excess serotonin

Farshad wrote:yeah I ordered magnolia bark.. its the Honokiol in the bark that is effective for the cannabinoid system right?

I also ordered plenty more of stuff to try increase cannabinoid system.. will try them out and see which ones the best .
does inositol have a short half life?

yes honokiol at cb1, and Jay mentioned it helping ocd but not sure its via ht6 receptor.
I think inositol has accumulative effect.

hmm the inositol  worked great first dose but today I dont feel much.. Maybe the effect is still there since yesterday

(edit) so I was outside again and I feel a lot more calm and less anxiety and more confident then yesterday.. I feel a inner peace and my emotions are stronger.

Are the NMDA and cannabinoid + cb1/cb2 linked??

Low cannabinoid is linked to enlarged amygdala but high cannabinoid is smaller amygdala, my question is how does the cannabinoid surpress the amygdala? is it  by activating the cb1/cb2 receptor in the amygdala or by activatin the NMDA to surpress the amygdala? and how does the NMDA surpress the amygdala? I know when cb1/cb2 are activated it stops cortisol or something from going in to the amygdala... or something similar.

Because if the cannabinoid surpresses the amygdala by activating the NMDA. I might aswell just take Pure NMDA instead since there are no effective ways in increasing expression of cannabinoid cb1 by a lot or increasing the amoung of cb1 receptors.

Farshad wrote:hmm the inositol  worked great first dose but today I dont feel much.. Maybe the effect is still there since yesterday

(edit) so I was outside again and I feel a lot more calm and less anxiety and more confident then yesterday.. I feel a inner peace and my emotions are stronger.

Are the NMDA and cannabinoid + cb1/cb2 linked??

Low cannabinoid is linked to enlarged amygdala but high cannabinoid is smaller amygdala, my question is how does the cannabinoid surpress the amygdala? is it  by activating the cb1/cb2 receptor in the amygdala or by activatin the NMDA to surpress the amygdala? and how does the NMDA surpress the amygdala? I know when cb1/cb2 are activated it stops cortisol or something from going in to the amygdala... or something similar.

Because if the cannabinoid surpresses the amygdala by activating the NMDA. I might aswell just take Pure NMDA instead since there are no effective ways in  increasing expression of cannabinoid cb1 by a lot  or increasing the amoung of cb1 receptors.

https://www.ncbi.nlm.nih.gov/pubmed/23562616
https://www.ncbi.nlm.nih.gov/pubmed/21420449
https://www.ncbi.nlm.nih.gov/pubmed/18084745
not sure about nmda but glutamate may be involved in emotions, schizos for example suffer low emotionality, also read about a guy who got troubles with emotions on regular plan...

Im gonna take a higher dose of inositol and see how I feel today.

also can someone explain what they mean with my receptors not getting sensitive and that I dont build tolerance, what does that mean??

The T allele of rs1049353 may cause lower receptor numbers and less activation. With this variation, the receptors also don't become significantly less sensitive when activated (R) - i.e. you don't build up tolerance.

ok I took some Magnolia lets see what happens

the one im using only has  2% honokiol per capsule (400mg).. Is that too little to feel any effects?

Swanson has 90% honokiol per capsule (200mg)..

did I get ripped off? im using Genesistoday magnolia bark


(edit) so far no effects from magnolia... maybe a bit more calm?..

(edit2) yeah I think the honokiol  % in the brand im using is too low.... but I can definitely tell it made me more calm and relaxed and warm..

does d aspartic acid/nmda cross the bbb?


Is it better to take NMDA or d aspartic acid to activate the NMDA receptors? I know when d asparic acid is ingested some bacteria in  your body can turn it into N-methyl-D-Aspartate and  thats what activates the NMDA.. would it be better to just take pure NMDA ?

Farshad wrote:ok I took some Magnolia lets see what happens

the one im using only has  2% honokiol per capsule (400mg).. Is that too little to feel any effects?

Swanson has 90% honokiol per capsule (200mg)..

did I get ripped off? im using Genesistoday magnolia bark


(edit) so far no effects from magnolia... maybe a bit more calm?..

(edit2) yeah I think the honokiol  % in the brand im using is too low.... but I can definitely tell it made me more calm and relaxed and warm..

does d aspartic acid/nmda cross the bbb?


Is it better to take NMDA or d aspartic acid to activate the NMDA receptors? I know when d asparic acid is ingested some bacteria in  your body can turn it into N-methyl-D-Aspartate and  thats what activates the NMDA.. would it be better to just take pure NMDA ?

Yeah, I used 2 bottles of Genesis brand. I don't know if Swanson really contains so much, it would cost a lot I think.
Ask Jay about NMDA. I didn't try nmda. I only read quite a lot of texts where it was mentioned as both an important thing but also harmul say for epilepsy or beneficial for schizophrenia (along with mglur2).

Well I took 3g of DAA and I didnt feel anything .. I was hoping it would activate my NMDA receptors  to surpress my amygdala. I have now ordered some Pure NMDA made by iforce nutrition, But I dont know how legit they are.. I saw this reddit thread: https://www.reddit.com/r/bodybuilding/comments/3lt0w6/beware_of_iforce_nutrition_shady_business/
but im hoping it will work if you read the reviews on this NMDA supplement you can see a lot of people say it helps with their sleep . Im assuming thats from activating the NMDA.
https://se.bodybuilding.com/store/iforce/intimidate-srt.html
kvavel how many Capsules of the magnolia bark did you take a day?

well so far my cocktail is:
inositol and magnolia bark

Im gonna take magnolia bark again alone and see how I feel in public.

inositol did work but not enough. I believe it does increaseCB1 activation but as you saw my SNP said I also have too few CB1 receptors ... so I need something that increases CB1 amounts of receptors . Might also try Maca  its a FAAH-inhibitor

also Black pepper is an endocannabinoid uptake inhibitor

and do you really think the Swanson magnolia that contains 90% honokil is fake? I thought swanson was a reliable company. But its also very cheap 7 bucks..

I took 2 capsules usually.

well I can conclude honokil not working tried 4 capsules.... Inositol best so far but not good enough. I ordered some KAVA(kava increases cb1) but apparantly its illegal in sweden and got sent back.. wtf... well now im just waiting for the NMDA to arrive.... this better work

ugh im so confused why DAA didnt work

You mean it doesn't work acutely and on demand. It's not phenibut. Real longterm cures have to work by changing mrna or stores of something or eliminating a threat like virus. Drugs often work faster because of crazy affinities at receptors.

oh so I have to take DAA daily . DAA has weak affinities  on NMDA receptors? so pure NMDA would have higher affinities ? that is if it crosses the BBB. But I was expecting it to immediately activate the NMDA receptors and calm my amygdala. Or are U talking about the honokil? I read many reviews about people feeling effect after first dose.

I would say magnolia officinalis is a far far closer to work correctly for anxiety.

So what would be the best way to increase NMDA activity besides DAA/pure NMDA?
I was thinking of trying Sarcosine. Should I go with just sarcosine or some modified sarcosine that maybe works better?

What else? will glycine  work? and d-serine?
which is better of these 3?

Glycine, probably. Gelatin has a lot. Also consider this
https://www.ncbi.nlm.nih.gov/pubmed/23711138
https://www.ncbi.nlm.nih.gov/pubmed/8137890
https://www.ncbi.nlm.nih.gov/pubmed/12183043
I tried l-serine, nothing to say. D-serine is mentioned to be toxic.

Have you guys tried Marijuana? Would it be plausible  for me to take Low dose marijuana once a day  to support my cannabinoid system? I know the THC in marijuana activates the cb1 receptors... But does it increase the Amount of CB1 receptors you have?

according to this https://herb.co/marijuana/news/build-cannabis-tolerance

Earlier research has found that chronic THC treatment decreases the amount of CB1 receptors expressed in a cell. In the science world, this is called downregulation.

so Marijuana ony increases it initially but long term decreases??

Farshad wrote:Have you guys tried Marijuana? Would it be plausible  for me to take Low dose marijuana once a day  to support my cannabinoid system? I know the THC in marijuana activates the cb1 receptors... But does it increase the Amount of CB1 receptors you have?

according to this https://herb.co/marijuana/news/build-cannabis-tolerance

Earlier research has found that chronic THC treatment decreases the amount of CB1 receptors expressed in a cell. In the science world, this is called downregulation.

so Marijuana ony increases it initially but long term decreases??

Well Marijuana and Cannibinoids work in opposite direction to NMDA pathway. Anything POSITIVELY tied to cAMP (say Forskolin) is positively tied to NMDA. So I doubt it will help much - though it may help Anxiety you are experiencing.

I thought CB1 was responsible for activating the NMDA system to surpress the amygdala during stress? I dont know anymore. I know that low cannabinoid system is linked to enlarged amygdala..

from wiki
``
These findings show that anandamide and 2-AG divergently regulate the HPA axis response to stress: while habituation of the stress-induced HPA axis via 2-AG prevents excessive secretion of glucocorticoids to non-threatening stimuli, the increase of basal corticosterone secretion resulting from decreased anandamide allows for a facilitated response of the HPA axis to novel stimuli.
```

so i can conclude anandamide and 2-ag decrease stress in the amygdala? And supposedly Marijuana contains a lot of cannabinoids that can increase the cannabinoid system cb1 ,cb2 and Im assuming anandamide and 2-ag too?

I did read https://www.selfhacked.com/blog/49-ways-increase-natural-cannabinoids-without-smoking-pot-including-ways-decrease-cannabinoids/ but all the methods seem relativity weak and  I dont think wont make a big difference.

On another forum some guy suggested for me to take a low dose THC preparation , thc is what I think increases just  cb1. But the thing is I want full cannabinoid system support ( anandamide etc)  . I think I will have to just take Marijuana .   But I will have to watch out for CBD because I think that blocks CB1.

hmmmmm

then again
according to this
The T allele may cause lower CB1 receptor numbers and less CB1 activation . The T allele of rs1049353 may cause lower receptor numbers and less activation. With this variation, the receptors also don't become significantly less sensitive when activated (R) - i.e. you don't build up tolerance

it says my problem is only CB1 receptors.... I dont know how all the cannabinoid receptors/stuff related to the system are connected. But so THC should do then... Does increasing cb1 increase faah/anandamide  etc?
I wonder if Marijuana has an effect on the whole cannabinoid system or just cb1/cb2. Also does marijuana just touch the cannabinoid system nothing else?

here are my other 2 cannabinoid genes that were marked as red flag on Selfdecode:

description( Contains Risk Alleles)
https://www.selfdecode.com/gene/crhr1/
desc(Contains Risk Alleles / Potentially bad gene)
https://www.selfdecode.com/gene/cnr1/

and ofc this 1 that i been talkin bout the most

https://www.selfdecode.com/snp/rs1049353/

SO I have 3 different mutations (bad low)  in my cannabinoid system?

im contemplating  trying various supplements to try and support my CB system or just straight go for CBD oil..

I made a list of  supplements  for  my CB system. Which ones are the ones that are most potent so I can just go for them straight instead of wasting money on the weaker supplements?



Galantamine
Oleamide
Palmitoylethanolamide
Resistant starch
Maca
Black pepper
Fish oil/DHA
Agmatine
DIM
KAVA
Echinacea
Butyric Acid
Lactobacillus acidophilus
Ruta Graveolens
Acmella Oleracea
helichrysum umbraculigerum

I made a new list, is this better removed some things I thought is weak


Lactobacillus acidophilus
Butyric Acid
KAVA
Diindolylmethane
Agmatine
Maca
Black pepper
Galantamine
Oleamide
Palmitoylethanolamide

CRHR1 and CNR1

It says I have these and they are contains Risk Alleles / Potentially bad gene. My question is what does this do? I know its part of the endocannabinoid system. Is the CNR1 gene same thing as the rs1049353 (TT) SNP? Both description says Low amounts of CB1 receptors. But then what is the CRHR1 responsible for? It says Contains Risk Alleles for that gene. Does it cause low levels of anandamide and 2-AG ?

Because if the CNR1 gene is same as the SNP (TT) then I think I know my 2  Issues.

1.  Low levels of CB1 activation and receptors (Havent seen any genes/SNP that say I have CB2 problems) so I will just Increase CB1 activation/receptors  with THC/CBD? Assuming thats the best way unless there are some drugs that help increase CB1?

2. CRH causes fear and anxiety (R, R2) via CRHR1 (R) and major depression (R). CRHR1 promotes anxiety in part by reducing cannabinoids in our amygdala. This happens when CRHR1 activation increases FAAH in the amygdala, which causes a reduction in the endocannabinoid anandamide (AEA)

So I will just  Block CHR (CRHR1) with  Antalarmin.

And I think I should be good

(edit) I will go for Astressin-B which is a CHR (not just CRHR1) antagonist you can find it pretty easy but its topical so hopefully it works.

In a new study, researchers at The Scripps Research Institute (TSRI) have described how two important molecules in the brain work together to trigger intense anxiety.

The new findings in animal models point to a novel interaction in the regulation of the brain’s stress response that may underlie the pathological anxiety related to symptoms of post-traumatic stress disorder (PTSD).

“Anxiety and stress disorders affect millions of people worldwide,” explained study leader Marisa Roberto, a professor at TSRI. “Understanding the mechanisms underlying these disorders is important for identifying potential new targets for therapeutic use.”

The researchers focused on the endogenous cannabinoid (endocannabinoid or eCB) system, which include natural lipid signaling molecules that bind to cannabinoid receptors in the brain. Cannabinoid (type 1) receptors control stress-mediating circuits by inhibiting neurotransmitter release — a sort of gating mechanism to keep anxiety in check.

In contrast to the stress-reducing properties of endocannabinoids, a peptide molecule called corticotropin-releasing factor (CRF) activates the stress response and promotes increased sensitivity to stress and anxiety when activated over and over again.

In the new study, published today in the journal Biological Psychiatry, the researchers investigated the interaction between the stress-promoting (CRF) and stress-constraining (eCBs) mechanisms in the central nucleus of the amygdala, a critical brain region involved in mediating emotional reactions. The findings suggest that overactive CRF signaling in this region produces a wide range of effects that override the stress-reducing capabilities of a major eCB called N-arachidonoylethanolamine (anandamide), turning chronic stress into unchecked, or pathological, anxiety.

“Anxiety is something that everyone experiences on a day-to-day basis,” said study first author Luis A. Natividad, a research associate in the Roberto lab. “But it is unclear what changes this otherwise natural process into something debilitating.”

To answer this question, Roberto’s lab teamed up with Roberto Ciccocioppo’s lab at the University of Camerino, Italy, and the lab of TSRI Professor Loren (“Larry”) Parsons, a renowned leader in the fields of endocannabinoid signaling, stress and drug addiction who passed away in 2016.

The researchers studied rats that were genetically selected for higher alcohol drinking and also display an anxiety-like phenotype. These rats exhibit a mutation in a gene called Crhr1 that increases CRF (type 1) receptor signaling.

Using behavioral, neurochemical and electrophysiological approaches, the researchers found that increased CRF signaling led to elevated activity of the anandamide clearance enzyme fatty acid amide hydrolase (FAAH). Increased CRF was also associated with drops in anandamide levels in the central nucleus of the amygdala. Together, increased FAAH activity and decreased anandamide signaling reduce inhibitory control of excitatory neurotransmission in this critical region, and lower the brain’s ability to regulate stress and anxiety.

The researchers concluded that long-term dysregulation of CRF-FAAH mechanisms in the amygdala keeps anandamide from doing its job. Without anandamide to balance out the system, the brain is primed to react to stress.

Follow-up experiments showed that inhibiting FAAH could blunt CRF’s effects and reduce signs of anxiety in the rats.

Roberto said the next step will be to further study this rat model to better understand relationships between high anxiety and alcoholism. She added that the rat model could also be useful for studying PTSD, where high anxiety is connected to a higher risk of developing alcoholism.

“The results of our study may be useful, not only in understanding the neurobiological basis of alcoholism, anxiety and possibly PTSD, but also in developing more efficacious pharmacotherapies to treat these disorders,” added Ciccocioppo.

The researchers dedicated this study to Parsons. Natividad added a note on Parson’s influence on the research and on the TSRI campus:

“Larry’s guidance throughout the study was critical in bringing together a cohesive story exploring the relevance of endocannabinoid signaling with downstream neural processing in a way that is unique to the field and has translational relevance to the human condition. He serves as a role model for me not only as a scientist, but also in terms of being a good colleague, mentor and friend to those around him. I feel privileged to have been part of his lab, his teachings and mentorship. He will be dearly missed.” Reference

CBD Oil might work, btw, a buddy of mine will be releasing it soon on Top Extracts. Bookmark the page Farshad, trust me, you'll like his brand much better!!!

hey man.. I think I have found my problem, It had nothing to do with neurontransmitters , I think my problem is high cortisol or should I say overactive CRF-1 . Thats why I think if I would do a  cortisol blood test it would show my cortisol normal but meanwhile it isnt my CRF-1 is just overactive, which I dont think theres any ways to test for is there? there is a drug called Metyrapone you can get it in Sweden, supposedly it blocks cortisol.. But I dont know if that would help my situation

on Wikipedia it says:

Mechanism
Metyrapone blocks cortisol synthesis[1] by reversibly inhibiting steroid 11β-hydroxylase. This stimulates ACTH secretion, which in turn increases plasma 11-deoxycortisol levels.

but wouldnt  blocking cortisol  decrease ACTH? since CRH activates CRF1 and CRF1 activates ACTH

hmm I think I understand the mechanism now saw this pic so it wouldnt work for my case.



(edit) hmm no I dont... wow im so stupid lol ..

If you had too high cortisol you'd look like Stay Puft Marshmallow Man from Ghostbusters due to Cushing's Syndrome.

I dont think I have too much cortisol but more like too much CRF1 activation . maybe its the same thing idk.

do you guys have an article on best supplements that decrease cortisol?