Caffeine Inhibits GABA

jandrade1997

Member
Joined
Nov 7, 2013
Messages
61
I'm trying to understand the Peatish position on this. I know Peat is a huge fan of GABA, for instance:
"The similarity between the structures and actions of glycine and GABA suggest that their “receptors” are similar, if not identical. For years, it has been known that progesterone and pregnenolone act on the GABA receptor, to reinforce the protective, inhibitory effects of GABA. Estrogen has the opposite effect, inhibiting GABA's action. Since GABA opposes estrogen and inhibits the growth of breast cancer, it wouldn't be surprising if glycine, alanine, etc., did the same."

But I've read some literature that pretty uniformly suggests that caffeine inhibits GABA release.

http://www.ncbi.nlm.nih.gov/m/pubmed/14664509/
http://www.ncbi.nlm.nih.gov/m/pubmed/2835648/

So, GABA seems to be extremely important, arguably the principle governor of protective inhibition (a role for which glycine seems to serve as an analogue and partial replacement). So how significant is caffeine's pretty potent inhibition of GABA? I would argue quite significant but many people on this forum know more than I. Ray Peat seems to suggest that protective inhibition is one of the primary ways to regenerate tissue is some of his newsletters. As such, should we be concerned about caffeine's inhibition of protective inhibition?
 
Joined
Nov 26, 2013
Messages
7,370
Caffeine blocks adenosine by similarity and this is where the investigation should begin since Ray Peat is also a fan of adenosine.

Ray Peat said:
Adenosine seems to have a variety of antioxidant functions, and one mechanism seems to be its function as an antiexcitatory transmitter. One of estrogen's excitant actions on the brain probably involves its antagonism to adenosine (Phillis and O'Regan, 1988).
 

jyb

Member
Joined
Nov 9, 2012
Messages
2,783
Location
UK
Is there a chance the effect on GABA is dose dependent? It wouldn't be the first time I read about a chemical having completely opposite effects when it reaches a fine threshold.
 

Dopamine

Member
Joined
Mar 1, 2016
Messages
473
Location
Canada
The acute effects of caffeine may seem to lower GABA but you need to look at the big picture... Caffeine significantly increases neurosteroids like progesterone and allopregnanolone which will increase GABA activity.

Caffeine Increases Pregnenolone & Progesterone In The Brain

Allopregnanolone affects sleep in a benzodiazepine-like fashion. - PubMed - NCBI

Tolerance to allopregnanolone with focus on the GABA-A receptor
"Endogenous GABA-A receptor agonists exist in the 3α-hydroxy metabolites of progesterone, testosterone and deoxycorticosterone, known as allopregnanolone, pregnanolone, androstanediol and tetrahydro-deoxycorticosterone (THDOC). These compounds are steroids and act as agonists at the GABA-A receptor, and hence are known as GABA steroids (Mellon and Griffin, 2002;Backstrom et al., 2003)."
 
Last edited:

Repas du soir

Member
Joined
Feb 11, 2018
Messages
112
From what I understand, GABA is supposed to be high during night time when you should be sleeping and healing. This is why you should drink coffee during the day and not drink any in the evening. I know caffein stays in the system for a long time, but this seems like a good habit regardless.
 

Mauritio

Member
Joined
Feb 26, 2018
Messages
5,669
Valid question for sure. Especially since the decrease in GABA is quite substantial.

Caffeine's effect on glutamate however is less clear, as per point 3 in this review. Short term administration seems to increase glutamate. Long term might be different.
And some studies show a brain protective effect, which suggest an anti-excitotoxic mechanism.
- Caffeine induces neurobehavioral effects through modulating neurotransmitters

Also Peat cites a study showing that caffeine ameliorated liver fibrosis by blocking the adenosine receptors, so it's not like peat is only talking favorably about them.

"Caffeine increases cells' energy efficiency, and
by opposing the effects of adenosine (secreted by cells that are stressed and energy-depleted), it can inhibit vasodilation, angioneogenesis (Merighi, etaI., 2007; Ryzhov, et aI., 2007), and fibrosis(Chan, et al., 2006)."

"Although caffeine is a stimulant that can
offset the sedative effects of GABA, it also
functions as .a neuroprotectant, protecting
against some of the effects of glutamate (Chino-poulos, et al., 2004)."
 

Similar threads

Back
Top Bottom