1565 replies to this topic

[manic_racetam]

Hey guys,

If anyone wants my 988mg (what's left after I took 2x 6mg) of sunifiram, PM me. I get skin itching and increased body temperature without any noticeable cognitive improvements whatsoever and I my intuition tells me that I should not take it anymore.

I bought it from NSN.

Cheers

My intuition told me the same thing. I tried it 2 or maybe 3 times and trashed the rest.

[KoolK3n]

Unitedpharmacies sells it also, no prescription required. I've been very impressed with them, thus far I've gotten propranolol and oxytocin both of which were delivered fairly fast, and at pretty great prices.

They are definitely my favorite online pharmacy at the moment.

http://www.unitedpha...tring=Donepezil

Naw. Unitedpharmacies has been receiving some HORRIBLE rep the past couple years, not to mention the prices being way to steep. Look at the prices at AllDayChemist: https://www.alldaych...lt/?q=donepezil. Way more affordable and more reliable.

[xsiv1]

Unitedpharmacies sells it also, no prescription required. I've been very impressed with them, thus far I've gotten propranolol and oxytocin both of which were delivered fairly fast, and at pretty great prices.

They are definitely my favorite online pharmacy at the moment.

http://www.unitedpha...tring=Donepezil

Naw. Unitedpharmacies has been receiving some HORRIBLE rep the past couple years, not to mention the prices being way to steep. Look at the prices at AllDayChemist: https://www.alldaych...lt/?q=donepezil. Way more affordable and more reliable.

Once ADC stopped taking CC, I discontinued using them and then, out of nowhere, they call me on my cellphone lol! At work no less. I'm like, "uh, er, not interested" click. Not that I was ordering anything scheduled per se but didn't think they'd go out and call someone because they logged out and didn't purchase through their means. Meh.

Also, as an aside, I've not experienced any itching with the use of Modafinil although I don't use it very often and in only 100mg doses. I've yet to try my 4 grams of Suni since, well, I'm kind of scared to be honest lol. I don't want to combine it with anything and I'm not really into the idea of using more than 2x a day. I'll gather more info as it comes in assuming the stuff doesn't expire for at the very least, a year. I've got 2 from NSN and 2 from LM. I'm assuming they've used the same supplier. I'm also a tad concerned about the actual quality and whether or not it's contaminated. There haven't been many glowing reviews as of late in this thread.

Have those who've initially responded positively to Suni discontinued for any reason that's related to it's side effect profile or even it's efficacy? I know we've got a few people here who are experiencing significant residual adverse effects but I'd like to hear from anyone who has responded early on in this thread about it.

Edited by xsiv1, 10 July 2013 - 09:59 PM.

[Climactic]

Once ADC stopped taking CC,

They do take Visa. I use a disposable number. After you place the order, you have to send the card# to them via the contact form on their site. Their website has changed now, so I don't know how the change affects this order placement.

I got my most recent package from them in 4 days after they shipped it.

I was about to discontinue sunifiram for being subjectively unreliable in its observed effects.

Edited by Climactic, 10 July 2013 - 10:01 PM.

[rikelme]

Skin itching? I had that but I assumed it was histamine release from modafinil, are you sure it's the Sunifiram? I haven't taken either of them since I got the itching, but it would be nice to find out it wasn't the Moda, because that was useful for me.

Yeah, more like tingling than itching. It happened two days in a row, about an hour I took it. First time, I thought, was just a coincidence, but when it happened again tomorrow, I was pretty sure it was sunifiram.

[xsiv1]

Once ADC stopped taking CC,

They do take Visa. I use a disposable number. After you place the order, you have to send the card# to them via the contact form on their site. Their website has changed now, so I don't know how the change affects this order placement.

I got my most recent package from them in 4 days after they shipped it.

I was about to discontinue sunifiram for being subjectively unreliable in its observed effects.

Once again helpful info man. Appreciate that. I've got a personal CC but have reduced the limit on it so that it's pretty low. Perhaps I should consider just going out and buying a disposable anyways. My "slush fund" CC is limited to 1G. No way in hell I'd give them my regular ones - was always under the impression that if the card was used upto 1000 and then beyond, it'd be declined and I could talk Visa out of their purchases since I'm assuming they'd be able to know where a purchase was made. Hmm, better safe than sorry I suppose. Thanks again C.

[rikelme]

Hey guys,

If anyone wants my 988mg (what's left after I took 2x 6mg) of sunifiram, PM me. I get skin itching and increased body temperature without any noticeable cognitive improvements whatsoever and I my intuition tells me that I should not take it anymore.

I bought it from NSN.

Cheers

Gone.

[xsiv1]

Skin itching? I had that but I assumed it was histamine release from modafinil, are you sure it's the Sunifiram? I haven't taken either of them since I got the itching, but it would be nice to find out it wasn't the Moda, because that was useful for me.

Yeah, more like tingling than itching. It happened two days in a row, about an hour I took it. First time, I thought, was just a coincidence, but when it happened again tomorrow, I was pretty sure it was sunifiram.

Aside from the itching, did you notice anything positive about it or any other unwanted side effects?

[rikelme]

Aside from the itching, did you notice anything positive about it or any other unwanted side effects?

Yes, increased body temperature. Not pleasant feeling overall, like my body was trying to communicate back to me that whatever I took is not doing anything good. No noticeable positive effects at all. I usually do mental multiplication of two two-digits number higher than fifty in my head and measure the time I can finish it as a benchmark to see if some nootropic works for me or not. My long term established baseline time is 19.5 seconds. Average of 50 multiplications on sunifiram - 19.7 seconds. So, at least for this task sunifiram doesn't help. For comparison, when I started taking NADH + methylcobalamin I reduced the time significantly, to the 15 - 16 seconds range.

[Introspecta]

I initially responded great then my next trial didn't enjoy the effects. First time the positive effects lasted about 5-7 days then I started to feel my blood pressure rising and was having trouble sleeping. The second time I felt the rise in blood pressure right off the bat. Kind of dissapointing. I may try again in a few months but I didn't get much for cognitive effects. My first time I was euphoric, talkative, increased color perception, clear headed. Second time I was maybe a little extra stimulated but thats about it. Kind of strange.

[jly1986]

I initially responded great then my next trial didn't enjoy the effects. First time the positive effects lasted about 5-7 days then I started to feel my blood pressure rising and was having trouble sleeping. The second time I felt the rise in blood pressure right off the bat. Kind of dissapointing. I may try again in a few months but I didn't get much for cognitive effects. My first time I was euphoric, talkative, increased color perception, clear headed. Second time I was maybe a little extra stimulated but thats about it. Kind of strange.

joelski28,
What was your dosage?

[Introspecta]

Dosage ranged from 10-50mgs three times a day. I was careless with dosing in the beginning but seemed to have best results that way but only short lasting. My second time I was more cautious and used 10mgs 3times a day which some may still say is high but no effects are noticed when dosing lower.

[Isochroma]

It's time for my report - a very important one indeed.

First, I am on the following: 25mg Sunifiram x 6/day + 500mg Oxiracetam x 6/day.

Today I received my 5g Methoxetamien (MXE) direclty from a Chinese chemical company with 98% purity.

I have zero tolerance and experience with dissociative arylcyclohexylamines (Ketamine, PCP, MXE, etc.) and it's been over a decade since taking DXM in recreational doses.

Being careful, in the day at 11:40a I scaled out an 8mg 'allergy-test' dose on my 1mg-accurate digiscale and ate it on a mostly-empty stomach.

After an hour only the slightest placebo-like effects were noted - a tiredness in the leg muscles and a bit of sleepiness.

I wasn't expecting much at 8mg.

So tonight I expected to have some fun on the MXE and scaled out 28mg which was taken on an empty stomach at 9:40p.

One hour later: same: virtually no effects but some minor lack of coordination that must have been only a few percent above placebo.

One hour after that I took another 25mg. An hour after that: nothing.

One hour after that I took another 30mg. An hour after that: nothing but very small effects.

I usually smoke a tiny bit of tobacco right before bed in the dark outside and did so agaiin - the nicotine buz briefly made me feel a tiny bit of what could be numbness in hands/feet - which promptly disappeared in two minutes.

A total dose in three hours of 83mg MXE in a totally naive user - and yes, DXM worked fine decades ago so it is not some genetic peculiarity.

Zero mental impairment and at the end I poked one of my fingertips with a sewing needle - full pain sensations.

And a horrifying realization occurred to me as I finished my tiny bowl of tobacco in the dark: two years ago my appendix ruptured and I was hauled in for emergency surgery. As all patients are - I was wheeled into the operating room and given the mask to put me 'out' - the surgery was successful and here I am now writing this.

Except, if it happened again I would likely die on the operating room table.

The anaesthetics that both end conscious awareness and kill all pain were a revolution that enabled the saving of many lives but now it's impossible for me. If I was in an accident now and had to be hauled in pronto for emergency surgery - the anaesthetics would not work or would stop working halfway through the surgery and I would be awake screaming in pain. Under those circumstances surgery is impossible and death likely.

In the case of an accident or appendix rupture or other unplanned incident there won't be time - likely 24+ hours required to desaturate - to depotentiate my NMDA receptors sufficiently to allow any kind of general anaesthesia:

Enflurane is one of the most commonly used general anaesthetics - but they all share common mechanisms of action the main one being NMDA blockade. Sunifiram is so powerful that it completely overrides such a blockade.

From: Volatile anesthetics and NMDA receptors. Enflurane inhibition of glutamate-stimulated [3H]MK-801 binding and reversal by glycine

"Glycine, a positive allosteric NMDA receptor modulator, markedly attenuated the inhibition of glutamate-stimulated [3H]MK-801 binding by enflurane, with an EC50 of approximately 0.8 microM. Thus, enflurane selectively inhibits glutamate activation of the NMDA receptors, and an allosteric modulator attenuates this action. These effects could reflect anesthetic action at the glycine binding site or at another, undefined site which influences activation of the ion channel. These findings raise the possibility that inhibition of transmission at NMDA receptors contributes to the development of the anesthetic state."

I am writing this on a non-tolerant hole dose of pure MXE late at night and feel nothing at all. Absolutely nothing.

My brain is totally awake and there is no pain relief of any kind - neither from pinpricks or my constantly aching joints and lower back.

In this state I could not be put under or kept under by general anesthesia and the pain sensations would certainly not be blocked.

To put it simply: if I required emergency surgery I would likely die awake on the operating room table. Given my current state and dose of MXE I say that likelyhood is about 50-60%, maybe 100%.

There has not been enough time for any of the few taking Sunifiram - which has only been available for a few months - to test the surgery requirement. My dose is high but Sunifiram is powerful even at low doses and there is no time to wait for depotentiation during a medical emergency.

ie. Sunifiram + Need for Emergency Anaesthesia = No Anaesthesia = Death on Operating Room Table.

Meanwhile I am left with 4909mg of absolutely useless MXE which cannot function as an anaesthetic.

Ketamine's MOA is identical and it is used for surgical anaesthsia, and other newer surgical anaesthetics use the same mechanism of action. There is absolutely no way that even a large dose of Ketamine would stop pain sensations on Sunifiram and it certainly would not be capable of inducing the unconsciousness required for surgery.

So I learned a valuable lesson today: it's not always good to have a brain whose NMDA receptors are so highly potentiated that they can't be shut down if needed to prevent pain and/or conscious awareness. In some crucial cases it's a lifesaving requirement.

Edited by Isochroma-Reborn, 12 July 2013 - 07:52 AM.

[Climactic]

Meanwhile I am left with 4909mg of absolutely useless MXE which cannot function as an anaesthetic.

I understand the interesting and important concern, but maybe it doesn't make sense to take sunifiram and MXE on the same day. How about discontinuing sunifiram for a few days, and then trying MXE?

Sunifiram's effects were easily canceled in the animal studies using specific standard antagonists that are named in the studies.

Edited by Climactic, 12 July 2013 - 07:54 AM.

[Isochroma]

Undoubtedly such a scheme would work but I need Sunifiram for its daytime nootropic activity so the MXE is headed for the toilet.

In the case of emergency surgery there is no time to wait for Sunifiram to desaturate.

Further, the potentiation may last longer than 24h. It might even be permanent - but even a 24h requirement will prevent emergency anaesthesia from working and during such medical emergencies there is no time to wait 24h.

If I had to wait that long for my appendectomy three years ago I would have died - I was going into shock as I was carted into the hospital - hell, I would not have survived six hours waiting.

This is a warning to everyone: I can absolutely guarantee that any general anaesthetic won't work as expected on Sunifiram - expect up to a 90%+ reduction in effectiveness.

Sunifiram thoroughly prevents NMDA blockade by even the most powerful molecules.

Worse, the duration of the remaining 10% of effects is much shorter than expected too: the tiny effects I felt have faded away far faster than the hundreds of MXE reports I have read and are about gone now.

Rather than an effective duration of about 3-4 hours, each dose I took seemed to deliver its tiny effect and then fade away within about 20-25 minutes - and none of the small effects I received had any pain-reduction component.

So you might find yourself waking up on the table during surgery.

Edited by Isochroma-Reborn, 12 July 2013 - 08:02 AM.

[Climactic]

This is a warning to everyone: I can absolutely guarantee that any general anaesthetic won't work as expected on Sunifiram - expect up to a 90%+ reduction in effectiveness.

Novel nootropic drug sunifiram enhances hippocampal synaptic efficacy via glycine binding site of N-methyl-D-aspartate receptor (2013)

The enhancement of LTP by sunifiram treatment was inhibited by 7-chloro-kynurenic acid (7-ClKN), an antagonist for glycine-binding site of NMDAR

The increase in phosphorylation of PKCα (Ser-657) and Src (Tyr-416) induced by sunifiram was inhibited by 7-ClKN treatment. The LTP enhancement by sunifiram was significantly inhibited by PP2, a Src family inhibitor. Finally, when pre-treated with a high concentration of glycine (300 μM), sunifiram treatments failed to potentiate LTP in the CA1 region.

Based on the above, I don't see why the effect of sunifiram won't be cancelable by using a more diverse but appropriate set of sedatives. However - will such specialist chemicals be available to the average anesthesiologist without prior notice? Probably not. I believe there may be merit to the concern you outlined.

Edited by Climactic, 12 July 2013 - 08:06 AM.

[Isochroma]

Correct. If you're hauled into a generic hospital for emergency surgery they won't have such specialty chemicals.

At that point survival will be a flip of the coin - unless you're good at taking the pain while awake.

There are other molecules that can kill pain but you'd still be conscious and awake on the table.

I know this is hard to believe but considering what has happened to the unlucky few with permapains - not only is it possible but my current experience indicates that the chance is better than 50% which is very bad.

Consider this: I should by lying semi-unconscious on my bed now floating and hardly feeling my limbs never mind pinpricks but instead I'm writing these posts with no spelling errors and I don't even feel like sleeping and it's midnight.

That level of anti-NDMA-blockade action tells me that a general anaesthetic just won't work as expected or not at all.

Edited by Isochroma-Reborn, 12 July 2013 - 08:10 AM.

[Isochroma]

And if you don't believe me here's more:

The role of the NMDA synapse in general anesthesia

"A theory of anesthesia is presented. It consists of four hypotheses. (1) The occurrence of states of consciousness causally depends on the formation of transient higher-order, self-referential mental representations. The occurrence of such states is identical with the appearance of conscious phenomena. Loss of consciousness will occur, if the brain's representational activity falls below a critical threshold. (2) Higher-order mental representations are instantiated by neural cell assemblies. (3) The formation of such assemblies involves the activation of the NMDA receptor channel complex. The activation state of this receptor determines the rate at which such assemblies are generated. (4) Modification of NMDA-dependent computational processes is the final common pathway of anesthetic action. Agents that directly inactivate the NMDA synapse necessarily have anesthetic properties; agents that do not directly affect the NMDA synapse will exert an anesthetic action, if they inhibit NMDA-dependent processes."

The inverse hypothesis is that if the NMDA pores are potentiated by a positive allosteric modulator (see the other study) then NMDA-antagonist anaesthetics will be diminished or their effect entirely abolished.

Even the racetams have some effect in this way and so do other agents but luckily they are very weak and so do not prevent anaesthesia - I have some reports of Piracetam decreasing MXE's effects and will post them tomorrow - but Sunifiram works at an exponentially higher level to completely sabotage such blockade. There is just no way I could not feel pain now and I will likely raise the dose tomorrow to 200+ mg or even a gram to prove the case.

[jly1986]

Isochroma,

The other possibility is that the product you received isn't really MXE. How sure are you that it is the genuine product?

[golden1]

You realize that oxiracetam or piracetam will stop most of the dissociation from mxe right? Besides that you should still be able to feel it pretty obviously since it has effects beyond nmda dissociation(reuptake/dopamine type stimulation). Also I don't think the result of anesthetics not working is that they give up and you die : P .. although it is a good point in general that it could interact with anesthesia, I doubt it would be an issue if you told the anesthesiologist what you were taking. ..and why throw out 5 grams of MXE because it conflicts with something else you are taking at the moment? Send it to me.. : )

[Isochroma]

I did receive small effects and purchased the MXE from a reputable Chinese chemical company.

Also, the flavor matched forum descriptions and so did the small effects.

As for the argument that it could have been cut: the other peculiar effect is that doses did not add up.

What I mean is that the small effects stayed at an equal level despite dose increases.

This indicates that the few blockable receptors were already blocked by the initial dose or two and after that more MXE did not add to the effect.

It's a crucial point I realized today because in a hospital the anaesthesiologist is trained to raise the dose to keep the patient 'under' - but in this case such a tactic is useless or dangerous due to other side-effects of the anaesthetic.

Let's say that with enough MXE or KET or whatever it might work but the toxic effects (bladder, etc.) at the dose required would themselves generate a medical emergency.

And yes, Piracetam and Oxiracetam do decrease the dissociation but not to this extent.

I searched many forums over the last week and found only three reports:

Methoxetamine + Racetams - Supplements - LONGECITY: This thread has little relevance.

BlueLight: Piracetam and Methoxetamine (MXE): Reports of decreased intensity with Piracetam but effects are still in evidence.

Bluelight: Piracetam with MXE.. problems: Reports of weaker MXE but still getting effects, and one report of a solid week of Piracetam reducing MXE tolerance.

Nobody reported abolishment of MXE effects.

Sunifiram is a different beast compared to racetams.

Repeat: Sunifiram is on a totally different level and completely prevents that which racetams only diminish.

Strangely, I am noticing now just after waking that I have a bit more energy like the old 15-30mg DXM next-day rebound.

I used to take 15-30mg DXM before bed to cut the cannabis-induced coughing during my before-bed night fun and regularly noticed the next-day rebound.

There are no other effects or aftereffects in evidence.

Edited by Isochroma-Reborn, 12 July 2013 - 04:31 PM.

[3AlarmLampscooter]

FYI, spinal anesthesia should still work fine, even if most general anesthetics are rendered useless/diminished.

[mkUltra999]

Just for the record, I take Sunifiram (and sometimes, Unifiram), Aniracetam, Noopept and Phenylpiracetam , and trust me when I tell you, none of them block the effects of MXE in the doses I take, and I take them daily. Additionally, just so you know, much of the very poor quality MXE produced that is floating around out there comes from China, a place known to produce garbage chemicals not limited to MXE. I cannot tell you how much poor quality MXE there is floating around, much of which I wouldn't put in my body. There is A LOT of it. There is more bad than good, or so it seems, so I would be mindful of that. And again, I take the above mentioned stack daily, which in no way negates the effects of MXE for me, so something to consider. I will say that Magnesium appears to negate the effects of MXE, and I can say with certainty that Centrophenoxine absolutely blocks many of the psychoactive effects of MXE. I know from first hand experience and there is research that supports that effect with dissociative compounds as well.

[Isochroma]

Undoubtedly the lower doses of Sunifiram taken by many will allow sufficient NMDA blockage to enable anaesthsia but the maximally effective nootropic dose will likely have a stronger effect. My dose is rather high but there are a few others taking similar doses.

As for spinal and local anaesthesia, cocaine-based anaesthetics [aminoamide / aminoester] will work because they operate on a different principle - but they are useless for general surgical anaesthesia.

Further, Unifiram is about to come on the market in bulk quantities. Unifiram has a substantially higher peak power than even Sunifiram and undoubtedly many will stack the two.

mkUltra999: What are your Sunifiram/Unifiram doses?

Edited by Isochroma-Reborn, 13 July 2013 - 12:07 AM.

[Isochroma]

Someone else commented on a side-effect of Sunifiram: minor itches.

They're so minor that I hardly noticed them but his report triggered a perceptive recheck: random itches that come and go are indeed present in my case too.

However, it might only be my usual seasonal pollen allergies. Winter will tell.

It's not a problem since they occur in random places so I'm not wearing down skin in one area.

Histamine potentiates N-methyl-D-aspartate receptors by interacting with an allosteric site distinct from the polyamine binding site

Abstract

Histamine potentiates activation of native and recombinant N-methyl-d-aspartate receptors (NMDARs), but its mechanisms of action and physiological functions in the brain remain controversial. Using four different models, we have further investigated the histamine-induced potentiation of various NMDAR-mediated responses. In single cultured hippocampal neurons, histamine potentiated NMDA currents. It also potentiated the NMDA-induced increase in intracellular calcium in the absence, as well as with saturating concentrations, of exogenous d-serine, indicating both glycine-dependent and glycine-independent components of its effect. In rat hippocampal synaptosomes, histamine strongly potentiated NMDA-induced [(3)H]noradrenaline release. The profile of this response contained several signatures of the histamine-mediated effect at neuronal or recombinant NMDARs. It was NR2B-selective, being sensitive to micromolar concentrations of ifenprodil. It was reproduced by tele-methylhistamine, the metabolite of histamine in brain, and it was antagonized by impromidine, an antagonist/inverse agonist of histamine on NMDA currents. Up to now, histamine was generally considered to interact with the polyamine site of the NMDAR. However, spermine did not enhance NMDA-induced [(3)H]noradrenaline release from synaptosomes, and the potentiation of the same response by tele-methylhistamine was not antagonized by the polyamine antagonist arcaine. In hippocampal membranes, like spermine, tele-methylhistamine enhanced [(3)H]dl-(E)-2-amino-4-propyl-5-phosphono-3-pentenoic acid (CGP39653) binding to the glutamate site. In contrast, spermine increased nonequilibrium [(3)H]5H-dibenzo[a,d]cyclohepten-5,10-imine (dizocilpine maleate; MK-801) binding, and suppressed [(3)H]ifenprodil binding, whereas histamine and tele-methylhistamine had no effect. In conclusion, the histamine-induced potentiation of NMDARs occurs in the brain under normal conditions. Histamine does not bind to the polyamine site, but to a distinct entity, the so-called histamine site of the NMDAR.

In the case of itches it seems Sunifiram is affecting histamine release in some as yet unknown way in skin cells or just below them.

Also, it seems like both Sunifiram and Unifiram will make great antidotes to PCP, Ketamine, MXE, etc. overdose - right now there's not much to be done when folks psycho on PCP arrive at hospital other than sedation / immobilization until the effects wear off. An injection of Sunifiram / Unifiram would likely abort the delerium-inducing NMDA blockade very quickly.

Edited by Isochroma-Reborn, 13 July 2013 - 01:00 AM.

[Introspecta]

I've experienced with MXE in the past with varying qualities. I got a batch once where I had to pretty much double the dose to get good effects. The vendor even marked down the product do to the bad reviews. Unfortunately ordering from an unknown lab in china where there are no reviews you could never be sure what your getting. It was much easier to get MXE back when I was using it though. If you search good enough you can find legit K and MXE sources. Some are based out of mexico and sell benzos and steroids along with K. Not so sure about MXE. K is so much cleaner than MXE. I really didn't care for the stuff. Too confusing.

[Isochroma]

I just remembered that the greatest circadian variation is not melatonin but histamine.

Brain histamine keeps us awake during the day. That's why antihistamines - to the extent they penetrate the blood-brain barrier - cause drowsiness.

Both histamine and Sunifiram / Unifiram potentiate the NMDA receptor at its allosteric site and both promote wakefulness.

Edited by Isochroma-Reborn, 13 July 2013 - 02:59 AM.

[Geoffrey]

Have those who've initially responded positively to Suni discontinued for any reason that's related to it's side effect profile or even it's efficacy? I know we've got a few people here who are experiencing significant residual adverse effects but I'd like to hear from anyone who has responded early on in this thread about it.

I had about a week-and-a-half off sunifiram (and any racetams) to flush it out of my system. I reported on the side-effects thread that I continued to feel the effects of it, often coming in waves, for at least a week after stopping. These included waking up feeling I was still on sunifiram, enhanced colours, increased clarity of mind, etc. But combined also (in the first 48 hours or so) with periods of lethargy and listlessness. No other negative withdrawal symptoms after the first 48 hours.

I am back on it now. The first day back I took one microscoop, unheaped and unpacked, I felt great at first, but then I began to feel lethargic and got brain fog for the rest of the day. The second day I took it at night before going to sleep, and then felt pleasantly wakeful all the next day. Following that, I have dissolved one microscoop, in a bottle of water, and take sips of it during the day. I can better control the point where it feels "too much" that way. For the past three days I have been taking about a half of the bottle per day, so about 2-3mg I would guess. Even so it seems accumulative at this dose, and I am taking the weekend off to rebalance.

Sunifiram seems very similar to racetams in so many of its effects. Bright lights, increased clarity, need for choline co-administration, plus a cumulative effect which makes dosing a bit complicated. One very good effect is on mood, and I'm still noticing the positive effects here several weeks into using it. Another is that if I want total wakefulness, taking 37.5mg r-modafinil (quarter of a tablet) while on sunifiram is very powerful, much more so than r-modafinil on its own. This dose can easily stop me sleeping many hours later. The effect is so strong that I would be scared (especially given Climactic's experiences) to take any more than that. I stress that this is on a very low dose of both. Finally, sunifiram on its own does not combine at all well with alcohol for me. I get drunk-like feelings (not pleasant ones) after half a glass of wine while on suni. In short, suni seems to potentiate lots of things, even things which are normally antagonistic, such as modafinil and alcohol. In order to drink socially on sunifiram, I have to take the aforementioned low dose of r-modafinil an hour or so before I go out, otherwise the effects of alcohol are too unpleasant.

[Isochroma]

The remainder of the MXE is to be flushed shortly - unfortunately it was useless for anything after a second test last night, other than creating muscle fatigue today. Worse, "Underexcitation of NMDA receptors, induced by even relatively low doses of NMDA antagonist drugs, can produce specific forms of memory dysfunction without clinically evident psychosis." The implication is that redistribution is unethical due to the insidious nature of such memory deficits. Couldn't remember if Sunifiram's second side was ethyl or methyl this morning after only two days of single doses.

Next, the hypothesis that Sunfiram / Unifiram may prevent antihistamine-induced sleepiness by preventing NMDA blockade or in the case of Sunifiram acting as an agonist plus positive potentiator at the allosteric site. It's rather weak but should be tested. I have to suffer through summer allergies due to effective doses of even the newest least-BBB-penetrating antihistamines causing not only drowsiness but dangerously rubbery legs while bicycle riding. Can't afford antihistamine now and the allergens are already too much reduced to test in my case.

Edited by Isochroma-Reborn, 13 July 2013 - 10:54 PM.

[Isochroma]

The newest hypothesis of schizophrenia's causation is NMDA hypofunction:

Altered Excitatory-Inhibitory Balance in the NMDA-Hypofunction Model of Schizophrenia [2008]

Is the Acute NMDA Receptor Hypofunction a Valid Model of Schizophrenia? [2011]

"Postmortem studies have shown alterations of subunit expression as well as trafficking complex and intracellular signaling proteins of NMDA receptors in prefrontal cortex of subjects with schizophrenia.3 Furthermore, recent imaging studies using a novel SPECT tracer for the NMDA receptor have reported the first in vivo evidence of an NMDA receptor reduction in medication-free schizophrenic patients.4 Besides, ketamine also induced a reduction of NMDA receptors in the human brain, which strongly correlated with the scores of negative symptoms.5"

Sunifiram and Unifiram are the first nootropics to market with sufficient power of positive allosteric NMDA modulation such that they may reverse the course of schizophrenic biodegeneration.

And the cream:

Allosteric modulation of NMDA receptor via elevation of brain glycine and D-serine: the therapeutic potentials for schizophrenia [2008]

"Ionotropic AMPA and NMDA glutamate receptors are ligand-gated ion channels that mediate fast synaptic transmission in the brain and play a crucial role in learning and memory. Dysfunction of these receptors is believed to be associated with a number of neuropsychiatric disorders, including schizophrenia. As direct activation of these ionotropic receptors can lead to excitoxicity, allosteric modulation of these receptors could minimize side-effects to achieve better therapeutic efficacy. Our review here focuses on the allosteric modulation of the NMDA receptor. Endogenous glycine and D-serine both act as co-agonists on the strychnine-insensitive GlyB site on the NMDA receptor, and along with glutamate, co-activate the NMDA receptor. Forebrain synaptic glycine and d-serine levels are regulated by the Glycine Transporter-1 (GlyT1) and the arginine-serine-cysteine transporter-1 (Asc-1), respectively; in addition to D-serine metabolism by D-Amino Acid Oxidase (DAAO). Together, these processes prevent the GlyB site from being saturated by the high extracellular levels of brain glycine, and perhaps d-serine, in vivo. Blockade of NMDA receptors by phencyclidine induces schizophrenia-like symptoms with the associated cognitive deficits. It was proposed that: a) blockade of GlyT1 mediated reuptake of glycine, or b) inhibition of D-amino Acid Oxidase, or Asc-1 will elevate brain glycine, and D-serine to upregulate NMDA receptor functions via glycine and D-serine co-agonistic allosteric modulation of the GlyB sites on the NMDA receptor. These approaches may provide novel treatments to schizophrenia, provided that some of the known adverse effects associated with existing GlyT1 agents can be safely and adequately dealt with."

The role of the mGluR allosteric modulation in the NMDA-hypofunction model of schizophrenia [2009]

"Schizophrenia is one of the most important forms of psychiatric illness and may be chronic and highly disabling. It has been suggested that specific neurochemical abnormality is due to dopaminergic overactivity in the brain. Schizophrenia is currently thought to be associated with a hypoglutamatergic state that is mimicked by acute Phencyclidine (PCP), an antagonist of the N-methyl-D-aspartate (NMDA) receptor subtype. Administration of PCP or ketamine in rodents has been used to model aspects of schizophrenia. Taken into consideration the role of glutamatergic system in development of schizophrenia and involvement of striatal dopaminergic receptors in generation of schizophrenia symptoms, it was planned to study functional interaction between NMDA and metabotropic glutamatergic receptors 5 (mGluR5) in schizophrenia-associated behavioral and memory disturbance and the role of mGluRs allosteric modulation in cortico-striatal synaptic plasticity. In our experiments investigation of dose-dependent effects of ketamine revealed that 0.3mg/kg ketamine induces statistical changes most of behavioral and cognitive parameters in rats. Changes in emotional state showed decrease of the number and total duration of groomings in open field experiments as wall as in passive avoidance task. Decrease of motor activity was also detected, while no significant changes were observed in number of defecations. In T-maze test it was shown that spatial memory was damaged. To determine whether mGlu5 and NMDA receptor interact to regulate complex behaviors that are relevant to cognitive disorders such as schizophrenia we focused on assessing whether the selective mGlu5 receptor antagonist 2-methyl-6-(phenylethynyl)-pyridine MPEP mimics or exacerbates the effects of the NMDA receptor antagonist. Ketamine-induced memory disturbance was significantly increased after injection of mGluR5 negative allosteric modulators MPEP. In in-vitro experiments the agonist at group I metabotropic glutamate receptors (mGluRI) (RS)-3,5-dihydroxyphenyl-glycine (DHPG,100 microM) evoked a persistent depression of the second component (N2) of the cortico-striatal field potential in rat slices. DHPG-induced plasticity was not NMDA-dependent. mGlu5 negative allosteric modulator MPEP diminishes the inhibition of synaptic responses induced by DHPG and completely blocked the late phase of depression. Our behavioral and in vitro data suggested that between NMDA and mGlu5 receptors there are functional interaction. Thus in some neurological or psychiatric disorders with NMDA dysfunction pharmacological manipulation of mGlu5 receptors could have therapeutic use."

Positive Allosteric Modulators of Type 5 Metabotropic Glutamate Receptors (mGlueR5) and Their Therapeutic Potential for the Treatment of CNS Disorders [2011]

"Positive allosteric modulators (PAMs) of mGluR5 receptor function were originally developed with the intent of indirectly increasing NMDA receptor function to alleviate some of the cognitive deficits associated with schizophrenia, as there is a wealth of evidence suggesting that NMDA hypofunction contributes to cognitive deficits observed in this disorder [19-21,32-34]. mGluR5 PAMs were hypothesized to be advantageous over orthosteric mGluR5 agonists such as CHPG because the latter compounds: (1) offer poor discrimination between mGluR receptor subtypes due to the high degree of sequence homology of the glutamate binding site; (2) exhibit poor brain penetrance following systemic administration, and (3) cause rapid mGluR5 receptor desensitization. In an effort to circumvent these issues, mGluR5 PAMs were developed to bind to the receptor at a site that is distinct from the orthosteric glutamate binding site, and increase the functioning of the receptor in the presence of binding of its endogenous ligand glutamate."

Allosteric Modulators for the Treatment of Schizophrenia: Targeting Glutamatergic Networks [2013]

"Schizophrenia is a highly debilitating mental disorder which afflicts approximately 1% of the global population. Cognitive and negative deficits account for the lifelong disability associated with schizophrenia, whose symptoms are not effectively addressed by current treatments. New medicines are needed to treat these aspects of the disease. Neurodevelopmental, neuropathological, genetic, and behavioral pharmacological data indicate that schizophrenia stems from a dysfunction of glutamate synaptic transmission, particularly in frontal cortical networks. A number of novel pre- and postsynaptic mechanisms affecting glutamatergic synaptic transmission have emerged as viable targets for schizophrenia. While developing orthosteric glutamatergic agents for these targets has proven extremely difficult, targeting allosteric sites of these targets has emerged as a promising alternative. From a medicinal chemistry perspective, allosteric sites provide an opportunity of finding agents with better drug-like properties and greater target specificity. Furthermore, allosteric modulators are better suited to maintaining the highly precise temporal and spatial aspects of glutamatergic synaptic transmission. Herein, we review neuropathological and genomic/genetic evidence underscoring the importance of glutamate synaptic dysfunction in the etiology of schizophrenia and make a case for allosteric targets for therapeutic intervention. We review progress in identifying allosteric modulators of AMPA receptors, NMDA receptors, and metabotropic glutamate receptors, all with the aim of restoring physiological glutamatergic synaptic transmission. Challenges remain given the complexity of schizophrenia and the difficulty in studying cognition in animals and humans. Nonetheless, important compounds have emerged from these efforts and promising preclinical and variable clinical validation has been achieved."

This needs testing and the cures may have already arrived on the market.

Edited by Isochroma-Reborn, 13 July 2013 - 11:58 PM.