Homeostasis

[Bejeeber]

At the conference there was mention of a CH study coming up where CH'er volunteers who are in cycle will have an attack induced with nitroglycerine. Then half of them will be given a placebo. 

I don't know that I could bring myself to volunteer for a study like that, but whoever does oughta be awarded several dozen congressional medals of honor IMO.   

[CHfather]

This study, published in 2013, shows that people with CH have "abnormal" hypothalamic "wiring" that is present even during periods of remission (in contrast to the position that has been stated here that hypothalamic abnormalities are only observed during attacks).  http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0057896

The abnormalities are different during an attack and when not having an attack, but regarding out-of-attack people, the differences are enough to tell a CH hypothalamus from a non-CH hypothalamus.  The authors write: >>>Using a cutoff of 0.2128, the test yields a sensitivity of 83.33% and a specificity of 100% in distinguishing CH patients during an ‘out of attack’ period from normal controls. <<<

There's also a very interesting suggestion here about CH pain. The abnormalities of the hypothalamic wiring during an attack are deeply connected to parts of the brain related to pain perception. The authors write:

>>>In the present study, we used a region-of-interest (ROI)-based method to determine whether the abnormal rs-FC between the hypothalamus and some pain-related regions or some other brain regions are present in CH patients during acute spontaneous CH attacks and CH attack intervals in the cluster period. Detection of abnormal rs-FCs of the hypothalamus in these groups revealed three critical findings. They are that: (1) there is an increased rs-FC between the hypothalamus and brain regions related to pain processing such as the ACC and the PCC during spontaneous CH attacks, (2) there is an altered rs-FC between the hypothalamus and brain regions beyond that is related to emotional modulation of pain during CH attack intervals, and (3) these regions have relatively high sensitivity and specificity.<<<  In another place, they refer to >>>functional abnormalities of pain information processing in CH patients.<<<

You can see where this is leading: that it might be that CH is so horrifyingly painful because the connection between the hypothalamus and these "pain information processing regions" leads the brain to wildly skew its normal perceptions of pain.  If this is true, and as brain science progresses, it suggests to me another possible avenue of treatment, dealing with how the brain perceives CH pain.  The authors don't say this . . . I'm just going with the flow.  Hopefully, a fully effective treatment will be available before that route is pursued.

Here's the conclusion of the article:

>>>In conclusion, our findings show that CH patients have a diffuse dysfunction of brain functional connectivity of the hypothalamus. It is mainly in the brain regions that are related to pain processing and modulation during the spontaneous CH attacks, and mainly in the brain regions that include the pain system and visual system during CH attack intervals. Moreover, these changes might be used separately to distinguish the different state of CH patients, as well as CH patients from normal controls.<<<

[CHfather]

Here's another study showing that the hypothalamus of people with CH (in cycle and also in remission) is different from the hypothalamus of people without CH.

>>RESULTS:  In patients with cluster headache, the hypothalamic N-acetylaspartate (NAA)/creatine (Cr) and choline (Cho)/Cr ratios were similar between those in cluster period and in remission. As a group, both NAA/Cr and Cho/Cr levels were significantly lower in patients with cluster headache in comparison with either the control [no CH] or chronic migraine groups.   CONCLUSIONS: This study provides evidence of persistent biochemical change of the hypothalamus in patients with episodic cluster headache. Low levels of NAA/Cr and Cho/Cr suggest that cluster headache might be related to both neuronal dysfunction and changes in the membrane lipids in the hypothalamus.<< http://www.ncbi.nlm.nih.gov/pubmed/16614022

This study shows the same thing for NAA/CR: http://www.ncbi.nlm.nih.gov/pubmed/16636250

[Lieutenant2]

Interesting stuff, for sure. And I am inclined to agree to the extent that it pertains to SIGNALING. It would be very hard to convince me that there is a physical malformation in the axons/dendrites of the cells in the hypothalamus. This is probably splitting hairs, since we tend to think of the signals in our brain as electric signals, but they're actually chemical signals. So is "bad chemical channels" the same as "malformation"? Yeah, that could be argued.

What I do know is that attempts to treat CH as a physical disorder (surgery, electrical stimulation, medication) have failed or are temporary at best. I also know that I am a refractory chronic who hasn't had a full CH attack since 11/08/2013, and I haven't touched prescription meds, tryptamines, or any medical devices. What I have done is treated what I feel was the root cause of my CH. There will be more to come on this. I just like to encourage people to think outside the box that has been built around us.   

[CHfather]

I just like to encourage people to think outside the box that has been built around us.

Couldn't agree with you more. Busting was the result of thinking outside the box (or in some ways, back into a box that had been discarded). D3. Oxygen! Tons of stuff. But I don't think that the idea that an "abnormal" hypothalamus is a major contributor to CH really affects the "box" very much -- not many people in the non-scientific CH community are trying to alter their hypothalamuses.

What I do know is that attempts to treat CH as a physical disorder (surgery, electrical stimulation, medication) have failed or are temporary at best.

It does generally seem that way, so far, with the possible exception of BOL, and of course that's why it's crucial to keep looking for treatments. But it doesn't mean that with more refined tools to analyze the physical disorder and more sophisticated ways of treating it, the physical solution (by which I am referring specifically to dealing physically or chemically with the hypothalamus) will not become available.  The idea, which I think you and Tony may have been suggesting, that CH is a particularized response to stress by some people's otherwise normal hypothalamuses, seems to be brought into question by what I have posted.  That doesn't mean that finding better ways to deal with stress/create better homeostasis isn't also a potentially fruitful avenue. If you and Tony say it is or could be, I'm sure not going to disagree. Physical/structural cause vs emotional/psychological cause are not mutually exclusive avenues to pursue.

I also know that I am a refractory chronic who hasn't had a full CH attack since 11/08/2013, and I haven't touched prescription meds, tryptamines, or any medical devices. What I have done is treated what I feel was the root cause of my CH. There will be more to come on this. I just like to encourage people to think outside the box that has been built around us.

I'm looking forward to the "more to come," as I'm sure many others are. I'm also a little confused. I had thought that you were one of the subjects who was taking the tryptamine 5Meo-DALT that you reported about in your other thread.  But here you say you haven't touched tryptamines since late 2013.  It is not necessary for you to clarify this either way; I'm just saying that I must have been operating under an inaccurate assumption about either your direct participation in that research or about when it took place and what you are using now to treat your CH.

My friend with the depression cure once explained to me why it's so hard to find an effective treatment for CH. "You can't give CH to lab rats" is what he said. With a condition that you can create or appropriately simulate in lab rats (those conditions include depression, obsessive-compulsive disorder, male pattern baldness, obesity, and anxiety, among many others), you can just keep giving the rats different substances until you find one that works/seems to work.  Then you can (eventually) proceed to test that on humans.  As everyone here knows all too well, people with CH are the "lab rats" in this model. The more people like you look for and test possible treatments, the better off the CH community is. And, to say it again, I am also glad that there are scientists -- far too few of them -- investigating CH in ways that are not feasible for the rest of us, which might eventually lead to explanations and treatments or even cures that our current technology is not capable of providing.

[Lieutenant2]

Thanks, CHfather! Couple interesting points. . .you mention 2-bromo-LSD (BOL-148) a something that treats a "physical" problem, but I don't see it that way. Psychedelics get their results because they are treating a mental/emotional issue. Psilocybin is probably the single best treatment for PTSD, and that disease is 100% emotional. Meds that treat the physical are those that alter a structure, so for example verapamil altering calcium channel ions. Psilocybin, LSD, LSA, and even BOL (it's just LSD with a bromine molecule stuck to it, high school chemistry) treat the mental state/emotions of the patient. I can't think of a single physical disorder that psychedelics do treat, honestly. People don't go on ayahuasca trips to Peru to cure cancer, but they sure do go for depression!   :-)

Also, yes. . .I (allegedly) was one of the first to trial 5-MeO-DALT. That experiment took place late last year, and the last dose I took was probably in February (as a test dose, not as a regular treatment). I sat on that info for a while, hoping to get someone smarter than me interested in it. But alas, no takers.

What I will say is that, for me and only me, a pretty unique combination of mild anxiolytics and overlooked neuroprotectives have had a long-term effect on making me totally pain-free. Could be a fluke, which is why I'm still playing around with it. But it sure as hell is a nice fluke!   

[jms]

Thanks very much for posting this discussion. I have been trying for over 10 years to solve the mystery of my son's CH. This information gives me a lot to investigate further. I appreciate the fact that you all have dumbed down a lot of this to layman's terms that I can understand. One thing that has been nagging at me lately is that the CH "event" leaves very quickly. For example my son tells me that he can be in extreme pain one minute and then the headache all of a sudden can be gone in the next minute. I know this is grasping at straws but can that "feature" of the CH be a kind of clue to the mystery? I'm just thinking outside the box as some have suggested, I think it's going to take those of us who are affected by this "condition" to further the momentum on solving this problem. Thanks again for the discussion!

[CHfather]

I don't know where to start with this . . . so I'm not going to go very far.  I think you are saying that psychedelics treat CH because they affect psychological states, particularly PTSD and depression. That is, they don't treat CH in some "physical" way, but only by affecting the person's psychology.  Actually, I don't think that's what you're saying; it's what you explicitly say: >>>Psychedelics get their results because they are treating a mental/emotional issue.<<<

The corollary can only be that it's not either of the other ways around that we might consider -- that people's depression and PTSD lift when they have a successful way of treating CH; OR that psychedelics affect both the "physical" thing that is CH and the "psychological" things that are PTSD and depression.

I see so many possible contradictions to what you’re saying that I wouldn't even know where to begin listing them.  I'm not saying that I am right and you are wrong; I am only saying that our views about this are so different that listing my quibbles doesn't seem worthwhile.  A fellow at another thread here at this site was saying today that we need a new paradigm to really understand CH.  Old fogeys like me famously resist new paradigms and find arguments against them, and often the new paradigms turn out to be correct and the old fogeys turn out to be wrong.  I will continue considering what you say; I just don't want to debate it.  And if you find an emotional/psychological treatment that keeps CH away (as you suggest you think you might have done), I'll be among the first to help you spread the word.

Just a final comment about the “physical” vs. “emotional” distinction you seem to be making.  You say >>Psilocybin is probably the single best treatment for PTSD, and that disease is 100% emotional. Meds that treat the physical are those that alter a structure, so for example verapamil altering calcium channel ions.<<

My response to that is that it seems fully clear that psilo treats PTSD by altering physical structures. The result as experienced by the person with PTSD is “emotional,” but the mechanism is physical. PTSD has specific physical manifestations in the brain, and it appears that psilo treats PTSD by repairing the damaged cells and causing/helping/allowing/something new cells to grow in the right places.

Unlike with CH, where structural abnormalities in the hypothalamus have not been directly observed (yet!), changes in the brain (the hippocampus, specifically) are directly observable in people with PTSD. (http://www.thedoctorwillseeyounow.com/content/stress/art1964.html?getPage=3) And those changes seem to be reversed, physically, by the administration of psilocybin.

Now, this study I'm about to link you to was done in lab mice. As it happens, in my last post I mentioned that scientists can "grow" lab rats with specific disorders, including all the symptoms of PTSD. 

Here's a report about the study: http://www.naturalnews.com/041393_psilocybin_psychological_disorders_magic_mushrooms.html   And here are the key paragraphs:

>>>Common symptoms, such as hyper-vigilance, memory fragmentation, flashbacks, dissociation, nightmares and fight or flight responses to 'triggers', are generally thought to be psychological and therefore treatable by learning to change thought processes. But new research suggests that they may in fact be the result of long term physiological mutations to the brain.

In the South Florida University study, the mice treated with low doses of psilocybin grew healthy new brain cells and their overactive medial prefrontal cortex regions (common in PTSD sufferers) were restored to normal functionality.<<<

To think a little more about this, it seems very unlikely that the mice “know” that they have PTSD. They are just reacting to stimuli and storing those memories in their brains, reinforcing the PTSD "circuitry." When their PTSD is undone, they probably don’t “know” that, either—they just react differently. As best as we can tell, mice do not have minds, as humans do, they only have brains. The outcome might have been “emotional” in some very vague sense, but the mechanism is entirely physical (by which I mean it occurs in observable physical structures).

Recent studies show that psilo creates its psychoactive effects by engaging, among other things, the emotional centers of the brain (through a physical mechanism, of course). [http://www.washingtonpost.com/news/to-your-health/wp/2014/07/03/psychedelic-drugs-put-your-brain-in-a-waking-dream-study-finds/] But that doesn’t mean that they only affect those emotional/dream state centers. As Sewell [RIP], Halpern, and Pope wrote in their paper about psilo and CH, >>given the apparent efficacy of subhallucinogenic doses, these drugs [psilo and LSD] might benefit cluster headache by a mechanism unrelated to their psychoactive effects.<< http://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=1&ved=0CCAQFjAA&url=http%3A%2F%2Fwww.maps.org%2Fmedia%2Fneurology.cluster.pdf&ei=IxEwVIy9JI-qyATx_IC4CA&usg=AFQjCNHG69S_yeeN4k3PNmK9n6mIi2ZVfA&sig2=kk5MWsIw6K6oso8VAyCdMg&bvm=bv.76802529,d.aWw   

As the PTSD studies seem to show, there are indeed, as these authors suggest, "physical" ways that psilo acts in the brain (e.g., causing new cell growth in certain areas) that are not directly related to psychoactive effects.  It's a frontier.

[Lieutenant2]

Yes, well. . .as much as I respect your opinion and your education, I will just disagree and leave it at that. I assure you, I speak from direct experience as a chronic CH patient who has not had a CH attack in 11 months, and I am not the only one, and there are a couple people with "PhD" after their names who are helping with this. . .so, would I be willing to bet a paycheck that I'm right here? Absolutely. Unfortunately, there is still much work to do, and arguing about it in a public forum is less than productive.   

Sometimes it's hard to see the forest for the trees. And even if I'm 100% wrong, don't you think there are enough people turning that same stone over and over and over? Once cognitive dissonance sets in, that pattern can become automatic.

[ThatHurtsMyHead]

I haven't read the entire thread, so hope my post isn't in left field (sometimes I get it all the way to right field . 

In the wayyyy back script machine - - The first treatment the doc "tried" on my CH (98' ish) was Zoloft.  It definitely lifted my mood, no doubt about that.  Didn't do beans for my CH.  I stopped it at about the 2 to 3 month mark if I remember correctly. 

I can definitely say my alternative CH treatment (Seeds / Fungus) has without a doubt lifted my mood, but only after the CH has left, not before (or during).

My own anecdotal observation is that I've seen / felt a better "lift" with the larger doses.  Threshold doses help the CH, but I don't quite feel the longer term mental lift I do with larger doses of M or Seeds.

2c.  That is all

J

[HugLife]

In this section of an interview with David Nichols he comments on treating physical conditions with psychedelics.

[urlhttps://www.erowid.org/culture/characters/nichols_david/nichols_david_interview1.shtml][/url]

Tania: Switching gears to the Iodo compounds, like DOI, did you mention that these are anti-inflammatory?

Dave: Yeah, that's very weird.

Tania: Some guy called in to Sasha's office, saying that he had rheumatoid arthritis, and he took 2C-I, and for two weeks he was pain-free. Which makes me wonder about medical applications for the Iodo compounds...

Dave: My son Chuck discovered that accidentally. He's an associate professor at Louisiana State University in New Orleans. He wanted to work with 5-HT2 agonists, because he's looking at serotonin receptors in Drosophila, and doing translational stuff into rats. He asked, "Is there a 5-HT2A agonist that's not a controlled substance that I can use?" Since DOI was not controlled, I sent him the isomers of DOI. His team had been using rat aortic epithelial cells--cells from the inside of a rat's blood vessels--and looking at models of atherosclerosis. The model they'd been using was to take these cells, and put in TNF-alpha (tumor necrosis factor-alpha), a pro-inflammatory substance. If you've seen the advertisements for Enbrel, for arthritis, drugs such as that block TNF-alpha receptors, so they block the pain. What they would do is put TNF-alpha directly into these cells and then they would look at what effect occurred in combination with other compounds--there were four or five compounds that they were looking at.

So his post-doc had some of those cells that were grown up and could be used, and he asked my son, "What if I run a test with one of our compounds in these?" And Chuck said, "Well, I don't have any anti-inflammatory compounds right now." "What about this DOI here?" Chuck laughed and replied, "That's a hallucinogen. That won't do anything." The post-doc said, "Well, I'm going to have to destroy the cells. Can I just go ahead and test it?" And Chuck said, "Yeah, go ahead." The guy came back a week and a half later and said, "The DOI completely blocked TNF-alpha at 20 picomolar." Which is like unbelievable, right?

Chuck said, "Nah. You made a mistake." So Chuck went in, made up his own fresh solutions, took the cells, ran the experiment, and reproduced the guy's data. He wrote me back and asked, "Is there any precedent for this?" And I said, "No, not that I know of." So he published a paper in J PET; it was the featured paper in the issue it was published in. This has extraordinary potency; there's no anti-inflammatory that has potency like that.

Jon: The dose levels you mentioned would not be psychoactive, so perhaps that's something that could be developed into a commercial medication.

[HugLife]

https://www.erowid.org/culture/characters/nichols_david/nichols_david_interview1.shtml

sorry, maybe this link will work.

[CHfather]

Thanks, THMH and HL. 

[CHfather]

I mentioned in an earlier post in this thread that part of the difficulty of finding an effective treatment for CH is that you can't give CH to lab mice and then just throw possible medications at them until one seems to work.  I have also suggested that I am hopeful that advances in brain science will mean advances in understanding and treating CH.

Here's a story from today, about a huge advance in finding a possible treatment for Alzheimer's: growing Alzheimer's cells in a gel.  It's exactly the kind of thing I am hoping might happen regarding CH (though it's a lot farther off for CH, of course). (By "kind of thing," I just mean some big breakthrough that changes the game, not necessarily this specific one.)

Here are a couple of early paragraphs:

>>>“It is a giant step forward for the field,” said Dr. P. Murali Doraiswamy, an Alzheimer’s researcher at Duke University. “It could dramatically accelerate testing of new drug candidates.”

. . . It allows researchers to quickly, cheaply and easily test drugs that might stop the process in the first place. The crucial step, of course, will be to see if drugs that work in this system stop AlzheimerÂ’s in patients.

. . . . .

Dr. Tanzi is now starting an ambitious project to test 1,200 drugs on the market and 5,000 experimental ones that have finished the first phase of clinical testing — a project that is impossible with mice, for which each drug test takes a year. With their petri dish system, Dr. Tanzi said, “we can test hundreds of thousands of drugs in a matter of months.”<<<  http://www.msn.com/en-us/news/us/researchers-replicate-alzheimer%E2%80%99s-brain-cells-in-a-petri-dish/ar-BB8W5er

To me, this is an example of why funding is so desperately needed to look for CH treatments.  The government provides about 500 million dollars a year for Alzheimer's research.

[Bejeeber]

...we can test hundreds of thousands of drugs in a matter of months.....

WOW. Cool.  8-)

[diamondmaker]

Have to add my two cents...

I have always contemplated how my CH episodes changed from 2-4 weeks to 2 months by the introduction of oxygen, the first med to work for me in any way. It appears to me that I went chronic in a cloud of triptan use... the second med to ever work for me. And I still think the triptans had something to do with it.

I have classified drugs into two classes. Blockers and lubricators. I look at it as a certain amount of current must flow, eventually, and blockers just prolong and aggravate the situation. I put steroids and triptans in this category, can't comment on others because they never affected my CH.

Lubricant is what is needed, something to help the current flow without overheating. I put psilocybin and ketamine in this category.

This is obviously a layman's description of what I see, but I think it has application in the search for a new paradigm. I do not find the idea of a psychological basis for our problems to be inconsistent with what I see.

In fact I have experienced a runaway fight or flight response. I feel my wiring overloaded and the system went haywire. For years before the psychedelics I was experiencing the "panic button" going off for no reason what so ever. At the worst, when I went chronic, I was getting adrenaline pumps every couple of minutes... very hard to deal with. I know it is the psilo and ketamine that are responsible for making that right again. Lube for the circuits. :

[Lieutenant2]

Very nice analogies, diamondmaker! In fact, I guess what we're really talking about here is both psychological/emotional AND physical, because there is of course a manifestation of it that is visible. Plus, it hurts like hell and we're not making that up, despite the attempts of some docs to call it psychosomatic pain!

I also work off of this whole concept of a "feedback loop" that we first need to interrupt before we start treating root causes, and that interruption can be very much physical. But I digress. . .probably a different topic altogether. Synaptic pruning and all.   

[didgens]

well.. maybe you can sit around a campfire and see if it triggers one ,, or light some incense. 

CHF yes I am in California .. and a couple weeks ago I looked at the Allergen web site because it will list what pollens are in bloom in your zip code. Right now we have ELM

http://www.pollen.com/allergy-weather-forecast.asp

[didgens]

I Also want to re-state .. that along with his CH's comes lots of allergy symptoms .. post nasal drip and Acid Reflux. 

[didgens]

That's a great article by the way CHF ,, it adds more credence to my belief that its something inhaled into the back regions of the deep sinus cavity that excites one of the 2 ganglion bundles back there.

[didgens]

heres a thought .. buy those swimming nose plugs and breathe through your mouth for a day or two ??? (sounds crazy ,, but then again we are our own lab rats right  ,, or at least my son is mine )   :

[didgens]

CHF you don't have to worry about hijacking ,, cuz I did  .. so as long as we are talking about this  (or at least I am) I have been wondering if the difference between people who suffer CH's and those that don't is how close to the back of the sinus cavity the ganglion lie.  what if these ganglion (sphenopalatine and/or trigimenal nerve) are just closer to the surface so irritants affect them ??  what if most peoples nerves and ganglions are just a little further back  maybe even 1/8 or 1/6th of an inch so that inhaled allergens don't irritate the ganglion or nerve ??  crazy thought I know .. but why not ?