Hi everyone,
I haven't posted here yet but I also participated in the group buy and have been trying CERC-501 consistently for about the past month now since receiving it and I wanted to post how I am doing on it so far.
I am trying CERC-501 for my emotional flatness and anhedonia. I have had severe depression for 4 years that has worsened despite (and also because of) the many treatments I've tried. The only thing that has ever returned my feelings and ability to care was ketamine. I had complete emotional recovery, but only right after ketamine infusions as I was coming off it, and then I would be nearly back to normal soon after. I felt the same kind of relief (though not as strong as ketamine) when I started trying dextromethorphan to get the feeling of ketamine at home between travelling out to get infusions. In the long run though, it made me worse.
At first I thought it was purely NMDA antagonism that may have been helping me, but when I tried memantine I didn't get the same kind of emotional recovery (though it has been one of the more consistently, mildly helpful medicines I have tried in its own right, just not in the same way). I know there are some differences in the NMDA blocking of memantine vs. something like ketamine/dextromethorphan, and I think that has a lot to do with it. But I started to think maybe the differences were also in part because ketamine and dextromethorphan are both kappa agonists and memantine is not.
There are probably a lot of different potential explanations for kappa agonism being helpful, but in my case I personally wondered if the antidepressant effects I felt from ketamine/DXM were some sort of rebound from their kappa agonism - especially because I felt nothing emotionally from ketamine (other than the disassociative trip) during the infusion, but had an extremely emotional experience coming off ketamine. Dextromethorphan has a pretty short half-life too, so maybe what I felt was actually some sort of kappa agonism afterglow. It's a total guess, but it led me to wanting to try CERC-501, since I believe kappa antagonism would be a better way to do this in the long term, as opposed to kappa agonists in the long term which feel detrimental. Also, kappa antagonism itself as a mechanism just sounded like one of the more promising ideas I'd heard in a while.
I tried CERC-501 starting at 10mg a day. I experimented with some different doses (5-10mg, 10-20mg, 20-25mg.) I definitely felt slightly worse at higher doses (though not worse than baseline). I wondered if that was because at a certain dose, with the half life being kind of long, the cumulative concentration of CERC-501 was enough to cause it to antagonize mu, which I guess it is known to do at about 25mg. About 10mg daily has been the best for me.
I've tried it with and without DMSO and I felt the effects were about the same for me. It seems to be absorbed just as well regardless of using DMSO, or at least to the extent of my ability to notice it. DMSO also made me smell like a little like creamed corn, so I kind of felt like it wasn't worth it for the similar results I was getting.
I definitely notice the smell and the sort of aftertaste that must be coming from the MTBE, as people have been talking about here. I think over the course of me taking it, I've noticed some gastrointestinal upset either coming from that or the CERC-501 itself. But otherwise, no side effects at all from the medication.
Though I'm not really bothered by it, I've tried heating CERC-501 to try to get rid of the MTBE in my toaster oven on warm, around 100-120 degrees fahrenheit for around 10 minutes. I did manage to get rid of the taste of it a little by heating it, but I stopped doing it because it seemed like I wasn't doing as well on days that I was heating it (could have also been coincidence). I don't know if it could compromise CERC at all, but if it does, I don't want to risk wasting the medication. Also, to get it to where I didn't taste the MTBE anymore completely, sometimes the CERC itself would melt a little/get sticky like Stinkorninjor mentioned - I have had it stick to my teeth before as well.
As far as the actual effects of the medication go, I do like taking it. It hasn't been the end all be all cure for my problems, but I didn't expect that or think it was possible. I am going to continue using it for as long as there is a supply for it, because I do feel some benefits from it and it makes day to day more manageable. CERC-501 is one of the few things I've even wanted to bother giving a chance to work in the long term and see where it goes. It feels safe and clean to take.
It helps my ability to tolerate things that would normally just frustrate me and ruin my entire day. It also helps me to take an interest in small ways in working again, which I used to love doing. It has helped me to enjoy some music again, or to actually want to sit down and listen to music. This is something that went away completely when I took Nuedexta (dextromethorphan/quinidine) for a couple months straight.
Sometimes, though still rare, I have quick moments where I look at something more like I used to before depression. I still wish I could hold onto those moments longer though. I feel more often now that I can see what is wrong with how I am and have been, and it makes me see the point more in wanting to get better and change that. This is something I'm not capable of understanding or acknowledging in my normal state, like my brain just completely shuts it out and numbs me to it beyond my control.
CERC-501/kappa antagonism really does feel more like it is disinhibiting something, rather than actively doing something. This isn't bad though, it feels more natural, like I'm not completely shut off and numb all the time, so it makes it actually possible for me to do or at least acknowledge things that would make me feel better. I think the only downside to it feeling so normal is that I might forget what I am actually normally like off the medicine. I would like to try tapering off it at some point to see how I feel, but I haven't done that yet.
Now that I've felt what CERC does on its own, like others, I'll be trying some other things with it. Memantine and NSI-189 have both helped me slightly in the past, so I'll be trying it with those. I think depression is a multi-faceted issue that can't necessarily only be addressed by one mechanism or one thing alone. For me, I think it was several of the mechanisms of ketamine happening at the same time that gave me such instant recovery. I think long term recovery is a different story and CERC-501 is something I can see helping in that.
But I also will keep looking for something else new to use with CERC-501, probably something glutamatergic, because I do feel like I am still missing something. I still lack the attachment and emotions/feelings tied to what I used to care about deeply. I still don't feel like myself and how I used to be as a person. I'm still just distracting myself a lot of the time. That's something it is hard to see myself ever getting back sometimes, but I'll keep trying and I'm glad to be taking something that can break me out of my normal patterns even a little, and hopefully help me at least get back up a bit from the low point I have gotten to.
Hope that helps anyone who was interested in hearing a personal experience on what CERC-501 feels like so far, and looking forward to hearing how others are doing on it.
