Gabapentin aka Neurontin – is an analog of GABA (Gamma-aminobutyric acid) and it has been sold as a medicine since 1993. It is also used as a recreational drug. It is often used with Phenibut. People usually call them GBP (Gabapentin and Phenibut), or GPP (Gabapentin and Phenibut powder).
I would like to start this article by saying that Gabapentin is not the same as Phenibut. Although they are both analogs, Gabapentin doesn't have an affinity for GABA receptors at all.
I'm going to show you how Gabapentin works in your brain and why it doesn't have any effects on GABA receptors.
Phenibut on the other hand does have an affinity for GABA receptors, which means that the substance actually binds to the receptor molecule, blockading it from binding with another molecule.
This is how Phenibut produces effects. It doesn't bind with every GABA receptor, but just the ones that are responsible for anxiety, sleep, memory, and sedation.
History of Gabapentin
The first clinical use of Gabapentin was in the early '90s as an analgesic (pain reliever), and anti-convulsant. It achieved a lot of popularity when it was found to be useful in the treatment of epilepsy and neuropathic pain.
Gabapentin is not approved by the FDA for any indications yet, but it has been granted orphan drug status since 2003 due to its potential as a treatment for epileptic children with Dravet Syndrome.
Its orphan status means that pharmaceutical companies have to conduct research in order to get FDA approval.
History of Phenibut
Phenibut was developed by Russian scientists in the 1960's. By the early '70s, it was already in use as a sedative, painkiller, neuroprotective and anti-alcoholism medication.
It remained a popular medication for a long time until its popularity began to fade out in the '80s due to liver damages that were reported as a result of phenibut consumption.
Around this time there was also an outbreak of synthetic Phenibut analogs on the market which led to many negative experiences among people who were using them.
The negative experience led to a further decline in the popularity of phenibut because people believed that all products containing phenibut could be potentially harmful and lead to liver damages.
Fortunately, modern scientific research has shown that only certain types of phenibut analogs are dangerous and can cause liver damage.
Phenibut has been proven effective for many conditions both emotional and physical:
Anxiety disorders
Depression
Posttraumatic stress disorder (PTSD)
Pain management including neuropathic pain (nerve pain)
Insomnia including sleep apnea (respiratory pauses during sleep).
The use of Phenibut for any of these purposes has not been FDA approved yet, since it's only an analog of GABA and has no affinity for the GABA receptors. At this point, there is no way to know how safe it is.
Here are some well-known side effects of Phenibut:
Stomach discomfort or pain
Liver problems such as jaundice (yellowing of the skin)
Nausea and vomiting have been reported to be very common with Phenibut consumption. It's possible that these side effects are really related to the Diazepam contained in the phenibut tablets sold on the market.
However, it's well known among users that phenibut can cause nausea and even vomiting when dosed at higher doses than usual, which means that people who consume phenibut should start with a lower dose.
Phenibut vs. Gabapentin
Phenibut and Gabapentin are not the same, but they are often used in the same cycle. It has been shown that people who use Phenibut regularly can build a tolerance very quickly.
They usually need to increase their dosage to experience the same effects as before.
Gabapentin is sometimes used in a Phenibut cycle because of its ability to reverse tolerance and reduce withdrawal symptoms and cravings.
Gabapentin affects GABA A receptors in a similar way as GABA itself does. It binds to the receptor molecules without activating them and blocks them from binding with another molecule, which means that Gabapentin doesn't produce any effects on its own.
The main reason why Gabapentin is useful as an additive in Phenibut cycles is that it enhances GABAergic effects by increasing the affinity for the GABA receptor of other molecules such as Phenibut, alcohol or benzodiazepines for example. It does this by enabling Phenibut to bind more easily with the receptor molecules.
Using Gabapentin and Phenibut together in the same cycle can minimize tolerance, improve sleep quality and reduce anxiety. It can also be used as an alternative to other medication that is responsible for liver damage.
In the ever-evolving world of nootropics, it's easy to get lost in the myriad of synthetic compounds and lab-derived formulas. But sometimes, nature presents us with brain-boosting marvels that have stood the test of time. One such gem is the Lion's Mane Mushroom, scientifically known as Hericium erinaceus.
As an avid researcher and self-experimenter in the nootropic space, I've always been drawn to substances that offer cognitive enhancements without straying too far from nature's blueprint. Lion's Mane piqued my interest not just because of its historical significance in traditional Eastern medicine but also due to the mounting modern scientific evidence supporting its brain-health benefits.
In today's world, where information is abundant but genuine knowledge is scarce, my commitment is to provide you with an evidence-based review. A review that not only leans on ancient wisdom but also aligns with contemporary scientific literature. This dual lens ensures that while we benefit from time-tested practices, we're also making informed decisions based on the latest research.
In this comprehensive review, we'll explore the depths of Lion's Mane Mushroom — from its origins and traditional uses to the cutting-edge research illuminating its potential as a powerful nootropic.
What Is Lion's Mane Mushroom?
The intriguing world of fungi has always been a source of wonder and discovery. Among the vast varieties, Lion's Mane stands out, not just for its unique appearance but for its history and therapeutic potential.
Lion's Mane Mushroom, known scientifically as "yamabushitake", is a treasured find across various countries. Especially prevalent in Asian regions like China, its reputation transcends its use as a food source. Thanks to numerous researchers like Fung ML, Wong KH, Lim LW, Naidu M, and more, there's now an expanding body of knowledge on this wonder fungus.
Scientific Classification, Nootropic, and Neurotrophic Mechanism
Lion's Mane Mushroom, Hericium erinaceus, belongs to the tooth fungus group. This edible mushroom is native to North America, Europe, and Asia. Aptly named for its cascading spines that resemble a lion's mane, this mushroom grows predominantly on dead or dying hardwood trees.
For centuries, Lion's Mane has held a special place in traditional Chinese and Japanese medicine. Renowned for its health-boosting properties, it was often consumed as a tonic to improve overall vitality. But its most revered benefit lay in its potential to enhance cognitive functions and nerve health. Ancient practitioners believed in its power to fortify the mind, improve memory, and increase clarity of thought.[1]
The relevance of Lion's Mane in the nootropic community primarily stems from its unique set of compounds known as hericenones and erinacines. These compounds have been found to stimulate the synthesis of Nerve Growth Factor (NGF).[2] NGF is a protein that plays a crucial role in the growth, maintenance, and survival of nerve cells, or neurons.
The promotion of NGF can lead to improved cognitive functions, potentially acting as a buffer against neurodegenerative diseases. This NGF-promoting property sets Lion's Mane apart in the world of nootropics, making it a valuable asset for cognitive health.
Nutritional Value and Culinary Delight
The fruiting body of the Lion's Mane, often found on beech and oak trees, boasts a unique flavor reminiscent of seafood. Besides its culinary appeal, it is laden with polysaccharides, vitamins, and various nutrients beneficial for nutrition.
Whether incorporated into dishes, tea, or coffee, or consumed in powder or supplement form, it adds a dash of health in every type. When shopping at grocery stores, it's vital to read instructions on the page or site for proper preparation and usage.
Therapeutic Properties and Research Insights
Researchers such as Inatomi S, Azumi Y, Chong PS, Sabaratnam V, and others have done extensive studies.[3] Their findings suggest that the Lion's Mane exhibits several activities beneficial for human health. Here are a few:
Brain Function and Cognition: One of its standout properties is enhancing brain cells and cognition. Adults who consume it regularly have reported improved nervous system functions. The mushroom’s polysaccharides are believed to play a crucial role in this.
Anti-bacterial and Ulcers: This mushroom exhibits strong anti-bacterial activity, particularly against H. pylori, a bacteria responsible for stomach ulcers.
Heart Disease and Cholesterol: Studies hint at its potential in reducing cholesterol levels, making it a candidate for combating heart disease.
Sleep Disorders and Therapy: Some adults have reported better sleep patterns, hinting at its potential therapeutic use in sleep disorders.
Anti-cancer and Anti-oxidation: Research is underway regarding its potential against cancer, obesity, and its anti-oxidation properties.
Considerations and Advisories
However, like all herbs and supplements, there are factors to consider:
Bleeding and Blood Clotting: There's a potential risk that it might interfere with blood clotting. If you're on medication for bleeding disorders, consultation with a healthcare provider is paramount.
Pregnancy: There’s limited data on its effects during pregnancy. It's always prudent to seek advice before consumption.
Allergies: Rarely, it might cause skin rash. Starting with a smaller size or number is wise, escalating based on individual tolerance.
Lion's Mane mushroom, with its rich biomass and variety of forms from supplement to powder, is making news on the front of natural wellness. While the logo of the mighty Lion's Mane might not be as recognizable as mainstream brands, its benefits are making waves in the scientific community.
Cultures worldwide are embracing it, not just for purposes of nutrition but for its potential therapeutic nootropic and health properties. It's a testament to nature's bounty, where even a single species can bring forth a treasure trove of benefits.
Nootropic Benefits of Lion's Mane Mushroom
The modern scientific realm is gradually uncovering the myriad of benefits associated with Lion's Mane Mushroom. Below, I'll delve into its therapeutic applications, shedding light on the research and anecdotal evidence supporting these claims.
Cognitive Enhancement and Neuroprotection
Lion's Mane is primarily celebrated for its neurotrophic effects, particularly its capacity to promote the synthesis of Nerve Growth Factor (NGF).
Studies have indicated that consistent consumption of this mushroom can potentially bolster cognitive functions, sharpen memory, and enhance focus.[4] These properties are not just beneficial for the aging population in warding off degenerative conditions but can also aid students, professionals, and anyone keen on optimizing their mental capabilities.
Furthermore, research suggests that its neuroprotective qualities can be a potent ally against conditions like Alzheimer's and other neurodegenerative diseases.[5]
Mood Regulation and Anti-Depressive Effects
Apart from its cognitive boosting capabilities, Lion's Mane also shows promise in the realm of mood regulation. Animal studies indicate its potential in alleviating symptoms of anxiety and depression.[6] This is thought to be due to its anti-inflammatory properties, modulation of the gut-brain axis, and influence on neurogenesis.
Immune System Enhancement
Historically used as a health tonic, it's no surprise that Lion's Mane has immune-boosting attributes. The mushroom is packed with beta-glucans, which are known for their immune-modulating properties. By enhancing the immune response, it might provide increased resilience against infections and diseases.[7]
Antioxidant Properties and Overall Vitality
The free radical theory of aging posits that oxidative stress is a significant contributor to the aging process and related ailments. Lion's Mane, rich in antioxidants, can counteract this oxidative stress, possibly leading to a reduction in inflammation and cellular damage. By doing so, it promotes overall vitality and longevity.[8]
The vast array of therapeutic applications of Lion's Mane underscores its versatility and potential in not just the world of nootropics, but also holistic health. The blend of traditional wisdom with modern research paints a promising picture of this unique fungus.
Lion's Mane Mushroom Side Effects and Safety Concerns
While Lion's Mane mushroom is generally regarded as safe for most individuals, it's essential to be aware of potential side effects and contraindications, ensuring optimal benefits with minimal risks.
Common Side Effects:
Gastrointestinal Disturbances: Some users report experiencing mild stomach upset or diarrhea after consuming Lion's Mane, particularly in higher dosages. This is possibly due to the high fiber content and the body's adjustment to new compounds.
Allergic Reactions: As with many natural substances, there's potential for allergies. Symptoms can range from a mild rash or itchiness to more severe reactions in hypersensitive individuals. It's crucial to start with smaller dosages and observe any changes.
Dizziness and Lightheadedness: A small percentage of users have reported feelings of dizziness or lightheadedness after consuming the mushroom. This effect is generally transient and diminishes with continued use.
Interactions with Other Medications:
Blood Thinning Medications: Due to its potential anti-coagulant effects, it might be prudent for individuals on blood thinners to consult with a healthcare professional before incorporating Lion's Mane into their regimen.
Hypoglycemic Drugs: Preliminary studies indicate that Lion's Mane might have hypoglycemic properties. Therefore, those on medications to manage diabetes should exercise caution and monitor blood sugar levels closely.
Based on personal observations and anecdotal evidence from fellow nootropic enthusiasts, the majority of users tolerate Lion's Mane well, with many praising its cognitive and mood-enhancing properties. However, as with any supplement, experiences can vary.
It's always advised to listen to one's body, adjust dosages as needed, and consult with a healthcare professional if uncertainties arise.
It's worth noting that the side effects associated with Lion's Mane are generally mild and transient. But a thorough understanding of potential reactions aids in making informed decisions and ensuring a positive experience.
Lion's Mane Mushroom Nootropic Dosage & Cycle
Navigating the vast landscape of nootropics, the question of optimal dosage often arises. With Lion's Mane Mushroom, determining the right amount is crucial not only for efficacy but also to ensure minimal side effects.
Optimal Nootropic Dosage:
Clinical Studies: The majority of clinical trials on Lion's Mane have used dosages ranging between 500mg to 3g daily. These dosages have shown potential benefits in cognitive enhancement and neuroprotection without significant adverse effects.[9]
Standardized Extracts: It's important to ensure that any Lion's Mane supplement is standardized to contain the active compounds, mainly hericenones and erinacines. A common recommendation is a daily dose of 1,000mg of a standardized extract.
My Cycling Considerations:
Tolerance Development: As with many nootropics, the body can develop a tolerance if consumed daily for extended periods. Cycling Lion's Mane Mushroom is not necessary, however, some people choose to cycle it for example, 30 days on, and 30 days off to maintain its efficacy, minimize potential side effects, and keep it budget-friendly.
Long-term Use: There's no conclusive evidence suggesting detrimental effects from long-term consumption. However, periodic breaks might enhance its benefits and reduce the chance of potential side effects.
Stacking with Other Nootropics:
Synergistic Combinations: Lion's Mane can be effectively combined with other cognitive enhancers. Popular stacks include coupling with Bacopa Monnieri for enhanced memory or with Rhodiola Rosea for stress relief and improved focus.
Cholinergic System: Due to its potential impact on nerve growth factor (NGF), Lion's Mane might synergize well with nootropics that influence the cholinergic system, like racetams or alpha-GPC.
Warnings and Guidelines: When stacking, it's essential to consider the combined effect of multiple substances. Starting with lower doses and gradually adjusting is a cautious approach.
Personally, I recommend using Mind Lab Pro which contains high-quality Lion's Mane Mushroom as well as other nootropics that work synergistically. I'll go more into detail below.
Why I Opt for Mind Lab Pro: A Superior Nootropic Blend
In a market saturated with various nootropic supplements and cognitive enhancers, discerning the right fit can be a daunting task. One name, however, has consistently risen above the rest in my journey with nootropics: Mind Lab Pro.
Here’s why I advocate for this exceptional blend, especially for its incorporation of Lion's Mane Mushroom:
1. Comprehensive Cognitive Enhancement: While standalone Lion's Mane offers numerous benefits, Mind Lab Pro takes cognitive enhancement to the next level by synergizing it with other potent nootropics. This all-in-one approach ensures a broad spectrum of cognitive benefits, from improved memory and focus to enhanced mood and creativity.
2. Premium Quality and Purity: Mind Lab Pro prides itself on using only the highest quality ingredients. Their Lion's Mane extract, for instance, is sourced meticulously to ensure it contains the most bioactive constituents. This commitment to purity translates into better results and fewer side effects.
3. Transparent Labeling and Research-Backed Formulation: Unlike many competitors who hide behind proprietary blends, Mind Lab Pro is transparent about the exact amounts and sources of each ingredient. Each component, including Lion's Mane, is backed by robust scientific research, ensuring users receive a product that's both safe and effective.
4. Holistic Brain Health: More than just boosting immediate cognitive functions, Mind Lab Pro is designed for long-term brain health. The inclusion of Lion's Mane, known for its neurogenerative properties, exemplifies this commitment. When combined with other ingredients like maritime pine bark or phosphatidylserine, the blend supports overall neural health, neuroplasticity, and resilience against age-related cognitive decline.
5. Cost-Effective and Convenient: While sourcing individual nootropics can be a hassle and often costlier, Mind Lab Pro offers a comprehensive solution in a single capsule. This not only simplifies dosing but also makes it a cost-effective choice in the long run.
In essence, while standalone Lion's Mane products offer notable cognitive enhancements, Mind Lab Pro elevates the experience by offering a holistic, research-backed, and quality-assured nootropic blend. It's a product crafted for discerning individuals who seek the best for their cognitive health and performance.
My Personal Reflections and Experiences with Lion's Mane Mushroom
Stepping into the realm of nootropics is an exploration, and Lion's Mane Mushroom was indeed a noteworthy chapter in my journey. This fascinating fungus, which appears more like something from a fairytale than a cognitive enhancer, took me by surprise with its profound effects.
A Natural Cognitive Enhancer: Unlike many synthetic nootropics, Lion's Mane provides a subtle, yet noticeable, elevation in cognitive functioning. Within a week of consumption, I experienced enhanced focus, and over a month, there was a noticeable improvement in memory recall and mental clarity.
Mood and Well-being: More than just cognitive enhancement, Lion's Mane brought about a sense of well-being. The days seemed brighter, and tasks felt less daunting. This was not a drastic shift but a gentle nudge towards a positive state of mind.
Interactions with Other Nootropics: Stacking Lion's Mane with other nootropics yielded varied results. While its combination with Bacopa Monnieri seemed to amplify memory-enhancing effects, I found that coupling it with stimulants like caffeine, or even Modafinil, required a careful balance to prevent overstimulation.
Safety and Side Effects: Throughout my experimentation, I noticed a few days of mild stomach discomfort when starting with a higher dose. This underscores the importance of starting slow and allowing the body to adjust. Also, I found that cycling, as usually recommended, helped in maintaining its efficacy over extended periods.
Purchasing Lion's Mane: Quality matters, especially when choosing a supplement. I've consistently sourced my Lion's Mane from reputable vendors, with Mind Lab Pro, being a personal favorite due to its commitment to quality, research, and transparent testing.
Overall, Lion's Mane Mushroom has solidified its place in my nootropic repertoire. It stands as a testament that nature, in all its wisdom, offers compounds that can enhance our cognitive capacities, promote neural health, and elevate our well-being.
As with any supplement, personal experiences might vary, but for those embarking on this journey, Lion's Mane is undoubtedly worth exploring.
The Intricate Relationship Between Mushrooms and Cognitive Health: An In-Depth Look
Mushrooms have always been a source of fascination, not only as a food source but also for their therapeutic potential. A plethora of articles and studies highlight the incredible medicinal benefits they offer. Among the various mushrooms, there's one that stands out in the realm of cognitive health: the Lion's Mane mushroom.
Studies Involving Mice and Humans
Pioneering studies, particularly those that involve mice, have shown promising results. In these studies, the mycelium extracts of the mushroom, when administered to mice, have demonstrated significant improvements in memory, energy and cognitive functions.[10] It is believed that these results stem from the mushroom's ability to stimulate nerve growth factor, which plays a vital role in maintaining and regenerating nerves in the brain.
But it's not just in mice. Clinical trials involving humans have been increasingly more frequent. A noteworthy study involved patients with mild cognitive impairment. Over the course of 16 weeks, the patients were administered mushroom capsules. The outcomes were promising. These patients showed significant cognitive improvement, especially when compared to the placebo group.
Alzheimer's Disease and Dementia
It's no secret that Alzheimer's disease and dementia are among the most challenging conditions that medical professionals face today. The doctor community has been on the constant lookout for potential treatments and preventive measures. The Lion's Mane mushroom, with its nerve-boosting activity, is emerging as a potential ally in this battle. While it's not a cure, early findings suggest that regular consumption might slow the progression of these diseases and enhance the quality of life for patients.
Incorporating Lion's Mane into Diet
As a food, Lion's Mane mushrooms can be a delightful addition to culinary dishes. They offer a seafood-like taste, often likened to crab or lobster. However, to harness its therapeutic potential, especially concerning cognitive health, capsules containing concentrated extracts are recommended. Before starting any supplementation, it's always best to consult with a doctor to ensure it's suitable for individual health conditions.
The relationship between mushrooms, particularly Lion's Mane, and cognitive health is intricate and profound. The mycelium, the root-like part of the mushroom, is where much of its power is believed to reside. As more articles and research papers delve into this topic, we're inching closer to fully understanding its potential and harnessing it for the benefit of patients worldwide.
Frequently Asked Questions (FAQ)
How does Lion's Mane Mushroom support cognitive function?
Lion's Mane Mushroom contains compounds known as hericenones and erinacines, which stimulate the synthesis of nerve growth factor (NGF). NGF plays a pivotal role in maintaining and regenerating neurons, thereby promoting cognitive function and neuroplasticity.
Can Lion's Mane Mushroom enhance memory and learning?
Several studies suggest that Lion's Mane supplementation can bolster memory and learning capabilities, likely due to its role in enhancing neuroplasticity and its neuroprotective effects.
How long does it take to notice the cognitive benefits of Lion's Mane Mushroom?
The onset of cognitive benefits varies among individuals. While some users report noticing effects within a few days, others might take several weeks. Consistency and appropriate dosage are key.
What is the half-life of Lion's Mane?
The specific half-life of Lion's Mane and its active components is not well-documented in the current literature. However, as with most natural supplements, the effects of Lion's Mane are often cumulative, with benefits becoming more noticeable after consistent use over weeks or months rather than hours.
Can Lion's Mane support brain health in an aging population?
Yes, several studies indicate Lion's Mane's potential in supporting cognitive function in the elderly, possibly reducing the risk of neurodegenerative diseases. Its ability to stimulate NGF production means it might aid in neuron maintenance and regeneration, vital for aging brains.
How does the neuroprotective effect of Lion's Mane work?
Lion's Mane offers neuroprotective properties primarily through its promotion of NGF synthesis, reducing inflammation in neural tissues, and its antioxidant capacity, which shields neurons from oxidative stress.
How does Lion's Mane affect sleep patterns and dream quality?
Anecdotal reports suggest that some users experience more vivid dreams and improved sleep quality with Lion's Mane supplementation. This might be related to its role in enhancing overall brain health, though direct scientific research in this area is still sparse.
Are there any dietary sources of Lion's Mane, or is supplementation the best approach?
Lion's Mane is not only a nootropic but also an edible mushroom. It can be cooked and consumed as part of a meal. However, for consistent and concentrated cognitive benefits, supplementation, which provides a standardized dose of its active compounds, is often recommended.
My Final Thoughts on Lion's Mane Mushroom
Navigating the intricate landscape of nootropics has exposed me to a plethora of compounds, each promising cognitive enhancement and improved brain health. Yet, few have left as lasting an impression as the Lion's Mane Mushroom.
Historically revered in ancient medicinal practices, Lion's Mane has found a rightful place in the modern nootropic community, not just because of tradition, but due to compelling research. The mushroom's unique ability to stimulate nerve growth factor synthesis underscores its potential in neuroprotection and cognitive restoration. These properties are particularly pertinent in an age where neurodegenerative diseases pose significant challenges.
My journey with Lion's Mane, both as a standalone supplement and within the Mind Lab Pro blend, has been largely positive. The subtle but palpable enhancements in memory, mood, and overall cognitive agility reaffirmed much of what the scientific literature has propounded. Yet, it's essential to note that while Lion's Mane stands out, it's not a panacea. Individual responses can vary, and it's always vital to approach supplementation with informed guidance and a well-researched regime.
As for sourcing, the burgeoning popularity of Lion's Mane means the market is rife with options. Yet, quality varies widely. That's where vendors like Mind Lab Pro shine, offering a meticulously crafted blend with premium Lion's Mane extract.
In conclusion, Lion's Mane Mushroom, with its unique neurogenerative properties and cognitive benefits, undoubtedly earns its spotlight in the nootropic world. Yet, like all supplements, it demands respect, understanding, and careful integration into one's cognitive health regimen.
Tropoflavin, a naturally occurring flavone, has recently garnered attention for its potential therapeutic applications in treating a range of central nervous system disorders. This compound, also known as 7,8-dihydroxyflavone (7,8-DHF), is found in Godmania aesculifolia, Tridax procumbens, and primula tree leaves.
Acting as a potent and selective small-molecule agonist of the tropomyosin receptor kinase B (TrkB), Tropoflavin has demonstrated efficacy in animal models for various conditions, including Alzheimer's disease, Parkinson's disease, and depression.
Today, I'll review the scientific literature surrounding 7,8-DHF as a nootropic, covering its chemical structure, mechanism of action, preclinical evidence, nootropic benefits, safety, and potential clinical applications.
So without further ado, let's dive in, shall we?
Overview of 7,8-Dihydroxyflavone as a Nootropic Compound
7,8-Dihydroxyflavone (7,8-DHF) is a naturally occurring flavonoid that has emerged as a promising nootropic compound. It has demonstrated a range of neuropharmacological effects in preclinical studies, including improving memory, promoting neurogenesis, and protecting against neurodegeneration.
Flavonoids are a class of polyphenolic compounds found in various fruits, vegetables, and other plant sources. They have gained significant attention in recent years due to their antioxidant, anti-inflammatory, and neuroprotective properties.[1]
These compounds have been shown to exert beneficial effects on the brain, including enhancing cognitive function and protecting against neurodegenerative diseases. 7,8-DHF is one of the most prominent polyphenolic compounds and is gaining traction as a nootropic. It has been studied for its potential effects on mood, memory, learning, anxiety, and other cognitive functions.
The neurological effects of 7,8-DHF are thought to be mediated by its interaction with specific receptors. It has been found to be TrkA, a receptor involved in nerve growth factor signaling, which is important for neuronal survival and plasticity.
7,8-DHF works by modulating the expression of various receptors, including glutamate receptor subunits and BDNF. It can also have an effect on synapse formation, energy metabolism, and acetylcholine release in certain brain regions.[2]
Chemical Structure and Properties of 7,8-Dihydroxyflavone
It contains two hydroxyl groups on the benzene ring and one hydroxy group on the pyrone ring. Let's take a closer look at the chemical structure of 7,8-dihydroxyflavone below:
Molecular Formula and IUPAC Name
The molecular formula of 7,8-DHF is C15H10O5, which indicates that it comprises 15 carbon atoms, 10 hydrogen atoms, and 5 oxygen atoms.
Its IUPAC (International Union of Pure and Applied Chemistry) name is 2-(3,4-dihydroxyphenyl)-3,7-dihydroxy-4H-chromen-4-one.
This nomenclature signifies the presence of a chromen-4-one core, which is characteristic of flavones and hydroxyl groups at positions 3, 4, 7, and 8, as reflected in its common name.
Chiral Centers and Stereochemistry
7,8-DHF exhibits planar geometry due to the fused benzopyrone structure in its core, which consists of a benzene ring (A-ring) and a heterocyclic pyrone ring (C-ring).
The B-ring is an additional phenyl ring attached to the C-ring at the 2-position. The molecule does not possess any chiral centers, and as a result, no stereoisomers are present.
This absence of chirality simplifies the synthesis, isolation, and analysis of the compound, as well as the investigation of its biological activities.
Physicochemical Properties
7,8-Dihydroxyflavone is a yellow, crystalline solid with a molecular weight of 286.24 g/mol. It is sparingly soluble in water due to multiple hydroxyl groups, which can bond hydrogen with water molecules.
However, the compound is highly soluble in polar organic solvents, such as methanol, ethanol, and dimethyl sulfoxide (DMSO). The compound exhibits a strong UV absorption profile, with λmax values in the range of 260-280 nm for the A-band and 340-360 nm for the B-band, which is characteristic of flavonoids.[3]
These UV absorption properties, along with the compound's fluorescence, can be exploited for its quantification and detection in various analytical methods, such as high-performance liquid chromatography (HPLC) and mass spectrometry (MS).
7,8-DHF Mechanism of Action: BDNF Modulation & Trkb Receptor Activation
When it comes to the mechanism of action, 7,8-DHF is known to promote BDNF (brain-derived neurotrophic factor) production by binding and activating its receptor TrkB. Without getting too technical, this, in turn, can lead to a cascade of cellular activities that are beneficial for maintaining proper neuronal function and promoting neurogenesis.
Let's take a closer look at the main modes of action of 7,8-DHF below.
Brain-Derived Neurotrophic Factor (BDNF) And Its Role in Neuroplasticity
The importance of brain-derived neurotrophic factor (BDNF) in maintaining and enhancing brain health has become increasingly evident with the discovery of its reduced expression in neurodegenerative disorders, particularly Alzheimer's disease (AD).
BDNF is crucial for various neuronal functions, as it facilitates synaptic transmission, synaptogenesis, and synaptic plasticity through its signaling with the TrkB receptor. This makes the BDNF-TrkB signaling pathway a promising target for developing therapeutic interventions aimed at combating neurodegenerative conditions.
Recent research has delved into the potential benefits of a small molecule TrkB agonist, 7,8 dihydroxyflavone (7,8-DHF), in mitigating the early effects of AD-related pathology. In a study conducted on the 5xFAD mouse model of AD, the mice were treated with 7,8-DHF for two months, starting from one month of age.[4]
The outcomes of this investigation have shed light on the therapeutic potential of 7,8-DHF in addressing AD-associated neurochemical alterations and pathological markers. Notably, the 7,8-DHF treatment led to a decrease in cortical Aβ plaque deposition, which is a major hallmark of AD.
Additionally, it protected cortical neurons from reduced dendritic arbor complexity, contributing to preserving the overall neuronal structure. However, it did not significantly influence the density of dendritic spines.
According to Aytan, Nurgul et al., the treatment also demonstrated neuroprotective effects in the hippocampus, preventing increased levels of choline-containing compounds and mitigating glutamate loss.
Tropomyosin Receptor Kinase B (Trkb) Receptor Signaling Pathway
The tropomyosin receptor kinase B (TrkB) receptor plays a crucial role in mediating the effects of BDNF on neurons. As a transmembrane tyrosine kinase receptor, TrkB serves as the primary receptor for BDNF, initiating a cascade of intracellular signaling events upon binding with the neurotrophin.[5]
The activation of TrkB by BDNF triggers several key intracellular pathways, which include the phosphatidylinositol 3-kinase (PI3K)-Akt, mitogen-activated protein kinase (MAPK)-extracellular signal-regulated kinase (ERK), and phospholipase C gamma (PLCγ)-protein kinase C (PKC) pathways. Each of these pathways contributes to different aspects of neuronal function and well-being.[6]
The PI3K-Akt pathway is vital for promoting neuronal survival and inhibiting apoptosis. Activation of this pathway by BDNF-TrkB signaling enhances cell survival by inhibiting pro-apoptotic factors and stimulating anti-apoptotic factors, ensuring the preservation of healthy neurons.
The MAPK-ERK pathway, on the other hand, plays a significant role in neuronal differentiation and proliferation. BDNF-TrkB signaling promotes the activation of the MAPK-ERK pathway, which in turn supports the maturation and differentiation of neurons and their integration into existing neuronal networks.[7]
The PLCγ-PKC pathway is crucial for regulating synaptic plasticity,[8] a fundamental process in learning and memory. BDNF-TrkB signaling modulates the activity of this pathway, ultimately leading to alterations in synaptic strength and connectivity.
This modulation facilitates the adaptation and reorganization of neural circuits in response to new experiences and environmental stimuli.
7,8-Dihydroxyflavone as a Trkb Agonist and Its Implications
7,8-Dihydroxyflavone (7,8-DHF) is a small molecule with the unique ability to selectively bind to and activate the TrkB receptor in vitro and in vivo, effectively mimicking the actions of BDNF.[9] This characteristic has positioned 7,8-DHF as a potential therapeutic nootropic agent for various neurological disorders and an attractive molecule for studying the effects of BDNF signaling pathways.
By acting as a TrkB agonist, 7,8-DHF exerts its nootropic effects primarily through the modulation of BDNF-related signaling pathways, which in turn leads to the promotion of neurogenesis and the enhancement of synaptic plasticity.
The implications of 7,8-DHF as a TrkB agonist are far-reaching, with potential applications in the prevention and treatment of a wide range of neurological disorders, including Alzheimer's disease, Parkinson's disease, and depression.
By simulating the actions of BDNF, 7,8-DHF helps protects neurons from damage, promote their survival, and facilitate the growth and maintenance of new neuronal connections. This capacity to promote neuroplasticity, improve cognitive function, and alleviate symptoms of neurological diseases has made 7,8-DHF a promising candidate for drug development and further research.
7,8-DHF Preclinical Studies: In Vitro and in Vivo Evidence
Now that we’ve seen the potential of 7,8-DHF as a nootropic and a treatment for neurological disorders let’s look at some studies conducted to evaluate its efficacy.
Cellular Models: Neuronal Differentiation and Survival
In vitro, studies have demonstrated that 7,8-DHF promotes the differentiation and survival of various neuronal cell types, including cortical neurons, cerebellar granule neurons, and hippocampal neurons. These findings suggest that 7,8-DHF can have potential therapeutic effects in preventing neuronal loss and promoting neuronal regeneration.[10]
Rodent Models: Hippocampal Neurogenesis and Synaptic Plasticity
In vivo, studies using rodent models have shown that 7,8-DHF administration enhances hippocampal neurogenesis, the process by which new neurons are generated in the hippocampus.[11] Additionally, 7,8-DHF has been found to improve synaptic plasticity, as evidenced by increased long-term potentiation (LTP) and decreased long-term depression (LTD) in the hippocampus. These effects are thought to contribute to the observed improvements in memory and cognitive function.
Neuroprotective Effects in Neurodegenerative Disease Models
Preclinical studies have also demonstrated the neuroprotective effects of 7,8-DHF in various animal models of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS).[12]
The compound has been shown to reduce neuronal loss, ameliorate cognitive deficits, and attenuate pathological markers in these models, suggesting potential therapeutic applications in human neurodegenerative conditions.
7,8-DHF Nootropic Benefits: Cognitive Enhancement and Neuroprotection
Regarding its nootropic benefits, 7,8-DHF exerts its effects mainly through 4 mechanisms:
Memory Consolidation and Retrieval: Hippocampal-Dependent Tasks
7,8-DHF has been found to enhance memory consolidation and retrieval in various hippocampal-dependent learning and memory tasks in rodent models, such as the Morris water maze, novel object recognition, and contextual fear conditioning.[13]
These findings suggest that 7,8-DHF can be a promising nootropic for improving memory function in both healthy individuals and those with memory impairments.
Synaptic Plasticity: Long-Term Potentiation and Depression
As mentioned earlier, 7,8-DHF has been shown to modulate synaptic plasticity by promoting LTP and reducing LTD in the hippocampus. These effects are thought to be mediated by its ability to activate the TrkB receptor and subsequently enhance BDNF signaling pathways.[14]
This modulation of synaptic plasticity contributes to the observed improvements in cognitive function following 7,8-DHF administration.
Antioxidant Properties: Reactive Oxygen Species Scavenging and Lipid Peroxidation
7,8-DHF possesses antioxidant properties, as demonstrated by its ability to scavenge reactive oxygen species (ROS) and reduce lipid peroxidation.[15] These effects contribute to its neuroprotective actions by mitigating oxidative stress-induced neuronal damage and dysfunction.
Anti-inflammatory Effects: Modulation of Microglial Activation and Cytokine Production
In addition to its antioxidant properties, 7,8-DHF has been found to exert anti-inflammatory effects by modulating microglial activation and reducing the production of pro-inflammatory cytokines such as TNF-α and IL-1β.[16]
This further contributes to its neuroprotective and nootropic effects by preventing inflammation-mediated neuronal damage.
Pharmacokinetics, Safety, and Dosage Considerations
Now that we’ve discussed the possible uses and benefits of 7,8-Dihydroxyflavone, let’s take a closer look at the pharmacokinetics and safety of this nootropic compound:
Absorption, Distribution, Metabolism, and Excretion (ADME): 7,8-DHF exhibits favorable pharmacokinetic properties, including rapid absorption, wide distribution, and efficient brain penetration. It is metabolized primarily by the liver, with the majority of the compound being excreted in the feces and a smaller portion in the urine.
Blood-Brain Barrier Permeability and Brain Tissue Penetration. One of the key features of 7,8-DHF is its ability to cross the blood-brain barrier (BBB) and penetrate brain tissue, which is crucial for its efficacy as a nootropic. Studies have demonstrated that 7,8-DHF reaches therapeutically relevant concentrations in the brain following oral administration, suggesting that it may be an effective candidate for targeting central nervous system (CNS) disorders.
Preclinical Safety Profile - Acute and Chronic Toxicity Studies: Preclinical safety studies have demonstrated that 7,8-DHF has a favorable safety profile, with no significant adverse effects observed in rodents' acute and chronic toxicity studies. However, further safety evaluations, including studies in higher animals and human subjects, are required to establish its safety profile for clinical use.[9]
Dose-Response Relationships and Optimal Dosing Regimen: While the optimal dosing regimen for 7,8-DHF in humans has not yet been established, animal studies have provided some insights into effective dose ranges. In rodent models, doses ranging from 1 to 50 mg/kg have been shown to exert nootropic and neuroprotective effects. The effective dose for humans may differ and will require further investigation in clinical trials.
People taking 7,8-DHF as a nootropic take 25 mg of 7,8 DHF 1-2 times daily. As with any nootropic, it is important to start at a low dose and gradually increase as needed in order to assess individual tolerance.
It is also recommended to cycle 7,8-DHF every 6-12 weeks. Cycling is the practice of taking a supplement for a period of time, then breaking it before starting to take the supplement again.
Taking a break from the supplement can help reset your body and reduce side effects while increasing effectiveness. Administering 7,8-DHF under the tongue (sublingually) is preferable because it improves bioavailability.
Side Effects and Drug Interactions of 7,8-Dihydroxyflavone
While preclinical studies have demonstrated a favorable safety profile for 7,8-DHF, potential side effects in human subjects remain largely unknown. As with any novel compound, it is essential to proceed with caution and monitor for potential adverse effects when evaluating its use in humans.
Some potential side effects that may be associated with 7,8-DHF, based on its mechanism of action and effects on the TrkB receptor, could include:
Headaches: BDNF and TrkB receptor activation regulate neuronal activity and excitability; 7,8-DHF administration might lead to headaches in some individuals.
Insomnia: Increased neuronal activity and enhanced synaptic plasticity may affect sleep patterns, potentially resulting in insomnia or disrupted sleep.
Gastrointestinal issues: As with many bioactive compounds, 7,8-DHF may cause gastrointestinal side effects such as nausea, vomiting, or diarrhea in some individuals.
It is important to note that these potential side effects must be further investigated in clinical trials. Given its ability to modulate BDNF signaling and TrkB receptor activation, caution should also be exercised when stacking 7,8-DHF with other drugs that target these pathways or have similar mechanisms of action.
Possible drug interactions to consider include:
Antidepressants: As some antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), have been shown to increase BDNF levels, co-administration with 7,8-DHF may lead to additive or synergistic effects, potentially increasing the risk of side effects.
Antiepileptic drugs: Some antiepileptic drugs, such as valproic acid, have been reported to modulate BDNF expression and TrkB receptor activation. Concurrent use of these drugs with 7,8-DHF may result in altered drug effects or increased risk of side effects.
Other nootropics: As some nootropic agents, like racetams and noopept, have been shown to modulate BDNF signaling or enhance synaptic plasticity, co-administration with 7,8-DHF may lead to additive or synergistic effects. This may necessitate dose adjustments or close monitoring for potential side effects.
Further studies are required to understand better the potential drug interactions involving 7,8-DHF and to establish appropriate dosing and safety guidelines for its use in combination with other medications.
Frequently Asked Questions (FAQ)
Now let's look at the most frequently asked questions about 7,8-Dihydroxyflavone.
What Is The Half-Life Of 7,8-Dihydroxyflavone?
Currently, there is limited information available on the half-life of 7,8-dihydroxyflavone (7,8-DHF) in humans. Most research on this compound has been conducted in vitro or in animal models. The elimination half-life in mice is <30 minutes.
Can 7,8-Dihydroxyflavone Be Used to Treat Neurodegenerative Diseases?
Preclinical studies suggest that 7,8-DHF has neuroprotective effects in animal models of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS).
What Is the Bioavailability of 7,8-DHF?
The bioavailability of 7,8-dihydroxyflavone (7,8-DHF) in animal studies is approximately 5% (in mice) due to its poor solubility and rapid metabolism. Despite this low bioavailability, 7,8-DHF can still cross the blood-brain barrier and affect the brain. Further research is needed to determine its bioavailability in humans and explore methods to enhance it.
How Does 7,8-DHF Make You Feel?
As a nootropic, 7,8-dihydroxyflavone (7,8-DHF) positively impacts cognitive function and mood. Individuals experience improved memory, increased focus, and enhanced learning capabilities. Additionally, due to its potential antidepressant and anxiolytic effects, 7,8-DHF helps alleviate feelings of anxiety or depression.
How Long Does It Take for 7,8-DHF to Work?
The onset of action for 7,8-DHF may vary between individuals, but preclinical studies in rodents suggest that effects on memory and learning could be observed within 1-2 hours after administration. Anecdotal evidence in humans suggests that most people start feeling the effects within an hour or two of taking 7,8-DHF.
Conclusion
7,8-Dihydroxyflavone is a promising nootropic compound with a range of neuropharmacological effects, including memory enhancement, neuroprotection, and modulation of synaptic plasticity. Its ability to activate the TrkB receptor and mimic BDNF signaling underlies many of these effects and highlights its potential as a therapeutic agent for various neurological disorders.
While the preclinical evidence for 7,8-DHF is compelling, further research is needed to fully understand its mechanism of action, safety profile, and optimal dosing regimen. Clinical trials in human subjects will be crucial for translating these findings into clinical applications and assessing their potential as a nootropic and neuroprotective agent.
The development of 7,8-DHF as a therapeutic agent may have broader implications for personalized medicine and neuroscience, particularly in the context of neurodegenerative diseases and mood disorders.
By targeting specific molecular pathways such as BDNF signaling, 7,8-DHF can provide a novel approach to treating these conditions and contribute to the advancement of personalized medicine in the field of neuroscience.
