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.
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. 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 
- There is actually reason to believe that DMAE may act as an anticholinergic
- DMAE causes birth defects
- Some nootropic users report depression and physical anxiety as a side effect of DMAE
- DMAE reduced lifespan in a study on quails
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. 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.
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.
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.  
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.
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. That being said, it is still fairly available online to those in the US who wish to purchase it.
The 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. 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.
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. 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.
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.
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.
- 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.
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.
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, 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. 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.
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.
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