Kratom and p450

[onmyway]

So I've been wondering about how the actives in kratom are metabolized, and whether or not an enzyme inhibitor might be useful for potentiation. Does anyone know what enzyme breaks down hydroxymitragynine? It would be easy to assume it's one of the p450s but who knows? I did a little googling and found nothing useful.

Also, wiki says that the oxidation product of mitragynine is a pretty strong kappa agonist. The article mentions oxidation as a result of storing the compound for a long time, not enzyme mediated in the body. I wonder if mitragynine is the major source of the disphoria that can sometimes come with kratom use (because it might get oxidized in the body). Has anyone experimented with just the hydroxymitragynine?

 

[negrogesic]

Yes, p450, likely CYP2D6, 2C19 and probably others to a lesser extent.....

Never tried the 6-hydroxy on its own. An interesting thing I noticed with kratom is a partial lack of cross tolerance with other opioids, even methadone (it was able to penetrate relatively large doses of methadone).

Yet, it also appears to have delayed opioid antagonist properties (perhaps slower acting than the agonists), which from what i remember is largely a result of the yohimbine-esque corynantheidine alkaloid. I suppose since a2-agonists like clonidine seen to alleviate some symptoms of opioid withdrawal, it is not strange than an a2-antagonist like corynantheidine would aggravate withdrawal symptoms. Not sure if there is some interaction with the adrenoreceptors and opioid receptors...

 

[onmyway]

I'm a little surprised that you can even notice kratom mixed with something like methadone, I guess maybe I've underestimated the plant. I would have thought that methadone had a much stronger affinity for mu receptors, and would eclipse the hydroxymitragynine kinetically (I don't have any first hand experience with methadone). I guess the partial lack of cross tolerance hints at a slightly different mechanism. I know there are several different types of mu receptors, I guess kratom might hit on different ones? or maybe it just interacts with the same receptors slightly differently. I sure don't know.

Anyway, I guess the normal stuff like grapefruit and tagamet will do something? From my limited experience, it seems like an active dose is pretty dang close to a nausea inducing dose. I was wondering if I might be able to potentate a little without increasing the nausea. or if trying to get some hydroxymitragynine might be worth it .

I don't know jack about how adrenergic receptors have anything to do with opiates. If anything, I'm surprised that an A2 antagonist would induce withdrawal symptoms, I would have thought that it would help. Seems like it would help with the shakes and the shits.

 

[4everfree]

I think that a lot of people underestimate kratom, Onmyway. Interesting about the "partial cross tolerance" mentioned~~~it's been my experience and that of many others that when they return to regular pharmaceutical opiates(like oxys) after a period of time on only kratom, that their tolerance to these regular opiates is considerably higher!

As far as potentiation by grapefruit juice goes, many of us have found that it does indeed potentiate kratom. I was told that only the white grapefruit juice does this,btw. Another thing about kratom is that there are huge differences between the effects of plain leaf kratom and kratom extracts, and again there are big differences between the various extracts themselves. ( The old FST...full spectrum tincture, that vendorused to carry was very likely one of the most powerful substances ever to be available on the net. I was scared of that stuff and the people who got hooked on it said that the WDs from that were WAY more severe than those of any opiate/opioid they had ever withdrawn from.) UEI is also a very powerful & addictive extract.

Something I've noticed is that just plain leaf kratom does not appear to be very addictive for people without a previous opiate addiction, but this is not the case for those who do. Anyway, I'm not a chemist but thought I'd throw in a couple of my first hand observations.

Does anyone know what happened to Riverhavens thread about CF5 ? I saw it here earlier & now it seems to have disappeared ?

 

[onmyway]

Does anyone notice things like depressed breathing rate or hypotension with lager doses of kratom? I haven't found anything about deaths related to this plant.

If it really increases tolerance to other opiates, is able to stave off withdraws with reasonable efficacy, and doesn't do things like drop your respiratory drive, well... it seems like we should be giving this shit away at free clinics everywhere.

I personally think methadone causes a lot of problems. I used to work in an ER where there where lots of methadone overdoses. The doc would shoot the dude up with narcan, dude would get up and sign out AMA, then somebody would find him face-down in the grass down the street because methadone has a much longer half-life than narcan.

 

[4everfree]

I've never heard of anyone having a depressed breathing rate from too much kratom, but it does tend to lower blood pressure. I think you're right that kratom should be available at free clinics. I've never hear of a single kratom related death or any serious health problems in long term users. It's certainly a much safer drug than methadone! It works very well as a long term maintenance drug & there are probably several thousand people doing just that.

Oh yeah, sorry about mentioning that vendor's name in the above post...on the kratom boards everyone speaks freely about the vendors & I just wasn't thinking. All I need now is another accusation of being a shill....

 

[Pegasus]

Sorry to bump an old thread, but I wanted to add that I experience both the anomaly that kratom works while on stronger opiates (incomplete cross tolerance with, say, methadone), and also that kratom raises your tolerance to other opiates if used regularly. Both are true, and they are not exclusive.

 

[onmyway]

i have learned that kratom works at both mu and delta receptors. in fact, i notice a significant antidepressant effect from sub-recreational doses of kratom, presumably from the delta activity. i think that is where the incomplete cross tolerance comes from.

now i take a few caps of regular grade powder every evening (not enough to really notice the opiate effects). i notice a brighter outlook the next day.