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Is Anandamide Abusable?

Cwest

Cwest

Bluelighter
Joined
Apr 4, 2011
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GTA
Hi I have looked around bluelight and have not found much information on anandamide (AEA).

I was wondering if anyone knew if it was abusable? Or if anyone can link me to threads discussing this?

thanks,
Cwest
 
FAAH inhibitors might be interesting. They not only inhibit breakdown of endocannabinoids, but they somehow increase their production: a positive feedback loop.

I might be wrong about this because I just yanked it off of various wikipedia pages.
 
The FAAH alone would work because your body already produces anadamide.

Unfortunately there are no human suitable FAAH inhibitors around.
 
There are a few FAAH inhibitors that have passed phase I (safety and tolerability in humans). Wikipedia gives 3 examples. Each of these is being explored as anxiolytic and analgesic.

There's probably an herbal FAAH inhibitor out there undiscovered too.

The thing about the positive feedback loop is interesting to me. Physiologically they're much rarer than negative feedback loops. I wonder if it was a typo or if the presence of anandamide actually does cause the production of more anandamide.
 
23536 said:
There are a few FAAH inhibitors that have passed phase I (safety and tolerability in humans). Wikipedia gives 3 examples. Each of these is being explored as anxiolytic and analgesic.

There's probably an herbal FAAH inhibitor out there undiscovered too.

The thing about the positive feedback loop is interesting to me. Physiologically they're much rarer than negative feedback loops. I wonder if it was a typo or if the presence of anandamide actually does cause the production of more anandamide.
Click to expand...

well if anyone is daring enough to try these FAAH inhibitors, please let me know what happens
 
I wonder how pharmaceutical companies feel when their experimental products get threads on BL. I mean, they're spending millions of dollars and putting their best face forward for the FDA and Bluelight is the 2nd result for it on Google.
 
I had some urb-597 but never tried it... does that mean its effects would essentially be that of anandamide?
 
according to this paper anandamide has a specific reuptake mechanism. wouldn't taking an FAAH inhibitor then lead to accumulation of anandamide in the axon terminal, where it doesn't exert cannabinoid effects? i don't know if the resulting concentrations of anandamide would be anywhere as high to cause some trouble, but it's a kind of detergent after all...
 
23536 said:
There are a few FAAH inhibitors that have passed phase I (safety and tolerability in humans). Wikipedia gives 3 examples. Each of these is being explored as anxiolytic and analgesic.

There's probably an herbal FAAH inhibitor out there undiscovered too.

The thing about the positive feedback loop is interesting to me. Physiologically they're much rarer than negative feedback loops. I wonder if it was a typo or if the presence of anandamide actually does cause the production of more anandamide.
Click to expand...
i know im a decade late buy nutmeg has strong faah inhibition
 
Skorpio said:
Interesting, do you have a source for this?
Click to expand...
Yes I do! :) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938946/#:~:text=In conclusion, this study provides,both FAAH and MAGL enzymes.

“In conclusion, this study provides further evidence that nutmeg extracts target the endocannabinoid system indirectly by inhibiting both FAAH and MAGL enzymes.”

Have you tried nutmeg? It provides such an intense stoning couples with some mild deliriant/halucinogen effects, stimulant effects and empathogenic effects. The most prevalent of them is the stoning, incredibly similar to weed except more potent and can have more side effects. When used in the “Space Paste” recipe, it is soooo great, if you haven’t heard of spacepaste I highly recommend researching it. It potentiates all the positive effects whilst nearly eliminating any of the negatives by combining it with a bunch of other psychoactive/psychotropic herbs and spices, a bunch of stuff that like cinnamon, cloves, black pepper ect. some of these herbs act on the cannabinoid system a bit themselves, potentiate alkaloids in nutmeg, surpress the side effects or have a little psychoactivity themselves. Heres a link to the recipe on DMT-Nexus (not sure if I can quote other forums, let me know if not) https://www.dmt-nexus.me/forum/default.aspx?g=posts&t=14275 somebody in the replies described what each ingredient does if your interested.

The compounds responsible for the FAAH inhibition are licarin A, 5'-methoxylicarin A and malabaricone C in order from strongest to weakest, it also contains myristicin, eugenol and i believe safrole which are all somewhat related to mda, myristicin being the closest. Any more questions about it feel free to ask.

edit: i believe if one were to add some tetrahydromagnolol, cbd and or cbn to the mix it would make the whole thing a lot more comparable to weed than it already is, since faah inhibitors stop our body from breaking down anandamide while promoting its production simultaneously and anandamide is only a ligand for the cb1 receptor and not cb2, by itself it doesnt provide all the sensations that good weed does.
 
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Borax said:
Yes I do! :) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938946/#:~:text=In conclusion, this study provides,both FAAH and MAGL enzymes.

“In conclusion, this study provides further evidence that nutmeg extracts target the endocannabinoid system indirectly by inhibiting both FAAH and MAGL enzymes.”

Have you tried nutmeg? It provides such an intense stoning couples with some mild deliriant/halucinogen effects, stimulant effects and empathogenic effects. The most prevalent of them is the stoning, incredibly similar to weed except more potent and can have more side effects. When used in the “Space Paste” recipe, it is soooo great, if you haven’t heard of spacepaste I highly recommend researching it. It potentiates all the positive effects whilst nearly eliminating any of the negatives by combining it with a bunch of other psychoactive/psychotropic herbs and spices, a bunch of stuff that like cinnamon, cloves, black pepper ect. some of these herbs act on the cannabinoid system a bit themselves, potentiate alkaloids in nutmeg, surpress the side effects or have a little psychoactivity themselves. Heres a link to the recipe on DMT-Nexus (not sure if I can quote other forums, let me know if not) https://www.dmt-nexus.me/forum/default.aspx?g=posts&t=14275 somebody in the replies described what each ingredient does if your interested.

The compounds responsible for the FAAH inhibition are licarin A, 5'-methoxylicarin A and malabaricone C in order from strongest to weakest, it also contains myristicin, eugenol and i believe safrole which are all somewhat related to mda, myristicin being the closest. Any more questions about it feel free to ask.

edit: i believe if one were to add some tetrahydromagnolol, cbd and or cbn to the mix it would make the whole thing a lot more comparable to weed than it already is, since faah inhibitors stop our body from breaking down anandamide while promoting its production simultaneously and anandamide is only a ligand for the cb1 receptor and not cb2, by itself it doesnt provide all the sensations that good weed does.
Click to expand...
Nice, I really like the approach in that study, moving from fractions to pure compounds. These results make intuitive sense, definately more than the phenylpropene to amphetamine hypothesis, which is kind of a reach imo (consider enzymatic flux and the total dose of myristicin. Even if the oxidation of the double bond to a ketone, and then trans animation occured simultaneously; they likely aren't coupled, and blood levels wouldnt approach psychoactivity).

I've had a handful nutmeg experiments, trying space paste a few of the latter times. I wouldn't say it was better than cannabis, as I still felt rather uncomfortable, but it was the closest neighbor. I couldn't justify doing nutmeg these days because the high lasts way too long. Same reason I don't do THC-P gummies.

Also, I worry about the other targets of nutmeg. When I googled licarin A to see what it looked like, it was mentioned as a protein kinase c inhibitor and malabaricone C as a sphingomyelin synthase inhibitor. I'd be moderately afraid of the long term effects of habitual use of these compounds.

I wonder if there are more potent MAG lipase inhibitors found in nature. 2-AG tends to be the bigger player with regard to total endocannabinoid tone (at least at CB1 sites).

I do wish they did the behavior experiments with the unfractionated extract to see if the convo of weaker MAGL inhibition and FAAH inhibition caused catalepsy in rodents.

Licarin A even looks a touch like that cursed BIAL FAAH inhibitor that put holes in people's brains during phase I trials. Though luckily not in that pyridine-N-oxide, that looks to my non-chemist eye like it wants to redox all over your electrophiles.
 
Skorpio said:
Nice, I really like the approach in that study, moving from fractions to pure compounds. These results make intuitive sense, definately more than the phenylpropene to amphetamine hypothesis, which is kind of a reach imo (consider enzymatic flux and the total dose of myristicin. Even if the oxidation of the double bond to a ketone, and then trans animation occured simultaneously; they likely aren't coupled, and blood levels wouldnt approach psychoactivity).

I've had a handful nutmeg experiments, trying space paste a few of the latter times. I wouldn't say it was better than cannabis, as I still felt rather uncomfortable, but it was the closest neighbor. I couldn't justify doing nutmeg these days because the high lasts way too long. Same reason I don't do THC-P gummies.

Also, I worry about the other targets of nutmeg. When I googled licarin A to see what it looked like, it was mentioned as a protein kinase c inhibitor and
malabaricone C as a sphingomyelin synthase inhibitor. I'd be moderately afraid of the long term effects of habitual use of these compounds.
Click to expand...

I wonder if there are more potent MAG lipase inhibitors found in nature. 2-AG tends to be the bigger player with regard to total endocannabinoid tone (at least at CB1 sites).

I do wish they did the behavior experiments with the unfractionated extract to see if the convo of weaker MAGL inhibition and FAAH inhibition caused catalepsy in rodents.

Licarin A even looks a touch like that cursed BIAL FAAH inhibitor that put holes in people's brains during phase I trials. Though luckily not in that pyridine-N-oxide, that looks to my non-chemist eye like it wants to redox all over your electrophiles.
Click to expand...
God I remember those trials, it completely ruined the prospect of pharmaceutical faah inhibitors for the foreseeable future. My hypothesis is that using it as space paste and adding tetrahydromagnolol, a good dose of cbd, a good dose of cbn, a full spectrum extract, plus maybe some l-theanine and dramamine would make the experience a lot more tame, less nauseous and anxious.

You could supplement chamomile to offset the sphingomyelin inhibion and capsaicin and oleamide to offset the the protein kinase c inhibition.

Maybe even find an herb that blocks the enzyme that metabolizes licarin A and malabaricone C to just leave us with the good one, assuming each one metabolizes differently.

To end the experience early, you can take yerba mate, lemon balm, honokiol, wild lettuce, magnolol, high dose CBD, black pepper, ginko biloba and maybe even vape some pure terpinoids like myrcene, beta-caryophyllene and limonene. Also dont forget to eat something sugary!
 
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