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bluebrain
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CLUSTERHEADACHE theory
« on: Apr 24th, 2007, 10:17am »
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Bluebrains theory.
If we ask any CH patient to characterize it, his first words will be EXTREME PAIN (kip scale 8-10), around the eye and surrounding area (forehead for the most) of the affected side of the head. My theory is based on an old theory (from the sixties) and on a different version but very much like the theory you can read in clusterbusters called Neurovascular headache and its treatment Hallucinogenic treatment of the ...(I prefer to call it subhallucinogenic). There are two structures involved in this type of headache, the ophthalmic artery branches and the trigeminal nerve specially those branches that run along with the branches of the opht. artery, intracraneal as well as extracraneal. No matter if it is chronic or episodic every CH has three distinctive phases. 1)NEUROLOGICAL, this phase has to do with the abnormal or absence of serotonin release at the presynaptic button, this reaction should happen as an answer to a vasodilatation stimuli (e.g. red wine). Serotonin has a vasoconstriction effect on the extracerebral intracraneal vessels through the 5HT 1B receptors. It seems that this abnormality is local, as if there is a local regulatory system that controls the tone of the artery (based on serotonin), this could explain why this headache is hemi lateral. I know that it has been mentioned that there is a sudden increase of serotonin metabolites in the urine during a CH seizure contrary to my postulate, I could agree that this happens at the very beginning of a CH seizure, all serotonin is released at one time, but there is no refill of the presynaptic vesicles resulting in less or none presence of serotonin and no vasoconstriction. Already there is a question that arises from this statement, why not give an extra dose of serotonin? Sorry but serotonin doesn't cross the brain blood barrier, then what about an axtra dose of tryptophan, unfortunately this could end in a serotonin shock. That's why we need a local serotonin substitute that should activate the local 5HT 1B receptors producing a vasoconstriction of the mentioned artery. This phase is painless.
2)VASCULAR, is as mentioned serotonin dependent. This phase depending on how fast it evolves can be divided in two subtypes; a) If the dilation of the blood vessel occurs more or less slowly (from one to forty minutes in my case), there will be painless symptoms or at the most slight pain (kip scale 4). This phase is called by some SILENT CH, PRODROMES or just PAINLESS phase. Not everybody experiences this phase. Best medicine at this stageis a 5HT 1B AGONIST or a serotonin like compound. b) The vasodiltation occurs suddenly and violently, EXTREME PAINFUL, almost all of the symptoms that characterize a CH are present. The trigeminal nerve fibers are activated mechanically by the extreme dilated artery running beside the nerve, at the same time and because of this activation there is a release of substance P and calcitonin-gene-related peptide (CGRP) from the nerve. The release of CGRP leads to even more dilation of these blood vessels and an activation of the pain-transmittingneurons. As far as we know, the use of a 5HT 1D/1F agonist will disrupt these signals. So what kind of medicine are we looking after? No doubt that the ideal will be some that could regulate the release and refill of serotonin "locally" (we musn't forget that serotonin has different effects in different parts of your body). The second best would be one that was 5HT 1B and 5HT 1D/1F receptor agonist. The majority of the medicine used today are 5HT 1B/1D/1F receptor agonist (e.g. sumatriptan and other triptans. ergotamin) but and this is a big but, they have some serious side-effects due to the presence of almost the same receptors in other organs and blood vessels than in the brain. Another unfortunate effect is that you can't use them (the majority) as preventive (profilaxis), only as abortives, due to its toxicity or to its short half-life.
I cannot say for certain but if you neutralize the extreme vasodilatation you will stop the pain.
Thats why psilocybin/psilocyn-based drugs are the most promising for us patients, because they replace the missing serotonin locally by what I call the two stage process, which I will write about if some one is interested.
This was extensive story, but maybe helpful.
Best wishes  
Bluebrain
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« Last Edit: Feb 27th, 2008, 8:43am by bluebrain » IP Logged
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Re: CH theory
« Reply #1 on: Apr 24th, 2007, 2:38pm »
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I've found Psilocybin/Psilocin to be the most effective CH medicine, with the least amount of side effects, and so far, all the side effects have been good.
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Re: CH theory
« Reply #2 on: Apr 24th, 2007, 9:14pm »
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Very interesting Bluebrain. Thanks for the info.
 
Can you please post the sources of the information you posted ? thanks.
 
Painfree wishes to you.
 
Annette
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Re: CH theory
« Reply #3 on: Apr 25th, 2007, 1:42pm »
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Hola Bluebrain  Smiley  Thanks for your theory, I believe in it. After one year painfree with monthly doses of psilo, last february I went into a cycle (may be a 6 months old batch was no potent enough).  It took me 2 weeks of  pain (20 hits?) to get a new batch, together with O2 and clustermasx. Since, aborted 100% of hits with O2 and 2 weekly doses of psilo later it was gone. Now it's more than a month I'm again painfree and coming back to monthly bases.
Annette, I think it's his theory after years of investigation, but lets him answer.
Saludos
Poli
 
Please, post the rest of your ideas.
« Last Edit: Apr 25th, 2007, 1:44pm by Poli » IP Logged
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Re: CH theory
« Reply #4 on: Apr 25th, 2007, 2:20pm »
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on Apr 25th, 2007, 1:42pm, Poli wrote:

Annette, I think it's his theory after years of investigation, but lets him answer.
Saludos
Poli
 
Please, post the rest of your ideas.

 
It would be wonderful to get the sources of the chemical and biochemical events that he described so that we can all look into it further.  
 
Yes, please do post the rest of your ideas. I would love to hear.
 
Thank you very much.
 
Annette
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Re: CH theory
« Reply #5 on: Apr 25th, 2007, 10:01pm »
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Bluebrain,
     Thanks for the post, it certainly has been stimulative.  My forehead does not see pain until there is rebound Quote:
(forehead for the most)
or I have a high Kip episode.  Different from what you describe?  I keep reading CH symptoms are not identical, though some symptoms are similar (circadian rhythms, length and duration, chemical imbalance to name a few).  Medications, though similar, do not produce the same results amongst CH'ers.  No correlation between the amount of time you have had CH and how severe it can be.  In my case, worse as time goes by.  There is something that puzzles me even more than CH.  With 18 posts, where did you get all that knowledge :O?  
 
From research on your topic:
Quote:
Triptans are a 5HT1B/1D agonist (a substance that binds to a specific receptor and triggers a response in the cell).

Quote:
The triptans with longer half-lives and greater 5-HT1B receptor potency had the lowest rates of headache recurrence.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed &list_uids=12656709&dopt=Abstract
 
Serotonin can be measured.
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1304187
 
http://www.news.cornell.edu/chronicle/97/1.30.97/serotonin.html
Your theory can be tested to some extent.
 
This is aside of the post, yet interesting pieces of information.  It does have to do with serotonin levels.
Evidence lack of serotonin can cause serious issuesSmiley
http://www.nlada.org/DMS/Documents/1066920620.52/serotonin.pdf
http://www.forensic-serotonin.com/biology-of-violence.html
 
Which brings me to this question.  I have not seen L-Tryptophan discussed.  And, I am too tired to research it.  Does anyone have experience with this amino acid?
"Clinical research tended to confirm tryptophan's effectiveness as a natural sleep aid and for a growing variety of other conditions typically associated with low serotonin levels or activity in the brain."
http://en.wikipedia.org/wiki/Tryptophan
 
Night Y'all,
Donnie
« Last Edit: Apr 25th, 2007, 10:08pm by pieface_49 » IP Logged

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Re: CH theory
« Reply #6 on: Apr 27th, 2007, 10:16am »
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on Apr 24th, 2007, 10:17am, bluebrain wrote:
Thats why psilocybin/psilocyn-based drugs are the most promising for us patients, because they replace the missing serotonin locally by what I call the two stage process, which I will write about if some one is interested.

I am very interested Bluebrain.
 
I like the neurovascular theory; although I personally would tend to put more emphasis on the hypothalamus i.e. is it really the trigeminal system activating the hypothalamus (as in migraine) or perhaps vice versa?  I would also like to know precisely what role the pineal gland plays in all this.
 
I agree that if we are talking neurovascular then CGRP (and to a lesser extent Substance P) is important in CH, but we can't ignore other important factors involved including NO (nitric oxide) - which I've been looking at closely recently - and VIP of course – cue pattie Smiley
 
Interesting stuff.
 
on Apr 25th, 2007, 10:01pm, pieface_49 wrote:
Which brings me to this question.  I have not seen L-Tryptophan discussed.  And, I am too tired to research it.  Does anyone have experience with this amino acid?

It has been discussed and Flo sums it up nicely here:
 
http://www.med-owl.com/clusterheadaches/tiki-index.php?page=Tryptophan
 
Many people have had good responses with 5-HTP, although for some it can make things worse (including me) albeit sometimes only in the short term.  As ever, Flo gives a very good overview here:
 
http://www.med-owl.com/clusterheadaches/tiki-index.php?page=5-HTP
 
-Lee
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Re: CH theory
« Reply #7 on: Apr 27th, 2007, 11:52am »
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on Apr 27th, 2007, 10:16am, LeeS wrote:

but we can't ignore other important factors involved including NO (nitric oxide) - which I've been looking at closely recently - and VIP of course – cue pattie Smiley

 
Lee, I was wondering when you were going to jump in here.
 Grin
 
Bluebrain, I'm also interested in the neurotransmitter cascade.  While I've taken a personal interest in VIP and Professor Goadsby's findings as to how it relates to CH, the more reading I do on this particular peptide makes me think that substance P could possibly pre-empt VIP.  Although I haven't seen studies directly related to CH, some researchers in Oregon studing the neurological path of temperature regulation are finding that the NK-1 receptor to be a major player in vasodilation, and the primary neurotransmitter for this receptor in humans is substance P.
 
  Quote:
they replace the missing serotonin locally by what I call the two stage process, which I will write about if some one is interested.

 
I'm interested (and you needn't post a laundry list of sources, as far as I'm concerned).  I just want your thoughts.
 
Pat
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Re: CH theory
« Reply #8 on: Apr 29th, 2007, 9:48am »
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Thank you all, nice to receive opinions, ideas, no matter if you disagree or agree with my theory (Bluebrains theory) everything will be wellcome and I'll try to do my best in answering your questions, more than happy. If I had to describe my theory, Iwould say that I like it because its simple, straight forward, it answers many (not all of them) of my own questions, and maybe it can also explain why psilocybin/psilocyn works so well to many of those who have tried it against CH. I'll start with introducing my self and in the following days I'll try to adress all your questions.
I am 53 years old, male, CH since 1990, episodic from 1990 until 1995 when it became chronic. In both phases I've experienced SILENT CH (painless) before each headache (painful, Kip scale 8-10). The silent phase has been crucial for me to understand what happens during a CH. I work as a research scientist at the Departament of Clinical Immunology, research lab, Copenhagen Hospital, being my field of research the humoral and cellular part of the blood.
Polly, me alegra saber que estás bién, saludos.
I'll try to write down a short reference list of the most important books and articles who have help me to came up with this theory. (In all I've read more than 200 articles, but if there is any who wants all the list, let me know it.
Best wishes, Bluebrain.
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Re: CH theory
« Reply #9 on: Apr 29th, 2007, 9:55am »
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Please please may I have the list of all the articles you have got? I would love to read them too. Thanks  Kiss
 
Thank you very much for introducing yourself and for sharing with us your experience and research.
 
Its wonderful to be able to decipher the mystery from the celllular level.
 
All the best and painfree wishes to you.
 
 
Annette
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Re: CH theory
« Reply #10 on: Apr 29th, 2007, 11:56am »
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on Apr 29th, 2007, 9:48am, bluebrain wrote:
If I had to describe my theory, Iwould say that I like it because its simple, straight forward, it answers many (not all of them) of my own questions, and maybe it can also explain why psilocybin/psilocyn works so well to many of those who have tried it against CH.

 
I'm not a Chemist or a Dr. just some uneducated slob in Kansas, but one thing I do know about CH is that there is nothing simple or straight forward about it. The beast is a tricky bastard. Good luck and keep working.
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Re: CH theory
« Reply #11 on: May 4th, 2007, 8:39am »
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I've used more than two hours writing my reference list but the message board told me that it was too long. Any sugestion on how could I do it.
Best wishes Bluebrain
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Re: CH theory
« Reply #12 on: May 4th, 2007, 9:17am »
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Just split your list into two (or three, or four  ...) parts. And post it into seperate answers.
 
 
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Re: CH theory
« Reply #13 on: May 11th, 2007, 9:19am »
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Good idea, but I'll start a new topic, which I think will be of great interest to all, specially to those who ask themselves why does or should work Psilocybin/psilocyn, LSD, LSA etc. Of course if any wants the complete version please let me know it.  
Best wishes
Bluebrain
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Re: CH theory
« Reply #14 on: May 12th, 2007, 11:52am »
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Hey BlueB,
Thanks for the interesting and informative posts.
 
I see you've listed your reference list, thank you. I know it's a pain sometimes getting these things posted. Sounds like you timed out the first time you wrote it. It's happened to me a bunch of times.  
 
If you have a list of links, I'd appreciate a copy via email and would like to add it to the CB site...along with a copy of your "theory" (which I can copy from here), if you don't mind. Let me know.
 
Bobw
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Re: CH theory
« Reply #15 on: May 15th, 2007, 2:43am »
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Hey BobW, Please do as you think is the best, no problem. Computers are not my strong side, I belong to the hippie generation rather than the computer generation. Today I'll try to finish the reference list and in the near future I'll describe the silent CH (my own) and will finish by describing why psilocybin/psilocin works.
Bob, may be you can help me with the following question:
Do you have any information about methysergide's catabolites, specially the chemical structure of them?
Best wishes
Bluebrain.
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Re: CH theory
« Reply #16 on: May 15th, 2007, 5:14am »
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Hi bluebrain
 
I'm not usually a great fan of wiki, but this appears to give a good overview, and some of the links may be useful too:
 
http://en.wikipedia.org/wiki/Methysergide
 
Here's a brief history of it (btw, the whole book is well worth a read if you haven't already done so):
 
Quote:
Certain results of the chemical modification of LSD proved valuable to medicinal research; LSD derivatives were found that were only weakly or not at all hallucinogenic, but instead exhibited other effects of LSD to an increased extent. Such an effect of LSD is its blocking effect on the neurotransmitter serotonin (referred to previously in the discussion of the pharmacological properties of LSD). As serotonin plays a role in allergic-inflammatory processes and also in the generation of migraine, a specific serotonin-blocking substance was of great significance to medicinal research. We therefore searched systematically for LSD derivatives without hallucinogenic effects, but with the highest possible activity as serotonin blockers. The first such active substance was found in bromo-LSD, which has become known in medicinal-biological research under the designation BOL-148. In the course of our investigations on serotonin antagonists, Dr. Troxler produced in the sequel yet stronger and more specifically active compounds. The most active entered the medicinal market as a medicament for the treatment of migraine, under the trademark "Deseril" or, in English-speaking countries, "Sansert".
 
LSD - My Problem Child: Albert Hofmann. Chapter 3: Chemical Modifications of LSD

 
-Lee
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