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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

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#1 tree

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Posted 17 February 2014 - 05:31 PM


Let me start at the beginning: I got a damn serious nervous breakdown while, ironically, studying to be a medical researcher. I have had medical problems as a child and my childhood was filled with stress and fear, so that undoubtedly sensitised me for further stress. I suspect I basically always had anxiety disorder but it never expressed itself as much as it did when I finally broke down and spend nearly a year in panic state.

I managed to overcome the panic attacks through meditation in the short time periods in between. As you can imagine I was hardly zen, yet it accomplished immense results. I honestly would never have recuperated as much as I did without meditation. No medication worked as I had hoped, and I was very certain I would become addicted to them had I tried them any longer.

Although I recuperated immensely, this is a very relative accomplishment. I was greatly improved over the completely disabled state I was in yet far, far, really far below the threshold for a normal person. Because I have a remnant of a working mind I managed to finish my education which was already in the final state, I didn't had to do much work yet it was a gargantuan undertaking from my part anyway. I figured things would improve further.

The panic disappeared completely, so did the nightmares, OCD and every other symptom/comorbidity except one: a diminished attention span, near continual stress and inability to relax. Every supplement I tried was a disappointment. They either did nothing, or only lasted a few months tops before I got nothing out of them anymore.

It took a long time, but I finally accepted what quite a lot of psychologists already knew: once sufficiently traumatized the brain holds on to the heightened sense of stress and anxiety and never lets go. It gets inscribed into your epigenetics and becomes your new default mode. The standard psycho therapy is insufficient to get rid of it completely.

There is plenty of research to show that remote (old) memories are stored in the frontal cortex, and that the brain does everything it can to make certain that fear-conditioning doesn't disappear. This makes sense if I was, say, a mouse and my brain made certain I would always be afraid of a predator after my initial encounter. For a human who went through general anxiety it's not particularly useful. I've been unable to continue my chosen career for years now, and although meditation keeps improving my condition, there is a clear ceiling which I can't breach for longer than a few moments, and this only works under good conditions. Perhaps meditation can achieve it one day, but I hardly want to spend my entire life trying to fix said life.

Imagine my interest when I read recent research which showed that a certain chemical can convince the brain to finally let go of learned trauma. PUBMED, Summary

My lifestyle is currently fine: there is nothing that will lead to new traumas. My diet is fine, I exercise. The weakest link is purely the emotional scar left in my mind. I strongly suspect that combined with my meditation, CL-994 can help to finally get rid of my stress-state.

It is however a rather expensive chemical. Aldrich-Sigma offers it at over 115 dollar for 5 mg. At the mid-dose used in the article that would be 10 mg/kg body weight, or 230 dollar per kg body weight. That's a bit much. Luckily there are cheaper sources like this one. Even cheaper sources may exist.

The reason I posted this is probably getting clear: I wanted to try it, but I don't want to risk financial difficulties for what may be another disappointment. If anyone else is interested in purchasing this drug, we could go for bulk, split the cost and save a lot.

#2 datrat

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Posted 17 February 2014 - 06:30 PM

Realizing that there will be a lot of hurdles to overcome; how do we actually get our hands on it at a reasonable price, I would be very interested in joining a group buy to try this.

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#3 tree

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Posted 17 February 2014 - 09:06 PM

There are several options to lower the price further.

There are Chinese labs which are open for negotiation and can produce a chemical at request. It may be worth checking their price ranges. We could also try to get more people in on it; there certainly isn't a shortage of anxiety sufferers.

Another option is to lower the dose. The authors focused on 30 mg/kg, but showed that 10 mg/kg resulted close to the same values of compound in the brain as 30mg/kg. Because of the high cost I wanted to test 10mg/kg. But the authors also tested the bio-availability at 1 mg/kg and it does show up in the brain, though of course at one tenth of the concentration. It's not clear to me whether the authors tested if these lower concentrations can also remove emotional trauma's, they only published results with 30mg/kg. However since it can travel to the brain and the effect was strong enough to remove the artificial trauma's to the mice completely, I suspect that we may also get result from 1mg/kg.

If bought in bulk from the cheapest source I could find, it would cost $1350 for 5 gram, that would mean a mere $0,27/kg or $10-20 for an adult! Quite the difference with a full dose from Sigma! Even if it doesn't work as well, it may still give people some results and an indication if the compound is worth investing in further.

Luckily Cl-994 (aka N-acetyl dinaline aka tacedinaline) has been used a lot in both cancer research and epigenetics. Some further look into publications might help to answer how research and dosages in mice translates in humans. But for now I assume the dosages are only weight dependent.

Edited by tree, 17 February 2014 - 09:09 PM.


#4 ceridwen

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Posted 17 February 2014 - 10:17 PM

I would really love to join the group buy

#5 ceridwen

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Posted 17 February 2014 - 10:21 PM

The problem is I got so bad that I also got dementia but my anxiety levels have as you say been reset as my new base level and I think that it would be much easier for whoever has to care for me if this trauma could be removed. I'm pretty desperate too
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#6 xks201

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Posted 17 February 2014 - 10:54 PM

I'd look into a relative thyroid hormone deficiency(not diagnosed by just measuring TSH) or iodine or selenium deficiency if this has impacted you to the point of disabling you from work. In other news, benadryl was used to remove negative memories from individuals at a dose of two pills per night..whatever that mg strength is (the mg strength per pill in the OTC stuff).

I hate to say it but my childhood was not the greatest and I know several people who had crazy childhoods (family murdered in front of them..abusive parents) who got over it...I think it has to do with hormone levels in response to the stress. Those who cannot produce the adaptation response don't adapt. If you can't even work odds are you have an enduring endocrine deficiency of some kind...most likely need more thyroid hormone and could benefit from thyroid glandular or pig extract or whatever.

Yes what you are going through is obviously a real response - but I think the cause lies more in the endocrine system than needing an exotic panacea chemical.

Edited by xks201, 17 February 2014 - 10:56 PM.

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#7 tree

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Posted 18 February 2014 - 12:00 AM

I'd look into a relative thyroid hormone deficiency(not diagnosed by just measuring TSH) or iodine or selenium deficiency if this has impacted you to the point of disabling you from work. In other news, benadryl was used to remove negative memories from individuals at a dose of two pills per night..whatever that mg strength is (the mg strength per pill in the OTC stuff).

I hate to say it but my childhood was not the greatest and I know several people who had crazy childhoods (family murdered in front of them..abusive parents) who got over it...I think it has to do with hormone levels in response to the stress. Those who cannot produce the adaptation response don't adapt. If you can't even work odds are you have an enduring endocrine deficiency of some kind...most likely need more thyroid hormone and could benefit from thyroid glandular or pig extract or whatever.

Yes what you are going through is obviously a real response - but I think the cause lies more in the endocrine system than needing an exotic panacea chemical.


The suggestion of thyroid hormone deficiency is made a lot in online communities. But I tried thyroid medication and it did nothing for me. I also used to be much more resilient and recuperated from stress normally. The brain has multiple mechanisms in place to keep anxiety in tact, once you get enough of it, it doesn't just go away. That is not unique to certain individuals. Of course not everyone gets pushed over the border for the same causes, and undoubtedly sensitivity differs per person. But that depends on countless factors. Psychological profile, a gene here, a gene there, infection in early childhood, some motherly epigenetic imprinting, who knows? But it's not thyroid hormone deficiency. And I don't see Cl-994 as a panacea; just as a good candidate. The last one I will try in fact. If it doesn't work I will exclusively focus on meditation and do-it-yourself psycho therapy. So far they are the only things which have delivered permanent results.

The benadryl account is interesting, I'm going to look into it.

#8 datrat

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Posted 18 February 2014 - 02:27 AM

benadryl was used to remove negative memories from individuals at a dose of two pills per night..whatever that mg strength is (the mg strength per pill in the OTC stuff).

xks, can you provide more information about that study? If we could get hold of an otc product that has proven results, that would be awesome.

At the same time I want to continue researching cl-994, since it definitely seems promising.

#9 tree

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Posted 18 February 2014 - 09:53 AM

benadryl was used to remove negative memories from individuals at a dose of two pills per night..whatever that mg strength is (the mg strength per pill in the OTC stuff).

xks, can you provide more information about that study? If we could get hold of an otc product that has proven results, that would be awesome.

At the same time I want to continue researching cl-994, since it definitely seems promising.


I think he means this research.

And here is the article on Cl-994.

Honestly I'm sceptical about the benadryl (diphenhydramine). The researchers found It suppresses aversive memory recall 10 minutes after exposure. But it hasn't shown to touch the epigenetic imprint which is the reason long term anxiety/negative memory/trauma doesn't go away. And it was only shown to work while on the medication, they didn't show permanent erasure. There is another article which shows that anti-histamines can prevent traumatic memory from being stored in the first place, which makes sense. But removal of long term trauma has never been shown with anti-histamines. Of course it's OTC as you said, so easy to test out. Though interestingly it has a lot of side-effects on the central nervous system.

In fact I think I might already have. I had a lot of allergies in the past and used plenty of anti-histamines. Allergies came way before the anxiety. In fact, I'd almost wonder if persistent use of anti-histamines could upregulate the HRH1 receptor. That's what usually happens when you try to block a receptor. Which would lead to heightened sensitivity to future stress and increased storage of aversive memory..

Edited by tree, 18 February 2014 - 09:59 AM.


#10 tree

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Posted 19 February 2014 - 11:06 AM

Anyway, I've tried to find more information on the safety of Cl-994 in humans but I haven't found much. There have been phase 1 trials, which are the trials focused on safety of a drug in humans. But I can't find the results of those trials. This is a bit unexpected. I may find the information but I'll have to search on another network, I don't have full access to literature on my own computer.

I'll post further information in his thread. Meanwhile if the people who wish to participate in the group buy can let me know (PM is good) how much they want to order then I'll have a better idea in what price range we have to think.

These are the prices from the cheapest source I managed to find. The lab is supposedly reliable and USA based (though I'm not in the USA, we may have to let someone else order to reduce handling cost).

mg $
100 - 89
300 - 188
1 - 465
5 - 1359

Keep in mind that although 30mg/kg was the only concentration for which result were published, 1 mg/kg and 10 mg/kg still resulted in the compound being present in the brain. I suspect 1mg/kg will get some results as well.

Edited by tree, 19 February 2014 - 11:09 AM.


#11 BlueCloud

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Posted 19 February 2014 - 01:08 PM

In fact I think I might already have. I had a lot of allergies in the past and used plenty of anti-histamines. Allergies came way before the anxiety. In fact, I'd almost wonder if persistent use of anti-histamines could upregulate the HRH1 receptor. That's what usually happens when you try to block a receptor. Which would lead to heightened sensitivity to future stress and increased storage of aversive memory..


Interesting. My experience mirrors yours. I also had a lot of allergies in the past, took many antihistamines, and for a while relied a lot on diphenhydramine and doxylamine ( both OTC sedating antihistamines ), almost daily, for my insomnia. The levels of my GAD also seems to have raised a lot during last years and I'm in a constant state of fight-or-flight mode all day. I'm starting to seriously think that antihistamines might be the culprit for my recent heighteneded GAD.
Here's another thread where we discussed antihistamines potential for up-regulating adrenergic receptors : http://www.longecity...ebound-anxiety/

#12 kobokok

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Posted 19 February 2014 - 02:51 PM

Have you guys looked into psychedelics in the treatment of ptsd/anxiety/depression? http://maps.org/
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#13 socialpiranha

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Posted 20 February 2014 - 01:15 PM

i must be missing something here, i don't see the connection between cl-994 and the study you posted?

#14 tree

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Posted 20 February 2014 - 01:27 PM

Have you guys looked into psychedelics in the treatment of ptsd/anxiety/depression? http://maps.org/


Let's try to stay on topic.

Edited by tree, 20 February 2014 - 01:28 PM.


#15 socialpiranha

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Posted 20 February 2014 - 01:53 PM

tree what is the relation between cl-994 and the study you posted?

#16 tree

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Posted 21 February 2014 - 02:47 AM

tree what is the relation between cl-994 and the study you posted?


Hm? I posted 2 article links in post 9. I don't know to which one you refer. The first study was in response to an earlier post about anti-histamines, the second was about Cl-994 and its epigenetic effect on aversive memory.

Here is the link again.

#17 celebes

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Posted 21 February 2014 - 02:59 AM

tree what is the relation between cl-994 and the study you posted?


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.

Edited by celebes, 21 February 2014 - 03:01 AM.


#18 socialpiranha

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Posted 21 February 2014 - 08:29 AM

ok yeah i just read post #1 and there was only a study that didn't even mention cl-994 must have missed post nine

#19 tree

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Posted 21 February 2014 - 08:49 AM

ok yeah i just read post #1 and there was only a study that didn't even mention cl-994 must have missed post nine


Actually my first post linked to that exact same study as well, so I'm not sure what you mean. Of course the link led to an abstract as the full article isn't free access and was too large to attach tot the post. I had to upload it first to a cloud storage. The second link in the first post was a news article which summarizes that study.

#20 tree

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Posted 21 February 2014 - 09:02 AM

tree what is the relation between cl-994 and the study you posted?


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.


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.

The only question on my mind is what other effects this could have, though epigenetics changes over a lifetime from the moment you are born, so that relativates things. It also requires only a single dose, not long term exposure. It will be a few days till I get to another network with full literature access, hopefully I will find the results of the phase 1 experiments.

#21 dijital

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Posted 22 February 2014 - 12:41 AM

The crucial question is how trauma-related studies with mice translate to humans and the real world. I think you'll need some kind of exposure and in many cases even response prevention for Cl-994 to work, but this shouldn't be a problem as long as you know where your anxiety comes from.

Can anyone shed a light on the question if there is a difference between what they call "remote fear memories" and "trauma memories"? Can there be remote/old memories that don't deserve the term "traumatic" but nevertheless cause persisting anxiety because of epigenetic priming?

A group buy would be fantastic. We got a ton of group buys for novel substances that might improve intellectual performance but very little for those suffering from mental disorders. From an ethical point of view, helping the latter should have priority.

#22 tree

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Posted 28 February 2014 - 07:20 PM

I've been busy but I managed to find the trial 1 results. The trial 2 results on the other hand have never been published. But they would have focused on cancer fighting properties and not aversive memory wiping so are less relevant than general safety tests. I'll digest the information and post monday/tuesday (and also respond to the question in the post above!).

#23 platypus

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Posted 28 February 2014 - 09:17 PM

I would not rule psychedelic therapy out, hasn't MDMA been used successfully in the treatment of PTSD?

#24 VERITAS INCORRUPTUS

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Posted 01 March 2014 - 10:41 PM

Diphenhydramine is not highly specific for H1-antagonism. While extremely common in use and readily available, it was an extremely poor choice for a scientific study investigating a ligand for a specific receptor effect. Those doing serious research should 'know better'. The anticholinergic component may or may not be a contributing factor; it is one significant variable that interferes with analyzing the H1 specificity of the observed phenomena.

A private research team I know is conducting trials with an agent with the same primary pathway of effect as the compound C-994. A target focus of the research is fear extinction to induce improved aversive response performance indices and persistent anxiolysis. A highly notable effect has been displayed in trials to date. It has exhibited a fairly robust anxiolytic and general mood elevating effect; along with the noted side effect of improved skin texture and tone :|? :) Fear extinction/aversive response assay trials are slated for a next phase assessment. The target goals of persistent anxiolysis, mood stabilization/elevation, and perceived functional enhancement parameters were primarily assessed.

They also have extensively trialed a Selective BZD-Receptor Modulator that shows pronounced and rapid onset anxiolysis with absolutely no detectable side effects at all see with classical BZD-Receptor agonists.
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#25 dijital

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Posted 02 March 2014 - 12:46 AM

Veritas, can you tell us more about those trials? Is this "private research team" going to publish any papers about their research in the near future? What compounds are they using?

#26 VERITAS INCORRUPTUS

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Posted 02 March 2014 - 03:56 AM

Veritas, can you tell us more about those trials? Is this "private research team" going to publish any papers about their research in the near future? What compounds are they using?


They are looking for equity investors for funding for further clinical trials and with a goal to take the company public as I am aware. All research substrates they have in testing are only classified by code names for IP protection. I believe they area anticipating to publish research within the upcoming year, but I am not too certain of the time frame. I have enough to keep me in good stead for a while though :)

#27 formergenius

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Posted 02 March 2014 - 07:34 AM

They also have extensively trialed a Selective BZD-Receptor Modulator that shows pronounced and rapid onset anxiolysis with absolutely no detectable side effects at all see with classical BZD-Receptor agonists.

This wouldn/t happen to be Emapunil, would it?

#28 VERITAS INCORRUPTUS

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Posted 02 March 2014 - 05:42 PM

No, my friend. These are proprietary agents they are doing R&D on that have been developed 'in house'. The structure of the aforementioned BZDR modulator is unrelated to Emapunil, though the characteristic anxiolysis sans adverse effect profile is highly similar. I believe it may very well engage the GABAergic system via the same pathway, but I do not have full access to that information.

#29 tree

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Posted 03 March 2014 - 05:55 PM

A private research team I know is conducting trials with an agent with the same primary pathway of effect as the compound C-994. A target focus of the research is fear extinction to induce improved aversive response performance indices and persistent anxiolysis. A highly notable effect has been displayed in trials to date.


Trials in humans? Has anything been published? Otherwise it's of little use.

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).

Interestingly, I found I made a mistake in assuming that the dosages in mice and humans are similar. They are much, much lower! Thanks to a conversion table (attached to this post) I found that the tested dosages are the following:

mg/kg mouse mg/m2 mouse mg/kg human mg/m2 human
......30......................90..................2.5..........................92.5
......10......................30..................0.83 (+- 0.8)...........30.71 (+- 30.7)
......1........................3....................0.08 (+- 0.1)...........2.96 (+- 3.0)

Keep in mind that only the 30/kg in mice was tested for its effect on aversive memory. The other dosages were only tested for availability to the brain. Still, that might mean that even 0.1 mg/kg in a human can have mitigating effects on stress/anxiety.

These correct figures mean that the results of the phase I (human safety) trial with Cl-994 (acetyl-dinaline) are pretty promising.
The researchers tested several concentrations for periods of several weeks (see article added to this post). Since the compound was thought to have no other effect but its cancer fighting properties, they did not test the effects of a single dose.

At the highest dose (15mg/m2/day for 2 weeks which converts to 0.41 mg/kg/day) there were numerous side-effects. Mostly, if not all, related to the fact that Cl-994 is a cytostatic agent. This means that it halts the division of cells by temporarily freezing them in the cell cycle. This can lead to a low count of blood cells which begins to restore itself after treatment is stopped.

But, at the lowest tested dose of 0.14 mg/kg/day for 6 weeks there were relatively few problems. Out of 6 people, none developed a low red blood cell count, 1 developed mild neutropenia (low neutrophil count) and 3 developed mild-to-medium anemia.

This might sound discouraging but these were people who took Cl-994 for 6 weeks. As you can see from the table, the duration mattered a lot. The same dose for longer periods caused considerably more side-effects, leading me to conclude that the side-effects of a single dose may be negligible. Especially if we keep to the low dose of 0.08 mg/kg (which correlated with the 1mg/kg in mice).

The only real danger with Cl-994 is the same danger as every drug which affects the epigenome. It may also activate genes that you don't want to be activated. But considering that Cl-994 freezes cells in a checkpoint of the cell cycle, a point in which the cell checks whether it is safe to divide or whether proliferation should be shut down for this particular cell, I honestly think this compound is about as safe as this class of medication is going to get. Perhaps one day a very selective compound can be made, but then we are talking many years into the future.

So, precluding that I find an even safer/more effective drug which wipes the epi-genome before the end of the week, I'm ready to order the chemical. The correct conversion from mice to human shows that I'll only need 4,8 mg. The minimum amount from the cheapest source will be 50 mg for $63. I suggest splitting up the price among the number of participants, meaning that the total cost of participation will roughly range from $30 - $6 excluding shipping. Pretty cheap I´d say.

In fact, if nobody else wants to join it will be cheap enough for me to order alone.

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Edited by tree, 03 March 2014 - 05:58 PM.


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#30 celebes

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Posted 03 March 2014 - 09:08 PM

How reliable is that cheapest source?





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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