178 replies to this topic

[Mind_Paralysis]

Alright there, ya wanker, ya pisshead. Alright there, ya indigent.  Keep a level head, don't get frustrated, be real, don't listen to too much music, don't worry about anyone who doesn't worry about you, stay focused, venture out of your comfort zone but stay true to your roots, thrive on the unfamiliar, stay confident but open-minded, partake an ongoing educated, keep your cool, and last of all: don't neglect your physical.

 

All right, perhaps I was a bit too harsh in my last post... a bit of exaggeration.

 

The part with a naturally increased sensitivity to trauma is true though. Only by blunting the response from the amygdala to that hyper-awareness can a more normal life be achieved.

 

Same as myself - telling me to cheer up and think positive about my slowness isn't actually going to make me less slow.

 

And being slow causes problems.

 

Same thing with hyper-awareness and hyper-response.
 

[gamesguru]

You complain about being slow?  So get up to speed, man.  People telling you to cheer up doesn't help you calm down?  So learn to chill yourself out, man.  People don't like the way you talk, so shove a broom up your ass.  After that, ya better shave and come suited up son... even if it's just to smoke spice in an underpass with your buddies (#gutterlife).  People will always judge you on first impressions and appearances, to learn to make a good one.

 

Very sorry about that.  It wasn't addressing anyone here in particular, just a pretend borderline audience who googled us for advice.  I'm not going to teach you mindfulness over a forum, I can give you a taste of it, maybe encourage a few baby steps.  But only you know if you're on the right path... and if you don't know where you want to go, it doesn't matter much which way you walk.

Edited by gamesguru, 27 August 2016 - 07:37 PM.

[Mind_Paralysis]

Out of curiosity GamesGuru, seeing as you have what I would like to call EDD - Emotional Dysregulation Disorder, what is your take on a potential revelation of a new, effective medication for the treatment of EDD?

 

Would you be willing to take a combined choline-inibitor and selective NAA-reuptake inhibitor? I.e, a drug which would simultaneously decrease your emotional response to events, as well as alter your analysis of the communication you receive from others.

 

What parts of the disease would you be the most interested in treating? And what is your assessment of the nature of the disease btw? Me, I obviously think it's a Neuropsychiatric Disorder, fairly similar to Hyperactive Attention Deficit - a difficulty in self-inhibition. What do you think about my musings regarding the evolutionary explanation of the existence of EDD? Does it hold up to further scrutiny? Could you recognize yourself as having such a function in a group?

 

 

I gotta' admit... the mad scientist in me totally want to strap you down to a surgical table and inject your frontal lobes with an NAARI, lol! And pump you full of acetylcholinesterase-inhibitors - just to see if this could FINALLY be the answer! xD

 

 

EDIT:

 

Btw... I finally found a connection between N-AcetylAspartate and Acetylcholine. Check this out:
 

 

NAA is the second-most-concentrated molecule in the brain after the amino acid glutamate. It is detected in the adult brain in neurons,^[2]oligodendrocytes and myelin^[3] and is synthesized in the mitochondria from the amino acid aspartic acid and acetyl-coenzyme A.^[4]

 

 

Acetyl-CoA is also an important component in the biogenic synthesis of the neurotransmitter acetylcholine. Choline, in combination with acetyl-CoA, is catalyzed by the enzyme choline acetyltransferase to produce acetylcholine and a Coenzyme A byproduct.

 

 

Well, well, well... sooo... EDD-ers have some sort of multi-dysfunction in their ratio of aCh and NAA... Too much aCh and too litte NAA. Now then... what can we do to change this relationship?

 

Btw, anybody else think the NAA is the key-component in the hyper-attention to emotional cues (since that alteration was noted in the PFC), while the aCh is the key-component in the hyper-activity in the amygdala?

 

Hmm... I just realized something... do we actually WANT to change the NAA-levels? Because wouldn't Hyper-attention to emotional cues, WITHOUT hyper-response from the amygdala, instead manifest as... ULTRA-HIGH-EQ?!! : O

 

In essence... would blunting the response to outer stimuli be enough? Meaning, that if EDD-ers are allowed to retain their hyper-attention, they would become the ULTIMATE hostage-negotiators, the PERFECT personal assistants, FANTASTIC mid-level bosses, et c, et c.

 

Ah' dunno'... It might be that you need to keep this relationship in balance, so it won't be enough to change just the response, but the filtering as well - especially if it has to do with acetate-fueled synthesis of competing compounds. But perhaps we really should consider not treating every facet of the disease...? These traits obviously exist because evolution ordained them as useful for a pack-animal.

Edited by Stinkorninjor, 28 August 2016 - 10:43 AM.

[gamesguru]

Uh, who said I have anything?  Just some jackass who hacked into my account and went spreading lies?  For all anyone knows, I'm a perfectly healthy dude with an addiction for posting crude science.  What're you, Sigmund Freud or Sherlock Holmes something?  Eat some frozen fruit and chill, bro.

 

The frontal lobes act as a sort of filter, computing the rights and wrongs, the trues and falses.  It is the executive who gives the final decision.  It is reduced in BPD.  Obviously the amygdala isn't reduced.  So I like the classic description of hyper-emotional and hypo-logical, a feminine state.  After something goes wrong, whether spilling coffee on my lap, arriving late to work and being sent home for the day, or flirting with a girl for days only to find out she's been a tease... anything someone says to trigger me, I find that puts me on a bad note and I am not quite the same for the rest of the day, even if someone (of course, not a colleague or friend) lets me vent and use them as a punching bag.

 

In another thread the tentative assumption was reached that higher acetycholine means more BPD symptoms (and we cried foul on bacopa and moodiness), so in that light, this AChE inhibitor suggestion seems to be very counterproductive.  Really, more attention needs to be paid to dopamine and glutamate.  So far the investigation there has been grossly insufficient.  Swell to tie up loose ends first, before moving onto less likely candidates... but, I digress...

 

The NAA (N-acetylaspartate) is something new to me.  Checked it up, and indeed, low NAA in the amygdala is a common finding in BPD populations.  The study I was reading also indicated decreased levels of brain creatine (just recommending fish and grassfed meats for that).  Soybeans, cocoa, and coffee beans apparently contain NAA and also NAG.  Four fifths of NAA is produced in the mitochondria, by a mitochondrial enzyme.  So my second thought (after soybeans) is to go the mitochondrial biogenesis route.

[Mind_Paralysis]

Made an edit, have a look-see what you think. = )

 

Btw, I gotta' double-check, but I think the low NAA was actually noted in the PFC and not the amygdala. Although now that I can see the very clear connection between NAA and aCh, I can see how it may well be that the amygdala is flooded with aCh, but terribly low on NAA.

 

The reason I myself am focusing on these other transmitters than the traditional ones, is because I honestly don't think they're involved in the pathology - pretty much every chemical they fruitlessly use to treat EDD in public healthcare is focused on Dopamine or Serotonin - and the results have, as of yet, been less than nil. Occam's razor implies then, that to continue to focus on those transmitters, must be a folly.

 

EDIT: Apparently there are signs towards a decrease in both the Amygdala and the PFC of NAA. Just seems as if maybe there's a greater deficit in the PFC - 19% less than controls, on average.

 

Intriguing...

Edited by Stinkorninjor, 28 August 2016 - 11:48 AM.

[gamesguru]

Yeah, I think it was specifically the dorsolateral PFC.

 

The serotonin and dopamine agents are effective in treating "heat of the moment" symptoms, e.g. moodiness and poor reasoning.  Even something like lithium orotate and green tea could be efficacious there.  They are not very effective, however, in treating the chronic ones: self-disturbance (a sort of amnesia of the self), the deficit of facial or emotional recognition (social anhedonia), and the general executive interpretation of social cues (which is reduced to a level similar to that of Asperger's).  Borderline personality is very complicated, with many symptoms, many causes, often too much dopamine in one area, but too little in another... too little noradrenaline in that same one area, but too much in that same other one!!  These sorts of irregularities makes it very difficult to address all symptoms, especially with one medicine...

[jack black]

Btw... I finally found a connection between N-AcetylAspartate and Acetylcholine. Check this out:

NAA is the second-most-concentrated molecule in the brain after the amino acid glutamate. It is detected in the adult brain in neurons,^[2]oligodendrocytes and myelin^[3] and is synthesized in the mitochondria from the amino acid aspartic acid and acetyl-coenzyme A.^[4]

Acetyl-CoA is also an important component in the biogenic synthesis of the neurotransmitter acetylcholine. Choline, in combination with acetyl-CoA, is catalyzed by the enzyme choline acetyltransferase to produce acetylcholine and a Coenzyme A byproduct.

Well, well, well... sooo... EDD-ers have some sort of multi-dysfunction in their ratio of aCh and NAA... Too much aCh and too litte NAA. Now then... what can we do to change this relationship?
.

This is very interesting. How did you think of NAA?
Could it be something as simple as too active ChAT stealing acetyl Coenzyme A from the NAA synthesis?

[jack black]

These traits obviously exist because evolution ordained them as useful for a pack-animal.

I did find a paper that seems to support it. However it's a bit over my head and not sure i get it right. Not sure if it relates to BPD either:
http://europepmc.org...cles/pmc4381234

BTW, searching for boosting NAA i found:

EPA: http://news.bbc.co.u...lth/6440979.stm
Li: https://www.biotechp...hium-part-one/v

These things are known for benefiting ADHD and BPD, respectively. I'm thinking this is very fruitful idea to explore further.

Edited by jack black, 30 August 2016 - 06:59 AM.

[Mind_Paralysis]

 

This is very interesting. How did you think of NAA?
Could it be something as simple as too active ChAT stealing acetyl Coenzyme A from the NAA synthesis?

 

 

Interesting question that - I actually seem to have some kind of enhanced long-term memory, but impaired short-term memory. I often simply... KNOW the answer to a particular question, in a way that isn't readily obvious even to myself.

 

I read about NAA in previous reports when trying to go over the neurobiology of EDD, but since my mind was focused on choline I forgot it - but then it just... CAME BACK to me - something I read triggered the connection, and I then dug up that 2014 overview of recent fMRI-scans.

 

I read something interesting the other day - a fellow with ASD had struggled with intuitive interpretation of information prior to intense Racetam-use, and apparently felt that such information-processing had been enhanced following use of certain nootropics. I myself was sceptical, seeing as that is how I ALWAYS process information - but I suppose if you gain access to another pathway of information-processing, then you actually become more efficient.

 

That's why I always wonder what would happen if I could suppress my disability... could I finally, finally, feel as if I'm using all of my potential...?

 

 

 

These traits obviously exist because evolution ordained them as useful for a pack-animal.

I did find a paper that seems to support it. However it's a bit over my head and not sure i get it right. Not sure if it relates to BPD either:
http://europepmc.org...cles/pmc4381234

BTW, searching for boosting NAA i found:

EPA: http://news.bbc.co.u...lth/6440979.stm
Li: https://www.biotechp...hium-part-one/v

These things are known for benefiting ADHD and BPD, respectively. I'm thinking this is very fruitful idea to explore further.

 

 

EXCELLENT find! : D The first paper definitely lays out a clear connection in the cholinergic systems in the amygdala and the PFC, so that's a heck of a find there, mate! I'm going to try and read up on it, burn-out permitting, but there's definitely something in there, after a cursory glance.

 

I definitely think it's possible that hyper-efficient ChAT could be stealing Acetyl Coenzyme A from NAA -synthesis - it could be a very efficient treatment-pathway - but I doubt it's that simple to suppress the symptoms.

 

Could you by chance run the data in the "Basal Forebrain moderates..." in comparison to the info regarding enhanced methylation of aCh in EDD-sufferers which I posted a few pages back? The study which lead me towards checking out Cholinergic activity among BPD/EDD-ers.

[PeaceAndProsperity]

In many ways autism and BPD represent the innate differences between extreme males and extreme females.

[gamesguru]

Yeah, I've heard that before.  Autism tends to turn anger inward, buuuut also tends to long-term, resource-based monogamous mating strategies.  Hardly manly in that respect.  And they both have communication problems.  Really similar disorders on the surface.

 

I'd upvote jack black's post today, but I've reached my quota for positive votes on the day

[jack black]

I've been reading on NAA some more: http://www.ncbi.nlm....les/PMC1919520/

Looks like it's lowered in AD, MS, stroke, schizo, alcoholism and other conditions. Probably a secondary change but interesting nevertheless.

[Sleepdealer]

If you want to raise NAA levels in the frontal lobe then the amino acid Sarcosine could probably help. It might highten acetylcholine too, not sure if that's good. It works for schizophrenics at least in increasing the metabolites in the left frontal lobe and there are a lot of testimonies. There might be some side effects like irritability towards the higher end, like above 1,5 grams of dosage. I'm about to try that stuff out as soon as it arrives and not for schizophrenia.

[jack black]

 

Could you by chance run the data in the "Basal Forebrain moderates..." in comparison to the info regarding enhanced methylation of aCh in EDD-sufferers which I posted a few pages back? The study which lead me towards checking out Cholinergic activity among BPD/EDD-ers.

 

 

I really can't do that. While the "Basal Forebrain moderates..." paper suggest higher ACh levels are beneficial for humans, the study is based on healthy university (Duke?) students, hardly a cohort representative of BPD and similar problems. On the other hand, the paper on PRIMA-1 methylation suggests too much ACh in BPD, although the evidence is weak. The only other source suggesting some sort of association of ACh with BPD is this: http://www.ncbi.nlm..../pubmed/9326751

 

It's possible BPD represents too much of the good thing (ACh), but we don't know for sure.

 

[Mind_Paralysis]

 

 

Could you by chance run the data in the "Basal Forebrain moderates..." in comparison to the info regarding enhanced methylation of aCh in EDD-sufferers which I posted a few pages back? The study which lead me towards checking out Cholinergic activity among BPD/EDD-ers.

 

 

I really can't do that. While the "Basal Forebrain moderates..." paper suggest higher ACh levels are beneficial for humans, the study is based on healthy university (Duke?) students, hardly a cohort representative of BPD and similar problems. On the other hand, the paper on PRIMA-1 methylation suggests too much ACh in BPD, although the evidence is weak. The only other source suggesting some sort of association of ACh with BPD is this: http://www.ncbi.nlm..../pubmed/9326751

 

It's possible BPD represents too much of the good thing (ACh), but we don't know for sure.

 

 

 

Hmm, yeah it's tricky...

 

I suppose until there's actually more studies, we won't know for sure. We do know that other mood-disorders, such as Bipolar, fluctuates between too much and too little Serotonin and Dopamine, and Schizophrenics definitely have waaay too much of something that's usually good: dopamine.

 

So there are certainly precedents among other disorders.

 

On another note btw...! : D I believe it was finally shown that HydroxyNorKetamine is the metabolite primarily responsible for Ketamine's Antidepressant effects, AND... it's a HIGHLY potent Alpha-7-nicotinic antagonist! When that AD finally comes to market... there might be some real deal dynamite to cannonize those BPD-symptoms, finally!
 

Oh, and I definitely think there'll be Hydroxynorketamine available in either a group buy or from nootropics-vendors, so we might be able to do some trialling of that soon enough.

 

 

EDIT:

Check it out guys! = ) Surprisingly meaty wiki-page actually.

 

https://en.wikipedia...roxynorketamine

 

Sub-anesthetic concentrations of (R,S)-ketamine metabolites inhibit acetylcholine-evoked currents in α7 nicotinic acetylcholine receptors

http://www.ncbi.nlm....les/PMC3534778/

 

The results suggest that the inhibitory activity of ketamine metabolites at the α7-nicotinic acetylcholine receptor may contribute to the clinical effect of the drug.

 

 

YES!! At last... we have... a gooooooooooooood drug... to pump into the EDD -brain... finally!

 

Gamesguru.

 

Are you prepared... to partake in an HNK group buy, and pump yourself full of the possibly most potent antidepressant ever created? And then... stay on this drug, for approximately 3 months?

 

Jack_Black: you know what you must do - ketamine is the most powerful anti-suicide drug there is - and this is the effective part of the molecule - AND it correlates to my theories regarding EDD pathology.

 

Your cousin... this could save her. MORE than save her...!

 

 

EDIT:

 

I spoke too soon in my excitement.

 

HNK's cousin, DHK - Dehydronorketamine, is actually far, far more selective as a potent alpha-7-antagonist. However, it does not show any significant antidepressant effects.

 

https://en.wikipedia...ydronorketamine

THIS IS GOOD!

 

Why? Because we want to inhibit response - and since it doesn't make rats try harder to survive a swim-test, then that means it won't perk them up, which means that it may stabilize response more than alter it.

 

Alas... a drug which inhibits emotional response, and FEAR-response, may not necessarily be as easy to gather a group buy around... Tricky stuff. I look forward to hearing you guys thoughts on the matter though.

Edited by Stinkorninjor, 04 September 2016 - 06:49 PM.

[gamesguru]

Not within the budget.  But anything to do with alpha7 is interesting.  Also have my eyes on PRE084, a sigma-1 agonist, antidepressive and nootropic promoter of GDNF.

[Mind_Paralysis]

Not within the budget.  But anything to do with alpha7 is interesting.  Also have my eyes on PRE084, a sigma-1 agonist, antidepressive and nootropic promoter of GDNF.

 

One day, we shall MAKE it within budget!

 

But, in the meantime... tell me... have you ever used Cannabis for self-medication? I recently uncovered that the analgesic AS WELL as anxiolytic effects of Cannabis can be attributed entirely to THC - which acts by decreasing activity in Anterior cingulate cortex - by activating cannabinoid receptors.

 

This is ALSO the mode of effect of TYLENOL! (Acetaminophen, Paracetamol, Alvedon, et c) It acts somewhat less directly though, by producing the metabolite AM404, which is actually an EXOgenous SCRI - Selective Cannabinoid Reuptake Inhibitor as well.

 

By downregulating the Cannabinoid receptors in the ACC, similar to how SSRI's downregulate the serotonin-receptors and then decrease anxiety, existential dread, EMOTIONAL pain, is blunted.

 

A researcher called Predrag Petrovic which is currently one of the people leading the charge towards reclassifying BPD as a Neuropsychiatric Disorder, similar to ADHD, is also one of the researchers regarding the role of the NAA in the human brain - I believe he is probably pursuing compounds which affect the NAA as a means of treating BPD.

 

 

I applaud the research, since there are many, many pain and anxiety-disorders which could benefit from emotion-pain-blunters - but I do think it's a too indirect mode of affecting core BPD-symptoms - sure, it'll inibit emotional response, but in a unnecessary round-about way, which is bound to cause more side-effects than direct targeting.

 

 

So, if you're up for checking out my AM404 -thread, there you may have something to try, which should be quite cheap - all we need to do is to create the metabolite of TYLENOL! : )

Edited by Stinkorninjor, 04 September 2016 - 08:51 PM.

[gamesguru]

My CB1 receptors in the ACC are already quite sufficiently downregulated, but they, and the existential angst, seem to come back when I come down from my stone.  I think an antagonist would be more up my alley, e.g. AM251, ibipinabant, falcerinol, or voacangine.

[Mind_Paralysis]

My CB1 receptors in the ACC are already quite sufficiently downregulated, but they, and the existential angst, seem to come back when I come down from my stone.  I think an antagonist would be more up my alley, e.g. AM251, ibipinabant, falcerinol, or voacangine.

 

The thing is, I think there's a difference between the sustainability of the medical and the recreational doses.

 

I have used approximately 3 grams worth of Acetaminophen (close to the limit of dosing, above that... you might be seeing liver-damage) for this purpose - eliminating anxiety, and existential dread - and I would say it actually works.

 

In theory, 4 grams + of Acetaminophen should be a very efficient emotion-dampener. However, unlike with Cannabis, I did not experience any sort of cognitive dampening, no brain-fog, nor does it feel activating either, as some strains of CB does.

 

There's a distinct difference between AM404, an indirect endogenous agonist and THC, an exogenous direct agonist.

 

But... there's also the problem with half-life - AM404 only last around 3-4 hours, as I understand it, and judging from Acetaminophen I would say that's about right. So, if AM404 was to finally come into use, it would have to be made into some kind of salt, perhaps it's possible to combine it with Lysine, so as to get that time-delayed effect.

 

 

You won't have that problem with the ketamine-metabolites! Both have a half-life of several DAYS as I understand it.

Edited by Stinkorninjor, 05 September 2016 - 09:06 AM.

[gamesguru]

As per the cognitive dampening, stuff like ginkgo, bacopa and tea un-dampens.  Plus, I was born retarded.  So it doesn't make much difference.  I like the sativa strains when I have to work at the desk.  Recently tried CBD for the first time in a few years, a strain with like 7% CBD 7% THC... rather impressed.  The CBD helps balance out the CB1 and DA receptors.. the tolerance, anxiety, demotivation, and memory loss.. in a way similar to memantine and adderall.

 

That much acetaminophen isn't good (for the liver and kidneys).  I'd just wait out for the HNK.

[jack black]

 

But, in the meantime... tell me... have you ever used Cannabis for self-medication? I recently uncovered that the analgesic AS WELL as anxiolytic effects of Cannabis can be attributed entirely to THC - which acts by decreasing activity in Anterior cingulate cortex - by activating cannabinoid receptors.

 

This is ALSO the mode of effect of TYLENOL! (Acetaminophen, Paracetamol, Alvedon, et c) It acts somewhat less directly though, by producing the metabolite AM404, which is actually an EXOgenous SCRI - Selective Cannabinoid Reuptake Inhibitor as well.

 

By downregulating the Cannabinoid receptors in the ACC, similar to how SSRI's downregulate the serotonin-receptors and then decrease anxiety, existential dread, EMOTIONAL pain, is blunted.

 

A researcher called Predrag Petrovic which is currently one of the people leading the charge towards reclassifying BPD as a Neuropsychiatric Disorder, similar to ADHD, is also one of the researchers regarding the role of the NAA in the human brain - I believe he is probably pursuing compounds which affect the NAA as a means of treating BPD.

 

 

I applaud the research, since there are many, many pain and anxiety-disorders which could benefit from emotion-pain-blunters - but I do think it's a too indirect mode of affecting core BPD-symptoms - sure, it'll inibit emotional response, but in a unnecessary round-about way, which is bound to cause more side-effects than direct targeting.

 

 

So, if you're up for checking out my AM404 -thread, there you may have something to try, which should be quite cheap - all we need to do is to create the metabolite of TYLENOL! : )

 

 

I have not used Cannabis for self-medication, but used Tylenol (Acetaminophen) a lot and considered it a mediocre pain reliever.  While I was aware of its anti-empathy properties: http://www.npr.org/2...affects-empathy

the cannabis-like activity is news to me.

 

I searched and the info seems to check out: http://sclabs.com/ab...-receptors.html

 

Based on this info, I popped 1000mg tylenol this morning while i was irritable from poor sleep and jet lag and sure enough, my irritability went away. But it could have been also from placebo effect, coffee, and breakfast that i had at the same time, LOL. Will experiment some more with this drug that could be outlawed in the USA soon ;-) http://www.cannabisc...ijuana-hysteria

 

Thanks also for the info on Mr Predrag Petrovic. I started reading his papers and sounds like he will be my hero for trying to revolutionize the current sad affair of psychiatric nomenclature and classification: https://www.research...nal_Instability

 

 

 

 

Edited by jack black, 05 September 2016 - 02:49 PM.

[Mind_Paralysis]

 

 

But, in the meantime... tell me... have you ever used Cannabis for self-medication? I recently uncovered that the analgesic AS WELL as anxiolytic effects of Cannabis can be attributed entirely to THC - which acts by decreasing activity in Anterior cingulate cortex - by activating cannabinoid receptors.

 

This is ALSO the mode of effect of TYLENOL! (Acetaminophen, Paracetamol, Alvedon, et c) It acts somewhat less directly though, by producing the metabolite AM404, which is actually an EXOgenous SCRI - Selective Cannabinoid Reuptake Inhibitor as well.

 

By downregulating the Cannabinoid receptors in the ACC, similar to how SSRI's downregulate the serotonin-receptors and then decrease anxiety, existential dread, EMOTIONAL pain, is blunted.

 

A researcher called Predrag Petrovic which is currently one of the people leading the charge towards reclassifying BPD as a Neuropsychiatric Disorder, similar to ADHD, is also one of the researchers regarding the role of the NAA in the human brain - I believe he is probably pursuing compounds which affect the NAA as a means of treating BPD.

 

 

I applaud the research, since there are many, many pain and anxiety-disorders which could benefit from emotion-pain-blunters - but I do think it's a too indirect mode of affecting core BPD-symptoms - sure, it'll inibit emotional response, but in a unnecessary round-about way, which is bound to cause more side-effects than direct targeting.

 

 

So, if you're up for checking out my AM404 -thread, there you may have something to try, which should be quite cheap - all we need to do is to create the metabolite of TYLENOL! : )

 

 

I have not used Cannabis for self-medication, but used Tylenol (Acetaminophen) a lot and considered it a mediocre pain reliever.  While I was aware of its anti-empathy properties: http://www.npr.org/2...affects-empathy

the cannabis-like activity is news to me.

 

I searched and the info seems to check out: http://sclabs.com/ab...-receptors.html

 

Based on this info, I popped 1000mg tylenol this morning while i was irritable from poor sleep and jet lag and sure enough, my irritability went away. But it could have been also from placebo effect, coffee, and breakfast that i had at the same time, LOL. Will experiment some more with this drug that could be outlawed in the USA soon ;-) http://www.cannabisc...ijuana-hysteria

 

Thanks also for the info on Mr Predrag Petrovic. I started reading his papers and sounds like he will be my hero for trying to revolutionize the current sad affair of psychiatric nomenclature and classification: https://www.research...nal_Instability

 

 

Ey, I'm just as glad as you are, in finding that someone like Dr. Petrovic exists! : D Someone who doesn't believe in the dusty old crap from the days of Freud!

 

It should be noted, that the studies generally used 2000 mg of Acetaminophen - so that's twice the dose. It's also the case that the effects are always very discrete - much like how Tylenol blunts pain, the effect comes creeping very discreetly, almost like a nootropic, more than a pain-medication, or anxiolytic.

 

And cheers for linking that paper! I had only just started uncovering his work, so I didn't know he had a nifty primer like that, and all!

 

You can read up more on Acetaminophen/Paracetamol and the effects of the metabolite AM404, which works as an SCRI (selective cannabinoid reuptake inhibitor) here:

 

 

http://www.longecity...nitive-decline/

 

http://www.longecity...l-modification/

 

 

If you want to keep experimenting with Tylenol, which I do think has GREAT potential, then I suggest that you purchase a quality Milk Thistle extract and a hefty supply of N-acetylcysteine - that should take care of the majority of the liver toxicity.

 

It's hard to say how well it would dampen toxicity, but NAC is a very effective antidote for the treatment of acute toxicity, so I think you should be able to hold at least at the maximum

prescribed dosage: 4000 MILLIGRAMS! o.o

 

 

The best thing would of course be pure AM404 instead, but what can ya' do...?

[jack black]

 

 I popped 1000mg tylenol this morning while i was irritable from poor sleep and jet lag and sure enough, my irritability went away. But it could have been also from placebo effect, coffee, and breakfast that i had at the same time, LOL. Will experiment some more with this drug

 

Next time i tried tylenol 1000mg for irritability (followed by kava extract) there was not much effect. Next to try is tylenol + green tea extract.

 

BTW, coming back to the main topic, the person in question here was slowly started on lamictal again in addition to the other drugs and there is a significant emotion control (except for days she skips a dose).

[jack black]

OK, one more thing i've been thinking lately. if lithium and lamictal are the best drugs we have for BPD, and since both are known for their NMDA antagonism, could BPD be simply overactive glutamate neurotransmission?

 

According to Symptoms of High Glutamate Levels in the Brain / Body (How to Tell If You Have High Glutamate Levels: https://area1255.blo...-levels-in.html

 

 

Well here we go, the symptoms of glutamate-excess are...!

• Insomnia [4] [5]
• Social Anxiety [6]
• Emotional Lability [7] (being over-emotional, crying at movies, music , smells etc)
• Agitation [8] (often impulsive aggression, or easy to provoke, and increased sensitivity to sensory input due to enhanced glutamate often leads to increased reactions, i.e, one with a lot of glutamate may get angry when pinched, coughed around, or when property is touched by the 'wrong' person)
• Racing Thoughts [9] (though this can be caused by other factors, like low noradrenaline, high noradrenaline, low dopamine, high dopamine, racing thoughts due to high glutamate is generally related to emotional scenarios, often not positive, often about or anticipating future events, often related to work).
• Hedonic Attachment [10] - High glutamate individuals are typically prone to exhibitionism, overt display of emotions and desires, and especially, an attraction to gaining, holding, or becoming one with anything that produces a 'good feeling', thus, you will hear a high level of report that the person with high glutamate 'wants to fall in love' or wants to try LSD', with a higher probability of the former, because high glutamate individuals are 'into' life in general, they produce fairly large amounts of oxytocin, and though are sometimes socially aversive, they also can be quite the opposite, all relating back to their need for attachment, and generally 'enjoying life'.
• Stress [11] [12] - Despite the above, high glutamate levels often lead to stress-states when things don't go as planned, having tons of glutamate allows one to overthink things, and for all emotions : including Anger or Sadness, to simmer, and many high glutamate individuals believe they can internalize their emotions, and often attempt to suppress them, until they explode, and feel the great need to unleash their emotions onto someone or something, but nevertheless, elevated/high glutamate individuals are thus prone to these scenarios, and particularly devastated during loss of a loved one, or loss of a relationship etc. This does not however, mean, that high glutamate individuals are those types who would generally become malicious, or take their feelings out on 'just anyone', in fact, they have a tendency to vent towards a friend, or utilize some other resources to get their feelings out.
• Shopping Spree's : [13] [14] : High glutamate individuals often feel an unusually intense attraction to novelty, and looking at objects/items through glass windows in a mall, and generally, cling to the idea of 'shopping' for new stuff, of course, what they shop for will depend on the person and their experiences, but high glutamate individuals are generally desire based shoppers versus need-based shoppers, that is, they shop for what suits their tastes, or visual appeal, or imagine what may provide them 'something to do', as opposed to shopping for 'traditional' reasons. So one with high glutamate is more likely to shop then, 'in-the-moment', than 'for stock and supply' or other, future need based items. 
• Other Addictions [15] : People with elevated glutamate are biologically more prone to all kinds of addictions, and the reinforcing Effects of various drugs.
• Mania [16] : Because high glutamate persons are characteristically opposite of GABA-dominant personalities, they are often Manic, and exhibit multiple behavioral components of several, past or present, BiPolar diagnosis.

 

  PHYSICAL SYMPTOMS OF HIGH GLUTAMATE IN MEN & WOMEN

• FREQUENT HEADACHES/Migraines [15].
• Frequent Nausea [16]
• Fast Heart Rate, or Low Heart Rate, higher chance of being high (tachycardia, or higher than normal at least) [17]
• Prone to high blood pressure when approaching early 30's [18].
• Inner Tension / Restlessness [19]
• Restless Legs Syndrome [20] (moving/jerking legs around at night due to restlessness, and strange surging sensations in legs that provoke one to move them, exercise them, cross them, curl them etc)

 

Well, it really does sound like BPD. Maybe what we call BPD is a mixed bag of things and one of the things is excitotoxicity.

 

Obviously, I'm not the first person to think of that (probably the 2nd): https://clinicaltria...how/NCT02097706

[jack black]

OK, one more thing i've been thinking lately. if lithium and lamictal are the best drugs we have for BPD, and since both are known for their NMDA antagonism, could BPD be simply overactive glutamate neurotransmission?

 

 

While I'm working on this hypothesis, I found out that all the mood stabilizers (anticonvulsants) that work in BPD have anti-NMDA activity.

Similar with cannabis, it helps in BPD (according to internet of course), and has anti-NMDA activity (i think, correct me if i'm wrong).

There are some other drugs used in BPD, one of them is Abilify. Turns out it increases NMDA receptor density. This must be because it blocks them, right (not entirely sure on this)? Piracetam belongs in the same category of anegdotal use and NMDAR density (it also modulates AMPAR). There are not many accounts of ketamine in BPD, but the little i found seems to indicate it works short term.

 

I have not figured out how ACh fits in this puzzle. The search goes on.

Edited by jack black, 09 September 2016 - 01:23 PM.

[jack black]

I have not figured out how ACh fits in this puzzle. The search goes on.

 

 

The plot thickens. It turns out, at least in some parts of the brain, ACh potentiates glutamate neurotransmission: https://elifescience...96-download.pdf

 

Hence, this would potentially explain why ACh makes BPD worse or why BPD subjects are sensitive to choline consumption.

This could also mean that both theories of BPD as ACh or glutamate excess are correct, while MDD is high ACh without excessive glutamate.
 

[Mind_Paralysis]

 

I have not figured out how ACh fits in this puzzle. The search goes on.

 

 

The plot thickens. It turns out, at least in some parts of the brain, ACh potentiates glutamate neurotransmission: https://elifescience...96-download.pdf

 

Hence, this would potentially explain why ACh makes BPD worse or why BPD subjects are sensitive to choline consumption.

This could also mean that both theories of BPD as ACh or glutamate excess are correct, while MDD is high ACh without excessive glutamate.
 

 

HUH!! Now that... is an awesome find actually!

 

Intriguing. I'm not too surprised though, because NMDA is a decidedly important part of other frontal cortex disorders - i.e ADHD. I've actually written a mini-essay on the subject, as you're probably aware.

And there's evidence that other disorders which involve difficulties in inhibiting behaviour, such as OCD, has a relation to glutamate.

(strangely enough, OCD actually seems to be a disorder which has a lot of activity bound to the Anterior Cingulate Cortex! See Catwoman's thread regarding this - SCRI's could be the drug of choice for that, in the future)

 

I would say that this relationship is similar to that in ADHD though - wherein both NMDA-antagonism and Dopaminergics are useful for treatment.

 

I still think DNK is worth a shot though - it might be more direct, since they do have over-methylation of PRIMA1 - that's a fact, so excess aCh is there.

 

Considering what you just found though, one can definitely question how involved in the disorder aCh is though.


Oooh, I just remembered this as well! I adviced a fellow with rapid-cycling bipolar this evening and he has such a sensitive brain that melatonin-supplementation turns him manic! I suggested MEMANTINE, because of this study:

 

Memantine: New prospective in bipolar disorder treatment

http://www.ncbi.nlm....les/PMC4274590/

 

Perhaps that's a suggestion to make for your cousin as well? It is an inhibiting medication, that's for sure!

Edited by Stinkorninjor, 09 September 2016 - 09:17 PM.

[jack black]

Re: memantine.
She is taking it already. Albeit a small dose with little effect. She was recently ramped up to a therapeutic dose of lamictal and there is a noticeable improvement. Lamictal is also anti glutanergic and some more.

Edited by jack black, 12 September 2016 - 02:55 PM.

[gamesguru]

Ferulic acid is an interesting natural NMDAR antagonist brought to my attention by sativa.  It's metabolized to chlorogenic acid, which has COMT inhibiting^[1] and sertonin promoting^[2] properties.  A large dose is needed, so I recommend beta testers a diet high in coffee, rice and pineapple.  Other examples are curcumin^[3], ginkgo^[4], and lithium^[5].  Love them all!  That may be an exaggeration, some would say a lie    A lot of the borderline symptoms (e.g. cognitive, emotive, self-dissociative, or neurotic) can be explained by excitotoxicity and cell loss; as the flux returns to baseline and nerves regrow, some symptoms are quelled.  I say some.  I'm just being modest

Ferulic acid is found in the seeds of coffee, apple, artichoke, peanut, and orange, as well as in both seeds and cell walls of commelinid plants (such as rice, wheat, oats, the Chinese water chestnut (Eleocharis dulcis) and pineapple).

[jack black]

Re: memantine.
She is taking it already. Albeit a small dose with little effect. She was recently ramped up to a therapeutic dose of lamictal and there is a noticeable improvement. Lamictal is also anti glutanergic and some more.

 

I guess I should qualify that the improvement is mostly in the emotional and communication sphere. Sadly, no improvement in the motivation and ability to finish the studies.