Acetylcholine Has Negative Effects On Gonadal Steroidogenesis

[Dopamine]

I did not say that nicotine increases acetylcholine. Where did you see me saying that? Since it is an agonist of the AChE receptors it is expected to trigger a feedback mechanism and it seems that it does that - i.e. increases levels of acetylcholilnesterase, which breaks down acetylcholine.
http://www.jneurosci.org/content/jneuro/3/4/871.full.pdf

So, yes, nicotine exposure should lower acetylcholine levels but nicotine itself is a powerful agonist of those same receptors and the net effect is probably still heavily cholinergic. This is probably one of the reasons Big Pharma had (misplaced) high hopes for nicotine as treatment for Alzheimer and it badly failed in pre-clinical trials.

I wasn't directing it at you when I said:

I think that to say nicotine increases acetylcholine may not necessarily be true just because it is an agonist of nicotinic acetylcholine receptors.

I think that most people in general have the idea that ACh increases cognition and nicotines pro cognitive effects must stem from increasing ACh. I've seen that claim many times on reddit etc...

 

[hef911]

I have been experimenting with ashwaganda and it has properties that inhibits acetylcholinesterase while also elevates serum testosterone and semen production, so like a lot of things in the peat community this also seems very contradictory. @haidut do you recommend taking ashwaganda for the testosterone stimulating effects or should it be avoided for the reasons you were mentioning?

Withanolides, a new class of natural cholinesterase inhibitors with calcium antagonistic properties. - PubMed - NCBI
"the withanolides 1-3 and 4-5 isolated from Ajuga bracteosa and Withania somnifera, respectively, inhibited acetylcholinesterase "
Clinical Evaluation of the Spermatogenic Activity of the Root Extract of Ashwagandha (Withania somnifera) in Oligospermic Males: A Pilot Study. - PubMed - NCBI
"Improvement in these parameters was minimal in the placebo-treated group. Furthermore, a significantly greater improvement and regulation were observed in serum hormone levels with the Ashwagandha treatment as compared to the placebo"

 

[sladerunner69]

Do you have some studies? If these agonist inhibit androgen synthesis by blocking the first step downstream from pregnenolone (as the study days) than even if nicotine upregulates 5-AR it won't be much good.

I am a pfs sufferer and I have gotten increased libido from smoking tobacco or chewing nicotine. However it also made me very tires. So that might play into increased 5ar emzyme but lower total test levels.

 

[Waynish]

@haidut what are your thoughts on Scopolamine? There were some studies showing rapid anti depressant action on par with Ketamine. I tried the patch and only got the classic anti cholinergic side effects.

Phosophilipid and citi choline supplements have, in the past (pre peat) made me seriously depressed, sheer agony almost to the point of hallucination. The occsional organic cigarette will make me anxious and melancholy (mixed state)

I'm bipolar 2 and I continue to wonder about the anti cholinergic approach. History of learned helplessness > paxil > hyperprolactinemia > bipolar disorder via kindling effect? > reliance on adderall/klonopin to stay reasonably functional. Possible benefits with 5adhp will update soon

@dilantinoid Updates? What have you discovered about Scopolamine?

 

[CoconutEffect]

@dilantinoid Updates? What have you discovered about Scopolamine?

Nothing positive, lost interest. Was tried under the supervision of a Mt. Sinai pyschiatrist.

 

[Broken man]

What about thiamine? I read that it increases acetylcholine too.

 

[Deleted member 5487]

What about thiamine? I read that it increases acetylcholine too.

Bump that question.

I quite nicotine couple days ago, now about to shake caffeeine as well.

Defiently want to quit small thaimine doses aswell if that is the case.

 

[managing]

Bump that question.

I quite nicotine couple days ago, now about to shake caffeeine as well.

Defiently want to quit small thaimine doses aswell if that is the case.

Old thread, but I just came across and I have an answer.

Thiamine does seem to be involved in acetylcholine release.
Possible involvement of thiamine in acetylcholine release

And thiamine deficiency leads to acetylcholine production impairment.
Possible involvement of thiamine in acetylcholine release

 

[baccheion]

Old thread, but I just came across and I have an answer.

Thiamine does seem to be involved in acetylcholine release.
Possible involvement of thiamine in acetylcholine release

And thiamine deficiency leads to acetylcholine production impairment.
Possible involvement of thiamine in acetylcholine release

Thiamine primarily affects/increases GABA. GABAergics at lower doses tend to increase acetylcholine and dopamine.

 

[dand]

Do you have some studies? If these agonist inhibit androgen synthesis by blocking the first step downstream from pregnenolone (as the study days) than even if nicotine upregulates 5-AR it won't be much good.

What’s your latest thinking on this ? To me, it does seem like nicotine inhibits androgen synthesis from how I feel but I also read this from you recently.

“Nicotine also inhibits the enzyme 3a-HSD, which degrades DHT into the less potent androstanediol. So, if it does increase 5-AR , the combination of the two would make it quite pro-androgen. The study below shows this effects is from physiological doses achievable by a smoker or a person using nicotine gums/patches.
Nicotine and cotinine effects on 3 alpha hydroxysteroid dehydrogenase in canine prostate. - PubMed - NCBI

And nicotine is also an aromatase inhibitor.
Nicotine blocks brain estrogen synthase (aromatase): in vivo positron emission tomography studies in female baboons. - PubMed - NCBI
Nicotine alters the expression of molecular markers of endocrine disruption in zebrafish. - PubMed - NCBI
Potential contribution of aromatase inhibition to the effects of nicotine and related compounds on the brain. - PubMed - NCBI

Peat said in a recent email exchange that nicotine's biggest benefit is probably on digestion, but I think those steroidal anti-estrogenic and proandrogenic effects are also something to keep in mind. Btw, even a single dose of 4mg nicotine daily was enough to see GI benefits and in fact a medical student famously took up smoking to cure his Crohn's disease.
'Doctors don't always know best:' Student claims he cured debilitating bowel disease by taking up smoking | Daily Mail Online“

 

[baccheion]

What’s your latest thinking on this ? To me, it does seem like nicotine inhibits androgen synthesis from how I feel but I also read this from you recently.

“Nicotine also inhibits the enzyme 3a-HSD, which degrades DHT into the less potent androstanediol. So, if it does increase 5-AR , the combination of the two would make it quite pro-androgen. The study below shows this effects is from physiological doses achievable by a smoker or a person using nicotine gums/patches.
Nicotine and cotinine effects on 3 alpha hydroxysteroid dehydrogenase in canine prostate. - PubMed - NCBI

And nicotine is also an aromatase inhibitor.
Nicotine blocks brain estrogen synthase (aromatase): in vivo positron emission tomography studies in female baboons. - PubMed - NCBI
Nicotine alters the expression of molecular markers of endocrine disruption in zebrafish. - PubMed - NCBI
Potential contribution of aromatase inhibition to the effects of nicotine and related compounds on the brain. - PubMed - NCBI

Peat said in a recent email exchange that nicotine's biggest benefit is probably on digestion, but I think those steroidal anti-estrogenic and proandrogenic effects are also something to keep in mind. Btw, even a single dose of 4mg nicotine daily was enough to see GI benefits and in fact a medical student famously took up smoking to cure his Crohn's disease.
'Doctors don't always know best:' Student claims he cured debilitating bowel disease by taking up smoking | Daily Mail Online“

He should've just looked into megadose vitamin D3.

 

[BigChad]

He should've just looked into megadose vitamin D3.

is nicotine in small amounts worth taking for the digestive, anti estrogen pro 5ar benefits then? what would be the safest way to ingest nicotine and what would be the best safe dosage daily or every other day? im new to nicotine, from my understanding you shouldnt be smoking it and should be looking for other ways to ingest it?

 

[baccheion]

is nicotine in small amounts worth taking for the digestive, anti estrogen pro 5ar benefits then? what would be the safest way to ingest nicotine and what would be the best safe dosage daily or every other day? im new to nicotine, from my understanding you shouldnt be smoking it and should be looking for other ways to ingest it?

I wouldn't know. Those that take it tend to use a patch.

 

[2ManyHistamines]

Wow! I am currently writing this from cholinergic hell! I though my life was depressing before. This is the greatest despair I have ever felt.

@haidut saves my skin once again. Looks like I just had my last cigarette. Time to finish Allen Carr’s book again, The Easy Way To Stop Smoking.

@haidut has now saved me from iron overload, histamine hell, and now hopefully from crippling acetylcholine sensitivity. I buy your products but where do I donate? I feel indebted

What the heck do I eat to come out of this? Chicken breast and Pepsi?

I have been eating more milk and egg yolks and apparently poisoning myself.

I am going to make some coffee I know that much.

 

[Frankdee20]

Wow! I am currently writing this from cholinergic hell! I though my life was depressing before. This is the greatest despair I have ever felt.

@haidut saves my skin once again. Looks like I just had my last cigarette. Time to finish Allen Carr’s book again, The Easy Way To Stop Smoking.

@haidut has now saved me from iron overload, histamine hell, and now hopefully from crippling acetylcholine sensitivity. I buy your products but where do I donate? I feel indebted

What the heck do I eat to come out of this? Chicken breast and Pepsi?

I have been eating more milk and egg yolks and apparently poisoning myself.

I am going to make some coffee I know that much.

Whole milk has more choline and then egg yolks have quite a bit, followed by liver and broccoli and peanut butter

 

[Dr. B]

@redsun @JamesGatz

 

[JamesGatz]

What about thiamine? I read that it increases acetylcholine too.

Interesting - I notice I get anti-androgenic effects if I take B1 consistently I maybe only crave a small dose once a week now - so many thing on RP seems to increase this hmm I think the only thing I've been taking to fight it is Caffeine

 

[Frankdee20]

Unfortunately, I do consume a lot of choline for one reason only being the benefits on liver health, as I am a miserable alcoholic.

 

[Jon2547]

I quit all choline and it has made such a big difference:

Over the years I used

choline in the form of bitartrate, and DMAE
I used galantamine
I used huperzine A
Alpha GPC

etc.

Talk about anhedonia!!

Quitting those, with the DMAE being the last to quit (about six months ago), my mood has improved significantly.

 

[iso1]

anybody tried low dose atropine ?