The Death of “Low Tar” Cigarettes… Or Maybe Not.

Is this the best the FDA can do?

Lots of cigarette news lately. To begin with, cigarette manufacturers will no longer be able to market specific brands as “low tar” or “light.” And while David Kessler, former head of the Food and Drug Administration (FDA), called for the regulation of nicotine levels in cigarettes, cancer researchers were backpedaling away from some questionable numbers about cancer risk from smokeless tobacco offered up by the National Cancer Institute (NCI). Meanwhile, the American Medical Association (AMA) called on the FDA to ban so-called e-cigarettes.

Covering nicotine news is inherently confusing, ambiguous, and tentative, since the product in question is a legal drug responsible for an immense amount of tax revenues. It is also addictive. The relatively inelastic nature of demand for nicotine products makes governments reluctant to, er, snuff out the tax bonanza in its entirety.

Nonetheless, Congress gave the FDA broad new regulatory power over cigarettes a year ago with the passage of the Tobacco Control Act of 2009.  Last week, various provisions of the bill became effective, including provisions that “prohibit the advertising or labeling of tobacco products with the descriptors ‘light,’ ‘mild,’ or ‘low’ or similar descriptors” without specific permission from the FDA.  (See earlier post). In addition, health warning labels will be strengthened on smokeless tobacco packaging.

“As FDA continues implementation of the Tobacco Control act, we are committed to assuring that the actions we are taking are grounded in science and are open and transparent with participation by various stakeholders,” according to a press release from the agency’s Center for Tobacco Products.

The problem, as a glance at the photograph above aptly demonstrates, is that the America tobacco industry is already a jump ahead of the FDA’s measured approach. The industry plans to “let the colors speak to smokers in the same way the soon-to-be banned words ‘mild,’ ‘light,’ and ‘ultralight’ did,” Stephen Smith wrote last year in the Boston Globe.

Thus Pall Mall Lights become Pall Mall Blues. Whereas Salem Lights will forever after be known as Salem Gold Box. And so on. “These tricks are now well-established,” tobacco control specialist Stanton Glantz of the University of California told the Boston Globe. “The real question for the FDA is, are they going to let them get away with these shenanigans?”

The FDA is changing colors on the packages, and roughing up the warning labels, and starting to zero in on menthol, but one of the things it won't be doing is lowering the nicotine levels in cigarettes. Former FDA chairman David Kessler, for one, insists that this is the only substantive change likely to make a difference in addiction rates. In an AP report by Michael Felberbaum, Kessler said: “The tobacco industry knew 40 years ago that there was a threshold below which people would quit. Reducing the level of nicotine in cigarettes will change smoking as we know it. It is the ultimate harm reduction strategy.”

Meanwhile, on another contested front, (see earlier post) the Partnership at Drugfree.org reported that the AMA called on the FDA to regulate electronic cigarettes, which to date the agency has declined to do.  “Very little data exists on the safety of e-cigarettes,” said AMA board member Edward Langston. “Because e-cigarettes have not been thoroughly tested, one cannot conclude that they are less harmful or less dangerous than conventional cigarettes.” E-cigarettes also come in different candy and fruit flavors, the AMA pointed out during the process of adopting the policy at its annual meeting in Chicago.

And finally, a Wall Street Journal report by Carl Bialik in April caused a good deal of embarrassment at the American Cancer Society, which conceded that it had stopped using its long-cited figure of a 50-fold increase in the risk of oral cancer among users of smokeless tobacco. The National Cancer Institute has also cited the 50-times risk figure in its literature. As it turned out, the original survey had been about dry snuff, a form of tobacco rarely used in America today. Other scientists have concluded that the increased risk of oral cancer from smokeless tobacco is on the order of a factor of 10, not 50.

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

Vitamin B6 May Lower Risk of Lung Cancer

Large European study confirms earlier findings.

It doesn’t mean you should start popping handfuls of B vitamins if you are a smoker or a former smoker (those who never smoked rarely get the disease). What it appears to mean is that people with the highest levels of vitamin B6 in their bodies may have as little as half the risk of developing lung cancer as people with very low levels of B6--also known as pyridoxine.

In a June 16 article in the Journal of the American Medical Association (JAMA) , dozens of researchers from around the world deconstructed a European medical database from the 1990s, containing medical data and blood test results for more than 380,000 people. They were looking for meaningful statistical correlations having to do with the 899 people in the study who eventually developed lung cancer.

According to Nathan Seppa in Science News, the international research team found that “people with vitamin B6 levels ranking in the top one-fourth of all the samples taken had less than half the risk of lung cancer as those with the lowest vitamin B6. A similar comparison found that people with high levels of [the amino acid] methionine seemed to have almost half the cancer risk of people with low levels. High folate levels seemed to give less protection.” The researchers calculated that having high levels of all three compounds could reduce lung cancer risk by as much as two-thirds.

Much remains unknown. Can smokers use B6 vitamin supplements to protect against lung cancer, or are the protective effects, if verified, due to a B6 level that reflects diet and other metabolic factors at work over decades? And, as always, there is the question of B6 from vitamin supplements vs. B6 from B6-rich foods like fish, beans, and grains.

A smaller prospective study undertaken in 2001 came up with similar results. Published in the American Journal of Epidemiology, the study involved 300 lung cancer patients in Finland between 1985 and 1993. The researchers looked at B6, B12, and folate, and found “significantly lower risk of lung cancer among men who had higher serum vitamin B6 levels. Compared with men with the lowest vitamin B6 concentration, men in the fifth quintile had about one half of the risk of lung cancer.” The researchers speculate that one of the mechanisms by which B6 could influence carcinogenesis is the role the vitamin plays in homocysteine metabolism. B6 is involved in the complex process of metabolizing homocysteine, another amino acid. Absent sufficient B6, homocysteine levels can build up in the body, causing heart disease and other ailments.

Mattias Johansson, et. al. (2010). Serum B Vitamin Levels and Risk of Lung Cancer Journal of the American Medical Association, 303 (23), 2377-2385

Graphics Credit: http://helios.hampshire.edu/

A High Old Time in Rhode Island

Feds release annual drug numbers.

[Map: Illicit drug use other than marijuana in the past month among people aged 12 or older based on 2007-2008 figures.]→

It’s time again for the government’s annual state-by-state survey of drug use in America.  Assembled by the Substance Abuse and Mental Health Services Administration (SAMHSA), the yearly numbers are argued over by states and agencies competing for federal health and medicine dollars. In this year’s sweepstakes, dark horse Rhode Island upset the reigning champion, the District of Columbia, as the state with the highest number of monthly users of illicit drugs other than marijuana. 

Usage figures were based on numbers compiled in 2007 and 2008. Overall, eight per cent of Americans aged 12 or older used an illicit drug other than pot in the prior month, essentially unchanged from last year’s report based on 2006-2007 figures. Using the percentage of monthly users as a yardstick, other states in the highest group included Arizona, Arkansas, Kentucky, Nevada, Oklahoma, Oregon, Colorado, and Tennessee. Among the states in the lowest group were Maine, Minnesota, Nebraska, Mississippi, New Jersey, the Dakotas, Wyoming—and the lowest of them all--Iowa.

According to SAMSHA, five states showed significant changes compared to a year ago. Iowa, Louisiana and Wyoming showed marked decreases, while usage of drugs other than marijuana in Hawaii and Oregon increased.

As for alcohol, SAMSHA pegs the national rate of alcohol use among people age 12 or older at 51.4 per cent. The highest rate of alcohol use was found in the 18-25 age group (big surprise there). This year the state drinking trophy goes to New Hampshire, with Utah coming in dead last, as usual. High-drinking states include Colorado, Massachusetts, New Hampshire, Rhode Island, Vermont, and Wisconsin. (What is it with New England?)

Interestingly, eight out of the ten lowest states for drinking are found in the South: Alabama, Arkansas, North Carolina, and Virginia, among others. However, the South makes up for it in tobacco usage. States with the highest prevalence of tobacco use were Arkansas, Kentucky, Ohio, West Virginia—and, okay, Wyoming. The state with the fewest smokers? Do you have to ask? Utah. The national smoking average still hovers around 24 per cent.

For a longer view, SAMSHA compared the current study figures with numbers compiled in 2002-2003. Iowa, Missouri, and Pennsylvania showed significant drops for drugs other than marijuana. Only Rhode Island and Tennessee showed marked increases.

Tennessee also showed increases in marijuana usage, while less pot was smoked in Florida, Iowa, Missouri, and Pennsylvania. Overall, usage decreased slightly compared to the 2002-2003 period.

The most meaningful change compared to the 2002-2003 period was a 2.5 per cent decrease in the use of cocaine among people 12 or older. Nationwide, the percentage of alcohol use remained almost identical (51.4 per cent).

Photo Credit: SAMSHA

Choline for Fetal Alcohol Spectrum Disorders?

Common supplement may reduce cell death in pregnancies.

A common dietary supplement markedly decreases defects in the skull and brain formation of  lab mice born to mothers exposed to alcohol, say researchers at the Medical College of Georgia.

Among the grisly list of potential effects caused by alcohol consumption during pregnancy, one involves a relatively obscure lipid called ceramide. Ceramide can markedly increase the rate of programmed cell death—a process known as apoptosis—and may be involved in the characteristic cranial defects seen in fetal alcohol syndrome.

In the study, 25 % of the mouse embryos exposed to alcohol showed characteristic defects in skull development, including diminished growth in the multi-layered membrane—the meninges--covering the brain.  Biochemists Erhard Bieberich and Guanghu Wang, in an article published in Cell Death and Disease, found that the supplement CDP-choline decreased cell death and protected the fetal cranium from damage due to maternal drinking episodes. According to Dr. Bierberich in a press release from the Medical College of Georgia, the result of alcohol on pregnancy is “a snowball effect. The neural crest is damaged, the meninges doesn’t develop properly and tissue like bone and brain that are regulated by the meninges don’t develop properly either.”

Choline is a precursor to the neurotransmitter acetylcholine. In addition, it has been known for decades that alcohol increases choline requirements. Choline is already added to some baby formulas and prenatal vitamins. Choline’s effects on stroke and traumatic brain injury are also being investigated.

A similar discovery twenty years ago concerning folic acid led the U.S. Public Health Service (USPHS) to recommend that all women thinking of becoming pregnant should consume supplemental folic acid daily in order to reduce their risk of having a pregnancy affected by spina bifida or other neural tube defects. The rate of occurrence of this kind of birth defect has been dropping ever since.

The researchers believe that “there is just a little window” four weeks after conception—while neural cells are forming numerous organs--when the alcohol-related cranial damage is likely to occur. Unfortunately, this window of disaster opens before many women have discovered that they are pregnant. 

Since warnings about the dangers of drinking during pregnancy are either not known or are ignored in many cases, researchers are always on the lookout for medications that could be given after exposure to alcohol--or even after birth of a baby to an alcoholic mother.  As early as 2005, researchers at Tripler Army Medical Center in Honolulu demonstrated that adding choline to the pre-natal diet of pregnant alcoholic rats suppressed physiological symptoms of fetal alcohol syndrome in the offspring. In a press release from the American Physiological Society, lead researcher John Claybaugh asserted that the results “are consistent with the hypothesis that supplemental dietary choline fed to the pregnant dam can prevent the alcohol-induced partial diabetes insipidus seen in the young adult offspring.”

The American Psychological Association, in the wake of a 2007 study published in Behavioral Neuroscience, announced that “giving choline to infants who were exposed in the womb to alcohol may mitigate some of the resulting problems” related to learning, attention, and motor skills. The researchers gave choline to rat pups exposed to alcohol during the third trimester. Alcohol-related hyperactivity and learning deficits decreased, the researchers say. “The data suggest that early dietary interventions may reduce the severity of some fetal alcohol effects, even when administered after birth."

 Despite such optimism, the issue is whether a choline supplement would be capable of rescuing cells after alcohol exposure, or whether choline would need to be taken ahead of time as a supplement.

What is not at issue is that pregnant women should not drink, and should be aware that fetal damage can occur very early in a pregnancy.

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

Wang, G., & Bieberich, E. (2010). Prenatal alcohol exposure triggers ceramide-induced apoptosis in neural crest-derived tissues concurrent with defective cranial development Cell Death and Disease, 1 (5) DOI: 10.1038/cddis.2010.22

Noteworthy Recent Posts on Drugs and the Brain

A few good articles.

Teasing Out the Effects of Environment on the Brain.

By Moheb Costandi

The Dana Foundation

Antidepressants: Are They Effective or Just a Placebo?

By Maia Szalavitz

Time Magazine

SSRIs and Suicide.

By Neuroskeptic

Neuroskeptic blog

Cannabis and mental health – two new studies give the “wrong” results!

UKCIA Newsblog

Under the Microscope: How does caffeine work?

By Professor Andrew Smith.

UK Independent

Photo Credit: http://degweb.org/

Gambling and Parkinson’s Disease

An addendum to the previous post.

Today, a group of Australians taking medications for Parkinson's Disease have filed a class action suit against makers of the drugs, according to a report in the Sydney Morning Herald.

 The Australian newspaper said that "The group includes people who sustained losses of hundreds of thousands of dollars and were involved in family breakdowns as a result of compulsive gambling allegedly linked to drugs they took between 1997 and last year. Most of the claimants developed gambling addictions but a few exhibited compulsive sexual behavior such as looking at pornography on the Internet.”

The drugs involved are dopamine agonists Cabaser and Permax. An agonist binds to particular receptor sites and mimics the action of the substance that normally occupies the site.

A study published in the May issue of Archives of Neurology concluded that, “Dopamine agonist treatment in PD (Parkinson's Disease) is associated with 2- to 3.5-fold increased odds of having an ICD (impulse control disorder)."

According to the study, 13% of the patients were adversely affected by the drugs, exhibiting impulse control problems with gambling (5 percent), sexual behavior (3.5 percent), shopping (5.7 percent) and binge eating (4.3 percent).

The case is not without precedent, according to the Herald. In 2008, “a jury in Minnesota awarded $8.2 million to a man who became a compulsive gambler after using Mirapex (made by Boehringer Ingelheim) to treat his Parkinson's disease. Other lawsuits are being considered in Canada, Britain and France.”


Photo Credit: http://gamingzion.com/

Triple Play for Addicts

Why cigarettes, alcohol and gambling are such a perfect fit.

The newer views of addiction as an organic brain disorder cast strong doubt on the longstanding assumption that different kinds of people become addicted to different kinds of drugs. By 1998, the Archives of General Psychiatry had already flatly stated the reverse: “There is no definitive evidence indicating that individuals who habitually and preferentially use one substance are fundamentally different from those who use another.” This quiet but highly influential breakthrough in the addiction paradigm has paid enormous dividends ever since.

From a genetic standpoint, the implication was that an addiction to alcohol, heroin, or speed did not necessarily “breed true.” The sons and daughters of alcoholics could just as easily grow up to be heroin addicts, and vice versa, due to the same brain anomalies.

There are numerous examples at hand. Recovering alcoholics and heroin addicts tend to be notorious chain-smokers, for one. Many prominent nicotine researchers lean toward the theory that those Americans who continue to be hard-core smokers, unwilling or unable to stop, may represent a biological pool of people who are genetically prone to addiction. Alcohol researcher George Vaillant,  who directed the seminal Harvard Medical School longitudinal studies, sees it the same way: “Alcoholism is a major reason that people don’t stop smoking. Those who keep on smoking after age 50 tend to be alcoholics.” 

There you have it. Throw a lasso around America’s cigarette smokers, and you are likely to snare the lion’s share of “drug abusers” and “problem drinkers” as well. This may also explain why there is such a huge overlap between gamblers and alcoholics, and between gambling and cigarette addiction. It is no secret to anyone who has been inside a casino that a striking percentage of the patrons are also smokers and drinkers. If gambling were truly capable of producing the hallmark symptoms of addiction, we would also expect to see such manifestations as continued use despite adverse circumstances, escalating use, and various forms of self-destructive behavior. It depends on whether the dopamine/serotonin patterns produced by addiction, involving midbrain dopamine neurons with divergent connections to the frontal cortex and other forebrain regions, are the same in compulsive gamblers as in alcoholics and other addicts. Many researchers simply do not believe that the alterations in neurotransmission brought about by behaviors are as powerful as the chemical surges produced by drugs, and therefore cannot result in a state technically called addiction. Others disagree.

Nonetheless, human neurostudies continue to show intriguing dopamine patterns during gambling and certain other forms of game playing. Part of what drives the destructive gambling cycle appears to be the intense, dopamine-driven arousal produced by the anticipation of reward—the jackpot.  Recent research has focused on the part played by midbrain dopamine in the anticipation of reward, otherwise known by addicts as “waiting for the man.” In the world of gaming, it is known as the classic “gambler’s fallacy—the expectation that after a series of losses, a win is “due.” Statistics say otherwise, and gamblers certainly know all about house percentages. Yet, the expectation effects of beating those odds may produce the same anticipatory effect on a disordered metabolism as drug-related activities. A very small, speculative, and intriguing study at Duke University suggested that dopamine agonists given for Parkinson’s disease might sometimes be a catalyst for excessive gambling behaviors in elderly patients, even those who had never shown an interest in gambling before.

As for shopping and sex, even an informed guess seems premature at this point.

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