A complete summary of natural and synthetic nootropics, how they work, their effects, and the relevant studies backing up all the claims.
Researching nootropics needs some serious brain power. There are a few great sources of information out there, but most are dealing in hype and disinformation. We at Cerebra Nootropics have made a guide with all the basics of what you need to know, to the point and summarized for clarity.
So let’s get started.
Sulbutiamine
Summary
Sulbutiamine was discovered in Japan in the 1950s in order to treat thiamine deficiency. It was additionally studied in the 80s and ’90s for its role in age-associated cognitive decline causing memory issues and other brain disorders. It has been shown to be useful in treating post-infection fatigue among other ailments.
Effects
- Helpful in maintaining a state of alertness (1)
- Possible improvement in memory (2)
- Shown to help with a social anxiety disorder (3)
- Fatigue reduction (4)
- Possible neuroprotective effects (5)
- Improved erectile function (6)
- Improved sports performance (7)
How it works
Sulbutiamine (isobutyryl thiamine disulfide) is a synthetic molecule that uses sulfur to bind two thiamine (vitamin B1) molecules. The lipophilic structure of sulbutiamine increases thiamine levels at levels higher than thiamine itself in the hippocampus, medulla, cerebellum, cortex, and kidney.
Side effects
Side effects have been reported in clinical trials including bladder infections, arthritic-type pain, digestive issues (diarrhoea, abdominal pain, constipation, gastroenteritis), back pain, breathing issues (asthma, bronchitis), insomnia, sinusitis, headache, kidney pain, vertigo & sore throat (8).
References
- https://www.ncbi.nlm.nih.gov/pubmed/7170385
- https://www.ncbi.nlm.nih.gov/pubmed/4059305
- https://www.ncbi.nlm.nih.gov/pubmed/10858919
- https://www.ncbi.nlm.nih.gov/pubmed/28755683
- https://www.ncbi.nlm.nih.gov/pubmed/22040892
- https://www.ncbi.nlm.nih.gov/pubmed/15776829
- https://www.ncbi.nlm.nih.gov/pubmed/21204296
- https://www.ncbi.nlm.nih.gov/pubmed/21982120
Rhodiola Rosea extract
Summary
Rhodiola Rosea is a herb in the Rhodiola genera. It has been used traditionally to reduce fatigue and exhaustion and is considered to be an “adaptogen”.
Effects
- Helps alleviate stress (1)
- Improvement in fatigue symptoms (2)
- Possible anti-cancer properties (3)
- Antidepressive effects (4)
- Improved exercise performance (5)
How it works
The main active ingredients in Rhodiola appear to be Tyrosol and Salidroside, its glucoside. There are other structurally related bioactive compounds that may play a role. It is also a high source of procyanidins, a molecule similar to other molecules found in green tea.
Side effects
No side effects have been reported in clinical trials (6).
References
- https://www.ncbi.nlm.nih.gov/pubmed/29325481/
- https://www.ncbi.nlm.nih.gov/pubmed/28219059/
- https://www.ncbi.nlm.nih.gov/pubmed/21520297/
- https://www.ncbi.nlm.nih.gov/pubmed/17990195/
- https://www.ncbi.nlm.nih.gov/pubmed/15256690/
- https://www.ncbi.nlm.nih.gov/pubmed/21036578
Reduced Glutathione
Summary
Glutathione is an antioxidant that is found in plants, animals, fungi, and some bacteria and archaea. Being an antioxidant, glutathione is capable of preventing damage to important cellular components caused by free radicals, peroxides, lipid peroxides, and heavy metals.
Effects
- Increased circulation (1)
- Possible treatment in arterial disease (1)
- Demonstrated improvement in psoriasis (2)
- Possible improvement in fatty liver disease (3)
How it works
Glutathione is composed of three dietary amino acids; L-glutamate, L-cysteine, and glycine, making it a tripeptide molecule. It is considered to be an antioxidant because it works in the glutathione system which regulates many cell oxidative processes.
Side effects
Due to a lack of research, little is known about the side effects of using glutathione supplements. Unverified sources report that taking glutathione long-term has been linked to lower zinc levels and stomach issues.
References
- https://www.mayoclinicproceedings.org/article/S0025-6196(11)62019-3/abstract
- https://www.ncbi.nlm.nih.gov/pubmed/24155989/
- https://www.ncbi.nlm.nih.gov/pubmed/7569285/
Phosphatidylserine
Summary
Phosphatidylserine is an amino acid derivative compound. It is also referred to as a phospholipid, a fat-based substance that covers and protects the cells in the brain and forms the structures that carry the messages between them.
Effects
- Shown to improve memory (1)
- Possible treatment for Alzheimer’s Disease (2)
- Helps to treat stress (3)
- Possible improvement in cognitive function (4)
- Helps alleviate depression (5)
How it works
Phosphatidylserine appears to contribute to and increase cell fluidity as part of the cell membrane. Enzymes within these structures appear to be influenced positively which may explain the effects on cognition (6).
Side effects
Due to a lack of research, little is known about the side effects of using phosphatidylserine. Unverified sources report that taking phosphatidylserine may cause minor side effects like insomnia and stomach upset when high doses of over 300mg are consumed.
References
- https://n.neurology.org/content/41/5/644.short
- https://www.ncbi.nlm.nih.gov/pubmed/26345866
- https://www.ncbi.nlm.nih.gov/pubmed/15512856
- https://www.ncbi.nlm.nih.gov/pubmed/22017963
- https://www.ncbi.nlm.nih.gov/pubmed/1693032
- https://www.ncbi.nlm.nih.gov/pubmed/6331412/
Magnesium L-threonate
Summary
Magnesium L-Threonate is a form of magnesium derived from the salt of L-Threonic acid.
Effects
- Potential reversal of Alzheimer’s Disease (1)
- Possible treatment for dementia (2)
- Shown to treat certain forms of memory deficit (3)
- Reduced sense of fear shown in rat studies (4)
How it works
Developed by MIT researchers, this formulation differs from other magnesium supplements because it crosses the blood brain barrier which is believed to increase cognitive function.
Side effects
Due to a lack of research, there is little known about the side effects of using magnesium L-Threonate in particular however excessive dosing of magnesium supplements, in general, may produce stomach upset, nausea, vomiting and diarrhoea.
References
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4172865/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6242385/
- https://www.ncbi.nlm.nih.gov/pubmed/24077207
- https://www.ncbi.nlm.nih.gov/pubmed/23764903
Lion’s Mane Mushroom (Hericium Erinaceus)
Summary
Lion’s Mane Mushroom (Hericium Erinaceus) is a mushroom found in East Asia, North America and Europe. It is believed to enhance cognitive function.
Effects
- May improve memory (1)
- Possible gastroprotective effects (2)
- Improved mental cognition in the elderly (3)
- Possible anti-depressive effects (4)
How it works
The exact mechanisms of Lion’s Mane Mushroom have not been well-researched however it is believed to improve the development and function of nerves and protect them from becoming damaged. It is also speculated that it may protect the mucous membrane layer of the stomach and improve negative conditions related to the stomach lining.
Side effects
Studies in animals suggest that Lion’s Mane Mushroom and its extracts are very safe, even at high doses.(8) Unverified sources also report that individuals with mushroom allergies should exercise caution as some people have reported reactions.
References
- https://www.ncbi.nlm.nih.gov/pubmed/29953363
- https://www.ncbi.nlm.nih.gov/pubmed/24302966
- https://www.ncbi.nlm.nih.gov/pubmed/18844328/
- https://www.ncbi.nlm.nih.gov/pubmed/29364170/
L-theanine
Summary
L-Theanine is a non-dietary amino acid and one of the main ingredients in green tea. Being a non-protein amino acid, it is not used by the body to make enzymes.
Effects
- Improves symptoms of depression (1)
- May help with asthma and airway inflammation (2)
- Helps with stress (3)
- May improve symptoms of schizophrenia (4)
- May improve cognition and brain function (5)
How it works
Neurotransmitters like GABA and glutamate are produced through the ingestion of L-theanine resulting in various effects on the brain and throughout the body.
Side effects
Research is limited on any serious side effects of L-theanine however very high consumption of tea has been connected to mild adverse effects such as headaches.
References
- https://www.ncbi.nlm.nih.gov/pubmed/27396868
- https://www.ncbi.nlm.nih.gov/pubmed/27908701
- https://www.ncbi.nlm.nih.gov/pubmed/26797633\
- https://www.ncbi.nlm.nih.gov/pubmed/25896423
- https://www.ncbi.nlm.nih.gov/pubmed/17182482
Ginkgo Biloba
Summary
Part of traditional Chinese Medicine for thousands of years, Ginkgo Biloba is a medicinal plant that is part of the family Ginkgoaceae.
Effects
- Helps with anxiety (1)
- Alleviation of PMS symptoms (2)
- Possible improvement in mental functioning (3)
- Potential use as an antioxidant (4)
How it works
The main bioactive constituents unique to ginkgo Biloba include bilobalide and ginkgolides, in addition to various other common phenolic compounds.
The supplement contains high levels of flavonoids and terpenoids, which are antioxidants thought to provide protection against harmful free radicals that cause oxidative cell damage.
Side effects
Due to a lack of research, there is little known about the side effects of using ginkgo Biloba. Unverified sources however report that some users have experienced nausea, diarrhoea, dizziness, headaches, stomach pain and/or rash/allergic reaction.
References
- https://www.ncbi.nlm.nih.gov/pubmed/16808927/
- https://www.ncbi.nlm.nih.gov/pubmed/19678774/
- https://www.ncbi.nlm.nih.gov/pubmed/14602503/
- https://www.ncbi.nlm.nih.gov/pubmed/11507743/
Dihydromyricetin (DHM)
Summary
Hovenia Dulcis, also known as Dihydromyricetin (DHM) is a traditional Chinese medicine that has been used for sickness caused by excess alcohol consumption.
Effects
- Protects against alcohol-related liver injury (1)
- May exert anti-inflammatory effects in nonalcoholic fatty liver disease (2)
How it works
A study on rats showed that a water extract from the fruits and seeds of the native plant reduced circulating alcohol levels 30 minutes before, during and after alcohol consumption (3).
Side effects
DHM has been found to be very safe and free of side effects in mice, even at very large doses (1).
References
- https://www.ncbi.nlm.nih.gov/pubmed/20673184
- https://www.ncbi.nlm.nih.gov/pubmed/26032587
- https://ci.nii.ac.jp/naid/110006281669
Ashwagandha (Withania Somnifera)
Summary
Ashwagandha is a plant in the Solanaceae or nightshade family. It is also known as Withania Somnifera, Indian ginseng, poison gooseberry or winter cherry.
Effects
- A possible neuroprotective agent for sleep deprivation (1)
- May help increase muscle mass in conjunction with training (2)
- May improve inflammatory markers and insulin resistance (3)
- Helps with stress and anxiety (4)
- Possible improvement in fertility (5)
- May improve cardiovascular endurance and sports performance (6)
How it works
It has been suggested by a number of studies that ashwagandha may reduce cortisol levels and create an anti-anxiety (anxiolytic) effect that bring a wide range of benefits to general health.
Side effects
Ashwagandha is a staple of traditional Indian medicine and has been used extensively for safety (7).
References
- https://www.ncbi.nlm.nih.gov/pubmed/27037574/
- https://www.ncbi.nlm.nih.gov/pubmed/26609282/
- https://www.ncbi.nlm.nih.gov/pubmed/26989739/
- https://www.ncbi.nlm.nih.gov/pubmed/23439798/
- https://www.ncbi.nlm.nih.gov/pubmed/19501822/
- https://www.ncbi.nlm.nih.gov/pubmed/21170205/
- https://www.ncbi.nlm.nih.gov/pubmed/23439798/
Alpha-GPC
Summary
L-Alpha glyceryl phosphorylcholine or Alpha-GPC is a choline compound found naturally in the brain that is also available as a non-prescription supplement.
Effects
- Increase of dopamine concentrations in the frontal cortex and cerebellum of the brain in animal studies (1)
- May increase attention span when used with caffeine and phosphatidylserine (2)
- Associated with improved learning (3)
- May enhance athletic power output (4)
How it works
Alpha-GPC rapidly delivers choline to the brain across the blood–brain barrier and is a biosynthetic precursor of acetylcholine. Acetylcholine is a neurotransmitter that is used to power neurons of the nervous system release in order to activate muscles.
Side effects
Alpha-GPC is available as a non-prescription supplement and is considered to be safe, however, loss of appetite has been reported in some assessments (6).
References
- https://www.ncbi.nlm.nih.gov/pubmed/23244432
- https://www.ncbi.nlm.nih.gov/pubmed/21156078
- https://www.ncbi.nlm.nih.gov/pubmed/1409797
- https://jissn.biomedcentral.com/articles/10.1186/1550-2783-5-S1-P15
- https://www.ncbi.nlm.nih.gov/pubmed/21414376
- https://www.ncbi.nlm.nih.gov/pubmed/21414376
5-HTP
Summary
5-HTP is a substance that increases levels of serotonin in the brain. Serotonin is a neurotransmitter that has been shown in some studies to increase feelings of happiness and well-being while decreasing depression.
Effects
- Shown to help with depression (1)
- May help recover serotonin after MDMA use (2)
- Shown to be effective in fibromyalgia treatment (3)
- May help prevent migraines (4)
How it works
5-HTP is converted into serotonin through the action of the enzyme L-amino acid decarboxylase (5).
Side effects
While 5-HTP has been shown to be very safe, nausea has been reported in some studies (6).
References
- https://www.ncbi.nlm.nih.gov/pubmed/28787372/
- https://www.ncbi.nlm.nih.gov/pubmed/17629409/
- https://www.ncbi.nlm.nih.gov/pubmed/2193835/
- https://www.ncbi.nlm.nih.gov/pubmed/3536521/
- https://www.ncbi.nlm.nih.gov/pubmed/16023217
- https://www.ncbi.nlm.nih.gov/pubmed/2468734
Piracetam
Summary
Piracetam (2-oxo-1-pyrrolidine-acetamide) is the first synthetic compound of the racetam family. It was originally developed by UCB Pharma in Belgium and is also known as Nootropyl or UCB6215.
Effects
- Shown to possibly increase oxygen and glucose consumption in Alzheimer’s patients (1)
- May improve working memory (2)
- Possible aid in dyslexia (3)
- Can be used as additional therapy in stroke patients (4)
- Possible neuroprotective effects in patients undergoing coronary bypass surgery (5)
How it works
Piracetam has a structure that is somewhat similar to GABA, a neurotransmitter and is thought to enhance cellular membrane fluidity via antagonization of inhibition of glucose uptake into erythrocytes induced by hypnotic drugs (6).
Side effects
Piracetam has some reported side effects including psychomotor agitation, dysphoria, fatigue, dizziness, memory loss, headache, and diarrhoea (7).
References
- https://www.ncbi.nlm.nih.gov/pubmed/3260597
- https://www.ncbi.nlm.nih.gov/pubmed/826948
- https://www.ncbi.nlm.nih.gov/pubmed/116285
- https://www.ncbi.nlm.nih.gov/pubmed/11346373
- https://www.ncbi.nlm.nih.gov/pubmed/18971883
- https://www.ncbi.nlm.nih.gov/pubmed/16284628
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4756795/
Phenylpiracetam
Summary
Phenylpiracetam, also known as Phenotropil, is a synthetic drug from the racetam family. It was initially derived from Piracetam with the addition of a phenyl group to its structure.
Effects
- May improve declining cognitive function due to brain trauma (1)
- Possible benefit to sufferers of epilepsy (2)
- May improve symptoms of depression in traumatic brain injury (3)
- Possible immune supportive properties (4)
How it works
Phenylpiracetam is derived from Piracetam with the main difference being that it has the addition of a phenyl group. The manufacturer reports claim that its enhanced lipophilicity makes it rapidly and efficiently absorbed.
Side effects
While possible side effects of Phenylpiracetam have not been extensively studied it is worth noting it is a derivative of Piracetam, of which some side effects have been reported including psychomotor agitation, dysphoria, fatigue, dizziness, memory loss, headache and diarrhoea (5).
References
- https://www.ncbi.nlm.nih.gov/pubmed/16447562
- https://www.ncbi.nlm.nih.gov/pubmed/18646385
- https://www.ncbi.nlm.nih.gov/pubmed/16447562
- https://www.ncbi.nlm.nih.gov/pubmed/22442801
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4756795/
Oxiracetam
Summary
Oxiracetam is a member of the racetam family of drugs. Structurally similar to Piracetam, it has a structural difference due to a single hydroxyl group.
Effects
- Possible memory improvement (animal studies) (1)
- May benefit cognitive decline (2)
- Possible psycho stimulation effects (3)
How it works
Being a member of the racetam family of drugs, Oxiracetam has similar mechanisms to Piracetam in being an AMPA modulator with the main difference being the possible increase and/or release of glutamate, acetylcholine, and D-aspartic acid.
Side effects
While possible side effects of Oxiracetam have not been extensively studied it is worth noting that it is a derivative of Piracetam of which some side effects have been reported including psychomotor agitation, dysphoria, fatigue, dizziness, memory loss, headache and diarrhoea (4).
References
- https://www.ncbi.nlm.nih.gov/pubmed/3594453
- https://www.ncbi.nlm.nih.gov/pubmed/2693996
- https://www.ncbi.nlm.nih.gov/pubmed/8146219
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4756795/
Aniracetam
Summary
Aniracetam is a synthetic supplement and part of the racetam family of drugs. It is a common racetam compound consisting of a pyrrolidone structure and is cholinergic in nature.
Effects
- Possible changes in serotonin and dopamine levels (1)
- May stimulate neurons in traumatic brain injury (2)
- Possible anxiety reduction (animal studies) (3)
How it works
Aniracetam is thought to work as a stimulant by acting on AMPA (excitatory) receptors by decreasing the rate of receptor desensitization.
Side effects
While possible side effects of Aniracetam have not been extensively studied it is worth noting that it is a derivative of Piraracetam, of which some side effects have been reported including psychomotor agitation, dysphoria, fatigue, dizziness, memory loss, headache and diarrhoea (4).
References
- https://www.ncbi.nlm.nih.gov/pubmed/6535371
- https://www.ncbi.nlm.nih.gov/pubmed/8199398
- https://www.ncbi.nlm.nih.gov/pubmed/11412837
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4756795/
Noopept
Summary
N-phenylacetyl-L-prolylglycine ethyl, also known by the brand name Noopept, is a drug patented in Russia and marketed as a nootropic for cognitive enhancement. It is often grouped with drugs in the racetam family despite being different as a result of not having a 2-oxo-pyrollidine nucleus.
Effects
- Possible increase in neurotrophin factors in people with cognitive disorders (1)
- May affect regions of the brain associated with anxiety (2)
- Possible antidepressive effects (animal studies) (3)
How it works
There is very little known about the action of Noopept as many studies are either unavailable or have not been translated from Russian. According to some researchers, however, Noopept easily crosses the blood-brain barrier due to the lack of difference between serum and neural concentrations after ingestion (4).
Side effects
Studies concerning the side effects of Noopept are not widely available however literature comparing it to Piracetam has shown it to be well-tolerated with fewer side effects (5). Side effects reported with Piracetam include psychomotor agitation, dysphoria, fatigue, dizziness, memory loss, headache and diarrhoea (6).