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Syntheso

'THE HPPD Stack' - let's create one

90 posts in this topic


Quite a few people have tried to create some 'stack' / supplement threads that haven't really taken off. I thought I would start one under some headings, and hopefully provoke some discussion in finding something that works quite well.
 
 
This is a work in progress, so please excuse the current incompleteness (many hands make light work ;) ). Let's work on it together. Please help me refine it with suggestions, studies, things I might have missed etc.
 
 
Eventually it would be nice to end up with a concise list of supp's and optimal doses based on group research and anecdotes. Generally I am trying to go for something that is more than merely palliative. Some bits I have copied from around the forum, so thanks to whoever found them  :) 
 
 
This is all theoretical/speculative. I am not a physician. Talk to your doctor before implementing any of these approaches.
 
 
Objective things we know about HPPD which we can target;
 
(I have copied this list from onedayillsailagain's Coluracetam hypothesis document).
 

- Shortened latency of the P2 component in flash Visual Evoked Potential (VEP) test

- Faster alpha rhythms
- Widespread cortical inhibition in eyes-open state
- Isolated and localized disinhibition of the occipital regions in eyes-closed state
 
 
Onto some ideas;
 
 
 
RESENSITIVE DOPAMINE RECEPTORS + INCREASE RECEPTOR DENSITY
 
Sulbutiamine
- synthetic derivative of thiamine (vitamin B1), crosses the blood–brain barrier more readily than thiamine and increases the levels of thiamine and thiamine phosphate esters in the brain
- increase of D1 dopaminergic (DA) binding sites was measured both in the prefrontal and the cingular cortex
- however  decrease of the DA levels in the prefrontal cortex
- modulatory effect of sulbutiamine on dopamernigic cortical transmission
- possible withdrawal syndrome after long-term use / tolerance
- "Sulbutiamine has additional effects at DA receptor subtypes other then the overall increase in D1 receptor density with chronic administration. It does improve mood and motivation, but this is transitory, with tolerance developing rapidly in contrast to the D1 receptor up-regulation. "
- also appears to increase cholinergic signalling in the hippocampus (http://www.ncbi.nlm.nih.gov/pubmed/4059305)
 
 
Summary: concerned about long term use of this.
 
 
CDP-Choline
- promotes partial recovery of the striatum dopamine and acetylcholine receptor function normally reduced with aging
+ it has been experimentally proven that CDP-choline increases noradrenaline and dopamine levels in the CNS
 
 
 
- - - - - - 
 
 
ALCAR
- retards the decline in the number of Dopamine Receptors that occurs in tandem with the Aging Process and (more rapidly) with the onset of Parkinson's Disease.
- enhances the release of Dopamine from Dopaminergic Neurons and improves the binding of Dopamine to Dopamine Receptors.

- can prevent the destruction of Dopamine Receptors by MPTP (a neurotoxin capable of causing Parkinson's Disease via Dopaminergic Receptor death.
 
studies to be quoted
 
 
- - - - - - 
 
Inositol
- increases D2 receptor density
+  "slight, albeit insignificant, increase in 5HT(2) receptor density"
 
 
 
- - - - -
 
- BDNF increase D3 receptor activity
 
- - - - - 
 
 
NMDA antagonists can upregulate D2 receptors. http://www.ncbi.nlm.nih.gov/pubmed/1382178
 
 
- - - - - 
 
Restricing Food Intake.
 
 
DOPAMINE SUPPORT
Given the apparent lack of dopamine in our system, ensuring the quality of our dopamine is as efficient as possible seems intuitive. This approach is not to do with increasing dopamine itself. 
 
L-Tyrosine
Dopamine pre-cursor
 
- - - - 
 
L-Phenylalanine
Dopamine pre-cursor
 
- - - -
 
Folic Acid
- helps increase dopamine levels in the brain
 

"The scientists found that mice with low amounts of dietary folic acid had elevated levels of homocysteine in the blood and brain. They suspect that increased levels of homocysteine in the brain caused damage to the DNA of nerve cells in the substantia nigra, an important brain structure that produces dopamine. Loss of dopamine causes the nerve cells to dysfunction, leaving patients unable to direct or control their movement in a normal manner." "Folic Acid Deficiency May Increase Susceptibility to Parkinson's Disease." Alzheimer's Disease Education and Referral Center of the National Institute on Aging (January 14, 2002). www.nia.nih.gov/Alzheimers/ResearchInformation/NewsReleases/Archives/PR2002/PR20020114folicacidparkinsons.htm 

W. Duan, B. Ladenheim, RG Cutler, II Kruman, JL Cadet and MP Mattson, "Dietary folate deficiency and elevated homocysteine levels endanger dopaminergic neurons." J Neurochem (2002) 80: 101-10. 

"Folic Acid is a necessary cofactor to the enzyme, tyrosine hydroxylase, which converts tyrosine to L-dopa. Folic acid also serves as a methyl donor in a number of neurotransmitter pathways, including the conversion of norepinephrine to epinephrine." 

"Glossary of Ingredients." NeuroScience, Inc. www.neurorelief.com/index.php?option=com_content&task=view&id=158&Itemid=48 

 

 

- - - -

 
 
Uridine
- modulates dopamine
 
 
- - - -
 

Fish Oil/EPA/DHA
- Supports dopamine
- Involved in visual parthway

 
- - - - 
 
Zinc
 
Zinc regulates the dopamine transporter in a membrane potential and chloride dependent manner.
The dopamine transporter (DAT), a membrane protein specifically expressed by dopaminergic neurons and mediating the action of psychostimulants and dopaminergic neurotoxins, is regulated by Zn(2+) which directly interacts with the protein. Herein, we report a host-cell-specific direction of the Zn(2+) effect on wild type DAT. Whereas low mumolar Zn(2+) decreased dopamine uptake by DAT expressing HEK293 cells, it stimulated uptake by DAT expressing SK-N-MC cells. Inhibition or stimulation was lost in a DAT construct without the binding site for Zn(2+). Also reverse transport was differentially affected by Zn(2+), dependent on whether the DAT was expressed in HEK293 or SK-N-MC cells. Pre-treatment of DAT expressing cells with phorbol-12-myristate-13-acetate, an activator of protein kinase C, attenuated the inhibitory effect of Zn(2+) on uptake in HEK293 cells and increased the stimulatory effect in SK-N-MC cells. Patch-clamp experiments under non-voltage-clamped conditions revealed a significantly higher membrane potential of HEK293 than SK-N-MC cells and a reduced membrane potential after phorbol ester treatment. Lowering chloride in the uptake buffer switched the stimulatory effect of Zn(2+) in SK-N-MC cells to an inhibitory, whereas high potassium depolarization of HEK293 cells switched the inhibitory effect of Zn(2+) to a stimulatory one. This study represents the first evidence that DAT regulation by Zn(2+) is profoundly modulated by the membrane potential and chloride.
 

- - - - 

 
L-Arginine
 
L-Arginine produces NO-independent increases in dopamine efflux in rat striatum

THE effect of L-arginine (L-ARG; 10-100 mM) on dopamine efflux from rat striatum was investigated using in vivo microdialysis. L-ARG (50 mM-100 mM), but not D-arginine (100 mM) nor L-citrulline (100 mM), produced a biphasic effect on dopamine efflux with an initial small reduction, followed by a large sustained increase. The effect of L-ARG was not prevented by nitric oxide synthase inhibition with NG-nitro-L-arginine methyl ester or 7-nitroindazole monosodium salt. Efflux of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) was reduced by L-ARG (10-100 mM), D-arginine (100 mM) and L-citrulline (100 mM). These data suggest that changes in dopamine, DOPAC and HVA efflux produced by high concentrations of L-ARG occur independently of NO, and that the use of high L-ARG concentrations are inappropriate when investigating the role of NO in striatum. 
 
 
- - - - 
 
 
Resveratrol
"Resveratrol may be useful to treat dysregulated dopamine neurotransmission, but it may enhance the risk of developing drug addiction."
 
- - 
 
Manganese (?)
 
- -

There is a brand called Dopavite (http://dopavite.com/) which contains its own formula for optimising dopamine.
 
 
 
INCREASING DOPAMINE (just palliative?)
There have been numerous reports on the forum demonstrating the efficacy of L-DOPA (Sinemet) in alleviating HPPD symptoms, thus indicating a lack of dopamine in HPPD.
 
Mucuna Pruriens
- suggested that this natural source of L-dopa might possess advantages over conventional L-dopa preparations in the long term management of PD. Assessment of long term
efficacy and tolerability in a randomised, controlled study is warranted
- reduced dyskinesias risk over synthetic source of L-DOPA
 
 
Concerns re increasing dopamine:
 
Whilst presumably increasing dopamine will help initially, and make one feel better, dopamine will eventually be downregulated. I would only consider this approach if you are going to supplement to keep your dopamine receptors sensitivised.
 
Might increase anxiety.
 
 
COMT INHIBITION
to prevent breakdown of dopamine

 
(thanks Brendan) 
 
  • Rhodiola Rosea
  • EGCG
  • Oleuropein
  • Quercetin
  • Vitamin C
tbc.
 
 
NMDA
 
Pregnenolone Sulphate (?)
 
Interestingly, unlike pregnenolone, pregnenolone sulfate is a negative allosteric modulator of the GABAA receptor[5] as well as a positive allosteric modulator of the NMDA receptor.[6] In addition, it has been shown to activate the transient receptor potential M3 (TRPM3) ion channel in hepatocytes and pancreatic islets causing calcium entry and subsequent insulin release.[7]
 
And here's another study: http://www.ncbi.nlm....pubmed/11861317.
And I also suggest this one (pregnenolone administration increases PregS concentrations+ its effects in schizophrenia): http://www.sciencedi...30645221100786X.
 
Piracetam
Subchronic treatment of aged mice with piracetam (500 mg/kg p.o. for 14 days) elevates N-methyl-D-aspartate (NMDA) receptor density by about 20% and normalizes the enhanced affinity of L-glutamate for the NMDA receptor. Since deficits at the level of the NMDA receptor might be one of the mechanisms underlying age-associated cognitive impairment, the effects reported for piracetam may be relevant for the cognition-enhancing properties of this drug.

 


http://www.karger.com/Article/Abstract/139100
 
 
 
- - - - 

 
Magnesium L-Threonate
- protection / upregulation of NMDA receptor

 
- - - - 
 
Magnesium Baths
 
- - - - 
 
Sarcosine (?)
increases the activity of NMDA receptors via the co-agonist glycine, both by inhibiting glycine transporter 1 and by acting as an agonist at the glycine site itself. 
 
 
- - - -
 
NAC
- antioxidant and NMDA properties
 

- - - -



UPREGULATE SEROTONIN RECEPTORS (?)

St John's Wort
- upregulates 5-HT receptors 
- other mechanisms

http://www.ncbi.nlm.nih.gov/pubmed/12775192

Tianeptine (pharmacuteical)
- SSRE. to be discussed. other mechanisms


Cannabinoid receptor agonists
- upregulate serotonin receptors
http://www.researchgate.net/publication/233418515_Cannabinoid_receptor_agonists_upregulate_and_enhance_serotonin_2A_(5-HT(2A)_)_receptor_activity_VIA_ERK12_signaling
 
NEUROGENESIS
 
Promoting growth factors - NGF, BDNF, GDNF, etc. 
 
 
HIPPOCAMPUS GROWTH

nrneurol.2012.27-f3.jpg

Creatine
- supplies energy to cells

 
 
- - - -
 
Resveratrol
 
 
GABA + ANXIETY
Whilst benzos have given me the biggest symptom reduction, ever, and are helpful for many HPPD sufferers, I am not interested in agonising GABA receptors, as I fear for their downregulation and for the body to not recover fully. That said, we could try to increase receptor densities...

Bacopa Monnieri
- upregulates GABA/reverses epilepsy; http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3306740/


Theanine (see http://www.longecity.org/forum/topic/54028-treating-anxiety-safely-effectively/)
- THEANINE could be a highly useful ANXIOLYTIC, since it DOES NOT function as a GABA RECEPTOR AGONIST but UPREGULATES THE PRODUCTION OF GABA within the brain, functions as a GLUTAMATE RECEPTOR ANTAGONIST, and enhances ALPHA-WAVE production within the brain.
 
NEUROPROTECTION
 
Taurine
- protects against excitotoxicity by stabilising calcium homeostasis
- increases GABA levels by acting as a gaba transaminase inhibitor.  
- also binds to glycine receptors.
 
 
GENERAL
 
Vitamin C
Vitamin B Complex
Vitamin D3 (N.B; fat soluble, take with fish oil)

much more to come...

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Nice one syntheso! I just wanted to say, re: Sulbutiamine, I took it a few times and definitely enjoyed it at the time. I think it may warrant further investigation.

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i think egcg is the strongest natural comt inhibitor, and green tea extract is cheap.  But as far as i can see from the few people on this board who mention it, it doesnt do much.

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Nice one syntheso! I just wanted to say, re: Sulbutiamine, I took it a few times and definitely enjoyed it at the time. I think it may warrant further investigation.

I tried it a few times and don't remember anything that noticeable happening. I have some, maybe I'll experiment with doses.

 

i think egcg is the strongest natural comt inhibitor, and green tea extract is cheap.  But as far as i can see from the few people on this board who mention it, it doesnt do much.

Cheers.

Added some new bits.

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ok guys its time for me to speak up there is so much talk on the new hppd online site of dopamine receptors compared to the old its getting f....ing ridiculous and have any of the so called related dopamine related or enhancing drugs helped anybody no! so letas cut the shit and the pseudo science and focus on what actually does and does not work

 

does work :

clonazepame :

possibly keppra over long too long periods of time

magnesium good for sleep helpd dp/dr and is harmless

fish oil ones low in mercury and high in epa and dha

Phosphatidle serine amazing for memory liquid pill orm powdered form from the same company didn't work for me

Vitamin d3 is more than a vitamin its a pro hormone needed for a lot.

lions mane very hard to find but helpfull

and exercise that's basically it.

 

ok shit that will mess you up:

DXM

resperidone

focusing to much on dopamine and not on the correlation between the meds that actually work for the majority of people that are pro cholernergic lik alpha gpc

and looking aT THE SEROTONIN CONNECION STARING US IN THE FACE ACTUALLY IM TIRED OF HAVING TO WRITE THIS SHIT sorry caps you guys just keep asking if its ok to smoke weed and keep focusing on dopamine and f...king sinemet which unless youre got parkasin related symptoms is shit!

 

fuck im gonna ban myself from this site soon the people on the old site understood way much more or actually what I need to do is write another fucking post explaining one and for all all the things ive picked up for the last 15 years of research so I don't have to keep repeating what OTHERS HAVE SAID TEN YEARS AGO AND PPS WHY AM I SOUNDING SO CRAZY AND ANGRY IM TIRED FUCK HPPD AND OVER SCIENTIFIC DOPAMINE RAMBLINGS  PEACE OUT.

 

 

 

PPS IM TRIALY PREGNENOLONE SO WHOEVER WROTE ABOUT IT YES IT SEAMS ON PAPER IT COUILD WORK AGAIN LOW DOSE AS ITS A HORMONE WHAT AM I DOING IM GETTING THE FUCK OTTA HERER

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I take L-Tryptophan for serotonin deficiency. I´m not depressed but it could be helpful in winter time when it´s not much sun. I think I sleep better also.

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ok guys its time for me to speak up there is so much talk on the new hppd online site of dopamine receptors compared to the old its getting f....ing ridiculous and have any of the so called related dopamine related or enhancing drugs helped anybody no! so letas cut the shit and the pseudo science and focus on what actually does and does not work

 

does work :

clonazepame :

possibly keppra over long too long periods of time

magnesium good for sleep helpd dp/dr and is harmless

fish oil ones low in mercury and high in epa and dha

Phosphatidle serine amazing for memory liquid pill orm powdered form from the same company didn't work for me

Vitamin d3 is more than a vitamin its a pro hormone needed for a lot.

lions mane very hard to find but helpfull

and exercise that's basically it.

 

ok shit that will mess you up:

DXM

resperidone

focusing to much on dopamine and not on the correlation between the meds that actually work for the majority of people that are pro cholernergic lik alpha gpc

and looking aT THE SEROTONIN CONNECION STARING US IN THE FACE ACTUALLY IM TIRED OF HAVING TO WRITE THIS SHIT sorry caps you guys just keep asking if its ok to smoke weed and keep focusing on dopamine and f...king sinemet which unless youre got parkasin related symptoms is shit!

 

fuck im gonna ban myself from this site soon the people on the old site understood way much more or actually what I need to do is write another fucking post explaining one and for all all the things ive picked up for the last 15 years of research so I don't have to keep repeating what OTHERS HAVE SAID TEN YEARS AGO AND PPS WHY AM I SOUNDING SO CRAZY AND ANGRY IM TIRED FUCK HPPD AND OVER SCIENTIFIC DOPAMINE RAMBLINGS  PEACE OUT.

 

 

 

PPS IM TRIALY PREGNENOLONE SO WHOEVER WROTE ABOUT IT YES IT SEAMS ON PAPER IT COUILD WORK AGAIN LOW DOSE AS ITS A HORMONE WHAT AM I DOING IM GETTING THE FUCK OTTA HERER

There has been quite a bit of success documented on this site with dopamine increasing drugs. I recall quite a few anecdotes about Sinemet and the COMT inhibitors trial where people 'felt like themselves' again and have even seen visual improvements (dopamine is required in visual processing). Also bear in mind that this is not pseudo-science, trials have been conducted. If you did not respond well to Sinemet, it does not mean that there is no dopamine problem in HPPD.

Yes, serotonin is involved somehow but there is no suggestion as to a useful serotonergic treatment. I haven't heard of one, at least. I've even experimented in this regard myself. I'm not even sure touching it is a good idea. We hardly know anything about serotonin (there is still question if it is really a 'pleasure' chemical). I am more convinced that aiding dopaminergic transmission will resolve other neurochemical imbalances.

Lion's mane mushroom is easy to get hold of. I am drinking some now  :P 

 

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Updates. Still lots more to come. Looking for your input!

Currently I am taking (spread throughout the day);

​750mg keppra
1,000mg CDP-choline
500mg ALCAR
2,000 mg vit C

vit b complex
vit D3 (cannot remember dose)
3,000mg eye q (fish oils)
1,500mg bacopa monnieri
1-3 g lion's mane mushroom mixed in a green tea
1 dopavite capsule

500mg magnesium l-threonate (before bed)

all in all, functioning very well. have been using this for around 2-3 months with the addition of CDP-choline only recently. ALCAR and fish oils were big noticers for me.

 

next on the bill will be uridine. then pregnenolone, I think.
 

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I'm doing a blinded experiment right now with Pregnenolone - I'm having my mom give me preg. or L-theanine (both in pure, bulk powders) in random amounts, while I take cognitive tests, heart rate, body temperature, and heart rate variability before and after. I'm almost certain I received pregnenolone yesterday because soon thereafter I felt really good. The feeling could only be described as a light 'high' (kind of warming, tingling sensation in the face/behind the eyes, kind of like a small marijuana buzz) along with increased working memory and enhanced resilience to stress. I did Duel N-Back before and after and my overall score rose some odd points and my 'average N-Back' rose to 2.55 from 2.45. After this lil' blinded trial, I'll probably opt towards taking it daily in the smallest amount I notice effects from.

 

L-theanine, if properly sourced and taken sublingually, helps me a bit. It just makes me much more calm; One day I took 800mg spread in about 4 doses and I felt extraordinarily 'chilled' and contented with my surroundings and what not. A few weeks ago I think it is what prevented me from having what I imagine was going to be some sort of breakdown - either that, or the anxiety caused from my other HPPD symptoms was just so severe that I truly experienced a panic attack, and what I thought was panic or fear before wasn't.

 

Now, along with my blinded Pregnenolone trial, I'm trying some other things.

(1) Inclined Bed Therapy: first night I woke up feeling more rested than normaly; back pain has gotten a bit better; only two days in thus far but I'm hopeful this can help me out a bit.

(2) CES: just received a refurbished OASIS II from MindAlive - last night was my first night and I used it directly before bed for 1hr. After tonight I plan on using it 2x/day, once directly before bed and once directly after waking.

  • If I don't get what I feel to be my desired results, I'm not going to give up on CES, though simply sell the current model I have and purchase a more modern version, perhaps the Fisher Wallace or the SOTA BioTuner
  • I may combine this with other things - micro-TENS, tDCS, heart rate variability training, or the Proteus Light and Sound Machine

(3) Proteus Light and Sound Machine: just came in today, in a way I have reservations due to the entrainment and I've seen people on erowid and other sites claim to have some intense psychedelic-like experiences... definitely not what I want in my current state of being; that being said, I've seen people claim that these devices have left them drastically more relaxed and peaceful, along with enhancing meditation. Norm Shealy, M.D., Ph.D. has a bunch of cool information on different things like this, but he has done studies where he increased progesterone, DHEA, oxytocin, etc. with his weird lil' aromatherapy acupoint products+light and sound machines and magnesium oil. He uses these devices for anxiety and depression all the time.

(4) Niacinamide: Just came in today; higher doses enhance serotonin uptake similar to Tianeptine; affects the same 'receptors' as some benzodiazapines; there is a book/textbook (I'll find it in my notes) where the author used extremely high doses to reverse anxiety in his case studies (from about 4-9g, ONLY 9g/day for a prolonged period of time caused some liver issues, which is what keeps some people from using this compound). Forum-goer Haidut on the Ray Peat Forums has a lot of great information on their experience with this, and claims that if you take a really large dose at night on say the weekend, you'll wake up feeling pretty 'blissed-out' so to speak, probably similar to abusing benzos, and then gradually 'come down' the next day. This isn't for recreational purposes, but simply to get in the max dose and receive the physiological benefits, though in a way that won't interfere with school/work

(5) Resistant Starch: I'm doing this more for the purported cognitive/emotional benefits derived from altering the microbiome, as opposed to BG reductions/better stools/dreams (though I will be tracking my BG since I just got a BG monitor); for those who are interested, in the TULIP thread, as well as a new thread dedicated to the microbiome, both on Longecity, there are dozens of studies showing RS and other things (GOS, MOS, etc.) increasing NGF, BDNF, and other nifty brain cell growth compounds; I'll also be consuming a large raw carrot salad each day and tracking my typical measurements, then possibly add other things such as Activated Charcoal, Bamboo Shoots, Flowers of Sulphur, Sodium Thiosulfate, and some other things (I'll try to get most benefits from food, hence the carrot salads, bamboo shoot recipes, and using retrograded starches, maybe retrograded lentils, peas, and so on)

(6) *EmWave: I received the original, not the EmWave2, off of Ebay for $16. Really helps a lot - there are times my 'coherence' plummets even when I'm thinking thoughts that I wouldn't have imagined were stressful. Attempting to learn and master the "Freeze-Frame" technique before I move on to other techniques

(7) Diet: Tracking my temps/hr/hrv/BG and will make changes based upon my readings and my cognition, mood, etc. Right now I'm more or less mixing what I enjoy from Dr. Peat and Paul Jaminet (Perfect Health Diet author/blog). Trying to really focus on the macro-mineral/electrolytes, so testing out how an abundance of sodium makes me feel along with the calcium I get from dairy (sodium can apparently enhance retention of magnesium, and anyhow the fruit and potatoes I eat have that, let alone epsom salt+baking soda baths); thinking about adding in kidney or 1 Brazil nut/day for selenium, along with TONS of heart for CoQ10, riboflavin, etc.

(8) Z-Health: A Z-Health master trainer I know hooked me up with a free copy of the "Z-Health Vison Gym" since I purchased the "R-Phase" package. I'll soon be doing visual exercises that some elite athletes use, and that some people have apparently used and thus have no more need for glasses/contacts (maybe can help with visual processing and the weird distortions I sometimes perceive); this will also incorporate movement exercises, 'brain-map' training, and breathing exercises.

 

Oh, on PregS - I've been speaking about the Pregnenolone analogues with Dr. Peat and he's given me some reasons to be cautious of them, though I'm not entirely turned off to using them. I can post the conversation(s) if anyone wants.

 

* I may sell the EmWave and the older Heart Math product I also obtained (that is to be used on Windows98/XP) as I can't use the software that accompanied either product on my laptop. I wanted to do extensive HRV training via the coherence coach and the 'video games' that really ramp up the intensity of training, then just use the device as a portable unit when out and about to remain level headed (sometimes I just feel soooo trippy/weird it's almost incapacitating). If I do this, I'll pick up the EmWavePro desktop/laptop unit with all the video game add-ons and the self-help meditation e-book and use that a couple hours a day. I may also give WildDivine a shot, too.

 

I'll post back with more later!

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Wow, lol, I was just typing something up and I accidentally exited out of the page somehow. I was going to say I'll post more here tomorrow or soon thereafter about things I'll be trying soon (infrared heat lamps, stronger incandescent bulbs, etc.) as well as things I want to try. But I wanted to quickly put it out there that you guys (and gals!) should look into CES. I'm really hoping that these effects last, or at least become cumulative (as I'll be doing more 'treatments' in the morning or midday, along with before bed). I've been running this current through my head (or, technically my ears, lol) for almost 2hrs now. The first hour my emotional and cognitive symptoms were gradually decreasing, which includes DP/DR. My visuals seemed to get a little worse (ever so slightly), but I believe this was just me becoming more mindful of everything since for once my thoughts weren't racing or overwhelmingly repetitive with a negative demeanor (worrying about my symptoms causing anxiety which then causes symptoms to get worse). It became evident, though, that something was going on when I had a spontaneous memory of watching some videos for class on the Stanford Prison Experiment.

 

That's when I decided to give it a second hour, and increase the intensity to its second highest (I believe) setting. I don't want to get my hopes up but right now my emotional/psychological symptoms are the lowest they've been in months (since I started TULIP which eradicated my symptoms until I stopped and stressors brought them back worse than ever), I have a slight tingly almost pleasant sensation in my head, and my visuals are much less 'trippy' than normal (my visuals are of moderate intensity, though when my DP/DR and/or anxiety/panic increases, so do my visuals, and it's not just visual snow, but the warping, trailers, etc; all extremely evident at night when I'm wearing blue-light blockers, too). Here's to hoping I wake up in a semi-positive state sans the anxiety-ridden demeanor!

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I'm doing a blinded experiment right now with Pregnenolone - I'm having my mom give me preg. or L-theanine (both in pure, bulk powders) in random amounts, while I take cognitive tests, heart rate, body temperature, and heart rate variability before and after. I'm almost certain I received pregnenolone yesterday because soon thereafter I felt really good. The feeling could only be described as a light 'high' (kind of warming, tingling sensation in the face/behind the eyes, kind of like a small marijuana buzz) along with increased working memory and enhanced resilience to stress. I did Duel N-Back before and after and my overall score rose some odd points and my 'average N-Back' rose to 2.55 from 2.45. After this lil' blinded trial, I'll probably opt towards taking it daily in the smallest amount I notice effects from.

 

L-theanine, if properly sourced and taken sublingually, helps me a bit. It just makes me much more calm; One day I took 800mg spread in about 4 doses and I felt extraordinarily 'chilled' and contented with my surroundings and what not. A few weeks ago I think it is what prevented me from having what I imagine was going to be some sort of breakdown - either that, or the anxiety caused from my other HPPD symptoms was just so severe that I truly experienced a panic attack, and what I thought was panic or fear before wasn't.

 

Now, along with my blinded Pregnenolone trial, I'm trying some other things.

(1) Inclined Bed Therapy: first night I woke up feeling more rested than normaly; back pain has gotten a bit better; only two days in thus far but I'm hopeful this can help me out a bit.

(2) CES: just received a refurbished OASIS II from MindAlive - last night was my first night and I used it directly before bed for 1hr. After tonight I plan on using it 2x/day, once directly before bed and once directly after waking.

  • If I don't get what I feel to be my desired results, I'm not going to give up on CES, though simply sell the current model I have and purchase a more modern version, perhaps the Fisher Wallace or the SOTA BioTuner
  • I may combine this with other things - micro-TENS, tDCS, heart rate variability training, or the Proteus Light and Sound Machine

(3) Proteus Light and Sound Machine: just came in today, in a way I have reservations due to the entrainment and I've seen people on erowid and other sites claim to have some intense psychedelic-like experiences... definitely not what I want in my current state of being; that being said, I've seen people claim that these devices have left them drastically more relaxed and peaceful, along with enhancing meditation. Norm Shealy, M.D., Ph.D. has a bunch of cool information on different things like this, but he has done studies where he increased progesterone, DHEA, oxytocin, etc. with his weird lil' aromatherapy acupoint products+light and sound machines and magnesium oil. He uses these devices for anxiety and depression all the time.

(4) Niacinamide: Just came in today; higher doses enhance serotonin uptake similar to Tianeptine; affects the same 'receptors' as some benzodiazapines; there is a book/textbook (I'll find it in my notes) where the author used extremely high doses to reverse anxiety in his case studies (from about 4-9g, ONLY 9g/day for a prolonged period of time caused some liver issues, which is what keeps some people from using this compound). Forum-goer Haidut on the Ray Peat Forums has a lot of great information on their experience with this, and claims that if you take a really large dose at night on say the weekend, you'll wake up feeling pretty 'blissed-out' so to speak, probably similar to abusing benzos, and then gradually 'come down' the next day. This isn't for recreational purposes, but simply to get in the max dose and receive the physiological benefits, though in a way that won't interfere with school/work

(5) Resistant Starch: I'm doing this more for the purported cognitive/emotional benefits derived from altering the microbiome, as opposed to BG reductions/better stools/dreams (though I will be tracking my BG since I just got a BG monitor); for those who are interested, in the TULIP thread, as well as a new thread dedicated to the microbiome, both on Longecity, there are dozens of studies showing RS and other things (GOS, MOS, etc.) increasing NGF, BDNF, and other nifty brain cell growth compounds; I'll also be consuming a large raw carrot salad each day and tracking my typical measurements, then possibly add other things such as Activated Charcoal, Bamboo Shoots, Flowers of Sulphur, Sodium Thiosulfate, and some other things (I'll try to get most benefits from food, hence the carrot salads, bamboo shoot recipes, and using retrograded starches, maybe retrograded lentils, peas, and so on)

(6) *EmWave: I received the original, not the EmWave2, off of Ebay for $16. Really helps a lot - there are times my 'coherence' plummets even when I'm thinking thoughts that I wouldn't have imagined were stressful. Attempting to learn and master the "Freeze-Frame" technique before I move on to other techniques

(7) Diet: Tracking my temps/hr/hrv/BG and will make changes based upon my readings and my cognition, mood, etc. Right now I'm more or less mixing what I enjoy from Dr. Peat and Paul Jaminet (Perfect Health Diet author/blog). Trying to really focus on the macro-mineral/electrolytes, so testing out how an abundance of sodium makes me feel along with the calcium I get from dairy (sodium can apparently enhance retention of magnesium, and anyhow the fruit and potatoes I eat have that, let alone epsom salt+baking soda baths); thinking about adding in kidney or 1 Brazil nut/day for selenium, along with TONS of heart for CoQ10, riboflavin, etc.

(8) Z-Health: A Z-Health master trainer I know hooked me up with a free copy of the "Z-Health Vison Gym" since I purchased the "R-Phase" package. I'll soon be doing visual exercises that some elite athletes use, and that some people have apparently used and thus have no more need for glasses/contacts (maybe can help with visual processing and the weird distortions I sometimes perceive); this will also incorporate movement exercises, 'brain-map' training, and breathing exercises.

 

Oh, on PregS - I've been speaking about the Pregnenolone analogues with Dr. Peat and he's given me some reasons to be cautious of them, though I'm not entirely turned off to using them. I can post the conversation(s) if anyone wants.

 

* I may sell the EmWave and the older Heart Math product I also obtained (that is to be used on Windows98/XP) as I can't use the software that accompanied either product on my laptop. I wanted to do extensive HRV training via the coherence coach and the 'video games' that really ramp up the intensity of training, then just use the device as a portable unit when out and about to remain level headed (sometimes I just feel soooo trippy/weird it's almost incapacitating). If I do this, I'll pick up the EmWavePro desktop/laptop unit with all the video game add-ons and the self-help meditation e-book and use that a couple hours a day. I may also give WildDivine a shot, too.

 

I'll post back with more later!

Thanks BPC!

Added theanine.

Could you provide some studies / more info on niacinamide ? 

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There are quite a few studies on the anxiolytic effects of Niacinamide, but studies suggest some neurotoxicity. I am on my phone at the moment so I can't post links to the articles right now.

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Currently looking into the following, need more research about possible negative effects. Check the links underneath to see the benefits they list;

Vinpocetine
http://www.nootropics.co.uk/vinpocetine.html

Aniracetam,
http://www.nootropics.co.uk/aniracetam.html

Noopept
see http://www.nootropics.co.uk/noopept.html

 

and, perhaps

Yohimbine.. ?  Hordenine ? Which are also on http://www.nootropics.co.uk

Anyone had any experience with these?

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The addition of Uridine has been very beneficial. Much clearing thinking, ability to perform tasks etc. Would love to hear some more reports on Uridine.

Mucuna - fantastic, I have to take upwards of 5g of a full spectrum product (6g is best), though, to notice an worthwhile effect. I will be taking Mucuna as and when.

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Have you been taking uridine without testing such as 23andMe, and if so, at what doses?

 

After symptoms that resemble serotonin syndrome from niacinamide, I stopped everything until I received PQQ and have thus started shining LEDs at my head again and take 20mg PQQ+5g Creatine daily; I've only been doing like 30 seconds at 2 spots on my forehead with the LEDs, and weekly, too (not EOD or 2 days on 1 day off). The results have been extraordinarily noticeable. I'm awaiting on a BioMat Pro and will also be adding Pregnenolone back in.

 

I'd be highly interested in taking uridine along with PQQ and Pregnenolone along with getting adequate red light to activate the mitochondria for proper steroid hormone conversion. Also, I'd like to add: I've been following Dr. Peat's work for sometime and now am kind of combining some of his recommendations (pregnenolone, tons of bright light exposure, not restricting carbs, etc.) with Paul Jaminet's and Dave Asprey's; but getting to the point - I've started up Bulletproof Intermittent Fasting again and it lights my brain up like nothing else. I completed a 36hr ketogenic fast to kick off receiving a bunch of Bulletproof Coffee, Upgraded Cacao Butter, Cocoa Powder, and Cacao Tea, but am now going to be doing BP-IFing along with eating lots of carbs after the fasting period. I believe this is working out well - I get carbs to start aiding my thyroid, yet in the morning I get chaperone mediated autophagy+other forms of autophagy along with the neuroprotection, oxygen utilization promoting, atp generating, GABAergic effects of ketones. Win-win.

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Have you been taking uridine without testing such as 23andMe, and if so, at what doses?

 

After symptoms that resemble serotonin syndrome from niacinamide, I stopped everything until I received PQQ and have thus started shining LEDs at my head again and take 20mg PQQ+5g Creatine daily; I've only been doing like 30 seconds at 2 spots on my forehead with the LEDs, and weekly, too (not EOD or 2 days on 1 day off). The results have been extraordinarily noticeable. I'm awaiting on a BioMat Pro and will also be adding Pregnenolone back in.

 

I'd be highly interested in taking uridine along with PQQ and Pregnenolone along with getting adequate red light to activate the mitochondria for proper steroid hormone conversion. Also, I'd like to add: I've been following Dr. Peat's work for sometime and now am kind of combining some of his recommendations (pregnenolone, tons of bright light exposure, not restricting carbs, etc.) with Paul Jaminet's and Dave Asprey's; but getting to the point - I've started up Bulletproof Intermittent Fasting again and it lights my brain up like nothing else. I completed a 36hr ketogenic fast to kick off receiving a bunch of Bulletproof Coffee, Upgraded Cacao Butter, Cocoa Powder, and Cacao Tea, but am now going to be doing BP-IFing along with eating lots of carbs after the fasting period. I believe this is working out well - I get carbs to start aiding my thyroid, yet in the morning I get chaperone mediated autophagy+other forms of autophagy along with the neuroprotection, oxygen utilization promoting, atp generating, GABAergic effects of ketones. Win-win.

Sounds like things are working well for you.. keep us posted. Am interested in the BP coffee, maybe when I have some cash.

I have 23andMe results but haven't looked at them in relation to Uridine. As per this thread, I began taking it, 250mg twice a day. Mainly for the modulating dopamine effects.

I occasionally intermittently fast and have found it quite useful.

 

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Synetheso, you're knowledge on these topics currently surpass me - mind helping me make sense out of all this:

 

http://www.jneurosci.org/content/12/6/2362.long "Therefore, under in vitro conditions in which PQQ is presented without an exogenous electron donor, it  appears as if the entire neuroprotective effect of PQQ is attributable to a direct oxidation of the NMDA receptor redox site. These results suggest the possibility of a novel role for PQQ, PQQ-like substances, and quinone-containing proteins in the brain, and may represent a novel therapeutic approach for the amelioration of NMDA receptor-mediated neurotoxic injury."

 

Currently, I'm going through all the Bozeman Science videos and Khan Academy videos to teach myself biology (my own research is currently more useful than what I'm learning in English classes and what not at college, haha). So I'm really just getting a hand on this stuff (spaced repetition and Bulletproof Coffee is helping!). But, when looking up NMDAR's on wikipedia, I find information that currently confuses me on the PQQ-NMDA® relationship:

 

"NMDA receptor function is also strongly regulated by chemical reduction and oxidation, via the so-called "redox modulatory site."[30] Through this site, reductants dramatically enhance NMDA channel activity, whereas oxidants either reverse the effects of reductants or depress native responses. It is generally believed that NMDA receptors are modulated by endogenous redox agents such as glutathionelipoic acid, and the essential nutrient pyrroloquinoline quinone."

 

PQQ is a 'redox agent' in many ways, yet at the NMDAr, according to that one study, PQQ acts as an oxidant. If oxidants 'depress native responses', and if one's HPPD is potentially caused by an NMDA-antagonist, does this mean that PQQ can 'depress' the response of the NMDAr's to NMDA-antagonists. For instance, PCP, Ketamine, and DXM are all NMDA-antagonists; I was laced with PCP and the night before and two nights after used tons of DXM and have used ketamine a few times previously. So, I have reason to believe my problems lie within NMDAr's. I feel as though PQQ is what has been giving me a cognitive edge in the past few days; so I can't see PQQ 'depressing' NMDAr's because I'd be screwed. All I can think of with my current (yet fortunately growing) knowledge of biology/neurology is that it is depressing what was done to my NMDAr's, not the NMDAr's themselves. 

 

If you have time to pick at this (if you even want to), I'd appreciate it. Thanks!

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Hey BPC. I'm not sure about that, your knowledge seems more advanced than mine to me! I will try and help though. I am merely inferring what I can from the literature.. I do not study biology formally.
 
If something is a ‘redox agent’ it means it has the effect of changing the oxidation state of atoms, either through reduction or oxidation.
 
In your case, we are presuming that the NMDA receptor is not functioning in a normal way (and, as I speculate, this is the case for most/all HPPD’ers). So presumably the response cannot be native, it will be altered: thus, from ‘oxidants […] depress native responses [at the NMDAR]', we cannot infer that PQQ depresses native responses. 
 
If PQQ is working for you, then we could perhaps infer that it is 'reversing the effect of a reductant', something that has ‘dramatically enhanced NMDA channel activity’ (does this mean upregulate ? ). In my thread about NMDA antagonism, I posited that perhaps there is NMDA hypofunction in HPPD, resulting in a diminished processing of traumatic memory and inability to recover from HPPD. The hypofunction could be due to a downregulation of NMDAR’s after upregulation, or another form of damage to the receptor. We could further speculate/infer from the above: Ketamine, PCP + other powerful NMDA antagonists act as reductants at the NMDA receptor. But does this make any sense, if reductants ‘dramatically enhance NMDA activity’ (NMDA antagonists presumably diminishing activity at the NMDA receptor).

The thing is, we are dabbling with correlation + causation here. I am not sure we can infer relationships between NMDAR agonism/antagonism and oxidants/reductants, which is what I think you were trying to do. I think we need to dig into the literature more. At this point, I really am not sure.
 
It would be good to discuss PQQ in relation to NAC. Quite a few people have had success with that here. It also acts the redox site of the NMDAR.

Please keep us updated about PQQ.
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Updates:

Doses of Mucuna Pruriens at 6g with
 

500mg CDP-choline
500-700mg ALCAR
2,000 mg vit C

vit b complex
vit D3 (cannot remember dose)
3,000mg eye q (fish oils)
1,500mg bacopa monnieri
1-3 g lion's mane mushroom mixed in a green tea
dopavite capsule

500-1,000mg magnesium l-threonate (before bed)

2-3 mugs of green tea a day

250mg uridine twice daily

...not quite cutting the mustard.

I still can easily fall asleep in the middle of the day after spreading the above out in the morning. My focus is better than usual, when I can motivate myself. I believe things could be a lot better if I did some psychotherapy, as mentioned in another post. The point is, though, that this is all helping quite a bit, but not enough. My visuals remain the same; mild-moderate.

I keep coming back to thinking about GABA, it's staring me in the face, but I am unsure how to proceed. It seems strange to think about because the main thing I am struggling with is lethargy/lack of motivation which seems to me more likely to be a dopamine issue, yet Mucuna isn't doing that much any more (I am not sure whether to increase my dose, or stop). The best ever mitigation of my symptoms was from an acute benzo dose, removing my visuals entirely for a number of hours, and restoring much of my cognitive function, at a time when it was completely defunct. I am avoiding GABA agonism as I am seeking a long term solution/recovery, so that's out of the question. GABA-wise, that leaves me with Bacopa which has been in my stack now for a while now, theoretically upregulating my GABA receptors (I should also mention that I only recently discovered it's serotonergic mechanisms which I shall include in the main post shortly) and Theanine, which I have tried before but not long term. I am looking to implement this when I next get back to my theanine supply. Inositol? I don't feel that this will be enough to give me what I am after. Even though GABA inhibits dopamine, I feel that if I enhanced it enough + the dopamine support I have already implemented, that I would function at more or less 100%; currently I feel like I am at about 80%. Quietening down some of the remaining hyperactivity is the last piece of the puzzle I feel. The question is how to do this sustainably.

I am interested in compounds that enhance dopamine and GABA transmission simultaneously. I haven't found anything promising yet.

On another note, I am keen to try Tianeptine, for various reasons.

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Also forgot to mention I tried CILTEP (chemically induced long term potentiation) from NaturalStacks a while ago, for 3/4 days. I found it help me focus more slightly, but I found it too stimulating. Had trouble sleeping those days even though I took it first thing in the morning. Possibly slightly worsened visuals. I will try it again another time to confirm.

Natural Stacks also have this; http://naturalstacks.com/products/magtech. Mmm yumm

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Thanks for the continuous updates, syntheso! Hoping that you can eventually get to 100% and be fully recovered. I'm hoping the same for everyone here, myself included.

 

I'll post here again later as to some ideas I have, things I'm trying, want to try, etc. but I've gotta rush and do some things currently. One question about something though: NSI-189...

 

I will be obtaining a gram or two in the next few weeks (unknown date; getting it from the second longecity group buy). I had previously only looked into the basic information about hippocampal neurogenesis and then found 2-3 studies unrelated to NSI, but related to the hippocampus and depression, alzheimer's, etc. So I put myself down to receive NSI. Now, I'm reading the studies/pharmacology/etc. (need more information, but don't know where to obtain solid information), and I'm a bit worried: NSI is partially derived from nicotinamide; niacinamide=nicotinamide, and niacinamide at large doses completely screwed me mentally and emotionally for 3-4 days (with another 3-4 days of feeling about 25% worse than I normally do). I'm just worried that I'm going to have some adverse reaction, lol. Should I even be worried? When I do receive it, I'll use the first day to simply test out 1mg and see how I feel (to rule out acute negative effects), then progress to 5 and eventually 10mg once a day. Not looking for any benefits until after 30 days, though. The new trial has a group using up to 120mg/day, so it seems safe.

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Bad news, and some hopeful news:

 

My experience with the BioMat began well, and now sucks, and I know why - the negative ions. Negative ions have been shown in a lot of different clinical trials to drastically lower serotonin, which, ironically, has helped in a lot of cases of depression, sleeplessness, etc. The thing is, I probably have really low levels of serotonin, or, at least, damaged 'receptors'. The BioMat works undoubtedly, and works 'well' (noticeable), yet the negative ions are starting to produce symptoms equivalent to that of my experiment with niacinamide: i.e. worse HPPD+depressive thoughts (which I normally never have), heightened anxiety and panic, night terrors (normally don't have), etc. I'm going to return it and thus have only lost about $200 (still a lot of money considering my families financial situation).

 

The hopeful news: I'll be discussing payment plans with a sales rep from Sunlighten - a company that manufactures their own and sells infrared sauans; they have home units of various sizes, along with portable units. The cool thing is, they have varieties that come in far infrared, or a more or less 'full spectrum' which has near, medium, and far infrared rays. The home units seem awesome (you can add chromotherapy and sound therapy additions, biofeedback-type devices, etc.). I'll probably get the cheapest portable unit. Other hopeful news: NSI will be coming in a few weeks, and my partial TULIP use has had benefits, so if I feel terrible for the next 3-7 days due to decreased serotonin, at least I know I'll feel better after that time, lol.

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So, I emailed a bunch of Z-Health trainers and I'm hopeful they'll get back to me so I can start doing Z-Health ASAP a few times/week. I'm going to make payments to become an "R-Phase" certified trainer through them, too, so I may as well work with some trainers prior to that. It will give me a foundation to do the visual exercises, too (which I may begin soon on my own). Also sent an email to Sunlighten to make sure I can work out a payment plan for a portable FIR sauna.

 

I found some interesting studies - when I go to back to my school for class (when I feel capable of staying there for more than an hour at a time, lol) I'll use their computers/databases to access the full-texts; they're interesting nonetheless:

 

http://www.ncbi.nlm.nih.gov/pubmed/24439959 Testing a Neurobiological Model of Depersonalization Disorder Using Repetitive Transcranial Magnetic Stimulation. "Conclusion: A single session of right-sided rTMS to VLPFC (but not TPJ) significantly increased physiological arousal capacity supporting our model regarding the relevance of increased VLPFC activity to emotional numbing in DPD. rTMS to both sites led to reduced depersonalization scores but since this was independent of physiological arousal, this may be a non-specific effect. TMS is a potential therapeutic option for DPD; modulation of VLPFC, if replicated, is a plausible mechanism." They hypothesized that the ventrolateral prefrontal cortex plays a large role in DPD.

 

http://www.ncbi.nlm.nih.gov/pubmed/20837362 Temporo-parietal junction stimulation in the treatment of depersonalization disorder.

"This is the first clinical trial of repetitive Transcranial Magnetic Stimulation (rTMS) in depersonalization disorder (DPD). After 3weeks of right temporo-parietal junction (TPJ) rTMS, 6/12 patients responded. Five responders received 3 more weeks of right TPJ rTMS showing 68% DPD symptoms improvement. Right TPJ rTMS was safe and effective."

 

http://www.ncbi.nlm.nih.gov/pubmed/20189190 Functional connectivity of the temporo-parietal region in schizophrenia: effects of rTMS treatment of auditory hallucinations.

 

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1911382/pdf/bullnyacadmed00589-0039.pdf THE TREATMENT OF DEPERSONALIZATION*

PAUL SCHILDER
 
http://www.nature.com/npp/journal/v25/n5/full/1395731a.html Hypothalamic-pituitary-adrenal Axis Dysregulation in Depersonalization Disorder
 
http://www.ncbi.nlm.nih.gov/pubmed/15089102 Depersonalisation disorder: a contemporary overview.
 
http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1516-44462012000400021&lng=en&nrm=iso&tlng=en Depersonalization and derealization syndrome: report on a case study and pharmacological management
 
Some of this reinforces what we already know to be true for some of us, such as 'hypofunctional' NMDAr's. What was interesting, though, was the dysregulated HPA-axis association. This actually may be true in my case as I've started tracking my heart rate and body temperature as a proxy for thyroid and endocrine function, as well as heart rate variability. My HRV is typically low (signifying a stressed, "non-coherent" state), and morning temps extremely low (similar to what is seen in hypothyroidism) and heart rate extremely high - sometimes up to 110bpm (stress hormones, probably). I'm more interested in how we can utilize the information of the VLPFC and temporo-parietal region to treat ourselves; since rTMS can't really be done at home, I wonder if tDCS, or better yet, HD tDCS, would be viable options, especially if 'targeting' those areas.
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