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

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Comments

  • benpal  On January 31, 2011 at 2:54 pm

    Isn’t that a good idea: take a pill to remove the positive effects of nicotine (having removed the negative ones by chewing or e-cigging instead of smoking it) and possibly replace them by negative secondary effects (Chantix).
    And then ask your doctor for a prescription of Prozac to help you suppress the anxiety and lack of attention.

  • benpal  On January 31, 2011 at 2:56 pm

    Wouldn’t that be Big Pharma’s heaven? Two or more drugs sold to replace nicotine.

  • Elaine Keller  On January 31, 2011 at 3:37 pm

    The process these scientists are looking at is called “tolerence,” where ever-increasing doses of the drug are required to continue receiving the same effect. Alcoholics who develp a very high tolerance can drink most normal people “under the table” as the saying goes before they become “drunk.”

    One thing that nicotine researchers who have been around the block a few times have noticed is that nicotine tolerance tends to be self-limiting. Prior to the 1980s most smokers worked their way up to a pack a day — and stayed there for life. The only reason that average intake rose after the 1980s is because the Surgeon General recommended that smokers who can’t quit switch to “reduced tar and nicotine” cigarettes. The unanticipated consequence was that smokers–without being aware of what they were doing–began smoking more to compensate for the reduced amount of nicotine.

    Given what these older researchers found, my guess would be that the number of human smokers who “can’t get enough” makes up a mighty tiny proportion of all smokers. Once again, the scientists latch onto a false idea about the cause of habitual smoking and seek a treatment that may do much more harm than good for many smokers–a la Chantix.

  • Michael J. McFadden  On February 1, 2011 at 2:56 am

    Paul, you wrote, “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?

    One of the strong reservations I have about this whole area of research is that by fiddling around with various “enjoyment centers” in the brain to ensure that our children don’t become alcholics, crack addicts, or tobacco smokers, we may end up creating a generation that simply has an increased “tendency” that may not be recognized for 50 years or more to commit suicide, give up sex in middle age and end up divorcing and living out their lives in loneliness, not being motivated to seek higher levels of achievement, or any and all sorts of obscure elements of change that will impinge negatively on our quality of life and perhaps even be passed onward toward future generations.

    I believe very little research has been done on this sort of question and I believe it would be very difficult to do. We’re stomping around in very dangerous and unknown territory for the sake of relatively small gains.

    Michael J. McFadden
    Author of “Dissecting Antismokers’ Brains”

    • Paul  On February 1, 2011 at 10:41 am

      From Aldous Huxley’s Brave New World:

      “And if ever, by some unlucky chance, anything unpleasant should somehow happen, why, there’s always soma to give you a holiday from the facts. And there’s always soma to calm your anger, to reconcile you to your enemies, to make you patient and long-suffering. In the past you could only accomplish these things by making a great effort and after years of hard moral training. Now, you swallow two or three half-gramme tablets, and there you are. Anybody can be virtuous now. You can carry at least half your morality about in a bottle.”

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