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Hey guys, I posted this in r/drugnerds the other day and didn't realize it went against any of the rules so I got slapped with a ban. I thought I was following the rules lol Anyways, I guess here might be a better place to discuss this anyways so here we go.
I've been thinking about trying to use capsaicin to induce cyp3a4 in order to increase the conversion of mitragynine to 7-ohm. Anyone ever try something like this before? I've noticed that taking CBD (a cyp3a4 inhibitor) blunts my kratom experience slightly (but im not completely sure if that's solely from enzyme inhibition tbh) and too much of it right before a burn seems to nullify effects almost completely. I'm thinking that potentially inducing cyp3a4 might give me a better burn and maybe even allow me to use CBD and kratom concurrently without any loss in effects. Maybe another cyp3a4 inducer like saint johns wort may be better, idk, I'm not really sure how powerful an inducer capsaicin is. If anyone else is interested ill report back with my results once I obtain the capsaicin and try it out. Any thoughts, comments or suggestions are welcome. This is just a wild idea I've had floating in the back of my head for a while now.
can you show me where you have read that this enzyme plays a part in this particular conversion? I have read (and felt) that cyp3a4 inhibition does not really potentiate or prolong the conversion process with kratom the way other morphine prodrugs
We're definitely on the same page as far as cyp3a4 inhibition not helping anything. Inhibition seems to kill my burns. I'm thinking about trying to induce more cyp3a4 instead of inhibiting it. I'm thinking that an increase in enzyme cyp3a4 might result in a better conversion of mitragynine to 7-OH and therefore a better burn.
"CYP3A4 mediates conversion of mitragynine to 7-OH. (A) Mitragynine was incubated in vitro with recombinant preparations of the five major human CYP isoforms alongside a reference substrate of each isoform as positive control. The relative percent remaining of mitragyine or reference substrate in each incubation was quantified by LC-MS/MS. Disappearance of mitragynine was most rapid in the presence of CYP3A4, whereas incubations with the other isoforms resulted in little or no decomposition. The activity of each preparation was confirmed by the nearly complete disappearance of the corresponding reference substrates. (B) Formation of 7-OH was monitored by LC-MS/MS during incubation of mitragynine with each of the recombinant CYP preparations. CYP3A4 resulted in the most robust conversion to 7-OH. All data points represent the means of two independent experiments with two incubations per experiment, with error bars representing ± SEM."
I often put cayenne pepper directly into the kratom I toss and wash. It is one of the effective means of potentiation to me, but it could just be the rush from pepper itself, or helping me absorb it, not the chemical thing you’re talking about. I notice if I constantly do it every dose it stops working, and more save it for extra umph.
About how much cayenne would you estimate you use? Ive seen straight up capsaicin capsules that I was thinking about trying but if I got some pepper I guess I could just cap some and then cook with it as well if it doesn't work out haha. Is it just a few shakes or a bit more than that?
interesting theory. I would imagine the amount needed would be either need to be extract-formulated somehow and taken BEFORE your kratom, or be taken some other way in a large amount being generally unpleasant?
Sorry i misread your title....i see that enzyme and immediatly brain goes to inhibition. Induction is probably a lot harder and trickier to pull off consistently? I don't know if I personally would want the discomfort of spicy kratom for that little bump-up. Thanks for sharing that link, also...very interesting read that I hadn't seen before. Can't really argue with those results. Maybe there is a better induction/production method beyond capsaicin? I am too stupid to know much else about other options,
Yes this works to up the conversion to 7-hydroxymitragynine but the timing of it is everything. I find you need to take the kratom first then wait 30-45mins then take the capsaicin or something really spicy. I've also used phenobarbital in a similar fashion to achieve the same enzyme induction with massive potentiation. This results in an extreme heavy nod however I would not recommend anyone doing that. Not only is it super dangerous but it's insanely addictive and can really mess you up or potentially kill you.
Choppy_Shores wrote:About how much cayenne would you estimate you use? Ive seen straight up capsaicin capsules that I was thinking about trying but if I got some pepper I guess I could just cap some and then cook with it as well if it doesn't work out haha. Is it just a few shakes or a bit more than that?
Yes, just a few shakes. The kratom is still by far the majority in the mix. I have my kratom on a playing card for toss n wash, and I kinda just coat the top with a few shakes of cayenne pepper, I can still see the green underneath. It’s probably like .1 or something but I’ve never paid attention to it on the scale
Cuttlefish wrote:
Yes, just a few shakes. The kratom is still by far the majority in the mix. I have my kratom on a playing card for toss n wash, and I kinda just coat the top with a few shakes of cayenne pepper, I can still see the green underneath. It’s probably like .1 or something but I’ve never paid attention to it on the scale
Be careful with the cayenne and especially the capsaicin capsules taking it way to often can potentially send you to the hospital with horrific ulcers from bad acid reflux or other stomach related issues. This doesn't happen to everyone but if you're sensitive to spicy stuff with acid reflux type side effects you do not want this to happen. It was fucking horrible some of the worst pain I've ever been in tbh.
That’s good to know, I didn’t know that. I’ve been doing it a few years at this point. Never capsules. I’ve always liked spicy food, but now you got me paranoid, not worth the risk
Cuttlefish wrote:That’s good to know, I didn’t know that. I’ve been doing it a few years at this point. Never capsules. I’ve always liked spicy food, but now you got me paranoid, not worth the risk
If it's been years you're most likely fine to continue doing what you're doing. It's sensitive individuals like myself that have to be really careful with capsaicin. Stomach issues also run rampant in my family so there's that lol.
Thanks for the insight mitragy9. Maybe I'll try it with some extra spicy ramen next. I tried it the other night with some tapitio spiked cheesy tomato soup and had a pretty good sedating burn. It definitely seemed to make it more sleepy than usual. Pretty much all my burns are energizing to some extent so that part was pretty interesting.
Choppy_Shores wrote:Thanks for the insight mitragy9. Maybe I'll try it with some extra spicy ramen next. I tried it the other night with some tapitio spiked cheesy tomato soup and had a pretty good sedating burn. It definitely seemed to make it more sleepy than usual. Pretty much all my burns are energizing to some extent so that part was pretty interesting.
Yeah it definitely seems to kick up analgesic effects another method of getting the same enzyme induction is with Quercetin. Quercetin is a plant flavonol supplement that can be found rather easily at various stores. I haven't gotten the timing right with it yet. But I believe this will work better than capsaicin for enzyme induction. The timing of when you take what can be pretty tricky though I find that if you take it before the kratom it results in blunted effects probably because you body is expelling the drug quicker. I will definitely experiment with this more and post when I figure out the optimal way of doing this.
Imo, potentiation of kratom and other substances being in general a waste of time and that it doesn't really work, unless it's another psychoactive that synergizes. The best "potentiator" is a couple extra grams, ideally of a different strain. I could be totally wrong on this, but I think it's subjective and possibly placebo..but hey, whatever works.
Playerpiano72 wrote:Imo, potentiation of kratom and other substances being in general a waste of time and that it doesn't really work, unless it's another psychoactive that synergizes. The best "potentiator" is a couple extra grams, ideally of a different strain. I could be totally wrong on this, but I think it's subjective and possibly placebo..but hey, whatever works.
Honestly don't knock it until you try it.. try eating a small snack that's very very spicy or take capsaicin 45mins after dosing. I guarantee it will give you a much more sedating analgesic effect. Unlike other "potentiators" this has actual documentation to affect the way your liver processes mitragynine and 7-OH. Other popular so called "potentiators" really aren't potentiators. They mainly have the potential to increase bioavailability(ex. tumeric, bioperine, blackpepper) imo stuff like tumeric will hurt kratom's analgesic effects due to enzyme inhibition however it does increase the overall duration. Meaning the drug will stay for much longer in the blood stream. When messing with liver enzymes it seems to be a trade between duration and overall potency.
Alright, I'm game. Can you recommend a good food item? I like spicy stuff, I put tabasco and pepper on everything, but that doesn't seem like it would be enough. Would straight cayenne pepper work, or is there something that has natural capsaicin in it? I don't want to spend the money on a supplement sort of thing.
And yeah, I have tried many potentiators but none have seemed to have an effect. Turmeric, magnesium although it has other benefits, agmatine, apple cider vinegar, benadryl, the red bubble process, and several others I can't recall right now. I've tried to potentiate other analgesics with similar results.
I have a few customers that swear by supplementing kratom with various dietary ingredients.... some of them are VERY knowledgeable (like nerd scientist knowledgeable) I know a capsaicin/turmeric combo is very popular, but I couldnt tell you any details on the timing (which I know is important). I admittedly have barely scratched the surface when it comes to the kratom combo's, I myself prefer kratom in its natural state.
If I think of it when I talk to them next, I will ask somebody I know who is knowledgeable in this field to chime in here.
Texas Family Harvest - for connoisseurs, by connoisseurs.
So I've experimented with Quercetin more for cyp3a4 induction and wow it works very very well. Once again the timing of when you take what seems to be important and this may differ for each individual. I've found it to result in pretty major potentiation of analgesic effects and also sedation it works even better than capsaicin for achieving this. For me the best way of taking Quercetin is to take it 10-15 mins before you take your kratom dosage. I took around 600mg in capsules and it resulted in a very noticeable increase in effects especially sedation. The kratom felt much warmer and much more "opioid like" I even had to take a bit of caffeine as to not fall asleep lol. I will definitely continue to experiment with this more but I can say for a fact Quercetin works for potentiating kratom and it does it well. It's definitely worth trying. I'm not sure how sustainable this will be but for every now and then this is probably the best potentiator I have tried so far.
I would appreciate that gumbyke, thanks alot! I like to get a little bit nerdy about this kind of stuff myself just for fun so any insight you could send my way would be absolutely awesome. I may have to try out that quercetin here soon, what's interesting is it seems like I experience a lower level of what you described happening with quercetin when I pair kratom with extra spicy foods. It's a little unfortunate for me that it doesn't seem to potentiate the energizing effects but the sedation and analgesia instead but this could still be extremely helpful for someone who requires a higher level of pain relief from time to time. Maybe even for helping me through a heavier panic attack. Thanks for doing that experiment for me, I'll have to give it a shot when I have funds for some extra supplements.
Wouldn't taking a potentiator raise your tolerance if used regularly? Or at least make taking kratom by itself not as effective. It seems like it's something you'd only want to do every now and then. Couldn't you get the same effects by just taking an extra gram or two? Not completely on topic but just wondering.
Playerpiano72 wrote:Wouldn't taking a potentiator raise your tolerance if used regularly? Or at least make taking kratom by itself not as effective. It seems like it's something you'd only want to do every now and then. Couldn't you get the same effects by just taking an extra gram or two? Not completely on topic but just wondering.
Yes if you continue to take the same dosage instead of correcting the dosage because of the potentiation. It just allows you to take less and get the same amount effects as taking the amount you usually do. But if you take the same amount or more then you usually do this will obviously spike your tolerance even quicker. I think potentiators are best used on occasion for extra strength or to stretch the product you have currently.
I dont really know the science behind it, I just know when me and my girlfriend eat ghost pepper wings, we get really good burns afterwards with kratom. Much better than usual. Take that with a grain of salt because cbd makes my kratom stronger as well.
Anyways, I guess here might be a better place to discuss this anyways so here we go.
