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Vorinostat

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

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#361 stefdude

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Posted 30 September 2018 - 02:32 PM

Tried out my Vorinostat from Stangelove.

 

No doubt about it, this stuff works. I waited a long time and was honestly very skeptical about the effects claimed in this thread and other websites. But after trying 100 mg split between sublingual and intranasal. The fear I approached is gone. I went directly into the feared situation and initially, I could perceive my previous feelings, but it felt different. I know now what people mean by it's "subtle". I tested it the next day and the normal feelings I'd have never appeared, just a sense of "clarity".

 

This is a powerful substance. 

Was your first test at 100mg?Isn't it a bit high?

 

Also to everyone, do you think a beta blocker would help the memory manipulation the Vorinostat does or will it weaken the effect since you will be experiencing less anxiety due to the Beta blocker?



#362 cbkid

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Posted 01 October 2018 - 05:10 AM

Was your first test at 100mg?Isn't it a bit high?

 

Also to everyone, do you think a beta blocker would help the memory manipulation the Vorinostat does or will it weaken the effect since you will be experiencing less anxiety due to the Beta blocker?

 

I have a similar question. Is it ok to use an anxiolytic with Vorinostat? Or are you supposed to feel the fear while on it, to be able to overcome it? 



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#363 Rtttt100

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Posted 01 October 2018 - 06:50 AM

Was your first test at 100mg?Isn't it a bit high?

 

Also to everyone, do you think a beta blocker would help the memory manipulation the Vorinostat does or will it weaken the effect since you will be experiencing less anxiety due to the Beta blocker?

 

Go big or go home. Haha, it probably was a bit high, the next time I try will be lower to see if that much is needed.

 

I tried low dose Propranolol (10mg) the first time. Still had the fear extinction effect, but I have no other experiences to contrast from.

 

I have a similar question. Is it ok to use an anxiolytic with Vorinostat? Or are you supposed to feel the fear while on it, to be able to overcome it? 

 

From my experience, using a low dose beta-blocker didn't prevent the fear from being overcome. In a way, Vorinostat is it's own "subtle" anxiolytic. The following days after there is no anxiety in those situations.



#364 CalmAmygdala

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Posted 02 October 2018 - 10:09 PM

Has anyone had a negative experience with vorinostat making their anxiety worse, or furthering entrenching their fear based memories?

I’m afraid this may have happened to me, I did one dose at 50-75 mg and went to class. I was anxious during class (I was on other compounds, I really regret it), and I am now feeling old anxiety/fear I thought I had gotten rid of. I’ve been experiencing it now consistently for 3 weeks and I’m worried it will stay. Anyone experienced this or have any advice?

#365 stefdude

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Posted 03 October 2018 - 08:23 AM

Has anyone had a negative experience with vorinostat making their anxiety worse, or furthering entrenching their fear based memories?

I’m afraid this may have happened to me, I did one dose at 50-75 mg and went to class. I was anxious during class (I was on other compounds, I really regret it), and I am now feeling old anxiety/fear I thought I had gotten rid of. I’ve been experiencing it now consistently for 3 weeks and I’m worried it will stay. Anyone experienced this or have any advice?

 

I've read only a couple of those reports.I believe you won't get any other advice other than undoing what happened with the same method, try vorinostat again but:

1)Chech your source.Is it legit and pure vorinostat?Is your dosage oral or sublingual?

2)Read the group buy thread and this one: https://www.longecit...ntion-problems/

For the second ctrl-f searching for vorinostat and hdac.You'll find some detailed success stories.The mindset is to fight an irrational fear, trying to be as focused as you can manage, telling yourself what would the proper reaction would be, if you didn't have that fear.I suggest you try the same scenario in meditation first and another day exposure therapy.I don't know if it's needed but try to be mindful, whether you experience anxiety or not you should be able to talk to yourself with logic.I don't see why that would fail, I've read almost all vorinostat reports, almost everyone has success.

 

Remember I told you you should fight an irrational fear?That fear has a strong element of memory-trigger-emotion buildup.You wouldn't take vorinostat and to to an area that you could be killed because the fear is not memory related or buildup, it is primary.I suspect the same applies to the normal anxiety one would get from a wrong stimulant or the wrong dosage of it.

 

If the fear is crippling and you are afraid to go against it only with vorinostat try medicating on it first.Or you can take a benzo for a few next exposures in an effort to desolidify the fear, and then try with vorinostat.Keep us updated.


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#366 BlueCloud

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Posted 03 October 2018 - 06:45 PM

I've been reading a bit lately about fear extinction, and there are some interesting new research and theories emerging. Contrary to what we may think , the process of fear extinction doesn't involve erasing the fear memory network  ( or loosening its connections ) in the amygdala, but creating a new memory network ( in the amygdala)  where the memory of that event is now encoded as "safe" or non-threatening. This new memory network inhibits the older one, but the latter still persists.

Unfortunately, it seems that the process of extinction is often linked to the context in which it happened, unlike the original fear memory. In other words, if you got some fearful event involving , say, a spider while sitting under a tree in a forest, the fear will trigger also if you encounter a spider in your living room next to your laptop. Context won't matter.

On the other hand , if you get a process of extinction involving spiders in your therapist office, the context in hard-linked to the spider. You won't fear spiders when you're in a place that looks like your therapists office, but the fear might trigger if you encounter the spider in another context, like in an old attic while dusting a book.

 

There's a lot of research presently trying to find ways to make the fear extinction process independant from the context.

It would be interesting if some of the people here that experimented with vorinostat could report  whether exposure to the same fear in a different context ( than the one they've been in after dosing) reappears or not.

Meanwhile, these articles are definitely worth reading and could give some more clues on how to use vorinostat efficiently. 

I don't know if Strangelove is still selling it, I might give it a try myself ( I have a long history of battling anxiety )

 

At the same time, however, this endeavor has been hampered by misconceptions as to the nature and significance of extinction, which is sometimes characterized as a process of “forgetting” or “unlearning” (implying that the loss of a CR may simply reflect the reversal of the plasticity associated with acquisition) rather than a new learning process accompanied by additional plasticity (e.g., Kitazawa, 2002)

In response to findings such as these, an alternative class of theories was developed that proposes that extinction is a form of new learning that counteracts the expression of the CR Bouton 1993Konorski 1948Pavlov 1927Wagner 1981. In colloquial terms, these “inhibitory” theories suggest that extinction is characterized by the development of a new connection between the CS and US representations that effectively says “now, in this place, the CS no longer predicts shock.” In associative terms, this process is described as the generation and strengthening of a second, inhibitory association between the CS and US representations, which acts in parallel with the excitatory association and directly opposes the tendency of the excitatory association to activate the US representation.

it seems likely that extinction involves a strengthening of connections between those same sensory pathways and a separate, GABAergic population of neurons that acts to inhibit the CR.

From :

"Behavioral and Neural Analysis of Extinction"   https://www.scienced...896627302010644    

 

 

 

 

Curiously, however, extinction produces a relatively transient suppression of fear; conditioned fear responses return under a variety of conditions including after the mere passage of time (i.e., spontaneous recovery) or if the extinguished CS is presented outside the extinction context (e.g., renewal) (Bouton, 1993). This suggests that memories of both fear conditioning and extinction are encoded in the amygdala, and contextual retrieval cues determine which memory is expressed in behavior. 

 

These phenomena indicate that extinction does not erase the conditioning memory, rather it causes new learning about the CS. Indeed, it appears that extinction training yields a new “safety” memory that inhibits retrieval of the fear memory.

Unlike fear memory, the expression of this safety memory is limited by context and time (Bouton, 1993)

 

From "Seeking a Spotless Mind: Extinction, Deconsolidation, and Erasure of Fear Memory".  https://www.scienced...896627311003904

 

 

 

 

Return of extinguished behavior is common following the passage of time (“spontaneous recovery”), when extinguished cues are encountered outside the extinction context (“contextual renewal”), and after presentation of the unconditioned stimulus (“reinstatement”). These effects provide support for the widely held view that extinction is a new form of learning and that conditioning and extinction memories may coexist in distinct neural circuits and be reactivated independently based on environmental or situational factors.

Fear extinction may reduce emotional elements, while leaving other associations (e.g., sensory) intact.

It is widely recognized that whatever is learned in extinction is more fragile than the original associations trained through CS-US conditioning, as evidenced by findings that the acquisition CR returns in a variety of situations. This apparent inability to abolish the memory of a conditioning experience may be adaptive: in nature, signals for danger may rarely coincide with actual threat. On the occasion when threat does exist, however, a rapid defensive response could promote survival. From this perspective, the fragility and transience of extinction seems appropriately balanced against the strength and persistence of conditioning.

From : "Rethinking Extinction "       https://www.scienced...89662731500817X

 

 


Edited by BlueCloud, 03 October 2018 - 06:52 PM.

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#367 jacobjerondin

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Posted 04 October 2018 - 01:20 AM

Wow, BlueCloud you deserve a medal for that amazing explanation. HDAC inhibitors like vorinostat are supposed to be amazing for memory, so I guess a key part of the mechanism is deeply ingraining a new memory where fear isn't present.

 

What you said doesn't explain the fearlessness that some people seem to be reporting after they take vorinostat, tho that could also be placebo to some degree.

 

I have a hunch that certain PDE inhibitors would combine excellently with vorinostat, as they regulate the amygdala in certain ways. Kanna and ibudilast are examples of two promising ones for this purpose.

 

 

 

On another note, has anyone successfully used this stuff for fear of talking to beautiful women/approach anxiety (which is highly linked to fear of rejection) in general? That's what I'm really hoping to use my vorinostat for, once it gets here. I don't have that many specifically moments where I can think of my anxiety in this area starting, it's just been pretty bad for many years now and I haven't been able to move past it very well.


Edited by jacobjerondin, 04 October 2018 - 01:33 AM.


#368 stefdude

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Posted 10 October 2018 - 01:58 PM

I've seen many of you use it sublingually and/or intranasally instead of orally.According to wikipedia the bioavailability (of oral I assume) is 1.8-11%.Could you be using extremely higher dosages (probably in the anti cancer range) than what you think?


Edited by stefdude, 10 October 2018 - 01:58 PM.

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#369 jacobjerondin

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Posted 13 October 2018 - 04:39 AM

I've seen many of you use it sublingually and/or intranasally instead of orally.According to wikipedia the bioavailability (of oral I assume) is 1.8-11%.Could you be using extremely higher dosages (probably in the anti cancer range) than what you think?

 

Ayyye stefdude I'm assuming you're same guy from pherotruth? I'm pherophreak on that forum (still not sure if pheromones actually work or not after trying a lot haha).

 

Anyway, that's a great point you raised and something we all really need to keep in mind. Using vorinostat in the anti cancer doses is probably a very unwise idea! So we need to remember to stick to the oral dosing or use very small doses sublingually/intranasally.



#370 stefdude

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Posted 13 October 2018 - 12:21 PM

*Stupid phone deleted the rest of my post after the first line*

 

Yep, same guy ;)

PM me if you want advice on pheros, some products are clearly superior, many are mediocre.I'll suggest a few depending on what effect you are looking for.

 

As for Vorinostat I ended up using 15mg sublingually and 15mg intranasally (total 30mg) and it worked wonderfully.Not a huge fear of anything but it clearly resetted everything back to zero.

I took the risk despite my previous concerns but I still want to know what are the differences in bioavailability.Not many oral reports, very little info on dosage, food or not, etc.


Edited by stefdude, 13 October 2018 - 12:27 PM.

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#371 jacobjerondin

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Posted 07 November 2018 - 08:14 AM

Thanks man, I'll PM you sometime soon when I have more time.

 

Was everyone's vorinostat just in a small white bag taped to a piece of paper folded into thirds? I believe that I received mine finally (I think customs got the first one I was sent) but I just want to make sure it is actually the vorinostat that came in and not something else since it's completely unlabelled.

 

I've done some sketchy things, but consuming a completely unlabelled white powder shipped over from Europe will have to be one of the sketchiest, haha. So I just want to be safe, any help is greatly appreciated.



#372 stefdude

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Posted 09 November 2018 - 01:08 PM

Even if someone doesn't have a big irrational fear or anxiety it's funny how you get used to minor anxieties/fears and you realize this when you are eliminating them completely while under the effect of Vorinostat.Very interesting.



#373 celticlion76

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Posted 14 November 2018 - 08:40 PM

Does anyone know If Strangelove has another batch available, or if there have been any updates?


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#374 Forever21

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Posted 26 November 2018 - 05:04 AM

Does Vorinostat lower sex drive/libido or make affects erection?


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#375 theobromananda

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Posted 29 November 2018 - 04:48 PM

Disclaimer: I am quite sensitive and have a somewhat clean lifestyle with intensive meditation and eastern adaptogens.

 

Does no one have any comment about intelligence-enhancing qualities? I am not talking about the studies but experiences - I took too large doses nasally in the beginning, but 8mg nasally now feels slightly psychedelic, like there is increased access to larger parts of the (body-)mind which are normally closed off. Secondary to the anxiolytic effects? The body also feels lighter similar to other psychedelics and the mind goes very quiet; really good for introspection.



#376 Falconranger123

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Posted 01 December 2018 - 11:32 PM

Does StrangeLove still carry vorinostat. I am quite interested in testing it’s properties after doing some research on this compound. Or does anyone know of any other head inhibitors that are useful for fear extinction ?

#377 Strangelove

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Posted 05 December 2018 - 02:35 PM

On another note, has anyone successfully used this stuff for fear of talking to beautiful women/approach anxiety (which is highly linked to fear of rejection) in general? That's what I'm really hoping to use my vorinostat for, once it gets here. I don't have that many specifically moments where I can think of my anxiety in this area starting, it's just been pretty bad for many years now and I haven't been able to move past it very well.

 

Yes, this is the most success I had with it, I have given a description in the past, I started asking out a few "random" girls when I started using it. 

 

Was everyone's vorinostat just in a small white bag taped to a piece of paper folded into thirds? I believe that I received mine finally (I think customs got the first one I was sent) but I just want to make sure it is actually the vorinostat that came in and not something else since it's completely unlabelled.

 

Sorry for the delayed reply in your PM, as Vorinostat is a prescription drug and I do not want to mislabel it (it is even worst with customs) I did not label it at all.

 

Does anyone know If Strangelove has another batch available, or if there have been any updates?

 

Yes, I still have more but not much, its the same 99.7% purity batch, I third-party tested carefully stored in the freezer. Due to past issues with paypal, I can only accept cryptocurrency for Vorinostat.



#378 theobromananda

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Posted 08 December 2018 - 07:11 PM

In this study, vorinostat was administered intraperitoneally to mouses in successive 5mg/kg(=5/12/mg/kg human equivalent) doses, which reversed early stress-induced visceral hypersensitivity and anxiety behavior. Does someone know anything about the pharmacodynamics of SAHA which could tell me which way of administration would be most similiar to the intraperitoneal injection? Do I have to inject myself to get SAHA into the gut and lumbosacral spine?

 

The implications of this treatment for psychotherapy for early childhood wounds, which are very hard to treat, is immense.


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#379 stefdude

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Posted 17 December 2018 - 07:37 PM

Do you think it needs to be stored in freezer?How fast does it deteriorate, if it does?

Does anyone use oral doses?How much and with or without food?

I believe sublingual has better absorption than intranasal.I haven't used oral in order to save material but I may try it eventually.



#380 Strangelove

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Posted 18 December 2018 - 05:39 PM

Do you think it needs to be stored in freezer?How fast does it deteriorate, if it does?

Does anyone use oral doses?How much and with or without food?

I believe sublingual has better absorption than intranasal.I haven't used oral in order to save material but I may try it eventually.

 

I always store the larger amount I have in the freezer, but it is stable.

 

Sublingual seems to have better absorption than oral for sure, but I have not tried much (just) oral doses, and I cannot comment on this.

 

I will probably do not try it intranasally, but anyone else, "brave" that did already?


Edited by Strangelove, 18 December 2018 - 05:42 PM.


#381 Strangelove

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Posted 21 December 2018 - 04:58 PM

Anyone that is interested I still have some Vorinostat left, please send cryptocurrency ($55 / 2grams) in the new addresses below, and give me your address in a private message.

 

BTC

3DPauCqFMC7R6zdqS4CkJE4upTMrT44D3y

LTC

M9ZeYEqxRPc38ShZJBieiw449udvKckLjx

ETH

0xd00f319c0990497852CE03121AA546CeDc00aF85

 

 



#382 jacobjerondin

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Posted 30 December 2018 - 05:01 AM

I always store the larger amount I have in the freezer, but it is stable.

 

Sublingual seems to have better absorption than oral for sure, but I have not tried much (just) oral doses, and I cannot comment on this.

 

I will probably do not try it intranasally, but anyone else, "brave" that did already?

 

Yeah I was going thru some really bad F-Phenibut withdrawal with a lot of irrational fear so I did a few lines of around 20 - 30 mg I believe. Didn't notice too much acutely but I think it did help me with the fear I was feeling and it seemed to calm me down somewhat too (I read somewhere that vorinostat restores GABAergic sensitivity). Hard to say exactly how strong it was because I was really feeling terrible when I took it but I think it seemed to help.


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#383 sbrown3897

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Posted 01 January 2019 - 10:41 PM

Anyone that is interested I still have some Vorinostat left, please send cryptocurrency ($55 / 2grams) in the new addresses below, and give me your address in a private message.

 

BTC

3DPauCqFMC7R6zdqS4CkJE4upTMrT44D3y

LTC

M9ZeYEqxRPc38ShZJBieiw449udvKckLjx

ETH

0xd00f319c0990497852CE03121AA546CeDc00aF85

Is there a way to pay by credit card?



#384 stefdude

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Posted 07 January 2019 - 11:16 AM

Intranasally works (no burn or other sides related to that RoA), I usually do half sublingually half intranasally.Sublingually may work better though.



#385 Infinite1

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Posted 09 January 2019 - 08:30 PM

Just a forewarning to others, I placed an order with SL on the 21st of last month. Haven't received anything from him nor any responses to my direct messages. 

 

Most likely a lesson learned here, don't purchase questionable things from dubious people on the internet.. such is life.  


Edited by Infinite1, 09 January 2019 - 08:31 PM.

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#386 theobromananda

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Posted 09 January 2019 - 10:45 PM

Just a forewarning to others, I placed an order with SL on the 21st of last month. Haven't received anything from him nor any responses to my direct messages. 

 

Most likely a lesson learned here, don't purchase questionable things from dubious people on the internet.. such is life.  

 

He may very well be very busy with life as he has indicated that in the past, but nothing in my or others interactions and exchanges with him indicate any ill-will or desire to defraud. Buying things on an experimental longevity forum is not Amazon.


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#387 jacobjerondin

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Posted 13 January 2019 - 06:49 PM

Strangelove is a great guy, he is indeed busy and there have been issues with customs as well unfortunately. Don't worry, he'll reship if customs gets to it. I already got mine from him despite the fact that customs seized the first shipment or something.


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#388 Mr Spock

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Posted 14 January 2019 - 11:47 AM

One should be very careful about impugning on someone's honesty on a public forum without good reason. I ordered from him and it did take quite a few weeks, if not longer, to get the goods; considering it's the xmas period being referred to I would have thought that would be taken into consideration....

I certainly closed my business for nearly 2 weeks to have a well deserved holiday.


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#389 Izan

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Posted 14 January 2019 - 11:35 PM

Strangelove is absolutely legit!

 

Will have a large new batch of vorinostat ready in about three weeks.


Edited by izan82, 14 January 2019 - 11:38 PM.

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#390 Infinite1

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Posted 15 January 2019 - 06:50 PM

Strangelove is a great guy, he is indeed busy and there have been issues with customs as well unfortunately. Don't worry, he'll reship if customs gets to it. I already got mine from him despite the fact that customs seized the first shipment or something.

Great! I'm looking forward to working with him, and of course the Vorinostat. These comments are certainly helpful and appreciated. 

 

Wasn't wish to derail the chain, please carry on! :)


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

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