Everything You Need to Know About Acetylcholine & Adaptogens
6 Minute Read

One neurotransmitter that doesn’t get nearly enough attention for the important roles it plays is acetylcholine. Unless you’re into brain biology or have a relevant condition like epilepsy or bipolar, you might not even have heard of it. But acetylcholine is one of the major biological factors that regulates stress responses and plays into anxiety. And if your levels are off, you’re likely not feeling your best.


So let’s look at acetylcholine’s role in stress and anxiety, why it matters, and how naturally supplementing levels of acetylcholine can improve your stress resilience and mood:


What Does Acetylcholine Do in the Brain?

Acetylcholine (ACh) is a neurotransmitter that plays numerous roles across the body – in the brain, across the central nervous system, and in several vital organs. Two of its most far-reaching functions are:


(1) Motor Function

Acetylcholine can be found in every motor neuron in your body; it’s basically the entire reason your muscles can contract. We’re talking heartbeat, digestion, blinking, movement – pretty much everything about being alive.


(2) Neuromodulation

Acetylcholine is a messenger but also a manager when it comes to neuronal activity in the brain. Ach activity, also called cholinergic activity, plays a role in arousal, learning, memory, attention, and REM sleep. Acetylcholine is the stuff that travels from the parasympathetic nervous system to tell the sympathetic nervous system to chill out and rest up after a stressful event.


ACh & Stress: How it Works

Cholinergic activity is vital to reversing the effects of a flight-flight-or freeze response, of which, unfortunately, many of us are chronically in a low-level state. Norepinephrine is the neurotransmitter that tells the sympathetic nervous system, “IN DANGER” and sets the stress response into motion, charging your adrenals and raising cortisol levels. Acetylcholine is the one that comes in after the danger’s passed. 


Once the parasympathetic nervous system decides everything is back to okay, it sends ACh to tell the sympathetic nervous system, “SAFE NOW”, which promotes biological rest and restoration – cortisol levels lower, your adrenal system slows, blood pressure and heart rate return to normal, and heightened arousal is reversed. 


What Happens When Your ACh System is Out of Whack?

Here’s the thing – when this communication comes out of balance, your stress response is unintelligible. And because we’re all chronically stressed despite not chronically being in danger, our brains get confused and super tired. Cortisol wreaks havoc on the body when levels are raised long-term, so when acetylcholine gets lost or doesn’t have the space/energy to properly communicate, you can bet your mental health isn’t on point. Likely, neither is your sleep. 


Low levels of ACh have been associated with:


  • Alzheimer’s
  • Parkinson’s
  • Bipolar Disorders I & II
  • Major Depressive Disorder
  • Schizophrenia


Something we found particularly interesting in the course of our research, is the prevalence of tobacco use in neuropsychiatric patients. Lifetime smoking rates in people diagnosed with bipolar, schizophrenia/psychotic disorders, and major depression are 83%, 90% and 59% respectively, while the general population rates are 32%. 


At first, this may seem irrelevant to our conversation, until you consider the fact that nicotine acts as an agonist for ACh activity – meaning it increases cholinergic activity. In fact, acetylcholine acts directly on nicotinic receptors. Population studies indicate that smoking may serve as a way to self-medicate. Obviously not the healthiest option, but an instance of utilizing bioactive plant compounds to manage stress responses and mood – which we’ll get to shortly.


But hold up – because life is about moderation; too much acetylcholine, especially in people who have increased sensitivity to cholinergic activity, can also have negative effects on stress and mood via overactivation of the parasympathetic nervous system. Known as cholinergic toxicity, too much acetylcholine can contribute to:


  • Depression
  • Anxiety
  • Sleep disturbances
  • Tremors
  • Dystonia
  • Neurocognitive issues/degeneration


Interestingly, much of the treatment to fight effects of dysregulated ACh work by increasing GABA levels in the basal ganglia. Remember, GABA is the all-important, calm-down neurotransmitter, and one of the key nootropics that can help manage stress response and sleep. You can check out our deep-dive article on GABA for more on that.


Why the goldilocks vibe? It all comes back to acetylcholine’s role in motor function: ACh signaling affects motor function of the emotion/mood/memory centers of the brain like the hippocampal, hypothalamic and limbic systems. This is why, while SSRIs for affect disorders target ACh almost accidentally via regulating serotonin levels, people with mood and psychotic disorders are often treated with seizure medications, because they directly target that motor-based acetylcholine signaling. 


Adaptogens & Acetylcholine Regulation: Biohacking Stress

There is no magic pill for regulating your brain’s acetylcholine activity (a) because no neurotransmitter acts in a vacuum – it needs a balanced support system to work, and (b) because too much acetylcholine may be as bad as too little, especially if the rest of your brain’s communication system is out of whack. 


As we saw, where drugs like SSRIs target ACh levels by isolating serotonin, simply raising those levels may cause other issues like too much REM sleep and decreased slow wave sleep, low mood, or even increase stress responses in some people predisposed to cholinergic sensitivity. Instead, to promote stress resilience physically and mentally, natural remedies like adaptogens can go a long way in helping your body back into homeostasis.


Adaptogens are bioactive plant-based compounds found in nature which support the body’s stress responses, especially the healthy version of the IN DANGER-SAFE NOW cycle, which is integral to managing chronic stress and supporting a balanced mood. Most adaptogens have a wide range of neuromodulating effects, and a few of them help regulate acetylcholine levels. These include:


  • Bacopa monnieri
  • Ginkgo balboa
  • Rhodiola rosea
  • Ashwagandha 


Why Use Ashwagandha for Stress Management

We definitely fan-girl out about ashwagandha at MTE. It is perhaps the most potent and multitalented of the adaptogens, plus, it’s got some of the most compelling clinical data behind it. Not to mention, like 6000+ years of use in traditional medicine across the world. That’s gotta mean something.


One of ashwagandha’s many talents is helping the brain and body adapt to stress. When it comes to the evidence that ashwagandha acts as a neuromodulator for acetylcholine, recent literature has revealed some pretty serious implications:


  • In an 8-week randomized, double-blind, placebo-controlled study, ashwagandha showed greater reductions in several stress markers, including blood pressure, anxiety, pulse rate, c-protein, and morning cortisol in chronically-stressed adults.
  • A 2012 double-blind, randomized, placebo-controlled study in adults with self-reported chronic stress showed ashwagandha supplements lowered cortisol levels.
  • In 2 double-blind, placebo-controlled studies from 2000 and 2013, ashwagandha supplementation led to greater reductions in adults presenting symptoms of anxiety disorder.


These are just a few snippets from a large body of research supporting and co-confirming ashwagandha’s anxiolytic and mood-boosting effects. Related studies indicate that a major mechanism that results in these anti-stress and mood benefits are because ashwagandha inhibits AChe (acetylcholinesterase), which is the complementary compound that breaks down acetylcholine. Basically, ashwagandha lets acetylcholine have more time and space to do the good stuff before letting AChe break it down.


Manage Stress & Mood with the Support of MTE

The wellness and supplement industry isn’t ignorant of the many benefits adaptogens like ashwagandha can offer us in a healthy way that’s already native to our bodies. And we’re no exception. MTE includes several adaptogens that support stress resilience by promoting positives like dopamine and GABA while supporting against negatives like adrenal overactivation and cortisol spikes. 


Using the things nature already figured out for us, MTE uses the power of bioactive plants to give you the tailwind you need to live your fullest, most fun life. Wanna know more? Check out our deep dive articles on adaptogens and ashwagandha.

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