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Opiates "insensitivity"

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farmacista

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So between 2017 and 2018 for a year or so i used to snorted heroin ... then took a vacation of 2 or 3 weeks during which i was only on methadone ... then when i returned home heroin didn't worked for me anymore ... i didn't get any high out of it ... just maybe a mild relaxation and some physiological symptoms like difficulty urinating ... i tried snorting fentanyl (sublingual tablets directly from the pharmacy, no adulteration involved. i'm pharmacist myself and i just took it pretending it was selled) if I remember correctly about 5 or 6 200 mg tablets, one of them properly use and the rest snorted ... and nothing just the same thing ... so the high isn't there anymore just the abstinence is still there so i'm still on methadone ... and is nothing like an high tolerance is insensitivity, no response pure and simple ... in the last year i started injecting cocaine so i did inject heroin too sometimes ... i had a weak flash, in my legs, it seems for some moments like my legs won't let me stand anymore, and sometimes a buzz around the head, like a fizz or something ... just for a few seconds, and it's not a strong flash like cocaine, then again no heroin high just some relaxation, useful to counteract cocaine but nothing like an heroin high (i tried to use heroin alone to perceive more effects from it but nothing). So all of this is very unusual ... Have you ever heard anything like this ? Is happen to you or someone you know ? Apparently there's nothing in the medical literature ... I can't possibly be the only one XD Quality of heroin isn't an explanation either, my friend have the usual effects from it
 
farmacista said:
So between 2017 and 2018 for a year or so i used to snorted heroin ... then took a vacation of 2 or 3 weeks during which i was only on methadone ... then when i returned home heroin didn't worked for me anymore ... i didn't get any high out of it ... just maybe a mild relaxation and some physiological symptoms like difficulty urinating ... i tried snorting fentanyl (sublingual tablets directly from the pharmacy, no adulteration involved. i'm pharmacist myself and i just took it pretending it was selled) if I remember correctly about 5 or 6 200 mg tablets, one of them properly use and the rest snorted ... and nothing just the same thing ... so the high isn't there anymore just the abstinence is still there so i'm still on methadone ... and is nothing like an high tolerance is insensitivity, no response pure and simple ... in the last year i started injecting cocaine so i did inject heroin too sometimes ... i had a weak flash, in my legs, it seems for some moments like my legs won't let me stand anymore, and sometimes a buzz around the head, like a fizz or something ... just for a few seconds, and it's not a strong flash like cocaine, then again no heroin high just some relaxation, useful to counteract cocaine but nothing like an heroin high (i tried to use heroin alone to perceive more effects from it but nothing). So all of this is very unusual ... Have you ever heard anything like this ? Is happen to you or someone you know ? Apparently there's nothing in the medical literature ... I can't possibly be the only one XD Quality of heroin isn't an explanation either, my friend have the usual effects from it
Click to expand...
You took 1mg of fentanyl?!
 
Yes, sorry i made a mistake, they were Abstral 200 microgram tablets so yes 1 mg in total ... but I'm insensitive so ...anyway there are 800 mg tablets so it's a safe dosage ... but i didn't get high XD it's the most strangest thing
 
Not long, less than a year, i did heroin before while on methadone and the high was normal so it's not related to that ... it's absurd really
 
farmacista said:
Not long, less than a year, i did heroin before while on methadone and the high was normal so it's not related to that ... it's absurd really
Click to expand...
I mean, before you have taken all of the above. How long has it been since you’ve had methadone? A week? 2 days?
 
You mean before the fentanyl thing, it was about a year. And it was about six months I after started methadone that heroin stopped have effects on me ... and also there isn't a difference in heroin's effect if i skip a day of methadone before doing heroin
 
MsDiz said:
So there you go... you’re a pharmacist. How long does it take for methadone to clear the body?
Click to expand...
Is not really relevant, I did heroin many times WHILE ON METHADONE and i did get why. Why all of a sudden that changed ? I don't really think is methadone related. Could be only for the fentanyl because I tried only one time with that, but it's not logical. It's probably the same problem with heroin and fentanyl
 
farmacista said:
So between 2017 and 2018 for a year or so i used to snorted heroin ... then took a vacation of 2 or 3 weeks during which i was only on methadone ... then when i returned home heroin didn't worked for me anymore ... i didn't get any high out of it ... just maybe a mild relaxation and some physiological symptoms like difficulty urinating ... i tried snorting fentanyl (sublingual tablets directly from the pharmacy, no adulteration involved. i'm pharmacist myself and i just took it pretending it was selled) if I remember correctly about 5 or 6 200 mg tablets, one of them properly use and the rest snorted ... and nothing just the same thing ... so the high isn't there anymore just the abstinence is still there so i'm still on methadone ... and is nothing like an high tolerance is insensitivity, no response pure and simple ... in the last year i started injecting cocaine so i did inject heroin too sometimes ... i had a weak flash, in my legs, it seems for some moments like my legs won't let me stand anymore, and sometimes a buzz around the head, like a fizz or something ... just for a few seconds, and it's not a strong flash like cocaine, then again no heroin high just some relaxation, useful to counteract cocaine but nothing like an heroin high (i tried to use heroin alone to perceive more effects from it but nothing). So all of this is very unusual ... Have you ever heard anything like this ? Is happen to you or someone you know ? Apparently there's nothing in the medical literature ... I can't possibly be the only one XD Quality of heroin isn't an explanation either, my friend have the usual effects from it
Click to expand...
Methadone has a higher affinity for receptors than morphine has, but most importantly it has a much higher activation through hiher intrinsic effiacy than heroin. This and the high oral bioavailability and lipidsolubility along with a different tolerance mechanism than Heroin as it Diphosphoriliates the receptors rather than the Monophosphoriliation of morphine based drugs leads to higher beta arrestin recruitment and much more tolerance development. Your receptors get much stronger dezentizited and the high beta arrestin recruitment further fucks up your tolerance and the methadone stays for weeks in your tissue. Many people have that effect that heroin doesnt get the high anymore after they have been on methadone for years even after being abstinent for a long time, but in your case this shouldnt be the case in the long term because 2 weeks is not enough for that to cause lasting chanegs in receptors conformation and receptor activity. It certainly can take 1-2 months to feel heroin to 100% again after taking high doses of methadone for 2-3 weeks.
 
Methadone also has affinity for NMDA antagonism unlike morphinans that aren't the reverse isomeric form from opioids: the mu agonism and NMDA antagonism are opposite handed on the morphinan, but some synthetic opioids are symmetrical in terms of overlapping those sites.

I could imagine coming off of NMDA antagonism of any degree along with mu over expression / upregulation to be quite a serious subjective experience.
 
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