76 replies to this topic

[outsider]

300mg/kg is a healthy dose. That is like ... 60g a day for me. I don't see why we don't experiment with lower doses

And it is even more toxic for your kidneys if I remember correctly.

When I snorted 100mg I had a little inflamation in my throat the next day. Maybe just coincidence but I doubt it.

LoL why were you snorting it? What effects did you expect?

At least it made you laugh. The reasoning behind it is that it's only 100 mg so I thought it would be small enough not to be a toxic dose. To get it where it's most useful, the brain. I got my inspiration from someone who did it and he said that he got the same effect from snorting it than from 1g oral.

I believe the effect is similar than the normal way but I experimented only for a couple of days. Of course you get a nice immediate effect. I could feel it 24 hours later but I don't remember if it was only from the oral dose or snorting or both. I tried oral only 4 times.

[kbal]

So no one tried nefiracetam? I'll get some by the end of this month and would appreciate any advice from a user.
BTW I read all those silly 300mg/kg dog tests. But will do some blood work tests before and after.

[LizerLife]

Anyone know the dosage range and half-life of nefiracetam?

[MoodyBlue]

Here's a post with a description for you: http://www.imminst.o...dpost__p__62828.

Also, while searching around I found a source for Nefiracetam with a good price, but I can't vouch for the quality (I've never order from them): http://www.ktbotanic...tam-p-9078.html.

Edited by MoodyBlue, 25 August 2010 - 01:55 AM.

[MoodyBlue]

Anyone know the dosage range and half-life of nefiracetam?

Here's a PubMed study which can answer your question: http://www.ncbi.nlm..../pubmed/1360528.

Here it gives an ideal dosage range and frequency of administration: http://www.pharmcast...ebral072302.htm.

Edited by MoodyBlue, 25 August 2010 - 02:07 AM.

[yowza]

So no one tried nefiracetam? I'll get some by the end of this month and would appreciate any advice from a user.
BTW I read all those silly 300mg/kg dog tests. But will do some blood work tests before and after.

Rather than taking the trouble of ordering it from China you could just order it in bulk here: http://www.ktbotanic...tam-p-9078.html

They have it in bulk for a good price.

[Ben]

Wasn't there testicular atrophy with this stuff?

[kbal]

Wasn't there testicular atrophy with this stuff?

Yes! If you are a dog that can afford 300 mg/kg/day, then you are in a biggg trouble!

Testicular toxicity

Watch out for decreased urinary osmotic pressure and a tendency of increasing urine volume too:

Early Pathophysiological Features in Canine Renal Papillary Necrosis

[Ben]

Wasn't there testicular atrophy with this stuff?

Yes! If you are a dog that can afford 300 mg/kg/day, then you are in a biggg trouble!

LOL!!!

Still, something to think about. I know I wouldn't risk it as so little is known about the compound.

[chrono]

I merged the two "Nefiracetam"-titled threads, as they had exactly the same topic and staggered date ranges.

I reviewed the nicotinergic mechanisms of nefiracetam here; this mechanism makes nefiracetam a lot more interesting as a nootropic.

And since the issue seems central to any discussion of this drug, here's a review of the toxicity abstracts:

General Toxicity

Single dose toxicity study of the new cognition-enhancing agent nefiracetam in mice, rats and dogs. Sugawara et al 1994
LD50 values of nefiracetam were 2005 mg/kg for male mice and 1940 mg/kg for female mice, 1182 mg/kg for male rats and 1408 mg/kg for female rats and more than 500 mg/kg for beagle dogs.


Thirteen-week oral toxicity study of the new cognition-enhancing agent nefiracetam in rats. Jindo et al 1994
Rats receiving 480mg/kg exhibited salivation, prone position, increased water consumption, increased levels of serum total cholesterol, total protein, albumin and total bilirubin, increased liver weight and hypertrophy of liver cells. 120mg/kg produced only liver cell hypertrophy. 30mg/kg [HED:4.8mg/kg] showed no toxic effects in the areas examined.


Thirteen-week oral toxicity study of the new cognition-enhancing agent nefiracetam in dogs. Sugawara et al 1994
Dogs given 60mg/kg+ had decreased sperm production and spleen problems. 180mg/kg produced renal problems. 20mg/kg [HED: 10.8mg/kg] resulted in no toxicity in this model.


Fifty-two-week oral toxicity study of the new cognition-enhancing agent nefiracetam in rats. Hooks et al 1994a
Most notable toxicity observed in the kidney, liver (related to metabolism), and salivary glands, urinary bladder, spleen, pancreas and adrenals. Toxicity was observed decreasingly at 300, 100, and 30mg/kg [HED: 4.8mg/kg]. 10mg/kg [HED: 1.6mg/kg] was non-toxic in this model.


Fifty-two-week oral toxicity study of the new cognition-enhancing agent nefiracetam in dogs. Hooks et al 1994b
Kidney and testicle toxicity at 90mg/kg. One animal showed slight kidney problems at 30mg/kg [HED: 16.2mg/kg]. Non-toxic at 10mg/kg [HED: 5.4mg/kg].


Antigenicity study of the new cognition-enhancing agent nefiracetam. Wagai et al 1994
No immunogenicity or antigenecity found in mice or guinea pigs


Mutagenicity study of the new cognition-enhancing agent nefiracetam. Shimada et al 1994
Very high doses in vitro showed slight chromosomal abberations, but not at clinical levels.


Oncogenicity studies of the cognition-enhancing agent nefiracetam in mice and rats. Kajimura et al 1994
No evidence of oncogenicity found.

Renal

Examination of lesions in the urinary bladder and kidney of dogs induced by nefiracetam, a new nootropic agent. Kashida et al 1996
300mg/kg administered for 11 weeks; some damage seen after 1 week, and sometimes-fatal hemorrhaging and necrosis by the end.


Effect of nefiracetam, a neurotransmission enhancer, on primary uroepithelial cells of the canine urinary bladder. Goto et al 2003
Metabolite M-18 found to be primary cause of urinary bladder lesions (in vitro).


Comprehensive evaluation of canine renal papillary necrosis induced by nefiracetam, a neurotransmission enhancer. Tsychiya et al 2003
300mg/kg induced RPN in dogs after 11 weeks, due primarily to M-18. No necrosis observed in rats or monkeys.


Investigation on urinary proteins and renal mRNA expression in canine renal papillary necrosis induced by nefiracetam. Tsuchiya et al 2005
The mechanisms of M18-induced renal necrosis was determined to be changes in renal clusterin mRNA.


Early pathophysiological features in canine renal papillary necrosis induced by nefiracetam. Tsuchiya et al 2005
300mg/kg for 7 weeks produced epithelial swelling and degeneration in the papillary ducts, leading to RPN. As a comparison, ibuprofen at 50mg/kg had a similar effect after 5 weeks.

Reproductive

Reproductive toxicity studies of the new cognition-enhancing agent nefiracetam in rats and rabbits. Watanabe et al 1994
Administered for 9 weeks pre-conception. No effect on fertility; some adverse effects on fetal development


Male reproductive toxicity study of nefiracetam in rats. Harada et al 1995
Male fertility was reduced as a result of 1500mg/kg for 4-9 weeks, with a lesser effect at 500mg/kg.


Investigation of testicular toxicity of nefiracetam, a neurotransmission enhancer, in rats. Shimada et al 2003
Using 1500mg/kg, decrease in serum and testicular testosterone levels observed after a single dose. A decrease in sperm count was recorded after one week, and atrophy of seminiferous tubes and multinucleated giant cells were seen after a month.


Testicular toxicity induced in dogs by nefiracetam, a neutrotransmission enhancer. Shimomura et al 2004
Testicular testosterone was decreased 4h after a single 300mg/kg dose (but not 180mg/kg). Serum testosterone was decreased at 1-2 weeks, and serum estradiol increased. 180mg/kg produced seminiferous atrophy, and 300mg/kg multinucleated giant cell formation; these effects occurred at 4 weeks, but not after 1.

What stands out to me:

• The severity of toxicity was dependent upon dose and length of usage.
• Most of the worrying effects occurred at clinically irrelevant dosages.
• Toxicity did appear at clinically relevant human equivalents (see bold text in General Toxicity). The lowest confirmed non-toxic dosage conversion was 1.6mg/kg for humans, or 112mg for a 70kg person; the lowest toxicity was seen at 4.8mg/kg, or 336mg (these are both per day, not per dose). A standard dosage is 200mg, several times a day. In light of this, I think a good case can be made for moderation in dosage (I would probably set an upper limit of 100mg if I was going to use it often) and/or frequency. See mention in my review of nicotinic activity at very low dosages.
• All studies except the two by Hooks et al. were conducted by Daiichi Pharma; these exceptions were conducted at a private contracting lab, and I strongly suspect, funded by Daiichi.

Edited by chrono, 06 November 2011 - 02:18 AM.

[zodiac]

Thanks much, Chrono. Bumping this so more are aware of this latest compilation of relevant info. 4.8mg/kg hits much closer to home than the crazy initial studies that had everyone chuckling. ;P

[medievil]

Shame as nefi is the most impressive thing i ever tried.

[medievil]

Here's a post with a description for you: http://www.imminst.o...dpost__p__62828.

Also, while searching around I found a source for Nefiracetam with a good price, but I can't vouch for the quality (I've never order from them): http://www.ktbotanic...tam-p-9078.html.

I got mine from nootropichub, you can order a small ammount to give it a trial there.

[chrono]

Shame as nefi is the most impressive thing i ever tried.

Well, I hope you can give us a more detailed account of your experience sometime Did the beneficial effects manifest immediately, or did they require some time of constant usage? Because of the toxicity concerns, I'd probably want to save this for 'special occasions,' so to speak.

[JChief]

I'm sure manic_racetam would have interesting input as well! Manic?

Update: Manic's thread

Edited by JChief, 30 November 2011 - 12:25 PM.

[1thoughtMaze1]

Dear Dan,

Many thanks for your e-mail.

At your request, we would like to offer to you as follows:

Nefiracetam
Price: $695/50mg     
Delivery lead-time: In stock 
Above pricing includes shipping via FedEx courier to your facility
Payment terms: Net 30 / via check or pay by credit card via our website: http://www.lgmpharma...make-a-payment/
 
Please advise if the above offer meets with your approval, and I look forward to our co-operation on this product.

Please let me know if you require any further information etc.

Best regards,
Robert Hoppes

LGM Pharma
6400 Congress Ave
Suite 1400
Boca Raton, FL 33487
Tel:  1-561 981 9994 x 117
skype: robert-lgm
Fax: 1-561 892 0580
www.lgmpharma.com

Makes you think about some of the pricing of the products we buy and what they really are!

[manic_racetam]

Shame as nefi is the most impressive thing i ever tried.

Well, I hope you can give us a more detailed account of your experience sometime Did the beneficial effects manifest immediately, or did they require some time of constant usage? Because of the toxicity concerns, I'd probably want to save this for 'special occasions,' so to speak.

Hey chrono, in response to your question, the effects seem to be immediate and in my experience acute dosing has been very effective.

I want to add though, that the toxicity concerns are based mostly on dog/rat studies. It obviously has the potential to be toxic in lower dosages but without correlating human toxicity studies it's all speculation. It's been a while since I've read through all the studies you compiled on toxicity to reach the 100mg/day safe zone, so sorry if there are human studies referenced in that.

Don't get me wrong, I'm not saying it's safe. It's basically the most effective thing I've found for improving focus with ADD, but I don't take it chronically due to safety concerns. Personally my lowest effective dose was 150mg twice or thrice daily. (I love saying thrice;) )

[manic_racetam]

I'm sure manic_racetam would have interesting input as well! Manic?

Update: Manic's thread

Shame I never posted a report on this. I actually had one all written up in the comment section of my profile, but didn't realize the limit on character count and lost a huge section of text when I tried to post it. That discouraged me and I never rewrote it.

But reading back in my journal from that time period it seemed to have quite an effect on cognition. The most striking result though was on the quelling of addictive urges. I almost forgot but I had become pretty seriously addicted to gambling at that time (back in March-May or so) and an unexpected side effect was the complete destruction of any urge to gamble. I'm pretty sure nefiracetam was the catalyst to quitting altogether (thanks nefi).

But here are some applicable excerpts from my journal during that trial (chronological order):

Learning a new language gives you an emotional freedom of expression. It removes emotional stress associated with ideas that were formed in your native language during childhood. You are given a clean slate in expression without disruption of emotional interference. A reworking and rewiring of your brain in a way. The purest emotional states I've experienced in adulthood took place in the context of my second language.

I believe that learning it without literate aid was of emotional benefit as well. My mind had no chance to grasp onto any of it's old language reference which is intimately interconnected with emotional memory. This gave an almost effortless experience of immediate transcendence into a freedom... a freedom never before known to me.

The thing I enjoy the most about this substance nefiracetam is that it seems to give me the mental clarity and fluency of a hypomanic ani-oxiracetam state without the emotional side effect. It's a seriously clear and concise... scientific headspace with unparalleled precision. Yes, I likey. I'm really hoping for not too serious side effects that would cause me to discontinue this substance.

An aside: I just heard we're heading to the casino. I find it strange that I have very little desire to go. I would refuse, but I almost feel like going in order to experience what it's like to have no addictive desire and still experience the gambling situation. So we're off. I'll report back on my experience later.

I'm really enjoying the relief from impulsive urges. It's almost like a silencing of an incessant and familiarly terrorizing voice or something. That's a mild exaggeration. But it is nice. For example thinking about going to the casino, let me try... When I imagine the unlikely possibility of winning $8k at the dragon seven table it doesn't have the same gripping obsession that it used to have. The idea still seems attractive and when looking in retrospect there is a bit of regret for not betting the 200 when I had the chance. But it's not as consuming as it used to be. And if they offered to go to the casino right now I'd decline. I'm tired and I need to sleep. And last time I went it seemed like a total waste of time, energy and money. The thrill was removed.

Honestly I must also critique the day today. As I was standing on the corner near work, I looked at the landscape. I can remember it's appearance. Clear, concise, and physically honest. But it lacked a sort of emotional depth that is usually present in a landscape. It could be partially due to the hot and dry weather but I'd give a lot of the credit to the nefiracetam. Almost like an anti-psychotic medication would have a bit of a dulling effect on your emotions. The strange thing is that the cognitive functioning is not hindered in the slightest.

Would this be an effective treatment for bipolar or schizophrenia? Let me do a quick google search. nope.

......I'm also really glad that this nefiracetam has stopped my urge to gamble. That mental obsession was even worse than the stupid alcohol. And I thank god that it's left me as well.......

Another side note is that nefiracetam increased the awareness of body sensations for me. It was really a cool experience to just sit in a comfortable position with my eyes closed and pay attention to the cascade of normally unnoticed sensations coursing through my human body. I'd say in relation to body sensations it was at least in the same magnitude that oxiracetam increased the clarity of sound.

[medievil]

Shame as nefi is the most impressive thing i ever tried.

Well, I hope you can give us a more detailed account of your experience sometime Did the beneficial effects manifest immediately, or did they require some time of constant usage? Because of the toxicity concerns, I'd probably want to save this for 'special occasions,' so to speak.

Im not good at describing an experience, but ill give it a try.

- Completely blocks any sort of stimulant paranoia, i get paranoid right away probably because i was progressing to shizophrenia.
- Feels simular to nicotine in several ways.
- Blunts the euphoria of stimulants
- Makes me cognitively alot sharper and easier to process things
- I found that acutely 120mg was as good as 800mg of this stuff, so stayed at the low doses due to the price too. I never noticed any effects building up, if anything there was some tolerance occuring.
- Massive synergy with methylene blue and amphetamine, im very impressed by that combination.

This noopept is terrible shit between, nefiracetam is far superior, noopept only takes away my motivation

[dreth7]

So based on the above studies, objectively, 100mg dosage for a 70kg person would be non-toxic? Is this explicitly confirmed by the posted studies or only speculated.

Thanks, Rob

[JChief]

Don't know if this was mentioned but has anyone seen this source? CoA offered indicates >99.9% purity. And forgive my ignorance on the matter but is $100+ for 100mg right? I thought 100mg was, like, one dose? Someone help me make sense of this!

[manic_racetam]

Don't know if this was mentioned but has anyone seen this source? CoA offered indicates >99.9% purity. And forgive my ignorance on the matter but is $100+ for 100mg right? I thought 100mg was, like, one dose? Someone help me make sense of this!

This is an educated guess but that looks like a chemical synthesis lab to me. There are a few online. Some newer experimental compounds are only available through such companies. They likely synth compounds to order, so have much smaller batches which has a high labor+materials cost. They probably also produce chemicals as pure as possible with a smaller margin for contaminants/impurities than other companies.

All of these factors drive the cost much higher. I'm guessing their clients are mostly universities and big pharma type companies that can afford to pay a very high price for a very pure product.

The products mass produced for supplementation etc, probably have higher thresh-holds for impurities, and the larger batch size I'm sure brings price down a lot.

My 2¢

[Googoltarian]

Don't know if this was mentioned but has anyone seen this source? CoA offered indicates >99.9% purity. And forgive my ignorance on the matter but is $100+ for 100mg right? I thought 100mg was, like, one dose? Someone help me make sense of this!

Analytical sample. And as such its quite cheap.

Just finished reading about nefiracetam metabolites, and what struck me is that authors didn't thought about its hydrolysis to 2,6-dimethylaniline which is quite toxic, and could be the cause of those side effects.
 nefi.gif   2.1KB   17 downloads
^My proposition for alternative metabolic pathway.
 nefi2.GIF   18.86KB   22 downloads
^Metabolites from literature.

Also an idea for a drug candidate:
 maybe.gif   1.37KB   14 downloads

In J. Med. Chem. 2000, 43, 4499-4507 similar replacement of functional groups is made - sunifiram (13) and compound 19 - resulting substance is weaker, but nevertheless works.

[dreth7]

So manic are you still using nefi/ would you recommend usage for university?

[Baten]

Nefiracetam is FAT soluble for anyone wondering. It also has a nasty taste, somewhere on the level of noopept. Only prami and sulbatiamine taste worse.

[manic_racetam]

Nefiracetam is FAT soluble for anyone wondering. It also has a nasty taste, somewhere on the level of noopept. Only prami and sulbatiamine taste worse.

Finally someone else who can comment on the taste Really bad. Not as bad as prami but I'd say it's worse than sulbutiamine. Very bitter!

Partially soluble in water though, most of it will mix in with a little film floating on the top (in my experience anyway). But never mix it with water, bad idea unless you enjoy gagging a whole glass of liquid down.

[Baten]

Partially soluble in water though, most of it will mix in with a little film floating on the top (in my experience anyway). But never mix it with water, bad idea unless you enjoy gagging a whole glass of liquid down.

I just received my 10g today to experiment with. Since I didn't know about the taste and solubility, I decided to put 1g in water "attack dose"-style.
Just like you said, parts mixed in the water + other fatty parts + bitter tasting.. great.. :P
I took about a gram of alpha gpc to make sure I'd get no headaches, and to be honest, I didn't notice any noticeable effects.
The ringing in my ears which I always have got a bit modulated, so it's definitely doing something brain-wise.

I'll experiment some more when actually studying later, 100mg to 300mg this time. Maybe "less is more" with nefi.
Taking it together with pira and prami could be interesting..

Edited by Baten, 13 December 2011 - 10:17 PM.

[manic_racetam]

Partially soluble in water though, most of it will mix in with a little film floating on the top (in my experience anyway). But never mix it with water, bad idea unless you enjoy gagging a whole glass of liquid down.

I just received my 10g today to experiment with. Since I didn't know about the taste and solubility, I decided to put 1g in water "attack dose"-style.

Ha! I made the same exact mistake. Don't know why I didn't consider that it might taste terrible, but it's a mistake you only make once

The first day I took it in a dose of about 1 gram probably. That's before I had a scale so it was all estimated based on volume. I didn't notice much either the first time I took it, except for a mild brightening of colors. It gave me a very tense head though, as if there was something constricting around my scalp. I'd almost call it a head-ache but it was slightly different. Anytime I go over 600mg in one day I get that head-tension feeling.

[Baten]

Yep, I also expierenced a tension in the sides of my head + a bit of a headache the next day. High nefi doses don't seem to be recommended...
It looked sugary like uridine monophosphate, I really didn't imagine it tasting so bitter haha.

I think I'm gonna put 50mg nefiracetam + 500mg pramiracetam in my capsules and take some when studying. Will report back.

[jillin]

would any of you guys mind revealing the source of your nef as i've been searching for the longest time to no avail?