Suppression

Acetylcholine and its ligands

Category: Natural chemicals

Type

Involuntary and voluntary

Introduction and description

Acetylcholine (often abbreviated ACh) is a naturally produced ‘endogenous’ neurotransmitter within our [and many other animals’] bodies. Not only do we have Acetylcholine itself, but there are a number of acetylcholine like drugs [ligands]that mimic the effects of acetlycholine.

Acetylcholinesterase ([AchE) acts like a balancing chemical. It converts acetylcholine into the inactive metabolites choline and acetate. Its role is to clear excess or free acetylcholine from the synapse. Thus an acetylcholinesterase inhibitor acts like acetylcholine by boosting whatever acetycholine exists naturally in the system, for this reason I have treated them together.

Certain neurotoxins work by inhibiting acetylcholinesterase, thus leading to excess acetylcholine.

There are two main classes of acetylcholine receptor (AChR): 

  • nicotinic acetylcholine receptors (nAChR) 
  • and muscarinic acetylcholine receptors (mAChR).

 They are named for the ligands used to activate the receptors – nicotine and muscarine – both agonists.

Effects

So what effects do these two classes of chemical have? Acetycholine is found in both the peripheral nervous system (PNS) and central nervous system (CNS).

In the peripheral nervous system (PNS)

Acetylcholine in simplified terms helps to stimulate the parasympathetic nervous system – it acts as a relaxant. Thus any reasonably moderate sized ‘dose’ of acetylcholine, drugs that mimic acetylcholine or acetylcholinesterase inhibitors will have the following effects peripherally: 

  • Miosis – the pupil of the eye becomes constricted 
  • Saliva – saliva production is stimulated 
  • Perspiration – perspiration production may be stimulated 
  • Lungs and bronchi – these become constricted. 
  • Heart rate – slows 
  • Stomach pancreas and intestines – are stimulated. Overall it promotes weeing and pooing 
  • Penis – is stimulated, men get an erection, but they don’t get ejaculation because it takes an excitatory response to get the ejaculation, this is one reason men can have erections in the mornings after a night’s sleep – because they are very relaxed 
  • Muscles – Generally the muscles tone up. In clinical use, they are administered to reverse the action of muscle relaxants 
  • Bladder – there is the need to wee 
  • Liver – glucose production can be reduced as the ‘flight’ response has been stilled and glucose is not needed 
  • Adrenal gland – again on the whole, adrenaline and noradrenaline production is reduced because the parasympathetic system is being stimulated. This is one reason why the heart slows down

At higher doses or over dose, however, things start to become a bit more dangerous and in these cases we get the following effects

  • Miosis – the pupil of the eye becomes completely constricted and people cannot see as well, everything may look very dark, because of the muscle problems the person may have difficulty focusing and get blurry vision 
  • Blood pressure – there may be low blood pressure from excessive vasodilation 
  • Saliva – saliva production is over-stimulated, there is excessive dribbling and swallowing 
  • Perspiration – perspiration production may be stimulated and people become wet through from sweat and cold 
  • Lungs and bronchi – these become extremely constricted. Most indirect acting ACh receptor agonists work by inhibiting the enzyme acetylcholinesterase. They increase the action of acetylcholine by delaying its degradation; some have been used as nerve agents (Sarin and VX nerve gas) or pesticides. Victims of organophosphate-containing nerve agents, for example, commonly die of suffocation as they cannot relax their diaphragm. 
  • Muscles – Generally the muscles tone up, but after a while, you can get "fasciculation" or "muscle twitch", a small, local, involuntary muscle contraction and relaxation which may be visible under the skin. Another name for this is Myoclonus - a brief, involuntary twitching of a muscle or a group of muscles. As the dose increases you can get muscle paralysis. As Meyler says "these muscular effects can serve as a valuable sign of approaching overdose"! Meyler cites two cases of overdose where the respiratory difficulties produced necessitated mechanical ventilation 
  • Heart rate – slows to dangerous levels at which point you can get bradycardia proceeding to dysrhythmia and even asystole. Note:  An arrhythmia is a disorder of the heart rate (pulse) or heart rhythm, such as beating too fast (tachycardia), too slow (bradycardia), or irregularly. Asystole colloquially known as flatline, is a state of no cardiac electrical activity, hence no contractions of the myocardium and no cardiac output. 
  • Stomach pancreas and intestines – are over stimulated. This is why some medicines based on acetylcholine are used to treat atony of these organs [atony means muscle weakness] they help to stimulate muscles that have lost their strength where people can’t digest their food or go to the loo as easily. But over stimulation can lead to diarrhoea, excessive urination and loss of bladder control and may also lead to vomiting.  
  • Bladder  – there can be loss of bladder control – incontinence 
  • Penis  – is stimulated, men get an erection, and it stays 
  • Liver – glucose production is reduced as the ‘flight’ response has been stilled and glucose is not needed, but it can be so excessive that people can feel quite weary, even overwhelmingly tired as opposed to just relaxed, glucose is not delivered to muscles and the brain. In some drugs, over dosing can lead to liver failure - hepatotoxicity 
  • Adrenal gland  – again on the whole, adrenaline and noradrenaline production is reduced because the parasympathetic system is being stimulated. This is one reason why the heart slows down

In the central nervous system (CNS)

If you read the descriptions in medical text books about acetycholine on the central nervous system, they are hugely convoluted and impenetrable. Chemically, doctors think that the neurons get stimulated and for this reason alone, drugs of this type are administered to treat the symptoms of Alzheimer's disease.

To quote "In the central nervous system, ACh has a variety of effects as a neuromodulator upon plasticity, arousal and reward. ACh has an important role in the enhancement of sensory perceptions when we wake up and in sustaining attention. Damage to the cholinergic (acetylcholine-producing) system in the brain has been shown to be plausibly associated with the memory deficits associated with Alzheimer's disease. ACh has also been shown to promote REM sleep"

But this is over complicated. In layman’s terms, Acetycholine relaxes the Intellect and as a consequence all the systems of the right brain as opposed to the left brain – emotions, the sensory systems, perception and so on can become more active and we are as a consequence more likely to be able to have a spiritual experience. And interestingly enough it is the Nicotinic receptors that seem to be having the most effect in the central nervous system.

Any drugs that are agonists and thus mimicking acetycholine act in a similar way and these include nicotine. 

If we now look at the acetycholine receptors we also find that there are other key agonist functions 

  • The alpha7 subtype in particular seems to be particularly involved in cognitive processes and their ‘improvement’. 
  • The alpha4beta2 subtype seems involved in pain relief, more effective even than opioids – a function which is currently under investigation. There also appears to be a sort of chain effect on dopamine – dopamine is released as a by-product of agonist action. Although the alpha4beta2 subtype of nAChRs, seems to be the primary receptor in pain relief, other receptors alpha3 , alpha4, and alpha7 subunits seem to be also present throughout the pain pathway. 
  • Both the alpha7 and alpha4beta2 receptors are involved in relief from anxiety 
  • The alpha6beta2 subunits regulate nicotine-evoked dopamine release

Acetylcholine as a 'medicine'

Knowing about acetylcholine is important to understanding, but one would never take acetylcholine directly as a medicine. 

If you administered it orally it would be ineffective, as it is hydrolised in the stomach by acid catalysis.  You can't inject it either, as it is hydrolised in the blood both chemically and by enzymes [esterases].

Furthermore there is no selectivity of action which has the potential to be dangerous, as you may need a small boost to heal one area of your body, but that boost might result in an overdose elsewhere.  Good medicine is selective medicine.

Acetylcholine sources

In order to ensure we maintain our acetylcholine balance or boost our supplies in an area in which thesupply has become depleted, then we have two options - food and ligands.

  • Food - Acetylcholine is made from Cholineand the enzyme Acetyl coenzyme A, thus foods containing Choline will help.  The body is also able to use Methionine and convert this to Choline if the choline food supply is a bit low.  

 

How it works

The way it works to give you a spiritual experience depends on the dose.

High dose

If you overdose you could die from suffocation or heart failure and any effects produced spiritually are being caused by near death effects and hypoxia, so the mechanism is different from that produced by a moderate dose.
Over dose and high dose leads to paralysis [contraction] of the muscles needed for breathing, it also stops the beating of the heart. But at a certain point – finely tuned and highly balanced -there may be a point at which the muscles are paralysed, but the heart still beats – very slowly – leading to oxygen deprivation from which we might get a spiritual experience.
Generally speaking, however, this is not a route one would choose for rather obvious reasons, but this is how many spiritual experiences gained through inadvertent ingestion or attack by toxins work.

Moderate dose

Acetlycholine, acetylcholine like drugs and acetylcholinesterase inhibitors work at moderate doses like the mechanism of total relaxation. Ideally you need to fast before hand or at least not have any meals for some time before this mechanism is used [so first thing in the morning is good] and from the list above there is an obvious reason why – our concentration will be disrupted by the constant need to wee and poo.
The overall effects of acetycholene and the drugs that mimic it are then.

  • You will be lying rested and relaxed.
  • Your heart rate will be low
  • You may have an erection
  • Your pupils will be constricted
  • Your lungs will be constricted – smaller
  • You might be salivating a bit - dribbling in other words
  • Your blood vessels will be dilated
  • Your breathing at this stage will be quite shallow 

Already of course you will feel better, you are relaxed and at peace and we have not even got to the spiritual experience.
Relaxation at this level is a very ‘healing’ experience and can help people enormously by toning down the adrenaline, reducing the constant ‘flight’ response that in the end wears people out – particularly their heart and gives them indigestion and bowel problems, constipation and heart burn.
But the total relaxation techniques also have an effect upon the functions of reason and memory. This is not a chemical effect, it is a logical effect. Because we are at peace, the mind becomes stilled. We receive wisdom and inspiration.
But we also get the effects on the central nervous system from the dopamine giving us pain relief, bliss, and relief from anxiety.

Advantages

A benign and at moderate doses a safe way of achieving the more productive forms of spiritual experience.

 

Disadvantages

We have to be very careful , because any class of drug within this category could be addictive. In effect, the drug could be as addictive as tobacco and nicotine

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