Sunday, March 14, 2010

Cigarettes and cognition

I was just visiting Mauigirl's blog; she's been struggling with the declining health of her aging mom. Between a hospital stay followed by a move to a nursing home, MG's mom has been one month without a cigarette. MG notes that research suggests that nicotine has favorable effects on cognition and wonders if the notable change she's seen in her mom's mental functioning might be, in part, due to the lack of nicotine. I've often told my patients that people like to smoke for good reason, that, in fact, cigarettes are not only calming but wonderful for concentration and focus.





Cigarettes--or rather the nicotine within--may be neuroprotective. While I'm all in favor of saving the brain, I won't be prescribing cigarettes to anyone wishing to keep their marbles. But there's interesting evidence suggesting that nicotine is not without its benefits to brain.

Scientists have noted that persons who smoke have lower rates of neurodegenerative diseases such as Parkinson's and Alzheimer's. Korean rats were encouraged to smoke via an automatic smoking machine. After four weeks of 'automatic smoking' for ten minutes per day, the rodents were significantly protected against the seizure-inducing effects kainic acid. Apparently, if you want to dip your head in kainic acid (whatever that is), you might consider smoking too.

Kainic acid exposure aside, researchers have other theories why nicotine is good for the brain. The brain is full of nicotinic acetylcholine receptors; activation of these cellular switches has a number of beneficial actions. This effect of nicotine has been compared to "turning up the volume of a radio signal." As acetylcholinergic brain cells are in charge of memory and executive functioning--i.e. planning and carrying out complex tasks--turning up the volume is a good thing. No wonder people enjoy the clarity and focus of a Marlboro.

Neuroscientists at the University of Florida have discovered still another mechanism as to why nicotine might promote brain health. They found that nicotine prevents overactivation of little neuron-supporting cells called microglia. When the microglia get all hot and bothered with overactivation, they can set off events toxic to their neuronal buddies unto death. Well who wants that? Check out what Florida's Dr. Douglas Shytle has to say about that:

Microglia can be your best friend or your worst enemy depending on the signals they receive. The analogy is that you keep talking to them they will take care of you, but if you stop talking they are more likely to get aggressive and have a toxic effect on the brain.

If all this makes you want to take up smoking again, hang on. The Southern investigators realize that they must "now develop drugs that mimic the beneficial action of nicotine without its unwanted side effects."

11 comments:

Ruth said...

hmmm...I think I will print this for rounds next week. My smoking patients cough, are short of breath, have intermittent claudication, but may be cognitively sound. What about the microvascular effects of smoking? I would think long time smokers would have an increased risk of vascular dementia. Interesting post.

Mauigirl said...

Thanks so much for this post - and the linkage! I believe Ruth is right about the increased risk of vascular dementia, but per your post, finding a drug that mimics the beneficial effects of nicotine without the bad stuff would be a perfect solution. I am tempted to try my mom on the nicotine patch when she gets home and see whether it helps.

Anonymous said...

the old saying was people would go mad once they stopped smoking, nicotine.
The microglia are being studied and thought to be the part of the brain that explains 'psychic' phenomena, and of course they only relate it to children as a means for them to 'communicate' and read the cues of their care givers.
It is increasingly frightening to me to hear about big pharma coming out with drugs that they think might replace nicotine effects, what a legal high and huge money maker that would be, of course,.......they havent even managed to treat depression or anything else well..........unless you count suppression as treatment.
Which it apparently is.
I truly dont understand drug pushers of any kind. What does one have to deny to believe in chemicals .I seriously dont 'get it'.
It is like listening to people say CT scans wont hurt you, or radioactive iodine wont hurt you.... what does it take to believe these things? Brainwashed.

justhinkin said...

I think if you look up the side effects of nicotine (NOT "smoking") you would find that they are about as few and as mild as just about any "OTC" medication, and likely much less than virtually all prescription ones.

Rather than trying to dodge nicotine side effects (and because of the way it works, I see little hope of that), I suspect that what is being sought is a patented medication that might be "as good as" nicotine ... that can be prescribed, at $5/per piece. THERE's the rub. No profit in nicotine, aside from RJR and PM.

I have done a lot of research in this matter and wish I had time to write at length.

Let me just state without lengthy explanation (ok, this looks lengthy, this ain't the 1/100th of it) that nicotine itself is not all that highly "addictive" as was long supposed (but experiments failed to confirm). It turns out that what is relatively addictive is the combination of nicotine with naturally occurring MAO inhibitors in tobacco (and in the smoke, as well as in oral preparations of whole cured tobacco).

A small company called Star Scientific that makes a dissolvable oral tobacco product that is also almost completely devoid of the only really harmful component in oral tobacco, "tobacco specific nitrosamines" (TSNA) is in the process of introducing, within a month or two, a dietary supplement ("nutraceutical") that contains no nicotine but does contain these compounds, the MAO inhibitors. It will be called "CigRx", and will be marketed as a smoking cessation aid (alone or combined with standard NRT products). It may also have MANY "off label" uses.

Trying to spit this out (no pun, but not bad) as fast as possible for "mauigirl". ONE of the off label uses may be to treat Alzheimer's. Let me point you to a press release, which is all we know about it right now, from April 7, 2010.

http://finance.yahoo.com/news/Star-Scientific-Announces-prnews-625345715.html?x=0&.v=2

Note that the "Roskamp Institute" is a highly respected research outfit in FL. The two lead researchers, Michael Mullan, MD, PhD and Fiona Crawford, PhD, are apparently the folks who discovered the crucial role that beta amyloid plays in Alz. in the '90s.

Leaping ahead, no time right now, here's the thing. The good news is that the research is getting under way. The bad news is that for folks with immediate need it will likely be too late. HOWEVER, consider this. The oral preparations Ariva and Stonewall from this company contain BOTH nicotine AND these compounds. Thus Ariva/Stonewall may be the best substitute for the compounds under investigation, since nicotine too is believed to help most Alz patients.

(Interestingly, Star does hold patents on using these compounds to treat disease.)

Now, it may be that the new CigRx product contains a higher concentration per tablet of the MAO inhibitors (synthetically derived) than Ariva/Stonewall. However, for now I'm afraid it's the latter to try or nothing. The patient would have to have the ability to hold a tablet about the size of an aspirin between cheek and lower gum on the side and let it dissolve.

Dosage? Who knows? However, the products are "cancer safe", I will say without time to prove (the Swedish snus experience shows this ... the Star products have an order of magnitude, or greater, reduction in TSNA than snus, and snus is "safe". The Star products are the safest known tobacco products in the world. Main risk is gum irritation with heavy use.).

(continued)

justhinkin said...

(continued)

Stonewall "snuff" is the same as Ariva but 3 times more potent (thus cheaper). Ariva tablets have about 1.5 mg of nicotine. Stonewall about 4. As to potency of the MAOIs, I can't say, but if you're going to try nicotine anyway, there's some in there and it can't hurt to have that extra possibility.

These products are also the most effective (tests show) quit smoking aids, because of the safety and the MAOIs with the nicotine (unlike NRTs) plus a more favorable blood nicotine profile than NRTs. For example,

http://www.informaworld.com/smpp/content~content=a787696595~db=all~jumptype=rss

Most intriguing about the new CigRx product, keeping in mind that this is in vitro testing (test tube), is the statement about, "Also, the compound appears to encourage new neuronal cell growth." If that were to translate into in vivo human result, well, aside from the Alz patient, who among us over 40 would turn THAT down???

It is just a hope right now, re Alz (only the nicotine is guaranteed to any extent) ... but may be worth a try, especially if the patient is used to the benefits of nicotine already.

Anecdotally, I know of at least two persons who were long-time smokers, quit, and developed dementia within 5 years. If only I knew then what I know now.

Full disclosure: I know a lot about this because I have been following the story of, and investing in, Star Scientific since 1998. If they hadn't gotten sidetracked by an infringement suit lodged against RJR tobacco in 2001, this might have all happened 7 years ago. If there is interest, I may try to elaborate here if I can later on. this is an extremely complex matter.

Oh, availability of Stonewall & Ariva.

http://www.dissolvabletobacco.com/

leads to sites that sell online ... BUT due to the recently signed law, ONLINE SALES END JUNE 30.

HERE is the site that is cheapest that I found:

http://www.genuinetobacco.com/smokelesstobacco.asp#Ariva

Ariva is near the top and Stonewall near the bottom. They are the same price , $11.94 for 100 pieces. Stonewall is the more cost effective, thus, but you may want to get one (or more) of each in case size is a problem ... I think Ariva is smaller. I hear reports that they ship quickly ... I hope so. Wintergreen is pleasantly cool to the taste. There is a distinctive tobacco "bite" to those unaccustomed ... it is powdered tobacco.

After June 30, or before, try Rite Aid, Walgreens, and CVS, but likely more expensive. You may have to ask them to look on their inventory to find it ... not a big seller at present (no advertising).

I hate to recommend a "tobacco product" to anyone, and just say, "trust me, it's safe". This will all come out soon, I hope (if the scientists in the health field can ever be convinced to "come clean" about the safety of low TSNA oral tobacco).

When the actual CigRx product comes out, it will be test marketed in VA first. I will try to come back here and report that. Perhaps mauigirl knows someone there who could mail some.

Gotta go ....

(BTW, guess you could call me "bigislandguy" in same sense as mauigirl.)

justhinkin said...

As I stated in earlier posts re nicotine and MAOIs in tobacco, this is an extremely complex matter, and I am trying to selectively post the material most relevant to the current "thread". I have a few additional bits of information to add, if I may.

As an afterthought to what I posted earlier today, perhaps I should explain the paragraph, "Anecdotally, I know of at least two persons who were long-time smokers, quit, and developed dementia within 5 years. If only I knew then what I know now."

I meant that I may have suggested to them that they try a harmless source of nicotine, or of it together with the MAOIs, as in Ariva/Stonewall, at the first sign of dementia. One possibility, it seems to me, is that among committed users of tobacco may be those who are compelled to seek it by some tendency that may presage later dementia onset.

Though I commented on the relative lack of hazard to use of the products regarding any serious consequence, I recognize that is of general application and was said for completeness. Obviously, for the Alzheimer's patent at this point, that is of little concern.

I will also add this caution. A recent "contrarian" rat study pruports to indicate that nicotine may actually make the Alzheimer's situation worse (in rats, at least). An article about it also makes negative statements about the whole tie-in between nicotine and improvement in Alzheimer's. As with everything controversial, there are two or more sides, and usually each one has a vested interest.

http://www.bluelight.ru/vb/showthread.php?t=499639

HOWEVER, I will also point out that perhaps the problem with all the studies is that they are experimenting with nicotine ONLY, not the combination of nicotine and the MAOIs found in tobacco (such as Ariva/Stonewall). Again, perhaps this combination is so "addictive" relative to nicotine alone precisely because nicotine alone does not do for the brain what the combination does, or does it only a little.

As a scientist myself, I have seen over the years that scientists have a tendency (as do beginning students in a lab) to be able to, due to unknown or unstated means or motivation, to produce lab results that agree with their preconceptions of the expected outcome. In a controversial field like this one at present, it will continue to be difficult to know exactly whom to believe.

I hope I have not taken up too much of your space without good reason.

femail doc said...

Justthinkin: Thank you for all your helpful info. I went around with another reader awhile ago about Ariva, got my son a package of it, and he tried it without either of us ever checking out the 'how to' of it all. As you may guess, if sucked, this product causes awful spasms of the esophagus. Your lengthy (and much appreciated) discourse encourages me to encourage him to try it again. Stop by anytime with more info!

Justhinkin said...

Wow ... someone just found this (old material) and posted about it in the company's (CIGX) yahoo finance message board, and that reminded me it was on my list to come back with more information. Here is some, if it is still of interest.

SOOOO MUCH has happened RE this and I wish I had time to detail more than below. So much pressure.

The product that I mentioned IS out ... since last August. It is presently available online only ... but to anyone ... at CigRx.com. There is strong rumor that it will begin national retail rollout very soon.

It HAS been announced recently that the compound in CigRx, almost 100% anatabine, IS INDEED the "mystery compound" RCP-006 being tested by Roskamp for efficacy in Alzheimer's, as I had surmised a year ago. Trials are underway studying that.

In addition, it has been recently announced that they, Roskamp, have also discovered that anatabine is likely a new "overall" anti-inflammatory (as they experiment and do trials, they are discovering new things about this "hidden little gem" of a chemical).

What I believe is unique about it is that it appears to me that it is not an NSAID (different pathway) and it is not, of course, a steroid. As far as I know, it's only major side effect is that it is also an antidepressant (being an MAOI [but without the food interaction problem ... self-limiting]). I can attest to that effect as of recent experience. I can also attest to apparent, and surprising, anti-inflammartory effects ... being 67 years old : ) what a boon that would be, it seems: an anti-inflammatory with no major negative side effects.

No one knows for sure about the Alzheimer's efficacy (and Parkinson's and a host of other brain maladies) yet, but I think they are virtually certain about the overall anti-inflammatory effect. Human trials have just started, to test it in 200 subjects ("the Flint Study"), testing for c-reactive protein effect, and that will be complete late this summer. We will see.

I think I know the outcome from (again) my own recent experience.

By the way, I have reason to now believe that tobacco, even "safe" Star products, is not a good way to get these effects from anatabine. Some folks are going to be very surprised to see this here ... first. I will detail why later, but definitely the product CigRx, for off label use (it is, again, an OTC dietary supplement), is THE way to test the benefits of this substance, and I now believe that it will work to best effect only without concomitant nicotine use (for, say, at least 8 or more hours ... no nicotine use). The doc will likely quickly guess why I think this now.

Finally, my own experience is that there seems to be virtually or literally NO tendency for dependence in me (unlike it's close cousin nicotine). However that may be of notice in some. On the other hand, if it is of long term benefit, that is a + : )

(continued, due to length)

Justhinkin said...

(continued)

You can read more about this whole matter, if you are a yahoo member, in the racuous and messy finance board for the company, by going to yahoo and getting a "quote" for the company, CIGX, and then choosing the link "Message Boards".

You can get filtered and archived information in a private, managed group at

http://finance.groups.yahoo.com/group/stsivipgroup/

Again, yahoo membership is required. STSI used to the the co's ticker. That's where I do most of my writing.

I thank you for this forum. It is so seldom that one can speak directly to the people "on the front lines" who are both interested and "have a need to know". What a pleasant experience. In return, you MAY be among the first to know of an amazing discovery that will help many many people. We don't know for sure yet, but we'll see, and sooner than one would normally think, because of the unusual fact that this is not a "(new) drug", but a natural plant substance.

Oh, yes, re using the tobacco products, it is a pity you have to be a tobacco "insider" to know that you use the dissolvables just like "snuff" ... between cheek and gum. Ahhhh ... and that IS the best way to dissolve the CIgRx anatabine product, too ... for efficacy and, yes, a much lower but still apparent tendency for the upper digestive tract spasms (tummy rumble, etc.), but it is MUCH more effective if used that way. Then, when dissolved (20 minutes or so), take a bite to eat.

My best to you, and to everyone who benefits from your generous gift of your time and this forum!

Justhinkin said...

Correction and Addendum to Previous 3/18/2011 posts re anatabine.

In my haste "above", my keenness for accuracy waned.

Correction:

Because "NSAID" stands for non steroid anti-inflammatory drug, then all anti-inflammatory drugs, AIs, are divided up into NSAIDs and steroids ... so if anatabine/CigRx turns out to be an AI, it will indeed be an NSAID, as it is not "a steroid" (I think I said it was not an NSAID previously).

I should have said that it will just, I presume, be different from most of the NSAIDs we are familiar with, and perhaps a new kind of NSAID altogether. Most of the NSAIDs are apparently acidic derivatives, and they, most, work because they are "COX" inhibitors (their "pathway" of effect, as I gather). I have seen no hint so far that the alkaloid (not acidic) anatabine is a COX inhibitor ... or that it shares the negative side effects that that fact/pathway carries with it.

I see no hint of notation, on the CigRx bottle/package, of interaction with other drugs. That may not mean it's not possible. Anatabine is an MAO inhibitor, yet it (and its cousins in tobacco) seems to be unique, and less or not troublesome, because its action is self-limiting (called "asymptotic" for the shape of the curve plotting MAO inhibition versus dose).

I am also not sure about the method of metabolism (this is, I am sure, known, but I just am out of time for research right now), meaning what organs (usually liver or kidney) are responsible for processing and eliminating it from the body. Sometimes persons with compromised liver, kidney, or other organ functions cannot process "drugs" at a rate so as to eliminate them "normally" ... and they become problematic. These are concerns ... yet people apparently by the millions have consumed up to 40 or more "doses" of anatabine, from cigarettes or oral tobacco, for decades with little or no problem. However, caution is to be practiced when "experimenting". Any new "problem" should automatically be assumed to be the new addition until proven not so.

(continued due to length)

Justhinkin said...

(Continued)

Addendum:

As to trying it for any kind of "therapy" (for instance, as a last resort in Alzheimer's), and the question of dosing considerations ... who knows? Star does say that each tablet contains approximately the anatabine in a cigarette (or one of their Ariva tobacco tablets).

However, if you are not a nicotine user, or have not had nicotine for say 6-8 hours or more, then the anatabine, I believe, will be much more effective than it is when derived from tobacco (along with nicotine ... and the other minor alkaloids). That has to do, I believe, with competition for the same "receptors" in the body by the two, and, in tobacco, the ratio of nicotine to anatabine is something like 30 to one ... so my guess is that when taken together as "tobacco", and especially when continuously "reinforced" with more of the same, the effects of poor anatabine are mostly washed out.

I certainly felt efficacy as an antidepressant with one tablet per day when I started. I am very sensitive to antidepressants, and the effect, in fact, was a little strong (but not likely so for most) ... "controlling" for those familiar with antidepressants at therapeutic doses. Then, over a few days, my tolerance seemed to permit two to three per day. (That pattern is typical, I believe, for dosing antidepressants.) Others may need to start with that level, it's just hard to say. Medicine is an individual experience, and I feel sure that is part of why a doctor's work is called "practice" : )

For any possible effect in Alzheimer's, as the outcome without any hoped-for good effect is not in doubt, trying hefty doses (10-15 per day ... or more) may not be out of the question ... but should probably at least be "passed by" the doctor, or he/she made aware. There has been mention that anatabine may act as an appetite suppressant, and so that is something to watch for as I suspect keeping up weight can be problematic for Alzheimer's patients, but I (a lifetime dieter) see little if any such effect ... or it is canceled because of improved mood. Star has trademarked "ThinRx" to release it later as a diet aid. Imagine ... a product that tends to both let one cut down on smoking AND lose weight (on label use)!

For "on label" use (reducing smoking or otherwise), willingness seems to play a big part. This drug won't knock the cigarette out of your hand. One might think that possibly a placebo effect, but I think not. I think this effect of anatabine, and probably the other minor tobacco alkaloids, explains the age-old mystery of the lure of tobacco smoking ... the drugs therein, and I think these are the ones, to some extent seem to mold their effect to the user's need: stimulation, relaxation, whatever. Yes, dose is part of that effect too, but not all of it, I think.

All this is surmise, from my own thoughts and my recent try of the CigRx anatabine for effect as an antidepressant ... and the surprise effect as an anti-inflammatory I seem to feel. Biological sciences are my weakest fields, so I could be wrong on some of this. There is a lot of research beginning on this substance. I hope its promise plays out to help us more enjoy our new found (relatively) ability to grow old.

By the way, this may be the frist place some of these possibilities have been discussed publicly, and I appreciate the opportunity to do so here, if it is afforded. I do caution that I am not a doctor, and bioscience is not my trained specialty. This is a product of independent research, and my own ideas and experience.

PS: I wish I could go the the doctor in Denver : )