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Boost Your Biology Newsletter - By Ergogenic Health - Issue #21

Hey everyone, What a crazy, fun week it's been! I have just started smashing out some old school st
Boost Your Biology Newsletter - By Ergogenic Health
Boost Your Biology Newsletter - By Ergogenic Health - Issue #21
By Lucas Aoun • Issue #22 • View online
Hey everyone,

What a crazy, fun week it’s been!

I have just started smashing out some old school styled whiteboard webinars on my Instagram. This is just the beginning of some more video content to come. In fact, I am working on building a private platform so keep an eye out!

Dynorphins are a family of endogenous opioids that primarily bind to kappa opioid receptors (KORs).
Dynorphin is also involved in stress-induced dysphoria (The opposite of euphoria) pain-induced dysphoria, anhedonia (the inability to experience pleasure), anxiety, depression, and psychotic effects. 
Additionally, Dynorphin reduces glutamate release.
Chronically elevated dopamine is thought to play a role in schizophrenia and upregulating Dynorphin, likely through interactions at the D1 and NMDAr complexes.
Finally, Dynorphin mediates the effects of social defeat stress and upregulates from early childhood social isolation.

You may be wondering which compounds and other endogenous chemicals interact (both positively and negatively) with the Kappa Opioid System.
They are as follows…
  1. Lion’s Mane (Agonism).
  2. Menthol (Agonism).
  3. Amentoflavone (Antagonism).
  4. Hesperidin (Agonism).
  5. Salvia (Heavy agonism).
  6. Testosterone (Downregulates expression).
  7. Forskolin (Antagonist)
  8. Nicotine (Long term up-regulator).
  9. Cocaine (Long term up-regulator).
  10. Ketamine (Anti-Dynorphinergic).

The End Goal of Manipulating the Kappa Opioid System
We want to DOWN REGULATE and reduce the function of this receptor site to promote elevated mood, improve anhedonia, and combat depression.
Having over-expression of Kappa Opioid activity is not something we want to have chronically elevated, since it can severely mess with someone’s mood and wellbeing.
Both agonism and antagonism can be beneficial for either acute dysphoria or long term euphoria.

One anecdote I found about Kappa Opioid Modulation that was particularly interesting…
The very first time I took Forskolin back in winter 2012-2013 it gave me short window of relief from anhedonia. The radio was on and I suddenly found the music very beautiful and felt uplifted. But then I rather quickly reverted back to my anhedonic self and only got mild effects upon repeat. I think that simply breaking the anhedonic homeostasis was the reason it helped. Couple other things worked kinda similarly initially.” – Longecity User

Microdosing Mint Every Night For Kappa Downregulation?
Menthol is a weak KOR-agonist, according to Wikipedia.
There was also an article published in the Tobacco Regulatory Science journal about how menthol increases nicotine cravings by upregulating nicotinic acetylcholine receptors.
Are you thinking what I’m thinking?
If we found a way to supplement menthol over a long enough period of time, we’d (hypothetically) upregulate acetylcholine receptors and downregulate kappa opioid receptors.
As many of you know, KORs are not something you want to have a lot of activity at, since KOR antagonists relieve depression and anxiety while agonists cause them.
If menthol were to downregulate KORs, that could possibly lead to decreases in depression and anxiety.
Salvia – The Most Dysphoric Substance Known To Mankind?
I don’t know much about the salvia leaf, but some facilities are using it as a form of addiction treatment.
But I would like to share this anecdotal testimonial from somebody who used the salvia leaf for Kappa down regulation:
Anecdotal experience using Salvia Leaf for KAPPA downregulation.
“I microdose salvia pretty regularly (0.05g of plain leaf, vaporized) and it is helpful for my (admittedly mild) depression. Some people suggest getting enough salvinorin A that you actually feel some dysphoria, but I find a smaller dose to be better for a more consistent dosing protocol, since I do that about two times a day from four to seven days a week.
If I am consistently consuming enough that I get some acute dysphoria, then after a few days I cease using it, because it’s unpleasant enough that I lose the motivation to dose. The effect is pretty mild but it does hit a few targets for me (quiets obsessive thoughts, increases motivation), but I haven’t been doing it long enough to notice longer term effects. I do think microdosing is a viable approach to taking a lot of substances like these, though. (Longecity User)”

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Lucas Aoun

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