The brain-blood barrier (BBB) is a semi-permeable “security system” that keeps blood cells separate from the extracellular fluid surrounding the brain. The BBB does admit the oxygen and nutrients transported by the blood cells, and it prevents harmful substances like bacteria or poisons from getting to the brain.
The BBB has epithelial cells that provide a lining and control what gets in and out. Researchers have found that very small and/or fat-soluble compounds can bypass the BBB. Such compounds include alcohol, cocaine, anti-depressants, anti-anxiety medications and many hormones. Bigger compounds like insulin or glucose need to be helped across the barrier by specific proteins that are located in the walls of the brain’s blood vessels. The transporter proteins pull the desired compounds out of the bloodstream and into the brain.
Nootropics That Do and Don’t Cross the Blood-Brain Barrier
The following is a comprehensive list of nootropics, a description about them, and an indication as to whether they cross the blood-brain barrier or not. If you are wondering about a specific nootropic, I recommend using the search function.
Any Acetyl group (yes)
Acetyl L-Carnitine or ALCAR enhances cognition. It is popular with athletes because it also lowers cholesterol and helps burn fat.
N-Acetyl L-Cyteseine or NAC is an amino acid that regulates the dopamine and glutamate levels in the brain. It improves concentration and motivation.
N-Acetyl L-Tyrosine or NALT is a variant of the amino acid L-Tyrosine, and it helps produce norepinephrine and dopamine. It helps keep the brain working when subjected to physical stress like sleep deprivation or extreme cold.
5-HTP is an amino acid extract that the brain converts into serotonin, a neurotransmitter that reduces food cravings and improves mood. 5-HTP is generally used to control weight, promote good sleep and enhance mood.
AC-11/Uncaria Tomentosa/Cat’s Claw (yes)
AC-11 is an extract from a plant called Cat’s Claw, and it produces antioxidants that can repair damage caused by stress. Some people believe it can also reduce inflammation of the brain.
CDP-Choline, also known as Citicoline, is believed to increase the amount of dopamine receptors. It is also thought to prevent memory loss and to improve concentration.
D-Ribose is a supplement that boosts energy levels. It can be used to treat depression, chronic fatigue, pain and stiff muscles.
L-Arginine is an amino acid that can relieve migraines and is used to treat some dementias. It is popular with athletes, for it boosts endurance and physical performance.
L-Carnitine is a brain booster that can support the neurons, reduce fatigue and increase alertness. It is related to ALCAR.
Also called “Levdopa,” it is used to treat Parkinson’s disease. As a nootropic, it can improve learning abilities, especially vocabulary.
L-Glutamine is an amino acid that reduces stress and improves such cognitive functions as creativity and logic. It further helps the brain by making glutamate and GABA and providing neurons with glutamic acid.
L-Lysine is an essential amino acid that improves memory and the ability to organize one’s thoughts. L-Lysine is also used to treat herpes outbreaks, and it can improve digestion.
L-Ornithine (not by itself)
L-Ornithine or Ornithine is an amino acid that reduces ammonia levels in the blood and therefore improves endurance.
L-Taurine or Taurine is an amino acid that is often used in energy drinks. When combined with caffeine, it improves alertness and cognition; it is also an anti-oxidant.
L-Tryptophan or Tryptophan is an essential amino acid that can boost serotonin levels. When used as a nootropic, L-Tryptophan can be used to treat depression, anxiety, ADHD, insomnia, eating disorders, memory loss and pain.
L-Tyrosine is an amino acid that improves cognition and memory, and it keeps the brain working when subjected to physical stress like extreme cold or high altitudes. The amino acid is also used to produce dopamine and noradrenaline.
L-Aspartic Acid (yes)
L-Aspartic Acid is a foundational building block for proteins and the production of other amino acids in the body. Taking L-Aspartic Acid can improve metabolic function, support improved energy and combat depression and fatigue.
L-Cysteine is predominantly taken to reduce the effects of the aging process. Taking L-Cysteine can also improve the health of hair and the strength of the immune system.
L-Methionine is an important amino acid that has been used in the treatment of mood disorders in those with chronic diseases.
L-Glycine is a small molecule amino acid that is essential for producing proteins the body uses to manufacture organ tissue. Taking L-Glycine is known to improve digestive function as well as the immune system. It can also help build muscle tissue and reduce inflammation in the body.
L-Leucine is one of the principle essential amino acids the body needs to repair muscles and tissues. It can also improve energy levels and stabilize blood sugar.
L-Glutathione is a naturally occurring protein and antioxidant in each cell in the body. One of its functions is to protect the cells from free radicals.
One of the most famous nootropics, Alpha-GPC increases choline, dopamine and serotonin levels in the brain. It therefore improves both memory and mood.
Alpha Lipoic Acid (ALA) (yes)
Alpha Lipoic Acid is a fatty acid that may help repair nerves. As a supplement, it acts as an anti-oxidant and protects the body from inflammation.
One of the racetam drugs, Aniracetam has been found to have anti-anxiety effects in lab tests with animals. It is also being studied as a possible treatment for degenerative neurological diseases.
Ascorbic Acid/Vitamin C (yes)
Vitamin C is an essential vitamin most famous for its ability to prevent people from getting colds. As a nootropic, it can treat depression.
Bacopa monnieri is a perennial herb that can enhance memory and cognition. It has also been used to treat asthma, epilepsy, inflammation and indigestion.
Caffeine is a stimulant and the original nootropic. Low doses can increase alertness significantly, while higher doses can greatly improve performance, making it popular with students, writers and other people who perform intellectually challenging tasks.
Catechins are four molecules found in green tea that can improve cognition. Catechins can improve health overall and help burn fat.
Centrophenoxine is a supplement that is sometimes described as a “brain repair” drug, because it is every effective at removing wastes like lipofuscin from the brain and repairing cellular damage. It improves memory and has been used to treat Alzheimer’s disease.
Choline is a nutrient that helps the brain work by maintaining communication between the neurons. It also stimulates the neurons to produce acetylcholine, a neurotransmitter that improves cognition. Although choline does cross the BBB, it does not do it as easily as CDP or Alpha-GPC.
Choline Bitartrate (Yes)
Choline Bitartrate is a choline mixed with tartaric acid and is sometimes described as a “choline salt.” Choline Bitartrate boosts memory and mood, and it helps the brain repair damaged membranes and make new brain cells.
Choline Citrate (Yes)
Choline Citrate improves memory and concentration, and it can even be used to treat Alzheimer’s disease. Athletes like Choline Citrate, because it helps repair muscles and other tissues.
Cobalamin (Vitamin B12)
Cobalmin or Vitamin B12 improves memory and the ability to think quickly. It can also improve physical health and may increase energy.
Co-Enzyme Q-10 (yes)
Co-Enzyme Q-10 generates energy and keeps cells healthy. It is an antioxidant that some researchers believe can be used to treat degenerative diseases of the nervous system like Parkinson’s disease.
Docosahexaenoic acid or DHA is one of the omega-3 fatty acids, and it improves mood. It is also a major component in synapses, which are the part of the brain cell that cause neurons to transmit messages to each other.
Dehydroepiandrosterone or DHEA is a steroid hormone that the brain, adrenal glands and gonads produce. As a nootropic, it can improve memory and cognition, increase energy and stimulate the production of estrogen and/or testosterone.
DMAE is an alcohol that can be found in some foods like fish, and it can be manufactured within the human brain. A relative of choline, it can increase alertness and improve mood, and it might help treat ADHD.
Dopamine is a neurotransmitter that is famous for elevating mood. It can also improve the ability to learn and form memories, and it improves sleep and cognition. Although dopamine can’t cross the BBB, it appears that l-dopa can.
Eleutherococus senticosus (yes)
Eleutherococus senticosus is an Asian shrub sometimes called Siberian Ginseng. It can be used to fight fatigue and combat cognitive decline in older people.
Folic Acid (Vitamin B9)
Folic Acid, also known as Folate or Vitamin B9 is an essential vitamin that helps create SAMe, a compound that naturally prevents depression. Folate is better known for preventing neural tube birth defects.
Although GABA can’t cross the brain-blood barrier, it can still calm people, much to the surprise of scientists. GABA is an anti-anxiety drug that can also cause the release of human growth hormone and is thus popular with body-builders.
Ginkgo biloba (yes)
Gingko bilboa has been used as both food and medicine for generations. As a nootropic, it is believed to improve long-term memory, attention and executive function.
Ginseng is an herb that has also been used in alternative medicine for generations, often as an aphrodisiac. As a nootropic, it improves memory, mathematic ability and attention.
Glucuronolactone is a molecule often used in energy drinks. It boosts energy.
HGH or Human Growth Hormone increases energy. It is popular with athletes, for it also increases endurance and helps them build bone density and muscle mass.
Huperzine-A prevents choline in the brain from breaking down and improves memory. It may also stimulate neurogenesis or the production of new nerve cells.
Hydergine can improve cognition and is often used in conjunction with another nootropic to enhance the effects. It is also believed to be a treatment for dementia and other degenerative disorders of the nervous system.
Idebenone is a synthetic form of Co-Enzyme Q-10 that studies with rodents indicate can improve memory and learning ability. It is also used to treat degenerative diseases of the nervous system
Inositol (not without help)
Inositol or Vitamin B8 improves concentration and increases energy. It also enhances communication between neurons and stimulates choline activity.
Kava Kava (Yes)
Kava Kava is a supplement made from an herb that contains an active ingredient called kavalactones that affect the transmission of GABA in the brain. Kava Kava can improve cognition in people suffering from anxiety.
Lecithin is composed of fatty acids, and it is a source of choline, which provides many benefits to the brain.
Lion’s Mane (Yes)
Lion’s Mane is a mushroom that has been used in the traditional medicine of the Chinese. Some studies indicate that Lion’s Mane can help patients with impaired cognition by improving mental functioning.
Magnesium Threonate is the only form of magnesium that can be absorbed by the brain. It helps both long and short term memory.
Melatonin is a hormone produced in the body believed to have restorative effects on the brain after stress. It is also used to treat insomnia.
Also sold as Provigil, Modafinil has been approved by the FDA to treat wakefulness disorders like narcolepsy. Researchers have found it can also improve memory, but the long-term effects are not yet wholly understood.
Mucuna pruriens (yes)
Mucuna pruriens comes from a bean called the Velvet Bean, and it produces a lot of L-DOPA.
Niacin (Vitamin B3)
Niacin or Vitamin B3 helps boost energy in the brain, and it may also reduce cholesterol. Niacin can be found in a variety of foods.
Nicotine can improve alertness, memory and fine motor skills. It is highly addictive, though, and is considered problematic at best.
Oatstraw/Avena Sativa (yes)
Also known as “green oat grass”, the extract from oat straw is believed to help improve concentration. Oatstraw extract can be used as a stimulant and a treatment for joint pain. On the nootropic front, it has been shown in one study to improve performance in cognitively demanding task.
Omega-3 fatty acids are often found in seafood, and they contain DHA and EPA that help keep the brain healthy. Omega-3 can also treat attentional deficits and mood disorders including depression.
Oxiracetam (yes, but water soluble)
Double blind studies have demonstrated that Oxiracetam is a powerful nootropic that can improve memory. It can also enhance attention, concentration and the ability to think logically, and some believe it can be used to treat dementia and other degenerative neurological disorders.
Phenylethylamine or PEA is an organic compound that can be found in foods like chocolate. It’s a supplement that can improve mood.
Propionyl L-Carnitine or PLCAR is a close relative of ALCAR, and it boosts energy. Athletes use it to increase fat loss and endurance.
Pantothenic acid (Vitamin B5)
Patnothenic acid or Vitamin B5 is another member of the B Complex that improves brain health. It processes sugars and delivers the resultant energy to the brain, and it may reduce mental fog.
Pemoline or Cylert is a stimulant that increases the brain’s dopamine levels and may improve memory. It has also been used as a treatment for narcolepsy and ADHD.
Sometimes sold as “Noofen,” Phenibut is a relative of GABA. It can calm people and thus reduce anxiety and stress, and it can increase the brain’s dopamine levels.
Phenylalanine is an amino acid that can be converted into L-tyrosine and increases the brain’s levels of norepinephrine, epinephrine and dopamine. It can also increase the number of neurotransmitters that affect memory, concentration and critical thinking.
Picamilon is a popular nootropic that is composed of niacin and GABA. After crossing the BBB into the brain it breaks down into its parts.
Piracetam (yes, but water soluble)
Piracetam improves memory, learning and concentration. It was developed in 1964 by Dr. Corneliu E.Giurgea, the godfather of nootropics.
Pramiracetum is one of the most powerful Racetam cognitive enhancers. It can prevent the forgetfulness caused by amnesia-inducing drugs like alcohol, and it can improve memory overall.
Also known as P5, Pregnelone is a hormone that the brain, liver and adrenal glands produce. As a nootropic, it improves memory and mental performance, and it may repair damage caused by stress.
Pterostilbene can be found in blueberries and grapes and contains lots of antioxidants. Studies with rats indicate that it can improve motor skills and reverse declines in cognition.
Pyridoxine (Vitamin B6)
Pyrodoxine or Vitamin B6 may help people with degenerative neurological disorders by improving their cognition. Some scientists believe that it decreases the homocysteine levels in their blood and thus reverses declines in cognitive abilities.
Pyritinol is a supplement that is used to treat learning disabilities, and some countries also use it to treat dementias. It improves cognitive function and reaction time.
Pyroglutamate (PCA) (yes)
Pyroglutamate or PCA is an amino acid that can improve cognition and memory. Studies have shown that is effective in treating people with dementia and alcohol-induced memory loss.
Quercetin (no, most flavonoids cannot)
Quercetin is a bioflavonoid that has some of the same effects as caffeine, but to a lesser degree. It is also an anti-oxidant that can prevent or slow the development of atherosclerosis and some forms of cancer.
Resveratrol can enhance the release of norepinephrine, which is a neurotransmitter that acts as a stimulant. It is also believed to improve concentration, awareness and other mental functions.
Rhodiola Rosea (yes)
Rhodiola Rosea is a supplement that is commonly used to treat depression and improve mood. It can also improve mental performance and reduce fatigue.
Serotonin is a neurotransmitter that is famous for improving mood. It also increases confidence and mental flexibility.
Researchers have found that Sulbutiamine increases memory. It can also be used to treat Vitamin B1 deficiency.
Also known as L-Theanine, the amino acid Theanine promotes relaxation. It may also improve the quality of one’s sleep and relieve anxiety.
Ubiquinol is a derivative of COQ10 and is also a powerful anti-oxidant. Like COQ10, it helps keep the brain working and it prevents cognitive declines like those seen in Alzheimer’s disease.
Vasopressin or AVP is a hormone that helps the body retain water and causes blood vessels to constrict. Some studies suggest that when vasopressin gets into the brain, it can influence bonding and other social functions, and it may improve memory and motivation.
Vincamine can be used to treat the cognitive declines associated with aging. It is also a vasodilator and increases the diameter of the blood vessels and thereby increases blood flow to the brain.
Vinpocetine contains periwinkle extracts and is also a vasodilator that increases blood flow to the cerebral cortex. It may improve memory in people suffering from age-related memory loss, and it also reduces inflammation.
The word “nootropic” was coined in the 1970s by Corneliu E. Giurgia, a Romanian chemist and psychologist. The word comes from the Greek words for “mind” and “to turn or bend.” Some nootropics like gingko or caffeine have been used for generations, and some have been established as having known medical purposes. Some nootropics, by contrast, are new and still being studied to determine their efficacy and safety. As the brain itself is still not wholly understood, nootropics should be used carefully. People who take other medications should consider the possibility of drug interactions.
A special thanks goes out to the Reddit Nootropics subreddit as they had compiled most of the information here. Here are some other sources for this article.