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Thread: How does hydroxyzine potentiate opioids?

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    How does hydroxyzine potentiate opioids? 
    #1
    Bluelighter kratom luver's Avatar
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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?
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    #2
    Bluelighter Mr Blonde's Avatar
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    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.
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    #3
    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 ).
    Some people can get a small amount of euphoria from certain Antihistamines alone, though it's quite rare.
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    #4
    Bluelighter kratom luver's Avatar
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    Apparently they are used clinically to reduce the dose requirement for opioids as they have an 'analgesia-sparing' effect.
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    #5
    ^ 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).
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    #6
    Bluelighter jasoncrest's Avatar
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    Quote Originally Posted by kratom luver View Post
    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.
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    #7
    Bluelight Crew BingeBoy's Avatar
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    They share the same metabolic pathway in the brain


    Im moving this to ADD , they will give you a more detailed answer there
    Last edited by BingeBoy; 27-11-2008 at 18:38.
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    #8
    Bluelighter Methacodone's Avatar
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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.
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    #9
    Administrator sekio's Avatar
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    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.
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    #10
    Bluelighter Methacodone's Avatar
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    True.

    sorry if I misunderstood anyone...
    i did mean Hydroxyzine is NOT an Antidepressant....
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    #11
    Bluelighter Nagelfar's Avatar
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    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 fašade 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...
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    #12
    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...
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