Cognitive Enhancers

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Summary: Coenzyme Q10 (often called CoQ10) is a vitamin-like substance used in the treatment of a variety of disorders primarily related to cellular energy production, metabolism, and oxidative injury. Research shows coenzyme Q10 to be most promising for neurodegenerative disorders such as Parkinson’s disease and certain encephalomyopathies for which coenzyme Q10 has gained a high popularity.


Introduction

What is CoEnzyme Q10?

Coenzyme Q10 (2,3 dimethoxy-5 methyl-6-decaprenyl benzoquinone) is a fat-soluble, vitamin-like quinone commonly known as ubiquinone, CoQ, and vitamin Q10. It is available in more than 100 single-ingredient and combination-ingredient products, and in 2002 it accounted for more than $200 million in sales in the United States. [R]

Coenzyme Q10 was first isolated in 1957 in beef mitochondria, and is found in highest concentrations in tissues with high energy turnover such as the heart, brain, liver, and kidney.

CoQ10 is a ubiquitous compound vital to a number of activities related to energy metabolism.

Because dysfunctional energy metabolism has been cited as a contributing factor for a number of conditions, coenzyme Q10 has been indicated in the treatment of cardiac, neurologic, oncologic, and immunologic disorders.

Although the Dietary Supplement Health and Education Act of 1994 does not allow claims for treatment of specific diseases in the United States, coenzyme Q10 has been cleared for treatment indications in other countries, such as for congestive heart failure (CHF) in Japan since 1974.

“Coenzyme Q10 (also known as ubiquinone, ubidecarenone, coenzyme Q, and abbreviated at times to CoQ10, CoQ, or Q10) is a coenzyme that is ubiquitous in animals and most bacteria (hence the name ubiquinone). It is a 1,4-benzoquinone, where Q refers to the quinone chemical group and 10 refers to the number of isoprenyl chemical subunits in its tail.

This fat-soluble substance, which resembles a vitamin, is present in all respiring eukaryotic cells, primarily in the mitochondria. It is a component of the electron transport chain and participates in aerobic cellular respiration, which generates energy in the form of ATP. Ninety-five percent of the human body’s energy is generated this way. Therefore, those organs with the highest energy requirements, such as the heart, liver, and kidney, have the highest CoQ10 concentrations.

There are three redox states of CoQ10: fully oxidized (ubiquinone), semiquinone (ubisemiquinone), and fully reduced (ubiquinol). The capacity of this molecule to act as a two-electron carrier (moving between the quinone and quinol form) and a one-electron carrier (moving between the semiquinone and one of these other forms) is central to its role in the electron transport chain due to the iron–sulfur clusters that can only accept one electron at a time, and as a free-radical–scavenging antioxidant.” – Wikipedia


Benefits & Effects

What Are The CoQ10 Benefits?

  1. Enhances and Sharpens Mental Capabilities
  2. Boosts Energy and Reduces Fatigue
  3. Boosts Mitochondrial Health & Function
  4. Reduces Stress and Free Radicals Damage
  5. Supports Fertility
  6. Combats Statin Drug Side Effects
  7. Cancer Prevention Potential
  8. Powerful Antioxidant & Neuroprotectant
  9. Protects Blood Vessels and Enhances Blood Flow

Supporting research:

Enhances and Sharpens Mental Capabilities

Coenzyme Q10 may also present significant benefits to your cognition. Studies found that individuals with higher levels of CoQ10 showed greater mental sharpness, increased mental energy, and greater performance on a variety of mental tests. In contrast, those with lower levels of Coenzyme Q10 had greater difficulty concentrating, experienced brain fog, were slower in their mental processing, and showed general cognitive decline. Some researchers suggest that taking Coenzyme Q10 early enough may decrease your chances of suffering memory loss as a result of aging.

Boosts Energy and Reduces Fatigue

Some studies also show that Coenzyme Q10 may help to reduce physical fatigue, increase energy, improve exercise capacity, and expedite recovery from exercise.

Boosts Mitochondrial Health & Function

In studies of eight to 44 patients, Coenzyme Q10 demonstrated positive trends in reducing symptoms associated with selected mitochondrial abnormalities including the mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome, Kearns-Sayre syndrome, and the myoclonus epilepsy with ragged-red fibers (MERRhF) syndrome. [R]

Reduces Stress and Free Radicals Damage

Oxidative damage (or free radical damage) of cell structures plays an important role in the functional declines that accompany aging and cause disease. As both a water- and fat-soluble antioxidant, CoQ10 has been found to inhibit lipid peroxidation, which occurs when cell membranes and low-density lipoproteins are exposed to oxidizing conditions that enter from outside the body. [R]

Supports Fertility

The antioxidant properties of CoQ10 could help improve sperm quality and reduce the decline in the number and quality of eggs in women. Supplementing with CoQ10 seems to help and may even reverse this age-related decline in egg quality and quantity.

Female fertility decreases with age due to a decline in the number and quality of available eggs. CoQ10 is directly involved in this process. As you age, CoQ10 production slows, making the body less effective at protecting the eggs from oxidative damage. [R]

Combats Statin Drug Side Effects

Statins are drugs that help lower cholesterol but often come along with a host of side effects.

Patients suffering from statin-related muscle pain, muscle strength degradation, and decreased aerobic activity can increase performance through daily intake of CoQ10 without other symptoms.

“Statin drugs can induce rhabdomyolysis (muscle death) which release rhabdomyosarcoma cells into the bloodstream, degrading other tissues. Human rhabdomyosarcoma cells treated with a CoQ10 supplement alongside simvastatin reversed muscle death and killed off remaining sarcoma cells.” [R]

Cancer Prevention Potential

Low levels of CoQ10 have been associated with up to a 53.3% higher risk of cancer and indicate a poor prognosis for various types of cancer [R]

CoQ10 plays a critical role in the protection of cell DNA and cell survival, both of which are strongly linked to cancer prevention and recurrence.

Powerful Antioxidant & Neuroprotectant

Antioxidants are necessary for neutralizing harmful compounds known as free radicals, which are created when cells undergo oxidation. Free radicals can promote cell death, mutate DNA, and damage cell membranes. CoQ10 may help to eliminate free radicals and prevent the damage they can cause. Some studies even suggest that CoQ10 may recharge other antioxidant compounds and nutrients.

Within mitochondria, coenzyme Q10 has been found to protect membrane proteins and DNA from the oxidative damage that accompanies lipid peroxidation and neutralize free radicals directly that contribute to nearly all age-related diseases (heart disease, cancer, diabetes, neurological disease, etc.). [R]

Protects Blood Vessels and Enhances Blood Flow

According to Nootropics Depot, one of the most popular companies that manufactures nootropics, CoQ10 can protect your blood vessels and enhance your blood flow. This is partly caused by preservation of nitric oxide, a signaling molecule that relaxes the arteries. This may improve overall circulation and cardiovascular health.

COQ10 can reduce the damage oxidized Low-density Lipoprotein (LDL) can do to blood vessels, as well as reduce plaque buildup in the arteries.


Mechanism of Action

How Does CoQ10 Work?

Coenzyme Q10 is vital for the proper transfer of electrons within the mitochondrial oxidative respiratory chain, whose main function is adenosine triphosphate production. Coenzyme Q10 also appears to increase adenosine triphosphate levels by preventing the loss of the adenine nucleotide pool from cardiac cells.4 Additionally, coenzyme Q10 has demonstrated activity in preventing lipid peroxidation as an antioxidant scavenger and an indirect stabilizer of calcium channels to decrease calcium overload.

Much of the basic research in support of coenzyme Q10 supplementation has focused on the CHF model. The myocardium of patients with CHF demonstrates increased oxidative stress as well as decreased concentrations of coenzyme Q10 as confirmed by tissue assays.8 These levels appear to correlate with CHF severity in the animal and human model, with coenzyme Q10 supplementation protecting against ischemia and reperfusion injury in animal studies.


Dosage

How To Take CoQ10?

The standard dose for CoQ10 is generally 90mg for a low dose and 200mg for the higher dose, taken once daily with a meal due to its reliance on food for absorption.

There generally isn’t too much of a therapeutic effect of CoQ10 supplementation (mostly taken with the ‘just in case’ mentality that pervades multivitamin supplementation), although for people who have previously experience a heart attack or damage to cardiac tissue as well as for people on statin therapy supplementation becomes much more important. CoQ10 supplements can be either the oxidized form (ubiquinone) or reduced form (ubiquinol) as both forms seem pretty equally potent in increasing circulating levels of total CoQ10 in the body. ‘Total CoQ10’ refers to the sum of both forms, since CoQ10 can readily swap between forms as it acts in the body. – Examine.com


Frequently Asked Questions

What is CoQ10?

Coenzyme Q10 (CoQ10) is a natural antioxidant synthesized by the body, found in many foods, and available as a supplement. It comes in two forms: ubiquinol, the active antioxidant form, and ubiquinone, the oxidized form, which the body partially converts to ubiquinol. Many multi-ingredient supplements contain both forms of CoQ10. In general, coenzymes support enzymes in their various biochemical functions. CoQ10 is a vital participant in the chain of metabolic chemical reactions that generate energy within cells. It is found in every cell of the body (the name ubiquinone stems from its ubiquity), but is present in higher concentrations in organs with higher energy requirements such as the kidneys, liver, and heart. Many medical studies demonstrate CoQ10 benefits when taken as a supplement, most of which stem from its vital role in oxygen utilization and energy production, particularly in heart muscle cells.

Why is CoQ10 necessary?

Coenzyme Q10 is beneficial for heart health in many ways. It assists in maintaining the normal oxidative state of LDL cholesterol, helps assure circulatory health, and supports optimal functioning of the heart muscle. CoQ10 may also help support the health of vessel walls. In addition, Coenzyme Q10 may play a role in reducing the number and severity of migraine headaches, and improving sperm motility in men. Some research has indicated therapeutic value in high doses to slow the progression of Parkinson’s disease, but a 2011 study by the National Institute for Neurological Disease and Stroke found no benefit in slowing symptoms or neural degeneration. A few small clinical trials have indicated CoQ10 supplementation may help prevent and treat inflamed gums, a condition known as gingivitis.

What are the signs of a Coenzyme Q10 deficiency?

Studies in both animals and humans have associated significantly decreased levels of CoQ10 with a wide variety of diseases. Since this enzyme is found in high concentration in heart muscle cells, deficiency has been associated with cardiovascular problems including angina, arrhythmia, heart failure and high blood pressure. Problems with blood sugar regulation, gingival (gum) health, and stomach ulcers have also been associated with CoQ10 deficiency. Those who are taking statins to lower cholesterol are at particular risk for deficiency, because not only do statins reduce cholesterol levels, but they also block CoQ10 synthesis in the body. Low CoQ10 levels in patients on statins can contribute to the common side effects of statin therapy such as fatigue and aching joints and muscles.

How much, and what kind of Coenzyme Q10, does an adult need?

There is no official Daily Value recommendation, but its suggested at least 90 to 120 mg of supplemental CoQ10 for any adult taking statin medications and for those with a family history of heart problems, or who is at increased risk for cardiovascular disease. This dosage is also appropriate for otherwise healthy men and women as a preventive measure and to help maintain a healthy cardiovascular system. CoQ10 is fat-soluble, so take the supplement with a meal containing fat. Seek out the soft-gel ubiquinol form when taking CoQ10 as a standalone supplement, as this has greater antioxidant efficiency than the ubiquinone form.

Is COQ10 harmful?

Of course not! The coenzyme Q10 (CoQ10) is vital for human metabolism, and is best known for its roles in glucose and fatty acid conversion to ATP, the form of energy used to power most body functions and as a powerful antioxidant in cells, inhibiting lipid peroxidation in cell membranes, DNA and low-density lipoproteins (LDL). Studies show that when taken daily, CoQ10 supplements are capable of significantly reducing oxidative damage. Also note that CoQ10’s levels in skin decline with age, which may also make your skin more susceptible to oxidative damage. The key thing that impacts the effectiveness of CoQ10 supplements is that many of them have relatively poor bioavailability due to limited solubility. Thus, it is helpful to go for solubilized forms of CoQ10 which allow for 90-100 percent of dissolution, and which have been improved absorption.

Summary: Modafinil is a powerful stimulant that promotes ‘wakefulness’ and treats sleep disorders. It prevents daytime sleepiness and fatigue, as well as offering nootropical benefits such as enhancing mood, increasing mental alertness, increasing motivation, improving reaction time, reducing fatigue, and even enhancing memory.


Introduction

What is Modafinil?

In use by the French army, the American Air Force, the Indian Air Force, and Canadian astronauts….. (astronauts!) (R). Modafinil is a powerful stimulant that promotes wakefulness and treating daytime sleep disorders such as narcolepsy – excessive, uncontrollable daytime sleepiness. Besides tats, it offers nootropic benefits such as enhancing mood, increasing mental alertness, increasing motivation, improving reaction time, reducing fatigue, and even enhancing memory.

As a prescription medicine, Modafinil is available in the US, Canada, the UK, and almost every developed country today. It is also available in the UAE where I had it prescribed for a month. Aside from the original name, it also sells under brand names Provigil, Modvigil, and Alertec. It’s a eugeroic (a class of medical drugs that promotes wakefulness and alertness) used to treat conditions such as narcolepsy, a disorder that decreases the ability to regulate sleep-wake cycles, as well as the effects of shift work and similar sleep disorders. It’s used off-label by students, businesswomen, men, and shift-workers due to its nootropic effects.

Modafinil, sold under the brand name Provigil among others, is a medication to treat sleepiness due to narcolepsy, shift work sleep disorder, or obstructive sleep apnea. In OSA continuous positive airway pressure is the preferred treatment. Wikipedia

Benefits & Effects

What Are Modafinil Benefits?

  1. Improves Alertness
  2. Reduces Fatigue
  3. Improves Cognition
  4. Reduces Daytime Sleepiness
  5. Enhances Learning Capacity
  6. Effective Neuroprotectant
  7. Reduces Anxiety and Anger Response
  8. Reduces ADHD and Multiple Sclerosis Symptoms

Supporting Research:

Modafinil Improves Alertness

Although its effects are comparable to amphetamines like Adderall, which produce a temporary increase in cognition, Modafinil reports providing smoother and jitter-free energy. It also has fewer side effects and better toleration. Furthermore, it has low abuse and addiction potential. I don’t think I ever heard of any “Modafinil addict.” Definitely not Dave Asprey.

Reduces Fatigue

Modafinil increases resistance to fatigue more than amphetamines, along with improving mood, motivation, and reaction time. It is also effective at reducing “impulse response,” i.e., bad decisions. A study on forty-one military subjects receiving Modafinil shows better scores in not only fatigue but also reaction time. Additionally, measurable scores are showing in performance, mood, logical thinking, and even memory. (R)

Improves Cognition

It improves cognitive function by increasing wakefulness and enhancing mental performance during a sleep-deprivation state.
A by-product of the ground-breaking stimulant Adrafinil, Modafinil acted faster and was promoted as a different drug in the 1970’s. After extensive clinical trials, Modafinil got the FDA’s approval to use as hypersomnia treatment. (R)

Reduces Daytime Sleepiness

Modafinil is useful for shift workers. It is used to help pilots staying alert throughout operations by the American military.
According to the World Health Organization, off-label users take Modafinil as a Nootropic. Moreover, with that, reports showing they get the most cognitive boost as well as most of the compelling benefits when they are not sleep-deprived. It is useful for both, still. (R)

Enhances Learning Capacity

Modafinil is powerful strengthening the ability to learn and expanding the capacity to process information. Research confirms that it reinforces mental endurance and performance, especially in cases of drug dependence and ADHD individuals. According to the clinical trials, Modafinil enhances mood, performance, response time and even memory in healthy individuals as well as those who are sleep-deprived.

Effective Neuroprotectant

Experiments further suggest Modafinil promotes brain health. In brain tissue, its inhibitors properties decrease the manifestation of damaging free radicals, thereby making it an effective neuroprotectant (R), (R), (R).

Reduces Anxiety and Anger Response

Although less of a featured trait, Modafinil seems to have the ability to reduce anxiety as well as decreasing anger. A result of the reduction it allows in the reactivity stimuli within the brain (R). There is a paradoxical study (R) for the curious cats like myself. The research shows that on the contrary, Modafinil increases aggression and anxiety in a subject taking a 100mg dose. When the treatment is doubling to 200mg, the items display a reduction in anxiety. It’s a case where less is not more and more is more.

Reduces ADHD and Multiple Sclerosis Symptoms

Modafinil is one of the standard stimulants for the treatment of attention hyperactivity deficit disorder (ADHD). Furthermore, research suggests that it is an effective treatment for memory impairment in cases of multiple cases of sclerosis. Current clinical trials measure modafinil as a treatment for conditions such as depression, psychosis, seasonal depression, and even drug addiction. It confirms that it strengthens mental performance, thereby becoming beneficial in ADHD and drug dependence. (R) (R)


Mechanism of Action

How Does Modafinil Work?

The unique mechanisms of action differentiates Modafinil effect from the traditional stimulants though they are similar. Modafinil activates neurons by focusing on the hypothalamus and amygdala, unlike amphetamine, methylphenidate, and other central nervous stimulants that only induce wakefulness by general widespread neuronal activation. The precise mechanisms of Modafinil action have not been identified regarding locating a single site of action, though it modulates the brain’s histamine, serotonin, norepinephrine, orexin, and dopamine systems. However, it is evident that Modafinil’s effect on numerous essential neurotransmitters is at the heart of its potency, both as a eugeroic and nootropic.

Orexin Neuropeptide

Orexin neurons exist in the hypothalamus but project to many different parts of the brain including several areas that regulate wakefulness. Leading cause of Narcolepsy is lack of orexin, which Modafinil addresses by acting on orexin neurons. Activation of these neurons also increases production of histamines and other important neurotransmitters that are related to wakefulness and alertness.

On Histamine

Histamine is known to allergies and local immune responses, it also plays an essential part in regulating the sleep/wake cycle. Modafinil actions elevate hypothalamic histamine, a known wakefulness mechanism.

On Dopamine

Dopamine is an essential neurotransmitter associating with stimuli/reward response, and therefore can enhance mood as well as increase motivation and focus. Modafinil works by blocking the receptors that remove dopamine from synapses, which raises levels of dopamine available for instant use in the brain. Unlike amphetamines, which stimulate the release and increase of dopamine levels in a high but rapid amplified manner. This indirect gradual action on the dopamine system is a primary feature of how Modafinil works in the brain. It decreases the “rush” type of euphoria that associates with addiction.

On Norepinephrine

Modafinil increases the availability of norepinephrine, a stimulant neurotransmitter that promotes wakefulness and increases alertness in the hypothalamus. How Modafinil increases norepinephrine levels isn’t clear.

On Glutamate

Modafinil elevates levels of glutamate, the primary neurotransmitter in the brain which is responsible for excitement, by activating the extracellular release of glutamate in the hypothalamus. Glutamate plays a crucial role in human’s psychological functions, playing a significant role in Modafinil’s enhancing effects. Such effects include increased memory, focus, and even brain modification. Not all that Modafinil has to offers is clear, but more than 40 years of extensive research reveals its powerful effects.

Pharmacokinetics

Absorption

Modafinil is well-absorbed with peak plasma concentration reached approximately two to four hours after administration. Food has no effect on overall modafinil bioavailability; however, absorption (tmax) may be delayed by approximately one hour if taken with food.

Distribution

Modafinil is moderately bound to plasma protein (approximately 60%), primarily to albumin, which indicates that there is a low risk of interaction with strongly bound drugs.

Biotransformation

Modafinil is metabolised by the liver. The chief metabolite (40 – 50% of the dose), modafinil acid, has no pharmacological activity.

Elimination

The excretion of modafinil and its metabolites is chiefly renal, with a small proportion being eliminated unchanged (< 10% of the dose).

Half-life

The effective elimination half-life of modafinil after multiple doses is about 15 hours.

For patients 6 to 7 years of age, the estimated half-life is approximately 7 hours and increases with increase in age until half-life values approach those in adults (approximately 15 hours). This difference in clearance is partially offset by the younger patients’ smaller size and lower weight which results in comparable exposure following administration of comparable doses. Higher concentrations of one of the circulating metabolites, modafinil sulfone, are present in children and adolescents as compared to adults. [R]

The electronic Medicines Compendium (eMC)

Effects in Comparison to Amphetamines

Modafinil vs Amphetamines: despite causing the lesser motor activity increase when comparing to methamphetamine, a 1997 study still reported that Modafinil is a better inhibitor of sleep drive and a producer of more periods of wakefulness. Although it is possible to get to addiction to Modafinil is also being proposed as a treatment for methamphetamine and cocaine addictions, restoring normal levels of learning ability and generally yielding more positive results than amphetamines. [R]

Effects on Exercise and Sports Performance

Modafinil enhances sports and exercise performance by the duration of time before exhaustion and reduces the feelings of fatigue. In 2004, it got banned by Anti-Doping Agencies. (R)

Effects on Cognitive Abilities

Several years of research explain that Modafinil improves a big range of psychological feature talents. From memory and fluid intelligence to each abstract and personal memory, government performance, pattern recognition, and performance on tasks that requires a high level of thinking. Further research also states that Modafinil’s effects may be most marked among low-performing subjects. Though Modafinil might end up in anxiety, clinical trials have examined that it improves mood in healthy subjects. (R) (R)


Dosage

How to Take Modafinil?

Modafinil is safe for continuous use at moderate doses (100-200 mg). Large-scale clinical trials show no significant indications of tolerance over periods of up to several months.


Side Effects

What Are Modafinil Side Effects?

Commonly reported side effect of modafinil (although minor) can include anxiety, insomnia, headache, nausea, digestion issues, dizziness, diarrhea, dry mouth, and inflammation. Many of these side effects are temporary. If they persist, its advisable to seek professional advice.


Conclusion

Everyone responds differently to nootropics, but decades of research have shown modafinil is safe, effective, and well-tolerated. If you’re into maximizing cognitive abilities and minimizing fatigue, modafinil is a nootropic worth trying. My personal experience with it has been very interesting and positive. I mostly noticed the massive interest in learning as well as the capacity to process information. Nevertheless, I still prefer Adrafinil over Modafinil, even though they are almost identical products.


Frequently Asked Questions

What is Modafinil?

Modafinil is a medication that promotes wakefulness through a variety of mechanisms. Although Modafinil is structurally like central nervous system stimulants like amphetamines, its effects and mechanisms of action are notably different. Modafinil influences the activity of the neurotransmitters dopamine, norepinephrine, glutamate, GABA and serotonin. Dopamine is one of the neurotransmitters that seems to be most strongly affected. Modafinil inhibits the reuptake of dopamine through specific dopamine transporter channels but is very selective as to which ones it inhibits. Serotonin activity increases in both the amygdala and frontal cortex with Modafinil use.

How Long Does Modafinil Stay In Your System?

Modafinil is a medication that promotes wakefulness. It’s prescribed to treat narcolepsy, hypersomnia, obstructive sleep apnea and shift work sleep disorder. Modafinil is widely used off-label as a cognitive enhancing drug. Individuals who use Modafinil as a cognitive enhancer claim that it dramatically improves focus and concentration, especially when taken to counteract fatigue. The effects of Modafinil are long-lasting compared to other medications.
The half-life of Modafinil ranges from 12 to 15 hours, although the metabolism of Modafinil can be affected by several factors, including genetic predispositions, kidney and liver health. Allergy and hypersensitivity are the only contraindications to using Modafinil. Scientists are still trying to understand precisely how Modafinil achieves its effects. Modafinil targets several neurotransmitters, including dopamine and norepinephrine.

How Long Does Modafinil Stay In Your Urine, Hair And Blood?

Depending on various factors, urinary excretion of unchanged Modafinil ranges from 0 percent to 18.7 percent. Most Modafinil is excreted as one of two major circulating metabolites: modafinil acid or modafinil sulfone. Modafinil and its metabolites may be present at testable levels in the urine for up to 30 hours following ingestion. Modafinil and modafinil acid can be tested for in plasma, serum and urine. Modafinil is not usually tested for in routine drug screenings and its use is unlikely to cause false positives for stimulants such as amphetamines.

Where to buy Modafinil?

If you’re in Abu Dhabi/Dubai, you can order Modafinil through our page here. However, if you are somewhere else, although I know a few websites that advertise it, I never have personally bought from them nor trust them enough to list or recommend them. You can try by doing a Google search, and be cautious, and learn about its legal status in your country of residence.

Further & Related Readings

  1. Adrafinil
  2. Phenylpiracetam
  3. Agmatine Sulfate

Summary: L-theanine is a natural amino acid, often called the “natural xanax”. It almost only exists in green tea leaves. It works brilliantly in unwinding and relaxing the body and brain without causing drowsiness, while reducing stress and increasing cognitive function. Due to not causing drowsiness, it is the perfect choice to combine with stimulants of any sort to take the edge off.


Introduction

What is L-Theanine?

L-theanine is a relaxing, non-sedating amino acid that is synergistic with stimulants to ‘take the edge off.’ Especially with coffee, it synergizes so well resulting in clean energy, furthermore preventing the nasty caffeine crash that many people experience after caffeine intake. It is also useful on its own, promoting relaxation and minimizing stress without causing drowsiness. A combination of L-theanine with caffeine at a 2:1 ratio is increasing in popularity as a remarkably synergetic combination that boosts cognition and attention.

It is an amino acid that naturally exists in green tea leaves as its main active ingredient, and that is the only source that provides it. It is famous for its fantastic nootropic features such as improving memory, expanding learning capacity, as well as providing a calming, zen-like effect.

L-Theanine, for the most part, is a relaxing but not sedating amino acid that is synergistic with stimulants such as caffeine as it can ‘take the edge off’. It is effective by itself in the standard supplemental dosages as well, and although it can be attained via a diet high in green tea ingestion that is the only dietary source of L-Theanine. Examine.com


Benefits & Effects

What Are L-Theanine Benefits?

  1. L-Theanine Reduces Anxiety & Stress
  2. L-Theanine Improves Memory, Attention, and Cognition
  3. Theanine Enhances Sleep Quality
  4. Promotes Longevity and Increases Lifespan
  5. Reduces Symptoms of Depression
  6. Promotes Relaxation without causing Drowsiness
  7. Significantly Reduces Symptoms of Schizophrenia
  8. Enhances Blood Flow and Stimulates Nitric Oxide Production
  9. Reduces Negative Effects of Caffeine & Improves Cognitive Boosting Effects
  10. Additional Benefits

Supporting Research:

L-Theanine Reduces Anxiety & Stress

A review by researchers of a small set of trials concluded that there are benefits of L-theanine in reducing acute stress and anxiety in people with stressful conditions. [R]

Oral intake of L-theanine in rats at feasible dosages reduces circulating biomarkers of stress with or without an actual stressor being present. Therefore, it reduces the adverse effects of stress such as memory impairment. Reductions of perceived stress reported in human subjects given oral theanine at the standard dosages. [R] [R] [R]

L-Theanine Improves Memory, Attention, and Cognition

In a 16-week long study on individuals with mild cognitive impairment, supplementing with l-theanine shows an improved delayed recognition as well as immediate recall comparing to those receiving a placebo during a mental exercise. Furthermore, attention span and alertness levels increased during the memory test. [R]

Theanine Enhances Sleep Quality

Theanine enhances sleep quality. In a study measuring sleep time with individuals supplementing with L-theanine, sleep time increases by 11 and up to 21%, therefore making it a valuable compound for achieving better nighttime sleep. (R)

Promotes Longevity and Increases Lifespan

In a study using the model organism C. elegans, L-theanine shows to promote longevity and promote healthy and increased lifespan. Due to those findings, the study suggests that the compound might have similar effects on mammals and humans (R)

Reduces Symptoms of Depression

L-Theanine intake for a period of eight weeks during an open-label study helped easing depressive symptoms, anxiety, sleep disturbance, as well as cognitive impairments in subject suffering major depressive disorder. (R)

Promotes Relaxation without causing Drowsiness

Theanine is proving to be a great agent in promoting relaxation without the accompanying effect of drowsiness. The company developing ‘suntheanine’, l-theanine supplement, won the 1998’s Food Ingredient Research Award for the outstanding research and findings. (R)

Significantly Reduces Symptoms of Schizophrenia

In persons diagnosed schizophrenia receiving 400mg L-theanine in addition to antipsychotic medication for eight weeks were able to reduce anxiety as well as psychopathology symptoms significantly. (R)

Enhances Blood Flow and Stimulates Nitric Oxide Production

Theanine appears to promote nitric oxide formation at relatively low concentrations and is likely practically relevant following oral ingestion. (R)

Reduces Negative Effects of Caffeine & Improves Cognitive Boosting Effects

Theanine and caffeine are typically found together in tea. A combination of caffeine and theanine together significantly improves alertness, reduce fatigue, and improves task-switching accuracy.

High dose caffeine (250 mg, equivalent to 2.5 cups of coffee) has some negative effects, such as jitters and increased blood pressure. Theanine was able to mitigate the increase in blood pressure.

“L-Theanine decreases the negative and jittery effects of caffeine in rats.

However, human studies found that L-Theanine helps reduce caffeine jitters, although the changes were not significant.

L-Theanine changes the pharmacological profile of caffeine in humans, as the combination of caffeine and L-Theanine have somewhat different cognitive enhancement effects. “- Selfhacked

Additional Benefits

Large studies in humans have not been undertaken; however, several smaller-scale studies (fewer than 100 participants) have shown increased alpha wave generation and lowered anxiety, along with benefits to sleep quality in people with ADHD. [R]

L-Theanine

Mechanism of Action

How Does L-Theanine Work?

L-theanine has a comparable chemical composition to glutamate, an amino acid that assists in the transmission of nerve impulses in the brain. Thereby, providing a host of benefits for the mind. It has a remarkable ability of crossing the blood-brain barrier, which means that it reaches the brain directly. Furthermore, it has positive effects on stress levels proving to increase both dopamine and serotonin levels in brain; which are two of the brain’s feel-good chemicals. Green tea is known to be effective at helping people relax due to the positive impact on those neurotransmitters.

Theanine is an antagonist of the NMDA receptors (albeit with fairly weak efficacy) and can inhibit synaptic release of glutamate via blocking the transporter competitively. Theanine may also reduce glutamate levels, but this is also a fairly weak mechanism requiring a high concentration of theanine – Examine


Dosage

How to Take L-Theanine?

The effective l-theanine dose is 200mg. For optimal nootropic results, take l-theanine with caffeine (coffee or supplement, whatever suits you) at a 2:1 ratio. As a stack, it would be:

  • L-Theanine 200mg
  • Caffeine 100mg

For those interested, you can actually purchase a supplement pre-made that has 200 mg Theanine & 100 mg Caffeine pressed into one capsule. I’ve personally used and still use Nootropic Depot’s.

Note: if you have anxiety or hypertension, you may want to skip caffeine entirely as it aggravates the symptoms.

Experimenting is the best way to find out how you react to it.


Side Effects

What Are L-Theanine Side Effects?

L-theanine is very safe as very high doses have failed to cause toxicity. However, that doesn’t mean you should go for such high dosage. (R)

L-theanine is exceptionally reliable. Furthermore, it is classified Generally Recognized as Safe by the Fraud and Deception FDA in the US.


Conclusion

L-Theanine is a natural safe amino acid offering many benefits. It’s a popular choice for individuals wanting a simple and effective way to boost their mental performance. Alone, with caffeine, or even with an advanced nootropic stack; L-theanine is worth trying.


Frequently Asked Questions


Further and Related Readings


SummaryAdrafinil is a stimulating nootropic that fights fatigue, increases the brain’s capacity of processing information, boosts energy, as well as enhances subjective well-being. It metabolizes in the body into the widely popular Modafinil (Adrafinil vs Modafinil comparison below). It’s a useful supplement for pulling through long, mentally demanding tasks, learning new topics, or working in shifts as opposed to fixed schedule.



Introduction

What is Adrafinil?

Adrafinil is a synthetic nootropic supplement that acts as a central nervous system stimulant. Previously known as Olmifon, and often mistaken with Modafinil, it is a stimulant that does not produce amphetamine-like effects.

It is a precursor to Modafinil. That means it leads to increased concentrations of modafinil in the body.  Adrafinil combats fatigue, boosts energy, improves attention, concentration and focus. It’s also known to enhance mood, motivation, and reaction time. Its potential cognitive benefits extends further to improving memory and increasing the brains capacity of learning, digesting, and processing information.

A 1970’s invention by French pharmaceutical company Lafon Laboratories, which manufactured, branded and marketed the invention in Europe under the name Olmifon. It spread throughout Europe and became widely prescribed by practitioners for narcolepsy and related sleep disorders that has symptoms of heavy and excessive daytime drowsiness. As well as widely used off-label for its nootropic and stimulating effects.

In 2011, production of Olmifon ended when the french regulating authorities reversed its legality.

Its unregulated in the US, Canada, and most other countries around the world. It’s found in drugstores and online on many vendors and is widely used for combating fatigue, enhancing energy, and boosting overall cognitive function

Adrafinil is a eugeroic that was formerly used in France to promote alertness, attention, wakefulness, mood, and other parameters, particularly in the elderly. – Wikipedia

Adrafinil vs Modafinil Comparison

Many people often compare adrafinil vs modafinil upon hearing of it. Usually because they try to get modafinil and find out its prescription medication, so they go for the non-[rescription, online-available alternative.

What popularizes it the most as a nootropic is the fact that its the closest legal, prescription-free to the “limitless” modafinil. But for those who knew and were familiar with it before this movie association know its profound effect and can differentiate between it and that of modafinil. In fact, many users actually report preferring adrafinil vs modafinil for certain, slightly different nootropic effects that each produces.

Although Adrafinil metabolizes into Modafinil after ingestion, it still requires a higher dosage to reach the level of effectiveness that one would feel from modafinil. For example, modafinil is mostly prescribed in dosages of 100 to 200 mg. Adrafinil often sells in the lowest dosage being 300mg. So in order to achieve the same concentration level of modafinil using adrafinil, one would have to be aware of this and measure the dosage following that pattern, as required.

Modafinil is often prescribed therapeutically in doses of 50mg being the lowest effective. For comparison, taking 300mg Adrafinil, which is the smallest manufacturing dose, would actually be more effective than the lowest effective dose of modafinil.

Although it cannot be an exact figure due to the fact that breakdown and metabolizing varies from each individual to another, a general and easy way of understanding and remembering the math of adrafinil vs modafinil in terms of dosages, or at least how I personally measure it when taking either one, is that that 100mg of Modafinil is more or less equals to 300mg Adrafinil.

Personal Thought

From my personal, own experience: the effect of Adrafinil 300mg  is much more felt in comparison to Modafinil 100mg. During the period I was prescribed Modafinil, I would have to take 200mg in order to achieve what I would achieve from 300mg of Adrafinil. 


Benefits & Effects

What Are Adrafinil Benefits?

  1. Increases Mental Clarity & Heightens Focus
  2. Promotes Wakefulness & Boosts Energy
  3. Improves Learning Capacity & Memory Formation

Supporting research:

Increases Mental Clarity & Heightens Focus

Although it is initially developed for its wakefulness-promoting qualities, Adrafinil continues showing significant cognitive benefits as well. For individuals suffering daytime exhaustion due to night work or sleep difficulties, adrafinil increases the physical and mental energy required for an active life. It also improves mental clarity and heightens focus.

Promotes Wakefulness & Boosts Energy

Adrafinil is an overall beneficial stimulant, preventing daytime drowsiness and dramatically increasing energy and attentiveness without the hyperactivity and jitteriness associated with stimulants. Users report a profound sense of well-being, stress reduction, and overall enrichment experiences. Those outcomes are primarily due to Adrafinil’s impact on dopamine.

Improves Learning Capacity & Memory Formation

In addition to promoting wakefulness and increasing energy, adrafinil holds many nootropic benefits such as improved learning capacity, better memory creation, as well as recollection. Reports indicate that it sharpens focus and increases the ability to maintain it, along with providing mental clarity, and easing mentally demanding work, especially that which extends over a prolonged period.


Mechanism of Action

How Does Adrafinil Work?

Adrafinil acts on the adrenergic system, the part of the nervous system that releases adrenaline. Typically considered in charge of the “fight or flight” response, a rapid release of adrenaline boosts energy and increases alertness. While not all of adrafinil’s actions are entirely understood, it is assumed to replicate the positive effect of adrenaline release by supporting adrenergic neurotransmitters.

The Breakdown

Adrafinil is a synthetic prodrug, which means that its an inactive compound that metabolizes into an active form inside the body. The process of metabolizing it produces the drug, modafinil, which is an FDA-approved treatment for necropsy and similar sleep disorders. The pharmacological effects of adrafinil are practically identical to those of Modafinil.

Though the exact chemical mechanisms of it are unclear, researchers hypothesize that in its metabolized form it functions as an adrenergic receptor agonist. One of its first actions is the enhanced production and release of the neurotransmitter hypocretin, which in turn triggers the increased production of dopamine, histamine, and norepinephrine; all of which are directly related to alertness and energy, which considerably explains adrafinil’s stimulant qualities.

The remarkable mood and cognitive effects it produces result from different actions, such as the positive modulation of glutamate receptors, and inhibiting the breakdown of glutamate. Those actions lead to better neuronal communication, which improves memory and focus and creates better cognitive functions.

Serotonin Neurotransmitter

It also stimulates the release of serotonin, which enhances mood by reducing anxiety levels. It also inhibits the breakdown of dopamine, a neurotransmitter that is mainly responsible when it comes to the brain’s pleasure and reward responses.


Dosage

How to Take Adrafinil?

Recommendations vary greatly among different users. The lowest dose Adrafinil is produced in is 300 mg. However, most nootropist would say, and prefer, a dose of 600mg taken once in the morning. And the highest yet credible dosage is 1,200mg taken as 2 doses. A morning dose of 600mg and an afternoon “boost” dose of another 600mg.

At the doses of 300 to 600mg, it is a safe and very effective nootropic. It is a potent nootropic, therefore it’s advised to give your body a chance to adapt to it at lower doses and only gradually increase as you feel required after evaluating the effect of 300mg.

Due to its potency and wakefulness-promoting properties, it is advisable to take it in the morning or early afternoon only to avoid interfering with the sleep cycle, otherwise you wouldn’t be able to fall asleep easily at night. (although that doesn’t apply to those who know that time is actually an illusion).

It is also advisable to take it on an empty stomach to allow for optimal absorption. It kicks in and effects start to be felt around 45 minutes to an hour after ingestion.

For continuous and prolonged use, it is very advisable to use on a sequence (or cycle) of two weeks on, and one week off to detox and maintain tolerance as well as prevent potential dependency for certain people.


Side Effects

What Are Adrafinil Side Effects?

The most typical side effects of adrafinil are headaches, dizziness, nausea, and stomach discomfort. The most severe relates to liver function. Additionally, there is potential for increased risk of high blood pressure and heart problems when taking high doses.

Should you experience any side effects, stop using and seek professional medical advice.


Conclusion

Adrafinil’s mixture of mental and physical benefits make it valuable for individuals looking for more energy, stamina, and psychological acuity. Its a powerful nootropic with potent stimulant qualities. Used responsibly, it offers a unique and profound nootropic boost that one grows to appreciate.


User Experience

Here is three random experiences from adrafinil reddit nootropic community on their thought of adrafinil:

I love adrafinil for a once-every-couple-of-weeks ‘I need to work 11 hours today’ usage. I can take 300mg at 6:30 or 7 in the morning, and still be alert and clear headed at the office when 7 or 8pm rolls by. But I try not to use it any more than once a week, because of the possible liver implications. – WhatAboutLightly

Adrafinil is very strange for me. I noticed somewhat sporadic efficacy. Additionally, for me, I was getting bad headaches. I called them “core headaches” as they seemed to originate from the very “core” of my brain. and not in the front like other areas. now I am still uncertain if this was because of adrafinil or phenylpiracetam. but once I started experiencing core headaches frequently even without taking any nootropic whatsoever, I quit adrafinil. It did go away after a while, but again I am not sure if this was just a rebalance or due to…other things I have been up to. Good write up though. I am not certain I can answer any of the questions since I haven’t gone back to adrafinil yet…thinking of trying modafinil if I can manage to procure it, and see if that has a cleaner, more mildly-stimulating/focusing effect like I was looking for. – multipl3x

My simple protocol for Adrafinil is to only take it if I sleep poorly. and know that I still need to perform the next day. For me that means that I take it infrequently, but it’s a lifesaver every time. – stevetheguy


Frequently Asked Questions

What is Adrafinil used for?

Adrafinil (INN; brand name Olmifon) is a eugeroic that was formerly used in France to promote alertness, attention, wakefulness, mood, and other parameters, particularly in the elderly. It was also used off-label by individuals who wished to avoid fatigue, such as night workers or others who needed to stay awake and alert for long periods of time. Additionally, “adrafinil is known to a larger non scientific audience, where it is considered to be a nootropic agent.”

Adrafinil is a prodrug; it is primarily metabolized in vivo to modafinil, resulting in very similar pharmacological effects. Unlike modafinil, however, it takes time for the metabolite to accumulate to active levels in the bloodstream. Effects usually are apparent within 45–60 minutes when taken orally on an empty stomach.

Can adding Adrafinil to a daily Adderall regimen for ADHD help?

Speaking from experience, J. Robert says: I had been taking a moderate level dose of adderall and experiencing the typical side effects associated with it. I researched Modafinil and took trail doses after discussing with my psych. I have since lessened my dose of adderall to a minimum 15 mg prn and am primarily on Armodafinil(the adrafinil/modafinil successor) now hoping to remove the adderall component in the near future. My experience has been overall positive. I am more focused cognitively without the overall body stimulant side effects I was getting from the adda. The one negative for me is sleep difficulty if the dose is taken later than upon getting up in the AM.
Trying a test dose while decreasing or eliminating the adderall might provide a better result for you cognitively. make sure you discuss with your psych

Further and Related Readings

  1. Modafinil, Phenylpiracetam, Oxiracetam
  2. The Ultimate Nootropics FAQ