Glutamate: Why it might matter for our mental health

ByMarch 21, 2018Uncategorized

The human brain is the most complicated object in the known universe. The exact number is up for debate, but scientists believe there are something like 86 billion neurons in each of our brains. And those neurons aren’t lonely, either: each one connects to approximately ten thousand other neurons.

Unlike us, our neurons don’t network with handshakes and business cards. They use chemicals called neurotransmitters to communicate with other neurons, muscle cells, and gland cells. This process is important in just about everything we do, and although there’s still a lot that nobody knows about neurotransmitters, it seems like a safe bet that having them function properly is important.

Depending how you count, we have approximately 100 neurotransmitters. But, sort of like the elements that make up the universe, a couple of these neurotransmitters are much more abundant than others. Unless you’re a neuroscientist, most of the peptide neurotransmitters probably won’t ring a bell. But some of the small-molecule neurotransmitters might be familiar:

dopamine
norepinephrine
epinephrine (adrenaline)
serotonin
GABA
glutamate

These are the ones that people talk about, and sometimes misuse in overconfident assessments of various phenomena. It felt good when I looked at my cell phone? Must have been a spike in my dopamine levels. I’m feeling a bit sad lately? I really must be lacking in serotonin.

Although our society continues to race ahead of our scientists, using neurotransmitters as explanations without any deeper understanding of them, there can also be bits of truth in these explanations. For example, many researchers and clinicians still believe that serotonin has something to do with depressive episodes, even though pretty much everyone has agreed that a simple lack of serotonin isn’t their cause. And dopamine is probably related to reward and pleasure, even though this mechanism isn’t as simple as it was originally made out to be.


So what about the other neurotransmitters on that short list above? At the bottom are GABA and glutamate, respectively the main inhibitory and excitatory neurotransmitters in our brain. You can find some good explanations of the excitatory vs. inhibitory thing online, but for now it’s good enough to know that an excitatory neurotransmitter makes it more likely that the receiving neuron will fire; an inhibitory one does the opposite.

via GIPHY

For a number of years, it’s been hypothesized that the interplay between GABA and glutamate has had something to do with anxiety and mood. GABA has gotten a good amount of attention as far as potential treatments are concerned, most notably with benzodiazepines like Klonopin and Valium, which offer short-term relief of anxiety by enhancing the effect of GABA at a receptor.

But the role of glutamate has been recognized more slowly, and only recently has this rather abundant neurotransmitter taken on a central role in research. For anxiety more generally, and OCD in particular, there’s strong preliminary evidence that dysregulation of glutamate could play an important role in creating some of those unpleasant symptoms.

This, of course, leads researchers to believe that treatments which get glutamate activity back to normal might help people feel better. That’s why many of the investigational drugs being studied right now do exactly that. For example, there’s exciting new research on a compound called BHV-4157, a tripeptide prodrug of the glutamate modulating agent riluzole. A tripeptide is just three amino acids linked together. And a prodrug is basically a precursor to a drug that needs to be metabolized into an active drug.

BHV-4157 is being developed for the potential treatment of OCD as adjunctive therapy to standard of care treatments in those who have experienced an inadequate response to standard pharmacotherapy. In other words, these researchers are hoping it might help people who are already trying the widely accepted treatment options for OCD (like Prozac or Anafranil) but aren’t getting the desired results from them.

via GIPHY

Although riluzole was originally used to treat ALS, it had promising results for augmentation of OCD treatment in a study at Yale University. Now more research is needed on compounds like BHV-4157 to see if they bear out the hypothesis that dysregulation of this excitatory neurotransmitter could be a contributing factor in OCD.

We’ll be following closely for more results from studies of glutamate modulators, hoping along with everyone in our community that promising new treatment options might be on the way sometime soon. There are few things more exciting (but not necessarily excitatory) than new research on mental health, so please feel free to let us know what you’ve been hearing about lately.


If you have OCD, you might be eligible to participate in a study involving an investigational medication that would be added on to your current treatment. To learn more, click here.

Patrick Carey

Author Patrick Carey

Patrick writes for our blog, app, and website. On weekends he drinks a ton of coffee and wishes he had his own dog.

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