The End of Combusted Tobacco?

With E-cigarettes, a mixed bag of possible outcomes.

E-cigarettes represent a controversial and uncertain future for nicotine addiction, and for this reason they have attracted acolytes and naysayers in what feels like equal measure.

It has been almost 8 years since e-cigarette imports first reached our shores, and the FDA’s determination that they are subject to regulation as tobacco products brings the industry to a crucial crossroads.

On the one hand: “Marked interdevice and intermanufacturer variability of e-cigarettes… makes it hard to draw conclusions about the safety or efficacy of the whole device class.”

On the other hand: “Published evaluation of some products suggest that e-cigarettes can be manufactured with levels of both efficacy and safety similar to those of NRT [nicotine replacement therapy] products… they could play the same role as NRT but at a truly national, population scale.”

So which will it be? Is there an outside chance that the decision by the FDA’s Center for Tobacco Products will represent the first step in dealing with nicotine products currently “designed, marketed, and sold” outside the regulatory framework established for NRT?  A stalemate presently prevails. Writing in the New England Journal of Medicine, Drs. David Abrams and Nathan K. Cobb, Johns Hopkins professors affiliated with the American Legacy Foundation, a tobacco research and prevention organization funded with lawsuit money from the major tobacco companies, highlight the irony: In order to market e-cigarettes as smoking cessations devices, manufacturers must seek approval from the FDA to market pharmaceutical products, “an expensive and time-consuming process than no manufacturer has yet attempted.”

Thus, questions about nicotine content, additives of various kinds, and assorted carrier chemicals go unanswered. Yet these are precisely the questions that need answers before e-cigarettes can be viewed as tools in the harm reduction armamentarium. Cobb and Abrams note that current e-cigarettes “represent a single instance of a nicotine product on a shifting spectrum of toxicity, addiction liability, and consumer satisfaction.” But the market dictates that “to compete with and displace combusted tobacco products, e-cigarettes will need to remain relatively convenient, satisfying, and inexpensive,” regulation notwithstanding.

Still, the harm reductionists’ dreams for the product remain seductive, because “surely any world where refined nicotine displaces lethal cigarettes will experience less harm, disease, and deaths? That scenario is one endgame model for tobacco control: smokers flee cigarettes en masse for refined nicotine and ultimately quit all use entirely.”

Critics say fat chance: “As Big Tobacco’s scientists shift from blending leaves and additives to manipulating circuit boards, chemicals, and dosing schedules, they’re unlikely to relinquish their tolerance for risk and toxicity that prematurely kills half their users in their efforts to ensure high levels of customer ‘satisfaction,’ addiction, and retention.”

Once again, it is the dictates of the market that may end up shaping the future of tobacco, and making the plans of harm reductionists look naïve indeed. “Tobacco companies and their investors,” write Cobb and Abrams, “need millions of heavily addicted smokers to remain customers for decades, including a replenishing stream of young people. No publicly traded company could tolerate the downsizing implicit in shifting from long-term addiction to harm reduction and cessation.”

The marketing innovations most likely to stem from tobacco companies entering the market for e-cigarettes are those most likely to “sustain high levels of addiction and synergistic ‘polyuse’ of their existing combusted products,” while simultaneously crimping competition from NRT manufacturers and independent e-cigarette manufacturers. Tobacco companies are past masters at manipulating things like nicotine content, vaporization methodologies, flavorings, and unknown additives. They will surely bring this expertise to bear in seeking a major bite out of the e-cigarette market while maintaining acceptable profit margins on traditional cigarettes.

The authors suggest that the FDA could weight the matter in harm reduction’s favor by using its product-standard authority “to cripple the addictive potential of lethal combusted products by mandating a reduction in nicotine levels to below those of e-cigarettes and NRT products and eliminating flavorings such as menthol that make cigarettes more palatable.” Tax breaks for e-cigarettes would further load the dice.

But not today. The FDA’s proposal calls for warning labels or product safety and quality standards for e-cigarettes—but not for at least two years. Two years is a long time in a fast-emerging market already valued in excess of $2 billion. The authors call the delay disturbing, “given the variability in product quality and a documented spike in cases of accidental nicotine poisoning.”

In conclusion, the authors believe that for smokers hoping to quit, “NRT products still represent safer, more predictable choices, even if they are more expensive and less appealing.”

Photo credit:  http://www.rstreet.org/

Addiction in the Spotlight at Neuroscience 2013

Testing treatments for nicotine, heroin, and gambling addiction.

Several addiction studies were among the highlights at last month’s annual meeting of the Society for Neuroscience (SfN) in San Diego. Studies released at the gathering including therapies for nicotine and heroin addiction, as well as some notions about the nature of gambling addiction.

And now, as they say, for the news:

— Transcranial Magnetic Stimulation (rTMS), the controversial technique being tested for everything from depression to dementia, may help some smokers quit or cut down, according to research coming in from Ben Gurion University in Israel. Abraham Zangen and colleagues used repeated high frequency rTMS over the lateral prefrontal cortex and the insula of volunteers. Participants who got the magnetic stimulation quit smoking at six times the rate of the placebo group over a six-month period. Work in this area is limited, but there is some preliminary evidence that some addictions may respond to this form of treatment. azangen@bgu.ac.il

—Speaking of the insula—a site deep in the frontal lobes where neuroscientists believe that self-awareness, cognition, and other acts of consciousness are partially mediated—research now suggests that out-of-control gamblers may be suffering, in part, from an overactive insula. People with damage to the insular region are less prone to both the “near-miss fallacy (where a loss is perceived as “almost” a win) and the “gambler’s fallacy (where a run of luck is “due” to a gambler after a string of losses). The volunteer gamblers played digital gambling games while undergoing functional MRIs. Luke Clark of the University of Cambridge, along with researchers from the University of Iowa and the University of Southern California, uncovered a “specific disruption of both effects” in a study group with insula damage. This ties in with earlier research demonstrating that smokers with insula damage lost interest in their habit. This one remains a puzzler, and further research, that brave cliché’, is needed, especially since disordered, or “pathological” gambling is now classified in the DSM5 as an addiction, not an impulse control disorder.  lc260@cam.ac.uk

—And speaking of stimulation, if you go deep with rat brains, you can stimulate a drug reward area and reduce the motivation for heroin in addicted rats. Deep brain stimulation (DBS), an equally controversial treatment approach, now in use as a treatment for Parkinson’s and other conditions, is a surgical procedure involving the implantation of electrodes in the brain. When Carrie Wade and others at the Scripps Research Institute and Aix-Marseille University in France electrically stimulated the subthalamic nucleus and got addicted rats to take less heroin and become less motivated for the task of bar pressing to receive the drug. Earlier work had demonstrated a similar effect in rats’ motivation for cocaine use. “This research takes a non-drug therapy that is already approved for human use and demonstrates that it may be an option for treating heroin abuse,” Wade said in a prepared statement.  clwade@scripps.edu

—Too much stimulation leads to stress, as we know. And George Koob, recently named the director of the National Institute on Alcohol Abuse and Alcoholism, discussed his work on the ways in which dysregulated stress responses might act as triggers for increased drug use and addiction. Koob focused on the negative reinforcement of stressful emotional states: “The argument here is that excessive use of drugs leads to negative emotional states that drive such drug seeking by activating the brain stress systems with areas of the brain historically known to mediate emotions and includes the stress/fear-mediating amygdala and reward-mediating basal ganglia.” For Koob, “stress can cause addiction and addiction can cause stress.” gkoob@scripps.edu

—Finally, hardcore gamblers show a boost in reward-sensitive brain areas when they win a cash payout, but less activation when presented with rewards involving food or sex. The study features more volunteers playing games inside fMRI machines, and purports to demonstrated that problem gamblers are less motivated by erotic pictures than by monetary gains, “whereas healthy participants were equally fast for both rewards.” This “blunted sensitivity” in heavy gamblers suggests the possibility of a marker for problem gambling, in the form of a distorted sensitivity to reward, said Guillaume Sescousse of Radboud University in The Netherlands, during a mini-symposium at the conference. “It is as if the brain of gamblers interpreted money as a primary reward…. for its own sake, as if it were intrinsically reinforcing.” g.sescousse@fcdonders.ru.nl

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)

The Mysteries of the Blunt

Why do so many smokers combine 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 authored by Arpana Agrawal and Michael T. Lynskey of Washington University School of Medicine, and 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://stuffstonerslike.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/

Challenging the Received Wisdom on Tobacco Addiction

What does it take to get hooked on nicotine?

--Smokers who smoke five or fewer cigarettes per day can still become addicted to tobacco.

--Tobacco addiction can also be present in non-daily smokers.

--Nicotine withdrawal symptoms do not necessarily begin within 24 hours.

These and other controversial assertions come from Joseph R DiFranza, a physician with the Department of Family Medicine and Community Health at the University of Massachusetts Medical School. Dr. DiFranza recently authored a provocative examination of smoking truisms in an article for the online publication Harm Reduction Journal.

In an attack on what he calls the Threshold Model of Addiction, DiFranza defines the model as follows:

In brief, the threshold model maintains that until tobacco consumption is maintained above a threshold of 5-10 cigarettes per day (cpd) for a prolonged period, smokers are free of all symptoms of tobacco addiction. It holds that declining blood nicotine levels trigger withdrawal symptoms so quickly that addicted smokers must protect their nicotine levels by smoking at least 5 cpd. The threshold model states that until addiction is established with moderate daily smoking, smoking is motivated and maintained by peer pressure, pleasure seeking and the social rewards of smoking.

DiFranza breaks this prevailing paradigm into a half-dozen hypotheses, offering his opinion on the state of scientific evidence that, in his view, refutes every one of them:

--Hypothesis 1. Tobacco addiction cannot occur in nondaily smokers, or even in daily smokers who regularly consume fewer than 5 cpd.

DiFranza’s response:   “Although it is difficult to prove a negative, this hypothesis would be supported if study after study demonstrated that all surveyed subthreshold smokers (individuals who smoke < 5 cpd) have no symptoms of addiction…. Since no studies have demonstrated a complete lack of addiction symptoms in any representative population of subthreshold smokers, the peer reviewed literature soundly refutes the hypothesis that tobacco addiction requires as a prerequisite the daily consumption of 5-10 cigarettes. The threshold model and the DSM are wrong. “

--Hypothesis 2. Tobacco addiction requires prolonged daily use as a prerequisite.

Response: “Many subjects developed symptoms quite soon after the onset of intermittent tobacco use. These findings have been replicated in several longitudinal studies, in cross-sectional studies showing symptoms of addiction in nondaily smokers, and by case histories showing the same.”

Hypothesis 3. Nicotine withdrawal symptoms begin within 24 hours in all smokers.

“The standard subject in all early smoking studies was an adult who had been a heavy daily smoker for decades. Such individuals do experience nicotine withdrawal soon after their last cigarette. A problem arises when this observation is inappropriately generalized by applying it to all smokers, including children, novices and nondaily smokers.”

Hypothesis 4. Addicted smokers must maintain nicotine above a threshold blood concentration to avoid withdrawal.

“Since a person must smoke at least 5 cpd to maintain a minimum nicotine level throughout the day, another approach to testing this hypothesis would be to determine if all smokers that experience withdrawal symptoms smoke at least 5 cpd. This test has been completed over a dozen times, and always with the same result. Withdrawal symptoms have been reported in smokers of fewer than 5 cpd in every study that has examined this issue.”

Hypothesis 5. Psychosocial factors maintain smoking over the several years it may take to reach threshold levels of smoking.

“There must be thousands of studies that demonstrate that social factors such as socioeconomic status, smoking by family and friends, cigarette advertising, the availability of cigarettes, smoking depictions in movies, and attitudes and beliefs are predictive of which youth will try smoking. However, if such factors sustain tobacco use until tobacco addiction develops, they should predict which smokers will advance to addiction in prospective studies. But this has not been shown. None of more than 40 psychosocial risk factors for the onset of smoking was able to predict the progression to tobacco addiction. The author is aware of no studies that establish that peer pressure of other social factors sustain adolescent or young adult smoking over the 4 or 5 years it may take for smokers to reach threshold levels of smoking. “

Hypothesis 6. Increasing tolerance to the pleasurable effects of smoking drives the escalation in tobacco use up to the threshold of addiction.

“The author is not aware of any studies that demonstrate that smokers must smoke more cigarettes over time to obtain the same amount of pleasure (for example smoking 10 cpd to obtain the same pleasure initially obtained from smoking 1 cpd. Indeed, our data indicate that the pleasure obtained from smoking each cigarette actually increases in proportion to the degree of addiction, with pleasure ratings correlating strongly with addiction severity. While this is only one study, it directly contradicts the hypothesis that non-addicted novice smokers obtain much more pleasure from each cigarette than do addicted heavy smokers.”

Photo Credit: http://nikotin.floridadmat.com/

Germs in Tobacco

Bacteria found in major cigarette brands.

It’s not enough that smoking causes all manner of cardiopulmonary complications, or that more than 3,000 chemicals and heavy metals have been identified as additives. Now comes evidence that tobacco particles extracted from cigarettes contain markers for hundreds of known bacteria. Lung infections in some smokers may be caused by germs on shredded tobacco, rather than the act of smoking itself.

According to a report by Janet Raloff in Science News, Amy Sapkota and a team of researchers at the University of Maryland screened tobacco flakes from cigarettes for bacterial DNA using known markers. In an online paper for Environmental Health Perspectives, the scientists explored the bacterial metagenomics of cigarettes using standard cloning and sequencing processes. The team provided evidence for the presence of Campylobacter (a cause of food poisoning), E. coli, several Staphylococcus varieties, as well as a number of bacteria, such as Clostridium, which is directly associated with pneumonia and other infections. Fifteen different classes of bacteria in all, with no significant variation from one cigarette brand to another. 

The time has come, Sapkota and coworkers conclude, “ to further our understanding of the bacterial diversity of cigarettes,” given the more than 1 billion smokers worldwide.  Smoking is now recognized as a risk factor for a basketful of respiratory illnesses, including influenza, asthma, bacterial pneumonia, and interstitial lung disease. In light of this, the authors have advanced their study as solid evidence that “cigarettes themselves could be the direct source of exposure to a wide array of potentially pathogenic microbes among smokers and other people exposed to secondhand smoke.”

In 2008, researcher John Pauly and coworkers at the Roswell Park Cancer Institute in Buffalo, New York, helped provide early evidence by conducting a tobacco flake assay and publishing the results in the journal Tobacco Control. The scientists opened a package of cigarettes “within the sterile environment of a laminar flow hood. A single flake of tobacco was collected randomly and aseptically from the middle of the cigarette column and placed onto the surface of a blood agar plate. The test cigarettes included eight different popular brands, and these were from three different tobacco companies.”

And the results? “After 24 hours of incubation at 37 degrees C, the plates showed bacterial growth for tobacco from all brands of cigarettes. Further, more than 90% of the individual tobacco flakes of a given brand grew bacteria.” Pauly believes that “the results of these studies predict that diverse microbes and microbial toxins are carried by tobacco microparticulates that are released from the cigarette during smoking, and carried into mainstream smoke that is sucked deep into the lung.”

In a recent study published in Immunological Research , Pauly and others expanded on their findings, writing that “Cured tobacco in diverse types of cigarettes is known to harbor a plethora of bacteria (Gram-positive and Gram-negative), fungi (mold, yeast), spores, and is rich in endotoxin (lipopolysaccharide).” This time out, the researchers conclude that “lung inflammation of long-term smokers may be attributed in part to tobacco-associated bacterial and fungal components that have been identified in tobacco and tobacco smoke.”

Cigarette manufacturers already use antibacterial washes during the curing process in order to reduce infection by fungi and bacteria.

If the findings are sound, they could place the argument over secondhand smoke in a vastly different light—cigarettes smoke may be taking the rap for respiratory infections cause by extant bacteria. With smoking rates in the U.S. holding at a steady 21 percent of the population, the issue is not trivial.

Graphics Credit: http://commons.wikimedia.org/

Sapkota, A., Berger, S., & Vogel, T. (2009). Human Pathogens Abundant in the Bacterial Metagenome of Cigarettes Environmental Health Perspectives, 118 (3), 351-356 DOI: 10.1289/ehp.0901201

Pauly, J., Smith, L., Rickert, M., Hutson, A., & Paszkiewicz, G. (2009). Review: Is lung inflammation associated with microbes and microbial toxins in cigarette tobacco smoke? Immunologic Research, 46 (1-3), 127-136 DOI: 10.1007/s12026-009-8117-6

Rethinking the Patch

Quitters do better on 6-month regimen.

It may sound like dream propaganda for the makers of nicotine patches. And it is. Moreover, at least one of the study authors has worked in the past as a consultant for GlaxoSmithKline, maker of Nicoderm CQ, one of the best-selling brands of transdermal nicotine patches.

So there is every reason to dismiss a recent study by researchers at the University of Pennsylvania School of Medicine, published in the Annals of Internal Medicine, which strongly suggests that the currently recommended regimen of two months isn’t long enough. It should be tripled. Which also triples sales.

There’s only one catch: There is reason to believe that the results are legitimate, and that smokers who are trying to quit would be more successful if they stuck with the patch for longer periods than currently recommended on the manufacturer’s box.  For some time now, tobacco addiction researchers, and centers such as Mayo Clinic’s Stop Smoking facilities, have recognized the need for extending the manufacturer’s suggested period of use.

Referring to the patch on its Stop Smoking web site, Mayo Clinic says: “You typically use the nicotine patch for eight to 12 weeks. You may need to use it longer if cravings or withdrawal symptoms continue.”

And from the field come reports of abstaining smokers independently choosing to use the patch longer, often by cutting the patches into eighths or sixteenths in order to accomplish a long, slow taper at the end of the process. By following this route, a nicotine addict need not be aware of the precise day or moment when his nicotine fix from the patch has dropped to placebo levels—further evidence that nicotine addiction is a chronic condition that may not respond to treatments of only two to three months in duration. 

One early development during the marketing of the patch that helped set the short-term use pattern were reports in the 1990s of heart attacks by patch users. Subsequent research showed that rare cardiac problems had arisen in patients who had continued heavy smoking while on the patch, and that there was little evidence of a direct link between nicotine patches and heart attacks. (Recent heart attack victims are advised to wait six weeks and use patches with caution.)

The study concludes: “Transdermal nicotine for 24 weeks increased biochemically confirmed point-prevalence abstinence and continuous abstinence at week 24, reduced the risk for smoking lapses, and increased the likelihood of recovery to abstinence after a lapse compared with 8 weeks of transdermal nicotine therapy.”

One limitation of this particular study, acknowledged as such by the authors, is that “participants were smokers without medical comorbid conditions who were seeking treatment.” In other words, the study cohort consisted of highly motivated smokers.

And another problem is cost: Few health insurance companies cover the full cost of patches, including Medicaid. The additional cost per quitter, the study found, was about $2,400 for the extended regimen.

Nonetheless, any uptick in success rates for smoking cessation programs should be noted and taken under consideration.

Photo Credit: www.drugabuse.gov

Leave E-Cigarettes Alone, Judge Tells FDA

Ruling halts FDA confiscations.

The Food and Drug Administration (FDA) lost its battle Thursday to keep electronic cigarette manufacturers from bringing e-cigarettes to America. According to a report in the Washington Post, U.S. District Judge Richard J. Leon “determined that electronic cigarettes are tobacco products and are not subject to such restrictions.” The FDA had been contending that e-cigarettes were in fact novel and untested drug delivery devices, and as such, had not been approved by the agency for sale to U.S. consumers.  "This case appears to be yet another example of FDA's aggressive efforts to regulate recreational tobacco products as drugs or devices," the judge wrote in his decision.

The FDA had been confiscating imports of e-cigarettes but had not put together an entirely coherent strategy with respect to the smokeless electronic cigarettes, which heat liquid nicotine into an inhalable vapor. Two suppliers of e-cigarettes brought suit against the agency for the confiscations.  According to the Washington Post article, the judge took a further slap at the FDA, callings its stance on e-cigarettes a “tenacious drive to maximize its regulatory power."

For its part, the FDA maintains that e-cigarettes are more akin to nicotine gum, which is subject to  FDA regulation. The agency also questions claims by e-cigarette manufactures that their products "alleviate nicotine withdrawal symptoms." Furthermore, the FDA has voiced health concerns, based on studies showing that electronic cigarettes contain carcinogens and toxic chemicals such as diethylene glycol. (See my earlier post). The e-cigarette makers had argued before the judge that their products are not substantially different than the Marlboros and Salems sold everywhere.

According to the Wall Street Journal: “Health groups including the American Lung Association have called for e-cigarettes to be removed from the market, saying their safety is unproven and children may be attracted to them.”

As a reader commented on another e-cigarette post here: “I think it will be interesting to see how this all plays out. Judge Leon just gave the FDA a slap for trying to stop the import of e-cigs, some places are allowing them because it doesn't violate the Clean Air act and some places, like NJ are restricting the sale and use. We'll see a lot of battles over the next year or two.”

Graphics Credit: http://topnews.net.nz/

Top 50 Smoking Awareness Blogs

Addiction Inbox makes the cut.

Addiction Inbox is pleased to find itself listed among the "Top 50 Smoking Health Awareness Blogs" by the Pharmacy Technician Certification web site.

Here is the description included in the listing:

"An exhaustive, comprehensive, and stimulating catalogue of information pertaining to the science of substance abuse, the Addiction Inbox counts nicotine amongst its list of dangers. Expect to see articles regarding tobacco control alongside psychological studies on the physical, emotional, and mental elements of addiction."

Thanks go to Ashley M. Jones for the listing, and for bringing it to my attention.

The latest numbers on cigarette smoking from the American Heart Association show that 23.5 % of white males are smokers, with female smokers having closed the gap considerably with a smoking rate of 18.8 %.

26.1 % of black men are smokers, compared to 20.1 % of Hispanic males, and 16.8 % of Asian men. For women, blacks smoke at a rate of 18.5 %, followed by Hispanic women at 10.1 %, and non-Hispanic Asians at 4.6 %.

The tragic winners, and thus the losers, of the smoking sweepstakes are Native Americans, who show smoking rates of 35.6 % for men and 29.0 % for women.

Graphics Credit: www.chantixhome.com

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FDA Bans Flavored Cigarettes

An unintentional boost for cigar sales?

When is a cigar more than just a cigar? When its appearance allows it to circumvent the intent of the Food and Drug Administration’s first ruling related to cigarettes, that’s when.

In its first official ruling since Congress passed legislation giving the agency authority to regulate tobacco (see my earlier post), the FDA banned so-called flavored cigarettes. Cigarette makers can no longer add vanilla, clove, chocolate, or any other fruit or candy flavors to their product. Menthol, for now, is exempt from the ban.

FDA commissioner Margaret Hamburg said that 90 percent of adults who smoke began doing so as children. The president of the Campaign for Tobacco-free Kids agreed, calling flavored cigarettes “starter products” for young smokers in a Dow Jones Newswires report by Jennifer Corbett Dooren.

By law, the agency cannot ban regular cigarettes outright. However, as Gardiner Harris reported in the September 23 New York Times, “the legislation left some details vague. For instance, the agency is required to ban flavored cigarettes, but the law did not clearly define what constituted a cigarette."

Huh? As it turns out, a cigarette is in the mind of the beholder. The FDA maintains that the ban applies to all cigarette-type tobacco products, including those that are “labeled as cigars or as some other product.” A spokesperson for the Campaign for Tobacco-Free Kids agreed: “The FDA demonstrated that they’re serious about enforcing the ban on flavored cigarettes, and serious about preventing tobacco companies from circumventing that ban,” according to the New York Times article.

Not so fast, argued Norman Sharp, president of the Cigar Association of America. Sharp told the Times that the ban clearly did not apply to cigars: “We feel this should go a long way to clearing up any confusion in the marketplace.”

Well, not exactly. An exasperated spokesperson for cigarette maker R.J. Reynolds, also quoted in the article, said: “It’s hard to understand. We need clear and timely guidance so all of us can work together so that we can understand what we need to be doing.”

What about the small brown cigarillos sold by an R.J. Reynolds subsidiary?

“They are not cigarettes,” the spokesperson said.


Photo Credit: http://politics.mync.com/tag/cigarette/

addiction drugs smoking nicotine

Low-Nicotine Cigarettes: Deadlier Than Regular Brands?

More tars, more cancer.

Now that the U.S. Congress has passed legislation enabling the Food and Drug Administration (FDA) to monitor the tobacco industry for the first time in history (see my earlier post), one of the primary issues the agency must deal with are health claims on behalf of allegedly less-toxic brands of “low-nicotine” cigarettes.

It has long been understood, and demonstrated clinically, that people addicted to nicotine will smoke “light” cigarettes harder, and in greater numbers, in order to compensate and obtain the same amount of nicotine they are used to--thereby staving off withdrawal. [See graphic at right for the secret of why light cigarette smokers must puff harder.]

As prominent tobacco researcher N.L. Benowitz wrote in a National Cancer Institute (NCI) monograph:

“In brief review—when faced with lower yield cigarettes, smokers can smoke more cigarettes per day, can take more and deeper puffs, can puff with a faster draw rate, and/or can block ventilation holes. Using these last four techniques, a smoker can increase his or her smoke intake from a particular cigarette several fold above the machine-predicted yields.”

In the description of a patent for a low-tar and low-nicotine technique in 1995, Duke University Researchers wrote:

“Unfortunately, it has been discovered that only a small proportion of the total smoking population (e.g., less than 25%) has substituted low tar cigarettes (e.g., cigarettes that deliver less than 10 milligrams of tar) for conventional and more hazardous cigarettes. Also of note, only about 2.0-3.0% of total cigarette sales are accounted for by very low tar cigarettes (e.g., cigarettes that deliver less than 3 milligrams of tar). Moreover, even among the cigarette smokers who have substituted low tar cigarettes for conventional cigarettes, it has been discovered that these individuals will tend to smoke low tar cigarettes more intensively in order to extract more tar and nicotine than the nominal values listed on the pack. This, of course, defeats part of the objective of the low tar cigarettes.”|

Moreover, there has never been any significant body of evidence to suggest that switching to lights or ultra-lights in a way actually contributes to the success of smoking cessation efforts. According to the National Cancer Institute, there are no health benefits for smokers of light cigarettes, period.

In a letter published in the August 21 issue of Science, Marshall E. Deutsch argues that cigarettes with reduced nicotine may in fact “increase tobacco related death and disease” and are therefore potentially more dangerous than regular smokes.

Deutsch’s argument is that by smoking more cigarettes with lower concentration of nicotine, smokers “will be subjected to more of the ‘tars’ (the cancer-causing ingredients of the smoke) in their attempts to get their usual dosage of nicotine, (the ingredient responsible for heart disease and stroke). In the end, smokers of low-nicotine cigarettes will remain at the same risk for heart disease and stroke but increase their chances of developing cancer.”

It’s never too late to quit, and the earlier the better: The National Cancer Institute tells us that smokers who quite before age 50 cut their risk of dying by 50 % over the next 15 years, compared to those who keep smoking.

Graphics Credit: www.tobaccoinaustralia.org.au

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Obama Comes Clean

Signs nicotine control act, admits he still lights up.

The new anti-smoking legislation, the Family Smoking Prevention and Tobacco Control Act, prevents the advertising of tobacco to children and puts tobacco under the purview of the Food and Drug Administration for the first time.

In signing the bill, Obama was compelled by reporters to admit to his nicotine addiction during a press conference. "Look, I've said before that as a former smoker I constantly struggle with it. Have I fallen off the wagon sometimes? Yes," Obama said in an article about the news conference by Sheldon Alberts of Canwest News Service.

Typically, for a smoker who can’t quite quit, Obama defended himself by saying, "I don't do it in front of my kids. I don't do it in front of my family."

Obama was said to have convinced his wife to support his bid for the presidency by agreeing to give up cigarettes—a campaign pledge he has not been able to keep, by his own admission.

During the Tuesday press conference Obama compared his addiction to nicotine to an alcoholic's need for a drink. "I don't know what to tell you, other than the fact that, you know, like folks who go to (Alcoholics Anonymous) you know, once you've gone down this path, then, you know, it's something you continually struggle with, which is precisely why the legislation we signed was so important, because what we don't want is kids going down that path in the first place."

During the press conference, an exasperated Obama sought to turn the questions away from his own lingering addiction. "First of all, the new law that was put in place is not about me. It's about the next generation of kids coming up," he said. "So I think it's fair . . . to just say that you just think it's neat to ask me about my smoking, as opposed to it being relevant to my new law. But that's fine. I understand. It's an interesting human interest story."

Graphics Credit: obamasmoking.com

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House Tobacco Bill Moves to Senate

Bill would give FDA control over nicotine products.

It is one of the most popular drugs in America, used and abused by millions. Yet it is not regulated by any government agency. There is no federal testing, no quality control, no standards of any kind. As representative Jared Polis (D-Colorado) memorably told the U.S. House of Representatives: “Tobacco use is the single largest cause of preventable death in our country. Yet it continues to receive less regulation than a head of lettuce.”

That deplorable situation may soon change, as the U.S. Senate takes up a bill recently passed by the House. The legislation would give the Food and Drug Administration (FDA) broad new powers to regulate the tobacco industry for the first time in history.

The house bill is similar to one passed last session, which died in the Senate after it was opposed by the Bush administration. According to reports by Duff Wilson in the New York Times, the legislation would enable the FDA to “approve or reject current and proposed tobacco products and ingredients, based on scientific and health findings.” The FDA would be able to restrict harmful chemicals and reject new tobacco products, but in a major concession to Philip Morris, the nation’s largest cigarette maker, the bill “would not allow a complete ban of tobacco products, or permit the agency to order the complete removal of nicotine.” The Times article also said the bill would lead to larger and more graphic warning labels on cigarette packs.

Senator Edward Kennedy (D-Massachusetts) said he plans to introduce the bill later this month. The legislation is supported by President Obama. An official statement released by the administration said that tobacco use “is a major factor driving the increasing costs of health care in the U.S. and accounts for over a hundred billion dollars annually in financial costs to the economy.” Attempts to mandate FDA regulation of tobacco have been made repeatedly over the past decade.

Tobacco industry supporters have vowed to fight the bill on the Senate floor. Senator Richard Burr (R-North Carolina) said he was considering a filibuster. House Republican Virginia Foxx, also of North Carolina, derided the legislation as “an unnecessary and expensive regulatory scheme at the expense of our rural farming communities.” North Carolina is the country’s leading tobacco growing state.

A spokesperson for the American Heart Association said the Senate was expected to act quickly on the bill: “This has certainly been a passion of Senator Kennedy’s and a legacy he can leave to the public health of America.”

Photo Credit: Winston-Salem Journal

smoking nicotine

Tobacco Industry Loses Crucial Court Case

Jury awards $8 million to widow of addicted smoker.

In a court decision that attorneys for Philip Morris called “profoundly flawed,” a Florida jury last week awarded $8 million to the widow of a man who died of lung cancer, ruling that nicotine addiction was the cause of his death.

Attorneys for Altria, the parent company of Philip Morris, argued in Hess v. Philip Morris USA that the deceased man had been fully aware of the dangers of smoking, and had been fully capable of quitting, had he chosen to do so.

Philip Morris will most certainly lodge an appeal, given that the closely-watched “Hess case” is the first of an estimated 8,000 similar cases filed in Florida in the wake of a class-action suit against cigarette makers in 1994. In 2006, the class-action suit was overturned by the Florida Supreme Court, which ruled that smokers had to prove in individual court cases that cigarettes were the immediate cause of their health problems.

Attorneys for the widow, Elaine Hess, argued that Philip Morris sold cigarettes that were “defective and unreasonably dangerous,” according to a Miami Herald report by Patrick Danner. Phillip Morris attorneys argued that smoking had simply been a “lifestyle choice” for Stuart Hess. Hess, the tobacco lawyers asserted, voluntarily chose not to follow the advice of family members and doctors, who told him to quit smoking.

According to the Miami Herald report, Hess “tried various means to quit smoking, including hypnosis, Nicorette gum and even going cold turkey. But all of his attempts failed.”

While technically the Hess case has no bearing on the individual court cases to come, attorneys said it was expected to serve “as a template for the other cases,” Danner wrote in the Herald article. Murray Garnick, a senior vice president and associate general counsel for parent company Atria, said in a press release that the verdict was the result of “an unconstitutional and profoundly flawed trial procedure. Fundamental fairness requires the plaintiff to establish basic liability before a jury can award damages.”

Photo Credit: http://snus-news.blogspot.com/2008_01_06_archive.html

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The Patch and How to Use It

Take the Fagerstrom test.

The U.K. Guardian, in partnership with the British Medical Journal, recently offered its readers a short version of the Fagerstrom test, a questionnaire used for assessing the intensity of physical addiction to nicotine. The Guardian article then made recommendations about which patch strength smokers should be using, based on their scores.

Here is a longer version of the Fagerstrom test, with scoring assessment, followed by the Guardian’s recommendations about patches:

Fagerstrom Test for Nicotine Dependence *

1. How soon after you wake up do you smoke your first cigarette?
-- After 60 minutes
(0)
-- 31-60 minutes
(1)
-- 6-30 minutes
(2)
-- Within 5 minutes
(3)

2. Do you find it difficult to refrain from smoking in places where it is forbidden?
-- No
(0)
-- Yes
(1)

3. Which cigarette would you hate most to give up?
-- The first in the morning
(1)
-- Any other
(0)

4. How many cigarettes per day do you smoke?
-- 10 or less
(0)
-- 11-20
(1)
-- 21-30
(2)
-- 31 or more
(3)

5. Do you smoke more frequently during the first hours after awakening than during the rest of the day?
-- No
(0)
-- Yes
(1)

6. Do you smoke even if you are so ill that you are in bed most of the day?
-- No
(0)
-- Yes
(1)

* Heatherton TF, Kozlowski LT, Frecker RC, Fagerstrom KO. The Fagerstrom Test for
Nicotine Dependence: A revision of the Fagerstrom Tolerance Questionnaire. British Journal of Addictions. 1991; 86:1119-27

0-2 Very low dependence

3-4 Low dependence

5 Medium dependence

6-7 High dependence

8-10 Very high dependence

[Scores under 5: “Your level of nicotine dependence is still low. You should act now before your level of dependence increases. “]

[Score of 5: “Your level of nicotine dependence is moderate. If you don’t quit soon, your level of dependence on nicotine will increase until you may be seriously addicted.”]

[Score over 7: “Your level of dependence is high. You aren’t in control of your smoking–-it is in control of you!”]

The U.K. Guardian’s scoring assessment

Which patch to use:

--2 points = light nicotine dependence. Start with the 7 mg nicotine patch.

--3 or 4 points = moderate nicotine dependence. Start with the 14 mg nicotine patch.

--5 or 6 points = heavy nicotine dependence. Start with the 21 mg nicotine patch.

Graphic Credit: Electronic Illustrators Group

smoking addiction nicotine

E-Cigarettes and Health

Smokeless nicotine comes under scrutiny.

You may never have heard of it—but it’s the newest drug in town. It’s called an electronic cigarette, or “e-cigarette.” Electronic cigarettes use batteries to convert liquid nicotine into a fine, heated mist that is absorbed by the lungs. No smoke, but plenty of what makes cigarettes go, if you don’t account for taste—or ashtrays and smoke rings.

In an attempt to work around the world’s growing ban on cigarette smoking in public places, a Hong Kong-based company developed the first e-cigarette in 2004. Since then, other companies have done the same, claiming that e-cigarettes are much healthier than regular smokes.

Last month, that claim was vigorously disputed by the World Health Organization (WHO). In fact, WHO said electronic cigarettes can be deadly. Stressing that the device had not been adequately tested, Douglas Bettcher, the director of WHO’s Tobacco Free Initiative, told the Associated Press that “there’s no experience in pharmacology yet of nicotine replacement therapies which actually inhale nicotine in the lungs.” Replacement therapies such as skin patches and gum have undergone thorough clinical testing, Bettcher said. For these reasons, “the World Health Organization does not consider the electronic cigarette to be a legitimate nicotine replacement therapy.”

The anti-smoking group Action on Smoking and Health (ASH) doesn’t think much of e-cigarettes, either. In the U.K. Times Online, ASH director Deborah Arnott said that “at the moment we don’t know enough about this product. Quality control in China is not the highest, and our advice is it’s best to use nicotine products like gums and patches. The electronic cigarettes fall into a regulatory gap and they haven’t been chemically tested.”

So far, electronic cigarettes are being actively marketed in China, Great Britain, Canada, Brazil, Israel, Sweden, and other countries. The cartridges containing the liquid nicotine are available in several flavors, and battery life is estimated at one to three days for most units. The e-cigarette web site www.e-cig.org offers a list of “best places to use your electronic cigarette,” such as airplanes, in church, at the mall, in a restaurant, bar or hospital, or “at your kid’s school recital.”

According to China View News , a “changeable filter contains a liquid with nicotine and propylene glycol. When the user inhales as he would when smoking, air flow is detected by a sensor and a micro-processor activates an atomizer which injects tiny droplets of the liquid into the flowing air, producing a vapour.”

The unit, which looks like a long cigarette, is powered by a rechargeable battery. Propylene glycol is a commercial product sold as a low-toxicity version of antifreeze, among other applications.

E-cigarettes are readily available for purchase online, and at least one American firm has announced plans to market versions of e-cigarettes domestically. However, none of the manufacturers to date seems to be working through the existing regulatory framework, which in most countries calls for toxicity analyses and clinical studies. Jason Cropper, managing director of the Electronic Cigarettes Company, told BBC News that e-cigarettes “are certainly healthier than smoking cigarettes. Tests have been done on mice in the lab and they have shown they are not harmful.” However, Cropper said, no human trials had been undertaken because they are too expensive.

The World Health Organization became involved in the matter after several e-cigarette manufacturers began using the World Health Organization’s logo on advertisements and product inserts. “It’s 100 percent false to affirm this is a therapy for smokers to quit,” Bettcher said. “There are a number of chemical additives in the product that could be very toxic.”

Meanwhile, The Ruyan e-cigarette, a joint effort by Ruyan Holdings Ltd. of Hong Kong and Ruyan America, Inc., won Most Innovative Product of 2008 at the Tobacco Plus Expo in Las Vegas last May.

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