced by extracting nicotine from existing tobacco, or by genetically engineering tobacco with a lower nicotine content.

“Adolescents initiate smoking for social reasons, with friends, and later begin to smoke for pharmacologic reasons related to dependence,” the authors conclude. “Presumably a cigarette with very low nicotine content would be less likely to support the transition from social to dependent smoking, although the threshold level of nicotine to prevent this transition is not yet known.”

Benowitz NL, Dains KM, Hall SM, Stewart S, Wilson M, Dempsey D, & Jacob P 3rd (2012). Smoking behavior and exposure to tobacco toxicants during 6 months of smoking progressively reduced nicotine content cigarettes. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 21 (5), 761-9 PMID: 22354905

Photo Credit: http://chronicle.uchicago.edu

High-Risk Haplotypes in Smokers

It’s getting harder to interpret genetics studies, and that’s a good thing.

Reporting the results of published studies concerned with genetic risk factors has always been a tricky proposition. Beyond the inevitable, and too often ideological nature/nurture split, there has been an unfortunate history of false positives in the rush to make news with a “gene for” alcoholism or schizophrenia or belief in God.

But single gene theories are mostly a thing of the past, and results tend to be broader and more tentative, as befits the state of our knowledge about genes and risk in a post-epigenetic landscape. Nonetheless, there’s no denying that genes play a strong role in all kinds of behaviors and processes. A large group of U.S. tobacco researchers went looking for associations between genetic risk factors and the ability to stop smoking successfully, and published their results in the American Journal of Psychiatry. The group came down strongly in favor of the proposition that genetic variations in the chromosome 15q25 region help dictate who manages to quit smoking and who does not.

The genetic variants in question are for nicotine receptors, and are called CHRNA5-CHRNA3-CHRNB4. They compose a “high-risk haplotype” that Li-Shiun Chen and coworkers believe to be involved in the ability to quit. (A haplotype is a combination of DNA sequences on a chromosome that are transmitted as a unit). People with these genetic variants “quit later than those at low genetic risk; this difference was manifested as a 2-year delay in median quit age.” However, this association tended to wash out at very high levels of smoking. Nonetheless, “pharmacological cessation treatment significantly increased the likelihood of abstinence in individuals with the high-risk haplotype,” compared to the low-risk group.

The suspicious haplotypes did not reliably predict tobacco abstinence across all groups that were studied. And any pharmacological treatment at all vastly increases abstinence rates, compared to placebo, while those who smoke the fewest cigarettes per day have the best shot at abstinence no matter what. In one sense, all the study is saying is that anti-craving drugs are more likely to be effective in smokers “who are biologically predisposed to have difficulty quitting.” Other smokers may not need them at all as a quitting aid—which is very much as common sense would have it. But further research in this area may allow medical workers to genetically identify smokers who will definitely require a pharmacological booster shot to overcome their crippling addiction.

In brief, the study says that success in quitting may be directly modulated by certain types of genetic variation among smokers. And genetic variations influencing quitting success may be different from gene variants controlling for “severity of nicotine dependence” (how many cigarettes you smoke), and whether you get addicted in the first place. It is all very complicated. But it’s the sort of thing that gives researchers hope when they contemplate deploying forms of personalized medicine in addiction treatment.

Study limitations abound. The work looked at only one genetic locus, while the success of smoking cessation might depend on multiple gene sites. The placebo arm was relatively small, and the smoking reports were obtained through a combination of biochemical confirmation and self-reporting.

Baker, T. (2012). Interplay of Genetic Risk Factors (CHRNA5-CHRNA3-CHRNB4) and Cessation Treatments in Smoking Cessation Success American Journal of Psychiatry DOI: 10.1176/appi.ajp.2012.11101545

Graphics Credit: (Li-Shiun Chen)

Researchers Eye a Cheap, Organic Alternative to Chantix for Smokers

Meet cytisine, available in Bulgaria for 25 cents a pill.

A clear majority of American smokers say they want to quit. But each year, only a small percentage of them manage to do it. For individual smokers, the will is there, but what’s sometimes missing is the money.

For many smokers, cessation aids like nicotine patches and anti-craving medication are effective. But they are relatively costly, and insurance coverage for such products varies widely. Chantix, the top-of-the-line smoking cessation aid introduced by Pfizer five years ago as a very expensive prescription drug, was discovered by modifying the chemical attributes of an existing plant substance called cytisine.

But what if cytisine itself, found in various plants, including the golden rain tree, a small shrub native to the Alps—worked almost as well as Chantix, but for only pennies a day? Cytisine, packaged as Tabex and marketed by a Bulgarian firm, has already been on the market in Central Europe and Russia for more than 40 years. In Russia, a four-week course of Tabex costs $6.  Chantix will cost smokers about $250 for a 12-week run, or about $3-$4 per pill. In Poland, Tabex sells for about 25 cents per pill.

Moreover, as David Biello pointed out in Scientific American, when Chantix (known as Champix in the U.K.) was first approved for use against cigarettes, “the leaves of Cytisus laburnum, or the golden rain acacia tree, were used as a tobacco substitute by soldiers in World War II.” Later, clinicians in the U.S. paid scant attention to reports of a cheap Bulgarian plant-based supplement that smokers in Russia and Central Europe were using to help break their nicotine addiction. Instead, researchers structurally modified cytisine to produce varenicline, or Chantix. It makes for a more effective drug, but there are always tradeoffs: It is expensive and time-consuming to produce drugs through a process of total syntheses, and they will always come at a considerable cost premium relative to their organic originals. That is partly how pharmacology works, and it’s a good thing, providing you have the money or the health insurance to be able to afford the finished product.

Recently, a group of researchers at a smoking cessation clinic in Poland studied the effect of cytisine, a “partial nicotine agonist,” in a clinical trial published
 in the New England Journal of Medicine. The double-blind trial showed that cytisine was not as effective as Chantix, but significantly more effective than a placebo. Dr. Robert West of University College, London, and lead author of the study, said the “net improvement in the abstinence rate with cytisine was 6 percentage points. The relative rate of abstinence in the cytisine group as compared with that in the placebo group was 3.4.”

“It wasn't compared head-to-head against the Rx drugs, but its reasonable efficacy makes it sound like a cheaper alternative,” said Dr. David Kroll, Professor and Chair of Pharmaceutical Science at North Carolina Central University. “Like nicotine, it can cause side effects like headaches and nausea,” he added.

So is cytisine an eventual possibility in the U.S., where it is not currently licensed and available? Is it something that the National Institute on Drug Abuse is interested in? When I asked NIDA director Nora Volkow that question in an interview last week, the answer was yes. “The data look very interesting,” Volkow said, referring to the New England Journal of Medicine Study.  “The beauty of cytisine is that it’s not just inexpensive, you can also get a response in three weeks.” She added that “we don’t know yet whether we can improve it,” by, for example, combining it with other cessation aids. “The main side effect of cytisine is nausea, but not suicidal ideation,” she said.

An earlier survey in the Archives of Internal Medicine of the admittedly sparse research showed similar results in several placebo-controlled double-blind studies. Cytisine, the Marxist-Socialist answer to cigarette addiction, works about as well as standard nicotine replacement therapy, like patches and gums.

“I hope this drug will be available throughout the world at a cost that every smoker can afford,” said West. And that might be a problem. Cytisine is not currently legal in the U.S. or Canada. Tabex itself was withdrawn from some of the European countries in which it was formerly available, after several Central and Eastern European countries joined the European Union and began adhering to stricter licensing rules.

Meanwhile, a third of the world is still out there smoking tobacco. It seems sensible to have some modest help available for smokers in poverty who want to quit and financially need to quit. “I have long been concerned that effective treatments to help smokers to stop are not affordable by the majority of smokers in the world,” West said. “There are still regulatory hoops to go through, but I hope that before long this drug will be available throughout the world at a cost that every smoker can afford. It should be cheaper to take this drug than to smoke, wherever you are in the world. It is not a magic cure by any means; stopping is still extremely difficult for many people. But it could save many hundreds of thousands of lives, if not millions, which is quite a thought.”

As Dr. Volkow put it: “We urgently need medications for smoking. Five million people die per year” from smoking-related causes in the U.S.

West R, Zatonski W, Cedzynska M, Lewandowska D, Pazik J, Aveyard P, & Stapleton J (2011). Placebo-controlled trial of cytisine for smoking cessation. The New England journal of medicine, 365 (13), 1193-200 PMID: 21991893

Cigarette Sadness

The chemistry of sorrow during nicotine withdrawal.

When you smoke a cigarette, nicotine pops into acetylcholine receptors in the brain, the adrenal glands, and the skeletal muscles, and you get a nicotine rush. Just like alcohol, a cigarette alters the transmission of several important chemical messengers in the brain. “These are not trivial responses,” said Professor Ovide Pomerleau of the University of Michigan Medical School. “It’s like lighting a match in a gasoline factory.”

Experiments at NIDA’s Addiction Research Center in Baltimore have confirmed that nicotine withdrawal not only makes people irritable, but also impairs intellectual performance. Logical reasoning and rapid decision-making both suffer during nicotine withdrawal. Acetylcholine appears to enhance memory, which may help explain a common lament voiced by many smokers during early withdrawal. As summarized by one ex-smoker, “I cannot think, cannot remember, cannot concentrate.”

But there is another, less widely discussed aspect of nicotine withdrawal: profound sadness. Profound enough, in many cases, to be diagnosed as clinical unipolar depression.

 Of course, people detoxing from addictive drugs like nicotine are rarely known to be happy campers. But quitting smoking, for all its other withdrawal effects, reliably evokes a sense of acute nostalgia, like saying goodbye to a lifelong friend. The very act of abstinence produces sadness, joylessness, dysphoria, melancholia—all emotional states associated with unipolar depression.

Work undertaken by Dr. Alexander Glassman and his associates at the New York State Psychiatric Institute has nailed down an unexpectedly strong relationship between prior depression and cigarette smoking, and the findings have been confirmed in other work. This sheds important light on the question of why some smokers repeatedly fail to stop smoking, regardless of the method or the motivation.  The problem, as Glassman sees it, is “an associated vulnerability between affective [mood] disorders and nicotine.”

Now a group of Canadian researchers, working out of the Centre of Addiction and Mental Health (CAMH), and the Department of Psychiatry at the University of Toronto, believe they have isolated the specific neuronal mechanisms responsible for the profound sadness of the abstinent smoker.

Writing in the Archives of General Psychiatry, the investigators, who had access to what the CAMH proudly calls the only PET scanner in the world dedicated to mental health and addiction research, gave PET scans to 24 healthy smokers and 24 healthy non-smokers. Non-smokers were scanned once, while heavy and moderate cigarette smokers were scanned after smoking a cigarette, and also after a period of acute withdrawal. Earlier research of this kind had focused on nicotine’s effect on dopamine release. But Ingrid Bacher and her coworkers in Toronto were measuring MAO-A levels in the prefrontal and anterior cingulate regions, two areas known to be involved in “affect,” or emotional responses. When patients suffering from major depressive disorders get scanned, they tend to show elevated levels of MAO-A. The so-called MAO-A inhibitors Marplan, Nardil, Emsam, and Parnate are still in use as antidepressant medications. In general, the higher the levels of MAO-A, the lower the levels of various neurotransmitters crucial to pleasure and reward. A high level of MAO-A would suggest that the enzyme was significantly altering the activity of serotonin, dopamine, and norepinephrine in brain regions involved in mood.

The researchers found that smokers in withdrawal had 25-35% more MAO-A binding activity than non-smoking controls. “This finding may explain why heavy smokers are at high risk for clinical depression," says Dr. Anthony Phillips, Scientific Director of the Canadian Institutes of Health Research's (CIHR's) Institute of Neurosciences, Mental Health and Addiction, which funded this study.

Although researchers involved in these kinds of drug studies almost always claim that the work is likely to lead to new pharmacological therapies, the plain truth is that such immediate spinouts are rare. But in this case, it does seem like the study provides a clear incentive to investigate the clinical standing of MAO-A inhibitors as an adjunct therapy in stop-smoking programs. “Understanding sadness during cigarette withdrawal is important because this sad mood makes it hard for people to quit, especially in the first few days,” said Dr. Jeffrey Meyer, one of the study authors.

As one addiction researcher noted, an associated vulnerability to depression “isn’t going to cover everybody’s problem, and it doesn’t mean that if you give up smoking, you’re automatically going to plunge into a suicidal depression. However, for people who have some problems along those lines, giving up smoking definitely complicates their lives.”


Bacher, I., Houle, S., Xu, X., Zawertailo, L., Soliman, A., Wilson, A., Selby, P., George, T., Sacher, J., Miler, L., Kish, S., Rusjan, P., & Meyer, J. (2011). Monoamine Oxidase A Binding in the Prefrontal and Anterior Cingulate Cortices During Acute Withdrawal From Heavy Cigarette Smoking Archives of General Psychiatry, 68 (8), 817-826 DOI: 10.1001/archgenpsychiatry.2011.82

Photo Credit:http://jenniferonmars.wordpress.com

Teachable Moments in the Life of a Cigarette Smoker

Child surgery makes smoking parents more likely to try quitting.

Here’s a strange one: Doctors at Mayo Clinic wanted to find out whether children undergoing surgery had any effect on the smoking behavior of their parents. And it did—but the effect appears to be short-lived.

The Mayo researchers began from the already well-tested proposition that smokers who have surgery are more likely to quit smoking. In fact, they quit at twice the rate of smokers who haven’t had surgery. Not hard to understand, intimations of mortality and all that. They pass through a teachable moment, the scientists write in Anesthesiology, defined as “an event that prompts behavioral change.” As for smokers with kids, doctors have always had recourse to two tactics for creating teachable moments for cigarette cessation. First, they could point to increased illness and asthma in the innocent children of smokers. And when that didn’t work, they could throw in the cold fact that children exposed to secondhand smoke have a higher risk of respiratory complications during and after surgical anesthesia. And in a further queasy irony, “the increased frequency of conditions such as middle ear diseases caused by secondhand smoke may also make it more likely that children will require surgery.”

For documentation, the investigators turned to the massive National Health Interview Survey (NHIS), a questionnaire served up annually to 35,000 households by personal interview. About 12% of children in the NHIS survey in 2005 were exposed to secondhand smoke. Of the thousands of children undergoing surgery, there was an increased likelihood that a parent of one of them would inaugurate a no-smoking attempt. But these quitters were no more likely to succeed in their attempt than any other quitters.

However, “parents having surgery within the previous 12 months was associated with more quit attempts, more successful attempts, and a greater intent to quit among those still smoking.” What happened to the indestructable bond between parent and child? It appears that concerns about one’s own health trump concerns about the health of offspring when it comes to quitting cigarettes. “We can only speculate about why surgery was a significant factor associated with sustained abstinence when experienced by the smoker but not the smoker’s child.”

There are plenty of limitations to these kinds of self-reported surveys, but it is hard not to speculate, along with the researchers. One obvious implication: the chances of a smoker quitting are at their maximum when parent and child both have surgeries.

“Our current findings suggest that having a child undergo surgery can serve as a teachable moment for quit attempts,” said Dr. Warner. “The scheduling of children for surgery may present us with an opportunity to provide tobacco interventions to parents, who are apparently more motivated to at least try to quit – but who need assistance to succeed.”

Shi, Y., & Warner, D. (2011). Pediatric Surgery and Parental Smoking Behavior Anesthesiology, 115 (1), 12-17 DOI: 10.1097/ALN.0b013e3182207bde

Photo Credit: http://special-needs.families.com/

For Smokers, Nowhere to Run and Nowhere to Hide

(With love and apologies to Martha and the Vandellas.)

That wonderful song goes on to declare:

'Cause I know
You're no good for me
But you’ve become
A part of me.

The song is not about cigarette addiction, but it could be. Full Disclosure: I smoked cigarettes myself for almost 25 years. And then, after several failed attempts, I quit. I out myself on this subject because a paper from the May 25 issue of the New England Journal of Medicine (NEJM) decries what the authors call the “denormalization” of smoking—and I find myself agreeing with them, smokeless though I may be. I recently visited New York, coincidentally on the day that smoking outdoors in New York City became illegal. Okay, that’s not quite fair to say—it became illegal to smoke in Central Park, or at Brighton Beach, or along the newly pedestrian mallways of Times Square. There is no smoking along the High Line. There is no smoking at any park, beach, or pedestrian mall. As both the tobacco industry and anti-smoking activists well know, this was an iconic victory that has the potential to change smoking laws in virtually every other American city.

It’s a fascinating progression, starting in the 70s when the Civil Aeronautics Board decreed non-smoking sections on domestic airline flights, to the recent New York City Council Decision to ban smoking en plein air, so to speak. Thomas Farley, New York City Health Commissioner, summed it up as follows in a public hearing: “I think in the future, we will look back on this time and say ‘How could we have ever tolerated smoking in a park?’”

I’m not so sure on that, myself. James Colgrove, Ronald Bayer, and Kathleen Bachynski of the Mailman School of Public Health at Columbia University wrote the paper, entitled “Nowhere Left to Hide? The Banishment of Smoking from Public Spaces,” in the NEJM. The authors note that more than 500 towns and cities in 43 different states have already enacted laws banning smoking “in outdoor recreation areas.” At first, as the authors summarize the history, it all seems like a sensible compromise, built on common courtesy. First airplanes and buses, then restaurants and bars, began setting aside seats for non-smokers. By the early 90s, the first data on secondhand smoke was rolling in. Schools, convention centers, and finally even private workplaces either banned smoking or created smoke-free areas. But even then, the primary motivator, according to the researchers, was that secondhand smoke was “unpleasant and annoying,” not deadly. Smokers weren’t being asked to refrain from public smoking for the good of their own health, but as a courtesy to others.

The solid scientific evidence kept accumulating, however—even though tobacco cigarettes were, and still are, completely legal products for adult Americans to purchase and consume if they so choose. Now the arguments shifted to the innocent bystanders, those within the six-foot ring, the immediate smoke zone surrounding a smoker, and the elevated risk of lung cancer, heart disease, and asthma that smokers were subjecting them to. In 1993, the Environmental Protection Agency (EPA) classified secondhand smoke as a Class A carcinogen, and more school, stadiums and offices proscribed smoking.

So far so good, really, from a public health standpoint. But now comes the bend in the road. Suddenly, parks and beaches were being added to the no-smoking roster. “As the zones of prohibition are extended from indoor to outdoor spaces, however, the evidence of physical harm to bystanders grows more tenuous.” In 2008, the authors report, “The editor of the journal Tobacco Control dismissed as ‘flimsy’ the evidence that secondhand smoke poses a threat to the health of nonsmokers in most outdoor settings.”

This confusion was much in evidence at public hearings last fall on the proposed outdoor smoking bans. While Health commissioner Farley argued that 57% of New Yorkers showed nicotine by-products in their blood, he also argued that exposing young children to adults in the carnal act of smoking was detrimental to the public health and welfare. “Families,” he said, “should be able to bring their children to parks and beaches knowing that they won’t see others smoking.” This is really quite an astonishing assertion, given the range of bad habits youngsters are exposed to as they go about a normal day in the adult world. The authors are particularly concerned about this push to stigmatize smokers. “Given the addictive nature of nicotine and the difficultly of quitting smoking, strategies of denormalization raise both pragmatic and ethical concerns.” Furthermore:

The decline in U.S. smoking rates since the 1960s has coincided with the development of a sharp gradient along the lines of socioeconomic status. Whereas about one fifth of all Americans are smokers, about one third of those with incomes below the federal poverty level smoke. These data are especially pertinent to the question of bans in parks. Since smokers are more likely to be poor and therefore dependent on free public spaces for enjoyment and recreation, refusing to allow them to smoke in those places poses potential problems of fairness.

The anti-tobacco movement, frustrated by the slow pace of gains over several years of active efforts, with rates of smoking remaining essentially unchanged, has to face the fact that an outright ban on cigarettes is a ticket to black market, crime syndicate hell. But a de facto ban is something altogether different, and “steadily winnowing the spaces in which smoking is legally allowed may be leading to a kind of de facto prohibition.” More and more employers prohibit smoking in doorways, within ten feet of doorways, anywhere on university campuses, and so on. No one has voted to make cigarette smoking illegal. But the public space in which this legal activity can be pursued is disappearing. And here is where the tough questions start: “In the absence of direct health risks to others, bans on smoking in parks and beaches raise questions about the acceptable limits for government to impose on conduct,” the authors conclude. Not to mention issues of personal autonomy, individual choice, and the stigma attached to addictive behavior. Perhaps the ACLU will soon take an interest in the civil rights of outdoor smokers, where the only health being hazarded is the smokers’ own.

Colgrove J, Bayer R, & Bachynski KE (2011). Nowhere Left to Hide? The Banishment of Smoking from Public Spaces. The New England journal of medicine PMID: 21612464

Photo Credit: www.thinkstock.com

Smoking and Adolescent Attention Deficit

Are young smokers risking cognitive impairment as adults?

 Call it “nicolescence.” It’s that time of life when certain 18-and-unders discover cigarettes. Most adult smokers begin their habit before the age of 19, and a majority of adolescents have tried cigarettes at least once. But for some of them—those who were “born to smoke,” in a sense—early exposure to nicotine may influence adolescent cognitive performance in ways that adult exposure to nicotine does not. Furthermore, early exposure may result in “cognitive impairments in later life.”

These provocative notions are raised by a group of researchers at VU University, Amsterdam, The Netherlands, in a paper for Nature Neuroscience. And while the specifics of glutamate activity they have documented are fascinating, the leaps back and forth between adolescent humans and adolescent lab mice are dizzying. Nonetheless, the bold claims made in the paper prompted the scientists “to reconsider our views on the etiology of attention deficits.”

That may be more than many addiction researchers are willing to countenance, but the study makes an intriguing case for long-term effects on attentional processing. The Dutch researchers exposed adolescent rats to nicotine, assessed visuospatial attention and other markers associated with synaptic activity in the prefrontal cortex, and found impaired measures of attention and signs of increased impulsivity in adulthood after five weeks of abstinence. Adult rats exposed to nicotine for the first time did not show similar long-term consequences.

The molecular underpinnings for this phenomenon appear to be reduced glutamate receptor protein levels in the prefrontal cortex. Glutamate is a neurotransmitter involved in attention, among other cortical tasks. Glutamate levels were “altered specifically by adolescent and not adult nicotine exposure” in the lab animals, the researchers found.

The glutamate receptor mGluR2 is the likely culprit.  The researchers report that “a lasting downregulation of mGluR2 on presynaptic terminals of glutamatergic synapses in the prefrontal cortex persists into adulthood causing disturbances in attention…. Restoring mGluR2 activity in vivo in the prefrontal cortex of adult rats exposed to nicotine during adolescence remediated the attention deficit.”

The study concludes: “Not only from a behavioral, but also from a molecular point of view, the adolescent brain is more susceptible to consequences of nicotinic receptor activation.” In other words, there is at least some evidence that the neurotoxic effects of nicotine are potentially more severe in the early developmental stage called adolescence.

The Dutch study is not the only one of its kind. In 2005, Biological Psychiatry published a report on cognition in which adolescent smokers “were found to have impairments in accuracy of working memory performance irrespective of recency of smoking. Performance decrements were more severe with earlier age of onset of smoking.”

And a 2007 study published in Neuropsychopharmocology, based on testing and fMRI scans of 181 male and female adolescent smokers, concluded that “in humans, prenatal and adolescent exposure to nicotine exerts gender-specific deleterious effects on auditory and visual attention…” Boys were more sensitive than girls to attention deficits involving auditory processing, while girls tended to show equal deficits in both auditory and visual attention tasks. 

Counotte, D., Goriounova, N., Li, K., Loos, M., van der Schors, R., Schetters, D., Schoffelmeer, A., Smit, A., Mansvelder, H., Pattij, T., & Spijker, S. (2011). Lasting synaptic changes underlie attention deficits caused by nicotine exposure during adolescence Nature Neuroscience DOI: 10.1038/nn.2770

Photo Credit: http://smoking-quit.info/

From NINA to NSNA: No Smokers Need Apply

 Smoke-free workplace or job discrimination?

It started with hospitals and medical businesses. As more and more states adopted strict policies about smoking, state courts began to bump up against a vexing question—the legal system is being called upon to adjudicate the legality of refusing to hire smokers.

The issue has split the anti-smoking world into two camps, and shines light on the fundamental question: Is it legal to discriminate against tobacco consumers, usually known as smokers, for the use of a lawful product? Will courts uphold cases where employees have been fired for “smelling of smoke”?

20% of Americans continue to smoke. As the New York Times puts it, a shift from “smoke-free” to “smoker-free” workplaces reflects the general feeling that “softer efforts—like banning smoking on company grounds, offering cessation programs and increasing health care premiums for smokers—have not been powerful-enough incentives to quit.”

Join Together reports that under new “tobacco-free” hiring policies, “applicants can be turned away for smoking, or if they are caught smoking after hire. Policies differ by company, but some require applicants to take urine tests for nicotine.”

The chief executive of St. Francis Medical center in Cape Girardeau, Missouri, which recently stopped hiring smokers, said that it was “unfair for employees who maintained healthy lifestyles to have to subsidize those who do not. Essentially that’s what happens.”

The American Lung Association, the American Cancer Society, and the World Health Organization (WHO) do not hire smokers. However, the American Legacy Group, an anti-smoking advocacy organization that does hire tobacco users, argues that “smokers are not the enemy.” In the words of Ellen Vargyas, the group’s chief counsel,  “the best thing we can do is help them quit, not condition employment on whether they quit.”

As Dr. Michael Siegel of  the Boston University School of Public Health told the New York Times: “Unemployment is also bad for health.”

The issue has broader implications, as yet imperfectly explored. Will it become legal to discriminate against alcohol and drug users in general? How about junk food? Should a company be forced to saddle itself with the likely health costs associated with a junk food junkie?

And so on. This one bears watching.

What’s the Best Valentine’s Day Present of All?

Answer: a healthy heart.

Valentine’s Day is all about hearts, so it’s not surprising that February was picked as American Heart Month almost 50 years ago.

The Office on Smoking and Health at the U.S. Centers for Disease Control (CDC) wants you to know that, if you smoke, “the cells that line your body's blood vessels react to the poisons in tobacco smoke almost immediately. Your heart rate and blood pressure go up. Your blood vessels grow narrower. Chemical changes caused by smoking also make blood more likely to clot."

Furthermore: “Plaque clogs and narrows your arteries. This can trigger chest pain, weakness, heart attack, or stroke. Plaque can rupture and cause clots that block arteries. Completely blocked arteries can cause sudden death. Smoking is not the only cause of these problems, but it makes them much worse.”

Worse like this---------------------------------------------->

The 2010 Surgeon General's Report, "How Tobacco Smoke Causes Disease: The Biology and Behavioral Basis for Smoking-Attributable Disease," documents the crucial importance to heart health of being smoke-free.

Okay, don’t quit for yourself. Because face it, you don’t want to. But how about quitting for someone else? As the CDC reminds us, “because secondhand smoke also affects others and can increase their risk for heart attack and death, quitting smoking can help protect your loved ones.”

And here are some CDC resources for supporting a stop-smoking program:

For support to quit, call 1-800-QUIT-NOW (1-800-784-8669; TTY 1-800-332-8615). This service provides free support and advice from experienced counselors, a personalized quit plan, self-help materials, the latest information about cessation medications, and more. 

Online cessation services and resources are also available online at www.smokefree.gov. This Web site provides free, accurate, evidence-based information and professional assistance to help support the immediate and long-term needs of people trying to quit smoking.

Photo Credit: http://inventorspot.com/

Visual Cues and Addiction

Do smoking scenes in movies make smokers want to light up?

Smokers and former smokers will understand what I mean when I say that an addiction to smoking is like a pilot light that is always lit, always ready to whoosh into full flame with the application of a few milligrams of nicotine. And they will also understand that feeling, like a bolt sliding home, of instant identification that comes from seeing someone else smoking. Especially if you are not smoking, but wish to be.

It makes sense that a smoker or former smoker who sees someone smoking might find that image to be a trigger for nicotine craving. But we have to ask whether smokers trying to quit are really endangering their newfound abstinence simply by viewing “smoking content” on TV or in the movies. It seems a bit too prudish to be true. Yet, logic would seem to suggest that some sort of behavioral effect might be expected when a smoker in withdrawal sees an image of someone smoking.  Does, say, viewing scenes of smoking in a movie produce changes in brain function robust enough to trigger relapse in the absence of any other direct cues? Are environmental cues of this nature more dangerous to newly abstinent smokers than we thought?

“Our findings support prior studies that show smokers who exit a movie that had images of smoking are more likely to crave a cigarette, compared with ones who watched a movie without them,” said Dylan Wagner of Dartmouth College, in a Society for Neuroscience Press Release. “More work is needed to show whether brain activity in response to movie smoking predicts relapse for a smoker trying to quit.”

In a small study involving 17 smokers and 17 non-smokers, scientists at Dartmouth College set out to determine what differences might show up in a functional magnetic resonance imaging (fMRI) scan of smokers and non-smokers while they watched 30 minutes of a movie with several smoking scenes. The subjects were not told that the experiment was about smoking. But when they viewed smoking scenes, the brains of smokers showed increased activity in a portion of the parietal lobe of the brain called the intraparietal sulcus. The study was published in the January 19 issue of the Journal of Neuroscience.

What does this brain region do? As it happens, the neurons in the intraparietal sulcus encode information about the position and geometrical properties of objects. This part of the brain coordinates eye movement data and reaching movements.  Using a mouse or a joystick is a good example of an activity that involves the intraparietal sulcus.

The intraparietal sulcus, or IPS, has other functions, but primarily it serves, in the words of one study, as an interface “between the perceptive and motor systems for controlling arm and eye movements in space.”  Apparently, the habitual hand gestures used in lighting and smoking a cigarette, when viewed in a movie or commercial, triggered impulses from that part charged with controlling the routine gestural aspects of smoking--if the viewer were actually smoking.

Other studies point to additional aspects of this event-related change in fMRI scans. Writing in the Journal of Neuroscience in 2006, Hamilton and Grafton offer evidence that the IPS is also “uniquely sensitive to the goals of other people’s hand actions.” The intraparietal sulcus seems to “know” what those hand gestures mean, in a sense. Macaques in the lab were used to demonstrate that “cells in macaque IPL were show to respond selectively to both the performance and observation of an action within a sequence leading to a specific goal and not to the same action when it was part of a sequence achieving a different goal.”

This was a strong suggestion that “the IPS is not just a relay but has a central role in representing and interpreting the goals of observed hand actions.”

Perhaps, then, the idea that strong cues can be produced by images and associations is not so far-fetched. It is, for that matter, the founding theory upon which the modern advertising industry has been built, and while the argument over advertising’s effectiveness is never-ending, cigarette scenes in films might have to be considered a form of indirect advertising beamed directly to the parietal lobe of smokers (and perhaps former smokers as well.)

Hamilton, A. (2006). Goal Representation in Human Anterior Intraparietal Sulcus Journal of Neuroscience, 26 (4), 1133-1137 DOI: 10.1523/JNEUROSCI.4551-05.2006

Graphics Credit: http://aslittleaspossible.blogspot.com/

The Day After

How’s that no-smoking pledge going?

This post is not meant for most of you. Those of you who never smoked, or smoked and quit successfully—move along, maybe check out my earlier posts about smoking this month.

But for those of you who have decided to take the 35th annual Great American Smokeout seriously—for those of you who decided today, or yesterday, or recently, to quit smoking—I have a few remarks, if you have a moment. I’m fairly trustworthy on this subject. I’m a science writer, I follow the field of addiction science, and I smoked a pack of Camel filters a day for about 25 years. In addition, I quit smoking using the most recently available smoking cessation aids—nicotine patches and anti-craving medication, in this case Zyban, a.k.a. Wellbutrin.

I had decided, after the usual smoker’s run of unsuccessful independent quitting attempts, that the only real hope I had for success was to throw myself into the hands of my primary care physician. Happily, Dr. Joe is a young example of the last of the breed, a lingering remnant of a tribe that used to be known as family doctors. When I told Dr. Joe of my plans to quit smoking, he was overjoyed. Too overjoyed, it seemed to me. As it turned out, there were grounds for my suspicion. Dr. Joe had recently returned from a smoking cessation seminar at the Mayo Clinic in Rochester, Minnesota, with a grab bag of refinements and alternative approaches for setting up a no-smoking regimen. Furthermore, he made it clear that, if necessary—if I forced him to it through relentless noncompliance—he was fully prepared to order regular blood workups to detect and quantify my nicotine levels.

Of course, I instantly regretted setting a foot into this ring, but once Dr. Joe started flinging prescriptions for patches and pills my way, I realized I was in it up to my wallet (Insurance companies weren’t paying for nicotine cessation products, ever, at that time).

Most smokers know the current drill. A few weeks with nicotine patches or gum or nasal spray, combined with a short course of Zyban or Chantix to further reduce cravings, and then you are expected to fly out of the nest and spread the good news.  Most smokers know that even this controversial armamentarium is not going to completely spare them from a rare and special kind of suffering: addictive craving for nicotine.  It’s a mean, rough ride, as everyone knows.

But if you take a few of the major potholes out of the road, smooth over the really big bumps just a little, fill in the low spots a bit as well, you have a fighting chance—especially if you have tried and failed before (almost nobody pulls it off on the first attempt).

Here are the key features of the program, as my doctor worked it up for me:

--Stronger patches. Mayo Clinic and other institutions had made an important discovery, my doctor said. People weren’t wearing strong enough patches. There was a system of matching up patch strength to amount and duration of smoking, and then a step-down procedure, to less and less powerful patches, and it was all listed on the packages, but because of great nervousness over medical complications by a very few individuals who overdid the patch and then chain-smoked on top of that, the result was that the patches as marketed weren’t strong enough, many doctors felt. The advice was to start strong, with the strongest patch available (and perhaps there was even a patient or two who doubled up, ahem). 

--Longer patches. Start strong—and go long. The whole nicotine replacement plan is supposed to last a month or two. Phooey, said Dr. Joe. No telling in advance how long the process will take. There is no set timetable. How long would I be wearing patches and tapering the dose? As long as it took, Dr. Joe inferred, for me not to need them anymore. He seemed prepared to keep me on patches the rest of my life, if it kept me from picking up a cigarette. In the end, when I took off my final, tiny patch, I had been using them for a little less than six months. The recommended five-star treatment plan in the literature and on the packages calls for only 10 weeks, tops.

--Pharmaceuticals. It is admittedly hard to separate out placebo effects from drug effects, in the case of something as elusive as cigarette urges. But I do believe that Zyban took the edge off the worst of my cigarette cravings. It did not eliminate them, anymore than the patches eliminated them. But the medication effectively dissipated the grip of that moment of panic, when you have risen from your chair and set about finding your coat and car keys for a run to the gas station to buy a pack of cigarettes. Or at least that’s the way it felt to me.

--Exercise. Trite? You bet, and you can be sure that I winced and offered a tired smile when I heard my doctor bore in on the subject. Since I knew him to be a crazed bicyclist, I was prepared to disregard most of what he had to say. But his insistence sent me back to the research literature on exercise and its effect on dopamine, serotonin, acetylcholine, and endorphin levels. So I took him up on that firm suggestion as well, and found that, at the least, it helped with a period of rocky sleep in the beginning.

--Diet. No huge changes, just watching the sweets in an effort to avoid surging blood sugar levels. Fruit helps, since constipation is a common side effect of nicotine cessation—just the opposite of how it works with heroin. I continued to drink coffee, but for a while it didn’t taste as good.

--Relaxation. Quitting smoking makes you tense. You think I’m being funny? Quitting smoking makes you tense all over, mentally and physically. During the first few days you’ll notice that your body is clenched, held rigidly. Your posture is likely to be anything but relaxed; your physical movements can be jerky and awkward. A few minutes a day spent sitting with eyes closed, in a relaxed upright posture, thinking of nothing or concentrating on your breathing or meditating either formally or casually, can bring partial relief from all that tension. And on some days, that can be crucial.

--Determination. Unfortunately, it wasn’t until everyone around me—my wife, children, parents, close friends, work associates—had all, I sensed, basically given up on me, silently condemning me to the category of Lifetime Smoker, that I finally managed to make a successful run at a major life problem. There are better ways to work up your determination. Find and employ them.

With time, an involved partner, nicotine replacement, and the right medication, the deal can be done. There has never been a better time in history to be a smoker who has decided to quit.

Graphics Credit: http://adoholik.com/

Put Down Your Cigarette Rag (Don't Smoke)

By Allen Ginsberg (1971)

Dont smoke dont smoke dont smoke

Dont smoke

It's a nine billion dollar

Capitalist Communist joke

Dont smoke dont smoke dont smoke dont smoke

Dont smoke

Smoking makes you cough,

You cant sing straight

You gargle on saliva

and vomit on your plate

Dont smoke dont smoke dont smoke dont smoke,

Dont smoke smoke smoke smoke

You smoke in bed

You smoke on the hill

Smoke till yr dead

You smoke in Hell

Dont smoke dont smoke in living Hell Dope Dope

Dont smoke dont smoke dont smoke

You puff your fag

You suck your butt

You choke and gag

Teeth full of crud

Smoke smoke smoke smoke Dont dont dont

Dont Dont Dope Dope Dope Dont Smoke Dont Dope

Pay your two bucks

for a deathly pack

Trust your bad luck

and smoke in the sack

Dont Smoke Dont Smoke Nicotine Nicotine No

No dont smoke the official Dope Smoke Dope Dope

Four Billion dollars in Green

'swat Madison Avenue gets

t' advertise nicotine

and; hook you radical brats

Dont Smoke Dont Smoke Dont Smoke

Nope Nope Dope Dope Hoax Hax Hoax Hoax

Dopey Dope Dopey Dope Dope Dope dope dope

Black magic pushes dope

Sexy chicks in cars

America loses hope

and smokes and drinks in bars

Don't smoke dont smoke dont smoke,

dont smoke dont dont dont dont dont

choke choke choke choke kaf kaf

Kaf Kaf Choke Choke

Choke Choke Dope Dope

Communism's flopped

Let's help the Soviet millions

Sell 'em our Coffin-Nails

and make a couple billions

Big Bucks Big Bucks bucks bucks

bucks bucks smoke smoke smoke smoke

smoke Bucks smoke bucks Dope bucks big

Dope Bucks Dig Big Dope Bucks Big Dope

Bucks dont smoke big dope bucks

Dig big Pig dope bucks

Nine billion bucks a year

a Southern Industry

Buys Senator Jesse Fear who pushes Tobacco subsidy

In the Senate Foreign Relations Committee

Dope smokes dope smokes dont smoke dont smoke

Cloak cloak cloak room cloak and; dagger

smoke room cloak room dope cloak

cloak room dope cloak room dope dont smoke

Nine billion bucks for dope

approved by Time and Life

America loses hope

The President smokes Tobacco votes

Dont Smoke dont smoke dont smoke dont smoke

Dont smoke nope nope nope nope

30 thousand die of coke or

Illegal speed each year

430 thousand cigarette deaths

That's the drug to fear

In USA Dont smoke Dont smoke Dont smoke

Get Hooked on Cigarettes

Go Fight the War on Drugs

Smoke any other Weed

Get bust by Government Thugs

Dont smoke dont smoke the official dope

If you will get in bed

and give your girlfriend head

then you wont want a fag

Nor evermore a drag

Dont Smoke dont smoke Hope Hope Hope Hope

O Please Dont Smoke Dont Smoke

O Please O Please O Please

I'm calling on my knees

Twenty-four hours in bed

and give your boyfriend head

Put something in your mouth

Like skin not cigarette filth

Suck tit suck tit suck cock suck cock

suck clit suck prick suck it

but dont smoke nicotine dont smoke

dont smoke nicotine nicotine it's

too obscene dont smoke dont smoke

nicotine suck cock suck prick suck tit

suck clit suck it But dont smoke shit nope

nope nope nope Dope Dope Dope Dope

the official dope Dont Smoke

Make believe yer sick

Stay in bed and lick

yr cigarette habit greed

One day's all you need

In deed in deed in deed in deed smoke weed

smoke weed Put something green

in between but don't smoke smoke dont smoke

hope hope hope hope Nicotine dont

smoke the official dope

Dope Dope Dope Dope Dont Smoke

Smoke weed indeed smoke grass yass yass

smoke pot but not nicotine no no

indeed it's too obscene

put something green

in between your lips get hip not square

listen to my wail don't dare smoke coffin nails

ugh ugh ugh ugh the government Drug

official habit for Mr. Babbitt

Dont smoke the official dope

dope dope dope dope don't smoke

Dont Smoke Dont Smoke.

Original version: First Blues: Rags, Ballads and Harmonium Songs

Extended version: http://www.youtube.com/

Photo Credit: http://berkshirereview.net/

Smoking and Baby Poop

Telltale metabolites in meconium.

Attention pregnant smokers: You can run, but you can’t hide. A chemical analysis of your baby’s first official poop can establish whether your infant has suffered from prenatal exposure to tobacco smoke. The higher the levels of tobacco metabolites, the more likely the mother was an active smoker.

The authors of a study published in Environmental Health found that nicotine and assorted tobacco metabolites were easily detectable in an infant’s meconium, the black, tar-like substance that comprises the first stools from newborns. In a study of 337 babies, tobacco metabolite concentrations were higher in active smokers than in non-smoking women exposed to second-hand smoke only.

The researchers say the meconium method is not superior to other methods of measurements, but suggest it may be a useful adjunct in estimating “gestational exposure to other environmental toxicants that exhibit more variability during pregnancy, especially non-persistent compounds like bisphenol A and phthalates.”

One striking aspect of the study is that the researchers found nicotine and cotinine—a common nicotine metabolite--in most of the meconium samples analyzed. 80% of the samples contained nicotine. So it is not a question of exposure, it’s a question of the degree of exposure. Should we be concerned about the lower levels of exposure registered from second-hand smoke? Apparently so, since “meconium tobacco smoke metabolites were inversely associated with birth weight,” according to Joe M. Braun and coworkers. Braun suggested that additional biomarkers for tobacco exposure were important, based on his belief that tobacco smoke exposure during pregnancy is under-reported.

This looks like a potentially useful tool for epidemiological studies that enroll women and infants at birth. More studies of this kind are needed, because prenatal tobacco smoke exposure is increasingly implicated in “adverse infant and childhood health outcomes.”

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

A Shot for Cigarette Addiction?

NIDA’s Nora Volkow on addiction vaccines.

Nora Volkow, director of the National Institute on Drug Abuse (NIDA), predicted in a telephone interview on Friday that a vaccine for cigarettes could be available in as little as three years, if two large ongoing Phase 3 trials—the last major FDA hurdle—prove as successful as earlier studies.

NicVax (Nicotine Conjugate Vaccine) from Nabi Biopharmaceuticals, with a boost from a $40 million up-front cash infusion from GlaxoSmithKline Biologicals SA, is poised to become the first of a new kind of science-based addiction treatment—an avenue of approach that brings with it great promise, and a significant number of problems.

I asked Dr. Volkow if the NicVax studies had shown evidence that the effects could be overcome with greater levels of smoking. This is a hurdle that has plagued early research on a promising cocaine vaccine, as reported in the Archives of General Psychiatry (See my post "Cocaine Vaccine Hits Snag").  In the cocaine studies, researchers found that users could overcome the blunting effects of cocaine antibodies by ingesting as much as ten times their normal level of cocaine—clearly a dangerous outcome that could enhance the possibility of lethal overdose.  (See discussions at Neurotopia  and DrugMonkey).

“I am very sensitive to that issue,” Volkow said during a conference call from NIDA's Eighth Annual Blending Conference in Albuquerque, NM, where she was a featured speaker. “But the data we have give no evidence that smokers increase their cigarettes to overcome the antibodies. It was that piece of the data that led me to approve funding.”

In fact, said Volkow, “craving decreased after these vaccinations, so we would not necessarily expect smokers to try to overcome the effects. We’ve also seen a dramatic decrease in cocaine administration in animal models.” The matter of defeating a vaccine by overindulging remains a theoretical rather than an established risk, Volkow believes. 

Vaccines may operate somewhat differently that we think, she explained, by helping to extinguish the conditioned responses to craving cues as well. “We did not expect to see [anti-craving effects],” she said. “Craving is a product of memory, associated stimuli, the anticipation of a pleasant response. With cigarettes, if you feel nothing, the brain mechanism of conditioning that drives craving starts to weaken.”

The vaccine itself “is not totally stopping all of the drug from getting into the brain. But it affects the pharmacological properties, so users don’t get the expected outcome.  Nobody knows exactly how this might accelerate the extinction process—we haven’t done the studies. It’s going to be intriguing to have a product that has the capacity to make extinction much more universal.”

Volkow admitted that “we need to get a wider response,” since a significant number of smokers and cocaine users do not form antibodies from the vaccines. In addition, “we need longer-lasting responses so we don’t have to re-vaccinate.” The cocaine vaccine under study is in Phase 2 trials, and it will be several years before more definitive results are in.

The Blending Conference Volkow was attending was titled “Blending Addiction Science and Practice: Evidence-Based Treatment and Prevention in Diverse Populations and Settings.” Despite her emphasis on science-based treatments, Volkow stated firmly that social intervention and psychological treatment can be equally important, and characterized the supposed line between physical addiction and psychological addiction as an “obsolete distinction.” It is important to remember, she said, that “psychosocial interventions make biological changes in the brain” as well.

“People are desperate, and vaccines will be very helpful to those who develop antibodies. People want these magic bullets, but we don’t yet know how these vaccines will effect the therapeutic landscape.”

Graphics Credit: http://www.attcnetwork.org/