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Nootropics

Where To Buy Nootropics: Get The Biggest Bang For Your Buck

Corneliu E. Giurgea, the Romanian chemist who first synthesized piracetam, developed the concept of nootropic substance in 1972. It is a combination of the Greek words “νους” (nous) meaning “mind”, and “τρoπoς” (tropos) meaning “bend” or “change”. This is what nootropics do. Essentially, they positively alter the way in which your mind works.

nootropic brainNootropic drugs are a specific subtype of psychoactive substances. According to Giurgea, in order for a drug or supplement to be considered a nootropic, it must adhere to the following criteria:

  1. Enhances learning and memory
  2. Enhances resistance of learned behaviors to conditions that will disrupt them
  3. Protects the brain against physical of chemical injuries (such as concussions or neurotoxic drugs)
  4. Increases the efficacy of cortical/subcortical control mechanisms of the brain (such as improving reaction time)
  5. Typically lacks negative side-effects (i.e. sedation), and possesses low toxicity

Though these criteria lay out the foundation for what a nootropic is, most modern definitions are much more general. As a more common definition, nootropics are chemical substances or herbal supplements that enhance cognition and mental function. Read more…

Recommended Nootropic Suppliers

* Modafinil and Armodafinil supplier

 

Categories
DMAE Nootropics Picamilon Vinpocetine

The 5 Most Overrated Nootropics

The world of nootropics is one that focuses mainly on the cognitive enhancement of individuals who are seeking to maximize their potential. However, this also means that nootropics are a commercial enterprise, with vendors and salespeople seeking to maximize their profits. Due to the commercial nature of nootropics, and the fact that many are not FDA regulated, many suppliers make exaggerated or overemphasized claims about the benefits of their products.

Quite simply, there are many well-known “nootropic” substances that either don’t work as well as advertised or don’t work at all. The placebo effect may also plays a massive role in this, as many nootropics have not been thoroughly tested in double-blind experiments to ensure they work more effectively than a placebo. For this reason, anecdotal experience reports with nootropics are important, but many people tend to give them too much weight. In order to combat misinformation (and save you some money), we will be listing a few overrated and under effective nootropics and supplements on the market today.
 

DMAE

Dimethylaminoethanol, frequently known as DMAE and Deanol, is a chemical involved in a series of reactions needed by the body to synthesize Acetylcholine, a neurotransmitter that regulates memory and mood.

DMAE Deaner advertisement nootropic
DMAE advertisement from the late 50s
The p-acetamidobenzoate salt of DMAE was originally sold by Riker Laboratories as Deaner, for the management of kids with learning disabilities. It is not known whether that form of DMAE was more effective than the bitartrate salt that is more commonly sold as a nootropic supplement.

Riker retired Deaner from the shelves in 1984 because, — according to the FDA — the clinical studies didn’t prove that the drug was effective. As of today DMAE is still sold as a nootropic supplement, but it’s more frequently used as an active ingredient in anti-aging skin creams, due to its polyunsaturated fatty acid content.

DMAE has always been a popular and widely used supplement in the nootropic community since the end 90s to early-2010s, however, it is no longer a popular nootropic supplement today for several reasons:

  • DMAE is not an effective Acetylcholine percursor[1] [2]
  • There is actually reason to believe that DMAE may act as an anticholinergic[3]
  • DMAE causes birth defects[4]
  • Some nootropic users report depression and physical anxiety as a side effect of DMAE[5]
  • DMAE reduced lifespan in a study on quails[6]

Try instead: Centrophenoxine, CDP-Choline, Alpha GPC
 

Ginkgo Biloba

Ginkgo biloba is a species of tree that has the reputation of being used in traditional Chinese medicine. Ginkgo extract is used as a mild vasodilator, and can be commonly found at almost any supermarket sold in capsule form. Its wide availability makes it a very popular supplement, especially for those who are just getting introduced to nootropics or supplementation. Ginkgo has often been touted for its alleged abilities to enhance cognition, mood, and memory.

In the 1990s, Ginkgo was heavily marketed by the supplement industry as a natural compound that enhances memory and energy. The majority of clinical studies have found ginkgo supplementation to be relatively ineffective in people who don’t already suffer from some form of cognitive deficit. While studies have confirmed that ginkgo can help counteract cognitive decline, these studies were only conducted on older individuals (65+) who were already in the process of cognitive decline.[7] So while ginkgo might be a good option for older individuals, there is no evidence to suggest it will have an effect on the cognitive health of younger individuals.

https://www.youtube.com/watch?v=YOsehMqrb1E

However, recent studies have brought into question ginkgo’s ability to slow or prevent things like mild dementia and Alzheimer’s in the elderly. One clinical trial conducted with 3,000 elderly individuals found that ginkgo is no more effective at preventing these diseases than placebo.[8]

Another one of ginkgo’s most commonly claimed benefits is that of improving mood and sense of wellbeing. However, multiple studies have confirmed that ginkgo only has the ability to slightly improve mood among individuals who are effected with a pre-existing cognitive condition, and not among healthy individuals.[9] [10] [11]

So, while Ginkgo Biloba may be worth a try in older individuals who are already experiencing cognitive decline, most evidence suggests that younger individuals have little to no reason for supplementing ginkgo to achieve cognitive enhancement.

Try instead: Bacopa or Noopept
 

Picamilon

Picamilon is a pharmaceutical drug developed in the Soviet Union that is now used in Russia for the treatment of anxiety, among other disorders. Picamilon was recently in the news when the FDA decided that the drug did not fit into the category of dietary ingredients and subsequently banned picamilon from being included in any supplement formulas manufactured in the United States.[12] That being said, it is still fairly available online to those in the US who wish to purchase it.

Picamilon, Niacin and Gaba comparisonThe picamilon molecule is a synthetic combination of niacin and GABA. On its own, supplemented GABA cannot pass through the blood-brain barrier, meaning it will have no psychoactive anxiolytic effect. However, niacin is able to readily pass through the blood-brain barrier.[13] In theory, the picamilon molecule could cross over the blood-brain barrier, at which point it would be metabolized into GABA and niacin, thus producing an anxiolytic effect. Like phenibut, this anxiolytic effect has the potentially to improve the cognition of those whose minds are constantly preoccupied with anxious thoughts.

Picamilon Russian Nootropic
Russian Picamilon
This theory sounds promising and reasonable on paper, but there is, unfortunately, little to no evidence that it is accurate. While one Russian study concluded that picamilon did indeed cross over the blood-brain barrier, the details of its action once it crosses over have not been thoroughly analyzed.[14] Essentially all clinical experiments concerning picamilon are reported in Russian, making them inaccessible to the vast majority of the scientific community. This makes any evidence supporting picamilon dubious at best. At this point, there are no double-blind studies that test how picamilon works as an anxiolytic.

While it can’t necessarily be ruled out that picamilon has any positive effects on cognition and anxiety, there is not much evidence to believe it would. At this point, there is simply not enough research done on the substance to conclude that it is worth investing in.

Try instead: L-Theanine, Tianeptine, Phenibut
 

Vinpocetine

Vinpocetine is a classic nootropic compound often claimed to have memory-enhancing effects as well as the ability to improve brain metabolism. Vinpocetine is a semisynthetic analog of vincamine, an alkaloid derived from the periwinkle plant. It is still sold in some Eastern European countries as Cavinton for treating blood flow disorders in the brain, as well as cognitive decline caused by old age.

Vinpocetine and Vincamine comparison

Like many other drugs on this list, Vinpocetine appears to have positive effects on cognition only among people who are already experiencing age-related cognitive decline or brain injury.

  • One study found that vinpocetine was able to improve symptoms related to cognitive decline in elderly or injured patients who were suffering from cerebrovascular insufficiency.[15]
  • However, there are currently no studies that suggest vinpocetine has similar effects on healthy subjects.

That said, there is evidence that vinpocetine may be able to improve reaction time among healthy subjects.

  • A study conducted on 12 female subjects between the ages of 18 and 29 found that vinpocetine caused their reaction time to reduce by a few hundred milliseconds, depending on the dosage used. So, while vinpocetine may help improve reaction time, there is no current evidence that it will enhance memory and cognition.
  • Vinpocetine may likely help in sports where reaction time is a deciding factor, but there is no evidence (clinical or anecdotal) that it helps with learning and studying.
  • Vinpocetine is known to causes headaches, so it is a good idea to start low and experiment with ease, before stacking it with other nootropics.

Try instead: Piracetam, PRL-8-53
 

Adrafinil

Adrafinil is a prodrug to the ever-popular wakefulness-promoting drug modafinil. Essentially, this means that adrafinil is metabolized into modafinil once it is ingested. Adrafinil was once used as a prescription medication in France for enhancing wakefulness and attention but was discontinued in favor of using modafinil, which is far more potent.

How Adrafinil gets converted to Modafinil in the liver

Due to the fact that modafinil is a “prescription only” drug in many countries, many nootropic users have turned to Adrafinil for its purported cognition-boosting and memory-enhancing effects. While there is some evidence to suggest that modafinil can provide a modest boost in cognition and working memory,[16] Adrafinil does not seem to exhibit these effects as strongly. In addition to this, Modafinil’s cognition-boosting effects appear to be most effective in individuals who are sleep deprived or impaired in some ways, and not those who are already high achievers.

Because Adrafinil is a prodrug to modafinil, one would expect the two to have the same effects when taken in the correct dosages. However, even when enough adrafinil is taken to be metabolized into a full dose of modafinil, the effects do not appear to be as strong. While it is unknown exactly why this is the case, it likely has to do with the rate at which adrafinil is metabolized, as well as the fact that metabolic enzymes mutations are commonly found in the general population.

Adrafinil also appears to exhibit more side-effects than modafinil, including skin irritation, anxiety and elevated liver enzymes.[17] The latter is likely due to the fact that adrafinil is metabolized in the liver, and thus puts extra stress on it, causing it to produce more enzymes.

While adrafinil may have some potential to enhance cognition and memory, its effects are not nearly as potent as modafinil, even when taken at the proper dose. If at all possible, it would make far more sense to take modafinil or armodafinil, which is the active enantiomer of the drug.

Try instead: Modafinil or Armodafinil
 

Conclusion

While nootropics and cognitive enhancers will have different effects on different individuals, there are certain substances and supplements that simply do not have evidence backing up their ability to enhance cognition. Because the nootropics industry is one driven by profits just like any other, users need to be skeptical of the claims made by vendors. Many nootropics on the market are overrated and under effective, but thankfully there are many alternatives that are backed by research. Nootropics are often not cheap, so purchases need to be made wisely.

References   [ + ]

1. Is 2-dimethylaminoethanol (deanol) indeed a precursor of brain acetylcholine? A gas chromatographic evaluation. (1977)
2. Dimethylaminoethanol (deanol) metabolism in rat brain and its effect on acetylcholine synthesis. (1979)
3. Deanol and methylphenidate in minimal brain dysfunction. (1975)
4. Perturbations in choline metabolism cause neural tube defects in mouse embryos in vitro (2002)
5. DMAE sucks! – LONGECITY Forum
6. Effects of dimethylaminoethanol upon life-span and behavior of aged Japanese quail. (1977)
7. Long-term use of standardised Ginkgo biloba extract for the prevention of Alzheimer’s disease (GuidAge): a randomised placebo-controlled trial.
8. Ginkgo biloba for Prevention of Dementia
9. Specific memory effects of Ginkgo biloba extract EGb 761 in middle-aged healthy volunteers.
10. Phase II study of Ginkgo biloba in irradiated brain tumor patients: effect on cognitive function, quality of life, and mood.
11. Ginkgo biloba extract EGb 761® in dementia with neuropsychiatric features: a randomised, placebo-controlled trial to confirm the efficacy and safety of a daily dose of 240 mg.
12. FDA sends five warning letters over supplements containing picamilon
13. Effect of Huntington’s and Alzheimer’s diseases on the transport of nicotinic acid or nicotinamide across the human blood-brain barrier. (1991)
14. [Pikamilon pharmacokinetics in animals]
15. [Efficacy of cavinton in the treatment of patients with chronic blood flow insufficiency. Russian multicenter clinical-epidemiological program “CALIPSO”].
16. Modafinil, d-amphetamine and placebo during 64 hours of sustained mental work. I. Effects on mood, fatigue, cognitive performance and body temperature.
17. Modafinil: past, present and future.
Categories
Blog DMAE

Look at this beautiful DMAE ad from the 70s

This beautiful magazine advertisement from Eduardo A. Cánovas depicts the brain, that is, the primary target of Tonibral, one of the many names by which the p-acetamidobenzoate salt of DMAE was being sold, from the early 50s to the late 70s.

We already know by now that DMAE is basically useless as a nootropic, but what the hell, this is awesome, don’t you think?

DMAE Tonibral 70s ad

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Coluracetam Nootropics Racetams Reviews

Coluracetam Review: A Nootropic With Antidepressant Properties

The drug piracetam is often regarded as the first truly nootropic drug, due to its ability to promote healthy brain function and cognition without potentially debilitating side effects. The family of nootropics that are structurally related to piracetam, known as racetams, have also been held in high esteem by the nootropics community. Coluracetam is one of the many members of this nootropic drug class, but it has some unique properties that set it apart from the rest.

Introduction

ColuracetamColuracetam is a fairly new addition to the racetam category of nootropics, being developed and initially researched in the mid-1990s.[1] Coluracetam, known also by its research names of MKC-231 and BCI-540, was initially developed and researched by the Mitsubishi Tanabe Pharma Corporation in Japan as a potential treatment for Alzheimer’s disease. Coluracetam has also seen some limited research concerning its potential use for treating Major Depressive Disorder and Generalized Anxiety Disorder.[2]

Mechanism of Action

When ingested, coluracetam becomes present in nerve tissue within 30 minutes of administration. The concentration in the body begins to decrease about 3 hours after ingestion.[3]
The most definitive mechanism through which coluracetam works is high-affinity choline uptake (HACU). HACU is a crucial step in the process of the body’s converting of choline into acetylcholine, a vital neurotransmitter for cognition processes. [4] In essence, this means that an increase in HACU (caused by coluracetam) will also increase the activity level of acetylcholine in the nervous system. This is the basis for coluracetam’s ability to enhance cognition

My Experience with Coluracetam

My trial run for NootropicsDepot’s coluracetam lasted for one week, due to the fact that coluracetam’s effects seem to all take place rather quickly. In other words, the effects do not appear to be cumulative like some other nootropics. Typically, I took 30 mg orally in the morning, along with another 30 mg in the afternoon. If necessary, I took another dose later on in the day. Dosage recommendations for coluracetam range anywhere from 3 mg up to 100 mg or more, but this dose seemed to work just fine. Having experimented with coluracetam briefly a few months ago, I had a general feel for what dose might work.

Coluracetam powder nootropicDuring the time of this trial, I was not taking any prescription medications. In the morning, I was taking Vitamin B12, Vitamin D, potassium gluconate, fish oil, and turmeric. The effects I experienced from taking coluracetam have been very positive. However, bear in mind that this is only a subjective experience. The placebo effects cannot be ruled out (although I am convinced it was the coluracetam I felt), and experiences will vary between individuals. That being said, I will now go into what I felt are the major benefits of coluracetam:

  1. Motivation enhancement
    Right off the bat, coluracetam seems to provide a decent increase in motivation to engage in productive work. I felt a stronger desire to work on school work that I don’t find very interesting. It made it much easier to push through to get things done, leaving a very satisfactory feeling when things were accomplished.
  2. Stimulation
    This effect goes somewhat hand-in-hand with motivation enhancement. Coluracetam has the effect of making me feel more awake and alert. It seems to help me feel more ready and able to get work done. It didn’t make me feel “jittery” either – I felt quite relaxed the whole time.
  3. Reduction in fatigue
    Coluracetam appears to help alleviate both physical and mental fatigue. There were a few instances when taking it where I went from being exhausted and drained to energized and ready to go.
  4. Enhanced cognition
    This effect is very important for any nootropic compound. After all, it is the main thing that nootropics are purported to influence. Within half an hour of taking coluracetam, I felt much more able to formulate thoughts and translate them into writing. I also felt more able to connect ideas in my mind and get a better idea of the “bigger picture.” I also felt more naturally able to hold conversations with others, feeling much more engaged and fluent.
  5. Music enhancement
    While this is mostly unrelated to the topic of cognitive enhancement, listening to music while on coluracetam was very pleasant. The music itself felt more full, interwoven, and immersive than usual. Individual pieces of melody and minor details became more distinguishable than usual.
  6. Mood Boost
    After taking coluracetam, I can understand why it is being researched as a treatment for depression. It helped me remain more positive and upbeat throughout the day. I also seemed to make things more enjoyable in general.

Drawbacks

Coluracetam seems to be a very promising nootropic in terms of its multiple benefits and few side-effects. I did not experience any apparent increase in tolerance during the week I was taking it, even with multiple doses in one day. Experiments in which rats were given coluracetam for 14 days at a time seems to reinforce this.[5] The only possible side-effect I experience was mild to moderate headaches, which occurred throughout the week. This should be taken with a grain of salt because I am normally fairly prone to headaches in the first place. I’ve also heard that taking choline can alleviate headaches that come with racetam supplementation, so that could be a potential remedy.

Conclusion

All things considered, I was very pleased with the effects of coluracetam. I will certainly be implementing it into my nootropic stacks, as it is one of the most noticeable and useful nootropics I have personally taken. It seemed to have a real impact on my motivation, energy, and cognition. Everyone is bound to react differently to coluracetam, but I strongly encourage nootropics users to give it a try.

You can buy Coluracetam powder and capsules at NootropicsDepot.

Coluracetam
7.5
Focus
8.5
Mood
8
Memory
7.5
Stimulation
7
Relaxation
8
Safety
Reviewer 8.4
Summary
I highly recommend coluracetam for anyone who needs to spend extended periods of time working on demanding mental tasks. The cognitive boost and mental stimulation was extremely useful.

References   [ + ]

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Nootropics Tutorials

Nootropics: A Beginner’s Guide To Cognitive Enhancers

The realm of nootropic substances (aka cognitive enhancers or smart drugs), at the time around its conception, was reserved for the very select few who had access to these novel cognition-enhancing drugs. In recent years, nootropics have gained more widespread recognition, and are more accessible to average individuals than ever before, thanks to the rising number of online vendors and communities who make these substances accessible for all.

The term “nootropic” has been consistently more and more searched on google ever since 2011 (the year when the film Limitless was released) , and people’s interest in the subject will certainly continue to rise. Although nootropics still maintain a type of “fringe” status in the world of drugs, their infiltration into the mainstream is undeniable.

Nootropic Trend - Google searches of keyword "nootropics"

What is a Nootropic?

nootropic brainCorneliu E. Giurgea, the Romanian chemist who first synthesized piracetam, developed the concept of nootropic substance in 1972.[1] It is a combination of the Greek words “νους” (nous) meaning “mind”, and “τρoπoς” (tropos) meaning “bend” or “change”. This is what nootropics do. Essentially, they positively alter the way in which your mind works.

Nootropic drugs are a specific subtype of psychoactive substances. According to Giurgea, in order for a drug or supplement to be considered a nootropic, it must adhere to the following criteria:[2]

  1. Enhances learning and memory
  2. Enhances resistance of learned behaviors to conditions that will disrupt them
  3. Protects the brain against physical of chemical injuries (such as concussions or neurotoxic drugs)
  4. Increases the efficacy of cortical/subcortical control mechanisms of the brain (such as improving reaction time)
  5. Typically lacks negative side-effects (i.e. sedation), and possesses low toxicity

Though these criteria lay out the foundation for what a nootropic is, most modern definitions are much more general. As a more common definition, nootropics are chemical substances or herbal supplements that enhance cognition and mental function.

Caffeine
Caffeine

If we think in terms of this general definition, there is about a 90% chance you use a pseudo-nootropic substance regularly. Caffeine, the most popular drug in the world, is commonly classified as a nootropic, due to the fact that it is stimulatory and enhances attentiveness linked to cognition, learning, and memory. [3] [4]

Certain substances that don’t explicitly enhance cognition are still sometimes grouped in with nootropics. This would include substances that improve mood, reduce anxiety, or promote an overall feeling of wellbeing. Some examples of these substances are phenibut, sulbutiamine, and ashwagandha. Even if these supplements don’t have mechanisms that directly improve cognition, their mood-improving capabilities will tend to lead to an enhanced ability to focus and think clearly.

Who Uses Them?

Giurgea coined the term “nootropic” after he synthesized piracetam, which is, under Giurgea’s definition, the first substance to display purely nootropic properties. Piracetam has cognitive enhancing and neuroprotective capabilities while also possessing relatively few side effects. [5] Because of this, piracetam is commonly used to improve cognition in individuals who are experiencing the cognitive decline that comes with old age, dementia, or Alzheimer’s.

With the development of piracetam, other nootropic substances were investigated and researched for their applications in those who experience cognitive decline. Many drugs derived from piracetam (referred to as racetams) have been developed in hopes that they would yield even more benefits than piracetam. For instance, phenylpiracetam displays stimulant properties in addition to cognitive enhancement. [6] Likewise, aniracetam works as an anxiolytic. [7]

Modafinil is wakefulness-enhancing nootropic used by college students as a safer alternative to Ritalin and Adderall

Up until the past decade, these kinds of cognitive-enhancing drugs were only used extensively in clinical applications, such as treating cognitive illnesses. However, the past few years have seen tremendous growth in the use of nootropics among younger healthy individuals in hopes that they could improve their performance in work or academic studies. For example – modafinil (Provigil), a wakefulness-promoting nootropic substance, has seen increased usage among college students as an alternative to Adderall, due to the fact that it aids the brain in focusing on tasks for extended periods of time without fatigue. [8]

Many nootropic substances, such as the racetams and tianeptine (an antidepressant nootropic), are prescription drugs in Europe but are unscheduled in the United States. This has led to many of them being sold online by nootropic vendors, making them readily available for those who wish to purchase them.

Not surprisingly, Russia, the country that has developed a large number of nootropics (including Phenibut, Picamilon, Phenylpiracetam, Selank, Semax, Cerebrolysin, Emoxypine and so on), it’s the place where the keyword “nootropic(s)” is most popular in 2016[9], according to Google.

The increasing number and growth of online communities, such as the nootropics subreddit, has attracted the attention of younger individuals who seek to improve their cognitive performance and preserve their youthful cognitive capabilities. These online communities are extremely valuable sources of information on all things related to nootropics. They are open forums where anyone can ask questions about smart drugs and cognitive enhancement and engage in valuable discussion. Many newer nootropic substances have not been extensively tested in clinical settings, but anecdotal user reports can be found within these online communities.

Where Do I Begin?

If you are determined to make a go at nootropic supplementation, then logically the smart thing to do is implement the smartest ways to use smart drugs. You do not have to be a brain surgeon to begin effectively supplementing with nootropics, but understanding at least the bare bones of the foundations of a few related fields like neuroscience, neurology, and drug metabolism, is vital to getting the most out of them.

Ideally, you want a good working understanding of all the major mechanisms of action, including receptor systems involved in memory, mood and cognition (dopamine, GABAacetylcholineserotonin, etc).learning memory nootropics Attempting anything other could end up as catastrophically as fiddling with the kernel of your operating system without knowing how it works. The best way to go about it is to learn what happens to drugs inside the body, how the classic nootropics work (like Piracetam and Aniracetam), and what are some of the basic nootropic stacks.

Even though it can be a bit daunting at first, you will also want to learn how to access & read scientific researchwhat is acetylcholine (the learning and memory neurotransmitter), how it works, how the brain produces it and what is a choline precursor. Learning the major neurotransmitters, understanding the difference between excitatory and inhibitory neurotransmitters, all these are great places to start.

When first getting into the world of cognitive enhancement, the sheer number of substances out there can be very intimidating. Here is a short list that outlines some of the most popular and proven nootropics for beginners.

Wakefulness and Motivation

  • Caffeine and L-Theanine – Promotes wakefulness and is stimulating in general. The addition of L-theanine helps reduce the negative side effects of caffeine, such as anxiety. Additionally, L-theanine also improves cognition.
  • Modafinil, Armodafinil, and Adrafinil – These three compounds are chemically related. Armodafinil is the active isomer of modafinil and is thus generally more potent. Adrafinil is a prodrug to modafinil. In other words, it is metabolized into modafinil by the body. All three of these are used to promote wakefulness and reduce fatigue.
  • Rhodiola Rosea – A herb that acts as an adaptogen, meaning it aids the body in reacting positively to stressful stimuli. It typically reduces feelings of fatigue and is slightly stimulatory. It is also sometimes used to lessen the effects of caffeine withdrawal.

Note: Prescription drugs such as Adderall (amphetamine) and Ritalin (methylphenidate) are especially effective at increasing feelings of motivation. However, they carry additional side effects and risks of dependency, and should be used with caution.

General Cognition

piracetam nootropic adhd

  • Piracetam – The original racetam, was originally developed as a sleep-aid because of it’s GABA structure, when given to rats it improved their memory and cognition.
  • Noopept – Is chemically similar to piracetam but is active at a fraction of the dose (10 mg vs 1000 mg), and also increases the production of NGF and BDNF, two neurotrophic factors that promote the survival and differentiation of neurons. It typically provides an increase in cognitive ability along with mild stimulation.
  • Aniracetam – Provides cognitive effects that are similar to Noopept, but is also anxiolytic in nature. It is especially helpful in helping the brain associate different thoughts and piecing them together to form the “bigger picture.”
  • Phenylpiracetam – Similarly aids cognition like noopept and aniracetam, but it noticeably more stimulatory. It is also known to be more neuroprotective, and aids in preventing cognitive decline. It is a good alternative to Modafinil.

Note: Because racetams and noopept work through modulation of acetylcholine, they should be supplemented alongside a choline source, such as alpha-GPC or CDP-choline.

Mood Improvement

  • Tianeptine – Chemically a tricyclic antidepressant, tianeptine is novel in the fact that it improves mood while also serving as a neuroprotectant and cognitive enhancer.
  • Phenibut – an anxiolytic compound that may enhance cognition in stressful situations (like exams or a public presentation) through means of reduced anxiety.

Memory

  • Bacopa monnieri – Bacopa has been found to improve the formation, retention, and acquisition of memory. It is an adaptogen and is often taken for its anxiolytic properties
  • Huperzine A – an acetylcholinesterase inhibitor (a compound that prevents the breakdown of the neurotransmitter acetylcholine) extracted from the plant Huperzia Serrata.

What To Expect

Most nootropics rarely display immediate or noticeable acute effects on cognition and well-being (the only exception being stimulant nootropics like Modafinil and Phenylpiracetam) . In fact, they are typically used for long-term neuroprotection, and may not display immediate or noticeable results from use. The psychoactive effects of nootropics are more subtle than the effects of recreational drugs but are ultimately more beneficial. By definition, the daily use of nootropic substances should be far more sustainable than that of recreational drugs.

Nootropics are meant to be safe to use indefinitely though not all drugs sometimes referred to as “nootropics” will meet these criteria. For instance, phenibut, a GABAergic anxiolytic, is sometimes discussed as having nootropic capabilities related to anxiety reduction. However, phenibut has a fairly high risk of causing dependency or withdrawal, and should not be used on a daily basis.

coffe and modafinil pure nootropics
Modafinil is used by college students as a safer alternative to Ritalin and Adderall

Many people supplement multiple nootropics at once to maximize their cognitive benefits. These combinations of substances are referred to as “stacks”. For instance, one might stack caffeine and L-theanine because L-theanine is known to reduce the jitters and anxiety that come with caffeine. [10] When taking multiple nootropics, it is extremely important to research any potential negative interactions between substances. Examine.com is an invaluable resource for researching nootropics and their possible interactions.

Nootropics can certainly be of great benefit to those who wish to improve their cognitive function and protect their minds from degradation. However, nootropics will likely be far more beneficial when they are used in combination with exercise, a proper diet, and meditation.[11] Nootropics can only do so much, and are certainly not an excuse to neglect these other primary health factors.
In addition to this, nootropics should not be used to treat mental disorders unless under the direction of a trained health professional. It may seem tempting to use promising and novel nootropics to treat something like depression, but there is still some amount of risk involved with doing so, especially given the fact that many of the newest nootropics still require a great deal of research before they can be used clinically.

Even if “old” nootropics like racetams are totally safe, it is still a good idea to check out interactions if you’re taking prescription medications.

Up Next

References   [ + ]

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Fasoracetam Nootropics Racetams Reviews

Fasoracetam: How This Nootropic May Help You Focus Better

Originally known as NS-105, Fasoracetam is one of the newest nootropics on the market. Besides being the latest racetam to be discovered, it has some unique properties unlike any other racetam on the market. Let’s find out what makes this substance a truly unique nootropic, and why you should (or should not) try it.

One of the primary effects of Fasoracetam is the modulation of metabotropic glutamate receptors II and III (mGluR).[1] mGlu receptors have been shown to be involved in synaptic plasticity and neuroprotection. In addition, LY354740, am mGlu2/3 agonist, has been shown to be effective in generalized anxiety disorder.[2]

Fasoracetam is also the only racetam that significantly enhances cAMP formation[3] and that has been shown to be potentially effective in individuals with glutamatergic gene variants that are suffering from ADHD[4]. A Phase III clinical trial is near completion, but the drug is not currently listed as an ADHD treatment by the FDA.

Fasoracetam has also shown to have antidepressant effects[5] and to counteract learned helplessness, an avoidance behavior typically associated with depression. Fasoracetam, however, does not act on serotonin and other monoamines, and researchers think the antidepressant effect may stem from its ability to upregulate GABA-B receptors.[6]

Generally speaking, Fasoracetam has shown to be more effective with chronic use, and, in the ADHD study, most benefits were felt at week five onward.[7]
Fasoracetam ADHD

Mechanism of Action

In rat studies, fasoracetam restores the function of key receptors, glutamate mGluR II and III[8].  It also upregulates GABA-B receptors through receptor antagonism[9], a fact which may be related to its ability to reverse phenibut tolerance (which is one of the few supplements reported to relieve anhedonic depression). The GABA-B receptor is very important and has been found to play a role in cognition[10], anxiety and mood.

Alcohol, a very disinhibiting and fog-inducing compound (with pleasurable effects similar to phenibut) is thought to achieve its activity by activating GABA-B and A receptors (as well as dopamine).  However, because it downregulates these receptors, prolonged use may cause anxiety and cognitive disruptions.  Phenibut binds in a similar fashion to GABA-B.

FasoracetamBecause of its relatively narrow range of receptor targets, fasoracetam does not feel like a classic stimulant nor does it alter one’s feeling of wakefulness.  It lacks clinical dopamine activity but remarkably still managed to address ADHD symptoms, according to the study.  It is not clear how fasoracetam has such a specific utility in treating ADHD, more research on other neurotransmitters may be turned up in coming years, but judging on present evidence, it seems that Fasoracetam could reduce ADHD symptoms by modulating glutamatergic receptors.

That being said, the FDA does not list Fasoracetam as an ADHD medication and it should not be used as such. Only a professional can prescribe medications for ADHD and you should not self medicate.

Although it is a newer supplement without much of a user-base, it does appear to be well-tolerated even in large doses or extended periods. Among college students, it may soon become a mainstay, alongside other trusted nootropics such as Bacopa, Modafinil, and Noopept.

Acetylcholine

In addition to the findings surrounding glutamate and ADHD, rat studies have also revealed fasoracetam to have profound cholinergic activity.  Many common nootropics work by controlling acetylcholine, including several drugs used in the treatment of Alzheimer’s.

It increases the uptake of choline at sites in key brain regions involved in intelligence and mood, the hippocampus and cerebral cortex.  This, in turn, results in increased production and release of acetylcholine.[11]
This, similarly to what has been commonly reported with piracetam, may explain a need for choline supplementation in the case of symptoms such as low mood, headache or brain-fog.

Although I personally have only ever tried piracetam and aniracetam (and found, despite a slight cognitive boost, that they both caused a slightly lowered mood, with piracetam being more stimulating and anxiety-prone while aniracetam was calm and relaxing), I haven’t read any complaints of fasoracetam and depression (on the contrary it appears to be a robust antidepressant nootropic, similar to tianeptine). This is remarkable because excessive acetylcholine production is typically associated with low mood and depression. Even with something as mild as bacopa, reports of moodiness are easy to pin down.

Since all three of the mentioned racetams seem to operate through a shared mechanism of acetylcholine, it’s not clear how fasoracetam achieves a similar cognitive boost without side effects on mood.  Perhaps it has been less trialed and as more users sample it, more negative reports will pour in.  This seems unlikely, however, given multiple reports of antidepressant effects, and at higher doses, near euphoria.

Fasoracetam and coluracetam are interesting racetams with multiple mechanisms of action compared to piracetam. Although they both share a cholinergic effect, the former modulates mGlu receptors (as well as GABA-B receptors) while the latter interacts with a process named high-affinity choline uptake.  This may explain their calm, clear effects when compared with the more bland effects of piracetam.

Glutamate

Of the eight known metabotropic glutamate receptors, only one and five are believed to increase NMDA receptor activity and neural excitation (these two are postsynaptic).  The other six receptors all function to lower NMDA (and are presynaptic), lessen excitation and thus reduce potential neurotoxicity.

By slightly lowering glutamate activity and at the same time boosting GABA-B levels, fasoracetam offers a collected state of mind compared to piracetam’s more scattered one.  Normal tasks would flow much easier, and performance would be improved without adverse effect.
While OCD and more recently schizophrenia have been described as hyperglutamatergic, ADHD has always been thought of as a condition of low glutamate.[12]

However, fasoracetam may very well regulate the metabotropic receptors in both directions and benefit everyone equally (restoring both high and low activity of the receptors to normal).

It is not clear how to explain the remarkable improvements reported in samples of both schizophrenia and ADHD. An explanation may be the selectiveness for the presynaptic mGluRs (mGluR1 and mGluR5) coupled with the fact that these receptors both elevate cAMP and lower NMDA activity. Levels of these receptors in the body are both altered in schizophrenia (so fasoracetam would produce two favorable alterations for the schizophrenic patient).

Despite all this fine talk about schizophrenia and glutamate, most of the reports surrounding fasoracetam are concerned with ADHD symptoms, specifically motivation and focus.  It is not widely known for its use as psychiatric medicine, and it may be considered by ADHD patients who have not responded well to conventional treatments. Again, it is not approved by the FDA as an ADHD treatment, and we are not suggesting people suffering from that disease to use it without a medical prescription.

GABA

As stated above fasoracetam appears to have GABA-B antagonistic properties[13], and it may upregulate these receptors and thus diminish the tolerance to GABA-B agonists like Phenibut, Baclofen, and Alcohol, and may even act as an “antidote” to a Phenibut overdose.

Before many of the newer designer supplements hit the market and much was known about fasoracetam, Noopept was one of the more recommended supplements for alcoholics to recover cognitive capacities. But in light of this newer evidence, fasoracetam may address the issue more directly. Because of its activity here, fasoracetam may eventually find use in treating age-related memory decline, dementia, and even depression. For now, the research and hype seem to surround the potential treatment of ADHD symptoms.

Dosage and half-life

Buy Fasoracetam CapsulesNo dependence potential was noted in the rhesus monkey over the course of four weeks.[14]  However. users cannot be completely absolved of concern, due to interspecies differences and the possibility of an only mildly addictive substance requiring an exceptionally long habituation period.

If its use is not completely discouraged in elderly patients, significant caution and close monitoring are recommended.  Its metabolism and clearance depend heavily on the kidneys and at least one studied has reported significant accumulation in the elderly (whose renal function is typically compromised).[15]

It is typically taken at 10mg twice daily, but it is probably best to start with 5 mg and taper up. Even though the dosage is very low, bitterness is still a problem and the use of capsules or parachuting is recommended.

Although some work their way up to 30 mg in one dose, this may not be the most effective strategy (due to a short half-life of the compound) and this pattern of use is more likely to be helped along by a large meal.  A potent nootropic with a half-life of around 90 minutes, taking it even once a day may be enough for active levels to build up in your system, but tolerance will be close behind.

You can buy Fasoracetam capsules and powder at Nootropics Depot. Fasoracetam is not approved by the FDA as an ADHD treatment.

Fasoracetam
8.5
Focus
7.5
Mood
7.5
Memory
7.5
Stimulation
7.5
Relaxation
8
Safety
Reviewer 8.8

References   [ + ]

Categories
Biohacking Caffeine Modafinil Nootropics Tutorials

Hacking Sleep How-To: Sleep Less, Do More (or How I Survived 48h Hackathons)

I started out in an Engineering program at a Canadian University a couple years ago. Shortly thereafter I decided I wanted to be a programmer. Totally reasonable life choices, that came with some slightly less reasonable time demands.

You see when you’re in an engineering program pulling all-nighters to get work done start becoming fairly normal. And then if you want to become a programmer you now need to digest thousands of lines of documentation and code, which definitely doesn’t help you get all the schoolwork done in a nice timely manner. And then we compound that with the recent phenomenon of hackathons. Hackathons are 24-48hr long programming meetups where you, alone or in a team, write code hoping to create something interesting, like a mobile app, or program. As it currently stands, getting employed at a top tier tech firm is nigh nearly impossible for an undergraduate student without hackathon experience.

So this led me to try and find some way to make it easier for myself to stay awake, and get work done.
University students are often familiar with ADHD medication of some sort or the other. These include Ritalin, Adderall, Vyvanse, Biphentin and many others. But they’re only so effective and have some undesirable side effects.
But hey, I’m not trying to tell you to not take drugs here, drugs are bad, you know this from the millions of dollars spent by many governments vilifying them under one undiscriminating umbrella term. No, I’m going to teach you how to intelligently use drugs to get the results you desire.

A brief primer on the brain

Hackathons are great learning experiences, you get to try new frameworks and tools with minimal risk. You see, to build something in programming, you need to understand the tools and solutions that exist in that space. To engineer a better bridge, you need to understand how bridges work and are built. So we need to understand the human brain a little bit.

Most of you should know that a human brain is a biological electrochemical system consisting of cells called neurons. Neurons connect to each other and basically store you. Who you are, your memories, your ability to add numbers, everything is stored as connections in a dense mesh of cells in your cranium. Neurons communicate via signals triggered by electrical charges that cause chemical messengers to be released into a tiny gap in between them and accepted by another neuron on the other side.
So to hack it, we will either have to use electromagnetic phenomenon or chemicals.

Although transcranial direct current stimulation has been noted to positively influence wakefulness [1] wearing a magnet and electrical equipment on my head doesn’t seem too attractive so instead let us enter the wonderful world of neuropsychopharmacology.

synapseRight so about those chemical messengers.
Well, they’re called neurotransmitters. There’s oh so many of them. Their release is usually mediated by voltage differentials in the neuron itself (keep this in mind, it’ll come up later).
The place where two neurons connect is called a synapse, and there’s a tiny gap between them.
After crossing the tiny gap, which is also called the synaptic cleft, these little guys fall into receptor sites. Think of it as a jigsaw puzzle, a specific shape of receptor goes with a specific shape of neurotransmitter. But there are man-made chemicals as well that can fit into the receptor and cause interesting effects since they have somewhat similar shapes to the neurotransmitters. Not all these neurotransmitters lock into receptors, some are sucked back into the neurons via recovery vents. This is called reuptake.

The neurons also have some receptors along their bodies, which allow them to judge and react to the environment. For example slowing down if the environment tells them the person is tired or trying to go to sleep. Though these aren’t actively used to send messages along.

Well now we know a bit about the brain but what about sleep?
Sleep has a myriad of purposes, so I do not recommend long periods of severe sleep deprivation.
These include muscle recovery and repair.
Formation of long-term memories.
The brain also does housekeeping and maintenance, flushing out by-products of cellular function and rearranging neuron formations.[2]
At the end of the day, sleep is necessary, but that doesn’t mean we can’t engineer around having to sleep every night. But not sleeping at all for an extended period can have dire consequences, even death.

Wakefulness and receptors

Well, there are 3 main receptor types that I’ve identified that have something to do with wakefulness. Since many chemicals can affect the same receptor and the receptors often have subtypes these 3 receptor types provide a nice framework to reason about hacking sleep and chemical targets. I came to this hypothesis by looking at the mechanisms of actions of a plethora of drugs which are known to affect wakefulness.

These are the adrenergic, dopaminergic and adenosine receptors.
But I should mention that sleep is complex, so is the human brain, and other neurotransmitters like serotonin and glutamate also play a part. For a purely curious mind I recommend reading “Neuropharmacology of sleep” on NCBI.

Dopamine receptors

Dopamine

Ah yes dopamine, many of you have probably heard of it. It is responsible for reward-motivated behavior. If you study hard and get those grades for yourself and it makes you feel good, well it’s the dopamine. Too much dopamine and you’ll be lazy and not want to do anything, too little and you’ll get bored, yawn, maybe fall asleep(anyone else have 8 am engineering lectures?). It plays a very real role in sleep.[3][4]

You will usually have too little dopamine trying to pull all-nighters. We’ll be looking at drugs that increase dopamine concentrations in the brain and supplements that are easily metabolized to it to prevent depletion. You also want to block its reuptake to maximize signaling strength. Dopamine reuptake inhibitors, precursors or anything that increases dopamine transporter activity causing it to release more is your friend.

Adenosine receptors

Adenosine

Fewer people have probably heard of this one, but almost all of you have exploited this poor guy in the past. Ever drink coffee? Green tea? Energy drinks? This is the main target for all of those.

You see as you get sleepier, this pesky little molecule called adenosine builds up in your brain as a breakdown product of ATP (your cells generate energy via the ATP->ADP reaction). It binds to its namesake receptor, which in turn triggers some very calming effects like slowed heart rate, reduction in dopaminergic signalling, muscle relaxation etc. All effects we don’t want. So we drink coffee, which blocks these receptors, preventing adenosine in our brain from getting in and triggering its effects. So what you need are adenosine antagonists.

Adrenergic receptors

Epinephrine

These guys are responsible for triggering your adrenal system. The whole fight or flight response.
If you overstimulate them well you’ll be panicky, anxious, paranoid your heart will explode from the excessive beating. But a small amount can do wonders for alertness and wakefulness.
One should note that drugs that target the dopamine and adrenergic receptors can sometimes be found under the category of monoaminergics on online retail sites.

Drugs

Alright, time for the fun stuff. I didn’t just almost put you to sleep droning on about receptors and what-not for nothing. Time to teach you how to hack around the biological need for regular sleep. I can’t talk about all the drugs since new ones come out pretty often, but you can identify drugs that’ll work based on the receptors and underlying systems they target. For the best results, we want drugs that have different mechanisms of actions on these systems stacked together.

Amphetamines

AdderallRemember those drugs kids at school take we talked about earlier? Adderall etc.
They’re amphetamines or amphetamine derivatives, all of them, and share similar mechanisms of actions. They work mainly on the dopamine and adrenaline systems.

By increasing DAT (dopamine transporter) activity, they cause your neurons to dump more dopamine into the presynaptic cleft.
It works in the same way on the adrenergic system and also triggers similar effects on a myriad of other neurotransmitters like acetylcholine, glutamate, and serotonin.
But there are other drugs that can be acquired cheaper and without legal restrictions which have the same mode of action. They can often be found in supplements for weight lifting as stimulants or pre-workouts.

For example one drug that is rather easy to get at bodybuilding and supplement stores is Ephedrine. It’s similar to amphetamine in structure and affects the dopaminergic and adrenergic systems just like the most popular ADHD medication. It doesn’t work quite as well, though.

But these amphetamine derivatives also have a dark side.

First off if you take too much your neurons will fry themselves. Remember how I mentioned neurotransmitter based transmission is triggered by electric currents in the cells? When a super excited neuron dumps a ton of dopamine, the tiny electric charge causing it is enough to damage it, permanently. But then it cascades, and the next neuron in queue attempts to pass on the signal, frying itself in the process and so on and on. Don’t worry, there’s millions of them, or actually do worry a little bit. Neurons are easily excited, and like a very very old man with a myriad of health problems, too much excitement can and does kill it.[5]

Secondly, regular use of ADHD medication can and does cause a dependency. So you’ve effectively given yourself ADHD and can’t really function without it.[6]

Third, amphetamine use severely drains your neurotransmitters. You need to replenish them. Keep reading and I’ll tell you how.
They also cause stress and fatigue in the underlying systems, namely the adrenergic and dopaminergic systems and to a lesser extent the serotonergic system.
So if you feel burnt out afterwards, try taking half the dose or less the next time. a 10% constant boost is better than a 20% boost followed by a 80% degradation.

The brotherhood of Modafinil

Modafinil

Now let’s consider a slightly more exotic drug. Modafinil. This guy been around for a long time and the militaries around the world love it. I just found out my home nations (India) air force includes it in contingency plans. Brilliant! Soldiers that don’t need to sleep. Now if only they could find planes that didn’t fall out of the sky on a regular basis.[7]

Modafinil works via the dopaminergic and adrenergic systems.[8]
It works as a dopamine reuptake inhibitor, which means stronger signals due to more dopamine in the presynaptic cleft, and it increases norepinephrine levels in the synaptic cleft in a similar way to amphetamines.

An important factor to keep in mind is that it’s a low-affinity binder, which means:

  • It works slowly (expect 2 hrs)
  • Its mild (you won’t necessarily feel it, but trust me, when it’s 4am and you look around and everyone but you is yawning, you’ll know it worked)
  • It won’t prevent you from falling asleep if you really want.

You can buy Modafinil and Armodafinil, an improved analog of Modafinil, at ModafinilXL.

Adrafinil

Adrafinil

This guy gets metabolized to modafinil in the liver. A strange queasiness might be felt in the liver as the enzyme activity increases. Not as effective as modafinil since a lot of it is destroyed in the metabolic process.

Hydrafinil

Hydrafinil

Some people absolutely love this stuff. The name is a marketing play and the molecule itself doesn’t have much in common with modafinil.[9] Though common criticisms are that it looks funny, clumps easily, has a very short duration of effect and it’s as effective as Modafinil.

Flmodafinil

Flmodafinil

AKA CRL-409,40 (or Bisfluoromodafinil), current heavyweight champion of the modafinil alternatives world. Basically modafinil with two fluorine atoms added to it. This increases the bio-availability of the drug by increasing its lipophilicity (it crosses the blood brain barrier easier since it’s more fat soluble)[10]

Recommended dose is 50-100 mg, up to 200mg if you plan on staying up for 48hrs.

Fladrafinil

Fladrafinil

AKA CRL-409,41 (or Bisfluoroadrafinil) I recommend you do not take this. It’s basically adrafinil with two fluorine molecules and all anecdotal reports say it doesn’t work very well. If you do try it, write to us and tell us how it went!

Modafinil and it’s derivatives is a lot safer than amphetamines and stimulants like Adderall, but still don’t take a massive dose. I can tell you from personal experience that staying awake for 3 days in a row isn’t fun.

Good ol’ cuppa joe

Caffeine

So far we’ve targeted the dopaminergic and adrenergic systems. Let’s look at adenosine real quick.
Your best bet (and cheapest) is to simply drink a cup of coffee.
Many in the nootropics community love a little bit of l-theanine with their coffee, feel free to try that if coffee makes you too jittery.

But don’t drink too much coffee. It’ll backfire.
If you drink large amounts of coffee continuously, your brain reacts by upregulating adenosine receptors on the neuron heads and by increasing the amount of adenosine in your brain, and this causes you to be constantly sleepy, tired and to need coffee to barely function. If you’re at a hackathon, hold up on the coffee till it’s near the end and you absolutely can’t function without it.

I found myself continuously getting addicted to coffee, requiring it to just stay awake and then going through a painful withdrawal/cleanse, so I switched to green tea.
There are more powerful and targeted adenosine receptor blockers though they aren’t very well known or easily found. These belong to the Xanthine family of molecules. Write to us if you have any hands on experience with them, we’d love to interview you.

Recovery

“But I feel like shit after pulling all-nighters or going to hackathons!”

Well duh, what’d you expect to feel like? A million bucks?

Here’s what happened, your brain depleted a ton of its neurotransmitters thinking your thoughts. Energy stores are also depleted. I highly recommend taking a dopamine precursor afterward or even as part of your drug stack.

N-Acetyl-L-Tyrosine, better known as NALT, is a crowd-pleaser in that category. The main part of those four letters is the T, and it stands for tyrosine. Tyrosine is an amino acid that is readily metabolized to dopamine. Dopamine is further metabolized to norepinephrine which you depleted stressing your adrenergic system. Bam! Two birds, one stone.
Mice treated to have extra dopamine also have a stronger reaction to modafinil and caffeine and ended up recovering better from sleep deprivation than untreated mice.[11]

So what about the adenosine we blocked?
Well, there isn’t much you can do about that. Take a nap, even if it’s a quick 10-30-minute nap or you just close your eyes and think about stuff during your waking stint. It’ll flush some of the adenosine out of your brain. It’ll also help you get over writers block if you feel incredibly fatigued before you can afford to sleep properly.

And finally, eat something, even if you’re not hungry from all the stims in your body. I’m not going to go into dieting and what proper foods are. But hopefully, you know this part.

Best of luck with your endeavors, whatever they may be.
And remember I’m not a doctor and even if I was, you take advice from a stranger on the internet at your own risk.

References   [ + ]

Categories
Bacopa Nootropics

Bacopa Monnieri: The Most Impressive Natural Nootropic

Bacopa monnieri, commonly referred to as Bacopa, it’s a plant that has been used for thousands of years in Ayurvedic medicine. In India, it is also referred to as Brahmi. In the last two decades, many Ayurvedic plants, like Ashwagandha, Brahmi, and Gotu Kola, have been shown to be effective not only in Ayurveda classic books but also in scientific studies; the extract, in particular, has been shown to be as effective as some prescription medications.

Background and Benefits

Perhaps more than other top nootropics, Bacopa highlights the importance of the individual and the makeup of his biology on any given day. Although it reliably promotes enhanced memory and vivid dreaming, other effects are less consistent, often due to the large variety in potency between the different products on the market. Luckily, in the last few years, a standardized and pharmaceutical grade extract has been developed, named Bacognize®.

Bacopa Ayurvedic Medicine BenefitsIt is known to produce clarity or a slight fog, making you relaxed or slightly moody, with the potentiality of leading to mild physical symptoms (like muscle aches and intestinal bloating). In spite of all this critical talk, Bacopa is one of the most underestimated supplements, and this article will paint it as one with profound healing and nootropic abilities. Confused? Don’t worry; we got you covered!

Some of the benefits of Bacopa (according to both scientific research and anecdotal experiences) are:

  • It is neuroprotective[1] and significantly improves acquisition and retention of memories.[2]
  • It also increases acetylcholine synthesis and promotes neurogenesis by enhancing the activity of BDNF and NGF[3]
  • It has anxiolytic[4], antidepressant[5] and anti-stress effects.[6]
  • It is an antioxidant and increases lifespan in animal studies.[7]
  • It is anti-inflammatory[8] and cardioprotective.[9]
  • Bacopa may also help people with epilepsy[10], as well as children with ADHD.[11]

The sedative effect of Bacopa is almost always in the foreground, though anecdotal reports show that this effect happens most strongly at the beginning and tends to disappear after a month (or two) of consistent use. In fact, studies have shown that Bacopa’s peak nootropic effect is seen after two months[12], and keeps on getting stronger as time passes, while the anxiolytic effects are usually felt right from the first dose.

Anecdotal Reports

Before we get into the specifics of Bacopa, let’s have a look at some of the anecdotal experiences in the nootropics community to get a better understanding of how it works in healthy individuals outside the lab.

From Reddit user Nedzilla55

[…] My first nootropic experience, and it was a good one. I noticed acute effects of lowered anxiety, and over the course of a few months noticed increased memory. This amazing herb is subtle enough that I feel normal, but noticeable enough that I felt less stress and anxiety. I didn’t even realize how great it was until I got off of it, and started experiencing my usual increased anxiety. It wasn’t like an acute “Wow, I feel so calm” feeling, more like a background calm. Like turning down the volume of anxiety a couple of notches. Looking back at it, the 6-7 months I used it I was in a much better place mentally. […]

From Reddit user YoungRedPiller —

So I’ve been taking Bacopa Monnieri for about a month at this point. […] I’ll try to explain my experience with it so far.
I’ve heard that the memory effects take at least 8 weeks to show effect but I’ve been feeling some quite significant changes in my ability to recall events that have happened in the past month. It’s also improved the quality of these memories. This is a very nice effect that is very appreciated because I feel if i stick it out for another month my memory will improve noticeably.
One other effect that it’s had that I didn’t really expect it to have was that it made me completely apathetic. To everything. Studying, reading, music, doing anything at all. I’m completely careless to everything and my motivation to do things is very little. But when I start doing things, I don’t want to stop. It’s had a profound effect on my attention. I don’t know if the attention is because of the apathy or something but attention is another aspect that I like about Bacopa. Also due to the apathy, my anxiety is also very minimal in any situation. I completely have a fuck it attitude. Very appreciated as I used to be quite hyperactive.
It’s made me very calm, serene and genuinely carefree. […]

From Reddit user Tester12311

The first month: Contrary to anecdotal reports, I could definitely feel the bacopa kicking in. It acted almost as a mild downer and a definite anxiolytic. I felt calm, chilled out, and careless. […] Many initial reports include drowsiness and upset stomach. Though Bacopa did make me drowsy at first, I can only think of very specific instances with stomach upset which could easily have been as a result of what I ate that day. Besides these mild effects, there was not much else for Bacopa within the first month.
The second month and now: Throughout this entire period of taking Bacopa, I would constantly test my memory to see if it was improving. […] To be completely honest, it is very difficult to measure how much I can and cannot remember. But I can say that when people ask me if I remember something they said the week previous, I am more likely to respond positively. I am also more lucid with conversation topics as I can tie together the flow of a conversation from one topic to another. One can assume that my immediate working memory has greatly improved. […] Bacopa’s anxiolytics effects have also had a nice influence on my life. I am less nervous about social interactions especially with women or job interviews. It has gotten to the point where I really just do not care what people I don’t know think of me. […]
One of the most gratifying and prominent effects that I feel from Bacopa is the attention boost. I have a have a very strong grip on whatever I am doing. It has made reading and studying easier. I can sit and become enamored by a book. I hated reading before Bacopa. I love it now. […]

Learning and Memory

Bacopa Extract PowderBacopa is perhaps most notable for its ability to enhance memory and cognitive performance in mice.[13] In humans, this translates most clearly to improved consolidation of memories into long-term memory.[14] In these respects, bacopa has received a comparable amount of attention (in academic journals) as more mainstream and publicized herbal cognitive enhancers, such as ginkgo.

Later sections will expound on neurotransmitters, serotonin and acetylcholine in particular, which have, respectively anti-stress and pro-cognitive effects. Like other herbal nootropics, its mechanism also relies on adaptogenic properties or lowering stress (this is touched on below, from the perspective of “cytokines,” the body’s natural inflammatory agents).

While not as pronounced as the effect on long-term memory, Bacopa may also be useful for short-term memory, concentration, focus, motivation, and the likes. Clinical studies have found it effective against ADHD[15]. Another study has drawn the same conclusions[16]. This is especially encouraging for those who want to stay away from Adderall, Ritalin, and other pharmaceutical choices, and into other choices which may be more sustainable and less taxing on the psyche.

Inflammation

Inflammation, like oxidation, is too often presented in the press, and almost never in a light which sheds true insight on its value; gradually the public loses interest in the hype and falls into more conservative waters. Despite any skepticism, bacopa has real and impressive anti-inflammatory properties[17]. These anti-inflammatory properties are closely related to its anti-dementia effects, which are as potent as curcumin, and like curcumin may open the avenues in Alzheimer’s research for more potent semi-synthetic derivatives.

Cytokines are compounds which the body releases in response to stress or infection, and although they help to control certain illness, they can quickly lead to runaway inflammation. Many herbal nootropics work in part by regulating this runaway, negative feedback “loop.” Although it is perhaps not as strong as curcumin, there are a few studies and books summarizing bacopa’s effects on inflammation.

Epilepsy

It has been shown in multiple studies to be as effective as common antiepileptic meds. This is likely related to its effect as a modulator of GABA[18], although a direct modulation of glutamate cannot be ruled out as a contributing factor.[19]

Oxidative Stress

The anti-stress effect may be directly related to the antioxidant capacity, as suggested by evidence[20]. Although antioxidants are beaten to death in the media, it is important in the absence of rigorous ORAC testing (free radical savaging capacity) to recognize when a particular food or supplement shows promising activity[21]. Ginkgo, bacopa, turmeric and ginger all show potential here. You can look up the antioxidant and anti-inflammatory ratings for turmeric and ginger to get a rough idea of their potency.

Serotonin and BDNF

Besides its broad antioxidant properties, perhaps the most studied mechanisms of Bacopa have been centered on serotonin[22][23]. It has been shown to upregulate the serotonin transporter (SERT) and to increase brain-derived neurotrophic factor (BDNF) in an animal model of depression[24]. The magnitude of the BDNF effect is supported by studies investigating bacopa’s ability to substantially improve the growth and survival of dendrites and axons: the fragile, spindly structures allowing for communication between neurons.

Dopamine and glutamate

Although bacopa is known to restore dopamine function[25], and as mentioned above, glutamate function as well, it is still not clear the extent to which these factors play into its nootropic qualities. The acetylcholine, serotonin, antioxidant and (as we will touch on later) the cardiovascular properties all likely outshine dopamine and glutamate in this respect.

Physical Health

Bacopa Monnieri has been implicated in increasing specifically cerebral blood flow independent of overall blood pressure[26] it can also decrease blood pressure (both systolic and diastolic) independent of heart rate[27] by releasing nitric oxide — a molecule that helps cells communicate with each other — from the endothelium.

Bacopa is also cardioprotective, and in research has been showed to protect from several cardiotoxic substances, such as isoprotenerol.[28] and may likely have a protective effect for everyday cardiotoxic activities like smoking. drinking, and taking stimulants.

Although it has primarily been studied on opiate (morphine) related kidney damage (where it was found to be effective[29]), it may serve in the otherwise healthy as a general tonifying agent in the kidneys.

Contraindications

Due to its cholinergic activity, those with a known mood disorder should approach bacopa extremely cautiously. High acetylcholine levels have even been used in lab mice to simulate bipolar and borderline features[30].

Bacopa has a potent stimulatory effect on the thyroids. Persons with known thyroid conditions are accordingly advised to consult a healthcare professional before considering bacopa.
As said before, it is known to accumulate heavy metals. Nowadays, most nootropic suppliers have certificates of analysis, and this is not raised as a concern.

Closing Remarks

Buy Bacognize capsulesAlthough bacopa’s initial sedative effect may be partially balanced out by natural energizers, such as ginseng, cocoa or royal jelly, we are recommending you consult a healthcare professional before beginning such an aggressive regimen. It is instead more strongly recommended to simply lower the dose, particularly when using the 50% extract which some people may find too intense.

By the way, you can buy Bacognize capsules and powder at Nootropics Depot. Or, if you’re on a tight budget, check out Powder City’s bulk 50% extract and 20% extract capsules. I personally recommend the capsules as the powder has an unpleasant taste. The dosage depends on the type of extract you have, typically a 50% extract like Bacognize is taken 300 mg once or twice a daily, while a 20% extract is taken at 500-650 mg two to three times a day. It is typically taken with food.

The good news is that much of bacopa’s nootropic effect is cumulative. Although it does take up to four to six months to see full effects, modest effects can still be observed from switching to the lower dose after a mere two months. This is especially true when it is paired off in the long-term with other highly effective and synergistic supplements. You could even take it just one summer, completely remove it from your stack after that point, and still theoretically retain some of its nootropic qualities.

Bacopa Monnieri
6.5
Focus
7.5
Mood
8.5
Memory
5
Stimulation
9
Relaxation
9
Safety
Reviewer 8

References   [ + ]

1. Neuroprotective role of Bacopa monniera extract against aluminium-induced oxidative stress in the hippocampus of rat brain (2006)
2, 14. Chronic Effects of Brahmi (Bacopa monnieri) on Human Memory (2002)
3. Bacopa monnieri and L-deprenyl differentially enhance the activities of antioxidant enzymes and the expression of tyrosine hydroxylase and nerve growth factor via ERK 1/2 and NF-κB pathways in the spleen of female wistar rats. (2013)
4. Anxiolytic activity of a standardized extract of Bacopa monniera: An experimental study. (1998)
5. Antidepressant-like effects of methanolic extract of Bacopa monniera in mice (2015)
6. Antistress effects of bacosides of Bacopa monnieri: modulation of Hsp70 expression, superoxide dismutase and cytochrome P450 activity in rat brain. (2002)
7. Bacopa monnieri promotes longevity in Caenorhabditis elegans under stress conditions (2015)
8. The Ayurvedic plant Bacopa monnieri inhibits inflammatory pathways in the brain. (2016)
9, 28. Cardioprotective Effect of Bacopa monneira Against Isoproterenol-Induced Myocardial Necrosis in Rats (1997)
10, 19. Decreased glutamate receptor binding and NMDA R1 gene expression in hippocampus of pilocarpine-induced epileptic rats: neuroprotective role of Bacopa monnieri extract. (2008)
11, 15. An open-label study to elucidate the effects of standardized Bacopa monnieri extract in the management of symptoms of attention-deficit hyperactivity disorder in children. (2014)
12. Effects of a Standardized Bacopa monnieri Extract on Cognitive Performance, Anxiety, and Depression in the Elderly: A Randomized, Double-Blind, Placebo-Controlled Trial (2008)
13. Effect of bacosides, alcoholic extract of Bacopa monniera Linn. (brahmi), on experimental amnesia in mice (2004)
16. A Randomized Controlled Trial Investigating the Effects of a Special Extract of Bacopa monnieri (CDRI 08) on Hyperactivity and Inattention in Male Children and Adolescents: BACHI Study Protocol. (2015)
17. The Ayurvedic plant Bacopa monnieri inhibits inflammatory pathways in the brain. (2016)
18. Decreased GABA receptor in the cerebral cortex of epileptic rats: effect of Bacopa monnieri and Bacoside-A. (2012)
20. Antistress effects of bacosides of Bacopa monnieri: modulation of Hsp70 expression, superoxide dismutase and cytochrome P450 activity in rat brain. (2002)
21. Bacopa monnieri as an Antioxidant Therapy to Reduce Oxidative Stress in the Aging Brain. (2015)
22, 23. Bacopa monniera leaf extract up-regulates tryptophan hydroxylase (TPH2) and serotonin transporter (SERT) expression: implications in memory formation. (2011)
24. Chronic Administration of Bacopa Monniera Increases BDNF Protein and mRNA Expressions: A Study in Chronic Unpredictable Stress Induced Animal Model of Depression (2014)
25. Neuroprotective potential of Bacopa monnieri and Bacoside A against dopamine receptor dysfunction in the cerebral cortex of neonatal hypoglycaemic rats. (2013)
26. Bacopa monnieri increases cerebral blood flow in rat independent of blood pressure. (2013)
27. Bacopa monnieri and its constituents is hypotensive in anaesthetized rats and vasodilator in various artery types. (2011)
29. Beneficial effects of Bacopa monnieri extract on opioid induced toxicity (2016)
30. Modeling bipolar disorder in mice by increasing acetylcholine or dopamine: chronic lithium treats most, but not all features. (2015)
Categories
Noopept Nootropics

Noopept Review: Effects, Dosage and Side Effects

Noopept is a cognitive-enhancing peptide synthesized in Russia in 1996, as a successor to prototypical nootropic drug Piracetam. It was based off the endogenous neuropeptide cycloprolylglycine.[1] Peptides are molecules consisting of 2 or more amino acids linked together by peptide bonds. Depending on the number of amino acids, peptides are called dipeptides, tripeptides, tetrapeptides, etc.

Overview

As said before, Noopept is a dipeptide. Peptides are not well absorbed in the GI tract and need to be injected via intramuscular or intravenous injection. Noopept, however, is a peptide that is only two amino acids long (dipeptide), and this allows it to be small enough to be absorbed orally, without being ripped apart by digestive enzymes and acids.[2]

It is commonly thought to be a racetam, but it is not since it does not have a pyrrolidinone nucleus.
It is said to be 1000 times stronger than Piracetam in effective dose level and nootropic activity[3], however, this statement doesn’t seem to have a scientific foundation.

The advantage of Noopept over Piracetam is its ability to stimulate the expression of the neurotropic factors NGF and BDNF.[4]

  • NGF (Nerve Growth Factor) prevents neuronal degeneration and promotes myelin repair. Dysregulation of NGF signaling has also been linked to Alzheimer’s disease[5] and other psychiatric disorders, such as dementia, depression, schizophrenia, autism.
  • BDNF (Brain-derived neurotrophic factor), like NGF, plays a significant role in neurogenesis. It controls synaptic function and plasticity and modulates neuronal survival[6].

The major metabolite of Noopept, cycloprolylglycine, has anxiolytic effect in animal models[7]. Scientists hypothesize this effect is a consequence of increased inhibitory transmission in the hippocampus.[8]

Another interesting effect of Noopept is its immune boosting ability. It reduces immunosuppression induced by cyclophosphamide, stimulates immune response to various antigens, and increases phagocytic activity of macrophages.[9]

Benefits of Noopept

  1. Improves memory recall and it is neuroprotective.
  2. Reduces brain fog and promotes mental clarity.
  3. May enhance focus and attention span.
  4. May have weak stimulant properties.
  5. Increases levels of neurotrophic factors NGF and BDNF.

How to Take

Noopept is sold in Russia in 10 mg tablets to be taken 2-3 times a day, but the most common dose is 20 mg twice a day.

Even though it is orally bioavailable, anecdotal reports indicate that oral and sublingual routes of absorption have different effects. The sublingual route has a stronger nootropic effect while the oral route is slightly more anxiolytic. No human studies comparing the absorption of Noopept via different routes have been conducted, however.

Noopept
Noopept, as it is sold in Russia

Another way that nootropic users like to take their Noopept is through nasal administration, by using either a solution or insufflating the powder by itself. For more information read our article on the intranasal administration of Noopept.

The effect of Noopept becomes stronger with chronic treatment[10] and the official drug package insert recommends taking Noopept in a “3 months on, 1 month off” cycle.

Side Effects

Noopept doesn’t have serious side effects or contraindications.
The most common reported side effects are irritability and problems with short-term memory. These side effects usually go away after a week of dosing and can be a consequence of excessively high dose.
Most nootropics have a bell-shaped response curve, so taking a higher dose than recommended will not necessarily make the positive effects stronger and could potentially increase the negative effects.

Noopept
7
Focus
5
Mood
7.5
Memory
6.5
Stimulation
6.5
Relaxation
10
Safety
Reviewer 7.7

References   [ + ]

Categories
Nootropics Tianeptine

Tianeptine: A Nootropic Antidepressant?

Tianeptine is an antidepressant, neuroprotective, and anxiolytic drug developed by French researchers Antoine Deslandes and Michael Spedding in the 1980s. It is currently marketed under the trade names Stablon and Coaxil in some European, Asian, and South American countries.

In the United States, Tianeptine is not FDA approved, mainly due to a lack of interest in the drug within the American pharmaceutical sphere. Although it is typically used in a clinical setting to treat depression and related illnesses, it has recently gained favor among nootropic users for its mood and cognition-boosting capabilities. It remains an unscheduled substance in the US, and can be purchased online via several nootropic vendors.

How it Works

Relation to Other Antidepressants

Chemical structure of TianeptineIn strict terms of chemical structure, Tianeptine is a tricyclic antidepressant (TCA) and is structurally similar to many prescription TCAs, such as amitriptyline and doxepin. However, Tianeptine’s mechanism of action varies drastically from classical TCAs

Most TCAs work as serotonin-norepinephrine reuptake inhibitors (SNRIs), increasing the levels of extracellular serotonin and norepinephrine. Tianeptine, however, has been found to enhance the reuptake of serotonin, which would consequently decrease serotonin levels in subjects. In addition, Tianeptine does not possess affinity for most neurotransmitter receptors, meaning it has little to no direct impact on norepinephrine and dopamine.[1]

These findings have led some researchers to question what is known as the monoamine hypothesis of depression, which has prevailed in medical circles for around half a century. Monoamines are a group of neurotransmitters that includes dopamine, serotonin, and norepinephrine, the three of which are linked to motivation and mood. The monoamine hypothesis of depression posits that depression is caused by a shortage of monoamine neurotransmitters in the brain.

Most classical antidepressants, (SSRIs, SNRIs, MAOIs, etc.) seek to restore balance to monoamine levels in the brain, thus alleviating symptoms of depression.[2] The fact that Tianeptine has little effect on monoamine levels, yet still alleviates symptoms of depression, has fortified the evidence that depression is much more complex than just an imbalance of monoamine neurotransmitters.

Mechanism of Action

So, then, how exactly does Tianeptine mitigate the symptoms of depression? Some researchers have hypothesized that depression is directly linked to lowered neuroplasticity (the ability of the brain to adapt to new stimuli) and that an increase in neuroplasticity in the human brain will contribute to reducing symptoms of depression. Studies conducted on Tianeptine’s action certainly support this idea.

Essentially, Tianeptine modulates the action of glutamate, the main excitatory neurotransmitter in the brain. Stressful situations tend to augment glutamate’s pathways, either causing too much or too little activity. These fluctuations in glutamatergic action lead to degradation of nerve and brain tissue. [3]

Glutamate

By keeping glutamatergic pathways under control, Tianeptine inhibits the body’s harmful responses to stress. This leads to increased neuroplasticity, which allows the brain to handle anxiety and depression more readily. The benefits of neuroplasticity also extend into the domain of nootropics by having a positive impact on cognition and working memory.[4] Tianeptine’s positive effects on neuroplasticity suggest that it may treat one of the root cause of severe depression rather than simply treat its symptoms. This would imply that Tianeptine has lasting effects on depression and cognition, even when it is no longer administered.

It was recently discovered in 2014 that Tianeptine works as a µ-opioid receptor agonist, which is believed to contribute to its anxiolytic properties. This could also be linked to the possible euphoric effects of Tianeptine that some users experience at higher (recreational) doses. Although Tianeptine acts on µ-opioid receptors, it does not have the high addictive potential that is associated with many opioid drugs.[5] That said, it is still a good idea to avoid taking Tianeptine for long periods of time without interruptions and/or at higher doses than those used in clinical practice.

Positive Effects of Tianeptine

  • Boosting mood and alleviating depression. [6]
  • Reducing anxiety and vulnerability to panic attacks. [7]
  • Improving overall brain health as a neuroprotectant.[8]
  • Enhancing cognition, memory, attention, and reaction time. [9]

Dosage Information

tianeptine stablon nootropicPrescription Tianeptine (Stablon) comes packaged in 12.5 mg tablets, which is considered a single dose. Tianeptine sold by nootropics vendors come in powder form, so doses should be measured out with a milligram scale to ensure accuracy.

Because Tianeptine has a relatively short duration of action (about 3-4 hours), three of these doses are taken throughout the day, waiting 3-4 hours between each dose. Tianeptine is administered orally, and there is no evidence that would warrant any other route of administration.

Recently some nootropic vendors have started selling tianeptine sulfate, which, according to them, is longer lasting compared to the regular sodium salt. There doesn’t seem to be any scientific evidence for this statement, however.

Side Effects, Tolerance, and Toxicity

Tianeptine has a similar side effect profile to more traditional antidepressants but does not cause the sexual dysfunction associated with SSRIs. It also does not exhibit anticholinergic effects that are common with TCAs. The most common side effects include nausea, constipation, abdominal pain, headache, and dizziness. However, all of these possible effects only occur in less than 1% of users.

Because Tianeptine is not monoaminergic in its mechanism of action, it is not considered a risk to take it alongside monoaminergic antidepressants. However, it should not be taken with MAOIs to avoid the risk of hypertension and seizures.

Tianeptine is considered safe to take indefinitely, although tolerance can develop over an extended period of use. If you find it necessary to take higher and higher doses to achieve any positive effects, it would be wise to taper off of the substance and take a tolerance break if you still want to use Tianeptine.

Although discontinuation symptoms of Tianeptine are not nearly as severe as with SSRIs and TCAs, it is still not recommended to suddenly stop usage. In addition, Tianeptine can be cycled with other antidepressant nootropics (like selegiline, NSI-189, or moclobemide) to stop tolerance from developing.

The LD50 of Tianeptine is estimated to be 980 mg/kg, so there is a very low chance of consuming a lethal or harmful dose on accident.

Summary

Tianeptine stands out among other antidepressants because of its novel modes of action. Rather than temporarily modifying a monoamine imbalance, it aids the brain in healing itself by increasing neuroplasticity.

It is unfortunate that its use has mostly been ignored by the American medical community, but its unscheduled status has opened up opportunities for nootropic usage. Because of its effects on mood, cognition, stress, and neuroplasticity, Tianeptine should definitely be considered by serious users of nootropics.

Tianeptine
6
Focus
10
Mood
6
Memory
7.5
Stimulation
8.5
Relaxation
6.5
Safety
Reviewer 8.9
Summary
I highly recommend Tianeptine to anyone who's looking for an antidepressant that does not impair cognition.

References   [ + ]