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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 11 to 35 of 35. Go back in thread:
Posted by Sigismund on May 13, 2009, at 2:59:24
In reply to Re: Little more, posted by linkadge on May 12, 2009, at 21:58:25
>Take the most effective antidepressant (ECT)
That's interesting to hear you say that.
Posted by SLS on May 13, 2009, at 6:42:01
In reply to Re: Little more, posted by linkadge on May 12, 2009, at 21:58:25
> >I am uncertain as to what are the effects on >serotoninergic neurotransmission after chronic >exposure. It is quite possible that >serotoninergic activity is enhanced rather than >suppressed.
>
> I suppose thats possible, although I havn't seen studies either way. I just personally don't think that enhancement of serotonin neurotransmission has a whole lot to do with antidepressant action. Take the most effective antidepressant (ECT), some of the most recent and comprehensive studies that ECT has not appreciable or measurable effect on serotonergic neurotransmission. I guess I am just arguing with the logic: "if it doesn't increase serotonin, it can't be an antidepressant".I am in complete agreement with you.
I think it is helpful to think of depression as a diagnosis fraught with a heterogeneity of etiologies that demand a heterogeneity of treatments. It might be that the SSRIs are the best choice for some people - regardless of how they work. As you indicate, it may still have little to do with serotonin. Still, it is becoming a more common finding that 5-HT1a receptors are subsensitive in at least some cases of major depressive disorder (MDD).
Antidepressants don't seem to work in 5-HT1a receptor knockout mice with respect to anxiety related behavior.
- Scott
Posted by desolationrower on May 13, 2009, at 10:34:01
In reply to Re: Little more, posted by SLS on May 13, 2009, at 6:42:01
well its probably related to 5ht1a receptors, since they can have biphasic effects on anxiety/mood. I forgot or never really knew their complete effects, and haven't found a good usmmary yet.
i know tianeptine causes 5htergic branching from extended use, similar to sris.
last time i got high (way high, i had time running backwards and noone was speaking english and i was god and all quarks and had fractured my timeline and had to reassemble it like a puzzle or i'd be alone forever) i had 90% of my anxiety go away for about a week and a half. I had forgotten abotu that, really the only time i can remember anxiety reduced.
-d/r
Posted by linkadge on May 13, 2009, at 20:14:18
In reply to Re: Little more » linkadge, posted by Sigismund on May 13, 2009, at 2:59:24
Well, to be honest, I don't know if I believe that ECT is the most effective antidepressant, but according to the medical establishment it is.
Basically I am showing that if you assume once piece of psychiatry's logic you reach a contradiction.
Linkadge
Posted by linkadge on May 13, 2009, at 20:21:06
In reply to Re: Little more, posted by SLS on May 13, 2009, at 6:42:01
Check out this study.
Linkadge
Posted by Jimmyboy on May 13, 2009, at 23:27:21
In reply to Re: Little more, posted by desolationrower on May 13, 2009, at 10:34:01
Well.. THC is a partial Kappa opoid agonist, if you really hammered those receptors it could have caused KOR downregulation --> less anxiety.
Posted by desolationrower on May 14, 2009, at 1:37:44
In reply to Re: Little more, posted by Jimmyboy on May 13, 2009, at 23:27:21
not seen this in kidb...where did you see it
-d/r
Posted by SLS on May 14, 2009, at 6:23:44
In reply to Re: Little more » SLS, posted by linkadge on May 13, 2009, at 20:21:06
> Check out this study.
>
> http://www.ncbi.nlm.nih.gov/pubmed/17429410?ordinalpos=41&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum
>
> Linkadge
Thanks.Interesting. That is the second abstract I have seen that casts doubt on the need for 5-HT1a receptor upregulation to produce an antidepressant response.
It is an easy argument to make that the probable heterogeneity of diatheses of phenotypic depressions allows for multiple mechanisms to be contributory to a therapeutic effect across the population. Post mortem studies of humans with MDD have demonstrated reduced 5-HT1a binding.
There are so many different reported biological correlates of Axis I affective disorders, it is difficult to invest in any one of them.
- Scott
Posted by linkadge on May 14, 2009, at 8:27:34
In reply to Re: Little more » linkadge, posted by SLS on May 14, 2009, at 6:23:44
>Interesting. That is the second abstract I have >seen that casts doubt on the need for 5-HT1a >receptor upregulation to produce an >antidepressant response.
>It is an easy argument to make that the probable >heterogeneity of diatheses of phenotypic >depressions allows for multiple mechanisms to be >contributory to a therapeutic effect across the >population. Post mortem studies of humans with >MDD have demonstrated reduced 5-HT1a binding.
And some studies have demonstrated increased binding.
http://www.futurepundit.com/archives/001768.html
>There are so many different reported biological >correlates of Axis I affective disorders, it is >difficult to invest in any one of them.True
Linkadge
Posted by SLS on May 14, 2009, at 10:25:40
In reply to Re: Little more, posted by linkadge on May 14, 2009, at 8:27:34
> And some studies have demonstrated increased binding.
>
> http://www.futurepundit.com/archives/001768.htmlThis can make sense. I almost hate to say something so simplistic, but a chronic decrease in available serotonin might force these 5-HT1a somatodendritic autoreceptors to become upregulated. I don't know. I don't know enough about the dynamics of this receptor to be certain. However, if this is true, then you have a positive feedback loop that allows the severity of symptoms to worsen over time.
- Scott
Posted by Jimmyboy on May 14, 2009, at 11:02:41
In reply to Re: Little more - thc/kappa or, posted by desolationrower on May 14, 2009, at 1:37:44
Well this is from wikipedia
Cannabis sativa
"The active component of cannabis, THC, is a partial kappa-opioid agonist and may account for the aversive affects of "paranoia" experienced during its use as well as some non-addictive properties of cannabis.[53][54]"
These are what they cite:
Smith PB, Welch SP, Martin BR (March 1994).
"Interactions between delta 9-tetrahydrocannabinol and kappa opioids in mice". The Journal of pharmacology and experimental therapeutics 268 (3): 13817. PMID 8138952.
http://jpet.aspetjournals.org/cgi/content/abstract/268/3/1381
^
Hampson RE, Mu J, Deadwyler SA (November 2000)."Cannabinoid and kappa opioid receptors reduce potassium K current via activation of G(s) proteins in cultured hippocampal neurons". Journal of neurophysiology 84 (5): 235664.
PMID 11067978http://jn.physiology.org/cgi/content/abstract/84/5/2356
As well as this:
The Journal of Neuroscience, February 1, 2002, 22(3):1146-1154
Motivational Effects of Cannabinoids Are Mediated by µ-Opioid and -Opioid Receptors
Sandy Ghozland1, Hans W. D. Matthes2, Frederic Simonin2, Dominique Filliol2, Brigitte L. Kieffer2, and Rafael Maldonado1"...protocols that reveal both THC rewarding and aversive properties. Absence of µ receptors abolishes THC place preference. Deletion of receptors ablates THC place aversion and furthermore unmasks THC place preference. Thus, an opposing activity of µ- and -opioid receptors in modulating reward pathways forms the basis for the dual euphoric-dysphoric activity of THC. "
I got this from a thread at mind and muscle which has more info
http://www.mindandmuscle.net/forum/index.php?showtopic=36315&st=0&gopid=550105&#entry550105
Posted by linkadge on May 14, 2009, at 17:53:23
In reply to Re: Little more, posted by SLS on May 14, 2009, at 10:25:40
There are a lot of new studies which are challenging old theories.
Originally they though that 5-ht2a receptors were upregulated in depression. Some new research is suggesting that they are downregulated or at least less responsive in depression than normal controls.
There is some evidence of an insensitivity to serotonin in mood disorders, especially those with comorbid diabetes. Agents like chromimum actually increase insulin sensitivity as well as serotonin sensitivity.
There is a decrease in temporal lobe 5-ht1a binding in depression in temporal lobe epilepsy. This is interesting because post synaptic 5-ht1a receptors exert anticonvulsant effects in animal models of epilepsy. ECT apparently increases the sensitivty of limbic 5-ht1a receptors (which may play a role in its anticonvulsant effect).
The problem with SSRI's is that by agonizing all the serotionin receptors they don't really exert a single clean effect. I think some of the work with monoaminergic or neuropeptide agonists/antagonists is going to slowly give us a better pictue of what is relavent in mood disorders.
Theraputic serotonergic targets (that I know of) include 5-ht1a,b,d 5-ht2a,c 5-ht3 5-ht7.
I'd personally like to see some more work on the development of selective serotoniergic modulators without the dopamine effect. We need drugs like rianserin and gepirone.
Linkadge
Posted by linkadge on May 14, 2009, at 17:55:01
In reply to Re: Little more - thc/kappa or » desolationrower, posted by Jimmyboy on May 14, 2009, at 11:02:41
Interesting, although I never noticed paranoia as a side effect of the potent kappa agonist salvoin-a. I mean, it did some strange things, but I don't really remember pot like paranoia.
Linkadge
Posted by Jimmyboy on May 14, 2009, at 19:52:36
In reply to Re: Little more, posted by linkadge on May 14, 2009, at 17:53:23
Hmm.. that is interesting, if 5ht2a receptors are actually downregulated in depression it seems strange that 5ht2a antagonism helps so much with panic /anxiety.
Posted by desolationrower on May 15, 2009, at 5:29:29
In reply to Re: Little more » linkadge, posted by Jimmyboy on May 14, 2009, at 19:52:36
> Hmm.. that is interesting, if 5ht2a receptors are actually downregulated in depression it seems strange that 5ht2a antagonism helps so much with panic /anxiety.
another good thread now on 5ht1a/2 and axiety vs. panic
http://www.mindandmuscle.net/forum/index.php?showtopic=38047&hl=interesting the kappa/thc thing, i wonder how much of thc's hallucinagenic effects are from that.
Posted by linkadge on May 15, 2009, at 8:51:18
In reply to Re: Little more » linkadge, posted by Jimmyboy on May 14, 2009, at 19:52:36
Here's the article.
http://www.futurepundit.com/archives/002127.html
Not sure why 5-ht2a receptor antagonists are theraputic for some people.
Linkadge
Posted by garnet71 on May 15, 2009, at 20:02:54
In reply to Re: Little more, posted by desolationrower on May 15, 2009, at 5:29:29
That was probably one of the most interesting posts I've read in a while. I've always thought I had the unanticipatory type of anxiety/panic; it just seems to come out of nowhere. But this is very confusing to sort through. Do you know any resources that further articulate the 2 supposed types of anxiety? I've never heard of this before and would like to read up on this. thx.
One of the reasons i'm confused I thought I had the unanticipatory type of anxiety is because it wouldn't explain how I can have this anxiety but handle stressful situations at work and acute crises so effectively, and much better than working in a non-stressful environment or dealing with more protracted, chronic problems. So if I had unanticipatory anxiety rather than the other type, it seems this would not be possible, while anticipatory anxiety would better explain it because I would be dealing with "the present"? Or am i totally lost here?
Either way, I think it would be helpful to find more information about this to find a better treatment for many of us w/inadequate anxiety treatment remedies.
Posted by linkadge on May 15, 2009, at 20:38:55
In reply to Re: Little more, posted by desolationrower on May 15, 2009, at 5:29:29
I never found salvorin to be hallucinognic. I never saw anything that wasn't there. It was more of a bleeching out effect where there were less bounaries between myself and other objects.
It was nice, like I had just faded into the woodwork.
Linkadge
Posted by ricker on May 15, 2009, at 20:49:32
In reply to Re: Little more, posted by linkadge on May 15, 2009, at 20:38:55
My take is chronic anxiety = anticipatory anxiety.... panic attacks = unanticipatory anxiety??
I've also noticed that as I age, my anxiety has transformed into more of a irritability issue. Hence my view that a nervous depression eventually manifests into bipolar 2.
Rick
Posted by Phillipa on May 15, 2009, at 21:07:01
In reply to Re: Little more, posted by ricker on May 15, 2009, at 20:49:32
Ricker in my case but older than you are the opposite tirered and really need sleep. Love Phillipa
Posted by desolationrower on May 16, 2009, at 22:40:09
In reply to Re: Little more » desolationrower, posted by garnet71 on May 15, 2009, at 20:02:54
> That was probably one of the most interesting posts I've read in a while. I've always thought I had the unanticipatory type of anxiety/panic; it just seems to come out of nowhere. But this is very confusing to sort through. Do you know any resources that further articulate the 2 supposed types of anxiety? I've never heard of this before and would like to read up on this. thx.
>
> One of the reasons i'm confused I thought I had the unanticipatory type of anxiety is because it wouldn't explain how I can have this anxiety but handle stressful situations at work and acute crises so effectively, and much better than working in a non-stressful environment or dealing with more protracted, chronic problems. So if I had unanticipatory anxiety rather than the other type, it seems this would not be possible, while anticipatory anxiety would better explain it because I would be dealing with "the present"? Or am i totally lost here?
>
> Either way, I think it would be helpful to find more information about this to find a better treatment for many of us w/inadequate anxiety treatment remedies.i looked at this a while ago. i'm not sure there is much i remember that wasn't covered in that thread. i'm not sure crisis/cronic maps to this distinction though.
its more of a worry prior to doing something and avoiding it, vs. panicing once you're in a stressful situation adn wanting to exit it. what-ifs ahead of time, or AHHHHH! during.
-d/r
Posted by Questionmark on May 17, 2009, at 8:39:42
In reply to Re: Little more, posted by linkadge on May 12, 2009, at 16:09:27
Very good observation.
That does seem a bit strange that they would say that.> >So we actually demonstrated a double effect: At >low doses it increases serotonin, but at higher >doses the effect is devastating, completely >reversed
>
> I don't understand the use of the word devastating in this context. Why is lowering serotonin 'devastating'? Tianeptine lowerse serotonin and the effect isn't devastating. Usually people don't use this kind of word when describing scientific findings. It is almost, as you suggest, an attempt to demonize the effects of marajuanna.
>
> Linkadge
Posted by Jimmyboy on May 17, 2009, at 16:03:20
In reply to Re: Little more » ricker, posted by Phillipa on May 15, 2009, at 21:07:01
So would Social anxiety ( no anticipatory anxiety )- not scared to socialize but start flipping out once I am in the situation - be considered panic I suppose? Therefore 5ht2a would be the relevent receptor? Thanks
JB
Posted by desolationrower on May 18, 2009, at 16:58:42
In reply to Re: Little more, posted by Jimmyboy on May 17, 2009, at 16:03:20
yeah, although TCAs are helpful for that too.
-d/r
Posted by garnet71 on May 23, 2009, at 23:53:41
In reply to Re: Little more, posted by desolationrower on May 18, 2009, at 16:58:42
When you take this test, the results will seperate your anxiety symptoms and cluster them in the categoris panic/avoidance, PTSD, GAD, and depression.
This is the end of the thread.
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