6 replies to this topic

[chung_pao]

Hello

I'm interested in Nootropics which doesn't cause tolerance.
Nootropics that you could be taking daily, 7 days a week, without dysregulation of the affected mechanism.

On this board, people often refer to the racetams as having a "cumulative effect".
I find this is true for me, which is why Piracetam is one of my favourites.

But please help me add to this list of Nootropics.

With a spontaneous lifestyle, you often can't play when you'll need to be at your best.
And besides, dysregulation such as abstinence is always a bitch. I've had the worst pains of my life during withdrawal from Adderal and caffeine.

What nootropics have you found to be useful without causing you to feel like shit the following day?

For me, it's been:

Huperzine A
Modafinil (only side effect is lack of parasympathetic activity and deep sleep, due to the 15 hour half life)
Piracetam
Alpha GPC
Curcumin (I find it has mao A/B inhibitory qualities)
Vinpocetine

I'm especially interested in a substitute for caffeine; such as MAO-B inhibition or simply increasing dopaminergic activity.
And unfortunately, none of the above have a direct effect on dopamine release (from what I understand).

Have anyone had experience with Sulbutiamine?
It's said to "reduce the release of dopamine from D1 dopamine receptors in the PFC, which causes the receptors to increase in density and number due to a mechanism of supercompensation"
Do you find this accurate?

What Nootropic have you found to have cumulative effects, and can be used without withdrawal/build-up of tolerance?

Edited by chung_pao, 24 December 2012 - 06:30 PM.

[Dissolvedissolve]

Sulbutiamine is an interesting chemical. I find it quite motivating and slightly energizing, with a bit of tiredness and a pretty reliable headache when it wears off. It synergizes quite well with caffeine, with caffeine providing energy and sulbutiamine motivation.

I'd beware of going from the study data on its dopaminergic effects. Its acute effects "feel" dopaminergic (apologies for the anecdotal evidence). Its pharmacology as a whole is quite complex, and the fact that it's two disulfide linked B1 molecules does not mean that enhancement of B1 activity is its route of action. Even if it is, the fact that it crosses the BBB means that it is, to some extent, bypassing your brain's typical homeostatic mechanisms for B-vitamins. Although it would seem to improve in the long run based on that single DA upregulation study, it actually has tolerance and withdrawal for most people, like every other stimulant I know of (other than perhaps modafinil, but modafinil is a very complex drug).

Here's some reading:
http://www.longecity...-and-tolerance/
http://www.drugs-for...ad.php?t=101487

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And I guess I'll go ahead and mention piracetam and noopept as the only nootropics I've found to be helpful on an extended basis. Noopept in particular makes me "feel smarter" even when I am not on the active part of my cycle. I don't notice any acute effects from magnesium or fish oil, but those seem to be pretty well-supported in the long-run, so I take those as well.

Edited by Dissolvedissolve, 24 December 2012 - 08:15 PM.

[renfr]

I'm not sure there are nootropics that don't build tolerance overtime. Most of receptors/enzymes get downregulated or upregulated if you ingest an agonist or an antagonist.
However there are very few receptors that doesn't have negative feedback response, an example is nicotinic receptors which upregulates when activated with nicotine but that is one rare exception.
The best thing to do is have some days off or substitute with other substances that do not cause cross tolerance.
For example for anxiety you could take a serotonin agonist and then change from time to time with a GABA agonist.
Even with cholinergics there is tolerance however there's no tolerance for some of their benefits such as supplying phospholipids to the brain to keep in good health the myelin sheath around axons.
Last time I went cold turkey from soy lecithin (10g a day for a bit more than one month), I had mild acetylcholine upregulation symptoms.

[machete234]

Although it would seem to improve in the long run based on that single DA upregulation study, it actually has tolerance and withdrawal for most people, like every other stimulant I know of

Dopamine reuptake inhibitors dont exactly have a withdrawel but I felt unmotivated to say the least after 1 month of heavy consumption and then stopping.
I needed at least 1 month without the drug to feel my normal level of motivation, joy of life etc
The chemical in my case was ethylphenidate.

A different story could be NE and DA releasers like amphetamines, there could be actually kind of a withdrawel.

And I guess I'll go ahead and mention piracetam and noopept as the only nootropics I've found to be helpful on an extended basis.

Im getting more interested in noopept.
Would you say that if piracetam worsens my mood that noopept could do the same?
Aniracetam had a more positive effect on my mood or at least didnt make it worse.

Edited by machete234, 24 December 2012 - 09:03 PM.

[Dissolvedissolve]

I'd like to respond, and hopefully this won't derail the topic.

Obviously amphetamine is more potent than methylphenidate and other NDRIs. Withrawal may be more pronounced for amphetamine than methylphenidate/ethylphenidate since it's both a releaser and reuptake inhibitor. That said, there's definitely tolerance and withdrawal with NDRIs. You report what seem to be withdrawal symptoms from ethylphenidate, another NDRI, and then say there is no withdrawal. That seems strange to me.

Here's what a quick google search turned up - downregulation of postsynaptic dopamine receptors in response to therapy with methylphenidate. I have no doubt you could find many other, better studies, but it shouldn't be necessary:

Adults' class='bbc_url' title='External link' rel='nofollow external'>http://www.ncbi.nlm.nih.gov/pubmed/12776228']Adults suffering from Attention Deficit Hyperactivity Disorder (ADHD) are known to have disturbed central dopaminergic transmission. With Single Photon Emission Computed Tomography (SPECT) we studied brain dopamine transporter and receptor activity in six boys with ADHD. Three months after initiation of treatment with methylphenidate we found a down-regulation of the post-synaptic dopamine receptor with a maximum of 20 % and a down-regulation of the dopamine transporter with a maximum of 74.7 % in the striatal system. This corresponded to a positive clinical response evaluated by neuropsychological questionnaires and tests. We suggest that dopamine transporter imaging by SPECT might be used to monitor psychostimulant treatment in children suffering from ADHD.

→ source (external link)

[chung_pao]

I'd like to respond, and hopefully this won't derail the topic.

Obviously amphetamine is more potent than methylphenidate and other NDRIs. Withrawal may be more pronounced for amphetamine than methylphenidate/ethylphenidate since it's both a releaser and reuptake inhibitor. That said, there's definitely tolerance and withdrawal with NDRIs. You report what seem to be withdrawal symptoms from ethylphenidate, another NDRI, and then say there is no withdrawal. That seems strange to me.

Here's what a quick google search turned up - downregulation of postsynaptic dopamine receptors in response to therapy with methylphenidate. I have no doubt you could find many other, better studies, but it shouldn't be necessary:

Adults suffering from Attention Deficit Hyperactivity Disorder (ADHD) are known to have disturbed central dopaminergic transmission. With Single Photon Emission Computed Tomography (SPECT) we studied brain dopamine transporter and receptor activity in six boys with ADHD. Three months after initiation of treatment with methylphenidate we found a down-regulation of the post-synaptic dopamine receptor with a maximum of 20 % and a down-regulation of the dopamine transporter with a maximum of 74.7 % in the striatal system. This corresponded to a positive clinical response evaluated by neuropsychological questionnaires and tests. We suggest that dopamine transporter imaging by SPECT might be used to monitor psychostimulant treatment in children suffering from ADHD.

→ source (external link)

It is these effects that are starting to scare me.
After my weeks on caffeine and bupropion I was convinced that my dopamine regulation was scarred for life; but it turned out well.

The body is a homeostatic machine. If you induce hormesis and disrupt homeostasis, it responds with the opposite effect of the stimulus.
For example, breaking down MAO by using MAO-inhibitors should, by this logic, cause the body to respond with elevated levels of MAO.
The effect of recovery and supercompensation is well documented for most mechanisms of the body.

That is why I think we should be more attentive to the mechanisms of the Nootropics we use. At least I am.

I've decided to try out a few new ones in search of favorable nootropic mechanisms that will enhance my performance, in the long haul.

Noopept, Sulbutiamine, Pyritinol, High dosing resveratrol (0,5g-1g), Alpha GPC.

From what I've read, Alpha GPC seems to be a pure benefit-only supplement. It's built on the basis that it supplies essential nutrients and building blocks, not stimulants of the body's mechanisms.

Please name the one that you have found useful in the category: Beneficial nootropics without tolerance.
This way, me and other people can avoid making mistakes destructive to our mental health, quality of life and personal economies.

Edited by chung_pao, 25 December 2012 - 02:00 AM.

[machete234]

You report what seem to be withdrawal symptoms from ethylphenidate, another NDRI, and then say there is no withdrawal. That seems strange to me.

Withdrawel for me is a very unpleasant opiate, alcohol, benzo withdrawel that is potentially life threatening being a bit down is not such a strong withdrawel for me.

For example people report mood swings when quitting pot but the substance itself is practically not physically addictive.
So I guess Im associating withdrawel with the more physical addictive substances.