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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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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

 

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Cholinergics Nootropics

What Is The Best Choline Supplement For Cognitive Enhancement?

Although any aspiring researcher will no doubt have encountered what was once classified as a vitamin, choline, many intriguing questions surround its use, questions which are not always addressed in the literature. The aim of this article is to provide the reader with an introduction to choline and its effects, as well as the different forms of cholinergic supplements and some of the most common combinations with other nootropics.

What is Choline?

Choline is an essential nutrient for intestinal, cognitive, and neuromuscular health. It is a water-soluble vitamin, and it is sometimes grouped with other B-complex vitamins as vitamin J.

An endogenous agent first isolated from ox bile, choline is distributed throughout the body, where it fulfills a variety of functions ranging from the liver to the brain, but it is notable for being the precursor to acetylcholine, an important neurotransmitter which is involved in many functions including memory, muscle control, and mood.

Acetylcholine

The forms found in the body are often very close (or exactly the same) as the ones you buy at your supplement store: CDP-Choline (also known as Citicoline) and GPC (glycerophosphocholine) both occur naturally in all animal brains.

CDP is actually the last step before phosphatidylcholine (an essential cell membrane component, like cholesterol), while GPC is the very next step after phosphatidylcholine. From there, it becomes plain old choline, then acetylcholine or betaine. The figure below helps paint a picture of what’s going on inside the brain. GPC appears in the center, while CDP is in the upper right corner. Now, you may wonder how GPC and CDP can occur before choline, that is, be precursors, and still be more effective supplements than plain choline? Surely supplementing the final step in the ladder would be better? Not quite. The answer lies in the fact that the precursor enjoys interesting effects of its own, as well as a higher bioavailability and blood-brain-barrier permeability.

Choline synthesis from Citicoline

Benefits

Across a range of experiments and ethnicities, elderly individuals show the greatest response to choline supplementation. Age-related memory decline is a complicated process, with many contributing factors. It seems likely that a reduction in the availability of choline in the brain is one of them. By addressing this issue, the severity of the mental decline might be lessened. Choline is also somewhat helpful in stroke recovery, with studies supporting citicoline[1] and Alpha-GPC.[2]

However, there may be benefits for healthy subjects too. A study showed that Donepezil, an acetylcholinesterase inhibitor, improves certain measures of learning and memory in young adults.[3]

Interestingly, it plays a role in physical health too, especially with the liver, which is the first organ to show signs of stress in deficiency, but also in certain autoimmune diseases. In cases where the rogue antibody attacks neuromuscular acetylcholine receptors, symptoms usually include impaired motor skills, and increasing the supply of acetylcholine (to compete with the antibodies) is the first line of treatment.

Natural Occurrence

The recommended daily intake ranges from 350 to 600 mg. It is found in reasonable quantities in many foods, with common sources including eggs, peanuts, grains, meats (especially organ meats), spinach and beets.So while athletes who eat a lot of whole foods are unlikely to benefit from supplementation, elderly and more sedentary individuals may. Those who eat more processed than whole foods may also benefit from a choline supplement because processed foods are often lacking in choline.

So while athletes who eat a lot of whole foods are unlikely to benefit from supplementation, vegans, elderly and more sedentary individuals may. Those who eat more processed than whole foods may also benefit from a choline supplement because processed foods are often lacking in choline.

Interactions & “Stacking”

Too little choline results in mental slowness or brain fog, while too much causes a low mood, dysthymia, and muscular stiffness.

Choline should not be combined with pharmaceutical or herbal acetylcholinesterase inhibitors, like Huperzine, Galantamine, and Donepezil, as this can overwhelm the neuromuscular junction with too much acetylcholine. Many snake and spider venoms work by inhibiting or activating the peripheral acetylcholine receptor, inducing death either by asphyxia (low acetylcholine) or convulsion (high acetylcholine).

When taken with Piracetam (or another “-racetam“), some people find that the Choline should be taken about two hours before Piracetam. So, one idea is to take choline with breakfast, and piracetam with lunch. There are reports of fatigue or brain fog, the fatigue moreso with aniracetam than piracetam, but this may be caused by either an excessively high dose, or also the “depressive” characteristic of aniracetam contrasted against a more stimulant characteristic of piracetam. This may explain why some users have opted for aniracetam without choline (after reporting fatigue, brain fog, and low mood when combining the two). But choline has still been reported to act synergistically with Pramiracetam and Noopept.

A question commonly asked is how often it should be taken, or at what time of the day. With most supplements, it does not make much difference how the dose is divided, but acetylcholine can interfere with the deeper stages of sleep, so taking it with breakfast is advisable. And, as explained above, piracetam itself is thought to deplete choline, so a common strategy is to take the choline a few hours earlier. This lends itself well to taking piracetam with brunch. Some users may choose to take piracetam twice a day, and choline once or twice a day.

Having given the reader a background on choline, we now turn our attention to the focus of the article, which is explaining differences between common forms of choline.

CDP-Choline (Citicoline)

CDP-CholineCDP-Choline is unique among choline sources for containing Cytidine, a compound related to Uridine, a media spectacle which once made rounds in the nootropic community, it has served as the basis to the “Mr. Happy stack” and inspired many nootropic enthusiasts.

After ingestion of Citicoline, there is a significant increase in choline and uridine plasma levels[4], after which the latter goes on to induce a plethora of beneficial effects, particularly on the dopamine system. Studies indicate it promotes dopamine release[5] and increases the densities of dopamine receptors. While offering the benefits of uridine, CDP makes no sacrifice in delivering choline.

Daily dose varies between 300 and 1000 mg.

Alpha GPC

Alpha GPC is glycerylphosphorylcholine (a metabolite of CDP-Choline) with an added acetyl group that makes it more lipophilic, thus able to cross the blood-brain barrier more easily.  The most bioavailable, pure, and blood-brain barrier permeable of all choline sources considered in our review, it also has interesting properties that other sources do not. It boosts HGH and physical performance[6]. It also improves the functioning of the vesicular choline transporter[7], as well as serotonin, dopamine[8] and GABA synthesis.[9]

Although highly effective in the elderly, this one in high doses carries a risk of hypercholinergic states. Even though it is not harmful, too much brain choline is reported to have a counterintuitive effect of causing brain fog, fatigue, or confusion. Used in moderation, this choline source can be very effective. Although expensive, a little goes a long way.

Daily dose varies between 300 and 800 mg.

Choline Bitartrate & Citrate

Behind lecithin, these are the most inexpensive and widely available forms of Choline and are commonly supplemented by those who suffer from fatty liver, hepatitis, and cirrhosis to enhance their liver detoxification pathways.

Choline bitartrate nootropicAs with any supplement, users have reported differing effects, but researchers are inclined to the view that both bitartrate and citrate are more or less identical in effect, with differing experiences being explained by individual differences. The foods you eat, how well you sleep, the mood you wake up in, and your activity level are all things which vary from day to day and things which might influence your response to choline, but these factors are not always included in the reports.

This would be a decent choice for someone looking for general health benefits, but it may not be the best solution for cognitive enhancement as these forms of choline do not cross the blood-brain-barrier as well as Alpha GPC and Citicoline.

Daily dose varies between 250 and 1000 mg.

Lecithin

Lecithin, the most natural form, commonly derived from soy or sunflower, it supplies a unique form of choline, phosphatidylcholine.

Soy lecithinPhosphatidylcholine is an interesting supplement by itself, it not only helps as choline precursor but also plays a role in cell membrane integrity by donating itself to components of the ”phospholipid bilayer” which was so passionately extolled by our high school biology teachers.

Although the least potent form of choline (the most potent being Alpha GPC and Citicoline), a higher dose can be used to a somewhat similar effect. It contains certain other “less essential” phosphatidyl groups (including phosphatidylinositol), which though not harmful, contribute little to the nootropic effects of lecithin. Because of this, a larger dose is needed than with most choline supplements.

Its bioavailability is as good, and there is no concern over contamination or purity, however, beware of cheap soy lecithin because it is often derived from genetically modified soy, so make sure you’re buying GMO-free soy lecithin. More importantly, it may not be as good as other choline precursors, as far as cognitive enhancement.

Daily dose varies between 500 and 2000 mg.

DMAE

Capable of improving acetylcholine synthesis[10], DMAE improves physical performance and alertness[11], as well as some measures of mood[12] in healthy volunteers, making it by definition a nootropic. However, even though it may look excellent on paper, it is not very effective as a cognitive enhancer, and it may even act as an anticholinergic according to some research.[13]

Daily dose varies between 100 and 500 mg.

Centrophenoxine

Although not strictly a “choline source,” Centrophenoxine (also known as Meclofenoxate) is a potently and selectively cholinergic supplement often used in dementia patients. It is an improved version of DMAE, and it has been found to improve memory, attention, and general cognition in young and aged rats.[14]

One of its remarkable properties is to increase acetylcholine release[15] while slowing down lipofuscin accumulation[16] [17], which is thought to cause Alzheimer’s disease.[18]

Daily dose varies between 200 and 800 mg.

ALCAR

Acetyl-L-carnitine has more rich and interesting effects on brain health than plain L-carnitine, suggesting the acetyl group plays a pivotal role, helping acetylcholine pathways.

It is known to significantly boost NGF[19], mitochondrial function, and alertness in both healthy and elderly subjects. Supplementation increases serotonin and noradrenaline synthesis in the cortex and hippocampus[20].

Daily dose varies between 400 and 2000 mg.

Phosphatidylserine

Although not strictly cholinergic, this supplement often taken alongside ALCAR, an acetyl donor, and both supplements can indirectly help in methylation as well as acetylcholine pathways.

Taken on its own, it is able to partially restore acetylcholine levels of aged rats. It has cortisol and stress-lowering properties, particularly after chronic administration.[21] Studies on spatial memory in healthy volunteers have been mixed, but against ADHD they have been more conclusive[22] [23], with a noteworthy effectiveness. Phosphatidylserine makes up an important part of the nerve membrane, its ratio to phosphatidylethanolamine and phosphatidylcholine determines the overall strength of the membrane.

Daily dose varies between 100 and 300 mg.

References   [ + ]

1. Citicoline in the treatment of acute ischaemic stroke: an international, randomised, multicentre, placebo-controlled study (ICTUS trial). (2012)
2. alpha-Glycerophosphocholine in the mental recovery of cerebral ischemic attacks. An Italian multicenter clinical trial. (1994)
3. Acute cognitive effects of donepezil in young, healthy volunteers. (2009)
4. Effect of oral CDP-choline on plasma choline and uridine levels in humans. (2000)
5. Dietary uridine-5′-monophosphate supplementation increases potassium-evoked dopamine release and promotes neurite outgrowth in aged rats. (2005)
6. Acute supplementation with alpha-glycerylphosphorylcholine augments growth hormone response to, and peak force production during, resistance exercise (2008)
7. Effect of L-alpha-glyceryl-phosphorylcholine on amnesia caused by scopolamine. (1991)
8. Modulation of monoaminergic transporters by choline-containing phospholipids in rat brain. (2013)
9. Evidence for an in vivo and in vitro modulation of endogenous cortical GABA release by alpha-glycerylphosphorylcholine. (1996)
10. Dimethylaminoethanol (deanol) metabolism in rat brain and its effect on acetylcholine synthesis. (1979)
11. The influence of 2-dimethylaminoethanol (DMAE) on the mental and physical efficiency in man. (1967)
12. Mood alterations during deanol therapy. (1979)
13. Deanol and methylphenidate in minimal brain dysfunction. (1975)
14. Age-related differences in memory and in the memory effects of nootropic drugs. (1990)
15. Effect of centrophenoxine on acetylcholine release in perfused cerebral ventricles of cats under dynamic electrophysiological control. (1979)
16. Neuronal lipofuscin in centrophenoxine treated rats. (1977)
17. Lipofuscinogenesis in mice early treated with centrophenoxine. (1978)
18. Lipofuscin hypothesis of Alzheimer’s disease. (2011)
19. Acetyl-L-carnitine treatment increases nerve growth factor levels and choline acetyltransferase activity in the central nervous system of aged rats. (1994)
20. Chronic acetyl-L-carnitine alters brain energy metabolism and increases noradrenaline and serotonin content in healthy mice. (2012)
21. Blunting by chronic phosphatidylserine administration of the stress-induced activation of the hypothalamo-pituitary-adrenal axis in healthy men. (1992)
22. The effect of phosphatidylserine containing Omega3 fatty-acids on attention-deficit hyperactivity disorder symptoms in children: a double-blind placebo-controlled trial, followed by an open-label extension. (2012)
23. The effect of phosphatidylserine administration on memory and symptoms of attention-deficit hyperactivity disorder: a randomised, double-blind, placebo-controlled clinical trial. (2014)
Categories
Nootropics Tianeptine

Tianeptine Abuse, Safety and Withdrawal Syndrome

Tianeptine is a tricyclic antidepressant whose mechanism of action has been puzzling scientists for years. In fact, unlike most antidepressants, Tianeptine does not target monoamines (serotonin, norepinephrine, dopamine). It is, therefore, a very effective solution for individuals suffering from depression and anxiety, especially those who are afraid of the side effects of currently available antidepressants.

A few years ago, a new mechanism of action has been unveiled that is now thought to mediate the beneficial effects of Tianeptine on depression and cognition: mu-opioid receptor agonism. So what does this mean for Tianeptine users? Is it time to starting worrying about potential opiate-like addiction and withdrawal symptoms? Let’s find out.

1985-2009: Discovery & 5-HT theory

Tianeptine was discovered by French researchers Antoine Deslandes and Michael Spedding in the 1980s. We do not know exactly when that happened, but the first study that mentions “Tianeptine” was published in 1986.[1]

The animal studies carried in the late-90s to early 2000s showed that Tianeptine may be part of a new class of drugs named serotonin reuptake enhancers (SRE). In short, these drugs enhance serotonin uptake, instead of inhibiting it, thus reducing the overall amount of serotonin (5-HT) in the synapse. Serotonin reuptake enhancers, therefore, have the opposite mechanism of action of SSRIs drugs like Prozac and Zoloft.

Monoamines

It is important to point out that, until a couple of years ago, depression was thought to be the result of a depletion of monoamine neurotransmitters[2] [3], and, in particular, serotonin. This is known as the monoamine theory of depression.

However, when experimenting with pharmaceutical agents that are known to cause monoamine depletion, researchers have failed to generate (or worsen) depression in healthy subjects.[4] In addition, the MOA of drugs like Opipramol, — and Tianeptine itself —, is unrelated to monoamines, and they still have been found an antidepressant effect. Nowadays the monoamine theory is no longer the ruling paradigm in depression research, and depression is thought to be a consequence of several different neurotransmitters and brain changes.

So the theory that Tianeptine is an SRE may have been influenced by the technical limitations of the time, as well as the popular theory that antidepressant work by “fixing” a monoamine imbalance. But that was going to change with two new discoveries.

2010-2014: New findings

A study published in 2010[5], first mentioned the fact that Tianeptine’s antidepressant effects may have nothing to do with serotonin and other monoamines. The researchers thought, instead, that the antidepressant effects may be due to glutamateric modulation[6]. Tianeptine, in fact, has shown to be neuroprotective and to promote neurogenesis, as well as reduce the release of glutamate, a neurotransmitter that is thought to be implicated in schizophrenia, anxiety, depression, psychosis and bipolar disorder.[7]

However, the real surprise came four years later, when a study[8] showed that Tianeptine activates mu-opioid receptors[9], the same receptors targeted by frequently abused opioid drugs such as morphine, heroin and oxycodone.

Abuse of Tianeptine

Tianeptine is a relatively safe drug. However, like many pharmaceutical drugs, it can be used for purely recreational purposes.

Many heroin users in Russia, in fact, were abusing Coaxil (one of Tianeptine brand names), long before scientific research proved that it works as an opioid agonist. An article, published in the newspaper “Moscow Komsomolec” in 2008, first raised the alarm about Tianeptine abuse in Russia. This was the about the same time that Krokodil — a cheap homemade heroin substitute[10] that it is famously known to destroy body tissues[11] and cause death in a manner of weeks — hit Russia and neighboring countries, when the former USSR country started a major crackdown on heroin production and trafficking.

The drug market has changed completely in past few years in Moscow. “The time of synthetics has come!”-say drug users.

Everything was clear before: heroin, cannabis, “clubbing” pills. Today the main drugs are so-called pharmaceutical drugs: drugs that cannot be sold without a prescription, but nevertheless they are sold in big quantities through dishonest pharmacists. The most widely-spread and most dangerous one is antidepressant Coaxil. Its affordable and life-threatening if injected intravenously. […]

-If you watch the process of making coaxil substance by drug users you will see quite clearly why. They crush the pills and dissolve them in water, very often it is tap water. Then they get a disperse substance and it’s particles cause damage to a vessel and build a thrombus (clot) inside it. The thrombus starts growing rapidly. The thrombus itself is a very good environment for various microorganisms and that provokes purulent complications. If a drug user by chance injects coaxil into an artery –then that develops thrombus not only in a big vessel, but even in small ones, called arterioles. In these cases gangrene starts very quickly. As a rule complications come in the first six months of using the drug, sometimes even sooner. Very often “neophytes of coaxil” slip up at first injection. The most careful and accurate can last maximum for a year.

As a consequence, Tianeptine is now a controlled substance in Russia and France.

Tianeptine is not the only drug of the tricyclic family of antidepressants that has been banned. Amineptine – a drug closely related to Tianeptine – was banned years ago due to liver damage and frequent abuse and addiction among patients who were prescribed it as a depression treatment. I would like to point out that, unlike Tianeptine, Amineptine is also a dopamine reuptake inhibitor, so it may have a higher recreational value compared to Tianeptine.

Safety of Tianeptine

Tianeptine is safe at the recommended dose (12.5 mg three times a day) and users may benefit from the neurogenic, neuroprotective and antidepressant properties of the drug without having to worry about addiction and withdrawal symptoms.

That said, Tianeptine is not the kind of nootropic that you take every day and “forget about it.” It is still a very potent compound, with multiple molecular targets, and I can easily imagine how some people — particularly those with a history of drug abuse — may be tempted to binge on it, in an attempt to emulate the effects of prescription painkillers.

It is, therefore, a good idea to cycle it with other antidepressant nootropics, like Coluracetam or NSI-189. Tianeptine has instant mood elevating properties, and some users report tolerance to the positive effects after repeated administration, so it may be a good idea to use Tianeptine as needed instead of taking it daily for extended periods of time.

Withdrawal Symptoms

Tianeptine withdrawal is characterized by high level of anxiety and excitability[12] akin to withdrawal from opioids. The severity of the symptoms is directly influenced by the dosage used and the length of time that the drug has been taken.

A Reddit user reported full-blown withdrawal syndrome akin to opiate withdrawal when using Tianeptine at an incredible dose of 250 mg to 1 gram (!) of Tianeptine sodium a day. You can find more details about his experience here. However, as said before, it’s no wonder that the user had those symptoms when talking about that sort of amount of drug in their bodies. In my experience, Kratom is an overall better opioid replacement as far as safety and risk of addiction.

If you are going to use Tianeptine long-term, we suggest Tianeptine Sulfate or Free Acid. The slightly longer duration of effect of these compounds means a lower risk of addiction and withdrawals (though it has not been scientifically tested).

Conclusion

In the end, I feel that Tianeptine is an incredible drug, one that can be truly life-changing for those who suffer from depression and anxiety. I discourage anyone from trying Tianeptine if they are just looking for a “legal high”.

It would be a shame if the drug were banned because a few subjects exploiting the legal status of this amazing substance in search of a poor man’s high.

That’s all for now — for any question or doubts leave us a comment; and if you have enjoyed the article consider following our Facebook and Twitter age.

References   [ + ]

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
Life Extension Nootropics Reviews

Cerebramin and the Cytamins – My Experience

Even though the first nootropic, Piracetam, was discovered by a Romanian chemist, we can truly say that Russia is the true motherland of nootropics. From the “oldies”, such as Phenibut and Picamilon, to the newest additions, Russia has always been the bleeding edge of nootropic research. Today we are going to talk about Cerebramin and other compounds of the cytamins family.

Cytamins are nucleoproteins complex isolated from the organs of healthy cattle. These compounds are part of a new family of compounds developed in Russia, and called peptide bioregulators, that are being researched as anti-aging treatments.

Peptide bioregulators

From 1971 to 1996, researchers at the St Petersburg Bioregulation and Gerontology Institute studied and documented the role of peptides in aging. [1] [2] What they discovered is the body releases tissue-specific compounds, of peptide structure, that mediate interactions between cells. As such, they were named peptide bioregulators.

The researchers then isolated and purified those peptides from the organs of healthy cattle and pigs and found out that they had a normalizing effect on the abnormal cells of senescent and/or sick animals. These promising peptides have been developed into a new class of pharmaceuticals, the cytomedins, (e.g. Cortexin, Thymalin and Epithalamin, which has been further developed into Epitalon) as well as para-pharmaceuticals, the cytamins, such as Cerebramin, Vasalamin and Retinalamin.

Cytamins?!

So what’s the difference between the cytamins and the cytomedins?
Cytamins are “interpolymer complexes of tissue-specific proteins with nucleic acids.”[3] Essentially, they are a mixture of compounds such as nucleoproteins, vitamins, peptides and amino acids. The patented technology of cytamins manufacture includes alkaline hydrolysis from tissue cells, consecutive precipitation of nucleoprotein complexes, their purification from ballast substances, and manufacture of the ready form as enterosoluble tablets or capsules.[4]

In the manufacturing of Cytamins only calves and pigs less than 12 months old are employed, and strictly from Russian farms where “no human-endangering infectious diseases including transmissive bovine spongiform encephalopathy has been registered”.[5] Also, Russia is known for “its epizootological and epidemiological safety in respect to prion diseases.”[6] Not only that, but electrophoresis and Congo red staining (the recommended method of testing for Mad Cow disease) are employed to check for the presence of prion proteins.

There are over 17 cytamins on the market, and they are manufactured at “Longvy Farm” in Russia. More information about the cytamins can be found at the official website.

Some of the most famous cytamins are:

  • Brain (Cerebramin)
  • Liver (Hepatamin)
  • Stomach and duodenum (Ventramin)
  • Pancreas (Pancramin)
  • Lungs and respiratory system (Bronchalamin)
  • Heart (Coramin)
  • Circulatory system (Vasalamin)

Dr. A.S. Bashkireva[7] tested the use of Cerebramin and Vasalamin on driving performance, in both healthy subjects as well subjects with depression, anxiety and other mood disorders. The results were that the cytamins were “very effective in the correction of psychoemotional disorders and for attaining stable psychic adaptation”. [8]

[…] 150 professional drivers (men aged 30-59 years) were examined using a clinical questionnaire to identify, estimate and compare neurotic states according to 6 scales of anxiety, neurotic depression, asthenia, hysterical type of reacting, obsessive-phobic disorders and neurovegetative disturbances. The drivers were divided into 5 groups, 30 persons in each: I group received Cerebramin→, II — Vasalamin→, III — Cerebramin→ + Vasalamin→, IV — placebo, V — no preparations. […] The analysis of the incidence of various PES revealed a statistically significant increase in the number of drivers with stable psychic adaptation in Groups I, II, and III after cytamin correction as compared to the baseline level (3.3-, 2.4-, and 2.3-fold, correspondingly, p<0.001-0.05). A statistically relevant decrease in the number of the drivers with unstable psychic adaptation in Groups I, II, and III after a cytamin course was noted in comparison with the baseline level (2.5-, 3.0-, and 3.3-fold, respectively, p<0.001- 0.05). […] A detailed examination of the drivers’ PES according to different scales convincingly demonstrated the efficacy of combined application of Cerebramin and Vasalamin in correction of anxiety (p=0.001), neurotic depression (p=0.0001), asthenia (p=0.0001), hysterical type of reacting (p=0.0004), obsessive-phobic states (p=0.0001), and neurovegetative disorders (p=0.003). […]
The presented results showed the occupational hazards and long driving experience being the risk factors for the development of BMD. The applied parameters of PES and early manifestations of BMD are informative criteria for assessing the life quality and professional suitability of lorry-drivers. Cytamins […] are very effective in the correction of psychoemotional disorders and for attaining stable psychic adaptation. [9]

Cerebramin: My Experience

In my anecdotal, and totally unscientific experience with Cerebramin (the cattle brain extract), I can’t say to have noticed any effect. However, I am 24 years old, and this supplement is to be used in the elderly, so I cannot make any real judgment. That said, I feel that “real drugs” like the cytomedins (eg Epitalon, a pineal gland peptide, and Cortexin, a brain peptide) have a huge potential, and I’d like to try them out in the future.

You can buy Cerebramin, Cortexin and other rare Russian nootropics at RUPharma.

Cerebramin
5
Focus
6
Mood
5.5
Memory
5
Stimulation
5
Relaxation
7
Safety
Reviewer 5.5

References   [ + ]

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

Categories
Nootropics Phenylpiracetam Racetams

Phenylpiracetam — Stimulant Nootropic: Effects, Dosage & Experiences

Those who spend any amount of time looking into nootropics will be very familiar with the racetam class of nootropics, a group of drugs that are structural derivatives of piracetam. These drugs display variance in the details of their effects, but they all exhibit neuroprotectant and cognitive-enhancing properties.
One of these piracetam derivatives, phenylpiracetam, is appealing to many nootropic users due to its many purported benefits.

Background and Benefits

phenylpiracetam nootropicPhenylpiracetam is frequently cited to display the following effects:[1][2]

  • Memory enhancement
  • Anti-amnesia
  • Antidepressant
  • Anticonvulsant
  • Antipsychotic
  • Anxiolytic

If phenylpiracetam does indeed have these listed properties, its appeal extends beyond just the sphere of nootropics. Any drug with that kind of resume is certainly impressive. Here we will examine this unique substance and its purported effects.

Phenylpiracetam, also known by its Russian pharmaceutical names Phenotropil and Carphedon, was developed in Russia in the 1980s as a piracetam derivative, with the hopes that it would display and expand upon the nootropic properties that make piracetam such a popular drug. Specifically, phenylpiracetam is a phenylated analog of piracetam, meaning that it is essentially a piracetam molecule with a phenyl group attached. Interestingly, some have theorized that phenylpiracetam’s purported stimulant effects may be due to the molecule’s similarity to phenethylamine (and, by extension, amphetamine).

These potential stimulant properties, along with phenylpiracetam’s ability to improve physical stamina, has led to the drug being banned from use in Olympic competitions.[3]

phenylpiracetam-nootropic-stimulant

Dosage, Mechanism, and Effects

Phenylpiracetam is typically sold by online vendors in its pure powder form or as pharmaceutical tablets. Most of these sources sell a racemic mixture of the molecule, but some of the studies done on the effects of phenylpiracetam were conducted using only the R-isomer.

Phenylpiracetam Phenotropil Nootropic
Original Russian Phenylpiracetam (Phenotropil)

A single dose of phenylpiracetam typically ranges from 100200 mg. Most prescription guidelines state that phenylpiracetam can be taken 2-3 times per day, as the drug will exert effects on the body for about 4-6 hours before receding. It should be noted that most anecdotal reports from users indicate that phenylpiracetam builds up a tolerance rather quickly, so it might not be wise to use it for days in a row. That being said, the drug appears to be relatively safe to use regardless of tolerance buildup.

Phenylpiracetam’s mechanism of action still remains largely uncertain. While various studies have been conducted on its effects, few have dealt with the specifics of its pharmacology. However, one study performed on rats found that phenylpiracetam decreased the density of nACh and NMDA receptors in the hippocampus when they had previously been given scopolamine, an anticholinergic drug.

Phenylpiracetam was also found to increase the density of the D1, D2, and D3 dopamine receptors[4]. Dopamine receptors are important for motivation, arousal, pleasure, and memory.

It also appears that phenylpiracetam’s enantiomers have unique effects and properties. Most notably, studies indicate that the R-enantiomer is mostly responsible for its stimulating and cognition-enhancing effects while the S-enantiomer may be more responsible for stopping cognitive decline.[5]

One of the drug’s biggest potential uses is for treating cognitive decline brought on by diseases like Alzheimer’s. Various studies have been conducted in Russia studying the effect of phenylpiracetam on cognitive decline caused by organic causes. These studies found that phenylpiracetam improved the cognition of those with Alzheimer’s disease, and showed minor effectiveness in improving the cognition of patients afflicted with epilepsy. The drug did not, however, appear to improve cognition for those whose cognitive decline was brought on by traumatic brain injury.[6] In a study conducted on 400 patients with ischemic stroke, phenylpiracetam was able to improve cognition when taken at a dose of 400 mg per day for one year.[7]

There is currently no research conducted on phenylpiracetam’s effect on cognition in young, healthy subjects, although anecdotal reports throughout the internet suggest that it does improve cognition among those with no cognitive disorders. One study conducted on rats found that the R-enantiomer of phenylpiracetam was able to enhance cognition, but this result has not been replicated in any study using the racemic mixture.[8]

Zhiliuk, Mamchur & Pavlov[9] found that Phenylpiracetam improves the processes of learning and storing conditional skills when studying cognitive processes and functional state of mitochondria in the neocortex of alloxan-diabetic rats.[10]

Gustov, Smirnov, Korshunova IuA and Andrianova argue that Phenylpiracetam is beneficial to people who develop cognitive deficits and/or depression after encephalopathy and brain injuries.[11] It increased quality of life in patients with encephalopathy after acute lesions (30 people), brain traumas (33 people) and glioma surgery (36 people). The average Mini Mental State Examination (MMSE) scores (a 30-point questionnaire) from baseline improved in all groups. Anxiety improved and depression declined substantially, resulting in less discomfort and better ability to execute everyday activities.[12]

phenylpiracetam memorySome preliminary studies have found phenylpiracetam to have antidepressant properties. However, this area of effect has not seen as much research as the area of cognitive enhancement. A study performed on rats found that when phenylpiracetam was administered to rats, it significantly reduced depression symptoms caused by a forced-swim test.[13] A study conducted on human patients with cognitive decline concluded that phenylpiracetam is able to alleviate symptoms of depression.[14]

Perhaps one of the most unique and attractive benefits of phenylpiracetam is its ability to act as a psychostimulant. However, this effect is not very well researched, although one experiment conducted on rats found that phenylpiracetam increases locomotor activity for upwards of 2 hours.[15]

Anecdotal Reports

As with any nootropic drug that has not seen as much clinical research as one might hope, it is useful to look at anecdotal reports from users to give a fuller picture of the drug’s effects. Obviously, individual user reports are especially prone to the placebo effect and should be weighed and judged by the reader with caution.

Reddit user The_Antagonist said –

At the peak of it’s effects (about an hour in) I feel intense focus, not especially jittery, unless stacked with something else, just pure attention, and a complete abolishment of any lethargy I would have been feeling previously. It’s not really a euphoric compound, but I’ve noticed it seems to make me significantly happier when I’m accomplishing something on it. It might be the racetam effects rearing their head, but solving mathematical problems, or gaining a more complete understanding of a concept just feels plain good. This attribute [in particular], for me at least, makes it a hell of a study drug.[16]

Reddit user Notlambda

I’m not a social butterfly. I’m retarded when it comes to explaining a concept or defending an argument.
On phenylpiracetam (or daily doses of piracetam), I’m a social genius. What it feels like is that I’m not the one saying the words that I’m saying. It’s like I feed a “command” into a register in my brain that is then picked up by whatever part of my cortex deals with speech, and then I find myself just saying the perfect words to explain everything concisely.
It’s like I’m watching somebody else be awesome, but that somebody else is me. It’s really nice because I can free the rest of my mind to think about concepts while the “other” me is doing all the talking.
It’s also very subtle. I’m explaining this like it’s a dissociative experience or something like that. It’s not.[17]

From user le_unknown

I’ve had great results with phenylpiracetam. Without a doubt, it has been the nootropic that works best for me. Gives me alertness (but no jitteriness, I just feel awake and normal – kills all drowsiness), focus, and a tiny mood elevation. I’m surprised I don’t see more people talking about it…[18]

Conclusion

Phenylpiracetam’s seemingly wide array of effects and benefits makes it well worth looking into. Most notably, phenylpiracetam seems to provide many of the benefits of piracetam, while seemingly being more potent or effective in certain areas. Phenylpiracetam seems to noticeably provide cognitive capacity improvement, mood elevation, and stimulation. Experiences will vary widely among individual users, so we would highly recommend you try phenylpiracetam for yourself to see how it works for you.

You can buy Phenylpiracetam in powder form as well as in capsules at NootropicsDepot.

Phenylpiracetam
8
Focus
8
Mood
7
Memory
9
Stimulation
6
Relaxation
8.5
Safety
Reviewer 9

References   [ + ]

Categories
Biohacking Coluracetam Nootropics PRL-8-53 Tutorials

Photographic Memory: Nootropics and Mnemonic Devices 101

Photographic memory, or eidetic memory, is the ability to vividly recall images after seeing them for a short period of time. A Google search shows over 16.000 results for “photographic memory nootropics”. Of all the articles I read, no one of them answer the fundamental question: Does photographic memory exist, and is it possible to achieve with a combination of mnemonic techniques, training, and nootropics?

What is Photographic Memory?

According to the Merriam-Webster dictionary[1]

Eidetic is the technical adjective used to describe what we more commonly call a photographic memory. The word ultimately derives from the Greek noun eidos, meaning “form.” The ability of certain individuals to recall images, sounds, or events with uncanny accuracy is a subject of fascination for researchers in the field of psychology. Among notable people who were reputed to have eidetic memories is the late television comic Jackie Gleason, who reportedly was able to memorize an entire half-hour script in a single read-through.[2]

There are only two case studies of eidetic memory in scientific research. Let’s take a quick look at them.

Case 1: The Mind of a Mnemonist

The first case study of a subject with an “incredible” (photographic?) memory was published in a Russian medical journal in the 1960s by psychologist Alexander Luria.

Alexander Luria was a famous Russian psychologist active in the mid-1900s. In the early days of his career, he met a young man named Solomon Shereshevsky. Shereshevky, — or simply ‘S.’, the acronym used in Luria’s writings — was a Russian reporter working for a local newspaper. Each morning the editor would meet with the staff to hand them a rather long list of assignments. Solomon was able to memorize the entire list by looking at the sheet of paper just once.

Solomon Shereshevsky Photographic Memory Nootropics
Solomon Shereshevsky

Even though he was not a brilliant student due to his shy nature, when S. was a schoolboy he could memorize every single thing he read without ever taking notes. Intrigued, Luria took S. to his lab and, over the course of several months, tested his memory using all kinds of complex mathematical formulas and rare languages. Once, he read him the first four lines of Dante’s La Divina Commedia in Italian, a language he could not understand, and he was able to recite it in a matter of seconds.

On the basis of the research’s findings, Luria diagnosed S. with a rare form of synesthesia, called ideasthesia.

Ideasthesia is a phenomenon in which letters, numbers, and other visual objects evoke a “perception”-like experience. Since humans are hardwired to memorize visual concepts more efficiently than letters or numbers, an individual with ideasthesia can memorize characters, numbers, and symbols after viewing them for a couple seconds

The theory of this phenomenon closely resembles the idea behind the Method of Loci (more on that later), a technique used by mnemonists to memorize many different chunks of information that would otherwise be difficult to memorize.

So what kind of visual perceptions did the Divine Comedy evoke?

The first line, Nel mezzo del cammin di nostra vita, he rendered into images this way: Nel, Nel’skaya, a ballerina; mezzo, she is together with (Russian vmeste) a man; del, there is a pack of Deli cigarettes near them; cammin, a fireplace (Russian kamin) is also close by; di, a hand is pointing toward a door (Russian dver); nos, a man has fallen and gotten his nose (Russian nos) pinched in a doorway (Russian tra); vita, the man steps over a child, a sign of life — vitalism; and so on, for 48 syllables.[3]

In 1968, after S.’s death, Luria published a book of his findings, The Mind of a Mnemonist. He wrote it for a non-scientific audience and I recommend it to anyone. The translated version can be easily found on the web with a quick Google search.

Case 2: The Girl with Eidetic Memory

Fast forward to the 1970s. A Harvard scientist named Charles Stromeyer III publishes a paper about a girl with an incredible ability. He gave her a sheet of paper with a pattern of 10,000 random dots, and the next day another random pattern with a different layout.

The girl was able to fuse the pattern in his mind and form a stereogram, which she saw as a three-dimensional image floating above the surface. A couple of days later, when questioned by the researcher, she could draw each pattern with astonishing accuracy.

The case study of Elizabeth – this is the name of the girl – was published in Nature. However, in a comical turn of events, the researcher later married the girl, and she was never tested again.

dot pattern photographic memory
A random dot pattern like the one given to Elizabeth

A couple of years later, in 1979, a researcher named John Merrit published the results of an eidetic memory test he had placed in magazines all over the country. After seeing Elizabeth results, he had hoped that someone might come forward and prove, once and for all, the existence of photographic memory. He figured that over 1 million people had tried the test. However, of the 30 people that were able to correctly figure it out, he went on to visit 15 of them, and nobody could repeat the experiment with the scientist looking over his/her shoulders.

So how was Elizabeth able to succeed in the test? Did she have some weird memory superpower?
Some say that the Elizabeth study was not real, but rather a silly prank between friends that got out of hand. nthomas from the Straight Dope forum explains it:[4]

When I was in a graduate seminar on the psychology of memory (about 16 years ago, at a major university) I was told by the professor, an expert in the field, that the “discovery” was, in fact, a hoax. As he told the story, “Elizabeth” was actually the girlfriend of the researcher, who had been talking to her about his interest in eidetic imagery. He had a reputation, however, for being rather gullible, and, for a joke, she, and a group of his other friends, cooked up a fake demonstration of her amazing eidetic powers. He was completely taken in, and became very excited at his amazing “discovery”. But before “Elizabeth” and her friends had the time (or maybe the heart) to let the victim in on the joke, things had got out of hand, and the discovery was already well known, and, before long, published.
The etiquette of scientific publication would make it difficult to get a story like this into the formal record, and, anyway, psychologists probably do not want it too widely known how easily they can be taken in. (Perhaps, also, people were reluctant to ruin the career of the poor, duped but not dishonest, researcher.)
[…]I got the impression from my professor that the hoax story was quite well known amongst memory researchers. Furthermore, my impression is that psychological opinion over whether eidetic imagery (as distinct from the ordinary, relatively unreliable, memory imagery, that nearly everyone experiences) really exists, is still much more divided than Cecil seems to believe. It may be the majority opinion that it is real, but a respectable minority of researchers have their doubts. The amazing abilities of “Elizabeth” do still occasionally get mentioned in the reputable psychological literature, however. Some serious scientists do seem to believe it. I myself am no longer sufficiently close to the “in group” of memory psychologists to have heard the hoax story again, or to check out how widely it is known or believed.

So there you have it: the only recorded case of a genuine photographic memory among ordinary human beings is, very likely, a hoax.

Kim Peek Super Memory
Kim Peek

That’s not to said that there aren’t folks with a really good memory. Kim Peek, the famous savant who was the inspiration behind Rain Man, could supposedly memorize each page of a 9,000+ page book, reading at a rate of 8 to 12 seconds per page (with each eye reading its own page). This has not been thoroughly tested, however.

The American actress and author Marilu Henner, on the other hand, can supposedly remember every day of his life. Again, this has not been tested in a clinical setting, and may just be a symptom of an obsessive-compulsive disorder.

Another savant, Stephen Wiltshire, has been called the “human camera” for his ability to draw objects around him several minutes (to hours) after having seen them for the first time. However, again, as precise he is, he takes liberties, so it is not clear if he truly has a “photographic” memory, but he’s the closest to it.

Stephen Wiltshire Eidetic Memory
Stephen Wiltshire

How to Develop Photographic Memory

Solomon, Kim, and Stephen are truly fascinating cases, but they are not normal guys – they have very rare abilities. So, can a normal human being develop photographic memory or the closest thing to it?

The answer is No. Photographic memory can’t be achieved, not even with nootropics. However, by taking nootropics and learning a few techniques, we can develop an exceptional memory. Let’s see how.

Memory: What is It, How to Improve it

There are several stages of memory formation: memory acquisition/encoding, working memory/short-term memory, long-term memory/consolidation, memory retrieval, and reconsolidation.

Five major pathways are essential for the formation, retrieval and reconsolidation of memory: dopamine, choline,AMPA, norepinephrine and adrenergic receptors, and neurotrophic factors (BDNF, GDNF, NGF).

  • Choline is essential for short-term memory and memory consolidation
  • Dopamine helps focus, motivation and general cognition[5]
  • Norepinephrine is a memory modulator[6] and it’s essential for memory retrieval[7]
  • AMPA improves synaptic plasticity and strengthen synapses
  • BDNF is important for long-term memory[8], learning, and synaptogenesis[9]

NGF is also important for neurons health and memory — but only in old subjects, as it actually impaired memory when given to young rats[10], so we’re not going to focus on it too much. Same for norepinephrine and adrenergic receptors, GDNF, Sigma, cAMP, PKA, CRE, CREBs and other minor neurotransmitters/neuromodulators.

References   [ + ]

Categories
Nootropics NSI-189 Recovery

NSI-189: A Nootropic Antidepressant That Promotes Neurogenesis

The use of antidepressant medications in America is a rapidly growing portion of the pharmaceutical industry. The number of people who take antidepressants has increased by almost 400% from 1990 through 2008.[1] In addition, eleven percent of Americans aged 12 years and older take some form of antidepressant medication.

Antidepressants have long been a troubled group of drugs in terms of side-effects, with even the most recent class of antidepressants (SSRIs) exhibiting potential side-effects like insomnia, sexual dysfunction, or even worsened depression. These troublesome side-effects have displayed a clear need for more effective treatment options.

Prozac capsules and packaging anti depression medication

Despite the apparent need for a more effective class of antidepressants, no new major milestones have occurred regarding antidepressants since 1987, the year fluoxetine (Prozac) was approved by the FDA.[2] Since the beginning of Prozac’s use to treat depression, SSRIs have dominated the area of medical treatment for depression. This era of depression treatment has been going on for about 29 years. However, some progress is being made in the development of new antidepressants. One of the newest experimental drugs for depression, NSI-189, also displays nootropic properties. Here we will be examining some of the claims surrounding the purported benefits of NSI-189.

Origins of NSI-189

NSI-189 is an experimental drug currently being developed and studied by Neuralstem Inc., a biotechnology company that commercially produces neural stem cells for therapy.[3] The research and development of NSI-189 began in the 1990s, during the years of Bill Clinton’s presidency.

The Clinton administration contracted Neuralstem to research the possibilities of creating a “super soldier,” one that was able to stay awake and alert for extended periods of time.[4] The researchers at Neuralstem recognized that a drug targeting the hippocampus could possibly alleviate the effects of sleep deprivation and exhaustion, and set out to find a drug that could induce neurogenesis. Neuralstem, finding their prospects to be promising, continued research in this vein even after the government program was canceled.

This preliminary research would eventually result in the drug NSI-189. Clinical research on NSI-189 has been in the works since 2011, and a phase 1b trial was completed in July of 2014.[5] Clinical phase 1 trials typically focus on finding the correct dosage range of the drug, which has been placed around 40 to 80 mg per day in the treatment of Major Depressive Disorder (MDD) and cognitive decline.

NSI-189 structure

Chemically speaking, NSI-189 is classified as a small-molecule benzylpiperazine-aminopyridine drug, making it structurally unique among other antidepressants. However, the drug has also seen increased interest in terms of its ability to stimulate nerve growth in the hippocampus.

According to the official Neuralstem, Inc. press release concerning the phase 1b trial, “[NSI-189] is a proprietary new chemical entity that stimulates new neuron growth in the hippocampus, a region of the brain believed to be implicated in MDD, as well as other diseases and conditions such as traumatic brain injury (TBI), Alzheimer’s disease, and post-traumatic stress disorder (PTSD).”[6]

The phase 1b trial of NSI-189 was “a randomized, double-blind, placebo-controlled, multiple-dose escalating trial evaluating the safety, tolerability, pharmacokinetics and pharmacodynamic effect of NSI-189 in the treatment of MDD.” Now that the trial has been completed, the results have been released, and they appear quite promising.

The study, which was conducted on 24 patients over the course of 28 days, found that NSI-189 administration reduced the symptoms of depression and cognitive decline significantly more than placebo. The drug was tolerated well by the subjects, and it “may also exhibit pro-cognitive properties associated with increases in prefrontal alpha coherence.” [7] [8]

Mechanism of Action

Selective serotonin reuptake inhibitors (SSRIs) attempt to treat depression by increasing levels of serotonin in the brain. This model of depression, known as the “monoamine hypothesis,” states that depression is caused by a shortage or imbalance of certain neurotransmitters in the depressed patient, mainly serotonin. However, this model has been quite drastically debunked in recent years.[9] Many researchers and psychiatrists now recognize that depression is far more complex than a simple chemical imbalance. New theories have emerged that recognize factors such as emotional trauma, environmental factors, glutamatergic dysfunction, and inflammation as potential causes of depression.

In short, depression is a complex web of interweaving causes and effects, both psychological and physiological. While scientists know from research that SSRIs and other antidepressants certainly have an effect in alleviating depression, the actual pharmacology behind the medications is far more unclear. Why do some respond to medication negatively? Why do some not respond at all? Because these questions are so intimately tied with genetic and biochemical factors, they are very difficult to address in a comprehensive manner.

These observations lead to two important points: First, depression is such a complex disorder that we don’t yet know the best way to treat it with medication. Second, SSRIs may be somewhat effective in alleviating depression, but we don’t completely understand why they work the way they do. Because the root causes of depression are still somewhat uncharted territory, exploration of new treatments that work differently than SSRIs is very important. By pioneering these treatments and observing their effects, the puzzle pieces that make up the full picture of depression can be pieced together into a comprehensive model.

NSI-189 vs Placebo Hippocampus
Topographs of average amplitude at 10-12 Hz showing increased high-frequency alpha in patients receiving NSI-189 at Day 28. Differences scores comparing conditions show most significant differences between total subjects receiving NSI-189 (left) vs. Placebo (right) in the left posterior temporal and parietal regions.

Some researchers, like those at Neuralstem, have noticed a correlation between reduced hippocampal volume and increased incidence of Major Depressive Disorder.[10] According to this theory, NSI-189 could potentially be a remedy to those suffering from depression by contributing to the growth of the patient’s hippocampus. Because the hippocampus is also so closely associated with memory, NSI-189 also has the potential to impact cognition.

This “hippocampal” model of depression is still in its infancy, and NSI-189 is one of the first drugs being researched that uses this specific form of treatment. Although it is known that NSI-189 increases hippocampal volume, the exact mechanism underlying this effect is still unsure. The results of the phase 1b trial even suggested that NSI-189s effect on hippocampal volume was not as drastic as that which was seen in animal studies.[11] Whether or not the increase of hippocampal volume persists after ceasing the medication remains to be determined. As the research and experimentation with NSI-189 continue, new research will shed light on this model for depression, and the medical community will be better able to understand the correlation between depression and hippocampal volume.

Purported Benefits

As mentioned above, the potential benefits of NSI-189 are:

    1. Improvement in behavioral responses associated with depression.[12]
    2. Reversal of hippocampal atrophy.[13]
    3. May enhance memory and cognition through increase neurogenesis, particularly in depressed subjects.
    4. Positive effects may persist after treatment ceases.[14]

    Subjective Experiences

    Because NSI-189 is still in its infancy as a clinical treatment for MDD and cognitive disorders, anecdotal information is important for those determining if they want to try NSI-189. This community poll conducted by /u/MisterYouAreSoDumb on /r/nootropics is useful for seeing various users’ experiences with NSI-189

    A Reddit user, Code_of_Error, relayed his experience with NSI-189 in a post on reddit[15]:

    I have been on NSI-189 Phosphate for three weeks now. I take 40mg orally once per day. I used to take it sublingually, but I learned that doing so may be counterproductive due to the possibility that too much is absorbed. Apparently, 40mg-80mg ORALLY was the sweet spot in clinical trials, so sublingual administration has too many unknowns to be worth it. Albeit, the freebase form is a different story.
    Anyway, I started exploring this substance in hopes of counteracting my chronic brain fog, slight depersonalization, anhedonia, general feelings of haziness, and slow cognition.
    Most notably, I have noticed an intensification of emotions, as well as pleasure. The first few days, I felt the inclination to tear up at every positive emotion. It felt ridiculous, but that has mostly leveled out. Although I am only three weeks in, I notice I am more inclined to look forward to plans. I am quicker to laugh and socialize.
    Prior to NSI-189, every emotion I experienced felt like nothing more than background noise. Now a days, all of my emotions feel more genuine, as if they’re at the forefront of my brain. When I experience anxiety, I no longer feel so dissociated from it. When I feel joy, it tends to last longer. Although these new perspectives are scary, I welcome the change. My default state of mind tends to be slightly perkier as well.
    I will admit that I am more guided by my emotions than I have been in years, and I am totally enabling it. I don’t recommend falling in love while on this substance. However, this substance is bringing me closer to my long-lost inner feelings. The effects aren’t perfect, and I still often feel that irritating haze (i.e., brain fog/dulled-out sensation/whatever ambiguous symptoms) to a degree, but I hope that my mental issues continue to improve as I stay on this. I’ve certainly made strides.
    Interestingly, I have noticed that I better able to “feel” the effects of nootropics while on this as well. Caffeine has a much more profound effect on me (comparable to when I first started using it), and the effects of tianeptine are as potent as ever. Again, I feel as if this speaks MORE to NSI-189’s ability to make you feel and less to its ability to reduce tolerance.
    Lastly, I would venture to say I am bit sharper mentally, and less likely to experience “cluttering” when I go to speak.
    Side effect wise, I only experience a mild fluttering (almost like a twitch) directly behind the inner half of my right eyebrow. Other than that, no headaches. I may have a mild reduction in sex drive, but nothing too troubling.
    Overall, I am looking forward to staying on this drug for a while. My mental symptoms are nowhere near gone, but I see enough benefits to keep going. Like many people who try an under-researched compound intended for depression, I feel as if I have little to lose.

    This is the experience of flare1028us, another reddit user:[16]

    Personally, I’ve found NSI-189 to be very useful. I’m taking 50mg freebase once daily in the morning. The acute effects for me are a gentle wave of calmness, improved long-term memory, and notably improved vision.
    The improved vision, as another redditor put it, is like my vision being “zoomed out” by 5%, like having a slightly larger field of view. Improved memory is the strong point of this substance. I find myself having vivid recollection of memories going back to my single digit ages. This has also allowed me to remember times when I encountered some of the same struggles I have to this day, and how I handled them – I feel better equipped to tackle them with better memory of what did and didn’t work in the past.
    As far as side effects, child-like emotions are coming on fairly strong. This is both good and bad. The good is that the sense of wonderment that we experience as children has come forth again, the bad being somewhat immature initial emotional responses. For example, jealousy – on a very childish level. It’s not debilitating, but it’s something to be mindful of.
    Speaking of being mindful, it has gotten a whole lot easier to practice mindfulness meditation and commit experiences I’ve gained through it to long(er) term memory.
    Interactions: Cannabis now gives me a mild headache, but if the high is balanced well (sometimes I’ll add some sublingual CBD), it is a very useful state of mind – for me it’s like being high with a better ability to remember the observations I make about my decisions and behavior that I may not come to so quickly in other states of mind. I tried taking piracetam once on NSI, and I’m never doing it again. Total dysphoria for most of the day from 3.5g piracetam in the morning. This stuff is supposed to reset piracetam tolerance, but I won’t be testing that until I’m off NSI-189 for a while.
    Tianeptine (sodium and sulfate) feels like it meshes really well with NSI-189, along with neurogenic peptides – took 200ug NA-Semax Amidate (sub-q) with NSI and went to yoga class (pretty intense class too). That was a level of control I would love to be able to gain every time I exercise in general.
    Hope this helps, I’m still waking up – I’ll answer questions if you have them

    Conclusion

    If NSI-189 proves to be an effective treatment for Major Depressive Disorder, it could have a potentially large impact on the direction of depression medication in the upcoming years. The long-standing dominance of SSRI drugs in the treatment of depression has left many wondering just how much longer it will be before the next major breakthrough occurs in depression treatment.

    A novel drug like NSI-189 could be the answer, and the studies concerning NSI-189 also give us a useful glimpse into the correlations between depression, hippocampal volume, and cognition. As we move further into the 21st century, the scientific community will undoubtedly continue to map more accurately the territory that is the human mind.

    References   [ + ]

    Categories
    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   [ + ]