How to upregulate the 5-ht1a Autoreceptor?

Hello, I'm a 19 y/o female with a severe case of PSSD. It is evident to me that 5-ht1a autoreceptor downregulation plays a huge role in PSSD. I have searched for many hours to try to figure out how to upregulate this autoreceptor, but I could not find anything. In addition, articles mentioning how antagonists at the 1A autoreceptor "decrease the sensitivity" of the autoreceptor as well as mentionings of WAY 100635 (a potent 5-ht1a antagonist) only preventing further downregulation of the 1A receptor but not upregulating anything confuse me. I previously thought a potent 5-ht1a antagonist could reverse this, but in addition to not having many readily available, I'm not sure if they would work to upregulate, as there seem to be so many factors involved in the upregulation of this receptor. Inositol, SJW and other supplements increase the sensitivity of this receptor temporarily somehow (I've read), and buspirone and other 1A agonists stimulate the receptor which helps pssd temporarily while doing nothing to upregulate it permanently. If anyone knows anything about how to upregulate this autoreceptor, please let me know... and of course correct me if I'm wrong about anything. I'm hoping to see a neuroscientist soon to see if he knows anything.

It was easy to find here
https://area1255.blogspot.ru/2016/02/how-to-increase-5-ht1a-receptors.html

5ht1a is implicated in anxiety and panic attack, it is very likely to be desensitized through excessive serotonin related actions.

I would prefer manganese which for example was found helpful in dyskinesia (high doses). Proteins may chelate Mn by the way, but on the other hand they are critically important for sexual functioning.

Also progesterone seems to counteract this receptor and this hormone is the source for prosexual allopregnanolone. 5ht1a desensitization is only one of consequences.

Where did you find about SJW and inositol? SJW is a powerful herb. The only problem is likely because it's not good for SERT. Both sups actually were mentioned in upregulating 5ht2a which in my opinion is much more prosexual and anti-anhedonic. You can find pharmd's story how he wanted to eat sugar after it and some anhedonia beating stories with sjw.

So maybe low dose sjw? lol

serotoninantagonist wrote:Hello, I'm a 19 y/o female with a severe case of PSSD. It is evident to me that 5-ht1a autoreceptor downregulation plays a huge role in PSSD. I have searched for many hours to try to figure out how to upregulate this autoreceptor, but I could not find anything. In addition, articles mentioning how antagonists at the 1A autoreceptor "decrease the sensitivity" of the autoreceptor as well as mentionings of WAY 100635 (a potent 5-ht1a antagonist) only preventing further downregulation of the 1A receptor but not upregulating anything confuse me. I previously thought a potent 5-ht1a antagonist could reverse this, but in addition to not having many readily available, I'm not sure if they would work to upregulate, as there seem to be so many factors involved in the upregulation of this receptor. Inositol, SJW and other supplements increase the sensitivity of this receptor temporarily somehow (I've read), and buspirone and other 1A agonists stimulate the receptor which helps pssd temporarily while doing nothing to upregulate it permanently. If anyone knows anything about how to upregulate this autoreceptor, please let me know... and of course correct me if I'm wrong about anything. I'm hoping to see a neuroscientist soon to see if he knows anything.

We've mentioned Lecozotan & WAY in the context of "possible" options but these options are more for MEN. 5-HT1A is primarily inhibitory on penile sexual arousal, it does not play a negative role in women and as far as "resensitizing". It may or may not happen. it may or may or may not be worth it.

With that being said, are there EMOTIONAL or COGNITIVE symptoms on your end? Such as : Anhedonia, Memory Problems (short-term etc) or extending into cellular problems, or problems with Thyroid?

You should get your hormones checked, thyroid included.
Many find their PSSD Symptoms resolve when they get T4/T3 back up to normal and Testosterone is at its sweet spot (women included).

If you want to antagonize 5-HT1A, you have two options.
1.) Find a source for Metergoline or Lecozotan. As WAY is far too expensive these days.
2.) Contact Tocris bioscience or another similar company through a university or associate and have them see if they can make an order. Though this process will result in a fair amount of "wait" (24-48 hours) just to look over details as they have strict policies on who they ship to.

Both options are possible, but #1 is a lot easier.

Thank you so much for responding with that very helpful information. That's interesting that 5-ht1a doesn't play a large role in females. I know you've mentioned how downregulation of the 1a autoreceptor is a major cause (or the cause) of PSSD, so I'm wondering if somehow upregulating it could reverse everything and if it's even possible to reverse (with an antagonist or something else). Would the antagonist WAY Lecozotan or metergoline upregulate the 1a receptor and reverse PSSD symptoms caused by downregulation of this receptor? Please correct me as well if I'm confused. I do have emotional anhedonia and short term memory problems but they were much worse before I began taking inositol. Since starting inositol a couple of weeks ago, my PSSD and all related symptoms have substantially improved. I know that inositol doesn't fix PSSD permanently so I'm wondering if you know of any supplements that can do this (make changes to the brain that last after you stop taking them). My symptoms are mainly:
1. genital anesthesia/lack of pleasure
2. anorgasmia
3. emotional anhedonia
4. brain fog
5. diminished interest

These symptoms have all improved with inositol and since reading your posts I have ordered berberine and icariin in hopes that they can reverse things for me. Do you know of any (other) supplements that can fix things?
Thank you so much.

serotoninantagonist wrote:Thank you so much for responding with that very helpful information. That's interesting that 5-ht1a doesn't play a large role in females. I know you've mentioned how downregulation of the 1a autoreceptor is a major cause (or the cause) of PSSD, so I'm wondering if somehow upregulating it could reverse everything and if it's even possible to reverse (with an antagonist or something else). Would the antagonist WAY Lecozotan or metergoline upregulate the 1a receptor and reverse PSSD symptoms caused by downregulation of this receptor? Please correct me as well if I'm confused. I do have emotional anhedonia and short term memory problems but they were much worse before I began taking inositol. Since starting inositol a couple of weeks ago, my PSSD and all related symptoms have substantially improved. I know that inositol doesn't fix PSSD permanently so I'm wondering if you know of any supplements that can do this (make changes to the brain that last after you stop taking them). My symptoms are mainly:
1. genital anesthesia/lack of pleasure
2. anorgasmia
3. emotional anhedonia
4. brain fog
5. diminished interest

These symptoms have all improved with inositol and since reading your posts I have ordered berberine and icariin in hopes that they can reverse things for me. Do you know of any (other) supplements that can fix things?
Thank you so much.

Supplement with Magnesium and Manganese.
Its mentioned in my article..
You can try St.John's Wort as well, but as Kpavel has also mentioned, it upregulates 5-HT2A as well.

Based on the studies with the female sexual dysfunction drug Flibanserin; I would say that would be a bad thing for females.
Flibanserin is a 5-HT2A antagonist and 5-HT1A agonist.
So given that logic, you probably wouldn't want to move in that direction plus you may be increasing Cortisol and further upsetting your likely already distorted hormonal function.

Area-1255 wrote:

serotoninantagonist wrote:Thank you so much for responding with that very helpful information. That's interesting that 5-ht1a doesn't play a large role in females. I know you've mentioned how downregulation of the 1a autoreceptor is a major cause (or the cause) of PSSD, so I'm wondering if somehow upregulating it could reverse everything and if it's even possible to reverse (with an antagonist or something else). Would the antagonist WAY Lecozotan or metergoline upregulate the 1a receptor and reverse PSSD symptoms caused by downregulation of this receptor? Please correct me as well if I'm confused. I do have emotional anhedonia and short term memory problems but they were much worse before I began taking inositol. Since starting inositol a couple of weeks ago, my PSSD and all related symptoms have substantially improved. I know that inositol doesn't fix PSSD permanently so I'm wondering if you know of any supplements that can do this (make changes to the brain that last after you stop taking them). My symptoms are mainly:
1. genital anesthesia/lack of pleasure
2. anorgasmia
3. emotional anhedonia
4. brain fog
5. diminished interest

These symptoms have all improved with inositol and since reading your posts I have ordered berberine and icariin in hopes that they can reverse things for me. Do you know of any (other) supplements that can fix things?
Thank you so much.

Supplement with Magnesium and Manganese.
Its mentioned in my article..
You can try St.John's Wort as well, but as Kpavel has also mentioned, it upregulates 5-HT2A as well.

Based on the studies with the female sexual dysfunction drug Flibanserin; I would say that would be a bad thing for females.
Flibanserin is a 5-HT2A antagonist and 5-HT1A agonist.
So given that logic, you probably wouldn't want to move in that direction plus you may be increasing Cortisol and further upsetting your likely already distorted hormonal function.

Flibanserin and WAY100635 share a rare D4 agonism feature. But many studies say 5ht2a is good for female receptivity

https://www.ncbi.nlm.nih.gov/pubmed/9473601/
but
http://europepmc.org/abstract/med/10216181

https://www.ncbi.nlm.nih.gov/pubmed/9430444/
and
https://www.ncbi.nlm.nih.gov/pubmed/18483155

https://www.ncbi.nlm.nih.gov/pubmed/15129779/
caber has high affinity btw

https://www.ncbi.nlm.nih.gov/pubmed/8773765/

Another sign of reduced ht2a density may be a reduction in head twitch. Those with past anxiety/restlessness should understand.

kpavel wrote:

Area-1255 wrote:

serotoninantagonist wrote:Thank you so much for responding with that very helpful information. That's interesting that 5-ht1a doesn't play a large role in females. I know you've mentioned how downregulation of the 1a autoreceptor is a major cause (or the cause) of PSSD, so I'm wondering if somehow upregulating it could reverse everything and if it's even possible to reverse (with an antagonist or something else). Would the antagonist WAY Lecozotan or metergoline upregulate the 1a receptor and reverse PSSD symptoms caused by downregulation of this receptor? Please correct me as well if I'm confused. I do have emotional anhedonia and short term memory problems but they were much worse before I began taking inositol. Since starting inositol a couple of weeks ago, my PSSD and all related symptoms have substantially improved. I know that inositol doesn't fix PSSD permanently so I'm wondering if you know of any supplements that can do this (make changes to the brain that last after you stop taking them). My symptoms are mainly:
1. genital anesthesia/lack of pleasure
2. anorgasmia
3. emotional anhedonia
4. brain fog
5. diminished interest

These symptoms have all improved with inositol and since reading your posts I have ordered berberine and icariin in hopes that they can reverse things for me. Do you know of any (other) supplements that can fix things?
Thank you so much.

Supplement with Magnesium and Manganese.
Its mentioned in my article..
You can try St.John's Wort as well, but as Kpavel has also mentioned, it upregulates 5-HT2A as well.

Based on the studies with the female sexual dysfunction drug Flibanserin; I would say that would be a bad thing for females.
Flibanserin is a 5-HT2A antagonist and 5-HT1A agonist.
So given that logic, you probably wouldn't want to move in that direction plus you may be increasing Cortisol and further upsetting your likely already distorted hormonal function.

Flibanserin and WAY100635 share a rare D4 agonism feature. But many studies say 5ht2a is good for female receptivity

https://www.ncbi.nlm.nih.gov/pubmed/9473601/
but
http://europepmc.org/abstract/med/10216181

https://www.ncbi.nlm.nih.gov/pubmed/9430444/
and
https://www.ncbi.nlm.nih.gov/pubmed/18483155

https://www.ncbi.nlm.nih.gov/pubmed/15129779/
caber has high affinity btw

https://www.ncbi.nlm.nih.gov/pubmed/8773765/

Another sign of reduced ht2a density may be a reduction in head twitch. Those with past anxiety/restlessness should understand.

Those are rat studies though, Kpavel.
I think by and large, the 5-HT2A receptors have a dampening effect in today's world. They facilitate emotional activity in the cortex and can increase creativity, so perhaps females might have more "fantasies" or increased libido to a degree, but long-term the Cortisol increases would be a problem.

Though, I haven't personally seen any particular studies that directly demonstrate the 5-HT2A receptors direct reproductive role in Women's arousal, when excluding for other factors.

There are these implications though.

--> https://www.ncbi.nlm.nih.gov/pubmed/28817365

--> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2795067/

--> https://www.ncbi.nlm.nih.gov/pubmed/21849982

Area-1255 wrote:

kpavel wrote:

Area-1255 wrote:

serotoninantagonist wrote:Thank you so much for responding with that very helpful information. That's interesting that 5-ht1a doesn't play a large role in females. I know you've mentioned how downregulation of the 1a autoreceptor is a major cause (or the cause) of PSSD, so I'm wondering if somehow upregulating it could reverse everything and if it's even possible to reverse (with an antagonist or something else). Would the antagonist WAY Lecozotan or metergoline upregulate the 1a receptor and reverse PSSD symptoms caused by downregulation of this receptor? Please correct me as well if I'm confused. I do have emotional anhedonia and short term memory problems but they were much worse before I began taking inositol. Since starting inositol a couple of weeks ago, my PSSD and all related symptoms have substantially improved. I know that inositol doesn't fix PSSD permanently so I'm wondering if you know of any supplements that can do this (make changes to the brain that last after you stop taking them). My symptoms are mainly:
1. genital anesthesia/lack of pleasure
2. anorgasmia
3. emotional anhedonia
4. brain fog
5. diminished interest

These symptoms have all improved with inositol and since reading your posts I have ordered berberine and icariin in hopes that they can reverse things for me. Do you know of any (other) supplements that can fix things?
Thank you so much.

Supplement with Magnesium and Manganese.
Its mentioned in my article..
You can try St.John's Wort as well, but as Kpavel has also mentioned, it upregulates 5-HT2A as well.

Based on the studies with the female sexual dysfunction drug Flibanserin; I would say that would be a bad thing for females.
Flibanserin is a 5-HT2A antagonist and 5-HT1A agonist.
So given that logic, you probably wouldn't want to move in that direction plus you may be increasing Cortisol and further upsetting your likely already distorted hormonal function.

Flibanserin and WAY100635 share a rare D4 agonism feature. But many studies say 5ht2a is good for female receptivity

https://www.ncbi.nlm.nih.gov/pubmed/9473601/
but
http://europepmc.org/abstract/med/10216181

https://www.ncbi.nlm.nih.gov/pubmed/9430444/
and
https://www.ncbi.nlm.nih.gov/pubmed/18483155

https://www.ncbi.nlm.nih.gov/pubmed/15129779/
caber has high affinity btw

https://www.ncbi.nlm.nih.gov/pubmed/8773765/

Another sign of reduced ht2a density may be a reduction in head twitch. Those with past anxiety/restlessness should understand.

Those are rat studies though, Kpavel.
I think by and large, the 5-HT2A receptors have a dampening effect in today's world. They facilitate emotional activity in the cortex and can increase creativity, so perhaps females might have more "fantasies" or increased libido to a degree, but long-term the Cortisol increases would be a problem.

Though, I haven't personally seen any particular studies that directly demonstrate the 5-HT2A receptors direct reproductive role in Women's arousal, when excluding for other factors.

There are these implications though.

--> https://www.ncbi.nlm.nih.gov/pubmed/28817365

--> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2795067/

--> https://www.ncbi.nlm.nih.gov/pubmed/21849982

need to read more but even this is mentioned

https://www.ncbi.nlm.nih.gov/pubmed/23551660/

kpavel wrote:

Area-1255 wrote:

kpavel wrote:

Area-1255 wrote:

serotoninantagonist wrote:Thank you so much for responding with that very helpful information. That's interesting that 5-ht1a doesn't play a large role in females. I know you've mentioned how downregulation of the 1a autoreceptor is a major cause (or the cause) of PSSD, so I'm wondering if somehow upregulating it could reverse everything and if it's even possible to reverse (with an antagonist or something else). Would the antagonist WAY Lecozotan or metergoline upregulate the 1a receptor and reverse PSSD symptoms caused by downregulation of this receptor? Please correct me as well if I'm confused. I do have emotional anhedonia and short term memory problems but they were much worse before I began taking inositol. Since starting inositol a couple of weeks ago, my PSSD and all related symptoms have substantially improved. I know that inositol doesn't fix PSSD permanently so I'm wondering if you know of any supplements that can do this (make changes to the brain that last after you stop taking them). My symptoms are mainly:
1. genital anesthesia/lack of pleasure
2. anorgasmia
3. emotional anhedonia
4. brain fog
5. diminished interest

These symptoms have all improved with inositol and since reading your posts I have ordered berberine and icariin in hopes that they can reverse things for me. Do you know of any (other) supplements that can fix things?
Thank you so much.

Supplement with Magnesium and Manganese.
Its mentioned in my article..
You can try St.John's Wort as well, but as Kpavel has also mentioned, it upregulates 5-HT2A as well.

Based on the studies with the female sexual dysfunction drug Flibanserin; I would say that would be a bad thing for females.
Flibanserin is a 5-HT2A antagonist and 5-HT1A agonist.
So given that logic, you probably wouldn't want to move in that direction plus you may be increasing Cortisol and further upsetting your likely already distorted hormonal function.

Flibanserin and WAY100635 share a rare D4 agonism feature. But many studies say 5ht2a is good for female receptivity

https://www.ncbi.nlm.nih.gov/pubmed/9473601/
but
http://europepmc.org/abstract/med/10216181

https://www.ncbi.nlm.nih.gov/pubmed/9430444/
and
https://www.ncbi.nlm.nih.gov/pubmed/18483155

https://www.ncbi.nlm.nih.gov/pubmed/15129779/
caber has high affinity btw

https://www.ncbi.nlm.nih.gov/pubmed/8773765/

Another sign of reduced ht2a density may be a reduction in head twitch. Those with past anxiety/restlessness should understand.

Those are rat studies though, Kpavel.
I think by and large, the 5-HT2A receptors have a dampening effect in today's world. They facilitate emotional activity in the cortex and can increase creativity, so perhaps females might have more "fantasies" or increased libido to a degree, but long-term the Cortisol increases would be a problem.

Though, I haven't personally seen any particular studies that directly demonstrate the 5-HT2A receptors direct reproductive role in Women's arousal, when excluding for other factors.

There are these implications though.

--> https://www.ncbi.nlm.nih.gov/pubmed/28817365

--> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2795067/

--> https://www.ncbi.nlm.nih.gov/pubmed/21849982

need to read more but even this is mentioned

https://www.ncbi.nlm.nih.gov/pubmed/23551660/

That's an interesting study, Kpavel.
Especially the part of aggression.
We know that Oxytocin plays differing roles in human aggression; on the one hand it increases "trust" and bonding in certain experiments.
It strengthens love and affinity for partners but we ALSO know that it increases territorial behavior when it comes to the partner.
--> http://gillab.ku.edu/sites/gillab.drupal.ku.edu/files/docs/SPPS516876_1.pdf
--> https://www.ncbi.nlm.nih.gov/pubmed/28864975
--> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4631637/

This seems to apply in a variety of conditions - and mostly regarding interaction WITH the partner. Although in some studies the effect was a pro-aggressive in offending peoples to the partner.

Area-1255 wrote:

kpavel wrote:

Area-1255 wrote:

kpavel wrote:

Area-1255 wrote:

serotoninantagonist wrote:Thank you so much for responding with that very helpful information. That's interesting that 5-ht1a doesn't play a large role in females. I know you've mentioned how downregulation of the 1a autoreceptor is a major cause (or the cause) of PSSD, so I'm wondering if somehow upregulating it could reverse everything and if it's even possible to reverse (with an antagonist or something else). Would the antagonist WAY Lecozotan or metergoline upregulate the 1a receptor and reverse PSSD symptoms caused by downregulation of this receptor? Please correct me as well if I'm confused. I do have emotional anhedonia and short term memory problems but they were much worse before I began taking inositol. Since starting inositol a couple of weeks ago, my PSSD and all related symptoms have substantially improved. I know that inositol doesn't fix PSSD permanently so I'm wondering if you know of any supplements that can do this (make changes to the brain that last after you stop taking them). My symptoms are mainly:
1. genital anesthesia/lack of pleasure
2. anorgasmia
3. emotional anhedonia
4. brain fog
5. diminished interest

These symptoms have all improved with inositol and since reading your posts I have ordered berberine and icariin in hopes that they can reverse things for me. Do you know of any (other) supplements that can fix things?
Thank you so much.

Supplement with Magnesium and Manganese.
Its mentioned in my article..
You can try St.John's Wort as well, but as Kpavel has also mentioned, it upregulates 5-HT2A as well.

Based on the studies with the female sexual dysfunction drug Flibanserin; I would say that would be a bad thing for females.
Flibanserin is a 5-HT2A antagonist and 5-HT1A agonist.
So given that logic, you probably wouldn't want to move in that direction plus you may be increasing Cortisol and further upsetting your likely already distorted hormonal function.

Flibanserin and WAY100635 share a rare D4 agonism feature. But many studies say 5ht2a is good for female receptivity

https://www.ncbi.nlm.nih.gov/pubmed/9473601/
but
http://europepmc.org/abstract/med/10216181

https://www.ncbi.nlm.nih.gov/pubmed/9430444/
and
https://www.ncbi.nlm.nih.gov/pubmed/18483155

https://www.ncbi.nlm.nih.gov/pubmed/15129779/
caber has high affinity btw

https://www.ncbi.nlm.nih.gov/pubmed/8773765/

Another sign of reduced ht2a density may be a reduction in head twitch. Those with past anxiety/restlessness should understand.

Those are rat studies though, Kpavel.
I think by and large, the 5-HT2A receptors have a dampening effect in today's world. They facilitate emotional activity in the cortex and can increase creativity, so perhaps females might have more "fantasies" or increased libido to a degree, but long-term the Cortisol increases would be a problem.

Though, I haven't personally seen any particular studies that directly demonstrate the 5-HT2A receptors direct reproductive role in Women's arousal, when excluding for other factors.

There are these implications though.

--> https://www.ncbi.nlm.nih.gov/pubmed/28817365

--> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2795067/

--> https://www.ncbi.nlm.nih.gov/pubmed/21849982

need to read more but even this is mentioned

https://www.ncbi.nlm.nih.gov/pubmed/23551660/

That's an interesting study, Kpavel.
Especially the part of aggression.
We know that Oxytocin plays differing roles in human aggression; on the one hand it increases "trust" and bonding in certain experiments.
It strengthens love and affinity for partners but we ALSO know that it increases territorial behavior when it comes to the partner.
--> http://gillab.ku.edu/sites/gillab.drupal.ku.edu/files/docs/SPPS516876_1.pdf
--> https://www.ncbi.nlm.nih.gov/pubmed/28864975
--> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4631637/

This seems to apply in a variety of conditions - and mostly regarding interaction WITH the partner. Although in some studies the effect was a pro-aggressive in offending peoples to the partner.

In this regard can we talk of flibanserin being another tool to create relation ? And what will be with nNos? I only talked of restored HTT here, honestly.

kpavel wrote:
In this regard can we talk of flibanserin being another tool to create relation ? And what will be with nNos? I only talked of restored HTT here, honestly.

Perhaps.
NNOS is tricky.
Too much is very BAD and promotes cell death.
Too little causes brain cognitive dysfunction and in some cases, sexual arousal difficulties.
--> https://www.ncbi.nlm.nih.gov/pubmed/17565706
--> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1867129/
--> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3121276/