![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 13 of 13. This is the beginning of the thread.
Posted by cisco on March 31, 2002, at 21:15:24
The answer was here all along....
I found this old Psycho-Babble post during a Google search for Buprenorphine Kappa Antagonism:"The mu receptor is most commonly associated with euphoria and pain relief. The kappa receptor is most commonly associated with sedation (nodding often seen in Heroin addicts).
Underproduction or over-removal (severe re-uptake) of these endogenous opioids can be the cause of many psychiatric disorders ranging from Bipolar Personality disorders to major depressive disorders that often times manifest themselves in severe drug abuse.
Unbeknownst to them, these patients use Opioid medications either illicit or pharmaceutical because they are compelled to attempt to replace the endorphins, dynorphins, and enkephalins (endogenous opioids) that naturally occur in their systems at insufficient levels.
When taking these patients into account, a better term than the word "addict" or DDP (drug dependent person) would be opiate receptor deficient (ORD)
Buprenorphine's superior efficacy when dealing with these disorders is due to the aforementioned unique pharmacological profile as a PARTIAL MU RECEPTOR AGONIST combined with a FULL KAPPA RECEPTOR ANTAGONIST.
FACT: Buprenorphine is the strongest kappa receptor antagonist currently legal to use anywhere throughout the world. There is a large body of evidence that implicates mu agonists in anxiety and depressive disorders
Fink et al 1970, Kline et al 1977, Angst et al 1979, Pickar et al 1981
Pfeifer et al 1986, Schmauss and Heimrich et al 1988, Frecksa et al 1989,
Matussk and Hoehe et al 1989.)
The kappa antagonism of Buprenorphine also offers a new approach in the treatment of depressive disorders. Clinical studies have shown that the overproduction or under-removal of the endogenous kappa agonist dynorphin can have a direct causal relationship with various depressive disorders.
Therefore, a kappa antagonist would be of great clinical value in this treatment paradigm.
Buprenorphine is the strongest kappa antagonist currently available for clinical use.
Buprenorphine's unique pharmacological profile referenced earlier make it the only medication that offers this concurrent treatment alternative.
Additionally, clinical studies suggest that Buprenorphine increases the levels of the neurotransmitter dopamine in the brain pathways that control pleasure indicating a third method of effect. Conventional antidepressants and antipsychotics work gradually over a period of weeks or months, whereas maximal benefit is
apparent with Buprenorphine in a matter of days and in some cases hours.
After undergoing treatment with Buprenorphine, patients report an almost immediate improvement in function, an elevation of mood, and a general feeling of contentment. The fact that a rapid alteration in mental state can be produced by a pharmacological agent suggest an alternate theory to that of treatment with conventional antidepressants and the slow adaptive changes that are associated with simultaneous psychotherapeutic treatment."Perhaps 'Kappa Antagonism' is more than just an "Absence of effect" at the Kappa receptors....
More Opiate Antagonism News:
Buprenorphine is a
mixed µ-agonist/k-antagonist compound (Leander 1987; Sadée et al. 1982) that has been used to treat various forms of addiction in humans (Bracken and Holford 1993; Kosten et al. 1989).
In preliminary studies (Johnson et al. 1989), buprenorphine administered 30 minutes after fluid percussion-induced traumatic brain injury in rats significantly improved neurological outcome at 4
weeks as compared to saline-treated controls Opiate antagonists have been shown to be of benefit in spinal cord injury (Bracken and Holford 1993) and possibly cerebral ischemia
(Adams et al. 1986; Estanol et al. 1985) in humans. Given these preliminary experimental data and the established safety of buprenorphine treatment in humans, buprenorphine appears to be a
potentially attractive therapy for acute brain or spinal cord injury in humans.I find this line of inquiry interesting, as Bup appears to be a very complex Med. Hope U enjoy it 2!
Cisco
Posted by JohnX2 on April 1, 2002, at 4:37:11
In reply to Buprenorphine, Kappa Antagonism and Depression, posted by cisco on March 31, 2002, at 21:15:24
This mentions that Buprenorpine is a "partial" mu-agonist. Is this medicine habit forming?Thanks,
John> The answer was here all along....
> I found this old Psycho-Babble post during a Google search for Buprenorphine Kappa Antagonism:
>
> "The mu receptor is most commonly associated with euphoria and pain relief. The kappa receptor is most commonly associated with sedation (nodding often seen in Heroin addicts).
> Underproduction or over-removal (severe re-uptake) of these endogenous opioids can be the cause of many psychiatric disorders ranging from Bipolar Personality disorders to major depressive disorders that often times manifest themselves in severe drug abuse.
> Unbeknownst to them, these patients use Opioid medications either illicit or pharmaceutical because they are compelled to attempt to replace the endorphins, dynorphins, and enkephalins (endogenous opioids) that naturally occur in their systems at insufficient levels.
> When taking these patients into account, a better term than the word "addict" or DDP (drug dependent person) would be opiate receptor deficient (ORD)
> Buprenorphine's superior efficacy when dealing with these disorders is due to the aforementioned unique pharmacological profile as a PARTIAL MU RECEPTOR AGONIST combined with a FULL KAPPA RECEPTOR ANTAGONIST.
> FACT: Buprenorphine is the strongest kappa receptor antagonist currently legal to use anywhere throughout the world. There is a large body of evidence that implicates mu agonists in anxiety and depressive disorders
> Fink et al 1970, Kline et al 1977, Angst et al 1979, Pickar et al 1981
> Pfeifer et al 1986, Schmauss and Heimrich et al 1988, Frecksa et al 1989,
> Matussk and Hoehe et al 1989.)
> The kappa antagonism of Buprenorphine also offers a new approach in the treatment of depressive disorders. Clinical studies have shown that the overproduction or under-removal of the endogenous kappa agonist dynorphin can have a direct causal relationship with various depressive disorders.
> Therefore, a kappa antagonist would be of great clinical value in this treatment paradigm.
> Buprenorphine is the strongest kappa antagonist currently available for clinical use.
> Buprenorphine's unique pharmacological profile referenced earlier make it the only medication that offers this concurrent treatment alternative.
> Additionally, clinical studies suggest that Buprenorphine increases the levels of the neurotransmitter dopamine in the brain pathways that control pleasure indicating a third method of effect. Conventional antidepressants and antipsychotics work gradually over a period of weeks or months, whereas maximal benefit is
> apparent with Buprenorphine in a matter of days and in some cases hours.
> After undergoing treatment with Buprenorphine, patients report an almost immediate improvement in function, an elevation of mood, and a general feeling of contentment. The fact that a rapid alteration in mental state can be produced by a pharmacological agent suggest an alternate theory to that of treatment with conventional antidepressants and the slow adaptive changes that are associated with simultaneous psychotherapeutic treatment."
>
> Perhaps 'Kappa Antagonism' is more than just an "Absence of effect" at the Kappa receptors....
>
> More Opiate Antagonism News:
>
> Buprenorphine is a
> mixed µ-agonist/k-antagonist compound (Leander 1987; Sadée et al. 1982) that has been used to treat various forms of addiction in humans (Bracken and Holford 1993; Kosten et al. 1989).
> In preliminary studies (Johnson et al. 1989), buprenorphine administered 30 minutes after fluid percussion-induced traumatic brain injury in rats significantly improved neurological outcome at 4
> weeks as compared to saline-treated controls Opiate antagonists have been shown to be of benefit in spinal cord injury (Bracken and Holford 1993) and possibly cerebral ischemia
> (Adams et al. 1986; Estanol et al. 1985) in humans. Given these preliminary experimental data and the established safety of buprenorphine treatment in humans, buprenorphine appears to be a
> potentially attractive therapy for acute brain or spinal cord injury in humans.
>
> I find this line of inquiry interesting, as Bup appears to be a very complex Med. Hope U enjoy it 2!
>
> Cisco
Posted by jay on April 1, 2002, at 9:15:45
In reply to Buprenorphine, Kappa Antagonism and Depression, posted by cisco on March 31, 2002, at 21:15:24
There are also a number of studies that suggest these pathways are also partially regulated with chronic antidepressant use, often the ones that strongly affect norepinephrine. I have read of Effexor being one of them. I really think a combo of high dose Effexor and Buprenorphine could be an excellent choice, maybe even with some Welbutrin added in.Jay
Posted by shelliR on April 1, 2002, at 17:49:57
In reply to Re: Is Buprenorphine habit forming?, posted by JohnX2 on April 1, 2002, at 4:37:11
John,
Some people like me have found it habit-forming. Others like Elizabeth have been on it for several years without needing to raise the dose. (You have to remember that many ADs, effexor and others, are also habit-forming.) I believe that my need to keep raising my dose has to do with my history of high doses of oxycontin, given by a pdoc last year to battle TRD. I do know that bupe is an easier drug to get off of than full opiates.
Shelli
Posted by Elizabeth on April 4, 2002, at 19:58:55
In reply to Buprenorphine, Kappa Antagonism and Depression, posted by cisco on March 31, 2002, at 21:15:24
Cisco says:
> The answer was here all along....The answer to what?
> "The mu receptor is most commonly associated with euphoria and pain relief. The kappa receptor is most commonly associated with sedation (nodding often seen in Heroin addicts).
These aren't the only effects mediated by these two receptor subtypes, but I do find buprenorphine very activating, more so than morphine, hydrocodone, or fentanyl (although I've never experienced "the nod" on any opioid). I've also heard that butorphanol (Stadol), a kappa-agonist analgesic, makes a lot of people feel crappy.
> Underproduction or over-removal (severe re-uptake) of these endogenous opioids can be the cause of many psychiatric disorders ranging from Bipolar Personality disorders to major depressive disorders that often times manifest themselves in severe drug abuse.
"Bipolar Personality disorders?"
Dare I ask who wrote this?
> Unbeknownst to them, these patients use Opioid medications either illicit or pharmaceutical because they are compelled to attempt to replace the endorphins, dynorphins, and enkephalins (endogenous opioids) that naturally occur in their systems at insufficient levels.
I think plenty of them are aware of it.
> When taking these patients into account, a better term than the word "addict" or DDP (drug dependent person) would be opiate receptor deficient (ORD)
It's probably more complicated than that (just like people who respond to Prozac weren't necessarily depressed because of "low serotonin levels"). But yeah, although I've never been addicted to anything, several pdocs have suggested that I might be "endogenous opioid-deficient."
> Perhaps 'Kappa Antagonism' is more than just an "Absence of effect" at the Kappa receptors....
Of course it is; buprenorphine blocks the effects of endogenous kappa agonists. I think that Goodman & Gilman has a table listing some of the effects of the different opioid receptor subtypes, but I'm not sure where my copy went.
John says:
> Is this medicine habit forming?That probably depends what you mean by "habit forming." But most likely, no it isn't. (A partial agonist is a drug that activates a receptor but doesn't cause the maximum effect at that receptor.)
And Jay says:
> I really think a combo of high dose Effexor and Buprenorphine could be an excellent choice, maybe even with some Welbutrin added in.Funny you should say that. I take Effexor and buprenorphine, and I'm doing better than I have in years. (Not interested in trying Wellbutrin again; I found that stuff pretty miserable.)
-elizabeth
Posted by Zo on April 5, 2002, at 0:15:14
In reply to buprenorphine stuff, posted by Elizabeth on April 4, 2002, at 19:58:55
Posted by Elizabeth on April 5, 2002, at 9:17:45
In reply to Hey, great to hear! Good ol' Effexor (nm) » Elizabeth, posted by Zo on April 5, 2002, at 0:15:14
:-)
I think Effexor is about comparable to Parnate or desipramine. It's easier to use, though. I only have to take it in two divided doses instead of six as I did with Parnate (had to do this to minimize paroxysmal hypertension), and it doesn't require serum level testing as desipramine did (you read about the "episode" I had when I was on desipramine, right?). It's really the buprenorphine that has done away with the residual depression that was causing me so much trouble.
-e
Posted by Cisco on April 5, 2002, at 16:19:30
In reply to buprenorphine stuff, posted by Elizabeth on April 4, 2002, at 19:58:55
Elizabeth:
> The answer to what?
When I asked, not long ago, what was the effect of Buprenorphine's potent 'Kappa Antagonism', you responed with "Absence of effect at the Kappa Receptor".
> Dare I ask who wrote this?
Dare you may: I'll go back and find the Author. Probably some Wack-O Hack-O-Matic.
> Of course it is; buprenorphine blocks the effects of endogenous kappa agonists. I think that Goodman & Gilman has a table listing some of the effects of the different opioid receptor subtypes, but I'm not sure where my copy went.If you were aware of this, why then the terse reply to my earlier question??
Buprenorphine and Effexor combined: Could it be the cutting edge treatment for TRD?
Cisco
Posted by shelliR on April 5, 2002, at 20:56:48
In reply to buprenorphine stuff, posted by Elizabeth on April 4, 2002, at 19:58:55
> Is this medicine habit forming?
>That probably depends what you mean by "habit forming." But most likely, no it isn't. (A partial agonist is a drug that activates a receptor but doesn't cause the maximum effect at that
receptor.)<I guess I would define habit forming in two ways.
Can you get off it once you start it: according to the information of Alexander Bodkin et.al, there is little withdrawal compared to full opiates.
Do people have to increase dose?
In the case studies of the 4 or 5 successful outcomes with buprenorphine (out of 7 who stayed in the study), most users did have to increase. At least one or two significantly over months and in one case through out a five year period.
Shelli
Posted by Zo on April 7, 2002, at 5:10:43
In reply to Re: Hey, great to hear! Good ol' Effexor, posted by Elizabeth on April 5, 2002, at 9:17:45
Posted by Elizabeth on April 7, 2002, at 21:17:59
In reply to Re: buprenorphine stuff » Elizabeth, posted by Cisco on April 5, 2002, at 16:19:30
> When I asked, not long ago, what was the effect of Buprenorphine's potent 'Kappa Antagonism', you responed with "Absence of effect at the Kappa Receptor".
Did I? That wasn't accurate. I should have said that not only does it lack kappa-opioid effects, it also blocks the effects of other kappa opioids (including endogenous ones).
> > Dare I ask who wrote this?
>
> Dare you may: I'll go back and find the Author. Probably some Wack-O Hack-O-Matic.<g>
> If you were aware of this, why then the terse reply to my earlier question??
I obviously wasn't thinking clearly. :-}
> Buprenorphine and Effexor combined: Could it be the cutting edge treatment for TRD?
*shrug* I think that for me, several of the standard ADs would have been fine with buprenorphine -- Parnate and desipramine worked as well as Effexor, but Effexor has fewer side effects. I don't know if anyone who's truly treatment-resistant would find this an especially magical combination, though.
What do you think?
-elizabeth
Posted by Elizabeth on April 7, 2002, at 21:51:14
In reply to Re: buprenorphine stuff » Elizabeth, posted by shelliR on April 5, 2002, at 20:56:48
> Can you get off it once you start it: according to the information of Alexander Bodkin et.al, there is little withdrawal compared to full opiates.
Yes, discontinuing buprenorphine is pretty easy. Extremely easy if you're comparing it to a full mu-receptor agonist.
Once, shortly after I'd stopped taking desipramine, I ran out of buprenorphine and wasn't able to get more for a couple of days. I was extremely depressed -- I had a terrible time. However, when I've been on antidepressants (Parnate, desipramine, Effexor), I've been able to miss a dose or two of buprenorphine without having too hard a time. So I think it was mostly just a relapse. There were some withdrawal symptoms -- shivering and irritability, mainly -- but the depression was about as bad as it had been before I'd gotten on the medications. (Irritability and depression made a particularly nasty mix.)
> Do people have to increase dose?
I haven't. This definitely varies, though.
> In the case studies of the 4 or 5 successful outcomes with buprenorphine (out of 7 who stayed in the study), most users did have to increase. At least one or two significantly over months and in one case through out a five year period.
Yes. I think it's probably common. But I've also heard several anecdotes about people taking opioids (oxycodone and MSIR as well as buprenorphine) who didn't develop tolerance. I'm not sure which is the rule and which is the exception.
And to Zo: I've never heard of anyone else becoming manic on any opioid, no.
-elizabeth
Posted by Zo on April 8, 2002, at 21:46:39
In reply to Re: buprenorphine stuff » shelliR, posted by Elizabeth on April 7, 2002, at 21:51:14
This is the end of the thread.
Psycho-Babble Medication | Extras | FAQ
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.org
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.