Daily Archives: July 7, 2016

Posted by Steven Novella on May 20, 2015

Nootropics are an emerging class of drugs that are designed to enhance cognitive function. They are part of a broader category of drugs known as performance and image enhancing drugs (PIED) which are used for enhancement of memory and cognition, sexual performance, athletic performance or musculature (also called lifestyle drugs).

It will probably come as no surprise to regular readers of SBM that nootropics and PIED are being abused and hyped without adequate evidence. One of the primary problems is that they are sold as supplements or as drugs, often over the internet without adequate regulation. One simple fix is to properly classify these drugs as drugs, and to properly regulate them as drugs.

Many of the cognition-enhancing supplements on the market make all the usual claims about natural enhancement meanwhile they predictably contain just vitamins, herbs which have not been shown effective, perhaps nootropics (see below), and often a stimulant, like caffeine. The only drug in the mix which is likely to have a noticeable effect by the user is the stimulant.

The risk of overuse of stimulants in supplements is well known.

Meanwhile, what does the science say about the safety and effectiveness of specific nootropics for specific indications? In short, sufficient high-quality studies to make definitive determinations are lacking. For many, however, there is some preliminary and pre-clinical data.

The concept behind nootropics is to target some metabolic or nutritional aspect of brain function, especially a function involved with memory or attention, and then to provide a nutritional precursor to that metabolic pathway, or a drug that enhances the activity of a neurotransmitter, enzyme, or other metabolic factor.

This is not an unreasonable line of research, but tweaking metabolic pathways is not a simple business, and our ability to extrapolate from the petri dish to animals and finally to net clinical effects in humans is very limited. No matter how promising a treatment looks in theory, we need clinical data to see if it has a measurable and lasting clinical effect.

The primary plausibility problem with the PIED category of drugs is that they are further extrapolating from data in disease states to the enhancement of otherwise healthy function. Just because a drug may enhance memory function in someone with Alzheimers disease, that does not mean it will enhance memory function to supernormal in a healthy individual.

It is true and likely relevant that the brain is a very metabolically hungry organ. Optimal brain function depends upon most metabolic and physiological parameters functioning well. For this reason the brain is often the canary-in-a-coalmine of biological function the first thing to go when something is off. Sick hospital patients, for example, are often sleepy or confused because their bodies are simply under stress, or their metabolic parameters are off. It can often be challenging to figure out exactly what is making a patient confused, because so many things can affect brain function.

Further, in everyday healthy life our brain function can be off simply from having insufficient sleep, not eating well, being depressed, or being physically or mentally exhausted.

Given our brains sensitivity it does make superficial sense that giving it a specific metabolic boost might help cognitive function. This is essentially what stimulants do. It still needs to be determined, however, that a specific metabolic tweak will have the desired effect. One potential problem with predicting whether a specific intervention will help is determining if that metabolic factor is the limiting factor in brain function.

Enhancing acetycholine (the primary neurotransmitter involved in memory formation) may enhance memory, but what if there is already plenty of acetylcholine and the limiting factor in memory function is something else entirely? This is probably why we cannot extrapolate from a disease state to a healthy state the limiting factors on function are likely different.

Therefore, from a plausibility standpoint, the idea of nootropics is possible, but very complicated, and we cannot make confident predictions from pre-clinical data alone or extrapolate from one condition to another. We need high-quality clinical studies for each specific clinical claim.

One of the most popular nootropics is piracetam. This is actually one of a large and growing class of drugs with many neurological indications, including seizure control and treatment of anxiety and depression. Piracetam has been studied specifically for memory and cognitive enhancement in dementia or cognitive impairment.

A Cochrane systematic review (last updated in 2012) found:

At this stage the evidence available from the published literature does not support the use of piracetam in the treatment of people with dementia or cognitive impairment. Although effects were found on global impression of change, no benefit was shown by any of the more specific measures.

They concluded that the data supports further research, but not current clinical claims or use.

In healthy individuals there are only a couple small studies, and they do not show any significant benefit. Therefore, even though piracetam is a popular smart drug the evidence for any significant effect is lacking, especially in healthy individuals.

Another highly popular cognitive enhancer is modafinil. This is a stimulant drug used for narcolepsy, ADHD, and cognitive fatigue resulting from neurological disease or injury. It is a controlled prescription drug, but has still managed to become highly popular as a cognitive enhancer, especially among students.

A recent study, however, highlights the difficulty in extrapolating from disease to healthy states. The researchers compared test performance on healthy subjects taking modafinil vs placebo. They found that the responses were delayed from subjects taking modafinil, but were not more accurate. In hindsight, this result makes sense.

As a stimulant modafinil increases brain function, including frontal lobe executive function. When performing a cognitive task there is often a tradeoff between speed and complexity of processing. Executive function sacrifices speed for complex higher cognitive function. If you have impaired executive function, this tradeoff is worth it. Modafinil can shift the balance back towards a more optimal state.

In the healthy individual, however, you are shifting the balance away from an optimal state, slowing things down without any further gains in accuracy. Therefore modafinil can be a net gain in individuals with ADHD, but a net loss in healthy individuals, and that is what the preliminary clinical data shows.

There are other nootropics but with a similar story basic science research which is used for marketing hype, but does not establish that the drugs (often sold as supplements) actually work.

Nootropics are an interesting and potentially very useful class of drugs which deserve further research. Their greatest potential is likely in various states of neurological disease or injury. Their use as smart pills, however, is dubious from a plausibility standpoint and lacks sufficient evidence.

Many smart pill products on the market cheat by including a regular stimulant, like caffeine. The effects of stimulants on healthy individuals is interesting while they create the subjective experience of being more alert and higher performance,
it is unclear if they actually improve performance, and in fact they may even decrease performance. Even if they do work, their effects typically develop tolerance quickly. Daily use of caffeine, for example, develops tolerance within three weeks, after which regular users are just staving off caffeine withdrawal and experience an overall net negative effect on their alertness.

Stimulant use is therefore potentially useful for alertness in the short term or for intermittent use, but it is unclear if it has a positive effect on cognitive performance. They are good for creating the illusion of cognitive enhancement, however.

Current non-stimulant nootropics are likely useless in healthy individuals.

If you are otherwise healthy and want to optimize your cognitive function, there are some things you can do that are likely to have a dramatically greater benefit than any smart pills on the market:

Original post:

The PIED Piper of Nootropics Science-Based Medicine

Nootropics are a class of cognitive enhancing supplements that are used to improve concentration and boost memory power. Nootropics are often used to increase attention spans, help individuals focus and as studying aids.

You will occasionally see Nootropics referred to as smart drugs as they are associated with increased intelligence, motivation, and mental energy.

However, unlike smart drugs which can often cause negative side effects with long-term use, nootropics must be safe, neuroprotective and pose a very low risk of side effects when used appropriate.

Many nootropics share similar mechanisms of action by enhancing increased communication between neurons, helping to balance neurotransmitter levels or by promoting brain cell health. They may help improve energy metabolism in your neurons, support neuroplasticity, or even stimulate the growth of new neurons and synapses.

What are Nootropics and how do they really work? Which are the best nootropics to use if you are a new user?

This article will provide a basic guide to nootropics and give you an overview of how to use these supplements to enhance your mental capabilities.

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Nootropics are broadly any type of neuro enhancing drug or natural supplement with very low prevalence of side effects. The actual definition of what makes a supplement a nootropic is somewhat of a loose concept.

The original description comes from Belgian pharmacologists S. Giurgea and V. Skondia who invented the first Nootropic a compound known as Piracetam in 1963.

They established the classification of Nootropics to refer to cognitive boosting substances with extremely low toxicity that can be taken for long-term use.

This highlights the fact that Piracetam and other Nootropics are able to improve brain functions without any of the negative side effects associated with brain stimulants.

Piracetam (known also by the name Nootropil) is one of the best known Nootropics and makes up part of the Racetam family along with Aniracetam, Phenylpiracetam, Pramiracetam, Oxiracetam, Nefiracetam, Coluracetam and Nebracetam. These are all synthetic compounds that have been created in the lab, but there are also a number of effective herbal and natural nootropic supplements.

For example, fish oil, grape seed extract, bacopa monnieri, yerba mate and even licorice are all natural nootropics. (Click here to see a full Nootropics List of supplements that are available.) You will often find these supplements combined together in a Nootropic Stack to further enhance their effectiveness.

What exactly do Nootropics do? Like smart drugs, Nootropics will not instantaneously give you a higher IQ or a better intellect. But they may boost your brain functions by increasing the production and signalling of various neurotransmitters.

Your brain is essentially a network of billions of neurons connected by synapses. These neurons communicate and work together through chemicals known as neurotransmitters. When neurotransmitters are able to send signals more efficiently, you experience improved concentration, better memory, mood elevation, increased processing ability for mental work, and longer attention spans.

With continued supplementation of certain nootropics, you can improve the synaptic plasticity of neurons, causing long lasting improvement to the health and functioning of your brain.

Other nootropics show effects of vasodilation which means they increase the blood flow to your brain. This supplies your brain with more oxygen, nutrients, and glucose the primary energy source used by the brain during long periods of focus.

The brain requires an immense amount of energy to perform its function, sustain consciousness and to pay attention to your external environment. Even though the brain is only 2% of your bodyweight, it constitutes 20% of your energy expenditure.

Performing mental exercises, learning new things, concentrating on your work and staying alert during the day all burn a lot of energy. By raising bloodflow and oxygenation, you can immediately experience greater capacity for memory and focus.

Supplements that can improve the energy supply to your brain cells (like Acetyl L-Carnitine, Caffeine, Creatine, Ginkgo Biloba, or Vinpocetine) can all enhance focus, mental energy and clarity. This type of nootropic is especially favored among students for studying as their effects are felt immediately.

Nootropics can also show signs of neuro-preservation and neuro-protection. These compounds directly affect the levels of brain chemicals associated with slowing down the aging process. Some nootropics could in an increase in the production of Nerve Growth Factor and Brain-Derived Neurotrophic Factor to stimulate the growth of neurons and neurites while slowing down the rate of damage as well.

Over time, this could potentially slow down signs of aging like loss of memory and even counter the development of disorders like Alzheimers disease.

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Below is a list of some of the most popular and best nootropics that are available today. Each supplement with have its own unique mechanism of action that is distinct from other nootropics.

You can either select the supplement that best matches your needs or goals, or you can combine several nootropic compounds together in what is known as a stack. A stack simply involves any pairing of substances that enhance and complement each other when taken simultaneously.

Most of the pre-packaged brain boosters available will stack together several different herbal or synthetic nootropics like those listed below, but you can also buy the bulk raw powder and mix your own capsules to design a formula that is right for you.

Racetam: As mentioned previously, racetams are a class of nootropics including the widely used Piracetam, Aniracetam, Pramiracetam, and Oxiracetam.

They all share a similar chemical structure with a Pyrrolidone nucleus. Racetams work by dramatically increasing levels of neurotransmitters and other chemicals required for proper brain function like glutamate and acetylcholine.

They have been tested to improve cognitive function, prevent damage to brain cells from alcohol consumption and other factors, and to increase the communication between the two hemispheres of the brain.

Choline: Choline is frequently found in a nootropic stack with racetams like Piracetam and Aniracetam. Taking choline supplements will cause greater production of the acetylcholine neurotransmitter in the brain.

Since Racetams result in increased uptake and demand for acetylcholine, stacking choline with this nootropic will further enhance your results. Studies have shown that choline supplementation can improve performance on memory tests as well as social behavior. Choline also plays a key role in the production of phospholipids that are incorporated into brain cell membranes.

Pyritinol: Pyritinol has anti-oxidant effects for supporting the long-term health of the brain. But its primary benefit is aiding glucose uptake for periods of extended mental strain. If you are studying or working for a long period of time,
your brain will start to diminish its glucose (sugar) stores which are the primary way that the brain derives its energy.

Psychological studies have shown that continuing to refuel your brain with glucose will improve concentration and cognitive ability during extended periods of mental work. Supplementing Pyritinol aids further in glucose uptake so that your mental energy levels are higher.

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Vinpocetine: Vinpocetine has been shown as one of the most effective nootropics for improving brain blood flow. After taking Vinpocetine, the blood vessels dilate and are able to circulate more blood to the brain.

This causes a number of immediately noticeable effects such as concentration boosting, better mental agility, and higher energy levels and motivation.

There are many more nootropics available out there and different ones can assist you in improving your brain in various different ways. For a full Nootropics List, keep reading this website and check out our many Nootropic reviews.

Which nootropic supplement you pick is largely a matter of personal preference. You might want to check out the pre-made nootropic products like Alpha Brain or you might prefer to design your own stack by purchasing ingredients like Piracetam powder.

The health and capabilities of your brain are one of the most important determining factors in a happy and successful life, so whatever you pick you can rest assured that you are making a smart investment.

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Continue reading here:

What Are Nootropics? A Guide to Nootropic Supplements