Nootropics of the future

[Lombergerh]

Not to rain on your parade, but in my experience Russian and Chinese research on "wonder drugs" tends to be fairly biased

Hm, what about Noopept? Everybody gave it very good feedback.

 

[sHR00m]

noopept is def acting in some way but if its a good or a bad one i cant really decide.

in small dosages its stabilizing the mind, enhancing vision, focus and is kinda stimulating. i think its weird acting, because it gives me better reflexes but also it seems to stretch time a bit, so i have more time to react than i usually would. which can be a pain in the ass if you have no patience. i had similar time-stretching experiences on methoxetamine and i believe both drugs act in similiar ways on that receptors. one being an nmda antagonist and noopept having nmda agonist capabilities. interestingly noopept also ended the dissociative effects of mxe for me, getting me back to baseline within 5 minutes.

anyway, i think noopept goes well with stimulants as well. but i kinda doubt its interesting effects have a real improvement for my daily life and my memory, except maybe keeping focussed and driving like a pro. since daily dosing is a bit tough with that potency sometimes i caught too much, resulting in unease and aggression, quite like stimulants could do. in retrospect the aggresion and stress might build up anyway if taken daily. it really isnt an anxiolytic. i have a feeling noopept does alot stuff in the body that wasnt advertised but i have yet to try piracetam and others for comparison.

i use a 5 mg bump one and off for adhd purposes tho which along with coffee and an occacional l-theanine capsule seems to do the job. i think other racetams might be less focussed on reflexes and more on memory, social interaction and other nootropic effects.

 

[Dunno]

I find racetams effective in lower doses. For noopept, I prefer 5 mg twice a day, although sometimes, 10 mg twice daily. Clinical trials testing its efficacy used 10 mg thrice daily. Humans can generally tolerate doses in the hundreds of miligrams without damage. Try 10 mg thrice daily and decrease of increase from there. Your milage may vary. Keep in mind that many users have reported irritability after persistent dosing, so an incentive exists to find the lowest effective dose.

Been taking 20mg for two days. Haven't noticed any improvement. Does it take a few days or weeks for it to take effect?

 

[wormdevil]

Not to rain on your parade, but in my experience Russian and Chinese research on "wonder drugs" tends to be fairly biased

Semax may be Russian but Cerebrolysin is produced by an Austrian pharma company. Austria, as many of you may know, is a pretty modern country, was not a part of the Eastern Block, and do not fancy eastern medicine mindset.

Also, for people concerned with prion diseases, the peptides used in Cerebrolysin are pretty small, a fact on which some people base the argument that it does not cause prion diseases. In fact, I haven't to date heard any prion diseases related to this, and it is not even mentioned in the monograph of the medicine.

Unlike many of the nootropics we discuss, this is a prescription medicine available in wide range of european countries, for several decades. I can't provide the numbers as I don't want to make a mistake, but it is not that hard to find.

Also, again, unlike a good portion of nootropics, you can go to pubmed.gov and find many articles related to it (lazy link). Improvements it brings are not marginal (at least in the elderly patients), and I remember an article with follow-ups after 8 months of administration showing statistically significant improvements, meaning that the effects are much less temporary than other nootropics. There is surprisingly low number of anecdotal reports complaining about effects being too subtle/unnoticeable, and considering that most people who take this as a nootropic do not get a prescription thus do not get the medicine from legitimate sources, this is pretty striking.

I understand that I am being a bit vague but unfortunately I don't have time to redo the lit review I did to pull out the sources. But here are some quick links to get some started.

Product Monograph
http://www.hypermed.com.au/HyperMED Clinical Research/EVER2010_Monograph_screen.pdf
A nice review that has links to a lot of primary literature
http://wiseyoung.wordpress.com/2009/02/10/271/
For those who fancy anecdotal reports
http://www.longecity.org/forum/topic/28171-cerebrolysin

Good luck!

 

[Gaius]

Not sure if it's been posted before but PKR inhibitors certainly seem like they may be a nootropic of the future.

http://www.ncbi.nlm.nih.gov/pubmed/22153080

The double-stranded RNA-activated protein kinase (PKR) was originally identified as a sensor of virus infection, but its function in the brain remains unknown. Here, we report that the lack of PKR enhances learning and memory in several behavioral tasks while increasing network excitability. In addition, loss of PKR increases the late phase of long-lasting synaptic potentiation (L-LTP) in hippocampal slices. These effects are caused by an interferon-γ (IFN-γ)-mediated selective reduction in GABAergic synaptic action. Together, our results reveal that PKR finely tunes the network activity that must be maintained while storing a given episode during learning. Because PKR activity is altered in several neurological disorders, this kinase presents a promising new target for the treatment of cognitive dysfunction. As a first step in this direction, we show that a selective PKR inhibitor replicates the Pkr(-/-) phenotype in WT mice, enhancing long-term memory storage and L-LTP.

Maybe it'd even be complemented by some cAMP induction via forskolin in combination with a PDE4 inhibitor.

We examined the cLTP induced in acute slices by application of Sp-cAMPS or a combination of the adenylyl cyclase activator, forskolin, and the phosphodiesterase inhibitor, rolipram. Under our conditions, cLTP was induced but only if inhibition was reduced. We found that this form of cLTP was blocked by a N-methyl-d-aspartate receptor (NMDAR) antagonist and required the low-frequency test stimulation typically used to monitor the strength of synapses. Interestingly, similar LTP could be induced by lowering the Mg(2+) concentration of the ACSF during forskolin/rolipram or Sp-cAMPS application or even by just lowering Mg(2+) concentration alone. This LTP was also NMDAR dependent and required only a few ( approximately 5) low-frequency stimuli for its induction. The finding that even low-frequency synaptic stimulation was sufficient for LTP induction indicates that a highly sensitized plasticity state was generated. The fact that some stimulation was required means that potentiation is probably restricted to the stimulated axons, limiting the usefulness of this form of cLTP. However, when similar experiments were conducted using slice cultures, potentiation occurred without test stimuli, probably because the CA3-CA1 connections are extensive and because presynaptic spontaneous activity is sufficient to fulfill the activity requirement. As in acute slices, the potentiation was blocked by an NMDAR antagonist. Our general conclusion is that the induction of LTP caused by elevating cAMP requires presynaptic activity and NMDA channel opening. The method of inducing cLTP in slice cultures will be useful when it is desirable to produce NMDAR-dependent LTP in a large fraction of synapses.

And while I'm at it, here's the full text of a review that analyzes publishes articles regarding trans-cranial direction stimulation and possible underlying mechanisms:
http://www.frontiersin.org/Neuropsychiatric_Imaging_and_Stimulation/10.3389/fpsyt.2012.00080/full

Transcranial direct current stimulation (tDCS) has been the subject of many studies concerning its possible cognitive effects. One of the proposed mechanisms of action for neuromodulatory techniques, such as transcranial magnetic stimulation and tDCS is induction of long-term potentiation (LTP) and long-term depression (LTD)-like phenomena. LTP and LTD are also among the most important neurobiological processes involved in memory and learning. This fact has led to an immediate interest in the study of possible effects of tDCS on memory consolidation, retrieval, or learning of various tasks. This review analyses published articles describing beneficial or disruptive effects of tDCS on memory and learning in normal subjects. The most likely mechanisms underlying these effects are discussed.

Yay! It's an LTP party!

 

[Quercetin]

An H3-receptor antagonist is a classification of drugs used to block the action of histamine at the H3 receptor. Unlike the H1 and H2 receptors which have primarily peripheral actions, but cause sedation if they are blocked in the brain, H3 receptors are primarily found in the brain and are inhibitory autoreceptors located on histaminergic nerve terminals, which modulate the release of histamine. Histamine release in the brain triggers secondary release of excitatory neurotransmitters such as glutamate and acetylcholine via stimulation of H1 receptors in the cerebral cortex.

Consequently unlike the H1 antagonist antihistamines which are sedating, H3 antagonists have stimulant and nootropic effects, and are being researched as potential drugs for the treatment of neurodegenerative conditions such as Alzheimer's disease.

 

[Lombergerh]

A little offtopic:
If you have a opportunity to have a new research nootropic peptide what would you choose?

 

[MeDieViL]

Which nootropic(s) have the least potential of aggravating bipolar or schizophrenia? Are any additionally useful antidepressants and/or anxiolytics?

nefiracetam def reverses stim psychosis for me, its very pro glutaminergic and hypoactive glut is implicated in shizophrenia, also raises GABA wich would benefit shizo.
It could have test toxic issues due to impairment of pregesterone conversion but this can be monitored with bloodtests, also its been safely trialled in humans for apathy after traumatic brain injury.

Pregnenolone
DHEA
Pro cholinergics
Cerebrolysin (only rodent model)

Il provide refs when asked.
Theoretically aniracetam wont make shizo worse while providing anxiolysis

 

[MeDieViL]

Not sure if it's been posted before but PKR inhibitors certainly seem like they may be a nootropic of the future.

http://www.ncbi.nlm.nih.gov/pubmed/22153080



Maybe it'd even be complemented by some cAMP induction via forskolin in combination with a PDE4 inhibitor.



And while I'm at it, here's the full text of a review that analyzes publishes articles regarding trans-cranial direction stimulation and possible underlying mechanisms:
http://www.frontiersin.org/Neuropsychiatric_Imaging_and_Stimulation/10.3389/fpsyt.2012.00080/full



Yay! It's an LTP party!

That combo has a long thread on longevity with succesfull reports, also for the above post it will help shizophrenia (based on rodent model).
http://www.longecity.org/forum/topic/51732-chemically-induced-ltp/

 

[Solipsis]

A little offtopic:
If you have a opportunity to have a new research nootropic peptide what would you choose?

Generally I'd like to ask you all to indeed please watch closely that you stick to the topic since we already have a plain nootropic thread... however this question does not seem necessarily off-topic to me since you are talking about new peptides (I consider them 'of the future' so to speak). To answer, based on a brief things I read on the forum here Selank sounds neat but it is so damn expensive.
More realistically I already have noopept here but have not tried it yet since I wanted to wait out the main portion of benzo withdrawal anxiety (which is slowly subsiding now).

Which nootropic(s) have the least potential of aggravating bipolar or schizophrenia? Are any additionally useful antidepressants and/or anxiolytics?

Aniracetam i heard is good anxiolytic

nefiracetam def reverses stim psychosis for me, its very pro glutaminergic and hypoactive glut is implicated in shizophrenia, also raises GABA wich would benefit shizo.
It could have test toxic issues due to impairment of pregesterone conversion but this can be monitored with bloodtests, also its been safely trialled in humans for apathy after traumatic brain injury.

Il provide refs when asked.
Theoretically aniracetam wont make shizo worse while providing anxiolysis

Please be careful making assumptions like that. I agree that anxiolysis does not imply worsening of such conditions but that should not be stretched to far with bad logic, plus there isn't even evidence that says we can use such indications.

To me aniracetam feels like it cranks up the amount of information streaming into me through my senses while I am already having a hard time processing information well at baseline. Yet aniracetam also allows me to process information more quickly and efficiently to make up for that broader bandwidth AND MORE. This seems to go hand in hand with anxiolysis because there is no more stress from incoming barrages of information.

In someone who does get the bigger bandwidth phenomenon but not the extra coping abilities, you could expect worsening of mental conditions since it would increase "overturn" and catalyze processes non-selectively.

This is just as much conjecture as what I am quoting, for sure, but I am just illustrating how different implications can be made and we should be careful. And additionally that it could very between people. Even if in trial models most subjects would show improvement it is quite possible that some part of the subjects can get worse (with statistical relevance as well)... in such a situation taking the drug could take you either direction, something I deem typical of catalysts, including psychedelics which can also make good things better and bad things worse.

Proliferall, wow yea that also made me lol pretty hard. Nootropic of the future? More like nootropic of the past. I'll skip, considering I don't react too well to caffeine anymore and get headaches from tyrosine to name a few things.

Unfortunately I don't have extra futuristic nootropic candidates to introduce here. The whole peptide thing already makes me visualize the movie Limitless.

I still don't understand how oligopeptides survive oral administration though... I thought all peptides or proteins were broken down to amino acids there, am I wrong are they just chopped into small bits and are tripeptides and heptapeptides small enough to pass?

Sorry if that is considered off-topic. 8)

 

[tyrael]

An extremely interesting/informative thread! (tbh didn't quite realise how many possible nootropics are out there, especially their accessibility :S)....

Apologies if this has been brought up (I haven't been through the entire thread yet) however I'm curious about (specifically) health care professionals (GPs, psychiatrists/-chologists, etc.) (however those working in related fields also) views on nootropics - how well known are they (amongst said peoples)? how well/frequency being prescribed? their impression on efficacy or even usefulness (beneficial or not?)? moral/ethical thought/opinions on the use of these substances?

Obviously there are many classes of nootropic drugs, however how much regarding addiction potential have these been looked into? In fact, how much study has been done on them in general?

Cheers.

....I still don't understand how oligopeptides survive oral administration though... I thought all peptides or proteins were broken down to amino acids there, am I wrong are they just chopped into small bits and are tripeptides and heptapeptides small enough to pass?....

Hmm, I also thought (no?) proteins are able to be administrated orally! Afaiw-aware - HIV/AID, antivirals, and other treatments utilising recombinant DNA technology all have to be administered parenterally (by-passing the hostile environment of the gut)

 

[dakotacology]

BPAP Benzofuranylpropylaminopentane and PPAP Phenylpropylaminopentane

In pre-clinical trial stages (BPAP), and substantially more potent derivatives of l-Deprenyl ....

Would welcome any opinion, thoughts, info as to potential
Pharmacokinetics and Pharmacodynamics

 

[MeDieViL]

I got some coluracetam, will report back in the future, a select group of longevity members have received samples.

 

[Jabberwocky]

are rc noots recommended in ppl with psych issues?

 

[MeDieViL]

Def not, need to be cautious if thats the case.

 

[Jabberwocky]

i was referring to you, medievil

 

[Solipsis]

For starters it depends on what issues, also: expect there to be more speculation than data on specific combinations of illnesses and nootropics.

Organic mental illness, dementia type of things... probably also aphasia and learning disorders... those are the kind of things expected to benefit most.
Then also depersonalization / derealization may be helped but I doubt things like bipolar disorder, psychosis or schizophrenia are indicated for RC nootropics since by definition they are so new that even presuming basic nootropic properties may be pushing it. So the indications that are a stretch for the established nootropics should not really be considered regarding your question. Especially given the sensitive nature of a lot of psychiatric problems, that may be exacerbated by unpredictable effects.

Finally, remember that on the one hand quite a number of nootropics "kick it up a notch", for example acetylcholine turnover, and (directly or indirectly related) have a tendency to produce anxiety. Not something people want, but with mental issues something to avoid in particular. However on the other hand there are anxiolytic nootropics. Aniracetam is a good example, picamilon as well but that is a strange one. Phenibut has a larger quelling component but I would not really call that nootropic personally.

I'd take no as the default answer ^ . Be careful.
(Strictly speaking there may be hidden potential we are not yet aware of, but as a rule: don't tinker or tamper yourself with something that is broken down)

 

[knockout_mice]

Yes. It think BPAP is a very promising nootropic. It's a potent CAE (catecholaminergic activity enhancer), it means that it stimulates the impulse propagation mediated transmitter release of dopamine and norepinephrine.

(-)-BPAP, a tryptamine-derived, 100 times more potent synthetic enhancer substance than (-)-deprenyl, made it clear that the enhancer effect of (-)-deprenyl is primarily responsible for the therapeutic benefits of this drug.

http://www.ncbi.nlm.nih.gov/pubmed/18771016

We investigated the effects of the novel catecholaminergic and serotoninergic activity enhancer R-(-)-1-(benzofuran-2-yl)-2-propylaminopentane ((-)-BPAP) on the synthesis and secretion of neurotrophins, nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and glial cell line-derived neurotrophic factor (GDNF), in cultured mouse astrocytes. The protein and mRNA levels of the neurotrophic factors were measured using the enzyme-linked immunosorbent assay and reverse transcription-polymerase chain reaction methods, respectively. The amounts of NGF, BDNF, and GDNF secreted from astrocytes into the culture medium increased by up to 120, two, and seven times higher than those of the control, respectively, by treatment with 0.35 mM (-)-BPAP for 24 h. The increases in NGF and GDNF induced by the treatment with (-)-BPAP was inhibited by concomitant treatment with actinomycin D for transcriptional blockade. Furthermore, the treatment with (-)-BPAP for 6 h increased the mRNA expression of NGF, BDNF, and GDNF. These results suggest that (-)-BPAP up-regulated neurotrophic factor synthesis in cultured astrocytes.

http://www.ncbi.nlm.nih.gov/pubmed/12147307

(-)-BPAP, the first tryptamine-derived selective and highly potent synthetic enhancer substance that opens a previously unknown possibility to keep the activity of the noradrenergic, dopaminergic, and serotonergic neurons in the brain on a higher activity level

http://www.ncbi.nlm.nih.gov/pubmed/16023777

The chemical reactions between (-)-BPAP and .OH were studied ... (-)-BPAP was proved to be a good radical scavenger. It was found that every atom of the benzofuran ring, except carbon 3, was capable of easily trapping the radical, where the most active site was carbon 1 on the furan part. ... Since the single radical trapping products were still radicals, these could trap further radicals by way of cascade without any activation energy. Thus, the double radical trapping products were very stable

http://www.ncbi.nlm.nih.gov/pubmed/11377187

I know you all love pubmed citations 8)

And READ this book: The Brain and Its Self
It's basically about selegiline and BPAP. (and learning, motivation, drive, human society...) Very interesting read indeed.

knockout_mice

 

[MeDieViL]

i was referring to you, medievil

I know what im doing and experimenting is what i do alot of the time (wich allowed me find working effective stuff that helps)

 

[Solipsis]

Wow that is awesome about the BPAP and how it releases controlled / regulated amounts of monoamines / catecholamines! I wonder how quickly the brain gets used to that, or maybe the bigger question is of the tolerance to the drug itself or how downregulation works with CAEs. I feel like I have a lot to learn about it, which is in some respect ironically ideal ?