18 replies to this topic

[NeuroNootropic]

Every time I take Selegiline I have a positive effect on motivation in just the 3rd week which disappears quickly after that. But during all of this I've noticed that it intensifies my already existing emotional bluntness and anhedonia. Why might this be? Is my dose too high? I've tried taking 5 mg every week day, 5 mg every Monday, Wednesday and Friday, and 5 mg twice a week but all of these dosages resulted in emotional blunting and anhedonia. What's weird is that if I skip a couple of days of not taking Selegiline my baseline anhedonia and emotional blunting decreases and I'm able to enjoy somethings again. I'm guessing I need a lower dose, but which dose specifically?

 

Has anyone had this problem with Selegiline before? How would I fix this and would it matter if I tried sublingual vs oral?

[Flex]

The half life of Brain MAO-B is afaik 4-6 weeks and is inhibited afaik after 10 days á 10mg Depernyl (forgot the exact days&doses)

so You could try to take one week and stop for 3 weeks or something like that.

 

I´m too lazy to  find the corresponding paper, let me know if Youre not able to find it.

Edited by Flex, 22 May 2015 - 11:18 PM.

[NeuroNootropic]

I thought MAO-B returned to baseline after 2 weeks of stopping Selegiline? Also, I really want to stay as stable as possible. If I take it for one week and stop for 3 weeks then I'll have fluctuations in motivation where one day I'll be motivated and the next extremely apathetic. And for me, I stop feeling any effects of Selegiline after about 2 weeks. Also, in the first week all it does is make me extremely tired.

[FW900]

Even thought this seems counter intuitive, try upping your dose.Taking selegiline in dosages high enough to inhibit MAO-A yields an antidepressant-effect and that could fix the anhedonia. I suggest a dose of 10mg per day sublingually.

 

Watchout for MAOI contraindications (SSRIs, ect) at this dose. I wouldn't worry about dietary restrictions, selegiline is devoid of the cheese effect until much higher dosages, and this is especially true whenever first-pass metabolism is avoided.

[Flex]

I thought MAO-B returned to baseline after 2 weeks of stopping Selegiline? Also, I really want to stay as stable as possible. If I take it for one week and stop for 3 weeks then I'll have fluctuations in motivation where one day I'll be motivated and the next extremely apathetic. And for me, I stop feeling any effects of Selegiline after about 2 weeks. Also, in the first week all it does is make me extremely tired.

 

The peripheral mao-b has a half life of 2 weeks, look for the brain mao-b.

If You have fluctuations despite mao-b inhibition, then the positive effects are related to the Amphetamine metabolite of selegiline.

 

Btw look into this

http://www.longecity...e-2#entry728682

 

This means that it could decrease its effectiveness, though perhaps not definite (?)

[NeuroNootropic]

Even thought this seems counter intuitive, try upping your dose.Taking selegiline in dosages high enough to inhibit MAO-A yields an antidepressant-effect and that could fix the anhedonia. I suggest a dose of 10mg per day sublingually.

 

Watchout for MAOI contraindications (SSRIs, ect) at this dose. I wouldn't worry about dietary restrictions, selegiline is devoid of the cheese effect until much higher dosages, and this is especially true whenever first-pass metabolism is avoided.

 

I've taken a combination of Moclobemide 150 mg b.i.d and Selegiline 5 mg last year and while it increased my motivation, it made me extremely irritable and asocial. I would get mad at everything and I couldn't stand interacting with other people. I wanted to be left alone all the time. I found an article online where the authors studied the effects of a combination of Selegiline and Moclobemide and found that while Moclobemide decreased DHPG (metabolite of norepinephrine), the combination actually increased it and they suggested that Selegiline increases norepinephrine levels in the body. I'm very sensitive to norepinephrine. Wellbutrin XL 150 mg makes my heart race and 300 mg XL makes me feel like I'm dying.

 

Also, 10 mg sublingual is a really high dose. Zelapar is a sublingual formulation and it only contains 1.25 mg of Selegiline. This dose is equivalent to 10 mg oral. Too bad there's no zelapar in Canada. Does the oral Selegiline HCL dissolve if you put it under your tongue? Or does it have a special coating that prevents that?

 

 

I thought MAO-B returned to baseline after 2 weeks of stopping Selegiline? Also, I really want to stay as stable as possible. If I take it for one week and stop for 3 weeks then I'll have fluctuations in motivation where one day I'll be motivated and the next extremely apathetic. And for me, I stop feeling any effects of Selegiline after about 2 weeks. Also, in the first week all it does is make me extremely tired.

 

The peripheral mao-b has a half life of 2 weeks, look for the brain mao-b.

If You have fluctuations despite mao-b inhibition, then the positive effects are related to the Amphetamine metabolite of selegiline.

 

Btw look into this

http://www.longecity...e-2#entry728682

 

This means that it could decrease its effectiveness, though perhaps not definite (?)

 

 

But I also have fluctuations with Rasagiline and that doesn't have any amphetamine metabolites. And Rasagiline worked a lot better for motivation, focus, and energy than Selegiline. Only problem is that it's extremely expensive with 60 1 mg tablets going for $500!

 

Yeah, I've seen that study. But I've also seen another study where Selegiline increased dopamine levels in the striatum by around 1600% after 2 weeks of chronic use. Though, I'm not sure if 1600% was the actual number because I read the article more than 2 years ago and I can't find it now, but I'm sure it was a high percentage, more than 100%. This was in rats though so I'm not sure if it translates to humans.

 

On another note, I've noticed that when I don't take Selegiline or Rasagiline after taking them for a long time, the second day I feel less anhedonic and more emotional. My enjoyment of food increases and I crave sweets. For example, last year I took Rasagiline 1 mg everyday for a month and developed a tolerance so I started to take it every week day but I skipped the weekends. This greatly reduced tolerance, but it also gave me a day of the week where I wasn't an emotionless robot. It was just on Sunday that I was less anhedonic and more emotional.

 

I've tried replicating this around 2 months ago with Selegiline, but this time around I wanted to see if it would last longer than just one day. And unfortunately, it did not. I just had one day where I was less anhedonic, and following days after anhedonia creeped back in.

 

What could this mean?

[Keizo]

What seems most effective for sublingual dosing with regular tablets (I got the Jumex brand): put the tablet or part of the tablet on a spoon, then add 1 to 4 drops of water. For my 1.25mg (quarter tablet) dose, I only need one medium to large drop. Let dissolve for 10-20 minutes.

This will create a more or less paste-like substance which you can smear on the underside of your tongue, and it will stick to it.

 

Putting the un-dissolved tablet (or part of tablet) under the tongue takes too much time and I think isn't as efficient. Maybe some brands have softer tablets though, these are very hard.

[OneScrewLoose]

The obvious conclusion to me is that selegiline is not right for you. I would try things like Prozac (few know it's a 5T2c antagonist, thus increasing dopamine in the ventral tegmental area), Wellbutrin, Vyvanse (causes the least dependence of any amphetamine, very steadily released in the body), L-Dopa + EGCG, and some others. Check your PM.

[FW900]

 

I've taken a combination of Moclobemide 150 mg b.i.d and Selegiline 5 mg last year and while it increased my motivation, it made me extremely irritable and asocial. I would get mad at everything and I couldn't stand interacting with other people. I wanted to be left alone all the time. I found an article online where the authors studied the effects of a combination of Selegiline and Moclobemide and found that while Moclobemide decreased DHPG (metabolite of norepinephrine), the combination actually increased it and they suggested that Selegiline increases norepinephrine levels in the body. I'm very sensitive to norepinephrine. Wellbutrin XL 150 mg makes my heart race and 300 mg XL makes me feel like I'm dying.

 

Also, 10 mg sublingual is a really high dose. Zelapar is a sublingual formulation and it only contains 1.25 mg of Selegiline. This dose is equivalent to 10 mg oral. Too bad there's no zelapar in Canada. Does the oral Selegiline HCL dissolve if you put it under your tongue? Or does it have a special coating that prevents that?

 

Zelepar is intended for people suffering from Parkinson's disease and dosages of it are usually kept low to achieve only MAO-B inhibition.

 

I don't think it is a high dose for your need. EMSAM is intended for depression and the target is to achieve MAO-A inhibition. Like sublingual, it also avoids first pass metabolism and the bioavailability likely surpasses it. The lowest dose is 6mg/24hr and the highest is 12mg/24hr. 10mg sublingual is a standard antidepressant dose.

 

Yes, oral selegiline (at least selgin) dissolves if you put it under your tongue. You might want to crush the tablet up so it dissolves more quickly.

[NeuroNootropic]

Has anyone else had this problem with Selegiline? I'm thinking that my dose may be too high.

[Keizo]

at 1.25mg sublingual every day I notice back & neck massages are less pleasurable 

it also makes me less socially anxious

Edited by Keizo, 05 July 2015 - 10:29 AM.

[Flex]

The obvious conclusion to me is that selegiline is not right for you. I would try things like Prozac (few know it's a 5T2c antagonist, thus increasing dopamine in the ventral tegmental area), Wellbutrin, Vyvanse (causes the least dependence of any amphetamine, very steadily released in the body), L-Dopa + EGCG, and some others. Check your PM.

 

Could You please mention possible Post-SSRI sexual dysfunction, when suggesting SSRI´s ?

http://wp.rxisk.org/...sfunction-pssd/

 

It might not affect everyone but You dont know whom and this lasts in some cases for decades

Otherwise those poor guys will stay on Forums like this in the attempt to revert their "brand new problem"

 

Edit: 5-ht2c inhibition is fairly not a big deal, at least for me.

I didnt felt anything great form the inhibition.

 

Mirtazapine or any other atypical Antidepressant does this, like:

Opipramol, mianserine, cyproheptadine

 

or the trycyclics, like: Clomipramine, amitriptyline, nortriptyline (and so on)

https://en.wikipedia...5-HT2C_receptor

 

Edit 2: All of those above dont cause PSSD

Mianserine is afaik the only one with problematic side effects like Agranulocytosis

 

IIRC, the 5-ht1B receptor has a inhibitory action on the VTA, though I wouldnt guarantee it.

 

If Youre interrested into VTA firing, then consider the Hippocampus

this one activates the NAC, which deactivates the inhibition of the VTA caused by the Ventral palladium

 

Glutamatergic Afferents from the Hippocampus to the Nucleus Accumbens Regulate Activity of Ventral Tegmental Area Dopamine Neurons

http://www.jneurosci...21/13/4915.full

See also Fig. 5.

 

Edit 3:

You dont want to be responsible for something like this ?:

 

Does anyone think about suicide?

http://www.pssdforum...cb8686d89b211ba

Edited by Flex, 05 July 2015 - 02:42 PM.

[OneScrewLoose]

First of all, all those drugs you listed are inverse agonist. For some reason, they do not seem to have the same doopamine-releasing effects in the VTA. here's the list:
https://en.wikipedia...eceptor#Ligands

Second, PSSD and it's mechanisms have yet to be illucidated though. it seems to have a large psychogenic component due to people regressing into depression and anxiety after discontinuation. Attached is a study that explores the occurances of PSSD in those who don't regress after discontinuation. It does occur, but seems quite rare.This study that explores that.

Also, be aware that Prozac is a relatively weak SRI compared to others like paroxetine. Worrying about PSSD from an SSRI is like worrying about tardive dyskenisia from a second-gn antipsychotic. Yes, it's possible, but not very likely relative to the number of people taking the drug.

[OneScrewLoose]

Oops, it didn't get attached. Here ya go.

Attached Files

•  PSSD.pdf   140.52KB   11 downloads

[NeuroNootropic]

Just wanted to make a quick update. I've been taking 1.25 mg sublingually for 7 weeks now (started on February 10). I take it on the weekdays and skip the weekends. Here's what I've noticed:

 

Benefits

• Slightly increased motivation
• Slightly improved focus
• Slightly decreased social anxiety
• Reduced brain fog, though it's not consistent
• Very slight decrease in anhedonia

Adverse effects

• Headache first 2 weeks
• Dizziness first 2 weeks

I haven't noticed any emotional blunting this time around and it's very slightly decreasing my anhedonia rather than increasing it. But, I've been taking it with methylfolate, which I started in September of last year. It could be that methylfolate is potentiating it.

 

It actually makes sense that methylfolate and selegiline would be synergistic as methylfolate increases BH4 and selegiline increases the activity of tyrosine hydroxylase (in low doses). Tyrosine hydroxylase requires BH4, along with other co-factors, to produce L-DOPA. I've noticed that not taking my multivitamin on a regular basis greatly decreases the benefits of selegiline. Not sure exactly why, but L-DOPA does require B6 to get converted into dopamine so it could be my B6 levels are getting depleted.

 

But, tolerance has been an issue. The first 4 weeks were great, the benefits were weak but apparent, but now the effects are so subtle that it's like I'm not taking selegiline. Not sure what to do now, should I increase the dose to 2.5 mg sublingual? Should I just take a week or two off and see what happens?

[NeuroNootropic]

I tried taking 2.5 mg sublingually but it just made me irritable, anhedonic, less motivated and just moody in general. I didn't experience any increased benefits from that high of a dose. I dropped back down to 1.25 mg sublingually but now it's even less effective than before I tried taking 2.5 mg. I think it may have something to do with tyrosine hydroxylase being downregulated. I've noticed that methylfolate isn't affecting me as strongly as it used to and methylfolate works by increasing BH4, which is a co-factor for tyrosine hydroxylase.

 

Also, in the first few weeks I started taking selegiline, I felt a strong stimulant effect as the tablet melted in my mouth. My heart would beat faster and stronger, but now I don't feel anything from taking it sublingually. So there's definitely some tolerance issues at play here.

 

 

[mbdrinker]

I have found impotant info in russian mashkovsky famous book on medical aids which is absent everywhere. Holy: i have not even supposed that jumex can be so harmful. To prove my words - take volume ii of the book and read just the last page about юмекс. You will find out that jumex blocks sinthesis of serotonin, noradrenaline and adrenaline which increases concentration of dopamine, ie it blocks transformation of dopamine into the last two with also bad impact on seratonin. No wonder it does not act as normal antidepressant. As a result levodopa would be less harmful and more antidepressive.

[kurdishfella]

weird for me dopamine makes my positive emotions more strong and hide the negative ones.

[mbdrinker]

I confirm this. It gives energy and mood boost, especially helpful for loosing weight on diet! Kind of reanimating. I just wanted to underline the fact that its effect is opposed to that of classical ads. Perhaps psychostimulation is not as dependant on sero and adrenaline as they claim. What matters is euphoria and mechanisms to get it can be different