Microdosing epinephrine for cognitive and sexual improvement

CCC and I touched on this in a PM exchange. I wanted to post a topic to get thoughts.

The most recent Dr Melcangi study showed that Finasteride lowered an enzyme actvity (PNMT) that converts nor-epinephrine into epinephrine.

In support of our hypothesis, results revealed a reduction in the levels of epinephrine, with a concomitant increase of norepinephrine levels, coupled to no effect on PNMT protein levels. These findings suggest that the altered hormonal levels were due to a reduction of the enzymatic activity rather than to decreased levels of PNMT.

"We believe that the present findings may help in explaining the various side effects reported by FIN users, in particular those related to sexual function "

" The noradrenergic system is also involved in the regulation of male sexual functions.[(50,51) The central control of erection is linked to ascending signals to the brain and descending ones to the spinal cord.[(51)]In addition, adrenergic innervation is strongly present in penile arteries and veins and in cavernosal smooth muscle.[(52)] In support, vascular control by the autonomic nervous system regulates erection.[(53)] The first phase of the erection cycle in humans is the flaccid state; then, upon stimuli, the penis reaches tumescence until complete rigidity, to conclude with the detumescence phase, back to the initial flaccid condition. Adrenergic control is involved in all erection phases.[(54)] Indeed, norepinephrine release in the penis induces the flaccid state by contracting the trabecular smooth muscle.[(55)]( Accordingly, in healthy men, a reduction in norepinephrine levels is associated with penile tumescence and erection, while an increased level of this hormone is associated with the transition from rigidity to detumescence.[(26)]Thus, norepinephrine is involved in transforming the penis from the erect to flaccid state.[(56)]In contrast to norepinephrine, epinephrine levels are increased in the tumescence phase in relation to the flaccid condition and then decreased in the rigid and detumescence phases.[(27)]Thus, these two hormones have opposite functions in penile erection. In human psychogenic and neurogenic erectile dysfunctions, the rigidity phase cannot be achieved. Interestingly, in these conditions, plasma norepinephrine levels are high in flaccidity, tumescence and detumescence phases, suggesting an impairment in adrenergic signals.[(27)] In summary, the balance of epinephrine and norepinephrine is crucial for achieving an erection.[(76,77)] Thus, based on the results we obtained, it is possible that FIN administration, by affecting PNMT enzymatic activity, is involved in the sexual problems reported by FIN users."

https://pubs.acs.org/doi/10.1021/acs.jmedchem.0c02039?ref=pdf


This microdosing approach having any efficacy comes with major assumptions,
this adrenergic imbalance decribed above continues post withdraw of Fin. (aka continues with PFS).

  • that microdosing epinephrine creates enough of a counter ratio in different conditions to mimic physiological ratios in “normal men”…
  • normal baseline state (may need a smaller microdose to help attention, memory, other cognitive functions)
  • “excitement” / tumescence phase (may need a larger microdose to “help” create the engorgement and “excitement” when sexual stimulation begins)
  • the wild car here, is that because its exogenous epinephrine, norepinephrine continues to be presumably remain high (not enough is turning over into norepinephrine). *norepinephrine release in the penis induces the flaccid state by contracting the trabecular smooth muscle.[(55)] Accordingly, in healthy men, a reduction in norepinephrine levels is associated with penile tumescence and erection, while an increased level of this hormone is associated with the transition from rigidity to detumescence. > This could cause an issue where continued high levels of NE “bocks” the actions of raise E.

I have 45-60 days before I get a penile implant. Any help getting my hands on a vial of epinephine (not an epi-pen though) would be greatly appreciated!

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Hi Brother, i think this is a great finding.
But it’s a bloody shame, such relevant findings by Melcangi seems to have no follow-up and no attention by the PFS foundation. How can we found a treatment if nothing is done with these findings. It’s also a shame you and CCC have to do this without any support of the Foundation.

Besides this maybe you can delete the PI ifyou are willing to try this stuff. You can always do a PI later

I don’t know if it make sence, but you can buy A source of PNMT over here:

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I want to at there was a user named @thisisarealbummer who mentioned the PNMT aspect before Melcangi did.
Hè recovered using a whole lot of thing, Hè used Rauwolfia serpentina root for the PNMT

Also epinephrine is used in the ER to shut down a priapism

i don’t get this idea around epinephrine for ED, because epinephrine (adrenalin) is generally vasoconstrictor and high epi associated with ED in most of the studies.

Maybe our problem is high norepinephrine, and not low epinephrine. I’ve found an article now stating: “Clinically, higher levels of serum norepinephrine have been reported in patients with psychogenic ED than in normal controls or patients with vasculogenic ED” or “The level of norepinephrine was higher in patients with psychogenic impotence than in the normal controls and patients with vasculogenic impotence (p less than 0.01), and it was significantly higher in negative responders than in positive responders in the psychogenic impotence group (p less than 0.001). There was no significant difference in the level of epinephrine among the groups.”

Edit- Found some more interesting info.

I saw a post here on forum how somebody recovered from cycling acetyl carnitine and rhodiola rosea, and now I’ve found article that both of these are norepinephrine boosters…

"3. L-Carnitine

Another amino acid, l-carnitine, is an excellent brain booster and natural antidepressant that works by increasing levels of both norepinephrine and serotonin.

If you decide to give it a try, be sure to use acetyl-l-carnitine (ALCAR), a highly bioavailable form of l-carnitine that readily enters the brain. (28)

  1. Arctic Root

Arctic root ( Rhodiola rosea ) is a popular adaptogenic herb that reduces depression symptoms as well as antidepressant medications. (29)

It works by decreasing cortisol levels while increasing levels of norepinephrine, serotonin, and dopamine. (30)"

Maybe there really is something to this all… disbalance between norepinephrine and epinephrine, or some kind of bad signaling

Another edit :slight_smile: -

"When you have too much norepinephrine, you’ll tend towards anxiety and insomnia.

A sudden burst can even trigger a panic attack. (Maybe this could explain our crashes?)

Conversely, a norepinephrine deficiency can leave you fatigued and depressed, with little interest in life."

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The level of norepinephrine was higher in patients with psychogenic impotence than in the normal controls and patients with vasculogenic impotence (p less than 0.01)

PFSers tend to have vasculogenic impotence as seen in Khera’s report. I also have it.

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Do you have good sensation? I ask just because I wonder how valuable having an implant would be if you have low desire and ability to orgasm. I can get hard just fine but find sex best avoided just because, in my experience, girls can’t handle it that I can’t really come. They feel sex is “pointless”. Therefore, for me, even if I were impotent, it would be better to wait for whatever possibility might exist of us getting research going and a therapy being revealed (than to get dick sliced open).

It had to be valuable for him not for you. Hè will have his reasons and an Implant can be a relationship-saver. Also "Dick Slliced open’ sounds offensive.

Yeah you could have put it a bit better but I do kindda agree. But it still is his own choice, even if some of us would rather wait for other opportunities.

Just sharing the perspective of someone who has erections but no feeling in case hearing peoples’ perspective can be of value.

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I Saw your doppler exam on FT. Although not the best results you wish, it not seems te be hopeless of irreversible. There are things you can try for your vasculogenis impotence. F.i. shockwave/gainswave, prp, stent, stemcell treatment (India/Mexico), botox injection, daily viagra, and possible many more things

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Very good work brother

If everyone could contribute the way you do we would probably have solid treatment protocols by now

You seen Melchangi’s new study, analyzed it, figured out what’s it’s suggesting and you are trying to make a treatment protocol based off of it.

Why is it that out of a whole forum of people you are the only one doing this … anyway awesome

I could add one more thing:

Melchangi’s findings certainly suggest that we could possibly benefit from increasing epinephrine. But there is another way to look at these findings as well. Maybe body is lowering epinephrine to protect us in our 5AR inhibitor induced imbalanced state. Maybe increasing epinephrine will make us worse.

Here is why I’m making this guess:

SAMe is the cofactor that allows the PNMT enzyme to convert Norepinephrine to Epinephrine. Myself and a handful of others took SAMe and got substantially worse specifically with insomnia. Therefore maybe the reason why we got worse from SAMe was working as a cofactor to allow the PNMT enzyme to make more epinephrine from norepinephrine. It’s something to keep in mind. But hell yea we need soldiers who are willing to try it either way.

The only other thing I can add is that dopamine converts to norepinephrine and like we already know the norepinephrine converts to Epinephrine. Well on 7/29/2020 the amount of dopamine in my urine was 129 ug/g. I increased dopamine production for approx 64 days and by 12/5/2020 my urinary dopamine increased to 163 ug/g. My norepinephrine which is next in the cascade increased as well. But guess what ! My urine epinephrine which is last in the cascade did not increase. In fact it went down a little. So my urine neurotransmitter experiment is consistent with what Melchangi is saying here. That even when norepinephrine increases (and in my case when dopamine increases) my epinephrine does not increase.

Also when my urinary dopamine and norepinephrine increased I fell into PFS onset level insomnia and stayed up for 8 days and lost 8 pounds of lean muscle and I’m 10 years into PFS. Why ? Why did I feel like I had too much adrenaline (epinephrine) when it did not even increase according to my urine test . So like others are saying here maybe the issue is too much norepinephrine or maybe it’s something at epinephrine receptor level that went “out of wack” when Allopregnanolone was inhibited temporarily while inhibiting 5AR. The point is this is not the only evidence of neurotransmitters imbalance I am seeing in my self. I’m seeing evidence of GABA and Glutamate receptor imbalance as well

Now one way to experiment is to try to increase epinephrine by taking cofactor SAMe. Another option is to go to the very beginning of the epinephrine cascade and take phenylalanine, tyrosine and DOPA and see what happened’s…I posted the cascade above so everyone can see what I mean

We should come up with a list of optional experiments based on this information and if volunteers want to trial the ideas then awesome

SAMe (2)|451x499](upload://dXcFk7jZezMMvhH2H7TPF80IJ72.png) increases) epinephrine at the end of the cascade does not…

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Urine tests have not shown to be particularly reliable so I wouldn’t use them as a basis for any conclusions.

Except that in this case my urine neurotransmitter results are consistent with Melchangi’s scientific study that did not use urine samples

I test once and have low dopamine and norepinephrine in my urine. I take supplements for 64 days and test again and my dopamine and norepinephrine in my urine is higher. Are you telling me that I can’t conclude that I probably increased the amount of dopamine and norepinephrine that my body was producing? After seeing that both values are higher in my urine ? Why do you think these values in my urine increased after taking all three things above dopamine in the chart I posted? Did these values in my urine increase by not producing more while taking all three things that make dopamine? I’m interested to hear more about your thoughts on this. In other words how did that extra dopamine and norepinephrine get in my urine…

So? Doesn’t mean that they’re accurate. There’s reasons why he didn’t use urine samples.

Just because you recorded higher levels after two months of supplementation again, does not make it one samples a reliable measure of those biomarkers which is why they’re tweely used in studies.