What this topic is mainly about: preventing tolerance to nicotine.
Since nicotine has basically cured my deep rooted procrastination issues my main priority is to maintain the motivational and executive functioning enhancing effects of the nicotine. I'm not even sure yet if tolerance develops to these effects but I'm going to do my best to make sure I maintain them either way. I'm also toying with the idea of trying other meds since my amazing response to nicotine is probably an indication of ADD.
Concerning nicotine; warding off desensitization of nicotinic acetylcholine receptors is a primary concern (hence combining the nicotine with a PAM). Related concerns might be PKA, PKC and downstream down-regulation of other receptors such as dopamine. The cardiovascular effects are already discussed elsewhere and I'll probably start with dealcoholized red wine or something in the near future.
A few possible options that _might_ prevent tolerance:
*A PAM might help. Galantamine is a PAM. I refer to the thread I linked to in the beginning for more info on this.
*Memantine can according to medievil reverse/prevent tolerance to nicotine and many other substances. I haven't investigated this very thoroughly myself yet though. How it would achieve this is interesting since it both works on NMDA receptors and is a nAChR antagonist. Perhaps something related to these mechanisms would also be worth exploring then.
*Extracellular adenosine is involved in nAChR desensitization so hypothetically something like tea/coffee might help too although I'm unsure to how that would work long-term considering the rapid tolerance to caffeine. Other substances with adenosine mechanisms might also be relevant such as modafinil.
*Taking periods off nicotine might help. Although I'd prefer not to personally since I have trouble getting things done without it (as I did before). I've paused for a day or two during a weekend and there isn't any withdrawal or cravings at all so far though.
I've got mild concerns regarding both galantamine and memantine and any caffeine gives me eye twitches yet the thought of developing a persistent tolerance to nicotine is far scarier to me. It might not even become an issue for me but what can be done to prevent tolerance to nicotine?
I've tried galantamine in doses varying from 1-4 mg the last few days. So far the effects are very mild if they are even noticeable. Subjectively I'd say it offers a mild potentiating effect on nicotine so far though although the prospect that a PAM could help against desensitization of nAChRs is a huge upside to me personally.
Brief description of my experience with nicotine.
When I first put on a piece of a nicotine patch I went from procrastinating, messy, unable to make decisions and unmotivated to getting things done, organized, efficient and highly motivated. I dread the thought of going back to my old habits and I'm working hard on changing them while the nicotine lasts (hence my absence from these boards compared to my regular posting in the past). It most certainly also isn't in my head since I've got an amazing amount of things done since I started the patch: everything around me is much cleaner and organized (both externally and cognitively), I secured several attractive competing offers for my masters diploma work, accepted the most interesting and challenging one of them and started plowing through tutorials in a couple of new programming languages among MANY other things. In just over two weeks of nicotine bliss I've done far more than during the rest of 2010. So you can see why I've been busy. I didn't really have time to log my nicotine use since I was so productive. Beyond merely the motivational aspects it has also given me clarity of mind and reduced my over-analytical inner dialogue significantly although I fear it might be coming back some due to tolerance although that might just be my mind playing tricks on me and trying to regain the part of my life it had previously.
Addendum: My current regimen
(very much still a work in progress; hence my post here instead of in the proper forum although I suspect chrono might be tempted to move this post since I'm including this but hands off for now)
Upon waking up:
1 g of ALCAR
800-900 mg of Piracetam
exercise
3.5 mg transdermal nicotine, (1/6 of a 21 mg GSK Niquitin Clear which I guess is the same as Nicoderm CQ. I follow pretty much the same routine as chrono described in an earlier post in another nicotine related thread; I secure the piece of patch in place with 3M Micropore surgical tape and store the remains of the patch in the initial packaging put in a ziplock bag that is then put in a book to press out the air before I seal it.)
With breakfast:
1 mg selegiline/deprenyl
2000 IU D3 in softgel form
LEF vitamin K EOD,
A few caps of fish oil.
a multivitamin on some days
With lunch:
More fish oil.
I've tried 1-4 mg of galantamine just to gauge the subjective effects. When I decide on a dose I'll take this with breakfast to cover more of my time with a nicotine patch on. I'm also unsure how long the PAM-effect of galantamine lasts and this might make me take it with a snack later during the day too.
At 14:00 or so:
800-900 mg of Piracetam
1 g ALCAR (often less if I've taken galantamine)
22:30
0.25 mg of melatonin, still deciding my dosage and time here but this seems to work pretty ok against my DSPS right now which is huge for me.
I also remove my nicotine patch somewhere between here and midnight.
I've used 3 mg of LDN before going to sleep in the past although my use is now much more sporadic right now since I didn't get any clear results from this. Some evidence of nAChR antagonism from naltrexone might make this route worth exploring some more though although the potential benefits from that are very unclear to me at the time.
I'll probably adjust a lot of the dosages over the next weeks because of the recent addition of galantamine although I think all of the current components in this regimen, with the possible exception of LDN, are real keepers. Probably more Piracetam and less ALCAR due to the AChE inhibition of galantamine.
Although my regimen is already somewhat polypharmaceutical, what would you urge me to modify/add considering my borderline miraculous response to nicotine? Deprenyl didn't have that much of an impact on my motivation yet nicotine has been amazing leading me to believe it isn't just dopamine related.My sage advice, less monotherapy, and more polypharmacy. More importantly, look at the body of evidence as a whole, and not selected results.
Concluding remark
Well, that's a lot of text and I would write even more if I had the time. If anyone has anything to say about nicotine tolerance (has it been an issue for you and how? what might help?), galantamine (especially with nicotine) or my regimen in general (additions, interactions, synergy, dosage etc.), feel free to post something.