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Promethazine Enhancing the effects of Opioids

4DQSAR

4DQSAR

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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?
 
1st generation antihistamines like Promethazine, Vistaril PAM, and Benadryl are overlooked by many because benzos are preferred. However, many people have not experimented with higher doses of Promethazine or Vistaril PAM and the sedative effects they provide. Of course benzos are stronger, but it is easier to get more of the antihistamines which have little to no withdrawal effects. I have also found out that these three 1st gen antihistamines seem to work better in the long term compared to most benzos as far as tolerance is concerned and they are not scheduled like benzos. That means early refills are allowed.
 
Them Witches said:
1st generation antihistamines like Promethazine, Vistaril PAM, and Benadryl are overlooked by many because benzos are preferred. However, many people have not experimented with higher doses of Promethazine or Vistaril PAM and the sedative effects they provide. Of course benzos are stronger, but it is easier to get more of the antihistamines which have little to no withdrawal effects. I have also found out that these three 1st gen antihistamines seem to work better in the long term compared to most benzos as far as tolerance is concerned and they are not scheduled like benzos. That means early refills are allowed.
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I have experimented with a lot of the first gen anti histamines and while I agree they can give good sedation and even a degree of anxilyses, and of coarse they stop the itches of opioids and for me they help with nausea, I use them for motion sickness for this reason and find good results.
For me I find the tolerence issue to be the total opposite to what you describe, for me tolerence to the sedation builds extremely quickly and then takes a very long time to reset.

If it wasn't for the tolerence issue for me I would used the first gen anti histamines more frequently.

However I don't believe I ever experienced any real opioid potentiation other than the initial sedation.
 
vision conquest said:
I have experimented with a lot of the first gen anti histamines and while I agree they can give good sedation and even a degree of anxilyses, and of coarse they stop the itches of opioids and for me they help with nausea, I use them for motion sickness for this reason and find good results.
For me I find the tolerence issue to be the total opposite to what you describe, for me tolerence to the sedation builds extremely quickly and then takes a very long time to reset.

If it wasn't for the tolerence issue for me I would used the first gen anti histamines more frequently.

However I don't believe I ever experienced any real opioid potentiation other than the initial sedation.
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I have a tall tolerance to benzos due to my alpha2, sedative/hypnotic, narcotic, antihistamine dosages including Ativan 2mg. I would like the Ativan to be at 6mg daily but I would have to lose or reduce some of my other medications. An extra 4mg of Ativan would not justify the trade off in my situation. I feel my tolerance to benzos seems to not reset because I was on Xanax for a decade, got off for 2 years, and started taking Ativan for the past year. Because of my Roxicodone 210mg, Methadone 30mg, Clonidine 0.9mg, Lunesta 3mg, Vistaril PAM 200mg, and Promethazine 75mg, I am limited on how much Ativan my doctor is comfortable prescribing & I do not blame him.

Sometimes I add Benadryl and Valerian Root Extract when I need more stress relief.
 
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bigjackaal96 said:
Because you actually get dopamine effects without It turning into Norepinephrine like with DPH.
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I don’t really understand this. It’s also a weak first gen antipsychotic, so it also blocks dopamine D2 receptors. Does this mean it increases circulating dopamine? I guess it would because D2 receptors became being blocked, the inhibitory effect is removed, therefore an increase in dopamine released.
 
I wish Inapsine (Droperidol) was commonly prescribed for daily use. It is badass for stress/anxiety/breakthru pain relief. I believe there is one or two companies that make a tablet form but they are not sold in the United States. The IV formulation took the wind out of my sail. It was followed up with Haldol IV and Promethazine IM... shhhiittt. Sedation City.

Clonidine IV is another one that mixes well with narcotics. It hits differently than the pill form. The pills still make any opioid better.
 
SeekingOblivion said:
I don’t really understand this. It’s also a weak first gen antipsychotic, so it also blocks dopamine D2 receptors. Does this mean it increases circulating dopamine? I guess it would because D2 receptors became being blocked, the inhibitory effect is removed, therefore an increase in dopamine released.
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ACH antagonists are very potent indirect D2 agonists, Think 0.5 ~ 8nM for D2. It D2 antagonism stops any extra Dopamine from being made into Norepinephrine which Is why DPH becomes rough. It D2 blocking being mild to moderate makes It safer because you'd need a much higher dose for It to cause issues.
 
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