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Promethazine Enhancing the effects of Opioids

4DQSAR

4DQSAR

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Feb 3, 2025
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An old paper and it matches very closely with what people have reported i.e. promethazine doesn't make opioids more potent but increase their duration of action.

For a while there was interest in 'opiate sparing' medicines but I suspect researchers ran into the issue of the simple YMMV issue i.e. titration would be needed and since in most cases opioid are only prescribed on a short-term basis, not practical.

I AM told that in the US people on methadone maintainanence often consume promethazine. Now what interests me here is a question. Are people using it for 'a buzz' or simply because the T1/2 of methadone varies hugely between individuals so if someone metabolizes faster than average, are they simply 'treating' that issue?
 
This is a thing. It’s partially a first gen antihistamine, so it cuts the itching, and it is wonderful antiemetic. But it also has a sedating, synergistic effect that people like.
 
clonidine works better IMO, it is 40 times stronger than xylazine. Clonidine also has a 16hr half life.
 
4DQSAR said:

An old paper and it matches very closely with what people have reported i.e. promethazine doesn't make opioids more potent but increase their duration of action.

For a while there was interest in 'opiate sparing' medicines but I suspect researchers ran into the issue of the simple YMMV issue i.e. titration would be needed and since in most cases opioid are only prescribed on a short-term basis, not practical.

I AM told that in the US people on methadone maintainanence often consume promethazine. Now what interests me here is a question. Are people using it for 'a buzz' or simply because the T1/2 of methadone varies hugely between individuals so if someone metabolizes faster than average, are they simply 'treating' that issue?
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The most famous way of using opiates and promethazine together is the codeine- promethazine cough syrup formulation mixed with purple soda or whatever, called "lean". Very popular with black rappers.
I never tried lean, per se, but I had the cough syrup prescribed to me at various times in my life. I don't know in what way the promethazine may have enhanced it, but it definitely got me really high. I just assumed that people liked the combo for the added depressant effect. But the promethazine component always seemed kind of gross to me and left me with a horrendous splitting headache. I preferred codeine without it, I guess I metabolize codeine well
I didn't know promethazine was an effective emetic. Good to know. So you are saying that it slows down elimination of the codeine or morphine metabolite?
 
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