7 replies to this topic

[jack black]

My notes on neurotransmitters based on the literature review (sorry, i didn't record all references, should be easy to find):

 

1. chronic stress increases corticosteroids (Cort) and glutamate (Glut) and promotes neuron loss and hence anxiety and depression.

More on high Glut here: https://area1255.blo...-levels-in.html

 

2. alcohol produces a release of dopamine (D), but hypodopaminergic state after stopping drinking. D1 receptor downregulation after chronic use (depression and ADHD).

 

3. acute and chronic nicotine use increases serotonin (Se) levels.

 

4. increased Se leads to lower ACh, D, NE, increased Cort (via 5HT4R blocked by L-lysine), increased Glut (see #1). More on high Se here: http://mindrenewal.us/page10.html

 

5. lowering Se potentiates ACh, D, NE, but increases aggression.

 

6. increased ACh leads to lower Se, D, NE, but promotes anxiety and depression (in susceptible individuals). More on high ACh here: http://mindrenewal.us/page13.html

 

7. ? decreased ACh potentiates Se, D, NE, but promotes mania (in susceptible individuals).

 

8. RAM sleep deprivation leads to lower ACh, higher Se, NE, Cort, and BDNF, but can interfere with memory formation.

 

9. Modafinil indirectly potentiates Se, D, NE, and orexin (hypocretin).

 

10. Tianeptine leads to lower Glu (via adenosine A₁ receptors blocked by caffeine) and Cort, potentiates AMPA and BDNF, and helps with memory formation. Decreases Se?

 

Conclusions:

Modafinil and Tianeptine should be synergistic for depression caused by chronic stress if caffeine, alcohol, and nicotine is avoided.

 

Of course this is a huge oversimplification as those effects can vary in different brain locations.

 

If you have corrections and/or additional info, please let me know. Initially i wanted to make a drawing about it, but it seems too hard to do it.

Edited by jack black, 13 November 2016 - 04:24 PM.

[jack black]

LOL, no takers?

Here is a little problem. I'm having headaches for the second day of that combo. No headaches with tianeptine alone. I don't think it's caffeine withdrawal as I didn't take much before (a coffee and a couple of tea per day), and I did drink tiny amounts of tea and coffee yesterday and today to see if headaches go away. They don't. Tylenol dulls them some. I'm taking tianeptine in the form of free acid 10-20 mg and modafinil in the form of adrafinil, 100-200 mg. I'm not sure if that matters. Also adrafinil is only 95% pure. I noticed the vendor discontinued it and replaced by 98% but much more expensive.

Thanks for any constructive feedback.

BTW, I checked blood pressure and it's fine.

Edited by jack black, 14 November 2016 - 04:44 PM.

[Mind_Paralysis]

I'll try and give some feedback on this tomorrow - currently mega-swamped in the brain from sleeping-agents. (3 mg melatonin, 25 mg Quetiapine, 2,5 mg Oxazepam)

 

I'm thinking the Modafinil + Tianeptine -combo is actually a bit TOO stimulating for some people though - you and me, probably not an issue, but for others? Definitely. I don't think this is a valid combo for anxious depression - because both agents aren't known to have any greater effect on anxiety (in fact, some people actually get anxiety from Moda, although not the majority), hence why I have doubts about the stim-combo.

 

 

[jack black]

I'll try and give some feedback on this tomorrow - currently mega-swamped in the brain from sleeping-agents. (3 mg melatonin, 25 mg Quetiapine, 2,5 mg Oxazepam)

 

I'm thinking the Modafinil + Tianeptine -combo is actually a bit TOO stimulating for some people though - you and me, probably not an issue, but for others? Definitely. I don't think this is a valid combo for anxious depression - because both agents aren't known to have any greater effect on anxiety (in fact, some people actually get anxiety from Moda, although not the majority), hence why I have doubts about the stim-combo.

 

Thanks! maybe you're right with the over-stimulation part, especially since tianeptine really doesn't have any activity on serotonin (5HT) or histamine and the net effect is serotoninergic and histaminergic in addition to the desired increase in D and NE for my ADHD-like symptoms.

 

But, i would not call tianeptine a stimulant as its anti-NMDA activity is anxiolytic and lots of users here noticed it. I noticed sedation from it too. this is why i'm doing this combo. But, i will take just tianeptine tomorrow and see if headaches go away (i took a total of 4 tylenols and 2 naproxens to function today).

 

i revised the points 9 and 10 due to additional literature review. Here is the up to date version:

 

1. chronic stress increases corticosteroids (Cort) and glutamate (Glut) and promotes neuron loss and hence anxiety and depression.

More on high Glut here: https://area1255.blo...-levels-in.html

 

2. alcohol produces a release of dopamine (D), but hypodopaminergic state after stopping drinking. D1 receptor downregulation after chronic use resulting in depression and ADHD-like.

 

3. acute and chronic nicotine use increases serotonin (5HT) levels.

 

4. increased 5HT leads to lower ACh, D, NE, increased Cort (via 5HT4R blocked by L-lysine), increased Glut (see #1). More on high Se here: http://mindrenewal.us/page10.html

 

5. lowering 5HT potentiates ACh, D, NE, but increases aggression.

 

6. increased ACh leads to lower 5HT, D, NE, but promotes anxiety and depression (in susceptible individuals). More on high ACh here: http://mindrenewal.us/page13.html

 

7. ? decreased ACh potentiates 5HT, D, NE, but promotes mania (in susceptible individuals).

 

8. RAM sleep deprivation leads to lower ACh, higher 5HT, NE, Cort, and BDNF, but can interfere with memory formation.

 

9. Modafinil potentiates orexin (hypocretin), downregulates GABA, and indirectly potentiates 5HT, D, NE, Glut, and histamine.

 

10. Tianeptine leads to lower Glut (via adenosine A1 receptors blocked by caffeine) and Cort, potentiates AMPA and BDNF, and helps with memory formation. No effect on 5HT.

 

 

[jack black]

Ok, I did 2 things differently today. I took vit c and took a smaller dose of adrafinil (100mg or less). No headaches. I also noticed face flush 1 hrs after the dose and realized it was probably histamine related. Histamine is known to trigger headaches and I actually had cluster headaches when I was younger.
Mystery solved.

[jack black]

I'm thinking the Modafinil + Tianeptine -combo is actually a bit TOO stimulating for some people though - you and me, probably not an issue, but for others? Definitely.

You are right and I was wrong. I totally forgot about tianeptine's agonist action on opiate receptors. Activation of those leads to down regulation of GABA neurons and hence dopamine release.

Now I'm taking tianeptine only with no caffeine and feel that stimulation. I'm missing coffee though.

[PeaceAndProsperity]

 

RAM sleep

I think my computer needs some of that.. 

 

Edit: btw http://mindrenewal.us/page10.html is missing anxiety. Heightened serotonin without a shred of doubt causes anxiety. This is one of the most obvious things, besides depression and fatigue. Serotonin is probably the thing to cause most anxiety issues (or not?) of all the neurotransmitters, if it is too high.

 

Edit2: also why is it that high acetylcholine causes some of the same issues as high serotonin, like depression, moodiness, fatigue, hyperemotionality (oddly serotonin can cause both hyperemotionality and reduced emotions) if SE and Ach are strongly opposing like SE and DA?

Edited by RatherBeUnknown, 19 November 2016 - 12:22 PM.

[jack black]

 

 

RAM sleep

I think my computer needs some of that.. 

 

Edit: btw http://mindrenewal.us/page10.html is missing anxiety. Heightened serotonin without a shred of doubt causes anxiety. This is one of the most obvious things, besides depression and fatigue. Serotonin is probably the thing to cause most anxiety issues (or not?) of all the neurotransmitters, if it is too high.

 

Edit2: also why is it that high acetylcholine causes some of the same issues as high serotonin, like depression, moodiness, fatigue, hyperemotionality (oddly serotonin can cause both hyperemotionality and reduced emotions) if SE and Ach are strongly opposing like SE and DA?

 

 

sorry about the REM vs RAM.

 

great question in the edit2. here is another related question waiting for answers: http://www.longecity...ss-and-anxiety/

 

maybe anxiety is all about the balance between GABA and glutamate and other neurotransmitters are involved indirectly? i don't know for sure.