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Answers To Curing Anhedonia/numbness/apathy, No. 2


Lioninwinter

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  • 3 weeks later...

Hello everyone!  I've been following this thread for a long time, years I think.  I've been battling anhedonia since October 2012.  I've been mostly winning but it's still a problem.  I will share some of the methods that have worked so far.

First, since people here are interested in the role of the 5-ht1a system in anhedonia, I would like to share this study: http://www.ncbi.nlm.nih.gov/pubmed/16408408

It shows that sleep deprivation can be used to desensitize the 5-ht1a system.  I tried this on myself to fight anxiety a month ago and found that it was also useful for anhedonia alongside 80-120 mg/day of caffeine.  After resuming an irregular but longer sleep regimen, the effects continued but are now wearing off somewhat.  I will probably attempt it again soon.  Also during this regimen I've been taking low, occasional doses of mirtazapine (10mg, 2-3 times a week).  Taking too much mirtazapine causes worsening of anhedonia and too little causes anxiety and panic to be too much to enjoy things.  Overall though, this routine has been relatively consistent in its effects.  I can even enjoy music without additional drugs, which is a major victory for me(I used to be an amateur musician before the anhedonia).

Also, here's a study showing how branched chain amino acid supplements can be used to deplete serotonin: http://www.ncbi.nlm.nih.gov/pubmed/23904096
and another: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC257796/

For my other methods, I'll summarize:  

phenibut, a GABA agonist, doses of 1-4 g once or twice a week.  Very effective, pretty much gets you high and if you don't overdo it/are responsible, it works ALMOST everytime.  Sometimes take long breaks, sometimes there is reverse tolerance/sensitization for me.

dissociatives, especially nitrous oxide, but not reliable long term because tolerance develops rapidly so long breaks are required to restore effectiveness.  

5-htp, but don't take more than the recommended dose.  I megadosed last May and it eventually caused serotonin syndrome and worsened my anxiety/panic disorder which I'm still recovering from.  5-htp is effective only for a few days a month in my experience.  Tolerance develops rapidly.

 
Caffeine in large doses, 100-400 mg/day.  Effective for two weeks, tolerance takes at least a month to recover, it makes me tired instead of energetic/hedonic if I take too much once tolerance has developed.

Oleamide, supposedly a cannabinoid receptor 1 (CB1) agonist, 100-400 mg/day, mildly effective for up to two weeks but not consistent.

Nutmeg essential oil, contains myristicin, purported to be a 5-ht2a agonist and mild maoi, helped sometimes, especially when combined with phenibut.  Effects are very mild though.

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helloo guys

 

I'm new here lol lucky me 

 

Soo i'm 100% positive that i have anhedonia, i didn't even know that something like this is a real thing.

 

It may sound silly but this is my story..May this year i started having nausea,stomach cramping,bloating,unusual bowel movements lost weight while being underweight (seriously?!)..doc did blood test it was all good and said that it probably happened because i was taking antibiotics and iron tablets at the same time, but somehow my brain got convinced that i have cancer, and yes your brain can do this to u!  Now i know that nothing's wrong with me but i guess a bit to late lol While waiting for resaults of the scan and blood which took a couple of days anxiety kicked in and i couldn't sleep or eat i even missed a day off from work just to stay in bed and sleep as much as i could. I was panicking really bad nothing like that has happened to me before in my life. After anxiety it's sister depression couldn't wait to kick in-.- and i ended up getting more and more exhausted, brain fog won't let me go,lack of concentration,i've become quite forgetful, irritability and apsolutely no motivation to go and socialize, i force my self to go to work to shower to pretty much get up and going. Music was my life but now i listen to it and feel nothing like i will move my head on the rhythm of the song but no excitement or joy like a couple of weeks ago it sucks, same is when watching movies and shows on tv or even when i see someone who looks attractive my mind knows that will like him but my "body" doesn't feel that (i don't know if that will make sense to u lol). In a couple of weeks i'll be 21 and have no positive emotions for it or looking forward to it.

I don't know how it got to here but all i know is that the more i think about it the more frustrated and sad i get and self pitty so i tend not to and it kinda works sometimes, the moment i catch my self thinking about it i distract myself in any way possible lol.

 

 

I'd like to ask ITSTREVOR what helped u overcome this thing? Because when i started reading about this on this site i was reading the first part and got till page 15/16 and i saw that you've tried quite a lot of medication and had a big interest in curing yourself.. And i kinda feel like the guy named handsup to be honest, i don't know if u remember him, i wonder what happened to him..?

 

i feel ya pain people

 

thanks for reading

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  • 2 weeks later...

Hello everyone!  I've been following this thread for a long time, years I think.  I've been battling anhedonia since October 2012.  I've been mostly winning but it's still a problem.  I will share some of the methods that have worked so far.

First, since people here are interested in the role of the 5-ht1a system in anhedonia, I would like to share this study: http://www.ncbi.nlm.nih.gov/pubmed/16408408

It shows that sleep deprivation can be used to desensitize the 5-ht1a system.  I tried this on myself to fight anxiety a month ago and found that it was also useful for anhedonia alongside 80-120 mg/day of caffeine.  After resuming an irregular but longer sleep regimen, the effects continued but are now wearing off somewhat.  I will probably attempt it again soon.  Also during this regimen I've been taking low, occasional doses of mirtazapine (10mg, 2-3 times a week).  Taking too much mirtazapine causes worsening of anhedonia and too little causes anxiety and panic to be too much to enjoy things.  Overall though, this routine has been relatively consistent in its effects.  I can even enjoy music without additional drugs, which is a major victory for me(I used to be an amateur musician before the anhedonia).

Also, here's a study showing how branched chain amino acid supplements can be used to deplete serotonin: http://www.ncbi.nlm.nih.gov/pubmed/23904096

and another: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC257796/

For my other methods, I'll summarize:  

phenibut, a GABA agonist, doses of 1-4 g once or twice a week.  Very effective, pretty much gets you high and if you don't overdo it/are responsible, it works ALMOST everytime.  Sometimes take long breaks, sometimes there is reverse tolerance/sensitization for me.

dissociatives, especially nitrous oxide, but not reliable long term because tolerance develops rapidly so long breaks are required to restore effectiveness.  

5-htp, but don't take more than the recommended dose.  I megadosed last May and it eventually caused serotonin syndrome and worsened my anxiety/panic disorder which I'm still recovering from.  5-htp is effective only for a few days a month in my experience.  Tolerance develops rapidly.

 

Caffeine in large doses, 100-400 mg/day.  Effective for two weeks, tolerance takes at least a month to recover, it makes me tired instead of energetic/hedonic if I take too much once tolerance has developed.

Oleamide, supposedly a cannabinoid receptor 1 (CB1) agonist, 100-400 mg/day, mildly effective for up to two weeks but not consistent.

Nutmeg essential oil, contains myristicin, purported to be a 5-ht2a agonist and mild maoi, helped sometimes, especially when combined with phenibut.  Effects are very mild though.

After reading this like 2 days ago or something, I looked up 5-ht1a antagonists, particularly supplements. Has anyone tried berberine yet? I'd like to get some info before trying it myself.

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I didn't know Berberine was a 5-ht1a antagonist.  This was very interesting to find out.  After doing some research I found this:

http://www.ncbi.nlm.nih.gov/pubmed/15350820

 

Berberine has many mechanisms of action.  Another user mentioned that it may inhibit dopaminergic activity, thus making anhedonia worse, but if 5-ht1a overactivity is the source of the problem, this side effect can probably be countered with other drugs/supplements that increase/disinhibit dopaminergic activity.  I know that berberine is relatively safe and is commonly used to treat gastrointestinal disorders.  I once considered taking this supplement for my IBS.  Now I have a new reason to try it.  If you don't try it, I probably will try it as soon as I can buy it and report the results.

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Hi guys im new to this thread but i think its great that people with our problem can work together to try and help other people, and judging by the precursor to this thread, im happy that trevor managed to cure himself and i hope one day that we can all live like normal people.

 

Now here is my personal story. From the ages of 16-21 i basically smoked the green urb/MJ drug every single day, multiple times through-out the day for 5 years. Overtime i developed social anxiety, and approximately around the same time (2-3 years ago) i developed anhedonia. 

For me; i don't feel depressed. I have an inability to laugh or cry. The only emotion i can feel is anxiety. I can still enjoy music and beating my meat to some extent though but not fully ...maybe 50-65%

 

I think its worth pointing out that i have never taken another drug accept for nicotine and on very rare occasions alcohol. So essentially this is a THC-induced anhedonia, although i have quit for approximately 6 weeks now, with no improvement.

 

It could also be possible that i am experiencing a negative symptom of scitzophrenia...so i guess its a waiting game for the positive symptoms to manifest.

 

I have read somewhere that chronic THC exposure during adolescence can result in depression/anxiety/apathy/anhedonia permanently. I contacted the scientist behind this study and she (Dr. Gabriella Gobbi) told me "you can eventually be treated with antidepressant drugs that have neurogenesis-stimulating properties, however there has been no significant research"

 

If anybody has THC/MJ drug induced anhedonia, it would be nice to talk to you

 

God bless everyone here

Edited by Londonscouser
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So after reading all the anhedonia threads, is there a consensus of which treatments are worth investigating first? It seems it is just a guessing game ,what will work for Someone may not work for others.

I have an appointment on Tuesday with my psychiatrist and I feel as lost as I did a year ago when I started seeing him.

Would anyone be able to suggest which medicationS would be worth looking into first? And, preferably, medication I can get prescribed, not something like NSI-189.

Thank you for your time.

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So after reading all the anhedonia threads, is there a consensus of which treatments are worth investigating first? It seems it is just a guessing game ,what will work for Someone may not work for others.

I have an appointment on Tuesday with my psychiatrist and I feel as lost as I did a year ago when I started seeing him.

Would anyone be able to suggest which medicationS would be worth looking into first? And, preferably, medication I can get prescribed, not something like NSI-189.

Thank you for your time.

 

 

Pramipexole (brand name Mirapex) can cure anhedonia. It may not for everyone but it definitely does from some.

 

I agree, it is a guessing game, even for the doctors! There is no med that cures anhedonia for everyone. Good luck at your appointment, I hope you find some relief soon!

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Memantine treatment reverses anhedonia, normalizes corticosterone levels and increases BDNF levels in the prefrontal cortex induced by chronic mild stress in rats.

http://www.ncbi.nlm.nih.gov/pubmed/22327556

Another NMDA receptor antagonist. Agmatine is an endogenous antidepressant that's also an NMDA receptor antagonist, and we all know what ketamine is. I think there might be something to this.

 

In any case, there's a supplement called l-arginine which the body turns into agmatine.

Edited by Racecarlock
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  • 2 weeks later...

Hi guys im new to this thread but i think its great that people with our problem can work together to try and help other people, and judging by the precursor to this thread, im happy that trevor managed to cure himself and i hope one day that we can all live like normal people.

 

Now here is my personal story. From the ages of 16-21 i basically smoked the green urb/MJ drug every single day, multiple times through-out the day for 5 years. Overtime i developed social anxiety, and approximately around the same time (2-3 years ago) i developed anhedonia. 

For me; i don't feel depressed. I have an inability to laugh or cry. The only emotion i can feel is anxiety. I can still enjoy music and beating my meat to some extent though but not fully ...maybe 50-65%

 

I think its worth pointing out that i have never taken another drug accept for nicotine and on very rare occasions alcohol. So essentially this is a THC-induced anhedonia, although i have quit for approximately 6 weeks now, with no improvement.

 

It could also be possible that i am experiencing a negative symptom of scitzophrenia...so i guess its a waiting game for the positive symptoms to manifest.

 

I have read somewhere that chronic THC exposure during adolescence can result in depression/anxiety/apathy/anhedonia permanently. I contacted the scientist behind this study and she (Dr. Gabriella Gobbi) told me "you can eventually be treated with antidepressant drugs that have neurogenesis-stimulating properties, however there has been no significant research"

 

If anybody has THC/MJ drug induced anhedonia, it would be nice to talk to you

 

God bless everyone here

Hi,

 

If you read my post on the previous page, you can see that I asked if anyone else has experienced anhedonia after smoking MJ. I smoked MJ only on 3-4 occasions, but the damage was already done. For 4 months, I felt completely empty in my head and unmotivated to do anything, I almost dropped out of school. Weirdly though, this numb state passed away and for a year (nov 2012-nov 2013) I was feeling completely normal, felt emotions again and everything. 

But then, totally out of the blue, overnight my brain decided to jump back into the anhedonic state. And I've been stuck in it since, which is almost 2 years now. I've only spoken to a therapist once, but she was pretty sure that it didn't have anything to do with the THC seeing as I did not chronically use it. Although if you ask me, I think a few times can be enough for some recessive genes to get activated by the THC, thus inducing anhedonia. 

 

I'm thinking that I should go and talk to a real psychologist to get this sorted out properly. Does anyone else also feel a stronger grip of anhedonia when hungover? It feels like 10x times more terrible, because you feel completely empty not only in your mind, but also in your body, so to say. It's like you're not even a part of this world. Thus I've tried to abstain from alcohol as much as I can. Going to hit the gym again and see if it shows any results. I haven't tried ANY medics yet, can you guys recommend anything that one can buy instantly from the pharmacy?

Edited by Levander
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I've been taking berberine as promised, 800-1600mg/day for over a week now.  It doesn't appear to have any significant serotonergic effect at the doses I've been taking, which I expected because the concentration in the study was 100mg/kg in rats.  Adjusted for me, that's about 70kg body mass --> 7g doses at a time.  That's about 17 pills per dose, something I'm not willing to do right now.  Even if it were effective at that dose, I believe I have a more effective method for long term suppression of 5-ht1a activity using the partial sleep deprivation experiment I mentioned last time.  By all the metrics I've been using to gauge my 5-ht1a activity, the sleep routine has definitely been the most effective of the methods I've tried.  Not only have I stopped having panic attacks, but I've even tried taking low doses of 5-htp (25-50mg) with positive results.  I've found that the key appears to be to have a balance of 5-ht1a activity and that it's as easy for it to go too low and cause classical depression as it is to go too high.  My sensitivity to 5-htp is still abnormally high, but is decreasing and I'm at the point where I can go out in public without taking medications to prevent panic attacks.  

 

Here is a reddit post that discusses the role of dopamine in reward perception: https://www.reddit.com/r/askscience/comments/3kctki/can_dopamine_be_artificially_entered_into/

 

On that page, one user posted this article, which makes a distinction between different aspects of reward and implicates the GABAergic system, opioid system and cannabinoid system in hedonic response: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2756052/#!po=12.5000

 

For those interested in the role of the GABAergic system in anhedonia, here is a study on phenibut which shows that it has affinity for the alpha 2 delta subunit of the voltage-gated calcium channel: http://www.sciencedirect.com/science/article/pii/S009130571530037X

 

Basically, alpha 2 delta ligands bypass the GABA receptors to cause suppression of the glutamatergic system.  Drugs of this class include gabapentin and pregabalin.

Edited by Alive Inside
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I've been taking berberine as promised, 800-1600mg/day for over a week now. It doesn't appear to have any significant serotonergic effect at the doses I've been taking, which I expected because the concentration in the study was 100mg/kg in rats. Adjusted for me, that's about 70kg body mass --> 7g doses at a time. That's about 17 pills per dose, something I'm not willing to do right now. Even if it were effective at that dose, I believe I have a more effective method for long term suppression of 5-ht1a activity using the partial sleep deprivation experiment I mentioned last time. By all the metrics I've been using to gauge my 5-ht1a activity, the sleep routine has definitely been the most effective of the methods I've tried. Not only have I stopped having panic attacks, but I've even tried taking low doses of 5-htp (25-50mg) with positive results. I've found that the key appears to be to have a balance of 5-ht1a activity and that it's as easy for it to go too low and cause classical depression as it is to go too high. My sensitivity to 5-htp is still abnormally high, but is decreasing and I'm at the point where I can go out in public without taking medications to prevent panic attacks.

Here is a reddit post that discusses the role of dopamine in reward perception: https://www.reddit.com/r/askscience/comments/3kctki/can_dopamine_be_artificially_entered_into/

On that page, one user posted this article, which makes a distinction between different aspects of reward and implicates the GABAergic system, opioid system and cannabinoid system in hedonic response: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2756052/#!po=12.5000

For those interested in the role of the GABAergic system in anhedonia, here is a study on phenibut which shows that it has affinity for the alpha 2 delta subunit of the voltage-gated calcium channel: http://www.sciencedirect.com/science/article/pii/S009130571530037X

Basically, alpha 2 delta ligands bypass the GABA receptors to cause suppression of the glutamatergic system. Drugs of this class include gabapentin and pregabalin.

Very interesting! So, have you tried either gabapentin or pregabalim?

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No, those are prescription only here and because I shop around for medicines so much(and have social phobia), I tend to avoid ones that I can't get immediate access to.  It's hard to get those drugs because they are considered to have some abuse potential.  My clinic doesn't even prescribe them I don't think, but I may ask my doctor the next time I see him.  I've only recently become aware of VDCC interacting drugs.  It was previously believed that phenibut was mainly a GABA-B agonist, but it turns out in that study I posted that it has a higher affinity for the alpha 2 delta subunit of the VDCC.

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Interesting you should mention use of 5htp. I once got a high off 5htp when combined with Citalopram. I didn't intend for it to happen as I was aiming for some pain relief but music sounded amazing amongst other things. I haven't touched since then 5htp mainly because I don't want to risk Serotonin Syndrome. That said I used 5htp consistently for a number of weeks on its own a long time ago but didn't notice it particularly effective towards my not so bad as it was then anhedonia.

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I think when I first tried 5-htp I had low serotonergic activity and tolerance and that's why it worked well for the first few days.  Tolerance developed after that and even 4x doses would have little or no effect on anhedonia.  However, last May I tried repeated megadoses of 750-1500mg/day after developing tolerance and recovered some of the effects until one day it caused serotonin syndrome.  I lowered the next dose to 500mg, waited 2 days before taking it and still it occured again.  I think it was the result of autoreceptor desensitization taking place during the megadose regimen.  Repeated exposure to serotonin and serotonergic drugs would theoretically further desensitize the 5-ht1a autoreceptors, leaving serotonin release unchecked and potentially causing a vicious cycle, which I think I was experiencing slowly as effects lingered for months despite no longer taking serotonergics(except for phenibut, which may indirectly cause serotonin to be released).  The lingering effects actually got worse over time.  Low doses of mirtazapine was the short term solution, but it wasn't until the partial sleep deprivation routine that symptoms really started to improve.

 

So now I use sleep deprivation or 5-htp whenever I need to adjust serotonergic activity.  Combined with phenibut, it almost guarantees at least some ability to enjoy the day.

Edited by Alive Inside
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  • 3 weeks later...

 

Memantine treatment reverses anhedonia, normalizes corticosterone levels and increases BDNF levels in the prefrontal cortex induced by chronic mild stress in rats.

http://www.ncbi.nlm.nih.gov/pubmed/22327556

Another NMDA receptor antagonist. Agmatine is an endogenous antidepressant that's also an NMDA receptor antagonist, and we all know what ketamine is. I think there might be something to this.

 

In any case, there's a supplement called l-arginine which the body turns into agmatine.

 

I've been trying L-Arginine 500mg I think for about 2 weeks now but not seeing much improvement in my anhedonia to be honest. I took it before a while ago but don't recall it being particular effective which is so disappointing. 

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We need to get some medical experts in here. Brief them on the condition, on people's responses to the condition, on the general lack of understanding when it comes to this condition. I'm just thinking that we need some people with expert knowledge of the human body. Plus, should we manage to have any breakthroughs on various treatments, those experts can then contact the people they know and start getting some studies done on those breakthroughs and treatments.

 

I'm thinking people from the National Center for biotechnology information. http://www.ncbi.nlm.nih.gov/

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