Noopept (*N-phenylacetyl-L-prolylglycine ethyl ester) *is a synthetic nootropic drug which has become increasingly popular in the last five years. Noopept was originally synthesized in 1996 based on Piracetam and the endogenous neuropeptide cyclopropylglycine.
Chemically, Noopept is a dipeptide conjugate of Piracetam. (A dipeptide is just a type of protein with two amino acid residues). Noopept is a prescription drug in Russia that is promoted as a nootropic agent or cognitive enhancer, and used clinically to facilitate recovery from neurological injuries ranging from traumatic brain injury to stroke.
Outside of Eastern Europe, however, Noopept is unscheduled and therefore sold as a dietary supplement.
Noopept is increasingly being used by healthy individuals in an effort to propel intellectual performance above baseline. However, thus far Noopept has only been shown to improve cognition in patients with organic brain syndromes.
Though Noopept is not a racetam because it lacks a 2-oxo-pyrollidine nucleus, it’s mechanism of action and subjective benefits overlap with Piracetam. Both drugs appear to confer modest cognitive benefits without the harsh side effect profile of psychostimulants (drugs like Adderall or Ritalin). In addition, both Noopept and Piracetam seem to modulate excitatory glutamatergic signaling. The evidence for a role for glutamate receptors in Noopept’s mechanism of action comes from studies showing that non-NMDA glutamate receptor antagonists abolish Noopepet’s effects.1
Anecdotal reports suggest that Noopept dispels brain fog and improves verbal fluency, working memory, introspection and reflection. Noopept may also help alleviate the tip of the tongue phenomenon.
Noopept possess over 1000-fold greater potency than Piracetam. For this reason, the typical dose of Noopept is 10-30mg, compared to 4800 mg for Piracetam. After oral administration Noopept is absorbed in the gastrointestinal tract, enters circulation and penetrates the blood brain barrier without modification.
Noopept and Neurotrophic Factors (NGF and BDNF)
One study2 reported that Noopept boosts nerve growth factor (NGF) and to a lesser extent brain-derived neurotrophic factor (BDNF) expression in rat brain. Both BDNF and NGF are neuropeptides (protein signaling molecules in the brain) that play a crucial role in supporting brain function.
The standard dose for orally ingested Noopept is 10 mg – 30 mg.
For example, one open label prospective study including 60 patients used a dose of 20 mg daily over a two month period to improve cognitive function in patients with mild cognitive impairment (MCI).3
The 10 mg – 30 mg dose is much lower than the typical dose for Piracetam, which is 4800 mg. This difference in dosages reflects the fact that Noopept is over 1000 times more potent than Piracetam. Though Noopept is technically not classified as a Racetam, structurally Noopept is a dipeptide conjugate of Piracetam and also shares a common mechanism with Piracetam.
Noopept can be taken in tablet or capsule form, sublingually (under the tongue), or by dissolving Noopept powder in water or another solvent (like glycerin). Because Noopept is a dipeptide with polar functional groups, it easily dissolves in water.
Noopept stacks well with Alpha-GPC and other choline sources. It is also advisable to take magnesium threonate (or another form of magnesium) alongside Noopept, to put a ceiling on neuronal excitability. Magnesium is a divalent cation that limits NMDA receptor activity and thereby protects against excitotoxicity.
Noopept Experiences (Anecdotal)
Noopept users have anecdotally reported a kind of psychostimulant-like effect.4
I began experimenting with dosages, and at first, took too much. I started with about 20mg 3 times daily, and even tried a 40mg doses to see what that was like. The results were immediate. My thought processes went into overdrive, and I almost needed to calm my mind a bit, because I was thinking a mile-a-minute with all the new stimuli. This eventually led to a bit of mind fatigue, so I lowered the doses down to 10mg and bought some Choline bitartrate (the only form I could find locally) to help replenish my levels. I recommend using a scale, as such a minute amount as ~15mg can change the effectiveness a lot.
Noopept may also mitigate some of the effects of Alcohol.5
I have read a couple reports of people being able to negate side effects of alcohol with noopept and I found this to be absolutely true. Appx. 16 hours after taking my first noopept dose I went out to drink some beers and put away 7-8 over 2 hours or so, an amount that would usually have me stumbling out of the bar while boisterously discussing government conspiracies with innocent bystanders (yes, I can occasionally be THAT guy). Much to my surprise, I felt ZERO impairment of coordination, belligerence, and other symptoms of sloppy drunkenness that I usually do with that amount.
Longecity members also report memory improvement.6
When it comes to memory I really notice a strong effect. It’s not like I have a constant feeling of my present memory capabilities, but memories I thought were long lost suddenly appears in a vivid fashion. Also, it’s much easier to keep track of how I got to a certain place in my mind, my spatial memory is clearly affected. I haven’t measured direct learning though, but I have all reasons to expect it is improved.
And enhanced sociability7:
After some week something totally unexpected happened. It suddenly were A LOT easier to deal with people! To understand the revolution here you must understand that I’ve always had great problems with understanding other peoples irrational rules (social customs) and behaviours, and therefore I’ve had a hard time accepting them.
Not everyone has reported that Noopept is beneficial. For example, one Longecity user reported the following8.
1) I was less productive on average this past week at work than is typical. early in the week, it was an effect similar to amphetamine. You “feel” more productive, but you’re really not.
2) My clarity of thought has declined. My typing this moment is slower than usual and I am having trouble spelling. Writing in general has gotten worse. I feel very “spacey”.
3) My mood after a few days changed for the worst. Anger, irritability, lack of social inclinations… Worse, I was very curt with a contact of a client, to the point the person reported back to my client that I was “negative”. This has never happened before, and made my day hell yesterday. I am unsure what the long-term effects will be.
Before trialling Noopept yourself, it is difficult to predict whether Noopept will confer tangible cognitive benefits, simply because individual neurochemistry is so diverse from person to person. Some users will experience enhanced clarity while others will feel spacey from Noopept. Perhaps in the future, when pharmacogenetics has advanced and psychiatry has fully integrated genetic analysis into personalized treatment algorithms, we will be able to predict who will stand to benefit the most from certain medications.
The genetic kit offered by 23andMe represents the first step in this direction toward tailoring pharmacologic choices to genetics.
The effects of Noopept include the following[ref]http://www.brainprotips.com/noopept/#Literature_Summary[/ref]:
- ↑ global cognitive function
- ↑ Neurotrophins (Brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) expression)
- ↑ anxiolysis (decreased anxiety), ↑ memory consolidation, ↑ retrieval
- ↓ cytokines (inflammatory molecules)
- ↑ activation of inhibitory interneurons (hippocampus)
- ↓ hyperglycemia, ↓ BMI, ↓ pain sensitivity
- ↓ oxidative stress, ↓ glutamate toxicity, ↓ anoxic injury
- ↑ learning and memory
Note: many of these effects are inferred from studies conducted *in vitro *and in animal models. It is unknown whether and to what extent these effects might translate to humans.
Subjectively, my experience with Noopept has been that it enhances verbal fluency, mental clarity, gently increases alertness, and facilitates introspection.
Noopept Half Life
In one pharmacokinetic study conducted in rats, a 50 mg/kg dose of Noopept administered in a water solution resulted in peak Noopept serum concentrations after 10 minutes, with a half-life of about 7 minutes. After 25 minutes, no Noopept was detected in plasma or brain9.
The official package insert for Noopept (translated from Russian to English) states that the half-life of Noopept in humans is 0.38 hours or 22.8 minutes. The Noopept half life in humans differs from the kinetics in rats due to interspecies differences in absorption, clearance and metabolism.
However, the nootropic effects of Noopept are probably not directly related to the half-life due to the fact that Noopept has a biologically active metabolite that is structurally similar to cyclopropyl glycine, which itself has nootropic properties. Anecdotally, Noopept users have reported that the duration of subjective benefit for Noopept is around 60-90 minutes.
Neurobiology of Noopept
- Noopept rescues cognitive deficits in various models of brain injury and exhibits neuroprotective, anxiolytic, antiamnesic, psychostimulatory, and antidepressant properties.
- Pretreatment with Noopept prior to neurotoxic amyloid-beta exposure improves PC12 cell viability, reduced the number of apoptotic cells, attenuated reactive oxygen species (ROS) and calcium, and enhanced mitochondrial membrane potential. Noopept pretreatment also reduced tau hyperphosphorylation at Ser396 and rescued alterations in neurite growth elicited by amyloid beta.10
- Though Noopept is rapidly metabolized in human serum, it has a biologically active metabolite structurally similar to cyclopropyl glycine and its effects on brain waves have been noted for over 70 minutes.
- Noopept and Piracetam elicit similar EEG patterns. In one study, Noopept (10 mg/kg) more effectively ameliorated electroshock-induced cognitive deficits than Piracetam (200 mg/kg). Though Noopept is not a racetam, it’s mechanism of action is analogous to piracetam, involving enhancement of cholinergic signaling and modulation of AMPA receptor excitatory currents. Structurally, Noopept is a dipeptide conjugate of Piracetam.
- Acute administration of Noopept increases the expression of nerve growth factor (NGF) mRNA and to a lesser extent, brain-derived neurotrophic factor (BDNF) mRNA in rat hippocampus. Crudely speaking, BDNF and NGF are neuropeptides that act as “fertilizer” for the brain. They provide trophic support for neurons and promote synaptic long-term potentiation (the neurophysiologic correlate of learning and memory).
|**Effect||Synopsis||Experimental Paradigm||Journal Impact Factor||Abstract**|
|↓ apoptosis, ↓ ROS, ↓ intracellular Ca, ↓ tau hyperphosphorylation, ↓ alterations in neurite growth||Noopept protects against amyloid beta neurotoxicity in PC12 cells||PC12 cell culture; MTT assay to determine cell viability; western blot; immunocytochemistry and morphometry||2.76||Neuroprotective effect of novel cognitive enhancer noopept on AD-related cellular model involves the attenuation of apoptosis and tau hyperphosphorylation (2014)|
|↓ cytotoxicity of amyloid oligomers||Due to hydrophobic interactions with toxic amyloid oligomers, noopept prompts rapid sequestration into larger amyloid aggregates. This process rescues the cytotoxic effects of amyloid oligomers||Neuroblastoma SH-SY5Y cells; cell viability assays; fluorescent staining of apoptotic and necrotic stress; assessment of intracellular oxidative stress||4.33||Neuroprotective and nootropic drug noopept rescues α-synuclein amyloid cytotoxicity (2011)|
|↑ inhibitory hippocampal neurotransmission||Noopept treatment enhanced the inhibitory component of total current induced by stimulation of shaffer collaterals in CA1 pyramidal neurons without affecting the excitatory component.||Hippocampal slices from Wistar rats||0.358||Nootropic dipeptide noopept enhances inhibitory synaptic transmission in the hippocampus (2015)|
|↑ cognitive function||Noopept treatment (20mg/day) improved global cognitive function in stroke patients (n=60)||Open prospective study in humans||Noopept in the treatment of mild cognitive impairment in patients with stroke (2011)|
|↑ BDNF (hypothalamus), ↑ BDNF mRNA (hippocampus, hypothalamus), ↓ SAPK/JNK 46/54, ↓ pERK 1/2||Noopept treatment decreased activity of stress-activated MAPKs (SAPK/JNK 46/54 and pERK 1/2) in rat hippocampus and increased BDNF and BDNF mRNA in hypothalamus and hippocampus.||Interrogation of protein expression in rats||On the mechanism of noopept action: decrease in activity of stress-induced kinases and increase in expression of neutrophines (2010)|
|↑ BDNF (hippocampus), ↑ NGF (hippocampus)||Expression of the studied neurotropic factors in the cerebral cortex was below the control after single administration of Noopept, while chronic administration caused a slight increase in BDNF expression. In the hippocampus, expression of mRNA for both neurotrophins increased after acute administration of Noopept. Chronic treatment with Noopept was not followed by the development of tolerance, but even potentiated the neurotrophic effect.||Northern blot analysis in rats||0.358||Noopept stimulates the expression of NGF and BDNF in rat hippocampus (2008)|
|↑ anxiolysis, ↑ memory consolidation, ↑ retrieval||The minimum effective dose of noopept is thousand times lower compared with piracetam. Noopept promotes anxiolysis while facilitating memory consolidation and retrieval. Noopept exhibits antioxidant, anti-inflammatory properties while protecting against glutamate and calcium-induced neurotoxicity.||Review||The original novel nootropic and neuroprotective agent noopept (2002)|
|↓ cytokines||Noopepet decreased IL-6, TNF-alpha after inflammatory challenge with Lipopolysaccharide (LPS)||Mouse model of inflammation using LPS||0.358||Efficiency of noopept in streptozotocin-induced diabetes in rats (2013)|
|↑ activation of inhibitory interneurons (hippocampus)||Bath application of Noopept increased the frequency of spike-dependent spontaneous m1PSCs, putatively mediated by activation of inhibitory interneurons terminating on CA1 pyramidal cells.||Bath application of Noopept increased the frequency of spike-dependent spontaneous m1PSCs, putatively mediated by activation of inhibitory interneurons terminating on CA1 pyramidal cells.||Peptidergic modulation of the hippocampus synaptic activity (2011)|
|↓ hyperglycemia, ↓ BMI, ↓ pain sensitivity||Both preventive and therapeutic doses of noopept ameliorated streptozotocin-induced diabetes in rodents||Rodent model of diabetes using the selective pancreatic beta cell toxin Streptozocin||0.358||Efficiency of noopept in streptozotocin-induced diabetes in rats (2013)|
|↓ oxidative stress, ↓ glutamate toxicity, ↓ anoxic injury||Noopept but not piracetam attenuated neurodegeneration induced by oxygen-glucose deprivation, glutamtae toxicity and oxidative stress||in vitro culture of cerebellar granule cells||0.358||Neuroprotective properties of nootropic dipeptide GVS-111 in in vitro oxygen-glucose (deprivation, glutamate toxicity and oxidative stress (2000)|
|antiamnesia||Noopept rescued deficits in retrieval of passive avoidance responses after compression-induced damage to the frontal cortex||Rodent model of compression-induced cerebral ischemia||0.358||Antiamnesic effect of acyl-prolyl-containing dipeptide (GVS-111) in compression-induced damage to frontal cortex (2000)|
|↑ learning and memory||Noopept rescued cognitive impairments induced by bilateral frontal lobectomy||Bilateral frontal lobectomy in rats||2.148||The novel substituted acylproline-containing dipeptide, GVS-111, promotes the restoration of learning and memory impaired by bilateral frontal lobectomy in rats (1997)|
Where To Buy Noopept
For Noopept, Nootropics Depot offers the best compromise between value and quality.
|**Vendor||Noopept Cost||Noopept Cost/gram||Estimated Shipping Cost||Purity (recent batch)||Certificates of Analysis**|
|Peak Nootropics||$14.99 (10g)||$1.50/g||$5.65 (USPS Priority)||101.4%||Independent COA by Colmaric Analyticals|
|PowderCity||$7.87 (5g)||$1.57/g||$1.73 (Standard Post)||98.1%||Available Upon Request|
|Absorb Health||$19.99 (10g)||$2.00/g||Free||N/A|
|Nootrico||39.99 (20g)||$2.35/g||$2.00||99.56%||Independent COA by Colmaric Analytics|
|New Star Nootropics||$11.80 (5g)||$2.36/g||$3.65 (USPS First Class)||Independent COA by Bruker HNMR and LCMS|
|LiftMode||$11.88 (5g)||$2.38/g||Free||99.82% (HPLC)||Independent COA by Colmaric Analytics|
|Ceretropic||$11.99 (5g)||$2.40/g||$5 (USPS First Class)||> 99.5%||COA|
Noopept and Alcohol
Strictly speaking, Noopept and alcohol are not contraindicated, since no documented interactions exist between the two substances.
However, because Noopept mitigates the intoxicating effects of alcohol, it is possible that co-administration of Noopept and alcohol would result in excessive alcohol consumption, because the effects of alcohol wouldn’t be “felt” as strongly. Or in other words, you might not feel as drunk as you actually are by adding Noopept into the mix, leading to overdrinking.
It is always best to exercise caution when engaging in polypharmacy or combining substances.
Some psychonauts have ingested megadoses of Noopept as high as 600mg, or 20 times the highest recommended dose of 30mg. One individual reported the following subjective effects after ingesting 600 mg of Noopept:
Well, I didn’t experience anything too out of the ordinary compared to a regular Noopept dosage of 20 to 40 mg’s.
Eyesight: Brighter colors, increased visual acuity, enhanced pattern recognition.
Hearing: Enhanced appreciation for music.
Touch: No noticeable increase in sensation.
Smell: Slight change. Nothing to write home about.
Focus: Spent my time rummaging through Reddit articles, listening to obscure electronica music and Youtube videos for four hours before eventually going to sleep.
Memory: I recalled about fifteen minutes worth of my dreams upon waking up this morning.
Dreams: Odd and out of the ordinary. Had a dream that a spider crawled into my penis. Woke up and for a split-second hallucinated the spider crawling out and into my bed. Reminds me of the time I awoke to a fifteen or so second hallucination of my mother standing by my bed telling me to wake up at which point she vanished into thin air. Freaked me out for a few hours.
Overall it wasn’t anything spectacular. Obviously a waste of Noopept and will not be megadosing again anytime soon.
It is unlikely that Noopept megadoses will confer any added benefit than the standard 10-30mg dose, and the risks of bodily harm are significant.
In general, excessive doses of nootropics can result in overstimulation without euophoria (hence, Nootropics have little abuse potential). Megadoses of nootropics can also result in impaired functioning. For example, it is well-documented that the psychostimulants Ritalin (methylphenidate) and Adderall (mixed amphetamine salts) improve cognitive performance (in a subset of subjects) at low doses but impair cognition at high doses.