onedayillsailagain

Spend it all on prostitutes

I'd probably order a bunch of hard-to-get research nootropics which I've wanted, but don't have access to (yet), and of course enough to hand it out like candy.
Seeing as you said all the money in the world; I'd put up a 10 million dollar prize to whoever finds the cure. I'm sure that would get some attention to our cause.
Donate 2000 BTC to each verified HPPD'er so they don't have to worry about income ever again.

Also, I'd hire a butler. And buy an invisibility cloak.

 

 while in vitro glutamate (NMDA) antagonism by kynurenic acid is also inhibited

^This is the most interesting part, I find. Anti-amnesic effect can happen in various ways; the substance needn't necessarily work on the same system I'd think. But that it inhibits KYNA antagonism is highly interesting. Though I wonder whether it inhibits biosynthesis, release, or binding. Nonetheless, very nice find BPC. I will check to see what schizophrenics think of Oxiracetam; several studies indicate the possibility of too much KYNA mucking around with their NMDARs, so it should help them as well.

Re: MgT upregulating NR2B; from what I've found, this is what you don't want happening. NR2A is the one you want to upregulate.. But again; still have to look further in to it, but this is how it seems to me now.

Ha! I got the criteria question (#9) wrong. Screw the DSM anyway

I'm not sure whether Ketamine in and of itself can cause HPPD. Perhaps some individuals have had their HPPD triggered by Ketamine after abusing other substances.

Hmm interesting! I found that these help for photophobia:


They're called "night vision glasses" or "driving glasses" I believe. What they do is block out blue light.
I would suggest using another model than the one in the picture; it doesn't fit comfortably.

 

But correct me if I'm wrong, it looks like I may have severely decreased NMDAr's/damaged glutamatergic system functioning; decreased acetylcholine; decreased 5-HT2A receptor density; messed up GABAa subtype receptors; and lastly, increased dynorphin A expression. Eeeek!

Well, fortunately most of those can be mitigated. Several ligands could mitigate NMDAR loss, LMM for the ChAT decrease IIRC, stress alone would mitigate 5HT2A receptor density loss, perhaps Kava Kava for GABA-A upregulation, and well.. Dynorphic expression is increased with almost any recreational substance (ab)use.

@BPC: Thanks. Pregnenolone is quite interesting; I might give it another shot one of these days. 3 grams per day sounds a bit extreme though; generally speaking 50mg is already considered a high dose from what I've read. Yes indeed; neurogenesis probably exerts its best effect when learning/experiencing new things, however I think that that in and of itself should suffice to mediate at least some noticeable change, if sufficiently active. 60ml/day Cerebrolysin would be inconveniently large and expensive.. I think 7,8-DHF may be better in that case. Which studies on DXM and PCP are you referring to? I would very much like to read them, too see if there are any similarities in MoA that may be able to specify the exact mechanism/subtype that causes NMDAR-related dissociation.

@Syntheso: No problem, you've helped enough by starting this thread; it has been quite inspiring! Best of luck with uni; that biomedical course sounds like it could come in handy.

I found one interesting news article:

 

Scientists have discovered that by deactivating a major switch in the brain that is linked to learning and memory, memories become jumbled, like "hitting random notes on a keyboard," and lose their sense of association.

"You see a face and think of a name, you see your office, and you think you need to work; everything is associative," says Dr. Joe Tsien, neuroscientist at the Medical College of Georgia at Georgia Regents University. "But in mice lacking an NMDA receptor, you can tell the memory patterns are dull and dissociated."

This revealed that normal mice had brain activity that played "dynamic rhythm," while mice with a faulty NMDA receptor had brain activity that played "random noise."
Dr. Tsien says that the mice with a faulty receptor form the initial patterns of association but do not remember them. He explains that "their tones are flat, the association is poor, while everything we register in the healthy brain is associative."

Original study

Also something interesting to note:
 

 

"Lamotrigine attenuation of ketamine-induced effects in humans
In addition to metabotropic glutamate receptor agonists and glycine, glutamate release can be decreased by lamotrigine (3,5-diamino-6-[2,3-dichlorophenyl]-1,2,4-triazine), an anticonvulsant that stabilises neuronal membranes and attenuates cortical glutamate release via inhibition of use-dependent Na+ channels and P- and N-type calcium channels, and via its effects on K+ channels. Anand et al (2000) have recently shown that lamotrigine reduces the neuropsychiatric effects induced in healthy humans by sub-anaesthetic doses of ketamine. However, further studies are needed because lamotrigine affects other neurotransmitter systems (e.g., 5-HT, GABA and dopamine) and it is unclear whether these effects are direct or secondary to the effects on glutamate release."

Source
Nevermind the Lamotrigine; the glycine is what interests me here. This may explain the lack of efficacy I've experienced with glycine, even at high doses. Then again, I haven't been able to find whether this is regarding long-term use or short term, as the inhibition of glutamate release may simply be an adaptive homeostatic response.

Anyhow.. will attempt to look further in to this some time this week. Having some troubles with cognition lately due to sudden unilateral deafness. Going to see a doc tomorrow, so hopefully if and when it's resolved, I can resume investigation in to this at a better pace.

Hey BPC,

if you're worried about its resemblance to niacinamide, then perhaps another neurogenic approach is more suitable for you. I don't recall, but have you tried Cerebrolysin?
Actually, considering the amount on non-drug therapies you are doing (I applaud that; I haven't seen anyone who has tried harder in that area as far as I can remember), it may be very warranted in your case. Unfortunately, the current 7,8-DHF buy is closed, but that would be a good alternative.

edit: Just saw your post in the other topic re:Cerebrolysin. You get the drift it seems, haha. But have you used it yet or not?

Hey BPC! That would be nice to have some info on that Hmm I haven't really looked too much further in to it yet, though I have found that Naurex (should've known haha) is developing subtype specific ligands; NR1/NR2-A/B/C/D. However, lead selection won't occur until the end of Q2 this year, and Phase 1 is planned to start late 2015.. And seeing as they tend to be delayed, and apparently also secretive, I wouldn't count on any of the info being available any time soon. In any case, it does seem that NR2B antagonism seems more viable for the immediate future than NR2A agonism.

Anyhow.. really hope I can continue my GLYX trials in the next few days; it should be most interesting to see what my experience is at a full dose.
Even if it doesn't work, I've recently come to realize (thanks to somebody pointing out the obvious that I had somehow missed) that partial agonists are competitive antagonists under circumstances when there is a full agonist present. Thus, if it doesn't work, then perhaps the NMDARs were not sufficiently activated because of this. This is why I now have D-Aspartate, which I'll try after GLYX. I'll also order some D-serine; D-serine + D-Aspartate should be more or less the most potent NMDAR activation currently available. I've been trying to find out about how significant the excitotoxicity concerns are with the latter. People have taken the combination before without ill effects though; so perhaps I will do just that without too much fretting over potential excitotoxicity. Or, alternatively, co-administrate Cerebrolysin to mitigate some of it.

Also, it seems from what I've read that D-serine is considered subjectively superior to Sarcosine/Glycine.

Some more links:
The regulatory role of long-term depression in juvenile and adult mouse ocular dominance plasticity

D-Serine Augments NMDA-NR2B Receptor-Dependent  Hippocampal Long-Term Depression and Spatial Reversal  Learning

D-aspartate prevents corticostriatal long-term depression and attenuates schizophrenia-like symptoms induced by amphetamine and MK-801

D-aspartate: an atypical amino acid with neuromodulatory activity in mammals.

New insights on the role of free D-aspartate in the mammalian brain.

An interesting blog; a collection of data, contrasting NMDA antagonism against KOR agonism, stating that NMDA antagonists are actually a better model for DP than they are for psychosis:

Salvinorin A as the most complete mimetic of schizophrenia

Longecity:

"Healing the mind from DXM induced psychosis"

"New Nootropic D-serine" (with experiences and combo's)

Odisa,

Arent you in keppra currently? I took lamotrigine for 3 months at 200mg but did nothing.

Nope, I haven't used Keppra in over 8 months I think.

It's ok I guess..,I've had some success with this healer over here for my hppd but I haven't noticed any further improvement this past week...

What does keppra and lamictal do ? I'm not sure I can take naloxone as I had a horrible reaction to jdtic and many drugs/supplements for that matter..

Hmm well I hope at the very least that you're enjoying yourself

Keppra/Levetiracetam works as described here.

Lamotrigine, on the other hand, works as a sodium channel blocker, aside from inhibiting calcium channels. This action is thought to be responsible for its ability to reduce glutamate release. The latter is hypothesized to help depersonalization, due to the observation that administration of the NMDA antagonist Ketamine causes acute elevation of glutamate release, which theoretically would agonize all glutamatergic receptors but the NMDAR, and the glutamate elevation is believed to be responsible for dissociation.

I still find this theory strikingly odd; it totally ignores the fact that NMDARs are also highly important for learning, memory, perception, emotion, etc. If indeed, as this theory says, dissociation is caused by elevated glutamate levels agonizing glutamatergic receptors other than the NMDAR, then I'd think adding the NMDAR co-agonist D-serine would enable the NMDAR to use up this excess glutamate, thus reducing the agonism at other glutmatergic receptors. Unless it is of course caused by NMDAR antagonism (which I think is far more likely), in which case this may not suffice to activate the receptor, and may require co-administration of a NMDAR full agonist. This, of course, is not considering the possibility of excitotoxicity, which could be prevented in various ways.

That said, if you want to try it, I don't see why not. If you don't see any improvements after a few weeks, then just stop (of course discuss it with your doctor before quitting any medication).

As for Naloxone; refer to the link odysseus posted. I also question whether what you had was indeed JDTic; if I recall collectly, every person who has tried it, has gotten it from the same source and has had more or less the same reaction. Either way, I would not let it discourage you from trying Naloxone if you have access to it.

Here's a copy-paste of something I was gonna post in Missjess' thread, before I realized it didn't belong there:

Currently I'm trying to develop an approach to effectively, yet safely agonize the NMDARs, which could - in theory - aid DP and subsequent body distortions. Not sure what the implications for visuals would be though. I've narrowed it down to activating the synaptic NR2A subunit of the NMDAR, which should be without excitotoxic effect. However no ligands currently exist to do this, so the best I've come up with so far is a combination of D-serine and an extrasynaptic NMDA antagonist (e.g. Nitromemantine) in an attempt to funnel D-serine to the NR2A (which is preferably selective to D-serine). All that remains is to cross-reference literature on classic NMDA antagonist dissociatives, and see whether there is a subunit specificity through which their dissociative effect is mediated. So far, however, it seems controversial with conflicting evidence, and as always it's just a guesstimate.

Any input anyone?
 

Extrasynaptic NMDARs oppose synaptic NMDARs by triggering CREB shut-off and cell death pathways.

Opposing roles of synaptic and extrasynaptic NMDA receptors in neuronal calcium signalling and BDNF gene regulation.

Synaptic and Extrasynaptic NMDA Receptors Are Gated by Different Endogenous Coagonists

Synaptic versus extrasynaptic NMDA receptors: Role in PCP-induced neurotoxicity and development of locomotor sensitization

Excitotoxicity in vitro by NR2A- and NR2B-containing NMDA receptors

DIFFERENTIAL ROLE OF NR2A AND NR2B NMDA RECEPTORS IN MEDIATING PHENCYCLIDINE-INDUCED PERINATAL NEURONAL APOPTOSIS AND BEHAVIORAL DEFICITS

Substitution for PCP, disruption of prepulse inhibition and hyperactivity induced by N-methyl-D-aspartate receptor antagonists: preferential involvement of the NR2B rather than NR2A subunit

NMDA Receptor Subunits Have Differential Roles in Mediating Excitotoxic Neuronal Death Both In Vitro and In Vivo

Hey Missjess, hope you're enjoying Brazil!

Keppra/Levetiracetam is indeed worth a shot, as some have had success with this. Same goes for Lamictal/Lamotrigine, however it seems to me that its efficacy is to a lesser extent.
 

I would suggest you try Naloxone; currently it is the most efficacious treatment for dissociation from what I've been able to find. It does require intravenous injection, but could also be done intramuscularly at home.

Best,

odisa

Well, I don't know to what extent this is relevant to sinuses, but I've been completely deaf in one ear for a few days now (why? ear drops. oh the irony), and dissociative and cognitive symptoms are definitely much worse. Probably due to the ensuing vertigo. I could imagine ear problems resulting from blocked sinuses to be equally conducive to exacerbation of symptoms, so I do suppose taking proper care of your sinuses can help in that regard.

Hi joe,

what doe you mean by "sinus ct landmark"?
edit: nevermind I guess; I see it's a scan of sorts. Would you care to elaborate?

Hey guys, just popped in to wish you all luck with NSI-189. Hope it serves you better than it did me.

I'm still waiting for Ceretropic to add it/an analogue to its selection; perhaps then I will try it again.

No problem. Yes; I doubt Perphenazine would do anything for the visuals, but perhaps it could be useful for co-morbid symptoms. edit: didn't see StateOfRegret's post. Hmm, from a glance it seems like it's slightly better than other AP's, but honestly I'd just avoid AP's in general. edit 2: it's 5 times more potent than Thorazine.. Hmm, I'm not well informed on Perphenazine, but I would definitely not touch it.

Ah I see.. Hmm then your options are indeed limited; you will have to be referred to a neurologist to get Sinemet.
Yes, I took Mucuna, but only once, so I can hardly evaluate it. I will try it again, however.

Sorry to hear things haven't improved much.. at least you're still looking for a solution!

I'm not sure about combining L-DOPA or Mucuna Pruriens with an SNRI: Dopamine is the precursor to Norepinephrine after all, so that may be conflicting. Also, apparently Dopamine inhibits Norepinephrine release when agonizing the D2 receptor. I would proceed cautiously, and preferably discuss with a doctor. Is the effexor/venlafaxine helping at all?

There should be little issue combining it with Clonazepam/Klonopin though.

Cheers!

Bump. Its pharmacological profile does seem interesting. Perhaps low-dosing this could be beneficial?
Anyone else have any experience or thoughts to add?

Hey hppd33,
 

hope you're doing alright. Can't Gerard prescribe you Sinemet? If not, perhaps try Mucuna Pruriens (e.g. Now Foods standardized to 15% L-DOPA). Although not containing Carbidopa, the DOPA decarboxylase inhibitor preventing breakdown in the stomach, it has shown to be equally (and in some cases more) effective than Sinemet for Parkinson's, ultimately indicating there's probably a currently unidentified natural DOPA decarboxylase inhibitor present in it. In other words; try Mucuna Pruriens; it should be at least somewhat indicative of whether or not Sinemet could help you.

Perphenazine is Nardil, correct? Looking forward to your experience with it; MAOI's tend to have a higher efficacy rate than first- and second-line treatments.

Best,
odisa.

BPC: Yes, I'm not saying they don't, just that I rather not bear the obvious effects in order to see improvement. Most certainly not on a chronic basis. That said; it is a PDE5 inhibitor. I'm not sure how close PDE's are related, but perhaps PDE4 inhibitors are worth investigating? Though, I have tried some I believe, and have not experienced any benefits through these. Though, if you want to try it; go ahead I'd start with micro-dosing though.

hppd24years; I'm not sure what your intentions are with that gibberish, though it's not contributing to anything good. If it's an attempt at mocking this thread, then the least you could do is constructively criticize the ideas proposed and discussed, so that we can all benefit.

That sounds very interesting! Are you saying you know of a source?   Are we talking group buy here? 

Yes, the company that supplied GLYX-13 does offer custom synthesis, so I could get a quote on that. Could be a group buy if you guys are up for that, however I suppose I should check out whether the price is reasonable first.

Well, fainting is dissociative to the extreme

Yes true. I had a little brain fart when answering your question earlier. The relief comes right after nearly fainting, in the "recovery" phase.

Indeed. Hehe.. unfortunately poppers are dissociative. As for your latter suggestion... No thanks, haha!

Did your "love-light keep burning all night long"? Haha, sorry. Thanks for the link; I guess I'll just try double dosing then.

Thanks syntheso. You wouldn't happen to know how much total or percent L-DOPA was in that full-spectrum? I used this one, 2 caps, totalling 120mg L-DOPA, because I figured that would be close to the doses people were seeing benefits with.

Yes, I suppose generally anything that raises GABA levels could cause eventual downregulation, such as Glutamate decarboxylase enhancers or GABA transaminase inhibitors.
And what a co-incidence then, haha! Didn't notice it was a music site. Cheers!

edit: If you like, I can see if I can find out what the pricing is on Emapunil.

Glad to hear this syntheso!

May I ask, was it only today that you started seeing benefits? I have some Mucuna Pruriens extract which I only tried once.. Perhaps worth a longer try.
Do keep us posted