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It appears that it's very likely that not only does kratom raise cross tolerance, but also likely does have at least partial agonists and possibly full on antagonists at the MORs that block at least some of the effects of other middle of the road affinity opioids like the condones and presumably morphine/heroin. I've never actually studied the MOR binding affinities of common opioids...just Narcan, bupe, naltrexone, and genuine fentanyl hcl.
I just stole the following copy pasta from a circlejerk poster who seemed to know their shit and had a good quality posting history. Bear in mind I couldn't access the actual paper quoted, and yes I actually tried.
...[So the different alkaloids do different things this is from two papers: Mitragynine and the oxidized analogue 7-hydroxymitragynine, are partial agonists of the human mu-opioid receptor and competitive antagonists at the kappa- and delta-opioid receptors. Mitragynine pseudoindoxyl and its corresponding corynantheidine analogs show promise as potent analgesics with a mechanism of action that includes mu opioid receptor agonism/delta opioid receptor antagonism and mitragynin pseudonoxl antagonizes kappa.
The following is taken from a table testing agonism or antagonism with their EC50 and IC50 values. Number in brackets are antagonism, all values are in micromolar concentrations:
mu kappa delta
mitragynine 0.339 ± 0.178 [8.5 ± 7.6 (1.4)] [>10]
paynantheine [2.2 ± 10] [>10] [>10]
speciogynine [5.7 ± 2.8] [>10] [>10]
speciociliatine [4.2 ± 1.6] [>10] [>10]
7-OH 0.0345 ± 0.0045 [7.9 ± 3.7] [>10]
I cannot access the paper to see the numbers for Mitragynine pseudoindoxyl.
Pretty much you want nanomolar concentrations as when you start getting above 5 micromolar the effect is pretty weak and not as relevant. So mitragynine is a potent agonist of mu at 339 nanomolar, but not a significant antagonist at kappa and delta. Paynantheine and speciogynine have modest antagonism at mu, but about 100X less potent than mitragynine agonism. 7-OH has the most potent agonism at mu with 34.5 nanomolar and modest antagonism at kappa. If I remember, I saw the paper on Mitragynine pseudoindoxyl and it was a potent enough for mu agonism and kappa and delta antagonism but I don't know the numbers.
Edit, sorry can't get the table to format correctly, but you can see the numbers for mu first, kappa second, delta 3rd.]
So, first off I honestly don't know what IC50 and EC50 values represent or how they're related. I assume it's a different type of measurement than Ki affinity values.
Yo nodson, can you make heads or tails of this science speak? What say ye resident kratomfag?
Also I forgot your answer to my question about the recommended strain or 2-3 strains from your favorite vendor you mentioned. Which strain is the most potent (preferably red or at least green instead of white vein), and which strain is least stimulating regardless of potency? I'm ordering a few sample packs today and need to know what to get for my old people.
Also, since 7-ohm is created through oxidation of mitragyne or w/e, does that mean kratom left in a jar with some extra oxygen for a year will age it positively like fine wine? I'm thinking of buying a kilo or two half kilos before Indonesia bans exporting or the US bans importing kratom from Indonesia, since apparently that country exports 95% of our country's kratom production. If it only gets better the longer it ages, might as well get it now right?
On a side note, I am considering dropping my bupe dose every 5 days from 4>3>2.5>2>1.5>1.25>1>0.8 to 0.1mg 100ug at a time, to 50ug, then switching to kratom+ULDN for a few months to see if it does more good than harm for me, instead of switching to low dose naltrexone.
Still not convinced it's necessarily a good idea or even a step forward, but I'm just considering it. Anyone have any thoughts on the matter? An anon asked me what my endgame was as I'm approaching one year on bupe having started on 24mg/day subbed and currently on 4mg/day snorted/plugged, and apart from definitely dropping down to 2mg/day snorted/plugged within 2-6 months, I really have no idea beyond that. My fear is that kratom is too short acting and way too much work to encapsulate like 5-40 capsules minimum every single day, and that I'd end up mentally addicted again because in theory I should maybe feel something when I dose kratom, which rewires the Pavlovian cause>effect link in my mind. Also, dosing 3-4x aka (every 4-5 hours )per day may not be doable for me with my new career I'm starting in August.
It sounds like I've already answered my own question in that I haven't had more than one day of strong cravings to use per month in the last 5-6 months minimum. It's like I forgot how good it feels/felt. Either way, there's no way using full agonists besides kratom is remotely a good idea for at least 5 years and most likely forever. That ship has sailed and I don't need to lose another spouse or something equally important largely caused directly or indirectly by full agonist opioid use. That shit multiplies depression long term IMO even if you don't get clean.
tl;dr OP IMO it definitely raises cross tolerance and also does partially block oxy/pst/heroin related usage, but IME only really in terms of euphoria for the most part, and only when both your kratom and other opioid dosage/tolerance is high enough that most or all receptors end up occupied. When someone uses lower doses of both opioids regularly, I presume the blocking effect is less of a concern.
If I needed pain relief, I'd still combine them in low doses. With higher doses, I'd wait at least 6 hours after last kratom dose to use another opioid. If you use to get high, wait at least 18-24hr since last kratom dose.