MAOI plus stim combo (shock horror)

[streetsurfer]

Ok, besides from hypertensive crisis is there any other reason not to combine maoi and stimulant?

I went behind my Dr's back and combined Selegaline and Ritalin.


http://www.ncbi.nlm.nih.gov/entrez/q...&dopt=Abstract

http://www.biopsychiatry.com/maoi-stim.htm

http://www.priory.com/psych/selegiline.htm


initally I had the dose too high and went totally manic but now I have reduced it I have found it so damn effective. I have come up with some brillant ideas on things, some I plan to pursue a patent on (and that isn't mania talking).

Now, I am a nurse, I have my own BP moniter, not some dumbshit that doesn't have a clue (though I bow to the many greater intelects purusing this thread )
The only other thing I can think of is acute arythmia, is this likely to be a problem in a 27yo healthy male?

Also, my understanding of how it potentiates the ritalin is it slows down the clearance from the dopamine receptors????
Does this mean it would have the same effect on your brain as taking high/prolonged doses of ritalin?

Is my tolerence going to go way up?

Any thoughts / info would be greatly appreciated

But read the fucking links before you start lecturing me...... please

 

[fastandbulbous]

Depending on the dose of selegeline (deprenyl) you took, it can inhibit MAO-B alone (under 10mg) or also competetively inhibit MAO-A as well (>15mg). Inhibiting MAO-A is by far the biggest concern when it comes to CNS stimulants as this is responsible for the extremes of the pressor response (eg hypertensive crisis). This should be avoided at all costs unless you have a desire to die in about the most horrible fashion I can think of.

Inhibition of only MAO-B means that only the metabolism of dopamine is significantly inhibited out of the three main monoamine neurotransmitters (dopamine, noradrenaline and serotonin), but the inhibition is non-competetive and irreversible. Basically, low doses of psychostimulants can be tolerated (and feel like a much larger dose), but larger doses can become dangerous, even life threatening, due to the possibility of developing hyperthermia. In the past, I've combined low doses of selegeline (2.5mg) with low doses of amphetamine (10mg) to good effect, but if you don't know what you're doing it's best to avoid combining the two. Don't know how it effects tolerance issues.

One important thing that has to be said (in a very loud voice): Selegeline is an inhibitor of MAO-B at theraputic dosage levels (under 10mg/day), but as mentioned above can inhibit MAO-A if the dose is larger. Combining any MAO-A inhibitor with a psychostimulant is very foolish and to be avoided at all costs. The inhibition of the breakdown of pressor like amines (noradrenaline/adrenaline/tyramine) in conjunction with a sympathetic NS stimulant can cause blood pressure to go through the roof, with potentially fatal results (blood vessels in brain 'bursting' due to high BP and causing bleeds into the brain).

 

[BilZ0r]

^ Exactly, it's destorying your biochemical safety barrier in regards to overdosing on a stimulant. I don't know the details, but it is likely that now doubling/tripling your dose which works, could lead to a dose which could put you into dangerous territory.

Also, my understanding of how it potentiates the ritalin is it slows down the clearance from the dopamine receptors????

It stops the break-down of dopamine and noradrenaline released via the action of methylphenidate.

Does this mean it would have the same effect on your brain as taking high/prolonged doses of ritalin?

In a way, but the synaptic time course of each release will be much higher because you've essentially got no way of clearing the neurotransmitter.

 

[phase_dancer]

So, streetsurfer, as with some of the responses you received in Aus drug discussion, I hope you see that there is serious potential for hypertensive crisis, particularly with your original dosages of 10mg selegiline and 40mg ritalin.

 

[nanobrain]

also, don't forget that selegeline tends to cumulation invivo and with daily admin not exceeding therapeutic dose, you may still cross over into MAO-A inhibition territory.

as of late, i have been again experimenting with selegeline and psychedelics / stimulants with some interesting effects, will post observations later.

anyone have any info on whether the MAOI-A induced excessive pressor activity may be modulated by B-blockers (propranolol)?

 

[BilZ0r]

^ Classical pharmacology says Beta-blockers make it worse, by stopping the noradrenaline mediated dilation of blood vessels, but keeping both the alpha-receptor mediated contraction, and no changing at all the real problem, serotonin.

 

[streetsurfer]

Puts on a nasal "see I told you so voice"
"So, streetsurfer, as with some of the responses you received in Aus drug discussion, I hope you see that there is serious potential for hypertensive crisis, particularly with your original dosages of 10mg selegiline and 40mg ritalin.

Did I ever dispute that? Let me ask you this; Is it better to live a life of non funtioning, loneliness and unforfilled potential or take a managed calculated risk and making your life a masterpiece

I would take a risk far greater than this to get the results I am having. Oh, and you may like to read this post I made just before I started this combo directed towards that guy who was intent on combineing Moclobemide and mdma.

http://www.bluelight.ru/vb/showthread.php?p=3506529&highlight=underfunded#post3506529

Does that seem like I am aware of the implications?

And before you say it, the difference between him and me is that;

(1) he is obviously a squid and doesn't have the slightest clue
and while what I know if SFA compared to alot on here, I think I have a better than average gasp of the issues here

(2) I am not doing this to get high and have a fun time, I am doing this to treat a chronic affliction that has up until now cast an almost constant shadow over my life. My D&A use has very much fallen by the wayside now. Meth feels dirty and nasty compared to this combo and MDMA very similar.

Back to topic, can you have higher cerebral BP than your systemic BP as a whole thereby risking CVA?

I have also thrown Gabapentin into the mix for its (debateable) mood stabilising properties and its purported benifet of people having anterior cingulate issues which by many of my symtoms it seems I may well be, unsure of the results as yet, think it may smooth things out a bit more. Any (constructive) comments, thoughts?

Some people have talked about the danger of using selegaline when you are young yet I can't find any references to this??

Will I build up a tolerence? Should I cycle it either on / off or with another antidepressant like maybe Tianeptine? Is my depression likely to relapse or will it keep working to a degree up untill the point it's residual MAOI inhibitionitory effects have worn off?

Strangely, since I started ritalin a few months back I have noticed the emergence of dyslexic type symptoms where I had none before...thoughts?

Would it be unwise to add other cerebral activators such as pirecetam or Picamilone to potentiate the gabapentin? (interesting link http://smart-drugs.net/depression-new-drugs-page2.htm )

Because I cycled to mania at a higher dose is that nesseserally an indication of Bipolar?

My thought thus far, I don't think this is going to be a combo that will be useable long term. Since begining this combo I have been very much disorganised, chaotic even, yet massively creative, insightfull, pro-social and driven.

There is no way I could work a regular job like this but it has been extreamely usefull for the project I am putting in 12 - 16 hour days on at the moment.
I guess you could call it a low grade mania, what I put to you is; Is that nessesarily a bad thing, especially compared to my depression where I was amotivated, chaotic, agitated, anxious and also not able to work?
Is there any more reason I will crash from this mania than I would get a resultant euphoria from my depressive episodes?

Please be constructive and don't berate, please look at it for what it is and not recite medical rehetoric.
Many Thanks

 

[BilZ0r]

To be honest, I've got to say, to me there is a hint of mania in your posts allready.

Because I cycled to mania at a higher dose is that nesseserally an indication of Bipolar?

No.

I think your mixing with serious psychopharmacology, and I don't think you're doing it in a responsible way. MAO-B inhibitors aren't antidepressants, they are euphoriants. It's like, I've seen about 5 people online and IRL get into opioids because they enjoy them, and they think they "treat their depression". They read all of the crap on hedweb, and take it as fact, and use it as justification to get on whatever treatment they enjoy.

You need to realise that these drugs can have perminant effects on you, and they might not be what you want. If your serious about treating whatever problems you think you have, then you have to be awear that psychological treatment with pharmacological ones is always going to better than either by itself...

Will you build up a tolerance? Certainly. Will your depression come back when you stop? Right now it seems likely, and it could very well be worse, because you'll be dealing with the withdrawal effects of your stimulant.

 

[freshout]

wow

Hey streesurfer,
Ok, this isnt giving you a hard time at all, this is just instinctual, im a pharmacy student, so the things your doing is making all my learning go "arrrrrhhhhghgggggggg!!!!!!!!!!!!!!!!!!!!!!!!!!"
But it i suppose can be done, at a relative dose anything will be safe, but i agree with the 10mg rule.
But if you are trying to regulate a semi permiant state of mania, that is really bad. Its worse than taking lots of drugs for small amounts of time. A body kept at high stress levels for large periods of time, break faster, remember that. You'll have to crash sometime, even if it is just a mild depression, it will be there.
Just be careful with yourself, as you know, combos add to the danger

 

[stvip]

"Neural degeneration following chronic stimulant abuse reveals a weak link in brain, fasciculus retroflexus, implying the loss of forebrain control circuitry"
Eur Neuropsychopharmacol. 2002 Aug;12(4):287-97.

Recommended reading.

People who have never experienced real depression and chronic mental/emotional exhaustion cannot commiserate since they do not - cannot understand its nature and the urgency of alleviating it. However, one should tread carefully on one's purported gradus ad paranssum - especially when there are several paths available, and at least some of them are mine laden.

 

[specialspack]

One important thing that has to be said (in a very loud voice): Selegeline is an inhibitor of MAO-B at theraputic dosage levels (under 10mg/day), but as mentioned above can inhibit MAO-A if the dose is larger. Combining any MAO-A inhibitor with a psychostimulant is very foolish and to be avoided at all costs. The inhibition of the breakdown of pressor like amines (noradrenaline/adrenaline/tyramine) in conjunction with a sympathetic NS stimulant can cause blood pressure to go through the roof, with potentially fatal results (blood vessels in brain 'bursting' due to high BP and causing bleeds into the brain).

Is this true with reversible MAO-A inhibitors as well?

 

[streetsurfer]

Thanks for all the replys guys. Yeah even in my last post there was like you said, a hint of mania and it makes perfect sence that keeping me in that high energy state would have some kind of consequences.

I have stopped the ritalin for the past few days, my energy levels and creativity are very much diminished but I still feel so damn good compared to just about anything I have tried.

The combo of Ritalin and Selegaline is seriously psychologically addicting. I far prefer it to meth any day for euphoria and higher thought/creativity.
I have pushed the enevolpe with this combo and found that while a bit gets you high, alot doesn't get you much higher... seems to be a definete cealing which is fine by me cos I don't feel the need to get wasted now.

I may restrict the ritalin for times when I need serious creativity or social occasions meanwhile if anyone could shead some more light on some of the questions I asked above would be gratefull

Cheers

 

[fastandbulbous]

Is this true with reversible MAO-A inhibitors as well?

Yes - it will definitely happen with the beta-carboline alkaloids such as harmaline, but the degree of severity (with competetive inhibitors of MAO-A) is dependant upon the affinity for the enzyme. Compounds with a high affinity such as harmaline (~10-6M) require a higher concentration of a sympathiomimetic drug to displace the inhibitor from the active site. As a higher concn. of the sympathioimetic drug effectively means taking a higher dose, you can see that's pretty foolish. Some of the RIMA's used clinically have less affinity and are displaced by a lower concn (and hence are safer), but most MAOI used clinically to treat depression (eg tranylcypromine, phenelzine) are irreversible, non-competetive inhibitors and are by far the most dangerous

 

[specialspack]

Yes - it will definitely happen with the beta-carboline alkaloids such as harmaline, but the degree of severity (with competetive inhibitors of MAO-A) is dependant upon the affinity for the enzyme. Compounds with a high affinity such as harmaline (~10-6M) require a higher concentration of a sympathiomimetic drug to displace the inhibitor from the active site. As a higher concn. of the sympathioimetic drug effectively means taking a higher dose, you can see that's pretty foolish. Some of the RIMA's used clinically have less affinity and are displaced by a lower concn (and hence are safer), but most MAOI used clinically to treat depression (eg tranylcypromine, phenelzine) are irreversible, non-competetive inhibitors and are by far the most dangerous

Ok, let me see if I've got this right:

RIMAs were developed because they don't cause the "cheese reaction" with tyramine, because tyramine will displace the inhibitor?

It's ok to take RIMAs with PEAs - there's been lots of attempts with harmala and mescaline?

It's not a good idea to take RIMAs with amphetamine or MDMA

 

[fastandbulbous]

Personally I wouldn't mix an MAOI (clinical RIMAs included) with an amphetamine or a phenethylamine (I'm aware people have combined harmala alkaloids & mescaline) as if it does go wrong, it's a pretty nightmarish scenario (tripping intensely combined with a hypertensive crisis - or even just really high blood pressure. That sort of headache while tripping is something I'd do my best to avoid). As with anything though, some people are bound to want to try - al;l I can say is any PEA with pressor activity is best avoided (you have to treat each one individually)

 

[nanobrain]

^what f&b said. some PEAs combine very badly with selegeline, i have read some nightmarish reports of 2C-T-7 / selegeleine combo that went horribly wrong; had a personal out of control freakout with 2C-C and selegeline.

for what its worth coming from me, i would caution strongly all but those intimately familiar with their own metabolic nuances and specific idiosyncratics against attempting such "pharmaquazihuasca" combos to "push the envelope"

selegeline discontinuation on its own brings withdrawal symptoms even at 5mg/d, with 10mg/d plus stims, the comedown is bound to be long and painful. mania will be the last of your concerns.

 

[streetsurfer]

yeah, it has been making me highly irritable as well as creative and along with a mild but scary hypertensive episode I had today it has caused me other problems I won't go into so I need to change something. May ditch the selegaline and just go gabapentin and ritalin..... shame, it was nice to feel so good

 

[yaesutom]

Wow - interesting.

Well, I don't like the idea of touching any irriversable inhibitors..

But I will say, i've combined harmaline + amphetamine, or moclobemide + amphetamine many times, so many times to where.. well, there is just no difference, with anything - its not potentiated at all, same heart rate etc, after testing small doses first etc , well its always been 100% fine.

Then again i'm a guy who can eat some harmala + DMT, and slam down some pizza, I do not follow any "maoi diet" I do think the whole 'diet' thing is typically overblown (for reversable mao-a inhibitors like harmaline) often, i mean people fasting for 24 hours and stuff before taking the harmala/line then worried about how many days they should go without "eating" etc afterwards.

Yeah.. dunno.. with me, taking harmaline never seems to affect much of anything, of course I wouldnt touch anything like MDxx with it.. but amphetamine isn't potentiated at all etc. with me.

 

[streetsurfer]

Hey all, sorry to bump this up again but got a couple more questions and I thought some people may be interested in my expeience's.

I was in a deep dark depression when I was taking this. I had just given up prozac and was taking 4 - 6 ritalin per day and I still couldn't funtion at all. I started this combo and got an instant and dramatic response to the point where I became very much manic, something I have never experienced before, at least not as profound as that.

In any case I was pretty out of control and I was dosing all over the place. At one point I was taking (oh the told you so bitchs are gunna have a field day on this one) 20-30mg of selegaline and 40 - 60mg of ritalin together as well as alcohol and meth at times and lots of chocolete.

I was monietering my bp all the time and while I became hypertensive it never became anything close to being a concern.
Now here is the interesting bit.

I cut my dosage right down to 10mg per day and cut out the ritalin. Now if I have ritalin or a bit to much chocolete I get extremely HYPOtensive. Faint, tingling of the extremitys, weak pulse, bradycardia.
Now I imagine it has crassed over in its selectability to both mao a and b but why the drop in bp? Is this like a bundle branch block? could I spontainiously arrest?
Also I would like to trip for NWE, maio's are supposed to block the effect right? What about if I dropped the dose back so it was selective again? What would be the effect then?
And a last word to the itolduso's this is the first time I have had real relief in my life, I have directing, I have motervation and should I drop dead tomorrow I would regret nothing

 

[BilZ0r]

MAOIs don't block the effect of hallucinogens, and for a lot of them, they potentiate them.

Why you get hypothensive... I'm not sure... Anyone else.