Primer to Mental Supplements – Nootropic vs Cholinergic vs Racetams

Editors Note: This evidence-based exploration of mental supplements was set forth by Sol Orwell and Kurtis Frank. You can usually find them collating scientific research on supplements and nutrition over at Examine.com

Types of Mental Supplements

Nootropic – An umbrella term of importance 

The term Nootropic is used to refer to drugs/supplements/foods that have cognitive enhancing properties. It is derived from Noo- (the mind) and -tropic (towards), and is an umbrella phrase for any substance that could benefit your mind.

The researcher who originally coined the term nootropic (Corneliu Giurgea, inventor of Piracetam), proposed that anything considered a nootropic must be very safe and have no possibility of harming the body.

This idea is a problematic ideal – it’s hard to provide proof that a substance has absolutely no harmful effects on your body. Even his own piracetam would not fit that fill; a study showed it to be thin blood as effectively as Aspirin, and would cause problems if taken with prescription blood thinner. So we will talk about safety, but don’t dive in head first.

The word nootropic is so broad and vast that we need to categorize them further. Nootropics can work in different ways, and the following categorizes how they work (they all work to benefit your memory and/or cognition).

• Neurotransmitter Modulator: molecules which alter the concentrations of neurotransmitters in the body. These are either substrates for the neurotransmitters (L-Tyrosine and 5-HTP), enzyme inducers or inhibitors that modify neurotransmitter levels (MAOIs or Huperzine-A) and reuptake inhibitors that allow more neurotransmitters to stay in the synapse (SSRIs).

• Neurotransmitter Mimetics: molecules which act on receptors themselves, rather than needing to modify levels of neurotransmitters. This includes compounds like nicotine or ephedrine, which directly activate receptors.

• Transmission Modulators: These are things that, regardless of what happens at the synapse, alter the cellular effects and action potential of neuron. These either act at the receptor level (such as Honokiol or Aniracetam positively influencing GABA or AMPA receptors without directly acting on them) or on the axon (Levetiraetam and calcium channels)

• Structural Modification: These are compounds that modify the structure of the neuron. Regardless of what the action potential decides to do or the synapse contains, these merely make the neuron itself more structurally robust. At the least, they repair the structure of a poor neuron. Piracetam, Bacopa Monnieri, and Phosphatidylserine all fall in this category

• Therapeutic Compounds: These are characterized by having cognitive enhancing properties in persons with impaired cognition, but do not act in a unilateral manner. Instead, they only really benefit those with impaired cognition; the magnitude of benefit is lessened when used in an otherwise healthy person

These categories are not exclusive by any means. For example, yohimbine is an antagonist of alpha-adrenergic receptors (second bullet) and secondary to this it inhibits noradrenaline reuptake (first bullet). Piracetam is highly therapeutic (fifth bullet) possibly working via structural means (fourth bullet) although there is some evidence for it acting on calcium channels weakly (third bullet).

That being said, finding a nootropic compound that doesn’t fall into one of the above 5 categories is near impossible. This at least gives us a footing to begin wading through the vast world of nootropic compounds

Cholinergerics – An important class of molecules 

Cholinergic compounds are those that interact with acetylcholine or its receptors, and thus induce acetylcholine-like effects (cholinergic-like effects). Acetylcholine is a neurotransmitter highly involved in learning and memory formation, and tends to be one of the main focuses of many nootropic supplement regimens.

Cholinergic compounds can either be those that increase acetylcholine levels by supplying the substrate (choline or Alpha-GPC supplementation) or inhibiting its degradation (acetylcholinesterase inhibitors; Galantamine is the reference drug here, and Huperzine-A is also commonly touted).

Direct agonists of acetylcholine receptors exist, with the most commonly used direct agonist in usage (by lay persons) currently being nicotine.

Overall, the goal of any cholinergic is to induce more acetylcholine signalling to target neurons in the hope that it increases learning and memory formation.

Racetams – A heterogenous and popular category 

The term Racetam was born alongside the molecule piracetam, and refers to the common 2-pyrollidone structure in these molecules (If we look at the structures of levetiracetam, aniracetam, piracetam, nefiracetam, etc. we will always find a pentacyclic ring with a nitrogen in it and a double bonded oxygen one carbon away from it. This is the 2-pyrollidone group).

Racetams are actually categorized based on their physical structure, not what they do inside your body. It just so happens that when a molecule has this functional group, it tends to be highly  neuroactive.

For example, although piracetam has a variety of activities, the one that is pertinent here is rheological; binding to a cell membrane and improving fluidity (the fourth bullet).

Aniracetam is an AMPAkine, binding the the glutamate receptor subset known as AMPA and facilitating signalling through this receptor. Nefiracetam has been implicated in acting on another glutamate receptor, NMDA (which Aniracetam doesn’t do anything to).

Levetiracetam was synthesized off of Piracetam to enhance the inhibition of Calcium V2.2 channels (third bullet of altering signalling) and as such has a better role in epilepsy management.

So why are racetams popular? Racetams are akin to designer drugs for your mind, and it attracts a lot of people interested in neural benefits that do not care for “natural therapies.”

Although all known racetams are synthetic, there are some compounds borne from traditional medicines with similar (although not exact) structure to the pyrrolidone group on racetams; morus alba (white mulberries) and loganolactone (longan fruits) have a racetam-like structure that might be worth investigating.

So what can you eat? 

In Part 2 we will go over the various popular nootropics, including cholinergics and racetams. In the meantime, eggs are a great source of choline (a cholinergic), and small fatty fish (sardines, mackeral, herring) are good sources of both fish oil as well as phosphatidylserine (two structural modifying nootropics). Additionally, as mentioned earlier, longan fruits and white mulberries could have possible cognitive enhancing properties. It might be prudent to start to train your taste buds to enjoy tea, as tea can also be phrased as ‘water soluble extraction’ and opens up an entire world of plants to sneak into your diet.

So there you have it – a quick primer. Nootropics are supposed to enhance brain function, and they do so in roughly five primary ways. Cholinergics specifically target acetylcholine in order to help with memory function, and racetams are designed-drugs that can function in a variety of ways.