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Best description I have heard so far https://europepmc.org/article/med/30037616


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Abstract

It is thought that an ill defined biochemical cascade may lead to protracted withdrawal symptoms subsequent to discontinuance of routine use of benzodiazepine class drugs and establish chronic illness in some patients. In this review, published findings are presented that support the novel concept that withdrawal from benzodiazepine class drugs can trigger elevated and sustained levels of a potent oxidant called peroxynitrite via potentiation of the L-type voltage-gated calcium channels, and in the later stages of withdrawal, via excessive N-methyl-D-aspartate receptor activity, as well. Potentiation of L-type voltage-gated calcium channels and excessive N-methyl-D-aspartate receptor activity both result in calcium influx into the cell that triggers nitric oxide synthesis. In pathophysiological conditions, such increased nitric oxide synthesis leads to peroxynitrite formation.

 

The downstream effects of peroxynitrite formation that may occur during withdrawal ultimately lead to further peroxynitrite production in a system of overlapping vicious cycles collectively referred to as the NO/ONOO(−) cycle. Once triggered, the elements of the NO/ONOO(−) cycle perpetuate pathophysiology, perhaps including reduced GABAA receptor functioning, that may explain protracted withdrawal associated symptoms while the vicious cycle nature of the NO/ONOO(−) cycle may explain how withdrawal becomes a chronic state.

 

Suboptimal levels of tetrahydrobiopterin may be one risk factor for the development of the protracted withdrawal syndrome as this will lead to partial nitric oxide uncoupling and resultant peroxynitrite formation. Nitric oxide uncoupling results in superoxide production as calcium-dependent nitric oxide synthases attempt to produce nitric oxide in response to L-type voltage-gated calcium channel-mediated calcium influx that is known to occur during withdrawal. The combination of nitric oxide and superoxide produced, as when partial uncoupling occurs, react together in a very rapid, diffusion limited reaction to form peroxynitrite and thereby trigger the NO/ONOO(−) cycle.

 

The NO/ONOO(−) cycle may explain the nature of the protracted withdrawal syndrome and the related constellation of symptoms that are also common in other illnesses characterized as NO/ONOO(−) disorders such as myalgic encephalomyelitis/chronic fatigue syndrome and fibromyalgia.

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LaCorte S. How chronic administration of benzodiazepines leads to unexplained chronic illnesses: A hypothesis. Med Hypotheses. 2018;118:59‐67. doi:10.1016/j.mehy.2018.06.019

 

The author, S. LaCorte is on the Board of Directors of the Benzodiazepine Information Coalition (BIC). According to BIC’s website, he holds a Juris Doctor (JD) degree (i.e., a degree in law).

 

Here’s some background about Medical Hypothesis - the journal in which this piece was published:

Medical Hypotheses is a forum for ideas in medicine and related biomedical sciences. It will publish interesting and important theoretical papers that foster the diversity and debate upon which the scientific process thrives.

 

Medical Hypotheses was therefore launched, and still exists today, to give novel, radical new ideas and speculations in medicine open-minded consideration, opening the field to radical hypotheses which would be rejected by most conventional journals.

 

Citation:

Medical Hypotheses - Journal - Elsevier

https://www.journals.elsevier.com/medical-hypotheses

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the web address wont work for me but thanks for sharing. my interpretation of what you relayed was that huge changes of the amount in ones system can cause protracted withdrawal symptoms which i generally agree with (but im not a medical professional).
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Well good grief, I didn't even notice the web address in the subject title, it worked for me.  ::)
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  • 1 month later...
Would one of the admins (Pamster?) please post this in the Supplements and Alternative Therapies group?  Maybe some doctor or nutritionist there can recommend supplements that can help overcome this process.
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  • 1 year later...

Anything new to share on this topic?

The theory sounds very sound, and there is a decade old book written on the subject by Martin Pall.

 

What is a practitioner's thoughts on modalities to try to impact this chronic cycle??

 

Also, if this holds true, then supplements to raise NO would make us worse, right?

 

 

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Has anyone tried agmatine sulphate? It is an amino acid with fairly potent positive Nitric Oxide modulation properties.

 

Just responded in another thread on the idea that the NO/ONOO cycle Pall describes is the cause of protracted benzo withdrawal as put forth by LaCorte.

 

I tried daily injections of hydroxocobalamin (a form of B12). 2mg/day up to 10mg/day. I thought it might be working at one point but ultimately could not see any sustained benefit.

 

I also did up to 6,000mg of agmatine sulphate per day. It likewise seemed to be working but then the benefit reversed and I actually had a rebound effect after about 6 weeks where I was worse off than when I started. But, the agmatine really did seem to have a significant benefit for the first month. I'd tried to replicate that at a lower dose that might be more sustainable, but so far that has not worked out.

 

 

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