MAOI: Parnate

[AlphaMethylPhenyl]

I mean it can take 12 weeks for the effect to peak. I'd give it that long, especially if you're treatment-resistant.

 

[Bravoncius Roxford]

Just an update. I went with moclobemide in the end. I felt immediate relief within a couple of days of taking it, but after several weeks I stopped noticing it. It also did something funky to my bowels, but I can't say what. IBD (not to be confused with IBS) patients often have excess gut serotonin and I wonder if the drug somehow amped it up locally.

During the time when it was working, it felt great and I would endorse this drug. My sex drive went up, I had more wakeful energy, and my spiraling suicidal thoughts were gone. I was taking 150mg twice daily, btw.

The twice daily dosing was a pain because I could never get the timing just right along with my other medications, plus taking it with food. It still worked better than an SSRI ever did though.

The fact that you responded so positively indicates to me you shouldn't give up. MAO-A inhibition increases primarilly NE. It's NE>ST> DP. You can enhance the antidepressant effect of the drug by increasing the dose to 600 mg a day, and changing your diet to include more protein for more tyrosine and typtophan, cutting out the junk food for decreased inflammation, cutting out sugar which depletes catecholamines, taking omega-3s which are great for brain health and exercising. Also, you need more time. The neuroadaptive changes in the brain that result in the antidepressant effect, such as downregulation of D2 receptors, increased BDNF secretion, dowregulaton of 5-HT2c receptors, and increased synthesis and release of beta-endorphin, can take in some cases as much as 6 months to happen. But when it does happen, it's like magic. You will wake up one morning feeling like a million bucks, and the mood lift is sustained for years. Give it a shot again!

 

[fastandbulbous]

I've thought about selegiline. I used to take it as part of my nootropic stack but I didn't find it very antidepressant for some reason.

What I like about parnate is that it seems to cover all the neurotransmitters. But moclobemide seems to do that as well. My concern with that drug, as mentioned in the wiki is, "with long-term use of moclobemide, there is a significant down-regulation of B-adrenoceptors" -- I don't like this, it means that the body gets less responsive to adrenaline, which would really suck in my day to day life! I do a lot of exercise and what not. I also don't like that it apparently increases prolactin initially... my prolactin is already elevated.

My doctor knows nothing about MAOIs but is willing to go on my say so. I don't trust taking parnate because I'm going to make a food mistake.

An increase in prolactin is generally related to a reduction in dopamine (some antipsychotics could grow breasts on the incredible hulk). Selegeline isn't bad, as it's an irreversible inhibitor of MAO-B (the one that metabolizes dopamine), but a reversible inhibitor of MAO-A (noradrenaline), as long as the dosage doesn't go too high. Start eating tablets like they're sweeties and it's an irreversible inhibitor of both, with all attending problems (eg hypertensive crisis and death).

Slap me down & call me silly, but has no one suggested S-ketamine, which has been approved by the FDA for refractory depression?

 

[AlphaMethylPhenyl]

^That's a good idea. I think ketamine is really only now becoming a mainstream thing.

I guess also cause this is about MAOIs.

Would be interested to hear about oral selegiline vs the patch. I know that the patch reduces l-meth conversion, but I don't know too much past that, other than that there's less danger due to where MAO is metabolized?

 

[dragonix]

The fact that you responded so positively indicates to me you shouldn't give up. MAO-A inhibition increases primarilly NE. It's NE>ST> DP. You can enhance the antidepressant effect of the drug by increasing the dose to 600 mg a day, and changing your diet to include more protein for more tyrosine and typtophan, cutting out the junk food for decreased inflammation, cutting out sugar which depletes catecholamines, taking omega-3s which are great for brain health and exercising. Also, you need more time. The neuroadaptive changes in the brain that result in the antidepressant effect, such as downregulation of D2 receptors, increased BDNF secretion, dowregulaton of 5-HT2c receptors, and increased synthesis and release of beta-endorphin, can take in some cases as much as 6 months to happen. But when it does happen, it's like magic. You will wake up one morning feeling like a million bucks, and the mood lift is sustained for years. Give it a shot again!

A name like that is a needle in a haystack Jack. You make Johnny Randazzle look like he doesn't belong inside The Roxbury!

A million bucks? A Big Pharma doctor can make me feel like that you're telling me?

 

[dragonix]

On a more serious note I get depressed easy these days without He Shou Wu now if I can stop mixing it with drugs (I guess it in/ex?hibits MAO-B properties I feel great on it but it isn't fixing my addiction).

Hope you find what works for you I stopped trusting many modern drugs a long time back sorry for gruff duncey tone I still know little about why exactly and carry a deranged alcoholic persona with me I will try to exit quietly now out the door I came in I have no knowledge to add to the matter at hand here really just my demented bias

 

[Foreigner]

Sorry I didn't return to this thread sooner. I really appreciate all the complex technical talk on this page, it has shed a lot of light on the pharmacology of this for me.

An increase in prolactin is generally related to a reduction in dopamine (some antipsychotics could grow breasts on the incredible hulk). Selegeline isn't bad, as it's an irreversible inhibitor of MAO-B (the one that metabolizes dopamine), but a reversible inhibitor of MAO-A (noradrenaline), as long as the dosage doesn't go too high. Start eating tablets like they're sweeties and it's an irreversible inhibitor of both, with all attending problems (eg hypertensive crisis and death).

Slap me down & call me silly, but has no one suggested S-ketamine, which has been approved by the FDA for refractory depression?

I used ketamine for years for depression, in fact I wrote about my early experiences on bluelight. The situation earlier this year was different. I was in isolation with an abusive partner and was too unwell to escape. I had no friends or family around to rescue me. I fought him daily to not mentally hijack me and it caused significant neurodepletion. Living with a narcissist will do that. I don't live there anymore and I'm getting back on track now. I needed an anti-depressant that boosted neurotransmitter levels because the psychological warfare of living with an abusive asshole is a real brain drain.

At the time, ketamine did not help me. I could theorize about the science behind that, but I'll just say anecdotally that I think ketamine is good for PTSD recovery, but it doesn't work when the trauma is happening right now. It has to be in the past.

All of the major life changes I've undergone in the past months have left me feeling pretty shaken. I'm considering antidepressants again. I might give moclobemide another try, but this time I might go for 300mg twice daily. I was on a super low dose, 150mg twice daily.

Or I could just try ketamine, now that I'm not around an emotionally unstable jerk.

 

[AlphaMethylPhenyl]

Sorry I didn't return to this thread sooner. I really appreciate all the complex technical talk on this page, it has shed a lot of light on the pharmacology of this for me.



I used ketamine for years for depression, in fact I wrote about my early experiences on bluelight. The situation earlier this year was different. I was in isolation with an abusive partner and was too unwell to escape. I had no friends or family around to rescue me. I fought him daily to not mentally hijack me and it caused significant neurodepletion. Living with a narcissist will do that. I don't live there anymore and I'm getting back on track now. I needed an anti-depressant that boosted neurotransmitter levels because the psychological warfare of living with an abusive asshole is a real brain drain.

At the time, ketamine did not help me. I could theorize about the science behind that, but I'll just say anecdotally that I think ketamine is good for PTSD recovery, but it doesn't work when the trauma is happening right now. It has to be in the past.

All of the major life changes I've undergone in the past months have left me feeling pretty shaken. I'm considering antidepressants again. I might give moclobemide another try, but this time I might go for 300mg twice daily. I was on a super low dose, 150mg twice daily.

Or I could just try ketamine, now that I'm not around an emotionally unstable jerk.

Sorry to hear that. We at MH are there for you

Interesting bit about ketamine.

Why did you stop your MAOI in the first place? Did you try all three (nardil, parnate, and moc.)?

Maybe you have something other than depression. Dunno.

I think MDMA is getting good looks for PTSD. Other than that, I can't imagine that microdoses would hurt. As for full doses, you need preparation.

Assuming here you tried SSRIs, Wellbutrin, Remeron, and the whole mix?

 

[Rectify]

Inspired by Parnate:

GLEE
1-(3,4-methylenedioxyphenyl)-2-carbomethoxy-3-methylaminocyclopropane

PEE_WEE
1-phenyl-2-carbomethoxy-3-methylaminocyclopropane

 

[Transcendence]

I have no personal experience with MAOIs, but have tried multiple antidepressants in all the other major categories. My depression is not severe but it is treatment resistant, and only ketamine infusions seem to mostly clear it. Too expensive and impractical sadly. Anyway, I have tried Mirtazepine from 15-45mg and find it to be at least slightly more effective than SSRIs/SNRIs, maybe similar efficacy as bupropion or tianeptine for depression and as effective as high dose SSRIs for anxiety without negative sexual side effects or as much emotional blunting.

Unlike SSRIs, I do not find starting mirtazepine to increase anxiety, insomnia, or induce nausea. The worst side effects when starting are fatigue/oversleep and excessive appetite (although not nearly to the degree of something like Seroquel, it seems to make sugar taste better to me). Sleep is improved from 7.5mg-22.5mg but temporarily disturbed at 30+mg as it becomes more activating and the daytime fatigue subsides. Therapeutic effects become evident faster than with SSRIs as well.

Personally it is probably not effective enough to take indefinitely but I would give it the nod over other antidepressants I've tried. I am considering trying an MAOI and I am under the impression that the dangers are generally overblown, but I am not sure that my depression is bad enough to warrant it and I do not know if my doctor would allow me to continue taking d-amphetamine in combination with an MAOI. I will say that I have had many psychiatrists from young to old across the country, and none of them have ever mentioned an MAOI as an option, even when discussing ECT and ketamine. I find this curious.

 

[Transcendence]

An increase in prolactin is generally related to a reduction in dopamine (some antipsychotics could grow breasts on the incredible hulk). Selegeline isn't bad, as it's an irreversible inhibitor of MAO-B (the one that metabolizes dopamine), but a reversible inhibitor of MAO-A (noradrenaline), as long as the dosage doesn't go too high. Start eating tablets like they're sweeties and it's an irreversible inhibitor of both, with all attending problems (eg hypertensive crisis and death).

Slap me down & call me silly, but has no one suggested S-ketamine, which has been approved by the FDA for refractory depression?

I have not tried the new s-ket nasal spray, but have had ~dozen IV infusions of ketamine in clinics. As hopeful as I was for an FDA approved arylcyclohexylamine, I think the s-ket spray makes no sense apart from profit motive. R-ketamine is probably more effective for depression, nasal ROA is markedly less effective therapeutically than IV or even IM admin per my anesthesiologist and the literature I've seen. It is not more convenient because you cannot take it home, you must drive to a hospital and then stay there for at least an hour every time you take it. Finally, most insurance plans will fight against covering it and it is otherwise comparably expensive and inconvenient as ketamine infusions with significantly less therapeutic benefit.

If they could put methoxetamine in a spray and let me take it home, that would be cool, but I bet even the normies would heavily abuse it.

 

[plumbus-nine]

If they could put methoxetamine in a spray and let me take it home, that would be cool, but I bet even the normies would heavily abuse it.

Oh you don't even need the nose for MXE to be good, initially I only did sublingual some 5-20mg, it was one of the greatest drug experiences so far. Also thought they should make an XR pill out of that stuff and market as an antidepressant. The difference is that with K one's supposed to be good with occasional use 1-2x a week and then develop a protracted antidepressant effect while with MXE different people might profit from being constantly on a very low dose of it. Don't know whether tolerance would render it ineffective after some time or not, as long as one isn't exceeding these low dosages. There's also a paper suggesting MXE for treatment resistant depression but with the worldwide ban it's gone forever.. the MXE derivates currently available, at least some of them, have potential too but they will also be banned sooner or later. It sucks that K is the only constant thing around because I and many find it to be cold and clinical, and I get the same amount of rebound/comedown time from most if not all arylcyclohexylamines, so these with longer duration make a better math, and those more potent are easier on the bladder.

When I was younger (17-22) I was using DXM for its rapid and sustainable antidepressant effects, it made a difference like night and day in my ability to keep a job or socialize but over time it turned against me, nowadays it's just a psychosis inducing agent.

I have no personal experience with MAOIs, but have tried multiple antidepressants in all the other major categories. My depression is not severe but it is treatment resistant, and only ketamine infusions seem to mostly clear it. Too expensive and impractical sadly. Anyway, I have tried Mirtazepine from 15-45mg and find it to be at least slightly more effective than SSRIs/SNRIs, maybe similar efficacy as bupropion or tianeptine for depression and as effective as high dose SSRIs for anxiety without negative sexual side effects or as much emotional blunting.

I was on antidepressants for most of my adult life (around 15 years), tried almost all of the SSRIs, some SNRIs and others like bupropion, opipramol, tianeptine etc. Not for depression but social anxiety. None of them did any real good besides the first months on venlafaxine, where I was hypomanic - a good state to be for somebody with anxiety disorder, but also dangerous and imo it should be a warning sign not to continue on antidepressants because later I'd develop treatment resistant depression and physical addiction to SSRIs. Emotional blunting as well, that was welcome though, and sexual side effects - it's still fucked up now, after being down on 37.5mg venlafaxine, and I have little hope for a full recovery for the more near future. Libido's gone and if I get some then premature ejaculation and blunted orgasm. Also I grew some tits and belly, blame more the morphine for than SSRIs but these aren't innocent about lowering dopamine (thus possible anhedonia) and increasing prolactin (makes one lethargic as well as does grow tits afaik).

Only MAOI I've tried was moclobemide and found it to be absolutely useless, just gave me brain fog but no positive effects. Still, would try out Parnate or Nardil but they're not available here, nor is selegiline.

 

[speedlimitssuck89]

Just an update. I went with moclobemide in the end. I felt immediate relief within a couple of days of taking it, but after several weeks I stopped noticing it. It also did something funky to my bowels, but I can't say what. IBD (not to be confused with IBS) patients often have excess gut serotonin and I wonder if the drug somehow amped it up locally.

During the time when it was working, it felt great and I would endorse this drug. My sex drive went up, I had more wakeful energy, and my spiraling suicidal thoughts were gone. I was taking 150mg twice daily, btw.

The twice daily dosing was a pain because I could never get the timing just right along with my other medications, plus taking it with food. It still worked better than an SSRI ever did though.

nice. so you'd say it initially helped with anhedonia?

 

[Foreigner]

nice. so you'd say it initially helped with anhedonia?

It initially helped with everything, and then the effect wore off after about a month. I stopped it without tapering and there were no problems, which was a nice change compared to other antidepressants I've taken in the past.

 

[fastandbulbous]

Oh you don't even need the nose for MXE to be good, initially I only did sublingual some 5-20mg, it was one of the greatest drug experiences so far. Also thought they should make an XR pill out of that stuff and market as an antidepressant. The difference is that with K one's supposed to be good with occasional use 1-2x a week and then develop a protracted antidepressant effect while with MXE different people might profit from being constantly on a very low dose of it. Don't know whether tolerance would render it ineffective after some time or not, as long as one isn't exceeding these low dosages. There's also a paper suggesting MXE for treatment resistant depression but with the worldwide ban it's gone forever.. the MXE derivates currently available, at least some of them, have potential too but they will also be banned sooner or later. It sucks that K is the only constant thing around because I and many find it to be cold and clinical, and I get the same amount of rebound/comedown time from most if not all arylcyclohexylamines, so these with longer duration make a better math, and those more potent are easier on the bladder.

When I was younger (17-22) I was using DXM for its rapid and sustainable antidepressant effects, it made a difference like night and day in my ability to keep a job or socialize but over time it turned against me, nowadays it's just a psychosis inducing agent.


I was on antidepressants for most of my adult life (around 15 years), tried almost all of the SSRIs, some SNRIs and others like bupropion, opipramol, tianeptine etc. Not for depression but social anxiety. None of them did any real good besides the first months on venlafaxine, where I was hypomanic - a good state to be for somebody with anxiety disorder, but also dangerous and imo it should be a warning sign not to continue on antidepressants because later I'd develop treatment resistant depression and physical addiction to SSRIs. Emotional blunting as well, that was welcome though, and sexual side effects - it's still fucked up now, after being down on 37.5mg venlafaxine, and I have little hope for a full recovery for the more near future. Libido's gone and if I get some then premature ejaculation and blunted orgasm. Also I grew some tits and belly, blame more the morphine for than SSRIs but these aren't innocent about lowering dopamine (thus possible anhedonia) and increasing prolactin (makes one lethargic as well as does grow tits afaik).

Only MAOI I've tried was moclobemide and found it to be absolutely useless, just gave me brain fog but no positive effects. Still, would try out Parnate or Nardil but they're not available here, nor is selegiline.

I was doing a literature search for a pharma firm, concerning mxe and it's antidepressant effects, with an eye on getting a patent on one of the isomers, up until my wife died, then everything just stopped (not just the literature search, but my whole life). I need to get back on the ball, as I told my wife I wanted to leave this world a better place than the one I was born into, and mxe's antidepressant effects seemed the way to do it. Yeah, the financial rewards would be nice for something to leave for my two nieces and my stepson, but mone has never been a motivating force with me (as long as I could afford the basics of life). Basically just a hippie at heart, but one with a gift for envisaging how drug molecules interact with receptors (and my wife said it would be criminal if I didn't do something good with it )

 

[fastandbulbous]

Just an update. I went with moclobemide in the end. I felt immediate relief within a couple of days of taking it, but after several weeks I stopped noticing it. It also did something funky to my bowels, but I can't say what. IBD (not to be confused with IBS) patients often have excess gut serotonin and I wonder if the drug somehow amped it up locally.

During the time when it was working, it felt great and I would endorse this drug. My sex drive went up, I had more wakeful energy, and my spiraling suicidal thoughts were gone. I was taking 150mg twice daily, btw.

The twice daily dosing was a pain because I could never get the timing just right along with my other medications, plus taking it with food. It still worked better than an SSRI ever did though.

Moclobemide is also useful as a drug to allow DMT oral activity (ask Ismene!)

 

[yaesutom]

In interested in trying to find a doc who will let me try the selegiline patch. Nothing has ever worked except straight up hard stimulants - that is true happiness but they make me act weird and hyper fixate.

 

[paranoid android]

It initially helped with everything, and then the effect wore off after about a month. I stopped it without tapering and there were no problems, which was a nice change compared to other antidepressants I've taken in the past.

You had no withdrawal at all? That's a nice change from shit like effexor goddamn. I would try Parnate if i actually needed it though. From everything ive seen from talking to people when i was locked up in the psych ward and online is that most antidepressants dont actually work. It doesn't help that in Canada atleast psychiatrists are so goddamn conservative and hate anything that causes euphoria. I don't think depression would be nearly as hard to treat as it is if doctors where more willing to try alternative treatments like ketamine or even amphetamines. I don't remember even being depressed when on ketamine or stimulsnts for that matter.

 

[Foreigner]

You had no withdrawal at all? That's a nice change from shit like effexor goddamn. I would try Parnate if i actually needed it though. From everything ive seen from talking to people when i was locked up in the psych ward and online is that most antidepressants dont actually work. It doesn't help that in Canada atleast psychiatrists are so goddamn conservative and hate anything that causes euphoria. I don't think depression would be nearly as hard to treat as it is if doctors where more willing to try alternative treatments like ketamine or even amphetamines. I don't remember even being depressed when on ketamine or stimulsnts for that matter.

In BC you can get ketamine therapy, but a psychiatrist has to declare you treatment resistant first. Which is hard to do.

I will never take SSRIs again. They don't work and their mechanism is poorly understood. Plus they take weeks to start doing anything.

I use ketamine on my own. I IM 15mg once per week during my worst lows and that seems to be enough. The hospitals and clinics are all doing heroic k hole doses which I don't approve of. And the Rx nasal spray is hella expensive.

Anti depressants are a scam except for citalopram, mirtazapine and old tricyclics. The huge meta-analysis they did in the UK a few years ago shows that those three are the only specific of antidepressants to truly work. Yes I know citalopram is an SSRI which contradicts my earlier statement, but for some reason it works where the other SSRIs do not.

 

[Fertile]

...Waiting for someone to ring-substitute parnate...