1569 replies to this topic

[Venom]

Hello all, did someone who got some cognitive decline ilnesses like alzheimer, schizophrenia or parkinson used dihexa and what your changes in this term (cognitive)?

[xks201]

Not yet as only several received small samples. Main synthesis is not complete yet

[redFishBlueFish]

I wouldn't say it is that spooky it just feels like my depth perception (which was already very good) is even better. Like I said I used to race street bikes around tracks for fun and that requires pretty much the best depth perception you can possibly have. Now it feels better. Colors feel enhanced still. Not in a psychadelic type way- more so just an improvement in vision or spatial processing almost. 

 

This is a huge problem with me. My depth perception is wacky. I can judge far and close, but when it comes to anything in motion, I am literately guessing and hoping for the best. Is there anyway to measure this kind of perception or is it up in the air?

[jabowery]

 

Found it here:

 

http://www.longecity...ndpost&p=676677

 

Thanks.

 

 

I'm looking into subcutaneous.  When you're dealing with a potential "unobtanium" of limited supply, it just plain makes no sense to say things like "its so powerful the route of administration doesn't matter".

 

 

According to patent application "Enhanced pharmacokinetic profile of hydrophobic substances", hydrophobic drugs are best _not_ administered subcutaneously because "hydrophobic substances tend to partition into subcutaneous adipose tissue the absorption of these substances into the vascular system would be expected to be limited following subcutaneous administration (Walder, Immunopharmacol. Immunotoxicol. 3:101-119, 1991)".

 

Is this patent ignoring the inherently time-released nature of subcutaneous delivery?  I mean if the hydrophobic drug is stable, won't the adipose tissue slowly release a previously-absorbed hydrophobic drug yielding high bioavailability integrated over time?

Edited by jabowery, 21 August 2014 - 05:21 AM.

[Venom]

Xks i cant send pm to you so i ask here: "Is your group buy already full or i can join if u have free spots?"

[Nemo888]

http://newsroom.cumc...=autismsynapses

[christallire]

http://newsroom.cumc...=autismsynapses

 

That doesn't mean new synapses are not pruned for people who is not having autism.

Edited by christallire, 22 August 2014 - 12:50 PM.

[Nemo888]

I guess we will know the trial results in a few months as the new synapses mature. Though the lack of posting lately by the guinea pigs is a bad sign. Watch for social and communication deficits, being easily irritated, disliking affection and a strong tendency to isolate.

Edited by Nemo888, 22 August 2014 - 01:55 PM.

[Metagene]

I guess we will know the trial results in a few months as the new synapses mature. Though the lack of posting lately by the guinea pigs is a bad sign. Watch for social and communication deficits, being easily irritated, disliking affection and a strong tendency to isolate.

lol the guinea pigs might just be back in school.

[jabowery]

I guess we will know the trial results in a few months as the new synapses mature. Though the lack of posting lately by the guinea pigs is a bad sign. Watch for social and communication deficits, being easily irritated, disliking affection and a strong tendency to isolate.

 

One can report an infinite amount of noise but the reality is in these self-experiments the polite, if not ethical thing to do is stick to the most pertinent facts -- which means not reporting the vast majority of subjective experiences and sticking to standardized measurement results.

 

If I were to get all touchy-feely I'd report, not only as pertinent but as salient, the anecdote that, as of yesterday, I was credited with having made an invention that will have a substantial impact.  I do _not_ attribute this to my having ingested Dihexa and I think others would make the same judgement if they knew all of the pertinent facts.  

 

If I were to be chatty, I'd be relating all manner of far less pertinent self-observations that would do little but obscure the vitally important data obtainable from a longitudinal report of repeated applications of the same quantitative measurement standard -- in my case the "Odd One Out" test at Cambridge Sciences and things, such as apneatic events during sleep, that can impact cognitive performance and confound attempts to detect deleterious side-effects.  Even if I improve dramatically in this series of measurements it does not say that it is due to Dihexa since we don't know what the expected rate of improvement is in the absence of treatment.  All I am attempting to ascertain with this series of objective measurements is loss of capacity in this area of "fluid reasoning".  Yes, that is very limited but at least it is valid.

Edited by jabowery, 22 August 2014 - 05:58 PM.

[sk_scientific]

I guess we will know the trial results in a few months as the new synapses mature. Though the lack of posting lately by the guinea pigs is a bad sign. Watch for social and communication deficits, being easily irritated, disliking affection and a strong tendency to isolate.

 

Non-sense, troll.  People are busy.

[christallire]

I got my synth and DMSO, but I will not ingest dihexa until DHEXA returns.

Honestly, I was worried about majority of guinea pigs are disppeared.

 

will share my experience after ingested it though.

[neuroatypicow]

i'm not disappeared! just diffuse, translucent, diaphanous...

i'm in my second cycle of NSI+Dihexa. so far so great. no problems, other than the dihexa we got from DHEXA tends to form small clumps when dosing sublingually, so i'm having to interact with it a lot with my tongue to break it up. that means i get to taste its grainy bitterness. yuck

[therein]

We are still around and feeling well, we are just busy.

[christallire]

Alright,

Since our guinea pigs are still alive and kicking, i decided to try dihexa out.

 

doing base line test because of choline method, 

I'll write my test results as well.

 

Base line:

 

before choline + dha + uridine + lion's mane method

Lumosity 1300 LPI

Odd one out 13pt avg

 

After taking choline ... method for 2 weeks:

Lumosity 1500 LPI

odd one out 21pt avg

 

i'll start/preparing for DMSO 50% concentrate with topical application of DIHEXA 5mg.

Dose will definately increase overtime, will see what happens.

 

Wish me luck

Edited by christallire, 24 August 2014 - 07:59 AM.

[crazepharmacist]

I take it the group buy is over for this compound? Is there any way to acquire Dihexa currently? If no, when can we reasonably expect nootropic vendor(s) to start carrying it?

[megatron]

 

I don't know why people are making such a big deal about the topic derailment at this point. We are reporting Dihexa's effects as we experience them but we are also trying to refrain from over-reporting as that means we would be reporting potential placebo effects as well. I am making sure to only post my experiences when I am fairly certain that they aren't just placebo.

 

While it makes sense not to post about topics and links irrelevant to Dihexa on this thread, we are also not getting a lot of updates about people's experiences lately. I don't see anything wrong with talking about topics somewhat related to Dihexa in the meantime. It keeps the group engaged and interested if anything.

I think Thereins got the right idea. Jabowery and others were posting information that was entirely relevant in my opinion. I wish i could post more frequently, I've been very busy with work related projects lately.

I'm on day 29 ~27mg QD.
Still feel very clearheaded. I can't remember the last time I've been really 'foggy'.
I do regular resistance training at respectable, but not overly impressive weights. Since dihexa, my lift numbers have increased with little change in diet or routine. This is significant to me because I've been 'stalled' on them for 6+ months. Increased myelination in the PNS could be contributing to increased muscular coordination? Does anyone have other theories to explain such a change?

 

I've sent out close to 20g this past week. Hopefully we should be hearing from other members, should they decide to share their experiences.

 

 

An update would be interesting. 

[Nemo888]

I am deliberately skeptical. An echo chamber is not a good place to learn. Seen too many times how that plays out in the military. Please don't let that come across as disrespectful. I am stirring the pot, not tipping it over.

[X_Danny_X]

is this still expensive to buy individually?  

[DHEXA]

Apologies everyone, a family member came down unexpectedly with severe health problems. I do still have a few grams available, for those who have been asking. I won't be able to ship until sometime next week though. I'll post an updated log at that time as well. I'm still healthy and well as far as i can tell.

[jabowery]

Insofar as Jan's Huntington's, since:

• I haven't seen any deleterious effects in myself or reported from others (or, for that matter, from the animal models),
• I can't find unequivocal evidence of greater bioavailability via subcutaneous injection (see my prior post regarding the patent on hydrophobic drug administration)
• I'm still hopeful that the Nyles7 synthesis will come through

 

I've decided on a compromise solution to the problem of limited supply in the face of the purported low (1%) oral bioavailability:

 

10mg daily oral

 

Thus far she's received:

 

8/16 21mg, 8/17 20mg, hiatus as I reconsidered route of administration, 8/24 10mg, 8/25 10mg, 8/26 10mg, 8/27 9mg

 

This is all oral and I try, usually with success, to make it before she's eaten in the morning.  There was some wastage in these early doses as I dealt with oral administration issues like the hydrophobic nature of dihexa and the fact that Jan's movement disorder doesn't permit me to dump the milligram-scale measured dose directly from the weighing paper into her open mouth.  I've settled on taking a very small square of paper towel, pouring the dihexa onto it and rolling it up as a quasi-capsule.

 

The data from Singing Coach is limited to the current high score achieved in each of a number (about 10) of "easy" songs like "Twinkle Twinkle Little Star", "The Farmer in the Dell", etc.  They don't let you capture even that data without manually transcribing it from their interface, so I haven't yet recorded it in any form other than screen shots.  Nor do I have the time to monitor her sessions with SC even if I could schedule her sessions.  Any time she feels up to it is a good time for her to try to tolerate SC and I'm surprised she can tolerate it as well as she has during the establishment of her baseline given her debilitated state in stark contrast with her history as an opera singer.  If she doesn't improve I suspect she will become discouraged but I have tried to moderate her expectations.

Edited by jabowery, 28 August 2014 - 05:08 PM.

[StevesPetRat]

Steve I speculated that it was increasing strength but I didn't know exactly the mechanism or speculate on it. There are probably one thousand ways this compound could be doing it. No one really knows.

Ah, OK, it was DHEXA with the PNS myelination hypothesis.

I do regular resistance training at respectable, but not overly impressive weights. Since dihexa, my lift numbers have increased with little change in diet or routine. This is significant to me because I've been 'stalled' on them for 6+ months. Increased myelination in the PNS could be contributing to increased muscular coordination? Does anyone have other theories to explain such a change?

Given that some people are also reporting mild but measurable increases in BP, is simple increased epinephrine production a possible mechanism? Again, I really want this to have an effect on nerve conduction / health (e.g. would be great not to have fasciculations and / or numbness every time mild pressure is applied to a nerve), but isn't that more likely to be a long term outcome?

[xks201]

Why not give her 30mg....

[jabowery]

Why not give her 30mg....

 

A few reasons:

 

• I tested myself with only 20mg
• She's 140lb and I'm 220lb
• The measured effects on animal models were more pronounced in neurologically damaged animals
• The folks here at longecity who have taken higher doses, while they have not reported any problems, are not me. 
• I'm noticing changes in her at 10mg -- nothing I can point to as being caused by the existing dosage of dihexa necessarily, nor can I rule it out at this point.  The changes are a mixed bag even though singing coach score is improving (quite possibly ordinary training effect).  The negative changes I see I did anticipate as they are all just reemergence of symptoms present at earlier stages of her HD (but went away with further degeneration, as is expected in HD degeneration -- or so I've been told).  Still -- nothing is happening that I can't reasonably attribute to other things at this point which is why I'm not reporting them.  I'm just being cautious.
• I'd like her dose to remain constant until the Nyles7 synthesis is delivered and a lower dose is more likely to last long enough for that.

Edited by jabowery, 29 August 2014 - 06:15 AM.

[Nemo888]

Wouldn't increasing autophagy be a better idea?

Novel targets for Huntington's disease in an mTOR-independent autophagy pathway

Abstract

Autophagy is a major clearance route for intracellular aggregate-prone proteins causing diseases such as Huntington's disease. Autophagy induction with the mTOR inhibitor rapamycin accelerates clearance of these toxic substrates. As rapamycin has nontrivial side effects, we screened FDA-approved drugs to identify new autophagy-inducing pathways. We found that L-type Ca²⁺ channel antagonists, the K⁺_ATP channel opener minoxidil, and the G_i signaling activator clonidine induce autophagy. These drugs revealed a cyclical mTOR-independent pathway regulating autophagy, in which cAMP regulates IP₃ levels, influencing calpain activity, which completes the cycle by cleaving and activating G_sα, which regulates cAMP levels. This pathway has numerous potential points where autophagy can be induced, and we provide proof of principle for therapeutic relevance in Huntington's disease using mammalian cell, fly and zebrafish models. Our data also suggest that insults that elevate intracytosolic Ca²⁺ (like excitotoxicity) inhibit autophagy, thus retarding clearance of aggregate-prone proteins.

 

_________________________________________________________________________________________________________________________________________________

 

Rapamycin and mTOR-independent autophagy inducers ameliorate toxicity of polyglutamine-expanded huntingtin and related proteinopathies

Edited by G Kroemer

1. ¹Department of Medical Genetics, University of Cambridge, Cambridge Institute for Medical Research, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0XY, UK
2. ²Department of Medicine, University of Cambridge, Cambridge Institute for Medical Research, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0XY, UK

Abstract

The formation of intra-neuronal mutant protein aggregates is a characteristic of several human neurodegenerative disorders, like Alzheimer's disease, Parkinson's disease (PD) and polyglutamine disorders, including Huntington's disease (HD). Autophagy is a major clearance pathway for the removal of mutant huntingtin associated with HD, and many other disease-causing, cytoplasmic, aggregate-prone proteins. Autophagy is negatively regulated by the mammalian target of rapamycin (mTOR) and can be induced in all mammalian cell types by the mTOR inhibitor rapamycin. It can also be induced by a recently described cyclical mTOR-independent pathway, which has multiple drug targets, involving links between Ca²⁺–calpain–G_sα and cAMP–Epac–PLC-ε–IP₃ signalling. Both pathways enhance the clearance of mutant huntingtin fragments and attenuate polyglutamine toxicity in cell and animal models. The protective effects of rapamycin in vivo are autophagy-dependent. In Drosophila models of various diseases, the benefits of rapamycin are lost when the expression of different autophagy genes is reduced, implicating that its effects are not mediated by autophagy-independent processes (like mild translation suppression). Also, the mTOR-independent autophagy enhancers have no effects on mutant protein clearance in autophagy-deficient cells. In this review, we describe various drugs and pathways inducing autophagy, which may be potential therapeutic approaches for HD and related conditions. http://www.nature.co...dd2008110a.html

 

____________________________________________________________________________________________________________________________________________

 

Also relevant to the taking of Dihexa.

 

 

Loss of mTOR-Dependent Macroautophagy Causes Autistic-like Synaptic Pruning Deficits

Highlights

• •ASD human brain shows dendritic spine pruning defects and impaired mTOR-autophagy
• •mTOR overactivation causes spine pruning defects in Tsc2+/− ASD mice
• •Neuronal autophagy enables spine elimination with no effects on spine formation
• •Loss of neuronal autophagy underlies spine pruning and social interaction deficits

Summary

Developmental alterations of excitatory synapses are implicated in autism spectrum disorders (ASDs). Here, we report increased dendritic spine density with reduced developmental spine pruning in layer V pyramidal neurons in postmortem ASD temporal lobe. These spine deficits correlate with hyperactivated mTOR and impaired autophagy. In Tsc2+/− ASD mice where mTOR is constitutively overactive, we observed postnatal spine pruning defects, blockade of autophagy, and ASD-like social behaviors. The mTOR inhibitor rapamycin corrected ASD-like behaviors and spine pruning defects in Tsc2+/ mice, but not in Atg7^CKO neuronal autophagy-deficient mice or Tsc2+/−:Atg7^CKO double mutants. Neuronal autophagy furthermore enabled spine elimination with no effects on spine formation. Our findings suggest that mTOR-regulated autophagy is required for developmental spine pruning, and activation of neuronal autophagy corrects synaptic pathology and social behavior deficits in ASD models with hyperactivated mTOR.

 

_________________________________________________________________________________________________________________________________________________

 

Dihexa may need follow up with something to accelerate autophagy and dendritic pruning to be actually helpful.

And yes Minoxidil is one. Imagine getting smarter and growing your hair back. Clonidine could be used to reduce the elevated BP and also induces autophagy.

 

[Flex]

And whats about NMDA ?

 

Chronic blockade of extrasynaptic NMDA receptors ameliorates synaptic dysfunction and pro-death signaling in Huntington disease transgenic mice.

http://www.ncbi.nlm....pubmed/24269729

 

Would DIHEXA rather rise the quantity of NMDA receptors ?

 

[Nemo888]

And whats about NMDA ?

 

Chronic blockade of extrasynaptic NMDA receptors ameliorates synaptic dysfunction and pro-death signaling in Huntington disease transgenic mice.

http://www.ncbi.nlm....pubmed/24269729

 

Would DIHEXA rather rise the quantity of NMDA receptors ?

That's a good question.

 

Ketamine is mediated by mTor(increases it, slowing synaptic pruning and autophagy), memantine is not . Memantine supposedly blocks NMDA and is also used to treat Alzheimer's.

 

I suppose ketamine should be out of any stacks if you are taking dihexa.

 

[jabowery]

Nemo888, thanks for the leads for future treatments.  I'll be particularly interested when animal models of neurodegeneration show harm-free remediation from orally bioavailable versions of these treatments as profound as that demonstrated by dihexa.

 

At present, the only means of clearing toxic brain metabolites that has been demonstrated in mammals is slow wave sleep, and Jan has been denied the treatment known to enhance that which is compatible with her form of sleep disorder:  Xyrem.   See my prior post on the nasty experience with the University of Iowa's sleep specialist.

Edited by jabowery, 30 August 2014 - 07:12 PM.

[drg]

Any info on the group buy?

[Haray]

Any info on the group buy?

 

count me in