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The Anhedonia Thread

anhedonia depression attention l-dopa ssre adaptogen quetiapine consummatory anhedonia

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#61 nupi

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Posted 27 November 2012 - 01:40 PM

I know it was advised that you would check liver function on Agomelatine occasionally but I am truthfully a bit surprised that it should be very bad - any URL for that claim?

#62 Bruce6815

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Posted 28 November 2012 - 12:56 AM

I know it was advised that you would check liver function on Agomelatine occasionally but I am truthfully a bit surprised that it should be very bad - any URL for that claim?


Sure, from the manufacturer, Servier:

http://www.servier.c...agomelatine.pdf

And from the British health agency:

http://www.mhra.gov....pdate/CON199558

Note that these warnings are new, just went out in October/November 2012.

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#63 Vieno

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Posted 29 November 2012 - 12:58 PM

Okay everybody, my examinations have proceeded and here's where I stand now.

It has became clear to me that the stimulus induced pleasure that I'm lacking (i.e. consummatory anhedonia) is an opioidergic and dopaminergic/norepinephrinergic problem. Activation of the mu-opioid-receptor causes this pleasure I'm missing, but the process happens through dopamine and apparently opioids alone are not always enough to produce pleasure (anecdotal reports, google for opioid resistance etc.). The role of norepinephrine is not so clear.

About a week ago I started low-dose naltrexone (LDN) to see if increasing endogenous opioid production would help. A highly successful and respected doctor-researcher agreed with my views and believed LDN would help with consummatory anhedonia: therefore, he prescribed it for me. Naltrexone is an opioid antagonist but when taken at low doses (1-5mg/day), it blocks opioid receptor stimulation only temporarily and eventually (in some hours) increases endogenous opioid (endorphins etc.) production to 200-300%. I take it on evenings. On the first night I wake up much earlier than normally and my dreams have gotten much more vivid but that's all: no other effect. Therefore, after some days and after trying different doses I stopped taking it (temporarily) and tested something else. It must be noted that long-term use of LDN modifies the brain in a beneficial way (helps with multiple sclerosis, chronic fatigue syndrome, fibromyalgia etc.) and may be helpful in this way too, but this is extremely speculative in the case of anhedonia: no evidence.

So I tried a number of things. 200mg of codeine did nothing. 150mg of dextromethorphan did nothing. 480mg of L-DOPA with some green tea extract did nothing. 600mg of L-DOPA with lots of green tea extract together with LDN (taken on previous evening) did nothing except made me puke. I was hoping that increased endorphin production together with dopamine agonism would do something, but no. The L-DOPA I use is Mucuna Pruriens extract standardized to 15% of L-DOPA meaning that it contains a significant amount of other Mucuna ingredients which should advance the bioavailability.

There is a possibility that I'm genetically a slow metabolizer of codeine to morphine and therefore trying out a different opioid such as morphine might be worth trying. However this is unlikely. I would like to try the combination of a potent opioid like morphine with a strong stimulant like amphetamine, but have previously tried Concerta (methylphenidate) for my mistakenly assumed ADHD and all it did was made me ill (similarly to my L-DOPA experience). I also don't want to just try out all the possible combos. I prefer learning the mechanisms first, if possible: I don't want to do damage to my brain.

What can be the cause of my consummatory anhedonia? Is there reason to expect some other stimulant to work better than L-DOPA (and methylphenidate) such as a strong MAO-B inhibitor or amphetamine? Should I focus more on norepinephrine agonism and seek for an opioid + norepinephrine-dopamine stimulant combination? Since 150mg of dextromethrophan failed to work, is there reason to expect ketamine or some its derivative or a larger dose of dextromethorphan to work?

Edited by Vieno, 29 November 2012 - 01:03 PM.


#64 medievil

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Posted 29 November 2012 - 02:52 PM

Perhaps MDAI will work for anhedonia, it shifts balance to phasic release instead of tonic (the opposite causes SSRI anhedonia). Im trialling it atm as adjunct to my stimulants, far superior to SSRI's.

#65 medievil

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Posted 29 November 2012 - 04:16 PM

Ill reply to you later vieno to lazy atm.

#66 Vieno

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Posted 29 November 2012 - 04:18 PM

Perhaps MDAI will work for anhedonia, it shifts balance to phasic release instead of tonic (the opposite causes SSRI anhedonia). Im trialling it atm as adjunct to my stimulants, far superior to SSRI's.


What balance? Dopamine or something else?

Also, if mu-receptor is responsible for pleasure then how does that relate to phasic dopamine? Mu-receptor activation = phasic dopamine burst? But isn't phasic dopamine more about anticipation, motivation and reward?

Pleasurable stimulus > endorphin release > mu-receptor activation > phasic dopamine burst > pleasure? Does a MAOI increase tonic dopamine btw?

E: Yea ok no worries.

Edited by Vieno, 29 November 2012 - 04:18 PM.


#67 medievil

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Posted 29 November 2012 - 04:24 PM

no da doesnt cause reward, its just MU agonism that induces reward, not the da increase it causes.

Its all connected, as i said before i cant feel opiate reward without amphetamine, that doesnt mean DA causes reward, it just means phasic da has to be there before MU can actually cause reward, but its still MU that does it.

My roof is full of pleasure, the dopamine is the ladder but without the ladder good luck getting on my roof, something like that, lets say there are many differened ladders in the brain before you can get on my orgasmic roof.

naltrexone is often used in rehab to block the high of all recreational drugs in a injection.

Yet that injection doesnt cause anhedonia wich makes the story more complex then i tought.

Edited by medievil, 29 November 2012 - 04:22 PM.


#68 medievil

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Posted 29 November 2012 - 04:32 PM

BTW I read a Russian study on combining SSRIs and naltrexone to beat the anhedonia of recovering heroinists. Not surprisingly, it did help. But no medicine in my mind can fill up an empty life...


Hmm there must be a neurological difference btw substance induced reward and normal baseline reward, the study showing that in shizophrenics the prefrontal cortex instead of another area processes unpleasant stimuli on a area that normally causes reward kinda confirms this, despite that substances that are rewarding abolish the anhedonia while the neurological problem of the brain that has shut down normal reward to be able to allow unpleasant stimuli (far more important for survival) because of brain issues still exists.

Also DXM is a rewarding recreational substance wich does not increase dopamine at all.

#69 Vieno

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Posted 29 November 2012 - 04:51 PM

Actually, with reward I didn't mean pleasure but feelings of succeeding etc.

But anyway, decreasing tonic dopamine should make room for greater phasic spikes, so we should aim for that right? How to do it? Google finds almost nothing. Some suggest D2-receptor antagonists.

And DXM did nothing to me. If DXM can induce euphoria without manipulating dopamine activity, then my problems must not be related to dopamine? Although I'm not sure if euphoria is what DXM induces, some just suggest it for anhedonia.

Edited by Vieno, 29 November 2012 - 04:54 PM.


#70 Galaxyshock

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Posted 29 November 2012 - 05:59 PM

And DXM did nothing to me. If DXM can induce euphoria without manipulating dopamine activity, then my problems must not be related to dopamine?


What kind of logic is that?

#71 Vieno

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Posted 29 November 2012 - 07:40 PM

And DXM did nothing to me. If DXM can induce euphoria without manipulating dopamine activity, then my problems must not be related to dopamine?


What kind of logic is that?


I have no idea. Trying to figure out what the hell was I thinking 8O

Anyway. About MDAI/other serotonin releasing agents: is SSRI induced anhedonia consummatory?

#72 nupi

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Posted 29 November 2012 - 07:49 PM

if dxm only ever gave me bad trips, there something to learn from that?

#73 Vieno

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Posted 29 November 2012 - 07:58 PM

if dxm only ever gave me bad trips, there something to learn from that?


No.

Want to be more insightful?

#74 medievil

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Posted 29 November 2012 - 08:49 PM

Actually, with reward I didn't mean pleasure but feelings of succeeding etc.

But anyway, decreasing tonic dopamine should make room for greater phasic spikes, so we should aim for that right? How to do it? Google finds almost nothing. Some suggest D2-receptor antagonists.

And DXM did nothing to me. If DXM can induce euphoria without manipulating dopamine activity, then my problems must not be related to dopamine? Although I'm not sure if euphoria is what DXM induces, some just suggest it for anhedonia.

DXM, opiates, alcohol (atleast not like it should) and benzo's arent rewarding for me either, it relates to shizophrenia, perhaps you have something simular shizo like (dont make that scare you, ADHD and AVPD are also shizo like disorders in a way. It would explain lack of reward from DXM and opiates.

Actually, with reward I didn't mean pleasure but feelings of succeeding etc.

But anyway, decreasing tonic dopamine should make room for greater phasic spikes, so we should aim for that right? How to do it? Google finds almost nothing. Some suggest D2-receptor antagonists.

And DXM did nothing to me. If DXM can induce euphoria without manipulating dopamine activity, then my problems must not be related to dopamine? Although I'm not sure if euphoria is what DXM induces, some just suggest it for anhedonia.

Zyprexa kinda normalises phasic dopamine and is the only ap that has been reported to work for anhedonia.

#75 Vieno

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Posted 29 November 2012 - 09:19 PM

You and I may have something similar, but IMO using psychiatric terminology sucks ass because it is so miserably defined. I spent half a year driving myself crazy over whether I'm depressed or not until I realized that depression has no definition. Therefore I'm much better just describing my exact symptoms such as consummatory anhedonia. Same goes for schizophrenia. I don't think its fruitful to call a certain physiological aspect schizophrenic, because schizophrenia, just like depression, can mean many things. You and I seem to have much in common so we can look for same treatments: but I refuse to call myself schizo.

Any more detail knowledge on that "normalizing" function of Zyprexa? Is it adaptogenic?

Btw how's the MDAI experiment going?

Edited by Vieno, 29 November 2012 - 09:21 PM.


#76 medievil

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Posted 29 November 2012 - 09:31 PM

"because schizophrenia, just like depression, can mean many things."

Well its basicly the worst you could possibly get of a certain subtype of disorders, you can just have only a few negatives like depression but neurochemically if it relates to shizo, its something shizo like and the treatments are likely to be simular (such as amphetamine for negatives in shpizo, amp for ADHD and amp for AVPD) i know shizo sounds bad but its like worst possible outcome for ppl that have neurochemical issues that kinda relate.

I no longer have anything related to the predromal shizo i had, or shizo like things i had as a kid (really small things) so at this point im definatly not a shizophrenic, yet i relate to it, thinking like this makes it possible to find working treatments, like you and me are simular.

Very well, its alot better then SSRI's, smooths out stims perfectly and helps ocd alot but its early.

#77 medievil

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Posted 29 November 2012 - 09:36 PM

Any more detail knowledge on that "normalizing" function of Zyprexa? Is it adaptogenic?


Its the only AP that does this, and why is not known, its closely related to clozapine wich is a extremely effective antipsychotic however it can induce a disorder that kills you, but because its so damn good as a ap its still in use for some with regular check up to avoid deadly reactions, olanozapine seemed to have kept some of its magic.

#78 Vieno

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Posted 30 November 2012 - 12:27 AM

It's not that I wouldn't dare to call myself schizo, I've labeled myself insane many times. Turns out I'm in as right mind as one can be so I think I was misdiagnosing myself xD

I have to say that things like social anxiety and OCD can't exist without psychological problems. A thought disorder is a prerequisite for their diagnosis. Therefore, if you truly suffer from social anxiety and OCD, no med can cure them. If you don't, then you shouldn't use the terms because it gets confusing.

Gonna get me some MDAI soon...

#79 airplanepeanuts

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Posted 30 November 2012 - 12:28 AM

I spent half a year driving myself crazy over whether I'm depressed or not until I realized that depression has no definition. Therefore I'm much better just describing my exact symptoms such as consummatory anhedonia.

I think the 'Not enough Serotonine' definition works.Try 5-htp or SAM-e for example and if you were depressed you will notice a difference. You might still not enjoy life because of anhedonia but that hopeless, senseless feeling is gone- you are not depressed anymore (if it works for you).

I think if you are anhedonic depression might be a secondary disease: because of the anhedonia your life sucks and as a response you get the blues.

Edited by whitetealeaves, 30 November 2012 - 12:37 AM.


#80 Vieno

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Posted 30 November 2012 - 12:33 AM

I spent half a year driving myself crazy over whether I'm depressed or not until I realized that depression has no definition. Therefore I'm much better just describing my exact symptoms such as consummatory anhedonia.

I think the 'Not enough Serotonine' definition works.Try 5-htp or SAM-e for example and if you were depressed you will notice a difference. You might still not enjoy life because of anhedonia but that hopeless, senseless feeling is gone- you are not depressed anymore (if it works for you).

I think if you are anhedonic depression might be a secondary disease: because of the anhedonia you're life sucks and as a response you get the blues.


No way man, "not enough serotonin" is the lousiest definition ever. Let me tell you something... depression is psychology, it is physiology, it is everything between earth and heaven. It's anxiety, it's the opposite: it's an overstimulated brain and an oversedated brain. It's anhednia, it's excessive emotionality. Besides... "not enough serotonin" may NEVER be the case: a lot of research these days says there's nothing backing up the serotonin hypothesis. That's why SSRIs suck, except possibly for anxiety, which, well, isn't necessarily depression - that's semantics. And semantics btw is extremely important, but unfortunately most people don't know how to practice it! So we got this terminology that sucks ass.

Anyway, the only criteria I meet for any depression is anhedonia. Trust me, I've been turned away thanks to the lovely Beck Depression Inventory. But I don't call myself depressed. I refuse to use that diagnostic term. But you're right about one thing, anhedonia indeed depresses me. Just doesn't make me what is called "clinically depressed".

#81 medievil

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Posted 30 November 2012 - 12:38 AM

I have to say that things like social anxiety and OCD can't exist without psychological problems. A thought disorder is a prerequisite for their diagnosis. Therefore, if you truly suffer from social anxiety and OCD, no med can cure them. If you don't, then you shouldn't use the terms because it gets confusing.

not sure what you mean with this.

Also i suffer from anhedonia but not depression, i dont get depressed when im anhedonic as i know its just temporary untill i have stuff again that removes it, like going to work is unpleasant but its over soon so it wont depress me.

#82 Vieno

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Posted 30 November 2012 - 12:40 AM

I have to say that things like social anxiety and OCD can't exist without psychological problems. A thought disorder is a prerequisite for their diagnosis. Therefore, if you truly suffer from social anxiety and OCD, no med can cure them. If you don't, then you shouldn't use the terms because it gets confusing.

not sure what you mean with this.


Just saying that OCD for example requires you to have irrational thoughts. So if you have OCD, make sure you think rationally before medicating it.

Also i suffer from anhedonia but not depression, i dont get depressed when im anhedonic as i know its just temporary untill i have stuff again that removes it, like going to work is unpleasant but its over soon so it wont depress me.


Yea, that attitude is keeping me going too. I'm not that blue anymore because I'm confident I'll figure this out, but when I didn't see any ways to fix this I was really depressed.

#83 airplanepeanuts

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Posted 30 November 2012 - 12:42 AM

Well if you want your personal definition fine. But it is very convenient to break stuff down. And the low serotonin=feeling depressed thing just works. Sadly anhedonia does not seem to be that uncomplicated.

#84 medievil

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Posted 30 November 2012 - 12:44 AM

Oh but in the past for example amphetamine just completely wiped my ocd away, leaving me completely confused why on earth i had those irrational toughts as without ocd it just didnt make sense, couldnt understand it all anymore like, as much as someoene that you explain it too without ocd. Stims no longer wipe it away but my ocd is so mild its no problem.

#85 airplanepeanuts

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Posted 30 November 2012 - 12:48 AM

Oh but in the past for example amphetamine just completely wiped my ocd away, leaving me completely confused why on earth i had those irrational toughts as without ocd it just didnt make sense, couldnt understand it all anymore like, as much as someoene that you explain it too without ocd. Stims no longer wipe it away but my ocd is so mild its no problem.


Yeah but I think that stims might just mask the problem. Also anhedonia.

#86 medievil

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Posted 30 November 2012 - 12:53 AM

Oh but in the past for example amphetamine just completely wiped my ocd away, leaving me completely confused why on earth i had those irrational toughts as without ocd it just didnt make sense, couldnt understand it all anymore like, as much as someoene that you explain it too without ocd. Stims no longer wipe it away but my ocd is so mild its no problem.


Yeah but I think that stims might just mask the problem. Also anhedonia.

They didnt mask it they removed it, the day after (long after they stopped working) i remained completely OCD free, completely normalised thinking, masking would feel differened, like you would barely notice the ocd but it would still be there, unlike complete normalised thinking where you are completely confused as to why you had those irrational toughts, even if your depressed in the comedown and dont feel good at all, still normalised thinking.

I dont think stims mask anhedonia in my case, i cant feel opiates without stims, on stims i can so they definatly seem to fix some kind of neurological problem, ive allways felt like they normalised my thinking/brain (response to other substances etc).

Ive had other stuff that helped my ocd but it was still there, i think the term mask can be used there more.

#87 airplanepeanuts

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Posted 30 November 2012 - 12:57 AM

Well somewhere you wrote that pseudoephedrine fixed your anhedonia for a short time. That worked for me too some years ago. But only for a day or so. It was quite remarkable and also disturbing when it went away.. I only took it once I think I'll try it again. I guess it's no long term solution though.

Edited by whitetealeaves, 30 November 2012 - 12:58 AM.


#88 Vieno

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Posted 30 November 2012 - 12:58 AM

Please, let's not talk this stuff here. I apologize for starting these discussions, my bad. I couldn't resist the temptation to start to talk off-topic... I made this thread to figure out the mechanisms of anhedonia and not to talk about semantics, psychology, meaning of life etc. I know it's tempting for all of us to share our own views on what are mental disorders, what is the right way to deal with them and so on, but really, this thread is purely for physiological studying. So please, let's not continue this and let's get back to the original topic! :)

#89 medievil

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Posted 30 November 2012 - 01:48 AM

As you wanted to try MDAI, maybe try a few other rc's too that are easy to order online and check out your response:
MPA or ethylphenidate
Phenibut
Methoxetamine ( in uk n ethylketamine perhaps as its illegal here now)
5 meo dalt (think your from uk? as it says london, its easy to buy there psychedelic you can try in treshold doses)
AKB45/UR144 (not sure wheter ur will work as its selective for CB2) AKB45 seems like the most gentle good cannabinoid they sell from what ive read.
AMT

All those things are damn easy to order and legal nearly everywhere, some suggestions ppl here could play around with.

Cannabinoids make me feel horrific without a serotogenic btw, with a ssri or some mdai they work well tough and weed worked for my anhedonia.

Edited by medievil, 30 November 2012 - 01:57 AM.


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#90 medievil

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Posted 30 November 2012 - 01:54 AM

You seem simular to me, what worked for me was GHB, treshold psychedelic doses, and stimulants, opiates only on stims. MDAI and weed kinda in the past but only tried that once. MDAI on its own never helped my anhedonia tough so if your like me dont get your hopes up too much.





Also tagged with one or more of these keywords: anhedonia, depression, attention, l-dopa, ssre, adaptogen, quetiapine, consummatory anhedonia

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