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Nicotine addiction slashed in test of new cigarette smoking strategy
November 14, 2007 -  Scientists are reporting the first successful strategy to reduce smokers’ nicotine dependence while allowing them to continue smoking. The study provides strong support for proposals now being considered in Congress to authorize FDA regulation of cigarette smoking, according to the research team.

The key to the clinical trial’s success was providing smokers with cigarettes of gradually decreasing nicotine content over a number of weeks. If such cigarettes were federally mandated, smokers would find it easier to quit, and more young smokers could avoid addiction, according to the scientists. Tobacco company products marketed as low-nicotine alternatives, in fact, do not change the level of nicotine taken in by smokers, they added.

The research was carried out by scientists at UCSF and San Francisco General Hospital Medical Center and is reported in the November 14 issue of the journal "Cancer Epidemiology, Biomarkers & Prevention."

Legislation giving the FDA authority to regulate tobacco products is currently being considered in Congress. Such regulatory authority would empower the agency to develop and enforce standards to make cigarettes less harmful — including the reduction of the nicotine yields so that cigarettes would be less addictive, said Neal Benowitz, MD, leader of the study team and an expert on the pharmacology and health effects of nicotine and other smoking products.

Smoking and health experts have been concerned that reducing the nicotine content of cigarettes would lead to smoking a greater number of cigarettes and therefore increased exposure to other tobacco smoke toxins, as is seen in smokers of the currently marketed low-nicotine yield cigarettes, Benowitz said. The new research on reduced-nicotine content cigarettes strongly counters that prediction.

In the study, 20 healthy adult smokers smoked their usual brand for a week and then followed a six-week regimen of smoking cigarettes with progressively decreased nicotine content.

At the end of this period, they were free to return to their usual commercial cigarette brand, and most of them did. When tested one month later, they were smoking about 40 percent fewer cigarettes per day, with a comparable reduction in nicotine intake, compared to when the study began. Even more promising, one fourth of the smokers quit smoking entirely while the study was in progress, the researchers found.

"This study supports the idea that if tobacco companies were required to reduce the levels of nicotine in cigarette tobacco, young people who start smoking could avoid becoming addicted, and long-time smokers could reduce or end their smoking, Benowitz said.

"This could spare millions of people from the severe health effects of long-term smoking," he added.

Benowitz is a UCSF professor of medicine, psychiatry and biopharmaceutical sciences, and chief, Division of Clinical Pharmacology and Experimental Therapeutics at SFGH.

In 1994, Benowitz and colleague Jack Henningfield proposed in the "New England Journal of Medicine" that federal regulations should require cigarette manufacturers to gradually reduce nicotine content of all cigarettes sold in the U.S.

Scientists have conducted studies to test nicotine-reduction strategies, using commercial low-yield cigarettes. Such cigarettes do reduce nicotine yield when tested by smoking machines because manufacturers have engineered the cigarettes to burn faster, and they have used highly porous paper and ventilation holes above the filter. These cigarettes contain significant levels of nicotine and such "cigarette engineering" does not lead to decreased nicotine intake, because smokers are easily able to obtain the nicotine by taking more frequent and bigger puffs, Benowitz and his co-authors noted.

In contrast, in the new study, the absolute content of nicotine in the tobacco was reduced so that it was very difficult or impossible to compensate by smoking more intensely.

In addition to the reduced smoking and nicotine levels, the UCSF scientists looked for changes in exposure to carbon monoxide, tobacco smoke carcinogens and cardiovascular disease risk factors. All these remained stable or decreased, indicating that smokers were not exposed to higher levels of tobacco smoke toxins when they switched, and therefore would not be put at risk by a nicotine reduction intervention.

Benowitz and his colleagues are now conducting a much larger and longer clinical study on the effectiveness and safety of reducing nicotine levels in cigarettes. They plan also to examine whether reduced-nicotine cigarettes result in reduced addiction potential among adolescent experimental smokers.

University of California - San Francisco

Is fear of gaining weight keeping many women from trying to quit smoking?
November 07, 2007 -  ANN ARBOR, Mich. - Is a fear of getting fatter partly to blame for the fact that nearly one in five American women still smokes, and many don’t try to quit"

Although there are many possible reasons for the stubborn persistence of smoking, fear of weight gain is high on the list for many women, says a University of Michigan Health System researcher who has devoted much of her career to studying this issue.

Several years ago, she and her team reported that 75 percent of all women smokers say they would be unwilling to gain more than five pounds if they were to quit smoking, and nearly half said they would not tolerate any weight gain. In fact, many women started smoking in the first place because they thought it might help them stay slim.

Now, new U-M research findings published in the October issue of Addictive Behaviors show that women who smoke tend to be further from their ideal body image, and more prone to dieting and bingeing, than those who don’t smoke.

Cigarettes are well known to suppress appetite and weight, says Cindy Pomerleau, Ph.D., director of the U-M Nicotine Research Laboratory. "So it’s hardly surprising that women who have trouble managing their weight or are dissatisfied with their bodies are drawn to smoking," she says.

In another recent study, published in August, the U-M team found that overweight women smokers who were overweight as children were far more likely to have started smoking in their early teens than women whose weight problems started later in life. They also had worse withdrawal symptoms when they tried to quit.

Once they make a serious attempt to quit, evidence suggests that most weight-concerned smokers can be just as successful in kicking the habit as others.

"The problem here is getting women who are concerned about their weight to be willing to try to make a quit attempt," says Pomerleau, "and then helping them gain a sense of control over their weight."

Women who are highly concerned about weight tend to be concerned about other aspects of their appearance as well, she notes. What they need to understand, she says, is that smoking has an impact on many aspects of appearance and attractiveness. Among other things, it causes wrinkled skin, thinning hair, cracked fingernails, yellowed teeth and terrible breath.

Pomerleau, a research professor of psychiatry, is working on a book about women, smoking and weight loss that will draw together research findings, helpful tips and real-life examples of women who quit tobacco while also containing their weight.

Some beliefs about smoking and weight are true, she says. For instance, nicotine suppresses the appetite and increases resting metabolic rate. Smokers on average weigh less than people who have never smoked, and that smokers who quit tend to gain weight. Adding to these perceptions are tobacco advertisements that portray female smokers as slim and successful.

Even so, the effect of quitting on weight is often less dramatic than many women fear, Pomerleau says. A rough rule of thumb is that one in four women who quit smoking will gain less than five pounds, and another two out of four will gain five to 15 pounds. Only one in four women who quit will gain 15 pounds or more.

But Pomerleau’s own research suggests that many women smokers start out with an unrealistic image of how they would like their bodies to look. This may make their dread of gaining weight even worse.

In her paper in Addictive Behaviors, she reports the results of a study of 587 women between the ages of 18 and 55, including 420 smokers and 167 women who had never smoked. An equal proportion of both groups was overweight or obese, with a body mass index of 25 or more.

In the study, the smokers and non-smokers were asked to look at silhouette pictures of ten different body types, ranging from thinnest to fattest, and to choose which one their current body type was closest to, and which one they wanted to look most like. They were also asked questions about their self-image and their eating habits, about how concerned they were about gaining weight if they quit smoking, and about how sure they were that they could stay off cigarettes even if they gained weight.

The smokers chose an ideal body shape that was slimmer than the non-smokers chose, and further from how they perceived themselves as looking. They also had more problems with limiting their eating. Smokers who were overweight were especially doubtful about their ability to stay off tobacco if they started to gain weight.

This study, Pomerleau says, suggests that if women smokers are to succeed in quitting, they may need extra help in achieving a more realistic body image and paying attention to unhealthful eating patterns, particularly if they are already overweight.

At the same time, Pomerleau and her team have found that the earlier in life a weight problem starts, the more likely a woman is to start smoking.

In a study of 89 overweight women smokers, those who remembered being overweight before they reached junior high school reported that they had started experimenting with smoking at around age 13 - compared with women whose weight problems didn’t start until junior high or after, who hadn’t tried smoking till they reached age 15.

The women who were overweight as children also reported more nicotine-withdrawal symptoms when they tried to quit smoking, especially symptoms like anger, irritability and trouble concentrating. The study was published in the August issue of Eating Behaviors.

These studies, and others that the U-M team have done, all point to the importance of finding new strategies to help women quit smoking without losing control of their weight. Although severe dieting during a smoking cessation attempt has not been shown to be helpful in either quitting smoking or controlling weight, it may be unrealistic to expect women with strong weight concerns to put these concerns on hold for several weeks or months while they try to quit tobacco.

"What we would like to work for is a kind of compromise strategy, where the focus is on the smoking cessation, but women can also take some passive and active measures to control their weight," Pomerleau says.

Passive measures include things like nicotine patches and gum, and medicines like bupropion, which can help in controlling weight gain while keeping nicotine withdrawal symptoms at bay.

Another option for women is to launch their stop-smoking effort early in their menstrual cycle, so that the bloating that can happen soon after they snuff out their last cigarette won’t be compounded by the bloating that comes along right before their period begins.

Finally, although strenuous dieting is not recommended, Pomerleau says, women can start immediately to rebalance the energy-in/energy-out equation by not substituting eating for smoking, and by increasing their physical activity. Even brief bouts of exercise, such as stretching or walking, can be effective in distracting a woman when the urge to smoke strikes, she says, and they burn a few calories too.

University of Michigan Health System

Smoked cannabis proven effective in treating neuropathic pain
October 25, 2007 -  Smoked cannabis eased pain induced in healthy volunteers, according to a study by researchers at the University of California, San Diego (UCSD) Center for Medical Cannabis Research (CMCR.) However, the researchers found that less may be more.

In the placebo controlled study of 15 subjects, a low dose of cannabis showed no effect, a medium dose provided moderate pain relief, and a high dose increased the pain response. The results suggest a "therapeutic window" for cannabis analgesia, according to lead researcher Mark Wallace, M.D., professor of anesthesiology at UCSD School of Medicine and Program Director for the UCSD Center for Pain Medicine.

The paper, to be published in the November issue of the journal Anesthesiology, is the second published study out of the CMCR. Headquartered at UCSD, the CMCR is collaboration between UCSD and UC San Francisco that was funded by a state-funded initiative in 1999 to rigorously study the safety and efficacy of medicinal cannabis in treating diseases.

The study used capsaicin, an alkaloid derived from hot chili peppers that is an irritant to the skin, to mimic the type of neuropathic pain experienced by patients with HIV/AIDS, diabetes or shingles - brief, intense pain following by a longer-lasting secondary pain. The subjects were healthy volunteers who inhaled either medical cannabis or a placebo after pain was induced. The marijuana cigarettes were formulated under NIH supervision to contain either zero, two, four or eight percent delta-9-tetrahydrocannabinol (THC.)

"Subjects reported a decrease in pain at the medium dose, and there was also a significant correlation between plasma levels of THC, the active ingredient in cannabis, and decreased pain," said Igor Grant, M.D., F.R.C.P.(C), professor and Executive Vice-Chair of the Department of Psychiatry, the director of the CMCR. "Interestingly, the analgesic effect wasn't immediate; it took about 45 minutes for the cannabis to have an impact on the pain," he said.

The results, showing a medium-dose (4% THC by weight) of cannabis to be an effective analgesic, converged with results from the CMCR's first published study, a paper by UCSF researcher Donald Abrams, M.D. published in the journal Neurology in February 2007. In that randomized placebo-controlled trial, patients smoking the same dose of cannabis experienced a 34% reduction in HIV-associated sensory neuropathy pain-twice the rate experienced by patients receiving a placebo.

"This study helps to build a case that cannabis does have therapeutic value at a medium-dose level," said Grant. "It also suggests that higher doses aren't necessarily better in certain situations - something also observed with other medications, such as antidepressants."

The researchers stated that more and larger studies need to be conducted to measure the efficacy of cannabis, noting that medical marijuana could play an important role in treating patients who don't respond well to the usual pain relievers or can't tolerate drugs such as ibuprofen or opioids used for severe pain.

"The results of this study might help guide others doing clinical research into pain management," said Wallace.

University of California - San Diego

Smoked cannabis proven effective in treating neuropathic pain
October 25, 2007 -  Smoked cannabis eased pain induced in healthy volunteers, according to a study by researchers at the University of California, San Diego (UCSD) Center for Medical Cannabis Research (CMCR.) However, the researchers found that less may be more.

In the placebo controlled study of 15 subjects, a low dose of cannabis showed no effect, a medium dose provided moderate pain relief, and a high dose increased the pain response. The results suggest a "therapeutic window" for cannabis analgesia, according to lead researcher Mark Wallace, M.D., professor of anesthesiology at UCSD School of Medicine and Program Director for the UCSD Center for Pain Medicine.

The paper, to be published in the November issue of the journal Anesthesiology, is the second published study out of the CMCR. Headquartered at UCSD, the CMCR is collaboration between UCSD and UC San Francisco that was funded by a state-funded initiative in 1999 to rigorously study the safety and efficacy of medicinal cannabis in treating diseases.

The study used capsaicin, an alkaloid derived from hot chili peppers that is an irritant to the skin, to mimic the type of neuropathic pain experienced by patients with HIV/AIDS, diabetes or shingles - brief, intense pain following by a longer-lasting secondary pain. The subjects were healthy volunteers who inhaled either medical cannabis or a placebo after pain was induced. The marijuana cigarettes were formulated under NIH supervision to contain either zero, two, four or eight percent delta-9-tetrahydrocannabinol (THC.)

"Subjects reported a decrease in pain at the medium dose, and there was also a significant correlation between plasma levels of THC, the active ingredient in cannabis, and decreased pain," said Igor Grant, M.D., F.R.C.P.(C), professor and Executive Vice-Chair of the Department of Psychiatry, the director of the CMCR. "Interestingly, the analgesic effect wasn't immediate; it took about 45 minutes for the cannabis to have an impact on the pain," he said.

The results, showing a medium-dose (4% THC by weight) of cannabis to be an effective analgesic, converged with results from the CMCR's first published study, a paper by UCSF researcher Donald Abrams, M.D. published in the journal Neurology in February 2007. In that randomized placebo-controlled trial, patients smoking the same dose of cannabis experienced a 34% reduction in HIV-associated sensory neuropathy pain-twice the rate experienced by patients receiving a placebo.

"This study helps to build a case that cannabis does have therapeutic value at a medium-dose level," said Grant. "It also suggests that higher doses aren't necessarily better in certain situations - something also observed with other medications, such as antidepressants."

The researchers stated that more and larger studies need to be conducted to measure the efficacy of cannabis, noting that medical marijuana could play an important role in treating patients who don't respond well to the usual pain relievers or can't tolerate drugs such as ibuprofen or opioids used for severe pain.

"The results of this study might help guide others doing clinical research into pain management," said Wallace.

University of California - San Diego

Severely mentally ill at high risk for cardiovascular disease
October 17, 2007 -  A psychiatrist at Washington University School of Medicine in St. Louis writes in the Journal of the American Medical Association (JAMA) that although mortality from cardiovascular disease has declined in the United States over the past several decades, patients with severe psychiatric illness are not enjoying the benefits of that progress.

In a commentary article in the Oct. 17 issue of JAMA, John W. Newcomer, M.D., professor of psychiatry, of psychology and of medicine and medical director of the Center for Clinical Studies at Washington University, reports that those with illnesses such as schizophrenia, bipolar disorder and major depression lose 25 to 30 years of life expectancy compared to the general population. And although suicide does claim the lives of many psychiatric patients, most of those premature deaths are due to cardiovascular disease.

"This is really a double hit," Newcomer says. "Not only are these patients dealing with the serious burden that accompanies their psychiatric disorder, but they also have an increased risk and an increased burden from major medical conditions like diabetes, heart disease and stroke. Ultimately, it is the unrecognized risk factors and the under-diagnosed and under-treated conditions that significantly shorten the lifespan."

Newcomer says several factors conspire to elevate risk including reduced access to appropriate medical care. Major mental disorders significantly impair a person’s ability to work and learn, so patients tend to have lower incomes and poorer dietary habits, often relying instead on fast food. In addition, patients with serious psychiatric illness are much more likely to smoke - between 50 percent and 80 percent smoke cigarettes - and although the severely mentally ill make up only between 5 percent and 10 percent of the population, they consume a disproportionate amount of all cigarettes smoked in the United States. Many psychiatric medications also tend to contribute to weight gain, in part by making people less active and sometimes by stimulating appetite, and weight gain can be a prominent side effect of some antipsychotic drugs in particular.

"All of this adds up," Newcomer says. "They are more likely to eat more high-fat food and to burn fewer calories, so it’s not surprising that this population also tends to have higher rates of overweight and obesity."

But that’s not the whole story. Newcomer also reports that patients with severe mental illness are significantly less likely to receive therapies of proven benefit for problems with cholesterol, diabetes, hypertension or heart disease. Those who have survived a heart attack are less likely to receive appropriate medications, cardiac catheterization procedures or bypass surgery than heart-attack patients without mental illness.

Regarding preventive care, Newcomer cites data from a national study of 1,500 patients with chronic schizophrenia. They participated in the National Institute of Mental Health-funded Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study. The CATIE study found that 88 percent of patients entering the study with high cholesterol did not take lipid-lowering drugs. Another 30 percent with diabetes at the start of the study received no anti-diabetes medications, and 62 percent of those with high blood pressure were not taking any antihypertensive medication.

Those with severe psychiatric illness also are less likely to be screened for high cholesterol, high blood pressure or diabetes despite the evidence of increased risk in general and specific evidence that some antipsychotic drugs can have adverse effects on body weight, glucose metabolism and lipid levels.

A solution, Newcomer argues, will emerge only if psychiatrists and primary-care providers can work together.

"This requires coordination," he says. "And coordination between psychiatric professionals and primary-care providers is not easy when they often are physically located in different places. There are transportation issues and scheduling issues. For healthy people, the need to make an extra appointment lowers the probability that it will actually happen, and research further indicates that when patients with severe mental disorders have to go across the hall, it reduces the probability they will get care. If they have to cross the street, the probability gets even lower. If it’s across town - well, without case managers and others working closely with these patients, in general those follow-ups won’t happen."

Newcomer says another problem is that lifestyle interventions that encourage healthy eating, smoking cessation and exercise can be difficult enough in the general population, but they are even more difficult when patients with schizophrenia or other mental disorders are involved. He says such behavioral interventions have been shown to work even in those with severe psychiatric illness, but achieving success requires extra commitment and resources from the health-care community.

Getting psychiatrists to change their routine is important. Newcomer says that to lower risk of cardiovascular complications, psychiatrists may need to regularly weigh their patients, take blood pressure and screen appropriately for blood glucose, cholesterol and triglycerides.

"We’re not saying psychiatrists should start prescribing lipid-lowering agents or diabetes drugs, but they are on the ‘front lines,’ seeing psychiatric patients much more than primary-care providers," Newcomer says. "It’s important that psychiatrists begin to employ some of these basic screening techniques."

He also says that it’s vital that patients with severe mental disorders receive needed psychiatric medications, even though some of those drugs may contribute to weight gain, abnormal lipid levels and risk for cardiovascular disease and diabetes.

"If you have a serious psychiatric condition like schizophrenia, you really need to take medication," Newcomer says. "Clearly we don’t want people to stop taking their medicine, but in some cases, there may be alternative drugs that have fewer effects on risk for obesity or diabetes. Combinations of diet, exercise and selected medication are being studied to lower these risks without losing the benefits that antipsychotic drugs provide for these patients with severe psychiatric illness."

And Newcomer believes if such strategies can be developed and implemented, it is possible to quickly lower rates of cardiovascular disease and increase life expectancy in this population.

"I think there’s some ‘low-hanging fruit’ here," he says. "Just getting psychiatrists engaged in this type of general health monitoring should help. Most of these patients already are seeing a physician, and if that physician and medical team can screen for cardiovascular risk factors, we may be able to intervene and find ways to lower that risk significantly."

Washington University in St. Louis