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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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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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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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