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Vorinostat

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

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#301 Mr Spock

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Posted 26 June 2018 - 08:00 AM

Hello everyone, I thought you would ask... I have prepared all envelopes over the weekend and sent one-third today. I will send another third tomorrow, and what is left on Wednesday. The envelopes and packaging is a little different (than the NSI-189 envelopes that you might got) it might possibly help with rare issues with customs. I also have cut the upper part of the Ziploc bags and you might want to put the Vorinostat, in a new bag.

Still not received it.

I am now concerned, as it shouldn't take this long for it to get to me here in the Uk



#302 Strangelove

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Posted 26 June 2018 - 08:40 PM

Still not received it.

I am now concerned, as it shouldn't take this long for it to get to me here in the Uk

 

Someone received it in the UK today, maybe you got one of the last envelopes. I would not worry just yet, from tracking in the past I have seen envelopes get out of the country the same day, and rarely stay three days before they leave for abroad.



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#303 Strangelove

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Posted 26 June 2018 - 08:45 PM

>I have sent all envelopes except a few (two in Germany, one in Russia) I will send on Monday

 

Man, I have been on the tip of my toes since you wrote that the last 1/3rd got out on wednesday... oh well

 

Yes sorry, I sent it today and I added half a gram for the delay. I am a little worried with the customs from these two countries, especially German customs are very careful. I will get in detail about dosage, and in what ways vorinostat has been useful for me.



#304 celticlion76

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Posted 28 June 2018 - 12:50 AM

Hi, I did not receive in the UK yet either was it sent as the last batch too?



#305 ISayLonger

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Posted 28 June 2018 - 09:36 AM

Haven't received in the UK either, FWIW. Hopefully UK customs isn't playing tricks

#306 Strangelove

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Posted 28 June 2018 - 04:18 PM

As of now only Muad' Dib received it in the UK, but give it a little more time, it will be an extremely bad lack if all envelopes have been withheld. Even if they hold one for testing they should not keep the others. From my experience, I really think is a delay and not a long one.

 

This is my experience with Vorinostat as of now.

 

As it has been discussed in the past, vorinostat is not an anxiolytic for everyday use, but something to help to go over situations that make us stuck, and hopefully rewire our brain and help us erase conditioned fear from past experiences. In my experience with 10-50 mg doses, the effects you can consciously perceive are very subtle but you can still see that you can go over difficult to face events more calmly and initiate new behaviors. They were a few times that I had a very strong anxiolytic effect when I was in fearful state thinking that some damaging event was ready to unfold. 
 
If I abstract a little from my experience, the fear-reducing effect is most observable in situations that could threaten our well being in evolutionary terms, for me is mostly connected with social events like a speech in a crowd and (surprisingly at first) dating. I guess everyone could try it on different occasions, but I will mention one case of events that has been the most helpful for me.
 
I am a fan of psychology in general, and some years back I started looking in some more practical aspects on dating psychology and theory from "pick up artists", in what females find attractive and why, in personality characteristics of males. Mostly out of curiosity I tried to start conversations with appealing females, in the back and forth commute to work and few other occasions, were (in a more friendly) fashion I spoke to tens of women over a two years period, but somehow I found it extremely difficult to show direct interest and ask for a phone number even when using large dose of phenibut or other anxiolytic something seemed not right.
 
It was a random occasion (after using vorinostat) that surprisingly I asked for a phone number, as well in another occasion send a text message in an ex that I have been thinking for years but I always got stuck. It was like "maybe I should text her" (got no weird feeling that something is not right and did it). It may not seem much, but in both cases I was stuck for years, and it was a random effect, I did not use Vorinostat with the intention to ask someone out (I never do this if I am not 100% sure for a positive reply) or (eventually) text my ex, I just got unstuck. This got me thinking that there is something to it, thinking in what ways I could get the most benefits.
 
My best experience so far (same with StevesPetRat) was to get over a serious relationship with not too much pain, I was surprised both of the strong anxiolytic effects I got with 50mg, continuing with a dose every other day for 300mg in total I was in a state that I will probably need more than a couple months to get not thinking about it, been in a low mood. I started realizing that there is some strong component of fear in separation, probably a primal evolutionary fear that a good chance has been lost to "spread your genes" apart from the emotional connection. From a past experience, Vorinostat did not just give immediate anxiolytic effects, but thinking it over in a much calmer state, curbed the negative emotions permanently.
 
Having tried it in different circumstances, the most benefits and my favorite activity these days to use vorinostat for is an idea I got from Tim Ferris. I will think what is the one action that if I get unstuck and go forward will have the most beneficial effects in my life. I will use a 100mg vorinostat dose these days, and then think in a very detailed manner everything unfolding in the worst case scenario. I will stay calm and in control and calmly think all the counteractions I can manage and if the end result is something I can live with. If this is done a few times using vorinostat could have major positive implications like start a venture like a business or change in career you have been thinking for years, deciding to end a failing long term relationship, or anything else that was holding you back due to fear of the unknown and comfort of a supporting routine. I got unstuck after the third time and took the first steps towards a part-time startup (I still need my day job) in a far more collected state. It was an old idea, that I now got to progress, having the fear that if this will not work out I might get stuck some more years in my current day job. I still do the 100mg calm down session once a week, the results are very cumulative.
 
You can use it for PTSD, specific phobias for anyone that has it (speaking in crowds for me) or anything else that would curb fear/anxiety without a loss in cognitive abilities that benzodiazepines can give. Although the anxiolysis you get from Vorinostat seems to be very effective in some cases. As I said before I was going to meet my girlfriend for the possible break up and Vorinostat calmed me like a xanax dose will do with no loss of cognition due to its hypnotic effects, but does not work as gaba anxiolytics and I do not know what kind of anxieties might curb.
 
The best use for me right now is to use it strategically with fearful/anxious thought patterns that if I can go over would have long-term implications. As I also described in a previous post public speaking in small groups is far easier now, asking out for dates had a snowball effect from that first event (it was a common reaction while on Vorinostat) even when I was not thinking much about it in my pc, sending facebook messages for a date out, and now is far easier also. At this time I will continue with going over specific future situations in my mind thinking the worst case scenario in as much detail I can, using 100mg doses and calmly thinking my options. It seems true in a good degree that doing what you are afraid the most (but you leave it aside) its often the first thing you should act on... I also recently started reading the book below to get a framework of how to think about risk and fear.
 
 
Something else I want to try after repairing my old oasis CES device is to test, if the 100Hz frequency that activates the right insula to suppress fear from the right amygdala, could possibly give better results while on vorinostat.

Edited by Strangelove, 28 June 2018 - 04:22 PM.

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#307 theobromananda

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Posted 28 June 2018 - 08:59 PM

Thanks for the detailed describtion, @Strangelove!

I mostly got interested in SAHA after reading the following study, which used rats. No "method" needed at all, SAHA just reverses childhood stress and downregulates SERT in the gut through acetylation of H4K12 to a normal state, alleviating IBS and other symptoms of anxiety disorders. It is probably a breakthrough technology when trying to change ones attachment type from anxious/avoidant to a safer one. A study that virgin mice treated with SAHA showed spontaneous mothering instincts towards newborn mice leads me to believe that the affected epigenetic markers in the lumbosacral spine are mostly related to attachment, and also related learned fear/anxiety. Multiple anecdotes of persons getting over a seperation seems to support this thesis.

 

 

 

Early-life stress-induced visceral hypersensitivity andanxiety behavior is reversed by histone deacetylaseinhibition

 

Stressful life events, especially in childhood, can havedetrimental effects on health and are associated witha  host  of  psychiatric  and  gastrointestinal  disordersincluding  irritable  bowel  syndrome  (IBS).  Early-lifestress  can  be  recapitulated  in  animals  using  thematernal  separation  (MS)  model,  exhibiting  manykey phenotypic outcomes including visceral hypersen-sitivity  and  anxiety-like  behaviors.  The  molecularmechanisms  of  MS  are  unclear,  but  recent  studiespoint to a role for epigenetics. Histone acetylation is akey epigenetic mark that is altered in numerous stress-related disease states. Here, we investigated the role ofhistone acetylation in early-life stress-induced visceralhypersensitivity.  Interestingly,  increased  number  ofpain  behaviors  and  reduced  threshold  of  visceralsensation were associated with alterations in histoneacetylation  in  the  lumbosacral  spinal  cord,  a  keyregion in visceral pain processing. Moreover, we alsoinvestigated whether the histone deacetylase (HDAC)inhibitor,  suberoylanilide  hydroxamic  acid  (SAHA),could reverse early-life stress-induced visceral hyper-sensitivity  and  stress-induced  fecal  pellet  output  inthe MS model. Significantly, SAHA reversed both ofthese parameters. Taken together, these data describe,for the first time, a key role of histone acetylation inthe  pathophysiology  of  early-life  stress-induced  vis-ceral hypersensitivity in a well-established model ofIBS. These findings will inform new research aimed atthe development of novel pharmaceutical approachestargeting the epigenetic machinery for novel anti-IBSdrugs.

 

 

 


Edited by theobromananda, 28 June 2018 - 09:00 PM.


#308 Mr Spock

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Posted 29 June 2018 - 04:21 PM

Got it today :)



#309 Mr Spock

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Posted 29 June 2018 - 04:25 PM

@Strangelove Your dosing is much higher than you've recommended: is that because lower doses had no effect?

 

Also, you've probably have answered this before,but will you be able to supply in the future, or is that it?



#310 kimlie

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Posted 29 June 2018 - 07:03 PM

I would also like to read more about dosages and how to administrate.

Do you eat that 10-100mg? 

 

Experiences with sublingual administration, or other methods?



#311 Painkillerrr

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Posted 30 June 2018 - 10:22 AM

@Strangelove Your dosing is much higher than you've recommended: is that because lower doses had no effect?

 

Also, you've probably have answered this before,but will you be able to supply in the future, or is that it?

 

 

I would also like to read more about dosages and how to administrate.

Do you eat that 10-100mg? 

 

Experiences with sublingual administration, or other methods?

 

are you all guys asking for dosage serious?? there are tons of pages here and on reddit and tons of study with TONS of information even about dosage, and when you ask: "Your dosing is much higher than you've recommended: is that because lower doses had no effect?"  speaking about a "cancer drug", not choline nor caffeine, a "cancer drug", seems you are conscious about what you are going to take and that you have not even spent a minute looking for information on it.



#312 kimlie

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Posted 30 June 2018 - 11:20 AM

are you all guys asking for dosage serious?? there are tons of pages here and on reddit and tons of study with TONS of information even about dosage, and when you ask: "Your dosing is much higher than you've recommended: is that because lower doses had no effect?"  speaking about a "cancer drug", not choline nor caffeine, a "cancer drug", seems you are conscious about what you are going to take and that you have not even spent a minute looking for information on it.

Relax, I just seek more information. :)

I have spent 2 months reading. I have read everything on reddit, longecity and every page online with the words "vorinostat", "saha", "zolinza" combined with "fear", "anxiety" etc. through advanced google searches.

If you check my internet log, theres at least a thousand pages with those words in it.

 

But this information evolves, and maybe people have tested other ways to administer, etc.
And when it's not specified in Strangelove's post, there's no need to answer back at me like that just for asking.


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#313 Mr Spock

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Posted 30 June 2018 - 01:59 PM

are you all guys asking for dosage serious?? there are tons of pages here and on reddit and tons of study with TONS of information even about dosage, and when you ask: "Your dosing is much higher than you've recommended: is that because lower doses had no effect?"  speaking about a "cancer drug", not choline nor caffeine, a "cancer drug", seems you are conscious about what you are going to take and that you have not even spent a minute looking for information on it.

If you read what I actually wrote, then you'd understand what I was asking, rather than jumping to a different conclusion.


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#314 PsychoAndroid

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Posted 30 June 2018 - 05:05 PM

thanks Dr.Strangelove, I received it a couple of days ago. (at least I hope that suspicious white powder was from you..)



#315 jacobjerondin

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Posted 01 July 2018 - 10:01 PM

Dang, did I completely miss my chance? I really meant to put in an order last weekend but sadly forgot :"(



#316 PsychoAndroid

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Posted 02 July 2018 - 07:18 AM

So I tried my first 150mg dose this morning, but unfortunately I didn't notice anything.

Maybe it is one of those 'too good to be true' medications...

Although, in some cancer research papers I found that vorinostat has a rather poor bioavailability (~48%) and very short half-life of ~2 hours. I will take a slightly higher dose next time, since I am generally quite resistant to all drugs I ever tried. Maybe I just metabolize stuff too fast and didn't get enough.


Edited by PsychoAndroid, 02 July 2018 - 07:59 AM.


#317 ISayLonger

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Posted 02 July 2018 - 08:51 AM

150mg you'd think you'd at least feel some side effects ;)

On the topic of potency, how has the vorinostat been stored all these months since the original purchase?

#318 Strangelove

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Posted 02 July 2018 - 12:06 PM

150mg you'd think you'd at least feel some side effects ;)

On the topic of potency, how has the vorinostat been stored all these months since the original purchase?

 

It has been very well packed in the fridge, I still use it (even mine was from a 2grams bag outside the fridge) I am pretty sure is not a matter of potency, its more of individual results, how you use it, and what do you expect, as I said before it does not have a conscious effects in the majority of times for me, the only cases it had a strong anxiolytic effect was.

 

During a buphedrone dose that gave me anxiety.

A meeting that I tried to save my relationship with my ex, that time I was really surprised at how strong the effect was a few minutes after the sublingual dose.

A prostatitis flair up (under control now) that the pressure and tension of the prostate disappeared for two days half hour after a 100mg dose.

 

This is pretty much the few times I had a strong conscious effect, BUT

 

One example I used it, for an event last week, was in a Latin dance performance I was in a stage with a very large crowd, feeling no anxiety at all, that I found surprising, even when at the time of ingestion (two hours before) I felt nothing. Apart from propanolol (that I did not use, as I was sure I had some, but I was mistaken) I 'll use vorinostat and only smaller doses of propranolol in large on-stage events. 

 

It may not work for some, but at least you should use it when at the same time push yourself into an event (or even thinking something) that gives you fear.

 

For anyone that wants to make an experiment with the Tim Ferris idea, of (seriously) thinking in detail, everything that can go wrong in your important future plans, I take a walk, listening to beta binaural beats, with 100mg vorinostat thinking all in the worst case scenario, and the possible counteractions.

 

I tried using larger doses (going up to 100 mg sublingual for a minute before I swallow) because it seems I get better long-term effects, without any side effects.


Edited by Strangelove, 02 July 2018 - 12:12 PM.

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#319 ISayLonger

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Posted 02 July 2018 - 12:25 PM

Good to hear.

Personally my interest is two fold.

1) My mother has breast cancer (currently in remission with hormone therapy + a plethora of adjuncts, including sodium butyrate — however the doses required for sodium butyrate because it's so weak are not comfortable/sustainable)

2) The most progress I've made with my depression in the last year has been with Acetyl-L-Carnitine of all things. Supposedly this works via mGluR2 upregulation via HDAC2 inhibition (or perhaps direct Histone2 acetylation or something; there's some mixed opinions). It took 5 days of consistent dosing before I reached what I considered a breakthrough. However after a while the increased acetylcholine production started to outweigh the benefits (I'm very sensitive).

Anyway, my point is even if someone doesn't feel anything (or notice anything) on the first dose, this is epigenetic therapy we're talking about — give it some time/keep at it. I know most people here are interested in the "take 100mg then immediately face and eradicate your fears" aspect of HDACs/memory, and we know from some people's personally experiences this concept works, but we don't actually know for sure *why*/*how* it works. We're very early on in the science/research of that stuff. Everything published so far could be refuted/rewritten in a couple years (happens all the time), replaced by science that shows that the effects on fear acquisition/consolidation are ongoing and/or take longer dosing and/or aren't purely epigenetic but also rely on downstream neurochemical/regulation changes (amygdala, anyone?) from the system-wide epigenetic effect.

So! I don't think HDAC inhibitors are likely to be "too good to be true". I could see them doing *more than we'd like*, but if taken enough I think it's impossible they won't do anything — un-suppressing half the genes in your brain/body is a big deal.



#320 PsychoAndroid

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Posted 03 July 2018 - 08:32 AM

Gave it one more try with 250mg (~3.8mg/kg).

I still can't say that I feel anything, not any side effects nor any reduction in anxiety.

I will give it a long break now, before my DNA becomes all tangled up  :wacko: :|?

Also I have to read up on the theory behind it again, maybe fear extinction could still occur even if there are no perceptual effects, but then to engage in those situations one would have to combine it with another temporary anxiolytic.



#321 ISayLonger

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Posted 03 July 2018 - 10:38 AM

What RoA? I think everyone should be trying well aimed intranasal — between the general increased bioavailability of the nasal cavity, + the percentage that crosses the olfactory bulb, dodging the BBB, I imagine the neural availability for vorinostat probably jumps 2-3x..



#322 airplanepeanuts

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Posted 03 July 2018 - 01:30 PM

I was in a very negative mood again today for the possible break up, and I certainly felt the effects, together with the PTSD research, it should have effects in the brain. I am only worried for a possibly very high bioavailability, but I ll try to snort a tiny dose first if anxious, and report back. 

Did you ever get around to snort it?



#323 Bushi84

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Posted 03 July 2018 - 10:22 PM

Did everyone get theirs? 



#324 theobromananda

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Posted 04 July 2018 - 01:47 PM

Has just arrived. Thank you so much!



#325 celticlion76

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Posted 04 July 2018 - 09:26 PM

No, my batch did not arrive in London UK. :sad:

 

Anyone else??

 

 


Edited by celticlion76, 04 July 2018 - 09:26 PM.


#326 kimlie

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Posted 06 July 2018 - 07:58 AM

I have started experimenting with 20 and 50mg doses. I have very positive results so far with PTSD-symptoms and performance anxiety.

I will come back with a more detailed report after more sessions.
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#327 theobromananda

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Posted 06 July 2018 - 12:25 PM

After one 40mg experiment I have found that it does exactly what is described by musicman, tree and strangelove. I understand why some may call it subtle, but I find it immensely strong for changing habits, removing old anxieties & fear, and learning. If you do not have a certain degree of awareness of yourself, you'd think nothing is happening. Absolutely powerful stuff!


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#328 celticlion76

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Posted 06 July 2018 - 08:07 PM

Did everyone get theirs? 

Really annoying!  My batch still not arrived. Did anyone else in the U.K not receive theirs yet?



#329 celticlion76

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Posted 06 July 2018 - 08:07 PM

Did everyone get theirs? 

Really annoying!  My batch still not arrived. Did anyone else in the U.K not receive theirs yet?



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#330 airplanepeanuts

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Posted 06 July 2018 - 08:30 PM

After one 40mg experiment I have found that it does exactly what is described by musicman, tree and strangelove. I understand why some may call it subtle, but I find it immensely strong for changing habits, removing old anxieties & fear, and learning. If you do not have a certain degree of awareness of yourself, you'd think nothing is happening. Absolutely powerful stuff!

 

I agree. But wait if the change will last. 







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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