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Vorinostat Group Buy - Fear Extinction and Learning and Memory enhancement

hdac inhibitor hdaci hdac fear extinction learning memory long-term memory vorinostat saha

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#1 musicman4534

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Posted 15 November 2016 - 01:58 AM


Hey folks,
 
To go along with the HDAC inhibition discussion thread, I'll be organizing a vorinostat group buy. It's main use is fear extinction and long-term memory enhancement. HDAC inhibition has shown to be able to give people "child-like" learning abilities, which can be useful for many things from remaking social habits to learning a language or instrument (and of course studying). Please see the other HDAC inhibitor thread and my article on reddit for more information on HDAC inhibition. I will copy this entire article to these Longecity threads shortly, as well as begin to update the HDAC discussion thread with more information on how HDAC inhibition works and how we can use it.
 
Vorinostat's approved by the FDA and prescribed by doctors for cancer treatment, so this group buy should be very straight forward. The prices vary a bit online, but should be $100 per gram maximum, probably will be around $50 a gram. Once I get an idea of how much we need total I'll get an exact price point and let you all know. It won't need to be a custom synth, so this should go quickly and I'm aiming to have it completed by mid December so we can all get some Vorinostat for the new year :)
 
There was already a couple small group buys for vorinostat in the CL-994 thread along with some information and anecdotes, so I encourage people to take a look at that thread too.

I'm hoping to send out emails to suppliers for exact price points in a week.

 

Cheers!

Evan


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#2 Water Buffalo

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Posted 15 November 2016 - 08:24 AM

I'm definitely in for a gram or two.

Edited by Water Buffalo, 15 November 2016 - 08:31 AM.


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#3 taohansen

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Posted 15 November 2016 - 12:58 PM

I'm in for a gram.



#4 Fozzyred

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Posted 15 November 2016 - 01:40 PM

I'm in for 2 grams if it's closer to $50. In for 1 gram if closer to $100.



#5 Whalefallen

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Posted 15 November 2016 - 11:07 PM

In for a gram!

#6 airplanepeanuts

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Posted 16 November 2016 - 12:23 AM

I am in for a gram, if you are shipping to Germany.



#7 musicman4534

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Posted 16 November 2016 - 02:24 AM

No prob, I was just in Germany! In my experience Germany can have tough borders in some cities though, so you may have to pay $40 extra dollars or something to get your package ;)



#8 Isak2044

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Posted 16 November 2016 - 09:14 AM

I'm also in for 1g, would u ship to Norway though?

#9 Stephen Clark

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Posted 16 November 2016 - 10:27 AM

In for 1g

#10 gedanken

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Posted 16 November 2016 - 03:49 PM

In for 1g please.


Edited by gedanken, 16 November 2016 - 03:49 PM.


#11 musicman4534

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Posted 16 November 2016 - 04:18 PM

I'm also in for 1g, would u ship to Norway though?

 

No prob

SaveSave


Edited by musicman4534, 16 November 2016 - 04:18 PM.


#12 Brazzo

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Posted 16 November 2016 - 08:42 PM

In for 1 gram



#13 swolo

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Posted 16 November 2016 - 09:23 PM

In for 1 gram. Thanks for doing this, really hope this makes an impact on my life.

#14 airplanepeanuts

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Posted 16 November 2016 - 10:47 PM

No prob, I was just in Germany! In my experience Germany can have tough borders in some cities though, so you may have to pay $40 extra dollars or something to get your package ;)

If you'll be back, maybe bring it by my house :)

 

What can you do against tough borders with 40 dollars by the way?



#15 musicman4534

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Posted 17 November 2016 - 01:27 AM

Here's a quote from @tree summing up his vorinostat usage:

 

 

 

@ tree -- Also, out of curiosity, what do you mean by this comment: "As a conclusion I wanted to add that there was a second groupbuy and the Vorinostat worked as well as before. Because of that I won't be organizing a third groupbuy". Why is there not going to be a group buy because Vorinostat worked well?

Because I don't need to buy more. There isn't anything left that induces major anxiety, the vorinostat worked perfectly. I might try some leftover vorinostat on the minor inducers as well. What remains is brain fog, which unfortunately wasn't affected by vorinostat. The only things that seem to work against my brainfog is meditation and focus exercises. Perhaps the extra vitamin B did something, but it would be a minor factor compared to the other 2.


I'm not sure if it CAN entrench fear. I've tried Vorinostat several times, with increasingly less care for routine, and every time it just deleted the anxiety I felt with the traumatic/anxiety-inducing situation I re-experienced. Even when I felt anxiety coming up it was still erased and straight afterwards I couldn't feel ANY fear even when I actively tried to feel it. If Vorinostat could strengthen or create a trauma it would have done so at that point, but it didn't. I think it's only capable of erasing, not creating, traumatic anxiety and disconnect it from internal/environmental triggers.

 

This goes along with what I've experienced and read. Fear is built up in us, and builds up in some more than others. It is an evolutionary trait, but since we have no lions to be afraid of anymore, it manifests often times as just social anxiety or other various unneeded, detrimental fears and anxieties.

 

The original vorinostat group buys focused on fear extinction, but I'd like to test its memory-enhancing properties as well, since HDAC inhibitors enhance learning and memory to quite a degree.



#16 musicman4534

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Posted 17 November 2016 - 03:36 AM

I've been asked by several people about how to prepare for a vorinostat session and what kind of preparation is needed.

 

Taking Vorinostat is not like taking LSD... your fears aren't brought up to the surface to be hashed out. They are dealt with underneath your consciousness at the layer of DNA transcription. An HDAC inhibitor effectively puts priority on the present. For example, because of how fear is processed in our brains, social anxiety can build up over years and can compound itself based on tons of factors. This translates to you feeling anxious while just grocery shopping, even though there is obviously no apparent danger to you... because of upbringing, certain key events in the past, or drug abuse, there is this unwarranted social anxiety. What that's going to change to when you take vorinostat is like you're given a "clean slate." Unless you are actually going through a very traumatic experience in the present moment, you really shouldn't be feeling any fear, right? Vorinostat makes this apparent, and overwrites past fear memories with the current "clean slate." It doesn't get rid of any memories... in fact, it can help you remember lots memories. What it does is overwrite the inflated fear memories associated with certain events/situations with a clean slate. In order to overwrite the fear linked to these events/situations, all that needs to be done is the fear-inducing memory needs to be brought up. This can be done either through meditation or through an actual experience. I believe an actual experience might be more thorough, but studies and anecdotes show near-equal success with either.

 

It makes sense then that you don't need to prepare carefully like you would an LSD trip or something, but rather you'd like to prepare a session that's going to let you be exposed to normally fear-inducing situations. If crowded areas normally make you weirdly afraid for no reason, go to the supermarket. If you have a fear of studying complex academic literature as @tree did, peruse scientific literature while on vorinostat. I had various social anxieties from my years smoking pot. The first time I took vorinostat I meditated and this actually got rid of a lot of my fears without having to even leave my bedroom, but, the second two times, I took it before class, and then before casually hanging out with some friends and walking around town. The combination of these three situations on ~150mg of vorinostat each was amazing, and I'm looking forward to trying more sessions, though a lot of my anxieties and fears were dealt with during those three sessions. I read elsewhere that it got rid of someone's shyness. He said he had always been shy but he found himself going up to people and just having conversations, something very unlike him. This was when he was only taking an HDAC inhibitor for its memory benefits, but noted this other effect as well not even knowing it had fear extinguishing properties. Added bonus :)

 

This brings me to other theories of how vorinostat can be used! But, I will save that for another post, maybe tomorrow, because I'll keep to talking about sessions for now.

 

It is important to realize that HDAC inhibitors are not like most supplements or nootropics. They are quite powerful drugs that should be used wisely. While the basic framework of a session is very loose and varies depending on what you'd like to do... memory enhancement, fear extinction, addictive behavior cessation, learning an instrument, social behavior re-forming... what is important is that we use this compound safely. An HDAC inhibitor holds open histones to allow transcription to take place longer/stronger than usual. If dosages from 15-150mg are used acutely, the histones won't be held fully open for much longer than usual, just enough for the desired mental effect. However, if high dosages of vorinostat are taken daily, this can hold open histones fully for a very extended amount of time, increasing transcription dramatically and arresting the cell cycle, which can cause undesired side-effects. When I took vorinostat at 150mg, I barely even noticed I was on it at first... it is quite subtle as it doesn't act through any neurotransmitter/receptor directly.

 

So, stick to low dosages of 15-150mg, and do not do two sessions two days in a row. Leave room for a full return to baseline. The half life is only a couple hours, with a duration of effect of about 4 hours. It takes about 30 minutes to start fully working. 

 

Also, HDAC inhibitors are implicated in addiction formation and cessation. If you take cocaine while on an HDAC inhibitor, you will become addicted faster than usual, but if you take it after using cocaine, it will have the opposite effect and help you heal, return to baseline, and stop addictive behaviors. So, it is important to separate the use of other drugs and vorinostat. It would be wise to take vorinostat alone. Of course things like Alpha-GPC and fish oil are okay... one of the past users of vorinostat took 2mg propranolol along with it, which probably helped the effect even... so there is leeway. Just think things through a bit before your session, and plan things out.

 

Having said all that, in my experience vorinostat was very user-friendly and beneficial while going out and about, especially in class. I am looking forward to exploring its learning-enhancing properties this time around. I'm thinking about taking 25mg before certain classes during which I know I'll need the learning boost.

 

I'll be continuing to post studies in the HDAC thread as I find/re-find them.


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#17 Santa Bear

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Posted 17 November 2016 - 05:07 AM

I'm in for a gram or two, however the best place to reach me is on reddit. We've already met i'm wayycold, if you could please communicate with me on reddit if it isn't too much of an inconvenience.

Thank you 



#18 fntms

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Posted 17 November 2016 - 05:07 AM

1g for me please.

#19 StevesPetRat

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Posted 17 November 2016 - 05:56 AM

$100 worth, whatever mass that ends up being.

It works well for performance anxiety (ok, N=1)

Edit: Poker! I used it for poker!

Edited by StevesPetRat, 17 November 2016 - 05:57 AM.


#20 Meggo

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Posted 17 November 2016 - 06:39 AM

i'm in for 2g


Edited by Meggo, 17 November 2016 - 06:39 AM.


#21 p3x888

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Posted 17 November 2016 - 07:51 AM

In for $100.

 

I checked out the side effects of this and they aren't nice. Did anyone of those that took it before experience any of the side effects?



#22 StevesPetRat

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Posted 17 November 2016 - 11:10 AM

Did anyone of those that took it before experience any of the side effects?

 

No, though I think most of those are a risk from chronic administration (which typically runs 300 - 400 mg per oral daily, not a handful of 100 mg IN doses).



#23 KieranA001

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Posted 17 November 2016 - 04:28 PM

In for a gram, PM me details.

 

Kind Regards,

 



#24 musicman4534

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Posted 17 November 2016 - 06:11 PM

Hey folks, Sunday I'll add up everyone's orders and put in a request for a price point Monday morning. Another user and I have been messaging back and forth about sourcing and we both separately settled on one supplier as being a good candidate (which I thought was cool lol). I will look into a few at first anyway.

 

I'll be posting some studies here on vorinostat/SAHA specifically for us to take a look at.

 

The side-effects related to Zolinza (vorinostat for cancer) are from daily dosages of >300mg. These aren't seen with lower dosages of vorinostat, one, because not 100% of HDAC is inhibited at the dosages we'll be taking it at, and two, it is not active long enough to significantly alter gene expression patterns system-wide. The dosages seen in studies on HDAC inhibition related to cognition are just high enough to produce changes in the brain, which is more sensitive to changes in HDAC, dopamine, etcetera than the body. The dosages translate to about 15-150mg. I actually just wrote a little about this in the HDAC discussion thread:

 

 

 

 

from oldmustysad sent 13 hours ago
You mention in your article about HDAC inhibitors meant directly for memory, do you have any more information on those or links to more resources on classes of HDAC's and their associated proteins?

 

Question I got asked on Reddit and decided to write about it a bit and copy it here.

 

This is an interesting question when it comes to HDAC inhibition, or any type of drug for that matter, because there's selectivity for effect, selectivity for a specific HDAC protein, and selectivity for a body part like the brain. What they found with crebinostat, an HDAC inhibitor meant specifically for cognitive improvement, isn't necessarily a selectivity for a specific body part or effect, but a selectively to inhibit only the HDAC proteins implicated with memory. It inhibits mainly HDAC1, 2, 3, and 6, similarly to vorinostat, but with even more selectivity. It doesn't inhibit HDAC4, 5, 7, and 9 as much. If you want to learn more about what the different HDAC proteins do, I'd start by taking a look at these articles I posted,

 

https://www.dropbox....inI_zh5eUa?dl=0

 

which includes crebinostat's pioneering study. If you'd like to take a closer look at specific HDAC inhibitor effects or HDAC proteins, take a look at the studies in the HDAC discussion thread on Longecity, or go to PubMed, put in a search term like the one I've put in, HDAC6 memory, and sort by relevance. This is a quick and easy way to get into the literature.

 

Other than crebinostat and neurostat, the latter of which the structure is not even known publicly yet, there hasn't been much research done to find HDAC inhibitors that act solely on memory. This is because of the overlap in selectivity regarding specific effects, body parts, and HDAC proteins.

 

Enhancing selectivity for a specific HDAC protein, like HDAC3, isn't enough to narrow it down to only acting in the brain. The HDAC proteins that act on memory, addiction, fear, etcetera also act elsewhere in the body no matter what. These are mainly HDAC1, 2, 3, and 6. Even crebinostat would act elsewhere in the body at higher dosages. There has been a lot of talk and fear about the lack of selectivity for the brain, but before I wrote my HDAC article this was one of the things I looked into.

 

The way I see it is that by taking low dosages we are already increasing selectivity for the brain. We do the same thing with every other drug/nootropic we take for the brain... we take less cocaine, less Huperzine A, less phenibut, less coffee, less Alpha-GPC than we need to to have an appreciable effect anywhere else other than the brain. if we took too much, we'd have severely overblown effects in the brain, and side-effects would begin to appear in the body. Some of the researchers studying HDAC inhibition's cognitive effects mentioned the brain as being "primed for HDAC inhibitor use." This is because the mind is sensitive to the effect. The way HDAC inhibitors are used for cancer is they are prescribed in incredibly high dosages daily, which inhibit nearly 100% of HDAC, hold open the DNA on histones system-wide for a disordinate amount of time, as well as alter HAT/HDAC and other proteins' expression system-wide. A low-dosage, acute dose of an HDAC inhibitor does not inhibit 100% of HDAC, does not hold open histones, and will barely be noticed by our cells, including our brain's, but our *mind* will notice the change in cognition. This is because there only needs to be a small increase in the amount of transcription taking place for the desired effect to occur in our minds. In this way, we're increasing selectivity for our minds by taking lower dosages.

 

In regards to HDAC protein selectivity, the different HDAC proteins overlap in effect. You'll read one study saying HDAC3 in implicated in addiction, then another saying that HDAC2 and 11 are implicated in addiction, and in actuality both are true... HDAC1, 2, 3, possibly 6, 11, and possibly others are all implicated in addiction, as well as DNMT1, which controls methylation. HDAC1, 2, 3, 6, and 11 all have studies linking them to long-term memory, and several are implicated in fear extinction as well... I think that what is important right now is finding an HDAC inhibitor that sticks to inhibiting class I, IIb and IV HDACs, is safe, well-studied, and doesn't have any other effects other than HDAC inhibition. A couple other Longecity users found vorinostat a couple years ago that fits this bill, and after looking into it I fully agree with them.

 

In regards to selectivity of effect, it would be near-impossible, unless we began using weird, specific brain implants that secreted HDAC inhibitors, to separate HDAC inhibition's effects on memory, learning addiction, and fear, because these are all linked to similar mechanisms. HDAC1, 2, 3 and 6 are all implicated. HDAC 6 does stand apart, however, with effects on beta-amyloid plaque and tau fibrils. Crebinostat hasn't been studied nearly as much as vorinostat, and one problem they may find is that it is lacking in certain effects dealing with addiction and fear, as the relationships between HDAC8, 9, 10 and 11 haven't been fully researched. HDAC11 is at least partially implicated in addictive behaviors, so using a more pan-inhibitor like vorinostat may be more beneficial, or a compound somewhat in between crebinostat and vorinostat that also inhibits HDAC8 and 11 to a degree, for example. In a way, the way HDAC proteins are used in the brain already increases selectivity for certain mental processes, mainly the ones I've already described... learning, memory, fear and addiction.

 

 

 

It is a very safe molecule at dosages we'll be taking it at, but it is important to know how it works and that it is a powerful compound and shouldn't be treated like fish oil. The magic of HDAC inhibitors is that it holds open transcription after HAT activates it, but this is also a very powerful effect when you look into it! We only need to lengthen and strengthen the window of transcription slightly to produce a powerful effect on cognition, not hold open transcription for days to the point where our cells can't replicate lol



#25 datrat

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Posted 18 November 2016 - 01:08 AM

Please put me in for 2 grams.

#26 izan82

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Posted 18 November 2016 - 11:43 AM

put me in for 1 gram please if it's close to 100 us dollars. and 2 grams if the price is close to 50 us dollars. thank you sir.



#27 monowav

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Posted 18 November 2016 - 12:28 PM

1g pls or whatever ~$100 would get


Edited by Jacob Gordon, 18 November 2016 - 12:29 PM.


#28 ceridwen

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Posted 18 November 2016 - 12:35 PM

1g please

#29 Water Buffalo

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Posted 18 November 2016 - 04:10 PM

put me in for 1 gram please if it's close to 100 us dollars. and 2 grams if the price is close to 50 us dollars. thank you sir.


Just to clarify my earlier post, I want to go with this option too.

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#30 musicman4534

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Posted 18 November 2016 - 11:41 PM

Hi folks,

 

I wanted to copy @neuralis's story he just posted in the CL-994 thread here to share. The anecdotes they shared about vorinostat a year ago or so during the first couple group buys were very positive and were what really sparked me to start looking further into HDAC inhibitors.

 

 

 

Hi, Tolerant! I will gladly share my experience with Vorinostat in more depth and by doing so, I hope to answer your questions.
 
I have been struggling with some kind of anxiety disorder ever since I was 14. These days I see 2 types of distinct anxieties in my life. Though they are not entirely exclusive, there is some overlap. The first type of anxiety rises out from unfelt emotions and traumatic experiences that haven't been properly integrated. An PTSD complex. The only way to recover is to feel these emotions and to give these experiences an meaning that fits into our coherent self-narrative in the present. This I believe fits the bill for the anxiety of most people.
 
The second type of anxiety is something more personal to me. It is the anxiety of living with schizoid personality disorder. It adds a whole another layer of anxiety perceived in interpersonal space and some very devious mechanisms for avoiding facing this anxiety. Dismantling this personality disorder is excruciatingly hard work. Though most people never have to know the anxiety that this disorder brings with it, I believe a lot that I have had to face in recovery so far is not unique at all. For instance I believe that the idea of reclaiming full self assertiveness can be as frightening to someone who is just slightly traumatised as it is to a schizoid. Only difference is that a schizoid first needs to cross a huge relational gap. This is where Vorinostat has helped me immensely by removing a lot of that superficial anxiety I talked about. So that I can be present to the fact of being scared to death on the prospect of doing something and still going through with it. These are the kind of experiences that make us grow, schizoid or not.
 
You were quite right in your assumption about how I used to feel my anxiety. It was just anxiety. The anxiety, singular, varying in strength, always there. I had an idea that it was composed of smaller anxieties for quite some time, but it wasn't until I had shaved off considerable amount of this anxiety using Vorinostat I could really see how it stemmed from all these past hurts. It's like the resolution got turned up. Over time I've learned to identify specific anxieties, to realise their original sources, to see what internal/external factor may trigger them in the present and most importantly how to heal them with the help of Vorinostat.
 
I have been involved in some kind of cognitive work ever since february. Amongst other things I worked with Dr. Nathaniel Branden-s sentence completion exercises for self-esteem. It's very simple yet incredibly powerful tool for deep psychological exploration. I believe that Vorinostat on it's own, dosed passively, can bring on a profound change. But coupled with deep level cognitive work it can do so much more. What seems to be the most beneficial is cognitively contrasting experiences. I will give you an example of what I mean by that:
 
Couple of months ago I bought myself a new pair of headphones. The kind you wear over your ears. And when I went into the public with them I got extremely uncomfortable wearing them. A silly thing to have an anxiety about, but there it was. I decided to dug into the anxiety to see why wearing these headphones had triggered me so badly. Soon I knew what was the event from my past that was bubbling up the surface like this. Knowing where it was coming from didn't do anything for lessening the anxiety though. So the next day I dosed 20mg of vorinostat sublingually and went out for a stroll with my earphones. By that time I had so accustomed to the effects of Vorinostat that I wasn't even surprised that this time I experienced none of that previous anxiety. It just wasn't there, I was free to enjoy the music as I pleased. Here I was in a identical situation that to the one that had one day earlier caused me great deal of distress, yet there was not a trace of that anxiety. To cognitively make that connection, to be present to the contrast between these two experiences and to see the fact that this anxiety had no basis in reality can be deeply healing. Not that vorinostat itself is healing you, just when the anxiety has been removed, the bodies innate capacity for healing is able to kick in.
 
I would like to share another experience with you which had profound repercussions for me. It happened after I smoked weed for the first time after taking a break for 6 months. It put me into a state of pure anxiety. It's not possible for me to put it into words how awful I felt. Just terrible anxiety. I had to take a trip outside in order to take care of something. Just seeing another person at a distance was enough to make me panic. When I had to pass someone, it got so bad, I just dissociated. My body became like a robot I was controlling using a remote control. Really nasty place to be. I was aware how this was all something from the past rushing to the surface and the next day I started thinking whether this kind of anxiety wouldn't be something vorinostat could take care of. Everything I had read about it and my own experiences pointed to to yes. Yet it didn't seem possible, this anxiety was too powerful. I was really afraid to test it out, I wasn't sure I could cope with the disappointment. One week later I decided to give it a go. I dosed 50mg sublingually and snorted another 50 mg. Half an hour later I smoked some weed. I just couldn't believe when there was no anxiety. Just me, being a little stoned, without a trace of anxiety. I had no idea that it was even possible to feel this kind of freedom within myself. This time I had to also take the same kind of trip outside I had done the week before. I saw people and I couldn't care less that they were there. They we're just going on about their own business, there was no reason why that should in any way effect me. I was awestruck by that difference to the point I couldn't help but shed a few tears, right there on the street, for all the times I used to feel so bad. I didn't think this kind of change was ever possible.
 
This experience changed something at a deep level in me. I could notice it in my internal dialogue as well as my interactions with others. Yet I wasn't quite able to put my finger on it. Only  few weeks later when I happened to do something humiliating I realised what had happened. My normal reaction at this situation would've been to relentlessly shame myself, but I was surprised to see I had automatically jumped on being compassionate to myself instead. Then it dawned on me. I used to be extremely ashamed of being me, of having all these problems. And all that shame was gone. A part of me had been healed.
 
After this I've had other similar profoundly healing experiences. In a very short time I've gone from experiencing myself as something coarse and harsh to something as soft as cotton wool. It is possible I would've gotten here on my own, but with the help of Vorinostat I've healed at a rate beyond any of my dreams.
 
I've used about 1.5-2 grams over the course of 5-6 months with doses ranging from 10-100mg. I have to concur with others on the point that it's best not taken on consecutive days. Not even every other day. It just doesn't work when taken too often. The only side effect I experienced was slight lightheadedness and wooziness with doses over 50mg or when I dosed too often. I'm not really literate of the science behind this drug, but I like to think that recovery is just something that cannot be rushed. The body and mind need time to adjust for these kinds of changes to take place. This seems like pushing the limits as it is.
 
If I were to never have another dose again it would be okay. I am now at a point where I am healing without it's assistance. My last dose was a month ago.
 
If anyone wants something clarified or has any further questions I would be happy to help! 

 

 

 


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Also tagged with one or more of these keywords: hdac inhibitor, hdaci, hdac, fear extinction, learning, memory, long-term memory, vorinostat, saha

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