FAAH is one of those random acronyms that makes neuroscience outsiders’ eyes glaze over, but it’s a crucial mediator in our endocannabinoid system.

FAAH is a nerve enzyme that can shorten your high or, in its absence, prolong it. Overproduction of FAAH can lead to depression, loss of appetite, irritability, anxiety and a host of other issues. Not coincidentally, these are the same symptoms that heavy weed users experience as marijuana withdrawal, especially following periods of cannabis dependence

The 3-dimensional structure of the FAAH enzyme is shown here bound up with a commercial chemical used to help map FAAH’s structure. FAAH, according to current thought, pulls apart used anandamide neurotransmitter molecules for disposal. FAAH sucks in the anandamide through the membrane access channel, uses a water molecule to bust it in half in the acyl-chain binding pocket, then squirts out the pieces through the cytosolic port. Illustration courtesy of the Journal of Molecular Biology.

Though not as serious or dangerous as the addiction and withdrawal from other recreational drugs like alcohol and opioids, a significant minority of pot smokers can get addicted to marijuana (technically categorized as marijuana use disorder) and experience withdrawal symptoms.

FAAH is the component of the endocannabinoid system that acts as a cleanup molecule to break apart the endocannabinoid neurotransmitter anandamide (AEA).

What is FAAH?

FAAH is a specific enzyme your own nervous system makes to keep your nerve signaling running smoothly — specifically the nerve signaling that goes on in your endocannabinoid system. This is the same subdivision of your central nervous system that reacts to cannabis, producing the trademark weed high, as well as being the site of most of medical marijuana’s therapeutic benefits.

FAAH breaks down anandamide, which is a crucial nerve signaling chemical that helps regulate mood, memory, perception, sleep, appetite and a host of other important physiological functions — a linchpin of the mammal endocannabinoid system. Part of this balance requires FAAH to bind with AEA and take it apart for reuse or disposal once it has done its job.

FAAH is coded in your DNA by a gene of the same name. The FAAH gene and the enzyme it codes also helps you break down other fatty acids used for different signaling purposes, according to GeneCards.org.

“This gene encodes a protein that is responsible for the hydrolysis of a number of primary and secondary fatty acid amides, including the neuromodulatory compounds anandamide and oleamide,” the gene summary states.

Your specific genetic code for FAAH can dramatically impact how you respond to cannabis and is one of the critical components behind Strain Genie’s cannabis health report.

What does FAAH stand for?

FAAH stands for “Fatty acid amide hydrolase.” Let’s break that down, no pun intended. 

Fatty acids are any kind of molecules based on a chain of carbons with some oxygen and hydrogen snapped onto the end. Fatty acids throughout your body have different classifications and functions, but for now, just know that both anandamide and the main cannabis components THC and CBD are fat-soluble molecules.

Amides are molecules that perform some task in the body. They contain a specific arrangement of carbon, hydrogen, and oxygen in addition to some nitrogen.

So far, we’ve learned that “Fatty Acid Amide” describes the kind of molecule FAAH is there to break down; anandamide is a fatty acid that performs a function in the body and also contains nitrogen (notice the “amide” suffix). This makes it an amide in addition to being a fatty acid.

Ase” is a Greek suffix from the word meaning “to separate.” As such, it’s applied to enzymes, which are chemicals throughout the body that breakdown and remove other chemicals.

The “hydro” part refers to the catalyst (H2O) FAAH uses to break anandamide up into arachidonic acid and ethanolamine. Any process using water to foment the reaction called “hydrolysis.” (“Lysis” is another Greek suffix meaning “break down”).

FAAH Anandamide Hydrolysis diagram

So, FAAH uses hydrolysis to break down fatty acid amides (i.e. anandamide). It’s all in the name!

Why are researchers studying Fatty acid amide hydrolase?

Researchers are studying FAAH as a target for pharmaceuticals because controlling levels of FAAH may produce some of the same health effects that excite clinicians about the potential for cannabis-based medicines.

Cannabis-based pharmaceuticals work by flooding the system with chemicals similar to anandamide and other endocannabinoids. Medicines that stop the body’s production of FAAH could have a similar effect by maximizing the amount of anandamide floating around in your nervous system. 

So, while cannabis medicines increase the number of cannabinoid transmitters artificially through the addition of THC (read up on how THC mimics AEA), removing FAAH proportionally increases the amount of AEA naturally produced by the body.

In other words, if you give the janitors the day off, the trash is gonna pile up. 

In the case of someone with chronic pain or an inflammatory autoimmune disorder, however, that extra AEA could be treasure rather than trash, because it could help reduce those symptoms without any of the side effects of consuming cannabis. Pharma companies have had little success in clinical trials, though, using the few different FAAH inhibitors they’ve developed in the lab — in fact, a 2016 clinical trial led to serious injuries and one death among the volunteers.

Interestingly, cannabidiol (CBD), THC’s non-psychotropic twin chemical in weed, has proven to weakly inhibit production of FAAH. This is one of the reasons patients using synthetic prescription THC (dronabinol or Marinol), report a shorter, more intense high than people who consume whole marijuana that includes CBD. By binding with FAAH molecules, CBD knocks them out of service, allowing the THC and ADA more time to squirt around in your brain and produce their hallmark effects.

Did you know? CBD weakly inhibits the production of FAAH, which could result in a longer-lasting effect of THC. This could be counteracted by the mitigating effects that THC has on THC’s binding affinity.

The endocannabinoid system in heavy pot users gets conditioned to produce more FAAH and less anandamide because of all the THC flooding the system. Your brain is trying to resume balance, so ups the ante to remove what it perceives as an excess of anandamide.

The theory goes that taking a drug to inhibit FAAH could provide similar therapeutic benefits to toking up. But instead of your endocannabinoid system getting flooded with THC, it’s flooded with your own naturally-occurring anandamide, as there will be proportionately more of it in your system. This means, according to researchers best guesses and some rodent studies, you get the medical benefits of cannabis without the artificial high.

Are FAAH inhibitors dangerous?

A drug that inhibits FAAH is under study to ease the symptoms of marijuana withdrawal, though targeting FAAH may have a number of other medical benefits that drug researchers have yet to demonstrate. 

FAAH Inhibitor breakdown

Not that they haven’t tried. Pfizer started, then canceled clinical trials of FAAH inhibitors to treat osteoarthritis pain and inflammation and cancer pain because they weren’t effective enough to bother with the expense of continuing. 

Unfortunately for these patients who may have hoped for relief from FAAH inhibitor research, one FAAH inhibitor drug under study proved deadly.

Six volunteers with depression developed serious neurological conditions that put five in the hospital and one in the grave during a 2016 inhibitor trial by Bial, a French pharma company. This prompted Johnson & Johnson to suspend similar research.

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