56 replies to this topic

[David555]

I've been struggling for some mental issues for several years now:

 

• anxiety
• anhedonia
• low mood
• fatigue
• depression
• poor stress response
• headache
• gone-like libido

I don't exacly know the origin of these problems but now I can only suspect overtraining (going to gym was almost a compulsive behaviour for me) and caffeine overuse which I had been practicing for years..

 

Anyway - I decided to do something about it and found the whole nootropics world. Shortly after that, I started the Uridine+EPA/DHA+A-GPC stack.

 

I felt noticeable improvement in the initial days - deppresion seemed to be significantly lowered, I felt a joy of life which was almost a forgotten feeling for me. Although, I felt that "darkness" is just around the corner. Well - I said to myself - I have to keep on taking the stack and it will get better for sure.

 

It didn't. After couple of days I got the worst headache I ever had. It was placed in my frontal lobe, kind of between the eyes and felt like there was a huge pressure in my brain. I felt "wired" like hell but inable to focus at the same time, sleep was not an option, I had a constant mind chase in my brain. There was also one more symptom - my eyebrows were jittering, my eyes started burning and tearing and I had a paresthesia-like feeling along my face - something with trigeminal nerve maybe. Not to mension about complete anhedonia. First thing I did was increasing a choline intake but it only made it worse. I stopped taking any drugs. The crisis lasted two more days after withdrawal and then all symptoms faded.

 

I've been trying to manipulate dosages after that, adding/removing some stack components but every time I got the same symptoms. Even taking fish oil alone gives me headache and makes me feel significantly worse. 

 

 

Since then I took brain MRI, brain CT, Sinus CT, talked to a neurologist, ENT, endocrinologist, even a dentist (I decided to pull out the tooth which had been treated by canal root some time earlier), bought a tons of vitamins, supplements and shit. Unfortunately I am no closer to any solution.

 

Since the crash i described above I've been experiencig "tired and wired" feeling, insomnia, headaches (only in the front half of my head) and that god dammned paresthesia and eyes jittering. I also developed erectile dysfunction and sever lack of libido (I'm 25).  I get insomnia quite often. I feel completely no joy or motivation whatsoever. I feel washed out of every emotions, feeling of pleasure and my life is strictly based on cold calculation. My stress resistance is terrible - I feel constant anxiety (however I developed some techiques to deal with it) . I also became extremely overreactive, nervous and inpatient. Did I mention about a constant headache?

 

What's interesting, mornings are usually better than evenings. After about 3-4 hour of being awake I start to feel worse and my headache is increasing, along with the paresthesia feeling and deppresion/anhedonia. I noticed, that it is strongly connected to stress. Having a couple days off, which I spent on pacing/meditating makes me feel noticeably better but it's not permanent.

 

I believe I depleted something. Not Ach obviously. Not dopamine either - I ate few tubes of l-tyrosine and every time it seemed to worsen my insomnia and anxiety. GABA - taking Ashwagandha relieved my anxiety which is my strategy now, however it did not helped with insomnia/anhedonia/deppresion. Anyway - i stick to that. Serotonin - that's my point of interest now. I am planning to buy 5-htp and see what happens. I bought a weak sleep supplement which contains 1mg of Melatonin and it definetly helps, I feel sighificantly better and falling asleep much, much faster.

 

Assuming my serotonin was depleted - would bumping ACH deplete it even further and raise ACH to enormous level? This: http://mindrenewal.us/page13.html does not look very convincing but it kind of backs this theory up.

Edited by David555, 07 June 2016 - 01:47 PM.

[thedevinroy]

You check for kidney damage?


Sent from my iPhone using Tapatalk

[David555]

Well i have had two urine tests and several blood tests. They all came out fine.

[thedevinroy]

So we can rule out insomnia and fatigue from poor uric acid metabolism.


Sent from my iPhone using Tapatalk

[thedevinroy]

Do mints or anything high in menthol make the twitching worse?


Sent from my iPhone using Tapatalk

[David555]

I tested myself quite well till now and found literally nothing. All I found is fatty liver but I am quite sure it's because i starter to elevate my mood by eating junk food. Apart from that, liver is working fine (I checked it).


Haven't checked it. Why would it?

Edited by David555, 07 June 2016 - 03:21 PM.

[thedevinroy]

Anyway, it sounds like your choline metabolism is screwed up. Choline production can lead to a decrease in serotonergic activity as well as using up your methyl groups. One way to test is to take some ALCAR and for a little while. If mood continues to improve, you were over methylated, if the opposite, you are under methylated and should look into taking Pitacetam to use up your acetylcholine stores.


Sent from my iPhone using Tapatalk

[thedevinroy]

Menthol by the way increases muscarinic receptors, so an increase in twitching would mean that you already have quite a bit of acetylcholine running around your brain.


Sent from my iPhone using Tapatalk

[David555]

I have tried ALCAR - I can't say it improved antything. Instead, made me overstimulated, "wired" and anxious. I have not been taking it for a long time though. 

 

Wouldn't simple serotonin bump (by using 5-htp for instance) decrease my ACH level? I am a bit prejudiced to nootropics now

 

 

Edited by David555, 07 June 2016 - 03:46 PM.

[thedevinroy]

Also seems that uridine decreases B vitamins including B12.


Sent from my iPhone using Tapatalk

[thedevinroy]

Serotonergic supplements tend to decrease libido. Have you tried just straight ALA? The ALCAR/ALA combo increases libido and repairs nerve damage from stress. Just thought it would be a nice fix. And yeah it will make you wired for a week or so, but you'll calm down and be able to sleep better over time, at least I was able to. Found just regular Cat's Claw powder plenty potent to calm my nerves before bed time during that process.

Edited by devinthayer, 07 June 2016 - 04:12 PM.

[David555]

Well, maybe I put it in a wrong way. Women attract me physically but I feel completely unmotivated to get into relations with other people. I literally hate being around people. It's not phobia to be clear. The just exhaust me, including women.

 

Also, it's hard for me to distinguish a deppression from libido problem. Ashwagandha, for example, gives me very vivid "porn like" dreams and concrete wood in the morning. Testosterone itself may be quite OK, the lack of pleasure is my biggest problem now. 

 

As for Your question - I only tried ALCAR.

 

I really don't want to put any strain on my body now, therefore maybe it would be safer to try the other way - to "treat" undermethylation with some methionine and other supplements.

 

Also - as I am reading the articles about methylation, I'm more and more convinced that undermethylation may be a cause, however I find some of the over methylation symptoms familiar as well. One of them is particulary interesting:

 

- histamine 

 

I have never had any allergic reactions in my life but for several months now, my sinuses a swollen and nose is blocked without any reason at all. I took an allergy test with no solid proof of allergy. Antihistamine drugs helps and provides imidiate relief (I use Fexofenadine). 

[thedevinroy]

Sorry I know it's a commitment. What kind of Ashwagandha are you using? What brand of extract... Sensoril, KSM-66, etc.


Sent from my iPhone using Tapatalk

[thedevinroy]

Methylation is just a concept to help you self medicate. It's scientific purpose is null. Really is just a tool for inspiration and nothing more.


Sent from my iPhone using Tapatalk
Too much histamine can certainly cause insomnia.


Sent from my iPhone using Tapatalk

[thedevinroy]

Your description of disinterest in human beings has more to do with chronic stress, perhaps affecting the amygdala. The amygdala is responsible for how we feel about people, from happiness to socialize down to sexual preference. If it gets stressed out, the neurons begin to change - some shrink, some lengthen. Long term ALCAR use was used in a rodent study to prevent or reverse that type of "damage". Their focus was on GDNF and Artemin.

Not saying ALCAR is the right choice. What I am saying is that you need to bump up GDNF and reduce stress. The best way to do that is to stop eating junk and start a well rounded exercise routine, especially one with moderate to intense endurance cardio.

Edited by devinthayer, 07 June 2016 - 04:43 PM.

[David555]

Yes, I'm not over excited about it but it's seems to be worth of investigating. I don't see any supplements to help it (methionine is widely found in a diet) do I am gonna stick with stress managment and diet. Thank You for all Your interest :-)

As for ashwagandha, I use ksm-66.

Edited by David555, 07 June 2016 - 05:24 PM.

[David555]

One more question - which nootropic would be best for mood enchancement? I tried noopept but that's not what I am looking for.

[gamesguru]

you ate a few tubes of tyrosine? intense. royal jelly, bilobalide, naringin, nobiletin, ibogaine and exercise all induce GDNF. something like flax, GTE, Mg/Zn would be okay for mood.

[thedevinroy]

Mood enhancement is a tough one. Dopaminergic receptors seem to down regulate quickly, so anything you take long term will likely have withdrawal symptoms. Just the nature of the beast. For temporary relief, MAO inhibitors are pretty awesome.


Sent from my iPhone using Tapatalk

[thedevinroy]

And KSM-66 is pretty good stuff. If you want to use it for a slight mood boost, double or triple your dose.

I fear non-competitive MAO inhibitors are potentially damaging. That's why I said temporary. I mean things like cocoa and coffee and various herbs. Maybe Rhodiola. I've tried Hordenine and was thoroughly disappointed with it's duration, but after trying Selegeline, I'm pretty glad I didn't pursue a sustained release. Haven't felt the same since. Not sure if it was its anticholinergic pathways or just straight fried my system with monoamines. Never so high in my life then on Selegeline.

Edited by devinthayer, 08 June 2016 - 01:47 AM.

[psychejunkie]

One more question - which nootropic would be best for mood enchancement? I tried noopept but that's not what I am looking for.

 

Your problems are more like a Cerebral Vascular Damage or Cerebral Blood Flow Disorder due to Cholinergic System overstimulation and maybe Alcohol comsumption along with your nootropic Stack.

 

You can try a Ketogenic Diet (like Steak and Eggs) or Fasting for a week or two to enhance your mood and increase Neurogenesis and Detoxification.

[David555]

 

 

And KSM-66 is pretty good stuff. If you want to use it for a slight mood boost, double or triple your dose.

 

 

Holy crap, i took 300 mg last night (which is far more than my usual dose - 100 mg before bed). Magic. I felt like somebody took a huge burden off my head. Paresthesia wore off and my contantly strained head muscles became relaxed. Headache dissapeared and my head was... light. Not to mention about noticeable mood elevation (slight euphoria). Not sure whether it was caused stress reduction, serotonin boost or some anticholinergic action but it worked perfectly. 

 

 

Your problems are more like a Cerebral Vascular Damage or Cerebral Blood Flow Disorder due to Cholinergic System overstimulation and maybe Alcohol comsumption along with your nootropic Stack.

 

You can try a Ketogenic Diet (like Steak and Eggs) or Fasting for a week or two to enhance your mood and increase Neurogenesis and Detoxification.

 

 

 

I definetely did not try any alcohol during that. However I did notice, that food intake reduction makes me feel better but I wasn't sure why it happens or how long should I sustain such diet. And yes, it seems like some kind of vascular issue - headache can be described as tension headache.

 

Like I said, it grows during stress situations, near the end of the working day. But there is on particular situation, which drives me crazy - driving a car. I used to love it but now it's a nightmare. Initialy it's fine but after - let's say - 40 mins I am unable to focus or even look on the road. Sometimes I even have to pull over and sit with closed eyes to regenerate, otherwise my forhead would explode. 

 

To be clear - it's not that I can't focus. My attension is not affected but it's ransomed with a pain and discomfort. Like my brain was processing too much, overstimulation or sth...

Edited by David555, 08 June 2016 - 06:56 AM.

[Doc Psychoillogical]

I've had similar issues in the past; the major culprits were either:

Cortisol levels, Thyroid function, Diet/exercise, changes in seasons/allergies, indulging irrational thoughts, lack of social stimuli, attempt to achieve pleasure by taking supplements, and lastly believing happiness can be found and sustained. Live life to pursuit of what makes you happy, thereby unknowingly you'll be living more and more happily everyday.

 

 

[David555]

, you are under methylated and should look into taking Pitacetam to use up your acetylcholine stores.

 

 

Overally, that's the direction I am heading now. I just wonder - what is the mechanism of depleting ACH by Piracetam? Is it achieved by stimulating a release of ACH?

 

I am asking, because - assuming that I am struggling with excess amount of ACH - it is not clear to me whether it means I have too much ACH stored or too much ACH released/produced. If it's the first - ok then. If the second - I am afraid it may worsen some symptoms and I should be careful. Also it would mean that there some issue with ACHe...

 

Shit, self-experimentation sucks :P

 

 

Sorry for unprofessional langauge, I know it all looks like bro-science at it best and English is not my native language

[psychejunkie]

 

, you are under methylated and should look into taking Pitacetam to use up your acetylcholine stores.

 

 

Overally, that's the direction I am heading now. I just wonder - what is the mechanism of depleting ACH by Piracetam? Is it achieved by stimulating a release of ACH?

 

I am asking, because - assuming that I am struggling with excess amount of ACH - it is not clear to me whether it means I have too much ACH stored or too much ACH released/produced. If it's the first - ok then. If the second - I am afraid it may worsen some symptoms and I should be careful. Also it would mean that there some issue with ACHe...

 

Shit, self-experimentation sucks :P

 

 

Sorry for unprofessional langauge, I know it all looks like bro-science at it best and English is not my native language

 

 

You'd better try Fasting/Ketogenic Diet for few days before taking any other medication down to your system.

[thedevinroy]

, you are under methylated and should look into taking Pitacetam to use up your acetylcholine stores.

Overally, that's the direction I am heading now. I just wonder - what is the mechanism of depleting ACH by Piracetam? Is it achieved by stimulating a release of ACH?

I am asking, because - assuming that I am struggling with excess amount of ACH - it is not clear to me whether it means I have too much ACH stored or too much ACH released/produced. If it's the first - ok then. If the second - I am afraid it may worsen some symptoms and I should be careful. Also it would mean that there some issue with ACHe...

Shit, self-experimentation sucks :P


Sorry for unprofessional langauge, I know it all looks like bro-science at it best and English is not my native language

I am so glad that you liked the effects from Ashwagandha. I didn't realize you were taking such a low dose. I take 1200mg of KSM-66 a day. For instance, Jarrow has a 300mg pill in a 120 count. They were using Sensoril which was a bit more stimulating (and 50% stronger) but switched to KSM-66 not too long ago. They are both top of the line extracts... I just always liked the Sensoril better. Same price, less pills for the same compounds.

Racetams work to deplete choline stores by increasing choline uptake possibly by increasing phospholipid synthesis and acetylcholine receptor densities. It might also have other effects that reduce choline (like increasing other enzymes?) and has a an affect at reducing re-uptake as well which means once it's in your head, it is more likely that it stays there until it's gone - doesn't find its way back to the body as fast.

Just to be clear, no one can be overloaded with too much ACh or uridine leftover for more than a few days. It doesn't even last that long in your system. Thus, if this is your problem, your whole system is producing more than it consumes. Racetams will only help you consume more choline in your brain. It's likely not a permanent solution even if it does work.

On the other hand, some people do get lasting (side) effects from racetams. So... It's hard to tell. Increases in twitching mean it is a bad idea to continue on that stack.

Anyhow, I will agree with you that it sounds like you are overstimulated with something and your cholinergic system seems to be out of whack. My guess is that neuroplasticity screwed you. When we stress our brains in a time where the brain is receptive to information and transformation, we get lasting effects via the neuroplasticity phenomenon - the brain that changes itself. This is how people get tinitus from medications - the brain fights back the changes from the medicine and adjusts at a cellular level to cope with its new experience.

I say go big on reducing effects from stress and taking back your neuroplasticity starting with Ashwagandha. It reduces effects from stress, relieves headaches, and it boosts GDNF via the RET receptor. Use that motivation to get yourself to a gym and on a treadmill, then sign up for a team or league or class to an intense new sport. Learning while exercising has an amazing synergy for a long lasting mood enhancement and positive neuroplasticity especially when combined with socializing in a pleasant atmosphere to help reset your amygdala.

Edited by devinthayer, 08 June 2016 - 11:15 AM.

[David555]

 

 

, you are under methylated and should look into taking Pitacetam to use up your acetylcholine stores.
 

Overally, that's the direction I am heading now. I just wonder - what is the mechanism of depleting ACH by Piracetam? Is it achieved by stimulating a release of ACH?

I am asking, because - assuming that I am struggling with excess amount of ACH - it is not clear to me whether it means I have too much ACH stored or too much ACH released/produced. If it's the first - ok then. If the second - I am afraid it may worsen some symptoms and I should be careful. Also it would mean that there some issue with ACHe...

Shit, self-experimentation sucks :P


Sorry for unprofessional langauge, I know it all looks like bro-science at it best and English is not my native language

(...)
Just to be clear, no one can be overloaded with too much ACh or uridine leftover for more than a few days. It doesn't even last that long in your system. Thus, if this is your problem, your whole system is producing more than it consumes. Racetams will only help you consume more choline in your brain. It's likely not a permanent solution even if it does work.

(...)

 

And that may be the whole case. I definetely don't use any cholinergic drug and yet, problem still exists so whatever happend, it seems to be permanent. Also, I believe my problems have been modulated by stressful job (actually, I know for fact, that since the moment I started working here my headaches became unbearable). Luckily, I'm leaving this firm in two weeks to a more peaceful one. I hope for the best. Who knows, maybe it's simply overstressful style of life which sucks every piece of energy. One way or another, managing stress seems to be the key so I'm gonna go for it.

 

At this point I take Ashwagandha, Ginseng (400 mg/dayu) and plan to buy some 5-htp before bed. 

 

As for racetams - I may have some noopept left. I never used it alone, always with choline/a-gpc. I'll give it a try without any choline source and see what happens. After all, nothing worse can happen anymore.

 

Thank You so much for explaining what I asked about. I'll give some feedback shortly.

[gamesguru]

you can definitely take too much choline, as mentioned its going to be usually a case where your body isnt excreting it properly. fish body oder, not sure if that has to do with choline per se, or its metabolites... but it certainly depends on excess choline consumption. thus other side effects may also be expected. for mood enhancement, consider Tianeptine

 

as for MAOIs, curcumin, quercetin and tea [1] are milder than rhodiola, which has many harsh properties. (unfortunately, im afraid, their MAO activity is also milder... they all three also inhibit COMT and DNA methylatranferase)

 

as for cardiovascular health, ginkgo is a potent vasodilator. and rutin has the desirable effect of reducing capillary permeability WHILE ALSO reducing blood thickness [2], making the blood thinner and improving circulation by reducing leakage (tiny holes in the artery often lead to end-stage failure).

Edited by gamesguru, 08 June 2016 - 01:20 PM.

[fntms]

The ginseng OP is taking has cholinergic effects by reducing acetylcholine transferase.

[David555]

Ok, time to share some thoughts. I have been reading a lot and giving much thought to it and it seems, that some of my claims may have been wrong however the clue of the problem remains the same - serotonin.

I lifted ashwagandha dosage to 3x300mg every 3 hours and it was too much. Today I took 2x300 mg with 6 hours interval in between and it feels much more reasonable. The main effects Ash is giving me come from its ache inhibitory properties. It obviously results in massive stress reduction. I can say now, that achetylcholine overload was never an issue sińce I am experiencing it right now (in mild degree however) and it feels totally differrent. Yeah, my head feels full but there is no such pain, just fullness. Not to mention about personalny change - cold and logical. Even my English became much smoother.

All in all - achetylcholine plays a huge rolę during ashwagandha supplementation in my case. Despite its ache inhibitory action, the symptomem are mostly bearable.

I have a few question though.

I am kind of afraid about that inhibition. Wouldn't it cause any negative issues like:

- ach receptora downegulation
- ach enzyme upregulation
- chat enzyme downegulation

? I am aware, that ashwagandha isn't nearly that strong in its action to cause any severe disregulation but let's consider the worst case, for the sake of safety. Also, can somebody please give me a clue how to influence those 3 potential phenomenons?

Now back to my primary symptoms which were headaches and severe depression. I've read a lot during last few days and here's what I've found.

As I suspect, serotonin "deficiency" may be playing the main role. Considering my chronic caffeine intake - which in my opiniom I have always been a bit oversensitive to - I basfully suspect Tryptophan Hydroxylase downregulation.

Here's why I think that way. I noticed, that despite everyday complete anhedonia some situations give me a brief shot of what we could call a pleasure but it's intensive As hell and much more enjoyable than it 'should' be. For instancce, I avoid listening to music sińce it sucks all that what is left of my life energy. However, there are days when I operate a bit better than usual so I decice to put my headphones on. Then, I get a literal 'shot' of euphoria and pleasure. But it's brief, very brief. 10-15 tops. After that I experience a Rapid mood drop and brain fog, which makes music merging to cacophony that makes no sense and further listening is pointless sińce I do not actually listen at all anymore, I just hear sounds.

Situations like this happen all the time. I remember going to Itally once. I was visiting Toscania. One I saw the classical 'Italian' sights I felt a warm feeling of joy, gratefullness to be there (I personally love Italy). However this feeling lasted a couple od mins and then - crash. I knew it was unntaural to have such drastic mood swings and I know it now. Feels like something is being depleted in such situations.

At this point I have experimented with all neurotransmitters using their precusors and/or agonists except serotonin (I mean all of the Big Four). I experienced a sick rage on dopamine, cold logic on acetylcholine and complete indifference on Gaba. Each of this experiences differ from what it suppoused to feel, none of them was worth keeping because all of them where in shade of that fucking anhedonia, complete unability to feel pleasure ot at least well being. Therefore serotonin is my next shot.

Now the question is - receptors or its production? I doubt I have downregulated receptors. I have never used any drugs in my life. Actually, I have been excersising regulary for the last 6 years and been regulary using caffeine (sometimes in excessive amounts) which should led me to upregulation of those receptors (according to researches I read). My stronger than usual reactions to mild stimuli seem to back this hypothesis. Now, During Ashwagandha supplementation, after initial euphoric reaction I feel a stable but very, very subtle mood lift and my anhedonia has been lifted but also not very much. May I say it's because receptors further upregulation which ashwagandha is known to cause?

Also using caffeine and chronic stress I have been living in may have downregulated my Tryptophan Hydroxylase and now my ability to produce 5-htp may be decreased. There is also AADC but at this point I don't think anything would be wrong with it.

Anyway - I ordered 1 g of 5htp, just to see if AADC works fine and how my receptors would react to it. Then I plan to buy Bacopa and upregulate TH. Any advices/comments?

Edited by David555, 10 June 2016 - 07:50 PM.