122 replies to this topic

[Rational Madman]

I'm becoming increasingly convinced that dopa decarboxylase and tyrosine hyrdroxylase enzyme alterations are of more importance, and thus, the co-administration of MAO inhibitors, tyrosine, NADH, or anti-Parkinson's drugs might be more efficacious than the more deleterious Memantine.

Altough only based on one anecdotal report, a good friend of me with severe depression has used MAO inhibitors, LDOPA and other stuff with amphetamine and he got completely tolerant, so i'm doubtfull those things would work, imo receptor downregulation is the biggest issue.

He now noticed a COMPLETE reversal of nicotine, tramadol, klonopin and amphetamine tolerance since he added in acamprosate, wich also modulates glutamate, but isnt a direct NMDA antagonist and may be a good alternative for memantine, altough he does take 10 mg memantine with it, he couldnt tolerate higher doses of memantine.

I'm wondering if the tolerance was due to a depletion of serotonin, which might lead to increased obsessive behaviors, and diminish the focus enhancing effect of amphetamine salts.

[medievil]

I'm becoming increasingly convinced that dopa decarboxylase and tyrosine hyrdroxylase enzyme alterations are of more importance, and thus, the co-administration of MAO inhibitors, tyrosine, NADH, or anti-Parkinson's drugs might be more efficacious than the more deleterious Memantine.

Altough only based on one anecdotal report, a good friend of me with severe depression has used MAO inhibitors, LDOPA and other stuff with amphetamine and he got completely tolerant, so i'm doubtfull those things would work, imo receptor downregulation is the biggest issue.

He now noticed a COMPLETE reversal of nicotine, tramadol, klonopin and amphetamine tolerance since he added in acamprosate, wich also modulates glutamate, but isnt a direct NMDA antagonist and may be a good alternative for memantine, altough he does take 10 mg memantine with it, he couldnt tolerate higher doses of memantine.

I'm wondering if the tolerance was due to a depletion of serotonin, which might lead to increased obsessive behaviors, and diminish the focus enhancing effect of amphetamine salts.

I doubt it, he was taking amphetamine with parnate wich also stops serotonin breakdown. From my observations i became 100% sure tolerance is only due to receptor downregulation.

[Rational Madman]

I share your penchant for the Islay scotches and would never say no to a taste of Lagavulin, Laphroig or Caol Ila. I loathed whiskey with a passion prior to my first sip of the wonderfully peaty Lagavulin 16 y.o. A glass of red wine has pretty extensively documented health benefits and I drink that too occasionally. Regarding other alcoholic beverages I very much enjoy traditionally made and prepared absinthe too, none of those Czech excuses though.

That said I still consider alcohol in general a guilty pleasure rather than anything that enhances my cognition in any way and I keep my intake very very low. Of course we shouldn't discount the more individual effects alcohol has on our biochemistry, what works for you might not work for me. I read your post in your regimen thread regarding alcohol and while it was very interesting and historically educational it didn't include enough scientific data to convince me of the merits of alcohol itself. If it works for you and your intake is moderate I say go for it, perhaps you should keep track of exactly how much you drink though since the more intelligent someone is the better they are at rationalising their bad habits. I know this from experience and you seem very intelligent and exceedingly good at rationalising your use of alcohol. I'm sure you see past what might be wrongfully interpreted as preachy and see that I'm merely advocating honesty to oneself in conjunction with moderation. I would never give up alcohol entirely myself I would certainly encourage others to taste some of the finer things in life, some of which contain a generous amount of alcohol.

Some of my troubles with alcohol and the stark difference in how we respond to it might also be psychological - I believe alcohol has a detrimental effect on my cognition whereas you believe it enhances yours. Thinking makes it so.

Thanks for the recommendations and I'll make sure to try some of them at social functions where drinking is somewhat expected.

Well, indeed, I should be emphatic about not passing the threshold of moderate consumption, which is a boundary that I'm ever mindful of---even if my postings make me sound like a constant inebriate. Indeed, even though drunkenness has become almost a rite of passage into adulthood, I don't think that I've ever entered a state where I've ceded complete control to the influence of alcohol. Nor have its effects rendered me unable to function the following day, or appreciably affected my reliably vivid episodic memory. Like I said, though, I find some forms of alcohol more agreeable than others, and although some beverages can cause an uncomfortably stupefying feeling---but more commonly, a mild malaise---I haven't found these adverse effects to be terribly disturbing---since they're often of a more transient nature. So I guess my advocacy is driven largely by a desire to end the sort of normative demonization that has led many to overlook its therapeutic potential, and unfortunately, accentuate detrimental effects that can be easily managed. But not everyone has the same level of tolerance, or the inclination to regularly drink, so to each his own.

Absinthe, huh? That's pretty wild.....

Edited by chrono, 30 September 2010 - 10:47 AM.

[chrono]

A paper showing that weekly nicotine administration still produced tolerance to some of its effects, which makes my assumption about occasional use more problematic (though I'm sure it's less than is seen with daily use).

Sensitization and tolerance with episodic (weekly) nicotine on motor activity in rats.
MacPhail RC, Farmer JD, Jarema KA.

Weekly dosing produced tolerance to nicotine's decreasing effects on vertical activity and increases (i.e., sensitization) in horizontal activity at all doses, and these effects persisted for at least 3 weeks. Experiment 2 partially replicated the results of Experiment 1 and indicated further that small sequential dose variations generally had little influence on nicotine tolerance and sensitization. The present results on horizontal activity extend prior findings of sensitization to weekly nicotine to include a broad range of doses. Results also showed that tolerance, but not sensitization, occurred to nicotine's effects on vertical activity over a comparable dose range. Further research is warranted on the importance of episodic, or recurring intermittent exposures in determining nicotine's effects, and those of other nicotinic agents, on behavior.

PMID: 17261359 [PubMed - indexed for MEDLINE]

I've upped my nicotine usage to about 3x a week for the past two weeks now, and there is definitely a noticeable lessening of its effects. At this point, it feels more like L-tyrosine (maybe not even as strong as NALT), and is more just a slight warmth/support in my brain, rather than a significant motivator.


A few more papers talking about the nicotinic mechanisms involved in tolerance, which probably aren't useful enough to warrant posting the full abstracts here:

• Mecamylamine blocks the development of tolerance to nicotine in rats: implications for the mechanisms of tolerance.
• Nicotine activation of alpha4* receptors: sufficient for reward, tolerance, and sensitization.
• Tolerance to nicotine in mice lacking alpha7 nicotinic receptors.
• Evidence of cellular nicotinic receptor desensitization in rats exhibiting nicotine-induced acute tolerance.
  
• Deletion of the beta 2 nicotinic acetylcholine receptor subunit alters development of tolerance to nicotine and eliminates receptor upregulation - an interesting implication for our discussion of other nicotinergics; do those which don't affect beta2 still produce upregulation?
  
• Cellular nicotinic receptor desensitization correlates with nicotine-induced acute behavioral tolerance in rats.
• Chronic nicotine cell specifically upregulates functional alpha 4* nicotinic receptors: basis for both tolerance in midbrain and enhanced long-term potentiation in perforant path.
• Decreased withdrawal symptoms but normal tolerance to nicotine in mice null for the alpha7 nicotinic acetylcholine receptor subunit.

My favorite wines are Châteauneuf du Pape and the more full-bodied Rhônes. Gah, but I'm not going to think about that right now, because they're definitely not in the budget atm -_-

EDIT: God dammit, I really wish I hadn't brought that up. Now I'm going to be thinking about it all day.

Edited by chrono, 30 September 2010 - 11:36 AM.

[aLurker]

I also fear that the motivational aspects might be subject to a certain degree of tolerance in my own case since I've recently started going back to bad habits such as browsing these forums. As a rule of thumb the less time I spend obsessing here the more real work I get done. Hopefully breaks or nicotine use in conjunction with something else might help. I considered cycling nicotine with rhodiola (also slightly motivational and OTC) but decided against it since the MAOI A effects would seriously suck in conjunction with deprenyl and nicotine. I'll simply have to procure a more serious arsenal of meds and see what works.

[aLurker]

My bad habits of avoidance, escapism, procrastination and obsessive research are also pretty OCDish. For instance: I never buy something in the grocery store without comparing, over-analyzing the ingredients and nutritional facts. That's not necessarily a bad habit but it goes for everything in my life: I can't make decisions without explicitly thinking over every aspect and I have real trouble in making priorities. I seriously WANT to stop refreshing this forum to see what's new and get some real work done but I keep getting distracted and going back. I guess there are lots of people with similar addictions to facebook though and all of my problems can probably be explained by some ADD-related rationale involving my PFC and executive function. I have a tendency to get overly involved with a specific subject for a few months before I drop it and the rest of my life takes a toll because of it. Before this I was obsessed with head-phones and hung out on head-fi.org. I only bought like three pairs of headphones but I could probably name dozens and their pros and cons along with technical specs. A lot of analytical work compared to what I actually did, and in lack of a better word, accomplished. I found headphones so intriguing I couldn't do much else even though I knew it was hurting other areas of my life. The more rational thing to do might have been to get a job and work and then spend half an hour or so to decide which headphones to by with my newly acquired money. Even though I was able to prioritize and plan in theory I couldn't bring myself to execute the actions required.

I also realize that pursuing narrow interests with gusto might be more of an aspergers thing than OCD though. I might have been slightly puzzled by social interactions during my adolescent years but a very persistent and ongoing obsession with psychology has made my social skills increasingly sharp and perceptive not only on an intuitive level but also on a more theoretical plane. I seem to have been a pretty likable guy to begin with though and I've always had several close friends and no trouble with the opposite sex. So if I ever had anything even remotely close to aspergers I've well and beyond compensated for it with theoretical knowledge, empathy, overanalysis and learned behaviors.

I've got lots of areas of interest but I find it very hard to control how I pursue my interests - my time here on this forum for instance would have been much better spent regarding something actually related to my education which is quite technical but admittedly totally unrelated to neurochemistry/health. The lack of control I feel I have over my behaviors in combination with my overly analytical mind makes for a very frustrating combination. Surely I should be reading about other things right now and there is no real reason why I shouldn't be able to do this since I find them interesting too yet I feel it is much harder than it should be since I immediately get distracted by other thoughts that I feel an almost uncontrollable urge to pursue right away.

What diagnosis my ADD/Aspie/OCD-related problems might get is pretty irrelevant but they might indicate what substances might help me overcoming my bad habits. Nicotine has worked pretty good although I'm starting to suspect that it isn't enough on its own in the long run due to tolerance issues. Even though I suspected I was trapped by my own thoughts sometimes I didn't realize the full extent of my problem until I tried nicotine. Everything seemed much clearer and decisions were suddenly much easier to make since everything had much clearer priorities.

Both atomoxetine and memantine show promise when it comes to overcome these issues. Atomoxetine might improve executive function and ADD by its actions in the PFC. Memantine might reverse tolerance to nicotine, alleviate ADD and help against obsessive habits. I'll probably try both at some point in time although now I'm overanalyzing which one I should try first and that's probably a bad sign.

Edited by aLurker, 30 September 2010 - 01:41 PM.

[aLurker]

Medievil, would you consider your impressively extensive pharmacological research as a part of your OCD or how closely related do you think the two are? To be a little bit more specific; can you resist an urge to research something and go "I won't research that now, I've got more pressing matters to attend to". This is almost impossible for me.

Sorry to deviate from the topic at hand for those whose primary interest is nicotine tolerance. To make the discussion more relevant I might mention that nicotine might help against OCD too.

Edited by aLurker, 30 September 2010 - 02:07 PM.

[maxwatt]

Try Lang Bin, a South East Asian concoction of betel nut, licorice and tobacco, chewed until too disgusting to tolerate, then the seed an plant fibers are spit out. Also effective in my experience is l-serine protein powder with caffeine; two grams and 200 mg. Has to be cycled to remain effective, but not addictive as nicotine is.

Chrono: see if you can find a Gigondas, somewhat less costly than Chateau Neuf but often every bit as good. If still too pricey, some Australian Shiraz are a reasonable approximation, even in the ten-buck chuck category.

Edited by maxwatt, 30 September 2010 - 02:36 PM.

[medievil]

Medievil, would you consider your impressively extensive pharmacological research as a part of your OCD or how closely related do you think the two are? To be a little bit more specific; can you resist an urge to research something and go "I won't research that now, I've got more pressing matters to attend to". This is almost impossible for me.

Sorry to deviate from the topic at hand for those whose primary interest is nicotine tolerance. To make the discussion more relevant I might mention that nicotine might help against OCD too.

I'm not sure what post your quoting, nothing shows up,

Well, Memantine works INCREDIBLY well for my OCD, and nicotine helps too, i dont think my pharmacological research has anything to do with my OCD but rather with my ADD wich makes me overfocused on the things that intrest me, this is seen with many ppl that have ADD, they have a particular subject and do extensive research on it.

The only thing that pulls me away from my computer and get motivated to do all the stuff i want is AMT (wich also works GREAT for ocd and is a ton better compared to amphetamine imo).
You need motivation, and only dopaminergics can give you that

[medievil]

aLurker do you have bad motor coordination problems? (seeing you mention asperger).

[aLurker]

I'm not sure what post your quoting, nothing shows up,

Well, Memantine works INCREDIBLY well for my OCD, and nicotine helps too, i dont think my pharmacological research has anything to do with my OCD but rather with my ADD wich makes me overfocused on the things that intrest me, this is seen with many ppl that have ADD, they have a particular subject and do extensive research on it.

The only thing that pulls me away from my computer and get motivated to do all the stuff i want is AMT (wich also works GREAT for ocd and is a ton better compared to amphetamine imo).
You need motivation, and only dopaminergics can give you that

You're probably right. All my issues basically fall under the ADD umbrella despite my tirade. My coordination is excellent. Overly focused on things that interest me fits me to a tee.

[aLurker]

I've seen stuff about Acomprosate indicating it can work against tolerance for other substances such as morphine [1] [2] and medievil mentioned it could work against amphetamine tolerance. I don't know about nicotine though.

Acamprosate attentuates cue-induced reinstatement of nicotine seeking behavior in rats

Acamprosate is a glutamate modulator that has been used in the treatment of alcoholism. This investigation tested the hypothesis that acamprosate can inhibit cue-induced relapse to nicotine self-administration (SA) in the rat. Rats were trained to lever press for food under a FR5 schedule, then implanted with jugular catheters. After recovery, daily nicotine SA sessions (0.03 mg/kg/infusion) were conducted under a FR1 schedule (days 1-5), FR2 schedule (days 6-8) and then a FR5 schedule (days 9-30 days). Delivery of nicotine was accompanied by the illumination of a cue light directly above the active lever. Next, extinction sessions were run for 14 days, during which responses on the active lever did not result in the infusion of nicotine or the illumination of the cue light. Beginning on the following day, rats received twice daily injections of saline or acamprosate (50, 100 or 200 mg/kg/i.p.) for 7 days. On the 7th day, the response to the previously conditioned cue was tested. The rats were pretreated with acamprosate and the conditions were the same as nicotine SA, but only saline infusions were delivered. Pretreatment with acamprosate attenuated cue-induced nicotine seeking behavior. These findings suggest that acamprosate might be efficacious in reducing nicotine seeking behavior.

Hard to draw any conclusions from that study though.

Edited by aLurker, 30 September 2010 - 05:36 PM.

[medievil]

Anecdotal reports on acamprosate for tolerance:

You know, my life has significantly changed, from about a 20 [ on a 1-100 scale ] to about a 60-85. Every aspect of it, has changed. This change started occuring, when I started taking Acamprosate. I was afraid of taking it because, if i took 2 pills, it would equal 666 milligrams of Acamprosate.........

Im taking Parnate, Memantine, Ropi occaisionally, .5-1mg Klonopin, 25mg Tramadol, 0-30mgs Dex every day ...................... nothing was working, at ALL. All hope was lost..... then the Acamprosate came in the mail. So i ate it. Day 2: ate another pill of 333 Acamprosate...... = mild anxiety reduction, reduced OCD, a kinda Smoooooothhhhissh feeling, like life is just plain less stressfull, like life isn't gonna just crush me into pieces any second.

on that same night, I took 20mgs MEmantine, ( went straight from 10mgs) .....and noticed no negative effects. Only increased mood, decreased Social Anxiety ..... Then next day, another 20mgs Memantine, = brain fog. But, still, the Acamprosate + Klonopin + Trihexyphenidyl like made the whole MEmantine Brain Fog thing SO much eaiser. seriously.

One major point i must make........................------ my Chronic pain/Fibromyalgia, which is Moderate to Severe in intensity, has been part of me ever since about 3 years ago. Thats part of the reason why i used to Go running every day, otherwise my Pain and RLS would get so bad, i would feel almost suicidal --- I am not exaggerating one bit, = complete truth. ----

The Acamprosate ( 333-1666 mg / daily ) has done the following :

*Totally freaking changed the direction and tone of my life,[[ from a Flatline, hopeless everyday existence, with no desire to get out of bed, ]]......... to now, when Every day, I wake up with just a little bit of hope.....that the day is not going to suck like the last ~1,460 of them - [ note: i did have occaisional good days, like probably 15-20 of them, during the course of those 3 or 4 years or something , it wasn't all bad ] .

*Made my crazy medication regimen WORK [it was just plain not working, before Acamprosate ]

*Made Amphetamine Work again. And I only take ~ 12.5-15 mg Memantine/day. ---- my Amphetamine has NOT worked, since April, when i think i just got completely tolerant to it.

* Reduced my Depression SIGNIFICANTLY.......i think, this is a result of a Beneficial combination of the Acamprosate + Memantine's effects.


------- My official evaluation of Acamprosate, is that it feels like a weak Benzo, with Weird but significant reduction in Fibromyalgia/chronic pain, + extremely small, almost unnoticable, memory impairment.

So, by itself, i don't know how much it would help anything. What I do know, is that is Dramatically potentiates EVERY single one of my medications, and makes them work again ----- Amphetamine, Caffeine, Klonopin, Tramadol,

!!!!!! - Acamprosate is similiar to Gabapentin + weak Benzo, [ By itself ]. But combined with all my other meds, I am now actually starting to recover, and have made significant progress.

Its freaking awesome. My OCD told me for months, that Acamprosate was the wrong option, that it wouldn't work. Lol......OCD was wrong, for the, infinitiv time. Thank you CrayzyMed, for changing my life.

http://www.dr-bob.or...sgs/114108.html
Re: Memantine?
Posted by AndrewB on July 29, 2002, at 0:58:17
In reply to Re: Memantine?, posted by velaguff on July 26, 2002, at 13:31:34
> Well, guess you read my earlier post on this a few days ago....I haven't tried it yet, but I've ordered some, and I will try it with Tramadol soon. I'll definitely keep you posted. An "Andrew B.", who may no longer be posting, said some time ago, when I only read w/o posting, that it definitely prevented Adderall poopout. His main concern was ADD treatment. It DEFINITELY prevents poopout on rats, and I think that's generally a pretty good indicator for humans, mammals even if seemingly different respond much alike to most drugs.
----------------

I haven't posted in a long time but, if you don't mind, I'd like to offer my experience with memantine and amphetamine poop-out.
I've been taking memantine for about 2 years with adderall. Adderall alone will lose its effectiveness with me in a few days if I don't take it with a drug like memantine.
I take adderall mainly for energy, motivation and just plain enthusiasm for life. Though Adderall probably helps my concentration, I can't say that I'm taking the stimulant for ADD. Like some others, I take a stimulant as part of of an effective drug therapy for treatment resistant depression, or, more specifically, dysthymia.
And, by the way, I feel very good, really blessed. I've been happy and stable for quite a while now. I was pretty miserable for the first half of my life. Who knows what the future holds, but so far the second half of my life is shaping up to be something kind of wonderful.
Back to the memantine. I used to take two 10mg tablets a day to prevent poop-out. Now I take one tablet along with 333mg of acamprosate taken 2 times a day.
Acamprosate is, like memantine, approved for use in Europe and is in late stage trials in US and is expected to be approved in the US in the not to distant future. Acamprosate has a somewhat similar mechanism of action to memantine, its approved use though is for helping alcoholics quit and remain sober. It takes away the cravings for alcohol. It has no side effects, toxicities, or drug to drug interactions to my knowledge.
DAAIR is a good source for Memantine (www.daair.org). Acamprosate can be obtained with a prescription from a European mail order pharmacy. Acamprosate is quite a bit less expensive than memantine and is effective for poop-out by itself at a dose of 333mg. taken 3 times a day.
I recommend taking memantine even if one is taking acamprosate, as I believe memantine has an overall neuroprotective effect for the nervous system.
For example, the free radical damage which seemingly occurs with even standard prescription dosages of amphetamines is prevented by memantine. Memantine also confers strong protection to the hippocampus, which, as you are probably aware, tends to be severely atrophied in depressives. One doctor/researcher, after reviewing the results of a recent clinical study, stated that memantine could quite possible be a preventative of Alzheimers.
Regardless of such speculation, it seems depressives and bipolars tend to have dysregulated glutaminergic systems in one aspect or another. This glutaminergic dysregulation may have a central role in some depressions and bipolars disorders. However, even where glutaminergic dyregulation is not causal to the depressive or bipolar symptomology, care should be taken, I believe, to correct the dysregulation because of the numerous deleterious effects of glutaminergic dysregulation upon the nervous system. Memantine prevents one of the 3 types of glutaminergic receptors from becoming overactive.
By the way, occasionally, my Adderall has pooped-out even while on acamprosate and memantine. This is seemingly due to having my brain temperature get to high for long periods of time when vigorously exercising. When this happens, I have to stop taking adderall for one and a half days to restore its effectiveness.
I hope this is of some help,
Best wishes,
AndrewB

[medievil]

I'l make a better post on acamprosate, its mechanism of action and stuff in my nmda antagonist thread, it does look like another good alternative to memantine.

[aLurker]

Since a couple of users here have been sending me PMs telling me they're going to try nicotine let me just state here for the record that my personal experience now also tells me that tolerance is a real issue (along with the vascular effects). I intend to take a break from my continuous nicotine usage now. It still seems to give me energy and focus but those aspects aren't really productive when my lack of drive and executive function uses that to do irrelevant stuff. I feel that the vast improvements in motivation and executive function aren't really there for me anymore so I'd rather forgo the minor improvements it might still give me now in hope of reversing tolerance for a later point in time.

I'm still very glad I tried nicotine since in the two weeks or so it worked it was really amazing and I managed to straighten out a lot of things in my life during that period of blazing productivity. I wish everyone who decides to give this a try good luck. A good reason to actually try nicotine is that if you respond to it like I did you'll know within an hour or so and then you can decide if it seems worth the risks (you might want to read the nicotine and vasoconstriction thread). Beware of tolerance and it might be good to use it sparingly to avoid this.

I might make some other changes to my regimen now too. I'll keep you posted.

[medievil]

Stop it now! tolerance will keep on getting worse and when you run out youll spend half the day searching the house for some leftover patch, i'm actually concerned your allready addicted at this point.

Edited by medievil, 30 September 2010 - 09:57 PM.

[aLurker]

Stop it now! tolerance will keep on getting worse and when you run out youll spend half the day searching the house for some leftover patch, i'm actually concerned your allready addicted at this point.

lol, you're on nicotine, amphetamine, AMT and going to rave parties and you're concerned that I might be addicted to a sixth of a nicotine patch. :D

Thanks for the hopefully unfounded concerns. I'm more concerned how I'll manage my ADD-symptoms from now on.

[medievil]

Stop it now! tolerance will keep on getting worse and when you run out youll spend half the day searching the house for some leftover patch, i'm actually concerned your allready addicted at this point.

lol, you're on nicotine, amphetamine, AMT and going to rave parties and you're concerned that I might be addicted to a sixth of a nicotine patch. :D

Thanks for the hopefully unfounded concerns. I'm more concerned how I'll manage my ADD-symptoms from now on.

Yes, take it from a guy like me, if i warn you about something its for real! .

[aLurker]

True, you're right waaay too often. This would be a good time to stop that.

[aLurker]

No cravings to speak of yet and no urge to put the patch back on again so far so good.

Now that I'm off the patch I'm also considering bupropion. Could help me judging from ADHD studies, anecdotes regarding motivation/decision making and this was also interesting. It also seems a lot more benign than atomoxetine regarding side effects. Of course the prospect that it might be bad for my otherwise very good memory disheartens me somewhat since I rely on that to get by. A lot of the stackable stuff I've already got should attenuate the negative effects though. I guess the ALCAR, piracetam and galantamine should be good for this purpose and I'll probably ditch the deprenyl if I go that route. Nice to have options at least when nicotine doesn't seem to work right now. I'll look into how bad the memory side effects are from bupropion and if they are lasting or merely a transitory phase until receptor up-regulation occurs (wishful thinking).

Edited by aLurker, 01 October 2010 - 03:28 PM.

[aLurker]

Short update on my nicotine use:
Nicotine doesn't seem to be addictive at all for me beyond the desirable psychological effects. It kills my appetite and I think it made my hands colder, especially in the beginning. Tolerance seems to be an issue for me though since after two weeks of regular use I lost most of the motivational aspects but after a week long break I tried it for a few hours yesterday and they seemed to be back. I'll probably use nicotine more seldom now, mostly because of the tolerance issue.

[aLurker]

I just found this thread where nicotine tolerance and memantine are discussed, highly relevant stuff.

Edited by chrono, 12 October 2010 - 08:10 PM.
fixed link, because I changed the thread title

[medievil]

Recently posted by kimberct on mind and muscle:

Personally, I've been taking 20mg for nearly a year now. Having become a grandmaster at tapering drugs, I'm not worried should I ever decide to stop. I haven't noticed any tolerance to its effects. I cannot say, however, if the drug is still working or I've simply gotten better. On the other hand, it did not prevent nicotine tolerance for me recently. MeDieViL, who I believe is new to memantine, has claimed that it does prevent nicotine tolerance for him.

I'm on 40mg of memantine and i'm guessing that its the higher wich makes the difference and that 20mg isnt enough, still its important to post the negative experience here too.

[FunkOdyssey]

No cravings to speak of yet and no urge to put the patch back on again so far so good.

Now that I'm off the patch I'm also considering bupropion. Could help me judging from ADHD studies, anecdotes regarding motivation/decision making and this was also interesting. It also seems a lot more benign than atomoxetine regarding side effects. Of course the prospect that it might be bad for my otherwise very good memory disheartens me somewhat since I rely on that to get by. A lot of the stackable stuff I've already got should attenuate the negative effects though. I guess the ALCAR, piracetam and galantamine should be good for this purpose and I'll probably ditch the deprenyl if I go that route. Nice to have options at least when nicotine doesn't seem to work right now. I'll look into how bad the memory side effects are from bupropion and if they are lasting or merely a transitory phase until receptor up-regulation occurs (wishful thinking).

Bupropion was more motivating for me than amphetamine, methylphenidate, deprenyl, and every other supposedly motivating drug I've tried. I've never been so productive in my life as I was while I was on bupropion. I was coming home after an 8 hour day at work and studying for another 5 hours easily, with no concentration difficulties, and I actually WANTED to do it. It was insane compared to my norm.

Edited by FunkOdyssey, 13 October 2010 - 06:00 PM.

[aLurker]

No cravings to speak of yet and no urge to put the patch back on again so far so good.

Now that I'm off the patch I'm also considering bupropion. Could help me judging from ADHD studies, anecdotes regarding motivation/decision making and this was also interesting. It also seems a lot more benign than atomoxetine regarding side effects. Of course the prospect that it might be bad for my otherwise very good memory disheartens me somewhat since I rely on that to get by. A lot of the stackable stuff I've already got should attenuate the negative effects though. I guess the ALCAR, piracetam and galantamine should be good for this purpose and I'll probably ditch the deprenyl if I go that route. Nice to have options at least when nicotine doesn't seem to work right now. I'll look into how bad the memory side effects are from bupropion and if they are lasting or merely a transitory phase until receptor up-regulation occurs (wishful thinking).

Bupropion was more motivating for me than amphetamine, methylphenidate, deprenyl, and every other supposedly motivating drug I've tried. I've never been so productive in my life as I was while I was on bupropion. I was coming home after an 8 hour day at work and studying for another 5 hours easily, with no concentration difficulties, and I actually WANTED to do it. It was insane compared to my norm.

Wow, that's like the holy grail for me.

How long did it take for these effects to manifest themselves? I saw some old posts where you hypothesized that memantine might work to prevent bupropion tolerance too but I haven't seen anyone try the combo. Heard of anyone on bupropion and memantine?

Edited by aLurker, 13 October 2010 - 06:37 PM.

[FunkOdyssey]

How long did it take for these effects to manifest themselves? I saw some old posts where you hypothesized that memantine might work to prevent bupropion tolerance too but I haven't seen anyone try the combo. Heard of anyone on bupropion and memantine?

Right away. It did seem like tolerance was developing over time and I wondered if memantine would address that. I think no one has attempted it to date.

[medievil]

How long did it take for these effects to manifest themselves? I saw some old posts where you hypothesized that memantine might work to prevent bupropion tolerance too but I haven't seen anyone try the combo. Heard of anyone on bupropion and memantine?

Right away. It did seem like tolerance was developing over time and I wondered if memantine would address that. I think no one has attempted it to date.

Where do you think this motivation comes from? Increased NE or the increased DA in the prefrontal cortex?

[FunkOdyssey]

How long did it take for these effects to manifest themselves? I saw some old posts where you hypothesized that memantine might work to prevent bupropion tolerance too but I haven't seen anyone try the combo. Heard of anyone on bupropion and memantine?

Right away. It did seem like tolerance was developing over time and I wondered if memantine would address that. I think no one has attempted it to date.

Where do you think this motivation comes from? Increased NE or the increased DA in the prefrontal cortex?

I'm not sure. NE is very important for motivation, I think it could easily be NE alone. IIRC bupropion acts more like an NE releasing agent than a reuptake inhibitor, that may also be relevant.

[medievil]

Ive no idea what effects NMDA antagonist has an NE density, will do some digging.

[KimberCT]

How long did it take for these effects to manifest themselves? I saw some old posts where you hypothesized that memantine might work to prevent bupropion tolerance too but I haven't seen anyone try the combo. Heard of anyone on bupropion and memantine?

Right away.  It did seem like tolerance was developing over time and I wondered if memantine would address that.  I think no one has attempted it to date.

Where do you think this motivation comes from? Increased NE or the increased DA in the prefrontal cortex?

I'm not sure.  NE is very important for motivation, I think it could easily be NE alone.  IIRC bupropion acts more like an NE releasing agent than a reuptake inhibitor, that may also be relevant.

Ahhhhh, that would explain why bupropion gave me terrible anxiety even at very low doses.  Being a fairly weak NRI/DRI, I was stumped as to why it had such a negative effect on me.