49 replies to this topic

[Mind_Paralysis]

I received the compound earlier this week. The compound has been sent for NMR testing and all of the US orders have been shipped and should be arriving tomorrow. The international orders will be shipping tomorrow morning and hopefully you will be receiving it next week. I will provide tracking information when I can. 

 

Good luck everyone.

 

YES!! :D Awesooome!

 

Now this, this be exciting! First ever truly, well-documented selective Kappa-antagonist trial in the wild! I am very very pleased by this news.

 

 

Now, on to some of the specifics of trialling a drug such as this - we probably need to give it about the same time as a regular antidepressant to actually gain full efficacy - yes, in theory the effects are immediate, within minutes, like other opiates, BUT... we can't be entirely certain about that - so if you trial it, give it a full couple of weeks before you write it off - the effects may be subtle at first.

 

And then we have the dosing - what dosing did the studies use, again? 10 mg? We have to remember, that this is not a hard number - it's a lot like any other drug, there are individual dosing-differences - some of you may require only 5 mg, while others may require 15 mg.

 

And then finally, we have the issue of potential UP-regulation of the kappa-receptors, as a result of antagonism - DOWN-regulation of the Kappa's have been reported when the use of low doses of kappa-agonists have been implemented, resulting in antidepressant action. This is problematic... because it COULD imply that the kappa-receptor system is especially prone towards over-regulation, in order to correct imbalances. However, many receptor-systems only seem to regulate heavily up or down in ONE direction, not the other.

So, it's not a given that this will happen, but still, we need to be prepared for it: set aside a few smaller than average dosages, to be used for the end of your trials - these will then be your tapering dosages, so as to avoid any grave upregulation of the kappa-receptor.

 

 

NOW THEN... how often should one dose? Once-daily, orally, seems to be an effective method in the trials, and the half-life is pretty good, up to 40 hours, which makes it unlikely to induce any severe discontinuation-symptoms, judging from other compounds with such a half-life. (other AD's)

 

Looking at the half-life duration of action of other opiate ligands, I find that the effects of agonists appear to last LONGER than their half-life...! 0_o The half-life of agonists all appear to be utterly pitiful as well - no wonder people get addicted! Those drugs have absolutely disgusting pharmacokinetics.

 

Looking at the more comparable antagonists, Naloxone and Naltrexone, the half-life and DOA seems to either follow each other, or once again, the DOA IS MANY TIMES LONGER THAN HALF-LIFE! 0_o

 

The implications here are CRAZY! Perhaps we should not worry too much about upregulation after all... these effects are quite encouraging.

 

 

References:

-----------------------

Evaluation of CERC-501, a selective kappa opioid antagonist in preclinical models of alcoholism

http://www.drugandal...0442-2/abstract

 

"...daily administration of 10mg/kg CERC-501 reduced ethanol consumption on four consecutive test days, indicating that it did not produce significant tolerance"

 

 

Major Depressive Disorder and Kappa Opioid Receptor Antagonists

https://www.ncbi.nlm...les/PMC4871611/

 

"In mouse forced swim assays, 10 mg/kg oral dose of CERC-501 was found to reduce immobility responses... A synergic effect was also observed for CERC-501 (3 mg/kg, po) and citalopram (3 mg/kg, ip) in combination...
In clinical trials, CERC-501 displayed rapid oral absorption and a terminal half-life of approximately 30–40 hours in healthy subjects ^[107]. Plasma exposure of CERC-501 increased proportionally with increasing doses and reached steady state after 6–8 days for once-daily dosing ^[107]."

 

(All I keep finding is the data from bloody mice-testing... where's the human dosing at?? Of course, we could just recalculate - humans generally use LOWER dosages of drugs than mice)

 

 

Incorporating Alcohol Pharmacotherapies Into Medical Practice.

https://www.ncbi.nlm...books/NBK64042/

 

"Naltrexone's duration of action (which is greater than 24 hours) allows a variety of flexible dosing schedules."

 

[brighterpath]

The rest of the shipments were sent out today, and the NMR result from the lab will be back tomorrow. Sorry about the delay, I got busy at the end of last week, and we had a federal holiday on Monday in the U.S.. I will message everyone your tracking information. 

[Mind_Paralysis]

The rest of the shipments were sent out today, and the NMR result from the lab will be back tomorrow. Sorry about the delay, I got busy at the end of last week, and we had a federal holiday on Monday in the U.S.. I will message everyone your tracking information. 

 

EXCELLENT! = ) My thanks for your hard work, Brighterpath!

Now, I am very, very curious to see the NMR-results...! Here's to hoping for a 99% purity, of, well, CERC-501! Instead of 99% purity of... well, something else.

[brighterpath]

If anyone on this thread is not a part of the other one, please check out the sister thread:

 

http://www.longecity...e-5#entry818665

[keystroke]

Is it still possible to buy some CERC-501 from the group buy? I would like to get some. Have been following this thread but didn't realize my old ImmInst account worked. Thanks!

[brighterpath]

Hey Keystroke, I still have compound left from our groupbuy. Feel free to shoot me a message. 

[brighterpath]

Since I now know that my particular condition is more about the glutaminergic system than the opioid system, I am happy to sell the rest of my CERC-501 stash. I do not plan to order more in the future, for the time being. If anyone would like the rest of this substance please let me know. 

[SoundsAboutRight]

Anyone have any CERC-501 left? Drop me a PM

[Cube]

It's been 2 months has anyone had any significant results negative or positive?

[Mind_Paralysis]

It's been 2 months has anyone had any significant results negative or positive?

 

Good question - I only had a small amount, so I could only report on that - the acute effects are slight antidepressant effects, slight anxiolytic effects, slight stimulatory effects, and even slight ANALGESIC effects. (odd that I seem to be the only one reporting that... wonder why that is? especially since it's the only effect I've reported that's LESS likely to be placebo - I didn't anticipate it)

 

However, the long-term effects could be much different, that is usually the case with antidepressants (even though this is bound to be a completely different type of antidepressant).

 

SO... guys... what are the effects? How did you feel after 3-4 weeks worth of this drug?

[Cube]

Thanks for the reply stinkorninjor,
Given the level of response i guess the search continues.

[vere]

I meant to post on here sooner. I have actually been still using CERC intermittently at very small doses. My opinion of it remains pretty similar to my initial opinion, as posted over on this thread: http://www.longecity...gonists/page-6 

 

After originally taking it for about a month straight the first time around, I had gradually stopped noticing its effects. Either I got used to the feeling of being on it, or I became tolerant to it. So, I stopped for about another month solid. Getting off CERC didn't seem to be a problem, but I did lower my dose pretty gradually until I was just taking dust. 

 

Eventually I started using it every couple days at doses of 5mg or less, which is what I'm doing now. I noticed that it seems to be pretty much as effective at 5mg as it was at 10mg. Particularly, I prefer doing lower doses because I feel that even at 10mg, I start to feel some of the effects of the mu opioid antagonism, as it accumulates in my system over the course of a couple days of taking it. (The mu opioid antagonism part of it feels like it puts me in a worse mood and also causes some strange pains around my body. I haven't been able to notice if it is analgesic at lower doses - but I definitely don't have the issue with pain at doses < 10mg). I'm also taking it at the minimum effective dose to hopefully preserve my supply of it for longer. 

 

I hope that people don't call off CERC - it's been a helpful medicine for me and I think would for others. I think it's not everything people wanted kappa antagonism to be, myself included, but I think it is a good medicine overall and I wish this is what psychiatrists were handing out to depressed patients instead of SSRIs.

 

I use CERC on select occasions now, for what I believe it does best. From trying out so many different medicines I have started to get a sense for what I need to help myself out of different states. Depression isn't just a uniform state, it's made up of a variety of states.

 

One of these for me is a fear-driven type of anxiety. For example, something as common as getting cut off by someone in traffic might remind me of all of my fears about the world that make me so hopeless, what I hate about people, a spiral of negative thoughts that my mind can't break away from. In these situations I am also constantly paranoid that something bad is going to happen - like I'll be watching the person in the lane next to me, waiting and just expecting them to cut me off. That leads to anger. This is one of the few things I can "feel", but in these moments I still don't care about things - I am just overcome with anger, frustration, and hopelessness. 

This is the main thing that CERC helps me with. By taking it in specific situations, or when I can tell I am going to have that kind of day from the time I wake up, I use it for what I know it's good at. I think the reason CERC works so well for fear is because the kappa opioid receptor really does mediate fear and anxiety. 

 

I had taken nuedexta/dextromethorphan for quite a while which I think had possibly upregulated my kappa receptors, among other terrible things for me, like being an SNRI. I had distinctly been worse since taking that somewhat long term, and I think CERC has helped me get over that. I hadn't even noticed that after taking nuedexta I had stopped listening to music at all because it just sounded different and wasn't enjoyable, until I took CERC and it gave me that back a little.

 

CERC doesn't give me back a full range of emotions, but unlike most antidepressants I have tried, it doesn't make me more numb - so I find that to be a pretty significant. Sometimes the only emotion driving me is frustration. This is obviously not a good thing, but medicines like SSRIs get rid of everything negative and everything positive for me, making me completely complacent and not even able to care to change anything in my life to get better. CERC doesn't make me forget or ignore negative things, it just makes me feel more like my old self, more able to laugh off stupid things instead of letting them ruin my entire day. 

 

I am now in a better place overall than before taking CERC, whether that be by circumstance or managing my depression with a couple different medicines that work alright for me. I have definitely not had any negative long term effects from taking it so far, no noticeable upregulation of kappa receptors. That's a huge deal to me, since almost all medications I have taken have made me worse or not helped at all. 

 

While I can't necessarily attribute any specific lasting benefits directly to CERC, I will say that one of the biggest changes in my life since taking it has been my ability to do my work, even a little, on most days now. I wasn't doing any of my personal work before CERC - only playing games mindlessly - and it had been that way for at least a year and a half. 

 

The most negative thing I have to say about CERC is that sometimes, inconsistently, I think I may have a slight rebound from dosing it for only a day, and then letting myself come off of it. Usually this rebound is about two days after dosing CERC - the half life is pretty long. The rebound, if there is one, is short lived though, and it's hard to even say if the it is just my own disappointment at returning to how I normally am. But, I have had a couple times where I felt distinctly more of that fear-driven anxiety and anger the second day after coming off CERC. I did not notice any problems coming off it long term though, I think this just comes from the spike of doing it for only one day and stopping.

 

I am positive my true problem with emotional flatlining and anhedonia stems from the glutamatergic system though, and I don't think CERC has much to offer for that part of my depression. But that doesn't make it a bad medicine at all. It's effective at what it does, and considering I don't have many medicines I can speak even that highly of, I think it is worth other people trying if they have the opportunity. I hope people will also become more enthusiastic about CERC, as well as glutamatergic medicines. I think they both have a lot of potential to help people in ways other medicines have not yet been able to.

 

Edited by vere, 23 September 2017 - 08:31 AM.

[Mind_Paralysis]

Cheers for giving us more data there, Vere. = )

 

Btw, have you trialled Lamotrigine yet? It would be truly awesome to see what happens when you combine glutamatergic and opioid manipulation in one sweet package! Might be like Tianeptine+!

 

Also, does anyone know if there's any new data on the drug? The trial for depression failed, but there's still a trial for Anhedonia and another trial for... can't quite remember? But there's two trials going.

[tolerant]

Hi vere,

 

Thanks for sharing. I am wondering, did you try to get rid of the impurities by heating the compound as was suggested on these forums?

 

Thanks,

 

tolerant

[samson75]

@Stinkorninjor :

it failed the depression trial ? So it's abandonned for that purpose ?

[brighterpath]

Hey guys,

 

Sorry about the long silence. I was off of cerc 501 for a while then recently went back to it at 20mg per day. I have been using it without heating it, and without a solvent this time, and it seems to be working well. I am currently on moclobemide, memantine, and microdose lithium as well as other more regular supplements. 
 

I am probably doing better than ever. The current stack seems to be working very well for me and it has made me both more social and completely gotten rid of any hint of depression at its best. However, it is very high maintenance and quite fragile. It has not gotten me to where I want to be 100%. I am also getting pretty bad muscle cramps, and I think this may be from moclobemide or taking all of the drugs together. Still trying to figure that out. 

 

I have taken all of these drugs alone for extended periods of time in the past, and they were not nearly as useful as they are together. I find them very synergistic, and I think CERC 501 plays an important role in regulating the dopamine receptors somehow. In the past, I have had success with salvia withdrawals, and ketamine trials, so I think d2 receptors are involved somehow (memantine is a partial agonist as well). 

 

CERC 501 has been sold by Cerecor to another company in a private sale. I don't believe their depression trial results are out yet. The sale may delay the final product coming to market, if it ever does, but I would love to see it become available.

[Mind_Paralysis]

Hey guys,

 

Sorry about the long silence. I was off of cerc 501 for a while then recently went back to it at 20mg per day. I have been using it without heating it, and without a solvent this time, and it seems to be working well. I am currently on moclobemide, memantine, and microdose lithium as well as other more regular supplements. 
 

I am probably doing better than ever. The current stack seems to be working very well for me and it has made me both more social and completely gotten rid of any hint of depression at its best. However, it is very high maintenance and quite fragile. It has not gotten me to where I want to be 100%. I am also getting pretty bad muscle cramps, and I think this may be from moclobemide or taking all of the drugs together. Still trying to figure that out. 

 

I have taken all of these drugs alone for extended periods of time in the past, and they were not nearly as useful as they are together. I find them very synergistic, and I think CERC 501 plays an important role in regulating the dopamine receptors somehow. In the past, I have had success with salvia withdrawals, and ketamine trials, so I think d2 receptors are involved somehow (memantine is a partial agonist as well). 

 

CERC 501 has been sold by Cerecor to another company in a private sale. I don't believe their depression trial results are out yet. The sale may delay the final product coming to market, if it ever does, but I would love to see it become available.

 

Memantine?? While DP/DR-ed?? : O That's very dangerous dude, I wouldn't use that. Neither would I use Ketamine - remember how NMDA-antagonists can trigger DP/DR? I'd replace it with Lamotrigine, personally.
 

 

I think you're right about CERC-501 depression results, but I could have sworn you mentioned a failed trial, just prior to us completing the group buy... It was a rather small study though, as I recall it.

 

Interesting note regarding your dosage - am I correct in assuming that you are using a higher dosage now than before? I recall you starting out at 10 mg - I suppose this is logical, since the solubility is low regarding this drug, so a higher dosage would be necessary to get the same bio-availability as when used with DMSO.

 

 

I agree that the drug warrants more research btw! = ) I mean, it clearly has some effects, and the side-effects profile is very good - so definitely a mechanism that could be helpful to some people.

[vere]

Stinkoninjor - I haven't tried lamotrigine yet but I think it's an interesting thought! I typically think of it as sort of the "opposite" of what I need, being a glutamate release inhibitor, but I always like to test out things even if I think they might not be beneficial, since I know it's not all that black and white. I was thinking of trying out Riluzole for this reason as well, if I can get my hands on it.

 

Tolerant - I did heat CERC for a while, one dose at a time, in a toaster oven. It was quite the process though, and I eventually gave up on doing it and I couldn't tell if it was altering the effectiveness of the dose. I've been feeling fine taking it despite the impurities. Still can't tell if any digestive upset is due to CERC itself or the impurities, but that's the only side effect I can say I've noticed and it's not that bad. 

 

As far as how CERC is doing in clinical trials, the last I remember is this article from a while back stating it proved to be clinically significant in its trial for treatment resistant depression. I think the trial was actually terminated for other reasons, not due to its lack of success, which is good news! - It says:

 

"The five-site trial was terminated early due to recruitment issues and eight subjects in total were randomized."

 

Like brighterpath said, I saw CERC-501 was sold to Johnson & Johnson I believe, and the CEO of Cerecor retired, while Cerecor's other medicines like CERC-301 are still in development by Cerecor: http://www.fiercebio...-j-license-deal

 

And then this appears to be the current trial ongoing, for anxiety, anhedonia, mood disorders:

 

https://clinicaltria...cerc-501&rank=2

 

I'm glad to hear CERC is working for you again, brighterpath. I think you're probably right about CERC's connection with dopamine receptors, among other things. I think it is great to find a combination that works for you, since these kinds of issues are so multifaceted. Personally, I've been switching between a couple medicines that work for me as well. I also take memantine occasionally, and D-cycloserine is another one that has really helped me in some big ways.

 

Also interesting that you mention the muscle cramps - I also experienced some increased abnormal muscle pains at only higher doses of CERC. My best guess was the mu antagonism that kicks in at higher doses. But what you're experiencing may be different than what I did, given the other medicines you are taking as well.

 

I think it's interesting about memantine and DP/DR - although my initial thought would be that it would cause DP/DR, like Stinkoninjor said, my friend who has some mild DP/DR issues also tried memantine and felt some relief from it. While memantine causes its own sort of brain fog, maybe it's not the same as the feeling of derealization? My friend said that because she was more relaxed, she felt more connected to reality despite feeling more "out of it." Kind of paradoxical, I know, since NMDA antagonists are straight up dissociatives. But I wonder if it helps when DP/DR originates from prolonged states of stress/anxiety, when there is some sort of hyper glutamatergic origin that memantine helps to lessen.

[brighterpath]

When I was going through the ketamine trials, I felt such relief from my symptoms of anhedonia while I was actually ON ketamine, I started to wonder what did it. I felt similar relief after using salvia sublingually, before I couldn't feel it's effects anymore. Dopaminergic stimulants used to work amazingly well, until they all stopped working as well. 

 

For a while, I thought I must be dopamine deficient, then my neurologist who treats parkinsons patients mentioned that parkinsons patients, who literally lack dopamine, do not get derealization. So simply increasing dopamine didn't seem to be the answer. My current theory, from my experience with these drugs, is that my symptoms are due to an imbalance in d1 and d2 receptor functions. 

 

I find the brain fog worsening by a lot on high dose of memantine, but on low doses I feel more of a relief. Memantine also acts as a d2 agonist, so I wonder if that's where the relief is coming from. And also, Lamotrigine is also an NMDA antagonist, no? I thought memantine would do a similar job to lamotrigine. 

 

Overall, I am looking at d2 receptor agonists/partial-agonists/antagonists, and it seems like certain atypical antipsychotics like ability may fit the bill. In fact, there's at least one documented case of doctors treating DR/DP with abilify and having the symptoms resolve completely. There are more experimental substances that I've found which is a pure d2 agonist.

 

 

 

 

[ISayLonger]

Anyone got any left they'd like to sell?