Pharmacology How is that even possible? ᴍᴀᴏɪꜱ, ꜱᴇʀᴏᴛᴏɴɪɴ ꜱʏɴᴅʀᴏᴍᴇ

[red22]

Thanks for the contribution. More details about the phenelzine/MDMA experience, please, including how long you had been taking phenelzine and the dose progession.

The reality of drug-drug interactions vis a vis MAOIs is EXTREMELY complex and nuanced.

Yeah, here's a negative account that I should have included in this thread. Having read that most of what has been written about MAOIs is exaggerated, one person decided to push the envelope and attend MDMA therapy while on Parnate. His first experience, probably an introductory dose, went OK, but during his second experience he blacked out and wound up in the hospital.

"The first time the effects were stronger than normal but the second time I got serotonin syndrome, blacked out and almost died, ended up in hospital."

fluffelicious, 2022-05-27, re: Low dose MDMA while on an MAOI


Also, did you do the combo to challenge the warning? Were you nervous about this experiment?

And if you could elaborate on "complex and nuanced" at all it would be appreciated.

 

[tachyphylaxis]

Reversible inhibitors tend to be more forgiving re: drug-drug interactions, but that is hardly a sure thing. I will tell you what I personally would NEVER ingest while on an MAOI: Demerol, DXM, Tramadol, Kratom/its alkaloids. Meperidine is NOTORIOUSLY toxic with MAOIs. There are probably others that I can't think of rn. Doctors have given SSRIs with MAOIs without inducing serotonin syndrome. It's in the literature. The side effects were still pretty bad IIRC, and they stated outright that the results of their investigation made it a dead issue as far as they were concerned. No need to go further, because it is hard to imagine that ever being beneficial to anyone because the side effects are just too much.

I would not touch DXM. No way. Not worth the risk. I won't even take it for a cough although that might well be fine. Enough documented deaths here for me, IIRC.

It is conceivable that I have way more personal experience taking various drugs with MAOIs than all but at most hundreds of people out there. I just realized that. They simply aren't prescribed that often (unfortunately). Years ago, when I was really into "the lifestyle" or whatever u wanna call it, I tried a LOT of things. I have taken hundreds of milligrams of PEA IV while on at least 90mg/day of Parnate. It SUCKED. Absolutely horrible. Like 3/4 of the way to a panic attack with no upside. It felt precious little like amphetamine. I have taken 100-200mg of Parnate itself IV (for a while I had no insurance and had to use research-grade). It almost made me cream my pants for a moment. The only reason that is still on the market is because if u abuse it, you WILL end up with major health problems, namely thrombocytopenia. Take enough Parnate, and that WILL happen. Platelets have lots of MAO (MAO-B I think), as many of you I'm sure already know.

Note that I am speaking about irreversible MAOIs only. I don't know enough to say much about RIMAs in this respect.

I have had the good fortune for most of these years to have a really competent doctor treating me. And I'm old enough now that most of the stuff that could be problematic just doesn't interest me. The main thing I want to try is an IV infusion of DMT or something like that, or likewise with ketamine or something that is not e.g. an analog of PCP. But I don't have much money, and can't afford to get scammed. Am kinda interested in RC opioids, but it's probably best to just leave that one alone. The risk/reward is just not there.

Also, keep in mind that I've been on these drugs forever, so my experience is not indicative necessarily of what anyone else's would be. The main reason I am writing this (other than drugs being on my mind lately), is to stress that both of the following propositions are true:

-- There is a lot of misinformation out there about them. It's insane. Most I can say about that aside from recounting my personal experience is that I defer to Gillman lol. Overall, the risks are insanely overblown.
-- Interactions can be HIGHLY idiosyncratic, and if your number comes up, that's just how it goes. And some of them (epinephrine, Demerol, DXM, etc) are VERY, VERY dangerous


Ihave had two doctors prescribe the combination I'm on in all these years. The one who initiated it is retired now, and the person I've been seeing since is the guy he recommended. In both cases, they don't rely much on what the literature says. You can't. It's too poorly understood and there just isn't that much current literature on it, which is a shame. The first guy, the one who initiated this, did so mostly shooting from the hip. There is precious little else to go on! He started me at 5mg d-amphetamine twice a day, and that was AGGRESSIVE. He knew that the dose was gonna be high in the end and didn't want to torture me for years getting there lol You can make an argument for starting at 1.25mg bid. It took 1.5 years to titrate up to where I am. He did this in a way that balanced the risk/reward for him.

Anyway, the gist of what I'm saying are the two points I highlighted above. Yes, RIMAs are PROBABLY more forgiving. Probably.

 

[tachyphylaxis]

Thanks for the contribution. More details about the phenelzine/MDMA experience, please, including how long you had been taking phenelzine and the dose progession.



Yeah, here's a negative account that I should have included in this thread. Having read that most of what has been written about MAOIs is exaggerated, one person decided to push the envelope and attend MDMA therapy while on Parnate. His first experience, probably an introductory dose, went OK, but during his second experience he blacked out and wound up in the hospital.

"The first time the effects were stronger than normal but the second time I got serotonin syndrome, blacked out and almost died, ended up in hospital."

fluffelicious, 2022-05-27, re: Low dose MDMA while on an MAOI


Also, did you do the combo to challenge the warning? Were you nervous about this experiment?

And if you could elaborate on "complex and nuanced" at all it would be appreciated.

What I'm getting at by "complex and nuanced" is really more like "this just isn't that well understood in actual living human beings." The first doctor that I had was capable of going on and on in excruciating detail about what is still unknown. It dovetails with the mechanism of action of amphetamine more broadly, actually, and even moreso as to what exactly that means when it comes to actual people taking the drugs lol. My current doctor has emphasized that many times over the years: that what he is doing is practicing medicine, and that yes, obviously he knows what the current thinking is on all this, but when it comes down to it, he basically just orders tests now and then and does the rest based on intuition (meaning that the knowledge just comes with experience as well as education) and knowledge of what the actual frequency of various adverse events are, etc.

Tl;dr: it varies so much from person to person (and probably even with only one person over time!) that no one can tell you what's gonna happen, even tho usually it's probably nothing. But there is a huge chasm between probably and certainty. That is really the problem. The chances of something going wrong are remote, but still way higher than with most drug combinations.

 

[tachyphylaxis]

Also, keep in mind that from a medical perspective, one also has to think about like "what happens if my patient accidentally takes a double dose?" Stuff like that. Because I have indeed done that by accident a handful of times. It is uncomfortable. It's not a medical emergency, but definitely uncomfortable. It's also just about guaranteed to happen given enough time.

Also relevant here is how long I have been taking MAOIs. When I first started on Parnate, it lit me up like a firecracker. My pupils were dilated fairly often in the first year. It's not like that anymore. I just feel ok to good, and have virtually no social phobia, whereas.not on the drug it is crippling. When I first started on Parnate, it was so insanely prosexual that sometimes it was actually difficult to even tolerate. I also took Nardil and Marplan for years too with and without amphetamine. In the beginning (even before amphetamine), it was hard to sleep and I was hypomanic sometimes.

For people in general, I would advise leaving MAOIs alone except for Ayahuasca-type stuff or as medication that u are gonna take every day. They should NOT be used to potentiate [insert drug X] here--with, again, some exceptions, like DMT. See, the ritual itself that developed over God knows how many years is what keeps people who do that safe. They don't have to know WHY, and it really isn't even that important why.

 

[tachyphylaxis]

I knew someone who indiscriminately f-ed around with Parnate and God knows what else, and they had a hypertensive crisis and died.

 

[red22]

–Any details on his experimentation?

 

[red22]

A case of MAO inhibitor/MDMA interaction: agony after ecstasy

 

[minakosunrise]

I was prescribed a low dose of parnate for 4 months and while maoi's are the only effective antidepressants ive ever tried (not counting opioids lmao) i wound up having hypertensive crisises left and right. I went to the er twice where they didnt know anything at all about maois and I had easily a dozen other incidents i treated at home with benzos and blood pressure medication. protriptyline, reign & bang energy drinks, 7oh/extracts, a tablespoon of aged cheese, 4f-mph, the phenylalanine in a 2 liter of diet coke, low doses of meth and vyvanse; all raising bp to 180/100+. i took 5mg of dxm once and had cev's. a bunch of nootropics gave me terrible headaches in the back of my neck even if my bp read normal. I was on kratom powder for a lot of this but I had plenty of reactions without aswell. I know normally drug interactions are overblown but maoi's aren't to fuck with regardless of what ken gillman says.


also curiously the novitum generic of parnate is absolutely worthless, it is sedating like an antihistamine and blunts like an ssri. the strides generic is nice and zippy. I didn't have as many reactions on bifemelane but i found it overall cost prohibitive while being less effective (and it tastes horrible).

 

[red22]

I have taken hundreds of milligrams of PEA IV while on at least 90mg/day of Parnate. It SUCKED. Absolutely horrible. Like 3/4 of the way to a panic attack with no upside. It felt precious little like amphetamine.

I've been taking PEA, continuously for about 3 months now (along with Selegiline).

[ … ]

I mean, it just seems too good to be true, it brings such a powerful euphoria and stimulation.

 

[MedicinalUser247]

What's the logic behind designing something like this ? https://en.wikipedia.org/wiki/3,4-Methylenedioxy-N-propargylamphetamine

 

[minakosunrise]

spitballing here but selegiline favors mao-b over mao-a 25 fold vs parnate which favors mao-a 5 times over mao-b. at standard doses deprenyl only fully inhibits mao-b which only effects dopamine & gaba where as parnate also inhibits norepinephrine & serotonin. phenethylamine releases an equally balanced amount dopamine and norepinephrine (as well as it's impact of taar1 & vmat2 leading to enhanced monoamine transmission); so selegiline leaves mao-a free to handle excess the norepinephrine and with all the remaining "amphetamine-like" peripheral sides coming from the l-meth metabolite (which i personally find rather pronounced even on it's own)- as opposed to the panicky adrenergic surge inevitable with parnate's full blockade build-up. in my expirience selegiline was way more forgiving when mixed with monoamine releasers.

 

[tachyphylaxis]

All I can say is that is what happened to me. I tried it orally at sane doses, too. It did not resemble amphetamine. It could be different with selegiline. I have no idea. I never was able to get my hands on PEA when I was using selegiline.

I was prescribed a low dose of parnate for 4 months and while maoi's are the only effective antidepressants ive ever tried (not counting opioids lmao) i wound up having hypertensive crisises left and right. I went to the er twice where they didnt know anything at all about maois and I had easily a dozen other incidents i treated at home with benzos and blood pressure medication. protriptyline, reign & bang energy drinks, 7oh/extracts, a tablespoon of aged cheese, 4f-mph, the phenylalanine in a 2 liter of diet coke, low doses of meth and vyvanse; all raising bp to 180/100+. i took 5mg of dxm once and had cev's. a bunch of nootropics gave me terrible headaches in the back of my neck even if my bp read normal. I was on kratom powder for a lot of this but I had plenty of reactions without aswell. I know normally drug interactions are overblown but maoi's aren't to fuck with regardless of what ken gillman says.


also curiously the novitum generic of parnate is absolutely worthless, it is sedating like an antihistamine and blunts like an ssri. the strides generic is nice and zippy. I didn't have as many reactions on bifemelane but i found it overall cost prohibitive while being less effective (and it tastes horrible).

You were taking Kratom powder and 7oh with Parnate? I wouldn't touch that one if you paid me. It's not just "despite what Ken Gillman says". Amphetamine + MAOI is an accepted practice. Ken Gillman doesn't claim that it's something that doesn't require due care, etc. He is speaking in the context of so many doctors refusing to even consider it at all. When I started out on Parnate, I was very cautious and added things back in cautiously over time. Ultimately, this varies a lot from person to person. I got lucky in this respect, I guess. When I first started taking Dexedrine with MAOI, my doctor started with like 2.5mg bid and worked up to 60mg/day over a year and a half. It went much faster towards the end. In the beginning, he was very conservative. It was a long time ago, but I remember him urging me to be patient several times, as there is simply no way to predict how any one person is gonna respond, and also that I should look at it in terms of orders of magnitude change, not so much just the dosage itself.
I guess I got lucky and/or you are unlucky.