Might be onto something big in the treatment of Depersonalization Disorder

[mushubeans]

I'm x-posting this from r/drugnerds where I got a small amount of feedback.

http://en.wikipedia.org/wiki/Depersonalization
For those of you who don't know, depersonalization is a disorder consisting of dissociation from the self and one's surroundings. To find out more, click the link or ask me as I have the disorder myself.
I've been doing some researching lately into the k-opioid receptor and its role in dissociative disorders such as DP. I've been interested in this because one of the only known treatments for depersonalization is naloxone, an opioid antagonist that binds to the kappa receptor. Naloxone has been shown to have a diminishing effect on depersonalization as shown here: http://www.ncbi.nlm.nih.gov/pubmed/11448093 Now everybody with DP knows about naloxone treatment, however it's not a very viable option as the effects only last a few hours before the depersonalization returns.
Here's where things get interesting though, salvia, as many of you are aware of, is a k-opioid agonist and exerts its effects through that receptor rather than the classic 5-HT. This has lead salvia to be classified as a dissociative rather than a psychedelic. Then I found this quote from psychforums.com:
"Lack of emotional awareness, depersonalization, derealization, dissociation
Kappa opioid network(fear) causes oxytocin and vasopressin supression. It seems mu opioid probably does this as well but at higher levels.
http://www.ncbi.nlm.nih.gov/pubmed/1665795
This causes lack of emotional awareness of others - lack of "empathy" in fearful situations. It probaly also causes lack of emotional awareness of self experienced as depersonalization. Even higher levels start to cause dissociation - which is infact desensitization - loss of senses. First you lose mammalian emotions(depersonalization - loss of familiarity with self, derealization - complete loss of familiarity) then, via a different mechanism, senses(dissociation). "
So in theory, a near pure kappa opioid antagonist such as JDTic http://en.wikipedia.org/wiki/JDTic could potentially eliminate the symptoms more effectively than naloxone, which exhibits a relatively weak antagonization of the receptor.

 

[neurotic]

interesting... bumping this thread

 

[endotropic]

Assuming that the kappa antagonism is the basis for the therapeutic effect, it's very strange that the naloxone effect diminishes so much. I know with 5-HT receptors antagonists can sometimes drive downregulation/desensitization. Does anyone know if that's also the case with kappa antagonists?


Thinking downstream a little bit - if kappa agonism suppresses oxytocin, then antagonism probably increases it? If that contributes to naloxone's therapeutic effect maybe oxytocin nasal spray will have some benefit?

 

[twoci]

It's unclear based on the literature I've seen that kappa antagonism is responsible for naloxone's therapeutic effect in treating DD. Can anyone point me to an article that states as much? Also it's important to note that naloxone is only beneficial to a somewhat small subset of patients. At this point, I don't think we quite understand why that's the case.