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Opioids Is morphine/opium affected by SSRIs/SNRIs?

suidomreh

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As the title says, is morphine/opium affected by SSRIs/SNRIs? What about antidepressants that affect dopamine like NDRIs? I have read studies that say that some effects of morphine are actually increased by these medications, but it only mentioned medical purposes and not euphoria or anything like that. But I am wondering if it might actually hinder the recreational value, by reducing euphoria. I have tried to use morphine/opium while on an SARI called Trazodone and that completely negated the euphoria, but Trazodone works differently and affects the receptors that are responsible for releasing dopamine. I know that these medications do work on the same enzyme as codeine does to turn into morphine and would probably screw that process up, but as far as I know, SSRIs/SNRIs shouldn't really affect morphine/opium as it does not need to do that and go through that enzyme. I am unsure about NDRIs and stuff like that. Thanks.
 
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fairnymph

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As far as I know & have observed, not at all. But I also wouldn't have expected trazadone to negate their euphoria. I haven't found any of the meds you mentioned to have any effects, good or bad, on opiates - but I also don't experience any euphoria from opiates.
 

Keif' Richards

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In one way or another, I believe you'll find that all drugs interact with each other to a certain degree, be it chemically, biologically or just the bare subjective experience of having a new drug added to your cocktail, however, there is no distinct in vivo interaction between Opioids and SSRI antidepressants.
 

Jekyl Anhydride

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As the title says, is morphine/opium affected by SSRIs/SNRIs? What about antidepressants that affect dopamine like NDRIs? I have read studies that say that some effects of morphine are actually increased by these medications, but it only mentioned medical purposes and not euphoria or anything like that. But I am wondering if it might actually hinder the recreational value, by reducing euphoria. I have tried to use morphine/opium while on an SARI called Trazodone and that completely negated the euphoria, but Trazodone works differently and affects the receptors that are responsible for releasing dopamine. I know that these medications do work on the same enzyme as codeine does to turn into morphine and would probably screw that process up, but as far as I know, SSRIs/SNRIs shouldn't really affect morphine/opium as it does not need to do that and go through that enzyme. I am unsure about NDRIs and stuff like that. Thanks.
Fluoxetine or Prozac is known to screw with CYP450 3A4 and 2D6 to a lesser degree but you'll have to narrow down exactly which AD's you are interested in to get a more precise answer, as searching for interactions between opioids and 4+ classes of AD's is a tall order.

Fluoxetine was chosen as the model inhibitor for this study because it is a clinically important inhibitor of multiple CYP enzymes with varying potencies for each isoform. From in vitro data, fluoxetine is predicted to be a moderate inhibitor of CYP2D6, but a strong inhibitor of CYP2C19 and CYP3A4.
https://www.rxwiki.com/clinical-trial/effects-multiple-dose-fluoxetine-and-metabolites-cyp1a2-cyp2c19-cyp2d6-and-cyp3a4

Now for Prozac and Morphine, the altering of 3A4 can affect UGT2B7 which is what converts Morphine to the powerful M1 Morphine 6 Glucuronide.

Evidence for the Alteration of UGT2B7-Catalyzed Glucuronidation of Morphine by CYP3A4


Obviously 2D6 can alter the demethylation of Codeine into morphine.

Here's a good read for the CYP450's and their effects on most common opioids.

Opioid Therapies and Cytochrome P450Interactions

But as you can see, many things can effect even just one isozyme:






 

Jekyl Anhydride

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Thank Ya,

Kleinerkiffer and myself have been trying to get to the bottom of the C-6-G / morphine debate among researchers. While morphine has always been thought of as the only or main active metabolite of Codeine or 3-MethylMorphine, Codeine-6-Glucuronide might play an even larger part as many people are poor metabolizers of codeine.

The analgesic activity of codeine was suggested to be largely due its metabolite morphine [9][10][11][12]. However, of late, Vree et al. (2000) developed a different view of codeine's affinity to the mu-opioid receptor and its analgesic activity. The authors argued that the analgesic activity of codeine was due to its glucuronide conjugate rather than to its O-desmethyl metabolite, morphine [13]. ...

&

Eighty per cent of codeine is conjugated with glucuronic acid to codeine-6-glucuronide. Only 5% of the dose is O-demethylated to morphine, which in turn is immediately glucuronidated at the 3- and 6-position and excreted renally. Based on the structural requirement of the opiate molecule for interaction with the mu-receptor to result in analgesia, codeine-6-glucuronide in analogy to morphine-6-glucuronide must be the active constituent of codeine. Poor metabolisers of codeine, those who lack the CYP450 2D6 isoenzyme for the O-demethylation to morphine, experience analgesia from codeine-6-glucuronide. Analgesia of codeine does not depend on the formation of morphine and the metaboliser phenotype.
www.researchgate.net/publication/12235968_Codeine_analgesia_is_due_to_codeine-6-glucuronide_not_morphine

However you can't deny that ultra rapid metabolizers can be overwhelmed with morphine from codeine. I think it's the combination of the two, M+C-6-G, but morphine has taken all the credit until now. Maybe someday they'll come to a consensus.



..and then there's:

- Glutethimide, this one is a strong inducer, meaning that a lot of CYP2D6 will be expressed leading to an increase of morphine production. But the drug itself is classified as a hypnotic sedative thus increasing the side effects and dangers of codeine. In the worst case this can lead to respiratory depression and death so proceed with caution and start with extremely low doses and have a friend around in case you overdose.

Best feeling in the world. I have been looking for any other drugs to come close to how good Doriden (glutethamide)&Codeine makes me feel and haven't found anything.
Hands down the most wonderful feeling in the world.
I remember taking them when I was 18- 19 years old and I would feel guilty after taking them because I knew I shouldn't of loved taking them so much.
It's been 25 years since my last dose and I still have the urge to take them!! Heroin sucks because I compare it to D&C and can't even touch it. taking codeine alone either.
or a new option that works on all opioids, not just codeine:

~Proglumide~

CCK receptor antagonists such as proglumide have been demonstrated to reverse tolerance to opiates, reducing the dose of opiate required to produce analgesia (Kellstein et al, Pain; 1991 ). Consequently, proglumide has been demonstrated to boost opiate analgesia, meaning that a markedly reduced dose of opioid is required to achieve the same level of analgesia. This has been shown to occur, without any potentiation in respiratory depression (US-A-4576951 ) or any effect on the development of opiate dependence (Paneria et al., Brain Research; 1987).
https://patents.google.com/patent/CA2542837A1/en


So yeah, there's plenty to ponder regarding the Codeine postulations..


862041-Codeine-and-CYP2D6
 

Keif' Richards

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Just so everybody is aware, while these SSRI's certainly can, depending on the drug in question, have a serious effect on enzyme activity, however, for the most commonly prescribed SSRI antidepressants today, the effect upon enzyme activity is actually quite minor. There are some SSRI's that were known to have a pretty serious effect upon certain Opioids (re: Fluvoxamine -> Methadone), but the aforementioned drug has been discontinued for the most part, with one of the reasons being that it did have the potential to screw with other prescription medications. This drug is still available, but not commonly prescribed for obvious reasons.

For those with "normal; average" enzyme activity should really have no fear when considering adding SSRI therapy to their treatment regimen. The charts and stuff are definitely fun to look at and informative, but truthfully, there's no reason for anyone to refrain from adding a potentially life-changing medication to their Opioid prescription or vice versa, but as always, your prescriber has the final word and his opinion should be the one trusted although we are always happy to provide our opinions and references.
 

fairnymph

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Thanks for the extra inducers, JA. I have extremely low CYP2d6, almost none. I've been prescribed codeine - mostly as Fiorinal w/ codeine, so not a great example due to the other active compounds, especially as I know caffeine helps my menstrual cramps, which is what I took the med for from age 16-19 until I needed to move up to hydrocodone - but also straight codeine/APAP, both CWE'ed & not. It definitely feels different from morphine (I actually prefer codeine), & likewise hydrocodone & hydromorphone feel distinct. Accounting for potency, ofc.

Glutethimide sounds way too sedating for my tastes, but proglumide could be promising.

I agree KR. Though I'd like to try fluvoxamine.
 

LucidSDreamr

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There was a recent paper linked in the chronic pain sub reddit that showed that ssri's reduce opioid analgesia. Analgesia isn't exactly euphoria but thought I'd mention it.
 

Jekyl Anhydride

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Yeah another article was just published a couple weeks ago about SSRI's and opioid Prodrugs like Hydrocodone, Tramadol, etc.

Antidepressants Can Interfere With Pain Relief Of Common Opioids-Predicting inadequate postoperative pain management in depressed patients: A machine learning approach

Widely-prescribed prodrug opioids (e.g., hydrocodone) require conversion by liver enzyme CYP-2D6 to exert their analgesic effects. The most commonly prescribed antidepressant, selective serotonin reuptake inhibitors (SSRIs), inhibits CYP-2D6 activity and therefore may reduce the effectiveness of prodrug opioids.
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0210575


With regards to Keif's post, the OP was asking about morphine, AD's and enzymatic interactions. Not the safety of combining the two, which is why no inferences to discontinuing either class of meds was offered. Just the possible reduced efficacy of the opioids. Seeing as how OD is meant for in depth discussion, these subjects should be fine to delve into for those that understand the material at hand. It should go without saying though that your doctor makes the final call and this is merely something for study, discussion and maybe to bring to his or her attention if you feel that it's pertinent to your situation.
 

LucidSDreamr

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<---

Sounds like ppl on SSRIs need higher doses or non pro drugs like hydromorphone instead of hydrocodone.

...but you wont see the bitch ass CDC putting that into their prescribing guidelines they pull out of their ass
 

Jekyl Anhydride

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<---

Sounds like ppl on SSRIs need higher doses or non pro drugs like hydromorphone instead of hydrocodone.

...but you wont see the bitch ass CDC putting that into their prescribing guidelines they pull out of their ass
Tell me about it..

In a New England Journal of Medicine article, one of the pain specialists advising the CDC recommended that pain patients "use coping and acceptance strategies that primarily reduce the suffering associated with pain and only secondarily reduce pain intensity." That opioids are never an effective chronic pain treatment is quickly becoming conventional wisdom, and the American Medical Association has even begun to advise physicians to abandon the pain rating scale when assessing patients.
Accept and cope your way to a better life of pain.. Yeeaahh 8)
 

fairnymph

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^^^Whoever agreed to publish that, &/or helped write it, I wish upon them my chronic pain x infinity. Fuckers. My 10yrs of extremely safe h use (& I've gone DOWN in dose despite ever worsening pain) to self treat certainly disputes that.
 

Hezman94

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The synthetics are especially fentanyl and tramadol and methadone and tramadol. tramadol and other anti ds can be dangeorus

I took tramadol for a week when i first got on fentanyl as thought id be in withdrawal from my oxys going from 70 to 20mg , i felt a load worse headaches, paranoia, anxiety, dizziness,
 

suidomreh

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Thanks for the replies guys. The antidepressant I am taking is Effexor, which is an SNRI. I don't think it is really affecting the effectiveness of the opium I am taking. And if it is, it is probably affecting the small amounts of codeine and not the morphine. I feel like an NDRI like Wellbutrin would have a high chance of affecting it though. Because it works on dopamine, which is what opiates release to give the euphoria. But I may be wrong. Or the way in which it affects dopamine might not be a negative way. If anyone has had personal experience with an antidepressant that works on dopamine while on opiates, please let me know you experience.
 

fairnymph

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The synthetics are especially fentanyl and tramadol and methadone and tramadol. tramadol and other anti ds can be dangeorus

I took tramadol for a week when i first got on fentanyl as thought id be in withdrawal from my oxys going from 70 to 20mg , i felt a load worse headaches, paranoia, anxiety, dizziness,
Agreed. The synthetics all have nasty side effects for me outside of methadone (still interested to try meperidine though), & are much less effective for my pain. But obviously they care most about their own asses, not actual opiate users/pain patients.
 

Jekyl Anhydride

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Funny you should mention Venlafaxine-Effexor

The antinociceptive effect of venlafaxine in mice is mediated through opioid and adrenergic mechanisms.

Venlafaxine-induced antinociception was significantly inhibited by naloxone, nor-BNI and naltrindole but not by beta-FNA or naloxonazine, implying involvement of kappa1- and delta-opioid mechanisms. When venlafaxine was administered together with various agonists of the opioid and alpha2- receptor subtypes, it significantly potentiated antinociception mediated by kappa1- kappa3- and delta-opioid receptor subtypes.
Venlafaxine and mirtazapine: different mechanisms of antidepressant action, common opioid-mediated antinociceptive effects--a possible opioid involvement in severe depression?
When mice were tested with a hotplate analgesia meter, both venlafaxine and mirtazapine induced a dose-dependent, naloxone-reversible antinociceptive effect following ip administration. Summing up the various interactions of venlafaxine and mirtazapine with opioid, noradrenergic and serotonergic agonists and antagonists, we found that the antinociceptive effect of venlafaxine is influenced by opioid receptor subtypes (mu-, kappa1- kappa3- and delta-opioid receptor subtypes)...

This opioid profile of the two drugs may be one of the explanations to their efficacy in severe depression, unlike the SSRIs and other antidepressants which lack opioid activity.
Another interesting factor is the SAR. One of these is Tramadol and the other is Venlafaxine-Effexor

 
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