ADHD Neurotransmitters ? Glutamate Matters

[David Baxter PhD]

Intuniv Answers: ADHD Neurotransmitters ? Glutamate Matters
by Dr Charles Parker, CorePsych Blog
August 29, 2010

Thanks to Intuniv we have a new neurotransmitter to consider ? and it must be considered in the context, as with any other ADHD med, of the Therapeutic Window. Glutamate, as you will soon see in these pages, as well as several others [PEA, Dopamine, Norepinephrine, and indeed Serotonin] can all make a difference as we regularly address the specifics of ADHD neurotransmitter corrections. For this post: specific glutamate considerations.


These are previous CorePsych Blog posts on Intuniv:

• Intuniv Overview
• Intuniv Dosing Details
• Drug Interactions With Intuniv
• Intuniv and Addiction Indications
• Metabolic Challenges Using Intuniv
• Intuniv Details Beyond ADHD Indications

Details About Glutamate
Amy Arnsten, PhD at Yale: See this summary page for details of this interesting ADHD science. This paragraph is from that page:

Goldman-Rakic used a spatialworking memory paradigm to uncover the neural basis of working memory abilities, and found that representational knowledge is encoded by networks of prefrontal cortical (PFC) pyramidal cells with shared stimulus properties, engaged in recurrent excitation. [ed note: good working memory diminishes the possibility of ADHD.]

These recurrent excitatory connections depend on glutamate actions at NMDA receptors. Spatial tuning is heightened through GABAergic, inhibitory connections between networks with dissimilar spatial properties (e.g. Rao et al, J. Neurosci 20: 485, 2000). The working memory abilities of the PFC are also highly dependent on the neuromodulatory environment, whereby loss of catecholamines in PFC is as detrimental as destruction of the PFC itself (Brozoski et al, Science 205: 929 1979).
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Another reference:

Russell VA, Wiggins TM, Increased Glutamate-Stimulated Norepinephrine Release from Prefrontal Cortex Slices of Spontaneously Hypertensive Rats Metabolic Brain Disease 25: 297, 2010
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Bottom line in the office:

1. Excess glutamate alone presents as ADHD with hyperactive and significant ODD symptoms.
2. Diminished glutamate often presents as inattentive, and may be associated with ODD symptoms, but less overt anger.
3. Excess glutamate with both excess dopamine and norepinephrine appears as untreatable with any ADHD meds, even though symptomatically presenting as ADHD. The characteristic refractory, paradoxical response to stimulant meds, and to Intuniv often leads to the diagnosis of bipolar ? but the dysregulation is in the neurotransmitters, not the appearances.
4. Number 3 is always associated with other biomedical issues including food sensitivities measured, e.g., by IgG ? such as gluten sensitivity.
5. Measure when in question. Why spend more time guessing?

Still don?t get the relevance? Take a look at this video on Dopamine and Glutamate-
Remember, this video is a patent oversimplification ? dopamine does modulate glutamate, as does norepinephrine, but the interplay with many other neurotransmitters is not addressed in this short clip.