Tag Archives: Smoking Research

Scripps Florida Scientists Find Blocking a Neuropeptide Receptor Decreases Nicotine Addiction

Findings could point towards more successful smoking cessation efforts.  The study was published in an online Early Edition issue of the Proceedings of the National Academy of Sciences, the week of November 24. Scripps Florida is a division of The Scripps Research Institute.

The neuropeptide, hypocretin-1 (Orexin A), may initiate a key signaling cascade, a series of closely linked biochemical reactions, which maintains tobacco addiction in human smokers and could be a potential target for developing new smoking cessation treatments.

“Blocking hypocretin-1 receptors not only decreased the motivation to continue nicotine use in rats, it also abolished the stimulatory effects of nicotine on their brain reward circuitries,” said Paul Kenny, Ph.D., the Scripps Research scientist at Scripps Florida who led the study. “This suggests that hypocretin-1 may play a major role in driving tobacco use in smokers to want more nicotine. If we can find a way to effectively block this receptor, it could mean a novel way to help break people’s addiction to tobacco.”

Cigarette smoking is one of the largest preventable causes of death and disease in developed countries, and accounts for approximately 440,000 deaths and $160 billion in health-related costs annually in the United States alone. Despite years of health warnings concerning the well-known adverse consequences of tobacco smoking, only about ten percent of smokers who attempt to quit annually manage to remain smoke free after one year, highlighting the difficulty in quitting the smoking habit.

In the study, Kenny and a postdoctoral fellow in his laboratory, Jonathan Hollander, Ph.D., blocked the hypocretin-1 receptor using low doses of the selective antagonist SB-334867, a commercially available compound often used in research.

“While hypocretin 2 systems, otherwise known as orexin B, have been mainly implicated in regulating sleep,” Kenny said, “hypocretin 1, also known as orexin A, appears to be more involved in regulating motivated behavior. Our previous studies in close collaboration with other Scripps Research scientists have shown that hypocretin-1 receptors play a central role in regulating relapse to cocaine seeking. With that in mind, it seemed reasonable to test whether it was involved in nicotine reward as well.”

The new study indeed showed that blocking the receptor in rats significantly decreased nicotine self-administration and also the motivation to seek and obtain the drug. These findings suggest that hypocretin-1 receptors play a critical role maintaining nicotine-taking behavior in rats, and perhaps also in sustaining the tobacco habit in human smokers.In addition, the study highlighted the importance of hypocretin-1 receptors in a brain region called the insula, a walnut size part of the frontal lobe of the brain. A highly conserved brain region, all mammals have insula regions that sense the body’s internal physiological state and direct responses to maintain homeostasis. The insula has also been implicated in regulating feelings of craving. In a recent groundbreaking study, it was reported that smokers who sustained damage to the insula lost the desire to smoke, an insight that revealed the insula as a key brain region that sustains the tobacco habit in smokers. Until the new study, however, the neurobiological mechanisms through which the insula regulated the persistence of tobacco addiction remained unclear.

The new study sheds light on this question, showing that hypocretin-containing fibers project significantly to the insula, that hypocretin-1 receptors are expressed on the surface of neurons in the insula, and that blockade of hypocretin-1 receptors in the insula, but not in the adjacent somatosensory cortex region (which also records and relays sensory information), decreases nicotine self-administration. The effects of blocking hypecretin-1 receptors only in the insula, however, were less than blocking these receptors in the brain as a whole, suggesting that hypocretin transmission in other brain regions may also be playing a role in nicotine reward.

Working with scientists from Scripps Florida’s Translational Research Institute, Kenny and his colleagues are now searching for new antagonists at hypocretin-1 receptors that are less toxic than the compound used in the published experiments in the hopes of furthering the development of a human therapy.

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In addition to Kenny and Hollander, authors of the paper, titled Insular Hypocretin Transmission Regulates Nicotine Reward, were Qun Lu, Michael D. Cameron and Theodore M. Kamenecka, also of Scripps Research.

The study was supported by the National Institutes of Health’s National Institute on Drug Abuse.

About The Scripps Research Institute

Picture of San DiegoThe Scripps Research Institute is one of the world’s largest independent, non-profit biomedical research organizations, at the forefront of basic biomedical science that seeks to comprehend the most fundamental processes of life. Scripps Research is internationally recognized for its discoveries in immunology, molecular and cellular biology, chemistry, neurosciences, autoimmune, cardiovascular, and infectious diseases, and synthetic vaccine development.

Established in its current configuration in 1961, it employs approximately 3,000 scientists, postdoctoral fellows, scientific and other technicians, doctoral degree graduate students, and administrative and technical support personnel. Scripps Research is headquartered in La Jolla, California. It also includes Scripps Florida, whose researchers focus on basic biomedical science, drug discovery, and technology development.

Scripps Florida is currently in the process of moving from temporary facilities to its permanent campus in Jupiter, Florida. Dedication ceremonies for the new campus will be held in February 2009.

Contact: Keith McKeown
Scripps Research Institute

Nicotine Addiction Linked to Studies on Autism

American researchers have recently discovered a connection between two proteins in the brain, linking nicotine addiction and autism.

According to a study presented at a Society for Neuroscience meeting, there is a physical and functional association between these two conditions.

The study showed that the neurexin-1 beta proteins, which are a part of the brain’s chemical communication system, are related to a certain type of nicotinic acetylcholine receptor and play an important role in the proper formation and maturation of synapses.  Proper synapse function is critical to the central nervous system’s ability to connect and control other body systems.

Little Girl with AutismPrevious studies had reported that while such nicotinic receptors are absent in the brain of autistic patients, there are quite a few number of these receptors in the brain of addicts.

Findings revealed that nicotine increases the neurexin-1 levels in the brain of smokers, bringing more nicotinic receptors to the synapses and making them more efficient.

Scientists believe drugs used to curb nicotine addiction can also be effective in alleviating autism symptoms.

Source: PKH/HGH, PressTV

There May be a Very Good Reason Why Coffee and Cigarettes Often Seem to go Hand in Hand

A Kansas State University psychology professor’s research suggests that nicotine’s power may be in how it enhances other experiences.

For a smoker who enjoys drinking coffee, the nicotine may make a cup of joe even better.

And that offer another explaination why smoking is so hard to quit.

“People have very regimented things they do when they smoke,” said Matthew Palmatier, assistant professor of psychology at K-State. “If you think about where people smoke or who they smoke with, you realize that it occurs in very specific places, often with a specific group of people.

Maybe it’s a reason why nicotine is so addictive — if you get used to having that extra satisfaction from things you normally enjoy, not having nicotine could reduce the enjoyment in a given activity.

“People may not be smoking to obtain a pleasurable drug state. They may be smoking in order to regulate their mood, and that effect could make nicotine more addictive than other drugs.”

Palmatier said much previous research on nicotine addiction has looked at the drug itself rather than the other factors he is studying.

“The approach we’re taking is out of left field,” he said. “But it seems to be one of the best explanations as to why people smoke.”

Palmatier has a grant from the National Institute on Drug Abuse to understand how this phenomenon can be used to better design tobacco addiction treatments, usually offered in stop smoking aids, like patches and pills. He began psychological research in addiction as a graduate student and later began researching the reinforcing effects of nicotine.

Coffee and Cigarettes“The big picture is trying to figure out why people smoke,” Palmatier said. “There are a lot of health risks, and the majority of smokers already know what they are. They want to quit but can’t. It’s not because nicotine is a potent drug; it doesn’t induce significant amounts of pleasure or euphoria. Yet, it’s just as difficult if not more difficult to quit than other drugs.”

At K-State, Palmatier studies rats that are allowed to self-administer nicotine by pushing a lever. The main source of light in their testing environment shuts off when the rats earn a dose of nicotine. After about a minute, the light comes back on to signal that more nicotine is available.

By manipulating this signal, Palmatier and his colleagues found that the rats weren’t really that interested in nicotine by itself.

“We figured out that what the rats really liked was turning the light off,” Palmatier said. “They still self-administered the nicotine, but they took more of the drug when it was associated with a reinforcing light.”

Palmatier and colleagues published a paper on their research in the August issue of Neuropsychopharmacology.

Palmatier has begun looking at how rats respond to sweet tastes after having nicotine. He said preliminary results show that nicotine has comparable effects on sweet tastes. That is, rats respond more for sugar-water solutions after getting nicotine.

“The taste aspect is really important because we can actually figure out how nicotine is increasing the subjects’ behavior,” Palmatier said. “If it makes a reward more pleasurable, then it may increase the palatability of a sweet taste.”

Palmatier said that a future phase of research would be determining whether nicotine can make unpleasant experiences more tolerable, helping explain why lighting up after a bad day at work can be tempting.

Contact: Beth Bohn
Kansas State University

Genetic Achilles Heel May Support Nicotine Addiction

Do genes play a role in tobacco addiction?

Recent studies suggest they may, particularly the CHRNA5 gene.

A University of Michigan press release notes a genetic variation suggests a finding that may help explain the path that leads from that first cigarette to lifelong smoking.

In the press release studies smokers and non-smokers to find if you have the less common rs16969968 form of the CHRNA5 gene and you smoke a cigarette you are more likely to get hooked.

Yet another reduction in the possible scope for free will.

Study on Genetics, Genes and Smoking

In a paper published in the September Issue of the journal Addiction, a multi-university collaborative team of researchers specializing in statistical genetics, gene analysis, and trait analysis reports an association between a variant in the CHRNA5 nicotine receptor gene, initial smoking experiences, and current smoking patterns.

The genetic and smoking data come from 435 volunteers. Those who never smoked had tried at least one cigarette but no more than 100 cigarettes in their lives, and never formed a smoking habit. The regular smokers had smoked at least five cigarettes a day for at least the past five years.

The regular smokers in the study were far more likely than the never-smokers to have the less common rs16969968 form of the CHRNA5 gene, in which just one base-pair in the gene sequence was different from the more common form. This kind of genetic variation is called a single nucleotide polymorphism or SNP.

Smokers were also eight times as likely to report that their first cigarettes gave them a pleasurable buzz.

“It appears that for people who have a certain genetic makeup, the initial physical reaction to smoking can play a significant role in determining what happens next,” says senior author and project leader, Ovide Pomerleau, a professor of psychiatry at the University of Michigan Medical School and founder of the U-M Nicotine Research Laboratory.

“If cigarette smoking is sustained, nicotine addiction can occur in a few days to a few months,” he adds. “The finding of a genetic association with pleasurable early smoking experiences may help explain how people get addicted — and, of course, once addicted, many will keep smoking for the rest of their lives.”Among those who ever try smoking this gene explains only part of the difference between those who become addicted and those who do not. Expect more discoveries of genes that contribute to the odds of getting addicted.

Achilles HeelWe are witnessing an acceleration of the rate of discovery of genetic factors that influence behavior. This acceleration in the rate of discovery will accelerate as DNA testing costs continue to drop. So expect to see many more reports of genes that influence behavior.

Source: Randall Parker, FuturePundit

The Sooner You Quit Smoking, the Better Your Chances of Recovery

Studies suggest that ex-smokers may face increased health risks from cigarettes for years to come.

Some of the damage that cigarettes inflict on the body subsides quickly, halving the risk of heart disease and stroke within five years after a smoker quits.

But the effect of smoking on risks of cancer and other diseases can persist for decades, experts say.

Even Sen. John McCain (R-Ariz.), 71, who quit smoking in 1980, still faces some increased risk of cancer from smoking two packs a day for 25 years, studies suggest.

President Barack Obama (D-Ill.), 46, who says he has struggled to stay off cigarettes since quitting last year, may have less long-term risk because he smoked fewer cigarettes per day.

Better to Quit Smoking When Still Young

A major message of the research is that people who quit at a young age are far better off than those who put it off until later.

Obama and McCain, both of whom waited until their mid-40s to quit, would have been measurably better off if they had stopped a decade sooner, experts said.

Young Girl Smoking“If you quit by age 35, by the time you’re 45 you look pretty much like a never-smoker in most of our profiles of risk,” said Terry Pechacek, associate director for science at the federal Centers for Disease Control and Prevention’s office on smoking and health.

The danger intensifies as smokers approach their 30th year of addiction, Pechacek said.

The risk of getting lung cancer for a person who has smoked for 30 years can be six times greater than the risk for someone who has smoked for 20 years.

Some of smoking’s effects may be irreversible. For example, the chronic bronchitis that many smokers develop heals only partially. And quitting cigarettes often has little effect on emphysema, which stems from the damage that cigarette smoke can cause in the lung’s fine structures.

“That stuff doesn’t repair itself,” said Dr. Norman Edelman, chief medical officer for the American Lung Association.

Getting other risks down to normal can take time. A study published last month in the Journal of the American Medical Association found that among women who smoked for 20 years on average, it took 30 years after quitting for their risk of lung cancer to reach normal levels.

Yet heart disease risks declined much more rapidly, the study found. Within five years of quitting, the excess risk from smoking had fallen by 61 percent.

“Clearly there are immediate benefits for some diseases,” said study co-author Stacey Kenfield, a researcher at the Harvard School of Public Health. “It’s never too late to stop.”

Cancer risks are more difficult to get back to normal because of how that disease progresses in the body, experts said.
Genetic damage

Each cigarette has the potential to inflict small bits of genetic damage that can accumulate over time and cause cancer later in a smoker’s life. The longer a person smokes, the more cells get damaged, and the longer it takes for the body’s repair mechanisms to remove the damaged cells.

Smoking is Like Climbing a Mountain

Pechacek of the CDC compared the process to climbing a mountain; smoking more cigarettes takes a person farther up the slope. “If you smoke too long, [you] may not have enough years left to get back down to the base,” he said.

One measure of an ex-smoker’s risk is expressed in “pack-years,” the number of packs smoked per day multiplied by the number of years a smoker was addicted. McCain, who smoked two packs a day for 25 years, would have about 50 pack-years, while Obama, who smoked less than one pack a day for about as long, would have fewer than 25 pack-years.

Smoking Risk Calculator

Memorial Sloan-Kettering Cancer Center in New York has posted an online lung cancer prediction calculator (at mskcc.org/mskcc/html/12463.cfm) that uses pack-years and other information to assess an ex-smoker’s risk of developing cancer. Some researchers have debated the usefulness of pack-years in such predictions, arguing that overall duration of smoking matters more than the number of cigarettes smoked.

Like many smokers who try to kick the addiction, Obama says he has suffered smoking relapses since first attempting to quit last year. Such setbacks are less important than the ultimate goal, Pechacek said.

“Usually it takes three or four quits before a person is successful,” he said. “We need to stop looking at those as failures, because really they’re steps toward success. You’re building the skills you need to quit.”

Source:  Jeremy Manier – Chicago Tribune

Smoking Gets Into Your Skin Too

Smokers can add a new health risk to the ever-growing list of hazards posed by their habit: the unsightly and often painful skin condition known as psoriasis.

We all know that smoking can effect the health of the skin, including increasing skin wrinkles, but this recent study indicates the odds of developing other serious skin conditions.

American and Canadian investigators who analyzed data from the long-running Nurses Health Study find smoking increases the risk of psoriasis by 78 percent when compared to never smoking.

The link between smoking and psoriasis is long-lasting too. Former smokers have a 37 percent higher risk overall, and the risk doesn’t decline until 20 years after a person kicks the habit.

Heavier smokers fare worse than lighter smokers too. In the study, psoriasis risk went up with the number of “pack-years” smoked. A pack-year is defined as smoking 20 cigarettes per day for one year.

Even exposure to secondhand smoke appeared to increase the danger, with a higher risk seen for study participants who were exposed to smoke while their mothers were pregnant or when they were children.

Skin Irritation from Smoking“These findings, along with well-established hazardous health effects of smoking, provide clear incentives for smoking cessation in those at risk for and suffering from psoriasis,” study author Hyon K. Choi, M.D., Dr.P.H., was quoted as saying. “Beyond the potential effect on psoriasis, smoking cessation would lead to a better overall clinical outcome in psoriasis patients, who often suffer co-morbidities related to smoking.”

This article was reported by Ivanhoe.com, which offers Medical Alerts by e-mail every day of the week. To subscribe, click on: http://www.ivanhoe.com/newsalert/.

SOURCE: The American Journal of Medicine, published October 29, 2007

Click to learn more about > psoriasis.

OJ Helps With Nicotine Withdrawal

If you quit cold turkey – drink plenty of Orange Juice to help your nicotine withdrawl symptoms.

You’ll get over the irritability, anxiety, confusion and trouble concentrating and sleeping that come with nicotine withdrawal a lot faster if you drink a lot of orange juice during this time.

Why, you wonder? Here is what researchers have found.

oj.jpgOJ makes your urine more acidic, which also clears nicotine from your body faster, says Thomas Cooper, D.D.S., a nicotine dependency researcher and professor of oral health sciences at the University of Kentucky in Lexington.

“Besides,” adds Dr. Jorenby, “the citrus taste in your mouth makes the thought of having a cigarette pretty disgusting.”

Even though OJ is high in sugar, perhaps drinking some Vitamin C rich orange juice while you are quitting smoking may give you that extra support for the time being.

Women Smokers Grow More Facial Hair

The effects of smoking can show up in ways you may not expect.

Although the mustache on the women in this picture is obviously fake, what we are about to tell you isn’t.

The Medical College of Wisconsin has reported a link between smoking and increased facial hair in some women.

Girl with Fake Moustache Women who smoke at least one pack of cigarettes a day have a fifty percent greater chance of growing more facial hair.

This study at the Medical College of Wisconsin has found increased facial hair in women apparently has something to do with the effects of smoking on the ovaries and the production of hormones.

So if you are a women smoker and find you are growing more facial hair as you age you could be adversely effecting your hormonal balance due to the risks of ingesting the chemicals in cigarettes.

Opioid Receptors – Emotions and Cravings Explained

“It appears that smokers have an altered opioid flow all the time, when compared with non-smokers.

And smoking a cigarette further alters that flow by 20 to 30 percent in regions of the brain important to emotions and craving” as explained in an WikiPedia article.

This may help us understand a link between cigarettes and desire to smoke.

Picture of the BrainLearn More About Opioids

Smokers enjoy their habit because it stimulates the flow of “feel good” chemicals in the brain, according to a new study involving just a handful of test subjects.

Smoking Increases Risks for Head and Neck Cancers for Men And Women

Smoking significantly increases the risk for head and neck cancers for both men and women, regardless of the anatomic site.

Published in the journal Cancer, a large, prospective study confirmed strong associations between current and past cigarette smoking and malignancies of the head and neck in both genders.

Cancers of the head and neck include cancers of the larynx, nasal passages/nose, oral cavity, and pharynx.

Worldwide, more than 500,000 people are diagnosed with these cancers every year. According to the National Cancer Institute (NCI), men are more than three times more likely than women to be diagnosed with head and neck cancer and almost twice as likely to die from their disease.

Neck ImageWhile tobacco use has long been identified as an important risk factor for head and neck cancers, the new study finds that smoking plays a greater role in the development of head and neck cancer in women than men.

Dr. Neal Freedman from the NCI and co-investigators analyzed data from 476,211 men and women prospectively followed from 1995 to 2000 to assess gender differences in risk for cancer in specific head and neck sites.

Analysis showed that the risk of smoking leading to any type of head and neck cancer was significantly greater in women than in men. While 45 percent of these cancers could be attributed to smoking in men, 75 percent could be attributed to smoking in women.

“Incidence rates of head and neck cancer were higher in men than in women in all categories examined,” conclude the authors, “but smoking was associated with a larger relative increase in head and neck cancer risk in women than in men.” To reduce the burden of head and neck cancer, public health efforts should continue to aim at eliminating smoking in both women and men.

Article: “Prospective Investigation of the Cigarette Smoking-Head and Neck Cancer Association by Sex,” Neal D. Freedman, Christian C. Abnet, Michael F. Leitzmann, Albert R. Hollenbeck, Arthur Schatzkin, CANCER; Published Online: August 27, 2007, 2007 (DOI: 10.1002/cncr.22957); Print Issue Date: October 1, 2007.

Note: This story has been adapted from a news release issued by John Wiley & Sons, Inc.