383 replies to this topic

[NeuroNootropic]

Cycling is an option, but not practical in my opinion. I don't want to be free from anhedonia for a week or two only to have it return the week after. Not only is that depressing, but it also affects various aspects of life. For instance, the first 2-3 weeks on Rhodiola I was more social, but now I want to be left alone. Because of this, making new friends is very difficult. My motivation also greatly decreases, i.e. the first 2-3 weeks I'll be much more open to trying new things, but after that short period I become amotivated.

[airplanepeanuts]

Cycling is an option, but not practical in my opinion. I don't want to be free from anhedonia for a week or two only to have it return the week after. Not only is that depressing, but it also affects various aspects of life. For instance, the first 2-3 weeks on Rhodiola I was more social, but now I want to be left alone. Because of this, making new friends is very difficult. My motivation also greatly decreases, i.e. the first 2-3 weeks I'll be much more open to trying new things, but after that short period I become amotivated.

My experience is that Rhodiola has to be cycled. Taking it all the time, it made me tired even though it's a stimulant. It can also cause ringing in the ear and can be hard on the stomach. It's good stuff nevertheless.

It is depressing but with with anhedonia one should not expect that it will just go away for good.

[Galaxyshock]

I know the feeling that something helps for a while but then poops out. It's harder to do tolerance-preventive measures with Adaptogens because their effects are complicated, compared to let's say stimulants. Which is why cycling is the best method with them. I agree with airplanepeanuts that anhedonia is a battle that doesn't just end easily. Maybe one can vanish it temporary with euphoriants but that usually just leads to habit and addiction, and leaves one worse. Occasional use of something recreational perhaps is alright, just to get a few positive experiences and realize that the pleasure capabilities are there.

Perika was by far the most sustainable help (it's also NMDA-antagonist along with SNDRI). Not perfect but very therapeutic and works long-term. I'm taking a break from it now, I guess I had a bit of a honeymoon with it as I'm still not completely anhedonia-free, but a lot of positive changes have remained even in the absence.

[NeuroNootropic]

An update on Jiaogulan: it improved my anhedonia symptoms in the first week, but after that it just made me worse. I'm also taking a break from Rhodiola, I stopped taking it yesterday.

I have an appointment with my psychiatrist in about 2 weeks. I'm going to ask him about trying a memantine and rasagiline combo. Though, rasagiline has no generics and might not be covered by my insurance in which case I'll ask for a selegiline prescription. I've read that memantine at 30 mg/day can treat depression or at least help it. Memantine has also been shown to reverse anhedonia in rats:

Memantine' class='bbc_url' title='External link' rel='nofollow external'>http://www.ncbi.nlm.nih.gov/pubmed/22327556']Memantine is a N-methyl-D-aspartate (NMDA) receptor antagonist and several studies have pointed to the NMDA receptor antagonists as a potential therapeutic target for the treatment of depression. The present study was aimed to evaluate the behavioral and physiological effects of administration of memantine in rats exposed to the chronic mild stress (CMS) model. To this aim, after 40 days of exposure to CMS procedure, rats were treated with memantine (20 mg/kg) for 7 days. In this study, sweet food consumption, adrenal gland weight, corticosterone levels, and brain-derived-neurotrophic factor (BDNF) protein levels in the prefrontal cortex, hippocampus and amygdala were assessed. Our results demonstrated that chronic stressful situations induced anhedonia, hypertrophy of adrenal gland weight, and an increase of corticosterone levels in rats, but did not alter BDNF protein levels in the rat brain. Memantine treatment reversed anhedonia and the increase of adrenal gland weight, normalized corticosterone levels and increased BDNF protein levels in the prefrontal cortex in stressed rats. Finally, these findings further support the hypothesis that NMDA receptor antagonists such as memantine could be helpful in the pharmacological treatment of depression.

→ source (external link)

Rasagiline/Selegiline should help with motivational anhedonia.

I'm also thinking of adding in low dose naltrexone to help with consummatory anhedonia.

What do you guys think? Has anyone here taken any of the aforementioned substances and if so, what were the benefits and side effects?

[magniloquentc0unt]

My personal SSRI experience tells me that serotonin does play a role in anhedonia
That said, I'd try moclobemide instead of Resagiline

[OpaqueMind]

I've had problems with getting excited about things for a long time ie. it didn't happen. I was one of those who recieved NSI-189 and have been using it for almost two weeks now, and I can say it's had tremendous effects on my mood and well-being. This has had knock-on effects on my anticipation of things, but since I'm not very future-oriented anyway it doesn't make a huge difference. Still, I would imagine that lots of cases of AA come from depression, or past depression and the atrophy of brains structures involved in such. Did you know that even if depression remits that the hippocampus stays atrophied and inclines you to relapse into depression at a later date? SSRIs may well work by promoting neurogenesis in the hippocampus. The mechanism by which NSI works is by increasing neurogenesis profoundly in the hippocampus (causing up to 20% growth in rodent studies) and other areas of the brain. You guys should totally get in on the next group buy if you have had a history of depression or depression itself.

[magniloquentc0unt]

I've had problems with getting excited about things for a long time ie. it didn't happen. I was one of those who recieved NSI-189 and have been using it for almost two weeks now, and I can say it's had tremendous effects on my mood and well-being. This has had knock-on effects on my anticipation of things, but since I'm not very future-oriented anyway it doesn't make a huge difference. Still, I would imagine that lots of cases of AA come from depression, or past depression and the atrophy of brains structures involved in such. Did you know that even if depression remits that the hippocampus stays atrophied and inclines you to relapse into depression at a later date? SSRIs may well work by promoting neurogenesis in the hippocampus. The mechanism by which NSI works is by increasing neurogenesis profoundly in the hippocampus (causing up to 20% growth in rodent studies) and other areas of the brain. You guys should totally get in on the next group buy if you have had a history of depression or depression itself.

Very interesting, thanks for sharing. Any source of reports/anectodes you'd like to mention?

[OpaqueMind]

Sure, if you head on over to the NSI thread you'll see various anecdotes of different peoples experiences on the last few pages. It seems that everyone who has tried it and reported back has experienced a pretty profound and positive effect on their well-being. Personally I didn't even realise I was feeling pretty down until I started NSI - my depressed baseline had become the norm, thus faded from consciousness. I imagine many more people are actually depressed than they believe, it's just that they've been that way for so long that it no longer clicks.

[NeuroNootropic]

My personal SSRI experience tells me that serotonin does play a role in anhedonia
That said, I'd try moclobemide instead of Resagiline

I've tried Moclobemide in the past at 150 mg twice a day, but it made me very sedated. Do you think my dose was too low? I faintly remember you using it or wanting to use it in the past. Maybe I should try 300 mg twice a day.

[lourdaud]

My personal SSRI experience tells me that serotonin does play a role in anhedonia
That said, I'd try moclobemide instead of Resagiline

I've tried Moclobemide in the past at 150 mg twice a day, but it made me very sedated. Do you think my dose was too low? I faintly remember you using it or wanting to use it in the past. Maybe I should try 300 mg twice a day.

Same here. Excellent anti-depressant but always made me tired for ~5h upon taking it.

[magniloquentc0unt]

No i have not taken it, but if tianeptine remains so weak on the energy motivation front ill try it.
Honestly sedation with moclobemide is something i had never heard of.. Rather the opposite actually

Edited by magniloquentc0unt, 27 August 2013 - 11:34 AM.

[lourdaud]

No i have not taken it, but if tianeptine remains so weak on the energy motivation front ill try it.
Honestly sedation with moclobemide is something i had ever heard of.. Rather the opposite actually

I've seen many anecdotal reports on it.

For around 5h upon inhibiting MAO-A, I'll get tired and my blood pressure will drop significantly. MAO-A inhibits the breakdown of melatonin, I think this may be what's causing it.
See this for example http://www.ncbi.nlm..../pubmed/3097249

[magniloquentc0unt]

Interesting.. and saddening
Did you suffer from sleep disorders? insomnia/hypersomnia?
I am already very underaroused and sleepy.
but who knows, strange balances...

[lourdaud]

Interesting.. and saddening
Did you suffer from sleep disorders? insomnia/hypersomnia?
I am already very underaroused and sleepy.
but who knows, strange balances...

Yeah, my sleep is shit and I'm constantly yawning..
However, after these initial 5 h, moclobemide is really energizing, antidepressive and pro-social. I got the best results from taking 300 mg in the afternoon.

Worst of all however is how MAO-A inhibition will mess up your sleep architecture and circadian rhythm, which is why I finally decided to get off moclobemide.
"YMMV", though. Some people report these problems going away over time.

[magniloquentc0unt]

Interesting.. and saddening
Did you suffer from sleep disorders? insomnia/hypersomnia?
I am already very underaroused and sleepy.
but who knows, strange balances...

Yeah, my sleep is shit and I'm constantly yawning..
However, after these initial 5 h, moclobemide is really energizing, antidepressive and pro-social. I got the best results from taking 300 mg in the afternoon.

Worst of all however is how MAO-A inhibition will mess up your sleep architecture and circadian rhythm, which is why I finally decided to get off moclobemide.
"YMMV", though. Some people report these problems going away over time.

and, all in all, do you feel that moclobemide has helped you? any """permanent""" improvement after discontinuation?
I wonder if all receptors downregulate, and if so, how fast and to what extent...

[lourdaud]

Interesting.. and saddening
Did you suffer from sleep disorders? insomnia/hypersomnia?
I am already very underaroused and sleepy.
but who knows, strange balances...

Yeah, my sleep is shit and I'm constantly yawning..
However, after these initial 5 h, moclobemide is really energizing, antidepressive and pro-social. I got the best results from taking 300 mg in the afternoon.

Worst of all however is how MAO-A inhibition will mess up your sleep architecture and circadian rhythm, which is why I finally decided to get off moclobemide.
"YMMV", though. Some people report these problems going away over time.

and, all in all, do you feel that moclobemide has helped you? any """permanent""" improvement after discontinuation?
I wonder if all receptors downregulate, and if so, how fast and to what extent...

Can't say I'm worse off than I was before but definitely no improvement after discontinuing the med, no.

[NeuroNootropic]

No i have not taken it, but if tianeptine remains so weak on the energy motivation front ill try it.
Honestly sedation with moclobemide is something i had ever heard of.. Rather the opposite actually

I've seen many anecdotal reports on it.

For around 5h upon inhibiting MAO-A, I'll get tired and my blood pressure will drop significantly. MAO-A inhibits the breakdown of melatonin, I think this may be what's causing it.
See this for example http://www.ncbi.nlm..../pubmed/3097249

I'm thinking of trying a combination of memantine + moclobemide + modafinil (MMM). Memantine has been shown to improve depression in this study: http://www.ncbi.nlm....pubmed/17545748

Memantine acts as an NMDA receptor antagonist, nAChR antagonist, 5-HT3 antagonist, and D2 agonist. Moclobemide acts as a reversible MAO-A inhibitor which mostly just raises norepinephrine and serotonin. Modafinil acts on the orexin, dopamine, and histamine systems. Moclobemide increases prolactin while memantine decreases it. I'm not sure if Modafinil has any effect on prolactin. Modafinil should be able to alleviate the sedation of moclobemide and could also provide an additional antidepressant effect.

What do you guys think of this combo

Also, where is everyone now in severity of anhedonia? Mine is still the same: severe, almost complete numbness.

[lourdaud]

I tried everything (modafinil, caffeine, amphetamine, bupropion, HIIT, bright light therapy etc) to offset the sedation from moclobemide but nothing worked. I may be sensitive though, some people seem to do fine on it.
Don't touch memantine, it's shit. And MAO-A inhibition seem to mess with "NMDA" already.

[magniloquentc0unt]

No i have not taken it, but if tianeptine remains so weak on the energy motivation front ill try it.
Honestly sedation with moclobemide is something i had ever heard of.. Rather the opposite actually

I've seen many anecdotal reports on it.

For around 5h upon inhibiting MAO-A, I'll get tired and my blood pressure will drop significantly. MAO-A inhibits the breakdown of melatonin, I think this may be what's causing it.
See this for example http://www.ncbi.nlm..../pubmed/3097249

I'm thinking of trying a combination of memantine + moclobemide + modafinil (MMM). Memantine has been shown to improve depression in this study: http://www.ncbi.nlm....pubmed/17545748

Memantine acts as an NMDA receptor antagonist, nAChR antagonist, 5-HT3 antagonist, and D2 agonist. Moclobemide acts as a reversible MAO-A inhibitor which mostly just raises norepinephrine and serotonin. Modafinil acts on the orexin, dopamine, and histamine systems. Moclobemide increases prolactin while memantine decreases it. I'm not sure if Modafinil has any effect on prolactin. Modafinil should be able to alleviate the sedation of moclobemide and could also provide an additional antidepressant effect.

What do you guys think of this combo

Also, where is everyone now in severity of anhedonia? Mine is still the same: severe, almost complete numbness.

i wouldnt worry about prolactin too much, ive been interested in moclobemide for a while and have recently read a paper about cathecolamines and pituary hormones concentrations after administration of single doses of moclobemide. it mentions that 300mg doses had no effect on prolactin, and 450 and 600mg doses only minimally increased prolactin concentration. of course, this might vary with continued administration.

Also,while it is true that *more serotonin = less dopamine = more prolactin*, it is also known that moclobemide increases testosterone in male patients which, which, to me, might very well mean *more testosterone = more dopamine = less prolactin*

personally i wouldnt mess too much with substances which have very variegated/misteryous mechanisms of action

I tried everything (modafinil, caffeine, amphetamine, bupropion, HIIT, bright light therapy etc) to offset the sedation from moclobemide but nothing worked. I may be sensitive though, some people seem to do fine on it.
Don't touch memantine, it's shit. And MAO-A inhibition seem to mess with "NMDA" already.

have you tried taking moclobemide before bed? 5 hours of sedation and light sleep, and then you would have a couple of hours of "stimulated" REM phase: that's be interesting

Edited by magniloquentc0unt, 19 September 2013 - 02:34 PM.

[magniloquentc0unt]

http://europepmc.org...n00052-0039.pdf

"The administration of multiple doses of moclobemide to depressed male patients caused a significant rise in plasma
testosterone. This stimulatory effect is unlikely to be mediated by the hypothalamo-hypophyseal axis, since there was
no concomitant change in the luteinizing or follicle stimulating hormone level (Markianos et al 1991)."


http://onlinelibrary...2.tb00229.x/pdf


Neuroendocrine effects
[...] In 12 depressed patients, 400 to 600 mg moclobemide
(administered daily over 4 weeks) produced a significant increase in plasma testosterone,
but failed to alter plasma levels of prolactin, LH or FSH (106). Moreover, daytime plasma
melatonin levels were not changed in healthy subjects taking single oral doses of moclobemide
(146).

[NeuroNootropic]

magniloquentc0unt, how's your anhedonia? I remember you posted about moclobemide in an old post, but I don't remember if you tried it or not. I think you mentioned that it wasn't available in your area, correct? It's actually pretty cheap here in Canada, I think it costs $12 for 60 tablets of 150 mg. Could you not order it from an online pharmacy?

What medications are you taking at the moment?

[protoject]

Is it normal to feel really crappy from moclobemide? because I swear it makes me worse. If I kept taking it would there be an improvement?

[magniloquentc0unt]

magniloquentc0unt, how's your anhedonia? I remember you posted about moclobemide in an old post, but I don't remember if you tried it or not. I think you mentioned that it wasn't available in your area, correct? It's actually pretty cheap here in Canada, I think it costs $12 for 60 tablets of 150 mg. Could you not order it from an online pharmacy?

What medications are you taking at the moment?

No, i probably mentioned that it IS available in my area, and is actually used as a first/second line treatment. I have not tried it yet, but is the next one on my list. I have been on Tianeptine for the past 6 months and i found it a very benign, althou mild med. Had zero side effects and it helped a bit on some areas, like anticipatory anhedonia! If someone mentions something, an activity, a book or idk, i happen to think "this might be interesting", whereas before there would be just apathy. It is just not as strong as i wish it would be. Also i have a bit less difficulty getting out of bed in the morning, but i could still fall asleep in every place, so hypersomnia symptoms only remotely improved. When i started Tianeptine, i was looking exactly for that, a mild antidepressant. Now, 6 months on it, i realize it might not be enough. Id say the tianeptine is 1/3 as strong as the fluoxetine i was on years ago was.

Is it normal to feel really crappy from moclobemide? because I swear it makes me worse. If I kept taking it would there be an improvement?

I dont know, but many report making it feel them sleepier/sedated for the first 4-5 hours after dosing, probably due to melatonin oxidase inhibition

Edit: heres a link to a couple of very detailed experiences reports about moclobemide. The first one is a bit... "approximate" on the language and form, but the content is there.. the second one is way more detailed and kinda mirrors my situation, thats probably why i got so excited... http://www.drugs-for...ad.php?t=215143

Edited by magniloquentc0unt, 02 October 2013 - 08:47 AM.

[protoject]

Yep, I've read those as well already (and revisited for a refresher). I dont think it makes me sleepy it just makes me feel like crap. Even at 50 mg. It's like I can't concentrate on anything and my brain feels retarded. It also worsens my insomnia. I paid money for this!!! lol. I admittedly haven't taken it for more than 2 days at a time. What I'm wondering is, if it does make me feel like crap, is there a chance that perhaps it's because I've only been on it for such a short time? This is my optimistic side asking the question, but I think the outlook is bleak. I just want it to work because I'm severely dysthymic (and other problems).

Is there anyone out there who didn't like moclobemide at first but it became better???

[lourdaud]

Yep, I've read those as well already (and revisited for a refresher). I dont think it makes me sleepy it just makes me feel like crap. Even at 50 mg. It's like I can't concentrate on anything and my brain feels retarded. It also worsens my insomnia. I paid money for this!!! lol. I admittedly haven't taken it for more than 2 days at a time. What I'm wondering is, if it does make me feel like crap, is there a chance that perhaps it's because I've only been on it for such a short time? This is my optimistic side asking the question, but I think the outlook is bleak. I just want it to work because I'm severely dysthymic (and other problems).

Is there anyone out there who didn't like moclobemide at first but it became better???

This! That's exactly how moclobemide make me feel for 5 h upon taking it. After that it was alright, to be honest I'd say it's the best AD I've tried. Had it not caused insomnia and impaired sleep quality I'd probably still be on it (taking it at bed time with some heavy hypnotic did work but this made me feel never truly rested..)

[magniloquentc0unt]

did you notice improved cognition after those 5 hours? And you both have had insomnia issues beforehand?

[protoject]

I have chronic insomnia issues before hand, so I'm really sensitive to some drugs that have insomnia listed as an effect. I didn't notice improved cognition 5 hours afterwards. It also gave this strange analgesic effect.

I'm considering maybe dosing pegabalin at night to fight against the insomnia of the drug. I use eplivanserin too but it's not very robust in overlaying that kind of insomnia.

[magniloquentc0unt]

funnily enough my shrink suggested i try moclobemide without even knowing that i was already thinking of it.
I'm wondering, does mocolobemide cause side effects similar to the SSRI in terms of emotionality? im thinking of emotional blunting and apathy...

[Sholrak]

I've from a years to now had bad both anticipatory and consummatory. The thing has worked to me for the anticipatory has been the ciltep stack. Even if I haven't taken it that day I can feel the LTP running, and a direct consequence of that it's the anhedonia reduction. And more even now, 10+ days without taking it and still the improvement is there and remains. Hard to explain, but beautiful. It's a cheap and highly valuable option, if you wanna give it a try.


I have Rhodiola on my way. How's the anxiety question exactly? It raises it or downs it? I would like to have your opinions (there seems to be lots of Rhodiola users here) while it arrives to know what to expect from it. It's Eclectic Institute brand.

Edited by Sholrak, 07 October 2013 - 04:37 PM.

[nupi]

It should reduce anxiety but has a reputation to poop out after a while, probably should be cycled