Stimulants Selegiline with Vyvanse - have I microdosed amphetamines?

[Bioshockszz]

I take 30mg Vyvanse daily. Today I tried 2.5mg Selegiline. Now what I am worried about is that Metabolites of Selegiline include L Amphetamine - how much L Amphetamine metabolites from 2.5mg Selegiline I don’t know.


Vyvvanse metabolises into D Amphetamine. Now what I am worried about is I have about permanently reducing tolerance and increasing dopamine sensitivity through micro dosing ie is the metabolites of Selegiline equivalent to a microdose of amp? I took the elvanse at 12pm and the selgeline at 3pm. The permanent reversal of tolerance can apparently lead to problems sleeping, tics etc.


But what I’m thinking is that I am gradually getting d amp throughout the day and I’m getting l amp from the Selegiline once it metabolised, so I might not have actually microdosed there? Does the fact that one is L Amp and one is D amp change this?


Either way I did not get a good feeling at all from the Selegiline so I won’t be using it again. But have I effectively microdosed there? I have been very worried about causing potential permanent changes and I should have researched more.

I believe the phenomenon is called hormesis and is subject to debate? I feel okay now but I probably took both too late in the day. The Selegiline was horrible for me I could really feel the amp metabolites which were too much for me, similar too IR Dex which doesn’t work well with me either. I know Vyvanse metabolites to dex, but it’s mechanism works really well for me.

Back to the point I read the microdig even once can cause the permanent effects on sensitisation. What are people’s thougts I am paranoid at the moment.

 

[Scrofula]

Howdy, welcome to bluelight, and round two of the inexplicable anti-Parkinsonian agent questions. Those are generally bad things to play with.

SELEGILINE IS NOT SAFE TO USE RECREATIONALLY.

IT IS NOT SAFE TO TAKE WITH VYVANSE unless your doctor gave you instructions, which you then need to follow.

It's also not safe to take meth/amphs or other drugs for a week or two after this.

Selegeline does produce a small amount of levo-amphetamine when metabolized. Less than you probably get from the dandruff of a Benzedrine user. That makes it easy to call "clinically insignificant" without trying to figure out where you got the idea of permanent tolerance changes or micro-dosing. I mean, follow-up and I'm happy to discuss, I just needed to get the warning up before I make dinner.

Selegiline's an irreversible MAO-B inhibitor, but can inhibit MAO-A in high dose (I'm looking up how high). Because it has a low oral absorption, that means there's potential to get higher-than-intended doses by tweaking your guts, which is something the BL audience does my default, mainlining grapefruit juice and doing DIY colon resections. It comes as a patch too, which no BL member has ever used on their arm, they either smoke or suck on them, so . . . don't do that.

That means it could easily turn into a blanket MAO-I (so no backup A or B) and suddenly cheese is lethal. Being irreversible, you'd have to wait for the enzymes to turn over, not the drug to clear, before you could feel safe eating chocolate. That could take over a week.

It's safer than old-school MAOIs, but it is NOT SAFE for off-label experimentation.

 

[Bioshockszz]

Howdy, welcome to bluelight, and round two of the inexplicable anti-Parkinsonian agent questions. Those are generally bad things to play with.

SELEGILINE IS NOT SAFE TO USE RECREATIONALLY.

IT IS NOT SAFE TO TAKE WITH VYVANSE unless your doctor gave you instructions, which you then need to follow.

It's also not safe to take meth/amphs or other drugs for a week or two after this.

Selegeline does produce a small amount of levo-amphetamine when metabolized. Less than you probably get from the dandruff of a Benzedrine user. That makes it easy to call "clinically insignificant" without trying to figure out where you got the idea of permanent tolerance changes or micro-dosing. I mean, follow-up and I'm happy to discuss, I just needed to get the warning up before I make dinner.

Selegiline's an irreversible MAO-B inhibitor, but can inhibit MAO-A in high dose (I'm looking up how high). Because it has a low oral absorption, that means there's potential to get higher-than-intended doses by tweaking your guts, which is something the BL audience does my default, mainlining grapefruit juice and doing DIY colon resections. It comes as a patch too, which no BL member has ever used on their arm, they either smoke or suck on them, so . . . don't do that.

That means it could easily turn into a blanket MAO-I (so no backup A or B) and suddenly cheese is lethal. Being irreversible, you'd have to wait for the enzymes to turn over, not the drug to clear, before you could feel safe eating chocolate. That could take over a week.

It's safer than old-school MAOIs, but it is NOT SAFE for off-label experimentation.

Hi Sir,

I appreciate your response but your lack of knowledge on the things I have mentioned doesn?t provide me with much comfort. At doses lower than 10mg, selgeline is MAO-B inhibitor only and has actually been found to be neuroprotrctive with amphetamines at these doses.

With regards to microdosing amphetamines and the potential to permantly affect the dopamine receptors and reverse tolerance you need to research this also. It?s not a proven fact but ?hormesis? is widely discussed online. So the fact that the l Amphetamine metabolites from Selegiline are very very low worries me even more. I just don?t know if this sensitivity could occur from a microdosing of l amp in this way.

Its also in no way a recreational dose. The only thing I overlooked was the potential ‘microdosing sensitisation of Amphetamine” effect which if you do a quick google if you will find much content on. It is questionable but either way I’m trying to find out if Selegiline constitutes a microdose of Amphetamine?

 

[Bioshockszz]

The amphetamine metabolites from Selegiline may also be responsible for its therapeutic effects according to a research paper so that would make it clinically significant

This is around microdosing: https://www.google.co.uk/amp/s/amp....l6/sensitizationupregulation_of_dopamine_via/

this potential permanent effect really worries me if I have microdosed l amp from the selegeline

 

[CFC]

Bioshockszz: you haven't microdosed. You take 30mg vyvanse daily, which means there's always some in your body.

By the logic you're using, anyone who takes any drug is microdosing because at some point the serum or tissue concentration will always be 'micro'.

You should also probably try reading more about sensitisation and how it works before assuming you know Scrofula's level of knowledge. His post is perfectly valid.

 

[Bioshockszz]

Bioshockszz: you haven't microdosed. You take 30mg vyvanse daily, which means there's always some in your body.

By the logic you're using, anyone who takes any drug is microdosing because at some point the serum or tissue concentration will always be 'micro'.

You should also probably try reading more about sensitisation and how it works before assuming you know Scrofula's level of knowledge. His post is perfectly valid.

Scrofulas knowledge on drugs is probably vast and I appreciate his response but his knowledge on selegeline was clearly lacking that is all I was saying, it’s not an MAOI-A inhibitor at 2.5mg

Well it seems to be a problem specific to stimulants and dopamine receptors. There was a research paper where this sensitisation occurred in rats for two weeks and primates for 2 years, sometimes even permanently, when microdosing amphetamines. There?s also anecdotes from users of Ritalin and other stims.

i hope you?re right and think you?re right that I haven?t microdosed but I?m not 100% convinced.

i won?t be taking selegline again, not because it?s an MAOI but because of the metabolites. Even if they weren?t a microdose I don?t react well to l amp or l amphet

do you know what percentage of selegeline gets converted to l amp? It’s not anywhere on the internet. Say it’s 10%, so 0.25mg l amp. Why is that not a microdose? Just playing devils advocate as you seem to be unaware of this microdosing causing reverse tolerance to stims and dopamine regulator sensitisation that I have seen a lot of anecdotal evidence on

 

[Scrofula]

I'm sorry, OP, think you misunderstood me.

I have to double-down on the boilerplate first: THIS WILL NOT LOWER YOUR AMPH. TOLERANCE, VIEWERS AT HOME. BUT MIGHT KILL YOU.

At normal doses (for depression and Parkinson's disease), it inhibits MAO-B. So we can both agree on that, right? At high doses it also inhibits MAO-A. Bluelight users thrive on ways to increase oral absorption of drugs, so that's necessary to point out here, even if you'd never take super-therapeutic doses.

At your stated dose of 2.5mg, even 100% conversion to l-amphetamine could be neglected. You were expressing concern over a dose that would be less than a milligram absorbed, and a final brain exposure in the tens of micrograms.

That is not a form of micro-dosing with any clinical relevance. If you have a ref. for how the l-amphetamine produced from selegiline metabolism contributes to therapy, I would love to see it.

That enantiomer, for one thing, has no appreciable interaction with dopamine systems. It's main role as a nuisance comes from acting as a sympathomimetic--it increases heart rate and blood pressure, causes vasoconstriction that clears your sinuses, but has no reinforcement by itself.

There are anti-depressants that work by blocking norepinephrine reuptake or stimulating NE autoreceptors in the brain; but these would require an unsafe equivalent of l-amphetamine to make it a viable therapy.

The only things that permanently affect dopamine receptors do so by killing the neurons that express them, which usually kills the person hosting them. Otherwise they turnover in an ebb and flow depending on circumstance. It's an odd thing for a typical blueligher to worry about anyway--most of them dream of ways to reverse tolerance, especially for dopaminergic drugs.

The hormesis you mention does not relate to taking microscopic doses of random drugs for opposite effect--that falls more under homeopathy, which is not a real thing. It's closer to how therapeutic doses of stimulants help with ADHD but wind up making me unfocused at the doses I take. And anyway, the l-amphetamine produced doesn't involve dopamine receptors.

It is, like I said, dangerous to combine selegiline with amphetamines, and it will not reverse tolerance to them.

 

[Bioshockszz]

I'm sorry, OP, think you misunderstood me.

I have to double-down on the boilerplate first: THIS WILL NOT LOWER YOUR AMPH. TOLERANCE, VIEWERS AT HOME. BUT MIGHT KILL YOU.

At normal doses (for depression and Parkinson's disease), it inhibits MAO-B. So we can both agree on that, right? At high doses it also inhibits MAO-A. Bluelight users thrive on ways to increase oral absorption of drugs, so that's necessary to point out here, even if you'd never take super-therapeutic doses.

At your stated dose of 2.5mg, even 100% conversion to l-amphetamine could be neglected. You were expressing concern over a dose that would be less than a milligram absorbed, and a final brain exposure in the tens of micrograms.

That is not a form of micro-dosing with any clinical relevance. If you have a ref. for how the l-amphetamine produced from selegiline metabolism contributes to therapy, I would love to see it.

That enantiomer, for one thing, has no appreciable interaction with dopamine systems. It's main role as a nuisance comes from acting as a sympathomimetic--it increases heart rate and blood pressure, causes vasoconstriction that clears your sinuses, but has no reinforcement by itself.

There are anti-depressants that work by blocking norepinephrine reuptake or stimulating NE autoreceptors in the brain; but these would require an unsafe equivalent of l-amphetamine to make it a viable therapy.

The only things that permanently affect dopamine receptors do so by killing the neurons that express them, which usually kills the person hosting them. Otherwise they turnover in an ebb and flow depending on circumstance. It's an odd thing for a typical blueligher to worry about anyway--most of them dream of ways to reverse tolerance, especially for dopaminergic drugs.

The hormesis you mention does not relate to taking microscopic doses of random drugs for opposite effect--that falls more under homeopathy, which is not a real thing. It's closer to how therapeutic doses of stimulants help with ADHD but wind up making me unfocused at the doses I take. And anyway, the l-amphetamine produced doesn't involve dopamine receptors.

It is, like I said, dangerous to combine selegiline with amphetamines, and it will not reverse tolerance to them.

Thanks that all makes sense and has put my mind at ease.

i will tell you why I tried the selegeline, it wasn’t for reverse tolerance. The vyvvanse works so well for me but only in the morning. A second dosing causes insomnia. IR dex does not work well with me at all. And even in the morning vyvvanse has its ups and downs a bit. When vyvanse works it makes me exactly the person I want to be, it improves my work and personal relationships.

through some research I found the selegeline could potentiate, extend and smooth the vyvvanse. That seemed perfect to me but obviously it hasn?t had the desired effect which I think is due to its metabolites. It did potentiate and extend to some extent but definitely not smooth the vyvvanse. If you have any suggestions I would appreciate it.

My doctor has nothing to suggest, to be fair we have tried a lot. I was thinking rasagaline but I know that will be. A big no in your eyes

 

[Bioshockszz]

Oh and here’s your ref for how the metabolites of selegeline could be the reason for the therapeutic benefit so I still doubt your claim they are insignificant https://www.ncbi.nlm.nih.gov/m/pubmed/6803190/

But I agree if L Amp doesn’t touch the dopamine receptor then it can’t cause the effects I describe. However that is what I wasn’t sure of and is why I said in the OP I wasn’t sure if the fact the L Amp was the metabolite made a difference. I’m sure it has SOME effect on dopamine receptors at least so again playing devils advocate, why does that not constitute a microdose? Also you are making it sound like the smaller the more insignificant but the argument around this theory is the smaller the more effective as a “microdose”. Is tens of micro grams not a micro dose?

and in answer to your question why would I be worried: permanent changes to dopamine In such a way would be great for confidence etc. But there would be problems with sleep and potentially tics etc

i am also highly sceptical of the whole microdosing of stims leading to permanent changes but there is one research paper and quite a few anecdotes to back it up so it can’t be completely written off

 

[zephyr]

Im just curious as to why there seems to be some kind of argument about drug knowledge as clearly theres a lot on this board, its not a competition as to who is the drug genius and the OP did come asking for advice and took his own anyway.

 

[Bioshockszz]

There’s no argument whatsoever, there’s just questioning of points and presentation of evidence. Questioning is how you learn, just accepting things is the worst thing you can do in life. Also getting things wrong is how you learn not getting things right and I’m playing devils advocate and I’ve said that. If you knew what that means it means putting a point forward with the expectation or hope that someone will disprove that so you can be certain what the other person is saying is true. Have no interest in being a drug genius on an Internet forum. I have an interest in finding what works with vyvvanse to enhance my day to day life and progress my career even further although this particular thread was more about getting confirmation that I have not microdosed with the stated effects I was worried about. I’m curious why you have posted without adding anything valuable to the discussion

 

[Bioshockszz]

Also 90% sure I agree with Scrofula, the last post was just a few counter arguments that are actually quite valid and as I said devils advocate points.

 

[Scrofula]

Ok, let's look at the last 10%, cause that's the only thing between me and winning Zephyr's contest. That and dick pics.

There's micro-dosing, and then there's "micro-dosing". One of them is just a research tool, and the other either confuses dosing regimes or blends into pseudoscience.

A pharma company may give microdoses to humans to see what the metabolic products are, while being certain they won't kill them. Then, you have something like ketamine, which at high doses is an anesthetic, but at lower doses may be effective on depression.

Mostly it seems to be an excuse to eat shrooms and LSD every day. To boost creativity or something.

I always think of my experience with the dangerous and powerful hallucinogen, deliriant and amnestic drug diphenhydramine. I used to micro-dose that every night, for years, to promote a hypnogogic state. But most people don't describe taking a Benadryl to fall asleep "micro-dosing". They'd say the 2.5 grams I've taken before "dangerous over-dosing".

So it's a relative description, there's no scientific basis for what's a micro-dose and what's a normal dose. If tens of micrograms isn't a microdose, should you try nanograms? What about a single molecule? Or, drinking water that USED to have a molecule in it? So that the water "remembers"? That's called homeopathy, and is an imaginary therapy to sell water at steep markup.

You can't restore tolerance except with abstinence. You can't prevent it and still get the effects you want. Vyvanse makes you feel good for a while, then wears off. Such is the way of all drugs. If an exogenous substance alters your brain chemistry, your body, life itself, is about shifting back the other direction. There's no escape from equilibrium.

My own dorm-room stoned way of looking at it, is it's not an equilibrium that we want anyway. You can take a smoker, stabiliized on a stimulant addiction, pulsing his cigarettes on a regular, even frequency. Spikes, and decay, in nicotine concentration, every 46.9 minutes. You could average it to equivalent 2.4mg circulating through his plasma, but if you swap a skin patch with a constant 2.4mg delivery, he will be unhappy. Bitchy. It's the pulses that he's after, not the drug itself.

If you want the positive, you need the negative.

Your link stuff:

When looking this stuff up, watch out for sloppy annotation. There's OG racemic Deprenyl, and studies on both (+) and (-) - deprenyl's by themselves. Selegiline is exclusively the (-) isomer, which corresponds to the l-stereoisomer. Then you have to be careful, because formally that's the R-isomer.

This is only important because the R can't change when metabolized to methamphetamine, and R-methamphetamine is levo-methamphetamine. And levo-amphetamine, but this abstract says the product is mainly l-meth in rats. Levometh v. dextrometh & levometh v. levoamph will make all my fellow tweakers show up with conspiracy theories about how it's all really levo-isopropylbutylamine now, not even the racemic-ISO from back in the day when the cartels were honest, so I'm not going to go further on that.

And then I found this abstract which just says feeding (+)/(d)/S-deprenyl to rats makes them addicted and tweak out, but feeding them (-)/(l)/R-deprenyl/selegiline doesn't.

For your link, they compare Sinemet piss to selegeline piss. It's hard to tell what benefit they're talking about: deprenyl treatment favored different breakdown products from Sinemet. I'd have to know what rationale they were pursuing in 1982. But they weren't necessarily saying meth/amps (levo- ones, remember) per se were the cause of whatever benefit they meant, either.

But 1982 was a big year for this drug, because this one did an elegant experiment and altered urine pH so people pissed out the meth/amphs and it didn't change anything.

It's all complicated because anything you squirt in your brain is going to affect dopamine levels. Anything you look at will too.

Here's a paper that says buccal doses at normal dose will inhibit MAO-A too which means serious drug interactions. Be careful.

 

[Scrofula]

Hey, that reddit article, I already argle-bargled all about it here (nice of reddit to not link). Probably smarter people than I am answered it better in other threads in NPD.

Bottom line with that is there's nothing to do with anything other than how rats are used to test amphetamine effects. Transferable info for human use: zero.

I should check NPD more often maybe.

 

[Bioshockszz]

Hey, that reddit article, I already argle-bargled all about it here (nice of reddit to not link). Probably smarter people than I am answered it better in other threads in NPD.

Bottom line with that is there's nothing to do with anything other than how rats are used to test amphetamine effects. Transferable info for human use: zero.

I should check NPD more often maybe.

The other thread sort of 99% convinced me. The is 1% of me a little bit paranoid just because levo Amphetamine does slightly affect dopamine, I believe 3-7 times less than d Amphetamine.

Last thing if i took 2.5mg selegeline yesterday when Can I be sure it has no longer has an effect on me: 1 or 2 weeks? Should I avoid my vyvvanse in that time? I struggle without vyvvanse. Anything else I should avoid?

i like your analogy to the smoker and the constant delivery it makes sense. The only difference is when my elvanse works well it makes me a person who is sociable and has attention at what your typical person would have as a baseline state. It’s not a high or a kick I get like a smoker might, it’s functional and puts me what might be on a par with your typical person. Hence why I am looking for extended and smoother coverage

The selegeline seems to really have affecting my digestion. I took at 3pm in the afternoon and I have had wind all night and next morning. My head also doesn’t feel great. Foolish to take it, without doctors prescription I know, lesson learned.

if I took 2.5mg selegeline Saturday at 3pm and that is the only time I have ever had it, what is the risk of starting the vyvvanse On Monday morning, realistically?

 

[Bioshockszz]

This gives me some confidence that I will be safe with my vyvvanse: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4805402/

Having combined the two yesterday, although I didn’t feel great (in fact the selegeline was horrendous), I felt nothing like raised blood pressure.

 

[AlphaMethylPhenyl]

Isn't amp metabolized by COMT?

 

[Bioshockszz]

The Selegeline doesn’t appear to have cause the sensititization that I was worried about.

I have also eaten cheese and continued with vyvanse with less increase in blood pressure than what I would get from a cup of tea so t is almost certainly MAOI B inhibitor only at 2.5mg.

with regards to the metabolites however there are only three, so the paper I posted about the metabolites causing the therapeutic benefits of selegeline were almost certainly the amp and methamp.

i can also verify from my own experience that the negative feeling or potentially even crash I got from the selegline was almost identical to what I get from IR Dexedrine but much more pronounced. I don’t know if this is because I got a little bit of amp from the selegline and my body wanted more but it was just like an amplified version of a dexedrine crash.

i can also see why they would trial it as an adhd drug because I felt it had many similarities to the IR dex both positive and negative.

Scrofula - while I agree with you around the sensitisation, from personal experience there is no way in hell that the l amp and l methamp metabolites from selegeline are clinical insignificant, not a chance. I don’t know what MaOB inhibition feels like, but I don’t feel much else now. So unless MaOB inhibition feels identical to dex and that cause what I felt the first day then in my experience, the research paper suggesting that’s selegeline’s therapeutic benefits are cause by its metabolites is very accurate. And what that benefit is doesn’t matter - you can replace the word benefit with “effect”. Because supposing that “benefit” was caused by the metabolites, it wouldn’t be a “benefit” for everyone because dex isn’t a benefit for everyone. The effect, benefit (or not in my case) felt exactly the same as the effect from dex

 

[Scrofula]

Amphetamine isn't a catecholamine, so it's not a substrate of COMT directly. But there will be dozens of metabolites of selegiline, not just three, and whether or not it's actual levo-methamphetamine having some kind of therapeutic value itself, and not the fact that it is produced instead of a toxic dopamine-interfering product (as is the case for d-deprenyl), I don't know but really doubt. IOW, the benefit is because it does NOT make addicting dextro-amphetamine.

The MOA of selegiline is pretty well established--it inhibits MAO-B but not MAO-A in your guts. Which is why when taken orally, you can still eat cheese--any excess tyramine in your diet will still be metabolized by MAO-A before reaching your bloodstream.

The conversion of selegiline to levo-methamphetamine occurs in your liver during first-pass metabolism; little of the levo-meth circulates in your brain. This also means that less than all of oral selegiline enters your brain. Unless you bypass first-pass metabolism--in that case you get a higher dose of selegiline than orally, and you start shutting off MAO-A as well.

If that happens, you have inhibition of both enzymes, and interactions with all your medications, including Vyvanse. Interactions that can be fatal.

You don't "feel" MAO inhibition, unless it's killing you. It certainly does NOT "feel like dex". Do you feel your liver enzymes being inhibited when you drink grapefruit juice? Not unless you're having serious reactions.

There are several other papers showing selegiline failing as a therapy for anything other than major depressive disorder, and as a Parkinson's disease therapy, and they've been published since 1982. Not one of them invokes levo-meth/amphs as a mechanism. Even if they did, it would not be through some kind of special interaction with dopamine receptors. Even if that was the case, you realize you've been flooding your brain with much larger doses of dextro-amphetamine? So it isn't possible for you to be "micro-dosing" amphs. And even if you were, micro-dosing is not a real thing.

 

[Bioshockszz]

That’s what I was implying: that the effects I felt from selegeline we’re not MaOB inhibition but it’s metabolites, hence why I said unless MaOB inhibition feels the same as dex, then it must be the metabolites that I felt. Given that I have taken dex it and it felt very very similar, I highly suspect that it was the metabolites and more than likely the amp and methamp that caused the effects.

micro-dosing does exist: it’s taking very small doses of something. Micro by definition is a millionth so if you took 1000000th of the therapeutic dose you are micro dosing. I agree there is no evidence that it can cause irreversible or long term sensitisation of dopamine receptors, which is what I was paranoid about only because I though got I had potentially done it. That said I wouldn’t write it off just because a research paper hasn’t said it exists, especially when there are plenty of anecdotes out there for all the different stims that this “phenomena” has occurred and especially when it’s a fact that research papers can contradict themselves in so many ways. I certainly wouldn’t be willing to risk it.

when you say about I would have been flooding my brain with much larger doses of dextroamphetamine, you are sort of completely missing the point on microdosing as you have done on a previous post. Flooding my brain with dex and dopamine or whatever was never the worry for me, so the quantity of the metabolites of selegeline was never an issue for me: the higher the better if the microdosing theory was true, in fact. It’s the fact they were very low dosee of metabolites that was the worry (if 2.5mg came out of selegeline - great that’s not a micro dose). Microdosing for increased sensitisation or reverse tolerance is about taking a very very very small dose of something you are used to in higher quantities - and it does seem very dubious AND it is only anecdotal AND more than likely complete BS - just saying that’s what the theory or “claim” from some people. So when you were saying the l amp is very very small especially when it gets to the brain, I still think you’re re-enforcing the fact that it’s a micro dose insofar as the microdose “theory” goes. It is L-AMP and not D-AMP though so
all that said I do not believe Selegiline constitutes a microdose of d amp, it’s just something I was paranoid about at the time