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Dr. Bob is Robert Hsiung, MD,
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Posted by zeugma on October 31, 2006, at 17:57:37
In reply to effect of melatonin on seratonin?, posted by iforgotmypassword on October 30, 2006, at 12:52:55
> MAIN QUESTION: does anyone know if melatonin reduces seratonin activity anywhere, at specific receptors, or just in general? or does it increase seratonin?
Melatonin probably lowers serotonin levels in many regions of the brain. Serotonin levels are highest during wakefulness, and melatonin levels are highest in the period of drowsiness leading to sleep, in what was probably the normal course of things before Edison, 12 hours after the first exposure to significant amounts of sunlight (an hour or so after sunrise?).
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> i am replacing all lights in my house with yellow "bug" lights (to hopefully block the blue) so i can actually sleep given all the time i spend in bed. i always have to sleep with the light on due to fear and general anxiety. yellow aparently does not cancel out melatonin production. blue does.>>this is interesting. The receptors in the retina that are sensitive to blue and yellow light are said to be dopaminergic (probably D2) receptors. I have extreme color-insensitivity, in fact unless on a significant dose of Ritalin I can barely process color at all. (Don't hire me to decorate your house.) Now besides Luvox, the class of meds that tends to produce circadian sleep disorders is the D2 antagonists, a.k.a. typical antipsychotics. Atypicals such as Risperdal are much less prone to this effect, probably because the 5-HT2A antagonism (which seems to promote normal melatonin release) counteracts the D2 antagonism and consequent retinal insensitivity to yellow- which is, more or less, the color of the sun. Ritalin actually helped me with circadian issues more than any other med. it certainly helped me see color.
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> another huge factor is if it reduces seratonin, it may help my bruxism and akithisic feelings, and hopefully reduce apathy and give energy. (and less catecholamine and acetylcholine suppesion?)
>Buspar is actually somewhat helpful with bruxism issues. So is Klonopin, and benzodiazpines stimulate melatonin release.
-z
Posted by zeugma on October 31, 2006, at 18:00:28
In reply to Re: effect of melatonin on seratonin? » linkadge, posted by johnnyj on October 31, 2006, at 9:20:27
> I melatonin is increased in the blood stream by luvox how does this equate to reduced melatonin output? Wouldn't this be the opposite? So luvox might guard against cancer? This is very confusing>>
Luvox can produce continuously elevated levels of melatonin. I don't know what effect this would have on proneness to cancer.
-z
>
> johnnyj
Posted by iforgotmypassword on October 31, 2006, at 18:11:14
In reply to Re: effect of melatonin on seratonin? » linkadge, posted by zeugma on October 31, 2006, at 17:26:32
even though i do spend a lot of my life in bed miserable, i spend just as much time pacing and talking non-stop... and i chew through my teeth all day. i don't even have to be agitated. it is often associated with agitation that i have, tho. it is purely akathisic and started with paxil years ago. i even start twitching again on most ADs, even dopaminergic ones. (i figure its a paradoxical response analagous to what levodopa does to parkinsonian people.)
i knew it was akithisic related and it was a lot more encouraging to find attitudes supporting this:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=10665633&query_hl=3&itool=pubmed_docsum
ECT, that seems to reset the RECEPTORS of the brain seems to have a remarkable therapeutic effect in at least this one case:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=12972988&query_hl=1&itool=pubmed_docsumi think my problems are basically the opposite of a depressed person. i think my problems lie in what causes akithisia. serotonergic OVER activity. or sertonin receptor hypersensitivity. which of course causes dopaminergic and acetylcholinergic failure. like how it treats OCD. it basically unplugs the anterior cingulate and possibly the parts of the frontal cortex that depend on it (what we usually blame for cases like mine.) this all leading to extreme terrible problems with executive function and apathy. the story of my life.
does anyone know of any drugs that help this?
i am looking into 5HT-2a agonists, but they all seem illicit. maybe that is why i love them so much. i literally have feelings again on mushrooms. apart from being kind of wacky from an illict drug, it's the closest i feel to normal. i don't think it's exactly a solution for my executive functionning though.
Posted by iforgotmypassword on October 31, 2006, at 18:24:00
In reply to Re: effect of melatonin on seratonin? » iforgotmypassword, posted by zeugma on October 31, 2006, at 17:57:37
thank you so much, i am so glad that this may make so much sense for me... i hope.
i tried buspirone... may have helped SLIGHTLY. i think i really need something that has a bit more definite effect.
i like the idea of how 5HT-2a agonism may reduce D2 antagonism. maybe paradoxical D2 antagonism, and it's basically being a failed antipsychotic that causes akithisia in some, practically negates it's ability to help with me.
i may increase my estrogen (i'm transgenedered) which i think is supposed to increase 2A sensitivity.
i also worry if i may be a psuedo-'tardive' case, which they say is much difficult to treat. being that i still have problems years after Paxil. (like 5 years.)
Posted by iforgotmypassword on October 31, 2006, at 18:29:09
In reply to thank you. » zeugma, posted by iforgotmypassword on October 31, 2006, at 18:24:00
what i said: "i like the idea of how 5HT-2a agonism may reduce D2 antagonism. maybe paradoxical D2 antagonism, and it's basically being a failed antipsychotic that causes akithisia in some, practically negates it's ability to help with me."
but you were talking about antagonism in risperdal. sorry i have trouble reading, and tend to not be able to read unless i pseudo speed-read. (if i try to read normally i get confused so i can never read books, stories or long personal letters to me properly!) i have to make multiple passes often to make sure i didn't misinterpret.
Posted by zeugma on October 31, 2006, at 19:13:09
In reply to wondering in my case..., posted by iforgotmypassword on October 31, 2006, at 18:11:14
illicit vs. non-illicit is a somewhat arbitrary distinction IMO.
excessive 5HT could lead to bruxism, apathy, etc.
You are correct that 5HT2A agonism leads to DA release. other 5HT2 receptors probably inhibit dopamine, so it is a complex matter.
What is your response to nicotine?
-z
Posted by iforgotmypassword on October 31, 2006, at 20:22:51
In reply to Re: wondering in my case... » iforgotmypassword, posted by zeugma on October 31, 2006, at 19:13:09
how does nicotine affect serotonin receptors?
_____i never got addicted to nicotine, but i also have asthma, and really had bad feelings about my mother who used to smoke all the time.
i got addicted to pot (literally), and kind of wondered if it had to do with the tobacco i would put in to make joints easier to take.
it was odd because i kept using pot long after it was even slightly enjoyable. i would just get paranoid and draw into myself even further, and behave pretty dingbatty and annoying around people. i would get scared and couldn't be around people and be wrecked for days. i could not find out why it was hard to stop.
i may try nicotine again, but i really practically felt no response to patches. i literally gave up after one day though.paradoxially though, galantamine did seem to help me, at least with communicating with people and sort of reintegrating into purposeful activity.
short lived however, and not very affordable given it was just a supplement version i was kind of ambivalent about depending on given how unreliable dosing is with supplements. i think this also lead to early discouragement, and it kind of made me feel rough and agitated.
thank you for your input.
Posted by johnnyj on October 31, 2006, at 20:35:54
In reply to Re: effect of melatonin on seratonin? » johnnyj, posted by zeugma on October 31, 2006, at 18:00:28
Thank you I will ask my doc about the melatonin issue. Even if luvox makes blood levels higher would light in the morning tone this down? Before meds I slept great and used to take a while to get going in the morning.
Do you think that luvox is, how should I say, harmful overall? What about long term effects of increased melatonin on the circadian rythm? I know things are out of whack right now to a degree.
I have ocd, anxiety issues and this results in a depressive state to some degree. I thought luvox might be a good choice as I really don't get tired and sleepy like I normally used to and that is what I need to feel better...sleep.
I am only on lunesta right now and it has side effects too. I may try to quit it since I have stopped lithium and started meds for allergies. I felt that lithium was not good for me and things actually slowed down after I quit lithium. Lunesta seems to make me more depressed and dizzy. I am finding quite a few people that have anxiety/nausea/dizziness on lunesta after a few months. It is happening to me now. So, I may try to wean off even thought I am not sure how to do this cold turkey as I might feel better quicker but not sleep better. Of course my pdoc will approve any of this.
Benzo's seem to make me depressed but the pdoc wants to try luvox and klonopin. Do you think a different ssri may be better?
Posted by Phillipa on October 31, 2006, at 22:14:21
In reply to Re: effect of melatonin on seratonin? » zeugma, posted by johnnyj on October 31, 2006, at 20:35:54
I'm confused too as luvox is the only SSRI that has no side effects for me and lets me sleep. So in a nutshell is it good or bad for sleep. It has a short halflife and I'm down to 25mg with valium and the pdoc gave me the new paxil pexeva? Never heard of it before . I may or may not try it. She also said I've taken benzos for so many year over 30 that they didn't work anymore so take the valium and add seroquel amount up to me too. Love Phillipa
Posted by zeugma on November 1, 2006, at 5:03:14
In reply to Re: effect of melatonin on seratonin? » johnnyj, posted by Phillipa on October 31, 2006, at 22:14:21
> I'm confused too as luvox is the only SSRI that has no side effects for me and lets me sleep. >>
That's great!
So in a nutshell is it good or bad for sleep.>>
For you, it sounds like it is better for sleep than the other SSRI's.
Responses to these meds are so variable, that genralizations can't be made without understanding that there are many hidden variables at work (if genomic testing and so on were routine, this might be different, but for now, all we can do is trial and error, and if it works, then stay with it if the s/e/ are not unbearable).
The sleep doc responded to my question about Lexapro (dx: CNS hypersomnolence, narcolepsy) by saying that it helped sleep in some, and worsened it for others. So you never know until you try it.
-z
Posted by zeugma on November 1, 2006, at 5:42:25
In reply to Re: effect of melatonin on seratonin? » zeugma, posted by johnnyj on October 31, 2006, at 20:35:54
> Thank you >>
you're welcome.
I will ask my doc about the melatonin issue. Even if luvox makes blood levels higher would light in the morning tone this down? Before meds I slept great and used to take a while to get going in the morning. >>
I'm not sure about morning light effect with Luvox. I mean, i have absolutely no idea. I was prescribed a light box years ago, and the problem was, in two words, noncompliance and misdiagnosis. I was already developing narcoleptic symptoms, which are accompanied by migraine-like headaches, photophobia (which made me averse to sitting under the box for an hour), etc., (although they are more shortlived than most migraines) and the interference in my sleep was related to this, and morning light probably (I only say this because I wake up early nowadays, am exposed to daylight, but it doesn't help. At all.) is not the right tx for this.
>
> Do you think that luvox is, how should I say, harmful overall? What about long term effects of increased melatonin on the circadian rythm? I know things are out of whack right now to a degree.>>I don't know. There is probably a genotype influence as well, which is useless at the moment since there is no protocol as far as I know for this, except in experimental studies.
luvox is also a sigma-1 agonist, but so far, beyond reversing PCP effects in rats, little is known about this effect: it is one of those 'theoretical' AD effects that have not been demonstrated in the clinic.
>
> I have ocd, anxiety issues and this results in a depressive state to some degree. I thought luvox might be a good choice as I really don't get tired and sleepy like I normally used to and that is what I need to feel better...sleep.
>Luvox is considered sedating for an SSRI. But it is simply impossible to predict what will happen. Luvox is more prone to melatonin-related s/e than other SSRI's, but I don't know to what extent that causes the 'sedation' that is observed with Luvox administration.
>
So, I may try to wean off even thought I am not sure how to do this cold turkey as I might feel better quicker but not sleep better. Of course my pdoc will approve any of this.>>good. the issue has come up of posters dispensing advice without qualifications, and I have none. I have read a lot about sleep disorders and their treatments because I have suffered from them, and I have discussed these matters with sleep specialists. When I asked point blank about whether or not Lexapro was good/bad for sleep disorders, (as I wrote in my post to phillipa) she simply said the effects were variable. I wouldn't take melatonin or Rozerem on Luvox, but the Rozerem ads on the radio advise against this, too, and I assume they have good reason to do so.
-z
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>
Posted by zeugma on November 1, 2006, at 5:53:58
In reply to nicotine » zeugma, posted by iforgotmypassword on October 31, 2006, at 20:22:51
I know my own problems have an etiology partially based on exposure to prenatal nicotine, which is a factor in ADHD (which I have). When I asked my pdoc about what effect this had on my CNS, he said (I think, it was a long time ago and an emotional issue for me, so i was not able to pay complete attention to his answer) that it would adversely affect the dopamine system. I am interested in investigating its effect on serotonin, though.
I experienced euphoria upon smoking, but most of my life, I have had no money to support any habit of any kind. The euphoria was related to a feeling of social ease, and is mimicked by high doses of Ritalin. Klonopin lowers anxiety, and helps me socialize superficially (which is a necessity in order to work with others) but doesn't make me feel 'natural' around others. Nicotine would create this sensation for a few minutes; Ritalin at high doses made this long enough to actually normalize (well, somewhat normalize) my social patterns (its effect on sleepiness was also a factor in this).
is there any possibility you can get galantamine prescribed?
-z
Posted by linkadge on November 1, 2006, at 7:15:39
In reply to wondering in my case..., posted by iforgotmypassword on October 31, 2006, at 18:11:14
I understand that certain oleamides potentiate the 5-ht2a receptors. Something to look into.
Linkadge
Posted by linkadge on November 1, 2006, at 7:17:44
In reply to Re: wondering in my case... » iforgotmypassword, posted by zeugma on October 31, 2006, at 19:13:09
>You are correct that 5HT2A agonism leads to DA >release. other 5HT2 receptors probably inhibit >dopamine, so it is a complex matter.
That depends on the area of the brain though doesn't it.
5-ht2a agonism increases dopamine release in parietal lobes? 5-ht2a antagonism increases dopamine release in the frontal cortex.
Linkadge
Posted by linkadge on November 1, 2006, at 7:19:34
In reply to Re: effect of melatonin on seratonin? » johnnyj, posted by zeugma on November 1, 2006, at 5:42:25
I've seem some studies showing sigma-1 agonists are active in forced swim tests.
Linkadge
Posted by linkadge on November 1, 2006, at 7:21:08
In reply to Re: nicotine » iforgotmypassword, posted by zeugma on November 1, 2006, at 5:53:58
Nicotine acts as a kind of presynaptic 5-ht1a autoreceptor agonist. It decreases hippocampal serotonin, and serotonin firing in the DRN. This is the supposed mechanism for its anti-anxiety effects.
Linkadge
Posted by linkadge on November 1, 2006, at 7:21:37
In reply to Re: nicotine » zeugma, posted by linkadge on November 1, 2006, at 7:21:08
Posted by zeugma on November 1, 2006, at 8:14:33
In reply to Re: nicotine » zeugma, posted by linkadge on November 1, 2006, at 7:21:08
> Nicotine acts as a kind of presynaptic 5-ht1a autoreceptor agonist. It decreases hippocampal serotonin, and serotonin firing in the DRN. This is the supposed mechanism for its anti-anxiety effects.>>
This is very interesting, since one of the reasons REM activity declines sharply from birth to adulthood is postulated to be the stimulation of 5HT 1A receptors.
One of the cardinal symptoms of major depression is increased REM activity. A study of nortriptyline responders vs. nonresponders found that the difference between the two groups was that the responders had downregulated presynaptic 5HT 1A receptors, while nonresponders did not.
I have often felt like my baseline is a state of antidepressant withdrawal (hypercholinergic activity, zero REM latency). maybe it's better described as a state of constant nicotine withdrawal?
-z
>
> Linkadge
Posted by linkadge on November 1, 2006, at 8:42:30
In reply to Re: nicotine » linkadge, posted by zeugma on November 1, 2006, at 8:14:33
But, doesn't nicotine enhance REM sleep ?
Its important to destinguish presynaptic from postsynaptic. I think post-synaptic 5-ht1a receptor agonism decreases REM sleep.
Presynaptic autoreceptor agonism would likely increase REM, since it would decrease serotonin release, and hence decrease postsynaptic 1a agonism.
Some people think that anxiety is a hyperserotoniergic state, and that depression is a hyposerotonergic state. Serotonin can be highly anxiogenic, expecially firing in the amygdala, and DRN. The reason SSRI's are anxiolitic for some is complex. I think its got nothing to do with serotonin uptake. All of the currenly available SSRI's also increase the activity of the potent GABAergic neurosteroid allopregnanalone some 20 times. Has this more to do with SSRI anxiolysis than serotonin uptake inhibition?
Especially since the recent findings that those who posess short alleles of the serotonin transporter, and hence lower baseline serotonin uptake, actually suffer more stress related events, including depression after stressfull life events.
SSRI withdrawl still persists with me too. Zero latency for REM sleep, as well as profound pessimism. Got to love the way SSRIs mess with the brain.
Linkadge
Posted by iforgotmypassword on November 1, 2006, at 9:56:16
In reply to Re: effect of melatonin on seratonin? » Phillipa, posted by zeugma on November 1, 2006, at 5:03:14
i know this prolly sounds counter productive to you guys. :( but this may help my akithisia and apathy as i was hypothesizing. if it causes any endogenous-feeling typical depressive feelings i could stop or maybe deal with it given the other drugs i am on (aricept, wellbutrin, lamotrigine; sorry wellbutrin kindof defeats the purpose of nicotine.)
what are oleamides? i found something that said that oleamide itself has some remarkable effect on choline acetyltransferase in vitro, increasing it's activity, and in animal studies reversing anticholinergic scopolamine doping effects notably.
http://www.jstage.jst.go.jp/article/bbb/67/6/67_1284/_article/-char/en
i don't know if this means its safe and tested or out on the market, but i think i read quickly in the search results that it can be given to farm animals. they seem to like what causes quick development, and i guess optimal nutritional balance, which i guess is ironically tied into the animals health. (i'm vegetarian, so i speak sort of oddly about things that involve making an animal healthy to kill it, sorry.)
what are other examples of oleamides? and what is the nature of their potentiation of the 5HT-1a receptors? in oleamide itself, it seems to imply that A LOT may have to be administered to have the effect. are any different kinds more biologically active, or less killed off by the body, or something like that, so that less is needed?
Posted by iforgotmypassword on November 1, 2006, at 10:21:28
In reply to Re: nicotine, posted by linkadge on November 1, 2006, at 8:42:30
btw, oleamides don't potentiate 5HT-1a post-synaptic receptors do they?
>But, doesn't nicotine enhance REM sleep ?
ironically, there has been conflicting information that wellbutrin causes increased REM. It is odd. Some say it causes an increase, some say a decrease. The one's saying a decrease seemed to lump it in with other antidepressants and didn't seem to be linked to a study. (i could only read the abstract, not the refs, unless there is a way to do this on pubmed.)
this one however seems to imply less easy to understand effects:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=15122973&query_hl=3&itool=pubmed_docsumthis was the one saying REM latency was reduced:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=7840365&query_hl=3&itool=pubmed_docsumnow that i read more recent ones, all others seem to note latency decrease, confusing. i guess i may be wrong.
the one on REM increase i think i read and had ingrained, after obsessively reading basically all biopsychiatry.com, way way back.
strange drug.
i still do not know how to interpret what nictonic receptor activity does. arg. and there seem to be more nictonic-type receptors than with other receptors too, right?
the idea of wellbutrin increasing REM is one of the reasons i wanted to try it (i finished a course on it once, and wondered if that mechanism is what helped, i also felt much more rested after sleep.) i was hoping a pro-muscarinic effect was involved.
Posted by linkadge on November 1, 2006, at 12:57:00
In reply to nicotine. oleamide and post-synaptic 5ht1a Rs, posted by iforgotmypassword on November 1, 2006, at 10:21:28
Oleamides are fatty acids. I think they are produced in the body from oleic acid. I think all of them potentiate 5-ht1a. Some of them are 5-ht2a agonists, and some of them are 5-ht2a antagonists.
Oleamide is metabolized by FAAH, fatty acid anandamide hyroxylase (?). There are FAAH inhibitors in the pipelines for depression and anxiety disorders.
Consuming more oleic acid may result in more oleamides in the brain.
Linkadge
Posted by Phillipa on November 1, 2006, at 18:48:34
In reply to Re: nicotine » zeugma, posted by linkadge on November 1, 2006, at 7:21:08
Nicotine never calmed me it made me anxious . Love Phillipa
Posted by linkadge on November 1, 2006, at 19:55:17
In reply to Re: nicotine » linkadge, posted by Phillipa on November 1, 2006, at 18:48:34
Nicotine has a mixed anxiolitic anxiogenic profile. For some people it is very calming. Other people find it anxiety provoking.
Linkadge
Posted by iforgotmypassword on November 1, 2006, at 20:06:03
In reply to Re: nicotine, posted by linkadge on November 1, 2006, at 19:55:17
apparently people with lyme often all do bad on stimulants. somehow i am okay on wellbutrin now, but this is the first time that i took lamotrigine first before taking wellbutrin. i notice last time i took lamotrigine, whenever i went off of it i would rebound into completely randomly flipping out over nothing again. after the rebounds, it took a while to renormalize how i would deal with spontaneous nonsensical feelings.
wellbutrin before lamictal took three tries. the first which had me so upset i put my head through a wall. i was not expecting that at all and no one warned me of anything. i should have looked it up to see that it is a stimulant.
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