9 replies to this topic

[genesis svk]

Doe's anybody have any experience with selegiline? Is there any addiction to it? I'm using 2.5 mg/day as nootropic and stimulant but I'm afraid that when I discontinue then I will have symtoms like parkinson disease due to decreased level of dopamine and dopamine receptor sensitivity or down regulation of DA receptors.

[MP11]

Doe's anybody have any experience with selegiline? Is there any addiction to it? I'm using 2.5 mg/day as nootropic and stimulant but I'm afraid that when I discontinue then I will have symtoms like parkinson disease due to decreased level of dopamine and dopamine receptor sensitivity or down regulation of DA receptors.

Does less dopamine provoke these symptoms? I've never heard of it before but also haven't looked into it too much. I'd like to hear more about it if you have any links or other info.

[dopamine]

Doe's anybody have any experience with selegiline? Is there any addiction to it? I'm using 2.5 mg/day as nootropic and stimulant but I'm afraid that when I discontinue then I will have symtoms like parkinson disease due to decreased level of dopamine and dopamine receptor sensitivity or down regulation of DA receptors.

I highly doubt Selegiline in low doses would cause a serious pathology like Parkinson's disease, even over extended periods of time. However, 2.5 mg/day probably won't produce any kind of stimulant effect, as Selegiline is not a stimulant; rather, it is a relatively selective MAO-B inhibitor, with some neurotrophic effects independent of the latter mechanism of action (comparisons are often made with BPAP, a "catecholamine activity enhancer" substance). I would think more about why you are using the drug in the first place, rather than about possible downstream effects on the DA system.

[rabagley]

Doe's anybody have any experience with selegiline? Is there any addiction to it?

Nobody has reported physical or psychological addiction. The effects (increased confidence and libido are frequently reported) can be so useful as to incentivize continued use, but in my experience, this is below the threshold of addictive behavior.

I'm using 2.5 mg/day as nootropic and stimulant but I'm afraid that when I discontinue then I will have symtoms like parkinson disease due to decreased level of dopamine and dopamine receptor sensitivity or down regulation of DA receptors.

That's extremely unlikely. Selegiline is a permanent, selective MAO-B inhibitor (at doses under 20mg/day). The word "permanent" is significant. The affected MAO-B must be replaced as selegiline completely destroys it and a part of the process that makes MAO-B. It will take several weeks for the effects of even a few days' use to fully wear off and dopamine levels will slowly return to normal (or a tiny bit higher).

Also, you have Parkinson's when the glial cells in the substantia nigra are damaged and dopamine concentrations fall off. It's not a receptor problem, it's a production problem. If anything, because selegiline is also a PEA upregulator and neuroprotectant for glial cells, every dose of selegiline you take reduces your chances of getting Parkinson's disease by protecting those dopamine factories.

There are downsides to chronic use, however, related to (as you suspected) reduced sensitivity of dopamine receptors. There is also the potential that accumulation in your tissues may cause selegiline to lose it's MAO-B selectivity becoming a simple MAOI (and then you need to pay very close attention to your diet to avoid cheese, wine, and other sources of taurine). To avoid these issues: take vacations from the nootropic dose (1 month on 2 months off) or only use the nootropic dose before "big events" where the increased confidence and/or libido will be helpful. I take the neuroprotective dose for my age (1mg 2x week) and I have 5mg pills that I take when I need to. If I take one of the 5mg pills to help with a presentation, I skip the next two low doses.

As long as you're not taking 5-10mg/day for decades, the effects are likely to be positive. Even then, the effects may be more positive than negative, but there are risks to be aware of. But don't get yourself in a twist over what you've already taken. You're doing just fine.

[Application]

Just my experience... but, I used the patch form of Selegiline (EMSAM) for a couple of weeks in extremely low doses. I mean like a couple of hours per day maximum of the lowest dose patch. I found it extremely stimulating to the point of causing agitation sleep problems and other side effects.

When I discontinued it, my mood and energy plummeted and eventually bottomed over a period of about 10 days before recovering back to pre-usage levels (not depressed). Maybe others are less sensitive to the meth metabolites of this drug, but I never felt much else.

[rabagley]

Just my experience... but, I used the patch form of Selegiline (EMSAM) for a couple of weeks in extremely low doses. I mean like a couple of hours per day maximum of the lowest dose patch. I found it extremely stimulating to the point of causing agitation sleep problems and other side effects.

When I discontinued it, my mood and energy plummeted and eventually bottomed over a period of about 10 days before recovering back to pre-usage levels (not depressed). Maybe others are less sensitive to the meth metabolites of this drug, but I never felt much else.

Um, probably not. There's a nearly 100% chance that you felt was an incredibly high dose of selegiline in your brain resulting in a substantial upregulation of dopamine. Take a look at this document on EMSAM, specifically page 3: http://www.selegilin...iline-EMSAM.pdf

Transdermal dosing results in substantially higher exposure to selegiline and lower exposure to metabolites compared to oral dosing, where extensive first-pass metabolism occurs

In fact, the measured blood plasma levels of selegiline indicate that a 6mg transdermal dose provides the same plasma levels as a 200mg oral dose (20-40x the typical 5-10mg nootropic dose), but with much lower metabolite levels than even a 5mg oral dose. Most of the metabolites are produced in the gut and first pass through the liver. The transdermal form of selegiline is an incredibly powerful dosing agent.

Finally, as was also discussed in the other selegiline (deprenyl) thread, the isomer of methamphetamine (L-methamphetamine) produced by the metabolism of selegiline is completely inactive in the human body, so it's not really possible that that the low levels of that metabolite that occur with transdermal dosing caused any of the effects you noted.

Edited by rabagley, 28 December 2007 - 10:56 PM.

[StrangeAeons]

I'm a little astonished at the prevalence of selegiline here on the boards. I had heard about and considered it before I signed up here, but I was under the impression that at doses about 1mg there was risk of "bleedover" as far as MAO selectivity (i.e. it could turn into good ol' fashioned antidepressant MAOI's) thus requiring significant dietary restriction of tyramine and tryptophan to avoid hypertensive crisis or serotonin syndrome. Apparently nobody here has voiced any worries about the "cheese effect".
Personally I don't touch anything that has anything to do with dopamine. I was on Geodon for a while (a dopamine antagonist) and that was hell; but I was also on Requip (a dopamine agonist) and as soon as I got to the third dosage in my free starter pack, that was hell too; it actually felt about the same as the withdrawal sensation I got from the Geodon. Damned idiosyncratic neurophysiology.

[rabagley]

I'm a little astonished at the prevalence of selegiline here on the boards. I had heard about and considered it before I signed up here, but I was under the impression that at doses about 1mg there was risk of "bleedover" as far as MAO selectivity (i.e. it could turn into good ol' fashioned antidepressant MAOI's) thus requiring significant dietary restriction of tyramine and tryptophan to avoid hypertensive crisis or serotonin syndrome. Apparently nobody here has voiced any worries about the "cheese effect".

My understanding is that selegiline starts to lose it's MAO-B selectivity around the 20mg/day oral dose. The notoriously (albeit selectively) conservative FDA has stated that there is no need for dietary warnings at doses below 20mg/day.

There are people who worry about accumulation in tissues resulting in an eventual loss of MAO-B selectivity. Based on the half-life (2 hours), I don't think that's possible. They're mistaking the length of time that selegiline affects MAO-B levels for the presence of selegiline in your system. There's also some belief that if the selegiline is all out of MAO-B to suppress that the MAO-A must fall. This seems to ignore the observations that it's a threshold concentration of selegiline which causes the MAO-A to be suppressed.

I wouldn't worry about nootropic doses of selegiline (5-10mg) having that much effect on your ability to eat old cheese, though I would be careful with nootropic dose over any length of time simply based on the observation that trying to permanently alter neurotransmitter levels rarely achieves the intended goal (this includes personal observations of SSRI, SNRI and MAOI side effects in my own family). I would definitely take frequent vacations (month on, month off, at an absolute minimum). Personally, my chronic usage is 1mg twice a week of the liquid citrate. This seems to avoid the MAOI effects entirely.

I would be especially careful with the transdermal delivery of selegiline. The 6mg EMSAM patch (the smallest patch) results in blood plasma levels equivalent to a 200mg oral dose. It's spectacularly different, and would be very dangerous to take with any assumption about equivalent effects.

Personally I don't touch anything that has anything to do with dopamine. I was on Geodon for a while (a dopamine antagonist) and that was hell; but I was also on Requip (a dopamine agonist) and as soon as I got to the third dosage in my free starter pack, that was hell too; it actually felt about the same as the withdrawal sensation I got from the Geodon. Damned idiosyncratic neurophysiology.

That reluctance is smart. Stay with it. Personally, I very rarely take nootropic doses of selegiline (one 5mg tablet every two months or so). I do take a neuroprotective dose on a chronic basis (which I cut out for a week if I've taken the nootropic dose), but I don't notice any of the nootropic effects with my twice-weekly dose.

[superdopa]

I've used selegiline for months at a time and when i come off it I don't really crash or anything like that. It's more like I just feel like the old me. Not as quick off the ball, less motivated, difficulty focusing; all problems i had before using selegiline.

[gray.bot]

My understanding is that selegiline starts to lose it's MAO-B selectivity around the 20mg/day oral dose. The notoriously (albeit selectively) conservative FDA has stated that there is no need for dietary warnings at doses below 20mg/day.

I would be especially careful with the transdermal delivery of selegiline. The 6mg EMSAM patch (the smallest patch) results in blood plasma levels equivalent to a 200mg oral dose. It's spectacularly different, and would be very dangerous to take with any assumption about equivalent effects.

You've gotta be careful with these numbers for the following reason:

1- genarally, an oral dose will be absorbed at 10%
2 - at a maximum, if eaten with a heavy meal with fat in it, the absorption is increased 3-5 times (maximum of 50%)

This is where I think the FDA got the 20mg a day oral dose - they figure at the best someone taking 20mg will maximally absorb 10mg which is the threshold for MAOA selectivity.

BUT

When it comes to a manufacturer stating how strong their EMSAM patch is - which is more impressive, 40% stronger or 200% stronger?

I believe they have taken the lower oral absorbtion dose as the basis for the the calculation, and hammered the 'selegiline isn't absorb orally, buy our patches today!' angle.

Because you can simply dissolve a selegiline tablet under your tounge sublingually and absorb all of it directly.

10mg under the tounge is different to eating a 10mg pill, which is different to eating a 10mg pill with a big meal which is definitely different to 10mg EMSAM patch (well they come in 6, 9 and 12 but you get the idea)

It's not what you put in that counts, it's what you actually absorb!

(don't get me started about gut issues, antibiotics or the like)