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How does hydroxyzine potentiate opioids?

kratom luver

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Obviously it is a CNS depressant and it adds to the sedation of the opioid taken in conjunction with the antihistamine, but I do have two questions that baffle me:

* How does it enhance the euphoria (rather than sedation) induced by the opioid? Is there inherent euphoriant properties of the drug itself? Is this added euphoria due to the anticholinergic properties of the drug? They say that anticholinergics induce a feeling of wellbeing or euphoria and contribute to the antidepressant properties of tricyclic antidepressants - is this the case?

* How does it enhance the analgesia (pain killing) effect of opioids?
 
I've never gotten euphoria from anti-cholinergenics. Beside which, non-deliriant anti-histamines also make opioids better for me, I'm a fan of promethazine in particular.

I think that it adds to the 'euphoria' for people by making them nod more, I love nodding; the more of that I get, the better.

As for analgesia, it doesn't add to it. It will only potentiate the CNS depressant effects, and lessen the histamine reaction.
 
Apparently Hydroxyzine does help pain meds "find" the pain.
I've only gotten euphoria from Antihistamines in conjunction with Diazepam and weed (and ofcourse Opiates =D).
Some people can get a small amount of euphoria from certain Antihistamines alone, though it's quite rare.
 
Apparently they are used clinically to reduce the dose requirement for opioids as they have an 'analgesia-sparing' effect.
 
^ yeah as a chronic pain patient a lot of the first generation antihistamines have a slight opioid-sparing effect for me especially in IV shots in the ER with morphine... they also reduce the itchiness (pruritis) and nausea and increase the sedation of course.

Those first generation antihistamines (promethazine, diphenhydramine, doxylamine) usually cause euphoria in a small amount of the population and the closely related muscle relaxant orphenadrine epitomizes this effect... from the wiki entry on ethanolamines (that class of antihistamines):

The effects of centrally-acting ethanolamine antihistamines and related drugs can in the case of some drugs create a type of euphoria, a euphoria which is particularly marked with orphenadrine, an antihistamine closely related to diphenhydramine which is used for low back pain, other disorders of skeletal muscle and some aspects of Parkinsonism; the euphoria is significant and reliable enough for orphenadrine to be considered a miscellaneous antidepressant and method for treating adverse effects of opioids.SOURCE

They discovered in the '50s when these antihistamines were first being used that it helped some people with depression. Advanced research on the ethanolamine antihistamines are what led to the discovery of the tricyclic antidepressants... antihistamines are very weakly serotonergic and the tricyclics are similar to the anithistamines (especially the nasty anticholinergic effects and sedation) but more specifically serotonergic and noradrenergic. The new SNRI's are also similar to the tricyclic's but even more focused in their effects so they don't have the anticholinergic and sedatove effects. They don't add to the analgesia of opioids like antihistamines but directly treat neuropathic pain like the tricyclics (hence the FDA approval for use in nerve pain and cymbalta (duloxetine) in particular being used for fibromyalgia).
 
Obviously it is a CNS depressant and it adds to the sedation of the opioid taken in conjunction with the antihistamine, but I do have two questions that baffle me:

* How does it enhance the euphoria (rather than sedation) induced by the opioid? Is there inherent euphoriant properties of the drug itself? Is this added euphoria due to the anticholinergic properties of the drug? They say that anticholinergics induce a feeling of wellbeing or euphoria and contribute to the antidepressant properties of tricyclic antidepressants - is this the case?

* How does it enhance the analgesia (pain killing) effect of opioids?

The mechanism is not fully understood.

Try to find some stuff on pubmed.com on antihistamines and opiates.
I've read there that Antihistamines increased the amount of the Opiate that would bind to the receptors when they're both taken simultaneously.
There is even a study (which I'm trying to find now!) about Naloxone reversing some effects of some antihistamines...

There's a lot to discover in that field.
 
They share the same metabolic pathway in the brain


Im moving this to ADD , they will give you a more detailed answer there
 
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Hydroxyzine is NOT a CNS depressant.
I don't know where you guy(s) got that info from, but it def. IS NOR a CNS depressant.

It's actually used for Antihistamines, Miscellaneous anxiolytics, sedatives and hypnotics.

Not no where do I see a depression/depressant on there.

I have been RX'd Hydroxyzine for about 6 months now. I take 4 a day, and get 120/month.
It's used to treat anxiety; pain; allergies; allergic urticaria; sedation; nervousness; itchiness; Nausea; Vomiting; etc.

I'm also on Methadone at 80mg/daily, and currently tapering down Benzo's using Clonazepam.
It doesn't seem as potent when you're on stronger drugs such as Methadone and Clonazepam.
But it does help me get by a little easier. It's great for Morning sickness (Nausea, vomiting, etc.)
Hydroxyzine does potentiate methadone, but not as much as you think.

When I wasn't on benzo's, I was on Promethazine, a similar drug to Hydroxyzine. Promethazine DEF. potentiates my methadone.
It's also great for Nausea/Vomiting.
BUT, Hydroxyzine comes with more relief than prometh, such as anxiety, nervousness, etc.

That's why I switched from Promethazine to Hydroxyzine.
I get the 25mg ones.
 
Sedative and hypnotic drugs are considered depressant drugs? Not in the sense of 'antidepressant' but in the sense they depress or reduce nervous system activity.
 
True.

sorry if I misunderstood anyone...
i did mean Hydroxyzine is NOT an Antidepressant....
 
Speaking of anti-cholinergenics, anyone try megadosing on Bentyl? I did in prison, everything became really defined, like when you are editing an image and you use the "sharpen" effect to make it more and more crisp until it's too much so, light seemed brighter but not blinding, just more "clear". And I felt so toxic, in a general sense, no nausea or anything, mostly due to the perception change, felt hot and jittery, so much so that I made myself regurgitate by pushing my fingers wedged into an "eye poke" hand formation down my throat. The first time I've ever initiated emesis for myself. Could have been a good idea to do so, I took a whole sheet, maybe, 60 little translucent blue capsules. Who knows what would have happened if I let it digest longer (only a minute or two before I made myself lose them) I didn't know much more about it than it was an anti-cholinergenic (and of course, what it is indicated in its normal dosage for; spastic bowel, I only got it because I was lying that I had IBS to get loperamide, and went along with this other treatment on a trial basis to keep up the façade to get my lope. Though since I was in prison with no internet resources, when I started feeling jittery and couldn't sit still (a bit panic stricken), I didn't want to risk it perhaps having more side effects than your usual anti-cholinergenics (which are usually not too fun of highs, to put it very lightly, anyhow. But I was in prison.)

Anyhow, Bentyl experiences from people who've taken it and let it fully digest would be interesting, it was just coming on so fast and so strong for me I think I made the right decision for my lacking knowledge of the substance, though I since read that it can be, theoretically, abused, there's not many colloquial reports on doing so...
 
There is many reasons I see for Hydroxyzine to potentiate Both Euphoria and Analgesia felt by opiate on both Acute and Chronic pain.

First its anti-histamine effect increase sedation and counter the histamine release of opioids (ichiness-nausea) which can be distasteful.

Second, its 5-HT2a antagonism also increase sedation but also increase amount of serotonin avable for other receptors which can create anxiolitic effect. The antipsychtic effect is created because many of psychotic symptoms involve 5-HT2a overstimulation.

Third D2 antagonism, same as serotonin increased avable dopamine for other receptors and also same with antipsychotic effect,psychotic symptoms are often associated with D2 overstimulation.

Those three effects all increase possible ''high'' which can be seen as euphoria and even creating an euphoria (dopamine rush). As for the pain enhancement it would entirely be caused by distraction, just like how watching TV lowers the feeling of pain well a high does too.

It is good to mix with alot of things but I heard it inhibits CYP2D6 and thus block Codeine from being morphine...
 
Everyone wants to potentiate drugs to make them "stronger". I have used Hydroxyzine Many times to potentiate opiates and it does add to the "high" by many mechanism. I take 50 mgs a half hour before I take my opiates and then 50mgs an hour after.
 
IMO cane2left and mracid are excellent answers to your question.

* How does it enhance the euphoria (rather than sedation) induced by the opioid? Histamine release causes flushing and nausea. But also and importantly rats genetically engineered to be knock out at the histamine receptors display a increased conditioned place preference, a decrease the minimum drug required to voluntary consume it over say sugar water, a increase in dopamine release in the reward pathways like the ventral tegmental area.
Is there inherent euphoriant properties of the drug itself?
Hydroxyzine no. However, while diphenhydramine can cause changes in the brain similar to cocaine or other drugs of abuse in the nucleus accumbens it is not a linear effect with doses above or below causing no change and the change in activity greatly lasting much less than the drugs action. And only at toxic doses.
Is this added euphoria due to the anticholinergic properties of the drug? Hydroxyzine no. Hydroxyzine has no anticholinergic effects that's why it is not effective for Parkinson tremor.

They say that anticholinergics induce a feeling of wellbeing or euphoria and contribute to the antidepressant properties of tricyclic antidepressants - is this the case?
Muscarinic acetylcholine receptors antagonism may increase the effectiveness of antidepressant however they can cause serious side effects so it's best to try more selective antidepressants.

Muscarinic antagonism may play a important role at people with who require antipsychotics but experience side effects especially motor and flat mood increasing compliance with meds.

* How does it enhance the analgesia (pain killing) effect of opioids?
Hydroxyzine via histamine blockade
Diphenhydramine histamine and muscarinic blockade
 
Histamine has excitatory effects; opioids induce histamine release, which tends to attenuate their sedative and euphoric effects. So antihistamines potentiate opioid effects by blocking excitatory histamine receptors. Additionally, some antihistamines produce additive sedation when combined with opioids.
 
Im currently on rehab center and i get 90mg methadone, oxazepam 45mg and today i took 25mg hydroxyzine and i could even notice a little bit of euphoria even and i think thats because of the hydro because nothin like this happened untill i took it on top of these normal meds
 
First generation (those that cross the BBB) are noted for specifically producing euphoria, especially when combined with almost any of the 3,3,-diphenylheptanone class of opioid.

I don't think ANYONE has worked out why.

But by '3,3-diphenylheptanone' class I mean:

Methadone, dipipanone, phenadoxone others have been recorded as interacting with 1st generation antihistamines. It's almost certainly mediated by a combination of MAOI reuptake and likely anticholinergic activity.

Someone mentioned that these antihistamines are classed as 'opiate sparing' and I believe it's because it alters consciousness in a manner that makes pain less distressing.

In rodent studies the opiate sparing properties aren't as easy to quantify suggesting that it's the conscious sensation of pain that is altered.

I might add that I know of more than one person who got themselves into a worse position by mixing 1st generation antihistamines and opioids.

The UK had the infamous Diconal/Valoid disaster where users were learning that injecting pills containing 3,3-diphenylheptaone opioids with (in the UK case) cyclizine resulted in a huge rush. Even oral methadone is amplified by IV cyclizine. One problem is that cyclizine intended for oral administration is in the form of it's hydrochloride addition salt which isn't that water soluble. Cyclizine lactate is the only form intended for injection.

The death toll and limb loss among people who abused Diconal or oral cyclazine formulations was massive based on the size of the user base.

BTW Mitrazipine is now becoming recognized as being of great utility among those seeking to stop using opioids. It more or less stops the euphoria and at the same time prevents the depression so people are ONLY fighting to control physical symptoms.
 
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