Targeting Nicotinic Receptors and Profits

If there was any doubt that nicotine is truly a wonder drug, the existence and activities of the company Targacept should lay these doubts to rest. http://www.targacept.com/wt/page/index

Targacept, Inc. is a biopharmaceutical company engaged in the design, discovery and development of NNR Therapeutics(TM), a new class of drugs for the treatment of multiple diseases and disorders of the central nervous system. Our NNR Therapeutics selectively target neuronal nicotinic receptors, or NNRs. NNRs are found on nerve cells throughout the nervous system and serve as key regulators of nervous system activity.

Targecept has several NNR products in various phases of testing:

• ADHD - Phase 2 testing, partnered with AstraZenica
• Alzheimer's Disease, Phase 1 testing, partnered with AstraZenica
• Cognitive Dysfunction in Schizophrenia, ready to enter Phase 2 testing
• Major Depressive Disorder, ready to enter Phase 3 testing
• Depression / Anxiety Disorders, Preclinical

They also plan to develop nicotine receptor treatments for inflammation, smoking cessation, obesity, pain, addiction and Parkinson's Disease. There is a lovely color chart on their Product Pipeline page: http://www.targacept.com/wt/page/pipeline

Creating separate, narrowly-targeted treatments for all these condtions may mean that someone who is obese, has attention deficits, and is prone to depression will need a different pill for each condition. If these medications follow the pattern of other newly-approved pharmaceuticals, each will cost hundreds of dollars per month.

Nature's own NNR, plain old nicotine, controls the symptoms of most, if not all, of the conditions targeted by Targacept. Is it any wonder then, why smokers who are prone to anxiety or depression, who have problems concentrating, and/or who have memory impairments find it a Hurculean task to give up smoking?

Until recently, the most effective way of obtaining adequate nicotine was through tobacco smoke. Now that smokers have the option of switching to inhaling vaporized nicotine from an electronic cigarette, they are no longer subjected to the tar, carbon monoxide, and thousands of chemicals in tobacco smoke that trigger lung problems, heart disease, and cancer. By substituting electronic for their tobacco cigarettes, smokers can regain their physical health without having to pay the terrible price imposed by nicotine abstinence.

The Case for Nicotine Maintenance

When people who are nicotine-dependent reduce or eliminate their intake of nicotine, they become moody, depressed, anxious, and irritable. They start making mistakes no matter how hard they try to concentrate. They have problems remembering things. Given these circumstances, is it any wonder that most people resume smoking within the first two weeks after quitting?

How long would most of us be able to get away with moodiness, forgetfulness, and making mistakes on the job? And how do such symptoms affect the performance of every-day tasks such as balancing the checkbook, taking medications, shopping, driving the car, or supervising children?

Many researchers suspect that people who are highly dependent on nicotine are using it to self-treat underlying disorders. This would explain why, for so many would-be quitters, their "withdrawal symptoms" do not disappear within the promised week or two. They go on, and on, and on.

Nicotine is being studied as a potential treatment for such conditions as attention deficits, Alzheimer’s, depression, anxiety, pain relief, Tourette Syndrome, inflammatory bowel disease, ulcerative colitis, schizophrenia, and epilepsy, as well as both treatment and prevention of Parkinson’s. Nicotine has none of the serious adverse effects that prescription antidepressants, corticosteroids, anti-seizure, anti-anxiety, and schizophrenia medications can cause.

There are additional adverse health effects associated with nicotine abstinence. When people quit smoking, they gain weight. For many years, the idea that this weight gain is relatively small and totally harmless prevailed. But research has shown that the average weight gain is not 5 pounds, it is 7 kilograms—more like 15 pounds. And many people gain 20, 30, or more pounds.

There’s more. The Multiple Risk Factor Intervention Trial (MRFIT) studied lifestyle interventions including diet, exercise, and smoking cessation to prevent the onset of diabetes. To the surprise of the researchers, those who succeeded in smoking cessation developed diabetes at a higher rate (11.5%) than the control group (10.8%) that received no lifestyle advice. Absolute risk for cardiovascular death is much higher in people with diabetes. In the same study, it was found that more quitters (35%) developed hypertension than non-quitters (27%). The authors observed, “Weight gain after smoking cessation and the use of antihypertensive drugs may have counterbalanced the beneficial effect of the lifestyle intervention for the special intervention group smokers, while the lifestyle intervention was beneficial among nonsmokers.”

Nicotine replacement can postpone the weight gain. But currently available products are designed to provide low levels of nicotine and users are directed to decrease their use to zero. Once the user is weaned totally off nicotine, weight gain commences. Researchers at Harvard University found that ex-smokers who replaced higher proportions of their pre-cessation nicotine levels with nicotine gum gained less weight. It seems likely that full replacement of pre-cessation nicotine levels would prevent weight gain altogether. More importantly, permanent full replacement of pre-cessation nicotine levels prevents relapse to smoking.

Nicotine is not a carcinogen. Nicotine is not proven to cause heart attacks and strokes. Nicotine does not cause lung disease. Smoking can cause all of these, and it is the SMOKE--the product of combustion of the tobacco and paper, along with the thousands of additional carcinogens and toxins--that is the culprit.

The smoker you love may not be able to function without adequate levels of nicotine. And yet the attitude of the health organizations, anti-smoking groups, and even the FDA seems to be, “you should just quit or die.”

Electronic Cigarettes in the Military

The military should take a serious look at the electronic cigarette as a way of solving several problems. The military is reluctant to ban smoking because it helps troops remain alert and helps relieve stress. But it isn't the smoke that does it, it's the nicotine.

Tobacco smoking is an effective, but dangerous, way of getting sufficient nicotine. Currently available "nicotine replacement" products contain low levels of nicotine, by design, because the goal is to wean people totally off nicotine. With the e-cigarette, the user can control the amount of nicotine and take in enough to remain alert and relieve stress.

E-cigarettes deliver vaporized nicotine, without the tar, carbon monoxide, heavy metals, and multitude of toxins and carcinogens that tobacco smoke inflicts on its users. Over 13,000 people have signed the Electronic Cigarette Petition (http://www.thepetitionsite.com/1/kee...ttes-available). Users are reporting that they have been able to successfully substitute the e-cigarette for their tobacco cigarettes after trying every other method of quitting. They are also reporting greatly improved lung function and better blood pressure and cholesterol numbers.

There is every reason to expect that military personnel would see the same type of health improvements after switching to e-cigarettes, thus saving both the military and the VA substantial expenditures on tobacco-related illnesses.Since e-cigarettes deliver no side-stream smoke, and the exhaled vapor is non-toxic, there is no need to have people leave their work-station for "smoke breaks". Thus the military gains productivity improvements. E-cigarettes are battery operated, so there are no sparks and no fire hazard. One final benefit is that there will be fewer unsightly cigarette butts to deal with.

Failure to Communicate

When the FDA says "smoking cessation," what they really mean is "nicotine cessation." Simply ceasing to smoke isn’t good enough for them. And when the FDA says "Nicotine Replacement Therapy," what they really mean is "Nicotine Weaning." The FDA-approved NRT products supply levels of nicotine well below what smokers get from smoking tobacco. This is by design. The FDA and misguided health policy-makers are concerned that people will continue using the NRT products after they have stopped smoking. They call this "abuse potential."

The term "abuse" as applied to nicotine is misleading. The public has been brainwashed into believing that smokers light up to "get high." Addictive drugs that people actually do use for the purpose of getting high, such as alcohol, heroin, etc. impair the user's ability to think, reason, and remember. That's why they call it, "DWI," for Driving While Impaired.

Nicotine does the opposite. Nicotine enhances alertness, visual memory, and the ability to concentrate. People who don't need any help in this area have little trouble giving up smoking. People who have problems with attention deficits, memory lapses, and who have mood disorders can become dependent on nicotine to be able to function like "normal" people. "Dependent on" is a more accurate term than "addicted to."

For those who are dependent on it, trying to function without nicotine can cause cognitive impairment as serious as the impairment caused by using alcohol or street-drugs for recreational purposes. People don't get arrested for driving while smoking. But smokers who are trying to "be good" and reduce or stop using tobacco can become impaired enough to cause accidents. And this can happen, even when they are using FDA-approved NRT products, because those products just don't provide a "therapeutic dose."

Would we really want the U.S. President to be making decisions about whether to push the red button while he is trying to fight the effects of nicotine-deprivation?

Theoretically, these impairments are temporary. They call them "withdrawal symptoms" because they are supposed to disappear once the drug has cleared out of the users system. But for millions of nicotine-dependent people, the impairments appear to be permanent.

Electronic cigarettes provide a cleaner and--dare I say it?--healthier way for users to take in sufficient nicotine to remain unimpaired. Electronic cigarettes provide this nicotine without subjecting users, as well as the people around them, to the debilitating effects of tobacco smoke.

Former smokers who have managed to switch over to electronic cigarettes are concerned. If the FDA is allowed to “regulate” electronic cigarettes as a drug-delivery device, it appears likely that FDA will do one of two things: Keep electronic cigarettes off the market permanently, or reduce the nicotine content to such a low degree that they will be just as ineffective as the current "approved" products.

Common Sense

American Lung Association, American Cancer Society Cancer Action Network, American Heart Association, Campaign for Tobacco-Free Kids, and FDA: How about a common sense approach?

• Given what you know about the health effects of tobacco smoking, what are the odds that electronic cigarettes could be more dangerous? Or even as dangerous? Slim to none.
• Given the fact that the "carcinogens" that the FDA found in the e-cigarette cartridges are also found in the nicotine patch, gum, and lozenges, and these products have not proved to be more cancer-causing than smoking cigarettes, what are the odds that using e-cigarettes will cause more cancer than tobacco smoking? Fairly miniscule.
  
• Given the fact that users have reported that their desire to smoke tobacco is going away when they use an electronic cigarette, what are the odds that e-cigarettes will be taken up in droves by non-smokers and lead to smoking tobacco? Pretty darn slim.
• Given that nicotine gum and lozenges can be purchased at stores and over the internet in flavors such as mint, cinnamon, and cherry, and this has NOT attracted the attention of non-smoking children, what are the odds that non-smoking children will come running to inhale nicotine vapor just because it comes in flavors? Again, just not very darn likely.

So how about these ideas? They will help assuage a few of your fears, while keeping these life-saving products available.

1. Handle safety on a case-by-case basis, the same way that the safety of food is handled. If a problem emerges with contamination of a particular product, either the FDA or the Consumer Product Safety Commission can implement their tried-and-true product recall process for that particular batch.
2. Apply the same proof of age requirements for selling e-cigarettes as is required for selling nicotine gum and lozenges.
3. As for effectiveness, how about applying the principle of "buyer beware"? If the product doesn't work as expected, consumers can demand a refund and complain loudly, so others are not fooled.

If we do it your way, and pull the product off the market while long and costly research is conducted, thousands of people who now use an electronic cigarette may start smoking tobacco again. And please do not forget the 40+ million current tobacco smokers who might switch to these products if they stay available.

If your goal is to make sure that the rates of lung disease, cardiovascular disease, and cancer and deaths do NOT go down, then your way is best.

No Brainer

A Face Book poll called "The Smokeless Cigarette" has been created.


The question reads:

An artificial cigarette is invented that produces no first- or second-hand smoke; and 10000+ smokers try it, stop using tobacco, and stop wheezing and coughing. Should the invention be PULLED OFF THE MARKET until it can be proven safe and effective?

NO
YES

When put in this way, it sounds insane, doesn't it? It is utterly astonishing that the the American Lung Association joined with the Cancer Society, Heart Assn, and Campaign for Tobacco-Free Kids to prevail on the FDA to take electronic cigarettes off the market!

No doubt, they mean well, but they will cause untold harm if they get their way.

They say that electronic cigarettes have not been proven safe and effective. Well, more than 12,000 people have signed a petition asking the FDA to keep these available. Read some of the comments. You will see story after story. People are able to substitute inhaling vaporized nicotine from an electronic cigarette for some or all of their tobacco cigarettes. Many are reporting improved health. Even their doctors agree! You can see the petition and the signatures at http://www.thepetitionsite.com/1/kee...ttes-available,

So the users say that they ARE effective. Who would know better? As for safe, unless the CDC, FDA, AMA, ALA, ACS, AHA, etc, have been telling us big fat whoppers all these years about the dangers of tobacco smoking, just about ANYTHING would be safer to be using instead, no?

There are still 40+ million American smokers, many of whom would give up tobacco in an eye-blink if they knew that there is something out there that will allow them to do so without giving up being a productive, functioning, happy human being.

Safe and Effective

Why in the world are people – educated people, medical doctors for goodness sake—so up in arms about a product that tens of thousands of people are saying has enabled them to refrain from smoking what amounts to millions—perhaps billions—of tobacco cigarettes?

Several health and anti-smoking groups, including the American Lung Association, American Cancer Society Cancer Action Network, American Heart Association, and Campaign for Tobacco-Free Kids have brought pressure on the FDA to remove electronic cigarettes from the market. "No studies have been done on e-cigarettes to date regarding their health effects or their effectiveness as cessation aids," reads one sentence from their March 2009 joint statement.

Many, many studies have been done regarding the harmful effects of inhaling tobacco smoke. If those effects are as bad as the studies claim, it is hard to imagine anything more harmful. And, unless the government and all these health organizations have been grossly exaggerating the harm done by smoking, it is hard to fathom why they would not be jumping up and down with joy at anything that enables people to stop smoking.

E-cigarettes haven't been proven safe? How do you prove something is safe? You can't. All you can do is observe whether any harm occurs when people use that something. The FDA approved Chantix (varenicline) as a safe and effective treatment for smoking after short term use (12 weeks) by carefully-selected subjects in clinical trials. Folks with cardiovascular disease, high blood pressure, and history of cancer were disqualified from participation. But aren't these exactly the people who might be most motivated to seek help to quit smoking? Unfortunately, the trials also did not include anyone with a history of psychological problems such as depression and panic disorder.

However, after the drug became available and used by the general public, reports of extremely serious adverse effects started coming in, including potentially lethal heart rhythm problems, depression, aggression, and suicide. You don't get more serious than "death" as an adverse side effect. http://www.ismp.org/newsletters/acutecare/articles/20090507.asp

The FDA announced on 7/22/2009 that they had found "carcinogens and toxic chemicals such as diethylene glycol" in electronic cigarettes. www.fda.gov/downloads/Drugs/ScienceResearch/UCM173250.pdf


The FDA failed to mention that the same "carcinogens" (nitrosamines) are found in the FDA-approved nicotine replacement therapy (NRT) products such as the patch, gum, lozenges, and inhalers. http://tobaccoanalysis.blogspot.com/2009/07/tobacco-specific-carcinogens-found-in.html

The electronic cigarette has been in use by the general public for several years in Europe and almost two years in the U.S. So far there have been no reports of suicide, depression, aggression, or death caused by them. And despite the FDA finding 1% diethylene glycol (DEG) in one of the 18 cartridges, there have been no reports of antifreeze poisoning by e-cigarette users.

So why are the health groups screaming for e-cigarettes to be pulled from the market, but keeping totally silent about Chantix and FDA-approved NRT products?

Largely in response to pressure by such groups, the FDA wants e-cigarette sellers to file a New Drug Application and conduct clinical trials such to prove they are safe and effective as a "smoking cessation" product. The problem is that the manufacturers and retailers do not view this as a medical product.

At first many people purchased them to be used as advertised. E-cigarettes allow the user to obtain sufficient nicotine to remain alert, relaxed, and able to concentrate at times and places where smoking tobacco is not permitted. It didn't take people long to figure out that if this product could satisfy their requirements at those times and places, why not all times and places? So some users consciously tried and succeeded to stop smoking tobacco. But surprisingly, some other users reported that they had no intention of quitting tobacco, but found themselves less and less interested in smoking the other (harmful) type of cigarette.

It is easy to understand why some retailers decided to capitalize on this effect and began mentioning that their product can help people stop smoking. So, ironically, because e-cigarettes (according to users) are effective at extinguishing the desire to smoke tobacco, they have captured the annoyed attention of the government.

Electronic cigarettes are unquestionably safer than tobacco cigarettes, and may be significantly safer than some products that have smoking cessation as their goal. If by "effective" we mean that a product meets one's needs, users say that electronic cigarettes are effective.