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Topic: Fresh Research - Goadsby / anandamide (Read 763 times) |
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floridian
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Fresh Research - Goadsby / anandamide
« on: Jan 16th, 2004, 11:55am » |
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This abstract doesn't mention clusters, but the implications are clear - a compound that inhibits blood vessel dilation from CGRP and NO and eases up pressure on the trigeminal nerve. Unfortunately, ananadamide (and the ananadamide agonist THC) have a few side effects. As I write this, there are people in white lab coats looking for ways to tweak the anandamide molecule so that it doesn't make you paranoid, catatonic, forgetful, or reely hungry.
Quote:J Pharmacol Exp Ther. 2004 Jan 12 [Epub ahead of print]
Anandamide is able to inhibit trigeminal neurons using an in vivo model of trigeminovascular-mediated nociception.
Akerman S, Kaube H, Goadsby PJ.
Institute of Neurology.
Arachidonylethanolamide (AEA or anandamide) is believed to be the endogenous ligand of the cannabinoid CB1 and CB2 receptors. CB1 receptors have been found localized on fibers in the spinal trigeminal tract and spinal trigeminal nucleus caudalis. Known behavioural effects of anandamide are anti-nociception, catalepsy, hypothermia and depression of motor activity, similar to Delta(9)-tetrahydocannanbinol, the psychoactive constituent of cannabis. It may be a possible therapeutic target for migraine. In this study we looked at the possible role of the CB1 receptor in the trigeminovascular system, using intravital microscopy to study the effects of anandamide against various vasodilator agents. Anandamide was able to inhibit dural blood vessel dilation brought about by electrical stimulation by 50%, CGRP by 30%, capsaicin by 45% and nitric oxide by 40%. CGRP8-37 was also able to attenuate NO-induced dilation by 50%. The anandamide inhibition was reversed by the CB1 receptor antagonist, AM251. Anandamide also reduced the blood pressure changes caused by CGRP injection, this effect was not reversed by AM251. It would seem that anandamide acts both pre-synaptically, to prevent CGRP release from trigeminal sensory fibers, and post-synaptically to inhibit the CGRP-induced NO release in the smooth muscle of dural arteries. CB1 receptors appear to be involved in the NO/CGRP relationship that exists in causing headache and dural blood vessel dilation. It also seems that some of the blood pressure changes caused by anandamide are mediated by a non-cannabinoid receptor, as AM251 was unable to reverse these effects. It can be suggested that anandamide is tonically released to play some form of modulatory role in the trigeminovascular system. |
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notseinfeld
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Re: Fresh Research - Goadsby / anandamide
« Reply #1 on: Jan 16th, 2004, 1:05pm » |
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Cool:
Anandamide is a compound present in mammalian brains, including human brains. It binds to THC receptors, the same receptors that bind tetrahydrocannabinol, the active ingredient in marijuana. Recently anandamide was also discovered in chocolate, setting off a flurry of speculation about the powers of chocolate and the fate of chocaholics.
Guess if it acts like THC there's really very limited paranoia but indeed the short term memory would be hammered. Plus, laughing all day would be murder on the abs!
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floridian
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Re: Fresh Research - Goadsby / anandamide
« Reply #2 on: Jan 17th, 2004, 12:29pm » |
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Low levels of anandamide might be linked to the phospholipid problems in cluster heads described in earlier research (high phospholipid/choline ratio). Phospholipid enzymes are responsible for both anandamide production and splitting phosphocholine into choline - having these messed up could be one of the things needed to cause clusters. Not sure how yet, but the synthesis of anandamide and related compounds are dependent on essential fatty acids - fish oils, flax oil and related fats affect which metabolic pathway gets activated or supressed.
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pubgirl
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Re: Fresh Research - Goadsby / anandamide
« Reply #3 on: Jan 17th, 2004, 12:53pm » |
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Don't know if this is relevant Floridian, but I can prevent most migraines with large doses (1000 mgs a day) of GLA which is a fatty acid- I use Starflower or Evening Primrose Oil.
I only use it for a few weeks when I know my migraines are threatening to return but I think I might try taking it 365 days a year and see what happens to my CH.
Can't do any harm in any case.
Wendy
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| « Last Edit: Jan 17th, 2004, 12:54pm by pubgirl » |
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floridian
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Re: Fresh Research - Goadsby / anandamide
« Reply #4 on: Jan 17th, 2004, 1:57pm » |
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Pubgirl,
Flax and fish oils have been part of my regimen for the past few years - especially in summer when my CH gears up. GLA from evening primrose oil has similar effects. I can't say exactly how helpful they have been to me because I take several other things (melatonin, 5-htp, magnesium, turmeric, tea), but I think the whole program has helped. Two of the last four years I have been headache free, though I definitely was in a cycle and had other problems.
These essential fatty acids have been shown to be helpful for a lot of conditions - Consumer Reports now recommeds daily fish oil and consumption of fish to help prevent heart disease. GLA has been shown to help with PMS, and other related fats act similarly. Essential fatty acids can improve and stabilize mood (maybe an anandamide connection, maybe not). They are anti-inflammitory, and protect against some types of cancer. And the list goes on. Still too early to claim they do help with clusters, but they are Generally A Good Thing (tm), and might help some people with clusters.
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pubgirl
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Re: Fresh Research - Goadsby / anandamide
« Reply #5 on: Jan 17th, 2004, 3:03pm » |
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Thanks Floridian.
I'm definitely going to try taking it every day from now on and see what happens.
I'm episodic though, so it will be difficult to know whether I am blocking cycles or there wasn't one coming anyway. Still if I go pain free I won't care which it is!
I've also started giving my 4 year old Omega 3 oil every day as there is some pretty convincing evidence that it has powerful effects on concentration, learning and memory in young children.
Wendy
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floridian
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Re: Fresh Research - Goadsby / anandamide
« Reply #6 on: Jan 19th, 2004, 1:33pm » |
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Pubgirl,
here's an abstract that shows that the effects of IL-1 (one of the elevated inflammatory immuno-hormones in cluster headache) is reduced by EPA (fish oil), or EPA + GLA, but only partially by GLA alone. GLA is also more expensive than fish oils.
Quote:J Lipid Res. 2003 Oct; 44(10): 1984-91. Epub 2003 Jul 01.
Effects of dietary n-3 or n-6 fatty acids on interleukin-1beta-induced anxiety, stress, and inflammatory responses in rats.
The present study demonstrated that an omega (n)-3 fatty acid, ethyl-eicosapentaenoic acid (ethyl-EPA), supplemented diet significantly attenuated the stress/anxiety behavior of rats in the "open field" and elevated plus maze, which was induced by subchronic intracerebroventricular administration of proinflammatory cytokine interleukin (IL)-1beta. Ethyl-EPA also reduced the rise in serum corticosterone induced by IL-1. The n-6 fatty acid ethyl-gamma-linolenic acid (ethyl-GLA) had little effect on the IL-1-induced changes in behavior and the corticosterone concentration. Following IL-1beta administration, ethyl-EPA reduced the elevated prostaglandin (PG) E2 secretion and increased the secretion of antiinflammatory cytokine IL-10 from whole blood cells. Ethyl-GLA showed a similar antiinflammatory effect to ethyl-EPA. By contrast, n-6 fatty acid arachidonic acid (AA) had no effect on the behavior, immune, and endocrine changes induced by IL-1. AA alone enhanced the basal inflammatory response, raised serum corticosterone concentrations, and induced anxiety behavior in the elevated plus maze. The reduced growth rates of rats following the administration of IL-1 was attenuated by ethyl-EPA, and to a greater extent by ethyl-EPA plus ethyl-GLA, but not by AA alone or in combination with ethyl-EPA. Thus, ethyl-EPA would appear to antagonise the endocrine, immune, and behavioral effects of subchronic IL-1 administration. Ethyl-GLA only antagonised IL-1-induced inflammatory changes, whereas AA caused an increase in the secretion of corticosterone and PGE2, and induced anxiety-like behavior without enhancing the effects of IL-1.
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| « Last Edit: Jan 19th, 2004, 1:42pm by floridian » |
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CJohnson
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Re: Fresh Research - Goadsby / anandamide
« Reply #7 on: Jan 19th, 2004, 2:24pm » |
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Here it states that certain amounts of anandamide will inhibit cgrp release, but higher amounts will actually stimulate release of cgrp via VR1 receptors.
"The effect of anandamide, which activates both the cannabinoid 1 (CB1) receptor and the vanilloid receptor 1 (VR1), was studied on calcitonin gene-related peptide (CGRP) release from cultured primary sensory neurons, the majority of which coexpress the CB1 receptor and VR1. Concentrations of anandamide <1 µm produced a small but significant CB1 receptor-mediated inhibition of basal CGRP release while higher concentrations induced VR1-mediated CGRP release. The excitatory effect of anandamide was potentiated by the CB1 receptor antagonist SR141716A. In the presence of SR141716A at concentrations <100 nm, anandamide was equipotent with capsaicin in stimulating CGRP release. However, at higher concentrations anandamide produced more CGRP release than equimolar concentrations of capsaicin. Three and ten nanomolar anandamide inhibited the capsaicin-evoked CGRP release. In the presence of SR141716A, treatments which activated protein kinase A, protein kinase C and phospholipase C significantly potentiated the anandamide-evoked CGRP release at all anandamide concentrations. Although this potentiation was reduced when the CB1 receptor antagonist was omitted from the buffer, the CGRP release evoked by 300 nm and 1 µm anandamide was still significantly larger than that seen with nonpotentiated cells. These data indicate that anandamide may regulate CGRP release from capsaicin-sensitive primary sensory neurons in vivo, and that the net effect of anandamide on transmitter release from capsaicin-sensitive primary sensory neurons depends on the concentration of anandamide and the state of the CB1 receptor and VR1. These findings also suggest that anandamide could be one of the molecules responsible for the development of inflammatory heat hyperalgesia."
http://www.blackwellpublishing.com/abstract.asp?ref=0953-816X&vid=17 &iid=12&aid=11&s=&site=1
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pubgirl
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Re: Fresh Research - Goadsby / anandamide
« Reply #8 on: Jan 19th, 2004, 8:40pm » |
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Now I'm lost!
Floridian, does that mean I should take the oils of the fishes AND the flowers?
Wendy
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Stevieray
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Re: Fresh Research - Goadsby / anandamide
« Reply #9 on: Jan 20th, 2004, 12:03am » |
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Interesting about the flax seed oil? I have psoriasis as well as CHs. I was once told by a health food store clerk that taking flax seed oil would help the psoriasis problem along with taking vitamin D. I only have the psoriasis during the winter months when I am not out in the sun. As soon as the sun comes back and I can expose my skin to it the psoriasis goes away quickly. I wonder if the relationship between fatty oils sun and vitamin D have a similar relation in CHs. I know that I am solar powered anf my mental state is so much better in the summer and that I only get the beast in the winter months. I think I will try the flax seed oil again (yummy) to see if it helps with the CHs although... I haven't had one for SIX days now! Perhaps it will work as a preventative and I know it will help with the psoriasis as it is really bad this year.
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floridian
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Re: Fresh Research - Goadsby / anandamide
« Reply #10 on: Jan 20th, 2004, 10:49am » |
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Quote:| Floridian, does that mean I should take the oils of the fishes AND the flowers? |
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It depends - fish oil seems to be better for some things (including IL-1). It is also less expensive. But according to that one abstract, taking the two together had somewhat better effects. GLA shares many of the beneficial effects of fish and flax oil, and it may also be that GLA has effects that fish oils don't.
Quote:| Here it states that certain amounts of anandamide will inhibit cgrp release, but higher amounts will actually stimulate release of cgrp via VR1 receptors. |
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I think there's a trap that people tend to fall into - thinking in terms of simple shortages and simple excesses (and I think like that sometimes). For the body to work perfectly, it takes the right amount of the right molecule in the right place at the right time. And the other cells and molecules need to respond in the right way. Definitely complicated, but maybe the anandamide connection will prove helpful someday.
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