The brain needs acetylcholine to form memories. The nerve bundles of our “rest-and-digest” system require it to balance “fight-or-flight” activity. But can too much acetylcholine be bad? Check out this post to learn when an excess of this neurotransmitter might be unwanted and whether lowering its levels or activity can be beneficial. Can You Have Too Much Acetylcholine ?
Due to its wide range of roles throughout the body and brain, high acetylcholine levels or activity in certain brain areas have been implicated in the development, progression, or symptoms of a some health conditions listed in this article.
However, most of the studies we bring up dealt with associations only, which means that a cause-and-effect relationship hasn’t been established.
For example, just because depression has been linked with higher acetylcholine activity in certain brain areas doesn’t mean that depression is caused by too much acetylcholine. Data are lacking to make such claims.
Also, even if a study did find that too much acetylcholine contributes to depression, acetylcholine levels are highly unlikely to be the only cause. Complex disorders like depression always involve multiple possible factors – including brain chemistry, environment, health status, and genetics – that may vary from one person to another.
Assessing acetylcholine levels in the brain is extremely difficult. This is mostly because acetylcholine levels can’t be directly measured. A direct measurement would require brain tissue, blood from the brain’s circulation, or cerebrospinal fluid.
Even with indirect measurements (using state-of-the-art brain imaging techniques), acetylcholine levels may vary across brain areas and quickly change depending on many factors.
Therefore, whether or not a person can have “too much acetylcholine” is highly uncertain. However, science has suggested a link between certain health conditions and higher acetylcholine levels or activity in specific brain areas. Is Too Much Acetylcholine Bad?
There are no symptoms associated with high acetylcholine levels per se. Instead, people may only show symptoms of mental health, neurocognitive, or immune disorders. Your doctor will discuss your symptoms with you and run tests to pinpoint the underlying cause.
Low or high acetylcholine levels don’t necessarily indicate a problem if there are no symptoms or if your doctor tells you not to worry about it. Associated Conditions:
Although serotonin is the neurotransmitter most commonly associated with depression and other mood disorders , other major neurotransmitters — including acetylcholine — may also play important roles in these psychiatric conditions.
Although the exact role of acetylcholine in depression is not yet fully-understood, a handful of preliminary animal studies have reported that drugs which block nicotinic acetylcholine receptors (nAChRs) — such as mecamylamine — appear to have “antidepressant-like” effects in rodents [ 1 , 2 ].
Building on this, according to two early phase-II clinical trials in humans with treatment-resistant depression (TRD), mecamylamine was reported to alleviate some depression symptoms when used in combination with more traditional antidepressants (such as selective serotonin reuptake inhibitors , or SSRIs) [ 3 ].
Nonetheless, while acetylcholine may play some role in depression, it is likely to be only one piece of a much larger and more complex puzzle. In the meantime, most scientific research on the development and treatment of depression will likely continue to focus primarily on the role of other neurotransmitters, such as serotonin, which have relatively much more research behind their role in depression and mood disorders. Smoking And Depression
Interestingly, some of the preliminary findings described above may account for some of the widespread associations that many studies have reported between smoking and depression [ 4 , 5 , 6 ].
Specifically, some researchers have proposed that short-term ( acute ) nicotine exposure can result in a reduction (“ down-regulation ”) of acetylcholine receptors [ 7 ]. This may initially produce an “antidepressant” or “anti-anxiety” effect in relatively new smokers, which could in turn contribute to the development of an addiction to (or dependence on) nicotine.
However, chronic exposure to nicotine may eventually cause nicotinic acetylcholine receptors to actually increase in number, which would reverse these initial effects. Therefore, smoking may actually lead to increased negative moods and anxiety in the long term [ 8 , 9 ].
These adverse long-term effects, then, could potentially explain why rates of depression and other mood disorders tend to be higher in people who smoke [ 4 ]. 2) Hives
Scientists think that high acetylcholine may contribute to hives, as immune cells produce histamine in response to it [ 10 , 11 ].
According to one unverified hypothesis, people with hives seem to have higher acetylcholine in the skin, but their cells are less sensitive to it. This causes issues with sweating and histamine release. Drugs that block acetylcholine are being investigated for preventing outbreaks, but their effectiveness is still uncertain [ 10 , 11 ]. 3) Sleep Cycle Alterations
Acetylcholine increases during the dreaming, REM phase of sleep . Limited data suggest that choline supplements may even induce lucid dreaming by boosting acetylcholine in the brain. Acetylcholine levels are low during restorative, slow-wave sleep, during which memory is consolidated [ 12 , 13 ]. Factors That May Decrease Acetylcholine Levels
Because low acetylcholine is believed to be involved in the development of some diseases, there are many potential uses that have been proposed for substances that can block the acetylcholine system.
Many compounds and drugs may decrease acetylcholine levels or reduce its activity.
In general, drugs or other compounds that reduce acetylcholine levels — or otherwise inhibit its activity — are commonly known as “ anticholinergics .” ( To learn more about these substances and how they work, we recommend checking out our detailed SelfDecode posts on anticholinergics, which you can find here and here . )
Once again, these drugs may exert this effect by targeting one or more of the multiple different potential mechanisms and pathways related to the creation or release of acetylcholine.Some of the supplements, dietary compounds, and drugs that have been proposed to have some potential anticholinergic effects and mechanisms include: If you believe you have a health condition or other reason to try to influence […]