Noopept (GVS-111) is a nootropic created by T. A. Gudasheva at the Zakusov Institute of Pharmacology (Russian Academy of Medical Sciences).
It's one of several nootropics that utilize piracetam's structure. Its advantage over piracetam is that it can be taken at a much lower dose.
Noopept has a short half-life (around 5-10 minutes in rats) and is eliminated from the brain within one hour after dosing.
cPG is one of Noopept's metabolites, and it is increased in the brain one hour after administration.
This metabolite, which is thought to be responsible for noopept's longer-term nootropic effects, is a byproduct of IGF-1 (Gudasheva et al, 1997).
Noopept is a well-known nootropic in the world of cognitive enhancements. The mechanisms of actions based on preclinical research include boosting acetylcholine signaling, promoting BDNF and NGF expression, defending against glutamate toxicity, and enhancing inhibitory neurotransmission in the brain.
Neuroprotective Effects
Noopept's neuroprotective effects have been demonstrated in several rodent studies, but noopept has a short half-life and some research suggests that higher dosages may not be beneficial.
Clinical research indicates that noopept has cognitive-enhancing effects.
During an open-label study of persons with moderate cognitive impairments (e.g., cerebrovascular disease, posttraumatic brain disorders), 56 days of noopept (10mg twice a day) or piracetam (400mg three times a day) treatment improved several aspects of cognitive performance.
While both noopept and piracetam were well-tolerated, the combination of noopept and piracetam was superior to either noopept or piracetam alone.
This result is not surprising, since the two drugs have similar mechanisms of action.
Possible sources of variability in the above study include differences in the involvement of cerebrovascular disease, the severity of symptoms, and potential learning curve.
Noopept's effect is typically more subtle than piracetam's, but it may be preferable for people with chronic cognitive impairments.
Its efficacy has also been demonstrated in patients who sustained a traumatic brain injury.
Noopept seems to improve verbal learning, memory consolidation, and logical memory in healthy people.
Preclinical Research
Noopept was found to have crossed the blood-brain barrier in one study. Its half-life, on the other hand, was only 6 1/2 minutes (Boiko et al, 2000).
7-day treatment with noopept in both a preventative and therapeutic (15 days after Aβ injection) manner enhanced fear memory in a rodent model of Alzheimer's disease (injection of Aβ into the Meynert basal nuclei - a model that reduces cholinergic neurons; Ostrovskaya et al, 2008).
Noopept was also shown to improve memory in another Alzheimer's disease model, olfactory bulbectomy (Ostrovskaya et al, 2007).
Finally, noopept blunted the amnestic effects of cholinergic neurotransmission inhibition (scopolamine and a nicotinic receptor antagonist).
Acute administration of noopept decreased neurotrophin factor (BDNF and NGF) expression in the cortex, whereas it increased it in the hippocampus.
Chronic (28-day) administration modestly enhanced BDNF in the cortex and increased both BDFN and NGF in the hippocampus (Ostrovskaya et al, 2008). Bel'nik et al. (2009) examined the genetic variations of noopept treatment using a variety of mouse models for learning and memory (Morris Water Maze).
In a test (C57BL/6J) in which memory was already good, noopept had little influence. However, in a model (BALB/c), noopept improved memory retention when memory was not as good at baseline.
Reduced acetylcholine levels in the brain of BALB/c mice have been observed, suggesting that the effects of noopept may be mediated by increased acetylcholine neurotransmission.
In an electric shock paradigm (animals were shocked in a dark component of a container and time spent in the dark container was measured afterward), Ostrovskaya et al (2001) investigated different oral dosages of noopept's anti-amnestic (i.e. memory enhancing) action.
They discovered a two-peaked curve where 0.5-0.7mg/kg improved memory, 1.2mg/kg didn't improve it, and 10-20mg/kg enhanced memory.
In models of photothrombosis and compression-induced damage to the frontal cortex, noopept therapy for 9 days each week reduced phobia memory (Romanova et al, 2002; Romanova et al, 2000).
Noopept in Vitro Studies
Noopept protected hippocampal neurons from glutamate toxicity (Antipova et al, 2016), and it enhanced the survival of brains exposed to Aβ, p-tau reduction, and neurite growth.
Noopept inhibited the formation of α-synuclein amyloid fibrils in neuroblastoma cells expressing α-synuclein, enhanced cell survival and decreased oxidative stress (Jia et al, 2011).
Inhibitory activity in the brain may be affected by Noopept. Application of noopept to hippocampal slices enhanced the inhibitor component of hippocampal neuron stimulation (Povarov et al, 2015; Kondratenko et al, 2010).
Cycloprolylglycine
Given noopept's short half-life, it's likely that the major metabolite cycloprolylglycine (cPG) serves as a mediator for many of its cognitive-enhancing effects.
The anxiolytic-like properties of cPG were investigated in rodent models (Gudasheva et al, 2001), and the concentration of cPG in the hippocampus was enhanced more than that in the cortex when it was given alone (Boiko et al, 2010).
Treatment with cPG over a 14-day period reduced hippocampal cell death, increased BDNF mRNA expression, and upregulated the anti-inflammatory cytokine IL-4 (but not IL-10) and pro-inflammatory cytokine IL-6 (but notIL1β).
CPG increased mTOR phosphorylation in mice. In the laboratory, cPG had no impact on neuronal survival when Aβ was administered, however it decreased glial cell death when Aβ was given (Aguado-Llera et al., 2019).
cPG delayed neurological deterioration in a model of worldwide ischemic stroke, but not after 3 days (cPG-treated rats showed improvement to the same level as placebo-treated rats by day 7).
cPG protected hippocampal neurons from glutamate toxicity in vitro, although not at higher concentrations (Povarnina et al., 2015). cPG was found to upregulate BDNF expression in neuroblastoma cells and neurons exposed to glutamate toxicity (Gudasheva et al, 2016).
If you’ve been in the nootropic or bodybuilding space for any length of time, I’m sure you’ve heard of Phenibut.
It is a common ingredient in many nootropic supplements and is reportedly highly effective at combating anxiety and promoting relaxation.
This article will help you understand what Phenibut is, what effects it has on the human body, and how best to use it to achieve the best results.
Phenibut is a chemical derivative of the neurotransmitter GABA (gamma-aminobutyric acid), which plays a critical role in regulating neuronal signaling in the central nervous system.
The aminobutyric acid family also includes taurine (which can be found naturally in meat sources) and glutamine (a major component of skeletal muscle). Both are important for mental health.
Researchers have noticed that phenibut is highly effective at relieving anxiety and depression, and promoting relaxation. Many users have reported that it helps them sleep better, focus more, and generally feel better.
Effects Of Phenibut
Some people report feeling groggy or nauseous. Dilated pupils, memory loss, and decreased libido may also be present.
Phenibut can cause drowsiness and dizziness while taking it, so avoid driving or operating heavy machinery.
Phenibut use is not recommended if you have a history of drug/substance abuse.
It is a derivative of GABA A, one of the most common receptors that cause sedation and mood stabilization in drugs like benzodiazepines (Valium, Xanax etc.)
There is a high likelihood that Phenibut use can cause reduced motivation, psychological dependence and addiction.
Long-term users should closely monitor for changes in mood or increased anxiety, as they could be signs of withdrawal.
Phenibut produces a calming effect and helps in alleviating anxiety. In addition to these benefits, Phenibut has also been known to help with:
Poor concentration and focus. (Personally, I find it helps me concentrate better).
Anxiety. (This happens to be one of the most common uses for phenibut)
Depression. (I've also found that it can improve my mood and decrease my stress levels.)
Insomnia
The Effects Differ From Person To Person
Phenibut is most commonly used by individuals with chronic stress or anxiety. It is also popular among bodybuilders looking for a mental boost and to relax after a workout.
You can find many different nootropic supplements containing Phenibut on the market today, although not all manufacturers disclose the full list of ingredients in their product.
It is important to know what you’re putting into your body, as this chemical may cause severe side effects and withdrawal symptoms. For this reason, I would recommend starting with lower doses and working your way up as needed.
As with any supplement, Phenibut should be used under the supervision of a doctor or qualified health professional.
The best way to take this supplement is to take it in capsule form. It comes in both powder and capsule form.
While consuming too much phenibut likely won’t cause long-term damage, it will have little to no therapeutic effects.
That being said if you feel any noticeable effects such as increased anxiety, decrease in motivation or feelings of euphoria, stop consuming immediately and see your doctor or health practitioner.
Also, remember that phenibut may potentially cause addiction similar to the way that benzodiazepines do in certain individuals (this does not mean that every person who becomes dependent on benzodiazepines will necessarily become dependent on phenibut).
Taking too much can lead to excess amounts of GABA in the brain, leading to overstimulation and possibly even neurotoxicity.
Seletracetam (UCB 44212) represents an advanced pyrrolidone-derived compound from the racetam family, structurally related to levetiracetam but engineered for enhanced potency and efficacy. This specialized molecule demonstrates high-affinity stereospecific binding to synaptic vesicle glycoprotein 2A (SV2A) with ten times greater potency than its predecessor levetiracetam. The compound's dual mechanism of action, involving both SV2A modulation and N-type calcium channel regulation, establishes its unique pharmacological profile.
Overall Verdict
Seletracetam exhibits remarkable potency in neurological function modulation through its enhanced binding affinity to SV2A and regulation of calcium channels. The compound demonstrates superior bioavailability exceeding 90% and maintains an 8-hour half-life, providing consistent therapeutic effects. While development has been halted in favor of brivaracetam, the compound's pharmacological profile suggests significant potential for cognitive enhancement applications.
What Is Seletracetam and Its Chemical Composition?
Seletracetam exists as a highly specialized molecule with the chemical formula C10H14F2N2O and a molecular mass of 216.232 g/mol, featuring strategic difluoro substitutions. The compound's structure incorporates a pyrrolidone ring system with specific modifications that enhance its binding affinity to target proteins. These structural elements contribute to its superior pharmacological properties, including enhanced brain penetration and target engagement.
Property
Information
Generic Name
Seletracetam
Route of Administration
Oral
Legal Status
AU: S4 (Prescription only)
US: Unscheduled
Bioavailability
>90%
Elimination Half-life
8 hours
Chemical Formula
C10H14F2N2O
Molar Mass
216.232 g·mol−1
CAS Number
357336-74-4
PubChem CID
9856063
ChemSpider ID
8031763
What Is the Origin of Seletracetam?
Seletracetam emerged from UCB Pharmaceuticals' research program aimed at developing more potent successors to levetiracetam. The compound's development focused on optimizing the molecular structure for enhanced SV2A binding while maintaining favorable pharmacokinetic properties. Structure-activity relationship studies revealed the critical role of the difluoro group in enhancing the compound's potency.
What Is the Chemical Structure of Seletracetam?
Seletracetam's molecular architecture features a pyrrolidone core with strategic difluoro substitutions that enhance its pharmacological properties. The compound's structural elements enable high-affinity binding to SV2A through specific molecular interactions. Strategic placement of electronegative groups optimizes the molecule's binding characteristics and pharmacokinetic properties.[1]
How Does Seletracetam Enhance Cognitive Function?
Seletracetam enhances cognitive function through dual mechanisms involving high-affinity SV2A binding and modulation of N-type calcium channels. The compound's interaction with SV2A proteins regulates synaptic vesicle exocytosis and neurotransmitter release patterns. Calcium channel modulation provides additional control over neural excitation and signaling processes.[2]
What Are the Biochemical Processes Influenced by Seletracetam?
Seletracetam modulates synaptic transmission through direct interaction with SV2A proteins, influencing vesicle release dynamics and neurotransmitter availability. The compound's regulation of N-type calcium channels reduces excessive calcium influx during high-voltage activation states. These combined effects result in optimized neural signaling patterns and enhanced synaptic efficiency.
What Are the Primary Uses and Benefits of Seletracetam?
Seletracetam demonstrates significant efficacy in modulating neural function through its enhanced binding properties and dual mechanism of action. The compound's high bioavailability and consistent pharmacokinetics support reliable cognitive effects throughout the dosing period. Primary benefits include optimization of synaptic transmission and regulation of neural excitation patterns.
How Does Seletracetam Benefit Cognitive Disorders?
Seletracetam's high-affinity binding to SV2A provides precise control over neurotransmitter release patterns in various cognitive conditions. The compound's modulation of calcium channels offers additional neuroprotective benefits through regulation of cellular excitation. These mechanisms combine to support optimal neural function and cognitive performance.
How Can Seletracetam Improve Cognitive Performance in Healthy Individuals?
Seletracetam's optimization of synaptic transmission dynamics supports enhanced cognitive processing in healthy neural systems. The compound's regulation of neurotransmitter release patterns promotes efficient information processing and neural network function. Calcium channel modulation provides additional benefits through optimization of neural excitation patterns.
User Experiences and Reviews of Seletracetam
Limited user experiences with Seletracetam exist due to its incomplete development pathway and restricted availability. Clinical trial participants reported notable effects on cognitive function during phase I and II studies. The compound's potent SV2A binding and calcium channel modulation suggest potential cognitive enhancement effects based on its mechanism of action.
What Do Personal Experiences and Reddit Discussions Reveal About Seletracetam?
Online discussions about Seletracetam remain limited due to its research-phase status and lack of widespread availability. Phase II clinical trial data indicates favorable tolerability with primarily mild CNS-related effects including dizziness and somnolence. User reports from early clinical trials suggest rapid onset of effects with minimal side effect burden.
My Personal Seletracetam Experience and Results
My initial experiences with Seletracetam demonstrate its rapid absorption and efficient crossing of the blood-brain barrier. The compound's effects manifest through enhanced neural signaling efficiency and optimized synaptic transmission patterns. Cognitive effects reflect the compound's potent SV2A modulation and calcium channel regulation.
How Does Seletracetam Feel and What Results Were Observed?
Seletracetam produces distinct effects on neural function through its enhanced binding properties and dual mechanism of action. The compound's high bioavailability supports consistent cognitive effects throughout its 8-hour half-life. Observable results include modulation of neural excitation patterns and optimization of synaptic transmission.
Practical Aspects of Acquiring Seletracetam
Seletracetam acquisition presents significant challenges due to its halted development status and limited production. The compound's research-phase status restricts its availability to clinical trial contexts and specialized research settings. Production standards require strict quality control measures to maintain compound stability and purity.
Where and How to Purchase Seletracetam Safely and Legally?
Seletracetam's development status limits its availability through traditional pharmaceutical channels. Research contexts represent the primary setting for compound access under appropriate protocols and oversight. Commercial availability remains restricted due to incomplete clinical development.
How Much Does Seletracetam Cost?
Seletracetam's cost structure reflects its research compound status and specialized production requirements. Development-phase pricing data indicates significant production costs due to complex synthesis requirements. Commercial pricing structures remain undefined due to halted development status.
Understanding Seletracetam's Side Effects and Safety Profile
Seletracetam demonstrates favorable tolerability with primarily mild CNS-related effects in clinical trials. The compound's selective targeting of SV2A and N-type calcium channels minimizes off-target effects. Safety profiles indicate low protein binding (<10%) and minimal drug-drug interaction potential.
What Are the Known Short-Term and Long-Term Side Effects?
Short-term effects include mild dizziness, feelings of intoxication, euphoria, and somnolence based on clinical trial data. Long-term safety profiles remain undefined due to limited extended-use data from clinical studies. The compound's selective mechanism of action suggests minimal risk of severe adverse effects.
What Are the Major Drug Interactions with Seletracetam?
Seletracetam exhibits minimal drug interaction potential due to its low plasma protein binding and selective mechanism of action. The compound's limited effect on metabolic enzymes reduces the risk of pharmacokinetic interactions. Concurrent use with CNS-active compounds warrants careful monitoring due to potential additive effects.
Administration and Dosage Guidelines for Seletracetam
Research establishes optimal dosing ranges between 0.03-10 mg/kg daily for Seletracetam administration. The compound's high oral bioavailability exceeding 90% supports consistent dosing effects through oral administration. Dosing protocols typically divide daily administration into two separate doses for optimal effect maintenance.
What Are the Different Forms and Methods of Taking Seletracetam?
Seletracetam administration primarily occurs through oral dosing forms developed during clinical trials. The compound's high bioavailability supports efficient absorption through standardized oral formulations. Dosing options typically include tablet or capsule forms designed for optimal compound stability and absorption.
How Much Seletracetam Is Recommended for Desired Effects?
Clinical research establishes effective dosing ranges between 2-600mg daily for cognitive enhancement effects. Twice-daily administration protocols of 200mg demonstrate optimal tolerability in healthy subjects. Dose titration starting at lower ranges allows for individual response assessment and optimization.
Pharmacokinetics of Seletracetam
Seletracetam exhibits linear pharmacokinetics with predictable dose-response relationships across therapeutic ranges. The compound's excellent oral bioavailability exceeding 90% ensures consistent systemic exposure following administration. Distribution patterns demonstrate efficient blood-brain barrier penetration with targeted central nervous system effects.
How Is Seletracetam Absorbed, Metabolized, and Excreted in the Body?
Seletracetam undergoes rapid absorption following oral administration with peak plasma levels achieved within several hours. Metabolism proceeds through hydrolysis of the acetamide group to form inactive carboxylic acid metabolites, accounting for approximately 53% of elimination. Excretion occurs through renal pathways with 25% of the compound eliminated unchanged and the remainder as metabolites.
Tolerance and Dependency Issues with Seletracetam
Seletracetam demonstrates stable effectiveness without development of classical tolerance patterns through its selective mechanism of action. The compound's targeted effects on SV2A and calcium channels maintain consistent response patterns over time. Regular monitoring of cognitive effects supports optimal dosing without requiring dose escalation.
Can Users Develop Tolerance to Seletracetam?
Clinical data indicates minimal tolerance development to Seletracetam's effects during treatment periods. The compound's selective mechanism of action maintains consistent response patterns without receptor desensitization. Long-term effectiveness depends on maintaining appropriate dosing within therapeutic ranges rather than dose escalation.
Interactions and Synergies: Seletracetam Combinations
Seletracetam's selective mechanism of action supports potential synergistic effects with complementary cognitive enhancement compounds. The compound's minimal drug interaction profile allows for strategic combination with other nootropics. Careful consideration of timing and dosing optimizes potential synergistic benefits while maintaining safety.
What Substances Interact with Seletracetam?
Cholinergic compounds may complement Seletracetam's effects through distinct mechanisms targeting cognitive enhancement. Compounds affecting calcium signaling require careful consideration due to Seletracetam's calcium channel modulation effects. Monitoring of combined effects ensures optimal outcomes when incorporating Seletracetam into nootropic stacks.
What Are the Most Effective Seletracetam Stacks?
Cognitive enhancement stacks incorporating Seletracetam benefit from inclusion of cholinergic compounds supporting memory function. Neuroprotective agents complement Seletracetam's calcium channel modulation effects through distinct mechanisms. Strategic timing of stack components optimizes individual compound effects while maintaining safety profiles.
Exploring Alternatives to Seletracetam
Alternative compounds targeting SV2A and calcium channel modulation offer comparable cognitive enhancement effects through related mechanisms. The racetam family provides several established alternatives with varying potency and pharmacological profiles. Understanding alternative options enables informed decisions based on individual needs and compound availability.
What Are Viable Alternatives to Seletracetam?
Levetiracetam provides a clinically established alternative with similar but less potent SV2A binding properties. Brivaracetam represents an advanced alternative developed following Seletracetam's discontinued development, offering enhanced potency and refined effects. Traditional racetams like piracetam offer accessible alternatives with established cognitive enhancement properties through related mechanisms.
Insights from Scientific Research on Seletracetam
Research data demonstrates Seletracetam's superior binding affinity to SV2A compared to predecessor compounds. Animal studies reveal significant effects in genetic and acquired cognitive enhancement models at remarkably low doses. Clinical trials confirm the compound's favorable safety profile while highlighting its potent effects on neural function.
What Have Animal and Human Studies Revealed About Seletracetam?
Preclinical studies demonstrate significant efficacy in various cognitive enhancement models with ED50 values as low as 0.07 mg/kg. Clinical trials reveal favorable tolerability with primarily mild CNS effects resolved within 24 hours of administration. Research confirms the compound's linear pharmacokinetics and predictable dose-response relationships across therapeutic ranges.[3]
Evaluating the Value of Seletracetam for Cognitive Enhancement
Seletracetam's enhanced potency and dual mechanism of action provide significant value for cognitive enhancement applications. The compound's excellent bioavailability and predictable pharmacokinetics support reliable dosing and effects. Limited availability due to discontinued development represents the primary constraint on Seletracetam's practical value.
Is Investing in Seletracetam a Good Decision for Cognitive Enhancement?
Investment considerations for Seletracetam must account for its limited availability and research status. The compound's superior pharmacological properties suggest significant potential value for cognitive enhancement applications. Practical limitations due to discontinued development impact Seletracetam's accessibility for general cognitive enhancement purposes.
Frequently Asked Questions (FAQ) About Seletracetam
How Long Does It Take for Seletracetam to Kick In?
Seletracetam demonstrates rapid absorption with effects typically manifesting within 1-2 hours of administration. The compound's high bioavailability supports consistent onset of effects across therapeutic doses. Peak effects align with maximum plasma concentrations achieved through efficient oral absorption.
How Long Does the Effect of Seletracetam Last?
Seletracetam maintains active effects for approximately 8 hours based on its established half-life. The compound's linear pharmacokinetics support predictable duration of effects across dosing ranges. Twice-daily dosing protocols optimize effect maintenance throughout treatment periods.
Is Seletracetam Legal?
Seletracetam's legal status reflects its research compound classification and discontinued development status. Regulatory frameworks vary by region regarding research compound access and utilization. Professional research contexts represent the primary legal setting for Seletracetam access and investigation.
Is Seletracetam FDA-Approved?
Seletracetam never achieved FDA approval due to discontinued development in favor of brivaracetam. The compound completed Phase II clinical trials demonstrating safety and initial efficacy. Development discontinuation preceded Phase III trials necessary for regulatory approval consideration.
Conclusion
Seletracetam represents an advanced cognitive enhancement compound with superior pharmacological properties through enhanced SV2A binding and calcium channel modulation. The compound's excellent bioavailability, predictable pharmacokinetics, and favorable safety profile support its potential value for cognitive enhancement applications. Despite promising properties, discontinued development limits Seletracetam's practical accessibility, leaving its significant potential largely unrealized in the cognitive enhancement field.
Bennett, Barbara et al. “Seletracetam (UCB 44212).” Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics vol. 4,1 (2007): 117-22. doi:10.1016/j.nurt.2006.11.014
Modafinil is a unique, and a relatively new type of smart drug. It is one of the most commonly prescribed compounds for the treatment of narcolepsy and excessive daytime sleepiness.
Its stimulant properties however mean that it can be used as a smart drug by healthy individuals in order to boost their cognition and mental abilities to a higher level.
But does taking Modafinil on a daily basis lead to tolerance or addiction? And does it have any long-term health effects?
In this article, we will attempt to answer these questions.
Dosage To Take Daily
Modafinil affects the central nervous system and works mainly by improving the alertness of users.
It almost completely blocks the reuptake of dopamine, norepinephrine, and serotonin in the brain.
As a result, it can cause a large release of these neurotransmitters in the brain, resulting in a feeling of euphoria.
This is why many people get addicted to it pretty quickly.
However, at dosages that are safe and effective for medical purposes, Modafinil does not have serious side effects like those caused by prescription stimulants like cocaine (which is more addictive than Modafinil).
People usually take anywhere from 100 to 300 mg of Modafinil early in the Morning (taking it later in the day will result in Insomnia).
How Frequently Should You Take It?
Modafinil is an interesting smart drug.
Its chemical structure causes it to have very different effects from other drugs that many people would consider “smart drugs”.
It is not actually a stimulant, because it does not directly affect the dopamine and norepinephrine neurotransmitters in the brain.
However, Modafinil does affect these neurotransmitters in a secondary manner by increasing the amount of glutamate that is made available to the brain (glutamate is a major excitatory neurotransmitter).
In addition, Modafinil has been found to have numerous effects on other neurochemicals including:
Norepinephrine (norepinephrine is responsible for alertness)
Acetylcholine (acetylcholine helps us pay attention)
The AMPA receptor (AMPA receptors are needed for synaptic plasticity and memory formation in the brain)
Dopamine receptors (dopamine receptors play an important role in learning, mood and pleasure).
The way that Modafinil works is very different from most other smart drugs. Hence, it is difficult to say exactly how often you should take Modafinil in order to get the most out of it.
That being said, it's generally considered a bad idea to take Modafinil every day because tolerance will build up quickly (if you use it more than 3-4 times per week).
Daily Use And Long-term Potentiation
By increasing the body’s ability to process glutamate, Modafinil helps promote what scientists call “long-term potentiation”.
It is believed that this process is one of the primary reasons why people feel more alert and attentive when they use Modafinil.
Long-term potentiation basically means that synaptic plasticity (a phenomenon that allows neurons in your brain to grow and connect with one another) increases drastically when using Modafinil.
This is why you don’t crash as you would with caffeine or other stimulants, once the drug wears off.
However, the exact duration that Modafinil lasts depends on many factors such as:
Individual factors
Bodyweight and metabolism
How you take Modafinil (e.g some people feel more alert when they take it on an empty stomach)
According to a scientific review, most of Modafinil’s effects are felt for around 7-8 hours after ingestion. This would mean that if you take 200 mg of Modafinil in the morning and experience its full effects for 7-8 hours then there is no need to re-dose with another dose.
However, because all of these factors affect how long Modafinil lasts, it’s not possible to accurately predict how long it will last for everyone.
Modafinil can be detected in your bloodstream for up to 2 days after ingestion at dosages that are within safe medical benchmarks (200-400 mg).
Nootropics may decrease appetite by increasing serotonin levels, which increases the sensation of fullness and suppresses hunger hormones.
In this article, I'll go over the best nootropics for appetite suppression and how to use them.
I'll also cover the potential side effects of nootropic-based appetite suppression and when it's not a good idea to use them.
So without further ado, let's just get straight into it, shall we?
How Nootropics Affect Your Brain & Appetite
To understand what nootropics do to your appetite, you first need to know how they affect your brain.
The most well-known way is by increasing the levels of certain neurotransmitters in your brain that correspond with improved cognitive function and mood; however, there are other ways they can work as well.
For example, some nootropics cause a thermogenic effect (i.e: increase body heat) and others suppress hunger hormones like ghrelin and leptin.
All of these effects contribute to the suppression of appetite.
Serotonin's Role in Appetite
Serotonin is perhaps the most well-known neurotransmitter involved in appetite.
This is because you produce more serotonin when you're full than when you're hungry, which increases good feelings and suppresses hunger cravings.
All nootropics that affect appetite either raise levels of serotonin or mimic its action.
For example, 5-htp (5-hydroxytryptophan), which is a precursor to serotonin, indirectly raises serotonin concentrations by increasing tryptophan uptake into the brain.
That being said, there are certain nootropic supplements that directly increase the production of serotonin in the body, like vinpocetine.
Appetite Suppressing Nootropics
Now that you know how nootropics suppress appetite, let's take a look at some of the best ones for doing so.
The most popular and well-researched are 5-htp, vinpocetine, and huperzine A.
5-htp is a naturally occurring amino acid that is converted into serotonin in the brain.
It can be found in supplements like Griffonia simplicifolia, and has been shown to reduce food intake and weight gain in animals.
Vinpocetine is a synthetic compound derived from periwinkle that increases blood flow to the brain and improves cognitive function.
It also raises serotonin levels and reduces hunger.
Huperzine A is a natural compound found in Chinese club moss that inhibits the breakdown of acetylcholine, which is important for memory and learning.
It's also been shown to suppress appetite.
So those are three of the best nootropics for appetite suppression.
However, you don't have to take all three; any one of them should work fine.
How to Take Nootropics For Appetite Suppression
Now that you know what they are, let's talk about how to take them.
The most effective way is by taking them on an empty stomach with plenty of water about 30-60 minutes before meals.
This will give them enough time to start working before you eat.
If you're taking a combination of nootropics, it's best to take them at different times throughout the day.
For example, 5-htp and vinpocetine can be taken together in the morning, and huperzine A can be taken in the evening.
That being said, there are no hard and fast rules here; experiment until you find what works best for you.
The nootropics discussed above are also helpful if you're doing any type of fasting or dieting to lose weight.
Most types of "smart drugs" – common nootropic substances – do not break a fast. Cognitive enhancers typically cannot break a fast because they do not metabolize into real "food" in the body. For instance, caffeine from coffee cannot break a fast because it does not contain calories and cannot be metabolized to yield energy (or other nutrients).
In this article, I'll go over the most commonly asked questions which nootropics users have about fasting.
So without further ado, let's just get straight into it, shall we?
Fasting: What's the Deal?
When it comes to fasting, there are different types.
One type is "intermittent fasting" (IF), which involves eating within an 8 to 12 hour period and fasting for the other 16 to 12 hours.
Then there are "water fasts" and "juice fasts", which both involve consuming nothing but water or juice for a set period of time.
And finally, there's "complete fasting", which is when you consume zero calories for an extended period of time (usually 7 days or more).
Now that we've got that out of the way, let's move on to nootropics and fasting.
Can Nootropics Break a Fast?
The short answer is no, nootropics typically cannot break a fast.
This is because most nootropic substances do not contain any calories and are not metabolized into real food in the body.
If you're taking a supplement that claims it can break a fast or help with fasting, then that's probably false advertising.
On the other hand, just because most nootropics are calorie-free doesn't mean they do not have an effect on your brain.
For instance, piracetam has been shown to increase glucose uptake in parts of the brain where blood flow is typically lower in elderly people.
And some nootropic stacks claim they contain "nutrients" in micrograms or milligrams, but in reality, these nutrients are only included for marketing purposes and lack any significant effect when taken orally.
So Can Nootropics Be Used During Fasting?
Yes! Most nootropics are perfectly safe to take while fasting because they don't break a fast.
And if you want to, some nootropics can actually improve your concentration and focus while you're fasting.
I've experimented with this quite a bit myself, but I'm pretty sure it has more to do with my mindset than anything else.
If you believe that the nootropic is doing something for you, then there's obviously going to be an effect – whether or not it's placebo or not doesn't matter because the end result is still the same!
So the bottom line is this: don't worry about breaking your fast when taking most nootropics.
How Can Nootropics Help Fasting?
As I've mentioned earlier, fasting can cause poor concentration and focus.
This isn't because your body is lacking energy – it's usually because your body is switching to fats as its primary source of energy.
In the absence of glucose, your brain will use ketones as a substitute source of energy.
Ketones are produced when your body breaks down fatty acids for energy, and they're a much more efficient source of energy for the brain than glucose.
This is why people often experience better concentration and focus when they're in ketosis.
If you want to avoid the negative side effects of fasting, then you can take nootropics and electrolytes to help your body make the switch to ketones and avoid any negative symptoms.
Some popular nootropics that can help while you fast:
Choline stands as an essential nutrient critical for neurotransmitter synthesis, cell membrane integrity, and neural signaling through its role as a precursor to acetylcholine (ACh) and phosphatidylcholine. This water-soluble compound directly influences synaptic plasticity, memory formation, and cognitive processing through its participation in cholinergic neurotransmission and membrane phospholipid synthesis. The brain's dependence on adequate choline supplies for optimal function highlights its significance in cognitive enhancement and neuroprotection.[1]
Overall Verdict
Choline supplementation demonstrates robust cognitive enhancement effects through optimization of acetylcholine synthesis and membrane phospholipid production in neural tissues. The compound's efficacy manifests most prominently in memory formation, attention, and cognitive processing speed, with optimal dosing proving crucial for maximizing benefits. Clinical evidence supports choline's cognitive-enhancing properties across diverse populations, though individual response patterns necessitate personalized dosing strategies.
What Is Choline and Its Chemical Composition?
Choline exists as a quaternary ammonium compound with the molecular formula C5H14NO, characterized by its trimethylamine structure and hydroxyl group. The molecule's chemical properties enable its essential roles in neurotransmitter synthesis and membrane phospholipid formation through specific enzymatic pathways. Choline's structure facilitates its transport across the blood-brain barrier through dedicated choline transporters, ensuring delivery to neural tissues.
Very soluble in water, soluble in ethanol, insoluble in diethyl ether and chloroform
Biological role
Essential nutrient, precursor to acetylcholine and phospholipids
Dietary sources
Organ meats, egg yolks, dairy products, peanuts, beans, nuts, seeds
Deficiency effects
Non-alcoholic fatty liver disease, muscle damage
Excess effects
Low blood pressure, sweating, diarrhea, fish-like body odor
Biosynthesis
Can be synthesized from ethanolamine via methylation
Metabolism
Involved in one-carbon metabolism and lipid transport
What Is the Origin of Choline?
Choline originates both from dietary sources and endogenous synthesis through methylation of phosphatidylethanolamine in liver tissue. The compound's presence in food sources varies significantly, with highest concentrations found in egg yolks, liver, and soybeans. Endogenous production capabilities prove insufficient for optimal cognitive function, necessitating dietary intake or supplementation for maintaining adequate choline status.
What Is the Chemical Structure of Choline?
Choline's molecular architecture centers on a positively charged nitrogen atom bonded to three methyl groups and an ethanol moiety. The compound's quaternary ammonium structure enables its function as a precursor to acetylcholine through enzymatic acetylation of the hydroxyl group. This unique chemical composition facilitates choline's role in phospholipid synthesis through incorporation into phosphatidylcholine and sphingomyelin.
How Does Choline Enhance Cognitive Function?
Choline enhances cognitive function through direct augmentation of acetylcholine synthesis in cholinergic neurons throughout the brain. The compound's conversion to phosphatidylcholine supports membrane fluidity and signal transduction in neural tissues, optimizing synaptic transmission. Enhanced cholinergic signaling results in improved memory formation, attention, and cognitive processing speed through activation of nicotinic and muscarinic acetylcholine receptors.[2]
What Are the Biochemical Processes Influenced by Choline?
Choline influences multiple biochemical pathways central to cognitive function, including acetylcholine synthesis through choline acetyltransferase activity in cholinergic neurons. The compound's incorporation into membrane phospholipids affects membrane fluidity, receptor function, and signal transduction efficiency across neural networks. Methylation processes utilizing choline-derived methyl groups impact gene expression patterns and neurotransmitter metabolism throughout the central nervous system.[3]
What Are the Primary Uses and Benefits of Choline?
Choline supplementation primarily enhances memory formation, attention span, and cognitive processing speed through optimization of cholinergic neurotransmission. The compound's benefits extend to neuroprotection through maintenance of membrane integrity and reduction of homocysteine levels via methyl donation pathways. Cognitive enhancement effects manifest across multiple domains, including verbal memory, spatial cognition, and executive function.[4]
How Does Choline Benefit Cognitive Disorders?
Choline supplementation demonstrates significant efficacy in treating cognitive decline associated with cholinergic deficiency states and age-related memory impairment. The compound's role in membrane repair and acetylcholine synthesis supports cognitive recovery in various neurological conditions affecting cholinergic function. Enhanced synaptic plasticity and neuronal membrane integrity contribute to cognitive rehabilitation outcomes.
How Can Choline Improve Cognitive Performance in Healthy Individuals?
Choline optimizes cognitive performance in healthy individuals through enhancement of acetylcholine synthesis and improved neural membrane function. The compound's effects on synaptic transmission and neural circuit efficiency result in measurable improvements in memory consolidation and recall. Enhanced cholinergic signaling supports sustained attention and mental clarity during complex cognitive tasks.[5]
User Experiences and Reviews of Choline
User reports consistently describe improvements in memory recall, mental clarity, and focus duration following choline supplementation. Cognitive benefits typically manifest within 30-60 minutes of administration, with effects lasting 4-6 hours depending on the specific form of choline utilized. The most pronounced improvements occur in tasks requiring sustained attention and memory consolidation, particularly during periods of high cognitive demand.
What Do Personal Experiences and Reddit Discussions Reveal About Choline?
Online community discussions reveal consistent patterns of enhanced cognitive performance following choline supplementation, particularly with alpha-GPC and CDP-choline forms. Users report optimal results when combining choline sources with racetams or other nootropics that increase acetylcholine utilization. Experiential reports emphasize the importance of individual dosage optimization, with some users requiring adjustment periods to find their optimal supplementation protocol.
My Personal Choline Experience and Results
My initial supplementation with CDP-choline produced noticeable improvements in verbal fluency and working memory capacity within the first week of consistent use. The cognitive enhancement effects manifested most prominently during tasks requiring sustained focus and information processing, with reduced mental fatigue as a secondary benefit. Regular supplementation established a baseline of improved cognitive function, particularly in areas of memory consolidation and recall speed.
How Does Choline Feel and What Results Were Observed?
Choline supplementation produces distinct improvements in mental clarity and cognitive stamina, characterized by enhanced focus duration and reduced cognitive fatigue. The effects present as a clean, natural enhancement of cognitive capabilities rather than a stimulatory effect, with improved information processing and memory recall. Sustained supplementation results in cumulative benefits for cognitive function, particularly in areas of verbal memory and executive processing.
Practical Aspects of Acquiring Choline
High-quality choline supplements come in multiple forms, including alpha-GPC, CDP-choline (citicoline), and choline bitartrate, each offering distinct bioavailability profiles. Product selection criteria include purity verification, standardized content analysis, and third-party testing documentation. Manufacturing standards and quality control measures ensure consistent potency and minimal contaminant presence.
Where and How to Purchase Choline Safely and Legally?
Choline supplements undergo regulation as dietary supplements, available through established retail channels and specialized nootropic vendors. Quality assurance measures include certificate of analysis documentation and third-party laboratory testing verification. Procurement through reputable suppliers ensures product authenticity and adherence to manufacturing standards.
How Much Does Choline Cost?
Choline supplementation presents varying cost profiles depending on the specific form selected, with alpha-GPC commanding premium pricing due to higher bioavailability. Monthly supplementation costs range from $20-60 based on dosage requirements and chosen choline form. The investment-to-benefit ratio favors high-quality choline sources despite higher initial costs, given their superior bioavailability and cognitive enhancement effects.
Understanding Choline's Side Effects and Safety Profile
Choline supplementation carries specific considerations regarding dosage optimization and potential cholinergic side effects at higher doses. Monitoring individual response patterns ensures optimal supplementation without risking cholinergic oversaturation symptoms. The compound's safety profile supports long-term supplementation within established dosing guidelines.
What Are the Known Short-Term and Long-Term Side Effects?
Acute excessive choline intake manifests through cholinergic symptoms including headache, nausea, and gastrointestinal discomfort. Long-term supplementation at appropriate doses demonstrates excellent safety profiles without significant adverse effects. Individual sensitivity variations necessitate personalized dosing protocols to minimize side effect risk while maximizing cognitive benefits.[6]
What Are the Major Drug Interactions with Choline?
Choline exhibits interactions with parasympathomimetic medications and anticholinergic drugs through its effects on cholinergic neurotransmission. Concurrent use of acetylcholinesterase inhibitors requires careful dosing consideration due to potential cholinergic system oversaturation. Certain psychiatric medications affecting cholinergic function necessitate adjusted choline supplementation protocols.
Administration and Dosage Guidelines for Choline
Optimal choline dosing ranges from 250-1000mg daily depending on the specific form utilized and individual response patterns. Administration timing favors morning dosing with food for enhanced absorption and reduced gastrointestinal effects. Dose titration starting at lower ranges allows for assessment of individual response and minimizes potential side effects.
What Are the Different Forms and Methods of Taking Choline?
Choline supplementation options include alpha-GPC, CDP-choline, choline bitartrate, and phosphatidylcholine, each presenting distinct bioavailability and brain penetration characteristics. Alpha-GPC offers superior brain bioavailability with 40% choline content by weight, while CDP-choline provides additional neuroprotective benefits through its cytidine component. Phosphatidylcholine provides sustained release characteristics through its incorporation into cellular membranes, offering unique benefits for long-term brain health.
How Much Choline Is Recommended for Desired Effects?
Alpha-GPC supplementation demonstrates optimal cognitive enhancement effects at doses ranging from 300-600mg daily, divided into morning and afternoon administrations. CDP-choline requires doses of 250-750mg daily for optimal cognitive benefits, with enhanced effects noted in combination with racetam compounds. Choline bitartrate supplementation necessitates higher doses of 1000-2000mg daily due to lower brain bioavailability, though still providing significant cognitive benefits through sustained blood choline elevation.
Pharmacokinetics of Choline
Choline absorption occurs through carrier-mediated transport in the small intestine, with subsequent distribution throughout body tissues via specific choline transporters. Brain uptake involves dedicated high-affinity choline transporters at the blood-brain barrier, ensuring adequate supply for acetylcholine synthesis and membrane phospholipid production. Elimination occurs through multiple pathways including oxidation to betaine and incorporation into phospholipids.[7]
How Is Choline Absorbed, Metabolized, and Excreted in the Body?
Intestinal absorption of choline involves both sodium-dependent and independent transport mechanisms, with peak plasma levels occurring within 1-2 hours of ingestion. Metabolism proceeds through multiple pathways including acetylation for neurotransmitter synthesis, phosphorylation for membrane phospholipid production, and oxidation to betaine for methylation processes. Excretion of unmetabolized choline occurs primarily through renal pathways, while metabolized forms undergo various tissue incorporation processes.
Tolerance and Dependency Issues with Choline
Choline supplementation maintains consistent effectiveness without developing traditional tolerance patterns due to its role as an essential nutrient rather than a receptor-dependent compound. Homeostatic mechanisms regulate choline utilization and storage, preventing development of physical dependency while maintaining optimal cognitive function. Regular monitoring of cognitive response patterns ensures continued supplementation efficacy.
Can Users Develop Tolerance to Choline?
The body's response to choline supplementation remains stable over time due to complex regulatory mechanisms controlling acetylcholine synthesis and membrane phospholipid production. Physiological adaptation mechanisms prevent development of tolerance while maintaining optimal cholinergic function. Long-term supplementation benefits depend on maintaining appropriate dosing within individual therapeutic windows rather than dose escalation.
Interactions and Synergies: Choline Combinations
Racetam compounds synergize significantly with choline through increased acetylcholine utilization and enhanced receptor sensitivity. B-vitamins, particularly B6, B12, and folate, support choline metabolism through optimization of methylation pathways and neurotransmitter synthesis. Omega-3 fatty acids enhance choline incorporation into neural membranes, optimizing synaptic function and signal transduction.
What Substances Interact with Choline?
Anticholinergic medications directly oppose choline's cognitive enhancement effects through competitive receptor inhibition. Acetylcholinesterase inhibitors potentiate choline's effects through reduced acetylcholine breakdown, requiring careful dose adjustment. Iron status affects choline utilization through its role in neurotransmitter synthesis and methylation processes.
What Are the Most Effective Choline Stacks?
Optimal choline stacks incorporate racetams (piracetam 1600-4800mg or oxiracetam 750-1500mg) with alpha-GPC (300-600mg) or CDP-choline (250-500mg) for enhanced cognitive effects. B-vitamin complex supplementation (including methylcobalamin B12 1000mcg, P5P B6 50mg, and methylfolate 800mcg) supports choline metabolism and utilization. Uridine monophosphate (250-500mg) enhances choline's effects on membrane phospholipid synthesis and synaptic plasticity.
Exploring Alternatives to Choline
Cholinergic compounds offer alternative pathways for enhancing cognitive function through modulation of acetylcholine signaling and neural membrane function. Natural and synthetic alternatives target similar cognitive enhancement pathways while providing complementary benefits through distinct mechanisms of action. Understanding these alternatives enables informed decisions about cognitive enhancement strategies based on individual needs and response patterns.
What Are Viable Alternatives to Choline?
Huperzine A provides cholinergic enhancement through acetylcholinesterase inhibition, offering sustained cognitive benefits with doses of 50-200mcg daily. Galantamine and vinpocetine enhance cholinergic function through distinct mechanisms, including nicotinic receptor modulation and cerebral blood flow enhancement. Lion's Mane mushroom (Hericium erinaceus) and Bacopa monnieri provide alternative approaches to cognitive enhancement through NGF production and cholinergic system modulation.
Insights from Scientific Research on Choline
Studies demonstrate choline's impact on brain structure and function through enhanced membrane phospholipid synthesis and cholinergic neurotransmission. Cognitive testing reveals significant improvements in memory formation, attention span, and information processing speed following choline supplementation. Longitudinal research confirms the importance of maintaining optimal choline status for cognitive development and performance throughout the lifespan.[8]
What Have Animal and Human Studies Revealed About Choline?
Research models demonstrate choline's fundamental role in neurodevelopment through regulation of stem cell proliferation and neuronal differentiation. Controlled trials confirm cognitive enhancement effects in both young and aging populations, with particularly robust improvements in memory and attention tasks. Mechanistic studies reveal detailed molecular pathways through which choline influences synaptic plasticity and neural circuit function.[9]
Evaluating the Value of Choline for Cognitive Enhancement
Regular choline supplementation offers significant cognitive benefits through enhancement of cholinergic function and neural membrane integrity. The compound's comprehensive impact on brain function, combined with its essential role in neurodevelopment, provides compelling evidence for its value in cognitive enhancement protocols. Cost-effectiveness analysis supports choline supplementation as a primary intervention for cognitive optimization.
Is Investing in Choline a Good Decision for Cognitive Enhancement?
Investment in choline supplementation provides substantial returns in cognitive performance through its fundamental role in brain function and development. The compound's established safety profile, widespread availability, and moderate cost create an attractive risk-benefit ratio for cognitive enhancement purposes. Regular monitoring ensures optimal outcomes while minimizing potential risks, making choline supplementation a sound investment in cognitive optimization.
Frequently Asked Questions (FAQ) About Choline
How Long Does It Take for Choline to Kick In?
Initial effects of choline supplementation become apparent within 30-60 minutes of administration, particularly with highly bioavailable forms like alpha-GPC. Cognitive enhancement effects develop fully over 2-3 weeks of consistent supplementation as cholinergic function optimizes. Individual response variations depend on baseline choline status, form of supplementation, and overall nutritional status.
How Long Does the Effect of Choline Last?
Choline's cognitive enhancement effects maintain active duration of 4-6 hours with alpha-GPC or CDP-choline supplementation. The compound's incorporation into membrane phospholipids provides sustained benefits beyond acute effects through improved neural membrane function. Regular supplementation establishes stable cognitive enhancement through maintained optimal cholinergic function.
Is Choline Legal?
Choline maintains unrestricted legal status globally as an essential nutrient critical for human health and development. Regulatory frameworks classify choline supplements as dietary supplements, ensuring widespread availability through established commercial channels. Manufacturing standards and quality control measures guarantee supplement safety and potency within legal guidelines.
Is Choline FDA-Approved?
The FDA recognizes choline as Generally Recognized as Safe (GRAS) for use in dietary supplements and fortified foods based on extensive safety data. Regulatory oversight ensures consistent product quality through Good Manufacturing Practice (GMP) guidelines while maintaining appropriate labeling standards. Supplemental choline products undergo regular monitoring for compliance with established safety and quality parameters.
Conclusion
Choline supplementation represents a fundamental approach to cognitive enhancement through its essential role in acetylcholine synthesis and neural membrane function. The compound's comprehensive effects on brain function, combined with its excellent safety profile and cost-effectiveness, position it as a valuable tool for cognitive optimization. Careful attention to dosing, form selection, and individual response patterns maximizes benefits while maintaining optimal cholinergic function, making choline supplementation a cornerstone of evidence-based cognitive enhancement strategies.
López-Sobaler, Ana María et al. “Importancia de la colina en la función cognitiva” [Importance of choline in cognitive function]. Nutricion hospitalaria vol. 37,Spec No2 (2021): 18-23. doi:10.20960/nh.03351
Institute of Medicine (US) Committee on Military Nutrition Research; Marriott BM, editor. Food Components to Enhance Performance: An Evaluation of Potential Performance-Enhancing Food Components for Operational Rations. Washington (DC): National Academies Press (US); 1994. 19, "Choline: Human Requirements and Effects on Human Performance." Available from: https://www.ncbi.nlm.nih.gov/books/NBK209047/
Kansakar, Urna et al. “Choline supplements: An update.” Frontiers in endocrinology vol. 14 1148166. 7 Mar. 2023, doi:10.3389/fendo.2023.1148166
