On developing a drug to help mice quit smoking (maybe people too)

New research is being reported out of the Scripps Research Institute on how nicotine works in the brain of mice. We’ll assume for the sake of argument that this parallels how it works in humans.

In the ScienceDaily report we read:

Scientists from the Florida campus of The Scripps Research Institute have identified a pathway in the brain that regulates an individual’s vulnerability to the addictive properties of nicotine. The findings suggest a new target for anti-smoking therapies.

and

The scientists then worked out the biochemical mechanisms through which α5* nAChRs operate in the medial habenula to control the addictive properties of nicotine. They found that α5* nAChRs regulate just how responsive the habenula is to nicotine, and that the habenula is involved in some of the negative responses to nicotine consumption. So when α5* nAChRs do not function properly, the habenula is less responsive to nicotine and much more of the drug can be consumed without negative feedback from the brain.

The scientists are optimistic that their findings may one day lead to help for smokers who want to kick the habit. Based on the new findings, the Scripps Florida scientists have started a new program of research in collaboration with scientists at the University of Pennsylvania to develop new drugs to boost α5* nAChR signaling and decrease the addictive properties of nicotine.

Or let’s take a look at that same story in CBS, one of the minor reporting dialects common elsewhere on the web:

They hope to find a drug that will help smokers attack the addiction in an entirely new way. They are hoping to find a way to make smokers have a bad reaction to a cigarette and be slightly disgusted by it. They are hoping the drug will take all of the pleasure out of smoking, and thus, stop the urge to smoke.

The National Institute of drug abuse gave Scripps an 8 point 2 million dollar grant to develop drugs to literally kill the nicotine buzz.

Scientists say when someone first starts smoking, there is a natural nasty feeling that goes away as people smoke more often.

The grant gives scientists five years to develop drugs and Scripps is confident they will be able to develop a handful of pills that will finally get people to quit.

Now, that’s some fine writing!

But it did convey the little item about the substantial multimillion dollar grant to develop another smoking cessation tool. In a forthcoming post I’m going to address the point of how useful yet another of these quit smoking approaches might be given that we now have so many many alternatives that almost entirely remove the risk associated with using nicotine. At the least, these alternatives (such as smokeless tobacco or electronic cigarettes) reduce the health risks to the degree that in the long run there is little to distinguish use from abstention. But in the meanwhile….

The first question I have about this research is whether the currently dominant view of nicotine as a scourge is skewing the interpretation of their findings. How do we not know that this so called malfunction might in fact be a useful adaptation? If someone’s brain functions better on nicotine then wouldn’t it make sense that there would a compensating mechanism of allowing in the very thing that improves function?

There is just a hint at appreciating this with the absurdly obvious observation from one of the scientists involved in followup research:

“It has beneficial effects on anxiety and attention, among other things, thus making quitting very difficult”.

In other words, we have to work exceptionally hard to create just the right intervention to help you successfully wean yourself from something that is actually making your life better.

People use and quit drugs for many reasons. There are people who feel they need to quit caffiene. Not because they are suffering in any way but they don’t like the feeling of being in thrall to the drug. Though the occasional article surfaces about the potential negative effects of caffeine use few people end up thinking it is all that bad for you. But there are and always will be people obsessed with quitting it. And no matter how safe nicotine delivery becomes, and if you get away from smoking it, it is right in that caffeine ballpark right now, there will always be people obsessed with quitting it as well.

Now, the question is this. What would you think if NIDA granted a company 9 million dollars to develop a pill that you could take to make your morning cup of coffee cause you to chunder?

-Paul L. Bergen

The Elephant in the Living Room?

(When we were recently cc’d on this letter by Elaine Keller from CASAA.org, we thought it would make a great guest posting, and so we asked her, and, as you can see, she agreed.)

Dr. Michael Siegel of Boston University School of Public Health was interviewed on VP Live Sunday, January 16th.

It was a great interview and I have no disagreement with anything the good Dr. had to say. But I am bothered by what was left unsaid. Dr. Siegel is excited about the possibility that e-cigarettes might work well as a traditional “smoking cessation” treatment; that is, temporary nicotine reduction therapy followed by full nicotine abstinence. That’s all well and good for those who can do so, but….

Everyone seems to be ignoring the elephant in the living room: nicotine as self-medication.

I smoked for 45 years and every time I quit (and I did so numerous times), I became progressively more ill. The last time I quit nicotine (around 20 years ago), I became confused, forgetful, super-fatigued, and despondent to the point of considering suicide. During the 12 weeks of treatment when I used a nicotine patch, I had progressively more bothersome symptoms as the dosage was reduced. Even on the 21 mg patch, when I stopped smoking, I felt like I had a bad case of the flu, but the full force did not hit until around 2 days after I removed the last 7 mg patch. I was as impaired as any drunk trying to drive an automobile, as my visual memory wasn’t working properly. Try making left-hand turns when you don’t remember what you saw when you glanced right. Most of my mood impairment responded to anti-depressant treatment, but not the cognitive impairments. The cognitive impairments did not abate until I resumed smoking after 6 months of nicotine abstinence. By this time, I was on the verge of losing my job.

That experience triggered a couple of decades of research on my part. I learned that nicotine mimics the effects of acetylcholine throughout the body. Thus it can create the paradoxical combination of relieving stress while increasing alertness. It accomplishes the first by relaxing the skeletal muscles. It accomplishes the second by impacting neurotransmitters in the brain. I learned that depression is a common “withdrawal symptom” but that for about 20%, that mood impairment continues well past the time that nicotine would have cleared the system. I learned that nicotine is a potent anti-depressant. I learned that nicotine and nicotinic agonists are being studied as treatments for Alzheimer’s Disease, Parkinson’s Disease, Attention Deficit Disorder, Anxiety Disorder, Mild Cognitive Impairment, Chronic Fatigue Disorder, and other conditions.

Think about this. Doesn’t it make sense that people with a shortage of acetylcholine or with an imbalance in neurotransmitters would have some of their symptoms relieved by smoking? Doesn’t it make sense that these people would have the most difficulty giving up nicotine? Why is it considered morally corrupt for people like me to want to function normally and be a productive member of society, simply because we do so by continuing to use nicotine?

Yes, there are FDA-approved medications to treat most of the conditions I mentioned. The treatments are not 100% effective. In one study I read, a psychiatrist reported that an in-patient taking several anti-depressant medications came to him and said, “I’ll stop trying to kill myself if you let me smoke.” He reported that he allowed her to do so and was amazed by the sudden improvement in her affect.

Many of the recommended treatments have nasty side effects. In fact, the FDA-approved treatments for Attention Deficit Disorder come with black box warnings that they should not be used long-term. Hmmm… short-term treatment for a long-term disability?

My mother, who died a few months ago at the age of 88, was extremely impaired both mentally and physically by Lewy Body Disease. Near the end she was constantly hallucinating and could not stand or walk. Is this the future I face? When I learned that nicotine prevents the build up of Lewy Bodies in the brain, I vowed to never stop using nicotine. As far as I know, there is no other known preventive treatment for Lewy Body Disease.

I think most of the medical community is in denial about nicotine self-medication. Some believe that all smokers will be healthier if they stop using nicotine. Some acknowledge that there might be some people who seem to benefit from using nicotine, but believe that the percentage has to be miniscule. Therefore, let’s recommend that everyone stop using nicotine. In fact, let’s force them to do so–for their own good.

If 20 years ago, 20% of smokers suffered from severe depression when they stopped using nicotine, how many of those do you think quit in the interim? I’d say very few. What do you think the percentage would be today? How about those who are not depressed, but become so forgetful and inattentive when they don’t smoke that they can’t perform their jobs? Why does there appear to be an uptick in the number of people experiencing dementia? My best guess is that at least 30 to 40% of today’s smokers are self-medicating and are not healthier when they stop using nicotine.

Let’s say, for the sake of argument, my estimates are way off. Maybe half the self-medicating smokers learned to live with (or were forced to live with) their disabilities. Maybe the people impaired by nicotine abstinence make up only 10% of smokers. That is still millions of people in the U.S. – perhaps billions of people world-wide.

I am in hope that researchers and tobacco harm reduction activists will focus some attention on this very important issue. Lives depend on it.

– Elaine Keller

Why do we forget that people smoke for a reason?

One of our constant themes on this site and in our writing is that people derive benefits from nicotine. There really is no other conceivable explanation for its popularity. In other words, some people’s lives are made better, and in some cases simply not miserable, by using nicotine. We promote tobacco harm reduction (THR) which rather than arguing that abstinence is the best and only solution for all nicotine users takes the position that smokers should have the information about the risks of smoking and alternative products, and that there should be few barriers (including financial) of switching to safer methods of obtaining nicotine. Then, with the information, smokers can decide what course benefits them most. And while we think that it makes sense to switch to electronic cigarettes or smokeless tobacco (or to go ahead and just quit), the ultimate decision rests with the smoker.

We need to accept that smokers have good reasons for smoking. Part of THR is finding alternatives that will satisfy those reasons and letting smokers (and everyone else) know about them.

Recently a couple of us were putting together a document and wanted to cite another individual or group that researches or educates about harm reduction that also takes a welfare approach to nicotine. That is, that they have expressed the idea that nicotine provides benefits to some if not many people and that saving some of those benefit is an advantage of THR compared to simply demanding abstinence. We had great difficulty in finding such a person active in THR – at least, one who was explicit in stating their welfare approach. (If you are such a person, leave a comment and get a citation in that paper).

Nicotine and smoking are usually described as having no benefits and only costs. Continued smoking is explained as driven by the avoidance of withdrawal or of simple addiction with no sense that smokers are getting anything out of their habit but avoiding pain. This is obviously not the case – just ask the next smoker you run into.

Adding welfare into the equation restores user dignity by treating them as rational and normal human beings. Just because someone happens to smoke should not define them beyond the behavior itself; it certainly does not mean that by liking nicotine they have lost all sense of reason.

Perhaps some THR people also have concerns about appearing pure and don’t wish to even give the appearance of supporting any sort of nicotine use; it is, after all, easiest to maintain credibility and avoid confrontation by sticking to the status quo at least on some of the issues (and the abstinence-is-best approach is certainly the most popular). They will promote it as restricted to those who cannot quit, and maintain that abstinence is still preferable (which is in effect saying that the benefits are worthless, that better to be abstinent and less happy is preferable to being happy with a negligible risk attached).

The thing is that as much as we might pontificate about the taste of a particular wine or a coffee or the smoothness of a cigar, at the heart of our enjoyment lies the appreciation of a drug. We use and like drugs. They make us feel better and sometimes the cost has to be awfully high for us to give them up.

Smoking has many pleasures to offer but without the nicotine it would never have caught on. And what the central question is how do we deal with a drug with such subtle yet substantial positive effects but that in its most popular form causes such great health costs.

The lazy approach is to dismiss lifelong smokers as unique exceptions to normal rational consumer behavior. That offers the easy option of leaving these deluded souls out of the discussion about how we can improve their lives for them, rather than considering that they are reasonably rational individuals like everyone else who, having weighed the costs, determined that the advantages of smoking outweigh those of quitting. That is powerful testimony about a powerful benefit, and calls for us to offer something other than the lazy simply solution.

– Paul L. Bergen