253 replies to this topic

[YOLF]

I've seen 98%. That aught to do it. You just have to ask for corn or grain alcohol. At least in the US.

[Dazzcat]

Turns out I wasn't looking hard enough, came across a nz essential oil website selling 98% ethanol, which also contains <2% methanol, I gather they add the methanol so it's undrinkable? They have food grade, but the price jumps up to $150us per litre (I assume alcohol tax applies), ouch!

Edited by Dazzcat, 02 April 2014 - 08:58 PM.

[YOLF]

Damn I can get a 500ml to a liter for under $20 around the corner! Denaturing alcohol is so stupid, hazardous, and dangerous. It shouldn't exist and goes back to prohibition here in the states and never got cleaned up. It's actually dangerous and it's a skin irritant...

Check the liquor store before buying the web. You might need to check more than one, but you'll probably find it.

[VERITAS INCORRUPTUS]

Pure EtOH is a staple (and I don't mean for imbibing as an intoxicant, LOL)

Edited by VERITAS INCORRUPTUS, 02 April 2014 - 10:23 PM.

[mait]

Turns out I wasn't looking hard enough, came across a nz essential oil website selling 98% ethanol, which also contains <2% methanol, I gather they add the methanol so it's undrinkable? They have food grade, but the price jumps up to $150us per litre (I assume alcohol tax applies), ouch!

Methanol is no go. Better pay extra and go for food grade.

[megatron]

Can't we just go with DMSO? It is much cheaper. From googling, it doesn't seem to be dangerous in these small amounts. Just try to avoid getting it on your skin. I know it tastes awful, but it is most certainly manageable in such small quanta as we will be using.

Edited by Megatrone, 03 April 2014 - 01:20 PM.

[telight]

Turns out I wasn't looking hard enough, came across a nz essential oil website selling 98% ethanol, which also contains <2% methanol, I gather they add the methanol so it's undrinkable? They have food grade, but the price jumps up to $150us per litre (I assume alcohol tax applies), ouch!

Methanol is no go. Better pay extra and go for food grade.

Did you know that ethanol can be used as an "antidote" for methanol poisoning, methanol itself is not extremely toxic, its metabolites are though. Ethanol competes with metabolism of methanol in the liver while the kidneys work to excrete the not-yet-metabolized methanol from the blood. I doubt that much methanol would be toxic, especially considering how much ethanol you would take concurrently with it.

[RAFT LIFE]

Hey guys what are your thoughts on a potential synergy between EVP and ABT-239? Not that I have access to or am considering mixing the two, I am just curious for your input?

http://citeseerx.ist...p=rep1&type=pdf

[formergenius]

Can't it simply be dissolved in half a shot of vodka?

[YOLF]

Can't it simply be dissolved in half a shot of vodka?

I imagine it's possible. It's not $150 for a 500ml bottle of grain/corn alcohol at 98%. It's $16.95 at the liquor store! You just have to find the right one and each person is receiving powder, so it's up to them as to what they use.

When other things are dissolved in alcohol it's only 10% alcohol, it really shouldn't be a problem, it's just the complexity of the otherstuff that's in the alcohol that's worrysome and could potentially destroy the EVP-6124. So stay away from stuff with added sugars or flavors which has stuff in it other than EtOH and H20.

Edited by cryonicsculture, 03 April 2014 - 05:11 PM.

[Dazzcat]

Hey guys what are your thoughts on a potential synergy between EVP and ABT-239? Not that I have access to or am considering mixing the two, I am just curious for your input?

http://citeseerx.ist...p=rep1&type=pdf

Sounds like it's worth a shot, especially if tolerance becomes an issues with evp. Though what are the side effects of H3 antagonism? The combination could potentially lead to an array of side effects, evp on it's own appears to be well tolerated.

Edited by Dazzcat, 03 April 2014 - 08:19 PM.

[VERITAS INCORRUPTUS]

^^
ABT-239 was ultimately dropped from human trials after showing the dangerous cardiac side effect of QT prolongation...

[Dazzcat]

^^
ABT-239 was ultimately dropped from human trials after showing the dangerous cardiac side effect of QT prolongation...

Flag that then, I would think choline supplementation may be a safer bet for potentiation of evp, though not sure if this would work?

[VERITAS INCORRUPTUS]

^^^
100mcg of Huperzine A and you're set (AChe inhibitor)
Some choline though would be a good bet as well, probably alpha-GPC as best source...

[formergenius]

Correct me if I'm wrong, but wouldn't choline or an AChEI simply lead to more ACh available to displace the EVP-6124 from the binding site?

[VERITAS INCORRUPTUS]

Correct me if I'm wrong, but wouldn't choline or an AChEI simply lead to more ACh available to displace the EVP-6124 from the binding site?

EVP-6124 has been coined a co-agonist, though I coined it an allo-agonist.
It both function to cause direct agonist activity at the alpha7 binding site as well as to cause a PAM/sensitization of the receptor site to foster increased potency of the endogenous ligand, choline.

You stand corrected

[formergenius]

I must've missed the discussion on the classification, but you can understand why I asked the question considering it is proposed to be a partial agonist.

[Dazzcat]

Correct me if I'm wrong, but wouldn't choline or an AChEI simply lead to more ACh available to displace the EVP-6124 from the binding site?

This may shed some light onto this question,

http://aimday.se/wp-...oad/EVP6124.pdf

EVP-6124 was approximately 300 fold more potent than the natural agonist ACh (Ki¼3mM), measured inbinding assays using [3H]-MLA

Also this,

Since treatment with a7 nAChR agonists may benefit, AD patients, and they are often treated with an AChEI, we investigated the potential beneficial interaction between AChEIs and EVP-6124. Co-infusion studies of ABT-107 with donepezil demonstrated that the combination of an a7 nAChR agonist and an AChEI was not deleterious to cognition (Bitner et al., 2010). Since the doses of both ABT-107 and donepezil were efficacious alone, a ceiling effect may have precluded the observation of an additive effect of the combination. Accordingly, we tested the combination of previously established sub-efficacious doses of EVP-6124 (0.03 mg/kg, p.o.) and donepezil (0.1 mg/kg, p.o.) and found that the combined treatment completely reversed the scopolamine-induced deficit in the ORT. The results of this combination study further suggested that the pro-cognitive effects of AChEIs, which are dose limited by adverse effects, primarily gastrointestinal (Birks and Flicker, 2006), could be enhanced if AChEIs are combined in low doses with an a7 nAChR agonist in AD patients.

That is a dose of evp- an order of magnitude lower than what is usually required to get the same reversal of scopalamine-induced object recognition impairment in rats without donepezil. This result ain't as impressive when considering it's an AD model and scopalamine impairs a huge part of the ACh receptor system, so the success of the combination could be over stated when it comes to healthy subjects.

Edited by Dazzcat, 04 April 2014 - 04:40 AM.

[formergenius]

Yes that does seem to clarify it, thank you! I'll be honest; I haven't read in to it with much scrutiny. Whatever it exactly is; I want to try it regardless!

[Dazzcat]

There is nothing too unusual about it from what I can see (I've only read the one paper), just a fine tuned nicotinic agonist with high binding affinity that also has antiemetic properties (due to 5ht3 antagonism) which is seen as beneficial to reduce nausea that sometimes accompanies ACh receptor stimulation .

I'm still not convinced that is has positive allosteric activity as suggest above due to the lack of evidence supporting evp- binding elsewhere on the receptor other than the primary active sites (orthosteric site). Instead they use the term co-agonist to simply mean that it works best when it only occupies one orthosteric site and ACh occupies the other (a7 NAChR have two active binding sites), hence why having a healthy amount of ACh around is beneficial to avoid larger doses of evp- that leads to receptor desensitization and in our case, a considerable dent in the wallet.

Edited by Dazzcat, 04 April 2014 - 08:59 PM.

[VERITAS INCORRUPTUS]

^^^^
I believe these two article will illuminate the nature of the alpha7 receptor binding sites and orthosteric/allosteric profiles more accurately and clearly:

http://www.pnas.org/...08/14/5867.long
http://www.jbc.org/content/289/7/4515

[Reformed-Redan]

When will NSN stock this?

[Jbac]

Has anyone tried it yet? What effects are you guys who don't have AD and schizophrenia expecting. A boost in memorization ability? (is your day to day memory bad enough for you to notice a moderate improvement?)

[formergenius]

Has anyone tried it yet? What effects are you guys who don't have AD and schizophrenia expecting. A boost in memorization ability? (is your day to day memory bad enough for you to notice a moderate improvement?)

I'm not expecting anything, because I smoke and have no clue how it will interact. That said, I am hoping for both sensory gating enhancement and memory enhancement, primarily non-declarative memory. Right now, I feel like I'm living in the movie "Groundhog Day" memory-wise, so I should be able to notice an improvement I'd think.

[Dazzcat]

Has anyone tried it yet? What effects are you guys who don't have AD and schizophrenia expecting. A boost in memorization ability? (is your day to day memory bad enough for you to notice a moderate improvement?)

I'm not expecting anything, because I smoke and have no clue how it will interact. That said, I am hoping for both sensory gating enhancement and memory enhancement, primarily non-declarative memory. Right now, I feel like I'm living in the movie "Groundhog Day" memory-wise, so I should be able to notice an improvement I'd think.

That makes two of us, I suspect it ain't going to be noticeable at all due to the possibility that we will have desensitized a7 receptors from chronic nicotine exposure. At least this is more of a reason for us to give up right? There is some hope that it may make nicotine withdrawls a bit easier to cope with.

Edited by Dazzcat, 06 April 2014 - 10:28 PM.

[formergenius]

That makes two of us, I suspect it ain't going to be noticeable at all due to the possibility that we will have desensitized a7 receptors from chronic nicotine exposure. At least this is more of a reason for us to give up right? There is some hope that it may make nicotine withdrawls a bit easier to cope with.

Yes; this was my line of thought as well. If it doesn't have any nootropic benefits, perhaps at the very least it will have some sort of anti-addictive quality to it.

[VERITAS INCORRUPTUS]

Has anyone tried it yet? What effects are you guys who don't have AD and schizophrenia expecting. A boost in memorization ability? (is your day to day memory bad enough for you to notice a moderate improvement?)

I'm not expecting anything, because I smoke and have no clue how it will interact. That said, I am hoping for both sensory gating enhancement and memory enhancement, primarily non-declarative memory. Right now, I feel like I'm living in the movie "Groundhog Day" memory-wise, so I should be able to notice an improvement I'd think.

That makes two of us, I suspect it ain't going to be noticeable at all due to the possibility that we will have desensitized a7 receptors from chronic nicotine exposure. At least this is more of a reason for us to give up right? There is some hope that it may make nicotine withdrawls a bit easier to cope with.

Perhaps not via its direct partial agonist activity, but its ability to act as a co-agonist at the orthosteric binding site (sensitizing the receptor or in some way acting akin to an PAM capacity) it will have some positive impact in those with desensitized alpha7R.

It certainly should lend some positive impact within an attempt at smoking cessation:
http://www.ncbi.nlm....cles/PMC3306875
http://www.ncbi.nlm....pubmed/21901321

Edited by VERITAS INCORRUPTUS, 06 April 2014 - 11:00 PM.

[RAFT LIFE]

Id like to share this with the guys trying to quit smoking. I smoked 1 pack a day from 13 to 34 tried to quit 30+ times and the cognitive impairment was always what pushed me back. One day about a year ago I drank 2 large glasses full of ayahuasca tea, I will not describe the experience here, however when the experience ended I immediately knew I was no longer a smoker. From that point on I did not smoke and experienced no withdrawal, craving, or cognitive impairment whatsoever. I do not know if the tea has effected others in this manner but based on the smoking cessation I experienced I would not be surprised if this was a extremely common result.

[Dazzcat]

Id like to share this with the guys trying to quit smoking. I smoked 1 pack a day from 13 to 34 tried to quit 30+ times and the cognitive impairment was always what pushed me back. One day about a year ago I drank 2 large glasses full of ayahuasca tea, I will not describe the experience here, however when the experience ended I immediately knew I was no longer a smoker. From that point on I did not smoke and experienced no withdrawal, craving, or cognitive impairment whatsoever. I do not know if the tea has effected others in this manner but based on the smoking cessation I experienced I would not be surprised if this was a extremely common result.

Thanks for that Raft Life, interesting experience. Though I must say the positive effects from 5-ht2a agonists have been lost a long time ago from using them a little too much in my younger years, most notably psilocybin which is relatively similar to orally available DMT(this was before I started to smoke, I was a late starter). I would bank on that those who are more naive to psychedelics under the right environment and guidance may find them useful in this instance. Unfortunately, due to their highly illegal status and unpredictable nature, they ain't an appropriate option for most.

Edited by Dazzcat, 07 April 2014 - 02:31 AM.

[megatron]

The European shipment is still being held by Hungarian customs. Apparently, they wanted to see the test analysis reports, so these have been sent to them. 

Edited by Megatrone, 09 April 2014 - 01:30 PM.