450 replies to this topic

[Kingsley]

CACNA1C Gene disrupts l type calcium currents. Ethanol regulates this.
CACNA1C Gene disrupts l type calcium currents. Ethanol regulates this.

 

I like it.  Good find.

 

I did a bit of digging and read a few studies and it is plausible that SNP's related to the CACNA1C gene are implicated in our issues.  According to my research, the most significant such SNP that has been identified is rs1006737, and it has been linked to schizophrenia, bipolar disorder, depression, and cognition.  Turns out I have one copy of the risk allele (out of two possible).  However, around half of all people, and more than half of people of European descent, carry at least one copy of the risk allele, so it's by no means a smoking gun.

 

That's the problem with trying to pin a medical condition on a particular SNP.  Research consistently shows (with some exceptions) that this is almost never possible.  At best, particular SNP's may contribute modestly to one's chances of developing a condition.  For example, as a carrier of one risk allele of the above SNP, my chances of developing bipolar disorder are increased 18%.  So, for example, if bipolar disorder occurs in 5% of all people, then my risk is 5.9%. Not terribly significant.  This is typically the story with SNP's--they're just a drop in the ocean of genetic variability. 

 

I am interested in your experiences with gabapentin.  In what ways does it help you?  Does it help cognition?  Sorry if I missed previous discussion on it. 

 

*Edit: the previous version of my post characterized gabapentin as an NMDA antagonist but a bit more research revealed that this is not true.  It was first thought by researchers to be an NMDA antagonist but was later shown not to be.  Very interesting drug--I need to do more research.

Edited by Kingsley, 04 March 2016 - 07:31 PM.

[medievil]

Many riskgenes are implicated in several mental disorders, however if your at risk of shizophrenia youll have many gene allleleas or whatever its called, there are like 1000 implicated in shizo, just having one simular gene that relates means shit.

[medievil]

 

 

Will I one day recover from the binge drinking of the past year?

Offcourse, what symptions do you suffer from?

[medievil]

 

Piracetam lowers (or redirects?) Acetylcholine, maybe try that?

Naltrexone

Naltrexone's mechanism of action in alcohol dependence is not fully understood, but as an opioid-receptor antagonist is likely to be due to the modulation of the dopaminergicmesolimbic pathway (one of the primary centers for risk-reward analysis in the brain, and a tertiary "pleasure center") which is hypothesized to be a major center of the reward associated with addiction that all major drugs of abuse are believed to activate.

Suppose it's dopamine related since l-tyrosine and alcohol works well for you (and other dopaminergics like you stated). The anhedonia might stem from some issue with the above mentioned pathway, which alcohol stimulates. Suppose people with anhedonia are more prone to drinking since it relieves their symptoms. Now in comes Naltrexone, stimulating their reward pathways and improving their anhedonia, drinking is no longer necessary. Ergo, no more drinking.

//total speculation and most likely wrong. Naltrexone is rather benign though, I'm going to try it myself for similar problems. Alcohol personally makes me social, but also quite retarded so I don't drink much.

Might also be depression-related.

 

Low Dose Naltrexone sounds extremely interesting. I've been reading up on it most of this evening and there's tonnes of both anecdotal adn scientific evidence to support it's effectiveness. Unfortunately there's a lot of exploitive quack-like websites who try and sell it as an all encompassing miracle drug for all diseases, that just devalues it's validity.

Would you know of any reliable European sources of it?

It seems to come in both liquid and caspule form, some websites require a prescription, others don't. There seems a lot of shadey websites offering online prescriptions which I feel a bit uneasy about. I don't think my GP would be willing to write me a letter of support so I'm a little stuck.

 

GP? So your from england, im collecting anecdotes about the horrific healthcare the NHS offers, have you any negative experiences? I come from belguim and im absolutely shocked by the healthcare the NHS provides, i hope in the future to expose the NHS, its shocking how people in england think its good 

[medievil]

You guys are idiots. First dehydrate yourself by drinking and then you run with the alcohol still in your system? that's really fucking unhealthy. 

So? we arent all healthfreaks and like to live life

[medievil]

I share a lot of the same symptoms, and can definitely relate to the positive effects of hangovers, and similarly after effects of GBH.

I never noticed any aftereffects of GHB, what do you notice?

[medievil]

 

 

 But the old thought patterns are still there.

This depends wheter problems in your tought pattern are part of your personal issues, this is not a problem for me at all as i dont suffer from depression, just anhedonia and my tought pattern is fine.

[Helllllo]

Phenibut didn't effect me at the slightest. Tried a couple
Of sources and up to 6-7 grams of the stuff. Is that a potential clue?

[Helllllo]

Could you link me to that thread please?

[medievil]

Phenibut didn't effect me at the slightest. Tried a couple
Of sources and up to 6-7 grams of the stuff. Is that a potential clue?

Used to have the use, i only noticed it after trying it for 10 times or so

[Helllllo]

Sorry Kingsley, shouldn't have phrased it like that. Haven't tried Gabapentin yet but i'm really keen.

Out of curiosity. Does anyone think supplementing calcium citrate might be worth a shot? Tempted to go to the chemist and get some now.

[Helllllo]

How's this for a crazy hunch.

Bcl2 mitigates ca2 entry and mitochondrial ca2 overload through down regulation of L-type calcium channels in PC12 cells. Over expression of Bcl2 is related to a reduction of Ca2 entry through L type calcium channels.

Could or Bcl2 expression be extraordinarily high? Could the re-regulation of L-type calcium channels via ethanol use temporarily fix this? I think i'm onto something.

 

[Helllllo]

Something is definitely inhibiting our ca2 influx and during the hangover, our ca2 gets reregulated via the crac channel?

[Helllllo]

Just a little update. My grandpa had similar issues. Depression, depersonalisation. Trailed different medication for the longest time but nothing worked. He ended up dying from motor neuron disease. It's now known that motor neuron disease stems from altered cellular calcium homeostasis, I think that i inherited the trait. If anyone has had als in their family, let me know!

[Kingsley]

Something is definitely inhibiting our ca2 influx and during the hangover, our ca2 gets reregulated via the crac channel?

 

I do think that calcium channels are in some way implicated, though whether primarily or secondarily, who can say?  I've been focused on the idea of NMDA receptor hypofunction, which is one cause of reduced calcium influx, since the NMDA receptor is one thing that controls calcium influx.  If I understand you, I think you are suggesting another mechanism that could be at play, i.e. a problem with the calcium channels themselves?  Certainly possible, though I can't really comment without doing more research.  Interesting idea. 

[Kingsley]

Just a little update. My grandpa had similar issues. Depression, depersonalisation. Trailed different medication for the longest time but nothing worked. He ended up dying from motor neuron disease. It's now known that motor neuron disease stems from altered cellular calcium homeostasis, I think that i inherited the trait. If anyone has had als in their family, let me know!

 

My issues definitely run in my family, and my immediate family could most likely be diagnosed as ADHD-PI, though there is also some schizophrenia and bipolar in my more extended family.  I think it is all inter-related.  That is one of the reasons I have focused my research so much on schizophrenia, the NMDA receptor, and inflammation.

[Helllllo]

I've been experimenting with nmda agonists and anti-inflammatories without much success. I've been researching intensely over the past few days and had another one of those eureka moments. Read a study that Talked about tachkynin-1 receptor knockout in mice. The knockout replicated adhd-Pi symptoms as well as social withdrawal. The receptor also modulates l-type calcium channel activity. First study I found connecting the dots. The most interesting thing is that they used a substance to reverse this. An L type calcium channel blocker with a similar mechanism to alcohol on the calcium channels. It's called nifedepine and this study: http://www.ncbi.nlm....ubmed/22884624/

States that it can 'ameleriote behaviour abnormalities by opening up l-calcium channels' and up-regulating tacr-1.

I've said this to myself before but I hope this is our way out.

Edited by Helllllo, 07 March 2016 - 04:16 PM.

[Kingsley]

I've been experimenting with nmda agonists and anti-inflammatories without much success. I've been researching intensely over the past few days and had another one of those eureka moments. Read a study that Talked about tachkynin-1 receptor knockout in mice. The knockout replicated adhd-Pi symptoms as well as social withdrawal. The receptor also modulates l-type calcium channel activity. First study I found connecting the dots. The most interesting thing is that they used a substance to reverse this. An L type calcium channel blocker with a similar mechanism to alcohol on the calcium channels. It's called nifedepine and this study: http://www.ncbi.nlm....ubmed/22884624/

States that it can 'ameleriote behaviour abnormalities by opening up l-calcium channels' and up-regulating tacr-1.

I've said this to myself before but I hope this is our way out.

 

So has the sarcosine stopped working or diminished in effectiveness?

 

I did a bit of reading on the TACR1 gene and the study you cited.  Plenty of research has suggested that TACR1 and calcium channels could play a role in various affective disorders, though nothing definitive.  Also, it's unclear whether our problem would be too much calcium influx or too little; I tend to think too little, but who knows.  I guess it all comes down to the possibility that calcium channel blockers would help us or some subset of us, which could be interesting to try, though I've read a number of safety issues associated with them and have not seen too much research suggesting to me in a big way that it'd be helpful.
 

[Kingsley]

You might want to take a look at memantine, which is a noncompetitive NMDA antagonist that allows normal functioning of the NMDA receptor (unlike other antagonists) while preventing over-excitation of the receptor.  I found a study suggesting that it may also act as an L-type calcium channel blocker.  See http://www.ncbi.nlm....pubmed/24589577. 

 

I have read some reviews where people swear by memantine for cognitive clarity, while others say it hurts cognition.  I intend to try it sooner or later to see if it has anything to offer me.  I have stayed away from it so far since I'm skeptical of NMDA antagonists, but its mechanism is more complex than simply blocking the  NMDA receptor.  Who knows, it could be helpful.

 

Speaking of calcium, I recently added a calcium supplement (calcium citrate) back into my stack to see what would happen.  I have found benefit from them in the past, and my diet appears to be pretty deficient in calcium.  Plus, my stack had not been giving me the same effects lately so I wanted to experiment.  I was extremely surprised to get a powerful clarifying effect from the calcium supplements.  It's like a clean stimulation, which reminds me of my best experiences with NMDA agonists.  I wonder if some of my issues are caused or exacerbated by calcium deficiency, or maybe all the NMDA agonists I take depletes it.  Something to consider, especially if your diet lacks calcium.      

[medievil]

Verapamil us a calcium channel blocker that is pretty much side effect free, ive allways needed phenibut on top of clonazepam for stim anxiety but with just using 5 meo dalt with my stimulants was enough to fox my anxiety,im unsure about needing 5 meo dalt but its a psychedlic without any psychedelic effects, pretty much mostly having just stimulants effects, i allways tought it was a strong 5ht1a agonist as one thing but no date about its moa

[Helllllo]

I don't consume any calcium either and calcium has helped significantly. Go figure

[ThreeKings12341]

Good morning everyone
My first post

I am 24 years old and Ive been reading this forum for 2 years or something..

Had 8 years depression tried every antidepressant nothing worked

My depression condidtion was :
Body dysmorphic disorder since the age of 16 till 24
Compulsive thinking since the age of 6 when parents broke up and
compulaive perfectionism (age of 6) which i lost with 16 when dymophobic disorder evolved
Mid-depression (according diagnose) 16-24
Or even earlier :0

How i felt: lethargic, no interests in life,living in a cage (emotionally) feeling emotionaly
Numb .. I could do sports and everything but i couldnt live in the moment or enjoy anything at all . Couldnt sleep because of compulsive thinking
No concentration while listening to television or person accept if it was realllllly interesting ..
No libido and the standard stuff ..
I always was a sporty person and im still .. So on the one hand i was lethargic but on the other i did a lot of sports in some phases so i could loose bodyfat so i can get my body dysmorphic discorder better.

Heres the thing:

A year ago i tried my first experiment: vit b 12 plus folic acid

Very disappointed didnt work..

5 weeks ago NAC!!!! (N-acetyl-cystein)

After one hour i could concentrate . After 3 hours i could live in the moment and didnt feel social phobic and felt really euphoric about the positive warmness inmyself ... Since 5 weeks permanenlty a great condition!!

I take 1 till 1.5 mg everyday with vit c and vit b6 and milk thistle since yesterday
And newrly every day i felt good (cognitive wise and emotionally i would say permanently a positive feeling)

The thing is..before i took nac the first time(5weeks ago) I used 2 sleep 12 hours (with trittco) and 10 without (but woke up many times) and that for maaaaanny years

And now i sleep 3 hours and i feel really fit - (hypomania anyone? .. I talk a lot, i am very fast . I can concentrate 200 % , focus for hours on one subject .. I think my father used to have achd or bipolar 2 .. Im not sure what he has because he smokes everyday ganja and drinks 2 bottles of wine so asking him wouldnt
Make sense ...

Yesterday i had my blood test to see if i have amino acid defiiency (im pretty sure glutathione)
And other things like seretonin and so on

I stopped smoking since the 22.02
And im sure i slept actually 8 hours through on nac only back then but now still after 2 weeks of smoke abstinence no sign of having long sleeps accept taking trittco... I took ashwaganda today but that helped only the 2days after stopping smoking (soft laser therapy) once which is 10 days ago ... So i dont know ...i was hypomanic before the smoking therapy when i could sleep longer ( for the record: hypomania i feel since taking nac the first time) or drinking really heavy alcohol in my deprrssion state and feeling really good the day after but on the day of drinking feeling like real crap

Hmm i feel really great but i dont sleep a lot
I would say emotionally im in a much better state but im still emotionally dull like in my depression state but with a positive vibe 2 it

I can laugh more, i can cry now but i only have tears but dont feel any sadness.. Since nac permanently a positive overall feeling with no real downs like i used to know them ..
Of the age of 16-24 i maybe cried 1 or two times where i felt sadness but it was dulled also ...

Libido since nac is a up and down i would say..
Sometimes reaaaallly good.. And sometimes crap (i would say with porn its easier 2 get a better errection as with girlfriend ) ..- i know porn is not good . I was on abstinence thru the site yourbrainonporn.com but i didnt help back then ... I think i should check my weener properly..soon

So my questions )) -would be soo happy if i get answers

1.
so if i take nac and that helps immensive- i probably have a glutathione defiecy - right?
Does nac. Help so the glutathione gets in my body or brain where it should has to be ? I read something that a reduced gluthione oxidised after 1.6 minutes .. So if i feel good through nac alrwady .. That means also that the gluthione is higher intercellucar?

2.
What else should i consider taking if u read my story? Anything better for me? - im looking for the perfect solutions through doctors and especially through here because what u PEOPLE write is soooo FANTASTIC. I cant thank xou enough !!

3.
S-acetyl-glutathione anyone? Seems to be a high quality product which should be the best form to increase glutathione .. The brand is eumetabol .. German site .. Maybe u guys know anything about s-acetyl-glutathione

So are there any supplements 2 take so i can get away from the dulled emotional condition?

4.
anything to take to help my libido ..
Any suggestions? L-carnitine-got them but only took them 1 time and already have them for a long time? Or a viagra 1 week therapy?

5.
What could i trY taking so i sleep more so i dont get up after 2-3 hours of sleep starting with full energy ...
My hypermania state :
Im quick, focused dont spend a lot of money have neaerly every smyptom what a hympomaniac should have except that i dont spend so much money on studf because
I dont have the money... I can be really energized but if i want to relax i am able to just sit on a sofa and relax so
I can switch

6.
I would like 2 know how many people on earth have a hypomania ... And is this a hypomanie if i dont have any depression episode at all??!???!??
Somewhere i read 1-3 % ? I think on wiki but a hypomania with depression episode ..
Would love 2 know something about this

.Cheers ! And im so looking foward 2
Your answers.. People here THANKS for this godly MASTER-Thread

[medievil]

I would actually focus on glutamate modulators, glycine, sarcosine, agmatine, memantine, minocycline, d aspartic acid, nefiracetam, pregnenolone, dhea, allopregnenolone etc

[ThreeKings12341]

Puhh ..thank you so ill have 2 googlle what are the best products or what it is .lin first case .. And s -acetyl-glucosamine also right??

[medievil]

Nac has proven benefits for mental illness due to its effects on glutamate and not really glutatione, but your gonna have to try glutamate modulaters to see wheter thats true for you

[ThreeKings12341]

Whixh are glutmate enhacer products? You mean nmda-stuff? I googled and a lot of your suggestions seem to enhance the glutamte.. Which is about what u just mentioned ? Am i right? Sorry im not that good in these kinda studf but know already a lot since i hve taken nac

So what u mean is tryying everything u mentioned sepperately ? Or which blood test is the right thing i can do
At the doctors?

Any other questions u may can answer )

And thanks for replying ao fast

Edit:

Ahhh and yes .. Before i took nac in jannuary i took the first time bccas for training which has glutamine
Which helped back then already )

And a glutamine defieacy.. Could that come from my eating habbits?


My first thing today which j will buy is

L-glutamin from pure encapsulations

Is that a first good step?

Should i stop taking nac then if i try l-glutamin?

Edited by ThreeKings12341, 10 March 2016 - 03:29 AM.

[Apprentice_Bob]

Um. I'm sorry. Troll?

[ThreeKings12341]

Um. I'm sorry. Troll?

no? Why would i write i write so much then?
Ive been 8 years to psychiatrists and i am curious if i can find answers here ..

[Helllllo]

Tried nifedepine and it seemed to exacerbate my depression/ADHD-Pi. Not sure what I was expecting. I get really excited about something and feel a little silly after. My next theory on all of this is that our nitrous oxide levels are ridiculously shot. The hangover in theory should correct this. My mood during a hangover is something that could be compared to being induced by nitrous oxide. Giddy, light, in the moment. I know there's a pretty close link between nmda and nos. Low levels of nos can feel like chronic fatigue. Will look into trying something nitric oxide related soon. Just trying to find a magic bullet like I have with ethanol. I think I, we will.. Eventually.

[Helllllo]

Also seems like low nos could look like ADHD. Nos is also linked to striatal dopamine which is why we probably get the centre of attention kind of feeling during a hangover. Will see how I go.