The Categories of Nootropics
As you may know, there are several types of nootropics. Not all of these types work in the same way.
It is beneficial to know how each type of nootropic works before building a stack. This will allow for one to experience maximum efficiency in their regimen.
Below we will review some of the most common types of nootropics available today.
CHOLINERGICS
You may hear the term “cholinergic” coined quite frequently on this site and others. This is because cholinergic nootropics are the most common types available today.
Cholinergic typically refers to the neurotransmitter acetylcholine. Acetylcholine is vastly important in muscular movement and cognitive function.
Malfunction of acetylcholine and the cholinergic system has long been related to cognitive and neurological disorders. Acetylcholine dominates the parasympathetic nervous system.
The neurotransmitter controls most of our “automatic” actives as well as muscle movements and heart rate. Acetylcholine and the cholinergic system also have a large influence on cognitive function such as learning and memory.
Types of Cholinergics
Cholinergic refer to a large range of nootropics as this term simply refers to any substance affecting the acetylcholine system. Several types of brain supplements interact with the system in a different manner. Below are the different types of cholinergic.
Positive Allosteric Modulators (Acetylcholine)
Positive allosteric modulators are substances that enhance the signal at a receptor. The racetam group (piracetam, aniracetam, etc..) are positive allosteric modulators of the acetylcholine receptor.
This is a main method of action of most types of racetams. Racetams are not considered their own type of nootropic because they have other methods of action but primarily their effects are believed to be on the cholinergic system.
Acetycholine Precursors
Acetylcholine precursors are also considered to be types of cholinergic. This is because they directly or indirectly increase the amount of acetylcholine in the brain.
Choline is the most common type of choline precursor however there are also other compounds that act as intermediates in the production of acetylcholine (citicoline). Other cholinergic also mimic the effects of acetylcholine. Other supplements indirectly influence the amount of acetylcholine.
ALCAR helps in the synthesis of acetylcholine and centrophenoxine is thought to indirectly influence the amount of acetylcholine. Not all acetylcholine precursors work as nootropics by themselves and are often combined with positive allosteric modulators of the acetylcholine receptors like the racetams.
Acetylcholinesterase Inhibitors
Acetylcholinsterase inhibitors are very common in nootropic formulated blends. This is because they are very potent and require a very small dosage. Acetylcholinesterase inhibitors indirectly influence the amount of acetylcholine by eliminating an enzyme known as acetylcholinesterase. The acetylcholinesterase enzyme breaks down acetylcholine but is necessary in the body.
Without acetylcholinesterase the body couldn’t survive and would go into convulsions. Some acetylcholinesterase is needed in the body to terminate muscle movement however too much can cause negative effects on cognition. This is where reversible acetylcholinesterase Inhibitors come in. Reversible acetylcholinesterase inhibitors can work very well at increasing acetylcholine in the cholinergic system.
Cholinergic drugs
- Alpha GPC
- Centrophenoxine
- Citicoline
- Pyritinol
- Acetyl-L-Carnitine
Side effects
When used properly, cholinergic drugs will increase muscle strength in patients with myasthenia gravis. In eye drop form, they can reduce the intraocular pressure in glaucoma.
The adverse effects of cholinergic stimulants include mostly rash and digestive system complaints, including queasiness, loose stools, nausea, vomiting, abdominal cramps, muscle pain, increased salivation, increase in stomach acid production, and diarrhea. Rare and potentially more serious side effects include reduced heart rate, possibly leading to cardiac arrest, and weak, shallow breathing.
Cholinergic drugs should be avoided when the patient has any sort of obstruction in the urinary or digestive tracts, such aa tumor, or severe inflammation which is causing blockage. They should be used with caution in patients with asthma, epilepsy, slow heartbeat, hyperthyroidism, or gastric ulcers. The effects of the cholinergic drugs are to produce the same effects as stimulation of the parasympathetic nervous system.
These effects include slowing of the heartbeat, increase in normal secretions including the digestive acids of the stomach, saliva and tears. For this reason, patients who already have a problem in one of these areas, such as a slow heartbeat or stomach ulcers, should use these drugs with great caution, since the medication will make their conditions worse.
AMPAKINES
Ampakines unlike the racetams, get their own category. This is because ampakines are known to work on a primary system.
Ampakines do not affect the cholinergic system and instead influence the glutamatergic system. Glutamate is a neurotransmitter also very important in cognitive functioning. The two main types of glutamate receptors are the AMPA and NDMA.
It is thought that ampakines work as positive allosteric modulators at the glutamate receptors. The amplification at the receptors is thought to influence learning and memory. This is the main method of action of this type of nootropic.
Types of Ampakines
- Sunifiram
- Unifiram
- Aniracetam
Side effects/Negatives
One concern with ampakines is excitotoxicity. Excitotoxcity is a concern and is created by excess glutamate stimulation at the receptor which causes a build- up of oxidative stress.
Lots of substances are considered to be excitotoxic including alcohol and amphetamines. It is thought that newer ampakines like sunifiram have very little excitotoxicity however this is a field that needs more study and should be of concern to nootropic users.
DOPAMINERGICS
Dopaminergics are the third type of nootropic substance. A dopaminergic is any drug or supplement that somehow interacts with the dopamine system. Dopamine is another neurotransmitter highly prevalent in cognitive functioning.
It plays a huge role in memory formation, mood and focus/attention. Many dopaminergic drugs and supplements influence cognitive function but not all can be considered nootropic due to their dangerous side effects and safety profiles. Amphetamines for instance (Adderall, Ritalin), are dopamine reuptake inhibitors (DRI’s).
These types of drugs can greatly enhance learning, memory and focus however they are highly addictive and unsafe. Other dopaminergics include MAO b selective inhibitors (Selegiline). These types of dopaminergics are considered safer than DRI’s and can also help contribute to learning and memory. Even MAO b inhibiting drugs have complications and should still not be considered nootropic due to their side effects and safety. There are some dopaminergic nootropics that act as precursors or indirectly influence dopamine and/or the receptors.
Mucuna pruriens, L-tyrosine and phenylalanine all act as precursors to dopamine and can help to increase alertness, memory and mood. There are other nootropics that act partly as dopaminergics by affecting dopamine receptors or indirectly influencing levels in certain parts of the brain (sulbutiamine, citicoline).
Types of Dopaminergics
- Levodopa
- Ropinirole
Side effects
Augmentation is the commonest long-term side effect. Studies show about 7% of patients per year who are on dopamine agonist will develop augmentation. So even if patients have been well treated on a dopamine agonist for 5 years, they can still develop augmentation. If the dose of the drug that you initially started with has more than doubled over the years, you likely have augmentation and will likely require increasing doses.
If your symptoms, when they do break though, are more severe, intense and unbearable now than when you first initiated the medication, then you are probably augmented. If you now have moderate to severe symptoms in the early evening, afternoon or even morning, which was not the case years ago when you first started the medication, than you are probably augmented.
Sleepiness associated with dopamine drugs has several forms. First, patients may complain of becoming severely sleepily soon after taking the medication. Second, some patients may complain of having problems staying awake throughout the day even if they are not taking the drug during the day.
Third, patients may not necessarily feel overly tired during the day, but if they sit or rest at all, they cannot stay awake. Compulsive behaviors can take on any form (e.g., shopping, eating, gambling, sexual activities).
Less obvious forms may involve subtle personal behaviors like thoroughness or tidiness. I had a patient who lost his job because he was so compulsive about doing the job thoroughly that he never got jobs done. Often the patient is not aware of the compulsion, though the spouse or family members are.
If a behavior is out of character and excessive in nature, then think about the drug causing it. Reducing the dose may help, but there is no guarantee that the symptoms will not come back even at the lower dose.
