P21: New & experimental peptide, does it boost brain function?

Developed from Cerebrolysin, P21 or P021 is another peptide that is used to help stroke victims recover brain function and to aid neural regeneration in the case of Alzheimer’s Disease. Effects are highly cumulative. It is new to the market, so it has not been studied extensively yet. Developed by Ceretropic and is finally back in stock. Many prefer nasal administration. Stacks well with SEMAX. One reddit user claimed that stacking P21 with phenylpiracetam (a favorite of ours) led him to incredible new heights in cognitive abilities:

This is why I call it a paragon nootropic, because it doesn’t do what “imposter” nootropics do, that is make you feel that you are in some way performing better when you are actually not, but actually improves cognition without any “feel”. It is in this sense that P21 is truly special.

P21 use is also self limiting, if you take too much you notice a slight tiredness. Other than that there aren’t any side effects.

P21 combined with phenylpiracetam let me achieve the highest state of cognitive functioning that I have ever been able to achieve that I have measured (by brain training games and other games that quantify performance such chess and hexagon). [1]https://www.reddit.com/user/t3light

One study found that it had significant benefits against the age-dependent decline in learning and memory in rats, as well as brain neuron protecting qualities.

WARNING: This peptide is highly experimental. Very little research has been done on the effects and side effects of P21, generally only anecdotal evidence is available.

P21 DOSAGE

1 mg a day. Some recommend up to 2-4 mg a day to increase acute effects.

TIME TO EFFECT

Reports exist of Cerebrolysin having effects for up to six months after usage.

COST

At the time of publishing, the cost for P21 is $69.99 for 50mg and $119.99 for 100mg of solution.

BUY

Only available from Ceretropic currently. They developed the peptide, but it was out of stock for a long period of time. As of 12/13/2016 it was currently in stock again and available as a nasal spray which may make for more convenient dosing.

ANECDOTES

From the owner of Ceretropic which developed the peptide:

It gives a very nice sense of focus, and when I take it nasally, it gives me a rapid mood boost for a few minutes. It’s actually very pronounced. I do not notice the same mood boost when injecting it. Perhaps the nasal administration gets it to the brain a lot faster.

Reddit user Guacamolium:

3 mg was my max so far. It was great. Clean focus, improved mood, motivation enhanced. Might venture to 5 mg in the future but I’m sampling other stuff right now.

Follow-up post on stacking:

Today I dared take it (3mg) with 1mg SEMAX and 15mg ephedrine, 100 mg caffeine, and 100 mg theanine and whoah did it give me a push, but a crash as well, though I wasn’t well on sleep so that could be a factor.
I actually may try it again today.

Reddit user nacholunchable:

Too many variables to say what exactly P21 contributes, but ive been taking it with NASemax and Bromantane since friday, and today I wrote 3 papers on my own time and came into class to write 2 essays. Which together adds up to about 20 pages. (Not to mention shoveling an icy driveway for my mother and helping my girlfriend complete an online exam). Finals week blows, but I’d have gotten half of it done, max without this powerhouse combination.

Reddit user BeardDysphoria:

I’ve abused Adderall for a few long years to the point where I was suffering from just about every symptom of dementia. The most frustrating symptom was the speech and language difficulties; to be more precise, my speech was jumbled and I couldn’t find the right words….

On day 2… I noticed that my speech has improved greatly, as I didn’t stutter or seize up even once…..

I consider P21 to be another miracle drug.

PS: My visual acuity seems to have improved as well.

Not all experiences have been positive. ww41 gives an extremely detailed account of brain fog and irritability:

I became very irritable and annoyed while in the company of anyone else. I also had a headache accompanied by “brain fog” and dulled cognitive processes. These negative effects persisted throughout the day and by the evening I had decided to stop dosing P21 for fear that I was causing myself harm.

RESEARCH

[1] Rescue of cognitive-aging by administration of a neurogenic and/or neurotrophic compoundNeurobiol Aging. 2014 Sep;35(9):2134-46. doi: 10.1016/j.neurobiolaging.2014.02.017. Epub 2014 Mar 2.

Treatment with P021 inhibited the deficit in neurogenesis in the aged rats and increased the expression of brain derived neurotrophic factor. Furthermore, P021 restored synaptic deficits both in the cortex and the hippocampus. In vivo magnetic resonance spectroscopy revealed age-dependent alterations in hippocampal content of several metabolites. Remarkably, P021 was effective in significantly reducing myoinositol (INS) concentration, which was increased in aged compared with young rats. These findings suggest that stimulating endogenous neuroprotective mechanisms is a potential therapeutic approach to cognitive aging, Alzheimer’s disease, and associated neurodegenerative disorders and P021 is a promising compound for this purpose.

From Neurotrophic peptides incorporating adamantane improve learning and memory, promote neurogenesis and synaptic plasticity in mice, Bin Li, FEBS Letters Volume 584, Issue 15, 4 August 2010, Pages 3359-3365 posted on Longecity.org: “[P21] is neurogenic and neuroplastic and enhances cognition in normal adult mice.” “P21 is an attractive candidate for the development of pro-cognitive drugs to prevent and treat learning and memory disorders and neurodegenerative diseases such as AD [Alzheimer’s Disease].”

P21 is also currently being studied for its effects on halting rheumatoid arthritis.

The latest research shows that P21 or P021 may be an effective treatment for Alzheimer’s Disease and holds promise for being developed as a drug. It has shown to regenerate neurons which is increasingly being seen as the Alzheimer’s treatment of choice. From Neurotrophic factor small-molecule mimetics mediated neuroregeneration and synaptic repair: emerging therapeutic modality for Alzheimer’s disease in Molecular Neurodegeneration:

P021 is a neurogenic and neurotrophic compound which enhances dentate gyrus neurogenesis and memory processes via inhibiting leukemia inhibitory factor (LIF) signaling pathway and increasing brain-derived neurotrophic factor (BDNF) expression. It robustly inhibits tau abnormal hyperphosphorylation via increased BDNF mediated decrease in glycogen synthase kinase-3β (GSK-3β, major tau kinase) activity. P021 is a small molecular weight, BBB permeable compound with suitable pharmacokinetics for oral administration, and without adverse effects associated with native CNTF or BDNF molecule. P021 has shown beneficial therapeutic effect in several preclinical studies and has emerged as a highly promising compound for AD drug development.

SIDE EFFECTS

Very little information is available on any possible side effects.

Some discussion of the side effects is available in research posted on Longecity.org, Neurotrophic peptides incorporating adamantane improve learning and memory, promote neurogenesis and synaptic plasticity in mice:

Administration of the full-length CNTF protein in human clinical trials is known to cause anorexia, skeletal muscle loss, hyperalgesia, cramps, and muscle pain [12] and [13]. However, in the present study, we did not observe any alteration in either general physical state, body weight (Fig. 2A), exploratory behavior (Fig. 2C) or swim speed (Fig. 2D) during the period of the study, suggesting that treatment with compound P21 or P22 did not induce any apparent side-effects. In the water maze task, we did not observe any floating behavior suggesting that animals treated with P21 or P22 did not present any sign of depression or locomotor impairment. The only general behavioral characteristic P21 and P22 altered was the level of anxiety of the mice.

CONCLUSION

P21 may have a noticeable effect on boosting mood and positive benefits guarding against cognitive aging, but there is very little information out there either anecdotal or research based.

SOURCES

https://www.reddit.com/r/Nootropics/comments/2gns4f/has_anyone_been_taking_p21_long_enough_to_give_a/

http://www.disabled-world.com/health/autoimmunediseases/rheumatoid-arthritis/p21-protein.php

http://www.longecity.org/forum/topic/65066-cntf-based-peptide-p21/

https://molecularneurodegeneration.biomedcentral.com/articles/10.1186/s13024-016-0119-y

 

Updated: 06/08/2016 to add information about current unavailability

Updated: 12/13/2016 to note that it is back in stock and to add the latest research article and anecdotes.

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Working on a better brain for all of us, or die trying. We've been using nootropics for years and have set up this website to help others on their journey for better brain function, memory improvement, energy level increases, fatigue reduction, mood improvement, and more.

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