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Increasing levels of endocannabinoids

shibireru

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Dec 17, 2008
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Am I right in thinking that one could dramatically increase serum levels of N-arachidonoylethanolamine (anandamide) - anandamide especially but other endocannabinoids as well - by consuming the following readily obtainable substances:

  • Ibuprofen (inhibits cyclooxygenase which converts arachidonic acid into various prostanoids.)
  • Linoleic acid (converted into arachidonic acid)
  • Lecithin (consists of: phosphatidylethanolamine, phosphatidylcholine, phosphatidylinositol, phosphatidic acid)
  • Inositol
  • 5-lipoxygenase inhibitor (Zileuton/Azelastine/Diethylcarbamazine/nordihydroguaiaretic acid) (arachidonate 5-lipoxygenase converts arachidonic acid into leukotrienes)

Or do you suppose that fatty acid amide hydrolase is too abundant or too efficient for this combination to have a noticeable psychotropic effect? If so, are you aware of any fatty acid amide hydrolase inhibitors that can be obtained with relative facility?
 

Tsukasa

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You would need omega-3 and omega-6 fatty acids. Cocoa may contain alkaloids that inhibit the enzyme that breaks down anandamine. Stress can increase endocannabinoids, and so can lowered levels of leptin and elevated calcium.

Acetaminophen (tylenol) also works by modulating the cannabinoid receptors, which I think is worth a mention.
 

shibireru

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Acetaminophen (tylenol) also works by modulating the cannabinoid receptors, which I think is worth a mention.

Actually, I just learned that acetaminophen is a fatty acid amide hydrolase inhibitor. It has been shown to increase anandamide levels.

Edit: Nevermind.... stupid fucking Wikipedia. I should know better by now than to use it as a reference. I wasn't able to find a single study to corroborate this assertion.
 
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invert

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Actually, I just learned that acetaminophen is a fatty acid amide hydrolase inhibitor. It has been shown to increase anandamide levels.

Edit: Nevermind.... stupid fucking Wikipedia. I should know better by now than to use it as a reference. I wasn't able to find a single study to corroborate this assertion.
If you follow the link from the acetaminophen page on Wikipedia to the page on AM404, that page has references to articles apparently asserting that (1) AM404 is a metabolite of acetaminophen and (2) that AM404 inhibits FAAH... I've not followed up these references, but they sound like they should corroborate the assertion, maybe?
 

Riemann Zeta

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Their are real, honest-to-god peer-reviewed experimental papers out there regarding AM404 out there. It is indeed a FAAH inhibitor. The question is, since it is a prodrug of paracetamol, we can't really be sure how much of it is present in the brain after a given dose of the parent compound.
 

shibireru

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Even if AM404 is a FAAH inhibitor, since FAAH somehow mediates the conversion of N-acyl phenolamine into N-arachidonoyl phenolamine (AM404), the amount of FAAH inhibition one can achieve with acetaminophen must be fairly limited. But I guess some is better than none.
 
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Hammilton

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None of these produce noticeable psychoactive effects. I injected a few of the endocannabinoids thought to have recreational potential (dissolved in ethanol, btw- major pain, will never repeat).

Nothing happened.

There is no dose of APAP that will get you high no matter what you do.
 

shibireru

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None of these produce noticeable psychoactive effects. I injected a few of the endocannabinoids thought to have recreational potential (dissolved in ethanol, btw- major pain, will never repeat).

Nothing happened.

There is no dose of APAP that will get you high no matter what you do.

Earlier today I took an unknown but fairly large amount of lecithin, 200mg linoleic acid, 1 gram of inositol, 200mg of phosphatidylserine, 800mg of ibuprofen, 500mg of APAP, and 500mg of docosahexaenoic acid; I experienced a very marked shift in cognition. Obviously, I can't be certain that this wasn't the placebo effect, nor, if I were able to know that it hadn't been, would I be able to know that it was cannabinoid receptor agonism that was responsible for this change in my mental state, but I must say that it definitely resembled the state of mind into which I have entered ever time I have used cannabis - albeit less intense.

It wasn't enjoyable. (Although I have never gotten anything out of marijuana, either, but feelings of terror and confusion, so...)
 

macropsia

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Jan 14, 2009
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I have definitely noticed some kind of difference when smoking cannabis during a period of time when I was taking large amounts of NSAIDs for headaches. It wasn't too much, but I remember consistently feeling nonspecifically 'loopier'.
 

jamesmartin

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Ouf interesting stuff .

Does anyone know ? and even if we did , would it reduce our Cannabis tolerance? Which im sad too say is something that many of us stoners have .
 

23536

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go running!

Hippocampus. 2010 Apr;20(4):513-23.

Endogenous cannabinoid signaling is required for voluntary exercise-induced
enhancement of progenitor cell proliferation in the hippocampus.

Hill MN, Titterness AK, Morrish AC, Carrier EJ, Lee TT, Gil-Mohapel J, Gorzalka
BB, Hillard CJ, Christie BR.

Department of Psychology, University of British Columbia, Vancouver, B.C.,
Canada. [email protected]

Voluntary exercise and endogenous cannabinoid activity have independently been
shown to regulate hippocampal plasticity. The aim of the current study was to
determine whether the endocannabinoid system is regulated by voluntary exercise
and if these changes contribute to exercise-induced enhancement of cell
proliferation. In Experiment 1, 8 days of free access to a running wheel
increased the agonist binding site density of the cannabinoid CB(1) receptor;
CB(1) receptor-mediated GTPgammaS binding; and the tissue content of the
endocannabinoid anandamide in the hippocampus but not in the prefrontal cortex.
In Experiment 2, the CB(1) receptor antagonist AM251 (1 mg kg(-1)) was
administered daily to animals given free access to a running wheel for 8 days,
after which cell proliferation in the hippocampus was examined through
immunohistochemical analysis of the cell cycle protein Ki-67. Voluntary exercise
increased proliferation of progenitor cells, as evidenced by the increase in the
number of Ki-67 positive cells in the granule cell layer of the dentate gyrus
(DG) in the hippocampus. However, this effect was abrogated by concurrent
treatment with AM251, indicating that the increase in endocannabinoid signaling
in the hippocampus is required for the exercise-induced increase in cell
proliferation. These data demonstrate that the endocannabinoid system in the
hippocampus is sensitive to environmental change and suggest that it is a
mediator of experience-induced plasticity.


PMCID: PMC2847038
PMID: 19489006 [PubMed - indexed for MEDLINE]
 

Neuroprotection

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Apr 18, 2015
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The combination you suggested may help to some extent, although fatti acid amide hydrolase is very active and so would probably quickly destroy any extra endocanabanoids formed. Also, some of the substances mentioned may interact fore example Ibuprophen and ziluton and cause toxicity. e.g. cox enzymes produce prostaglandins important for protection of the stomach and blood vesal dilation. Although I don't know about its effects if used short turm and at low doses.
 

Neuroprotection

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Apr 18, 2015
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THC, the main psycho active compound of cannabis has been shown to cause a dramatic increase in cyclooxygenase enzyme expression via activation of canabanoid receptors. This could lead to neuronal inflammation, and negative psychological effects like paranoyer and depression.
Also what do you mean by loopier, was it negative or positive feeling.
If you enjoyed cannabis more with NSAIDs, it might be worth using them each time you smoke to protect the brain from some THC's toxicity.
 

St3ve

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Mar 15, 2013
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Runner's high increases endocannabinoid secretion. Other than that omega 3/6 supplementation should help.
 

MDpatient

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Oct 7, 2015
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Been told that running endocannabinoid secretion vs. a spliff is like comparing a drop to a gallon of water.
 

dopamimetic

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URB-597 anyone? ;) It has a bad reputation because of some probably adulterated batches which led to serious health problems, but the compound itself is in clinical human trials and doesn't appear to be that unsafe...
 
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