CL-994: capable of removing traumatic memories and persisting anxiety? (And resulting persistent attention problems?)
#211
Posted 12 November 2016 - 04:19 PM
#212
Posted 13 November 2016 - 01:43 AM
in 4 gb
PM MEH
Edited by Stephen Clark, 13 November 2016 - 01:44 AM.
#213
Posted 13 November 2016 - 06:59 PM
Below is a collection of quotes from this thread with my comments in italics which show that there seem to be two divergent views: (1) that you need successful extinction therapy for HDACi to work (I've omitted the studies referred to in this thread that show that without successful extinction training, the fear memory may actually strengthen!), and (2) that attempting to be calm while taking HDACi may actually ruin the fear extinction process. Very confusing and somewhat risky.
Celebes: "In short, taking a HDAC-inhibitor (like CL-994) creates a window where it's possible to eradicate fear conditioning. My impression is this would only really be useful in a therapeutic setting."
Tree: "Depends on what you call therapeutic setting. Keep in mind the mice didn't need any therapy for it to work. Just recalling memories (for instance by confronting yourself with the anxiety inducing situations) while the window is open is clearly sufficient. GAD sufferers usually have a few things which causes more anxiety than the rest so those are points of confrontation. But if anxiety has gotten to the point were it remains continuous then I'm not sure any confrontation is even required. The anxiety/stress switch is forceably and permanently set to high through epigenetic means. Enter Cl-994 which is an epigenetic resetter."
Question: Why would an epigenetic resetter selectively resest the anxiety switch? What if it resets the "calmness" or some other useful switch as well? Does the same apply to vorinostat? The mice didn't need any therapy for it to work? They did receive extinction training whereby the foot shock was unpaired with the tone so the fear memory could be extinguished!
...
Tree: In regard to the earlier question whether aversive memory wiping is the same as removing consistent anxiety/stress states, I recommend this popular science article. It explains the basics of epigenetic storage very well. Negative memories that are stored in the brain AND persistent anxiety are both the results from epigenetic switches being set. The process can be simplified by saying that methylation can be considered an off switch, and acetyl an on switch. While stress/fear causes genes to shut off due to methylation (including genes necessary to normalize stress responces) a compound like Cl-994 is very indiscriminate and hyper-acetylates proteins and genes. This causes them to become active again and effectively resets your entire epi-genome (to one degree or another, depending on dosage and accessibility in the body).
Same question: if it's so indiscriminate, will it hyper-acelate other genes, resulting in detrimental effects? Does the above information also apply to vorinostat?
...
Celebes: "TrkB and NMDA agonism are both fear extinctive in themselves (along with CB1, Mu, GABAB, 5-HT1A and H2). HDAC inhibition's upregulation of both (in the absence of therapy) is the most likely explanation for its effects. A big part of the phenotype of trauma or anxiety is just the direct consequence of diminished BDNF and NMDA activity (along with CB1, Mu, GABAB, 5-HT1A and H2). You would expect anything that corrected any of that to take a big chunk out of fear conditioning, which demonstrably it does. I think the 'window' was a misconception, an artifact of the design. What we're really doing here is disinhibiting the biological basis of 'resilience', As with anything involving changing the brain, that takes time.
And another thing: How many situations is exposure therapy actually useful in? Sure it works for phobias but those are pretty much defined by being irrational. How does it work with rational fear? Combat veterans: attack people who can't fight back? Assault victims: be the one doing the beating? Child abuse: become dependent on people who are nice to you? Bullying? Infidelity? Failure? Loss? Now all of those things are actually practiced by the people in those groups. But in an hour or two? What's more, the fear extinction studies exposed the rats to a single stressful event. How many people here have had exactly one stressful experience?"
If the first paragraph is correct, that is very encouraging. The second paragraph is what I was thinking: how do we replicate extinction learning in humans?
...
StevesPetRat: "Very interesting experiences, tree. I wonder if an HDACi could help with more general emotional / behavioral plasticity."
This is what I'm wondering also.
...
StevesPetRat: "But it sounds like one has to face the fear and then become unafraid during the treatment which if I could do I wouldn't really need the help..."
Exactly.
As I've investigated the use of HDAC inhibitors for fear extinction, I've also looked into how certain memories are formed, including fear, anxiety, negative reinforcement, positive reinforcement, reward, love, attachment, etcetera. The way different memories are made in the brain and what controls them is very important. HDAC doesn't control all memory, and if the ones it does oversee it doesn't control them all equally. There are many other transcription factor targets, as well as many other epigenetic regulator targets that affect various kind of memory other than HDAC. For example, DNMT3a affects addiction and, to some extent, certain types of reward, as seen in this study:
https://www.ncbi.nlm...les/PMC2928863/
This is how I understand it from all I've read... Fear and anxiety has totally different mechanisms and pathways in the brain from regular memories, reward, love, and anything else. They build over time, even if the trigger is no longer directly linked to danger. This makes sense evolutionarily if you think about it. You want to make sure that whatever brought into danger brings up awful feelings so you don't even think about doing it again. The degree to which it brings up fear and the degree to which you can actively combat it probably depends on the person, hence some people are prone to anxiety, PTSD, etc. and some people are less prone. This is key to understanding how HDAC inhibitors work... the fears associated with certain memories and situations are often overblown by our brain compared to how we should actually be reacting to the memory/situation. This is a protective trait built up throughout evolution. If you did something and a lion came up out of nowhere, you're brain is making sure you never want to do that again, even if you never even see another lion in your life... walking to that part of the desert is always going to bring up that fear, and may even build over time, even if you never see another lion. This happens in different parts of the brain, too, with certain pathways dedicated specifically to fear, and there have been studies showing that HDAC is unregulated or downregulated in specific parts of the brain depending on whether there's been a fear-inducing situation that has taken place. I'll try to find that study.
To answer the first question, HDAC selectively resets the anxiety and fear switch because, 1, HDAC happens to have a built-in propensity toward acting on transcription factors and parts of the brain having to do with negative reinforcement, fear, anxiety, avoidance, etc... it just doesn't act towards other emotions, because these are handled by different pathways in the brain and perhaps might not even be regulated by epigenetics as much, as they evolved into lifeforms after fear (love, happiness, connection, empathy, etc.) 2, an HDAC inhibitor works so well at eradicating fear because fear is the most likely emotion to be naturally attributed to a situation and unnaturally built-up. An HDACi, even at a small dosage, increases the priority of the present, so no matter what you've felt about the present situation (brought up through meditation or an actual experience) in the past, what the situation is doing in the present moment will be given full priority, which is usually felt as "nothing". In real time, how an HDACi feels is like nothing. No extreme, built-up emotions from the past come up. You can remember them if you try, you can remember everything that happened, but unless you're about to be hit by a bus, there will be no tightness in your chest, no anxiety, etc. Even if you were hit by a bus on an HDACi, as long as you were on it still after being hit, or took it again a couple days later, the fear that was learned from being hit by the bus on the HDACi can also be eradicated, so there should be no fear in using an HDAC. It's getting at the root of memory formation, at the transcription level, so it's impossible to have a "bad trip" or anything like that. It doesn't effect cognition, because it doesn't directly effect neurotransmission or anything upstream of CREB, which is anything above what BDNF is actually doing to DNA. It's really incredible, and nothing else we've used acts like this, so it's hard to wrap your mind around at first. You just have to try it.
To answer your second question, yes, HDACi hyper-acetylate other genes as well, but they're not nearly as sensitive as the brain. If you take high amounts of HDACi for a long period of time, you will arrest the cell cycle even. This is how HDACi are used to kill cancer. Most healthy cells can handle this, however. At the dosages we'd be taking them at the cell cycle won't be arrested... not even close. We just need enough increase in transcription to prioritize the present when it comes to transcribing memories. This is how children are able to learn and adapt so quickly... one of the reasons HDACi are described as "turning back the clock" on memory, or "feeling like a kid again."
To address your third question... The first paragraph is actually wrong. HDAC indirectly affects many things, neurotransmitters and receptors included, but this is nowhere near how it works. This is part of why it's so hard to wrap your head around at first... trkb, nmdar, ca channels, whatever you wanna talk about neurotransmission-wise in a cell above CREB, this isn't how HDACi works. It works at the transcription level by holding open transcription. This is what heightens "resilience," as you say. This is also how exposure therapy is actually brought to work by using HDAC inhibitors. Without HDAC inhibitors, it can be extremely hard for exposure therapy to work for a lot of things, especially PTSD. Even if it does work, the chance of relapse is incredibly high. This is because our fear centers in our brain and fear memories were built to keep fears alive for our protection. They're incredibly hard to overcome, and the only way to do so is to hold open the window of transcription when a memory is reactivated long enough for the present to become stronger than the past. The past will still be remembered, technically, but when you bring the memory up after your HDAC session, the most recent, non-fear-inducing memory will be what you feel.
In my experience, since HDACi helps form long-term memories in general, it has helped me learn how to act socially very much so. Once it gets rid of the fears of the past that used to get in your way, you're free to act in the present however you please, and almost everything is remember in incredible detail because you're on the HDAC. It's really amazing, and I can't wait to get more vorinostat.
Last question of yours... I don't think StevesPetRat read enough of the anecdotes or my posts because HDAC inhibitors do not bring up the past. It's not therapy through normal cognitive pathways, it's therapy through physical changes in transcription, and to the watcher, you, consciousness, it looks like the fear disappeared and you're left with nothing. Not a bad feeling of nothingness felt with the shitty medications doctors use to blunt people's emotions, but an unencumbered state of being from no longer being controlled by your past negative emotions and having the room to feel other emotions in a situation once again, as if you were a child.
#214
Posted 13 November 2016 - 09:08 PM
Hey musicman,
I posted in your PRL thread on reddit under the name "namesure" (an acronym of username, couldn't think of anything better at the time). I am amazed at how you are take your time to answer every question in such great detail. Thank you very much for that! What neuralis said in the post previous to yours sounds like a combination of the theories proposed by Dr John Sarno, and Ashok Gupta. Although initially formulated as theories of chronic back pain and chronic fatigue syndrome, they have been later extended to included anxiety. According to Dr Sarno, when neuralis says "So we create this small anxiety to keep us from venturing into this dangerous territory of our own minds", the words "small anxiety" can be substituted by "pain" or any number of other functional illnesses, like depression, IBS, chronic fatigue, fibromyalgia, etc.
I will be waiting with interest should you guys wish to reveal your own stories with anxiety and vorinostat, including dosing, etc. My main concern was whether vorinostat can be applied, without therapy, to generalised anxiety, which has snowballed beyond recognition from an initial stressful situation and has become debilitating. And I think the answer that seems to glean through a number of posts in this thread is a resounding "yes". Or, put another way, the exposure therapy in this case begins by itself every day upon waking up, because the state of anxiety is almost continuous.
Edited by tolerant, 13 November 2016 - 10:05 PM.
#215
Posted 16 November 2016 - 11:50 PM
So, ok, Vorinostat is capable of a lot of things. Can it be used to get rid of:
- fears of difficult conversations?
- fear of approaching women in clubs/bars?
- getting rid of anxiety/fear associated with talking to authorities inside the organization? (e.g. reporting to boss)
Trying to find practical applications
#216
Posted 17 November 2016 - 01:08 AM
So, ok, Vorinostat is capable of a lot of things. Can it be used to get rid of:
- fears of difficult conversations?
- fear of approaching women in clubs/bars?
- getting rid of anxiety/fear associated with talking to authorities inside the organization? (e.g. reporting to boss)
Trying to find practical applications
Yes, these are the types of things vorinostat can be used for. I have read of HDAc inhibitors getting rid of shyness. It doesn't change your personality, but it gets rid of the fears and anxieties that have built over a long time associated with certain events/situations.
#217
Posted 17 November 2016 - 03:35 AM
Are the healing qualities a permanent result of administering the dosage or does on need to keep taking the dosage on a regular basis?
#218
Posted 17 November 2016 - 05:24 PM
Pop over to the HDAC Discussion thread or Vorinostat Group Buy thread for more info, but to answer simply the effects from vorinostat become permanent either through repeated sessions of low dosages of 15mg to 50mg, or through one session of a regular dosage, which would be from 50mg to 150mg. This is because it acts through increasing transcription directly, independent of neurotransmitters, receptors, transporters, or any other pathways upstream of CREB in the cell. Never dose daily or in amounts above 150mg or you may arrest the cell cycle and increase the possibility of side-effects.
#219
Posted 18 November 2016 - 04:47 AM
I would like to offer couple of insights derived from my personal experience with anxiety disorders and Vorinostat.I've come to learn that anxiety is always an result of some old emotion or thought that hasn't been properly integrated. We may experience something that at the time is so overwhelmingly intense we just can not put it into it's proper perspective. So we set it on the side to be dealt with later. This doesn't change the content of what we have to experience and the thought of facing it may be as terrifying as it was actually to experience it. So we may postpone facing what we must indefinitely. So we create this small anxiety to keep us from venturing into this dangerous territory of our own minds. In effect we have become afraid of being afraid. Over time we are feeding this small anxiety that keeps on growing until it may even outgrow the original fear. So we start avoiding our anxiety. We have become afraid of the fear or being afraid. Though it doesn't necessarily have to be fear we are avoiding. It may as well be sadness, anger or even certain kind of happiness we are trying to avoid facing. This is what is in my mind is the essence of neuroticsism. Anxiety disorder can consist of hundreds of such unfelt emotions. The only way to recover is to go through all the protective layers we have created and feel what we have denied ourselves to feel.Easier said than done.And this is where Vorinostat may make all the difference. At least it has done it for me. It seems to remove all this unnecessary anxiety so that the underlying emotions can be dealt with and finally made peace with. The only way to beat your fear is to become best friends with it. When there's no anxiety about feeling fear, I find it is possible to stay present to the fact that at the moment I may be scared shitless at the prospect of doing something, acknowledge my fear in its totality and reassure myself that even though I'm feeling like I am about to die from anxiety I am actually safe. From this point it is possible to act despite being afraid and if you do it enough times with favorable results soon you will learn that there is no reason to be afraid of this particular thing. You will have your own experience to back it up. You can not grow if you are not willing to look your fear into its eyes.There are of course many other layers and aspects to effective recovery work, but I believe that Vorinostat combined with deep analytical therapeutic process and balanced body work is as close to panacea for non organic mental disorders as we are going to get.
Hi neuralis,
Thank you for sharing your experience. May I ask a few questions as follows:
1. Since you talk about "hundreds" of emotions, is it fair to assume that you did battle with a generalised type of anxiety, or at least an anxiety where you couldn't readily identify the triggers and the whole experience just morphed into a general type of discomfort?
2. How many times did you dose and what were your dosages?
3. Did you follow any cognitive or behavioural process before, during or after taking vorinostat and, if so, how did it affect the outcome?
Thanking you in advance.
tolerant
#220
Posted 18 November 2016 - 04:52 AM
I would also like to know the answers to these questions. Also, did you experience any side-effects? Anything counterproductive?
I would like to offer couple of insights derived from my personal experience with anxiety disorders and Vorinostat.I've come to learn that anxiety is always an result of some old emotion or thought that hasn't been properly integrated. We may experience something that at the time is so overwhelmingly intense we just can not put it into it's proper perspective. So we set it on the side to be dealt with later. This doesn't change the content of what we have to experience and the thought of facing it may be as terrifying as it was actually to experience it. So we may postpone facing what we must indefinitely. So we create this small anxiety to keep us from venturing into this dangerous territory of our own minds. In effect we have become afraid of being afraid. Over time we are feeding this small anxiety that keeps on growing until it may even outgrow the original fear. So we start avoiding our anxiety. We have become afraid of the fear or being afraid. Though it doesn't necessarily have to be fear we are avoiding. It may as well be sadness, anger or even certain kind of happiness we are trying to avoid facing. This is what is in my mind is the essence of neuroticsism. Anxiety disorder can consist of hundreds of such unfelt emotions. The only way to recover is to go through all the protective layers we have created and feel what we have denied ourselves to feel.Easier said than done.And this is where Vorinostat may make all the difference. At least it has done it for me. It seems to remove all this unnecessary anxiety so that the underlying emotions can be dealt with and finally made peace with. The only way to beat your fear is to become best friends with it. When there's no anxiety about feeling fear, I find it is possible to stay present to the fact that at the moment I may be scared shitless at the prospect of doing something, acknowledge my fear in its totality and reassure myself that even though I'm feeling like I am about to die from anxiety I am actually safe. From this point it is possible to act despite being afraid and if you do it enough times with favorable results soon you will learn that there is no reason to be afraid of this particular thing. You will have your own experience to back it up. You can not grow if you are not willing to look your fear into its eyes.There are of course many other layers and aspects to effective recovery work, but I believe that Vorinostat combined with deep analytical therapeutic process and balanced body work is as close to panacea for non organic mental disorders as we are going to get.
Hi neuralis,
Thank you for sharing your experience. May I ask a few questions as follows:
1. Since you talk about "hundreds" of emotions, is it fair to assume that you did battle with a generalised type of anxiety, or at least an anxiety where you couldn't readily identify the triggers and the whole experience just morphed into a general type of discomfort?
2. How many times did you dose and what were your dosages?
3. Did you follow any cognitive or behavioural process before, during or after taking vorinostat and, if so, how did it affect the outcome?
Thanking you in advance.
tolerant
#221
Posted 18 November 2016 - 06:42 AM
This is a question to everyone who has taken vorinostat for anxiety: did you at the same time as taking vorinostat take a GABA agonist (e.g. a benzodiazepine) or a calcium channel blocker (e.g. pregabalin) and, if so, did it effect your tolerance/dependence on these drugs?
#222
Posted 18 November 2016 - 05:32 PM
#223
Posted 19 November 2016 - 03:59 AM
neuralis,
Thank you so much for sharing your experience. I admire your bravery in facing your fears. I think you've answered many of the questions people may have about vorinostat and anxiety. The questions that come to mind which I would like to direct at you and all other people who have experience with vorinostat are the following:
1. Did every dose of vorinostat help in some way or were there doses that had no effect?
2. I understand that the transformative experiences preceded by doses of vorinostat which you described gave you relief by lowering your overall level of anxiety. What about other doses? Did they remove fear associated with a specific trigger or did they also provide overall relief?
Thanks,
tolerant
#224
Posted 21 November 2016 - 09:44 PM
#225
Posted 22 November 2016 - 05:40 AM
Thank you for relating your experience @neuralis. It sounds like a pretty impressive and effective drug so far.
I put myself into the current groupbuy and I hope I'm not derailing this thread at all , but I've had severe GAD for most of my life as well as panic disorder and ptsd, and the thought of eliminating all this somehow is exciting , yet strangely it also brings up a lot of fear in that when you've had something for so long that's a huge part of your life, personality and mannerisms, who or what do you become when it's suddenly removed? Especially if you've had it from a pretty young age like I have.
What fills the void that gets created and where does all that nervous anxious energy move to? It's as though you may have to learn to retrain yourself to be a somewhat normal person. Kind of like a form of stockholm syndrome, you've lived with the enemy known as anxiety for so long that you might not know what to do or be without it ?
#226
Posted 22 November 2016 - 02:46 PM
stillwater, this was one of the weirder, more interesting things during my experience, and something I read also in I think tree's? experience report. When it first hits you that this anxiety is gone there is a slight surprise and a feeling of sort of missing it, because you identified with it. I'd imagine the longer you've lived with a certain anxiety or fear the more it becomes a part of you and the harder it will be to adjust when it's all of a sudden gone. In my experience, and the way tree (i hope it was actually tree, someone in this thread in the past...) wrote about it, once it was actually gone, and once I realized it was actually gone, I actually welcomed it because there was so much room to fill that space with what I've always felt was "the real me" underneath the anxiety. It is similar to how neuralis said "I believe at first it is necessary to shave of the top of the anxiety before the components start to separate out and more targeted approach becomes available."
As HDAC inhibitors do not intrinsically change your mood or basic personality, and in fact enhance memory and memory formation while removing the anxieties and fears surrounding them, it seems, and I felt, that they are a very forgiving and overall helpful compound, not only for removing the fear and anxiety but creating a new life experience for yourself as well. The mechanism of vorinostat, I feel, really carries you safely from beginning to end, not dropping you somewhere in the middle. It is like neuralis said, remaining conscious of what you are doing, and trying to do mental work and being aware while you are doing vorinostat sessions is helpful and important. The vorinostat helps you remember and apply everything you try and learn during the session after the anxiety is stripped away, so the next time you're in that situation you have an entirely new mindframe you can work with in that situation without changing "who you are." Similarly to how neuralis said, you are the one doing the work and growing, and the HDAC inhibitor just gives you the tools you need to not only get past the anxiety and fear but really remember and solidifies what you learn while you do the work of navigating post-anxiety/post-fear space.
#227
Posted 22 November 2016 - 02:47 PM
Accidental second post so I'll just edit it.
I was thinking earlier, though, that it could be very helpful in some instances to go to therapy while on vorinostat, because bringing up situations in the mind is just as effective as experiencing them in real life when it comes to vorinostat. A session where certain topics are explored more thoroughly with a psychologist, where they could ask questions or find solutions that you wouldn't even think of, could be very useful in reaching deep fears and anxieties, and, after vorinostat releases the fear/anxiety, quickening the process of resolution and repair after a sort of back and forth with a psychologist.
I plan on using meditation more with my next batch, and I suppose this could also be done with a trusted friend, where you have someone or some agent there to help you think of different perspectives/other avenues of thought. In my experience, vorinostat alone helped me do this in real life situations as well, sometimes without me even realizing it. I read of one person having his shyness disappear, and he realized it when he just started talking to people all of a sudden lol
Edited by musicman4534, 22 November 2016 - 02:54 PM.
#228
Posted 22 November 2016 - 09:29 PM
@musicman4534 Thank you for the well thought out reply. A day later and I think of my post as something someone with an anxiety disorder would post, anxiety over losing anxiety, haha. I agree with using therapy to get through it and providing a solid base for the future. I do look forward to this.
#229
Posted 23 November 2016 - 03:31 AM
Hahaha that is the funny thing about this sometimes
I just nerd out over some compounds and think of all the ways you could use it, like what if we used vorinostat skydiving that would be beneficial right? Lol conquer fear of death
#230
Posted 23 November 2016 - 09:42 PM
Hahaha that is the funny thing about this sometimes
I just nerd out over some compounds and think of all the ways you could use it, like what if we used vorinostat skydiving that would be beneficial right? Lol conquer fear of death
I'm sure I don't need to tell you this, but what you propose would be going to far. There are some very rational fears (like a healthy fear of death) that are given to us by evolution. I also read someone mention that they gave some vorinostat to a girl at around exam time which made her completely anxiety-free, either before or during her next exam. If it's anxiety which interferes with her preparation for the exam, that is fine. But if it's healthy anxiety that drives her on, that would also be excessive and counterproductive.
I would also advocate that people begin dosing vorinostat with some sort of therapy lined up, and also start with small dosages (i.e. 10 mg) before they know how it affects them.
On another matter, I've got a question to those who have tried vorinostat (currently only musicman and neuralis are answering these, which I appreciate) : When you have taken vorinostat and then confront a situation which causes you fear/anxiety, does the fear/anxiety build up in a usual way, before it "disappears". That is, do you have to to endure it and push through it before you feel the liberating effects of vorinostat? Or does the "nothing" feeling come on as soon as you face your fear/anxiety?
Edited by tolerant, 23 November 2016 - 09:45 PM.
#231
Posted 25 November 2016 - 04:52 AM
#232
Posted 25 November 2016 - 06:15 PM
So for the purposes of fear removal, would 50mg 3x per week be sufficient? I don't have anxiety but wouldn't mind a boost in confidence. Or am I expecting too much? The main reason I'm asking is so that I can decide how many grams to buy.
#233
Posted 25 November 2016 - 06:32 PM
I personally have used dosages ranging between these two numbers and only a dozen doses in all. It's too early to tell if my anxiety reducing benefits will be permanent. But I would like to reiterate what others have mentioned by saying that it is not something you need to dose all of the time, or take in any way similar to a prescribed medication.
There is probably some refined dosage somewhere that would optimize helpfulness of the compound to each individual. But we have nothing official here to go by. Just the blind experiments of internet lurkers like myself desperate for some kind of relief.
This said, my personal recommendation is based only on my experience.
Begin by taking a small dose. Perhaps 20mg. Buy at least two grams to begin. This stuff is unbelievably hard to come by (which still surprises me, considering how many more dangerous/less helpful substances are so readily available in places like this).
If you benefit from the Vorinostat, it would be nice to have a little extra lying around for a similar friend in need.
#234
Posted 25 November 2016 - 08:28 PM
Hahaha that is the funny thing about this sometimes
I just nerd out over some compounds and think of all the ways you could use it, like what if we used vorinostat skydiving that would be beneficial right? Lol conquer fear of death
I'm sure I don't need to tell you this, but what you propose would be going to far. There are some very rational fears (like a healthy fear of death) that are given to us by evolution. I also read someone mention that they gave some vorinostat to a girl at around exam time which made her completely anxiety-free, either before or during her next exam. If it's anxiety which interferes with her preparation for the exam, that is fine. But if it's healthy anxiety that drives her on, that would also be excessive and counterproductive.
I would also advocate that people begin dosing vorinostat with some sort of therapy lined up, and also start with small dosages (i.e. 10 mg) before they know how it affects them.
On another matter, I've got a question to those who have tried vorinostat (currently only musicman and neuralis are answering these, which I appreciate) : When you have taken vorinostat and then confront a situation which causes you fear/anxiety, does the fear/anxiety build up in a usual way, before it "disappears". That is, do you have to to endure it and push through it before you feel the liberating effects of vorinostat? Or does the "nothing" feeling come on as soon as you face your fear/anxiety?
Hey tolerant,
According to the studies any anxiety or fear you may have in the present toward the situation at hand is not affected by vorinostat, just your past fears and anxieties tied to the memories that are built over time and brought up. This is seen in the fact that vorinostat and other HDAC inhibitors can also help someone learn a fear linked with a trigger, as in every time a mouse goes to eat it gets shocked, so it learns to fear eating (sad I know). The power in this for humans is that it gives us the power to live completely in the moment, and completely revise the feelings we have toward a situation. This is akin to how neuralis talked about vorinostat giving you the power or freedom to do the inner work necessary to complete a change in mindframe about a situation. The fear extinction happens, you are free in real-time to reassess the situation however you'd like, and then those are recorded using HDAC inhibitors' memory-enhancing effects. So, vorinostat doesn't blunt any emotions, even fear, it just prevents them from spiraling out of control or getting blowing out of proportion.
In my experience, the nothing feeling is instant. The fears don't have to surface to be hashed out, just the memory or experience. The interesting thing is that vorinostat helped me remember key moments in my last more vividly, but let me look at them deeper/in a new way due to there not being a lot of emotion tied to them. All the emotions didn't get dragged up with them, so I was able to kind of rethink through things. I did feel things about them, though, just not the same old feelings that always came up. New, fresh, workable feelings it felt like.
#235
Posted 25 November 2016 - 09:13 PM
So for the purposes of fear removal, would 50mg 3x per week be sufficient? I don't have anxiety but wouldn't mind a boost in confidence. Or am I expecting too much? The main reason I'm asking is so that I can decide how many grams to buy.
And it seems like my long-winded response totally ignored your question.
Despite an enormous decrease in anxiety, I'm still horrible at paying attention, sometimes.
I can't say wether or not someone without anxiety can really benefit from Vorinostat. That it in itself could give someone a confidence boost. But I can say that for me, it has vastly improved my life confidence by demolishing a pervasive, base-level of anxiety from the foreground of my mind.
I find my mind still wading toward catastrophic though sequences, out of 34 years of ingrained habit. But somehow, because of Vorinostat and an establishment of healthier living habits, I'm able to take a different path in my mind almost as soon as the fear-based thought sequences arrive. It's like my parasympathetic nervous system has a better ability to engage and I feel less threatened by thoughts of the future, and what others may or may not think of me. This has resulted in a definite increase in confidence and fulfillment of living.
But it's only a result of Vorinostat helping me to recover slowly from something I have always thought was "wrong" with me.
#236
Posted 26 November 2016 - 01:00 AM
...Below is a collection of quotes from this thread with my comments in italics which show that there seem to be two divergent views: (1) that you need successful extinction therapy for HDACi to work (I've omitted the studies referred to in this thread that show that without successful extinction training, the fear memory may actually strengthen!), and (2) that attempting to be calm while taking HDACi may actually ruin the fear extinction process. Very confusing and somewhat risky.
...
StevesPetRat: "But it sounds like one has to face the fear and then become unafraid during the treatment which if I could do I wouldn't really need the help..."
Exactly.
Last question of yours... I don't think StevesPetRat read enough of the anecdotes or my posts because HDAC inhibitors do not bring up the past. It's not therapy through normal cognitive pathways, it's therapy through physical changes in transcription, and to the watcher, you, consciousness, it looks like the fear disappeared and you're left with nothing. Not a bad feeling of nothingness felt with the shitty medications doctors use to blunt people's emotions, but an unencumbered state of being from no longer being controlled by your past negative emotions and having the room to feel other emotions in a situation once again, as if you were a child.
That was before I had tried it. It's definitely a lot easier to use than I had imagined.
#237
Posted 26 November 2016 - 10:59 AM
In my experience, the nothing feeling is instant. The fears don't have to surface to be hashed out, just the memory or experience. The interesting thing is that vorinostat helped me remember key moments in my last more vividly, but let me look at them deeper/in a new way due to there not being a lot of emotion tied to them. All the emotions didn't get dragged up with them, so I was able to kind of rethink through things. I did feel things about them, though, just not the same old feelings that always came up. New, fresh, workable feelings it felt like.
Hey musicman,
Thanks for replying. I don't want to labour this point too much, but earlier you wrote that you think it might be more effective to plunge yourself into a fear-provoking situation rather than just to meditate about it. And you gave an example of a fear of being in crowded places. Now you're saying that it's not the fear that has to be hashed out, but the memory. But surely someone who feels uncomfortable in crowded places would not have a memory of the first time they found themselves in a crowded place and what it was that made them feel uncomfortable, would they?
I guess what I'm getting at is that a lot, maybe most, people taking vorinostat will be taking it for anxiety relief, i.e. they will be taking it while experiencing anxiety. They will be taking it because they can't get rid of this anxiety and feel really bad. Sure, it is a bad idea to take vorinostat while experiencing some new traumatic situation. But short of that, according to the experiences shared here, vorinostat seems to get rid of anxiety like a benzo would, with the difference that with vorinostat the anxiety may disappear for good. This is not necessarily supported by science, but that seems to be the effect.
Lunast, can you maybe weigh in? Haven't yet heard from you on this point?
Edited by tolerant, 26 November 2016 - 11:55 AM.
#238
Posted 26 November 2016 - 03:22 PM
I touch on the mechanics of this in my original article on Reddit.
Essentially, every single bit of cognition in this case can be thought of as a memory... the fear, the trigger, and the original fear-provoking pains are all memories linked to each other in the brain, and also exist in different parts of the brain. When one is pulled up, the others are pulled up to varying degrees depending on the strengths of synapses connecting them. In some cases, even if the original event is muddied, buried or forgotten, what can remain are the fear memories and the triggers, which pop back up throughout life whenever the trigger is experienced, and can even be strengthened over time. When you experience this trigger on vorinostat, something that doesn't intrinsically hurt you but made you feel hurt in the past (something like childhood abandonment), every memory, the fear, the trigger, the pain-inducing events, all past experiences of it, whether you're conscious of them all or not in that moment, are brought up in your brain. Instead of transcription closing before the fear/anxiety can be re-analyzed, re-written and updated, vorinostat holds transcription open long enough for the present moment to be written in stronger than any past memories, including the past fear, trigger and event memories. When it comes to what we would call the actual memory of the event, the way we remember memories (separate pathways for every memory) allows us to still recall everything about the event after a vorinostat session, but fear goes through very specific pathways in the brain, and there can only be one memory high-lander when it comes to fear-inducing memories. When the current non-intrinsically-fear-inducing memory/experience is written in stronger than the past normally-fear-inducing memories, you don't get the fear from the past memories, or some of the past fear mixed with the current stillness... fear only listens to the strongest memory, this is how fear pathways work in the brain, so because vorinostat puts the present moment at the top, you will only feel the fear that might or might not be induced in the present moment, right there, while on vorinostat. Just like people have described in their experience reports.
There are people that have triggers and fears from deep memories they can't even remember, and this is the beauty of an HDAC inhibitor like vorinostat... It doesn't matter if you remember the original occurrence or not, because as long as you experience the trigger, every memory and fear that is associated with it does pop up to some degree or another in your brain, and any unnecessary fear that pops up with them is able to be overwritten. The updating of fear is under your consciousness, but the memories that pop up are still seen and can be evaluated by your consciousness. This is why I say that it is not necessary to "push through or learn through the fear" in order for it to disappear, it disappeared the moment it was brought up, but all the memories associated with the trigger and old fears are up for grabs to be seen fresh and learned from (in fact HDACis can help you remember fears long past). I'll try to draw a map of this on paper so it's easier to see. One doesn't have to reevaluate or try to look at the memories differently, but when you take vorinostat you'll see that it's kind of a natural thing to do when all of a sudden you're free of the fear and anxiety and you're left with this clear moment and memories. Like neuralis walking into the store not anxious of the people around him and he tears up... this is a very telling moment of the play between the fears having already been deleted, yet the mind and analysis of memories is just catching up.
I say to jump into a situation just because going directly into the situation will likely bring up more memories and bring them up more strongly and for longer compared to meditation, in my opinion. Also, the science does show the fear will stay away for good, and this is why researchers are so avidly studying HDACis for PTSD. I also wouldn't say vorinostat shouldn't be taken in a newly traumatic or fearful situation, because vorinostat will help you learn. What legitimately creates fears in adults is vastly different from what causes the beginnings of fears and anxieties in children and adolescents, first, and second, being on vorinostat during the situation will allow a more wholesome picture to be painted and remembered by your mind, not just a flash of fear and pain like usual. If you think back to the moment five minutes later, an hour later, two hours later and still feel fearful while on vorinostat, chances are there's some usefulness for that bit of fear. The different with being on an HDACi is that the fear will not balloon, and not become stronger than it needs to be. It enhances learning in general, so I'd say just about any situation, fear-inducing or not, can be enhanced by being on an HDACi. Like neuralis said about the anxieties that were present and then enhanced by marijuana, they were there to a degree before the pot all along, the pot just enhanced them, and then when he was on vorinostat they were taken care of even if the original moments or causes have not been outwardly remembered or identified.
Some of the persistent anxietes we have likely manifested through a combination of a couple weird experiences in infancy, being reinforced in subtle ways through childhood, and finally being reinforced simply through the trigger being experienced throughout time even after the original cause of the fear has been forgotten/buried. This ballooning is artificial and is meant to keep us safe from predators in the wild, but with us it just manifests as an annoying or even crippling anxiety, which can thankfully be taken care of by an HDACi.
#239
Posted 26 November 2016 - 03:46 PM
Edited by neuralis, 26 November 2016 - 04:07 PM.
#240
Posted 28 November 2016 - 01:46 AM
As someone with OCD, I'm wondering if it'd be more effective to exterminate our fear of superstition in general rather than targeting specific triggers while on an HDACi. Would that be efficient?
Perhaps it'd address many problems at once, in theory it'd possibly be attacking the nature of the disorder itself?
Edited by gedanken, 28 November 2016 - 01:51 AM.
Also tagged with one or more of these keywords: cl-994, epigenetic, anxiety disorder, trauma, ptsd, memory, add, group buy, anxiety
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