Microdosing epinephrine for cognitive and sexual improvement

Therapeutic Efforts
#1

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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#2

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:

1 Like
#3

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

#4

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.

#5

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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#6

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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#7

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).

#9

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.

#10

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

2 Likes
#13

SAMe (2)
SAMe (2)511×566 32.3 KB

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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#14

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

#15

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…

#16

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.

#17

Melchangi wanted to know exactly what was happening in the adrenal glands with norepinephrine to epinephrine production and used rodents I believe

We could make the claim “how do we know these results are accurate”

With this stuff nothing is ever going to be certain

If I take supplements to increase dopamine, norepinephrine and epinephrine and see both values increase in my urine with before and after testing I have no reason to believe that my results were not accurate. I’m going to lean towards trusting the lab over trusting your opinion which is based off nothing. I’m not saying that my urine values are telling me what was happening in the adrenal glands. But i am saying if I’m peeing out higher amounts in urine seen in before and after testing it was probable because I was producing more while on the amino’s. You have not convinced me otherwise.

I also crashed while on these supplements. So clearly they increased or decreased something significant to my disorder. I did not crash on amino’s simply because my body had more amino acids. Amino acids make neurotransmitters

#18

@orthogs show me your sources for your statement:

“neurotransmitters urinalysis not being accurate and not being used in scientific studies”

Here is info to the contrary:

“Studies have demonstrated a link between central nervous system neurotransmitter activity and urinary transmitter output”

“A study in rats examined the effects of oral ingestion of the serotonin precursor, 5-hydroxytryptophan (5-HTP), on specific brain regions. Serotonin levels were measured using brain tissue immunoreactivity and urinalysis”

“The researchers noted maximum serotonin immunoreactivity in the serotonergic dorsal raphe nucleus within 2 hours of administration”

“Urinary analysis of serotonin, 5-HTP, and 5-hydroxyindolacetic acid (the major metabolite of serotonin) mirrored the changes observed in immunoreactivity, suggesting a positive correlation between CNS and urinary serotonin levels”

“Another study in rats investigated the effect of induced hemiparkinsonism on the metabolism of catecholamines, as well as the relationship between cerebral catecholamine content and urinary catecholamine excretion”

“A positive correlation between urinary and striatal dopamine concentrations was demonstrated. Interestingly, the researchers concluded that measurement of urinary catecholamines and their metabolites is a prospective test for evaluating the status of the dopaminergic nigrostriatal system of the brain in experimental parkinsonism”

#19
#20

I read the whole thing. Not very carefully but a light read.

It’s certainly making it clear that urine neurotransmitter values are not representative of neurotransmitter levels in the CNS. I think we know that already though …

Also it’s making it clear that serotonin and dopamine produced in response to taking amino acids does not cross the blood brain barrier.

Lastly it’s saying that the only useful info that urine neurotransmitter values do provide is when you have before amino acid and after amino acid testing which I did have

Seeing that my constipation gets substantially better when I ever take the amino acids that produce serotonin I wonder if this means anything important. I read that most serotonin is actually produced in the gut and that serotonin in the gut helps stimulate bowel movements. So I wonder if the fact that this is saying that the extra serotonin from the amino acid supplementation can’t cross the blood brain barrier is not relevant as far as the specific benefits that I see when increasing urinary serotonin… because if the amino acid supplementation is making serotonin in my gut that’s helping me poop better . I don’t know Just throwing out ideas.

So I’ll agree urine neurotransmitter levels are unreliable as far as giving fool proof answers which you are clearly looking for. But I can’t in my own experience agree that they are not relevant. I’ll have to read everything in this study more carefully when I have more time

What’s your opinion on urine Allopregnanolone and 3a-diol levels?

This study address urinary serotonin and dopamine levels only it looks like.

Also the chart I posted still does not lie as far as SAMe being a co factor for norepinephrine to Epinephrine production. And myself as well as one of the moderators got worse from taking SAMe. SAMe obviously could be doing other things. But I find the fact that it’s a co factor involved in producing epinephrine that Melchangi is suggesting we may be low in is interesting. And my theory and opinion remains that it’s not a production being low vs high in epinephrine issue but rather a regulation issue. And I still think we should find out if more PFS people have high Allopregnanolone and 3a-diol in their urine or high pregnenolone sulfate in their Saliva like I do. We may want to consider urine Allopregnanolone and 3a-diol unreliable in general but what if several PFS patients have high amounts of Allopregnanolone and 3a-diol in our urine and if non PFS patients don’t…

Would this just a big unreliable by chance thing?

#21

Guys, help me a find a source for epinephrine!

#22

SAMe (2)
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Maybe consider trying to increase it on your own starting from the beginning of the pathway

People bring up valid points on why the amount of it in our urine can’t be one hundred percent replied upon as gospel. But that still doesn’t change the fact it’s made in the body using the things at the beginning of the pathway. Maybe epinephrine increasing in our urine is a sign our overall production of it increased maybe it’s not. What the body does with it is what the body is going to do with it.

Personally I think that if I take Phenylalanine, Throsine and DOPA and see dopamine and norepinephrine increase in my urine with out epinephrine increasing which for the record I already seen this happen I think it’s probable not something to ignore. But obviously this is guess work and there is no guarantees here.

So if PNMT enzyme is not working properly for what ever reason we can increase norepinephrine all we want and we may not be able to get that extra epinephrine which is the point of your trial. But the only way to know is to try.

I’ll run a trial on this. WTF not…
As soon as I start I’ll update this thread
Last time I crashed in November of 2020 I was on Phenylalanine, Throsine and DOPA . But I was also on several other things including SAMe…

This time I’m not taking SAMe. I’ll do the Phenylalanine, Throsine and L-DOPA. I’ll also stay on the L-Tryptophan, 5-HTP and vitamin B6 for serotonin production that I started back up a few days ago already anyway. This way I’m going for increasing serotonin and dopamine at the same time which based on what I read in theory is the better way to do it seeing that serotonin and dopamine should be balanced similar to how GABA and Glutamate should be balanced

I’m taking a huge risk here because everything I have listed here are all things I was taking when I crashed into horrible insomnia at the end of November 2020. But this time I’m not taking SAMe or taking anything to increase GABA and Glutamate. So I’m targeting just serotonin and dopamine this time to decrease the risk of crashing again hopefully. Also I have went back on the serotonin supplements 5 times now for short periods of time since crashing at the end of November 2020 and haven’t crashed again. So the major risk with this trial will be increasing dopamine, norepinephrine and epinephrine which I haven’t tried doing since I crashed last…

Melchangi is suggesting we are low in epinephrine as the possible cause of our sexual sides. Maybe epinephrine is being kept low for a reason because something else is out of wack and increasing epinephrine makes me crash…

Unfortunately this is what my life is. A PFS nightmare experiment. But this experiment is locked in and ready to go. I’ll just go right into it and start taking all three with the Phenylalanine, Throsine and L- DOPA. I’ll shoot for about 14 days. Hopefully last time I crashed was because I took everything for 64 days and it was just too much

You can try ordering the epinephrine from China…

#23

I read today that mucuna pruriens raise adrenaline… I don’t really know how else you can get a hold of it other than the black market (no joke).