Nootropics - Enciclopedia

Note: nootropic supplements can be found in the online smartshop.

Nootropics are herbs, amino acids or drugs that improve cognitive functions without harmful side effects. Substances such as amphetamines are not nootropics. Though it does increase your reaction speed and enhance concentration, you can’t use it daily without damaging your health.

The term nootropic is derived from two Greek words: ‘nous’, meaning intellect and ‘trepein’, meaning to turn. Nootropics are also known as smart drugs, neuro enhancers or memory enhancers. The name smart drugs also applies to a substance with a stimulating, sedating or psychedelic effect that are not controlled substances.

These substances can be sold in shops, which are referred to as smartshops. Most products sold in a smartshop do not enhance the cognition. To prevent confusion, this article will refer only to nootropics.

History of nootropics

Since the dawn of civilization, people have used herbs to enhance their cognitive abilities. Thousands of years ago, the Chinese prescribed ginkgo biloba and huperzine A to reduce forgetfulness and increase mental focus.[1]

In India, bacopa has been used for centuries to improve brain functions. This plant stimulates the blood flow to the brain and helps maintain a healthy mind. [2]. There are tons of similar historical examples of people using nootropic herbs.

The Romanian doctor Corneliu Giurgea first introduced the phrase nootropic.

In 1964, one of the first pharmaceutical nootropics was developed. It was called piracetam. It was originally intended to alleviate dizziness and travel fatigue. A decade later, piracetam was tested to see if it could also improve the memory, which it did. [3]

Piracetam is still used, but there are now many other synthetic substances designed to improve cognitive functions.

Legislation

Herbs and amino acids with a nootropic effect are, generally speaking, legal. In the Netherlands, a new law came into effect in December 2012 surrounding health claims. Only claims that have been proven with so-called double blind placebo studies are allowed to be listed on the package or marketing material.

An appointed council decides which claims are allowed on product packaging.

Since double-blind placebo studies are very expensive, it’s rare that these are performed to prove the effect of a herb. The enormous investment required can only be recuperated if the study leads to a medical patent. Herbs cannot have a patent on them and are not as thoroughly researched as a result.

However, there are other types of scientific research that demonstrate the efficacy of certain herbs. In addition, thousands of years of experience with a particular agent can also provide valuable information. However, this information should not be shared.

However, there are other types of scientific research that demonstrate the efficacy of these herbs. Thousands of years of usage experience with a particular substance can also provide valuable information. However, this information is not allowed according to the health claim law.

This makes it tricky to sell herbal nootropics. If you can’t fully indicate what use a product has, it’s, after all, a hard sell. It’s not illegal to provide specific advice, as long as this is not linked to one product. This means the customer has to find more extensive product information elsewhere. An unfortunate situation which sometimes affects Azarius as well.

Most chemical nootropics are listed as medicines. Even though these products don’t have dangerous side effects, they’re not allowed to be sold without a prescription.

Types of nootropics

Herbal extracts

There are actually a fairly large amount of plants and herbs with a nootropic effect. Herbs are often less potent than synthetic drugs but are safer to use and easier to obtain.

The mechanisms of plant-based nootropics are very diverse. For example, some extracts will improve blood flow in the brains; others may restore nerve damage or alter the balance of neurotransmitters in the head. It’s possible to combine different nootropic herbs to increase the effects.

The four most famous natural nootropics are:

• Ginkgo (Ginkgo biloba) has been known for centuries to have a beneficial effect on the mind. Scientific research has shown that this herb increases the cognitive and social abilities of dementia patients. [4]

• Brahmi (Bacopa monniera) ensures the enzyme that degrades acetylcholine is inhibited. This leads to an increase of the acetylcholine levels in the brains, which is beneficial because this substance is necessary for the good functioning of the brain.

• Huperzine A is a nerve protector. Furthermore, it inhibits the breakdown of acetylcholine, like bacopa, and has been found to have a beneficial effect on Alzheimer's patients. [2]

• Vinpocetine is a derivative of vincamine. This substance is originally found in the periwinkle herb. A placebo-controlled study has shown that vinpocetine enhanced memory in women.

Racetams

Piracetam was the first ever pharmaceutical nootropic and belongs to the racetams category. About twenty more racetams were developed, the most notable being aniracetam, oxiracetam and pramiracetam. All racetams operate in the same way; by stimulating specific receptors in the brain to release acetylcholine.[6]

As explained before, the brain needs the neurotransmitter acetylcholine to function properly. Some racetams also stimulate the glutamate receptor. Glutamate is an important neurotransmitter, especially when it comes to the quality of memory and the learning capacity. Some racetams thus have several effects.

A neurotransmitter is a substance that’s released at the end of a nerve to connect to the start of an adjacent nerve. It crosses a narrow gap as it were, also called a synapse. This is how a neurotransmitter transmits a message from the one nerve to the next. If you don’t have enough neurotransmitters, your brain is not functioning optimally.

Choline

Choline is often used together along with racetams, so as to enhance the effects of the pharmaceutical. [7] Racetams stimulates certain receptors, converting choline to acetylcholine. When more choline is present in the brain, more acetylcholine can be formed. Therefore, choline synergizes with racetams. In addition to choline, other acetylcholine intermediates are used in combination with racetams as well, such as acetyl-L-carnitine.

Ampakines

Ampakines are relatively new medicines with the strongest nootropic effects. These substances seem to be 1000 times more potent than piracetam. Two examples of ampakines are Sunifiram and Unifram.

They stimulate the AMPA and NMDA receptors, which in turn causes the glutamate levels in the brain to increase. They also increase the acetylcholine levels. [8] Therefore, ampakines have a positive effect on the attention span and alertness. Unlike amphetamine-like substances, such as Ritalin, there are no side effects such as restlessness, insomnia and anxiety. Note that unfortunately not enough research has been done to say anything about the long-term effects.

Vitamine B derivates

A small number of synthetic nootropics are derived from class B vitamins. Sulbutiamine is an example of a vitamin B1 derivative. This substance also ensures the release of more acetylcholine. Scientific research shows that supplementation of Sulbutiamine improves memory and increases alertness. Research on rats has shown that they can learn a task quicker if given this drug. [9]

Peptides

A peptide is a protein compound. There are various types of nootropic peptides available. By far the most famous is noopept (N-phenylacetyl-L-prolylglycine ethyl ester). This drug is derived from racetams. Its powerful effect is mainly attributed to the fact that it’s a peptide, which allows it to easily cross the blood-brain barrier. A low dose can have the same powerful effect as racetams. Noopept mainly stimulates the AMPA-receptor, which is responsible for the release of glutamate. [10]

Amino acids

The amino acid acetyl-L-carnitine is structurally very similar to L-carnitine, however L-carnitine has a more physical effect. It’s needed to release energy in the cells. Acetyl-L-carnitine on the hand can easily pass the blood-brain barrier en stimulates the brain’s production of acetylcholine, which means it works primarily on a psychological level. [11]

Other medicines

In addition to racetams derivatives, there are also other medicines that improve cognitive functioning. Again, to call it a nootropic, there should be no side effects. The drug Adderall does improve cognitive abilities but is also a stimulant. The same applies to Ritalin, a substance closely related to amphetamines that’s used to improved concentration in ADHD patients.

However, there are some drugs that don’t have a stimulating effect but do increase concentration. Modafinil one such drug. We don’t know exactly how it works, but it appears to improve the attention span of people who have ADHD. Additionally, it supports a good night’s rest and may help cocaine addicts get clean. [12]

Medical applications

Because nootropics improve memory and enhance cognitive abilities, it makes sense that these substances are primarily researched in relation to dementia patients. To determine whether or not dementia patients benefit from such substances, it’s necessary to perform a double-blind placebo study. Looking at the Pubmed database and we can draw the following conclusions:

• It’s been scientifically proven that dementia patients benefit from ginkgo biloba extract. [13]

• Other herbs listed in this article were not investigated as thoroughly, so we can’t say anything about their effects on dementia patients.

• Piracetam was part of a proper study and it appears it has no positive effect whatsoever on those suffering from dementia.[14]

• The use of acetyl-L-carnitine combined with other supplements seems to have no positive effect on Alzheimer patients. [15]

• Sulbutiamine was studied in a double-blind placebo-controlled trial and found to enhance certain cognitive functions in Alzheimer patients.[16]

These are hopeful results for dementia patients. Unfortunately, there are only a limited amount of trails on humans and instead quite a few on mice. For a better treatment of dementia, more research is required.

Combinations

Some people claim that taking noopept a few days before a psychedelic trip results in stronger visuals. For obvious reason, no scientific evidence of this exists, but there also no indications that this combination might be harmful.

What’s more, certain nootropics may work in synergy. The combination of piracetam with choline is very well known, but ginkgo biloba can also be combined with Bacopa monniera or huperzine A. They will increase each other’s effects because they function in different ways. They can be used at the same time without harm.

Side effects

We’ve established that nootropics are substances without severe side effects, but it’s possible to experience some light side effects after taking a nootropic drug. This includes mild nausea, vertigo and increased appetite. These side effects are never potent enough to endanger one’s health.

Contraindications

There are a number of circumstances which prohibit the use of nootropics. An overview per nootropic type:

Racetams should not be used if suffering from Huntington’s disease. Ticks (movement disorders) and psychic symptoms can become worse.

Choline is best avoided if suffering from manic depression, as it makes the periods of depression more severe.

Sulbutiamine (vitamin B1 derivative) should not be used if suffering from a bipolar disorder.

Amkanines have not been thoroughly researched and we can’t provide any information on contraindications. It’s advised to opt for something that has been proved to be safe.

Noopept is not an official medicine which means there’s little to no information on possible contraindications. It seems best not to use it when suffering from a bipolar disorder.

References

• Ginkgo biloba extract protects brain neurons against oxidative stress induced by hydrogen peroxide, Y Oyama, L Chikahisa, T Ueha, K Kanemaru, K Noda - Brain research, 1996 – Elsevier

• The chronic effects of an extract of Bacopa monniera (Brahmi) on cognitive function in healthy human subjects, C Stough, J Lloyd, J Clarke, L Downey, C Hutchison 2001 – Springer

• The nootropic concept and its prospective implications CE Giurgea - Drug Development Research, 1982 - Wiley Online Library

• A placebo-controlled, double-blind, randomized trial of an extract of Ginkgo biloba for dementia PL Le Bars, MM Katz, N Berman, TM Itil… - Jama, 1997 - jama.jamanetwork.com

• Psychopharmacological effects of vinpocetine in normal healthy volunteers Z Subhan, I Hindmarch - European journal of clinical pharmacology, 1985 – Springer

• Interactions between oxiracetam, aniracetam and scopolamine on behaviour and brainacetylcholine G Spignoli, G Pepeu - Pharmacology Biochemistry and Behavior, 1987 – Elsevier

• Profound effects of combining choline and piracetam on memory enhancement and cholinergic function in aged rats RT Bartus, RL Dean, KA Sherman, E Friedman… - Neurobiology of …, 1981 – Elsevier

• Novel nootropic drug sunifiram enhances hippocampal synaptic efficacy via glycine‐binding site of N‐methyl‐D‐aspartate receptor S Moriguchi, T Tanaka, T Narahashi… - …, 2013 - Wiley Online Library

• Chronic administration of sulbutiamine improves long-term memory formation in mice: possible cholinergic mediation J Micheau, TP Durkin, C Destrade, Y Rolland… - Pharmacology …, 1985 - Elsevier

• [Studying specific effects of nootropic drugs on glutamate receptors in the rat brain]. II Firstova, EV Vasil'eva, GI Kovalev - Eksperimental'naia i …, 2010 - europepmc.org

• Acetyl-L-carnitine enhances acetylcholine release in the striatum and hippocampus of awake freely moving rats A Imperato, MT Ramacci, L Angelucci - Neuroscience letters, 1989 - Elsevier

• A systematic review of modafinil: potential clinical uses and mechanisms of action JS Ballon, D Feifel - Journal of Clinical Psychiatry, 2006 - josephmatta.com

• Proof of efficacy of the Ginkgo biloba special extract EGb 761 in outpatients suffering from mild to moderate primary degenerative dementia of the Alzheimer type or multi-infarct dementia. Kanowski S, Herrmann WM, Stephan K, Wierich W, Hörr R. Phytomedicine. 1997 Mar;4(1):3-13. doi: 10.1016/S0944-7113(97)80021-9.

• Pharmakopsychiatr Neuropsychopharmakol. 1977 Mar;10(2):49-56. A double-blind investigation of piracetam (Nootropil) vs placebo in geriatric memory. Abuzzahab FS Sr, Merwin GE, Zimmermann RL, Sherman MC.

• A Phase II Randomized Clinical Trial of a Nutritional Formulation for Cognition and Mood in Alzheimer's Disease. Remington R, Bechtel C, Larsen D, Samar A, Doshanjh L, Fishman P, Luo Y, Smyers K, Page R, Morrell C, Shea TB.

• [Effects of the association of sulbutiamine with an acetylcholinesterase inhibitor in early stage and moderate Alzheimer disease]. Ollat H1, Laurent B, Bakchine S, Michel BF, Touchon J, Dubois B. Encephale. 2007 Mar-Apr;33(2):211-5.