THE ALCHEMIC HEALTH BLOG

All Mental Health

December 3, 2020

Nootropics: Brain Restorative Properties of Plant Flavonoid 7,8-Dihydroxyflavone

Cognitive impairment is something no one wants to go through, but we will all suffer from it at some stage in our lives. There are many reasons why one would start to suffer cognitive decline, but a major contributing factor is synaptic loss. The synapses are the junctions between neurons where chemical information is exchanged. Sensory, motor and cognitive impairments are associated with the increased destruction of synapses, which can lead to neurodegenerative conditions such as major depressive disorder, Huntington disease, schizophrenia, dementia, Alzheimer’s disease and amyotrophic lateral sclerosis.

Reduced levels of brain-derived neurotrophic factor (BDNF) have been detected in those suffering from neurodegenerative diseases. This important brain protein promotes the survival of neurons as it plays a role in the growth, maturation and maintenance of brain cells. BNDF serves as a neurotransmitter modulator and participates in neuronal plasticity, making it essential for learning and memory(1). It binds to its high affinity receptor TrkB (tyrosine kinase B), where its activation signals transduction cascades (IRs1/2, PI3K, Akt), crucial for CREB and CBP production, which encode proteins involved in β cell survival. Similar to insulin-like growth factor 1, BNDF has downstream signaling mechanisms incorporating both p-CAMK and MAPK that increase the expression if pro-survival genes(1). This signaling through TrkB receptor plays a central role in promoting synaptic transmission, synaptogenesis and facilitating synaptic plasticity, making it an attractive candidate for targeted therapies(3). BNDF is vital for optimal brain health and functionality, but as we age the expression of this protein decreases, further leading to cognitive decline and neurological diseases. Although through increasing BNDF signaling, pre-clinical studies demonstrate that this may be a potent way to prevent, arrest and even reverse abnormal neurodevelopmental disorders(4).

Recent studies into 7,8-dihydroxyflavone (7,8 DHF), a small TrkB agonist that mimics BNDF function, has shown similar effects as BNDF in promoting neuronal survival and regeneration following traumatic brain injury(2). 7,8 DHF is a naturally occurring plant flavonoid that has a longer half-life in comparison to BNDF, as well as being much smaller in molecular size, allowing it to penetrate the blood-brain barrier(2). It has been found to decrease cortical Aβ plaque deposition and protect cortical neurons against reduced dendritic arbor complexity, but has no impact on the density of dendritic spines. In addition to this it also protects against hippocampal increase in the level of choline-containing compounds and glutamate loss(3). 7,8 DHF promotes axon regeneration, inhibits the loss of hippocampal synapses, restores synapse number and synaptic plasticity, which prevents memory deficits(5)(8).

Huntington’s disease (HD) is a fatal neurodegenerative disease. Research has demonstrated a link between HD and reduced levels of striatal BNDF with an imbalance between its TrkB receptors and p75(NTR)(6). Thus, molecules with activity on the BNDF/TrkB/p75 system can potentially have therapeutic effects. After chronic 7,8 DHF administration, analyses revealed improved striatal levels of enkephalin, prevention of striatal volume loss, TrkBY816 phosphorylation recovery in striatum, normalized striatal levels of induced and neuronal nitric oxide synthase while ameliorating the imbalance of p75/TrkB(6). This supports its potential therapeutic role in those suffering with HD and other neurological ailments.

7,8 DHF has shown to protect people suffering from severe stress and traumatic brain injury (TBI). Post-traumatic stress disorder (PTSD) occurs after being exposed to a traumatic situation; this is characterized by cognitive deficits which include impaired explicit memory. 7,8 DHF significantly reverted spatial memory impairment and the increased long-term potentiation, supporting the idea that the activation of BNDF/TrkB pathway fulfills a protective role(7). When 7,8 DHF was taken alongside exercise, it has shown to improve brain function in those with traumatic brain injury. This combination enhances hippocampal functional connectivity, promoting enhanced levels of cell metabolism, synaptic plasticity and increases brain circuit function that facilitates greater rehabilitation after TBI(9).

Parkinson’s disease is caused by the destruction of dopamine producing neurons within part of the midbrain called substantia nigra. Studies show 7,8 DHF has potent neuroprotective effects through the activation of TrkB, which significantly improves dopamine-mediated behaviours and prevented the loss of dopaminergic neurons in the substantia nigra(10).

Due to the suspected low-water solubility, chemical instability, and poor bioavailability of 7,8 DHF, further research is on the way into increasing its absorption, thus potentially increasing its therapeutic effects. To overcome this, scientists fabricate stable 7,8 DHF loaded zein/lactoferrin composite nanoparticles which increases the chemical stability, water solubility and bioaccessibility(11). 7,8 DHF has an array of positive effects on numerous conditions and diseases, which warrants great interest in this natural compound. Even with its poor bioavailability, it still has noticeable cognitive enhancing effects and would work well in anyone’s nootropic stack to increase the brains overall health and functionality, warding off age related cognitive disorders.

Written by Luke Pavasovic
Director and Naturopath at Alchemic Health
facebook.com/alchemichealth
www.alchemichealth.com

References:
1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4697050/
2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5319242/
3. https://pubmed.ncbi.nlm.nih.gov/29510124/
4. https://pubmed.ncbi.nlm.nih.gov/26220903/
5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3895241/
6. https://pubmed.ncbi.nlm.nih.gov/28541476/
7. https://pubmed.ncbi.nlm.nih.gov/27068341/
8. https://pubmed.ncbi.nlm.nih.gov/24043773/
9. https://pubmed.ncbi.nlm.nih.gov/28315455/
10. https://pubmed.ncbi.nlm.nih.gov/27019033/
11. https://www.sciencedirect.com/science/article/abs/pii/S0141813019401244

October 22, 2020

Psychedelics: The Therapeutic Potential of Magic Mushrooms

Psychedelics substances have often been demonized in the past for their significant mind-altering and reality bending effects. When Western society first came into contact with these substances, they were viewed with fear, publicized with false information and scare tactics to deter users. They were made illegal which inhibited scientists from researching and truly understanding these substances. Thankfully the times are changing, with perspectives on these substances shifting, allowing the relaxing of laws which has opened the door for research on these compounds and their therapeutic potential.

One psychedelic that is paving the way in recent research is magic mushrooms and specifically the study of its main psychoactive constituent psilocybin. Psilocybin, a classic tryptamine hallucinogen and prodrug of pscilocin, is a non-selective serotonin agonist (activator) with high affinity for several serotonin receptors including 5-HT1A, 5-HT2A and 5-HT2C(1)(2). Both compounds naturally occur in more than 100 species of mushrooms, and are structurally similar to the endogenous neurotransmitter serotonin (5-HT)(1)(2). Because of this similarity in structure, psilocybin acts like serotonin, allowing it to activate serotonin receptors in numerous regions of the brain, including cerebral cortex and thalamus. Activation of 5-HT2A receptors in the thalamus (a brain region responsible for sensory input) appears to decrease thalamic activity, which leads to sensory alterations commonly known as hallucinations(2). The onset of hallucinogenic effects typically arises within the first 20-40 minutes and disappear within 3-6 hours, with the threshold of intoxication approximately 40mcg/kg. As mushrooms generally contain a low percentage of psilocybin, this would correspond to approximately 1-2g of dried mushrooms(2).

Psilocybin has an ancient and modern history of medicinal use. When consumed in a supportive environment, with the right psychological care, it is used to facilitate emotional breakthrough and renewed perspective(1). Evidence demonstrates that when used alongside the right support, it can be used safely to treat a range of psychiatric conditions such as depression, obsessive compulsive disorder, drug addiction, and end-of-life anxiety. Clinical studies show that these substances can have a rapid and lasting positive impact on mental health(1).

Studies show that psychedelics appear to dysregulate cortisol activity, producing an ‘entropic’ brain state, characterized by compromised modular but enhanced global connectivity, referred to as network ‘disintegration’ and ‘desegregation’(1). These effects correlate with important aspects of the psychedelics experience including ‘ego-dissolution’ and create changes in the personality domain of ‘openness’(1). These modulatory effects on consciousness, perception and cognition are due to the alterations in self-referential processing regions of the default mode network (DMN)(5).

Many of the therapeutic effects of psilocybin come down to its ability to promote both structural and functional plasticity in the prefrontal cortex (PFC) by robustly increasing neuritogenesis and/or synaptogenesis(3). It is also hypothesized to increase neurogenesis in the hippocampus, a brain region responsible for learning and memory(4). These changes in neural structure appear to be induced by the stimulation of the TrkB, mTOR and 5-HT2A signaling pathways, which could explain the clinical effectiveness of this compound(3).

Psilocybin doesn’t always have to be consumed at threshold doses to reap benefits. The phenomenon of microdosing (regular ingestion of very small quantities) has seen a rapid explosion in popularity in recent years. Individuals who microdose report minimal effects yet claim a range of long-lasting general health and wellbeing benefits(6). Small studies have been completed on microdosing with post study measures revealing a general increase in psychological functioning within areas of attention, mood, wellbeing, personality and creativity while seeing reductions in reported levels of depression and stress(6).

These are very interesting times in the field of mental health, seeing psychedelic compounds that were once feared now coming forward to help those in numerous areas by increasing aspects of psychological health. These drugs are still classified as illegal substances, but soon we will hopefully see the laws change so we can reap the therapeutic benefits within a safe and controlled environment. They have amazing potential to help an individual heal and overcome mental health issues.

Written by Luke Pavasovic
Director and Naturopath at Alchemic Health
facebook.com/alchemichealth
www.alchemichealth.com

References:
1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5640601/
2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6007659/
3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6082376/
4. https://pubmed.ncbi.nlm.nih.gov/23727882/
5. https://pubmed.ncbi.nlm.nih.gov/30965131/
6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6364961/

October 14, 2020

Two Hacks for Your Home

We all incorporate dietary, lifestyle and supplement factors into our life to sustain and enhance our health, but what about technology that assists with increasing your health as well? I would like to introduce to you two simple and noninvasive technological hacks you can install into your home that will help increase mood, lower inflammation, boost the immune system and help your overall health.

Negative Ion Generators
First of all what are negative ions? Ions are molecules that have gained or lost and electrical charge. They are created in nature as air molecules that break apart due to radiation, sunlight, and moving air and water. We have all experienced the effects of negative ions when walking at a beach or near a waterfall. When we are around these settings, we not only get a sense of euphoria because they are beautiful but also because these environments are abundant in negative ions.

Negative ions are odorless, tasteless and invisible molecules that when inhaled and enter the bloodstream, they are believed to produce an increase in mood chemicals such as serotonin and also increase the immune system through biochemical reactions. Positive ions are considered to be detrimental to health seeing as most forms of pollution, toxic chemicals and other harmful chemicals in the air carry a positive electrical charge.

Negative ions were discovered more than 100 years ago and widely used for air cleaning. There are numerous studies reviewing the effects of negative ions on humans and animals that have demonstrated increased psychological health, productivity and overall well-being(1).

Five studies on negative ionization and depression were evaluated by level of exposure intensity using meta-analysis. Results showed that negative ionization overall was significantly associated with lower depression ratings, with a stronger association observed at higher levels of negative ions exposure(2).

Negative ion devices have also demonstrated to help remove viruses from the air, effectively preventing airborne transmission of viruses such as influenza A. The device enables unique possibilities of rapid and simple removal of virus from the air(3).

So considering the science, implementing negative ion generators in your home is a simple way to increase overall well-being, psychological health, clean the air and also remove harmful pathogens at the same time. It is a cheap and effective technology to improve your health in your household.

Earthing/Grounding devices
Many of us have heard of grounding, the activity of letting your bare feet/skin come into contact with the Earth. Multi-disciplinary research has revealed that electrically conductive contact of the human body with the surface of the Earth produces intriguing effects on physiology and health(4). These effects relate to inflammation, immune responses, wound healing, and prevention and treatment of chronic inflammatory and autoimmune diseases(4).

Unfortunately, in our day and age, most of us are constantly in shoes and this insulates us from the Earth which inhibits us from grounding. Then when we get home and take off our shoes, our house or apartments are also insulated and even though we are bare foot in these locations we still are not reaping the benefits of properly grounding which balances out our body’s electrical voltage.

Grounding produces measurable differences in concentration of white blood cells, cytokines and other molecules involved in inflammatory responses. It also reduces pain and alters the number of circulating neutrophils and lymphocytes along with various circulating chemical factors related to inflammation(4).

Modern science has discovered that many of the most debilitating diseases, as well as the aging process, are caused by or are associated with chronic inflammation and oxidative stress(5). Research now reveals that direct contact with the surface of the Earth generates a kind of electric nutrition, with surprisingly potent and rapid anti-inflammatory and antioxidant effects(5).

One main hypothesis is that connecting the body to the Earth enables free electrons and ions from the Earth’s surface to spread over and into the body, where they can have antioxidant effects(4). Through this the Earth can prevent or resolve so-called “silent” inflammation(4).

Grounding also appears to improve sleep, normalize the day-night cortisol rhythm, reduces pain, reduces stress, shifts the autonomic nervous system from sympathetic toward parasympathetic activation, increase heart rate variability, speeds up wound healing and reduce blood viscosity(4).

Research has suggested that our disconnect from the Earth may be a major contributor to physiological dysfunction and unwellness(6). Considering this, we need to make an effort to physically reconnect our body to the Earth which helps our overall health and well-being. Seeing as this is hard for many people to do with the current modern life and living situations, grounding can be achieved through Earthing sheets or pads. These are devices that are connected to the power supply which is always grounded, allowing ions to flow from the Earth to the sheet or pad. By installing Earthing sheets in our beds, we can assure we gain the benefits of grounding our body’s at night while we sleep which is one of the most beneficial times. This technology may be expensive, but you cannot put a price on your health.

Written by Luke Pavasovic
Director and Naturopath at Alchemic Health
facebook.com/alchemichealth
www.alchemichealth.com

References:
1. https://pubmed.ncbi.nlm.nih.gov/30274196/
2. https://pubmed.ncbi.nlm.nih.gov/23320516/
3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4477231/
4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4378297/
5. https://pubmed.ncbi.nlm.nih.gov/28987038/
6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3265077/

September 24, 2020

Controlling Our Addictions

It’s recognised in our society today that addiction and substance abuse is prevalent, arising in anyone from any walk of life but can be more prominent in those suffering from the impact of depression, anxiety, PTSD and more. It is our mission to spread true drug education so people can take more care in what they do and have greater awareness to make the right educated choices for themselves. Along with this we want to guide people to rebuild their lives from addiction by providing the best support and tools to make this process easier and more successful.

To understand addiction, we need to understand the mechanisms at play and how the brain works. Rewards increase motivation to perform or repeat tasks and is broadly classified as natural or drug rewards(1). Natural rewards are vital for survival which include water, food and sex. In contrast, drugs are consumed for their ability to produce euphoria and pleasure(1). Although both natural and drug rewards activate similar systems within the brain, the stimulation that drugs create are often more powerful than what is produced by natural rewards(1). Considering this, drug rewards in the brain are so powerful they induce changes in neuronal communication that can alter controlled social use of the substance, to uncontrolled compulsive use in vulnerable individuals(1).

In recent decades, the role of the neurotransmitter glutamate has been extensively studied for the role it plays in aspects of drug addiction and how it may also be involved in mediating natural reward as well. Within the mammalian brain, glutamate is the main excitatory neurotransmitter that accounts for approximately 70% of synaptic transmission in the central nervous system(1). Drugs of abuse such a cocaine, nicotine, alcohol and heroin all alter glutamate transmission via different mechanisms. For example, cocaine blocks DAT and increases dopamine levels, this increase in synaptic dopamine levels activates presynaptic or postsynaptic D1 dopamine receptors, which indirectly increases glutamate transmission(1). When we look at nicotine which is another stimulant, it increases glutamate transmission by binding to excitatory α7 homomeric nicotinic acetylcholine receptors located on presynaptic glutamate terminals(1). Furthermore, alcohol and heroin along with other drugs of abuse all alter glutamate transmission in numerous ways.

As we can see, when individuals fall into the habitual nature of substance abuse, it will inevitably alter the function of glutamate. This dysregulation within this neurotransmitter system is what causes changes in the reward systems of the brain, increasing the urge to use the substance of abuse. So how can we help people suffering from substance use disorder (SUD)?

I would like to introduce to you N-Acetyl Cysteine (NAC), an amazing natural compound (amino acid) that has recently been studied for its ability to help people with addiction through regulating the glutamate system. NAC is effective in reversing neural dysfunction in people with SUD, as it is an antioxidant that impacts the glutamatergic functioning in the brain(2). Repeated use of an addictive substance may result in excess glutamate in the nucleus accumbens (an area in the brain critical for motivation and learning). By introducing NAC, it is thought to upregulate the glutamate transporter (GLY-1) that removes excess glutamate from the nucleus accumbens. As a result, it helps correct glutamate dysregulation which promotes abstinence or prevents relapse to a substance(2).

A number of studies demonstrate NAC’s great safety profile along with favorable tolerability in addition to being an over-the-counter medication/compound. Compared to placebo it was significantly superior in lowering craving symptoms which resulted in a reduction in SUD in people addicted to cocaine, nicotine and cannabis. The results of these studies coincide with the hypothesis of the involvement of glutamatergic pathways in the pathophysiology of addiction(3)(4)(5). It’s also shown effectiveness in surpassing methamphetamine cravings and considered a pharmacological treatment for dependency(6). This is huge when we consider methamphetamine is one of the most highly addictive psychostimulant drugs used around the world.

Alongside these neurological benefits, NAC also works as a liver detoxifier due to it being a precursor for glutathione (the master antioxidant in the body). As many substance of abuse are hepatoxic (causing liver toxicity), NAC has an additional benefit of supporting liver health(7)(8).

Considering this science, NAC may be a great tool for anyone suffering from addictive behaviours or tendencies, helping you take control of your life and mental health. This doesn’t just relate to substance addiction, but addiction of any nature, for example it has the possibility to help individuals who are addicted to technology and social media. Recommended doses in accordance to studies is 1000mg-2000mg per day on an empty stomach away from food. It’s Alchemic Health’s mission to help people with mental health issues, addiction being one of them. If you are looking for support, please do not hesitate to book a consultation today. I believe NAC’s intervention can help us take control over our impulses, allowing us to gain back our power in life.

Written by Luke Pavasovic
Director and Naturopath at Alchemic Health
facebook.com/alchemichealth
www.alchemichealth.com

References:
1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4633516/
2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5993450/
3. https://pubmed.ncbi.nlm.nih.gov/28898494/
4. https://pubmed.ncbi.nlm.nih.gov/24676047/
5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4009342/
6. https://pubmed.ncbi.nlm.nih.gov/25556383/
7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5241507/
8. https://www.ncbi.nlm.nih.gov/books/NBK548401/

September 18, 2020

Building Blocks for the Brain

There are numerous substances and herbs that help in facilitating the health and functionality of the brain. But what if we just want to feed the brain nutrients that help increase its overall health?

Today I want introduce to you three natural compounds uridine, citicoline and DHA, that when consumed help increase your brain’s health, plasticity, neurogenesis (growth of new brain cells) and synaptogenesis (growth of new brain cell connections). These three work synergistically together to increase brain phosphatides and synaptic proteins, that aid in overall brain health by inducing an increase in synaptogenesis and dendritic spines (the “back” of neurons thought to store memory) on hippocampal neurons(1). Several weeks of treatment with these compounds exhibited parallel changes in proteins known to be associated with pre- and post-synaptic membranes(1).

Uridine
Uridine is a nucleoside consisting of uracil and D-ribose and a component of RNA. It’s also known as beta-uridine or allo uridine and belongs to the class of organic compounds known as pyrimidine nucleosides(6). It is found abundantly in mothers breast milk, as one of its role is to facilitate brain development(1). It helps create the right environment for increased neuronal plasticity and synapse formation, which helps the brain adapt, learn, remember and regrow. Studies show uridine increases neurite outgrowth, helping brain cells grow and regenerate(2). It activates P2Y2 receptors which promotes the birth of new neurons and also repairs injured ones alongside nerve growth factor (NGF)(3). It has demonstrated to help people suffering from depression and bipolar by increasing mitochondrial health and improving the phospholipid structure of nerve cell membranes(4)(5). Furthermore, uridine administration not only improves memory and cognition but also has sleep-promoting and anti-epileptic actions(7).

Citicoline
Citicoline, also known as CDP-choline, is vitally important for the biosynthesis of phospholipids such as phosphatidylcholine, which help build cell membranes and protective nerve coatings(8). After it’s ingestion, citicoline goes through chemical reactions (hydrolysis and dephosphorylation) that produces two compounds cytidine and choline(9). These two compounds then by-pass the blood to brain barrier, enter the brain and are resynthesized into CDP-choline within brain cells. It boosts the production of acetylcholine (neurotransmitter responsible for muscle movement, thinking and working memory) but also has shown to increase dopamine and norepinephrine in the CNS(10). Citicoline has demonstrated to be neuroprotective in those with brain ischemia, stroke and trauma by inhibiting destructive processes, stimulating antioxidant glutathione synthesis and reductase, attenuating lipid peroxidation and restoring ATPase activity(9)(11).

DHA
Docosahexaenoic acid (DHA) comes from omega-3 fatty acids and is generally found fish oil but can also be sourced from flaxseeds and chia seeds. It is highly concentrated in the brain (making up 90% of the omega-3 fatty acids in your brain) and is a structural constituent of membranes specifically in the central nervous system(12). Since endogenous formation of DHA is relatively low, consuming DHA may contribute to optimal conditions for brain development but if low levels are sustained during childhood and adult life, this may lead to cognitive decline and major psychiatric disorders(12). It has demonstrated to be anti-inflammatory with a study showing 6-12 weeks of intake decreased concentrations of several inflammatory markers in the blood by 20%(13). It helps improve age related cognitive decline by positively influencing aspects of hippocampal neurogenesis (growth of new brain cells) which increases cognitive performance and memory, yet the mechanisms by which is does this is still unclear(14)(15).

As we can see, there are amazing benefits from consuming any three of these compounds but when taken together they synergistically help to amplify the positive effects to a greater degree. By improving the brain’s health through these natural compounds, we can expect better cognitive performance, increased learning abilities and memory due to their repairing, growing and rewiring abilities(1). By increasing the overall health of our brains, we will also acquire better stable moods and possibly increase motivation, this is theorized to happen due to the restoration of dopaminergic transmission and upregulation/modulation of dopamine receptors(16). This formula is a worthwhile investment for anyone, throughout all stages of life.

Written by Luke Pavasovic
Director and Naturopath at Alchemic Health
facebook.com/alchemichealth
www.alchemichealth.com

References:
1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3062998/
2. https://pubmed.ncbi.nlm.nih.gov/15939540/
3. https://pubmed.ncbi.nlm.nih.gov/23550835/
4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3080753/
5. https://pubmed.ncbi.nlm.nih.gov/21176029
6. https://pubchem.ncbi.nlm.nih.gov/compound/Uridine
7. https://pubmed.ncbi.nlm.nih.gov/21401495/
8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6120106/
9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3933742/
10. https://pubmed.ncbi.nlm.nih.gov/17171187/
11. https://pubmed.ncbi.nlm.nih.gov/11796739/
12. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4728620/
13. https://academic.oup.com/jn/article/139/3/495/4670362
14. https://www.ocl-journal.org/articles/ocl/full_html/2011/05/ocl2011185p242/ocl2011185p242.html
15. https://www.sciencedirect.com/science/article/pii/B9780124105270000211
16. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2592845/