Mind Therapy Center
Nootropics, the center of mind therapy, also referred to as “smart drugs,” are a variety of therapeutic substances that enhance memory, learning, and thinking in people, particularly when these abilities are compromised. This diverse group of substances has been divided into four subgroups based on their characteristics and effects: traditional nootropic compounds, substances that speed up brain metabolism, cholinergic, and plants and plant extracts with nootropic effects.
Everyone has fantasized about improving their intelligence, speeding up their learning process, retaining information better, and thinking and acting more quickly. There are substances on the market right now that promise different combinations of the aforementioned advantages. The term “nootropics” refers to this class of substances.
Although these drugs are more useful in situations where cognitive functions are obviously impaired, healthy people are still interested in them due to their capacity to boost intelligence and memory. The vast majority of these drugs are naturally occurring], do not require a prescription, and are typically available as food supplements or herbal extracts. They are somewhat harder to find in synthetic form, and some preparations do need a valid prescription to buy. Patients with cognitive impairments typically tolerate nootropics well; side effects are rare and typically mild when they do occur. Since the majority of nootropics take time to take effect after a single dose, sustained use is required to see the desired effects. On healthy people, however, it is still unclear how they will behave in the long run.
How Do Nootropics Work?
Cornelius E. Giurgea coined the term “nootropic” in 1972/1973 to refer to substances that primarily activate cognitive processes like memory and learning, particularly in conditions where these processes are impaired. They essentially disrupt the central nervous system’s (CNS) neuronal cells’ metabolism. The name is made up of the Greek words tropein, which means to lead, and nöos, which means thinking.
Nootropics have antihypoxic effects, improve the brain’s supply of glucose and oxygen, and safeguard brain tissue from neurotoxicity rather than acting directly by releasing neurotransmitters or acting as receptor ligands. Additionally, they stimulate phospholipid metabolism in neurohormonal membranes and have a positive impact on the synthesis of protein and nucleic acids in neurons. It has been discovered that some nootropics have an anti-aggregation effect, influence the removal of oxygen free radicals, and enhance erythrocyte plasticity. This enhances the blood’s rheological characteristics and enhances blood flow to the brain. These substances are metabolically active, but the majority of nootropics take a while to start working after a single dose and usually need repeated use. For them to improve brain metabolism and produce stable changes, they must be able to cross the blood-brain barrier.
Nootropics are used to treat memory, consciousness, and learning disorders in acute or subacute conditions. They are advised for brain damage that is already present and showing symptoms like memory loss, mental retardation, and changes in the nature of consciousness. The medical term for this condition is acute psychoorganic syndrome (POS). In most cases, it can be reversed, but in rare circumstances, dementia can develop. Brain injury, infection, stroke, or intoxication (alcohol, medications with a central anticholinergic effect, or carbon monoxide) can all result in acute POS. The POS group also includes delirium tremens. Chronic cognitive function disorders like mental retardation or memory loss may also be used as indicators. In these situations, nootropics are frequently administered, but their efficacy, particularly in cases of more severe dementia, is debatable. They appear to work better in people with mild cognitive impairments or what is known as benign senescent forgetting, which is a slowing of brain activity without the onset of dementia. Nootropics are occasionally used to treat attention and memory disorders brought on by exhaustion and fatigue. They are also used by patients with encephalopathy and children with minimal brain dysfunction syndrome, and their impact on myalgic encephalomyelitis (chronic fatigue syndrome) has also been studied. Patients with Alzheimer’s disease, schizophrenia, hyperkinetic disorder, or senile dementia are given nootropics as cognitive enhancers.
Typically, nootropics are very well tolerated. Their effectiveness depends on the dose size, and in practice, giving a dose that is too small is a common error. After the conscious disturbance has subsided, the course of treatment should be continued for at least two to three weeks.
Students in particular are interested in nootropics because of their alleged capacity to boost intelligence and enhance memory and cognitive functions. They are referred to as “smart drugs” among them. Since the majority of nootropics come from natural sources, students can buy them as dietary supplements or over-the-counter medications. Nootropics are also becoming more widely available online, like many other substances and medications. However, the use of nootropics by healthy people raises serious concerns because there isn’t enough clinical evidence to support their effectiveness, safety, and social effects, particularly when used over an extended period of time.
Natural vs. Synthetic nootropics: Benefits and Drawbacks
Natural drugs derived from various plant organs (such as flowers, leaves, roots, etc.) have the undeniable advantage of having a wider range of potentially advantageous pharmaceutical effects. This is a result of the complex chemical makeup of herbal drugs, which can have additive or synergistic effects. Additionally, natural nootropics typically have lower toxicity, which lowers the risk of negative side effects from an overdose. However, some substances can lessen the medicinal activity of other substances.
Because higher dosages of such a herbal drug are required to produce the desired result, plant extracts are frequently used. Additionally, there is a problem with storage, potential falsification, and authenticity verification. The benefits of synthetic compounds include their pharmaceutical purity, specificity of action, and potential for increased effect through chemical structure modification. They typically work at lower doses, but there is a higher chance of overdosing as a result.
The chemical name is 2-(dimethylamino)ethan-1-ol. In the human brain, the substance is physiologically present. Deanol is frequently promoted as a natural nutritional supplement. DMAE is found in many dietary supplements as tartaric acid salts (bitartrate salts). Fish, particularly salmon and shellfish, can also provide small amounts, especially in small amounts. Acetylcholine is the main neurotransmitter involved in learning and memory, and deanol is a choline precursor that enables the brain to produce it at its optimal level.
In vivo rat experiments, dimethylaminoethanol pyroglutamate increased the extracellular levels of choline and acetylcholine in the prefrontal cortex of the brain. It also enhanced spatial memory and lessened memory deficits brought on by scopolamine. Rats’ performance in the radial arm maze with dimethylaminoethanol cyclohexyl carboxylate fumarate was significantly improved. Humans who took supplements containing vitamins, minerals, and substances containing DMAE for three months showed improved alertness, attention, and overall mood, according to an electroencephalogram (EEG) analysis.
Additionally, DMAE enhanced sleep quality and had the power to bring on lucid dreams. Its administration has been studied in patients with minimal brain dysfunction syndrome and child hyperkinetic syndrome. The recommended daily DMAE bitartrate dosage is 500–2000 mg. It should not be used by women who are pregnant or nursing, or by people who have schizophrenia.
Two components make up the meclofenoxate molecule. The first component is a synthetic auxin, a 4-chlorophenoxyacetic acid that functions to exchange carbohydrates and is similar to the natural auxin, indoleacetic acid, found in plant cells. The previously mentioned 2-(dimethylamino)ethan-1-ol, also known as deanol, makes up the second portion of the molecule. When given parenterally, meclofenoxate is well absorbed.
In vivo (in rats), it markedly raised CNS choline levels. This rise in choline was accompanied by a rise in acetylcholine levels in the hippocampus. As a result, although it appears to be about twice as effective as deanol, its effects on the levels of choline and acetylcholine in the brain are comparable. Meclofenoxate (100 mg/kg, daily for 37 days) significantly reduced neuronal damage, proinflammatory mediator levels, and oxidative stress in rats and significantly improved memory impairment. Cerebrovascular dementia may be helped by the capacity to reduce memory impairments and neuronal damage. Meclofenoxate also improved long-term memory consolidation and mental alertness in an elderly population in a double-blind study. It might be a helpful therapeutic tool for reviving depressed cholinergic neurons and managing dyskinesias brought on by neuroleptics. Meclofenoxate is used to lessen the general slowdown in speech, thinking, and mental activity brought on by CNS intoxication and injury.
It also improves the status of qualitatively altered consciousness and has an antihypoxic effect. Additionally, it has been studied for the treatment of vascular dementia and Alzheimer’s disease. 500–2000 mg should be taken each day. It is thought that meclofenoxate is both safe and tolerable. Dizziness, agitation, nausea, and headache are a few potential side effects that can result from an overdose.
Since 1970, the ergot alkaloid nicergoline, also known as nicergoline, has been used in clinical settings. Nicergoline was first created as a vasodilator for the treatment of cerebrovascular diseases.
Current clinical applications include the treatment of vascular or degenerative syndromes marked by affective, behavioral, and somatic disorders, as well as cognitive impairment with diminished intellect. It is specifically used to treat memory loss, diminished alertness, concentration difficulties, mood swings, fatigue, and disorders of the vestibular and cochlea Nicergoline’s effects are diverse. It provided in vitro protection against -amyloid toxicity for cultured neurons.
Nicergoline has been demonstrated to be a potent medication for preventing neuronal vulnerability brought on by experimentally induced nerve growth factor deprivation, as well as improving cholinergic and catecholaminergic neurotransmitter function in rats in vivo. It promoted metabolic activity (resulting in increased oxygen and glucose utilization), acted as an antagonist of 1-adrenoceptors, increased arterial blood circulation, inhibited platelet aggregation, and had neurotrophic and antioxidant properties in rats in vivo. In mouse models of Alzheimer’s disease, nigroline also had an improvement in cognitive function. Vasodilation and an increase in cerebral blood flow were caused by nicergoline. Patients with vascular dementia have also shown it to be effective. In patients with ischemic stroke, nicergoline demonstrated a comprehensively positive impact on various facets of cerebral, systemic, and cardiac hemodynamics. Nicergoline improved alertness and information processing at the neurophysiological level in patients with multi-infarct dementia and Alzheimer’s disease, which resulted in clinical improvement at the behavioral level in both degenerative and vascular dementia, according to an electroencephalogram/event-related potential (EEG/ERP) mapping study.
The recommended dose per day is 30–60 mg. The most common side effects are headache, nausea, dizziness, diarrhea, and fainting. Nicergoline is not advised for use during pregnancy or lactation due to the lack of experience with it in pregnant women.
2-(2-oxopyrrolidin-1-yl) acetamide is the chemical name for piracetam. It is a cyclic derivative of acetamide and gamma-aminobutyric acid (GABA). Piracetam is thought to affect brain neurotransmission by altering Ca2+ and K+ ion channels, which results in a general increase in neuronal excitability. Through muscarinic receptors, it improved the action of the neurotransmitter acetylcholine. In rat models, it also affected n-methyl-d-aspartate receptors in vivo, increasing cell membrane permeability.
Additionally, piracetam has been shown to increase brain oxygen consumption, and it also increased in vivo adenylate kinase activity in the rat brain in relation to adenosine triphosphate metabolism. Cytochrome b5 is involved in the mechanism of electron transport in mitochondria, where it also increases permeability, and it appears to increase its synthesis. It enhanced interhemispheric transmission, reduced the severity of hypoxia-induced nerve cell damage, and elevated glucose metabolism in the rat brain. Piracetam has undergone tests for stroke, unconsciousness, alcohol withdrawal symptoms treatment, and alcohol-induced hypoxia prevention. Additionally, it enhanced rat models with xenobiotic-affected brain function. Piracetam improves erythrocyte plasticity, which leads to increased brain perfusion in addition to its metabolic impact on brain tissue.
Clinical applications included the prevention and treatment of post-traumatic cognitive and mental dysfunction as well as the enhancement of learning and memory abilities in children with developmental dyslexia. Oxiracetam, pramiracetam, etiracetam, nefiracetam, and aniracetam are the structural analogues of piracetam. Although their efficacy varies, these substances have similar effects to piracetam.
The recommended daily dosage of piracetam for acute treatment is 4–8 g. The maintenance dose is typically between 2-4 g/day, with kidney function taken into account. The only infrequent side effects of piracetam are insomnia, irritability, an increase in libido, and altered sexual function. With regard to piracetam during pregnancy, there is insufficient clinical experience.
Although piracetam should only be used during pregnancy after carefully weighing the anticipated benefits against the potential risks, animal studies have not revealed any teratogenic or other embryotoxic effects. It must not be used while nursing.
Pyritinol was created in 1961 by joining two molecules of vitamin B6 (pyridoxine) through a disulfide bridge. It is also known as pyridoxine disulfide or pyrithioxin (Figure 5). Similar to pyridoxine, it affects various organ systems differently; however, the CNS is the main organ system where pyritinol manifests observable pharmacological effects. Pyritinol penetrates the blood-brain barrier and builds up in gray matter, particularly in the cortex, cerebellum, cerebral nuclei, and hippocampus.
Numerous neurotransmitters have been shown to be affected in animal studies. Increased choline acetyltransferase activity was found in rat in vivo assays, which caused choline to accumulate in cholinergic neurons. Pyritinol helps the brain recover from deficits brought on by aging.
For instance, pyritinol metabolites improved cortical acetylcholine concentration and release as well as nucleic acid metabolism in the brain in old rats. In elderly diabetic rats, pyritinol oral administration either acutely or protractedly decreased formaldehyde-induced nociceptive behavior and tactile allodynia. In addition to acting as an antioxidant and enhancing cerebral circulation, pyritinol was also able to scavenge oxygen free radicals. When given to older mice, it also increased the concentration of the primary excitatory neurotransmitter n-methyl-d-aspartate. Pyritinol may be beneficial in treating learning and memory disorders brought on by malnutrition and deprivation, according to the results of a rat study. Improvements in response time tests but not in memory tests were observed in a study of healthy human males given pyritinol. Children with cerebral palsy have experienced a significant improvement in their learning capacity and motor development after receiving intramuscular injections of nandrolone decanoate and pyritinol. In human patients with cerebrovascular disorders, the combined effects of vinpocetine and pyritinol also reduced blood and plasma viscosity. Pyritinol can be used safely as an adjunct to any standard treatment of CNS diseases, such as developmental dysphasia and other cognitive disorders, for which there are currently few therapeutic options, due to its status as a dietary supplement in some nations. Even after repeated oral administration, no substance accumulation was seen, and even in patients with impaired renal function, toxic concentrations were not attained.
In real life, underdosing is typical. The amount taken should be 600 mg or more, but the minimum recommended daily dose is 300 mg, divided into three sub-doses. Non-specific skin reactions, headaches, oral mucosal inflammation, acute pancreatitis, diarrhea, nausea, and appetite loss are frequent side effects. Despite the fact that pyritinol crosses the placenta, tests on mice and rats revealed no teratogenic or embryotoxic effects.
Despite the fact that only trace amounts of pyritinol are excreted in human milk, careful consideration should still be given before administering any doses during lactation or pregnancy.
The lesser periwinkle, Vinca minor, contains the vincamine alkaloid, which is converted to vinpocetine semi-synthetically. Ex vivo studies have demonstrated vinpocetine’s ability to inhibit platelet aggregation, reduce blood viscosity, vasodilate cerebral arteries, and increase cerebral blood flow.
Vinpocetine also acts as a potent voltage-gated sodium channel blocker and a selective inhibitor of Ca2+/calmodulin-dependent cyclic nucleotide phosphodiesterase type I Ex vivo, vinpocetine improved brain cell tolerance to hypoxia and increased glucose and oxygen consumption through brain tissue. Vinpocetine changed the metabolism of glucose to more energy-efficient aerobic processes in vitro, interacted with glutamate receptors, and elevated brain adenosine triphosphate (ATP) levels.
Thus, vinpocetine provides both in vitro and in vivo significant and direct neuroprotection. For many years, this vasoactive alkaloid has been promoted as a supplement to vasodilators and nootropics to enhance memory. It is also regarded as a substance that is active in the treatment of stroke and other illnesses, such as circulatory issues in the brain.
To avoid having a hypersensitive reaction to it, it is advised that users only take 2–5 mg the first time. The dosage can then be increased to 10–30 mg per day, which has the potential to occasionally result in side effects like nausea, dry mouth, vertigo, headaches, and heartburn.
Vinpocetine use is not advised during lactation or during pregnancy.
Naftidrofuryl is a chemical ester of 2-(diethylamino)ethanol and 2-(1-naphthalenylmethyl)-3-(2-oxolanyl)propanoic acid. In order to improve walking and provide symptomatic relief, naftidrofuryl, a vasodilator with positive rheological effects on blood, has been used to treat intermittent claudication for many years/ The in vitro effects of naftidrofuryl on deoxyglucose uptake and glucose utilization have been demonstrated.
Additionally, naftidrofuryl inhibited the hypoxia-induced decrease in ATP levels in fibroblasts and endothelial cells in vitro. In vitro and ex vivo platelet aggregation caused by serotonin and epinephrine was inhibited. It inhibited serotonin-induced blood vessel contractions in mouse brains by having an antagonistic effect on platelets’ and vascular smooth muscle cells’ 5-HT2 receptors. Serotonin, also known as 5-hydroxytryptamine (5-HT), is an endogenous neurotransmitter that binds to 5-HT2 receptors, a subfamily of 5-HT receptors.
Serotonin plays a key role in atherosclerosis-causing vasoconstriction and platelet aggregation. The effects of naftidrofuryl on atherosclerosis were later demonstrated in a number of animal models. It also improved spatial information storage and exhibited nootropic effects in rats. Naftidrofuryl increased erythrocyte deformability and flow in a study conducted on human volunteers under double-blind conditions. The fact that the lactate/pyruvate ratio was reduced as a result of exercise in healthy human volunteers raises the possibility that naftidrofuryl improves the efficiency of aerobic metabolism in oxygen-depleted tissues.
Additionally, it has a favorable impact on how the neuron uses its energy. Alzheimer’s disease, senile dementia, and cardiovascular diseases are all treated with naftidrofuryl. Naftidrofuryl should be given orally at a dose of 300 to 600 mg/day in three divided sub-doses, swallowed whole, to treat patients with mild to moderate occlusive peripheral arterial disease. The metabolism of naftidrofuryl may be slower in elderly patients.
Therefore, for these patients, the dose might need to be reduced.
Naftidrofuryl is well tolerated, and it rarely causes side effects. Although the majority of these are digestive issues, liver damage has been reported once.
The compound known as dihydroergotoxine is a mixture of the methanesulfonate salts of the dihydrogenated ergot alkaloids dihydroergocornine (DHCO), dihydroergocristine (DHEC), alpha-dihydroergocryptine (-DHC), and beta-dihydroergocryptine (-DHC). One of the earliest nootropics still in use, the drug was created by Albert Hofmann in the 1940s.
It was initially used to treat hypertension, but later it was discovered, by chance, that patients with Alzheimer’s disease who were being treated for hypertension had better mental health. In rats, dihydroergotoxine stimulated local glucose utilization in the regions of the brain associated with learning and memory and increased neuronal metabolism. Patients with multi-infarct dementia between the ages of 74 and 79 have reported experiencing a similar effect. Dihydroergotoxine decreased monoamine oxidase enzyme levels, which are typically elevated in old age and modulated synaptic neurotransmission in the brains of elderly rats. Dopamine, norepinephrine, and adrenaline are catecholamine neurotransmitters that are depleted by monoamine oxidases, which are crucial for the normal metabolism of the brain. This impairs mental function.
In a rat experiment, hydergine increased the number of cholinergic receptors and controlled the release of the neurotransmitter acetylcholine from the hippocampus. Additionally, lipofuscin’s release was slowed by dihydroergotoxine, which has been linked to the deterioration of neurons in old rats. Both the peripheral and cerebral vasodilators, hydergine. It increased cerebral blood flow and oxygen consumption in monkeys.
Dihydroergotoxine shields the brain from hypoxia as well. Volunteers inhaled a mixture of gases that simulated high altitude conditions in a double-blind, placebo-controlled, quantitative EEG and psychometric study. This caused hypoxia, which decreased alertness, intellectual function, and performance depending on reaction time.
However, following the oral administration of hydergine, subjects who underwent the same conditions again experienced noticeably better outcomes. It is primarily used in elderly patients with Alzheimer’s disease, vascular dementia, and post-traumatic dementia.
It is non-toxic and generally safe, but it may cause nausea, indigestion, orthostatic hypotension, and blurred vision as side effects. It should not be used if you have hypotension, psychosis, or a slow heartbeat.
Low doses are frequently used in real life. Up to 6 mg per day is suggested. The effect of ergot alkaloids is enhanced when combined with piracetam and xanthine derivatives, which have bronchodilator and vasodilatory effects, respectively.
Phosphatidylcholine is a member of the class of substances known as phospholipids, which make up the majority of the lipids in cell membranes. Commercial lecithin is an oil-based mixture of these phospholipids. Phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, and phosphatidylglycerols are the other ingredients that are most common in supplements that contain lecithin. Palmitic, oleic, and linoleic acids are examples of fatty acids found in lecithin that are ester-linked to phosphatides. Soybean and sunflower oils are the main sources of lecithin used in commercial products today. Additionally, lecithin can be found in nut kernels, whole grain products, liver, and egg yolk.
As a precursor for the synthesis of acetylcholine, choline is slowly released from lecithin in accordance with the proposed mechanism of action. Lecithin’s mechanism of action seems to be obvious, but clinical trial results on its efficacy were less than convincing.
According to in vivo research findings, giving phosphatidylcholine to mice with a dementia model increased acetylcholine levels in the brain and enhanced memory. Lecithin does not appear to be beneficial in the treatment of Alzheimer’s and Parkinson’s disease patients, according to the findings of randomized in vivo studies. The data imply that inconsistent results may be caused by an inability to control the subject’s learning levels.
Supplemental phosphatidylcholine may not always improve memory, which raises the possibility that the dosage and duration necessary to produce a therapeutic effect may depend on factors unique to each individual subject. In comparison to healthy subjects with normal endogenous choline levels, students who have low levels of endogenous choline may experience a greater increase from phosphatidylcholine supplements, leading to a measurable improvement in explicit memory.
The fact that a person needs a higher concentration of lecithin in their blood to have a positive effect as they age is likely related to many signs of aging. Lecithin should be taken for prevention in doses of 1200 mg three times per day. The dosage for patients should be at least 10-15 g/day.
Panax Ginseng, or Ginseng
Ginseng is processed in one of two ways, depending on the amount of active ingredients and the strength of the therapeutic effects desired. It can be altered by peeling and drying the root, in which case it is known as white ginseng, or by steaming the root without peeling, in which case it is known as the “hotter” red ginseng.
Nitric oxide (NO) production has been demonstrated to be stimulated by ginsenosides in a number of systems. Human aortic endothelial cells cultured in vitro with purified ginsenoside Rb1 were induced to produce NO. The vasorelaxant and mildly hypotensive effects of ginseng are caused by its impact on the NO pathway.
In vivo, ginseng boosted the activity of the antioxidant enzymes glutathione peroxidase and superoxide dismutase in rats. In order to avoid increased oxidant accumulation and age-related oxidative protein and nucleic acid damage, supplements are recommended. In a rat model, ginsenoside also decreased simulated Alzheimer’s disease. As a result, it might someday be applied as a therapeutic agent for people who suffer from memory loss. By significantly increasing the expression of proteins linked to synaptic plasticity in the hippocampus, such as synaptophysin and n-methyl-d-aspartate receptor subunit 1, ginsenoside Rg1 supplementation improved the performance of old mice in the behavioral test.
Rats’ memories were enhanced by oral administration of a mixture of Ginkgo biloba and Panax ginseng extracts. Data on the effects of study drugs on rats suggested that a serotonergic transporter was involved as an important neurochemical correlate of rat behavior and memory effects. Ginseng has what is known as an adaptogenic effect on the human body. It reduced fatigue, improved the organism’s physical and mental toughness, and assisted the body in molding itself to any present requirements.
It is advised to take a standardized ginseng extract for a prolonged period of time at a dose of 200 mg per day. Ginsenoside concentrations are standardized and typically range from 1.5 to 7%. As an alternative, taking 0.5 to 2 g of dry root of ginseng every day is advised. Ginseng should not be taken by people who have hypertension or acute asthma. In excess, it can stimulate the body excessively, resulting in restlessness, insomnia, anxiety, high blood pressure, difficulty concentrating, headaches, and nosebleeds.
From early spring to late summer, the leaves and ripe fruit are harvested. To make alcohol extracts (tinctures), leaves are either dried and ground. Ginkgo kernels that have been hulled and roasted are also eaten. Free radical scavenging for antioxidant activity, antagonistic effects on platelet-activating factor, vasodilation, and a general decrease in blood viscosity are some of the mechanisms of action of Ginkgo biloba compounds.
Ginkgo biloba extract had specific neuroprotective effects that were demonstrated in an ex vivo rat study, and these effects may be helpful in treating chronic cerebral hypoperfusion. The pharmacological action of the extract involved cholinergic system and inflammatory mediator modulation. Ginkgo biloba extract contains triterpene lactones (ginkgolides A, B, C, and bilobalide) that have anti-oxidant, anti-inflammatory, and neuroprotective properties.
Additionally, the extract had an antagonistic effect on glycine and GABA type A receptors in a mouse experiment. Working memory and information processing speed significantly improved in a double-blind, placebo-controlled clinical trial where participants underwent validated neuropsychological tests before and after treatment with Ginkgo biloba extract.
On the other hand, a critical analysis of the data from several randomized clinical trials failed to produce compelling evidence that Ginkgo biloba extracts, whether taken in a single dose or over an extended period of time, had a positive impact on any aspect of cognitive performance in healthy human subjects under the age of sixty. Nevertheless, Ginkgo biloba extracts are frequently prescribed to treat neurological disorders and cerebral dysfunction. Standardized Ginkgo biloba extracts (24% flavone glycosides and 6% terpene lactones) should be taken in doses of 120–300 mg daily.
Regular dosages have not been associated with any negative side effects, but excessive consumption can occasionally cause mild stomach discomfort and headaches. People taking certain anticoagulants shouldn’t take the medication prior to surgery because it thins the blood.
Centella Asiatica, also known as Asian Pennywort
Traditional medicine uses of centella are numerous and vary by region. Fresh leaves are eaten as a salad, as a component of curry spice blends, or cooked as a vegetable in the countries of origin. a C. extract in ethanol. asiatica modulated the antioxidant defense system in cells in vitro, including superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glutathione and glutathione disulfide levels, to protect against amyloid-induced aggregated neurotoxicity.
The traditional remedy asiatica has potent antioxidant properties that lessen the buildup of amyloid in the brain. The primary component of the senile plaques and neurofibrillary tangles found in the brains of Alzheimer’s patients is amyloid-. This demonstrates C’s possible therapeutic and preventive benefits. Pure asiaticoside and methanol or ethyl acetate extracts of Centella asiatica were found to have anxiolytic activity in in vivo tests on rats in a maze that monitored social interactions, locomotor activity, and cage tests. Additionally, asiaticoside had no effect on locomotor activity, indicating that it has no sedative properties. The protective effect of Centella asiatica against anxiety brought on by lack of sleep, oxidative damage, and neuroinflammation has been demonstrated in another in vivo study in mice. This study also suggested that a NO modulating mechanism may be involved in this effect. An aqueous extract of C. demonstrated the nootropic effect in a study on young adult and juvenile mice. asiatica. Hippocampal CA3 neurons’ dendritic arborization and acetylcholinesterase activity were both elevated as a result of the treatment. therefore, C-treatment. asiatica can influence neuronal morphology and support brain function during the postnatal developmental stage.
The recommended daily dosage of vitamin C. Approximately 600 mg of dried leaves, or 60 to 120 mg of standardized vitamin C extract, make up asiatica. triterpenoid glycosides) (contains at least 85% of these compounds). Clinical studies indicate that oral administration of Centella extracts is generally well tolerated, and there are no known interactions with other medications.
Despite the fact that there have been no teratogenic effects reported, the medication should not be used while pregnant or nursing. It is also not advised for use by children.
Withania Somnifera, or Ashwagandha
The leaves and roots are harvested and primarily used in dried form. The leaves are used to make an infusion, and the root is used to make a decoction. Fruit can occasionally be taken as an emetic. Ashwagandha was found to increase the amount of hemoglobin, platelets, red blood cells, and white blood cells in a mouse study. Greater maximum aerobic capacity is ensured by an increase in red blood cells, which also increase the blood’s capacity to transport oxygen to the peripheral system.
Another study used rats as a model for tardive dyskinesia, a condition marked by involuntary neurological triggering that causes repetitive, spontaneous body movements like grimacing, sticking out the tongue, and lip movements that were simulated by reserpine injection. The pathophysiology of this illness involves lipid peroxidation products and oxidative stress.
Withania somnifera root extract was given to the rats over an extended period of time, and it significantly decreased lipid peroxidation, restored low glutathione levels, and undid the decline in brain superoxide dismutase and catalase levels brought on by reserpine treatment. As a result, Withania somnifera root extract may be an effective medication for treating tardive dyskinesia brought on by drugs.
The nootropic effect of ashwagandha and its potential as a treatment for Alzheimer’s disease have been confirmed by numerous studies in animal models. Another study found that the bioactive substance withaferin, a steroidal lactone belonging to the withanolides family, had potent anticancer properties both in vitro and in vivo. The recommended dosage ranges from 6 to 10 g of ground ashwagandha roots per day, which is equal to 750 mg to 1250 mg of extract. When a woman is pregnant or has hyperthyroidism, ashwagandha is not advised.
When taken at the recommended dosages, the medication is comparatively safe. Because gastrointestinal issues and vomiting can result from overdoses, treatment should begin with low doses and be gradually increased. Due to the herbal extract’s potential to act as a sedative in high doses, ashwagandha is best consumed in the evening.
It is occasionally used as a leafy vegetable in salads or soups in nations where it grows naturally. Bacopa monnieri methanol extract significantly reduced the harm caused by high NO concentrations when applied to rat astrocytes in vitro. The study findings supported the antioxidant activity of Brahmi plant extract, which has been proposed to produce NO by an enzyme-independent mechanism when stimulated by superoxide radicals.
An alcoholic extract of Bacopa monnieri was administered to albino rats, which resulted in increased protein kinase activity and an increase in protein in the hippocampus. The extract has enhanced memory retention and cognitive function, which has improved learning overall.
Bacosides A and B, a combination of two saponins, have been found to be the chemical compounds in this facilitating effect. In comparison to control mice, the expression of choline acetyltransferase in the hippocampus was examined in olfactory bulbectomy mice. Olfactory bulbectomy decreased cholinergic activity, which in turn decreased the expression of choline acetyltransferase in the hippocampus.
Bacopa monnieri alcohol extract was then administered, which reversed this effect and gradually improved the induced cognitive dysfunction. Bacopa monnieri alcohol extract enhanced escape latency in the Morris water maze test in a rat model of Alzheimer’s disease.
Additionally, the density of cholinergic neurons and the loss of neurons were both lessened. Research suggests that the herb Bacopa monnieri is a cognitive enhancer and neuroprotectant and may function as a potential adjunctive drug for treating Alzheimer’s disease because it inhibits the degeneration of cholinergic neurons.
Adults should take 5–12 mL of the liquid extract of Bacopa monnieri per day, while children aged 6–12 should take 2.5–6 mL. It is suggested that adults take 200–400 mg in divided doses of bacopa monnieri extracts standardized at 20% content of bacosides A and B and children take 100–200 mg daily in divided doses. There have not been any severe side effects reported. After consumption, mild sedation or digestive issues may sporadically occur.
Paullinia Cupana, the Guarana
At full maturity, the seeds, also known as “guarana nuts,” are harvested. They are first roasted, then mechanically crushed, sieved, and combined with water to create a bitter paste with a lot of caffeine. Guarana paste and hot water are simmered to create a coffee-like beverage. Additionally, guarana paste is added to syrups, and different alcoholic and non-alcoholic drinks are made from it. These drinks are primarily popular in Brazil. Guarana paste may occasionally be dried, powdered, and used to make tablets.
Guarana was found to have anxiolytic and panicolytic effects in an in vivo study where rats were repeatedly given the aqueous fraction of Paullinia cupana seeds before being put in a T-maze, a model of generalized anxiety and panic disorders.
The Morris water maze test was used to examine the effects of long-term administration of Paullinia cupana seed extract by gavage to rats at various doses on their cognitive behavior.
Rats with scopolamine-induced amnesia and controls showed the same results. Guarana suspension-fed mice significantly increased their physical stamina in response to stressful situations like forced swimming. A passive avoidance test in rats and mice showed that guarana partially reversed the amnesic effect of scopolamine after both single and chronic administration, indicating a beneficial effect on memory development.
According to studies, ingesting processed Paullinia cupana seeds had a sizable nootropic effect. A useful adjunct therapeutic option for treating or preventing memory deficits like those seen in Alzheimer’s or Parkinson’s disease may be provided by herbal medications that exhibit this property.
A tablet containing 75 mg of guarana extract, or about 12% caffeine, is the usual dosage. Guarana should not be consumed by anyone who has heart disease, is pregnant or nursing, has diabetes, insomnia, mental health issues, stomach ulcers, or who is taking theophylline.
The root is used as a tincture, as well as being powdered and made into tablets. It is also occasionally used to inject the above-ground components. Eleuthero has been shown to have antioxidant and antiradical properties in vitro, including the ability to inhibit lipid peroxidation.
An eleuthero aqueous extract reduced acute stress in mice during an in vivo study. The effects of an aqueous extract from eleuthero leaves on memory function were investigated in a study using healthy mice.
These in-vivo studies demonstrated that oral administration of the extract enhanced memory functions, and ex vivo studies supported the idea that the extract’s active ingredients, such as eleutheroside M and ciwujianoside B and C3, could pass through the BBB and exert their effects on the brain. This trio of substances, along with the leaf extract, exhibited dendritic elongation activity against primary cultured cortical neurons, which may be connected to better memory.
Additionally, studies on healthy volunteers found that the eleuthero active ingredients have an impact on lipid metabolism, physical fitness, and cell defense. Chronic lead poisoning in mine workers has been treated using the extract’s detoxifying properties. Additionally, Siberian ginseng has been applied to cosmetics. Eleuthero is to be taken orally once or twice daily in doses of 2-3 g of dried root or an equivalent preparation.
According to the Russian Pharmacopeia, a standardized liquid extract of the roots and rhizomes of Eleutherococcus senticosus is currently offered as an over-the-counter medication in a ratio of 1:1 with 40% ethanol (10 mg of the extract is equivalent to 120 mg of the crude herb). In the Russian medical system, an adult should take 20–40 drops of this extract orally each day.
However, more study is required to determine the best dosing schedule to enhance the cognitive function and physical performance of healthy adults. Rarely do side effects occur. Eleuthero raises blood pressure, so it is not advised to use it if you have hypertension.
Older plants’ rhizomes and roots are collected, dried, and then used to prepare extracts. An in vitro investigation found that the phenylpropanoid glycoside salidroside, which was isolated from R. rosea L., demonstrated a protective effect in cultured PC12 neuronal cells against hypoglycemia and serum-restricted cytotoxicity, most likely by altering the expression of genes linked to apoptosis, restoring the potential of the mitochondrial membrane, and reducing the generation of intracellular oxygen radicals. The effects of a single oral dose of R’s aqueous-alcoholic extract—which was made by extracting plant material with 2% ethanol diluted with tap water—were examined in an in vivo study. mice’s CNS activity was affected by rosea containing 1% salidroside and 3% rosavin. Predictive behavioral tests in the animal model were used to assess the extract’s adaptogenic, antidepressant, anxiolytic, nociceptive, and locomotor activity at different doses.
According to the finding, this extract significantly induced adaptogenic, antidepressant, anxiolytic, and stimulating effects; however, the effects were not dose-dependent. A different trial looked at R’s impact. pink L. In moderately anxious students, the effects of the extract on mood, anxiety, stress, and cognition were assessed. After receiving treatment for two weeks, the experimental group demonstrated a significantly lower level of anxiety, stress, anger, confusion, and depression as well as an improvement in general mood compared to the control group.
However, there was no discernible difference between the groups in terms of cognitive performance. For long-term use, 100–170 mg of rhodiola extract per day was recommended, with a rosavin content of 3.6–6.14 mg per weight of the extract. This would indicate consuming 360–600 mg of standardized Rhodiola rosea extract with 1% rosavin per day.
So far, no harmful side effects have been found. It is not advised for patients with manic-depressive psychosis because it affects human nature.
Children, women who are expecting or nursing, and people with high blood pressure should also avoid taking rhodiola.
Fruits and seeds are frequently used components. Crushed seeds can be used to make a tincture, and dried berries, shoots, and leaves can be used to make a tea. The fruits are consumed dried or marinated in sugar or honey to make jam, syrup, juice, or compote. They may also be frozen for storage. In addition to syrups and juices, a strong sweet wine can be made from the juice of the berries.
Schisandra fruits are known to the people of the Far East primarily as a tonic and stimulant against fatigue and exhaustion. An in vitro study was performed to determine the neuroprotective effects of dibenzocyclooctadiene lignan, schisantherin A, from the fruits of Schisandra chinensis against selective dopaminergic neurotoxin 6-hydroxydopamine-induced neural damage in human neuroblastoma cells. Pretreatment with schisantherin A provided neuroprotection against induced cytotoxicity, regulated the intracellular accumulation of reactive oxygen species and inhibited NO overproduction by reducing the overexpression of inducible nitric oxide synthase in cells.
In other in vitro and in vivo experiments, SH-SY5Y (human neuroblastoma) cells were incubated with 1-methyl-4-phenylpyridinium ion, and mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine were used to determine neuroprotection of schisantherin A. Pretreatment with schisantherin A significantly inhibited the induced cytotoxicity in SH-SY5Y cells.
In addition, schisantherin A provided significant protection against induced dopaminergic neuronal loss in a mouse model of Parkinson’s disease. These findings demonstrate that schisantherin A may have potential therapeutic value for oxidative stress-related neurodegenerative disorders, such as Parkinson’s disease. In vivo cognitive tests such as the Morris water maze and the passive step-down avoidance tests were performed with rats given oral doses of aqueous or 95% ethanolic extract of Schisandra chinensis (petroleum ether fraction) and showed that the extract could partially reverse the effects of decreasing activity of superoxide dismutase, catalase and the overall antioxidant effect induced by d-galactose, and to maintain normal levels of glutathione, malondialdehyde and nitric oxide in serum, prefrontal cortex, striatum, and hippocampus. The extract improved the overall induced cognitive deficit.
The optimal dose of dried schisandra fruit for human administration is 2–6 g per day. For an average human body weight of 60 kg, the dose is 0.03–0.1 g of fruit per kg of body weight. No serious side effects have been reported. Side effects have only occurred after regular ingestion of excessive amounts of fruits and included restlessness and insomnia.
Maca (Lepidium Meyenii)
Maca root is consumed either fresh or dried and has a distinctive taste and aroma. In South America, a sweet porridge or pudding called mazamorra de maca is made from dried roots, while the fresh root is cooked like potatoes. It can also be ground into flour, with a composition similar to cereal grains. A slightly alcoholic beverage called maca chica is made from the maca plant. Many growers mix and grind the leaves with the roots.
Polysaccharide fractions from maca leaves showed different in vitro scavenging capacities on 2,2-diphenyl-1-picrylhydrazyl, hydroxyl, and superoxide anion radicals. Researchers have recently been interested in the neuroprotective effects of Lepidium meyenii. Experiments in vivo and ex vivo tests have shown the effect of Lepidium meyenii in reducing latency in untrained and trained mice. In the swimming strength test, maca shortened the immobility time. It also increased the uterine weight of mice after ovariectomy. Lepidium meyenii appeared to positively affect latent learning in ovariectomized mice and exhibited antidepressant activity. Maca improved cognitive function, motor coordination, and endurance in middle-aged mice, increased mitochondrial respiratory function, and upregulated proteins associated with autophagy in the cortex.
These findings suggested that maca might be an effective functional food to slow age-related cognitive decline.
The optimal dose has not been determined; however, the amount of maca root powder used in many studies was in the range of 1.5–3 g per day for the average human adult.
So far, no serious side effects or contraindications to the extracts have been reported. Maca seems to be safe, effective, and non-toxic.
Nootropics are a heterogeneous group of drugs that affect the metabolism of neuronal cells in the central nervous system. They mainly improve cognitive function, especially in cases where there is damage or degeneration.
Most of these substances do not have an immediate effect after a single administration and must be used for some length of time before there is a measurable improvement. They are used in acute, subacute, and chronic conditions of memory, consciousness, and learning disorders and as a supportive treatment in patients with Alzheimer’s disease, schizophrenia, hyperkinetic disorder, or senile dementia.
Nootropics are usually very well tolerated. Side effects are rare and typically mild, but some complications can occur. For example, people with cardiovascular disease should not use guarana. This is probably due to the relatively high caffeine content. The available literature suggests that the cardiovascular effects experienced by those consuming up to 600 mg of caffeine per day are, in most cases, mild, transient, and reversible, with no permanent adverse effect. A typical dose of guarana is 75 mg of extract (approximately 12% caffeine) taken as a tablet. Each such tablet, therefore, contains an average of 9 mg of caffeine. Therefore, in order to get close to the limit of 600 mg of caffeine, a person would have to consume around 66 of these tablets per day. A nootropic that could help in this case is naftidrofuryl, which functions as a vasodilator with rheological effects on the blood and is directly used in treating cardiovascular disorders.
Some nootropics can also affect psychiatric problems; for example, rhodiola is not recommended for patients with manic-depressive psychosis, and dihydroergotoxine is also contraindicated in psychosis.
An expert should be consulted before the use of any of these nootropics. Ginseng and eleuthero are contraindicated in patients with hypertension. Ginkgo causes blood thinning, so people taking certain anticoagulants should not take it, for example, before surgery. Additionally, ashwagandha is best taken in the evening because it can act as a sedative in large doses. It is also indicated by its Latin name Withania somnifera, where the Latin species name somnifera means “sleep-inducing.”
Therefore, nootropics users should consider their state of health and mood before deciding to try a certain compound; however, if the recommended dosage is followed, no serious complications should occur.