“Nootropics” is a broad term for any chemical substance or compound that may improve brain function, enhancing or improving cognitive abilities and aspects of mood without negatively affecting the brain. Since there are many different ones, how they work or their mechanisms of action also varies.
While there is not a single answer to characterized how all Nootropic supplements work in general, for the most part, these types of brain supplements work with your natural brain chemistry and said to produce positive effects on learning capacity, memory, logical reasoning, focus, mental energy, motivation, mood and more via several different pathways.
Nootropic supplements either act to increase or modulate neurotransmitters, boost blood flow and oxygen to the brain, encourage enhanced cellular energy or influence hormones or neuroplasticity in order to promote a wide range of beneficial effects on mental performance, mood and the promotion of brain health.
There are also many types of Nootropics both naturally derived and synthetic which fall into different categories depending on their mechanisms of action or brain pathways they intend to target in order to optimize structures and functions.
Some Nootropics have undergone decades of research and testing, identifying their beneficial mechanisms of action but the brain is the most complex organ we have and their ultimate effects continue to be investigated, while science continues to make great strides in understanding how the brain works and functions.
While each individual Nootropics proposed mechanism of action and effects can be found in their article on this site, below provides a guide to the many suggested pathways they target to boost brainpower.
Neurotransmitters & Receptors
We think of neurotransmitters as chemical messengers or “information carriers” that transmit signals from one neuron to another. In order for them to communicate, they must cross small gaps called synapses.
According to their received message, they bind to the receptor on the dendrite of another neuron and may act to trigger changes on the receiving neuron, either having an excitatory effect (increasing the likelihood the neuron will fire) or inhibitory effect (decreasing the likelihood the neuron will fire) or acting as a neuromodulator (affecting a greater number of neurons at the same time and influencing other chemical messengers).
Neurotransmitters play a vital role in the communication between neurons, influencing everything from cognition and mood to sleep and play a huge however less obvious role in our daily lives and functioning.
In some cases, neurotransmitters may not function properly such as when too much of a particular one is released or not enough is made, too many get deactivated by enzymes or they get reabsorbed too quickly.
The system between neurotransmitters and receptors are what many Nootropics aim to target or enhance and may either promote the supply of precursors to raise their level, encourage their synthesis, inhibit their breakdown or enhance receptor sensitivity.
While approximately 100 neurotransmitters have been identified by scientists, the most common to Nootropics are Acetylcholine, Dopamine, Serotonin, Norepinephrine, Epinephrine, Glutamate and GABA.
Acetylcholine (ACh) is a natural and primary neurotransmitter essential for proper brain function. This chemical messenger plays an important role in many cognitive functions such as memory formation, decision-making capacity, learning and controlling our attention span. It is also linked to sleep cycles, the amount of REM sleep we get and promotes the creation of healthy synapses throughout the brain.
The cholinergic system relies on the neurotransmitter Acetylcholine to communicate, which can’t be synthesized without choline to produce it. We usually get our source of choline from food consumption such as egg yolks, liver, fish and others but it is known that a high percentage of people are deficient.
Since choline is a precursor to Acetylcholine, it is important to take choline supplements that are considered more effective at converting into this chemical such as Alpha GPC (a direct precursor to Acetylcholine) or Citicoline (also known as CDP Choline), a highly bioavailable form of choline.
Choline supplements are also commonly stacked or taken in combination with other Nootropics such as Racetams (Aniracetam, Pramiracetam, Oxiracetam, Piracetam, Noopept and others) to induce Nootropic synergistic effects.
Racetams can be considered “mental performance and productivity drivers” in the world of Nootropics, enhancing Acetylcholine receptor sensitivity while choline increases the level of this neurotransmitter.
Some other Nootropic supplements like Huperzine A or Galantamine have other proposed mechanisms of action for increasing Acetylcholine levels. They act to block the enzyme Acetylcholinesterase from breaking down this neurotransmitter, helping the body to retain generated Acetylcholine.
Glutamate & GABA
Glutamate is the brains main excitatory neurotransmitter, increasing neuronal activity and playing an important role in learning, memory, and maintaining the health of the brain.
It also converts into another major neurotransmitter GABA which functions to inhibit excessive excitation when too much stimulation is present in the brain, keeping Glutamate in balance and producing a calming effect that may help reduce feelings of anxiety and stress.
Approximately half of all brain synapses use Glutamate and proper brain function is reliant on its adequate levels, not too high nor too low. Low glutamate excitation can result in mental exhaustion, problems concentrating and depleted energy levels while too much, which can occur outside the cells, are hypothesized factors linked to the development of Alzheimer’s, Parkinson’s and ADHD.
While there are numerous types of Glutamate receptor sites, NMDA and AMPA receptors are considered to have Nootropic qualities. Both Racetams such as Aniracetam and Noopept are known to stimulate these types of receptor sites and have some modulating effect that may lead to improvements in memory, learning capacity, the ability to focus and boost energy.
In regards to GABA (gamma-aminobutyric acid), Nootropics like GABA, L-Theanine, Phenibut or Lemon Balm are all thought to mimic, enhance the activity or interact with GABA receptors producing relaxing effects.
Dopamine & Serotonin
Dopamine and Serotonin are well-known neurotransmitters associated with feelings of pleasure and well being. These chemical messengers play a role in regulating mood, motivation, appetite, sleep, working memory, concentration and learning.
These chemicals share similar related characteristic effects as key mood boosters but there are differences between the two. Dopamine-related effects can be addictive. “Smart drugs” like Adderall and Ritalin are direct dopaminergic stimulants while Vyvanse has a secondary mechanism of action still working to increase Dopamine levels.
While there are certain Nootropics that encourage elevated Dopamine levels or activity or influence or modulate Serotonin, they are generally not the primary targets of most Nootropics but they do tend to affect these systems to a certain degree contributing to their overall effects.
There are various different dopaminergic Nootropics such as Mucuna Pruriens, an herb rich in L-Dopa, a natural precursor to Dopamine and other neurochemicals such as Norepinephrine and Epinephrine. Other Nootropics like Sulbutiamine and Pregnenolone also promote dopaminergic activity.
Nootropics that influence Serotonin such as 5-HTP or L-Tryptophan are most commonly used to combat symptoms of depression, insomnia and tend to focus more on enhancing mood than cognitive related effects.
Norepinephrine & Epinephrine
Norepinephrine (noradrenaline) acts as both a stress hormone and neurotransmitter. It belongs to the group of compounds known as monoamine neurotransmitters which also includes Epinephrine, Serotonin, and Dopamine (also referred to as catecholamines), playing a role in regulating mood.
Both Norepinephrine and Epinephrine interact with the same receptors and both act to trigger the “fight or flight response” (fast movement and thinking response) when under high stress or in the face of danger in order to provide the body with extra energy and mobilize the brain for action.
Epinephrine (adrenaline) is released by the adrenal gland into the bloodstream and primarily acts as a hormone. Norepinephrine acts as both and is also released by neurons in the brain as a neurotransmitter which is associated with maintaining alertness and focused attention.
Low Norepinephrine levels or deficiency has been linked to various mental and physical conditions such as ADHD, depression and fatigue while levels that are too high which is less common and tends to accompany high Dopamine levels as well (closely linked in function and structure) cause anxiety and insomnia.
Some supplements and Nootropics most commonly used to enhance synthesis or increase levels of Norepinephrine are L-Tyrosine which is thought to act fast in relieving norepinephrine-related depression, L-Carnitine and Panax Ginseng. Other supplements like Melatonin are thought to reduce norepinephrine levels.
Blood Flow to the Brain
Healthy blood flow is essential for optimal brain function. Cerebral blood flow or the blood supply that reaches the brain carries oxygen, glucose (brain cells main energy source), vitamins, minerals and other nutrients the brain needs to fuel up and survive. Outwardly, it carries waste products away from the brain such as toxins, carbon dioxide and other wastes the brain doesn’t need.
The brain is only 2% of your body weight but gets 15%-20% of the total amount of blood supply indicating just how much nutrients and energy it needs. In fact, the brain is the most energy consuming organ we have.
When there is poor blood flow to the brain, symptoms such as brain fog, mental fatigue, problems with memory, difficulty concentrating, dizziness and frequent headaches can occur. There is also evidence that reduced cerebral blood flow can raise the risks of serious brain disorders such as vascular dementia.
There are many supplements to choose from when looking to improve blood flow to and throughout the brain but some of the most commonly used Nootropics for this purpose are Ginkgo Biloba, Vinpocetine and Bacopa Monnieri.
Another way in which Nootropics may support brain energy or brainpower is by enhancing mitochondrial function, organelles in brain cells or the cellular “power plants” that generate the main energy currency of the cell, ATP (adenosine triphosphate).
The highest concentration of mitochondria is found in the brain, the most energy dependent organ we have. The bulk of the brains ATP is used to help neurons fire, send signals and communicate with each other while a 1/3 is used for cell maintenance, making the health of mitochondria an extremely important factor for optimal brain function and cognition.
Mental fatigue and brain fog, which is characterized by temporary states of lack of mental clarity, difficulty forming thoughts, forgetfulness and problems focusing may be due to low brain energy.
Some Nootropics and supplements considered to help increase brain energy ATP and support mitochondrial function are CoQ10, Magnesium L-Threonate, Alpha Lipoic Acid, Acetyl-L-Carnitine, Creatine and Resveratrol.
Brain Aging & Neuroprotection
Nootropics are most commonly used for their benefits on mental performance in the now but they have shown a lot of potential for optimizing brain health, promoting healthy structure and functions that may help contribute to a continuous sharp mind in the future.
Some Nootropics can act as anti-oxidants for your neurons and other brain cells, helping to remove toxins such as excess potassium, lipofuscin and other waste materials that accumulate within the brain that interfere with normal cellular functions and are associated with neuronal damage.
While there are many factors involved in negative age-related conditions and problems with cognition, toxins which are considered to be key offenders in the degeneration of neurons in the brain are free radicals and their excessive build-up known as oxidative stress.
Brain aging is thought to be caused by free radicals, unstable atoms which damage brain cells over time. Additionally, synapse signaling systems, the junctions that allow neurons to pass chemical signals to other neurons and communicate are vulnerable to oxidative stress.
Pine Bark Extract, Bacopa Monnieri, Choline supplements are considered some Nootropics with anti-oxidant effects helping to neutralize and remove free radicals and may aid in protecting the brain against aging.
Other Nootropics may help protect neurons from other types of damage associated with cognitive decline. Lion’s Mane Mushroom may help protect against unhealthy proteins and additionally promotes NGF (Nerve Growth Factor) which plays a significant role in the maintenance, survival and regeneration of neurons that may help improve mild cognitive impairment.
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