Categories
Nootropics

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

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

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

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

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

Recommended Nootropic Suppliers

* Modafinil and Armodafinil supplier

 

Categories
Videos

DOCS: Superhuman – Geniuses (Video)

Where does genius come from? Is it the byproduct of tireless work, developmental happenstance or divine inspiration? The documentary Superhuman: Genius explores this phenomenon by portraying the lives and accomplishments of five individuals for whom cerebral superiority is second nature.

The film opens with Akiane Kramarik, a 13-year old girl from Idaho who has painted with the detail and sophistication of a grand master since the age of four. She interprets her passion for painting as a literal calling from God, in spite of a complete lack of religious upbringing in her household. In nine short years, she’s amassed an astonishingly accomplished collection of over 100 original paintings, and has published her works in numerous volumes. Her artistic intuition is guided by a force she herself does not fully understand.

Ben Pridmore is first shown browsing through the grocery store aisles for product serial numbers, and later reciting them with perfect recall to the check-out clerk. His memorization of long and complex numbered sequences is an amazement to spectators, and has earned him the top prize at three World Memory Championships. Yet his achievements have not translated into monetary success, and he remains an unemployed accountant.

The 1988 film Rain Man is perhaps the most popular of pop culture references to the enigmatic nature of genius. Superhuman: Genius traveled to Utah to meet Kim Peek (now deceased), the real-life inspiration for that Oscar-winning film. Diagnosed with savant syndrome at an early age, and told he would never be able to walk, communicate or learn as a result of his disorder, Kim has since gained notoriety for possessing the sharpest memory in recorded history, absorbing nearly 98% of everything he read.

The film also spotlights Ariel Lanyi, a 10-year old pianist and composer from Israel who was fed classical music from the moment of his birth, and Ainan Cawley, a wunderkind in the world of science who passed O Level Chemistry at the age of seven.

Each of their stories certainly inspire awe, but they also bring forth a series of perplexing questions about the human condition. Is the capacity for genius merely an untapped potential in all of us?

Categories
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 Videos

Donate to the International Longevity Alliance’s Major Mouse Testing Program

Donate to the International Longevity Alliance’s Major Mouse Testing Program

According to modern science aging is the accumulation of damage that the body cannot completely eliminate, due to the imperfections of its protection and repair systems. The good news is that the processes that constitute aging are amenable to medical intervention. We can slow down or even reverse some aspects of aging through the application of different therapies, which prevent or block some of these processes.

One of these processes of aging is cell senescence.

Senescent cells normally self destruct via a process called apoptosis, but unfortunately not all of them do. These “death resistant” senescent cells accumulate in the body with age and secrete toxic signals. This causes inflammation and damage to organs and tissues, increasing risks for cancer and other diseases of old age. This is why these cells are often called “good citizens but bad neighbors”. They remain partially functional, but their presence does more harm than good.

A new class of drugs known as Senolytics have recently demonstrated the ability to remove senescent cells to improve health. However, the potential of senolytics to increase health and lifespan beyond current maximums remains unknown. This is what we at Major Mouse Testing Program want to investigate – with your help!

Why is this study of particular interest?
It was discovered that senescent cells have increased expression of pro-survival genes, consistent with their resistance to natural cell death – apoptosis. Drugs targeting these pro-survival factors selectively killed senescent cells and improved health. Two such drugs were Dasatinib and Quercetin which were both able to remove senescent cells, albeit each in different tissue types. Even more excitingly it was discovered that a combination of the two drugs formed a synergy that was significantly more effective at removing some senescent cell types.

Venetoclax has also recently been discovered to be senolytic in nature and is a therapy we wish to explore as part of our combination testing. In cancer therapy Venetoclax has shown to work well with Dasatinib so we are interested in seeing if this can be applied to clearing senescent cells too.

Recent studies have shown removing senescent cells mitigates age related decline and improves healthy lifespan. Additional studies have shown that clearance of senescent cells is beneficial for cardiovascular health and lowers high cholesterol levels in the blood. This strongly suggests that Senolytics may be a viable therapeutic approach to combat aging.

In our study we have opted to treat already naturally aged mice. These mice will be 16-18 months old (equivalent to a human of approximately 60 years old). This has two advantages: we speed up research, and also demonstrate the feasibility of translating Senolytics to already middle aged or older humans.

Dasatinib and Venetoclax are already approved for use in humans to treat specific diseases, and Quercetin is a readily available supplement, so the application of these drugs or improved versions based upon them to prevent and postpone age-related damage to health could be developed relatively quickly.

Senolytics and Stem Cells
So far senolytics have only been shown to reduce the number of senescent somatic cells, but what effect do they have on stem cells? This has not been closely studied, and is a question we intend to fully answer in addition to the implications this presents for lifespan.

It is entirely possible that Senolytics taken alone may not extend maximum lifespan, but rather healthspan. Even if this is the case, it is no reason to be discouraged. What we learn in this first phase, paves the way for our next step – combining Senolytics with Stem Cell Therapy to encourage tissue regeneration.

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
Videos

How to Study Effectively: 8 Advanced Tips (Video)

These study strategies go beyond the basics – memorization techniques, methods of fighting procrastination by hacking akrasia, a way to win the respect of your professors, and more.

  • 0:55 – #1 Corson Technique
  • 2:30 – #2 Spaced Repetition
  • 4:09 – #3 Method of Loci
  • 5:50 – #4 Akrasia
  • 7:35 – #5 Improve Pomodoro Technique
  • 9:20 – #6 Focused and Diffused thinking
  • 10:50 – #7 Gauging
  • 11:49 – #8 Start Problem Sets Alone
Categories
Adrafinil Armodafinil Modafinil

Modafinil vs Adrafinil vs Armodafinil: Which One Is Better?

For individuals who fall asleep on the job or have difficulty focusing in class, finding an effective treatment regimen can be truly life-changing. There are different medications available, yet often they require a prescription from a medical professional. Finding a sympathetic doctor can prove difficult and costly, not to mention time-consuming. That is why purchasing nootropics online may be an effective way of dealing with it.

Modafinil is a drug designed to help with these conditions, and while it traditionally requires a prescription in the United States, it is possible to buy Modafinil online. There are three compounds in particular that are highly rated in the nootropics community for their ability to enhance wakefulness and focus. Let’s take a look at them.

Overview

  1. Modafinil
  2. Adrafinil
  3. Armodafinil

These are three drugs of the -afinils family, and are designed to help battle sleepiness. Having a limited amount of sleep can negatively impact cognition, and may cause a person to struggle at work or school. This not only reduces a person’s ability to function properly but, particularly in manual labour, could even put them in danger. In order to avoid this sort of situation, we can use an eugeroic, a wakefulness-promoting agent.

Modafinil, Adrafinil, and Armodafinil are the three most popular and researched eugeroics.

What is Modafinil?

buy modafinil onlineSome refer to Modafinil as a “smart drug” due to its ability to help people improve their focus. However, in clinical practice it is only used to treat narcolepsy and other sleep disorders, and any other use is considered off-label.

Modafinil is the active ingredient in Provigil, which was first sold back in 1998 as an evolution of Adrafinil, its “little cousin”. Some have compared Modafinil to the prescription stimulant Adderall, only without the jittery feeling many people experience when taking the medication. Instead, Modafinil is designed to simply boost response and reaction time while honing in on an individual’s ability to focus.

What is Adrafinil?

Olmifon, brand name of AdrafinilAdrafinil is another narcolepsy based medication often prescribed to help improve focus and to prevent falling asleep. It was originally sold under several brands Olmifon but it is not sold anymore and it can be bought over the counter. It is derived from Modafinil and metabolizes into the drug within the liver, but it is much less effective , and only a minority of individuals report positive effects from it.

Adrafinil was discontinued in the early 2000s after several cases of elevated liver enzymes and hepatotoxicity appeared. Modafinil and Armodafinil, on the other hand, are totally liver-safe, as they don’t need to be intensively metabolized like Adrafinil.

Therefore, we strongly advise not to use Adrafinil.

What is Armodafinil?

A third narcolepsy medication prescribed in the United States and the rest of the world, it’s the dextro (right) enantiomer, the one that gives the famous positive effect of Modafinil. It is designed to be stronger while having fewer side effects. In short, Armodafinil is Modafinil’s “big brother”.

This is a medication generally used by people who are simply unable to remain awake for longer than a few hours. Due to the potency, it is often less prescribed than the other two offerings. That being said, some people prefer Armodafinil as it feels “cleaner” than Modafinil.

Differences and similarities

All three compounds are designed to help improve someone’s focus, while allowing them to stay awake longer. These drugs are not just used by students, but also people who work do long shifts, looking for a pick-me-up. The medication is often used by truck drivers who need to stay awake and alert for long hours of the day. Helicopter pilots, and those who work emergency shifts in hospitals are also frequent users of Modafinil/Armodafinil.

While these three -afinils are used for the same kinds of conditions, the drugs are different in their own peculiar way. First of all, each drug delivers a different dosage and a slightly different kind of effect. Adrafinil is the lightest of the three as far as effects, it requires a higher dose, it’s very liver-intensive and doesn’t work for everybody. Someone who may not respond to general caffeine may be best suited for this kind of a medication, but, in general, it’s better to avoid taking it completely and go with Modafinil instead.

Modafinil is the most commonly used of the three. It is prescribed for narcolepsy, shift work sleep disorder, and chronic fatigue. That said, it is also frequently prescribed off-label for other conditions.

Lastly, there is Armodafinil. This is the strongest of the three, and it’s also more expensive. Due to this, many doctors prefer prescribing Modafinil and adjust the dosage accordingly. However, for those people who not only struggle with staying awake on the job but actually fall asleep multiple times throughout the week (if not multiple times during the day) this is the way to go. It does have the same half-life as Modafinil, so it does not last longer, but it delivers a stronger and cleaner effect.

Dosage and Variations

As with any kind of medication, it is important to understand the correct dosage. As college students will likely purchase the drugs through a Modafinil online pharmacy, they are not actually receiving a Doctor’s prescription, and they have to research the proper dosage themselves.

150 mg is usually the recommended dosage for Modafinil and Armodafinil. It should be taken once a day at roughly the same time of the day (should be at least an hour before work starts).

Now, while 100 mg is the recommended dosage, it is highly recommended to start off with a smaller dosage initially. It can take the body a bit of time to become accustomed to the drug within the system. Starting out with an initial dosage of 75 mg and increasing from there allows the body to become a bit more acquainted to the medication. Plus, this way it is possible for who’s taking the drug to determine what works for them and whether or not they need to take the full dose.

Adrafinil, the lighter of the three medications, typically recommends anywhere from 200 to 400 mg a day. Again, it is extremely liver-intensive, so it should only be user as a last-resort, or, — if you just can’t live without it — take liver protective supplements like Milk Thistle or N-Acetylcysteine (NAC).

Ideally, these are not everyday drugs. It is important to not have the body become accustomed to the drug. The body can form a dependency on the medications, which can cause functional problems when not taking them. Due to this, it is recommended to use eugeroics no more than three-four times per week. While the addictive potential of -afinils is very low (nowhere near amphetamine-based stimulants), the drugs do stimulate the production of Dopamine in the brain, and anything that stimulates those receptors possesses an intrinsic addiction potential.

Conclusion

For anyone who is struggling to remain awake, or it’s not able to focus when they need to, a drug like Modafinil can be thoroughly life-changing. Getting a prescription for one of these drugs may be difficult since some doctors are not interested in helping their patients if they do not qualify for a medical condition. Buying one of the three drugs from an online retail pharmacy not only reduced the amount of time away from work but saves money, all while boosting cognition and the ability to focus while using the medication.