A version of this post originally appeared on Diet vs Disease by Joe Leech
Nootropics, also known as “smart drugs” or “cognitive enhancers” are taken to improve brain function.
They are becoming increasingly popular, and a growing number of different nootropics are now available, including natural and synthetic versions.
Let’s look at the scientific evidence behind the best nootropic ingredients and evaluate if they actually produce their desired effects.
What are Nootropics?
Nootropics are drugs, supplements or other substances taken with the intention of improving cognitive function.
Cognitive function refers to a host of brain activities, including memory, motivation, attention, creativity, decision-making and problem-solving.
There are many different nootropics available, and each have their own unique chemical compositions, biological function and mechanisms of action.
Historically, nootropics were used in the 1970s in clinical trials to treat deficits in cognitive function, due to Alzheimer’s disease, ADHD, stroke or aging.
Now, an increasing amount of healthy people with no cognitive issues are taking nootropics in order to improve mental performance.
Though it’s difficult to judge exactly how prevalent recreational nootropic use is, an informal poll by the journal Nature found that 20% of their readers had taken some form of nootropics for non-medical reasons. People mainly used the drugs to stimulate their focus, concentration or memory.
Natural vs. Synthetic Nootropics
Natural nootropics include herbs, vitamins or other nutrients such as fatty acids or antioxidants, while synthetic nootropics contain artificial substances created by chemical synthesis in a laboratory.
Natural nootropics tend to be used in traditional medicine to nourish and protect the brain. You may even be consuming them in smaller quantities as part of your daily diet.
On the other hand, synthetic nootropics are often pharmaceutical agents, such as prescription drugs. They tend to be stronger and have more rapid and noticeable effects, but may also come with increased risks of adverse reactions.
10 Best Nootropics
Let’s take a look at some of the most popular nootropics and their effects on cognitive function.
1. L-theanine
L-theanine is a naturally occurring amino acid commonly found in green or black tea, or taken in supplement form.
Some claim that L-theanine can induce a state of calm focus, similar to that achieved by meditation.
In one randomized controlled study, 44 participants were administered a 97 mg dosage of L-theanine in combination with 40 mg of caffeine while they completed a demanding cognitive task.
Compared with a placebo, the L-theanine/caffeine supplement improved accuracy, alertness and tiredness. However, no significant effects were found for other cognitive tasks such as visual search, reaction times or mental rotation. It’s also unclear how much of these effects were due to the caffeine.
Elsewhere, L-theanine has been shown to increase levels of the neurotransmitters dopamine, serotonin and GABA in animals. These properties suggest a potential beneficial effect on learning and memory, but this has yet to be demonstrated in humans.
Administration of L-theanine has also been shown to alter brainwave patterns. Specifically, it can increase alpha waves, which indicate relaxation while remaining alert.
In one randomized controlled trial, a 50 mg dose of L-theanine (roughly equivalent to the amount found in 400 mls, or 14 oz, of black tea) produced a significant increase in alpha waves versus a placebo.
A recent review of 49 human tea drinking trials found that a combination of L-theanine and caffeine improved performance in attention-switching tasks and alertness, but to a lesser extent than caffeine alone.
L-theanine improved participants’ self-reported levels of relaxation, tension and calmness, but only at high doses of 200 mg (equivalent to eight cups of black tea).
This is an unrealistic amount for most people to achieve through tea alone, as it would require you to exceed the maximum recommended intake of 400 mg of caffeine per day (or about five cups of black tea).
L-theanine is not directly associated with any side effects and is generally considered safe to use. However, people consuming L-theanine in tea form should be mindful of the caffeine content. Over-caffeination can cause problems such as nausea, palpitations or insomnia.
2. Choline
Choline is important for brain development, liver function and the nervous system.
It’s an essential nutrient which means that it cannot be made in sufficient amounts by the body, so you need to obtain the majority of it through your diet. Foods high in choline include beef and chicken liver, eggs, salmon, cod, broccoli and cauliflower.
Choline is required to produce the neurotransmitter acetylcholine, which works within the muscles and central nervous system. It plays a role in alertness, attention, learning and memory.
Observational studies have demonstrated that high choline intake is associated with better cognitive performance.
Citicoline is a compound synthesised from choline-rich foods like eggs, beef and seafood, and is a common nootropic supplement.
A 2015 review found strong evidence to suggest that treatment with citicoline has a beneficial effect on cognitive impairments such as vascular dementia or post-stroke cognitive decline.
Similarly, citicoline was found to improve verbal memory function in a group of 95 older adults who had relatively inefficient memories.
However, these cognitive-enhancing benefits may not apply to healthy individuals without pre-existing cognitive impairments. A small study of 13 healthy men found that supplemental choline had no effect on reaction time, logical reasoning, vigilance, spatial memory or working memory.
3. Phosphatidylcholine
Phosphatidylcholine is made up of a phospholipid attached to a choline particle.
Its ingestion is intended to increase choline levels and promote acetylcholine production.
According to a biochemical analysis of blood plasma, Alzheimer’s patients have lower phosphatidylcholine levels compared with healthy controls. This suggests that phosphatidylcholine may have an impact on cognition.
Meanwhile, a study of mice with dementia found that phosphatidylcholine administration increased brain acetylcholine concentration and improved memory. However, there was no effect found in normal mice.
Large scale human studies are needed before we can draw any conclusions about the nootropics effects of phosphatidylcholine on healthy individuals.
4. Huperzine A
Huperzine A is a compound extracted from the plant Huperzia serrata, and has been used in traditional Chinese medicine.
Huperzine A is an acetylcholinesterase inhibitor. This means that it prevents the enzyme that breaks down acetylcholine from working, resulting in increased levels of acetylcholine. As mentioned above, acetylcholine plays an important role in the central nervous system.
A systematic review of 20 randomized controlled trials concluded that huperzine A treatment produced significant improvements in cognitive function and daily living activity in patients with Alzheimer’s disease. However, the study design was poor, so the results should be treated with caution.
In fact, a more recent systematic review concluded that the quality of evidence surrounding huperzine A as a cognitive enhancer in Alzheimer’s patients was not strong enough to support its usage.
Animal and in vitro (test tube) studies have demonstrated that the nootropic huperzine A is able to prevent cell death and promote new cell growth.
However, it’s important to remember that any cognitive-enhancing benefits of huperzine A demonstrated in animals, test tubes or Alzheimer’s patients may not occur in healthy individuals.
5. Rhodiola Rosea
Rhodiola rosea is an herb native to high latitude and altitude regions of the world, and has been used in Western and Asian traditional medicine.
It’s purported to have mental performance benefits, especially relating to reduced fatigue.
Several randomized controlled trials have investigated this link. A significant improvement in mental fatigue was demonstrated in 56 night-shift physicians who had taken a low dosage of rhodiola rosea over a 2-week period.
Similar beneficial effects have been demonstrated in students and sleep-deprived military cadets.
However, a systematic review found that many of the studies that reported a beneficial effect had methodological flaws, such as using unvalidated measures of fatigue. Other studies produced inconclusive or contradictory results.
An additional systematic review concluded that the evidence base is weak and inconsistent. Better-designed studies are required to make a more firm conclusion on rhodiola rosea’s effectiveness.
6. Panax Ginseng
Panax ginseng is an herb commonly used in Chinese medicine that’s said to have beneficial effects on memory.
A randomized controlled trial of 64 schizophrenia patients found that a 4-week course of treatment with panax ginseng produced a significant improvement in visual working memory.
Doses of 200 mg and 400 mg of panax ginseng in healthy subjects have also been shown to improve performance on an arithmetic task, and reduce self-ratings of mental fatigue.
However, another study has somewhat contradicted these findings, demonstrating that 200 mg doses of panax ginseng slowed down mental math performance.
In a small study of 30 participants, supplementation of 200 mg panax ginseng for over 4 weeks was associated with higher scores in mental health and cognition compared with a placebo. However, after 8 weeks, the scores were no longer different, which means benefits may disappear with continued use.
7. Ginkgo Biloba
Ginkgo biloba is a popular herbal supplement derived from the Ginkgo biloba tree, and is used to improve focus and memory.
It’s considered to be well-tolerated and safe, but ginkgo biloba has not been shown to have beneficial effects on people with acquired cognitive deficit.
Furthermore, long-term usage of these nootropics in older adults with memory complaints did not reduce risk of progression to Alzheimer’s disease.
The evidence available for healthy individuals also appears to be inconclusive. One study found that 120 mg of ginkgo biloba had no effect on memory functioning in 11 healthy adults aged 50 to 70 years old.
In young adults, a 360 mg dose was found to improve delayed and immediate word recall, but numeric working memory appeared to be impaired.
In another trial, 188 middle-aged participants took a 240 mg daily dosage for 6 weeks and showed improved memory recall, but no effect was demonstrated on recognition memory.
8. Modafinil
Modafinil is a stimulant that promotes wakefulness.
It’s a prescription drug approved to treat excessive sleepiness caused by narcolepsy, obstructive sleep apnea and shift work disorder.
Several randomized controlled trials have identified cognitive benefits from modafinil use.
During a 60-hour sleep-deprivation period, 300 mg of modafinil resulted in significantly higher alertness levels for up to 12 hours compared with a placebo.
Another trial found that during 64 hours of continuous brain tasks and sleep deprivation, cognitive performance (reaction time, logical reasoning and short-term memory) was significantly better in participants who had been given modafinil compared with a placebo.
Elsewhere, 32 participants took 200 mg of modafinil and showed significantly better performance in spatial working memory, planning, decision-making and visual pattern recognition memory. It also produced greater ratings of enjoyment during the task performance.
However, in the study mentioned above, modafinil did not improve paired-associate learning or creativity. Modafinil has also been shown to inhibit creative thinking in non-sleep-deprived participants and caused overestimation of cognitive performance in sleep-deprived subjects.
Keep in mind that these are single studies that used small numbers of participants. Larger scale systematic reviews and meta-analyses are required to determine whether or not modafinil is a truly beneficial nootropic for cognitive function.
9. Adderall
Adderall is a combination of amphetamine and dextroamphetamine.
It’s a stimulant that works to improve cognition by increasing levels of the neurotransmitters noradrenaline and dopamine in the prefrontal cortex area of the brain. This nootropic is highly effective in the treatment of ADHD.
Use of Adderall without a prescription is widespread, especially among students.
A meta-analysis of 48 studies examining the effects of amphetamine-based prescription stimulants such as Adderall found significant beneficial effects on working memory. However, the authors also concluded that these effects in healthy users are likely due to increased energy and motivation rather than a true effect on cognition.
The effects are similar to modafinil, but long-term use can lead to increased tolerance, dependence and even addiction. Adderall abuse can cause unpleasant symptoms when an individual stops taking it, and they may be left feeling tired and mentally “foggy” without it.
10. Bacopa monnieri
Bacopa monnieri is herb that has been used in Ayurvedic medicine for several centuries.
Traditionally, it’s used as an anti-inflammatory, analgesic, sedative, and antiepileptic. More recently, bacopa monnieri has become one of the most popular nootropics due to its supposed memory-enhancing properties.
A randomised control trial of 98 healthy older adults found that compared with a placebo, a daily dose of 300 mg was associated with improved memory acquisition and retention after 12 weeks.
An additional trial of 54 over-65s demonstrated a significant improvement in working memory compared with placebo with the same dosage and timescale.
Similarly, a trial of 46 healthy adults (18 to 60 year old) found that a 300 mg dose had beneficial effects on learning speed and memory capacity. These benefits were evident after 5 weeks but maximal effects were seen after 12 weeks.
However, a one-day trial found no significant effects on any measurements of cognition. So the research suggests that for maximal benefits, you need to use bacopa monnieri for a prolonged period of several weeks or months.
Bear in mind that many of these studies found that bacopa monnieri was associated with some gastrointestinal side effects such as diarrhea, abdominal cramps, and nausea.
Are Nootropics Worth Taking?
There are a wide range of nootropics available, all of which are taken with the intent to improve cognitive function, including alertness, memory, concentration or decision-making.
Many of these herbs, drugs or nutrients have been used for many years in traditional medicine and are generally considered to be safe and are well tolerated by most people.
There’s some limited evidence to suggest that taking bacopa monnieri, L-theanine, rhodiola rosea and panax ginseng offer small and specific cognitive benefits.
Stronger evidence suggests that modafinil has positive effects on cognition in people who are sleep-deprived, but its effects in non-sleep-deprived individuals are unclear.
Similarly, Adderall has been shown to improve working memory in several well-designed studies, but the exact mechanism by which this is achieved is unclear and long-term use can lead to addiction.
Most of the clinical trials involving nootropics have been done in people with pre-existing cognitive deficits, such as those with Alzheimer’s disease or vascular dementia.
The findings from these studies may not apply to healthy individuals without cognitive deficits.
If you do decide to take nootropics, they’re unlikely to have harmful effects, but long-term use can lead to addiction. Whether or not you should choose a natural or synthetic nootropic is down to personal choice.
Natural nootropics tend to be slower-acting and the research is still in its infancy. So far, there are inconsistent and contradictory findings for nootropics such as L-theanine, choline, phosphatidylcholine, huperzine A, rhodiola rosea, panax ginseng and ginkgo biloba.
On the other hand, synthetic nootropics, like modafinil and Adderall, have been researched more extensively, but they also carry a higher risk of side effects.
Overall, some nootropics do appear to have cognition-boosting effects, particularly in the short-term. That said, more long-term and high-quality studies are needed before we can make specific recommendations.
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