![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
[email protected]Shown: posts 1 to 14 of 14. This is the beginning of the thread.
Posted by undopaminergic on May 22, 2008, at 10:24:20
I just wanted to highlight the potential for kappa-opioid receptor stimulation to wreak havoc on dopaminergic neurotransmission.
I'm still only scratching the surface of this, but in short, it appears that kappa agonism has the potential to drastically reduce both pre- and postsynaptic dopamine D2 receptor density, and to dysregulate the dopamine transporter protein so that stimulant bidning to the protein is reduced.
Obviously, the above might result in reduced usefulness of many dopaminergic medications, from sulpiride to direct agonists to stimulants.
Kappa-opioid antagonists like buprenorphine may thus be more essential in many more cases than most of us imagined. Indeed, perhaps even full spectrum antagonists like naltrexone would be beneficial from the point of view of combatting lethargy, anhedonia and other hypodopaminergic symptoms.
Posted by SLS on May 28, 2008, at 13:28:57
In reply to Kappa opioid receptors and dopamine, posted by undopaminergic on May 22, 2008, at 10:24:20
> Indeed, perhaps even full spectrum antagonists like naltrexone would be beneficial from the point of view of combatting lethargy, anhedonia and other hypodopaminergic symptoms.
I know of one person who, upon adding 25mg of naltrexone to ongoing SSRI treatment, experienced a remarkable antidepressant effect. You can find his posts using the Dr. Bob Google search function and using the keywords "Wayne" and "naltrexone".
- Scott
Posted by Crotale on June 2, 2008, at 17:34:52
In reply to Re: Kappa opioid receptors and dopamine, posted by SLS on May 28, 2008, at 13:28:57
> I know of one person who, upon adding 25mg of naltrexone to ongoing SSRI treatment, experienced a remarkable antidepressant effect. You can find his posts using the Dr. Bob Google search function and using the keywords "Wayne" and "naltrexone".
This is true, but OTOH, I've heard reports of dysphoria and worsened depression from kappa opioids like butorphanol and pentazocine.
Crotale
Posted by undopaminergic on June 2, 2008, at 20:37:31
In reply to Re: Kappa opioid receptors and dopamine, posted by Crotale on June 2, 2008, at 17:34:52
> > I know of one person who, upon adding 25mg of naltrexone to ongoing SSRI treatment, experienced a remarkable antidepressant effect. You can find his posts using the Dr. Bob Google search function and using the keywords "Wayne" and "naltrexone".
>
> This is true, but OTOH, I've heard reports of dysphoria and worsened depression from kappa opioids like butorphanol and pentazocine.
>
> CrotalePrecisely. Hence, blocking kappa opioids - especially endogenous dynorphin - with naltrexone or buprenorphine may have antidepressive effects.
Posted by Crotale on June 17, 2008, at 23:53:37
In reply to Re: Kappa opioid receptors and dopamine, posted by undopaminergic on June 2, 2008, at 20:37:31
> Precisely. Hence, blocking kappa opioids - especially endogenous dynorphin - with naltrexone or buprenorphine may have antidepressive effects.
You'll get no argument from me there! I believe I may have been the first person on this board to report on the use of buprenorphine as an antidepressant, when I first started using it a few years back (I was posting under a different name). It's gratifying to see that people here are getting their doctors to try it, ordering Temgesic from abroad, etc. (I take Buprenex by IM injection.)
I had once actually asked the doctor who initially recommended it to me -- who had done some research on buprenorphine as AD -- whether he had any experience with k-opioids like Stadol (butorphanol) in depressed patients. He said his experience was that if Stadol and other k-opioids had any effect on mood, they tended to be dysphorogenic.
I've heard of people using BUP with success not only for classic "endogenous" depression but also for so-called "personality disorders" in which dysphoria was a major symptom.
Posted by christophrejmc on July 12, 2008, at 2:50:28
In reply to Re: Kappa opioid receptors and dopamine » undopaminergic, posted by Crotale on June 17, 2008, at 23:53:37
> I believe I may have been the first person on this board to report on the use of buprenorphine as an antidepressant, when I first started using it a few years back (I was posting under a different name).
You must not have heard of Elizabeth. She was here many years ago to challenge the then-dominant opinion here that opioids have no place in the treatment of psychological disorders. Hers are easily some of the best posts on this board, I would definitely recommend doing a search for her posts on buprenorphine.
-Chris
Posted by christophrejmc on July 13, 2008, at 7:43:12
In reply to Re: Kappa opioid receptors and dopamine » undopaminergic, posted by Crotale on June 17, 2008, at 23:53:37
> I believe I may have been the first person on this board to report on the use of buprenorphine as an antidepressant, when I first started using it a few years back (I was posting under a different name).
You must not have heard of Elizabeth. She was here many years ago to challenge the then-dominant opinion here that opioids have no place in the treatment of psychological disorders. Hers are easily some of the best posts on this board, I would definitely recommend doing a search for her posts on buprenorphine.
-Chris
Posted by Crotale on July 16, 2008, at 12:12:54
In reply to Re: Kappa opioid receptors and dopamine » Crotale, posted by christophrejmc on July 12, 2008, at 2:50:28
> You must not have heard of Elizabeth. She was here many years ago to challenge the then-dominant opinion here that opioids have no place in the treatment of psychological disorders. Hers are easily some of the best posts on this board, I would definitely recommend doing a search for her posts on buprenorphine.
I remember her, yes. As I recall, she got a lot of crap from some people on the board for being open about taking an opioid for depression and encouraging other people to try it. She was labelled a "drug pusher" and things of that nature.
I started taking buprenorphine in 1999. I remember going to see _The Matrix_ the day I started taking it and vomiting on my way to the theater -- interestingly, I was able to sit through the film without any problems, but I got sick again on my way home afterwards! (I reduced the dose to 0.15mg (0.5mL) for a few weeks until I was able to tolerate a full mL.)
-Crotale
Posted by Questionmark on August 6, 2008, at 23:46:13
In reply to Re: Kappa opioid receptors and dopamine » christophrejmc, posted by Crotale on July 16, 2008, at 12:12:54
Well we are grateful to both you and Elizabeth for shedding light on this topic and helping make people more aware.
Wikipedia (http://en.wikipedia.org/wiki/Kappa_opioid_receptor) states that the belief that kappa opioid receptor agonists are dysphoric is a misconception. I'm not sure. But if salvinorin A is the potent (and selective[?]) kappa opioid agonist it is accepted as being, then I am a bit skeptical that agonists of these receptors are exclusively dysphoric-- unless maybe you/they're referring to chronic activation over some extended periods (and not just acute activation). Because I know that while salvinorin A isn't by any means the most euphoric substance, and it seems like many people aren't particularly fond of its effects, there are many people (myself included) who do also enjoy its effects to some extent or another. And personally, although the very high dose, melt-into-the-world to become a cog-in-a-rapidly-spinning-mega-wheel can in certain ways be quite unpleasant, I have quite often been capable of enjoying lower doses. Anyway, the point of that rambling is that I think it may depend on... I don't know, other factors-- such as possibly, selectivity of the drug, potency and/or degree of kappa opioid receptor activation, etc.-- whether or not kappa receptor agonists are dysphoriogenic (sp.?). But again maybe it may simply be when receptor activation is sustained fairly frequently over a period of time (e.g., multiple days), and not just acute activation like I was talking about.
> > You must not have heard of Elizabeth. She was here many years ago to challenge the then-dominant opinion here that opioids have no place in the treatment of psychological disorders. Hers are easily some of the best posts on this board, I would definitely recommend doing a search for her posts on buprenorphine.
>
> I remember her, yes. As I recall, she got a lot of crap from some people on the board for being open about taking an opioid for depression and encouraging other people to try it. She was labelled a "drug pusher" and things of that nature.
>
> I started taking buprenorphine in 1999. I remember going to see _The Matrix_ the day I started taking it and vomiting on my way to the theater -- interestingly, I was able to sit through the film without any problems, but I got sick again on my way home afterwards! (I reduced the dose to 0.15mg (0.5mL) for a few weeks until I was able to tolerate a full mL.)
>
> -Crotale
Posted by Questionmark on August 7, 2008, at 0:04:37
In reply to Re: Kappa opioid receptors and dopamine » undopaminergic, posted by Crotale on June 17, 2008, at 23:53:37
Couple questions, if I may:
You mentioned personality disorders, and I recall reading about the potential utility of morphine for OCD. Do you (or anyone else) think buprenorphine or another opioid may be noticeably beneficial for extreme obsessiveness and/or detrimentally excessive, detail-oriented (i.e., can't see "the forest through the trees" type) perfectionism? Just curious since thus far no drugs can touch those issues without zombifying you (ok, me).
Also, since you have personal experience with BUP's antidepressive effects, I wanted to ask if it just made you feel less bad or depressed, so to speak, or if there were beneficial effects on self-respect (or confidence, or what have you) and/or energy and/or motivation and/or etc. Cos for example, SSRIs can often make people feel less depressed (or, at least, less "bad" or feel less pain), but they don't do a whole lot in the way of other aspects. Some, to some extent, but not very much. I dunno. Anyway you're thoughts would be appreciated.
Posted by Neal on November 19, 2008, at 1:30:24
In reply to Re: Kappa opioid receptors and dopamine » Crotale, posted by Questionmark on August 7, 2008, at 0:04:37
I started bup about 3 years ago and it helped me quite a bit. It was the missing ingredient for me, because the AD's only took me 8/10 of the way to normalcy. Helped with anxiety/social anxiety, and depression too.
Will not help everybody; if there are no recent studies, there should be. I know MacLean Hospital, which is an adjunct to Harvard studied it in 1995. Some were helped, some weren't.
Interesting fact: The only drug for depression in the doctor's toolkit for the last 10,000 years up to about 1950 was the opeoids. But anyone contemplating trying them has to consider the social stigma, driven by the drug hysteria concocted by the politicians.
Posted by Neal on December 4, 2008, at 1:19:28
In reply to Re: Kappa opioid receptors and dopamine, posted by Neal on November 19, 2008, at 1:30:24
Anybody reading the last post must realize that opioids are for depressed people, or people in physical pain only. They don't work to make you feel better about yourself, solve life problems, make you feel way cool forever. Only people in need should use them because addiction is real and not worth it really, without a real need.
Posted by aminated on December 16, 2008, at 14:29:39
In reply to Re: Kappa opioid receptors and dopamine, posted by Neal on December 4, 2008, at 1:19:28
I've been on buprenorphine for TRD for about two years now. I started at 8mg/day in two doses, now i take 4mg/day same way, and it still has a significant antidepressant effect--nothing very specific about it's effect, it just brings up my mood long-term and I also feel more motivated, but i think that's just a (secondary) result of lifting depression. (I was on 90mg/day morphine prior to BUP, but I moved to California and laws/harsssment of doctors left me no choice but to switch to BUP. Morphine worked better w/ fewer side effects).
Posted by Sunkistcat79 on January 2, 2009, at 11:22:26
In reply to Kappa opioid receptors and dopamine, posted by undopaminergic on May 22, 2008, at 10:24:20
In my present state (severe severe depression) my ability to comprehend and discuss at the level of these posts is diminished, but I still hope I am welcome to be involved. I am educated (BA in early childhood education) so the science realm for me generally involves observing and drawing pinecones with crayons.
However, I was once able to research, retain and understand this subject. Here's how:
Coming from a place where my only addictions involved food and people, I took oxycodone after a car accident. This happened right in the middle of a SEVERE depression. And, without any chance of any placebo effect (at first refused to take the oxycodone because i didnt know what it was), my depression INSTANTLY vanished.
Ok, you're thinking...DUH!
Well, it wasn't a "fun-party" experience. I felt alert and calm, happy- NOT in manic way, as i mentioned before, able to read and retain difficult academic studies on neurotransmitters, kappa receptors, thebaine, etc.
I was able to do the WORK on my self I had been trying to do for YEARS. My doctor understood this phenomenon and put me on Burprnorphine (subutex). Those vile bitter pills were the most delicious, welcomed taste I have EVER known.
My one side effect involved the end of my digestive track but every time I was reminded of this typically unpleasant situation, I smiled - knowing that I was happy.I made plans to get back together and then move in with my then ex-boyfriend. By the time I moved in, I spent the first night curled up in a ball in the corner, crying hysterically - his sweet words and hugs just made me sadder. None of it made sense - I had wanted to live with him for over a year and now I was...and I just wanted to die. Something wasn't working.
When I took my fist opioid, I was taking lexapro and wellbutrin. After a month, I weaned carefully off of them and that's when problems started (that's about when I moved in). I was sure then that somehow the 3 or 2 drugs interacted and I needed to continue with all of them. However, when I got back on the other two, there was NO change.
I KNOW how I felt on the opioids is how people are supposed to feel. I got upset by things still, but I was able to CONTRTOL it. That is something I have never been able to do.
I have always known and been told that I am very physically sensitive. Doctor presented this to my mother at my Apgar test. - so decreased endorphins would make sense, yeah?
I had a miracle before.
I NEED AND DESERVE ANOTHER ONE. very very very soon.
Please feel free to read my general post (posted within the hour from this one) on the newbie board.Please...ASK ME ANY QUESTIONS.
Provide me with any information - I'll try to find a way to read it.
Refer me to doctors who will study me (I'll submit to anything short of a spinal tap.Thank you for reading and responding.
This is the end of the thread.
Psycho-Babble Neurotransmitters | Extras | FAQ
Dr. Bob is Robert Hsiung, MD,
[email protected]
Script revised: February 4, 2008
URL: http://www.dr-bob.org/cgi-bin/pb/mget.pl
Copyright 2006-17 Robert Hsiung.
Owned and operated by Dr. Bob LLC and not the University of Chicago.