1565 replies to this topic

[Babychris]

you mean 10 nM/L of blood ?

[niner]

Hi guys. Figuring out how to hit a particular concentration is going to involve some guesswork. For a quick back-of-the-envelope calculation, people often start with 5 liters as the "volume". That's an estimate for adult blood volume. If you were to inject the drug intravenously, that would be sort of reasonable. If you take it orally, then you should add in the volume of the GI tract, or at least some amount of it. Sunifiram has a logP of 1.05, which means that it partitions about equally between water and the lipid component of the body. This should further increase the volume that we consider, since it will essentially go everywhere. I've seen total body water estimated as 42 liters, and if we were to add a little bit for lipids, 50 liters is probably safe. This doesn't take things like cell or protein binding into account, which could alter levels a lot, but sunifiram doesn't look very sticky to me. So...

10nm/liter * 50 liters * 246ng/nm = 123000ng. That's 123 ug, or 0.123mg.

That's a pretty small dose. I have no idea what the half life of sunifiram is, but it looks like it has pretty good PK. If you took an eighth of a milligram, you might be in the vicinity of 10nM at the peak concentration (Cmax), but then you would start falling off. The goal would be to spend as much time as possible near 10nM; some time over 10, and some time under 10, but never so far away that you lose the LTP effect. Ideally, you would reach a steady state concentration where the amount that you added from repeated doses balanced the amount that you lost from drug metabolism/elimination. I think you would probably want to dose a little higher; maybe a quarter mg, but exactly how often to dose is hard to say. In a mouse experiment ( http://www.ncbi.nlm....pubmed/12070754 ), the oral doses they used ranged from .01 to .1 mg/kg. We typically scale mouse doses by 1/12 when converting to human doses, so a 70kg human would get 70/12 *0.01 = 0.06 to 0.6mg, which is in the range I've guesstimated here. The time between doses would depend on the half life, which we don't know. Even at that, it's hard to say exactly how the dosing interval should relate to the half life, other than to say that it should be greater than one half life. Maybe several half lives.

At any rate, it looks like less is more with this compound. I'd probably try a quarter mg a couple times a day as a starting point. Do we have any good metrics for LTP? Without drawing blood and measuring concentrations, that's probably the best way to get a handle on the right dosing strategy.

[Isochroma]

Your theory doesn't match up to reality.

Instead of consuling some abstract studies and formulas how about reading peoples' experiences on this thread with different doses?

You're get much more relevant dose data that way then trying to box-in the immense complexity and variability of the human body and brain with those formulae.

Edited by Isochroma-Reborn, 14 June 2013 - 02:48 AM.

[Sun Nootropic]

looking forward to Coluracetam

[abelard lindsay]

Yes, since this study, for what it's worth, I am now coming to believe that my side effects are due to NMDA receptor oversensitization or overexpression, and not so much having to do with the AMPA receptor excesses as I previously believed. Am I on the right track? I know, I'm just speculating either way. I will be reading the studies and testing this new theory with NMDAR (NMDA receptor) affecting drugs as necessary over time. Thanks.

If you want to prevent NMDA over-activation, you might want to look at magnesium threonate:

http://www.ncbi.nlm....pubmed/23658180

MgT treatment reduced Aβ plaque and prevented synapse loss and memory decline in the Tg mice. Strikingly, MgT treatment was effective even when given to the mice at the end stage of their AD-like pathological progression.

At the molecular level, elevation of extracellular magnesium prevented the high-Aβ-induced reductions in synaptic NMDARs by preventing calcineurin overactivation in hippocampal slices.

Also, Idebenone has some good evidence that it can help prevent excitotoxicity.

http://www.ncbi.nlm..../pubmed/7824194

The novel free radical scavenger and electron-trapping agent, idebenone, protects cultured cortical neurons against necrotic degeneration induced by either a brief exposure to N-methyl-D-aspartate (NMDA) or a prolonged exposure to kainate. As opposed to the NMDA receptor antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]- cyclohepten-5,10-imine hydrogen maleate (MK801), idebenone rescued cortical neurons even when applied 30 min after the NMDA pulse, suggesting that the drug interferes with the chain of toxic reactions triggered by an excessive stimulation of excitatory amino acid receptors.

Edited by abelard lindsay, 14 June 2013 - 05:10 AM.

[Isochroma]

Qiubai: Will your company be selling Coluracetam soon?

[Hope47]

Took full scoop(provided by newstar) of sunifiram. Let's see what happens.

[3AlarmLampscooter]

I've been on Sunifiram for the last three days, and I can report it has definite cognitive enhancing properties.

My first dose of 5mg, my forward digit span increased from 12 to 15 and reaction time dropped from 252 to 220ms.

I've since tried doses up to 12mg, and thus far have had no adverse reactions. I've taken each dose with 300mg Centrophenoxine and (except the first one) 800mg Oxiracetam.

[Raza]

niner = awesome.

I'm going to try the 250µg dosing. 2-4mgs gave me negatives (a weird feeling in the head and possibly mood fluctuations later in the day, slightly increased impulsivity; not conductive to studying or practicing anything), so this is good news for me.

Now lets see if this stuff will dissolve in propylene glycol, 'cause I don't think weighting individual doses is going to work here.

Edited by Raza, 14 June 2013 - 08:49 AM.

[Babychris]

I need Coluracetam tooooo ! If someone (looking for isochroma :p) could give me the way to a legit seller, I would be grateful in some parts on my brain, and my soul.

[Rudy]

I need Coluracetam tooooo ! If someone (looking for isochroma :p) could give me the way to a legit seller, I would be grateful in some parts on my brain, and my soul.

Have you tried coluracetam before?
If you did for how long?

[Mr. Pink]

After reading all this the conclusion is that you must avoid this substance by all possible and impossible means.
1. Effect is not permanent - 5 days of euphoria and after that nothing substantial
This can be a sign of brain damage intentionally put by the "developers" into this shit to wash out the remnants of our brains.
2. No dual n-back tests proving better memory and thinking (unlike this substance CILTEP allowed me to immediately come to the 7th level of n-back which I had not been able to reach before)
3. Most of the thread is commerical promo like "i felt this or i felt that". This is just a sign of its psychedelic property. If you have exciting feelings your logical mind is switched off. We call that placebo in a scientific way.
4. What we try to achieve is intensification of the logical (mathematical) part of mind. It does not matter if you operate with words or numbers. Memory is the basis for all this but is not the only thing needed for it. What is needed is improvement of the left hemisphere switched off by the mass culture, upbringing, bad food and drugs, other satanic shit. So -
there no evidence (tests, results) proving improvement of functioning of the left hemisphere. THE RIGHT nootropic MUST PROVIDE improvement or UNBLOCKING of the definite brain areas (in the left hemisphere) responsible for word formation/counting operations. THERE IS NO A SINGLE TEST proving that the substance in question has any positive influence on that. ALL THE TALK IS ABOUT AVAILABILITY OF DIFFERENT CHEMICALS IN THE BODY which ARE SUPPOSED to be improving thinking.

i'd like to address 2, 3 and 4.

2. there's a lot of conflicting evidence about whether exercises like n-back actually transfers to tasks outside of the game. Also, n-back is more short term memory not LTP (anything longer than the few seconds). so i'm trying to get better at memory for exams, n-back doesn't mean anything to me because that's not an area of weakness (though for others it may be, given their abilities and the demands placed upon them). i just need memory. real memory (for more than a few seconds).

as to CILTEP: i found that stack to be good for motivation, but it negatively effected my memory, attention, and hence, logical thinking. it was created by someone with ADD, who is used to taking amphetamines. i can see how it is a good, safer alternative to amphetamine (people describe it as "adderral light"). however, just the claim of improving LTP, comes from a logical inference from mechanisms of action. The whole point of scientific experimentation is that logical validity isn't reliable (just because something should work a certain way because of a certain proven mechanism, doesn't mean it does in a complex biological system. (even if it helped your n-backing, that doesn't PROVE CAUSATION unless you actually performed a well controlled single subject experiment on it; my guess is you likely did a case-study - baseline phase and then intervention phase and nothing more).

3. there's research to suggest that memory and feelings are extremely related to memory. the more intense the emotion, the longer you remember the event, for example. i've experienced this effect every time i've studied.

4. again, disregarding the incredible effect of emotions on memory. i've got ridiculous logic skills which are far beyond the demands that life places on me, but my memory skills are far behind.

tl;dr: i'm not claiming sunny is good. just arguing that your premises are not logical.

[8bitmore]

niner = awesome.

I'm going to try the 250µg dosing. 2-4mgs gave me negatives (a weird feeling in the head and possibly mood fluctuations later in the day, slightly increased impulsivity; not conductive to studying or practicing anything), so this is good news for me.

Now lets see if this stuff will dissolve in propylene glycol, 'cause I don't think weighting individual doses is going to work here.

Any luck with the propylene glycol? Otherwise (found via Ampakines!? thread) I think water will prove quite a good idea for dissolving Sunifiram (DM-235). I am very interested in prospect of these micro-doses since I am personally non-respondent to the 5-20mg range. Ketamine, for example, proves that micro-doses can work VERY differently as compared to larger doses. Also, this is by no means trying to downplay the practical-intake doses found by Isochroma & co; it might merely suggest that different people need very different approaches/doses when it comes to Sunifiram.

[Greek86]

Just to quickly add to the thread. This morning after 9hrs sleep( which is oversleeping for me), I had a egg's and orange juice breakfast and continued to do my luminosity for the day without any supplementation. Afterwards I took a Multi-V, 900mg Omega-3 and 10mg Sunifiram. I have been taking 5-10mg 3 times per day for the last 4 days. Anyways, I went back and replayed a variety of games in Lumosity and here were my results and qualitative feelings on sunifiram:

-Games improved from previous play today but not by much
- I was in the top 5 for most of the games I played but not all
-I feel al little more motivated that earlier this morning.
-There is a slight pressure on my temples.
-I feel ADDish or Foggy minded. Im not sure what this is but i get it all the time on Sunifiram. Right now is particularly bad as I have proof read this and found some awful mistakes. Any suggestions on how to eliminate this?

Here are my general qualitative feelings on Sunifiram so far during my 4-7 day trial:

- I certainly feel that Sunifram gives me more energy for the day but as for a cognitive improvement, which is always hard to gage, I don't think it does that. It might even be impeding...
- I feel more refreshed in the mornings on less sleep. Not all morning but some of them.
- I have pushed myself harder in my work-outs. I'm not in very good shape, so don't take that a sign of anything significant.
-I find I can stay up later and be active longer, which i haven't been able to do since university.
- I'm not much of a drinker but I took it b4 going out and had four drinks( Canadian drinks - 1oz /drink) throughout the night. I was considerably buzzed but i don't drink very much and I would probably have been tipsy anyways. The next day I slept 11hrs and was considerably lazier than normal.
-Currently my hands and feet are cold, which is a sign of poor circulation.
- I have never experienced the vibrant colours that every speaks about on this drug. I have experienced that the first few times i tried piracetam over a year ago.
Just for some better context into my situation: In the past i have mixed it with the following: 30mg coq10,10mg pqq , up to 900mg omega-3's, 300mg Resveratrol, Uridine, TAU, AGPC, ALCAR and alcohol up to 4oz over the course of a night.

A bit about me:

I have tried all the major Racetams out there with the exception of nefiracetam. Personally, they all had something to offer(except for phenylracetam) but the effects for me were inconsistant and wore off. I also tried Noopept, which I also didn't experience any positive effects from. My favourite is Piracetam for presentations at work. I use a combo of ani+oxi for socializing and Pramiracetam for a stronger focus. I find all of them with the exception of Pramiracetam to exacerbate my ADD, as even typing of my office-mate is can become distracting. Unfortunately, my other challenges with racetams are 2 fold; the effects are inconsistant and I can't get the dosage right. As already mentioned, I have ADD and I have been prescribed Vyvanse but I have been trying to completely rid myself of the need for these stimulant drugs, which do really help with my functionality but are clearly not very healthy for everyday use. I find Vyvanse is a super-motivation/focus style drug with a boost in creativity at first but as the day progresses i feel dummer and my working memory falls of a cliff. Also, when I go back to my work it looks rushed, sloppy and lazier with primitive mistakes. Anyways, enough about my experimentations with nootropics, this is about Sunifiram.

Cheers,

[Babychris]

Coluracetam seem more promising than sunifiram. Let see this..

[3AlarmLampscooter]

Having not taken any Sunifiram yesterday, I felt a bit tired/out of it in comparison to baseline. Could have been a coincidence, or not. I took 10mg again today and felt effects similar to previous doses.

Another friend of mine tried 5mg and reported mild anxiety after the dose wore off, but positive effects "similar to adderall"

[andrea23]

but positive effects "similar to adderall"

what positive effects?

[RawProduce]

OK, all this crap about Sunifiram excitotoxicity or whatever-the-fuck has got to stop.

I went all guinea pig in the name of science and performed an experiment.

75mg Sunifiram, 1200mg modafinil with a 400mg booster several hours later with around 30mg noopept, maybe 1-2g of Lemon Balm, about the same amount L-Theanine and magnesium and calcium - all split over several doses.

No tinnitus, no head pressure, it's been over a week since I did this.

Get a new theory.

Edited by RawProduce, 17 June 2013 - 03:58 AM.

[Isochroma]

Thanks for taking the risk & time to check it yourself.

I was getting a bit nervous about adding Phenylpiracetam to my Sunifiram and now I am assured.

Modafinil / Armodafinil / Adrafinil are still out though - mostly because I don't like stims.

[golden1]

methamphetamine is notably neurotoxic and it's not like you can tell after one dose. well, I've never tried methampehtamine, but logically(from my experience with mdma/amphetamine/4-f-amphetamine/2-fma/benzo withdrawal/etc) I doubt you could tell after one dose.

just saying things can damage your brain and it won't be noticeable.

I personally don't think sunifiram is bad in this area though, but the above isnt really evidence. Not to mention people's brains differ greatly as does their health, genes, and nutrition and therefore their body's ability to deal with such stress.

[Sunwind]

What do you guys have to say about the cancer risk on Wikipedia? I'm far too stupid to understand all the chemistry and the scientific sources that are listed, but brain cancer or something isn't something I want from my Nootropic stack..

[golden1]

What do you guys have to say about the cancer risk on Wikipedia? I'm far too stupid to understand all the chemistry and the scientific sources that are listed, but brain cancer or something isn't something I want from my Nootropic stack..

oh god, that is new. thanks for the heads up, I don't have time to decipher it, but I'm sure someone can who has more of a reason to(I don't really take sunifiram often, I'm holding on to it.. for possible future use).

[Climactic]

OK, all this crap about Sunifiram excitotoxicity or whatever-the-fuck has got to stop.

I went all guinea pig in the name of science and performed an experiment.

75mg Sunifiram, 1200mg modafinil with a 400mg booster several hours later with around 30mg noopept, maybe 1-2g of Lemon Balm, about the same amount L-Theanine and magnesium and calcium - all split over several doses.

No tinnitus, no head pressure, it's been over a week since I did this.

Get a new theory.

This is very good to know, but L-theanine is known to be protective and presumably lemon balm too. Clearly you're taking them at these high doses for a reason. I don't presume you'd dare repeat the experiment limiting the L-theanine to 200 mg and the lemon balm too. (I personally recommend you don't.)

[zongler007]

i dont see this earlier too, can somone write more about this cancer ? i dont think that i can alone understand procces and i feel a lil bit scared...

[ThePhoeron]

What do you guys have to say about the cancer risk on Wikipedia? I'm far too stupid to understand all the chemistry and the scientific sources that are listed, but brain cancer or something isn't something I want from my Nootropic stack..

oh god, that is new. thanks for the heads up, I don't have time to decipher it, but I'm sure someone can who has more of a reason to(I don't really take sunifiram often, I'm holding on to it.. for possible future use).

Yeah, I just noticed that today as well, while working on a blog article on various nootropics (not yet published), including Sunifiram. It seems that the suggestion of cancer risk is specifically as a result of overstimulation of NMDA glutamate receptors through activation of the protein kinase C alpha, one of the primary mechanisms of action in the brain of sunifiram. That's the excitotoxicity.

I guess the question is, what's the dosage amount and frequency that causes excitotoxicity? Due to the bell-shape dose--response relationship, calculating this might be tricky. Since I'm only 140lbs, I should probably be sticking to doses less than 5mg. That being said, I do want to be as bold as Isochroma-Reborn and RawProduce and do a trial of high doses of sunifiram 3--4 times daily for 14 days, just to see.

From my own experience so far, as others also pointed out, lower doses have been more effective anyway. The days where I took 7--10mg of sunifiram three times daily, I always got brain fog and fatigue two hours after sublingual ingestion, which would peter off for about half-an-hour to an hour (longer the higher the dose). The two hours immediately after the dose were positive and effective. However, the days where I took 3--5mg three times daily, I only noticed the positive effects of sunifiram without any brain fog or fatigue. Since my stack is a little complex right now, particularly with the Epiphany D1s and EPIQ Piracetam Complex, I had to adjust the amounts of everything on different days to make sure it was the sunifiram doing this and not one of the others.

Of course, Isochroma-Reborn has mentioned that sunifiram is better taken orally rather than sublingually, so I have acquired a variety of colour-coded capsule sizes to package my stacks for oral ingestion. Out of curiosity, what are people using as fillers when making capsules? I won't need fillers for my full custom stack, that I described in a previous post, but if I want to make capsules for just sunifiram or noopept it would probably be useful to cut the tiny doses with something inert and easily digestible.

In other news, finally got my diamond scale so I actually know exactly how much sunifiram I'm taking now. Also put in my big order to New Star and it already shipped---I might have gone overboard a little bit... ordered half a kilo of piracetam, 100 grams oxiracetam, 20 grams noopept, and 10 grams sunifiram. That should keep me stocked up for the summer.

[Climactic]

It seems that the suggestion of cancer risk is specifically as a result of overstimulation of NMDA glutamate receptors through activation of the protein kinase C alpha, one of the primary mechanisms of action in the brain of sunifiram. That's the excitotoxicity.

Not quite the excitotoxicity. As far as I can tell, the two are wholly different concerns. When real excitotoxicity occurs, the neuron kill itself via apoptosis - there is no opportunity for cancer there. Per my understanding, the risk of cancer stemming from PKCa is unrelated to any risk of excitotoxicity, even though both NMDAR binding and the risk of cancer are elevated by PKCa.

Also note that the PKCa article itself has mentioned cancer for a long time now. The paragraph offers some explanation too.

Edited by Climactic, 17 June 2013 - 05:41 AM.

[ThePhoeron]

It seems that the suggestion of cancer risk is specifically as a result of overstimulation of NMDA glutamate receptors through activation of the protein kinase C alpha, one of the primary mechanisms of action in the brain of sunifiram. That's the excitotoxicity.

Not quite the excitotoxicity. As far as I can tell, the two are wholly different concerns. When real excitotoxicity occurs, the neuron kill itself via apoptosis - there is no opportunity for cancer there. Per my understanding, the risk of cancer stemming from PKCa is unrelated to any risk of excitotoxicity, even though both NMDAR binding and the risk of cancer are elevated by PKCa.

Also note that the PKCa article itself has mentioned cancer for a long time now. The paragraph offers some explanation too.

Fair point—I'll take the time to study the Excitotoxicity and PKCa articles a little closer. The brief, ambiguous statements under the "Safety" section made it seem as if they were linked, but as you said that might not be the case. I only vaguely remember reading something about apoptosis once, a while ago, so that's worth further study as well. We really do need some formal human studies for sunifiram though.

[owtsgmi]

I think water will prove quite a good idea for dissolving Sunifiram (DM-235). I am very interested in prospect of these micro-doses since I am personally non-respondent to the 5-20mg range.

I now dissolve about 10mg (a micro-scoop) of Sunifiram into a water bottle. I drink about a third of the bottle each morning and the effects are pretty consistent and good. I write "suni" on the cap so as not to confuse it with other water bottles. This is a great way to administer this stuff. When I take too much, I get brain fog, but taking a choline source usually clears it up pretty quickly.

[Q did it!]

I think water will prove quite a good idea for dissolving Sunifiram (DM-235). I am very interested in prospect of these micro-doses since I am personally non-respondent to the 5-20mg range.

I now dissolve about 10mg (a micro-scoop) of Sunifiram into a water bottle. I drink about a third of the bottle each morning and the effects are pretty consistent and good. I write "suni" on the cap so as not to confuse it with other water bottles. This is a great way to administer this stuff. When I take too much, I get brain fog, but taking a choline source usually clears it up pretty quickly.

Yes I have been doing the same for a while now too, it works well. I also dissolve many of my water soluble sups into my water and drink it throughout the day (I keep an up to date list of my regimen on my profile page). I have dropped SUNIFIRAM do to it just not setting with me right. It for me does not contribute towards the end effect I am looking for in Nootropics. It is still taken every now and then as a recreational noot.

[Sunwind]

is it difficult to weigh <10mg sunifiram with this scale?