Confusion about therapy related to norepinephrine

[judyinthesky]

Dear all!
Even before having ME in the sense of fatigue (my first symptom was change of HPA axis and extreme wiredness), I measured low on both adrenaline/ephedrine and noradrenaline/norepinephrine. This is always the case, in 24 hour urine testing as well as in salvia.

I am aware that many ME medication trials involve increase of noradrenaline such as in antidepressants.
But I usually react badly to them. I've tried Mirtazapine which increases noradrenaline and was wired, but at the same time it felt like it changed something important in my brain (brain terror issues are my worst symptom,)

Now my ME expert wants me to try Catapresan, which lowers norepinephrine.

I have problems with inflammatory, but not situational depression.

I'm extremely confused about my low adrenaline. My cortisol is low in salvia in the morning, but normal in blood. (Seems to be that in ME people it's often reversed or fucked up).

Is there anyone who also has low noradrenaline?
Or has experience with medication only working on noradrenaline?

I'm really reacting extreme to many psych meds. It's like my body would need it as per lab, but is in such an extremely wired state that I don't manage to get onto them.

Experience with Catapresan or similar?

Love, Judith

 

[hapl808]

I haven't tried those things, but I'm very curious about adrenaline issues. I've had that wired but tired for the last 25 years including when I was comparatively mild. I noticed early on that whether I slept or not made no difference in how much energy I had for work: if I had a big day of work, I could function solely on adrenaline for the whole day and feel pretty good, but then would have an awful crash at night. That nausea, post-adrenaline, poisoned feeling.

My cortisol when I've measured it is actually pretty normal I think. Did saliva tests (4 in a day) and serum tests and nothing terribly unusual. Ironically my sleep patterns were much worse when I was mild and moderate, now since I'm home 24-7 and control every aspect of my life and can't really work at all, my sleep pattern is healthier I guess.

But anything which is 'stimulating' will cause a PEM crash. An exciting phone conversation, a social visit from a friend, an interesting computer problem. All of those cause a bit of an adrenaline rush which temporarily make my symptoms better, but it's always followed by a crash.

In summary, no clue if it's dopamine or adrenaline or if I need more or less or whatever. Just seems heavily involved.

 

[Shanti1]

Is there anyone who also has low noradrenaline?
Or has experience with medication only working on noradrenaline?

Hi Judy,
My norepinephrine and epinephrine have tested low on two morning urine tests done two years apart. However, I believe my symptom picture is quite different from yours. I have lethargy, somnolence, slowness, no anxiety. Can't maintain my BP above 75/55 without meds/compression. No pots, just orthostatic hypotension.

Anyhow, I currently use atomoxetine (Strattera), a norepinephrine reuptake inhibitor and droxidopa (Northera) a synthetic norepinephrine precursor. I would be happy to go into more detail on my experience with both if it would be helpful.

 

[CSMLSM]

I would suggest looking into adrenal fatigue. I dealt with mine with cannabis and CBD before finding caryophyllene for the immune modulation required. CBD does help modulated the immune system but not like caryophyllene. I use Copaiba essential oil to source the caryophyllene.

I would not suggest THC for this, avoid unless in combination with CBD.

I also came off of an antidepressant (duloxetine/Cymbalta) with CBD and it worked way better with no side affects.
Like an antidepressant it may take 2-4 weeks to see major improvement in symptoms from my experience. Take every 4 hours under the tongue. This is what I use (available in US I think)-
Dragonfly CBD Cannabidiol Oil 1000mg 10ml | CBD | Boots

Adrenals need to recover and this will only happen when they are not constanly trying to produce cortisol, adrenaline/ephedrine and noradrenaline/norepinephrine. The cannabinoid system reduces HPA axis activation.
You are low in these things because the adrenals are fatigued and the function is breaking down.

I think it could be Adrenal fatigue causing HPA axis dysfunction maybe even glucocorticoid receptor blunting from that. This disrupts the whole system including the immune system.

I believe it is what caused most of my depression for sometime until actual (for a reason) depression came from decades of suffering.

You should find this very useful to watch-
(1) Learn about series- Doc Snipes walks us through HPA-Axis Dysfunction. Understand your ME/CFS triggers better with this video. | Phoenix Rising ME/CFS Forums

 

[Castorp]

Is there anyone who also has low noradrenaline?
Or has experience with medication only working on noradrenaline?

My worst symptom is a crushing and unrelenting fatigue 24/7 and different tests have shown that I have significantly low levels of noradrenaline and dopamine in blood. However, my doctors do not attach any importance to this issue. Nevertheless, I wonder whether to increase the levels of noradrenaline and dopamine may contribute to reduce my fatigue. In order to explore this possibility, I resorted to ritalin but it did not have any effect.

 

[CSMLSM]

My worst symptom is a crushing and unrelenting fatigue 24/7 and different tests have shown that I have significantly low levels of noradrenaline and dopamine in blood. However, my doctors do not attach any importance to this issue. Nevertheless, I wonder whether to increase the levels of noradrenaline and dopamine may contribute to reduce my fatigue. In order to explore this possibility, I resorted to ritalin but it did not have any effect.

I believe we have less of these substances produced because the source, the adrenals are fatigue and maybe have atrophy of the adrenals because over overworking them. This then causes glucocorticoid receptor blunting which leads to the adrenals trying to produce more because the natural feedback loop of the HPA axis becomes dysfunctional.

We need to get the adrenals to rest, so 1. Recover from the over work 2. So the glucocorticoid receptor blunting is undone and becomes normal again. I did this with CBD over years. I used to get serious pain and cramps in my adrenals which sit on top of your kidneys and major dysautonomia. I do not have any dysautonomia now.

Adrenal fatigue when I research it many years ago was ignored and seen as like ME/CFS, a patient creation. Now I think it is more recognised but not fully like ME/CFS, funny that.

This video helps cover a lot of stuff and is really good. The person explains really well for non science people if I remember correctly-
(1) Learn about series- Doc Snipes walks us through HPA-Axis Dysfunction. Understand your ME/CFS triggers better with this video. | Phoenix Rising ME/CFS Forums
I think it even covers the adrenal fatigue if I remember correctly.

 

[Learner1]

I would look into BH4, tetrahydrobiopterin, deficiency. BH4 is necessary for adequate catecholamine production and has been associated with ME/CFS. There is current research going on. Kuvan can be prescribed if you have a problem with making or recycling BH4.

HDRI is a New Jersey lab that tests for nitrotyrosine, a peroxynitrite marker, and NO. High phenylalanine and low tyrosine can also be indicators.

There are several genes involved in make Ng and producing it. Mutations can affect the amount of production or recycling, and give one a milder situation other than PKU that can be missed for years, and some of them are actually not so rare:

https://rarediseases.org/rare-disea...articularly sensitive to excess phenylalanine.

 

[Bergkamp]

Like an antidepressant it may take 2-4 weeks to see major improvement in symptoms from my experience. Take every 4 hours under the tongue. This is what I use (available in US I think)-

How much cbd do you take on a daily basis? I have AF too (evidenced by very low cortisol which I tested recently) and been taking it for a while but never noticed much from it.

I believe we have less of these substances produced because the source, the adrenals are fatigue and maybe have atrophy of the adrenals because over overworking them. This then causes glucocorticoid receptor blunting which leads to the adrenals trying to produce more because the natural feedback loop of the HPA axis becomes dysfunctional

Interestingly enough I have strong reason to suspect my glucocorticoid receptors are extremely sensitive because I recently (accidentally) took 2 pills of dexamethasone (a glucocorticoid) and it caused an extreme multiple day hyper (no sleep, adrenaline rushes, super high HR etc) state followed by a severe worsening of POTS, fatigue, dysautonomia, etc. The lab I tested my cortisol & DHEA at suggested 'increased receptor sensitivity' too although I don't know on what they base that.

Thanks for sharing that video, I'll check it out.

 

[CSMLSM]

How much cbd do you take on a daily basis? I have AF too (evidenced by very low cortisol which I tested recently) and been taking it for a while but never noticed much from it.

At first followed bottle
How to use
Using the pipette, administer oil under the tongue. Hold for 2 minutes to maximise absorption. We recommend starting with a 3 drop serving then varying as required. Do not exceed 40 drops per day.

But did go up to 6 drops. I also had some years prior using cannabis so maybe had a headstart a bit. Over time it will work better but you must be consistant and avoid any stressor as these will negatively influence the progress relatively. If you live in a legal area for cannabis the adition of THC to the CBD can work better but be careful, aim for 1:1 ratio and take orally. Expensive though as you can imagine, maybe you have ability to grow legally.

Interestingly enough I have strong reason to suspect my glucocorticoid receptors are extremely sensitive because I recently (accidentally) took 2 pills of dexamethasone (a glucocorticoid) and it caused an extreme multiple day hyper (no sleep, adrenaline rushes, super high HR etc) state followed by a severe worsening of POTS, fatigue, dysautonomia, etc. The lab I tested my cortisol & DHEA at suggested 'increased receptor sensitivity' too although I don't know on what they base that.

Maybe your adrenal fatigue has gone on so long that your body has adapted to the levels in some circumstances in the body and an increase of glucocorticoids is indeed meeting a more sensitive receptor in some circumstances. The adrenals will still need to be rested to improve the production of the hormones and bring to system into more balance. From what I understand of it.

I hope the video helps you understand your symptoms better so you can see where you are at. I need to rewatch again myself soon I read and watch so much.

 

[Bergkamp]

But did go up to 6 drops. I also had some years prior using cannabis so maybe had a headstart a bit. Over time it will work better but you must be consistant and avoid any stressor as these will negatively influence the progress relatively. If you live in a legal area for cannabis the adition of THC to the CBD can work better but be careful, aim for 1:1 ratio and take orally. Expensive though as you can imagine, maybe you have ability to grow legally.

Thanks. I live in Holland so that should be possible. What's the added benefit of THC?

Maybe your adrenal fatigue has gone on so long that your body has adapted to the levels in some circumstances in the body and an increase of glucocorticoids is indeed meeting a more sensitive receptor in some circumstances.

I think that's very likely what has happened indeed.

 

[CSMLSM]

Thanks. I live in Holland so that should be possible. What's the added benefit of THC?

The suppressd cannabinoid Anandamide binds both to CB1 and CB2. Caryophyllene binds only to CB2 and CBD raises Anandamide but if you have depression (likely with ME/CFS) the added THC adds the missing CB1 activation to balance mood. You hopefully will find the perfect combination or schedule for your own situation that will be personally unique to your disease progression as this is different for us all with ME/CFS.

I think that's very likely what has happened indeed.

I am sorry to say you likely have some atrophy of the adrenals. This does take time to address due to the recovery difficulty of the atrophy but is possible as I believe I have done this myself. I used to get cramps and surges of extreme pain in my adrenals. I thought it was my kidneys until I figured it out. Stress triggered it, stress triggers cortisol release in the adrenals. My adrenals just could not cope at the time.

 

[Shelagh]

What about a person like me who has low blood pressure for about 25 years (90/65), but good energy levels. I tested high cortisol, but I also have low progesterone, low thyroid (TSH 2.5), blacking out when standing up too fast. Can't take DHEA without it making me VERY tired after about 3-4 days. Is my case also adrenal burnout? I can't handle any stress at all. I use exercise to obtain energy. I MUST exercise to have energy. Many people choose to exercise, but I have to exercise to have energy and keep blood circulation normal. It all started after a vaccine 25 years ago. I did have CFS, but I slowly got out of it. But I'm still left with this problem and others. I can honestly say I have great energy levels at age 52, I can do hard physical work all day long. But something is wrong for my blood pressure to be like this.

 

[judyinthesky]

Hi Judy,
My norepinephrine and epinephrine have tested low on two morning urine tests done two years apart. However, I believe my symptom picture is quite different from yours. I have lethargy, somnolence, slowness, no anxiety. Can't maintain my BP above 75/55 without meds/compression. No pots, just orthostatic hypotension.

Anyhow, I currently use atomoxetine (Strattera), a norepinephrine reuptake inhibitor and droxidopa (Northera) a synthetic norepinephrine precursor. I would be happy to go into more detail on my experience with both if it would be helpful.

Yes particular the latter two medication! Thank you a lot!

 

[Shanti1]

Yes particular the latter two medication! Thank you a lot!

Hi Judy,
I hope you don't mind if I refer you to this post I made yesterday in the droxidopa thread:
https://forums.phoenixrising.me/thr...wisdom-regarding-this-med.42680/#post-2408808

It details my experience with both droxidopa and atomoxetine and the differences between them. Please let me know if you have any questions. My best to you.

 

[judyinthesky]

I would look into BH4, tetrahydrobiopterin, deficiency. BH4 is necessary for adequate catecholamine production and has been associated with ME/CFS. There is current research going on. Kuvan can be prescribed if you have a problem with making or recycling BH4.

HDRI is a New Jersey lab that tests for nitrotyrosine, a peroxynitrite marker, and NO. High phenylalanine and low tyrosine can also be indicators.

There are several genes involved in make Ng and producing it. Mutations can affect the amount of production or recycling, and give one a milder situation other than PKU that can be missed for years, and some of them are actually not so rare:

https://rarediseases.org/rare-diseases/tetrahydrobiopterin-deficiency/#:~:text=Tetrahydrobiopterin deficiency results in abnormally,particularly sensitive to excess phenylalanine.

A little too many abbreviations for my brain in this one

Are you saying there's a useful lab test for those low on certain Catecholamines and is this available in a common lab? BH4 you mean?

 

[judyinthesky]

I would suggest looking into adrenal fatigue. I dealt with mine with cannabis and CBD before finding caryophyllene for the immune modulation required. CBD does help modulated the immune system but not like caryophyllene. I use Copaiba essential oil to source the caryophyllene.

I would not suggest THC for this, avoid unless in combination with CBD.

I also came off of an antidepressant (duloxetine/Cymbalta) with CBD and it worked way better with no side affects.
Like an antidepressant it may take 2-4 weeks to see major improvement in symptoms from my experience. Take every 4 hours under the tongue. This is what I use (available in US I think)-
Dragonfly CBD Cannabidiol Oil 1000mg 10ml | CBD | Boots

Adrenals need to recover and this will only happen when they are not constanly trying to produce cortisol, adrenaline/ephedrine and noradrenaline/norepinephrine. The cannabinoid system reduces HPA axis activation.
You are low in these things because the adrenals are fatigued and the function is breaking down.

I think it could be Adrenal fatigue causing HPA axis dysfunction maybe even glucocorticoid receptor blunting from that. This disrupts the whole system including the immune system.

I believe it is what caused most of my depression for sometime until actual (for a reason) depression came from decades of suffering.

You should find this very useful to watch-
(1) Learn about series- Doc Snipes walks us through HPA-Axis Dysfunction. Understand your ME/CFS triggers better with this video. | Phoenix Rising ME/CFS Forums

Can't do cannabis or antidepressants

 

[judyinthesky]

How much cbd do you take on a daily basis? I have AF too (evidenced by very low cortisol which I tested recently) and been taking it for a while but never noticed much from it.

Interestingly enough I have strong reason to suspect my glucocorticoid receptors are extremely sensitive because I recently (accidentally) took 2 pills of dexamethasone (a glucocorticoid) and it caused an extreme multiple day hyper (no sleep, adrenaline rushes, super high HR etc) state followed by a severe worsening of POTS, fatigue, dysautonomia, etc. The lab I tested my cortisol & DHEA at suggested 'increased receptor sensitivity' too although I don't know on what they base that.

Thanks for sharing that video, I'll check it out.

Yeah we hear a lot about adrenal fatigue but I'm unsure what precisely can be done.

 

[CSMLSM]

Yeah we hear a lot about adrenal fatigue but I'm unsure what precisely can be done.

Overactive adrenals are caused by overactive HPA axis, then it causes adrenal fatigue causing underactive adrenals but at the same time the HPA axis keeps overreacting throwing a system that relies on feedback loops. This causes the system to brake down and become dysfunctional.
What we do about it is counter this with what is suppressed in ME/CFS to facilitate all this and everything else in ME/CFS immune related and this is the endogenous cannabinoid system.
By using CBD we may actually be increasing expression of CB2 and VDR receptors (found research link in last 2 days, been looking 10 years) and by using caryophyllene which is a CB2 receptor agonist to bind to these CB2 receptors down regulate the immune activation in ME/CFS. This down regulation in the brain reduces dysfunction of the PVN of the hypothalamus which had been affecting the HPA axis causing another point of HPA axis dysfunction. This allows your adrenals to rest, start to recover and heal eventually and will vary greatly between us all in.
The increase of the VDR will naturally help with people expressing low vitamin D symptoms but have normal or high intake of the vitamin and in the blood.
It will more importanly counter the VDR suppressing abilities of EBV.
VDR activation will then be more normalised and strengthen the intracellular innate immune system helping us rid persistant infections.

 

[judyinthesky]

Overactive adrenals are caused by overactive HPA axis, then it causes adrenal fatigue causing underactive adrenals but at the same time the HPA axis keeps overreacting throwing a system that relies on feedback loops. This causes the system to brake down and become dysfunctional.
What we do about it is counter this with what is suppressed in ME/CFS to facilitate all this and everything else in ME/CFS immune related and this is the endogenous cannabinoid system.
By using CBD we may actually be increasing expression of CB2 and VDR receptors (found research link in last 2 days, been looking 10 years) and by using caryophyllene which is a CB2 receptor agonist to bind to these CB2 receptors down regulate the immune activation in ME/CFS. This down regulation in the brain reduces dysfunction of the PVN of the hypothalamus which had been affecting the HPA axis causing another point of HPA axis dysfunction. This allows your adrenals to rest, start to recover and heal eventually and will vary greatly between us all in.
The increase of the VDR will naturally help with people expressing low vitamin D symptoms but have normal or high intake of the vitamin and in the blood.
It will more importanly counter the VDR suppressing abilities of EBV.
VDR activation will then be more normalised and strengthen the intracellular innate immune system helping us rid persistant infections.

I've never been in contact with EBV
But my HPA axis certainly dysfunctional
I don't see any difference when using high quality CBD

 

[CSMLSM]

What about a person like me who has low blood pressure for about 25 years (90/65), but good energy levels. I tested high cortisol, but I also have low progesterone, low thyroid (TSH 2.5), blacking out when standing up too fast. Can't take DHEA without it making me VERY tired after about 3-4 days. Is my case also adrenal burnout? I can't handle any stress at all. I use exercise to obtain energy. I MUST exercise to have energy. Many people choose to exercise, but I have to exercise to have energy and keep blood circulation normal. It all started after a vaccine 25 years ago. I did have CFS, but I slowly got out of it. But I'm still left with this problem and others. I can honestly say I have great energy levels at age 52, I can do hard physical work all day long. But something is wrong for my blood pressure to be like this.

I think you have overactive HPA axis issues with a thyroid issue, low blood pressure unsure, but looks like your adrenals are handling it still. Your current condition may be driven just by the brain inflammation in ME/CFS affecting the PVN of the hypothalamus rather than in conjuntion with Adrenal insuffciency due to fatigue or atrophy as a later stage like many of us do I suspect. Have you had a really chill life and avoided stress as much as possible or maybe just super strong adrenals
But the reaction to DHEA i am unsure, maybe the imbalance in the sex hormones is causing it.

blacking out when standing up too fast= blood pressure related/POTS ME/CFS.

hypothalamic–pituitary–adrenal axis (HPA axis or HTPA axis).

Hormonal stress response (openanesthesia.org)
Stress Response

Increased release of

• Sympathetic Nervous System: norepinephrine (spillover from nerve endings)
• Adrenal Medulla: epinephrine
• Adrenal Cortex: cortisol
• Pancreas: insulin, glucagon, and somatostatin

Decreased release of:

• Hypothalamus: gonadotropin-releasing hormone (hypogonadotropic hypogonadism)

Changes in:

• Thyroid hormones: normal TSH and free T4, decreased T3 and bound T3, increased reverse T3, “sick euthyroid syndrome“

Gonadotropin-Releasing Hormone (GnRH): Purpose & Testing (clevelandclinic.org)
The pituitary gland in your endocrine system uses gonadotropin-releasing hormone (GnRH) to stimulate the production of follicle-stimulating hormone and luteinizing hormone. These gonadotropins (hormones) make the sex hormones testosterone, estrogen and progesterone.

Stress | Progesterone-info
Because progesterone and it's metabolites and strong anxiolytics, reduce the response to stress and overworked adrenals. The stress hormone cortisol is also made in the adrenals which first produce progesterone before converting it to cortisol.

Looks to me like being high in cortisol means being low in progesterone.

Being high in Cortisol indicates your stress response (HPA axis) is overactive.

Stress response causes decrease of gonadotropin-releasing hormone.

Decrease of gonadotropin-releasing hormone causes lower production of progesterone and increase in cortisol.

Looks to me like the stress response (triggered HPA axis) causes progesterone to be converted to cortisol.

So overactive stress response can lead to low Progesterone.

Overactive HPA axis is being driven by the brain dysregulation/inflammation caused by ME/CFS, caused by ? EBV maybe or something else.

You likely have a separate issues with the thyroid and blood pressure (genetic maybe).

I am not a doctor just my opinion when asked on the internet

Is my case also adrenal burnout? I can't handle any stress at all. I use exercise to obtain energy. I MUST exercise to have energy. Many people choose to exercise, but I have to exercise to have energy and keep blood circulation normal

No, not adrenal burnout yet it seems. Exercise stimulates anandamide production and with your good adrenal state makes it possible to hack your body by exercising to make more anandamide and this is why it helps and gives you energy and improves things for you. Many of us do this before we biologically snap and go full on ME/CFS.

Exercise-Induced Endocannabinoids Boost Brain Plasticity | Psychology Today
Exercise works on the endocannabinoid system in two ways. It increases blood levels of anandamide and improves the sensitivity of anandamide receptors

We keep pushing and pushing and just one day we just brake or someone gives us a vaccine that pushes us over the edge biologically. The initial trigger (pathogen/immune insult) may have been silient for some time or not.

I did have CFS, but I slowly got out of it.

Maybe a period when your adrenals were struggling.