• N&PD Moderators: Skorpio | thegreenhand

Opiates and MAOIs: Contradicted?

samadhi_smiles said:
Is it like a serotonin syndrome that occurs?

From what I've been able to find out, there are several different types of drug interactions that can occur with MAOI's. One is a hypertensive crisis (which I also experienced about 20 years ago when I was stupid enough to take a CoTylenol tablet along with Nardil); and the other type seems to be more of an autonomic nervous system crisis, more along the lines of what I described in my Demerol-related post above.

As I've seen suggested on these boards and elsewhere, from now on whenever I go to a doctor and they ask me if I'm allergic to any drugs, I'm just gonna say "Yes, I'm allergic to Demerol". Even though I'm technically not "allergic" to it, at least it will get their attention and ensure that they won't give me Demerol. They seem to pay lots of attention to potential drug allergies, but, as I found out, they tend to dismiss or ignore the dangers of MAOI drug interactions.

JohnB
 
Yes, Demerol in particular seems to be contradicted. Is this something to do with demerol's Mechanism in comparison to a more simple morphine type opiate. Demerol is 'sloppier' I gather in its physiologic fx?
 
Here's what little I could find about the mechanism of the Demerol-MAOI interaction:

"MAOIs retard metabolism of pethidine [Demerol], but not its demethylation; therefore excess norpethidine is formed."

I'm no expert on this stuff, but it sounds like it results from a dangerous buildup of a pethidine (Demerol) metabolite, norpethidine. Perhaps this doesn't occur with other types of opiates. Make sense?

JohnB
 
MAO will increase levels of synaptic dopamine, althoughI have not noticed any contradictions with opium based alkaloids and moclebemide except at least 50% potentiating...I would still recommend to BE CAREFUL. half both doses and know how your body responds to MAOI.
 
Norpethidine isn't even an opioid. I dunno anything about it.

Johnnyzero- if ever there was a case where suing a doctor was justified, it's this case. What a fucking moron, I can't believe that any doctor would be stupid enough to actually administer pethidine AFTER he was warned!

There's plenty of warnings about this combination, he is definitely incompetent.
 
Ham,

Just to clarify: from what I've read, Demerol is technically an opioid, as opposed to an opiate. That means it's synthesized, in contrast to a natural opium derivative like morphine.

Supposedly, Demerol (meperidine) is typically synthesized by combining dichlorodiethyl methylamine and benzyl cyanide. Sounds like an episode of "Breaking Bad"...:)

As best I can tell, here is why Demerol is classified as an opioid: according to Wikipedia article "Pethidine exerts its analgesic effects by the same mechanism as morphine, by acting as an agonist at the μ-opioid receptor."

You're right about the lawsuit thing. However, after consulting with an attorney, he made the valid point that there seems, at least at this point, to be no lasting or sustained injury. Not being an overly-litigious guy, I guess I would tend to agree with him.

At least I feel that I did the right thing and filed reports with both the hospital & Dept. Of Health.

best,
JohnB
 
Just to clarify: from what I've read, Demerol is technically an opioid, as opposed to an opiate. That means it's synthesized, in contrast to a natural opium derivative like morphine.

Supposedly, Demerol (meperidine) is typically synthesized by combining dichlorodiethyl methylamine and benzyl cyanide. Sounds like an episode of "Breaking Bad"...

As best I can tell, here is why Demerol is classified as an opioid: according to Wikipedia article "Pethidine exerts its analgesic effects by the same mechanism as morphine, by acting as an agonist at the μ-opioid receptor."

you're not telling me anything I don't know quite well.

I said that norpethidine isn't an opioid. without the n-methyl group, it's not a tertiary amine, and not an opioid- it can't bind.

at least at this point, to be no lasting or sustained injury. Not being an overly-litigious guy, I guess I would tend to agree with him.

... except for all those panic attacks and the mental damage sustained when your brain overheated.... Kidding, but have you filed a complaint with the hospital itself? That's where I would have started.
 
Ham-milton said:
you're not telling me anything I don't know quite well.

I said that norpethidine isn't an opioid. without the n-methyl group, it's not a tertiary amine, and not an opioid- it can't bind.

You obviously know way more than I do (or ever wanted to) about opioids/opiates & biochemistry. I was just going by the manufacturer's own monograph, which starts with the following words:

Pharmacology: Meperidine is an opioid analgesic which acts predominantly as a mu-agonist.


Anyway, no need to split hairs about this. The bottom line is that it the damn stuff almost killed me last Saturday night. :)

Ham-milton said:
... except for all those panic attacks and the mental damage sustained when your brain overheated.... Kidding, but have you filed a complaint with the hospital itself? That's where I would have started.

Yes, I certainly did file a complaint with the hospital first thing. We'll see what their response is.

Supposedly, the NY State Department of Health follows up on all incident/complaint reports filed throught their Hospital Complaint Hotline. They will initiate contact with the hospital and, if necessary, will require that the hospital implement tangible procedural changes and/or improvements relevant to the incident. That's really all I want.

best,
JohnB
 
You obviously know way more than I do (or ever wanted to) about opioids/opiates & biochemistry. I was just going by the manufacturer's own monograph, which starts with the following words:

Pharmacology: Meperidine is an opioid analgesic which acts predominantly as a mu-agonist.

Yeah, I just mean that the current 'best understanding' of the problem with Pethidine+MAOI is because it causes norpethidine to build up.

I don't know much, or know if much is known, about norpethidine (that's pethidine, or meperidine without the n-methyl group). Opioids need a tertiary amine in order to be opioids (that's an N with three lines, or carbons, coming off of it in the picture). As Pethidine is also a DARI (I started a thread about this today) it would make sense that norpethidine is as well, possibly a stronger one, and that hypertensive crisis would result from norpethidine and an maoi.
 
My psychiatrist is considering trying me on an MAOI if my current tricyclic (doxepin) doesn't do it's job. I've currently done most of the SSRIs/SNRIs, all of them were epic failures for me. Also tried amitriptyline and mirtazapine a while ago, that was mainly for my insomnia issues though.

I honestly don't care about going on a MAOI now, as long as I can take benzos and opiates with it, then I'll be fine (aside from tramadol and pethidine, of course). But yeah, I will miss beer :(
 
well does anybody know the mechanism for potentiation then? Why would MAOIs potentiate opiates???

I'm utterly confused by this all. So it means I shouldnt take opiates on MAOIs. Disappointing. I wanted to smoke some tar on Aleph-1 :(

THAT sounded lovely.
 
samadhi_smiles said:
well does anybody know the mechanism for potentiation then? Why would MAOIs potentiate opiates???

I'm utterly confused by this all. So it means I shouldnt take opiates on MAOIs. Disappointing. I wanted to smoke some tar on Aleph-1 :(

THAT sounded lovely.

is aleph1 a MAOI? I know the related 2-ct2 and 2ct7 are to an extent. but I have no data on Aleph1.

you really are exploring unknown territory with Aleph-1 and combinations, Diacetylmorphine might be safe might not be, I don't think you will get a definitive answer. not from me!
if the only mechanism for danger is opioids which also have serotonin reuptake inhibition properties then the danger is limited to pethidine and tramadol methadone and dextromethorphan well as common ones.
if indeed this is the case and I am not saying it is, but if it were, hypothetically speaking of course, and YMMV... then I might be thought conceivable that morphine codeine oxycodone and diacetyl morphine which are not sris, might possibly be safe in combination with maois, maybe, but I am not sure.

read this paper:
http://bja.oxfordjournals.org/cgi/content/full/95/4/434
 
vecktor said:
then I might be thought conceivable that morphine codeine oxycodone and diacetyl morphine which are not sris, might possibly be safe in combination with maois, maybe, but I am not sure.
Yeah, that's pretty much the gist of the article. Any opiate/opioid that doesn't directly affect serotonin won't directly interact. Still, I cant discern the potentiating action of MAOIs on opiates such as morphine and codeine.

If by potentiating, do they mean increased analgesia or the euphoric properties of opiates? I'm curious about this as well, I'd like to try a mix of codeine and moclobemide.
 
I'm pretty sure that morphine and codeine based opiates are fine with MAOIs; it's the synthetic opioids that can have some problems.
 
^ then what do you think accounts for the potentiation I experienced on pod tea + b caapi + DMT???

It definitely was potentiated after smoking that stuff...

maybe its all in my head......
 
Well, MAOIs might potentiate classic opiates, but beyond a lowered dose, there are no dangerous side effects. I've never tried mixing the two so I have no idea if they potentiate.
 
Opiates increase serotonin and noradrenaline and dopamine levels in the brain. In the case of serotonin and noradrenaline it takes a long time for them to build up.. So its pretty safe to use opiates with MAOI, just as long as you count as more intense...

Look at moclobemide interactions... They think that the only way it interacts with opiates is with CYP inhbition..


samadhi_smiles said:
^ then what do you think accounts for the potentiation I experienced on pod tea + b caapi + DMT???

It definitely was potentiated after smoking that stuff...

maybe its all in my head......

its not all in the head.. as you know by now, opiates increase levels of dopamine and serotonin and noradrenaline and others, that are the things that MAO are supposed to "destroy".. so you have felt the effect that MAOI had on the boosted levels of amines that opiates increased by indirect action thru their action on their receptors.
 
I was prescribed 80mg methadone (for drug dependency) & 200mg Sertraline (for depression) & was drinking a lot on top and had no adverse side effects apart from seeing things move in the preriphery of my vision. When I stopped taking the sertraline I got 'brain buzz' which went in a few days. Obviously, my case doesn't prove a rule or disprove it.

Oh yeah sertraline and codeine or heroin was no different than with methadone from the adverse effects point of view.
 
pretty sure I mentioned earlier!! 8)
while CYP interactions do certainly play a role in the potentation. The MAOI also stops break down of dopamine in the synapse, which would also make the your normal dose a deal stronger with the extra dopaminergic activity (ontop of CYP issues)
 
Emsam, Opioids and Depression

We seem to still live in the dark ages when it comes to MAOI's and contraindications. Physicians and particularly psychiatrists, who once prescribed Parnate, Nardil and Marplan, for depression ( somewhat more effectively than modern SSRI type antidepressants), remember the days when hypertensive crises and even subsequent hemorrhagic CVAs were not uncommon, most often caused by tyramine related reasons due to aged foods, or cold medications like PPA or pseudoephedrine. However, there were somewhere around three (yes, 3) deaths which were possibly related to the concomitant use of an MAOI and meperidine (and only meperidine--no other phenylpiperidines or propionanilides {fentanyl}, and especially diphenylheptanones {methadone} were ever concluded to have a possible causative etiology, yet with all the hemorrhagic CVAs and any resulting litigation, along with the comparative efficacy of non-selective MAOIs and their widespread use, all opioids were absolutely verboten in patients receiving MAOIs.)

While non-selective MAOIs that inhibit both MAO-A (which metabolizes NE and 5-HT) and MAO-B (which metabolizes DA and PEA --phenethylamine for those of you not familiar with this less common acronym ) are not very common, especially outside of institutional settings, the selective MAO-B inhibitors like selegiline (Deprenyl capsules and Emsam patches) do not share these contraindications in standard doses ( up to 10 mgs per day po and 6 mgs per day transdermally ) are becoming a more common treatment for depression, in addition to selegiline's effectiveness as an antiparkinson medication.

My personal experience with selegiline and particularly the 6 mg Emsam patches has been truly remarkable, and I can say that this is only antidepressant that has ever completely eliminated my depression, which I had suffered from all my adult life. Occasionally, I came across an SSRI that induced temporary hypomania and seemed to work initially, but as soon as the hypomania went away, so did the drug's efficacy. The Emsam patches do not induce hypomania, but make it such that I do not need to take my morning methadone, alprazolam and Desoxsyn before I get up and shower. In other words, my state is relatively constant and I am not taking recreational drugs anymore, period (except for a very rare ketamine or DMT trip.) Even parafluorofentanyl, my previous absolute drug of choice, is not in jeopardy of being diverted from my lab (by me at least.) I have recommended Emsam to dozens of people who suffered from refractory depression and anecdotally, it is very effective in people that have anhedonic type depression with a substance abuse history (making it hard to tell your doctor.) It does not seem to work on the anxiety ridden type of depression where people just lie in bed all day long and worry and cry. I have been surprised how effective Emsam has been in substance abusers, and it is ashamed that a valid study is hard to do in people who are not in drug treatment but used controlled substances because of the ostracization factor. I am lucky to have found an amazing shrink who trusts me and believes what I tell him, because in the past, my advice was to never divulge drug use to your shrink.

My shrink and I have discussed the rest of the cocktail I am on and decided it is not a good idea to come off of them quickly or at all if I do not feel like it is necessary. I have however, decreased my methadone from 100 mgs a day to 60 mgs a day, and decreased my alprazolam from 2 mgs or more a day of Xanax to 0.5 mgs qd - 1.0 mgs bid of Niravam (an ODT --oral dissolving tablet-- version of alprazolam. Now I am prescribed 45 mgs per day of Desoxyn, but I take only 20 mgs bid. I find that the Desoxyn makes my thoughts clearer than I have ever experienced and they do not race from thought to thought constantly, so I do feel that I will be on that permanently because it is treating an ADD-like syndrome.

But, every single month, I must get Blue Cross/Blue Shield to give the pharmacist an override code each time I get my prescription for methadone filled and my prescription for Desoxyn (methamphetamine) filled because of the 6 mg Emsam patch. I am used to it now, after about a year of being on all these drugs (but oxycodone and oxymorphone do not cause a contraindication to come up on Walgreen's computer and no, I do not take these two drugs, but continue to get them because of past difficulties and my concern that if my depression came back, I would need to have easy access.) Every time there is a new pharmacist that fills the script, I often have to explain to him why a MAO-B selective MAOI should not be contraindicated, but as we continue with drug discovery, the problem of the limited capacity of human knowledge keeps arising (at physicians offices too.)

At the doses previously discussed, selegiline is almost completely selective for MAO-B, and as long as you do not suffer from hypertension, there is likely to be no problems taking Desoxyn or any amphetamine type drug with it, provided that you monitor your blood pressure daily. If you do have HTN, then you would want to make sure that the added drug does not increase either the systolic or diastolic pressure. But as far as opioids go, the contraindication warning is IMHO, nonsense. Methadone, which is a fairly strange opioid insofar as it affects NMDA and serotonin systems as well as opioidergic systems, is not going to cause any problems with a selective dose of selegiline. And meperidine in high doses has been known to cause convulsions due to a buildup of normeperidine. It has been suggested that this may be due to serotonin, but that idea IMHO is all but dead. Methadone, which has a direct agonistic effect on serotonin, has never caused a reported case pf serotonin syndrome, so it is hard for me to buy the rationale that serotonin is responsible for meperidine.

I do not remember if you said you were given prochlorperazine (Compazine), or promethazine (Phenergan), but these phenothiazine and phenothiazine-like anti-nausea medications have idiopathic side effects in far more people than meperidine. Meperidine is becoming less and less common in the US, but it is still used by older physicians that do not keep up with literature.

One of the reasons I am not on Bluelight and ADH much these days is that I am mostly focusing on my research and my writing. Recreational drug use no longer holds a place of importance in my life other than to help people who want to stop using drugs to self-medicate their depression.

MobiusDick
 
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