122 replies to this topic

[Ames]

I just want to chime in here, because I think that the nature of the effects of an a antagonist, such as Memantine, is being ignored when strategizing for optimal use. The following is conjecture, based on what I believe to be the proper framework for eliciting permanent structural change in the organism. While not based on any studies with memantine specifically, I believe that it deserves attention. However, consider it theoretical:

Think of it like this: Taking memantine is likely most akin to holding your breath/breathing slower to build a more efficient oxygen metabolism (a more apt metaphor is the effect that short term fasting has on the body, but I'll stick with the breathing analogy for simplicity). Short term oxygen deprivation leads to an improvement in O2 efficiency / VO2 max, while long term hypoxia leads to a maladaptive state that was worse than baseline. In the case of memantine and therapeutic hypoxia/fasting, you are stressing the system, and directing homeostasis toward greater efficiency/sensitivity as a result. In my experience, and based on a rather universal framework for stimulating adaptive change, chronic use would lead to a decline in specific measures of health. However, a short but intense regimen would stimulate the long term structural change that is desired.


Theoretically, an inhibitory regimen that is meant to stimulate maximum adaptive change should have the following qualities:

1. Maximum intensity
2. Minimum duration

I'll leave it up to you to decide what this means in terms of NMDA antagonist regimen. Be safe with your dosages. It is very possible to stress the system to a degree that is too high for the organism to recover from in a manner that is positive. A stress that is too intense or long will have the effect of causing the organism to maladapt instead of adapt. This is a general principal, not specific to the topic of this thread.

What will counter the effectiveness of the regimen:

1. Anything that works to relieves the stress that the inhibitory regimen is causing to occur (analogous to eating a piece of candy while fasting). This will limit the rate/depth of adaptation. However, if the organism doesn't adapt, and the stress persists for too long, then stress relief will be necessary to limit deadaptation and preserve the health of the organism for further adaptation in the future. The stressor can again be implemented the following day.

2. Levying the stress too often in one day. My personal experience is that no more than ONE application of an intense stressor per day is optimal for maximum adaptive change. I believe this to be a universal principal that works in line with the organisms mechanism of stress and relaxation (adaptation).

3. Not following a strict schedule is implementing the stressor at the same time of day. I believe the best time for this, in line with hormonal cycles, is in the the morning.

Signs that you are implementing an inhibitory regimen successfully enough to produce change:

1. You are at least minimally uncomfortable the first day. Stimulants provide immediate relief. True adaptogenic practice creates an initial period of discomfort/stress to which the body adapts in the manner that we desire. The discomfort should be short lived (hypothetically, 1-3 days). If its not, you may be dosing to high and stressing the system too much (reduce dose). If no discomfort is experienced, either you are completely adapted/healthy already or the dose is too low to produce change.

As you feel better, lower your dose and space them out if possible. Skip days. The less chronically stimulating your lifestyle, the longer your system will stay adapted. When you do stimulate the system, it should facilitate a maximum learning response do to your increased sensitivity. As sensitivity decreases, and the system is prompted to respond to motivating stimulation more often, the ability to learn/change form those simulations will decrease. At this time, you should again increase the intensity and decrease the duration of the stressor/adaptogen.

Like I said, a theoretical framework.

Although, you might be surprised what small regimental adjustments can do for your organisms response to stress. I'm not sure how pure a stressor a substance like memantine is, but the science tends to corroborate its effect as an adaptogen.

I realize that this model circumvents all of the neurochemistry discussed here. Its only a meta-framework to keep in mind when evaluating methods for affecting general adaptive responses of the organism.

Edited by golgi1, 24 October 2010 - 08:33 PM.

[aLurker]

I know medievil posted the abstract before but here is a link to the entire thing, which is a very interesting read:

The Role of NMDA Receptor Antagonists in Nicotine Tolerance, Sensitization, and Physical Dependence: A Preclinical Review

An excerpt for medievil to masturbate to:

All together, there appears to be general agreement that NMDA receptor antagonists inhibit the development of nicotine sensitization. NMDA receptor antagonists have also been found to inhibit the development of sensitization to the stimulant effects of other drugs of abuse like morphine, amphetamine, and cocaine.4,18,20,70 This finding indicates that glutamate receptor stimulation is a necessary step in the cascade of cellular changes leading to sensitization. These results are very intriguing, suggesting that NMDA receptors may be involved in sensitization to a variety of different drugs of abuse. Understanding the mechanisms underlying sensitization is of particular interest to the field of substance abuse, because this process may be involved in the craving that arises from repeated drug exposure.89

[FunkOdyssey]

Theoretically, an inhibitory regimen that is meant to stimulate maximum adaptive change should have the following qualities:

1. Maximum intensity
2. Minimum duration

I'll leave it up to you to decide what this means in terms of NMDA antagonist regimen.

Obviously, you are recommending a certain feline tranquilizer. You rascal.

[aLurker]

Methylphenidate Enhances the Abuse-Related Behavioral Effects of Nicotine in Rats: Intravenous Self-Administration, Drug Discrimination, and Locomotor Cross-Sensitization

Stimulant drugs, including D-amphetamine, cocaine, and methylphenidate, increase cigarette smoking in controlled human laboratory experiments. Although the mechanism(s) underlying this effect are unknown, it is possible that stimulants may enhance directly the abuse-related effects of nicotine. In the present study, we characterized the behavioral pharmacological interactions between methylphenidate and nicotine in the intravenous self-administration, drug discrimination, and locomotor cross-sensitization procedures. Adult male Sprague–Dawley rats were trained to respond for intravenous nicotine (0.01 or 0.03 mg/kg/infusion) or sucrose, and the acute effects of methylphenidate (1.25–10 mg/kg) were determined; in addition, separate groups of rats were treated with methylphenidate (2.5 mg/kg) or saline before 12 consecutive nicotine (0.03 mg/kg/infusion) self-administration sessions. Next, the discriminative stimulus effects of nicotine (0.03–0.3 mg/kg) and methylphenidate (1.25–10 mg/kg), alone and in combination with a low nicotine dose (0.056 mg/kg), were tested in nicotine-trained rats. Finally, the locomotor effect of repeated methylphenidate (2.5 mg/kg) was tested in rats previously treated with nicotine (0.2–0.8 mg/kg). Results indicated that acute methylphenidate increased the rate of nicotine self-administration at doses that reduced sucrose-maintained responding; furthermore, tolerance to this effect was not apparent following repeated methylphenidate. Methylphenidate, while not substituting for nicotine alone, dose-dependently enhanced the discriminative stimulus effect of a low nicotine dose. In addition, repeated nicotine exposure promoted the development of locomotor sensitization to methylphenidate. Taken together with recent clinical findings, these results suggest that methylphenidate may enhance the abuse-related behavioral effects of nicotine, perhaps increasing vulnerability to tobacco dependence.

Ritalin makes nicotine delicious. I doubt it prevents tolerance to a major degree though since the rats self-administrated it at an increasing rate. Impossible to tell if they continued to administer nicotine because it still gave them such a rush or if they just had to to avoid withdrawal. Asking the rats probably won't help so if anyone wants to chime in how mph changed nicotine for them feel free.

On a vaguely related tangent I wonder what's more unhealthy in the long run, methylphenidate in conjunction with nicotine or monotherapy with dex-amp. Both alternatives seem somewhat addictive and have vascular downsides but probably to differing degrees, arguably nicotine with methylphenidate could be neuroprotective (since they both have neuroprotective aspects on their own) in contrast to dex which isn't neuroprotective.

Edited by aLurker, 01 November 2010 - 05:56 PM.

[medievil]

Methylphenidate Enhances the Abuse-Related Behavioral Effects of Nicotine in Rats: Intravenous Self-Administration, Drug Discrimination, and Locomotor Cross-Sensitization

Stimulant drugs, including D-amphetamine, cocaine, and methylphenidate, increase cigarette smoking in controlled human laboratory experiments. Although the mechanism(s) underlying this effect are unknown, it is possible that stimulants may enhance directly the abuse-related effects of nicotine. In the present study, we characterized the behavioral pharmacological interactions between methylphenidate and nicotine in the intravenous self-administration, drug discrimination, and locomotor cross-sensitization procedures. Adult male Sprague–Dawley rats were trained to respond for intravenous nicotine (0.01 or 0.03 mg/kg/infusion) or sucrose, and the acute effects of methylphenidate (1.25–10 mg/kg) were determined; in addition, separate groups of rats were treated with methylphenidate (2.5 mg/kg) or saline before 12 consecutive nicotine (0.03 mg/kg/infusion) self-administration sessions. Next, the discriminative stimulus effects of nicotine (0.03–0.3 mg/kg) and methylphenidate (1.25–10 mg/kg), alone and in combination with a low nicotine dose (0.056 mg/kg), were tested in nicotine-trained rats. Finally, the locomotor effect of repeated methylphenidate (2.5 mg/kg) was tested in rats previously treated with nicotine (0.2–0.8 mg/kg). Results indicated that acute methylphenidate increased the rate of nicotine self-administration at doses that reduced sucrose-maintained responding; furthermore, tolerance to this effect was not apparent following repeated methylphenidate. Methylphenidate, while not substituting for nicotine alone, dose-dependently enhanced the discriminative stimulus effect of a low nicotine dose. In addition, repeated nicotine exposure promoted the development of locomotor sensitization to methylphenidate. Taken together with recent clinical findings, these results suggest that methylphenidate may enhance the abuse-related behavioral effects of nicotine, perhaps increasing vulnerability to tobacco dependence.

Ritalin makes nicotine delicious. I doubt it prevents tolerance to a major degree though since the rats self-administrated it at an increasing rate. Impossible to tell if they continued to administer nicotine because it still gave them such a rush or if they just had to to avoid withdrawal. Asking the rats probably won't help so if anyone wants to chime in how mph changed nicotine for them feel free.

On a vaguely related tangent I wonder what's more unhealthy in the long run, methylphenidate in conjunction with nicotine or monotherapy with dex-amp. Both alternatives seem somewhat addictive and have vascular downsides but probably to differing degrees, arguably nicotine with methylphenidate could be neuroprotective (since they both have neuroprotective aspects on their own) in contrast to dex which isn't neuroprotective.

There isnt any convincing evidence that amphetamine has vascular downsides if you dont have any vascular problems in the first place, that said comparing those drugs this way is nonesense, you have to go with the treatment that is the most effective for you, if both are as effective, perhaps then think about wich would be better in the long run.

[aLurker]

From a more pragmatic and practical stand-point subjective efficacy is of course a deciding factor. I was merely trying to ignite a discussion about a hypothetical versus-match, like Godzilla vs. Stalin.

Edited by aLurker, 01 November 2010 - 06:10 PM.

[medievil]

Its pretty much impossible to answer that question as its not clear if/how much amphetamine is neurotoxic in humans.

[medievil]

This post has been edited by aLurker: Today, 06:10 PM

Churchill vs godzilla

[aLurker]

For what it's worth: my money is on Godzilla. He's got plenty of versus fights under his metaphorical belt.

[Rain]

How does being on nicotine affect memory? Does it improve memory while on it? Are there any negative cognitive effects from long-term usage?

Also, does piracetam increase it's effects, or does this really have no effect on nicotine?

Edited by Rain, 01 November 2010 - 07:06 PM.

[aLurker]

How does being on nicotine affect memory? Does it improve memory while on it? Are there any negative cognitive effects from long-term usage?

Also, does piracetam increase it's effects, or does this really have no effect on nicotine?

Nicotine improves some aspects of memory even in healthy adults. There are some negative cognitive effects linked to tobacco but I don't know of any links directly with nicotine. Perhaps some nicotine's negative vascular effects are partly to blame and could therefore affect cognition in the long run but that's unsubstantiated speculation on my part. Nicotine alone could also very well be good for you cognitively even in the long run.

You should read this post by chrono on nicotinic receptors and piracetam. If you go back a little in that thread we discuss other racetams too.

Spoilers:

A subchronic administration of the cognition enhancer piracetam (200 mg/kg, once per day for 5 days) increased by 70% the number of binding sites of NMDA receptors in the EL mice. At the same time, this treatment decreased the density of neocortical nACh receptors in both EL and EH mice (by 55% and 40%, respectively)

There is no reason to believe that piracetam would be synergistic with nicotine, the opposite if anything although the number of receptors doesn't say anything about how sensitive they are. Personally I prefer aniracetam which potentates the response from a4b2 nAChRs.

Edited by aLurker, 01 November 2010 - 07:45 PM.

[Rain]

^ Thank you for the information!

What about your personal experiences with your memory while you are on it?

[aLurker]

I get an increased sense of what I would describe as clarity. My memory is very good to begin with and that might make it harder for me to notice any improvements subjectively but nicotine certainly doesn't hurt. In all likelihood nicotine improves my memory; mostly through better attention.

[medievil]

aLurker and nicotine, may this lovestory last through eternity .

[aLurker]

More of a stormy romance where you fall head over heals in love and the initial infatuation eventually fades with prolonged exposure to each other. After two weeks of being around each other constantly it just wasn't the same and I decided we needed some time apart. From that on it's been more of an on and off thing but the brief periods of time we have together are great.

Right now memantine is acting as a relationship councilor trying to mend our differences. The allegory actually holds quite well since most people put up with their relationship councilor to make things work between you and your love.

[Rational Madman]

For f**k's sake, not another Memantine user!

[medievil]

For f**k's sake, not another Memantine user!

Hahaha

The allmighty memantine cant be stopped rol!

Edited by medievil, 02 November 2010 - 09:44 PM.

[aLurker]

For f**k's sake, not another Memantine user!

Haha, what makes you say that? Everyone reacts differently so I figured it's worth a shot. I feel your own subjective experience clouds your judgement here. For instance, I hate bacopa with a passion but surely there are people who benefit from it and I feel they are welcome to try it as long as they are aware of the side effects. When it comes to tolerance prevention there aren't a lot of other options really.

[Rational Madman]

For f**k's sake, not another Memantine user!

Haha, what makes you say that? Everyone reacts differently so I figured it's worth a shot. I feel your own subjective experience clouds your judgement here. For instance, I hate bacopa with a passion but surely there are people who benefit from it and I feel they are welcome to try it as long as they are aware of the side effects. When it comes to tolerance prevention there aren't a lot of other options really.

Okay, give it a trial, but you can't say you weren't forewarned.

[medievil]

Okay, give it a trial, but you can't say you weren't forewarned.

How long have you taken it rol? At the start it does make you feel completely retarded but nearly everyone reports to be side effect free after the adaptation phase.

[Rational Madman]

Okay, give it a trial, but you can't say you weren't forewarned.

How long have you taken it rol? At the start it does make you feel completely retarded but nearly everyone reports to be side effect free after the adaptation phase.

I took it for several months, at a peak dose of 24 mg/day.

[medievil]

Okay, give it a trial, but you can't say you weren't forewarned.

How long have you taken it rol? At the start it does make you feel completely retarded but nearly everyone reports to be side effect free after the adaptation phase.

I took it for several months, at a peak dose of 24 mg/day.

What side effects did remain for you? I gues brainfog that wouldnt go away? I do think you generalise too much as most ppl found memantine a good med without much side effects, some cant tolerate it, including a good friend of me, however that usually doesnt appear to be the case.

Edited by medievil, 02 November 2010 - 11:47 PM.

[Rational Madman]

Okay, give it a trial, but you can't say you weren't forewarned.

How long have you taken it rol? At the start it does make you feel completely retarded but nearly everyone reports to be side effect free after the adaptation phase.

I took it for several months, at a peak dose of 24 mg/day.

What side effects did remain for you? I gues brainfog that wouldnt go away? I do think you generalise too much as most ppl found memantine a good med without much side effects, some cant tolerate it, including a good friend of me, however that usually doesnt appear to be the case.

The cognitive side effects were most worrisome, but they're quite subtle---but unmistakable.

[medievil]

Okay, give it a trial, but you can't say you weren't forewarned.

How long have you taken it rol? At the start it does make you feel completely retarded but nearly everyone reports to be side effect free after the adaptation phase.

I took it for several months, at a peak dose of 24 mg/day.

What side effects did remain for you? I gues brainfog that wouldnt go away? I do think you generalise too much as most ppl found memantine a good med without much side effects, some cant tolerate it, including a good friend of me, however that usually doesnt appear to be the case.

The cognitive side effects were most worrisome, but they're quite subtle---but unmistakable.

I agree that with memantine there can be suble cognitive side effects, but thats also the case with meds like lamictal and other mood stabilisers, so i really dont see a justified reason to dislike memantine like that, atleast you seem really against it.

[Rational Madman]

Okay, give it a trial, but you can't say you weren't forewarned.

How long have you taken it rol? At the start it does make you feel completely retarded but nearly everyone reports to be side effect free after the adaptation phase.

I took it for several months, at a peak dose of 24 mg/day.

What side effects did remain for you? I gues brainfog that wouldnt go away? I do think you generalise too much as most ppl found memantine a good med without much side effects, some cant tolerate it, including a good friend of me, however that usually doesnt appear to be the case.

The cognitive side effects were most worrisome, but they're quite subtle---but unmistakable.

I agree that with memantine there can be suble cognitive side effects, but thats also the case with meds like lamictal and other mood stabilisers, so i really dont see a justified reason to dislike memantine like that, atleast you seem really against it.

Yeah, but subjectively speaking, the adverse effects of Memantine were more appreciable.

[Rain]

Is it normal to feel crash after nicotine wears off? I've taken it a couple of times now, and the next day i felt so exhausted, but was fine as soon as i had more nicotine, i'm only using 3.5mg patches.

[tommix]

In my very friendly opinion-those who smoke - should be killed instantly.
We don't give a shit about your healthy, who smokes, but we care about our, who don't. I'm glad that almost in all europe smoking is very restricted in public places.

Smoking near to non smoker is THE SAME, as the non smoker will pee and your head, just remember that smokers. You're killing your kids, you caring those 2000 toxic shit with you all day in your mouth and breathing to the same room where your kids live. So you're bad parents too.

[health_nutty]

In my very friendly opinion-those who smoke - should be killed instantly.
We don't give a shit about your healthy, who smokes, but we care about our, who don't. I'm glad that almost in all europe smoking is very restricted in public places.

Smoking near to non smoker is THE SAME, as the non smoker will pee and your head, just remember that smokers. You're killing your kids, you caring those 2000 toxic shit with you all day in your mouth and breathing to the same room where your kids live. So you're bad parents too.

Interesting opinion, but seems completely irrelevent to this thread which has nothing at all to do with smoking.

[caruga]

Just tried nicotine for the first time--half a piece of 2mg nicotine gum (equivilent to 1 mere cigarrette?). The response was incredibly strong, but possibly not in a good way. I experienced intense euphoria and a kind of finger-snappy hyperactiveness. I feel much too hyper to concentrate, but if I could school this feeling and channel it it has the potential to be very productive. Right now I can barely settle down enough to write this. Will try a quarter piece tomorrow!

[aLurker]

Just tried nicotine for the first time--half a piece of 2mg nicotine gum (equivilent to 1 mere cigarrette?). The response was incredibly strong, but possibly not in a good way. I experienced intense euphoria and a kind of finger-snappy hyperactiveness. I feel much too hyper to concentrate, but if I could school this feeling and channel it it has the potential to be very productive. Right now I can barely settle down enough to write this. Will try a quarter piece tomorrow!

Go for the patches instead, both safer and smoother. Start with a low dose, it takes about 40 min before it kicks in with the patches though.

P.S. Since my most recent posts in this thread are about memantine I'll just say that the cognitive side effects were way too bothersome for me to continue taking it so I quit after a mere dozen days or so. One might argue that I was still adapting to it but I simply couldn't stand it any longer. D.S.

Edited by aLurker, 16 May 2011 - 10:59 AM.