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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 9 of 9. This is the beginning of the thread.
Posted by JahL on January 22, 2008, at 14:51:12
Hello people. Wow it's been a long time. I hope at least some of you have made some progress in the interim.
I'm hoping that one of you brainy psychopharmacologists can enlighten me a little.
I have a history of excellent responses to opioids and so when I came across this (http://news.bbc.co.uk/1/hi/magazine/7071010.stm) article on a plant called Salvia, which apparently works its magic via kappa-opioid receptors, I was naturally very interested.
I am not looking to discuss the rights and wrongs of hallucinogens (though I personally find them to be rather pleasurable), but rather, what the implications of such a mode of action might theoretically be for an opioid-responsive individual (ie me).
Thanks in advance for any thoughts.
Ta,
Jah.
Posted by ShawnThomas on January 23, 2008, at 19:01:02
In reply to Salvia and kappa-opioids., posted by JahL on January 22, 2008, at 14:51:12
The active component of Salvia divinorum, Salvinorin A, is a selective kappa1 opioid receptor agonist
(Ansonoff et al., 2006; http://pubmed.gov/16672569). I'm not sure how this could have any personal implications for you.Although some pain-relieving substances may act at kappa opioid receptors, substances marketed as drugs are not likely to affect kappa1 opioid receptors that are involved in the perceptual distortions and dysphoria associated with Salvia divinorum.
The key mechanism of action shared by most opioid analgesics is mu opioid receptor agonism (i.e., activation).
Shawn
Posted by kingcolon on January 30, 2008, at 18:19:07
In reply to Salvia and kappa-opioids., posted by JahL on January 22, 2008, at 14:51:12
> Hello people. Wow it's been a long time. I hope at least some of you have made some progress in the interim.
>
> I'm hoping that one of you brainy psychopharmacologists can enlighten me a little.
>
> I have a history of excellent responses to opioids and so when I came across this (http://news.bbc.co.uk/1/hi/magazine/7071010.stm) article on a plant called Salvia, which apparently works its magic via kappa-opioid receptors, I was naturally very interested.
>
> I am not looking to discuss the rights and wrongs of hallucinogens (though I personally find them to be rather pleasurable), but rather, what the implications of such a mode of action might theoretically be for an opioid-responsive individual (ie me).
>
> Thanks in advance for any thoughts.
>
> Ta,
>
> Jah.
>
> I'm not a psychopharm, but I'm on buprenorphine for chronic depression with excellent response. Bupe is a kappa antagonist, which is felt to be partially responsible for antidepressant properties. Kappa hyperactivity is possibly one mechanism of the opioid withdrawal syndrome, with its dysphoric effects. I would think kappa agonists would not be what you would want if you have depression or anxiety.
Posted by Dopamine123 on February 21, 2008, at 12:16:13
In reply to Re: Salvia and kappa-opioids., posted by kingcolon on January 30, 2008, at 18:19:07
"I would think kappa agonists would not be what you would want if you have depression or anxiety."
Yes kappa opioid agonists are known for their dysphoric effects.
"Kappa is the "ugly" opioid receptor whose endogenous ligand is dynorphin. The dynorphin/kappa-opioid receptor system is implicated in the unpleasant states of mind caused by chronic uncontrolled stress. Repeated use of cocaine, heroin, alcohol and other euphoriant drugs induce a compensatory up-regulation the dynorphin/kappa-opioid receptor system too, causing anxiety, anhedonia and dysphoria. Whereas mu opioids induce euphoria by enhancing dopamine release in the nucleus accumbens, activation of kappa opioid receptors inhibits dopamine release from the mesolimbic terminals. This deficiency is unpleasant because the mesolimbic dopamine system regulates hedonic tone and the capacity to experience (and anticipate) happiness."
Visit my blog about neuroscience/neurotechnology.
http://brainstimulant.blogspot.com
Posted by ShawnThomas on February 22, 2008, at 11:55:52
In reply to Re: Salvia and kappa-opioids., posted by Dopamine123 on February 21, 2008, at 12:16:13
Kappa receptors may be ugly in your opinion, but they are also a very important therapeutic target. Some kappa opioid receptor agonists that probably do not affect kappa1 receptors are effective analgesics; however, they are not associated with dysphoria. All of the FDA approved kappa agonists also affect mu opioid receptors.
CR665 is a selective kappa opioid receptor agonist that only affects the peripheral nervous system. The drug is beginning phase II clinical trials in the US (http://www.caratherapeutics.com/pipeline-business-strategy.php).
Cara Therapeutics claims that, "Therapeutic indications for peripherally-restricted kappa agonists include, but are not restricted to, post-operative pain and ileus associated with abdominal surgery, pancreatitis pain, dysmenorrhea, labor pain, and irritable bowel syndrome. In addition to their utility as analgesics, kappa agonists have been recognized to possess unique anti-inflammatory actions which may be useful in the treatment of diseases such as rheumatoid arthritis."Shawn
Posted by Dopamine123 on February 23, 2008, at 14:06:54
In reply to Re: Salvia and kappa-opioids. » Dopamine123, posted by ShawnThomas on February 22, 2008, at 11:55:52
"Kappa receptors may be ugly in your opinion"
That wasn't my opinion. It was the guy from biopsychiatry.com (David Pearce I think). Sorry if I gave you the impression that it was my opinion.
"only affects the peripheral nervous system."
By that I assume it doesn't affect the brain. A kappa agonist targeted to the brain could potentially cause hallucinations and dysphoria. So they are really two different types of drugs. Salvia gets to the brain, while the peripheral kappa agonist drugs do not.peripheral kappa receptors
http://www.caratherapeutics.com/terminology.php
"As a way to avoid these undesirable CNS effects, there has been an effort to develop opioids which selectively activate (agonist) peripheral opioid receptors such as kappa receptors, present on sensory nerves, outside the central nervous system."
Posted by Dopamine123 on February 23, 2008, at 14:10:49
In reply to Salvia and kappa-opioids., posted by JahL on January 22, 2008, at 14:51:12
Buprenorphine is supposed to have antidepressant properties.
http://opioids.com/buprenorphine/buprefdep.htmlIt is a partial mu-opioid agonist and a kappa-opioid antagonist. The kappa-opioid antagonist property may explain part of its antidepressant effect. That drug might be worth a try.
Posted by kingcolon on February 24, 2008, at 12:06:36
In reply to Re: Salvia and kappa-opioids., posted by Dopamine123 on February 23, 2008, at 14:10:49
> Buprenorphine is supposed to have antidepressant properties.
> http://opioids.com/buprenorphine/buprefdep.html
>
> It is a partial mu-opioid agonist and a kappa-opioid antagonist. The kappa-opioid antagonist property may explain part of its antidepressant effect. That drug might be worth a try.With all due respect, I just made this point a few posts back. And I would once again add that I'm on bupe and it has worked wonderfully for my rather treatment-resistant depression. The Bodkin article is a "classic" and I've found little in the way of trials other than his. Here is an article of interest that talks about cognitive deficits in people on buprenorphine and methadone.
I've noticed no problem--in fact, my attention and insight seems better on bupe.http://www.biomedcentral.com/1472-6904/7/5#B56
If anyone would like a copy of the full Bodkin study, I have it--you can get to me by kingcolon.
Posted by Dopamine123 on February 24, 2008, at 12:38:55
In reply to Re: Salvia and kappa-opioids. » Dopamine123, posted by kingcolon on February 24, 2008, at 12:06:36
> With all due respect, I just made this point a few posts back.
My mistake. I missed your post, sorry. I don't want to sound like I'm just parroting what you said.
This is the end of the thread.
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