LONGECITY

This is the wiki page on Anandamide.

 

inhibitors of FAAH lead to elevated anandamide levels and are being pursued for therapeutic use

According to this article:

 

 

But we already knew about FAAH, and about FAAH inhibitors. There are a lot of them, and many of them have gone into clinical trials (here’s a recent one). None have progressed, to my knowledge, despite trials for arthritis pain, anxiety and depression, etc.

Anyone aware of / interested in / has tried any useful FAAH inhibitors?

Apparently there have been some adverse reactions to some FAAH inhibitors (up to and including brain death).
 
FAAH inhibitors in the limelight, but regrettably
 

n January 2016, we were informed of the exceptional occurrence of serious adverse events (SAEs) in a phase I clinical trial conducted by the Biotrial Pharmacology Center (Rennes, France) on behalf of Bial-Portela & Ca. SA (São Mamede do Coronado, Portugal). The trial involved the compound BIA 10-2474, a drug designed to inhibit fatty acid amide hydrolase (FAAH). After two initial phases (single escalating doses up to 100 mg, and kinetics-food interaction studies) without any untoward SAE, the phase in question, which intended to examine the effect of multiple doses (5 or 6 daily doses), resulted in SAEs in 6 participants, who had all been administered the highest tested dose (50 mg). This was a threshold effect, since no SAE had been reported with the lower dose of 20 mg given to the volunteers previously. The most serious symptoms had central neurological features, the worst being those associated with a single case of coma which rapidly lead to brain death. Of the other 5 hospitalized participants, 2 had serious neurological damage (with clinical improvement apparently occurring within a few days). Because of these events, the trial was immediately suspended.

On the other hand, there are some naturally occurring FAAH inhibitors, so presumably they are safe in some quantity.
 
An Endocannabinoid Uptake Inhibitor from Black Pepper Exerts Pronounced Anti-Inflammatory Effects in Mice
 
Biochanin A, a naturally occurring inhibitor of fatty acid amide hydrolase

I would look at the naturally occurring compounds first rather than go synthesize something in trials.  At least there is some track record of humans consuming some of these compounds, albeit presumably in doses that don't have a profound effect.

Maca is a safe FAAH inhibitor.

https://www.ncbi.nlm...pubmed/29926378

1. An interesting study, I'd love for their to be a sustainable means to treat GAD(Generalized Anxiety disorder) without horrible effects from SSRI's. It's still subject to the Yerkes-Dodson Curve, Is my assumption. Invariably, you will probably still get diminishing returns as with all chemical treatments, thus implicitly unsustainable.

Can we just consume exogenous Anandamide or does it not make it through the gut?  I see that there are people purporting to sell Anandamide as a supplement.

And of course there are two routes to increasing Anandamide - slowing the breakdown and upregulating the production.  Is there anything known to upregulate the production of Anandamide?

The more I think about it the more this woman with elevated Anandamide is a very interesting case for anyone with issues with anxiety or chronic pain.  I think we should discuss all routes of elevating Anandamide, not just FAAH inhibitors.  

Anyone else have an interest?\

From Wiki: Low dose intake of anandamide has an anxiolytic effect, but high dose intake in mice shows evident hippocampus death.

Yikes.  I'll have to look at that carefully and figure out what they consider to be a high dose.

You can actually buy what is advertised as supplemental anandamide.  Given people's propensity to think if a little is good more is better, I'm surprised that we haven't had issues.  I wonder if it even makes it through the digestive tract.

Here's the study that Wikipedia article is referencing.
 
The “Dark Side” of Endocannabinoids: A Neurotoxic Role for Anandamide
 

They were injecting anandamide directly into the brain.  I have no idea how to convert that to an oral dose or even if anandamide crosses the BBB or makes it through the digestive tract.

I don't think that a natural FAAH inhibitor is likely to be a problem (people have consumed copious amounts of Maca without any major issue).  I'd also have an interest in natural substances that upregulate anandamine production (as opposed to inhibiting it's destruction).