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Nicotine-Related Antidepressant Drugs

Don't bone it before you read it!
  (+12, -1)(+12, -1)
(+12, -1)
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This is actually an idea that I have been pondering for several years off and on, and actively researching using myself as a guinea pig, so don't think "Cancer!" and fishbone it immediately.

There are a host of antidepressant medications approved for use in adults, and I was pretty much given the party pack of them around age 14. First, they put me on Prozac®. After an unprecedented reaction to the drug, I was put on Paxil® and later Wellbutrin®, both of which I reacted badly to.

As I studied the literature surrounding these drugs, I found myself immersed in a seedy world of selective-serotonin reuptake inhibition and receptor blocking. I knew that there had to be a better way, but what?

Wellbutrin® is the one drug that I carefully studied, and noted my responses to it. The generic name is bupropion hydrochloride, also marketed under the name Zyban® as a stop-smoking® aid. Wellbutrin® didn't work so well for me, in fact, it did nasty things to my brain chemistry for a while. When my prescription lapsed I decided to try something new.

I started smoking™. I quickly found that nicotine eliminated the symptoms of depression, and I couldn't figure out why. There was that little problem with cancer, though, so I tried other means of nicotine delivery, some quite unorthodox. They all worked regardless. I have somewhere a research log in which I determined the ideal daily dose of nicotine and other chemicals, in mg/kg, for the adequate treatment of severe depression.

My proposal is to use nicotine-related organic alkaloids as a viable alternative for synthetic selective reuptake inhibitors in people who demonstrate unusual negative reactions to these drugs. In the course of my research I have talked to many people who have had reactions to currently available drugs, including one woman who had a sudden and suicidal response to Effexor but no negative response to nicotine alkaloids.

The actual use of nicotine, in a natural or synthetic form, would be treated as an absolute last resort. There exist several compounds with a reasonably close molecular structure that hold less risk for addiction. I wish I had one of those.

Apparently, I outgrew the depression or something, but now I'm addicted to nicotine™.

Oh, for those of you worried about cancer, as far as I can recall it's not the nicotine that causes the cancer, but rather other compounds present in tobacco. If I'm wrong on this point, please correct me.

Headcleaner, Jan 08 2006

Nicotine as an antidepressant in rats http://www.biopsychiatry.com/nicotine.htm
Seems to confirm the idea author's suspicion of nicotine's antidepressant properties. [jutta, Jan 08 2006]

Survey: Nicotine and Schizophrenia http://ps.psychiatr...ent/full/50/10/1346
Lots and lots of detail. "Nicotine is involved with several neurotransmitters, including glutamate, acetylcholine, serotonin, and norepinephrine, but its effects on dopamine are likely the most relevant in understanding the high use of nicotine by patients with schizophrenia." [jutta, Jan 08 2006]

All about nicotine. http://www.nida.nih...tine/nicotine3.html
Good news about heart disease: "...trials suggest that use of nicotine replacements for smoking cessation does not increase cardiovascular risk." Possible bad news about AD effects: They might be due to other MAOI-like things in cigarette smoke, so gum or the patch may not cut if. [Monkfish, Jan 08 2006]

Hoffer on the use of niacin for schizophrenia http://www.lef.org/...port_hoffer_01.html
[ldischler, Jan 08 2006]

"Antidepressant effect of transdermal nicotine patches in nonsmoking patients with major depression." http://www.ncbi.nlm...46444&dopt=Abstract
Strangely, concludes: "Because of nicotine's high risk to health, nicotine patches are not recommended for clinical use in depression" [Monkfish, Jan 08 2006]

as far as I can recall it's not the nicotine that causes the cancer, but rather other compounds present in tobacco. If I'm wrong on this point, please correct me. http://www.vitaleth...cs.org/vtlnacnx.htm
There is no question that metabolites of nicotine are carcinogenic and that nicotine itself is a cancer promoter in laboratory animals [ldischler, Jan 08 2006]

Reminyl http://www.centerwa...t/drugs/dru666.html
from 'bulbs of the daffodil'; .. it is also worth noting that Reminyl® also acts upon nicotine receptors in the brain, stimulating them … as an anti-depressant, furthermore anecdotal evidence points to Reminyl® also having a potential role in weight loss, due to its appetite suppressant affects. [reensure, Jan 08 2006]

[link]






       Nicotine is clearly a psychoactive drug, and your idea to use it (or a chemical designed for similar effect) for treatment is eminently reasonable. It is commonly noted that just about every single schizophrenic smokes. I have seen it proposed that somehow the nicotine helps them hold it together,or feel better,or whatever - but it is left at that. It is sort of like those people in the 1700s that noted that ether made you sleep and feel nopain - hmmm,weird! Fun party drug! It took decades before someone thought of using it for surgery. It may very well be that although nicotine is empirically used by the schizophrenics because it makes them do better somehow, a study of why this is true might lead to the design of a less sloppy drug which can produce the same or better effect.   

       I do not mean to imply by this that because you like nicotine you are schizphrenic, [Head]. You are right about cancer and nicotine; you can get your fix from patches, gum or the snorter and be ok. It still does increase your risk for a heart attack.
bungston, Jan 08 2006
  

       My landlord is the nicest lady you'll ever meet, she's also a schizophrenic. She is on Haloperidol for treatment of her symptoms, and she smokes. I've actually talked to her about this in part of my research.   

       Nicotine does indeed help keep schizophrenics together, for reasons unknown. This may be related pharmacology at work. Thanks for the great anno!
Headcleaner, Jan 08 2006
  

       It doesn't seem like anyone wants to touch this idea with a ten-foot pole. Or maybe I'm just caught in the time difference, living in Florida and all.
Headcleaner, Jan 08 2006
  

       I don't know. Is being addicted to nicotine worse than being depressed? I haven't had experience of either, I'm afraid. I can't comment.   

       On another note, I don't think that 'nicotine' is a trademark, so it doesn't need the little symbol (™), but it was nice of you to go to all the trouble.
dbmag9, Jan 08 2006
  

       Smoking isn't a trademark either, I simply took the ™ as humour on the author's part - its good to see this idea backed up by your own research too, Headcleaner - and from what you have said there certainly seem to be positive results.
fridge duck, Jan 08 2006
  

       Schizophrenics and nicotine? Better to use niacin (nicotinic acid, an oxidation product of nicotine) which has been used for decades as a treatment for schizophrenia. See link--Hoffer on the use of niacin for schizophrenia.
ldischler, Jan 08 2006
  

       For what it's worth, smoking (and alcohol/drug use or abuse generally, for that matter) is associated with pretty much the whole gamut of psychiatric problems, including depression -- just more strongly with more severe problems.   

       Anyway, nicotine itself (in gum or patch form) seems like the thing to start with. The actual health risks are small, and there are arguments that it's much less addictive in slow-release forms. And physical addiction itself isn't necessarily that big a deal; conventional antidepressants are "addictive" in the sense that they cause withdrawal symptoms if stopped suddenly, most people put on opioids for medical reasons withdraw with no problems, and some of the worst addiction-like problems (like pathological gambling) don't involve physical addiction.   

       It seems kind of unfortunate that people are so leery of nicotine. Doctors aren't keen on it for obvious reasons, and it has some of the same image problems as other drugs that have a history of "recreational" use. And, of course, most clinical trials (and all marketing efforts) are funded by pharma companies, who have no incentive to prove the benefits of a drug they don't own the patent for (and that will actually compete with ones they sell). It also basically a short-acting stimulant, though, and the trend is towards drugs that seem to change brain chemistry gradually and for longer (you can also treat depression with amphetamines and similar drugs, but it's usually a last resort).   

       Interesting footnote -- a lot of psychiatric hospitals (including the one I work for -- in the woolier kinds of research, I have no real idea about clinical stuff like this) are now going smoke-free, which is controversial partly for the reasons you give.
Monkfish, Jan 08 2006
  

       This was never designed to compete with anything the pharmacological companies sell, I thought it up as another possible alternative for the small segment of the population that reacts badly to other drugs.   

       Apparently, people have been thinking along these lines already (thanks for the excellent links!), especially in regard to analog(ue) drugs being developed.   

       One of the points to bear in mind when considering the addictive potential of nicotine is the simple psychological addiction. Smoking is a habit, it becomes an ingrained part of a smoker's life, and can be something a smoker turns to when problems arise. As far as I have been able to tell, this stems from the initial reaction to nicotine, which varies from person to person.   

       Big thanks to [Monkfish] for the link about nicotine patches, this shows what I'm talking about here. 2 of the 12 subjects in the trial were forced to drop out because of nausea and vomiting. This may not be a clinically significant number given the size of the sample, but we can assume it is for the simple purpose of illustration. Other responses I have noted are extreme irritability, mild euphoria, and an increased ability to concentrate.   

       If work could be done to produce a similar synthetic compound, this could indeed be patented and sold just like other antidepressant drugs.   

       Now it's time for me to read the rest of the links and eat a burrito.
Headcleaner, Jan 08 2006
  

       I like this. I used to work in a mental hospital, and the amount of smoking that went on was truly phenomenal. There are a lot of other substances that interact with nicotinic receptors that are less habit-forming though, such as lobeline. Nutrition is also important, as is eliminating xanthines, but how to get people to do this? If they're diagnosed as schizophrenic, the chances are that they're already malnourished because of the drift down effect.
nineteenthly, Jan 08 2006
  

       I have tried almost every SSRI including Venlafaxine. Am now on a Tetracyclic and liothyronine (T3) and am still experiencing hypersomnia, slow cognitive processing and heavy laden limbs. Tried placing a 7mg patch on my spinal chord yesterday, and experienced complete remission of symptoms within 5 mins. Interestingly, I tried placing a patch on my arm today with little effect. Moved it back to my spinal chord, again complete remission. Considering staying on the patch in place of going onto Modafinal. Wondered if anyone new the likelihood of me becoming tolerant to nicotine and it losing its effictiveness?
Colonel Hapablap, Oct 12 2007
  

       //ideal daily dose of nicotine and other chemicals, in mg/kg//   

       I would strongly urge anyone against taking a kilogram of nicotine in a day.
theleopard, Oct 12 2007
  

       oh, [theleopard], you're such a baby! : )
k_sra, Oct 12 2007
  

       [+] utterly. Lots of depressives self- medicate by smoking, whether they're aware of it or not. In light of the current hysteria about smoking, it is important to realize that this is an issue. I'm not saying that smoking is a clever medication for depression (though the lifetime risks are lower from smoking than from long-term or recurrent depression); but health agencies need to be aware of the very real link between smoking and depression. It's going to become a big problem. I'm not convinced that nicotine substitutes are the entire answer - there's a whole slew of compounds in tobacco smoke, many with likely pharmacological effects. But as to the general idea proposed here, yes.
MaxwellBuchanan, Oct 12 2007
  

       //niacin / an oxidation product of nicotine//   

       Makes sense. I'd assume some niacin is produced when you burn (oxidise) tobacco, then.
BunsenHoneydew, Oct 12 2007
  

       //Tried placing a 7mg patch on my spinal chord yesterday, and experienced complete remission of symptoms within 5 mins.// That sounds odd. I would have guessed that 5min was way too quick to have any effect. In any case, I am pretty sure that placing it on your spine wouldn't make any difference to placing it on your arm: the nicotine has still got to go through your skin and get carried around your circulation to get anywhere useful. I may be wrong but it sounds odd to me.
MaxwellBuchanan, Oct 12 2007
  

       Re 7 mg patch: good. If it works it works. Someone else can figure out why it works. I think tolerance is unlikely. The nicotine patch is safe and if it does the job, better that than a different and unknown drug.
bungston, Oct 12 2007
  
      
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