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December 8th, 2007:

Nicotine Addiction Controlled By Influencing Brain Mechanisms?

American College of Neuropsychopharmacology

Study suggests nicotine addiction might be controlled by influencing brain mechanisms

Findings provide possible clues to addiction in humans, animals

Boca Raton, FL, December 8, 2007 –There is a clear link between GABA – a chemical substance of the central nervous system that inhibits neurons in the brain – and nicotine dependence, according to a study presented today at the American College of Neuropsychopharmacology (ACNP) annual meeting. Researchers discovered that nicotine has significant effects on brain GABA, a finding which could potentially help curb the pleasurable effects of nicotine and help people break their addiction to it.

“We found that GABA may provide a very useful target for nicotine addiction therapies,” said Graeme Mason, Ph.D., associate professor in the Magnetic Resonance Research Center in the Departments of Diagnostic Radiology and Psychiatry at Yale University School of Medicine and an ACNP member. “GABA is just one of a complex network of actors that promotes addiction, and we’re hoping that this research will ultimately lead us to ways to help people quit smoking.”

Mason sought to discover whether the enjoyable effects associated with smoking could be reduced in some way. When people use nicotine they may experience a sensation of reward, diminished anxiety, or a belief that they can focus more clearly or learn more easily. Researchers wanted to explore how a specific type of neuron that releases dopamine, a chemical that has been associated with pleasure, can prolong and intensify the pleasurable effects of nicotine. Although GABA inhibits those neurons, nicotine works against the ability of GABA to inhibit dopamine neurons after about 20 minutes, so the gratifying effects of nicotine are prolonged.

Researchers gave people who smoked regularly nicotine inhalers that deliver the same amount of the drug as in one cigarette. The amount of GABA in the subjects’ brains rose about 10%, but the brain was found to make GABA four times faster after using the inhalers, and the rate of new GABA generation remained high for at least 45 minutes. In other words, keeping the supply of GABA levels high has the potential to reduce the pleasurable effects of smoking, in terms of duration and intensity.

“While GABA is probably not the root of nicotine addiction, it is part of a complex network of actors that are involved in addiction,” Mason says.

Another study presented at the ACNP annual meeting which explored the role of GABA, genetics and environmental factors in smoking found that tobacco addiction is at least 50% determined by genetics. For this reason, researchers may be able to identify individuals who are vulnerable to nicotine dependence, and then implement prevention strategies accordingly.

For this study, Ming Li, Ph.D., Professor of Genetics in Psychiatry and Neurosciences at the University of Virginia recruited more than 2000 participants representing more than 600 families of smokers. They examined different regions on various chromosomes that showed linkage to nicotine addiction. Then they searched for susceptibility genes within these regions that appear to be associated with addiction. Some of these are the GABA-B receptor subunit 2 (GABAB2) gene on chromosome 9, and the GABA-A receptor-associated protein (GABARAP) gene on chromosome 17.

Li says the research could have significant public health implications because it could help curb smoking rates since researchers may be able to predict who is more prone to nicotine addiction. Tobacco is one of the most widely used substances; it kills more than 435,000 Americans each year, and despite increasing public awareness of the health risks associated with its use, little reduction in smoking prevalence has been achieved nationwide in recent years.

Tobacco Kills 100 Million

Public Health and Cancer Prevention: Success and Future Challenges in Cancer Policy

WEBWIRE – Saturday, December 08, 2007

PHILADELPHIA – Medical research has revealed much about cancer prevention, but is the information reaching all Americans, and are they acting on it? Today, at the American Association for Cancer Research’s Sixth Annual International Conference on Frontiers in Cancer Prevention Research, being held from December 5 to 8 in Philadelphia, Pennsylvania, researchers explore the question of how best to translate cancer prevention science into public health policy.

Quitting smoking and inoculation with the human papillomavirus (HPV) vaccine are two ways that major segments of the general population can drastically lower their risk of developing certain cancers, yet researchers have found that these messages are not necessarily translating into action by the public.

Policies to reduce tobacco harm: What works? Abstract no. A29

To discourage cigarette use, the strategies that are working best on a global basis are to

  • use large graphic package warning labels,
  • ban cigarette advertising,
  • institute smoke-free policies,
  • increase cigarette prices and
  • implement methods to prevent smuggling and counterfeiting of tobacco products,

say researchers at Roswell Park Cancer Institute involved in an International Tobacco Control (ITC) Policy Evaluation study. What hasn’t worked as well as hoped is mandating tar and nicotine levels in cigarettes, they add.

The researchers have been investigating progress on controlling tobacco use from the ongoing Framework Convention on Tobacco Control (FCTC), the treaty devoted to improving public health put forth by the World Health Organization.

The FCTC was adopted by WHO’s member states in May, 2003, and became legally binding for those countries that ratified the treaty in 2005. To date, 151 countries have done so, and are thus required to implement the policies within three years.

“For the first time ever, we are beginning to scientifically assess which governmental tobacco control policies are working and which ones are not” said K. Michael Cummings, Ph.D., MPH, chair of the Department of Health Behavior at Roswell Park Cancer Institute. “In the same way that evidence-based medicine has been built from rigorous evaluation of treatment options, our goal is to contribute to the development of a sound science base for tobacco control policies”

The ITC serves to study which policies are working best in countries that have imposed restrictions, says Cummings. Cummings started the study in four countries in 2002 with a $1.5 million grant from the Robert Woods Johnson Foundation, and to date, $35 million has been raised to expand the research into 15 countries, utilizing the aid of 60 investigators from 17 research institutes.

Because randomized clinical trials can’t be used to evaluate government policies, the ITC study uses as controls those countries that have implemented tobacco control policies and compares the effects on tobacco use behaviors in countries that have not, such as the United States. It is tracking tobacco use behaviors of 1,000 to 2,000 participants in each of the countries, Cummings says. “This is a new model for global public health research that can be used to evaluate other public health policies such as HIV, diet, and cancer screening” he said.

“It made sense for WHO to start off with tobacco as a focal point for action since tobacco use is the leading cause of preventable death in the world today and is a growing epidemic in the developing world” he said. Tobacco use was responsible for 100 million deaths in the 20th century, and that number is expected to grow to 1 billion in the 21st century, he says.

ITC researchers have found that boosting tobacco taxes, comprehensive advertising bans, smoke-free laws, and strengthening cigarette package warnings is an effective recipe for reducing tobacco consumption. “Our research on package warnings has revealed that these warnings, especially if they are large and graphic, are more effective than anyone realized, especially in poorer countries that can’t afford expensive counter-marketing campaigns” he said.

An example of a policy that hasn’t worked, Cummings says, is the European Union’s (EU) establishment of maximum emission standards for tar and nicotine. The goal was to make cigarettes less toxic, but the testing method adopted by the EU was flawed and cigarette makers increased filter ventilation to get around the new rules. Actual exposure to toxins didn’t change. “The well intentioned, but flawed EU policy has given smokers the false illusion that their cigarettes deliver less tar and nicotine, when they don’t” he said.

The ITC has also established the first international cigarette repository, which currently holds 10,000 cigarette pack varieties from 15 different countries. This research shows that tobacco manufacturers alter their products frequently without revealing that they are doing so, he says. “Foods and drugs are regulated so that consumers are informed when the products are altered. The same should be true for tobacco products” Cummings said.