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Pharmacology Liver enzyme inducers to combat edible cannabis immunity?

This thread contains discussion about a Pharmacology-related topic
Psychlone Jack

Psychlone Jack

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Hi guys. Don't post over in this neighborhood too often, but I'm pretty sure I'm in the right spot - if not, mods feel free to move it to Cannabis Discussion or wherever. :)

Okay, so, a little backstory on the issue: I came home from prison this time last year, started using cannabis again soon after. I started and quit cigs again after getting out and was vaping, so I didn't want to smoke. Thus, vapes and edibles it was. Regular d9 at first, but then also and later primarily all the Farm Bill alt-noids; d8, hhc, thc-o, thc-p, diamonds, etc. I ate, vaped, occasionally experimenting with pre-rolls, having forgotten that they tend to be the lowest of the low, and that further turned me from smoking for a while. Also, I hadn't figured out the same stores sold real weed yet lol. (non-legal state :( )

Things were going well enough all things considered, of course I experienced steady tolerance increase, but that's to be expected and I wasn't willing/couldn't take a t-break at the time due to a very nasty stomach illness, which never resolved but has mellowed. I was eventually able to take that t-break, 30 days. I needed it dearly - I'd started smoking bud again by this time, and could barely feel anything via that method, and couldn't feel anything at all, regardless of dose, with edibles. And I mean I TRIED, a homemade 1750mg brownie did nothing.

So fast forward to present day. Smoking flower is now my primary consumption method, and while I could probably use another t-break, I can get reasonably high off of a reasonable amount. But I still can't feel shit off of edibles. I've tried everything, all the brands that used to smack me, making my own, which I've known how to do for 20 years so I'm pretty sure it's not operator error, empty stomach, full stomach, taking with a lipid, NOTHING! My most recent fail was smashing 4 firecrackers I'd made with an 1/8th of Wedding Crasher, so approx. 175mg thc a piece. Didn't feel shit.

Like I said, my stomach never really got better, it still shows it's ass from time to time, and I'm looking for a new doctor now to try to figure the shit out, but in the meantime, it'd be super if I could stop hacking shit up all the time from smoking bud, and get off on edibles again. And yeah it could be my abuse of it last year, or some underlying medical thing. The reading I've done, that I think I've been able to understand correctly, says that the CYP2C and CYP3A enzymes are responsible for metabolism of cannabinoids, among many other things. Could taking a CYP2C19 inducer possibly improve how my body is metabolizing the thc? Reading through a list of possible candidates, the only ones I see I might have easy access to are aspirin, prednisone and St. John's Wort?

I am not a doctor, nor did I stay at a Holiday Inn Express last night, lol... I realize this is a stab in the dark, but if anyone could shed some light on this, is it a viable idea or any other suggestions?

Thanks.. ✌️
 
This is just a guess but apixaban is metabolized by 2C9 and it may be competing with THC, this is just something I see at first glance when looking at the pharmacokinetics
I'm not an expert in drug metabolism, there may be others who can chime in who know more than I do
 
Do you get apixaban levels monitored by the Drs? If so, competition with cannabinoids would likely result in higher plasma levels of the apixaban.



This paper suggests THC is primarily metabolized by cyp2C9. They show that co-administration with cyp2c9 substrate phenytoin actually increases phenytoin metabolism.

However, cyp3A4 is kind of considered the "garbage can" cyp enzyme, as it's got a giant and permissive active site, which can fit quite a large range of molecules. Often with selective inhibition of its preferred cyp enzyme, compounds can become cyp3a4 substrates.

I would be wary of using enzyme inducers to make thc orally active for you. Inducing cyp expression will have effects far beyond weed metabolism, and too much cyp activity can increase the rate in which toxic metabolites (of both drugs and compounds produced by normal human metabolism) are produced at higher levels. Taking these inducers on a daily basis (or simply enough to maintain steady state increases in cyp enzyme expression) seems more hazardous than continuing to smoke.
 
Skorpio said:
Do you get apixaban levels monitored by the Drs? If so, competition with cannabinoids would likely result in higher plasma levels of the apixaban.



This paper suggests THC is primarily metabolized by cyp2C9. They show that co-administration with cyp2c9 substrate phenytoin actually increases phenytoin metabolism.

However, cyp3A4 is kind of considered the "garbage can" cyp enzyme, as it's got a giant and permissive active site, which can fit quite a large range of molecules. Often with selective inhibition of its preferred cyp enzyme, compounds can become cyp3a4 substrates.

I would be wary of using enzyme inducers to make thc orally active for you. Inducing cyp expression will have effects far beyond weed metabolism, and too much cyp activity can increase the rate in which toxic metabolites (of both drugs and compounds produced by normal human metabolism) are produced at higher levels. Taking these inducers on a daily basis (or simply enough to maintain steady state increases in cyp enzyme expression) seems more hazardous than continuing to smoke.
Click to expand...

Thanks very much for your reply, man. And yeah, I'd very much rather my circulatory health take priority over that. I don't get my apixaban levels monitored, but dvt's aren't a new thing for me, I was first diagnosed at 23 and had a reoccurrance last year at 37. I very recently found a connect on extremely well priced high quality rosin, so hopefully that stays consistent and should allow me to cut down on the amount I smoke.

Thanks again. 👍
 
Experimented today, with mild success. Had a 500mg d8 gummy and two 100mg thc-o gummies on a fairly empty stomach, had been about 2.5 hours since I'd eaten anything. Ate half a slice of peanut butter toast and a spoonful of coconut oil, then the gummies, then chased with a cup of hot black coffee. Been 2.15 and I definitely feel them, not obliterated like I should be, but a noticeable stony edible high. First time trying coconut oil as an added lipid to aid the absorption, and while it's good to know it works to a degree, still not really efficient enough to be cost effective for me, unless this turns out to have a very long duration.
 
I don't know anything about that but I take milk thistle to help with my liver enzymes mainly because they're usually pretty high when I have blood work done because of my drinking.
 
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