Black Pepper Piper Nigrum Increases Serotonin Synthesis

[Sativa]

Don't forget Kava Kava! - works via GABA-B iirc, also contains a weak yet notable cannabinoid - Yangonin, active at the CB1 'receptor'.
I had some of my Kava 84% Kavalactone extract paste earlier... alongside Magnesium, and some homemade Sodium Salicylate...

Kava contributes calming via GABA, it also upregulates the GABA system, implying it enhances it's sensitivity. It has mild Cannabinoid effects also. (progesterone also works via GABA!)
Mg contributes potent glutamate lowering effect - aka a cushioning effect (via NMDA 'antagonism')
NaSalicylate lowers cortisol & estrogen (anti-aromatase) & inhibits the COX enzyme.

Almost anything Peaty will tend to shift the balance of neurotransmitters to GABA and away from Glutamate. Glutamate being the opposite of GABA and causing anxiety and seizures, while GABA promotes relaxation and calmness.
Increasing estrogen exposure will lower GABA and increase Glutamate.

Theanine is another interesting & useful substance, with potential.
Theanine is a dual GABAergic and NMDA antagonist.

motivation, pro-social behaviour - this is apparently what GABA-B upregulation feels like. Interestingly, serotonin causes the same feelings like this: serotonin ---> 5-HT1A ---> GABA release ---> GABA-B activation.

Yeah I wouldn't use phenibut anymore, I only use theanine.
Theanine gives the same effect as phenibut, but instead of through agonism it's through antagonism so it can be taken every day without tolerance.
Theanine blocks mGlu1, which is coupled with GABA-B.
So by antagonizing and upregulating mGlu1, it upregulates GABA-B.
...
The GABA-B upregulation happens after theanine wears off.

This method of enhancing/increasing the GABA-B system via 'upregulation' is sort of a sustainable indirect way of increasing it's 'baseline state'.

Magnolia Bark is another very interesting one - it not only potentiates GABA but also has significant calming cannabinoid activity!

re progesterone & GABA:

I did not know that Progesterone raises GABA-B instead of GABA-A. I do know that a metabolite of progesterone called allopregnanolone does raise GABA-A. Also androsterone raises GABA-A.

All in all, this lays the foundation for a super-combination that mimics aspects of progesterone, amongst other things...

• anti-catabolic == pro-anabolic
• pro-androgenic
• anti-cortisol
• anti-estrogen (anti-aromatase, boost liver detox)
• anti-glutamate (NMDA antagonism)
• pro-GABA (either via upregulation or direct activation aka agonism)

...palmitic acid increased pregnenolone, DHEA in the adrenals, while at the same time decreasing cortisol synthesis.
...
...ingesting larger doses palmitic acid from food may be more effective for androgen boost.
So, butter, cheese, milk, meat, cocoa fat, coconut oil etc are all good sources.

 

[Sativa]

Piperine activates 5-HT1A which decreases/dampens activity of all other serotonin receptors.

Taken together, these results suggest that the antidepressant-like effect of piperine in the mouse forced swim test may be mediated, at least in part, by the activation of 5-HT(1A) and 5-HT(1B) receptors.

Piperine also activates TRPV1 channel, which stimulates BDNF related pathways.
Piperine also has GABA & glutamate activity.

I think avid peaters might make overly hasty misinformed decisions based on the research results for serotonin turnover/activity for certain compounds... There are certain nuances in the world of pharmacology that are invaluable for making accurate & grounded interpretations/conclusions (based on research/experimental approaches etc)

(That paper is somewhat dated, 1983!! Things have moved on since then...)

Also, some peaters might simply be inexperienced in interpreting research papers and underestimate agendas which underlie some of the language and terms used/implied.

Anyway, I've observed a 'peater' near-obsession with things which have any hints of raising serotonin. This is understandable, but in the case of Piperine & that 1983 study, perhaps misguided conclusions have occurred. Just saying...
(cue Jamaican accent: "chill the f--- out man!" )

TLDR: Piperine activates the serotonin site (HT1A) that DAMPENS all other serotonin sites

 

[Kingpinguin]

Piperine activates 5-HT1A which decreases/dampens activity of all other serotonin receptors.


Piperine also activates TRPV1 channel, which stimulates BDNF related pathways.
Piperine also has GABA & glutamate activity.

I think avid peaters might make overly hasty misinformed decisions based on the research results for serotonin turnover/activity for certain compounds... There are certain nuances in the world of pharmacology that are invaluable for making accurate & grounded interpretations/conclusions (based on research/experimental approaches etc)

(That paper is somewhat dated, 1983!! Things have moved on since then...)

Also, some peaters might simply be inexperienced in interpreting research papers and underestimate agendas which underlie some of the language and terms used/implied.

Anyway, I've observed a 'peater' near-obsession with things which have any hints of raising serotonin. This is understandable, but in the case of Piperine & that 1983 study, perhaps misguided conclusions have occurred. Just saying...
(cue Jamaican accent: "chill the f--- out man!" )

TLDR: Piperine activates the serotonin site (HT1A) that DAMPENS all other serotonin sites

Nice finding 5-ht1a increases dopamine.
I also found several studies showing how piperine inhibits MAO-B. That also equalls more dopamine. Other MAO-B inhibitors like deprenyl have shown to length life span.

found some more research showing piperine
Inhibits prostaglandins
Inhibits histamine
Inhibits nitric oxide
Increases ATP synthesis
Increases BDNF

and as shown above increases 5-ht1A, blocks other serotonin receptors, inhibits the breakdown of dopamine leading to further increase in dopamine and also protects dopaminergic neurons.

seems pretty peaty to me