Introduction
In Parkinson's Disease, the temptation is to oversimplify the very complex biochemistry at play. We imagine that the causal effects are simply due to one of our neurotransmitter chemicals, dopamine, being in short supply.
In reality, the interactions between very many different neurotransmitters is super strong. It is not just the lack of one chemical that causes the problems in many cases, but actually it is the resulting lack of balance with other chemicals.
Also, it is not just the levels of neurotransmitters: the cell receptor population levels for these chemicals have an important role too, as these determine the body and brain’s sensitivity to the chemical, and hence how much is required to cause effects.
It is this balancing act we need to pursue in our medical care, not just trying to flood the system with a single chemical we believe we are in need of.
As such, to empower ourselves, we need to understand many different neurotransmitters, and their roles. For PD, in particular, we need to know about how other chemicals become out of balance with dopamine, and not just simplistically ascribe everything to a lack of dopamine per se.
We have previously considered the role in PD of imbalances/interactions between dopamine and:
In this article, we consider the role of acetylcholine.
Acetylcholine
Acetylcholine was the first neurotransmitter to be identified, originally called “Vagusstoff” (Vagus stuff) because of its association with the activity of the Vagus Nerve, which in itself is very important in PD.
Acetylcholine is the neurotransmitter that motor neurons of the Nervous System release in order to voluntary activate muscles, so has a vital role in movement, and hence in movement disorders. A common misconception is that dopamine is the neurotransmitter required for movement, and hence that without it we can't move our muscles. This is not quite the case: the main muscle movement neurotransmitter is acetylcholine. Dopamine is actually a reward chemical that is implicated in motivation, and is required only to motivate and hence initiate movement.
In the brain, acetylcholine has an important role in arousal, attention, memory and motivation, all of which can be badly affected by PD
Due to its muscle-activating function and role in the brain and autonomic nervous system, a large number of important drugs exert their effects by altering acetylcholine, and many other chemicals including natural venoms and toxins, and chemical weapons, work by inactivating or hyperactivating acetylcholine via their influences on muscles and movement, such as causing paralysis.
Acetylcholine activates or inhibits cellular functions by docking with corresponding cell receptors on the surface of cells. There are two main classes of acetylcholine cell receptor. These are named after “acetylcholine agonist” chemicals which are similar enough to acetylcholine to be able to dock with the corresponding receptor, and activate it: nicotine (found in tobacco and foods) and muscarine (a compound found in the mushroom Amanita muscaria). This is an indication that natural chemicals in diet and supplements could be used to influence the acetylcholine system.
An example of a chronic condition caused by acetylcholine imbalance is Mysathenia Gravis:
“Myasthenia gravis causes the immune system to block or destroy acetylcholine receptors… then, the muscles do not receive the neurotransmitter and cannot function normally… specifically, without acetylcholine, muscles cannot contract.”
The symptoms have a lot of overlap with those of PD:
“Symptoms of myasthenia gravis can range from mild to severe. They may include:
weakness in the arms, legs, hands, fingers, or neck;
drooping of one or both eyelids;
blurred or double vision;
trouble swallowing;
shortness of breath;
difficulty speaking.
acetylcholine and parkinson’s
The fact that imbalances in acetylcholine and dopamine are involved in Parkinson’s is highlighted by a Medical News Today article:
“An imbalance in levels of acetylcholine may have an effect on people with Parkinson’s disease, too. The body needs a balance of acetylcholine and dopamine, another chemical messenger, to control movements well.. many non-motor symptoms of Parkinson’s disease, such as memory problems, are [also] related to reduced levels of acetylcholine.”
“Parkinson’s disease is a condition that [can] cause involuntary movements, tremors, and difficulties with thinking mood… discovered that people with the condition often have a decrease in dopamine that allows acetylcholine to take over. When this occurs, muscles become too ‘excited’, which leads to symptoms such as jerking movements and tremors.”
“For this reason, some medications for Parkinson’s disease block the action of acetylcholine. This allows dopamine levels to rebalance, which can help relieve some symptoms. These medications are called anticholinergics. They can also help ease dyskinesias, which are excessive movements that can be side effects of other Parkinson’s medications. Anticholinergics are not for everyone. Side effects may include confusion, memory loss, hallucinations, and blurry vision.”
In fact, anticholinergics were the first drugs to be used for symptomatic relief of PD. However, according to the Parkinson’s UK website:
“Anticholinergics are not commonly used to treat Parkinson's. They might help with some Parkinson's symptoms but can make others worse. They can be used in younger people with a noticeable tremor. But older people who take anticholinergics are more likely to experience side effects such as confusion and hallucinations.”
Nevertheless, it is interesting that, although acetylcholine supplies or sensitivities may be low in people with PD, lowering it even further may be beneficial, because it is the imbalance with (the even lower amounts) of dopamine that is crucial.
Conversely to this, oversupply of acetylcholine may increase the dyskinesia side effect of long term use of dopamine supplementing PD drugs. I have personally found this to be true, because taking supplements which support acetylcholine, including alpha-GPC and citicoline, causes my dyskinesia to increase to dangerous levels. Likewise, if I do too much Block Therapy in the belly position, or on the side of the neck, both of which activate the Vagus Nerve, and hence release large amounts of acetylcholine, this also causes my dyskinesia to go wild, as does too much of other Vagus Nerve stimulating activities.
On the other hand, naturopathic doctors are finding these supplements beneficial if started early in the PD treatment, i.e. before habitualization to high amounts of the PD dopamine replacing drugs occurs. Indeed, increasing both dopamine and acetylcholine in the right proportions at the start of treatment (a difficult balancing act to get right), can be beneficial, which also then allows one to maintain lower dosages of the dopamine supplementation for longer, delaying dyskinesia in the first place.
Interestingly, several people with PD have found that [acetylcholine mimicking] nicotine gum and patches can have significant beneficial effects on symptom reduction. In some cases, they also report finding this can actually reduce dyskinesia, despite this being cholinergic. It seems that nicotine can activate muscles without having to flood the system with too much acetylcholine and causing dyskinesia. However, some people with PD (including me) are allergic to nicotine, nightshades and other alkaloids.
Botox works by blocking the release of acetylcholine. Botox is sometimes used to treat painful dystonias or hypertonic muscles in PD, by paralysing muscles in a flaccid state.
There is a lot of recent science research looking into the role of acetylcholine in PD, including as a target for therapies. For example, the 2022 article “Cholinergic system changes in Parkinson's disease: emerging therapeutic approaches" in the Lancet:
“In patients with Parkinson's disease… cholinergic system changes can occur in different brain regions.. these changes correlate with a range of clinical features, both motor and non-motor, that are [resistant] to dopaminergic therapy.”
“Postural instability and gait difficulties are associated with cholinergic system changes in thalamic, caudate, limbic, neocortical, and cerebellar nodes… in people with isolated rapid eye movement (REM) sleep behaviour disorders… suggests early compensation during the early stages of Parkinson's disease. Novel pharmacological and neurostimulation approaches could target the cholinergic system to treat motor and non-motor features of Parkinson's disease”.