• N&PD Moderators: Skorpio | thegreenhand

High functioning autism / Asperger's - Glutamatergic dysfunction & NMDA antagonism

If the pathology of autism spectrum leads to excess stimulation of these NMDAr's located on inhibitory interneurons then it makes sense that that would cause depression and that blocking that NMDA would help decrease the excitatory input to the inhibitory interneurons, but the question is why are the NMDAr's having issues - if it's because of an alteration in neural activity (a more primary effect of autism spectrum) leading to excess stimulation of NMDAr's then that's one thing (where NMDA dysfunction is just secondary, and NMDA antagonism wouldn't be too close to the root cure), another option is that there is something pathological about the NMDAr's themselves (and NMDA antagonism is closer to treating the root cause).
 
Yeah, that's what I'm currently thinking about too, Cotcha. I believe now that autism & schizophrenia have a shared common, NMDAr dysfunction. Making another topic about that.
 
I've just started taking DXM actually in the hope that it might potentially at least partly substitute for memantine. Fucking hate the SNRI type effects but at least, I do have alpha2 adrenergic agonists available, but its a stopgap measure at best. Stuff gives me the shits, literally.

But again, feel clear of mind and actively able to get up and do things. This, post-excitotoxicity (acute untreated barb withdrawal in prison, surprised the bastards didn't finish me off themselves the way they treated me. But damn, I actually feel like getting to the lab and doing some much needed work for a change, and whats more I can actually think fucking clearly. This, off a dose of one mouthful, plus a small sip of OTC benylin. Dosed BD.

God, who'da thought a fucking cough mixture could do something like this...damn!
 
Yeah, that's what I'm currently thinking about too, Cotcha. I believe now that autism & schizophrenia have a shared common, NMDAr dysfunction. Making another topic about that.

For a LARGE percentage of ASD persons (30-40% have elevated blood serotonin and lowered brain serotonin)-- a known serotonin dysfunction is extant

There are loads of data identifying polymorphisms that affect SERT and DAT - that are frequent in ASD

and serotonin messes with the GABA/Glutamate system:


[h=1]Serotonin as a Modulator of Glutamate- and GABA-Mediated Neurotransmission: Implications in Physiological Functions and in Pathology[/h]

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2430669/
 
Whilst I doubt (haven't yet tested it, been at home with only a face I'd recognize anyway around) I doubt that NMDAR antagonists would help with prosopagnosia, thats rather down to differences in oxytocin levels is it not?

One thing I can say is that whilst I have never tested oxytocin via nasal spray, I do plan to some day but have never gotten round to it. I have taken MDxx in several of its guises, known oxytocin secretagogues, and have found that behind the amphetamine type euphoria, the other effects, the people=addicting huggy shit, it just feels forced and as such, kinda false to me, empty. I don't feel 'empty' as 'me' in general, but the effects... theres just something being overlaid on the hardcoded wetware thats in a sense, being run on an emulator, one or more layers distant from the native architecture. Not something I'm that comfortable with really.
 
Ha I will laugh so hard when NMDA dysfunction / expression etc is incontrovertibly linked to autism as a significant part of the condition's cause, after one of the top autism researchers here in my country told me to my face that I was wrong about that suspicion..

However it's controversial to conclude from efficacy of a drug that it really directly targets something that is closely linked to the underlying problem. You can't diagnose ADHD purely by giving a person stims either.

Don't know if there is an autism model in rodents but I assume so... I guess gene knock-out that relates to NMDAR expression would be a better way?

Ah here we are:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3808979/
Mice with reduced NMDA receptor expression: more consistent with autism than schizophrenia?
 
Those of you interested in this topic might find interesting Kamila and Henry Markham's (director of the Blue Brain and Human Brain Projects) 'Intense World Theory' of autism spectrum disorders. In their exposition of the theory (http://journal.frontiersin.org/article/10.3389/fnhum.2010.00224/full) some space is given to the possible effects of hyper-gluytamatergia via NMDAR hyper-expression. Scroll down to 'Hyper-Glutamatergia' to cut to the chase.

The big caveat here is that changes were seen in a rat model of autism, in which embryos were exposed to sodium valproate in utero - evidence of changes in autistic humans remains thin (although surely not to an extent that warrants such certainty on the part of your researcher acquaintance, Solipsis!).

In the end, it's nice when personality traits seem to lie along a simple biochemical axis, but there are likely to be many intersecting axes of this type, and one needs to ascend to higher levels of abstraction before they are unified. For what is, though, I think the NMDAR theory is a good effort.
 
Just a small update from my side. As life can be a bitch, from times to times there are coincindences that are just too striking to be such ones.

In the therapy group I have been for some weeks now there is another person, diagnosed with Asperger's. History of dextromethorphan abuse. So for both of us it was the first time ever to not only meet another person with the same (for simplicity, let's call it disorder), but also both in NMDA antagonist enhanced state. This was mind blowing. Two aliens of the same species meeting in an alien world. For now it doesn't change nothing but it's the confirmation I've waited and hoped for.

As the thought of me being autistic is very new, I know little about the knowledge but I'd bet hard on NMDAr's. Not saying they are the cause, but a crucial part. It's just indiscribable- NMDA antagonists hit exactly that button that is required, and that nothing other, no other drugs out of all these things available is able to push. Normalization within seconds. CPU load down from a looping 95% to idle, if you know what I mean. Clarity. No more strangeness. But, foremost, no more anxiety. All these people out there are so freakin lucky not to know how it is to live in a constant state of anxious chaotic homesickness that can't be resolved.. (maybe this doesn't make sense, well words are limiting).

It's so... crazy.. to have this need for normality, to take a chemical that would de-normalize the average person to be normal.. and to be un-sober when sober.. Like the inverse of addiction. (Somehow I have to think of this ASD as being the ADHD of emotions.. )

And O-PCM more and more appears to be a very good candidate. At least out of what we have at the moment. Now it's four weeks or so I think and my brain almost completely adjusted to it. No signs of intoxication, neither from the outside nor for myself. Even these little things like slightly altered after-images when closing the eyes etc. are fading. It's just incredible. So normal. No physical side effects to speak of. Have the impression of immune system working better than before. Some stubborn semi-allergic rash on my right arm finally subsided. I'll slowly try to tritrate the pregabalin away now, or the buprenorphine, don't know which first.

It's so oppositing to any addictive drug consumption and fucking striking similar to ADHD on/off switch phenomenon. It feels like when the switch is "on" here, the brain wants to keep it this way even..and the clarity window gets extended more and more past the peak of effects without redosing.. etc.. need to explain this better at a later time, with some graphics maybe.

Just that I need the chemical to be normal. I feel heavily impaired and intoxicated without it. Yeah, like a medication one needs... but here it's a research chemical with fragile availability and time is working against me.. I don't want to have keep up trying more and more obscure research chemicals in the hope to find a substitute again when they will ban deschloroketamine ..

Probably I'll try to switch to O-PCE now when the adjustment is over. I'm not sure yet whether they completely substitute, or if there are tiny differencies in the trapping properties or whatever that make them act / feel different but I think it's more or less about a constant, well-titrated high trapping NMDA antagonism.

Only a single case report but still: The treatment of the behavioral sequelae of autism with dextromethorphan: a case report.

--

Jonneh, just started to read the link you've posted. Many thanks for this, also @Solipsis for your link!

From the Intense World Theory perspective, lessening of the excessive processing and storage capability of the autistic brain should also lead to a general “opening-up” to the world and environment.
This hits it to the point. It's also actually an instant unique .. well, opening-up associating feeling, when the O-PCM levels are falling and I redose. This chemical is great for experimenting and exploring this topic because it's so direct and fast acting, much like ketamine too but better (didn't have the chance yet to try pharm grade ketamine but think even with such the HCN1 affinity will add unwanted side effects and it's less potent, meaning more chemical load for the body, kidneys and such)
 
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How is O-PCM holding out for you? Mxe let me experience complete immersion in life for about 3 months, but the positives pooped out on me. Have you had your genome sequenced? 23andme showed I have very low levels of COMT. It would be interesting and possibly insightful to compare snp's of those that are experiencing this apparent NMDA dysfunction.
 
If only I could FIND the stuff, I'd give it a go in a heartbeat. Although would have to be careful about dosing and frequency, because I have a HUGE 'thing' for dissociatives. Although in my past use it did indeed include lots of holing, on all manner of dissociatives. Although dextromethorphan never was much cop compared to the rest it was still something that helped me a great deal in the likes of spatial perception when dealing with viewing, understanding and balancing equations.

But after the holes, for a fairly respectable time period, I felt again like I'd just been given a shot of nitroethane/nitromethane and a large jolt of N2O into the ol' engine.

It ISN'T like becoming 'normal', but rather a wiping clean the slate of comorbids. Doesn't fix dyscalculia, but that wasn't really expected of the arylcyclohexylamines. Certainly its like feeling alive as I SHOULD be. My normal, very, very much autistic as hell. But without comorbid crap. Personally I do not view autism, be it Asperger's or Kanner's as disorders. Perhaps its different from what aspie types would describe because the autistic phenotype is a most polymorphic, protean entity. For example I know very introverted aspies, and a Rett's girl who not only is a gymnast (she coaches special ed kids) and has one fucking FUNNY smartass mouth on her. Mute? like hell. Autism Squeaks WISHES she was NV, but no such luck for them lmfao. Got a mouth on her that she often as not, is using either to educate non-aspie/autie/rettdevil types (pillow angel? hah her reaction to that term...jesus H I am just glad I was not in a direct line of sight or heavy objects being launched violently at the offender)

And me being the classic autism type, and rocky, flappy, twisty-twirly-spinney line-things-neatly and repeatedly-up-in the lab stimmy as fuck. And you know what? I like it that way. I just feel sorry for those of the neurotypical persuasion who cannot get such delight from stereotypy. Because it's great.
 
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