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Thursday, 5 April 2018

Transcutaneous Vagal Nerve Stimulation - a Potential Cognitive Therapy?



 Sham device left and the real one on the right


In older posts there was quite a lot written about the vagal nerve and a method of stimulating it, called vagal nerve stimulation (VNS). VNS is already used by many thousands of people with epilepsy; more recently a much milder kind of stimulation has been developed to improve learning after a stroke.
This kind of therapy requires a 40 minute operation to attach the device inside the body. Even though it looks like VNS makes a dramatic improvement in rehabilitation following a stroke, I do not see children without epilepsy being fitted with internal VNS devices any time soon.
Traditionally VNS requires making a connection directly to the main vagus nerve, however the vagus nerve has many branches leading to it.
A German company Cerbomed has created a non-invasive, transcutaneous (through the skin) VNS device (tVNS) that stimulates the afferent auricular branch of the vagus nerve located in your ear.
“This device has received CE approval as indication that it complies with essential health and safety requirements. Thus, tVNS is safe and accompanied only by minor side effects such as slight pain, burning, tingling, or itching sensation under the electrodes.  
Given that the right vagal nerve has efferent fibers to the heart, tVNS is safe to be performed only in the left ear.”
There are several kinds of electric and magnetic stimulation already used in autism - Transcranial Magnetic Stimulation (TMS), transcranial direct current stimulation (tDCS) and ECT.
ECT was covered in this post:-

Manuel Casanova, neuropathologist and bilingual autism blogger is a fan of TMS

Transcranial direct current stimulation (tDCS) is a form of neurostimulation that uses constant, low direct current (DC) delivered via electrodes on the head; it can be contrasted with cranial electrotherapy stimulation which generally uses alternating current (AC) the same way.
It was originally developed to help patients with brain injuries or psychiatric conditions like major depressive disorder.

METHODS:


The authors present a case of an 18-year old patient with ASD treated successfully with tDCS; 1.5 mA of tDCS was applied once a day for 30 minutes for 8 consecutive days with the anode electrode over rTPJ (CP6 in the 10/10 electroencephalogram system) and the cathode electrode placed on the ipsilateral deltoid. Behavioral outcome was assessed using the Autism Treatment Evaluation Checklist prior to tDCS, after the final tDCS session, and at 2 months after tDCS. An additional, informal follow-up was also made 1 year after tDCS.

RESULTS:


Autism Treatment Evaluation Checklist showed substantial improvement in social functioning from baseline to post-tDCS, which was maintained at 2 months. The patient also reported lessened feelings of anger and frustration over social disappointments. Informal follow-up 1 year after stimulation indicates that the patient continues to maintain many improvements.

CONCLUSIONS:


Anodal tDCS to the rTPJ may represent an effective treatment for improving social functioning in ASD, with a larger clinical trial needed to validate this effect.



Conclusions—This study provides the first evidence that VNS paired with rehabilitative training after stroke (1) doubles long-lasting recovery on a complex task involving forelimb supination, (2) doubles recovery on a simple motor task that was not paired with VNS, and (3) enhances structural plasticity in motor networks.








Scientific Explanation of VNS Paired Stimulation for Tinnitus and Stroke Rehabilitation



Each time the vagus nerve is stimulated, it sends a signal up to the brain, which triggers the release of neurotransmitters (acetylcholine and norepinephrine)   broadly across the brain thus enabling neuroplasticity. In effect it is telling the brain to pay attention to the task at hand.
In someone having therapy after a stroke this might be learning to open a jar, but in autism it might be speech therapy.

The image below illustrates the therapy in action. While the patient is performing a rehabilitative exercise, the physical therapist pushes a button, which triggers the wireless transmitter to send a signal to the implanted device to deliver a small burst of electrical stimulation to the vagus nerve.





big clinical trial:-   www.vnsstroketrial.com/

Conclusion 
It does seem that using electricity in one way or another does have some therapeutic effect in some people with autism. The reason it may be effective in some people is not always entirely clear.
Personally, I like the idea of tVNS to potentially give a learning boost during 1:1 therapy to struggling learners with autism, just as VNS is being used in elderly people who have lost function in their limbs after a stroke and need to relearn how to control their muscles.
It appears that the amount of electricity used in stroke patients is much lower (one 60th) than in those with epilepsy. Perhaps it will be possible to develop a tVNS therapy that does cause any discomfort in the patient’s ear.  
Nobody is researching transcutaneous vagal nerve stimulation for improved learning in autism, given that some doctors at leading hospitals like Johns Hopkins do seem to like zapping people with autism, perhaps somebody should. There looks to be more science behind this than some other shock treatments, which do look quite crude, but do seem to help some people.  

Parkinson’s Disease and the Vagal Nerve
We saw in an earlier post that what goes on in the gut is communicated to the brain, bypassing the blood brain barrier, via the vagal nerve.  In that post it was mice who had their vagal nerve severed in the name of science.
Until recently a common therapy in humans with peptic ulcers was to severe the vagal nerve.  It turns out that these people are protected from developing Parkinson’s Disease. Interesting?







43 comments:

  1. Peter,yes,very interesting.As said to Kritika, my son has chronic constipation,this always has been a real problem, it says in the last link that parkinson´s patients started the process with constipation and the disease spreaded through the vagus nerve to the brain.Wordless.
    Valentina

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    1. Valentina, since you are looking at sarcosine (and I guess it is for NMDAr agonism), it might be interesting to know that a lot of people I know about with genetically diagnosed dysfunctional NMDArs also have constipation. Of course, there are many ways to get constipated, so this might not be the reason in your case.
      Also, have you checked the halflife of sarcosine? I thought that it was very short (2 hours) but I might be wrong.

      /Ling

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    2. Ling,DA and NMDA receptors interact with each other,DA release can be modulated by glutamate receptors.All this is dysfunctional in my son, and he always had chronic constipation.I didn´t know about sarcosine´s so short halflife.Iam afraid that by activating NMDARs with sarcosine or L serine I could be enhansing dopamine.They are used as antidepressants.What do you think? Valentina

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    3. Funny that you mention sarcosine, I have ordered it earlier today and will give it a try, see reddit.com/r/nootropics there was a post 2-3 days ago about sarcosine + nac mimicing alcohol afterglow (those of you who read more often here will know what im on about).

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    4. Valentina, I can't answer if L-/D-serine or sarcosine will change dopamine release in your son. I have not heard of that (eventual) effect before. I believe that enhancing hypofunctioning NMDArs will lower the signalling burden on all the other NMDArs. D-serine seems to have an effect on OCD/neuropathy, irritability and muscular functions (ability to use hands, legs, mouth and perhaps better motility).
      Also, I do not *know* if the halflife of sarcosine is so short, that is why I thought it would be good to check it up.
      Hope you find the right decision for your son, whatever it is!

      /Ling

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  2. Hi Valentina,

    I just read the following abstract a few days ago, and when I saw your post, I thought you may be interested:

    https://www.ncbi.nlm.nih.gov/pubmed/?term=black+garlic+5-ht4

    I found it because I was looking for 5-HT4 agonists, and black garlic has been coming up in a few of my other recent searches too.

    You may want to PubMed Black garlic, but I've found a few reasons why I think it may be helpful for ASD in general, and if it also helps with GI motility, it could be like two birds with one stone for you.

    I hope you find this interesting!

    AJ

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    1. Thanks AJ, your input has been really very helpful for me. Now Iam worried because l lysine, as an antagonist of 5 HT4 ,could be afecting GI motility.Could this be happening?He is on l lysine since 3 months ago.What do you think? I will get black garlic, sure will be of great help.
      Valentina

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    2. Hi Valentina,

      Thanks for the kind words, I really do hope that the info I post does help.

      It's interesting you point out Lysine, in my search for a 5-HT4 agonist, I noticed that Lysine was an antagonist, and I made a mental note not to try Lysine (unless a test shows that Lysine would specifically be helpful for my daughter).

      It was the following paper that made me look for a 5-HT4 agonist in the first place:

      https://www.ncbi.nlm.nih.gov/pubmed/29614380

      There are so many hypotheses about ASD, who knows which ones apply to each of our kids, but I've been trying the relevant therapies for many of key hypotheses, hoping to hit the right one.

      What is so frustrating about ASD for me is that we find one paper that seems to indicate that treatment X would be helpful, and another that seems to indicate that the same treatment may not be helpful. So it's really been trial and error.

      I don't know if you've seen any specific improvement on Lysine, but if you haven't (and if the constipation started / worsened around when you started Lysine), one approach may be to replace it with a Black Garlic supplement (Swanson has one, I just ordered it to test it out) and see if you see any improvements in the constipation and / or ASD in general.

      Please note that I'm not an expert on this, just going by what the paper says, but since you mentioned constipation and I had just read the paper on Black Garlic, I thought it may be worth a trial.

      If you do try it, or switch from Lysine to it, please share how it went.

      Hope all is well and that this info will be helpful Valentina!

      AJ

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    3. Valentina, I remember from looking in to SIBO protocols, low dose naltrexone was used in some protocols to help with the migrating motor complex of the bowels - supposedly helps nerve damage in SIBO that causes the constipation/diarrhea. I also remember reading somewhere that LDN is used in Parkinson’s. You may already know about this - wanted to mention just in case.

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    4. AJ and Tanya,when I realized a long time ago that what you fix on the one hand is unsettled by the other,I knew that this was not going to be easy at all.Lysine is used as an antiviral and also for anxiety, but being a serotonin antagonist, this is not clear to me,specially because it is suggested to be beneficial for people with schizophrenia,in an Iranian study.Constipation worsened in my son since taking lysine,so I will have to wean it off, no matter how great lysine can be.Tyler had suggested Naltrexone to me as an opioid antagonist, to inhibit excess dopamine,I didn´t know that it helps with SIBO damage, would be ideal this combo for my son, but it is ridiculously expensive and difficult to get.So, I will switch to serotonin agonist/ gut motility black garlic combo and let you know.The question I have is: by increasing serotonin you lower dopamine??Endless theme
      Valentina

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    5. Hi Valentina,

      I totally get it. When I find something that looks like it will help something I am looking to address, when I do more reading, it seems to negatively affect something else. Treating ASD is like playing Whack-a-Mole. You knock down one thing only to have something else pop up.

      I don't know the answer to your question in terms of impact on dopamine by using a 5-HT4 agonist.

      I really hope you get some benefit from the Black Garlic supplement, and not just in terms of the GI issues, but in terms of ASD itself. My daughter thankfully never had any GI issues, but I want to give her black garlic for ASD, so my hope is that it gives you benefits in both areas.

      AJ

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    6. AJ, it seems that 5HT4 agonists enhance dopamine release. Continue playing Whack a Mole!
      Valentina

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    7. Valentina, it is so confusing!! The more I read the more I realize I don’t want to test anything that has the potential to disrupt a stable mood and trigger mania.. Especially during adolescence., Whack a mole is the perfect description

      Delete
  3. Hi everyone,

    Interesting paper just came out for those with CDKL5 issues:

    The antidepressant tianeptine reverts synaptic AMPA receptor defects caused by deficiency of CDKL5.
    Tramarin M1, Rusconi L1, Pizzamiglio L2, Barbiero I1, Peroni D1, Scaramuzza L3, Guilliams T4, Cavalla D4,5, Antonucci F2, Kilstrup-Nielsen C1.
    Author information


    Abstract
    Mutations in the X-linked cyclin-dependent kinase-like 5 (CDKL5) gene cause a complex neurological disorder, characterised by infantile seizures, impairment of cognitive and motor skills, and autistic features. Loss of Cdkl5 in mice affects dendritic spine maturation and dynamics but the underlying molecular mechanisms are still far from fully understood. Here we show that Cdkl5 deficiency in primary hippocampal neurons leads to deranged expression of the alpha-amino-3-hydroxy-5-methyl-4-iso-xazole propionic acid receptors (AMPA-R). In particular, a dramatic reduction of expression of the GluA2 subunit occurs concomitantly with its hyper-phosphorylation on Serine 880 and increased ubiquitination. Consequently, Cdkl5 silencing skews the composition of membrane-inserted AMPA-Rs towards the GluA2-lacking calcium-permeable form. Such derangement is likely to contribute, at least in part, to the altered synaptic functions and cognitive impairment linked to loss of Cdkl5.Importantly, we find that tianeptine, a cognitive enhancer and antidepressant drug, known to recruit and stabilise AMPA-Rs at the synaptic sites, can normalise the expression of membrane inserted AMPA-Rs as well as the number of PSD-95 clusters, suggesting its therapeutic potential for patients with mutations in CDKL5.

    https://www.ncbi.nlm.nih.gov/pubmed/29618004

    I filed tianeptine away on my giant list of future potential option many months ago when I reviewed nootropic options.

    I don't know if it would benefit anyone outside of those with known CDKL5 issues, but if your ASD loved one does have known CDKL5 issues, this is definitely a must read abstract.

    Hope this helps someone!

    AJ

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  4. For anyone interested, day 6 completed and my son is doing so well with Bimuno (b-GOS) . Not sure how it took me so long to find out about this prebiotic. Cautiously optimistic:

    “Prebiotic feeding elevates central brain derived neurotrophic factor, N-methyl-D-aspartate receptor subunits and D-serine.”

    https://www.ncbi.nlm.nih.gov/m/pubmed/24140431/?i=2&from=/28242013/related

    “The intake of GOS also increased hippocampal NR2A subunits, and frontal cortex NR1 and d-serine.....The effect of GOS on components of central NMDAR signalling was greater than FOS, and may reflect the proliferative potency of GOS on microbiota.

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    1. Tanya,

      Me interested...very much. How do you say he is doing well? I mean did you see changes? I have ordered Pharm EPA which should be reaching here in another en days time. Though, I read about Prof Puri's EPA study being a classic case of bad science lapped up by the media. Anyway, if it works, it works...I am not peer reviewing a paper sent to me.

      Valentina, if you happen to read this, please share your experience with Restore. Ca n t believe all those people raving about its miraculous healing properties, worthy of nobel prize even (yes, someone really thought that) could be deceiving us..or could they? Well, please share how it goes.

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    2. Kritika, it’s still early, so by doing well I mean he is not reacting negatively to a prebiotic like those with SIBO do. the claim that b-GOS doesn’t cause the problems like other prebiotics is true for my son. Happy about that! So now we can continue on for at least 3 weeks and see what else happens :)

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    3. Oh yes Tanya...for us no news is good news. With our sons reacting massively to every drug and supplement, no adverse reaction is a big sigh of relief.

      Tanya, please give a feedback after another week and then I will order my bimuno.

      My sincerest wishes

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    4. Very interesting Tanya!
      BDNF, D-serine and NR2A are all things on my wishlist, so I'll have to look into this Bimuno-thing too.
      At the moment I have started up supplementation with baby formula containing GOS and MFGM/phospholipids. We'll see what happens when I add EPA for synergistic effects and eventually some more phospholipids acting as carriers.

      /Ling

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  5. Peter,could you explain me why or how sarcosine helps with OCD/mania asociated with glutamate and dopamine hyperactivity,since it is a glycine transporter antagonist,NMDA glutamate agonist? I ordered sarcosine but afraid to use it.
    Valentina

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    1. Valentina, it is claimed that sarcosine will increases glycine concentrations in the brain and so causes increased NMDA receptor activation.

      So if you have NMDAR hypofunction this might be helpful, but it have hyper function it would make things worse.

      Some research suggests that dopaminergic hyperactivity to be a feature of schizophrenia and that the glycine transporter 1 (blocked by sarcosine) affects dopamine release, as a result this is put forward as another explanation of why sarcosine helps some people with schizophrenia.

      You already have sarcosine in your body and it is found in plenty of types of food. So I think making a trial starting at a low dose is not a big risk.

      For schizophrenia, I think Sarcosine is an obvious choice, in autism it is only going to work for a sub-group.

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    2. Peter,there's a study about parkinson that says glycine uptake inhibitors enhancing NMDA receptors promote striatal dopamine reinnervention.Valentina

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    3. My sarcosine arrived yesterday and I tried it today for the first time, 500mg in the morning empty stomach and 500mg in the afternoon.

      The positive acute effects that I have noticed I would say is definatly the mental clarity with perceptional depth to daily life (in a somewhat distinct way than piracetam does).

      I do seem genuinly more interested in people and daily life activity but the effect is very short (onset happens at 30mins or so it seems and duration about an hour tops).

      Then 2.5hours after dosing Im left with a minor headache (similar to the type of headache I used to get from D-aspartic acid when I tried it a couple of times in the past).

      3 grams of taurine and 100mg of icariin (both strongly protective against glutamate excitoxicity) completely gets rid of this hangover for me when the headache starts to appear.

      Ill try be somewhat 'heroic' tomorrow and try 2x 1000mg sarcosine, Im pretty sure I can literally set my stopwatch at the 2.5hour mark for the headache to appear.
      However I want this confirmation of yet another headache to make 100% sure it is down to the sarcosine and not lifestyle factors and even then the studies that use sarcosine for depression for example use it for 6 weeks or so, so the acute effects could be very different from chronic use.

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    4. I forgot to say I got mine from brainvitaminz, profontal also sells it (but is expensive and has NAC merged with it in the bottle) but I wanted to try sarcosine on its own and I still got quite a fair few tabs of NAC left (which I had stopped due to some nosebleeds I sometimes seem to get on 1200mg nac in one dose).

      There is a discussion on reddit (for anhedonia related on the /r/nootropics channel) where people use NAC + sarcosine COMBINED and some people swear that it is the combination that has this very good synergy to it.

      I forgot to add in my previous post: the famous autism gaze avoidance/irritability was also present at 2.5hours after sarcosine intake, as an adult with ASD and a tons amount of selfknowledge this is easily detectable for me now.

      ALCAR for example also gives me gaze avoidance and irritability in the exact same way (yet l-carntine and gplc do not).

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    5. Hi Aspie1983,for possible GAD deficency, I will give my son Gotu Kola,but I think I should start at least one week before sarcosine. Valentina

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    6. Aspie, I must say that your self-experimenting results are very very interesting... Do you have a direct link to that reddit discussion on NAC + sarcosine?

      And please be careful with yourself, will you?

      /Ling

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    7. Sarcosine is also a co-agonist at the NMDAr glycine site, so it has many ways to up NMDA functioning:

      "We found that sarcosine is an NMDAR co-agonist at the glycine binding site. However, sarcosine differed from glycine because less NMDAR desensitization occurred with sarcosine than with glycine as the co-agonist. This finding led us to examine whether the physiological effects of NMDAR activation with these two co-agonists are the same."
      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2727032/

      We can also see that it is relevant which NMDA receptors you want to affect (or rather where):
      "We report that synaptic and extrasynaptic NMDARs are gated by different endogenous coagonists, d-serine and glycine, respectively."
      https://www.ncbi.nlm.nih.gov/pubmed/22863013

      Anyone who knows more about this little detail?

      /Ling

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    8. Hi Valentina,

      Ive heard about gotu kola before, some parents give it to their kids with ADHD and some claim it has some effects, im unaware if this herb affects GAD.

      All I know is that taurine (which is an osmolyte just like inositol which is used mainly in PCOS and OCD) pretty much never fails to calm me down, the effect can literally be felt within 30minutes calms down nerves, relaxes the mind and its dirt cheap (get it in bulk).

      Another herb that had a tremendous effect on calming me down and even is healthy is ashwagandha (this herb also improves thyroid levels and as many of you know alot of kids/adults with autism and asd often are hypothyroidism or have subclinical hypothyroidism).
      In fact ashwagandha (when taken for about 90 days) even lowers cortisol levels in healthy adults with stress.

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    9. @Ling

      Thanks first of all for your concern and Im well aware that certain herbs/meds do have side effects.

      https://www.reddit.com/r/Nootropics/comments/89u96j/a_third_and_final_followup_to_the_original/

      If you do a search on the /r/nootropics subbreddit for alcohol nmda and afterglow you will find many many posts of people with asd, autism, aspergers and even adhd who know (just like myself) that I become completely normal human being the day after binge drinking (now this is related to NMDA upregulation) and I do not get headaches at all! If anything I get a pronounced clarity of mind, my mind is free and I am open to social interaction with people.
      Vitamin d3 10.000iu and dextromethorphan comes closest to this effect for me, followed by piracetam and oxiracetam.

      These threads on reddit and many others was what made me look into PAM's/NMDA upregulators, as most people here might know by now glutamate and nmda is NOT the devil, the balance is the key, in fact glutamate and nmda activity is critical for learning, with lack of nmda activity (such as in shizophrenia) hallucinations can occurs, this is one of the reasons why memantine (yes a nmda antagonist) is used by people to reset tollerance to stimulants as nmda antagonism upregulates dopamine receptors.

      Agmatine is another NMDA antagonist for example.

      Now what happens during alcohol intake/dissociative use is alot of brain plasticity occurs (I feel this also the reason why alcoholics keep going for the bottle in a subconscious attempt to erase/allow to process their experience of negative emotions).

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    10. I witnessed this first hand on memantine myself, by keeping the NMDA receptor blocked I found myself only living in the NOW and being unable to create new memories, I felt at ease and 'OK' with everything, this also took away the stress I experience during improper social interactions, after all if failing social interactions has no meaning (ie. a memory) then no stress reaction occurs.

      With alcohol (yes alcohol is both a GABA PAM aswell as a NMDA antagonist) which has a far shorter duration.
      Plasticity changes (through very complex LTD and LTP mechanism) seem to upregulate NMDA receptors (this is proven by dozens and dozens of studies out there) after acute withdrawal.

      More or less the same happens to me with dextromethorphan, if I use it in the evening (only done it twice so far) the next morning I wake up I feel reborn and OPEN to social interaction at the same time I feel relieve from past trauma/negativity, its like literally hitting a reset button.

      Ketamine is also being researched for this (which has very rapid onset antidepressant effects in models of anhedonia and treatment resistant depression).

      Now ketamine also works through mTOR and AMPA receptors which both cordyceps and piracetam hit and these I have huge success with.

      After tons of personal experience I truely believe that is the actual transmission/lack of flow through the nmda receptors that is responsible for alot of the autism like problems.

      This is also why I think that sarcosine or d-aa on its own might not fix this.
      It works initially such as sarcosine giving me the clarity and perceptive depth (when there is still a decent amount of nmda receptors present) -> nmda receptors/flow of nmda receptors quickly attempts to bring back the autism like homeostasis -> less receptors/activity for the glutamate/nmda to attach to -> excitoxicity/headaches/neckpains.

      Every single time I had brief moments of feeling completely normal it happened overnight, this is why I personally believe the future may actually lie in short/semi potent nmda antagonist close before bed (this will also help sleep most likely as memantine very much improved my ability to fall asleep and stay asleep, while d-aspartic acid made me wake up 10+ times a night, even when taken in the morning and this makes sense as aspartic acid messes with melatonin buildup in the pinealgland during onset of darkness).

      Now admittedly I have only use sarcosine by itself and not yet combined with NAC (people it is critical to combine them), but I did still woke up this morning with a slight headache and this is also the reason I decided to not do the 1000mg sarcosine as I said yesterday.

      Also D-cycloserine (which also affects glycine/nmda channels through a different mechanism than sarcosine) has actual studies confirming that it can have its uses in autism/asd:


      A randomized, placebo-controlled trial of D-cycloserine for the enhancement of social skills training in autism spectrum disorders.

      https://www.ncbi.nlm.nih.gov/pubmed/26770664

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    11. @Ling again,

      I will give you my brief experience with compounds that affect NMDA that I have tried:

      * memantine - see above)
      * piracetam (upregulates ampa/nmda receptors with chronic use, protects brain mitochondria, improves brain bloodflow, effect against brain 'vasospasms') - improved willingness to get things, improved persistence when aiming for goals, less inflammatory like brain issues reflecting in less irritability and such, can be euphoric especially combined with coffee, more open to social interaction, effects last about 3-4hours, definatly atleast need to dose bi-daily.
      * oxiracetam (potentiates d-aspartic acid release when the neurons get activated, increases PKC, raises malate-aspartate shuttle, increase glutamine,glutamate,glutathione,vitamin c levels in the brain and improved brain bloodflow) - increased joy in daily activities and work feels more rewarding, increases perception awareness for the better by seeing more positive outcomes in things, improves on-the-go problem solving as I call it where for example if you got your keys in your hands while working and you need to place them somewhere, where normally you would go to hang them with the rest of keys on a rack you would now hang them around first object closest to you (breaking free of the need for daily structure?).
      I have only used oxiracetam briefly, but I liked the effect very much, shame the effects only seemed to last 2-3hours (with acute use, not sure of chronic use). Seemed to improve hedonic tone and being more spontaneous, increased creativity.
      Some evidence that oxiracetam could potentially help:

      Prolonged social recognition in male rats treated with alaptide or oxiracetam.
      https://www.ncbi.nlm.nih.gov/pubmed/11224110

      Oxiracetam pre- but not post-treatment prevented social recognition deficits produced with trimethyltin in rats
      https://www.sciencedirect.com/science/article/pii/S0166432805000768

      D-aspartic acid - briefly brought back emotions (though mostly negative ones), I did seem to be wanting more around people (but felt this was more because of the realisation of vulnerability came to the surface), headaches and insomnia were main side effects (used it for about 10 days twice throughout the years), more crying than usual (d-aspartic acid can increase prolactin so this is no surprise), no permanent negative effects it seemed to have had on me.

      Aniracetam (AMPA pam) - this one I responded absolutely horrible to for some reason, almost in a similar way as low dose clonazepam, it made me too disinhibited and I started hating people for no reason? absolutely horrible experience for me. Used it for one day and had a 48hours severe depression afterwards.

      Zinc, magnesium aspartate (ZMA) - more or less similar effect as D-asapartic acid.

      PQQ (modulates nmda redox site and mitochondrial biogenesis booster) - worked quite well for mood/social experiences but unfortunatly around 5-6 weeks in it seemed to give me some skin issues (Epidermal growth factor, which is allready upregulated in autism, seems to also be increased by pqq so this no surprise), really a shame I absolutely liked this supplement.

      NAC - mental stability and stress free live (it feels somewhat similar to this regard with memantine allthough I felt memantine was more potent with regards to this), improved my energy levels/antifatigue, possible insomnia if taken too late in the day, ended up getting nosebleeds sometimes when even dosing only 600mg, which is one of the reason I had stopped it.

      Taurine - just feels so good and right, no side effects at all noticed, only positives.

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    12. Forgot to add:

      Glycine - also seems to give me minor headaches (far less so than d-aspartic acid), felt somewhat different mentally not sure how describe it but according to studies in healthy people 3grams of glycine increases vasopressin levels the next day.

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    13. Thank you Aspie for that very extensive report!

      The description of your different experiences with these compounds is invaluable for pattern-seeking when dealing with non-verbal persons who can't express the finer details of their emotional and cognitive state.
      I will surely come back many times to your comments for reference!
      All the best,

      /Ling

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  6. Tyler, could you tell me at least your opinion of such a complex theme?
    Valentina

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    1. By complex theme, do you mean Sarcosine? I know very little about it other than what has already been posted in this discussion.

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    2. I mean, the problem with my son´s dopamine hyperactivity, i asume when he has the positive like psyco episodes from time to time and OCD/mania in general.Activating NMDA is the correct way? what about GAD and glutamate neurotoxicity? But if my son had ADHD also, I would need more dopamine in other areas? Adaptogen herbs could help like gotu kola and ashwaganda and adding noni as antipsychotic? Very complex my son´s profile.
      Valentina

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    3. There are 4 major dopamine pathways in the brain. If your son had very low dopamine levels, then he would likely have Parkinsonian symptoms rather than hyperactivity. Also, ADHD hyperactivity is very different from autism hyperactivity as studies have shown that stimulants make symptoms worse in the low-functionig autistic population.

      Also, I don't really think very highly of adaptogen herbs helping with specific conditions because they often have many different substances that in small amounts do a lot of different things. If a particular herb helps then fine, but it is always going to be subjective.

      Again if I were you I would try and manage the dopamine levels as best you can as you have done so, stay away from stimulants, and look at other neuromodulators that indirectly affect dopamine tone in the brain such as opioids, serotonin, and acetylcholine.

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    4. Tyler,Peter, I could try an acetylcholinesterase inhibitor, there is a study:"acetylcholinesterase inhibitors block acetylcholine-evoked release of dopamine in rat striatum". Here I can get Darial used in Alzheimer.
      Valentina

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    5. Valentina, your Darial is a brand name for Donepezil, which is quite well studied in autism. I suggest you google the studies. It seems to help some people but not others.

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    6. Peter, I found something better than donapezil, it is rivastigmine,it has much fewer side effects, no cardiac manifestations and no tolerance with chronic use. Rivastigmine acts on the frontotemporal lobe,the one that presented acute assymmetry when my son was almost 3.Here it is called Exelon from Gramon Bagó.
      Valentina

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    7. Valentina, Dr Chez has made trials with both Donepezil and Rivastigmine. I wonder which one he actually prescribes now.

      https://www.ncbi.nlm.nih.gov/pubmed/15119476

      Increasing cerebral acetylcholine should improve learning and this is the reason for vagal nerve stimulation in the above blog post.

      In autism, it may be relevant how old the person is. In one paper I read it was noted that Donepezil seems to have more measurable effect in young children than older ones.

      There is also Galantamine, which has also been studied. Being sold as a supplement in some countries, I expect it is the most widely used.

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    8. Peter, I could get donepezil, tomorrow Will get sarcosine, do you think would be a good match?I would start with 5 MG donepezil.
      Valentina

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    9. Valentina, I have not used either drug. It is always best to try interventions one at a time.

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