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How can I upregulate 5HT2A legally?

5ht2a

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#1 neurobliss

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Posted 14 January 2019 - 06:52 PM


I have a sense of detachment, blunted affect, and loss of motivation/zest for life which I believe is due to decreased glutamatergic transmission. Modulating monoaminergic neurotransmitters doesn't seem to help with this issue. I have read an article about 5HT modulating glutamate signaling, and it was suggested in there that the safest way to modulate glutamate levels without risking excitotoxicity is via 5HT2A agonism.

 

Microdosing LSD or mushrooms is not an option for me because I have two small children and I can't risk a felony conviction, therefore I want to figure out how to this legally. Can anyone suggest legal/safe supplements or herbs that might get the job done?

 

https://www.ncbi.nlm...les/PMC2430669/

 

As the author suggested, the interplay between glutamate and 5-HT receptors offers new possibilities in the treatment of a glutamate deficit: as a matter of fact, the use of glutamate agonists would induce neurotoxicity and convulsions, whereas it might prove a good strategy to act on 5-HT2A receptors which in turn modulate glutamate-mediated effects [23].


Edited by neurobliss, 14 January 2019 - 06:58 PM.


#2 Rocket

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Posted 14 January 2019 - 08:04 PM

I think lisuride is what you're after.


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#3 Galaxyshock

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Posted 15 January 2019 - 08:33 AM

St. John's Wort upregulates 5-HT2A.

 

Panax ginseng is non-psychedelic 5-HT2A agonist.


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#4 neurobliss

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Posted 15 January 2019 - 01:33 PM

I think lisuride is what you're after.

It's not available in my country.



#5 neurobliss

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Posted 15 January 2019 - 01:55 PM

St. John's Wort upregulates 5-HT2A.

 

Panax ginseng is non-psychedelic 5-HT2A agonist.

Thanks for the info! SJW doesn't seem to agree with me but I'm going to give P.ginseng a try.



#6 Rocket

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Posted 15 January 2019 - 03:10 PM

It's not available in my country.

 

You are in the USA. It is available as a research chemical. I have bought some for rat experimentation last year.



#7 neurobliss

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Posted 21 January 2019 - 05:17 PM

You are in the USA. It is available as a research chemical. I have bought some for rat experimentation last year.

Where did you buy it from? Whenever I tried these research sites in the past they want proof that you are a legit researcher. Have you tried lisuride yourself? What was your experience?

 

In the meantime, I wanted to give an update on ginseng. I got some high potency Changbai Red Ginseng and made a strong brew with it. There was definitely a strong effect with a first dose. My emotions felt stronger and I felt the need to work through some past traumatic experiences and cry, but not in a bad way, more like what people describe on entheogens. In the evening I felt really relaxed and experienced the return of thought fluidity and ability to think in images, which I rely on for my creativity.

 

So all in all, I would say it's pretty good stuff - thanks for recommending. However, from what I read it looks like the mood effects of ginseng tend to poop out after a few weeks so most likely not a long term solution.

 

I should add that I'm also taking Lexapro right now so my reaction might be related to SSRI potentiation. I also don't know if I can get the same effect from cheap supplements rather than from this very expensive root tonic which is not sustainable long term due to high price and amount of time involved in preparation. 

 

 


Edited by neurobliss, 21 January 2019 - 05:23 PM.


#8 jacobjerondin

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Posted 15 March 2019 - 01:34 AM

Pretty sure Lexapro will downregulate 5ht2a like all SSRIs will, not sure tho. How about NSI-189 (it will prob work for your symptoms without directly affecting 5ht2a afaik).

 

I have an idea that acorus calamus (american sweet flag, that is) could help you as well. Ignore the worries about carcinogenicity, those are based on some dumb studies of them giving rats massive doses for an extended period if I understand things correctly.

 

Maybe aniracetam too? I def helped me with zest for life and motivation (before it stopped working after 3 months, to prevent that maybe try taking a couple days off every week).


Edited by jacobjerondin, 15 March 2019 - 01:35 AM.

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#9 Ovidus

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Posted 15 March 2019 - 05:53 AM

I think lisuride is what you're after.

Very interesting

Is it OK for you to share what effects you were seeking and what you have experienced?
 

By any chance has there been appetite supression resulting from this? AFAIK, it is also on the short list of chemicals that are 5HT2C agonist.

I was researching a substance that can be both an appetite supressant as well as hypnotic and Lisuride  seems to fit the bill. Even though Lisuride is a dopaminergic drug and dopamine tends to amp you up, we know that there are a lot of exceptions to this rule.

 

Thanks a lot



#10 What-a-Riot

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Posted 10 April 2019 - 12:17 PM

@neurobliss

https://idealabs.ecw...icals-c20672606

lisuride source, company owned by a poster at ray peat forum, but don't let that throw you off, chemical is what it is  :)

you can find more infor on the specific product here

https://raypeatforum...-lab-r-d.12099/



#11 Rocket

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Posted 10 April 2019 - 02:01 PM

@neurobliss

https://idealabs.ecw...icals-c20672606

lisuride source, company owned by a poster at ray peat forum, but don't let that throw you off, chemical is what it is  :)

you can find more infor on the specific product here

https://raypeatforum...-lab-r-d.12099/

 

I have a good experiences with that particular company, Ideal Labs.


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#12 jacobjerondin

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Posted 12 April 2019 - 08:42 PM

I bought lisuride from idea labs (their stuff is hella legit btdubs and I have a ton of products from them, the dude behind those products, haidut, is a dang smart biohacker). I do have to warn y'all that lisuride seems super promising but it actually doesn't work well for motivation, stimulation, appetite suppression, or any of the nice effects you typically attribute to dopamine. Just made feel lazy and horny haha. You can orgasm multiple times if you're a dude on it and you'll never be so hard in your life, that's the only good thing I noticed really. I think it kinda works for anxiety too but it def won't be helpful for OP imo. You want phasic dopamine and dopamine agonists work tonically, which isn't helpful as I understand things.

 

If anyone wants to buy mine, I've been keeping it in the fridge and didn't use it much. I'll ship it for free and sell it for less than it would cost new from Idea Labs.


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#13 neurobliss

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Posted 03 May 2019 - 09:54 PM

Pretty sure Lexapro will downregulate 5ht2a like all SSRIs will, not sure tho. How about NSI-189 (it will prob work for your symptoms without directly affecting 5ht2a afaik).

 

I have an idea that acorus calamus (american sweet flag, that is) could help you as well. Ignore the worries about carcinogenicity, those are based on some dumb studies of them giving rats massive doses for an extended period if I understand things correctly.

 

Maybe aniracetam too? I def helped me with zest for life and motivation (before it stopped working after 3 months, to prevent that maybe try taking a couple days off every week).

Why do you think Acorus would help? It's interesting because I do find that brewing real Red Korean Ginseng root helps me with energy. I don't get the same effect from the capsules or any commercially prepared elixirs, only from my home made strong brew made from premium grade root.

 

I'm sort of familiar with TCM, and there's a ancient Chinese formula called Kai Xin San (according to my Chinese friend it literally means "happy pill"). According to studies, it outperforms any Western antidepressant. It's a combination of Red Ginsgeng (5HT2A agonist), Polygala (NMDA antagonist), Poria and Acorus. The first two ingredients is like micro-micro-dosing shrooms with ketamine, but I don't know what Acorus contributes to this.

 

Unfortunately I haven't been able to find this formula in the US but I can try to make my own concoction, although I probably will not get the exact proportions right. And to be frank, despite your reassurance, I'm still kind of freaked out about the toxicity...


Edited by neurobliss, 03 May 2019 - 10:02 PM.


#14 jacobjerondin

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Posted 06 May 2019 - 07:34 AM

Why do you think Acorus would help? It's interesting because I do find that brewing real Red Korean Ginseng root helps me with energy. I don't get the same effect from the capsules or any commercially prepared elixirs, only from my home made strong brew made from premium grade root.

 

I'm sort of familiar with TCM, and there's a ancient Chinese formula called Kai Xin San (according to my Chinese friend it literally means "happy pill"). According to studies, it outperforms any Western antidepressant. It's a combination of Red Ginsgeng (5HT2A agonist), Polygala (NMDA antagonist), Poria and Acorus. The first two ingredients is like micro-micro-dosing shrooms with ketamine, but I don't know what Acorus contributes to this.

 

Unfortunately I haven't been able to find this formula in the US but I can try to make my own concoction, although I probably will not get the exact proportions right. And to be frank, despite your reassurance, I'm still kind of freaked out about the toxicity...

 

I'm quite optimistic it would help because many report acorus calamus having psychedelic esque effects at high doses, tho getting to those levels often entails a good amount of nausea from the asarone. Calamus has been thought to contain something like TMA-2, a psychedelic similar to mescaline that should be very enjoyable and smooth.

 

The best thing to do would be to extract the active psychedelic/stimulating compounds as shown here: https://www.tapatalk...e-t3614679.html, that way you can avoid the nausea. That whole nature's herb forum and the big posters on there are huge resources by the way, very useful stuff tho I never got the essential oil stuff to work for me really. If you follow that guide, which seems difficult but really shouldn't be, you should get rid of the asarone meaning no nausea or toxicity so then you def have nothing to worry about!

 

NMDA antagonists don't help my anhedonia and lack of drive so I wouldn't recommend polygala, it always made me feel a bit dissociated. That's just me tho, some report great results. 

 

I think the best suggestion I can give you OP is to buy some psychedelic research chemicals like 4-aco-dmt, ald-52, escaline, things like that. They have all the great effects and safety (yes, despite the fact that they're not as well known they are extremely safe) of traditional psychedelics but you almost certainly will not get a felony or anything like that for ordering them because they're technically legal and very few ever get in trouble for ordering a small amount of them. I've used a number of those kind of psychedelics and love them.



#15 SnowMetal

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Posted 02 July 2020 - 07:08 PM

Wikipedia lists agmatine as a full agonist of 5-HT2a, although I've seen others who claim it's an antagonist. None of the research makes it clear without purchasing articles, so I've reached out to someone I know has worked extensively with agmatine and serotonin, to see what her verdict is. I'll let you know.



#16 Targz

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Posted 25 July 2020 - 11:42 AM

Agmatine Sulfate activates 5-HT2A receptors


Wikipedia lists agmatine as a full agonist of 5-HT2a, although I've seen others who claim it's an antagonist. None of the research makes it clear without purchasing articles, so I've reached out to someone I know has worked extensively with agmatine and serotonin, to see what her verdict is. I'll let you know.

 

Whoever is claiming it's an antagonist is probably ill informed or citing simple binding studies and making assumptions based off the misconception that 5-HT2A antagonism is anxiolytic (when it's really 5-HT2C antagonism that's the culprit), considering agmatine is antidepressant and anxiolytic. The misconception comes from the use of nonselective 5-HT2 ligands in research such as atypical antipsychotics and ketanserin.



#17 SnowMetal

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Posted 26 July 2020 - 08:31 PM

Whoever is claiming it's an antagonist is probably ill informed or citing simple binding studies and making assumptions based off the misconception that 5-HT2A antagonism is anxiolytic (when it's really 5-HT2C antagonism that's the culprit), considering agmatine is antidepressant and anxiolytic. The misconception comes from the use of nonselective 5-HT2 ligands in research such as atypical antipsychotics and ketanserin.

 

I've considered this, and I never did hear back from my associate on this. Nonetheless, concerning the possibility that agmatine modulates 5-HT(2A), I have to wonder if agmatine also is an agonist at 5-HT(2B), and is therefore a candidate for fibrosis at the mitral valve? This is one of the benefits of lisuride as a (2A) agonist, as it's an antagonist at (2B).



#18 Targz

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Posted 27 July 2020 - 01:38 AM

I've considered this, and I never did hear back from my associate on this. Nonetheless, concerning the possibility that agmatine modulates 5-HT(2A), I have to wonder if agmatine also is an agonist at 5-HT(2B), and is therefore a candidate for fibrosis at the mitral valve? This is one of the benefits of lisuride as a (2A) agonist, as it's an antagonist at (2B).

 

If it makes any difference, Agmatine does not bind to the 5-HT2C receptor either, and there's no known binding for 5-HT2B. AFAIK it's selective for 5-HT2A.


I've considered this, and I never did hear back from my associate on this. Nonetheless, concerning the possibility that agmatine modulates 5-HT(2A), I have to wonder if agmatine also is an agonist at 5-HT(2B), and is therefore a candidate for fibrosis at the mitral valve? This is one of the benefits of lisuride as a (2A) agonist, as it's an antagonist at (2B).

 

I'd also look at palmitoylethanolamide, which inhibits FAAH, increasing anandamide, which is known to upregulate 5-HT2A receptors in the cortex.
 


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#19 neurobliss

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Posted 30 July 2020 - 03:47 PM

Very interesting about PEA. I've actually used it for different reasons - to stabilize my mast cells and as preventative therapy for COVID - and it had a nice calming effect on me. I attributed that to histamine but now I'm wondering if it was actually due to 5HT2A receptor.

 

I did some more digging and found this combo that I think of trying although not sure on the right doses:

 

The antidepressant effect of a compound formed by co-ultramicronized palmitoylethanolamide (PEA) and luteolin (PEA+luteolin) was investigated in a mouse model of anxiety/depressive-like behavior. 129Sv/Ev mice were subjected to 6 weeks of corticosterone administration, and then behavior, neurogenesis, neuroplasticity, neurotrophic and apoptotic proteins expression were evaluated. The effect of PEA+luteolin compound treatment (1mg/kg, i.p.), on depression-like behaviour was assessed using different paradigms such as open field, novelty suppressed feeding, forced swim test and elevated plus maze. In particular in the open field, novelty suppressed feeding and elevated plus maze the time spent in the open arm was employed as an indicator of anxiety; forced swim test was used to evaluate the antidepressant capacity of PEA+luteolin on immobility time as an indicator of depression. Adult hippocampal neurogenesis and neuroplasticity were evaluated by immunohistochemical techniques; brain-derived neurotrophic factor and apoptotic protein (Bax and Bcl2) expression were studied by immunostaining and Western blot analysis. For the first time we demonstrated that PEA+luteolin compound exerts a significant antidepressant effect a low dose and may be considered as a novel therapeutic strategy in depression.


Edited by neurobliss, 30 July 2020 - 04:02 PM.


#20 neurobliss

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Posted 30 July 2020 - 03:51 PM

Agmatine has a very opposite effect of PEA on me, not very pleasant and more stimulating in nature. That could be due to NMDA antagonism or something else. Or may be PEA gets 5HT2A receptors in the right part of the brain while agmatine is too nonspecific.



#21 kurdishfella

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Posted 31 July 2020 - 02:21 AM

Put yourself in situations that cause you anxiety and stress.


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#22 neurobliss

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Posted 31 July 2020 - 05:26 PM

Put yourself in situations that cause you anxiety and stress.

I don't think anxiety and stress is the way to go but I see what you're saying. I used to self medicate by travel which is a form of positive stress and novelty and I can attest that it does work but with kids it was already difficult and in our current situation is next to impossible.



#23 Targz

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Posted 01 August 2020 - 10:18 AM

Put yourself in situations that cause you anxiety and stress.

 

You're thinking of 5-HT2C



#24 kurdishfella

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Posted 01 August 2020 - 11:05 AM

You're thinking of 5-HT2C

No I'm not. From what I know anxiey/stress increases serotonin activation on all serotonin receptors. But could eventually down regulate in response if the stress is long term.  And also increase dopamine in the PFC via 5ht1a.


Edited by kurdishfella, 01 August 2020 - 11:09 AM.


#25 neurobliss

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Posted 02 August 2020 - 03:53 PM

Either way psychological anxiety or stress over long term lead to depression but I do believe that novelty on other hand is good for neuroplasticity. You should be suggesting seeking novelty rather than stress.


Edited by neurobliss, 02 August 2020 - 03:54 PM.

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#26 kurdishfella

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Posted 02 August 2020 - 07:50 PM

I will suggest whatever I want to. if you dont want other peoples suggestions dont ask. the entitlement .


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