Posted by europerep on August 17, 2010, at 14:16:04
In reply to Re: Treatment Resistant Depression. » bleauberry, posted by ed_uk2010 on August 14, 2010, at 8:58:20
> It's not a diagnosis, it's an assumption - an assumption that endorphin deficiency is the underlying problem. Again, it is unwise to presume that we understand the mechanisms behind such a response.
>
> I think you have a tendency to present theory as if it were fact.
>but ed, I am sure you know all about dr. bodkin's "experiments" with buprenorphine back in the 20th century (haha), and he's still practicing it.. delta agonists have clearly been shown to exhibit antidepressant effects in mice, some tricyclics (definitely amitriptyline and nortriptyline) increase endogenous activity at delta receptors which contributed to their usefulness in pain, but very probably also to their high efficacy in depression, and one could go on like that.. these are facts, and I guess there is not one statement on here with which I agree more than when bleauberry said it would be irresponsible to not add the endogenous opioid system into the equation.. some patients with TRD show totally paradox reactions to opioids, i.e. feeling normal as was said, but also having less problems going off of them.. I didn't talk about it much because I wanted to make one comprehensive post about it, right now I just do not have the energy for it: I did try buprenorphine for the past 4 months, dosage up to 9mg/d (maximum in TRD is around 12mg/d).. it DID work in the beginning, and that was NOT due to the general opioid euphoria.. this euphoria is mu-receptor-mediated, and buprenorphine plasme levels peak at 45min to 1 hour after intake (sublingual).. also, "recreational" users say the effect is strongest at about an hour.. my improvement started some 4-5 hours after taking it - and subsided some 4-5 hours later.. I was very confused, until I found out that the response I had was basically identical to the plasma level over time-curve of nurbuprenorphine, the active metabolite, which is a delta-agonist.. but it has a much much shorter halflife, and so the effect disappeared quickly.. unfortunately I was not able to reproduce it after the first one to two weeks.. now I wonder what conclusions to draw from that... also, I was not "high", I cleaned up my kitchen for the first time in quite some time, and I did not only finish what I set as a target, but I looked for something else to do because I was quicker than I expected.. now I say I do "this", and ten minutes into it I am just unable to go on.. this is so disappointing... unfortunately, I think that there is no specific delta-agonist that I could try out to verify my hypothesis... but I have no doubt that there is something about it, and I think it's more than just a hypothesis that has yet to prove it's value.. it's by far no solution for everyone as I just experienced, but it is a solution for some... it scares me that it isn't one for me, who knows what will work instead, or if anything will work at all...
poster:europerep
thread:958488
URL: http://www.dr-bob.org/babble/20100811/msgs/958926.html