Alchemic Health

Ketamine – The Good, The Bad, The Ugly

The story of ketamine begins with the synthesis of phencyclidine, which was first synthesized in 1956 and found to have remarkable anesthetic effects on monkeys but in human trails it demonstrated to have unwanted side effects such as loss of sensation in limbs, producing sensory deprivation syndrome. Hoping to find an alternative drug, Dr Calvin Lee Stevens of Wayne State University synthesized numerous phencyclidine derivatives one of them being titled CI-581 which we now call ketamine. On August 3rd, 1964 the first human trials were conducted with subjects given intravenous ketamine and describing the experience like floating in space, disconnected from their body and environment. After its approval by the FDA in 1970, it was used on injured soldiers in the Vietnam War due to its large margin of safety. In the last two decades, clinical trials have found ketamine to be not only be useful for short term pain and chronic pain but also eases pain of a psychological nature such as PTSD, OCD, anxiety, depression and suicidal ideation. Due its mind altering and blissful nature, ketamine has also grown in popularity as a reactional drug sold on the black market.

Ketamine’s primary action is as a noncompetitive N-methyl-D-aspartate (NMDA) and glutamate receptor antagonist (meaning it inhibits these receptors) and also blocks HCN1 receptors. It partially agonizes (partially activates) op**te mu-receptors which provides its pain relieving properties(1). The antidepressants effects of ketamine are hypothesized to be caused from an increase in synaptic connectivity (increasing brain cell connections). Clinical trials suggested NMDA receptors play a significant role in depression and through ketamine’s NMDA antagonistic action, it works rapidly to control symptoms(1)(2). This may be due to an increase in glutamate levels, leading to synaptogenesis (the growth of new brain cell connections) and elevating levels of brain-derived neurotrophic factor (BNDF) which is an important growth factor within our brain and peripheral nervous system(1). In recent clinical applications of ketamine to patients with depression, 80% have shown an improvement in symptoms(3). Through these actions, ketamine may play an important role in helping people with specific neurological issues.

Even though ketamine is showing beneficial effects, the dose and duration makes it either a medicine or a poison. Ketamine usage has grown exponentially within the recreational market within the last decade and we are beginning to see some of the detrimental effects it may cause for the user if used in the wrong way. A recent study which conducted magnetic resonance imaging (MRI) on ketamine addicts of 0.5-12 years illustrated the possible brain damage that can occur from ketamine abuse. Even though the study was small with only 21 people recruited, the results demonstrate that lesions within the brain of ketamine addicts appeared within 2-4 years of usage(4). Cortical atrophy was usually evident in the frontal, parietal and occipital cortices, confirming that many brain regions in humans are susceptible to ketamine induced injury. Most patients consumed ketamine daily, with only a few consuming it 2-3 times per week, dosage ranged from 0.2g-3g per day, but on average they were consuming 1g per day(4). The damage was also increased when the patient mixed ketamine with other drugs such as alcohol, amphetamine and ecstasy(4). We also do not know the health status of these patients, how much they exercised, fluid intake, diet, sleep patterns etc., and it can be hypothesized that if they followed unhealthy lifestyle factors along with ketamine abuse then this would of most likely exacerbated the brain damage. So, with all this information we are able to see that ketamine is able to be very detrimental to neurological structures if abused recreationally.

Ketamine can further begin to become uglier the more it is abused, effecting numerous organs within the body. It has been shown in rare cases to cause chronic biliary colic, where patients present with biliary symptoms (nausea, vomiting, loss of appetite, fatigue and abdominal pain/cramps usually in the upper right quadrant) without evidence of gallbladder stones(5). This is due to ketamine’s effect on the gallbladder causing dilation in bile ducts, but once usage ceased the gallbladder returned to normal(5). Ketamine may cause renal (kidney) failure, and also lead to liver toxicity and damage(8). It also shown to cause severe lower urinary tract symptoms (LUTS) with CT scans on patients revealing decreased bladder volume, bladder wall thickening, mucosal enhancement and perivesical inflammation, with advanced cases identifying ureteric narrowing and strictures(6)(7). The damage to the liver, kidneys and lower urinary tract are primarily due to the metabolites of ketamine (norketamine, dehydronorketamine and hydroxylated ketamine metabolites with glucuronic acid) and not solely caused by ketamine alone(9). This clearly demonstrates the harmful and possibly irreversible effects of ketamine on numerous organs and that it is important to recognise symptoms in recreational users before it becomes too late.

As we can see, ketamine has its place within medicine and when used correctly can greatly help those with numerous conditions but when used incorrectly may wreak havoc on numerous parts of the body causing irreversible damage. I urge people to be responsible with usage if consuming this substance in a recreational setting, be mindful of your dosage and frequency of use. If any negative side effects occur, please reframe from usage and seek medical help if symptoms persist. If you decide to use this substance recreationally, may I suggest you consume enough fluids to flush your liver, kidneys and bladder frequently and consider consuming antioxidants (vitamin C and E, astaxanthin, R-alpha lipoic acid) to help mitigate the toxicity and damage of this substance. Be smart, be safe and be responsible with your health.

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

References:
1. https://www.ncbi.nlm.nih.gov/books/NBK470357/
2. https://pubmed.ncbi.nlm.nih.gov/10686270/
3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4810965/
4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3713393/
5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4898409/
6. https://pubmed.ncbi.nlm.nih.gov/20797465/
7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4544340/
8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4421282/
9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6197107/

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
Alchemic Health
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/