Before anyone reads this or makes a judgment I want to state that this is all the opinion of one person (me lol), I dont not state this as fact, but my personal hypothisis for what is at the root cause of the symptoms of psych med withdrawal
I first came across Nitric Oxide just a few days ago, 17 months into my extremely severe withdrawal syndrom from the SSRI medication Citalopram, as well as suffering a huge adverse reaction to trying to reinstate, I spend my time, as many others have before me, researching and trying to understand what is happening to me, and WHY, and how we could put things in place to at least help with healing, or stop further destruction...there had to be something ...right??
In November 2013 I stumbled accidentally across a story from a young man who had taken a Nitric Oxcide (NO) boosting supplement, claiming to increase NO by 950%...his reaction was catastrophic and degenerative and he continued to try drug after drug to make things better...
His symptoms so mirrored those of us who are suffering from what we call protracted withdrawal that I began to look for links between NO and withdrawal syndrome...
It is my belief, and has been for some time, that 'withdrawal' is a misnomer..I believe Dr Stuart Shipko is correct when he speaks of Toxic Brain Damage...many of us in withdrawal understand this fact but continue to use the term withdrawal for ease as it is what we have come to accept and understand, but the realities of this Toxic brain damage are, in my opinion, much more sinister
People tell me that time heals, and from what I have read and seen, yes, time has improved everyone I have read about or communicated with, and if you are able to function somewhat during this ''withdrawal'' period, then waiting it out is a good idea.
However, some of us, and Im yet to find anyone as severe as I, are looking at many many yaers of intense suffering, before even seeing small improvements, so I am searching out answers and will not stop..never..until Im healed
Something I think we all of us in withdrawal crave is to understand what is happening to us...to give us some sense of control, or take away some of the mystery and therefore fear of our own terrible condition, personally I think we need to turn to the SPECT scans, as its the only thing that has reliably shown up the damage done.
I know of 6 people who whilst in withdrawal have had a SPECT scan..each of these people have shown the same results...severe Hypoperfusion to areas of the brain, mainly the temporal lobes and frontal cortex..
(I would be most interested in hearing for anyone who has had a SPECT in withdrawal and what the findings were.)
I am aware that some people in the withdrawal community disregard these scans, I do not.
We know that SPECT scans show the damage, and we know that the damage causes severe blood flow restrictions to parts of the brain.
So an obvious answer for this would be Hyperbaric Oxygen therapy...and this is high on my list of treatments to use...its controversial, and some have tried it but with little success, but their protocol could have been entirely wrong..However, this post is not about HBOT, I will be writing about that soon
The reason I brought up the whole HBOT issue is that it DOES increase NO in the brain and this is very worrying as I believe NO to be what is poising us and killing our brain cells..
So....lets start by looking at what exactly NO is...Wiki describes it at this...
Nitric oxide, or nitrogen oxide,[2] also known as nitrogen monoxide, is a molecule with chemical formula NO. It is a free radical[3] and is an important intermediate in the chemical industry. Nitric oxide is a by-product of combustion of substances in the air, as in automobile engines, fossil fuel power plants, and is produced naturally during the electrical discharges of lightning in thunderstorms.
In mammals including humans, NO is an important cellular signaling molecule involved in many physiological and pathological processes.[4] It is a powerful vasodilator with a short half-life of a few seconds in the blood. Long-known pharmaceuticals such as nitroglycerine and amyl nitrite were discovered, more than a century after their first use in medicine, to be active through the mechanism of being precursors to nitric oxide
The Nitric Oxide Society are full of praise for this wonder molecule, and indeed it plays a vital role in our biochemistry, but like so many things, an excess can be so SO damaging
This was taken from a forum where a poster had recieved an article from dr. michale colgan ( famous nutritionist ) also author of famous book optmium sports nutrition
Nitric oxide is manufactured by an enzyme called nitric oxide synthase, which turns the amino acid L-arginine into citrulline and nitric oxide, both of which serve multiple bodily functions.
Throughout the brain, nitric oxide is an essential chemical messenger, which improves communication between neurons, release of neurotransmitters, and transmission and storage of information.1,2
Nitric oxide is also a free radical, what is called a reactive nitrogen species (RNS), but is relatively benign.1,3 Like many other biochemicals, however, it can multiply out of control. Then it cooks your brain. It happens like this. Various stressors, such as banging your head against a brick wall, cause certain defensive genes to turn on and cause the brain to manufacture pro-inflammatory gremlins called cytokines. These nasty little beggars stimulate the glial cells to produce large amounts of the inducible form of the enzyme nitric oxide synthase. The enzyme then gobbles up all the spare L-arginine and produces a ton of nitric oxide, which overwhelms other control chemicals and causes raging inflammation. Result: damaged brain cells all around.
The Glutamate – Nitric Oxide Link
Fear, anger and air pollution, also damage the mitochondria and reduce the supply of ATP.2,4,5 The protective electric fences around outer cell membranes lose power, and unwanted substances leak into the cell. Particularly opportunistic is the neurotransmitter glutamate, responsible for fast, excitatory neural transmission, just the sort of brain activity that increases in fear and anger situations. Glutamate attacks what is called the n-methyl-d-aspartate (NMDA) receptors on neurons, making a sort of hole through which calcium and other nasties can leak into the cell.2
Fear, anger and air pollution, also damage the mitochondria and reduce the supply of ATP.2,4,5 The protective electric fences around outer cell membranes lose power, and unwanted substances leak into the cell. Particularly opportunistic is the neurotransmitter glutamate, responsible for fast, excitatory neural transmission, just the sort of brain activity that increases in fear and anger situations. Glutamate attacks what is called the n-methyl-d-aspartate (NMDA) receptors on neurons, making a sort of hole through which calcium and other nasties can leak into the cell.2
Calcium is very nasty when it gets into the wrong place, as anyone who has had a heel spur or a calcified artery can attest. In brain cells it converts an enzyme called xanthine dehydrogenase to xanthine oxidase, a process which produces a mass of superoxide free radicals.6,7 Then all hell breaks loose. The excess nitric oxide already being produced by the brain stressor, combines with the superoxide to make the extremely damaging free radical peroxynitrite (0N00-).6,7 Peroxynitrite damages mitochondria, DNA, other proteins in brain cells and any other tissues that get in its way.6,8
Some of these clues come from recent research on the brain damage caused by drugs such as methamphetamine, damage that is very like early Alzheimer’s. In a representative study, Imam and colleagues at the US National Center for Toxicological Research, in Jefferson, Arkansas, showed that peroxynitrite is the major culprit.8 With every step of evidence, science is tying the brain damage caused by a wide variety of stressors to the major forms of dementia.
Links To Alzheimer’s
Links To Alzheimer’s
Cholinergic neurons in the hippocampus of our basal forebrain, express the neurotransmitter acetylcholine. These cells are more primitive in evolution than cholinergic cells in the cerebral cortex. They evolved in the brains of short-lived, ferocious animals, and are designed for shorter, more violent life than those in the cerebral cortex. They have higher levels of nitric oxide, to speed neural transmission for violent action, and lower levels of endogenous antioxidants, because they did not have to last very long. So they are more vulnerable to damage, and are the first to go in neurodegeneration.
It is exactly these hippocampus structures that show the most damage in Alzheimer’s disease, with large numbers of dead and dying cells, amyloid plaque blocking neural transmission, damage to mitochondrial DNA, and useless tangles of neurofibrils.9 In cell culture studies, the amyloid plaque itself causes further release of nitric oxide, thereby creating a vicious and progressive cycle of damage.10 Alzheimer’s patients also have increased brain levels of inflammatory cytokines, which as we saw above, increase production of nitric oxide even further.11
Similar mechanisms have now been found in multiple sclerosis. Inflammatory cytokines stimulate glial cells to produce nitric oxide by way of the enzyme nitric oxide synthase, which then increases peroxynitrite to cause extensive mitochondrial damage.12 Bagastra and colleagues at Thomas Jefferson University, recently found excess levels of nitric oxide synthase in every one of the brains of deceased multiple sclerosis patients, but in none of the control brains of people who had died without brain disease.13 Induced Parkinson’s disease in animals in which the substantia nigra cells are deliberately damaged, shows the same pattern of enzyme activation.14 So does Huntington’s disease.15
Stroke patients also show large increases in inflammatory cytokines and nitric oxide synthase, even up to three months after the stroke.16 Cerebral ischemia (restriction of blood supply) is also related to excessive glutamate stimulation of the NMDA receptor, with elevation of intracellular calcium and induction of nitric oxide synthase, which then raises nitric oxide levels.7
There are now hundreds of similar studies in the medical literature. In a major review of the research in October 2000, renowned expert on brain chemistry, Vittorio Calabrese, of the University of Catana in Italy, shows how this process occurs repeatedly with the stresses of usual urban life. He also reviews numerous other studies, showing that damage caused by excess nitric oxide is crucially involved in Alzheimer’s, Parkinson’s, Lou Gehrig’s disease (amyotrophic lateral sclerosis, ALS) Huntington’s disease and multiple sclerosis.1 Other researchers have shown that the same process of damage is a major determinant of the dementia caused by stroke, and by other forms of oxygen deprivation of the brain, and of various forms of brain seizure.15,16 Finally, the same process is implicated in common forms of epilepsy.17
Overall, the evidence shows that the brain degeneration caused in almost every one of us by excess nitric oxide, is also a major part of all common dementias, stroke and even epilepsy. I have covered only a fraction of these new discoveries in this short chapter, but I hope it is a representative and convincing fraction. If you fail to protect the brain from excess nitric oxide, then all other efforts to maintain your intelligence will come to naught.
This article can be viewed in full at the bottom of this blog (1)
In 2007 the Sahlgrenska Academy completed a dissertation that examined the effects reduced amounts of nitric oxide have on the symptoms of schizophrenia...the results were very interesting...
Research performed for the dissertation found that rats with characteristics of schizophrenia regain normal brain function if they receive drugs that reduce the production of nitric oxide in the brain
what was even more interesting for me was the comments under the article (2)
one reader remarked ''I could have told you this 10 years ago as I have repeatedly told my psychiatrists that my illness was triggered by taking the sports supplement l-arginine which is known to raise nitric oxide levels. An internet or vitamin book search will allways bring up the information that l-arginine should be avoided by people suffering from schizophrenia but doctors and researchers have not cottoned on to this yet.''
and another said ''I also took l - arginine and became psychotic and schizophrenic, the dosage was not high when I took it, but when an episode of major stress happened in my life I took this supplement to ameliorate it but I became psychotic. Unfortunately I was also predisposed to this ilness becouse I have positive family history''
So, why do I think that NO is responsible for our issues? a few reaons, NO we know increases during any brain trauma, well CT from psych drugs or indeed the impact of removing them at all is 100% a trauma to the brain, thus it increases NO...I also believe that any ''setback'' one encounters triggers a release of NO....this build over time to a critical mass causing first the delayed onset of SSRI withdrawal, and then subsequent ''waves'' of severe symptoms.
This study shows the impact of AD removal on NO levels http://www.ncbi.nlm.nih.gov/pubmed/16865538
There are many other known factors that can trigger a wave but I feel they can all come back to NO
1) Stress - we all know the term Oxidative Stress, it can be argued that adrenaline if not used for fight or flight can be turned into NO.
2) Diet, now this is where it gets really interesting....It has been well written about on the beyond meds site that Histamine intolerance seems to be relevant to psyc drug withdrawal, and we speculate that this is because alot of psyc drugs were made from antihistamine and that we are in some kind of rebound state from that....but what if Nitric Oxide is behind it all?
Martin L. Pall, Professor of Biochemistry and Basic Medical Sciences
Washington State University ...wrote an article called
Washington State University ...wrote an article called
A Common Causal (Etiologic) Mechanism for Chronic Fatigue Syndrome, Multiple Chemical Sensitivity, Fibromyalgia and Posttraumatic Stress Disorder
he points the finger at NO being responsible for all of these issues of the CNS (3)
and he says this
- mast cells which release histamine are activated by both nitric oxide and vanilloid stimulation (Chapter 7) and may therefore be part of the cycle mechanism
MAST CELLS ARE ARE ACTIVATED BY NITRIC OXIDE!!!!
it is the NO, causing the histamine intolerance
also Dr M.L Paull states - ''Excitotoxins can stimulate NMDA activity and up-regulate NO/ONOO- cycle biochemistry and should therefore be avoided. Excitoxins include monosodium glutamate, aspartame and possibly certain other flavorings such as hydrolyzed vegetable protein''
and thats another thing we know to avoid in withdrawal, but not because it upregulates NO...who knew?!?!?!
So those are some of the reasons I believe that Nitric Oxide is the ROOT CAUSE of the symptoms and presentation of withdrawal syndrome
So what can we do about it?????
Thats what I will be writing about over the next few days, there are ideas, some we are doing already, but not with NO in mind, and some we can think about
Congratulations on your new blog! This is some very interesting information, well-organized, and presented clearly. May you find success and happiness through your efforts!
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