first pass liver effects on cannabinoids/ THC ??

[MinnBobber]

What are the real world effects of cannabis and first pass liver metabolizing some into 11 hydroxy delta 9 THC?

The delta 9 THC is more psychoactive so could one say that the outcome after the liver is a "gain" in potency?

I find opposite info on delta 9 THC and the brain barrier:
One report says "portion of its molecules change into Δ11-HydroxyTHC, which is a much more psychoactive metabolite of Δ9-THC that takes much longer to cross the blood-brain barrier."
I'd say the majority of studies I find say delta 9 THC crosses the blood brain barrier easier" which to me also means faster.

?? If you bypass the first pass thru the liver, the cannabinoids are in the bloodstream so they go thru the liver
after one blood circulation, correct? How many cannabinoids disappear in that first blood circulation (by binding elsewhere), before they make their way to/thru the liver? OR if THC misses the first pass thru the liver, do the cannabinoids keep skipping it for some period of time??

I'm trying to compare different intake methods for best efficiency/ max benefits with minimum dose

 

[C No Ego]

THC has like a 5 second half life as it mimics the action potential of anandamide @ cb1... the time that ligand takes to be sent into the synaptic cleft is about 5 seconds( this does not include free flow circulation but is receptor engagement time span)... the plant cannabinoids via lipid oxygenation will act on LOX COX during free flow and then be available in those type cells . they will then work down through the bi-layers to reach PPAR and CYP450 at the endoplasmic reticulum.
if any of the phytos disappear in circulation it would be from COX LOX... as to 11 hydroxy it certainly has longer lasting effect but how THC converts I think is only @ first pass...

 

[Firebaall]

One of the best descriptions of what happens:

https://sapiensoup.com/human-metabolism-thc

 

[MinnBobber]

One of the best descriptions of what happens:

https://sapiensoup.com/human-metabolism-thc

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Thanks. Too bad the study used smoked cannabis instead of vaped flower.

I’d love to see vaped vs ingested study.

This article gave a figure of: ingested THC, after conversion to delta 11 hydroxy is 3x -7x as strong (bio availability of binding to CB1 receptors)

 

[Firebaall]

There's no difference between smoking THC-a and vaping THC-a. The only difference is in smoking, you're "vapourizing" additional compounds at higher temperatures. Smoking is actually vapourization, technically speaking...

 

[MinnBobber]

There's no difference between smoking THC-a and vaping THC-a. The only difference is in smoking, you're "vapourizing" additional compounds at higher temperatures. Smoking is actually vapourization, technically speaking...

...........................................................................................................................
There is a huge difference between smoking THC-a and vaping THCA-a.
Smoked cannabis is 90%+ combustion by-products of the whole plant material combusting while vaped cannabis is about 90% the "good compounds".

The study chart shows them smoking one joint which contains 15.8 mg of THC where only a small fraction of that makes it to the lungs vs vaping where 90% of the goodies get to the lungs.
Vaping is generally considered to deliver 3X or 4X of the beneficial elements vs combusting.
I'd love to see the same study where they vape 15.8 mg of THC for a more meaningful comparison.

Welcome to fuck combustion, where efficiency is another reason to vape

 

[Firebaall]

The temperatures that THC-a vapourizes at does not change. It's a constant that both vapourization and combustion achieve.

As to the finer points, independent of that fact: That link shows what happens concerning the metabolizing path of ingested vs inhaled. The real world results that you were asking for.

The general idea, is if you ingest you'll get about a 50/50 split of hydroxy THC and delta 9. That hydroxy form is 3x more potent since it passes the blood-brain barrier 3x easier than delta 9. Which is why people say it's stronger.

Although inhaling THC, bypassing the liver feels, "Higher" for a shorter time.

 

[C No Ego]

The temperatures that THC-a vapourizes at does not change. It's a constant that both vapourization and combustion achieve.

As to the finer points, independent of that fact: That link shows what happens concerning the metabolizing path of ingested vs inhaled. The real world results that you were asking for.

The general idea, is if you ingest you'll get about a 50/50 split of hydroxy THC and delta 9. That hydroxy form is 3x more potent since it passes the blood-brain barrier 3x easier than delta 9. Which is why people say it's stronger.

Although inhaling THC, bypassing the liver feels, "Higher" for a shorter time.

Edibles go to first pass and inhaling goes into the COX/LOX metabolism...decarbed tinctures metabolize like an inhalant or an reactive oxygen species .
THCv is more psychoactive because it actually takes longer to metabolize, compared to THC d9

 

[Firebaall]

decarbed tinctures metabolize like an inhalant or an reactive oxygen species .

That's only true of the partial amount that is absorbed sublingually. The bulk of a tincture ends up being swallowed, and doesn't bypass the liver on the first go around...

Also, we aren't talking about THCv. That's a subject that deserves it's own topic considering the research is not conclusive on it's affects, but even more so due to it's relatively high boiling point of 220 C.

 

[C No Ego]

That's only true of the partial amount that is absorbed sublingually. The bulk of a tincture ends up being swallowed, and doesn't bypass the liver on the first go around...

Also, we aren't talking about THCv. That's a subject that deserves it's own topic considering the research is not conclusive on it's affects, but even more so due to it's relatively high boiling point of 220 C.

Bile acids and cannabinoids - https://duckduckgo.com/?q=Bile+acids+and+cannabinoids&t=ffcm&atb=v165-1&ia=web
getting high on bile acids https://duckduckgo.com/?q=getting+high+on+bile+acids&t=ffcm&atb=v165-1&ia=web
tincture works through those bile acids for immediate absorption on par with inhalants .
yeah, I got my posts mixed up about someone posting how THCv metabolizes quicker than D9
Edit, no , you mention it a few posts up... I'm right on track

 

[Tranquility]

This seemed as good a place to post the article as any.

https://cannabislifenetwork.com/cannabosides-a-new-class-of-cannabinoid-prodrugs/

As we discussed, your liver possesses it’s own strategy to metabolize cannabis. But other than inside your body, how does one boil cannabis down into water-soluble Prodrugs? Prodrugs are medications or compounds that need to be metabolized (ie. broken down) before they become pharmacologically active.

But is there even a good reason for cannabis prodrugs, or is the risk not worth the reward?...​

 

[C No Ego]

@Firebaall . not able to edit post above, it seems I mixed up THCV with 11 hydroxy. lol, my mistake

 

[Firebaall]

No worries.

If my Reddit-kung-fu has taught me anything: It's usually counter productive to get too invested in side arguments/points.

 

[C No Ego]

No worries.

If my Reddit-kung-fu has taught me anything: It's usually counter productive to get too invested in side arguments/points.

ok, so back to original pount... 11 hydroxy takes longer to metabolize( half life) compared to D9 and is why effects are stronger eTC... if I am mistaken show how please and thank you

 

[Firebaall]

You're Close.

The effects of hydroxy THC being "stronger", is due to it's solubility, more than anything.

Delta 9 THC has poor water solubility, and a high fat solubility.

Hydroxy THC has a much better water solubility, and can pass the blood-brain barrier up to from as little as 3 times up to 9-10 times easier.

Combine this fact with how the ratios of each are created in the body, and it begins to make sense.

 

[MinnBobber]

You're Close.

The effects of hydroxy THC being "stronger", is due to it's solubility, more than anything.

Delta 9 THC has poor water solubility, and a high fat solubility.

Hydroxy THC has a much better water solubility, and can pass the blood-brain barrier up to from as little as 3 times up to 9-10 times easier.

Combine this fact with how the ratios of each are created in the body, and it begins to make sense.

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But which is more efficient/ most effective in giving THC brain effects:
1. Edibles that get “upgrade” to Hydroxy THC in the liver BUT suffer a big loss moving thru the gut or
2. Same dose taken sublingual with much less lost thru direct intake BUT bypasses liver so no initial conversion to Hydroxy THC???

Which provides stronger effects with the same dose?
It’s a pharmacokinetic question.

The sublingual is, of course, much much faster in its effects.

 

[Firebaall]

Pharmacokinetically speaking? I'd say hydroxy THC is stronger, hands down, due to it's increased bio-availability alone.

Subjectively speaking? Delta 9, if being "higher" for a shorter period is your metric, but then that flies in the counter balance of longer lasting/not as "high" with the hydroxy. I'd call it a tie, if relying on something as variable as "brain effect".

I've haven't seen any reputable sources that claim otherwise.

If you independently administer intravenously in equal amounts, you'd expect to see this.

 

[C No Ego]

You're Close.

The effects of hydroxy THC being "stronger", is due to it's solubility, more than anything.

Delta 9 THC has poor water solubility, and a high fat solubility.

Hydroxy THC has a much better water solubility, and can pass the blood-brain barrier up to from as little as 3 times up to 9-10 times easier.

Combine this fact with how the ratios of each are created in the body, and it begins to make sense.

our cells are lipid loving / lipophilic ... what pathway in a lipid cell makes a compound act better/stronger via water? is it COX/ LOX / which one?

 

[Firebaall]

Permeability is what you need to be looking at. How easily the compound passes the blood brain barrier is what you should be asking.

It's about how much exposure the THC has to the receptors.

Take a look here for a better idea of what we're talking about:

 

[C No Ego]

Permeability is what you need to be looking at. How easily the compound passes the blood brain barrier is what you should be asking.

It's about how much exposure the THC has to the receptors.

Take a look here for a better idea of what we're talking about:

yeah man great vid... I 've watched it a few times over the years... though that vid does not explain the water and 11 hydroxy metabolite. I mean, does the conversion to 11 hydroxy involve more hydrophylic mechanisms ?

 

[Firebaall]

Does it need to explain how it's created though? I mean we aren't discussing how and what happens when delta9 is metabolized into hydroxy. We are discussing the efficacy.

 

[Kimosabe]

I recently read a study where administration of CBD prior to inhalation of THC increased the effect (entourage) yet, if administered after THC binding to the ligand receptors, the effect would be one of reducig rather than enhancing the high. I have some highly concentrated CBD extract and gave it a try. Although not exactly scientific, I will sy I thought it made a significant difference.

 

[Sick Vape]

administration or inhalation of CBD 99.9% prior to THC/(vaping bud) does not increase the psychoactive effect of the bud for me. It decreases the effect of the bud on pain for me. It can even give me a nausea feeling and (liver?) pain at higher doses. But that is just me.
CBD rosin is somewhat different, as it can change the entourage effect, I feel.

I would love to see how they made that study. Do you have a link @Kimosabe ?

I somewhere read that there are up to 100 different metabolites of THC in your blood after (how long?) administration. There is maybe more going on than we think of.

Do some of you know what happens with THC-a in the liver? How does it get metabolised? Any ideas or anecdotal evidence?

 

[Tranquility]

I would love to see how they made that study. Do you have a link @Kimosabe ?

CBD offset THC
https://www.sciencedaily.com/releases/2019/09/190930131115.htm

 

[Sick Vape]

CBD offset THC
https://www.sciencedaily.com/releases/2019/09/190930131115.htm

Thanks @OldNewbie. Seems they could show in rat brains, what people feel and talk about since a while. I think it is an important study because they say they found what happens on a molecular level. That is quite a step.
But @Kimosabe says he read that CBD before THC increases the effects of THC and CBD after THC decreases the effects. Which would like add another possibility to change/adapt the effect of THC with CBD, depending on what you need. Which I find very interesting too.

edit: I think I can feel an changed effect if I vape THC flower and CBD together, sometimes.