what receptors control the amygdala?

[Hodor]

D-aspartic acid is present in all humans already - if you ingest proteins or amino-acid-rich foods then your body will produce aspartic acid from hydrolytic decomposition of those proteins. In fact your body *needs* aspartic acid to fucntion, it's one of the amino acids that make up all the protiens in your body!

Proteins are made up of L-amino acids though.

That said, I agree that eating D-aspartate and hoping that it will get methylated into NMDA to achieve a psychoactive effect is kind of like eating MSG to treat Generalized Anxiety Disorder because you've read that glutamate is decarboxylated into GABA.

 

[trainman04]

can someone tell me how extachly activation of nmda CALMS the amygdala **HEAVILY** supposedly

 

[Cotcha Yankinov]

I think you're missing the larger picture. There are NMDA receptors out there that could lead to fear behavior/anxiety, and there are NMDA receptors that could suppress fear behavior/anxiety. It depends on where the NMDA receptors are, and how exactly they are firing. Different types of NMDAr activation in different brain regions will lead to different effects, there is no one effect on NMDA receptors. Some NMDA receptors effect's could also depend largely on what other cell types are doing.

 

[sekio]

I was under the impression that NMDA receptors are generally excitatory and not inhibitory... NMDA antagonists are such a big class of drugs in comparison to NMDA agonists partly because of the theory that overactive NMDA receptors can cause excitotoxicity. Loss of brain cells is generally not considered fashionable.

 

[Cotcha Yankinov]

Its super odd to see how some things that we would guess are an inhibitory/long term depression type process are something thats rather more excitatory, as an example fear extinction

"Extinction of conditioned fear is an active learning process requiring N-methyl-D-aspartate receptors ~~

Here we show that infusion of the NMDAR antagonist CPP into the ventromedial prefrontal cortex (vmPFC) prior to, or immediately after, extinction training impaired 24 hr recall of extinction.

We suggest that NMDAR-dependent bursting in the infralimbic vmPFC initiates calcium-dependent molecular cascades that stabilize extinction memory, thereby allowing for successful recall of extinction."

Supposedly NMDA antagonists lead to seizures in mega-overdose because NMDAr do provide some input to inhibitory interneurons, I think thats similar to sodium channel antagonists. Typically they function as anti-excitatory/epileptic, but can lead to seizures in overdose because e.g. GABA interneurons express a lot of sodium channels

Therein may be some of the drive to develop sodium channel antagonists that have more selectivity for the overactive sodium channels (like esclicarbazepine, which seems to be essentially the memantine of sodium channel antagonists)

can someone tell me how extachly activation of nmda CALMS the amygdala **HEAVILY** supposedly

There are some studies showing that proper NMDA function is required to decrease amygdala related fearful associations that may not be relevant, proper NMDA receptor function in the amygdala seem to help us filter out unimportant stimuli that we shouldn't be associating with a fearful stimulus, something that schizophrenic patients seem to have problems with

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC311350/

 

[trainman04]

There are some studies showing that proper NMDA function is required to decrease amygdala related fearful associations that may not be relevant, proper NMDA receptor function in the amygdala seem to help us filter out unimportant stimuli that we shouldn't be associating with a fearful stimulus, something that schizophrenic patients seem to have problems with

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC311350/

yes thats my problem you described it extachly the same! But my problem is high serotonin not high dopamine.
Also I think my LOW nmda activity is related to Low cannabinoid function . In schizophrenia patients I think the Low NMDA is caused by something else.

 

[Cotcha Yankinov]

But my problem is high serotonin not high dopamine.

Like Sekio has pointed out, we cannot tell what is going on with our neurotransmitters just based upon how we feel.

Its thought that a subgroup of schizophrenia patients have hypo-glutamate issues, but they've checked very carefully objectively for that. If your cerebrospinal fluid was checked for dopamine metabolites, for all we know you could be running high on dopamine. You did after all respond to an anti-dopaminergic drug.

 

[trainman04]

Well its just based on the information I have gotten im not basing it on how I feel.

So I have ordered some Pure NMDA since D aspartic acid doesent seem to be working I took 3g in hopes of it activating my NMDA receptors felt nothing.

Do you guys know if activating the NMDA will increase other glutamate receptors too? Because I think you guys said the AMPA is involved in fear learning too. The other 2 glutamate receptors havent been talked much I dont know anything about them are they involved in fear too or what do they do ?

 

[Cotcha Yankinov]

Well its just based on the information I have gotten im not basing it on how I feel.

What information are you basing it off of?

 

[trainman04]

What information are you basing it off of?

well im not too worried about the serotonin stuff im more focused on the NMDA stuff now.

 

[trainman04]

how extachly does nmda reduce amygdala activity? are there like nmda receptors in the amygdala or somth when activated reduces the activity

 

[trainman04]

anyone know if allopregnanolone reduce amygdala activity and increase PFC activity?

 

[Dresden]

Amygdala is Greek for "Walnut." A pecan is known a "walnut very great" in China. I have Chinese cousins. That's all the gifts the giftie is geing you today..

 

[Limpet_Chicken]

Allopregnanolone might act as an antianxiety agent, I'd hazard a guess it might work as a neurosteroid-site GABAa agonist

 

[sekio]

It's not orally active though:

Allopregnanolone and the other endogenous inhibitory neurosteroids have short terminal half-lives and poor oral bioavailability, and for these reason, have not been pursued for clinical use as oral therapies

Have you considered looking into drugs that would decrease the parts of the brain around the amyglada to allow it to grow? Or eating a fresh rabbit or goat amyglada once every 72 hours to ingest the the amyglada growth hormones at the proper natural frequency </s>

 

[Cotcha Yankinov]

Time to saute my daily rat nucleus accumbens for anhedonia

 

[trainman04]

http://www.psypost.org/2017/02/rese...rns-chronic-stress-pathological-anxiety-47544

CRF combines with low cannabinoids that leads to pathological anxiety, Cannabinoid (type 1) receptors control stress-mediating circuits by inhibiting neurotransmitter release — a sort of gating mechanism to keep anxiety in check.
this suggests that CBD research needs to be done regarding anxiety control.
corticotropin-releasing factor (CRF) activates the stress response and promotes increased sensitivity to stress and anxiety when activated over and over again.
CRF is a peptide
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.

 

[sekio]

So logically activating CB₁ by smoking some weed would alleviate your anxiety, the same way FAAH inhibition would, by increasing the activation of CB₁ and decreasing the anxiety/fear response.

But don't mind me, I'm just using logic.

 

[trainman04]

I think CBD blocks CB1 and increases CB2. THC alone may be a better option to increase CB1. Astressin-B blocks CRH. For FAAH inhibition Pterostilbene + black pepper
and Maca combo. But I dont know if the latter are strong enough to produce an effect from FAAH inhibition. The whole purpose of anandamide is just to activate CB1 right? it has no anxiety allieving effect on its own?
also Anandamide (partial CB1 agonist) and 2-AG (full CB1 agonist). . Is there any way to inhibit 2-AG ? Is that what FAAH inhibition does increase anandamide and 2-AG?

But one thing I cant get out of my head is What if my CB1 receptors are in Low amounts... How the hell would I make my body create More/new cb1 receptors?

 

[sekio]

I think CBD blocks CB1 and increases CB2. THC alone may be a better option to increase CB1.

CBD does not totally block the effects of THC, it simply moderates them, that is to say, it does not block the receptors 100% at a normal dose. And most strains of weed sold for recreational use are mostly THC anyway. Even taking pure CBD does not produce typical effects of CB₁ blockade - it does not induce depression, anhedonia, or reduce appetite the same way rimonabant would.

" McPartland and Guy proposed that Cannabis and its many constituents work, in part, by “kick-starting” the [cannabinoid] system. "[ref]

anandamide is just to activate CB1 right? it has no anxiety allieving effect on its own?

CB₁ activation, in moderation, can help stop anxiety, no matter how the receptor is activated, either anandamide or THC. The thing is, anandamide is rapidly broken down in the stomach and liver so you can't eat it as a drug.

. For FAAH inhibition Pterostilbene + black pepper and Maca combo.

I don't think that's likely to be very strong at inhibiting FAAH. I know resveratrol doesn't really penetrate BBB and produce a druglike action, I don't see why pterostilbene would. As fat as I know there are no effective natural FAAH inhibitors.

How the hell would I make my body create More/new cb1 receptors?

I posted several studies in your other thread: among other things, sugar, regular moderate to strong exercise, acute administration of opioids (not chronic/long-term use), acute administration of cannabis/THC (not long term usage), chronic stress, some antidepressant drugs, probiotics (yogurt and the like), polyunsaturated fatty acids. Some of which are healthier than others. And there are even more things that increase natural production of anadamide but not expression of CB₁ too...

You certainly don't have anything to lose, THC has never caused any deaths. If you don't want to do that then eat more sugars, fats, and get some strenuous exercise... for 20 mins or more.Time yourself. See how you feel after...