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The Cure for Anhedonia


futureclarity

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I've struggled with MDD and anhedonia for the past 6+ years.  I am experiencing brain inflammation and a dysregulation in neuronal signaling due to chronic stress. Despite the fact that there are a host of studies that implicate glutamate (not serotonin or dopamine) in the pathophysiology of depression: [link removed] this type of depression is largely ignored by medicine. This youtube video does an excellent job of breaking this all down: [link removed]   [link removed]

 This glutamatergic hyperactivity causes neuronal degeneration, compromising how glutamatergic cells excite the regions of your brain involved in emotion, reward, and pleasure:
43253682_540643779720409_178560168659779584_n.png?_nc_cat=102&oh=99876ad911448c3e7b108b21d104d301&oe=5C1D4C51

Hence, the emotional blunting, lack of energy, disinterest, amotivation, etc. I've read many studies that suggested NMDA (glutamate) receptor antagonists like ketamine, memantine, and MK-801 are highly effective in reversing the symptoms of depression. To test this theory, I bought an over the counter NMDA receptor antagonist, Agmatine. About an hour after taking it, I noticed a lift in my energy, mood, and mental clarity that no prescription drug (Wellbutrin, Remeron, Lexapro, etc) had given me. I had no response to these prescription drugs because they were all targeting the wrong mechanism. I now understand that my brain lacks the ingredients necessary to heal itself from chronic inflammation. You can read more about the effects of inflammation-induced depression here: [link removed] . Now, after doing some research into what molecules work best, I've developed a stack of supplements that are meant to eradicate this type of depression on a multimodal level:

  1. DHA-500 (500 mg, 2X per day): An omega-3 fatty acid that reverses inflammation and enhances neuronal communication.
  2. Acetyl L-Carnitine (1000 mg): An antioxidant that helps enhance cognition, reduce inflammation and elevates mood.
  3. Activated B-Complex (1 tablet) Vitamin complex that provides a sustained boost in mental and cellular energy.
  4. Agmatine (500 mg): Molecule that reverses glutamate-induced excitotoxicity.

 I haven't tried them all at once yet, but I'm too excited to wait until I do to share this. I know the title is a bit sensationalist because I haven't actually figured out if this will treat anhedonia, but my goal is to raise awareness of this mechanism that I feel is a very important piece of the puzzle. Modern treatment is heavily based on the monoamine hypothesis of depression, which although significant, is not all-encompassing. Feel free to share your experiences with these supplements and contact me if you have any questions and concerns. Best of luck.

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  • 4 weeks later...

Initially, Agmatine worked well for me but started to lose it's potency over time. I'm now using Memantine as an NMDA antagonist. I've been taking the stack I mentioned for about a month and it's caused definite improvements in cognition. I feel more activated, present, and mentally clear now. However, there's not much change in terms of emotionality so I started on another anti inflammatory supplement. Fingers crossed.

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On 10/5/2018 at 12:27 AM, futureclarity said:

I've struggled with MDD and anhedonia for the past 6+ years.  I am experiencing brain inflammation and a dysregulation in neuronal signaling due to chronic stress. Despite the fact that there are a host of studies that implicate glutamate (not serotonin or dopamine) in the pathophysiology of depression: [link removed] this type of depression is largely ignored by medicine. This youtube video does an excellent job of breaking this all down: [link removed]   [link removed]

 This glutamatergic hyperactivity causes neuronal degeneration, compromising how glutamatergic cells excite the regions of your brain involved in emotion, reward, and pleasure:
43253682_540643779720409_178560168659779584_n.png?_nc_cat=102&oh=99876ad911448c3e7b108b21d104d301&oe=5C1D4C51

Hence, the emotional blunting, lack of energy, disinterest, amotivation, etc. I've read many studies that suggested NMDA (glutamate) receptor antagonists like ketamine, memantine, and MK-801 are highly effective in reversing the symptoms of depression. To test this theory, I bought an over the counter NMDA receptor antagonist, Agmatine. About an hour after taking it, I noticed a lift in my energy, mood, and mental clarity that no prescription drug (Wellbutrin, Remeron, Lexapro, etc) had given me. I had no response to these prescription drugs because they were all targeting the wrong mechanism. I now understand that my brain lacks the ingredients necessary to heal itself from chronic inflammation. You can read more about the effects of inflammation-induced depression here: [link removed] . Now, after doing some research into what molecules work best, I've developed a stack of supplements that are meant to eradicate this type of depression on a multimodal level:

  1. DHA-500 (500 mg, 2X per day): An omega-3 fatty acid that reverses inflammation and enhances neuronal communication.
  2. Acetyl L-Carnitine (1000 mg): An antioxidant that helps enhance cognition, reduce inflammation and elevates mood.
  3. Activated B-Complex (1 tablet) Vitamin complex that provides a sustained boost in mental and cellular energy.
  4. Agmatine (500 mg): Molecule that reverses glutamate-induced excitotoxicity.

 I haven't tried them all at once yet, but I'm too excited to wait until I do to share this. I know the title is a bit sensationalist because I haven't actually figured out if this will treat anhedonia, but my goal is to raise awareness of this mechanism that I feel is a very important piece of the puzzle. Modern treatment is heavily based on the monoamine hypothesis of depression, which although significant, is not all-encompassing. Feel free to share your experiences with these supplements and contact me if you have any questions and concerns. Best of luck.

Are these all available without a prescription?

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  • 4 weeks later...
On 11/8/2018 at 10:28 AM, LonelyHiker said:

Are these all available without a prescription?

Yes these can all be found on Amazon. I would recommend curcumin (with black pepper) and fish oil supplements. They have drastically improved my brain functionality and made me responsive to dopmaine agonists. I'm slowly getting my feelings back. Good luck.

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  • 1 month later...

@Andres1978 I have taken the whole stack, and although it did help, I continued to look for more effective options after my supply ran out. I have tried Mucuna Pruriens, Curcumin, Fish Oil, St Johns Wort, Acetyl L Carnitine, Mementine, a B Complex, Mood boosting probiotics, Agmatine, a mood boosting supplement (Sunny Mood), and Mirtazapine. Unfortunately, the most effective drug for emotions was the prescribed one. I responded to Mirtazapine only after clearing my inflammation with Curcumin. 

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  • 2 weeks later...

I have tried curcumin supplements and they seem to help. I also tried a probiotic supplement which worked well but cost too much to continue. Getting some motivation back requires reducing the anti anxiety medication which numbs me, but keeps me alive. I think I need to force myself to learn a language, do jigsaws or something else that amuses me. Ideas welcome

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16 hours ago, Extremebeginner said:

I have tried curcumin supplements and they seem to help. I also tried a probiotic supplement which worked well but cost too much to continue. Getting some motivation back requires reducing the anti anxiety medication which numbs me, but keeps me alive. I think I need to force myself to learn a language, do jigsaws or something else that amuses me. Ideas welcome

If you're a committed conscientious person, perhaps get a dog. 

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On 1/20/2019 at 10:32 PM, futureclarity said:

@Andres1978 I have taken the whole stack, and although it did help, I continued to look for more effective options after my supply ran out. I have tried Mucuna Pruriens, Curcumin, Fish Oil, St Johns Wort, Acetyl L Carnitine, Mementine, a B Complex, Mood boosting probiotics, Agmatine, a mood boosting supplement (Sunny Mood), and Mirtazapine. Unfortunately, the most effective drug for emotions was the prescribed one. I responded to Mirtazapine only after clearing my inflammation with Curcumin. 

I've been taking fish oil for a month now and I believe it's helping as I do feel better. Also B complex and St Johns wort daily. 

Still wake up feeling like death every morning but it wears off over a few hours when I get busy. 

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I am on a few prescribed medications but I gotta try fish oil (although I don't believe in it right now) and curcumin. Ketamine is being tested for depression here but it is next to impossible to get on it.

I got a pet, a kitten..well now a cat and sometimes I spend an hour playing with him when he is in mood. I prefer dogs and thought of getting one in the spring but I live in cities crowded houses and I don't know the rules, Dogs are definitely more fun than cats.

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  • 1 month later...
On 2/6/2019 at 7:59 AM, Extremebeginner said:

What kind of fish oil supplements?

I've been using Nutrachamp's Omega 3 Fish Oil (3,600) which is available on Amazon. A lot of fish oil is heavily processed, which causes it to lose nutritional value. Look out for labels that include "wild caught" to make sure they aren't fancy placebo pills'.

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