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FAAH Intro

Fatty acid amide hydrolase or FAAH metabolizes anandamide to Arachidonic acid.  Anandamide is our natural cannabinoid bliss molecule.

Anandamide will activate the cannabinoid/CB1 receptor and interact with CB1 receptor SNPs.

The endocannabinoid system got its name from cannabis since THC is closely related to the brain’s own anandamide.

Anandamide is taken from the Sanskrit word ananda, meaning bliss – because when it binds to the cannabinoid receptor, it has a calming effect.

Genetic deletion of FAAH in animal studies produces antidepressant-like effects, and this is thought to be mediated by increased serotonin and noradrenaline transmission (R).

Mice completely lacking FAAH experience less pain, seizures, and less motility (R).

We will generally want more anandamide and less arachidonic acid.  Therefore, having lower FAAH enzyme activity can have some good effects.

Anandamide enhances levels of adenosine outside of cells and induces sleep (R).

FAAH is found in the brain, small intestine, pancreas and muscle (R).


C is the more common allele.  Only 26% of the alleles in the global population are “A”.

I’m rs324420 AC.


A=lower FAAH.

AA=high anandamide, 5X higher risk for substance abuse, does better with lower fat, more Slow wave sleep, lower risk of PTSD (fear extinction in the amygdala) and less awake after 10mg amphetamines (but not 20mg).


C encodes the more common Proline, while the A allele encodes the Threonine (R).

The change displays normal enzyme properties but an enhanced sensitivity to degradation (R).

Functional in-vitro studies further revealed that the A allele decreased the production and activity of FAAH in humans (R).

AA=half FAAH enzymatic activity (R), reduced FAAH production, increased degradation of the enzyme, and less cellular stability (R).

These factors negatively impact FAAH, which increases anandamide.  (FAAH breaks anandamide down).

The Good

People with the A allele are less anxious and are thus less inclined to like marijuana.

They actually experience a decrease in happiness when smoking marijuana, compared with those with the normal FAAH gene, who find it pleasurable. If you naturally have more of the real thing you understandably have little use for marijuana (R).

Studies show that those with CC suffer more severe withdrawal when they stop using cannabis (R). 

For example, one community-based study of almost 2,100 healthy volunteers found that people with AA had roughly half the rate (11 percent) of cannabis dependence than those one or more C’s (26 percent) (R).

Both mice and humans with the A allele showed enhanced fear extinction (they learned more efficiently how to be unafraid) (R).

AA is calmer/less anxious, has lower enzyme activity, higher anandamide, enjoys pot less, less likely to get addicted to pot, does better with extinction therapy in PTSD (R).

A has decreased threat-related amygdala reactivity and increased reward-related reactivity in the ventral striatum indicating its role in stress adaptation (R).

When mice were genetically engineered to have the AA version of the gene, they were less anxious.  The mice showed similar changes in the neural circuits involved in people with lower anxiety and fear (greater connectivity between the prefrontal cortex and the amygdala).

A is less likely to develop cannabis dependence.

In some studies (but not all), A is associated with obesity (R).

The Bad

AA is at higher risk for substance abuse. AC is the normal risk (R). A has a synergistic effect on these conditions with the CB1 receptor gene (R).

In a study of 80 people and 1000 controls, AA was 5X more likely to abuse drugs (p = 0.00003) (RR2).

AA and AC have a higher rate of anorexia (R).

One study found the exact opposite effect if some studies above and showed increased startle reaction in A carriers to unpleasant images (R).

Similarly, genetically reduced FAAH activity may be a risk for the development of anxiety and depression in persons with repetitive childhood trauma.  Specifically, the A allele is a risk factor for these conditions when exposed to childhood trauma (R).

The A allele was associated with lower HDL levels (R):

  • CC=40.5,
  • AC=39.1,
  • AA=34.8

Each 1 mg/dl reduction in circulating HDL level is known to be associated with a 6% increase in the risk for cardiovascular disease (R).

Diet Interactions

In 451 obese Europeans undergoing a 6 week trial of a low-fat diet, subjects with AA experienced greater reductions in circulating triglycerides and total cholesterol levels) (R).

After weight loss, CC had an improvement on insulin and insulin resistance scores with an enriched monounsaturated fat hypocaloric diet (R).

People with an A allele lost less weight on this enriched monounsaturated fat hypocaloric diet. People with an A lost only 2.7 kg fat mass  (CC lost 3.4 kg) (R).

Drug Interactions

A psychoactive ingredient in cannabis helped people with IBS-C more when they had CC (R).

The A allele is associated with antipsychotic-induced weight gain (R).


G is the more common allele. 35% of the alleles in the global population are “A”.


G=maybe higher FAAH activity (R).

Associations With The G Allele

The presence of the G allele was linked with an increase of recollections of the traumatic event (R).

G subjects showed more intense recollections of traumatic events and of negative childhood experiences (R).

In one study, rs2295633 was the only FAAH SNP to reveal a significant difference in PTSD prevalence. G compared with AA subjects, presented with a higher PTSD diagnosis prevalence (P=0.001) (R).

Negative early experiences increased PTSD risk only in those subjects presenting at least one G (R).

The G allele could serve as a possible marker for increased PTSD risk in subjects exposed to brain injury and combat experiences (R).

GG=higher arousal and lower fatigue levels after amphetamine ingestion (R).

Increased arousal has been linked with reduced FAAH activity in animal models, thus suggesting possible higher FAAH activity in G allele carriers (R).


G=possibly higher FAAH.

GG=higher Arousal levels (lower fatigue) after amphetamine ingestion (R).

Increased arousal has been linked with reduced FAAH activity in animal models, thus suggesting possible higher FAAH activity in G allele carriers (R).

How to Increase Cannabinoids

Stress Reduction

Prolonged exposure to elevated glucocorticoids (cortisol), such as those induced by chronic stress conditions, significantly reduces hippocampal CB1 receptors (R), leading to lower cannabinoid function.

In fact, a recent study suggests that CB1 receptor deficiency may mimic the effects of chronic stress on emotional behavior (R).

Omega 6’s

Anandamide, 2-AG, 2-AGE, and other endogenous cannabinoids are derived from arachidonic acid (R).

Studies of piglets show that dietary levels of arachidonic acid and other essential fatty acids affect the levels of anandamide and other endocannabinoids in the brain (R). High-fat diet feeding in mice increases levels of anandamide in the liver (R).


Exercise increases anandamide, which is our natural CB1 activator (R, R2).

High-fat diet

A high-fat diet increases liver levels of the endocannabinoid anandamide (arachidonoyl ethanolamide) and increases CB1 receptors (R).

Nicotine or Galantamine

Activation of nicotinic receptors leads to increased cellular levels of calcium (Dani et al., 2001), which is known to stimulate release of endogenous cannabinoids such as anandamide (Piomelli, 2003) (R)

Fish oil/DHA

DHA increases cannabinoid synthesis and CB1 and CB2 receptors (R).


Testosterone and DHT increase the CB1 receptors (R).


Estradiol increases anandamide and inhibits FAAH (R, R2), but it increases FAAH production (R).


Tea/EGCG (Full agonist, Ki 33.6 μM) (R, R2) – according to another group, flavonoid-type compounds (catechins, anthocyanidins, flavones) lead to negligible or very high Ki values, which likely reflect a nonspecific molecular denaturation of the protein surface rather than a functional binding interaction (R)


THC/Marijuana – potent CB1 activator (R),

CBD oil (increases CB1 receptors) (R),

Oleamide (R),

Aspirin – COX-2 inhibitors activate the CB1 receptor (R).

Tylenol (R)

Palmitoylethanolamide – enhances anandamide (R)

Agmatine (R)

Echinacea binds to the CB2 receptor (R)

Genistein (R)

Chocolate – N-acylethanolamines (NAEs), N-linoleoylethanolamide and N-oleoylethanolamine inhibit FAAH (R)

Beta-caryophyllene – activates CB2 receptor (R)

Kava/yangonin (R)

Kaempferol, 7-hydroxyflavone and 3,7-dihydroxyflavone have been shown to concentration-dependently inhibit anandamide hydrolysis in rat brain homogenates, albeit at relatively high concentrations (IC50 values between 2 and 10 mM). Nevertheless, the authors of these studies showed a preliminary structure-activity relationship with 7-hydroxyflavone (7-hydroxyflavone and 3,7-dihydroxyflavone have been shown to concentration-dependently inhibit anandamide hydrolysis in rat brain homogenates, albeit at relatively high concentrations (IC50 values between 2 and 10 mM). Nevertheless, the authors of these studies showed a preliminary structure-activity relationship with 7-hydroxyflavone (R).

Caffeine can help with a stress-induced decrease in the CB1 receptor (R).

Benzodiazepines work in part through CB1 receptors (RR).

Health Tools I Wish I Had When I Was Sick

At SelfHacked, it’s our goal to offer our readers all the tools possible to get optimally healthy. When I was struggling with chronic health issues I felt stuck because I didn’t have any tools to help me get better. I had to spend literally thousands of hours trying to read through studies on pubmed to figure out how the body worked and how to fix it.

That’s why I decided to create tools that will help others cut down the guesswork:

  • Lab Test Analyzer – a software tool that will analyze your labs and tell you what the optimal values are for each marker — as well as provide you with actionable tips and personalized health and lifestyle recommendations to help you get there.
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  • SelfHacked Secrets – an ebook where we examine and explain the biggest overlooked environmental factors that cause disease. This ebook is a great place to start your journey if you want to learn the essential steps to optimizing your health.
  • SelfHacked Elimination Diet course – a video course that will help you figure out which diet works best for you
  • Selfhacked Inflammation course – a video course on inflammation and how to bring it down
  • Biohacking insomnia – an ebook on how to get great sleep
  • Lectin Avoidance Cookbook – an e-cookbook for people with food sensitivities
  • BrainGauge – a device that detects subtle brain changes and allows you to test what’s working for you
  • SelfHacked VIP – an area where you can ask me (Joe) questions about health topics

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  • TH

    thoughts on kaempferol as an inhibitor of faah?

    1. Joseph M. Cohen


      1. TH

        haven’t really had time to look further into it

  • Casso

    Thank you for taking the time to send me your mail . PS there is a clinic in Germany that got me feeling like new within three weeks they have being doing there treatments for over sixty years, but every time I came home I got ill very fast again . I did have the dao test in 2010 and my count was 40 half what it should have been between 80 = 120. But I did not think how much it was effecting me until I read you post ,now I am taking my daosin 3 caps 4 times a day for the last 2 days and I am feeling a good bit better. I walked out of hospital after being in for two years yes years .11 operations more meds than I can remember even chemotherapy treatment and that’s why I left the doctors could not tell me why I was on the chemo. I am 48 and have been very ill on and off since I can remember but I always new but was told I was wrong that it was what I was eating why else can you have good days and bad . Now I know I was right thank you for making it so clear because that’s what I have being looking for for many years. I can tell you where I have been Harley Street UK Europe ex. And have had all the test that can be done all for nothing the only blood test other than my dao was my Age was 1470 down to 460 but mostly around 900 again thank you any other ideas to clear my mind quicker would be great . NC . Ireland

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