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Anyone else taking Citicoline?

garcia

Aristocrat Extraordinaire
Messages
976
Location
UK
Garcia. Not that I disagree with these statements but what are you basing them on?
Hi Marco, look up the work of Dr Cheney, Dr Jay Goldstein, and Dr Martin Pall wrt NMDA receptors and ME/CFS. Let me know if you have problems, and I'll attempt to look up references.
 

Marco

Grrrrrrr!
Messages
2,386
Location
Near Cognac, France
Hi Marco, look up the work of Dr Cheney, Dr Jay Goldstein, and Dr Martin Pall wrt NMDA receptors and ME/CFS. Let me know if you have problems, and I'll attempt to look up references.

Thanks Garcia. Pall's model of multiple chemical sensitivity I'm aware of. Did Jay Goldstein specifically single out NMDA receptors?

Cheney I haven't noticed mentioning glutamate/NMDA receptors.

Any references would be most appreciated.
 

garcia

Aristocrat Extraordinaire
Messages
976
Location
UK
Hi Marco, I can't remember if Goldstein specifically singled out NMDA receptors, but he did mention them, and many of the drugs he recommended seemed to affect NMDA receptors.

I actually found out about the whole glutamate/NMDA thingy from Cheney. I think it was from one of his lecture notes online from way back. This is the kind of thing:
http://www.prohealth.com/library/showarticle.cfm?libid=8021
 

lansbergen

Senior Member
Messages
2,512
If Garcia is right patients who tried to inhibit NMDA receptors better stay away from levamisole.

Nature always will try to restore balance and when that is not possible will try to install a new balance.

It could be that by inhibiting activation numbers increase. When these higher numbers are activated by levamisole one can get in big trouble.
 

Marco

Grrrrrrr!
Messages
2,386
Location
Near Cognac, France
Hi Marco, I can't remember if Goldstein specifically singled out NMDA receptors, but he did mention them, and many of the drugs he recommended seemed to affect NMDA receptors.

I actually found out about the whole glutamate/NMDA thingy from Cheney. I think it was from one of his lecture notes online from way back. This is the kind of thing:
http://www.prohealth.com/library/showarticle.cfm?libid=8021

Much appreciated:)
 

perchance dreamer

Senior Member
Messages
1,702
Athene, you said citicoline helps you sleep better. What time do you take it?

I got the Jarrow Citicoline, 250 MG. The first day I took one capsule in morning. It felt like a very mild stimulant and mood enhancer. However, my sleep was really bad that night.

The next day I took 1/2 a capsule in the morning. It had less effect, but I slept fine.

Yesterday and today I also took 1/2 a capsule in the mornings, also. However, both days it made me really sleepy during the day.

I'll keep experimenting with the dose and timing because I really benefited from the subtle stimulant effect and need that.
 

beaverfury

beaverfury
Messages
503
Location
West Australia
Athene, you said citicoline helps you sleep better. What time do you take it?

I got the Jarrow Citicoline, 250 MG. The first day I took one capsule in morning. It felt like a very mild stimulant and mood enhancer. However, my sleep was really bad that night.

The next day I took 1/2 a capsule in the morning. It had less effect, but I slept fine.

Yesterday and today I also took 1/2 a capsule in the mornings, also. However, both days it made me really sleepy during the day.

I'll keep experimenting with the dose and timing because I really benefited from the subtle stimulant effect and need that.

Hi PD,

How are you going with the citicoline?
 

Lotus97

Senior Member
Messages
2,041
Location
United States
Thanks Lansbergen

I read on wiki that Levamisole also may have an antidepressant effect. I will read a few more of your posts.
I wonder how you come across levamisole and whether it helps with other me/cfs symptoms?

Regarding the excess choline in the brain, i dont know what the current research conclusion is. This is an interesting article i keep going back to by Rich Vank , and i guess it explains why i might get depressed on citicoline. http://www.mindandmuscle.net/forum/neuroscience-nootropics/40965-uridine-2.html

As you probably know, choline comes partly from the diet, and part of it is made in the body. The connection with the methylation cycle is that it is thought that the second largest use of methylation in the body (after the synthesis of creatine, thought to be number one) is the conversion of phosphatidylethanolamine to phosphatidylcholine. Phosphatidylcholine is an important phospholipid, making up the cellular membranes. It is also an important component of bile.

Some of the phosphatidylcholine is broken down, and the choline used for other purposes. A major one is the synthesis of acetylcholine. Acetylcholine serves as a neurotransmitter in parts of the brain, it serves as the neurotransmitter between the nerves and the muscle cells, and it serves as the neurotransmitter for the parasympathetic nervous system in general.

In chronic fatigue syndrome, it is my current hypothesis that choline, phosphatidylcholine, and acetylcholine are depleted. I realize that some of the magnetic resonance spectroscopy studies have concluded that choline is elevated in the brain, but I think this conclusion was based on a faulty assumption. In these studies, the ratio of choline to creatine was found to be higher than normal. It was assumed that creatine was unchanged between normal, healthy people and PWCs, so the conclusion was that choline was elevated. However, because of the partial methylation cycle block, I think we should expect that creatine is depleted in CFS, and if it is depleted more than choline is depleted, the ratio would be higher than normal, even though both these substances were depleted.

I expect that there will be an MRS study coming out soon that will report on absolute measurement of these metabolites, rather than simply ratios, and I expect that it will show that choline and creatine are both below normal in CFS.

I think that low acetylcholine would explain the results of blood flow studies in the forearm reported by Vance Spence's group at the U. of Dundee a few years ago. I think it can also help to explain why the ratio of sympathetic to parasympathetic nervous system activity in CFS is higher than normal, as shown in heart rate variation studies.

The assumption of constant creatine has carried over to the use of creatinine ratios in urine testing of various metabolites. The assumption of constant creatine to creatinine conversion rate has justified this practice for compensating for differences in urine dilution by water. Normally this is fine, and the creatinine production correlates with lean muscle mass, but is otherwise a constant. But in CFS, we see drops in 24-hour creatinine excretion in urine, and I think that is consistent with the partial methylation cycle block.

So that's the situation as I see it in CFS in most cases, and I'm hopeful that it will be borne out by work now underway.

Now, getting to your case, it sounds as though you have an unusual response to choline supplementation. Elevated acetylcholine in the central nervous system can cause depression. My guess is that your body may overproduce acetylcholine, or it may not be able to break acetylcholine down as rapidly as normal, and one or the other of these may account for the depression on supplementing choline. This sounds like a genetic issue, given the experience of your mother and your son as well. The rate-limiting step in the production of acetylcholine in the neurons of the central nervous system is the transport of choline into the neurons. The breakdown of acetylcholine is accomplished by the cholinesterase enzymes.
So I suspect that you may have inherited a genetic polymorphism that speeds up the action of the choline transporters, or a genetic polymorphism that slows the action of one of the cholinesterases.

As to what can be done if the acetylcholine level is too high, you are probably aware of scopolamine, which blocks muscarinic acetylcholine receptors, including in the central nervous system. I don't know if that would help you or not, but it's something to look into.
Some people were also reporting anxiety/overstimulation from Citicoline. Would this also be from too much acetylcholine or could something else about Citicoline cause that?
 

lansbergen

Senior Member
Messages
2,512
Some people were also reporting anxiety/overstimulation from Citicoline. Would this also be from too much acetylcholine or could something else about Citicoline cause that?

In my opion it is not too much acethylcholine but understimulated A7 nAchR's.

I need both nicotine as an agonist and levamisole as a positive modulator to stimulate these receptors enough to improve. .
 

adreno

PR activist
Messages
4,841
I generally find cholinergics to be anxiolytic. It is theoretically possible that excess ACh can overstimulate the NMDA, but this is probably rare. CDP-choline also increase the density of dopamine receptors in the striatum, and this could help to explain symptoms of irritability. Overall I find it to be a wonderful supplement.
 

perchance dreamer

Senior Member
Messages
1,702
I'm still experimenting, but I'm really liking the citicoline.

Taking 1/2 of a 250 MG cap made me sleepy for a lot of the day, so I started taking the full capsule again, first thing in the morning.

It does make me sleepy for a few hours, but later in the day I get a really nice mood boost and slightly more energy.

The full 250 MG citicoline no longer has a bad effect on my sleep; in fact, it's actually a little better now. I'm not noticing any better concentration or memory, but maybe that will come with time.
 

beaverfury

beaverfury
Messages
503
Location
West Australia
Some people were also reporting anxiety/overstimulation from Citicoline. Would this also be from too much acetylcholine or could something else about Citicoline cause that?

I wish i could add something to the technical side of the discussion but i don't understand the whole Acetylcholine, Muscarinic mechanism very well.

I would like to stress again that Citicoline has a major positive effect on my pain and energy symptoms of cfs.
To the point where my body feels pain free, clear and ready for action when i am taking it.
Its quite dramatic and curious.

But...in me at least, its negative effects of depression are intolerable. That leaves me somewhere between elated and despairing.

Maybe i have some genetic issue which makes it cfs-effective in me, so i wouldnt want to ram it down peoples throats.......On the other hand, maybe it deals with some common pathological problem in me/cfs(?)

Today i took a very small amount of citicoline sublingually and got a noticeable but more modest effect of both positive and negative. This may be a workable regime for me. I have to investigate the half life of citicoline, its interactions with other supplements/drugs or possible choline/phospholipid(?) alternatives.

One suggestion i got was perhaps upping an antidepressant to offset the depressive effects, or adding a muscarinic antagonist. This might be a good option. Rich Van mentioned scopolamine, but there may be many other choices.

Rich Vank discussed phospholipids ;
Given that the methylation cycle appears to be partially blocked in many or most
cases of CFS, use of citicoline might be a way to expedite the
replacement of phospholipids that have been damaged by oxidative
stress in CFS.

My bottle of Jarrows Citicoline says, ' Citicoline consumption promotes brain metabolism by enhancing the synthesis
of acetylcholine, restoring phospholipid content in the brain....'.

Maybe its the phospholipid action that is proving effective, in which case, i could take alternatives ?

I've got a lot of reading to do.
 

beaverfury

beaverfury
Messages
503
Location
West Australia
Just found this on Pubmed. In plain english i think it says citicoline is good for pain relief
http://www.ncbi.nlm.nih.gov/pubmed/21836465
The antihyperalgesic effect of cytidine-5'-diphosphate-choline in neuropathic and inflammatory pain models.

'The i.c.v. administration of CDP-choline (0.5, 1.0 and 2.0 µmol) produced a dose and time-dependent reversal of mechanical hyperalgesia in both carrageenan-induced inflammatory and chronic constriction injury-induced neuropathic pain models in rats. The antihyperalgesic effect of CDP-choline was similar to that observed with an equimolar dose of choline (1 µmol).

These results indicate that CDP-choline-elicited antihyperalgesic effect in different models of pain occurs through mechanisms that seem to involve an interaction with supraspinal α7-selective nicotinic ACh receptors, and γ-aminobutyric acid B receptors, whereas central opioid receptors have a role only in the neuropathic pain model.'

Wiki

Hyperalgesia
... is an increased sensitivity to pain, which may be caused by damage to nociceptors or peripheral nerves. Temporary increased sensitivity to pain also occurs as part of sickness behavior, the evolved response to infection.
Hyperalgesia can be experienced in focal, discrete areas, or as a more diffuse, body-wide form. Conditioning studies have established that it is possible to experience a learned hyperalgesia of the latter, diffuse form.

Hyperalgesia is induced by platelet-activating factor (PAF) which comes about in an inflammatory or an allergic response. This seems to occur via immune cells interacting with the peripheral nervous system and releasing pain-producing chemicals (cytokines and chemokines).[3]

The release of proinflammatory cytokines such as Interleukin-1 by activated leukocytes triggered by lipopolysaccharides, endotoxins and other signals of infection also increases pain sensitivity as part of sickness behavior, the evolved response to illness.[1][12][13]


 

beaverfury

beaverfury
Messages
503
Location
West Australia
...And this

http://www.ncbi.nlm.nih.gov/pubmed/16942753
The antinociceptive effects of centrally administered CDP-choline on acute pain models in rats: the involvement of cholinergic system.

(...Bla Bla BLa.....:sleep: )...Therefore, it can be postulated that CDP-choline exerts an antinociceptive effect mediated by a central cholinergic mechanism. Activation of specific alpha(7)-nicotinic cholinergic receptors through the activation of presynaptic cholinergic mechanisms appears to be involved in the antinociceptive effect of this drug.
 
Messages
1
Hi all :) just thought I'd drop a line and tell you how amazed I am by this conversation. I was looking for information on citicoline when I found you all. Cut a long story short, from what I see here citicoline is an excellent drug except for the side effect of depression. Now, this is interesting because rick Simpsons hemp oil is also an excellent drug except some ppl don't like the side effect of the "high" These ppl now use citicoline as it counteracts the high with the low of the citicoline for an outstanding healing and a balanced emotional effect. :) just thought I would mention it as the opposite may help balance things for you here as well. :)
 

liquid sky

Senior Member
Messages
371
880 lmmunomodulatory effects of levamisole in chronic fatigue syndrome

R Polasani MD. SA Schwartz MD PhD. Buffalo, NY Chronic fatigue syndrome (CFS) may be associated with

immunologic abnormalities, We describe a patient with CFS and coexisting lyraphopeniaand cellular iramunodcficicncy who responded to a'eatmcnt with levamisole. A 32 y.o. feraale developed CFS after a blood transfusion for post partura bleeding 4 years ago and since then she reports low grade fevers, insomnia, rayalgia, and severe lethargy. She had intermittent oral candidiasis which was successfullytreatedwithantifungals. Orallesionsconsistentwith Herpessimplexwereobservedbutatrialof acyclovirfailedtocause significant iraprovcmcnt. Laboratory evaluation was negative for active CMV, EBV or HIV infections as were seroassays for hepatitis B, lymc disease, and autoimraane disorders. Throat cultures were negative. Muscleenzymesandthyroidstudies,IgG,IgM,IgA,IgG subclasses, pneuraococcal, tetanus, and viral specific antibody titers werenormal. Flowcytometryshowednormalnumbersoft andB lymphocytes but the CIM count was in the low normal range. Functional immunoassaysrevealed diminishedproliferative responses to raitogens and antigens. A trial of the immunopotentiator, levamisole, at a dose of 50 rag 3 times daily for 3 days every 2 weeks was given for 3 months. At the end of this period the patient experiencedconsiderable improveraentof subjectivesyraptoras, including increased stamina. More objectively, this was accorapanied by significant changes in immunologic parameters, including an increase in CD4 counts and a major increase in lymphocyte prolifcrativc responses to mitogens and antigens. The patient continuestodowellforthepast6monthswithout specifictherapy. Thiscasesuggeststhattheimraunopotentiator, levamisolc,maybe useful in the managementof CFS associatedwith objectiveevidence ofcoexistingcellular immunodcficiency.

Interesting article on Levamisole and CFS. http://www.jacionline.org/article/S0091-6749(96)81098-0/pdf
 
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