I have suspected glutamate as being one part of the puzzle of this illness.
I discovered the Lamictal/Klonopin combo a decade ago and this combo has nearly eliminated my crashes. If I stop either or both, they come back.
Lamictal reduces glutamate and enhances GABA
Klonopin (through activation of glutamate decarboxylase) breaks down glutamate while also enhancing GABA. Other benzos don't work the same for me.
Tomorrow I will began an experiment with memantine, which is an NMDA antagonist. It will block glutamates activity at the NMDA receptor.
My hope is that memantine can replace Klonopin as I believe it to be a much healthier long term option.
Memantine has been used in Alzheimers patients to slow progression of disease....by blocking the harmful effects of glutamate.
My DNA testing has shown me that I already need to be very careful about glutamate due to some risk factors and is the other part of the reason I want to try memantine.
Heh.
I just found this article from 2013 explaining exactly what I'm thinking more or less. Spooky. I've been taking Lamictal/Klonopin since 2007, well before this was written.
https://www.healthrising.org/blog/2...fs-puzzle-the-neuroinflammatory-series-pt-ii/
Glutamate antagonists
N-acetylcsysteine (NAC) is usually thought of as an antioxidant but it also acts as a glutamate antagonist through facilitating the production of GABA. A number of small clinical trials have shown promising results for NAC administration in another disorder with sensory gating issues, Autism Spectrum Disorder (ASD) (Hardan et al, 2012). NAC is also fairly well established in the treatment of trichotillomania (compulsive hair pulling – a form of obsessive compulsive disorder (OCD).
NAC’s effectiveness in ameliorating a sensory gating deficit may therefore lie in its role as a
glutamate antagonist instead of (or indeed as well as) its antioxidant properties and role as a glutathione precursor.
Oral GABA supplementation has also been shown to have potential to prevent
metabolic syndrome and type II diabetes in a mouse model (Tian et al, 2011). Even more promising, neuronal damage caused by glutamate in ASD may be reversible by attenuating the over proliferation of glutamate receptors in the brain (Baudouin et al, 2012).
Another glutamate inhibitor, low dose naltrexone (LDN) has shown some efficacy with pain and mood in fibromyalgia.
Glutamate and ‘Neuroinflammation’
In fact, research is increasingly suggesting that oxidative stress, mitochondrial dysfunction and glutamate excitotoxicity
are intrinsically linked in a range of neuroinflammatory conditions (Coyle and Puttfarcken, 1993) presenting as various symptom complexes
“Thus, two broad mechanisms–oxidative stress and excessive activation of glutamate receptors–are converging and represent sequential as well as interacting processes that provide a final common pathway for cell vulnerability in the brain.
The broad distribution in brain of the processes regulating oxidative stress and mediating glutamatergic neurotransmission may explain the wide range of disorders in which both have been implicated. Yet differential expression of components of the processes in particular neuronal systems may account for selective neurodegeneration in certain disorders.”
In short, the same pathological process can result in a different constellation of symptoms and therefore result in a range of eventual diagnoses.
Oxidative stress, mitochondrial dysfunction and glutamate excitotoxicitymay also interact as a
‘feed-forward’ vicious cycle (Nguyen et al, 2011) :
“Our results conclusively demonstrate that not only glutamate excitotoxicity and/or oxidative stress alters mitochondrial fission/fusion, but that an imbalance in mitochondrial fission/fusion in turn leads to NMDA receptor upregulation and oxidative stress. Therefore, we propose a new vicious cycle involved in neurodegeneration that includes glutamate excitotoxicity, oxidative stress, and mitochondrial dynamics.”