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February 18, 2021

A Toxic Relationship – When Alcohol Meets Cocaine

Alcohol and cocaine are two of the most popular recreational substances on the planet. Alcohol is legal and easily accessible to anyone; cocaine is illegal but a highly sought after with the image of it being a high-end drug for the rich and famous. Both substances are toxic in their own way but what happens when they are taken together?

From a general perspective these two substances are usually consumed together. Cocaine is the most abused psychostimulant known to man, and it gives the user a euphoric confident high due to its ability to directly inhibit the reuptake of dopamine, serotonin and norepinephrine into pre-synaptic neurons(1). This inhibition elevates synaptic concentrations of these neurotransmitters, which is responsible for the high cocaine provides. Although the high can be euphoric, cocaine does also come with sides effects such as edginess, paranoia and irritability which is generally due to its effects on norepinephrine. Due to this, it is very common for people to add alcohol to the equation to level out the high and bring some calming effects to their neurological system – but is this safe?

Alcohol is used as a catalyst in chemistry, meaning it enables a chemical reaction and speeds these reactions up where they would usually take a long time. When we consume alcohol and it enters the liver, it can alter the chemical reactions thus changing the way some drugs work within the body. When a person consumes alcohol while cocaine is in their system, it changes its kinetics and metabolism which creates a new byproduct called cocaethylene. Cocaethylene is an ethyl ester of benzoylecgonine and is a psychoactive substance which has pharmacological properties similar to cocaine but has a half-life three to five times that of cocaine(2)(7). It has been shown to be more potent, increasing aspects of the high for the consumer but also the dangers, exerting more cardiovascular toxicity than either alcohol or cocaine alone(3). Because cocaethylene has a slower rate of elimination from the body, it makes it more attractive to the user due to its duration along with its increased potency. However, it greatly increases the risks of seizures, liver damage and compromises the function of the immune system(4).

Cocaethylene causes hypertension and increased systemic vascular resistance, while at high concentrations decreases myocardial function, slows cardiac conduction and is arrhythmogenic(5). The LD50 of cocaethylene is significantly lower than that of cocaine, carrying a 18-25 fold increase in risk for immediate death than cocaine alone(6)(7). Experiments suggest cocaethylene depresses the myocardium which is the muscular center layer of the heart between the outer layer (epicardium) and the inner layer (endocardium). This demonstrates how it’s a major contributor to cardiotoxicity(8).

Human studies show that when cocaine is ingested with ethonal in the system, 17% of the cocaine is converted to cocaethylene with subjects said to of experienced more intoxication with this combination(10). Alcohol also increased peak concentrations of cocaine by about 20%, this is due to alcohol increasing the absorption of cocaine(11). So it’s not just cocaethylene that is possibly dangerous but the fact that alcohol also increases the absorption of cocaine at the same time, this combination increases the potential of toxicity along with overdose. Higher blood concentrations of cocaine along with the presence of cocaethylene was associated with elevated heart rate, increased plasma cortisol concentration and higher cardiotoxicity(11). Some good news is most users of cocaine do not ingest enough alcohol to produce significant amounts of cocaethylene, but when excess alcohol is consumed along with cocaine, concentrations of cocaethylene are very modest according to postmortem studies(11).

I have personally seen people mix this combination of drugs in the past. With my understanding of its toxicity, I worry what this may be doing to people not only in the immediate future but also in the distant. It may increase the ricks of cardiovascular disease (CVD being the number one killer worldwide, taking an estimate of 17.9 million lives each year)(9). With CVD being caused primarily from lifestyle choices, this combination is a factor that may to increase the risks. I want people to be aware of this toxic combination and byproduct, so that they understand what they are potentially doing to their body, allowing them to make changes to avoid these dangers. So next time you are out and having a drink, take a second thought before you do that line, think of your health and heart before you start.

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

1. https://pubmed.ncbi.nlm.nih.gov/11920678/
2. https://pubmed.ncbi.nlm.nih.gov/9243342/
3. https://pubmed.ncbi.nlm.nih.gov/1432406/
4. https://pubmed.ncbi.nlm.nih.gov/9243342/
5. https://pubmed.ncbi.nlm.nih.gov/12215047/
6. https://pubmed.ncbi.nlm.nih.gov/7501674/
7. https://drugs.ncats.io/substance/FJO3071W5Y
8. https://pubmed.ncbi.nlm.nih.gov/8606535/
9. https://www.who.int/health-topics/cardiovascular-diseases#tab=tab_1
10. https://pubmed.ncbi.nlm.nih.gov/14636972/
11. https://www.sciencedirect.com/topics/neuroscience/cocaethylene

February 18, 2021

A Call for a Change of Perspective and Education

Let’s be honest, the war on drugs has failed and continues to fail. After decades of prohibition, recreational substances are still rampant and more accessible then ever before with the rise of silk road and other darknet sites. The common saying “just say no” has shown time after time not to work, and in fact may increase the urge to try substances because it is forbidden. Humans throughout history have shown their innate desire to seek altered states of consciousness, with most cultures having a sacred medicine, drink or even mushrooms that allowed them access to spiritual visions essentially having a psychedelic experience. Unfortunately, in these modern times, such things are not as widely accepted and are outlawed, but we still seek altered states through drinking our morning coffee for stimulation or having a glass of wine with dinner to end the day. At the end of the day, if someone wants to seek and take a drug they will do so despite the law and we see this within our society. Due to it being so taboo and outlawed, we lack true unbiased drug education within society. There is and always has been an immense push of scare tactics to deter people from taking drugs, but this also does not work which causes more misinformation and harm to the user. I am a true believer that if we want to saves peoples lives from the dangers of drugs, instead of trying to scare them away, we need to educate so that people truly understand how these substances work, their possible interactions with other drugs and how to mitigate the toxicity. I am not condoning the use of drugs by all means, but I am all for true unbiased education so that people have the knowledge to make the right choices which inevitably will save lives and create a safer environment for the user. When we change our perspective on drugs, we will change our reality and how our society approaches the subject. Instead of pushing the subject away and turning a blind eye to it, we need to face it and understand why people want to seek them and how they these substances work.

At Alchemic Health we dedicated to helping people with addiction and drug rehabilitation. Alongside this we also are here to spread unbiased information about drugs and how to counter their toxicity (if there is any) through natural therapies. Knowledge is power and we want to grant people the power to understand themselves and what they are consuming so that they may make the right choices for themselves. We need to be compassionate to all works of life as everyone is different and has had different life experience, stop demonizing people and actually take the time to understand them.

In the near future, I will be bringing you true drug education and ways to biohack your recreational experience to create a safer environment. I know if I tell you not to do it, you will most likely still do it, so I want to give you the right knowledge and education so that I know I have done my part to help saves lives and peoples health, stay tuned.

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

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

November 13, 2020

Longevity: Thymus Health and Regeneration

The thymus is an amazing little gland in the body that does some very important things. It’s part of the lymphatic system along with adenoids, spleen and tonsils and is also part of the endocrine system. It is located in the center of the chest behind the sternum and is responsible for producing progenitor cells which mature into T-cells (thymus-derived cells). The thymus also produces immune regulating compounds, hormones such as thymosin, thymopoietin and thymulin, as well as other peptides and interleukins. It is one organ that reaches maturity in utero and involutes as we age. The involution of the thymus changes it’s architecture, causing it to lose its organized structure and is replaced with adipose tissues as it becomes functionally less active(1). As we age, our thymus regresses and increases our susceptibility to disease and further aging due to the decline in T-cell output(1)(2). Advance aging correlates with a reduced ability of the immune system to generate antigen specific responses to pathogens. This profound change exhibited by the aging immune system is termed immunosenescence, affecting both innate and adaptive immunity(2). We can help slow down this regression or even regenerate the thymus gland through a number of interventions. By doing this we can reestablish a stronger and healthier immune system, helping ward off aging and age-related diseases.

A number of vitamins and minerals can help the health and functionality of the thymus as we age. High vitamin C intake has shown to suppress age-related thymic atrophy whilst promoting maturation of T-cells(3)(4). Vitamin A deficiency has shown to effect the production of thymosin-β4 and CD4 but high vitamin E intake enhances T-cell differentiation via TEC functions in the thymus(5)(6). Exogeneous melatonin leads to a marked reduction in signs of thymic aging, while being zinc deficient causes age related immunological dysfunction, including thymic failure(9)(10). However, when it comes to increasing thymus health and regeneration, one of the best tools for this job are bioregulatory peptides such as Thymalin.

Thymalin is a synthetic version of thymulin (H-Pyr-Ala-Lys-Ser-Gln-Gly-Gly-Ser-Asn-OH). It was first isolated from the thymus gland in 1977 and has been studied for its geroprotective effects, meaning it aims to affect the root cause of aging and age-related diseases. It regulates immune function via increased T-cell activity, lowering inflammation, raising immunoglobulin A and has shown to be neuroprotective. One study researched the effects Thymalin has on the elderly (60yrs+) over a 6-8 year period, receiving the peptide for the first 2-3 years of observation(7). The results showed the ability for bioregulators to normalize functions in cardiovascular, endocrine, immune and nervous systems. This restoration of homeostasis was accompanied by a 2.0-2.4-fold decrease acute respiratory disease, ischemic heart disease, hypertension disease, osteoarthrosis and osteoporosis(7). There was a significant improvement in the overall health state of the peptide treated patients which correlated with a decreased mortality rate during observations by 2.0-2.1 fold, demonstrating prevention in age related pathology and prolonging active longevity(7).

Other studies show it has pronounced antitumor effects, causing tumor growth arrest and also regression, some seeing growth suppression by 78%(8). Thymalin induced a significant increase in lymphoproliferative activity and the content of tissue basophils and plasmocytes in the thymus lobules(8). The results of other studies shows that thymalin significantly enhances immunological resistance to viral infections(11). Research demonstrates thymalin’s ability to regenerate the thymus gland, helping increase immunity whilst warding off age-related diseases.

A healthy lifestyle is the best way to attain a long and healthy life. If we want to help slow the onset of aging and age-related diseases, we need to incorporate lifestyle and nutritional factors into our life, supporting the body’s organs and systems as we get older. A healthy thymus is vital to longevity and if we support it throughout life with the right nutrients and even peptide technology, we can greatly affect and combat this major factor of aging. Living younger and longer without the diseases that primarily come with advanced age.

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

References:
1. https://www.ncbi.nlm.nih.gov/books/NBK539748/
2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3791471/
3. https://pubmed.ncbi.nlm.nih.gov/25608928/
4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3869442/
5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6296595/
6. https://pubmed.ncbi.nlm.nih.gov/9523031/
7. https://pubmed.ncbi.nlm.nih.gov/14523363/
8. https://www.pubfacts.com/detail/29797130/Effect-of-Thymalin-on-the-Tumor-and-Thymus-under-Conditions-of-Activation-Therapy-In-Vivo
9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5995606/
10. https://pubmed.ncbi.nlm.nih.gov/8582782/
11. https://pubmed.ncbi.nlm.nih.gov/8067076/

October 30, 2020

Longevity: Eliminating Senescent Cells

Let’s face it, many of us would love to stay youthful forever. With more understanding and science on how we progressively age, there may be ways to slow down aging, helping you live younger for longer. Aging is complex, it’s not as easy as addressing one mechanism because there are numerous aspects to this process. A major contributing factor to this process is the accumulation of senescent cells. Senescent cells are constantly created when a cell reaches its Hayflick limit, this is the limit when a cell can no longer divide through a process called mitosis. Each normal human cell can only replicate and divide forty to sixty times before it cannot divide anymore. Once it reaches this Hayflick limit it will either go through programmed cell death, apoptosis or becomes a senescent cell. Cellular senescence can also be induced by DNA damage, oxidative stress and oncogene activation. It is a process in which cells cease dividing and undergo distinctive phenotypic alterations, including profound chromatin and secretome changes and tumour-suppressor activation(1). The term senescence was first introduced by Hayflick and Moorhead to describe the phenomenon of irreversible growth arrest(1). The purpose of this cell-cycle arrest is to limit the proliferation of damaged cells, to eliminate accumulated harmful factors and to disable potential malignant cell transformation(2).

As we go through life, senescent cells accumulate, secreting proinflammatory cytokines which damage other cells and may trigger chronic immune reactions. This accumulation may also lead to tissue dysfunction and cancer whilst increasing the aging process(2). Our immune system has the ability to eliminate or deal with senescent cells, but this can become faulty as our age increases leading to less elimination. We are able to support our immune system in this process by looking after ourselves with how we eat and how often we exercise, but also through natural compounds that have senolytic activity (molecules that induce death of senescent cells and improve human health).

Fisetin
Fisetin is a natural flavonoid that is found in various fruits and vegetables, such as apples, grapes, cucumber and strawberries. Numerous studies have demonstrated the effect of fisetin against numerous diseases and it’s reported to have antioxidant, anticarcinogenic, anti-inflammatory, neurotrophic effects(4). It has also been found to have potent senolytic properties, reducing senescence which restored tissue homeostasis, reduced age-related pathology and extended median and maximum lifespan(3). As senescent cells resist apoptosis through upregulation of the senescent-cell anti-apoptotic pathways (SCAP), fisetin has demonstrated to overcome this(5). It has been identified that fisetin selectively inhibits BCM-X_L/BCL-2 pathways which have been shown to be the “Achilles’ heel” of senescent cells(6).

Quercetin
Quercetin is another natural flavonoid (plant polyphenol) found abundantly in vegetables and fruits. Evidence suggests that quercetin has therapeutic potential in prevention and treatment of different diseases including cardiovascular disease, cancer and neurodegenerative disease(7). It has shown to have antioxidant, anti-inflammatory and anticancer properties whilst possibly being able to retard the aging process. It does this through its restoring effect on cellular senescence by the down-regulation of senescence activities and up-regulation of gene expressions of antioxidant enzymes(8). When taken with other senolytics, it demonstrates to increase the selective elimination of senescent cells, decreasing the number of naturally occurring senescent cells and their secretion of proinflammatory cytokines(9).

Theoretically, by consuming fisetin with quercetin this will increase the elimination of senescent cells in the body, helping ward off age related diseases and also decrease aspects of aging. These are two compounds from nature that can help us all on the road to better health as we age. Taking these alongside other longevity protocols may help increase lifespan, keeping you younger for longer and protecting your body in the process. By clearing senescent cells, we help rejuvenate the body which improves longevity and long-term health.

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/PMC4214092/
2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6610675/
3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6197652/
4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3689181/
5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6842927/
6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5391241/
7. https://www.sciencedirect.com/science/article/pii/B9780128021477000322
8. https://pubmed.ncbi.nlm.nih.gov/29737207/
9. https://pubmed.ncbi.nlm.nih.gov/29988130/