1569 replies to this topic

[xks201]

The next 500mg I will take via this method. This should be the dose far stronger. 

[xks201]

How long does the state of hyperfocus last? 

 

Dihexa is very soluble in DMSO. The concentration I use is approx. 25mg Dihexa per 1mL DMSO. There are no chunks or anything left in the solution after having stirred or shaken it for a little while. DMSO should easily diffuse through the mucous membrane under the tongue. It is actually not that bad, as you don't taste the solution while holding it under your tongue. It is when swallowing it you get a good taste of it, but I've gotten quite used to it. 

 

I've just ordered some. If it can totally dissolve dihexa, it will definitely make it to systemic circulation in high %. When I use the method of administration I mentioned above, I definitely feel the hyperfocus state, but sometime when I get lazy and simply swallow the powder or do it sublingually, I simply feel nothing. However, disregard the state I felt I was in, there is no objective improvement in cognitive performance (dual n back).

 

 

[Amorphous]

The next 500mg I will take via this method. This should be the dose far stronger. 

 

I'd suggest you take it with 4 x 125mg instead of 1 x 500mg. Compare the effects of 125mg with that of the 700mg you took before. If it is equal or stronger, you better call it quit. If not, take 1 more of 125mg about 1-2 hrs later and make sure your blood pressure is okay. Please make sure you are safe or otherwise no one will ship our share. Can you do that after you ship our dihexa first? please

Edited by Amorphous, 09 October 2014 - 03:59 PM.

[Amorphous]

 

How long does the state of hyperfocus last? 

 

Dihexa is very soluble in DMSO. The concentration I use is approx. 25mg Dihexa per 1mL DMSO. There are no chunks or anything left in the solution after having stirred or shaken it for a little while. DMSO should easily diffuse through the mucous membrane under the tongue. It is actually not that bad, as you don't taste the solution while holding it under your tongue. It is when swallowing it you get a good taste of it, but I've gotten quite used to it. 

 

I've just ordered some. If it can totally dissolve dihexa, it will definitely make it to systemic circulation in high %. When I use the method of administration I mentioned above, I definitely feel the hyperfocus state, but sometime when I get lazy and simply swallow the powder or do it sublingually, I simply feel nothing. However, disregard the state I felt I was in, there is no objective improvement in cognitive performance (dual n back).

 

 

 

That is a good question. I didn't time it. The onset is about 10-20 mins and I can feel the hyperfocus state. It seems the hyperfocus feeling last a long time. As I'd start to do things, I didn't think of the feelings, but only noticed I was more efficient in doing whatever I was doing. I would say it lasts for a day or so.

[resveratrol_guy]

I think it bears reminding that more connections do not imply better mental performance. We can't expect to test on day 1, then use dihexa for several days, then test again and see an improvement. Computerized neural networks don't work that way, so there's no reason to believe that human ones do, either. The real question is: can we take a drug which upregulates connection formation and see an improvement in trained abilities, assuming that the training and the dosing overlap? Implicitly, answering this question objectively requires either a control group (not easily obtained) or an existing performance plateau which is much longer than the experimental duration.

 

There's probably something going on with respect to hyperfocus, but does improved focus translate into improved performance on very famliar tasks with additional training?

 

[jabowery]

I think it bears reminding that more connections do not imply better mental performance. ... Computerized neural networks don't work that way...

 
The problem with too many synapses in artificial neural networks is a tendency toward "overfitting".  Overfitting is basically seeing every case as a special case to be memorized without generalization to other, not yet observed, cases.  Its rather like an autist that takes the maxim "All generalizations are false." so seriously, it can't learn anything useful because all it has is edetic (perfect sensory) memory.

[resveratrol_guy]

 

I think it bears reminding that more connections do not imply better mental performance. ... Computerized neural networks don't work that way...

 
The problem with too many synapses in artificial neural networks is a tendency toward "overfitting".  Overfitting is basically seeing every case as a special case to be memorized without generalization to other, not yet observed, cases.  Its rather like an autist that takes the maxim "All generalizations are false." so seriously, it can't learn anything useful because all it has is edetic (perfect sensory) memory.

 

 

So this goes right to heart of the question as to how we should be measuring dihexa's effects. I'm willing to believe that if we take this stuff, we'll grow more connections. But in what testable manifestion would that result? So the opposite of eidetic memory is vertical abstraction, an extreme version of the hierarchical neocortex architecture discussed by Ray Kurzweil in this recent Ted video. People who overabstract small amounts of data might come to conclusions about the nature of reality by looking at a slice of pizza, for instance.

 

I suspect by default that the eidetic-vs-abstract dial is set genetically. So if an autist takes dihexa, he would be able to memorize more pages from the phone book. If a philosopher took it, he would develop a metatheory of metaphysics, or something like that.

 

In other words, maybe the assumption that more connections implies better brain game performance is only weakly true, despite the possibility that dihexa has profound effects when viewed through the lens of our location on the aforementioned dial.

 

By the way, this dial can be simulated computationally. But if you're correct, then it would seem that, in general, neural network designers usually opt to set the dial in the eidetic extreme.

 

So then, should we really be hunting for performance improvements in areas where we already function best? This might make sense in light of Jan's improvement on Singing Coach, which differs wildly from the hyperfocus (eidetic) state reported by others.

 

 

Edited by resveratrol_guy, 11 October 2014 - 03:24 PM.

[sk_scientific]

 

 

I think it bears reminding that more connections do not imply better mental performance. ... Computerized neural networks don't work that way...

 
The problem with too many synapses in artificial neural networks is a tendency toward "overfitting".  Overfitting is basically seeing every case as a special case to be memorized without generalization to other, not yet observed, cases.  Its rather like an autist that takes the maxim "All generalizations are false." so seriously, it can't learn anything useful because all it has is edetic (perfect sensory) memory.

 

 

So this goes right to heart of the question as to how we should be measuring dihexa's effects. I'm willing to believe that if we take this stuff, we'll grow more connections. But in what testable manifestion would that result? So the opposite of eidetic memory is vertical abstraction, an extreme version of the hierarchical neocortex architecture discussed by Ray Kurzweil in this recent Ted video. People who overabstract small amounts of data might come to conclusions about the nature of reality by looking at a slice of pizza, for instance.

 

I suspect by default that the eidetic-vs-abstract dial is set genetically. So if an autist takes dihexa, he would be able to memorize more pages from the phone book. If a philosopher took it, he would develop a metatheory of metaphysics, or something like that.

 

In other words, maybe the assumption that more connections implies better brain game performance is only weakly true, despite the possibility that dihexa has profound effects when viewed through the lens of our location on the aforementioned dial.

 

By the way, this dial can be simulated computationally. But if you're correct, then it would seem that, in general, neural network designers usually opt to set the dial in the eidetic extreme.

 

So then, should we really be hunting for performance improvements in areas where we already function best? This might make sense in light of Jan's improvement on Singing Coach, which differs wildly from the hyperfocus (eidetic) state reported by others.

 

 

 

This is precisely the kind of dialogue that I was hoping would manifest on this topic.  Though I haven't much to add at this time, I was contemplating the possibility of Dihexa use potentially contributing to neuropsychological abnormalities if synaptic growth forged peculiar connections between regions of the brain not usually connected; Like those seen in the case of Daniel Tammet, the ausperger's savant whose concurrent epileptic seizures caused irregular neurological activation schemas ultimately resulting in multiple comorbid forms of Synethesia (Grapheme-color, Spatial sequence, Number form and Misophonia) -- that is from what I have gathered of his demonstrations of combinatory systems and affect in his experience of mathematics.

Edited by sk_scientific, 11 October 2014 - 04:19 PM.

[jabowery]

I think it bears reminding that more connections do not imply better mental performance. ... Computerized neural networks don't work that way...

 
The problem with too many synapses in artificial neural networks is a tendency toward "overfitting".  Overfitting is basically seeing every case as a special case to be memorized without generalization to other, not yet observed, cases.  Its rather like an autist that takes the maxim "All generalizations are false." so seriously, it can't learn anything useful because all it has is edetic (perfect sensory) memory.

... 
So then, should we really be hunting for performance improvements in areas where we already function best? This might make sense in light of Jan's improvement on Singing Coach, which differs wildly from the hyperfocus (eidetic) state reported by others.

That's been at the back of my mind, having been involved with the La Jolla aspect of the revival of artificial neural networks back in the mid to late 80s. I've had a lot of hands-on experience with heuristics for synaptic pruning as a way of achieving more effective learning rather than over-fitting so it just seemed natural that a disease like Huntington's which results in loss of brain mass, would be "over-pruned" and might be remediated by additional synapses.

I have to say, however, that Jan's recent stalling out in her improvements in Singing Coach scores, combined with her understandable frustration, makes me wonder what exactly is going on here. That the stalling out occurred before I ran out of Dihexa for her is one datum of interest. Another is that she didn't express frustration until a couple of days after I actually ceased dosing her due to the Dihexa running out.

Edited by jabowery, 11 October 2014 - 05:46 PM.

[resveratrol_guy]

So in reference to the foregoing posts, we have the obvious problem that there seems to be a diversity of effects, but nonetheless something of neurological significance -- however abstract in its nature -- is clearly occurring. But more diverse effects require more data than simple effects, to even attempt to comprehend. While I don't think it would be desirable for this thread to degenerate into a subjective discussion of those effects, it may be the case they they're so abstract that this is unavoidable. And better that, than that we give up on this compound because we can't understand its clinical significance even though it strongly appears to exist. Moreover, beggars can't be choosers; we are starving for data here. What else can you brave guinea pigs provide?

 

Edited by resveratrol_guy, 12 October 2014 - 01:13 PM.

[jabowery]

So in reference to the foregoing posts, we have the obvious problem that there seems to be a diversity of effects, but nonetheless something of neurological significance -- however abstract in its nature -- is clearly occurring. But more diverse effects require more data than simple effects, to even attempt to comprehend. While I don't think it would be desirable for this thread to degenerate into a subjective discussion of those effects, it may be the case they they're so abstract that this is unavoidable. And better that, than that we give up on this compound because we can't understand its clinical significance even though it strongly appears to exist. Moreover, beggars can't be choosers; we are starving for data here. What else can you brave guinea pigs provide?

I'm trying to keep my reports about Jan contained within periodic updates, each of substantial length, so there won't be a lot of thread searching work involved by future researchers -- one of the most annoying aspects of longecity's software being there is no obvious way to search just a thread for keywords.

Having said that, I do need to interject, as very important, that Jan's psychiatrist has diagnosed part of her movement disorder as being the result of Tardive Dyskinesia predating any Dihexa ingestion. Tardive Dyskinesia is:

• Easily mistaken for Huntington's symptoms.
• Can be brought on as a side effect of anti-psychotics used to treat Huntington's.
• Is not apparently caused by loss of neural mass.
• Is frequently irreversible.

Jan suffered from the most severe case of insomnia her neurologist had ever seen in his career, and the only medication that appeared to work without very rapid tolerance build-up were large doses of anti-psychotics.  This is exactly the kind of medication protocol that can result in irreversible Tardive Dyskinesia.

 

It would be interesting to see animal models of Tardive Dyskinesia treated with Dihexa.  I suspect it may be ineffective or at least far less effective than it is with other neurodegenerative disorders.  If so, Jan may never recover full function.  

 

This is a sensitive subject for me as being her primary caregiver I feel some sense of responsibility for this outcome -- however I would, if not deprived of the authority to prescribe medication, have pursued Xyrem rather than antipsychotics, and I did what I could within the limits of our resources to reach out to the authorized specialists.  Indeed, her neurologist wanted to use Xyrem but was not authorized by law to do so as he is not qualified to diagnose narcolepsy which is the only legal application of Xyrem.  The FDA has become a force for evil, quite clearly.

[Peak Noots]

We would be interested to donate money for a synth on this compound

Please PM me if you would like to work together on getting this synthed. We would like a partner with knowledge in the compound.

 

PeakNootropics.com

[resveratrol_guy]

Jan suffered from the most severe case of insomnia her neurologist had ever seen in his career, and the only medication that appeared to work without very rapid tolerance build-up were large doses of anti-psychotics.  This is exactly the kind of medication protocol that can result in irreversible Tardive Dyskinesia.

 

It would be interesting to see animal models of Tardive Dyskinesia treated with Dihexa.  I suspect it may be ineffective or at least far less effective than it is with other neurodegenerative disorders.  If so, Jan may never recover full function.  

 

This is a sensitive subject for me as being her primary caregiver I feel some sense of responsibility for this outcome -- however I would, if not deprived of the authority to prescribe medication, have pursued Xyrem rather than antipsychotics, and I did what I could within the limits of our resources to reach out to the authorized specialists.  Indeed, her neurologist wanted to use Xyrem but was not authorized by law to do so as he is not qualified to diagnose narcolepsy which is the only legal application of Xyrem.  The FDA has become a force for evil, quite clearly.

This is what we get for following "do no harm" for centuries: a medical system optimized to minimize lawsuits by prescribing the most effective treatments constrained by the requirement of minimum harm. At best, this results in subpar outcomes vs. state-of-the-art. But as risk analysis genius Nassim Taleb would probably point out, when you cap the upside, then the expected (mean) outcome can only go one way: down.

 

You hit a raw nerve here. This is nanny medicine. Even a simple outcome-vs-risk rating system would be vastly superior: well, you could try A, which is low risk and would alleviate the aches and pains; but B would give you better chance of recovery, although you might get nasty side effects; and C looks spectacular but it was only tested last year on rats.
 

Do not empower the patient to use their brains. Decide for them because nanny knows what's best.

 

To that end, I hope that one of the mods or synth gurus here replies/PMs PeakNootropics in regards to the previous post. We need as many companies as we can get who are willing to produce compounds that may help people, and legally operate independent of the FDA quagmire.

[VERITAS INCORRUPTUS]

We are completing refinement of a successful strong route for full production in regards to the synthesis of Dihexa.  We as well have done bench scale synthesis of some analogues we are confident are overall superior, however, they are even more difficult to synth to scale and thus more costly to produce; as well, they would trend to have a lower demand within progressive research paradigms that exist.  We will be conducting further research within all these agents, which we now only have enough for in-house research, however, shortly we will look to make at least Dihexa available for those who wish to engage progressive research.  

 

I have sent inquiry to our lead chemist on this project and should be able to remit back shortly as to what the estimated time frame is for the full scale production to be completed.

We may as well have some amount of material above that which we presently require for our in-house research, so within that we may be able to make such immediately available within the site.

 

I will look to request for our webmaster to put it up within the site if there is some definitive time frame for material.  

 

Anyone with serious research intents are welcome to express interest and contact regarding this.  The greater the demand we might be alerted to, the more expediently it will be placed into production and related.  We may as well perhaps offer a special discounted price pre-order situation to those who so inquire.  Anyway, TLR is an agent to do whatever is within the best line to foster progress, so do not hesitate to let us know.

 

Thanks!

VI of TeamTLR.com

[jabowery]

Anyone with serious research intents are welcome to express interest and contact regarding this.  The greater the demand we might be alerted to, the more expediently it will be placed into production and related.  We may as well perhaps offer a special discounted price pre-order situation to those who so inquire.  Anyway, TLR is an agent to do whatever is within the best line to foster progress, so do not hesitate to let us know.

 

If I had the resources, I'd stretch my limited time and training to conduct a Dihexa animal model trial of both HD and Tardive Dyskenisia.

 

There are rodent models for both.

 

http://www.tardivedy...oms/animals.php

 

http://www.ncbi.nlm....pubmed/17712222

[VERITAS INCORRUPTUS]

Sounds good

 

We may also be willing to afford our proprietary SEP-OX BDNF enhancer, SNRB-OX, at a highly discounted pricing for researchers conducting such BDNF enhancing research, as within agents such as dihexa and otherwise.  

 

This is within promotion of greater understanding within this area as a whole and to determine if there may synergies within multiple concurrent routes that are elicited via different pathways, as we have seen to be the case in our in-house research.  Further exploration would as such seem warranted and within an outlook toward best progress.

 

Anyway, for those so inclined.

[focus83]

We as well have done bench scale synthesis of some analogues we are confident are overall superior, however, they are even more difficult to synth to scale and thus more costly to produce; as well, they would trend to have a lower demand within progressive research paradigms that exist.

 

Where are you taking your confidence from that your analogues are superior to Dihexa? As much as I admire your research enthusiasm, I am highly sceptical that these claims will indeed come true. I mean you haven't done any animal research I guess, let alone humal trials, have you?

[xks201]

It's hard for me to agree that you are even slightly responsible for a physician prescribing an anti psychotic for inability to sleep. That's absurd and now you can question the dhexa trial because blockade of dopamine receptors will interfere with any cognitive development. Tons of meds other than anti psychotics or xyrem could have been used. Now her body has energy from dhexa and obviously shes not burning any energy being bed ridden so I suppose that was to be expected if she is still bed ridden. Be careful what you tell a doctor

[jabowery]

It's hard for me to agree that you are even slightly responsible for a physician prescribing an anti psychotic for inability to sleep. That's absurd and now you can question the dhexa trial because blockade of dopamine receptors will interfere with any cognitive development. Tons of meds other than anti psychotics or xyrem could have been used. Now her body has energy from dhexa and obviously shes not burning any energy being bed ridden so I suppose that was to be expected if she is still bed ridden. Be careful what you tell a doctor

 

She's been off of the high doses of anti-psychotics for several months now.  There are other causes of movement disorder (including acute onset Parkinsonism) during anti-psychotic discontinuation.  She suffered acute onset Parkinsonism a few years ago which was so severe that she lost her drivers license (she shouldn't have been driving in any case by that time).

[xks201]

How long was she on anti psychotics? I have worked with people on those drugs and they all cause extreme cognitive dysfunction. Blocking dopamine will cause dopamine not to function AKA Parkinsons.  Answering the first question will tell me how much of this is iatrogenic. 

 

Maybe I misread your post on my phone but it was my understanding that she was recently prescribed the anti psychotic for insomnia.  So if this was in the past and she now has insomnia again and you are blaming it on you and dihexa when she had the condition before that makes no sense to me. 

 

I know you do a good job at sounding unbiased in your writing and displaying multiple points of view but that makes it quite difficult for me to understand what you are really thinking.  

Edited by xks201, 13 October 2014 - 05:34 PM.

[jabowery]

How long was she on anti psychotics? I have worked with people on those drugs and they all cause extreme cognitive dysfunction. Blocking dopamine will cause dopamine not to function AKA Parkinsons.  Answering the first question will tell me how much of this is iatrogenic. 

 

Maybe I misread your post on my phone but it was my understanding that she was recently prescribed the anti psychotic for insomnia.  So if this was in the past and she now has insomnia again and you are blaming it on you and dihexa when she had the condition before that makes no sense to me. 

 

I know you do a good job at sounding unbiased in your writing and displaying multiple points of view but that makes it quite difficult for me to understand what you are really thinking.  

 

She started on high doses of antipsychotics several years ago.  It partially controlled her insomnia.  She had parkinsonism clearly induced by Haldol.  When she was taking Resperal along with Seroquel, and then cold-turkeyed (on her own initiative) the Seroquel, she had acute Parkinsonism with onset within a week.  I figured out it was the Resperdal side effect being masked by the Seroquel and got her off both (the emergency room visit was quite a story but I'll save that for another time).  I had been minimizing her doses over these years by basically witholding medication until she woke me up complaining she couldn't sleep at which point I would give her one additional pill, until she woke me up again, etc.  This, of course, did wonders for my health but it was the only way I could keep her from taking all the pills at once to get to sleep.  Doing this I managed to get her dose reduced by a factor of 3 over time in conjunction with other measures.  Finally, several months ago, she started sleeping too much and I was able to get her totally off the antipsychotics.

 

The visit to the HD center for excellence had them saying this onset of hypersomnolence was not uncommon in HD as degeneration progresses.  That's why I thought the reappearance of her insomnia was possibly a good sign after she started taking Dihexa.  For a few weeks she took about 1/6 of her prior Seroquel dose to get to sleep but we've been able to get her off it now entirely and she no longer suffers either hypersomnolence or insomnia.

 

As I said earlier, the apparent Tardive Dyskinesia onset was several months to a year before she started on Dihexa and I haven't noticed substantial improvement there although I can't rule it out.

Edited by jabowery, 13 October 2014 - 07:21 PM.

[Healthy Tony]

Dihexa Trial 1 Results:

 

Last night I administered 500mg orally in capsule form 2 hours prior to sleep. 1.5hrs after dosing I experienced a notable wave of drowsiness pass over me, and I fell asleep within the next half hour. After a surprisingly rejuvenating sleep I woke up feeling fantastic. Today I am in a fantastic mood, feeling motivated, and anxiety-free. The only other noot that I've taken today is 2 drops of Selank, which seemed to have synergy in terms of mood brightening and anxiolitic effects. Overall this was a positive experience, but I was hoping for a little more, I will try dosing next time with Dihexa dissolved in DMSO solution.

[Healthy Tony]

Dihexa Trial 1 Results:

 

Last night I administered 500mg orally in capsule form 2 hours prior to sleep. 1.5hrs after dosing I experienced a notable wave of drowsiness pass over me, and I fell asleep within the next half hour. After a surprisingly rejuvenating sleep I woke up feeling fantastic. Today I am in a fantastic mood, feeling motivated, and anxiety-free. The only other noot that I've taken today is 2 drops of Selank, which seemed to have synergy in terms of mood brightening and anxiolitic effects. Overall this was a positive experience, but I was hoping for a little more, I will try dosing next time with Dihexa dissolved in DMSO solution.

 

Update: The mood brightening effects of the Dihexa + Selank ran out of steam after around 2-4PM. Overall experience was quite a letdown.

 

 

Dihexa Trial 2 Results (botched):

 

The plan was to take 250mg sublingually in a DMSO solution. Unfortunately due mostly to my own ignorance, this experiment was a bust. I failed to adequately dilute the DMSO, and the resulting solution caused an unbearable burning sensation inside my mouth. I promptly swallowed the entire mixture after less than two seconds, and washed it down with orange juice to get rid of the horrid flavor. No effects were felt from this trial. Tonight I intend to try again with a more appropriate solution.

[Healthy Tony]

Trial 3: Instead of going the sublingual route I ended up insulflating 40mg last night. Once again no discernible effects, so I will try upping the dosage tonight.

[sk_scientific]

I think that it will be interesting to see the results amongst those of us who have secured Dihexa, from the user DHXA, what the difference in effect will be following ingestion of the N-synth.  Xks_201 is sending me a sample this week, so I'll be certain to share my position on the matter in short order.

[Healthy Tony]

Trail 4: Moments ago I insufflated 100mg in two doses spaced ~5 minutes apart. So far no discernible effects; however, I will keep you guys informed!

 

Is there any reason to believe sublingual administration via DMSO solution would be more effective?

Edited by TheRockst4r, 20 October 2014 - 04:45 AM.

[xks201]

Nothing wrong with the old fashioned oral route if insufflation does nothing

[jabowery]

Spoiler

Dihexa Trial 1 Results:
 
Last night I administered 500mg orally in capsule form 2 hours prior to sleep. 1.5hrs after dosing I experienced a notable wave of drowsiness pass over me, and I fell asleep within the next half hour. After a surprisingly rejuvenating sleep I woke up feeling fantastic. Today I am in a fantastic mood, feeling motivated, and anxiety-free. The only other noot that I've taken today is 2 drops of Selank, which seemed to have synergy in terms of mood brightening and anxiolitic effects. Overall this was a positive experience, but I was hoping for a little more, I will try dosing next time with Dihexa dissolved in DMSO solution.

 
Update: The mood brightening effects of the Dihexa + Selank ran out of steam after around 2-4PM. Overall experience was quite a letdown.
 
 
Dihexa Trial 2 Results (botched):

The plan was to take 250mg sublingually in a DMSO solution. Unfortunately due mostly to my own ignorance, this experiment was a bust. I failed to adequately dilute the DMSO, and the resulting solution caused an unbearable burning sensation inside my mouth. I promptly swallowed the entire mixture after less than two seconds, and washed it down with orange juice to get rid of the horrid flavor. No effects were felt from this trial. Tonight I intend to try again with a more appropriate solution.

 

 

I assume by "dilute the DMSO" you mean dilute it in water.

 

I was interested as to whether subcutaneous injection of DMSO+Dihexa would be superior to skin (or mucosa) application.  In at least the following case, subcutaneous seemed to actually be inferior to skin application:

 

The absorption of phenylbutazone dissolved in an aqueous solution of DMSO was impaired when administered orally to the rabbit. Absorption of the same drug was not improved using the subcutaneous route simultaneously with DMSO. However, phenylbutazone could be detected in rabbit's blood for several hours when an ointment containing DMSO and 5% phenylbutazone was applied to the skin. When the DMSO content of the ointment was increased, the phenylbutazone levels increased.

 

 

[Nemo888]

Hopefully very dilute DMSO, the universal solvent.

Unexpected low-dose toxicity of the universal solvent DMSO. Abstract

 

Dimethyl sulfoxide (DMSO) is an important aprotic solvent that can solubilize a wide variety of otherwise poorly soluble polar and nonpolar molecules. This, coupled with its apparent low toxicity at concentrations <10%, has led to its ubiquitous use and widespread application. Here, we demonstrate that DMSO induces retinal apoptosis in vivo at low concentrations (5 μl intravitreally dosed DMSO in rat from a stock concentration of 1, 2, 4, and 8% v/v). Toxicity was confirmed in vitro in a retinal neuronal cell line, at DMSO concentrations >1% (v/v), using annexin V, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), and AlamarBlue cell viability assays. DMSO concentrations >10% (v/v) have recently been reported to cause cellular toxicity through plasma membrane pore formation. Here, we show the mechanism by which low concentrations (2-4% DMSO) induce caspase-3 independent neuronal death that involves apoptosis-inducing factor (AIF) translocation from mitochondria to the nucleus and poly-(ADP-ribose)-polymerase (PARP) activation. These results highlight safety concerns of using low concentrations of DMSO as a solvent for in vivo administration and in biological assays. We recommend that methods other than DMSO are employed for solubilizing drugs but, where no alternative exists, researchers compute absolute DMSO final concentrations and include an untreated control group in addition to DMSO vehicle control to check for solvent toxicity.

 

[Nemo888]

I am curious if Dihexa has changed any of the Guinea Pigs alcohol consumption patterns.

 

,...has demonstrated that the level of a protein known as brain-derived neurotrophic factor, or BDNF, is increased in the brain when alcohol is consumed in moderation. In turn, experiments in Ron’s lab have shown, BDNF prevents the development of alcohol use disorders.

https://www.ucsf.edu...roblem-drinking