Natural Nootropics 101: Unleash Your Superbrain
Nootropics are cognitive enhancers that may enhance brain function by improving blood flow, modulating neurotransmitters, or stimulating the nervous system. Beyond conventional stimulants, nootropic mushrooms, adaptogens, and amino acids may provide more stable benefits with fewer side effects than synthetic smart drugs, supporting memory, focus, and neuroprotection.
What Are Nootropics?
Nootropics, are cognitive enhancers, so-called smart drugs typically used to improve aspects of brain health and cognition. They can affect specific domains of cognition like thinking, learning, and memory, particularly when these functions are impaired. (1)
The name nootropics comes from the Greek words noos (mind) and tropein (to bend, to turn) symbolizing adaptability.
Unlike conventional stimulants that cause general activation followed by sedation, true nootropics have a stabilizing effect, activating impaired adaptive functions to optimize brain function. (2)
These cognitive enhancers can be classified into four main categories: classical nootropic compounds, substances increasing brain metabolism, cholinergic agents, and plant extracts with nootropic properties. (1)
Smart Drugs
Smart drugs, also known as synthetic nootropics or cognitive enhancers, are pharmaceutical compounds designed to produce immediate and potent effects on cognitive function. These include medications like Adderall, Ritalin, and Modafinil, which have strong stimulatory and dopaminergic effects that may lead to negative side effects due to overstimulation. (3)
They were primarily designed to treat cognitive impairment like Alzheimer’s and ADHD, but are often misused by students as brain doping. (4) (5) While these substances can significantly boost focus, alertness, and mental performance in the short term, they come with considerable drawbacks.
Research indicates they can adversely affect cardiovascular function by elevating heart rate and blood pressure, potentially leading to dependency, tolerance development, and a host of side effects including mood disturbances, insomnia, irritability, and anxiety (6) (7) (8) (9). Their mechanism of action typically involves direct manipulation of neurotransmitter systems, which explains both their potency and potential risks.
Natural Nootropics
Natural nootropics derive from plant sources and contain bioactive compounds like flavonoids, catechins, and other phytochemicals that support cognitive function in a more subtle way by modulating HPA axis activity and stress adaptation. (10) (11) (12)
Examples include compounds in mushrooms, coffee, herbs, and spices. These natural substances better align with true nootropics’ definition: enhancing brain function while protecting neural health with minimal side effects and low toxicity. Natural nootropics should support existing biochemical processes rather than forcing dramatic neurotransmitter changes.
While some nootropics can produce a mild stimulating effect, the differentiating factor between smart drugs and natural nootropics is the latter shall promote stability and adaptive responses, support brain health, while having lower risk of side effects or tolerance.
How Do Nootropics Work?
Nootropics can influence cognition by impacting pathways associated to cognitive impairment. Poor cognition stems from impaired brain circulation, accumulation of calcium, endothelial dysfunction, and glutamate excitotoxicity. (13) Nootropics may help counteract these processes by supporting blood flow, enhancing oxygen and nutrient delivery to brain cells, protecting against oxidative stress, and modulating neurotransmitter function. (14) (15) (16) (17)
The efficacy of natural nootropics—herbs, mushrooms, adaptogens—isn’t yet fully supported by science. Research is ongoing, and the evidence for efficacy varies significantly amongst different compounds. (2)
The potential pathways via which nootropics may enhance cognitive function, mainly studied on animal models due to limitations in humans, include:
Nitric Oxide
Nerve Growth Factor (NGF)
Brain-Derived Neurotrophic Factor (BDNF)
Energy Production
Cognitive processing requires a significant amount of ATP. Nootropics that enhance mitochondrial function and ATP production help improve cognition, particularly when energy creation is compromised.
Cholinergic Activity
The cholinergic system, which uses acetylcholine as its primary neurotransmitter, is fundamental to learning and memory. Many nootropics like alpha-GPC may enhance cholinergic activity by increasing acetylcholine synthesis, inhibiting its breakdown, or sensitizing its receptors. (1) (13) (25) (26) (27)
Dopaminergic Activity
Anti-Inflammatory Activity
Ion Transport
Proper ion balance is essential for neuronal signaling. Nootropics that regulate calcium, sodium, and potassium channels help maintain optimal neuronal excitability and signal transmission.
Stimulation or Sedation
By impacting the levels of excitatory (glutamate) or inhibitory (GABA) neurotransmitters, some nootropics can manipulate how activated the brain is, accelerating waking up (focus) or winding down (sleep), depending on the need.
These mechanisms often work synergistically, with many nootropics acting through multiple pathways simultaneously. For example, rather than forcing dramatic changes in brain chemistry, natural nootropics tend to support and optimize the way the brain works.
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Potential Benefits of Nootropics
Natural nootropics pose a potential for cognitive enhancement across various domains, including:
- Cognitive function: memory, processing, attention, focus, reaction
- Brain health: stability, inflammation, blood flow, neuroprotection
The evidence on many of these nootropics is still either lacking, not strong enough to draw conclusions, or anecdotal. Take note that most of the present data looks at animal models, while some research cognitive performance in humans. Below, we showcase potential cognitive improvements and possible mechanisms to understand the function.
Memory Recall
Memory recall is retrieving stored information from the brain, based on past events or learned information.
Bacopa monnieri (Brahmi) stands out for memory, with RCTs showing potential improvements in memory and cognitive skill in adults, (32) believed to occur due to the presence of triterpenoid saponins or bacosides. (33) In animals it reverses memory impairments, leading to improvements in memory retention and learning. (34) (35)
Lion’s Mane mushroom (Hericium erinaceus) may also offer complementary benefits for memory due to the presence of unique bioactive compounds—hericenones and erinacines—that demonstrate significant neuroprotective properties relevant to memory function. (36) (37) (38)
Multi-ingredient nootropic formulations like Bacopa, Panax Ginseng, and Coffee Fruit Extract have been shown to improve working memory performance, neural efficiency, and enhance accuracy and speed. (39)
Focus and Concentration
Focus is the active effort to direct attention to a single point, taking into consideration all relevant information around it.
Caffeine is one of the most effective natural stimulants that can increase focus and alertness, particularly in suboptimal situations like sleep deprivation. (40) (41) Due to its stimulating effect, caffeine has been combined with other nootropics like Bacopa, Ginseng, and PEA showing cognitive improvements, enhancing learning, memory, accuracy, and reduction in anxiety. (42) (39)
Disruptions in focus can be a result of overstimulation and high cognitive overload. Such hyperarousal leads to faster degradation, as it “wastes” brain’s energy bandwidth.
L-theanine is one of the supplements that may enhance the aspect of alertness, shadowing excessive arousal and easing the transition to alpha brainwave states, improving attention performance, resembling mental clarity. (43) (44) (45)
Mood Enhancement
The level of circulating neurotransmitters like serotonin and dopamine dictate a large portion of our mood, mental wellbeing, or the way one feels.
Certain amino acids like L-tyrosine and L-tryptophan (or 5-HTP) may help improve mood scores, which can greatly impact the reward pathway, dictating motivation and desire. L-tyrosine is a precursor to dopamine (hormone of satisfaction) and norepinephrine, and L-tryptophan is the precursor to serotonin (hormone of happiness). (28) (46) (47)
Lion’s Mane mushroom may also positively affect mood disorders via multiple pathways, contributing to neuronal health in regions associated with emotional regulation. (38) (36) Part of this lies in its immunomodulatory mechanisms that serve neuroprotective roles.
Another potent tool for mood enhancement might be Mucuna pruriens, due to its high L-dopa content which serves as a precursor to dopamine. Recent research from late 2024 highlights its therapeutic potential for treating depressive disorders. (48) (49)
Mucuna pruriens may offer several advantages over synthetic L-DOPA treatments, promoting similar benefits at lower toxicity and risk of side effects compared to synthetic alternatives. (48) While the evidence seems promising, researchers note the need of clinical trials in humans to draw stronger conclusions. (49)
Energy and Mental Fatigue
The brain needs a sufficient amount of nutrients to work at an optimal level. The majority of this brain energy depends on sleep, nutrition, and exercise. However, some supplements may affect the level of neurotransmitters that make us feel more focused, like caffeine masking fatigue by blocking adenosine, (40) (41) or tyrosine raising dopamine levels (50) increasing our feelings of motivation. Not every energetic sensation equals to more ATP produced by the brain.
Nutrient-wise, a large part of improving brain energy metabolism efficiency relies on sufficient levels of B-vitamins that help create energy. (51) One mechanism to increase brain’s bandwidth is to decrease stress, present as hyperstimulation which leads to excessive accumulation of glutamate—stimulatory neurotransmitter that increases excitotoxicity. (52)
Therefore, potentially effective supplements to delay brain fatigue and increase brain’s bandwidth (not direct ATP production per se) include:
- Creatine: increasing resynthesis of ATP in a high-energy demanding neural tissue
- L-theanine: reducing hyperexcitation, lowering cortisol and glutamate while stimulating alpha brainwave states
- Rhodiola Rosea: adaptation to stress by modulating the HPA axis, increasing resilience to stress
- Caffeine: blocking adenosine receptors that masks fatigue, improving alertness and focus
Neuroplasticity and Learning
Neuroplasticity—the brain’s ability to reorganize itself by forming new neural connections—serves as a fundamental mechanism for learning. Certain neurotransmitter molecules like brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are essential to maintaining and improving neuroplasticity.
While many articles on the internet cite adaptogens and mushrooms as potent stimulators of BDNF and NGF, the evidence on nootropics and neuroplasticity is still emerging, and relatively limited.
Beyond psychedelics, one mushroom that stands out for supporting neuroplasticity is Lion’s Mane. Its compounds, hericenones and erinacines, may stimulate Nerve Growth Factor (NGF) synthesis in the hippocampus. (53)
Neuroprotection
Neuroprotection refers to brain-protective mechanisms that may delay cognitive dysfunction, neurodegeneration, and brain aging. Underlying mechanisms include reducing excess glutamate, (54) improving brain circulation, (54) (55) and reducing plaque accumulation. (56)
Some supplements with promising neuroprotective potential include: *most research on animals
- Melatonin: beyond its role in regulating sleep and circadian rhythms. It acts as a powerful ROS/RNS scavenger with anti-inflammatory and immunoregulatory properties. (57)
- Flaxseed Oil: may improve hippocampal plasticity, alter GFAP expression, and modulate aspects of memory and anxiety. (58)
- Polyphenol extracts like red grape seed oil, Olews, or MecobalActive may reduce oxidative stress and inflammation. (59)
- Lion’s Mane: may increase NGF and/or BDNF synthesis in the brain, delaying cognitive decline and improving brain’s neuroplasticity.
- Curcumin: anti-inflammatory actions, reducing oxidative stress and plaque accumulation in the brain. (60) (61)
- Omega 3 FAs: anti-inflammatory actions, exhibiting strong antioxidant properties, protecting from neurotoxicity, which may mitigate neurodegeneration. (62) (63) (64)
Relaxation and Stress-Relief
Several supplements have shown promise in relieving stress and sympathetic overstimulation:
Rhodiola rosea has the potential to relieve stress-induced fatigue and depression. Clinical studies show it can significantly improve mental performance, reduce fatigue, and alleviate stress symptoms. Rhodiola works by influencing neurotransmitters (serotonin, dopamine, noradrenalin) and modulating stress-response systems. (65) (66)
L-theanine, commonly found in tea, has demonstrated potential for stress reduction and cognitive enhancement. RCT shows that four weeks of L-theanine administration (200 mg/day) significantly decreased depression, anxiety, and sleep disturbance scores. Improvements were noted in sleep latency, sleep disturbance, and reduced need for sleep medication. (67)
5-HTP (5-hydroxytryptophan) is a precursor to serotonin that easily crosses the blood-brain barrier and may increase concentrations of serotonin, melatonin, norepinephrine, dopamine, and beta-endorphins. Studies show 5-HTP supplementation can produce favorable responses in mood within 48 hours. (68)
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Most Effective Natural Nootropics List
As technology progresses, our productivity flourishes. With its rise comes an increase in cognitive load, as we need to process more information than ever. Many individuals seek natural ways to enhance cognition, memory, and mental performance to gain a competitive edge, learn faster, and get more done.
Beyond sleep, diet, and exercise which do the heavy lifting, brain function may be further optimized, enhanced, or supported by using nootropics. (69)
Caffeine
Caffeine stands as perhaps the most widely consumed natural nootropic in the world. This powerful stimulant works primarily by blocking adenosine receptors in the brain, preventing the onset of fatigue and maintaining alertness. (70) (71) (72) (73)
Benefits
- Enhanced alertness and concentration
- Improved reaction time
- Increased energy levels
- Potential memory enhancement
Caffeine is naturally found in coffee beans, tea leaves, cacao pods, and various other plants. Its effectiveness as a cognitive enhancer is well-documented, making it a staple for many individuals seeking improved mental performance.
When consumed in moderate amounts (doses of 100-600 mg), (74) (73) caffeine provides a reliable cognitive boost without significant side effects, though individual tolerance varies considerably.
Neurominerals
Neurominerals play crucial roles in brain development and brain function, serving as essential cofactors for numerous neurological processes (75) (76) (77) (78)
Key Neurominerals
- Iron: Critical for creating hemoglobin, which transports oxygen to the brain, ensuring optimal cognitive function
- Magnesium: Supports nerve transmission and helps regulate neurotransmitter activity
- Zinc: Essential for neurotransmitter function and neuronal communication
- Selenium: Provides antioxidant protection for brain cells
These minerals form the foundation of brain health and cognitive function. Iron deficiency, for example, can lead to cognitive impairment due to reduced oxygen delivery to brain tissues. Ensuring adequate intake of these neurominerals through diet or supplementation can support optimal brain function and enhance cognitive performance.
Mushrooms
Functional mushrooms have emerged as powerful natural nootropics with potential cognitive benefits.
Notable Cognitive-Enhancing Mushrooms
- Lion’s Mane: may aid in stimulation of NGF and BDNF, supporting neuronal health and potentially enhancing memory (19) (20) (21)
- Reishi: Contains triterpenes and polysaccharides that may reduce inflammation and support overall brain health (79) (80)
- Cordyceps: Improves oxygen utilization, potentially enhancing mental and physical performance (81) (82) (83)
- Chaga: Rich in antioxidants that may help protect brain cells from oxidative damage (84) (85)
These mushrooms contain bioactive compounds that support various aspects of cognitive function. Research suggests they may help improve memory, focus, and mental clarity while providing neuroprotective benefits. Their adaptogenic properties also help the body respond more effectively to stress, which can indirectly support cognitive performance.
Adaptogens
Adaptogens are natural substances that help the body adapt to stress and restore normal physiological functioning. These powerful plants and herbs can help improve resilience to both mental and physical stressors.
Key Adaptogenic Nootropics
- Ashwagandha: may reduce cortisol levels and alleviate stress and improve cognitive function (86) (87)
- Rhodiola Rosea: may enhance mental performance under stress and reduces mental fatigue (88) (89)
- Bacopa Monnieri: may improve memory formation and retention, visual processing, and reduce anxiety (90) (91)
- Ginseng: Enhances mental clarity and may protect against age-related cognitive decline (92) (93)
Adaptogens work by modulating the body’s stress response systems, including the hypothalamic-pituitary-adrenal (HPA) axis. By helping the body maintain homeostasis during periods of stress, these natural compounds can indirectly support cognitive function and mental performance. This makes them particularly useful in the modern, high-pressure environment.
Fatty Acids
Omega-3 fatty acids play a crucial role in brain health and cognitive function, influencing both communication between cells and cell function itself.
Important Fatty Acids for Cognitive Enhancement
- DHA (Docosahexaenoic Acid): A major structural component of the brain, particularly in the cerebral cortex (94)
- EPA (Eicosapentaenoic Acid): Supports brain health through anti-inflammatory effects (95) (96)
- ALA (Alpha-Linolenic Acid): Serves as a precursor to DHA and EPA
These essential fatty acids are critical for maintaining the structural integrity of neuronal cell membranes and supporting optimal neurotransmission. DHA, in particular, comprises approximately 40% of the polyunsaturated fatty acids in the brain and is essential for normal brain development and function.
Adequate omega-3 intake is key to support cognitive function, improve memory, and potentially slow age-related cognitive decline. Sources include fatty fish, flaxseeds, chia seeds, and walnuts, though supplementation is also common for those seeking cognitive enhancement benefits.
Amino Acids
Amino acids serve as the building blocks of proteins and play essential roles in neurotransmitter synthesis and brain function. (75)
Cognitive-Enhancing Amino Acids
- L-Theanine: Promotes relaxation without sedation and may enhance attention when combined with caffeine (97)
- L-Tyrosine: Supports the production of dopamine and norepinephrine, potentially improving cognitive performance under stress (98)
- Acetyl-L-Carnitine: May support mitochondrial function and energy production in brain cells (99) (100)
- L-Tryptophan: Serves as a precursor to serotonin, potentially supporting mood and cognitive function (101)
Amino acids help produce catecholamines, thus stimulating alertness. They serve as precursors to various neurotransmitters that regulate mood, attention, and cognitive function. For example, L-tyrosine is converted into dopamine, a neurotransmitter involved in motivation, reward, and focus. These compounds can be obtained through protein-rich foods or specific supplementation.
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4 Key Nutrients for The Brain
The human brain requires specific nutrients to function optimally throughout life. Modern neuroscience has identified several key nutrients that play crucial roles in brain development, maintenance, and protection against neurological disorders.
Choline
At its core, choline is a precursor to acetylcholine, a neurotransmitter vital for memory formation, learning, and muscle control. (102) Think of acetylcholine as the messenger that allows brain cells to communicate effectively.
Most nootropics promote cholinergic activity, which to an extent smoothens neural communication, allowing easier transfer of information, processing, and learning when sufficient levels are met. On the opposite, blocking or downregulating cholinergic activity impairs memory recall and working memory. (102) (103) (104)
During early development, choline’s importance is even more pronounced for brain development. (105) For adults, choline continues to play important roles in brain health.
Exercise may increase levels of choline, as it’s found to be higher in endurance-trained athletes. (106)
Omega 3
Omega-3 fatty acids, particularly EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid), play a crucial role in neural development, providing structural integrity to the brain and nerve cells.
DHA alone constitutes approximately 30% of the brain’s gray matter, highlighting its fundamental importance to neural structure. It is the predominant omega 3 that can impact numerous neurological functions including plasticity, myelination, and neurogenesis. (107)
When we consume omega-3s, we’re essentially providing our brains with the raw materials needed to maintain cellular integrity and function.
Beyond their structural role, omega-3 fatty acids demonstrate remarkable neuroprotective properties, particularly following traumatic brain injury (TBI). (108)
Omega 3’s possess a strong anti-inflammatory effect, which partly explains their neuroprotective role, downregulating neural inflammation to potentially delay cognitive decline. (109) (110)
B-Vitamins
B-vitamins play an important role in energy metabolism, converting nutrients into energy and building materials. Neural development greatly depends on B-vitamins, particularly B6, B9, and B12, which are involved in homocysteine metabolism. (111) (112)
At the cellular level, B-vitamins are essential cofactors in energy production. The brain, despite representing only about 2% of body weight, consumes approximately 20% of the body’s energy.
B-vitamins also play critical roles in the synthesis of key neurotransmitters like serotonin, dopamine, and norepinephrine which modulate mood, motivation, and cognitive function. Adequate amount of these vitamins is vital to regulate mood, as deficiencies are associated with increased risk of depression and anxiety. (113)
The synthesis of myelin—the protective sheath around nerves—depends on vitamin B12, which is essential for nerve metabolism and neural regeneration as well. (112) (114)
Fat Soluble Vitamins
Vitamin D, functioning more like a hormone than a vitamin, crosses the blood-brain barrier to influence gene expression related to neurodevelopment, neurotransmitter synthesis, calcium signaling, and neuroprotection. (115) (116) Research links low vitamin D levels with increased risk of depression and anxiety, (117) Additionally, vitamin D may exert neuroprotective effects and accelerate plaque clearance from the brain. (118)
Vitamin E serves as an antioxidant in the brain, protecting neural membranes from oxidative damage—particularly important as the brain is vulnerable to oxidative stress due to high oxygen consumption. (119) Vitamin A contributes to brain health through its role in gene expression, neuroplasticity, and maintaining hippocampal health. (120)
Fat-soluble vitamins may help maintain the complex relationship between the immune system and brain, potentially preventing neurodegeneration and cognitive decline. Together with choline, omega-3 fatty acids, and B-vitamins, these nutrients provide essential benefits to brain health, from structural support and energy production to neuroprotection and neurotransmitter regulation, influencing cognitive function and neurological resilience throughout life.
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