Pharmacology - Tylenol Metabolite as a Cannabinoid

[Jasim]

So I was doing some research on the mechanism of action of acetaminophen and stumbled across something very interesting.

Acetaminophen is converted in the body to N-acylphenolamine which is an agonist on CB1 receptors (the neuronal ones). In addition, it inhibits the reuptake of anandamide.

[top]N-acylphenolamine (AM404)

AM404.png

[top]Anandamide

Anandamide.png


To put it more clearly, Tylenol is converted to AM404 in the body. AM404 activates the same receptors that THC activates to cause its psychoactive effects. AM404 also prevents the neurons from recycling the body's endogenous cannabinoid, anandamide. This causes more anandamide to be left in the synaptic cleft and continue activating the same cannabinoid receptors.

Too bad swim doesn't smoke pot anymore. I would be interested in hearing if Tylenol had any kind of potentiation with marijuana.
I also wonder what it would take to turn Tylenol into AM404 to produce a synthetic cannabinoid? Would taking AM404 still have a similar effect? Or maybe greater amounts could be played with to determine any psychoactive properties or potentiation with cannabis. Oh the possibilities.

[klonopinz]

Not to swims knowledge or experience. Can't back it up with pharmacological or related lit, but Swim thinks that, being on of the most used drugs in human history, if acetaminophen had any potentiation effects on any drug what so ever, it would already be, at the very least, observed and documented on user review literature by Tylenol (as this would further increase sales but they can't really advertise it heh).
And given the broad and relatively close knit marijuana culture, word of mouth would have already reached all of us if it did... but swim can be wrong, as he doesn't even get any pain relief from it anyway whatsoever, so his experience might not be a normal one.

[Jasim]

^ True. I was really wondering about the metabolite specifically. Maybe we can get one of the chemistry guys in here to ask some conversion questions.
I dunno how difficult it would be though, that's one heck of a carbon chain to attach to acetaminophen. With 4 cis double bonds, would be a very messy synthesis (at best 1-2% product maybe?).

Suppose that's a lost cause. But What about carefully manipulating the metabolic system to produce more AM404? Theoretically interesting, but I guess no real usefulness to the potheads, lol.