The Blunt Facts About Blunts

Mixing tobacco with marijuana.

People who smoke a combination of tobacco and marijuana, a common practice overseas for years, and increasingly popular here in the form of “blunts,” may be reacting to some unidentified mechanism that links the two drugs. Researchers believe such smokers would be well advised to consider giving up both drugs at once, rather than one at a time, according to an upcoming study in the journal Addiction.

Clinical trials of adults with cannabis use disorders suggest that “approximately 50% are current tobacco smokers,” according to the report, which was published in the journal Addiction, and authored by Arpana Agrawal and Michael T. Lynskey of Washington University School of Medicine, with Alan J. Budney of the University of Arkansas for Medical Sciences.  “As many cannabis users smoke a mixture of cannabis and tobacco or chase cannabis use with tobacco, and as conditioned cues associated with smoking both substances may trigger use of either substance,” the researchers conclude, “a simultaneous cessation approach with cannabis and tobacco may be most beneficial.”

A blunt is simply a marijuana cigar, with the wrapping paper made of tobacco and the majority of loose tobacco removed and replaced with marijuana. In Europe, smokers commonly mix the two substances together and roll the combination into a single joint, the precise ratio of cannabis and nicotine varying with the desires of the user. “There is accumulating evidence that some mechanisms linking cannabis and tobacco use are distinct from those contributing to co-occurring use of drugs in general,” the investigators say. Or, as psychiatry postdoc Erica Peters of Yale put it in a press release, “There’s something about tobacco use that seems to worsen marijuana use in some way.” The researchers believe that this “something” involved may be a genetic predisposition. In addition to an overall genetic proclivity for addiction, do dual smokers inherit a specific propensity for smoked substances? We don’t know—but evidence is weak and contradictory so far.

Wouldn’t it be easier to quit just one drug, using the other as a crutch? The researchers don’t think so, and here’s why: In the few studies available, for every dually addicted participant who reported greater aggression, anger, and irritability with simultaneous cessation, “comparable numbers of participants rated withdrawal associated with dual abstinence as less severe than withdrawal from either drug alone.” So, for dual abusers, some of them may have better luck if they quit marijuana and cigarettes at the same time. The authors suggest that “absence of smoking cues when abstaining from both substances may reduce withdrawal severity in some individuals.” In other words, revisiting the route of administration, a.k.a. smoking, may trigger cravings for the drug you’re trying to quit. This form of “respiratory adaption” may work in other ways. For instance, the authors note that, “in addition to flavorants, cigarettes typically contain compounds (e.g. salicylates) that have anti-inflammatory and anesthetic effects which may facilitate cannabis inhalation.”

Studies of teens diagnosed with cannabis use disorder have shown that continued tobacco used is associated with a poor cannabis abstention rate. But there are fewer studies suggesting the reverse—that cigarette smokers fair poorly in quitting if they persist in cannabis use. No one really knows, and dual users will have to find out for themselves which categories seems to best suit them when it comes time to deal with quitting.

We will pass up the opportunity to examine the genetic research in detail. Suffice to say that while marijuana addiction probably has a genetic component like other addictions, genetic studies have not identified any gene variants as strong candidates thus far. The case is stronger for cigarettes, but to date no genetic mechanisms have been uncovered that definitively show a neurobiological pathway that directly connects the two addictions.

There are all sorts of environmental factors too, of course. Peer influences are often cited, but those influences often seem tautological: Drug-using teens are members of the drug-using teens group. Tobacco users report earlier opportunities to use cannabis, which might have an effect, if anybody knew how and why it happens.

Further complicating matters is the fact that withdrawal from nicotine and withdrawal from marijuana share a number of similarities.  The researchers state that “similar withdrawal syndromes, with many symptoms in common, may have important treatment implications.” As the authors sum it up, cannabis withdrawal consists of “anger, aggression or irritability, nervousness or anxiety, sleep difficulties, decreased appetite or weight loss, psychomotor agitation or restlessness, depressed mood, and less commonly, physical symptoms such as stomach pain and shakes/tremors.” Others complain of night sweats and temperature sensitivity.

And the symptoms of nicotine withdrawal? In essence, the same. The difference, say the authors, is that cannabis withdrawal tends to produce more irritability and decreased appetite, while tobacco withdrawal brings on an appetite increase and more immediate, sustained craving. Otherwise, the similarities far outnumber the differences.

None of this, however, has been reflected in the structure of treatment programs: “Emerging evidence suggests that dual abstinence may predict better cessation outcomes, yet empirically researched treatments tailored for co-occurring use are lacking.”

The truth is, we don’t really know for certain why many smokers prefer to consume tobacco and marijuana in combination. But we do know several reasons why it’s not a good idea. Many of the health-related harms are similar, and presumably cumulative: chronic bronchitis, wheezing, morning sputum, coughing—smokers know the drill. Another study cited by the authors found that dual smokers reported smoking as many cigarettes as those who only smoked tobacco. All of this can lead to “considerable elevation in odds of respiratory distress indicators and reduced lung functioning in those who used both.” However, there is no strong link at present between marijuana smoking and lung cancer.

Some researchers believe that receptor cross-talk allows cannabis to modify receptors for nicotine, or vice versa. Genes involved in drug metabolism might somehow predispose a subset of addicts to prefer smoking. But at present, there are no solid genetic or environmental influences consistent enough to account for a specific linkage between marijuana addiction and nicotine addiction, or a specific genetic proclivity for smoking as a means of drug administration.

Agrawal, A., Budney, A., & Lynskey, M. (2012). The Co-occurring Use and Misuse of Cannabis and Tobacco: A Review. Addiction DOI: 10.1111/j.1360-0443.2012.03837.x

Photo credit: http://www.hightimes.com/

(First published at Addiction Inbox on March 22, 2012).

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).

Rotting from the Inside

Smoking and the decline of the body. 

We all know smoking is bad for your health. It causes lung cancer and emphysema and contributes to heart disease. But that’s not the end of the list. Recently, Public Health England, a government organization, collected and analyzed research on the contribution smoking makes to other forms of internal body damage. Authored by Dr. Rachael Murray of the UK Centre for Tobacco and Alcohol Studies and the University of Nottingham, the study looked at the correlation between smoking and the musculoskeletal system, the cognitive system, dental health, and vision.

And the results of various meta-analyses are exactly as grim as we might expect. (You can download the PDF HERE.)

Bones, Muscle, and Tissue

Smoking does steady harm to the musculoskeletal system of habitual smokers. Osteoporosis in mature smokers may result from a loss of bone mineral density, a condition for which smoking “is a long established contributing risk factor.” There are a number of ways smoking can affect bone mineral density, says the report, including “decreased calcium absorption, lower levels of vitamin D, changes in hormone levels, reduced body mass, increased free radicals and oxidative stress, higher likelihood of peripheral vascular disease and direct effects of toxic components of tobacco smoke on bone cells.”

Moreover, smoking and broken bones go together like apple pie and ice cream, or in this case, bangers and mash. Overall in the UK, “current smokers have been reported to be at a 25% increased risk of any fracture,” the report concludes. The author notes that the greatest risk for smokers are seen at the hip and the lumbar spine, and women smokers in particular “were at a 17% greater risk of hip fracture at age 60, 41% at 70, 71% at 80 and 108% at 90.” The risk of fracture and the increased bone repair time decreases slowly in former smokers, and it may take 5 to 10 years before abstinent smokers see any statistical benefits.

Researchers have also documented a causal relationship between cigarette smoking and the onset of rheumatoid arthritis. But it is not known whether smoking cessation benefits existing patients with this condition.

As for soft tissue damage, a meta-analysis of 40 studies showed that smoking was associated with “a 33% increased prevalence of low back pain within the previous 12 months, 79% increased prevalence of chronic back pain and 114% increased prevalence of disabling lower back pain” among British smokers. Another study of 13,000 subjects showed that current and ex-smokers experienced up to 60% more pain in the lower back, upper neck and lower limbs than people who had never smoked. Smokers were also “74% more likely than non-smokers to have a rotator cuff tear,” Dr. Murray writes.

The Brain in Your Head

Chronic cigarette smoking hastens the decline in cognitive function that occurs with age. And there is a disturbing link between tobacco smoking and dementia: “A meta-analysis of eight studies published in 2008 reported that current smokers were 59% more likely than never-smokers to suffer Alzheimer’s disease and 35% more likely to suffer vascular dementia.” Earlier studies showed even higher risk percentages. Here, there is the possibility that smoking succession could reduce dementia onset. Two meta-analyses included in the report showed no association between former smoking and risk of dementia.

General cognitive impairment in adults over 50 is “consistently associated” with smoking, according to the UK report. “Faster declines in verbal memory and lower visual search speeds have been reported in male and female smokers aged 43 and 53, with the effect largest in those who smoked more than 20 cigarettes per day, independent of other potentially confounding factors.”

Dental Damage

Smoking is the primary cause of oral cancer, and the risk of developing it is three times less for non-smokers. Smoked and smokeless tobacco are linked to various non-malignant maladies of the soft and hard tissues in the oral cavity. Alcohol is a risk factor for oral cancer as well, “and is almost tripled in alcohol drinkers who smoke.”

Peridontitis, the inflammatory condition marked by bleeding gums and degeneration leading to tooth loss (and an associated greater risk of coronary heart disease) is three to four times as common in adult smokers. And although there are other confounding socioeconomic influences, smoking is also a risk indicator for missing teeth in older smokers and previous smokers. The increased peridontitis risk lasts for several years after smoking cessation.

As for cavities and general tooth decay (caries), “Although the association between smoking and prevalence of dental caries can be attributed to poor dental care and oral hygiene, a cross-section study with a four-year follow-up found that daily smoking independently predicts caries development in smokers.” 

A Dim View

Neovascular and atrophic age-related macular degeneration, the eye conditions that cause a gradual loss of vision, are causally related to cigarette smoking. "A recent meta-analysis reported significant increases in macular degeneration of between 78% and 358%, depending on the study design." Smokers tend to develop the disease ten years earlier than non-smokers, and heavy smokers are at particular risk.

Finally, a number of cohort and case-control studies show a statistically significant link between smoking and cataracts, the cloudy patches over the eye that cause blurred vision. In current smokers, the increased risk is pegged at about 50%. "Smoking cessation reduces risks over time, however, the larger the exposure the longer it takes for the risk to reduce and this risk is unlikely to return to that of a never smoker."

Photo credit: hhttp://www.healthcareaboveall.com/

Cigarettes and Genetic Risk

Evidence From a 4-Decade Study.

Pediatricians have often remarked upon it: Give one adolescent his first cigarette, and he will cough and choke and swear never to try another one. Give a cigarette to a different young person, and she is off to the races, becoming a heavily dependent smoker, often for the rest of her life. We have strong evidence that this difference in reaction to nicotine is, at least in part, a genetic phenomenon.

But so what? Is there any practical use to which such knowledge can be put? As it turns out, the answer may be yes. People with the appropriate gene variations on chromosomes 15 and 19 move very quickly from the first cigarette to heavy use of 20 or more cigarettes per day, and have more difficulty quitting, according to a report  published last year in JAMA Psychiatry. From a public health point of view, these findings add a strong genetic rationale to early smoking prevention efforts— especially programs that attempt to “disrupt the developmental progression of smoking behavior” by means of higher prices and aggressive enforcement of age restrictions on smoking.

What the researchers found were small but identifiable differences that separated people with these genetic variations from other smokers. The gene clusters in question “provide information about smoking risks that cannot be ascertained from a family history, including information about risk for cessation failure,” according to authors Daniel W. Belsky, Avshalom Caspi, and colleagues at the University of North Carolina and Duke University.

The group looked at three prominent genome-wide association studies of adult smoking to see if the results could be applied to “the developmental progression of smoking behavior.” They used the data from the genome work to analyze the results of a 38-year prospective study of 1,037 New Zealanders, known as the Dunedin Study. A total of 405 cohort members in this study ended up as daily smokers, and only 20% of the daily smokers ever achieved cessation, defined as a year or more of continual abstinence.

The researchers came up with a multilocus genetic risk score (GRS) based on single-nucleotide polymorphisms associated with smoking behaviors. Previous meta-analyses had identified several suspects, specifically a region of chromosome 15 containing the CHRNA5-CHRNA3-CHRNB4 gene cluster, and a region of chromosome 19 containing the gene CYP2A6. These two clusters were already strong candidate genes for the development of smoking behaviors. For purpose of the study, the GRS was calculated by adding up the alleles associated with higher smoking quantity. The genetic risk score did not pertain to smoking initiation, but rather to the number of cigarette smoked per day.

When the researchers applied these genetic findings to the Dunedin population cohort, representing ages 11 to 38, they found that an unfortunate combination of gene types seemed to be pushing some smokers toward heavy smoking at an early age. Individuals with a high GRS score “progressed more rapidly to heavy smoking and nicotine dependence, were more likely to become persistent heavy smokers and persistently nicotine dependent, and had more difficulty quitting,” according to the study. However, these effects took hold only when young smokers “progressed rapidly from smoking initiation to heavy smoking during adolescence.” The variations found on chromosomes 15 and 19 influence adult smoking “through a pathway mediated by adolescent progression from smoking initiation to heavy smoking.”

Curiously, the group of people who had the lowest Genetic Risk Scores were not people who had never smoked, but rather people who smoked casually and occasionally—the legendary “chippers,” who can take or leave cigarettes, sometimes have one late at night, or a couple at parties, without ever falling victim to nicotine addiction. These “light but persistent smokers” were accounted for “with the theory that the genetic risks captured in our score influence response to nicotine, not the propensity to initiate smoking.”

Naturally, the study has limitations. Everyone in the Dunedin Study was of European descent, and the life histories ended at age 38. Nor did the study take smoking bans or different ages into account. The study cries out for replication, and hopefully that won’t be long in coming.

Could information of this sort be used to identify high-risk young people for targeted prevention programs? That is the implied promise of such research, but no, probably not. The gene associations are not so dramatic as to cause youngsters with the “bad” alleles to inevitably become chain smokers, nor do the right set of genes confer protection against smoking. It’s not that simple. However, the study is definitely one more reason to push aggressive smoking prevention efforts aimed at adolescents.

(First published March 28, 2013)

Belsky D.W.  Polygenic Risk and the Developmental Progression to Heavy, Persistent Smoking and Nicotine DependenceEvidence From a 4-Decade Longitudinal StudyDevelopmental Progression of Smoking Behavior, JAMA Psychiatry,   1. DOI: 10.1001/jamapsychiatry.2013.736

Graphics credit: http://www.sciencemediacentre.co.nz/

Will Power and Its Limits

How to strengthen your self-control.

Reason in man obscured, or not obeyed,
Immediately inordinate desires,
And upstart passions, catch the government
From reason; and to servitude reduce
Man, till then free.
—John Milton, Paradise Lost

What is will power? Is it the same as delayed gratification? Why is will power “far from bulletproof,” as researchers put it in a recent article for Neuron? Why is willpower “less successful during ‘hot’ emotional states”? And why do people “ration their access to ‘vices’ like cigarettes and junk foods by purchasing them in smaller quantities,” despite the fact that it’s cheaper to buy in bulk?

 Everyone, from children to grandparents, can be lured by the pull of immediate gratification, at the expense of large—but delayed—rewards. By means of a process known as temporal discounting, the subjective value of a reward declines as the delay to its receipt increases. Rational Man, Economic Man, shouldn’t behave in a manner clearly contrary to his or her own best interest. However, as Crockett et. al. point out in a recent paper in Neuron “struggles with self-control pervade daily life and characterize an array of dysfunctional behaviors, including addiction, overeating, overspending, and procrastination.”

Previous research has focused primarily on “the effortful inhibition of impulses” known as will power. Crockett and coworkers wanted to investigate another means by which people resist temptations. This alternative self-control strategy is called precommitment, “in which people anticipate self-control failures and prospectively restrict their access to temptations.” Good examples of this approach include avoiding the purchase of unhealthy foods so that they don’t constitute a short-term temptation at home, and putting money in financial accounts featuring steep penalties for early withdrawal. These strategies are commonplace, and that’s because people generally understand that will power is far from foolproof against short-term temptation. People adopt strategies, like precommitment, precisely because they are anticipating the possibility of a failure of self-control. We talk a good game about will power and self-control in addiction treatment, but the truth is, nobody really trusts it—and for good reason.  The person who still trusts will power has not been sufficiently tempted.

The researchers were looking for the neural mechanisms that underlie precommitment, so that they could compare them with brain scans of people exercising simple self-control in the face of short-term temptation.

After behavioral and fMRI testing, the investigators used preselected erotic imagery rated by subjects as either less desirable ( smaller-sooner reward, or SS), or more highly desirable ( larger-later reward, or LL). The protocol is complicated, and the analysis of brain scans is inherently controversial. But previous studies have shown heightened activity in three brain areas when subjects are engaged in “effortful inhibition of impulses.” These are the dorsolateral prefrontal cortex (DLPFC), the inferior frontal gyrus (IFG), and the posterior parietal cortex (PPC). But when presented with opportunities to precommit by making a binding choice that eliminated short-term temptation, activity increased in a brain region known as the lateral frontopolar cortex (LFPC).  Study participants who scored high on impulsivity tests were inclined to precommit to the binding choice.

In that sense, impulsivity can be defined as the abrupt breakdown of will power. Activity in the LFPC has been associated with value-based decision-making and counterfactual thinking. LFPC activity barely rose above zero when subjects actively resisted a short-term temptation using will power.  Subjects who chose the option to precommit, who were sensitive to the opportunity to make binding choices about the picture they most wanted to see, showed significant activity in the LFPC. “Participants were less likely to receive large delayed reward when they had to actively resist smaller-sooner reward, compared to when they could precommit to choosing the larger reward before being exposed to temptation.”

Here is how it looks to Molly Crockett and her fellow authors of the Neuron article:

Precommitment is adaptive when willpower failures are expected…. One computationally plausible neural mechanism is a hierarchical model of self-control in which an anatomically distinct network monitors the integrity of will-power processes and implements precommitment decisions by controlling activity in those same regions. The lateral frontopolar cortex (LFPC) is a strong candidate for serving this role.

None of the three brain regions implicated in the act of will power were active when opportunities to precommit were presented.  Precommitment, the authors conclude, “may involve recognizing, based on past experience, that future self-control failures are likely if temptations are present. Previous studies of the LFPC suggest that this region specifically plays a role in comparing alternative courses of action with potentially different expected values.” Precommitment, then, may arise as an alternative strategy; a byproduct of learning and memory related to experiences “about one’s own self-control abilities.”

There are plenty of caveats for this study: A small number of participants, the use of pictorial temptations, and the short time span for precommitment decisions, compared to real-world scenarios where delays to greater rewards can take weeks or months. But clearly something in us often knows that, in the immortal words of Carrie Fisher, “instant gratification takes too long.” For this unlucky subset, precommitment may be a vitally important cognitive strategy. “Humans may be woefully vulnerable to self-control failures,” the authors conclude, “but thankfully, we are sometimes sufficiently far-sighted to circumvent our inevitable shortcomings.” We learn—some of us—not to put ourselves in the path of temptation so readily.

Crockett M., Braams B., Clark L., Tobler P., Robbins T. & Kalenscher T. (2013). Restricting Temptations: Neural Mechanisms of Precommitment, Neuron, 79 (2) 391-401. DOI: 10.1016/j.neuron.2013.05.028

Photo Credit: http://tommyboland.com/2011/05/27/white-knuckle-living/

A Weak Smoker’s Vaccine Might Be Worse Than None

New PET scans show wide responses to antibodies.

One of the brightest hopes of addiction science has been the idea of a vaccine—an antibody that would scavenge for drug molecules, bind to them, and make it impossible for them to cross the blood-brain barrier and go to work. But there are dozens of good reasons why this seemingly straightforward approach to medical treatment of addiction is devilishly difficult to perform in practice.

Last January, health care company Novartis threw in the towel on NicVax, a nicotine vaccine that failed to beat placebos in Phase III clinical trials for the FDA. And back in 2010, a report in the Archives of General Psychiatry demonstrated that a vaccine intended for cocaine addicts only generated sufficient antibodies to dull the effects of the cocaine in 38 percent of the test subjects. Moreover, it proved possible to overcome immunization by upping the cocaine dose, which sounded like an invitation to overdose.

And now, neuroscientists at the Society of Nuclear Medicine and Molecular Imaging annual meeting have presented a new study, the conclusions of which might help researchers understand why the vaccine results have been so mixed. The research “represents one of the first human studies of its kind using molecular imaging to test an investigational anti-nicotine immunization,” lead author Alexey Mukhin, professor of psychiatry and behavioral science at Duke University Medical Center, said in a prepared statement.


Subjects underwent two PET brain scan as they smoked nicotine labeled with radioactive C-11, one before the vaccine was administered, and one after. Ten subjects who developed “high-affinity antibodies” after vaccination showed a slight decrease in nicotine accumulation in the brain, as judged by the scans. However, another group of ten subjects, who showed “intermediate serum nicotine binding capacity and low affinity of antibodies” actually showed an increase in brain nicotine levels. What the PET scans showed was that “strong nicotine-antibody binding, which means high affinity, was associated with a decrease in brain nicotine accumulation. When binding was not strong, an increase in brain accumulation was observed.”

If the bond that holds the antibodies to the nicotine molecules is weak, the bond can break during passage through the blood-brain barrier, potentially allowing excess nicotine to flood in. This result, said Mukhin, tell us “we should care about not only the amount of antibody, but the quality of the antibody. We don’t want to have low-affinity antibodies because that can negate the anti-nicotine effects of the vaccination.”

Back to the drawing board? Not entirely. Another of the study authors, Yantao Zuo of Duke University Medical Center, said that “with reports of new generations of the vaccines showing potentially much higher potencies in animal studies, we are hopeful that our current findings and methodology in human research will facilitate understanding of how these work in smokers.”

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

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

World No Smoking Day.

Smokers’ Genes: Evidence From a 4-Decade Study

How adolescent risk becomes adult addiction.

 Pediatricians have often remarked upon it: Give one adolescent his first cigarette, and he will cough and choke and swear never to try another one. Give a cigarette to a different young person, and she is off to the races, becoming a heavily dependent smoker, often for the rest of her life. We have strong evidence that this difference in reaction to nicotine is, at least in part, a genetic phenomenon.

But so what? Is there any practical use to which such knowledge can be put? As it turns out, the answer may be yes. People with the appropriate gene variations on chromosomes 15 and 19 move very quickly from the first cigarette to heavy use of 20 or more cigarettes per day, and have more difficulty quitting, according to a new report published in JAMA Psychiatry. From a public health point of view, these findings add a strong genetic rationale to early smoking prevention efforts— especially programs that attempt to “disrupt the developmental progression of smoking behavior” by means of higher prices and aggressive enforcement of age restrictions on smoking.

What the researchers found were small but identifiable differences that separated people with these genetic variations from other smokers. The gene clusters in question “provide information about smoking risks that cannot be ascertained from a family history, including information about risk for cessation failure,” according to authors Daniel W. Belsky, Avshalom Caspi, and colleagues at the University of North Carolina and Duke University.

The group looked at three prominent genome-wide association studies of adult smoking to see if the results could be applied to “the developmental progression of smoking behavior.” They used the data from the genome work to analyze the results of a 38-year prospective study of 1,037 New Zealanders, known as the Dunedin Study. A total of 405 cohort members in this study ended up as daily smokers, and only 20% of the daily smokers ever achieved cessation, defined as a year or more of continual abstinence.

The researchers came up with a multilocus genetic risk score (GRS) based on single-nucleotide polymorphisms associated with smoking behaviors. Previous meta-analyses had identified several suspects, specifically a region of chromosome 15 containing the CHRNA5-CHRNA3-CHRNB4 gene cluster, and a region of chromosome 19 containing the gene CYP2A6. These two clusters were already strong candidate genes for the development of smoking behaviors. For purpose of the study, the GRS was calculated by adding up the alleles associated with higher smoking quantity. The genetic risk score did not pertain to smoking initiation, but rather to the number of cigarette smoked per day.

When the researchers applied these genetic findings to the Dunedin population cohort, representing ages 11 to 38, they found that an unfortunate combination of gene types seemed to be pushing some smokers toward heavy smoking at an early age. Individuals with a high GRS score “progressed more rapidly to heavy smoking and nicotine dependence, were more likely to become persistent heavy smokers and persistently nicotine dependent, and had more difficulty quitting,” according to the study. However, these effects took hold only when young smokers “progressed rapidly from smoking initiation to heavy smoking during adolescence.” The variations found on chromosomes 15 and 19 influence adult smoking “through a pathway mediated by adolescent progression from smoking initiation to heavy smoking.”

Curiously, the group of people who had the lowest Genetic Risk Scores were not people who had never smoked, but rather people who smoked casually and occasionally—the legendary “chippers,” who can take or leave cigarettes, sometimes have one late at night, or a couple at parties, without ever falling victim to nicotine addiction. These “light but persistent smokers” were accounted for “with the theory that the genetic risks captured in our score influence response to nicotine, not the propensity to initiate smoking.”

Naturally, the study has limitations. Everyone in the Dunedin Study was of European descent, and the life histories ended at age 38. Nor did the study take smoking bans or different ages into account. The study cries out for replication, and hopefully that won’t be long in coming.

Could information of this sort be used to identify high-risk young people for targeted prevention programs? That is the implied promise of such research, but no, probably not. The gene associations are not so dramatic as to cause youngsters with the “bad” alleles to inevitably become chain smokers, nor do the right set of genes confer protection against smoking. It’s not that simple. However, the study is definitely one more reason to push aggressive smoking prevention efforts aimed at adolescents.


Belsky D.W.  Polygenic Risk and the Developmental Progression to Heavy, Persistent Smoking and Nicotine DependenceEvidence From a 4-Decade Longitudinal StudyDevelopmental Progression of Smoking Behavior, JAMA Psychiatry,   1. DOI: 10.1001/jamapsychiatry.2013.736

Graphics Credit: http://cigarettezoom.com/

Big Tobacco Easily Evades “Light” Cigarette Ban

Color coding allows smokers to easily identify their former brands.

The tobacco industry has once again made a mockery of the Food and Drug Administration’s attempts to ban ‘light” cigarettes from the marketplace, by simply eliminated the objectionable wording and substituting an easily-decoded color scheme. In a brochure prepared for cigarette retailers marked “For trade use only: not to be shown or distributed to customers,” tobacco giant Philip Morris wrote that “some cigarettes and smokeless packaging is changing, but the product remains the same.”

Research done at Harvard demonstrates "the continued attempts of the industry to avoid reasonable regulation of tobacco products,” said Hillel Alpert, co-author of a new study on light cigarettes, in a prepared statement. The Family Smoking Prevention and Tobacco Control Act (FSPTCA) of 2009 highlights the banning of light cigarettes as a critical mission, since cigarettes marketed in this way are in fact no safer than regular cigarettes. What makes a cigarette Light or Ultra-light is a series of tiny holes drilled through the filter (See earlier post). This “filter ventilation” was calibrated to the descriptors: Ultra-lights had more holes drilled in the filter than Lights. Studies have demonstrated conclusively that such filter schemes do not make smoking safer or cut down on related diseases. A 2001 report from the National Cancer Institute documented how smokers were compensating for the ventilation holes by smoking more cigarettes, smoking them more intensely, or by blocking the filter holes with fingers or lips.

In a study for Tobacco Control, Gregory Connolly and Hillel Alpert of the Harvard School of Public Health documented the process. In 2010, Philip Morris sent manuals to retailers detailing how they were to deal with the new sales situation. Philip Morris made clear that “current pack descriptors such as light, ultra-light and mild will be removed from all packages.” All well and good. However, the Philip Morris material also specified how a series of new package names were to be doled out. Marlboro Light became Marlboro Gold. Marlboro Mild morphed into Marlboro Blue. And Marlboro Ultra-light reemerged as Marlboro Silver.

When the researchers commissioned a large public survey to document the state of affairs one year after the official “light” ban, they found that “88%-91% of smokers found it either ‘somewhat easy’ or ‘very easy’ to identify their usual brand of cigarettes by the banned descriptor names, Lights, Mediums or Ultra-Lights.” Sales figures for these brands in the first two quarters of 2010 were essentially unchanged, the authors report. They conclude that “the majority of smokers of brands in all categories correctly identified their brands’ pack color.”

The lesson here may well be that countries like Australia and the UK are on the right track: Plain packaging may be best. If lawmakers allow “misleading numbers, the use of colors, imagery, brand extensions, and other devices that contribute to deception” in place of words, nothing has really changed. “The findings of the present research strongly suggest that tobacco manufacturers have evaded one of the most important provisions of the FSPTCA for protecting the public health from the leading cause of preventable death and disease,” the authors conclude.

In a press release, co-author Gregory Connolly, director of the Center for Global Tobacco Control at Harvard, explained that the industry “was found guilty by a federal court in 2006 for deceptively promoting ‘light’ cigarettes as safer after countless smokers who switched to lights died prematurely, thinking they had reduced their health risks.”

Connolly G.N. & Alpert H.R. (2013). Has the tobacco industry evaded the FDA's ban on 'Light' cigarette descriptors?, Tobacco Control, PMID: 23485704

Photo Credit:http://www.mydiscountcigarette.net

Novartis Gives Up On Nicotine Vaccine

Another one bites the dust.

Novartis, a leading health care products company, called it quits on its NIC002 nicotine vaccine project, which failed badly three years ago in Phase II studies undertaken with an eye toward government approval. Novartis said it would terminate the license it has for the NIC002 vaccine with Cytos Biotechnology, for which it paid $38 million in 2007. The Phase II study “showed formation of nicotine-specific antibodies in patients but did not meet its primary endpoint of increased smoking cessation,” according to Genetic Engineering and Biotechnology News

Much the same arc was followed by Nabi Biopharmaceuticals, which announced in 2011 that its vaccine, NicVax, had failed to outdo placebos in Phase III clinical trials—the only addiction vaccine to advance that far in the approval process. The company’s own studies had shown happier results in 2007. In regulatory filings, the company claimed that the NicVax vaccine triggered a reliable antibody response, thus preventing nicotine molecules from reaching the brain. The antibodies bind with the nicotine molecules, making nicotine too large to cross the exceedingly fine blood-brain barrier of the brain. Roughly 15 per cent of smokers who received injections of NicVax were nicotine-free after one year in company-funded studies. For comparison, early studies of Chantix as an anti-smoking medication show a quit response rate in the range of 20 per cent for heavy smokers.

As I have previously written, the idea of vaccinating for addictions is not new. If you want the body to recognize a nicotine molecule as a foe rather than a friend, one strategy is to attach nicotine molecules to a foreign body--commonly a protein that the body ordinarily rejects--in order to switch on the body’s immune responses against the invader. A strong advantage to this approach, say researchers, is that the vaccinated compound does not enter the brain and therefore is free of neurological side effects.

There remain a wealth of questions related to the effects of long-lasting antibodies. And it is sometimes possible to “swamp” the vaccine by ingesting four or five times as much cocaine or nicotine as usual.

Drugs that substantially reduce a smoker’s craving for nicotine, like Chantix, may yet prove to be a more fruitful avenue of investigation. While several anti-craving medications have been approved for use by the Food and Drug Administration (FDA), no vaccines have made it onto the approved list. However, as the Genetic Engineering article reminds us, “all is not lost for the vaccine yet: in November of 2010, Duke University, in collaboration with Wake Forest University, commenced a Phase II clinical study with NIC002 performed with 65 smokers that aims to assess how nicotine antibodies, induced by vaccination, affect the pharmacokinetics of nicotine during cigarette smoking. The study is being conducted in the United States with funding from the NIH.”

Photo: Creative Commons / juliealicea1947

Have We Killed Half of our Soldiers with Cigarettes?

Two long-term studies yield grim stats, and women are no exception.

We know that smoking kills. But until the results of 50 years’ worth of observations on British male smokers was published by Richard Doll and coworkers in the British Journal of Medicine in 2004, we didn’t know how many.  Cigarettes will kill at least half of those who smoke them past the age of 30—possibly more. In older, specific populations, possibly as many as 2/3.

It took a prospective study of more than 34,000 British doctors, starting in 1951 and ending in 2001, to establish the grim parameters with some degree of precision. As the study authors of the 2004 summary paper put it: “A substantial progressive decrease in the mortality rates among non-smokers over the past half century… has been wholly outweighed, among cigarette smokers, by a progressive increase in the smoker v non-smoker death rate ratio due to earlier and more intensive use of cigarettes.” In other words, the great reduction in disease mortality rates achieved in the 20th Century, courtesy of better prevention and treatment, effectively never happened for long-term male smokers. Smoking in Britain and America took off in a major way between the two world wars, and sufficient time has now passed to conclude that “men born in 1900-1930 who smoked only cigarettes and continued smoking died on average about 10 years younger than lifelong non-smokers.”

As for women, it took a few decades longer to nail down the truth, because women did not begin smoking in peak numbers until the 1960s. While men born between 1900 and 1930 took to cigarettes in a big way, women born around 1940 were the first cohort of female smokers to consume a substantial number of cigarettes throughout their adult lives. This 20-year lag is crucial, because it means that solid numbers for female mortality rates require solid figures on mortality rates in the 21st Century. And now we have them, courtesy of the Million Women Study in the UK. The results were recently published in The Lancet by Kirstin Pirie and others. They are just as bad as you might have guessed, putting women on a firm equal footing with their male counterparts when it comes to smoking deaths.

The Million Women Study, a database originally used for the UK’s National Health Service Breast Screening Program, recruited female volunteers between the ages of 50 and 69. The figures were eerily similar to those from the earlier study of male British doctors: “If combined with 2010 UK national death rates, tripled mortality rates among [female] smokers indicate 53% of smokers and 22% of never-smokers dying before age 80 years, and an 11-year lifespan difference…. Although the hazards of smoking until age 40 years and then stopping are substantial, the hazards of continuing are ten times greater.” In this study, the researchers found little difference between female smokers and nonsmokers when it came to confounding variables like weight, blood pressure, or lipid profile. A four-year head start—beginning to smoke at the age of 15 rather than 19, say—can put women at a measurably greater risk for lung cancer deaths.  And a little goes a long way: “Even those smoking fewer than ten cigarettes per day at baseline had double the overall mortality rate of never-smokers.” Low-tar won’t save them, either. “Low-tar cigarettes are not low-risk cigarettes,” the investigators write, “and the Million Women Study shows that more than half of those who smoke them will eventually be killed by them, unless they stop smoking in time to avoid this.”

There it is again: Half of all smokers are going to die from smoking.  As the authors of the Lancet study wrote: “If women smoke like men, they die like men.”

In summary, those who stop smoking at age 50 gain about six years of life expectancy. Quit at 40, and you get an extra nine years. A non-smoker’s chances of living from 70 to 90 are three times higher than a smoker’s. The researchers found that the doctors who stopped smoking by age 30 managed to avoid almost all of the lifespan penalties associated with smoking—primarily lung cancer, COPD, and heart disease. (Only about 3% of smoking deaths are due to fires, accidents, poisonings, etc.). And even lifelong smokers who do not quit until the age of 60 are still rewarded with an extra three years of life span, on average.

Perhaps the saddest thing about the findings is the ways in which they suggest that British and American military commanders may have been sentencing countless numbers of soldiers to death for decades, through the simple act of giving away cigarettes in K-rations, and selling them cheaply in other circumstances. As the report in the British Medical Journal states, “widespread military conscription of 18 year old men, which began again in 1939 and continued for decades, routinely involved provision of low cost cigarettes to the conscripts. This established in many 18 year olds a persistent habit of smoking substantial numbers of manufactured cigarettes, which could well cause the death of more than half of those who continued.” In a perverse reminder of the Agent Orange scandal in Vietnam, American and British military command may have exposed their soldiers to a much greater threat, for a much longer period, with worse odds for survival.

One obvious confounding variable in such studies is alcohol. It requires a sensitive statistical analysis to work through correlations between drinking, smoking, and, say, liver disease.  But “the large majority of the excess overall mortality among smokers is actually caused by smoking,” the Lancet researchers maintain with confidence.  The overall point seems clear: These long-term results show that the risks from continual cigarette smoking are even greater than we thought.

The dismal bottom line of the two smoking studies is that we appear to be right on schedule for meeting the UN’s prediction of one billion tobacco deaths in this brave new century.

Pirie, K., Peto, R., Reeves, G., Green, J., & Beral, V. (2012). The 21st century hazards of smoking and benefits of stopping: a prospective study of one million women in the UK The Lancet DOI: 10.1016/S0140-6736(12)61720-6

Photo Credit: Ianier67 via Creative Commons.

States Quietly Defunding Anti-Smoking Programs For Kids

Only 2 cents of each tobacco settlement dollar goes to smoking prevention plans.

If there’s one thing we know about smoking, it’s that for every smoker who quits, we gain a net financial benefit. These health cost savings can be huge for states, which is why all of them have put in place smoking cessation plans and programs for their citizens. And they are able to run this programs because of the monies that come to them under the 1998 master tobacco settlement.

Perhaps it doesn’t come as a huge surprise, but it’s depressing, all the same: The Campaign for Tobacco-Free Kids estimates that states will spend less than 2 per cent of these court-mandated funds on actual programs to prevent kids from smoking. The report accuses the states of failing to reverse budget cuts to “programs that have set back the nation’s efforts to reduce tobacco use.”

The report was undertaken to access whether states have been using the estimated $246 billion over 25 years—plus cigarette taxes—to reduce tobacco use. What they found was that “states have failed to reverse deep budget cuts that reduced funding for tobacco prevention by 36 percent” from 2008 to 2012. Only North Dakota and Alaska are currently funding smoking cessation programs at the level recommended by the Centers for Disease Control and Prevention (CDC). Four states—New Hampshire, New Jersey, North Carolina, and Ohio—have allocated ZERO funds for tobacco prevention programs in FY 2013.

“Given such a strong return on investment,” the report concludes, “states are truly penny-wise and pound-foolish in shortchanging tobacco prevention and cessation programs.” The report declined to speculate on where the money actually goes, but noted that this was the “second lowest amount states have spent on tobacco prevention programs since 1999, when they first received tobacco settlement funds.”

The cries of outrage came thick and fast:

“The states have an obligation to use more of their billions in tobacco revenues to fight the tobacco problem. Their failure to do so makes no sense given the evidence that tobacco prevention programs save lives and save money by helping reduce health care costs."—Matthew L. Myers, President of the Campaign for Tobacco-Free Kids

"States with comprehensive tobacco control programs experience faster declines in cigarette sales, smoking prevalence and lung cancer incidence and mortality than states that do not invest in these programs."—John R. Seffrin, CEO of the American Cancer Society Cancer Action Network

"The paltry amount of money that states spend on tobacco prevention and cessation programs is extremely disappointing…. These programs work and it’s time for states to put more skin in the game."—Nancy Brown, CEO of the American Heart Association

"Too many states are failing their citizens by abandoning their responsibility to invest in proven programs that prevent people from smoking and help smokers quit…. Supporting these programs at recommended levels is not only the right thing to do, it's the smart thing to do — quitting smoking or never starting saves lives and saves money."—Paul G. Billings, senior vice president of Advocacy & Education at the American Lung Association

In 2007, the CDC concluded: “We know how to end the epidemic. Evidence-based, statewide tobacco control programs that are comprehensive, sustained, and accountable have been shown to reduce smoking rates, tobacco-related deaths, and diseases caused by smoking.”

Two cents on every dollar. About 20 percent of Americans smoke. “Tobacco companies spend more than $18 to market tobacco products for every one dollar the states spend to reduce tobacco use.” What’s wrong with this picture?

Photo Credit: http://www.tobaccofreekids.org

The Encultured Brain: A Book Review

How biology and culture jointly define us.

Anyone who follows academia knows that the broad category of courses known as the Liberal Arts has been going through major changes for some time now. In a sort of collegiate scrum to prove relevance and fund-worthiness, disciplines like sociology, anthropology, human ecology, cultural psychology, and even English, have been subjected to a winnowing process. The clear winner seems to anthropology, which has expanded its own field by connecting with modern findings in neuroscience while simultaneously swallowing up what was left of sociology.

It makes sense. Take addiction for an example. Anthropology is a natural and accessible discipline within which to connect the two often-conflicting facets of addiction—its fundamental neuroarchitecture, and the socioenvironmental influences that shape this basic biological endowment. In The Encultured Brain, published this year by MIT Press, co-editors Daniel H. Lende and Greg Downey call for a merger of anthropology and brain science, offering ten case histories of how that might be accomplished. The case histories are lively, ranging from the somatics of Taijutsu martial arts in Japan, to the presence of humor among breast cancer survivors. These attempts to combine laboratory research with anthropological fieldwork are important early efforts at a new combinatory science—one of the hot new “neuros” that just might make it.

I have corresponded with Daniel Lende, one of the book’s co-editors, and I am happy to disclose a mention in the book’s acknowledgements as one of the many people who formed a “rolling cloud of online discussion” with respect to neuroscience and the new anthropology. I am pleased to see that the thoughts of Lende and Downey and others on the emerging science of neuroanthropology are now available as a textbook.

The term “neuroanthropology” was evidently coined by Stephen Jay Gould. A number of prominent thinkers have dipped into this arena over the years: Melvin Konner, Sarah Hrdy, Norman Cousins, Robert Sapolsky, and Antonio Damasio, to name a random few, but the term didn’t seem to get a foothold of note until Lende and Downey began their Neuroanthropology blog, now at PLOS blogs.

The term has the advantage of meaning exactly what it says: an engagement between social science and neuroscience. Lende and Downey look ahead to a time when field-ready equipment will measure nutritional intake, cortisol levels, prenatal conditions, and brain development in the field. As such, neuroanthropology fits somewhere in the vicinity of evolutionary biology and cultural psychology. As a potential new synthesis, it is brilliant and challenging, representing an integrative approach to that ancient problem—how our genetic endowment is influenced by our cultural endowment, or vice versa, if you prefer.

 Lende is no functionalist when it comes to the neuroscience he wants to see incorporated in anthropology. His approach calls for applying a critical eye to any and all strictly brain-based explanations that ignore both environmental influence and biochemical individuality. The possibility that anthropologists may be incorporating neuroimaging technology into their working tool kit is a heady notion indeed. Anthropology may be a “soft” science, but it has always been about the study of “brains in the wild.”

Here, from the introductory chapter, is the short definition of neuroanthropology by Lende and Downey: “Forms of enculturation, social norms, training regimens, ritual, language, and patterns of experience shape how our brains work and are structured…. Without material change in the brain, learning, memory, maturation, and even trauma could not happen…. Through systematic change in the nervous system, the human body learns to orchestrate itself. Cultural concepts and meanings become neurological anatomy.” From the point of view of actual study, there is no choice but to join these two when possible—a task make more difficult by the rampant “biophilia” found among anthropologists and sociologists, as well as the countering notion among biologists that anthropology does not make the cut as a “real” science.

We have come a long way from the simplified view of the brain as some sort of solid-state computer, or, alternatively, a lump of custard waiting to be endowed with functionality by selective pressures from “outside.” We know by now that neural resources are frequently reallocated; that “physiological processes from scaling to connectivity shape what brains can do and why.”  We need to stop viewing culture as “merely information that is transmitted over evolutionary time and recognize that enculturation is, equally, the ways that our interaction with each other shapes our biological endowment, and has been doing so for a very long time,” Lende writes.

At bottom, says Lende, it is a simple notion: “Biology and culture jointly define us.” For example, Lende points to the way tool use affects cortical organization. Monkeys trained to use rakes to fetch food “evidence increasing cortex dedicated to visual-tactile neurons.” Lende wants us to incorporate neuroscience into the broader study of man. He writes that “the activation of neural reward centers, such as the mesolimbic dopaminergic system, is inherently bound up in sociocultural contexts, social interactions, and personal meaning-making.”

As an example, Lende contributes a chapter on “Addiction and Neuroanthropology,” in which he describes research he conducted on drug abuse among young people during a decade he spent in Colombia. Lende found that the addictive spiral “was not merely a neurological transformation, but a shift in habits, clothing, friends, hangouts, and other external factors that re-cued drug seeking behavior, drove addicts to take drugs, even when the young people sought to stay clean. Addiction is not simply in the brain, but in the way that the addict’s brain and world support each other.” And now, he writes, “This combination of neuroscience and ethnography revealed that addiction is a problem of involvement, not just of pleasure or of self. That decade showed me that addiction is profoundly neuroanthropological.”

In other words, tolerance and withdrawal aren’t enough. It is fiendishly complex: “The parts of the brain where addiction happens are not single, isolated circuits—rather, these areas handle emotion, memory, and choice, and are complexly interwoven to manage the inherent difficulty of being a social self in a dynamic world.”

Trying to pick apart the relative influences of nature and nurture comes to look, ultimately, like a fool’s game, “because changes in behavior exposed users to situations in which specific neurophysiological effects were cued with greater frequency; both environment and biology were moving together into a cycle of addiction.”

In a chapter titled “Collective Excitement and Lapse in Agency: Fostering an Appetite for Cigarettes," Peter G. Stromberg of the University of Tulsa argues that the dissociative environment in which college students often try cigarettes for the first time can lead to the loss of “the sense of agency,” meaning that people sometimes carry out activities without taking full responsibility for the decision to do so. As Stromberg writes, “Early smoking experiences typically occur in effervescent social gatherings marked by a high level of excitement and highly rhythmic activities, such as conversation and dancing." Cigarettes acquire a “symbolic valence” in such settings, and the ability to handle a cigarette adroitly confers what Stromberg terms “erotic prestige.” Furthermore, “As anyone who has ever been in a conga line can attest, we humans can be strongly motivated to entrain with rhythmic activities, even if those activities might be judged as unappealing in other contexts.”

If young people smoke at parties for many of the same reasons that they dance at parties—a “desire to increase status” and enter into “joint rhythmic play”—then potential nicotine addicts will be gently nudged into a position of associating party feelings with cigarette feelings, regardless of the actual physiology of nicotine. And, by fostering a dissociative mode of consciousness, college parties help foster the conviction that the use of cigarettes is not completely under one’s volitional control (“I was going to leave, but we danced all night.” Or, “the next thing I knew, the pack was empty”). The smoker may falsely attribute these feelings to the direct effect of the drug, rather than the set and setting.

This is only one example of the many ways in which a combination of neurobiology and anthropology can lead to new questions and fresh approaches. Where might all this be heading? “As research continues,” write Lende and Downey, “greater recognition of neural diversity as a fundamental part of human variation will surely become an even more substantive part of the neuroanthropological approach.”

Science, Academia, and Tobacco

A review of The Golden Holocaust: Origins of the Cigarette Catastrophe and the Case for Abolition

Part III

Academic collaborations come in many flavors. Just because the money is corporate doesn’t mean the studies that are funded are flawed by definition. But the cigarette industry’s academic philanthropy set new records for hubris, writes Robert Proctor, professor of history at Stanford University, in his new book, The Golden Holocaust. Duke University and Bowman Gray School of Medicine, both in North Carolina, are named for tobacco magnates.

Harvard has a long and dubious history of tobacco largesse.  Harvard’s Tobacco and Health Research Program kicked off in 1972 with a generous tobacco grant from the Tobacco Institute, who dreamed up the program in the first place. “The Harvard project made the industry look good and so was handsomely endowed, absorbing $7 million over an eight-year period.” Also in 1972, Harvard anthropologist Carl Seltzer testified for the industry in numerous public hearings, stating: “We do not know whether or not there is a causal relationship between smoking and heart disease.” In 2002, Harvard’s School of Public Health declared it would no longer undertake research sponsored by the cigarette industry. Many universities had already gone cold turkey, and after Harvard, bans were put in place by the Karolinska Institute, Johns Hopkins University, Emory University, and many others.

Proctor informs us that “Washington University in St. Louis has been another big sponge for tobacco money." In 1971, the university set a new world record for an industry grant to a single institution, and “millions more were eventually funneled into the School of Medicine, turning it into a hotbed of cigarette-friendly activism.” The irony of taking money from Big Tobacco to fund research on lung cancer is not lost on Proctor. A good deal of the research was aimed away from tobacco and toward possible causes like viruses. “The goal was clearly more than cancer cures,” he writes. “The industry also hoped to generate good PR and academic allies.” The industry was able to garner  sympathetic headlines, like “Helping in Fight against Cancer,” in the St. Louis Globe-Democrat.

The other academic hotbed thoroughly penetrated by Big Tobacco was UCLA, according to Proctor. “Tobacco collaborators at UCLA have attracted their fair share of criticism from public health advocates, and for understandable reasons.” The university picked up its own multimillion-dollar grant from cigarette makers for the Program on Tobacco and Health in 1974, and that wasn’t the first tobacco money the university had taken. “As with all such projects,” Proctor writes, “industry lawyers… played a key role in the decision to fund—with the companies also conceding that the decision ‘should be based more on public relations than on purely scientific grounds.’” The end came in 2007, when “UCLA’s dance with the devil” garnered a ton of unwanted press. Reports showed that UCLA had taken more than $6 million from Philip Morris for research “to compare how children’s brains and monkey brains react to nicotine.”

Proctor admits that singling out Harvard, Washington University and UCLA is somewhat misleading, “given that scholars throughout the world have gorged themselves on tobacco money. Indeed it may well be the rare institution that has NOT at one time or another dipped into this pot.”

Including Stanford, where Proctor teaches. Plenty of Stanford researchers have undertaken contract work and served as expert witnesses for the industry right in Proctor’s own backyard, where “at least eighteen faculty members have received monies (in the form of sponsored research) from the Council for Tobacco Research, with at least two of these—Judith Swain and Hugh McDevitt from the medical school—serving on its Scientific Advisory Board. Stanford pharmacologists were assisting the industry with its diethylene glycol studies as early as the 1930s…”

In the conclusion to his densely researched but surprisingly readable work, Proctor returns to the controlling irony of the book: “Our bizarre starting point is the well-stocked shelf of cigarettes, to which we respond by begging people not to purchase them.” He presents the dream of a world in which cigarettes have been abolished. To do so, he admits, would require a leap. “If phasing out tobacco seems out of reach, this is only because our imaginations are impoverished.” And he has scant patience for the “Prohibition failed” argument. It failed, he says, because people like to drink. “Tobacco presents us with a very different situation. Nicotine is not a recreational drug. Most people who smoke wish they didn’t, and most smokers (90 percent) regret ever having started.”

Graphics Credit: http://www.prwatch.org/node/7004

The Tobacco Industry as Disease Vector

A review of The Golden Holocaust: Origins of the Cigarette Catastrophe and the Case for Abolition

Part II

The famous Surgeon General’s Report of 1964, officially warning Americans about the dangers of smoking, and publicizing the cancer connection, is typically seen as a triumphal moment in American medical history. But according to Stanford history professor Robert Proctor in his book, The Golden Holocaust: Origins of the Cigarette Catastrophe and the Case for Abolition, the report was “flawed in a number of interesting respects.” [The author, above, with paraphernalia] For one thing, members of the advisory committee consulting on the report, many of them congressman friendly to the tobacco cause, succeeded in their attempts to have smoking referred to as a “habit” rather than as addiction—a shameful Orwellian turn that went uncorrected for 25 years.

Meanwhile, the industry continued to fund new institutes, and continued to give out research grants for “red herring” research. As an example, the highest-ranking officer of the American Heart Association received money from one of the industry’s fraudulent research arms.

As late as the early 80s, most smokers believed they suffered from a bad habit, rather than an addiction—even though a majority of them wished they didn’t smoke. That is an odd kind of consumer “choice.” Cigarette makers have spent millions to perpetuate this myth. Proctor views tobacco industry executives and lawyers as a unique form of disease vector, spreading the pernicious health consequences of smoking across the globe.

The 2008 World Health Organization (WHO) Report on the Global Tobacco Epidemic fleshes out this metaphor, suggesting that all epidemics have a means of contagion, “a vector that spreads disease and death. For the tobacco epidemic, the vector is not a virus, bacterium or other microorganisms—it is an industry and its business strategy.”

In an email exchange, I asked Professor Proctor to expand on this notion of a disease vector:

“We tend to divide "communicable" from "non-communicable" diseases,” Proctor told me, “when the reality is that many "non-communicable" diseases are in fact spread by communications.”

Examples? “Through ignorance and propaganda, for example, which can spread like a virus,” Proctor wrote. “We don't count the anthropogenic communications, oddly enough, even though these can be just as dangerous, and just as deadly. And just as preventable--by changing our exposure environments.”

In a recent article for Tobacco Control, Proctor laid out how the calculus of the disease vector plays out. We know, for example, that smoking will cause roughly 6 million deaths in 2015. And about a third of those will be from lung cancer. We know that 25 acres of tobacco plants will result in about 10 lung cancer deaths per year, starting 20 or 30 years down the road. Here’s a sick equivalence: “A 40 ft container of the sort shipped overseas or trucked by highway houses 10 million cigarettes, which means that each container will cause about 10 deaths.” Proctor works out the numbers for the value of a human life:

“Cigarette companies make about a penny in profit for every cigarette sold, or about $10,000 for every million cigarettes purchased. Since there is one death for every million cigarettes sold (or smoked), a tobacco manufacturer will make about $10,000 for every death caused by their products…. The value of a human life to a cigarette manufacturer is therefore about $10,000.” 

Proctor has even produced a “factories of death” chart, illustrating that arguably the world’s most lethal production plant is Philip Morris’s Richmond cigarette facility, which churned out 146 billion cigarettes in 2010, which adds up to about 146,000 deaths per year.

By 1964, researchers at Harvard had already identified the presence of radioactivity in the form of polonium 210 in cigarette smoke, and the cry went up for safety. As for the notion of safer cigarettes, Proctor says all cigarette filters function the same way—“basically like drinking through a somewhat thinner straw.” He goes even further, arguing that “filters have reduced smoke particle size, producing cancers deeper in the lungs, making them harder to identify and harder to treat.” (Scientists determined that the radiation source was the newer “superphosphate” fertilizers being used heavily on tobacco plants.)

 Next came mandated “tar and nicotine numbers,” which turned out to be misleading measures obtained from smoking robots. Then, “an opportunity presented itself to game the system, as we find in the brilliant trick of ventilation.” Manufacturers pricked tiny holes in the paper near the mouthpiece of cigarettes brands like Carlton and True, which consumers got around by covering the holes with fingers or with “lipping” behavior. “Low tars were a fraud, just as “lights” would be,” Proctor writes. Smokers just smoked harder, or differently, or more frequently. In 1983, pharmacologist Neal Benowitz at UCSF broke the official news in the New England Journal of Medicine: Smokers got just as much nicotine, whether they smoked high-, low-, filtered, unfiltered, regular, light, or ultra-light.  The industry itself had known this for more than 20 years. “Nicotine in the actual rod was rarely allowed to drop below about 10 milligrams per cigarette,” Proctor asserts, “and no cigarette was ever commercially successful with much less than this amount.” (A Philip Morris psychologist compared nicotine-free cigarettes to “sex without orgasm.”)

Indeed, almost every design modification put in place by tobacco companies over the past century, from flue-curing to filters, has served to make cigarettes deadlier than before. “Talk of ‘safer cigarettes’ is rather like talking about safer terrorism, or safer smallpox, or safer forms of drowning,” Proctor concludes.

And the industry testing continues. The point of tobacco-sponsored research is not simply to discredit an individual researcher’s work, but to create an aggregate bias in the pattern of research—a lot of “noise” in the signal. In other words, “you basically fund lots of research to dispute a hazard, then cite this same research to say that lots of scholars dispute it.” We are told about “mucociliary escalators,” which dredge the tar up and out of smokers’ lungs. We learn that “a rabbit will scream if nicotine is introduced into the eye.” We read excerpts from anguished letters to tobacco companies: “Do you suppose if I continue to smoke Camel Ultra Light Cigarettes and I should develop cancer it will be ‘Ultra Light Cancer?’”

Proctor brings us up to date: Harm reduction, he writes, has become the industry’s new mantra. “The companies now want us to believe that less hazardous products can be and are being made and marketed.” Proctor thinks harm reduction “may end up causing even greater harm” if products touted as “safer” make smokers less likely to quit. As for public health campaigns, “consumers are encouraged to stop consuming,” Proctor writes, “but producers are never discouraged from producing.” Or, as Louis Pasteur once wrote: “When meditating over a disease, I never think of finding a remedy for it, but, instead, a means of preventing it.”

So, what comes next? A glimpse of the future may already be here, in the form of cinnamon- and mint-flavored Camel Orbs, “which look like Tic Tac candy and contain about a milligram of nicotine in a highly freebased form.”

As for the industry’s success in corrupting scientists and academics through various means, the story is just as bad as you think it is: “It would take many thousands of pages to chronicle the full extent of Big Tobacco’s penetration of academia; the scale of such collaborations is simply too vast. From 1995 to 2007 alone, University of California researchers received at least 108 awards totaling $37 million from tobacco manufacturers….”

Part II of III.

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