• Log in with Facebook Log in with Twitter Log In with Google      Sign In    
  • Create Account
  LongeCity
              Advocacy & Research for Unlimited Lifespans

Photo
* * * - - 7 votes

CL-994: capable of removing traumatic memories and persisting anxiety? (And resulting persistent attention problems?)

cl-994 epigenetic anxiety disorder trauma ptsd memory add group buy anxiety

  • Please log in to reply
260 replies to this topic

#151 tree

  • Topic Starter
  • Guest
  • 56 posts
  • 11
  • Location:Europe
  • NO

Posted 16 January 2015 - 11:12 AM

Interesting. The question always is, how potent is it? With the heavier HDAC inhibitors, the entire cell cycle is temporarily frozen due to the heavy changes in epigenetics. This doesn't occur with L-carnitine leading me to think that it is less potent. Still mGlu2 receptors play a definite role in stress. 

 

PS There was a delay with the groupbuy, so if anyone out there is interesting in ordering vorinostat, they have a few days left to respond!



#152 Flex

  • Guest
  • 1,629 posts
  • 149
  • Location:EU

Posted 16 January 2015 - 05:55 PM

 

I would like to activate this thread by inserting some ideas/informations. Have you guys ever thought about the anti-anxiolytic mechanism of acetyl-L-carnitine? ALCAR works at the beginning of the treatment slightly anxiogenic, but after a while it is anxiolytic.

 

By inhibiting histonedeacetylases you reach some kind of hyperacetylation of histones. On the other side ALCAR does the some by being a donor for acetylgroups (1). The anxiolytic and antidepressant action of ALCAR is perhaps rather promoted by acetylation of other non-histone proteins like mGlu2 (2), but additionally L-carnitine also has an HDAC inhbitory potential (3).

 

ALCAR helps with neuropathic pain like HDACi.

 

To sum it up: ALCAR does donate acetyl groups and it also inhibits HDAC (L-carnitin does it). On the other side it works anxiolytic by acetylating other proteins, so this could suppress the fear to come up in special fear promoting situations and so hinder you to experience the fear again and to eradicate it or is this irrelevant?

 

Some thoughts on it?

 

 

(1) http://www.molecular...content/10/1/68

 

(2) L-acetylcarnitine causes rapid antidepressant effects through the epigenetic induction of mGlu2 receptors.

Nasca C, Xenos D, Barone Y, Caruso A, Scaccianoce S, Matrisciano F, Battaglia G, Mathé AA, Pittaluga A, Lionetto L, Simmaco M, Nicoletti F.

Proc Natl Acad Sci U S A. 2013 Mar 19;110(12):4804-9. doi: 10.1073/pnas.1216100110. Epub 2013 Feb 4.
PMID:23382250

 

(3) L-carnitine is an endogenous HDAC inhibitor selectively inhibiting cancer cell growth in vivo and in vitro.

Huang H, Liu N, Guo H, Liao S, Li X, Yang C, Liu S, Song W, Liu C, Guan L, Li B, Xu L, Zhang C, Wang X, Dou QP, Liu J.

PLoS One. 2012;7(11):e49062. doi: 10.1371/journal.pone.0049062. Epub 2012 Nov 5.
PMID:23139833

 

 

I´ve made a thread about natural compounds with HDAC inhibitory actions.

Click the tag: epigentic

at the top, which is right below the Headline.

 

or here:

Herbal and Compound derived epigenetic alterations via HDAC and others

http://www.longecity...dac-and-others/

 

The effects do work definite, at least, for prostata cells

 

Furthermore look at the table from the post #1

Ginger for instance has a HDAC2 activating effect and they are indeed good for something.

Simple activation of genes is not allways good as well as simple deactivation.

 

Take also a look at post #4

and table 1

According to this, it seems that epigentic alterations via herbs is quiet common.

 

I guess


Edited by Flex, 16 January 2015 - 06:15 PM.

  • Agree x 1

sponsored ad

  • Advert
Click HERE to rent this advertising spot for BRAIN HEALTH to support LongeCity (this will replace the google ad above).

#153 Alpharius

  • Guest
  • 52 posts
  • 20
  • Location:Berlin
  • NO

Posted 24 January 2015 - 06:36 AM

Ok so just a short update regarding ALCAR, HDACi and anxiety.I do not suffer heavy anxiety, just sometimes when I work to much or do have a lot of stress, also I used like someone else in this thread already described, to feel overwhelmed when reading a lot of scientific literature. Caffeine and stimulants are also anxiogenic to me.

 

I have used ALCAR now for 2 weeks. In the first days (3-4 days) ALCAR felt slightly anxiogenic to me. But now it is a some kind of "strange" feeling, in situations when I would somehow expect the tension and anxiety to build up, nothing happens. Like already described by Tree, it is a feeling of something taken away for me, it should be there but it is not. I have already tried different stuff like L-theanine or meditation which helped somehow, but ALCAR is a completely new experience. I use 500 mg daily.


Edited by Alpharius, 24 January 2015 - 06:37 AM.


#154 tree

  • Topic Starter
  • Guest
  • 56 posts
  • 11
  • Location:Europe
  • NO

Posted 25 January 2015 - 10:07 AM

The only supplement I use regularly is R-lipoic acid. It seems to have a strong calming effect on my thoughts. I did use either acetyl or L-carnitine combo with R-lipoic acid for a couple of months, but I never noticed the effects you described.

 

Correction: I took both forms of carnitine though not simultaneous.


Edited by tree, 25 January 2015 - 10:15 AM.


#155 AOLministrator

  • Guest
  • 181 posts
  • -14
  • Location:Ruhrpott
  • NO

Posted 25 January 2015 - 10:30 AM

You know that taking a zillion times the natural amount of lipoic acid will cause weird side effects over the years, like your amalgam fillings dissolving faster and such? Check people who take RDA 16000% of B6, they get hair loss and what not because apparently that much B6 will block absorption of other B-vitamins. Nothing ever was healthy if overdosed 100 times, except maybe ascorbic acid. One regular 300mg capsule has the equivalent amount of over 100,000kg of meat, one of the most richest sources for lipoic acid. So this shit is 100,000 times the natural dosage, given the most richest diet you can have of it. Very questionable if that can make much sense in your body at all.


Edited by Aolministrator, 25 January 2015 - 10:47 AM.


#156 tree

  • Topic Starter
  • Guest
  • 56 posts
  • 11
  • Location:Europe
  • NO

Posted 26 January 2015 - 09:29 AM

You know that taking a zillion times the natural amount of lipoic acid will cause weird side effects over the years, like your amalgam fillings dissolving faster and such? Check people who take RDA 16000% of B6, they get hair loss and what not because apparently that much B6 will block absorption of other B-vitamins. Nothing ever was healthy if overdosed 100 times, except maybe ascorbic acid. One regular 300mg capsule has the equivalent amount of over 100,000kg of meat, one of the most richest sources for lipoic acid. So this shit is 100,000 times the natural dosage, given the most richest diet you can have of it. Very questionable if that can make much sense in your body at all.

 

Well I don't have amalgam fillings. And I don't take 300mg capsules but a few 100mg caps spread out over the day. More importantly, I'm not taking it out of longevity or health concerns, but out of necessity.

 

So unless the other side-effects of long term use are worse than the state I'm in without lipoic acid, there is no reason for me to stop taking it. Do you have a reference to these side-effects?


  • Good Point x 1

#157 Ark

  • Guest
  • 1,729 posts
  • 383
  • Location:Beijing China

Posted 28 January 2015 - 08:42 PM

I'm in as well, thanks!

#158 Flex

  • Guest
  • 1,629 posts
  • 149
  • Location:EU

Posted 09 March 2015 - 05:31 PM

If one of You will have tried Vorinostat,

could someone do me the favour and, as posted in #152, try Chinese goldthread or Chinese skullcap to tell whether those herbs are working ?

 

Herbal and Compound derived epigenetic alterations via HDAC and others

http://www.longecity...dac-and-others/

 

It would be an interresting information for others as well, since HDAC inhibitors are quiet hard to obtain.



#159 tree

  • Topic Starter
  • Guest
  • 56 posts
  • 11
  • Location:Europe
  • NO

Posted 10 March 2015 - 12:04 PM

I'm a bit skeptical concerning herbal supplements. A strong HDAC inhibitor will temporarily stop cells dividing in the body, that is the reason you can't take vorinostat for long duration but only a single dose at a time. If either of these herbs did the same, the wouldn't be allowed to be sold over the counter. So they can't be very strong..

 

But aside from that, is it known if they cross the blood-brain barrier?



#160 Flex

  • Guest
  • 1,629 posts
  • 149
  • Location:EU

Posted 10 March 2015 - 05:24 PM

I cant say which compound in those herbs is responsible nor whether it crosses the BBB.

 

Dont underestimate the herbs. I guess that they are allowed because of low side effects, not because of their mechanism because not every mechanism is researched.

Otherway arround: if someone researches that they are in fact e.g. HDAC inhibitors, would this certain herb get forbidden ?

Take Coridalis yansuhuo, its an actual antipsychotic incl. comparable side effects as Rx antipsychotics( I tried both and both caused a "dulling" effect for weeks), but its still OTC

See:

..and possesses an antipsychotic-like pharmacological profile of D1, D2 and D3 receptor antagonism

https://clinicaltria...how/NCT02118610

 

Could be a treatment option for cocaine, where many other Antipsychotics fail

http://www.ncbi.nlm....les/PMC3878639/

 

Heres another example (it sounds quiet sensational tough..)

http://www.reuters.c...N0LU2ET20150226

 

In regards of banned herbs, I can only think of Thunder god vine.

It has unique mechanisms like altering the gene expression of a few targets, but its so toxic that You would consider it as a poision with health benefits as side effects.

 

-> Look, since You wouldnt be able to obtain it in the future anymore, I wanted to take advantage of the fact that some of You are able to try both and, given the herbs are working, to preserve this information for others.



#161 tree

  • Topic Starter
  • Guest
  • 56 posts
  • 11
  • Location:Europe
  • NO

Posted 11 March 2015 - 10:39 AM

I get your point. I decided to look at pubmed to find evidence that the herbs Scutellaria baicalensis (baikal skullcap) or Coptis chinensis (chinese goldthread)

work in a similar manner to Vorinostat and similar HDAC-inhibitors, but I couldn't find any article showing effect of either herb on anxiety, fear or emotion in general.

 

However I did find several articles that showed skullcap and goldthread as being the cause of hepatoxicity and hepatisis. 1 , 2 , 3   So I personally won't use them.



#162 AOLministrator

  • Guest
  • 181 posts
  • -14
  • Location:Ruhrpott
  • NO

Posted 13 March 2015 - 01:02 AM

I have a cure for your shit. Message me if you want to know.
  • Pointless, Timewasting x 4
  • dislike x 3
  • Disagree x 1
  • Unfriendly x 1

#163 tree

  • Topic Starter
  • Guest
  • 56 posts
  • 11
  • Location:Europe
  • NO

Posted 13 March 2015 - 07:21 AM

I really would like it if this thread remains about HDAC inhibitors like CL-994 and Vorinostat... I created it for a group-buy after all, not to discuss general treatments.



#164 Flex

  • Guest
  • 1,629 posts
  • 149
  • Location:EU

Posted 13 March 2015 - 05:00 PM

I have a cure for your shit. Message me if you want to know.

 

Why dont You turn Your ideas into money or something like that.

I bet the world would be such a better and efficient place with Your ideas.
 


  • Enjoying the show x 1

#165 NinefingerJoe

  • Guest
  • 65 posts
  • 3
  • Location:USA

Posted 13 March 2015 - 05:15 PM

I really would like it if this thread remains about HDAC inhibitors like CL-994 and Vorinostat... I created it for a group-buy after all, not to discuss general treatments.


Indeed.
I didn't feel like pouring through he multiple pages for this very reason. Did we get a group buy going or no?

#166 tree

  • Topic Starter
  • Guest
  • 56 posts
  • 11
  • Location:Europe
  • NO

Posted 15 March 2015 - 08:06 AM

There has been one already, and another one is ongoing due to unforeseen circumstances.. both for Vorinostat. If you wish to participate just let me know.



#167 AOLministrator

  • Guest
  • 181 posts
  • -14
  • Location:Ruhrpott
  • NO

Posted 26 March 2015 - 09:04 PM

I have a cure for your shit. Message me if you want to know.

 
Why dont You turn Your ideas into money or something like that.
I bet the world would be such a better and efficient place with Your ideas.


It is illegal and also too complicated. I was being quite generous offering it, but now I withdraw my offer.
  • Needs references x 1
  • Dangerous, Irresponsible x 1
  • Unfriendly x 1
  • dislike x 1
  • Disagree x 1

#168 tree

  • Topic Starter
  • Guest
  • 56 posts
  • 11
  • Location:Europe
  • NO

Posted 27 March 2015 - 12:06 PM

 

 

I have a cure for your shit. Message me if you want to know.

 
Why dont You turn Your ideas into money or something like that.
I bet the world would be such a better and efficient place with Your ideas.

 


It is illegal and also too complicated. I was being quite generous offering it, but now I withdraw my offer.

 

 

Except your 'offer' seems more about you flattering your own ego than genuinely wanting to help others... I suggest you get a different avatar to make this less obvious.

 

And perhaps seek help for your narcissism.


  • Enjoying the show x 2

#169 ledzep

  • Guest
  • 5 posts
  • 2
  • Location:istanbul

Posted 21 August 2015 - 10:05 AM

I'm bumping this thread and i want a second group buy if possible.



#170 tree

  • Topic Starter
  • Guest
  • 56 posts
  • 11
  • Location:Europe
  • NO

Posted 27 March 2016 - 12:10 PM

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.


Edited by tree, 27 March 2016 - 12:11 PM.


#171 tolerant

  • Guest
  • 470 posts
  • 55
  • Location:Bedroom

Posted 31 March 2016 - 02:35 AM

Hi tree,

 

Can you please share what type of medication your refer to in describing you experience? Is it mindfulness meditation or some other type?

 

Thanks,

 

tolerant



#172 tolerant

  • Guest
  • 470 posts
  • 55
  • Location:Bedroom

Posted 31 March 2016 - 07:12 AM

Also, as there were two group buys and a number of people tried the substance, would someone please come forward and share their experiences to complement those shared by three?

 

@ 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? 

 

I'm also greatly concerned that, as it appears to me, Vorinostat, like d-cycloserine, must be used in a very precise setting to work, i.e. one must be able to confront and reduce the fear in order for it to work; otherwise, the opposite effect may happen and the fear my become more entrenched. Or is it enough to face the fear and feel the emotional response? Also, while I strongly believe that everything (at least in my case) from CFS to pain to anxiety/depression is the result of fear conditioning (namely the fear of symptoms continuing -- check the work of John Sarno, his student Howard Schubiner, and especially Ashok Gupta), coming to the understanding in the first place that it is fear that is driving your condition, let alone be able to begin to conquer it requires some very heavy mental work, whether through meditation or other methods, which one not be able to achieve. If one is able to achieve it, that may be curative of itself. But it's a very onerous precondition for using a drug like Vorinostat.


Edited by tolerant, 31 March 2016 - 07:50 AM.


#173 tree

  • Topic Starter
  • Guest
  • 56 posts
  • 11
  • Location:Europe
  • NO

Posted 31 March 2016 - 08:26 AM

@ 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.

 


  • like x 1

#174 tolerant

  • Guest
  • 470 posts
  • 55
  • Location:Bedroom

Posted 07 April 2016 - 12:01 PM

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 is heartening, although it does sound too good to be true! 

 

I am still urging those who participated in the group buy and/or had experience with vorinostat to share it in this thread, as the experience shared beautifully described by tree is literally the only one that can be found on the Internet. 

 

I would also greatly appreciate it if someone has some left over vorinostat that they wouldn't mind selling, as it is not easy to obtain.

 

One more question I would fire at tree is whether the "nothing" type of feeling that occurred after vorinostat helped remove the emotional negative response to triggers actually translated to a better mood and quality of life, i.e. can you now actually enjoy reading dense scientific texts, or is it merely a neutral experience devoid of anxiety.



#175 tree

  • Topic Starter
  • Guest
  • 56 posts
  • 11
  • Location:Europe
  • NO

Posted 07 April 2016 - 12:44 PM

Though there were 2 group buy's, each had only 2 people (one of them being me). So there are only 3 people who got vorinostat. There were many more that showed interest in each instance but bailed out at the last moment. I guess that's not surprising seeing as how anyone interested in something like vorinostat must have a lot of fear. I only went through because I felt I had nothing to loose anyway and because I spend months reading the literature until I was convinced it was safe enough to try.

 

I lost contact with one of the participants, the other doesn't check longecity and I dealt mostly through email. Last time I asked the results looked very good, though he hadn't checked the long term results yet. I'll ask for an update.

 

I'm not sure I ever enjoyed reading dense texts but I sure did like learning, and that never went away. It was just crippled by anxiety. That anxiety got removed and I don't think joy for learning was diminished. Love for new experiences is pretty fundamental for humans though, not sure if that even counts as an emotional attachment. 

 

 

Yeah vorinostat is fantastic. Still keep in mind that vorinostat only removed the strong anxiety attacks/waves that come from re-confronting trauma aka the stress-inducers that got me my nervous breakdown. It hasn't affected the increased nervousness (that people with anxiety disorder so often have) or the brain fog and it definitely doesn't give confidence! I noticed even without feeling actual fear that I still felt doubt whether I was up for tasks. I had to regain confidence the old fashioned way(s) before I could regain my old skill at them. But being free from crippling waves of fear certainly helped immensely..!

 

The increased stress and stress-sensitivity has began to decrease over time as I feel more confident. In fact there seems to be a very strong correlation between brain fog and confidence. If there is a way for vorinostat to remove all of the nervousness/stress in a single go as well then I hope to find it. Perhaps there's a factor I'm missing.. But so far only meditation, confidence building and sport have worked against the basic nervousness/stress/restlessness. 


  • Informative x 2

#176 tolerant

  • Guest
  • 470 posts
  • 55
  • Location:Bedroom

Posted 08 April 2016 - 12:19 PM

Thanks for continuing to answer my questions. Sorry for the interrogation, but I've got nobody else to ask. I would be interested to know whether the person from the group buy who had positive results with vorinostat had generalised anxiety or also a form of PTSD with particular triggers. You make very fine distinctions between various states of emotion which I don't have the insight or experience to fully grasp. Yet I'm looking for similarities between the condition from which you recovered and my own condition. In the very first post of this thread you said that after you achieved significant healing through meditation, you were still left with constant stress and inability to relax. This corresponds to one of the ways in which I would describe my condition -- a debilitating, incapacitating inability to relax and a constant stress reaction to everything. Also, you mention that your biggest fear was that of getting sick. Do you mean by that the fear of your symptoms failing to resolve, becoming worse, the fear of continued incapacity due to your then current condition, or a fear of getting sick with something else? If it's the former, then it's also my greatest fear. That of failing to get better. In other words, "if God came down from heaven" (quoting Pulp Fiction here) and was able to persuade me that in exactly one month I will become well, then my guess is that I would become well there and then, without having to wait a month; or at least that I will start to becoming well there and then.

 

Another question I have is a technical one. Did you administer vorinostat in the form of a powder or some other form? This web page indicates that the vendor sells 10mM in 1 ml DMSO solution, but it is not clear the form of 200 mg and 500 mg quantities. I will inquire of the vendor which form those quantities come in, but I thought maybe you would give me a heads up as to the form in which vorinostat comes and how it should be stored.



#177 tree

  • Topic Starter
  • Guest
  • 56 posts
  • 11
  • Location:Europe
  • NO

Posted 10 April 2016 - 06:33 PM

Mostly I had a fear of getting even worse disease/problems but the idea that my problems wouldn't get better was a strong source of desperation/anxiety as well. But such fears overlap. I imagined often that one problem could arise from the other. I guess in the past they sometimes did. 

 

I used powder. In the animal fear-extinction experiments the compound is dissolved in DMSO and injected in the abdomen but I didn't felt like injecting myself without any kind of training. So I inhaled or used it sublingual. From the looks of that page I'd say they are all DMSO solutions. I *think* you can use them orally as well but you'd have to check literature, I don't know much about DMSO other than that it's a non-toxic solvent used in medicines.

 

 

 

 



#178 StevesPetRat

  • Guest
  • 565 posts
  • 86
  • Location:San Jose, CA

Posted 12 April 2016 - 06:57 AM

OK, I'll share my vorinostat experiences. Keep in mind this is not a very clean trial. I've tried probably well over 100 different noots and supplements the last couple years. My current stack/diet has a variety of vitamins, minerals, probiotic foods, nearly 1:1 ω3:ω6 ratio, no grains and relatively low carbs, natural and supplemental ACh and dopamine precursors, 5α-reductase enhancers, etc, etc, not to mention NSI-189, a few doses of Dihexa, and I'm probably forgetting plenty.

I have to describe the circumstances that led me to snorting lines of vorinostat and then sitting down at a poker table for the results to make much sense. After getting jaundice and very elevated liver enzymes from a prescription drug, my physical and mental health spiraled out of control for over a year. My extremities got cold, I lost sensation in my skin, my eyes dried out, I stopped sweating, 100s of splinter hemorrhages appeared in my finger- and toenails, I couldn't recognize myself in the mirror, I lost my sense of balance and dropped things constantly, experienced near constant muscle pain-- at one point my pee turned brown and my muscles literally shrank over the course of a few days as I had the sensation of barbed wire being pulled through them -- I had first a 3 week period and then a 2 month one of not being able to sleep more than 2 hours a night (and usually an hour at most), my guts locked up to the point where it felt like steel wool was passing through them, for 2 weeks my heart rate never dropped below 100 day or night (I know this because I got one of those little pulse oximeters and wore it in my "sleep") and then I developed POTS / orthostatic problems, and my startle reflex was so heightened that birds chirping would make me jump every single time they made a peep (yet at the same time very nearly being hit by a car made me do nothing but chuckle slightly, go figure). There are plenty of things I'm leaving out, but you get the idea. And of course for months and months, virtually every waking moment was filled with the sensation that I would die at any second, nothing would ever improve, there was no hope. In this darkest moment, doctors offered antidepressants that made everything worse and benzos that dulled me past the point of having anything even resembling human cognition (not that I was cogitating much to begin with), and the support offered by my parents was to put me up in a nice institution for a while where I was convinced (and not without reason) that drug after drug would be added to the blindfolded-dart-throwing psych treatment protocol until the last remaining bit of my personality was totally eradicated.

 

So eventually I implemented a highly restrictive diet that eliminated the outright terror and reduced the anxiety enough to where I was able to continue combing through medical literature, ultimately stumbling upon a paper on acute stress and epigenetic changes in ACh synthesis. Recognizing that solidly 80% of my symptoms could be linked to ACh  deficiency, boosting its synthesis caused a rapid improvement in my mental state and a reduction to some extent of the physical symptoms.

 

I had recovered enough to fall utterly head over heels for a girl for the first time in my life. Experiencing this for the first time in my mid 30's, I didn't handle it very well, and she left after a month. This plunged me into a depressive episode that none of my tricks could reverse. Unable to sleep, eat, focus, or act for a week during a time when I was unemployed and low on funds, I literally could not afford to feel that way, so I dusted off the NSI-189 that had been stashed in my "medicine cabinet" for almost a year. The reversal of not just the immediate depression but years of previous funkiness was amazingly rapid.

 

But of course my experiences had left their mark on my psyche. Any time I felt too happy, my mood crashed to painful despair. Any time I thought about the stuff I'd gone through, pain. Any time I thought about the girl I'd briefly known, pain. And while (for me anyway) pain can be an excellent motivator and a catalyst for change and growth (a source of eustress), this pain that I could not adapt to or learn from simply caused distress.

 

OK, that's out of the way. So, one thing I'd done when money was tight was go play poker. When I first started playing years ago, I was cool as a cucumber. But, after taking enough bad beats and experiencing the concomitant surge of adrenaline, my body "learned" to be excited during big hands. Even though, psychologically, I didn't experience it as fear, the physiological adrenaline rush had some hallmarks of a conditioned fear response. It certainly impaired my cognition and caused me physical and mental fatigue as repeated surges kicked in over the course of a play session. This limited play time and also caused me to make sometimes costly mistakes as my thinking wasn't as clear as it could have been. Propranolol (a β-blocker) had been somewhat effective in countering the physical symptoms, though it left me somewhat mentally dull and emotionally depressed.

 

I thought maybe vorinostat could help me "unlearn" my response at the poker table, so I took 50 mg up the nose and 50 mg sublingually, along with an extremely low dose of propranolol (2 mg, lowest prescribed is 10 mg, and I usually take 5 - 10 mg for performance enhancement) to take the edge off. I sat down, eventually got into a big hand, and felt... nothing. Because of everything that happened the past couple years, I've developed an acute and continual awareness of my emotional and cognitive state, the same way a golfer might be aware of his swinging mechanics. And so I was sitting there, clearly processing the hand, $250 on the line, experiencing no stress whatsoever, and really realizing how impaired my thinking had been even those times when I'd taken propranolol. And the next time I played poker, same deal -- without the vorinostat.

 

Now, if that were it, I wouldn't have written so damned much. But at the end of the night (I was only up $40. There was a big hand where I lost ~$100 on a 12% suck out by my opponent; sadly, vorinostat didn't improve my luck any), I went back to the parking lot. Unbidden, a memory of the girl I'd dated 5 months before floated to my mind. And for the first time in all those months, I could feel it lose its emotional salience. The pain was dulled. I ran into her a few weeks later, and, for the first time since our first kiss, I wasn't flustered and rendered stupid by her mere proximity.

 

Other things have changed. I no longer feel my mood crash out when I get too happy. Unless I'm very sleep deprived or under inordinate stress, I can reflect on the events of the past couple years without mental anguish. I banged my funny bone really hard while I was hitting my punching bag. As I sat there writhing in pain, I thought, "Hmm. Maybe I can get rid of this." And, with a few moments of calm meditation, the pain was gone. Maybe it's placebo; maybe it's some special effect of being on NSI-189 for 6 months. But I think it was from the vorinostat. I've since used it in other situations where I felt intense emotions were causing cognitive impairment with similar effect.

 

If it were only my experience, I might not have bothered sharing. But I ended up giving some to a friend of a friend who was experiencing severe test anxiety and cognitive impairment. She sat there and took a practice test. Afterwards, I asked her how she felt. "Well, I felt like panicking, but then I didn't panic." She'd also had an interview that had gone badly a week or so before. I asked her if it bothered her. "Yeah, every time I think about it, I still get upset." I asked her how she felt about it now. ".... Huh. I don't feel anything about it this time."

 

I think back to when I was a kid. I would get physically or mentally hurt, yet bounce back in no time at all. But at some point during adulthood, my mind learned to take "bad things have happened" and use that data to predict "bad things are going to continue to happen." Pain is a part of life. But when we ruminate on that pain, when we imagine that it will continue indefinitely, that's when it becomes distress. Crudely peaking, while NSI-189 helped me cope with the emotional baggage, I feel like vorinostat turned off that learned response and reset it to the more youthful resilience.

 

Take this highly uncontrolled pair of anecdotes for what you will.


  • like x 3
  • Well Written x 1
  • Informative x 1

#179 neuralis

  • Guest
  • 84 posts
  • 12
  • Location:EU
  • NO

Posted 13 April 2016 - 09:30 AM

It's regretful I missed both of the group buys. Vorinostat caught my attention first when this thready originally popped up. And now after reading the anecdotes I'm quite confident it would be beneficial to the process of change I'm in right now.

 

 

Tree, could you perhaps share the quote on getting this synthesized?

 

Thanks! :)



sponsored ad

  • Advert
Click HERE to rent this advertising spot for BRAIN HEALTH to support LongeCity (this will replace the google ad above).

#180 dijital

  • Guest
  • 26 posts
  • 2
  • Location:planet earth

Posted 14 April 2016 - 01:04 PM

It's hard for me to make sense of your experience Stevepetrat, because from theory that is not how Vorinostat is supposed  to work. When you're revisiting the traumatic memory on a HDACi for the first time, you shouldn't feel calm. It's not like Vorinostat should have immediate calming effects, but rather restore neuroplasticity in fear extinction processes. Fear extinction and memory reconsolidation needs some time, and in that time frame, reprocessing the traumatic memory doesn't feel good, most of the time it is a rather painful experience. So my guess is that your first reaction sitting on the poker table was the result of the propranolol + some placebo effect. I'm not saying the Vorinostat didn't do its work, but that's something you should test the next time playing poker, without propranolol.

 


Edited by dijital, 14 April 2016 - 01:08 PM.

  • Good Point x 1





Also tagged with one or more of these keywords: cl-994, epigenetic, anxiety disorder, trauma, ptsd, memory, add, group buy, anxiety

0 user(s) are reading this topic

0 members, 0 guests, 0 anonymous users