So in this article, I will be covering what I find to be one of my most successful nootropic stacks as of yet. Before, I made a nootropic stack that was just a hodgepodge of spices. But after passively experimenting with spices and herbs in different situations, I finally found a nootropic stack that is an improvement over the previous one I mentioned.

Transition between Old to New Nootropic Stack

Let me start by explaining changes I’ve made down the line between this new stack and my previous herbal nootropic concoction.

Before, I combined cocoa, coffee, turmeric, black pepper, tulsi, and ginger given that they separately had beneficial effects on the brain, and also acted synergistically to raise monoamine neurotransmitter levels in the brain.

Cocoa Isn’t as Good as Coffee for Enhancing Cognition

So first of all, I decided that I want to cut cocoa out of my current nootropic stack. That’s because cocoa doesn’t give me a significant boost to my cognition- the stimulant effect is mostly felt in the body peripherals and in the heart. Whereas the caffeine & MAO inhibitors[1] in coffee positively affects cognition extremely more so than theobromine. That’s because caffeine has an extra methyl group that allows it to pass the blood brain barrier easily; in comparison, theobromine has one less methyl group and cannot easily pass the blood brain barrier[2].

Moreover, the theobromine does not stick well to the adenosine receptors for the same reason (one less methyl group). In fact, theobromine has 2-3 times worse affinity to A1 and A2A receptors than caffeine does[2].

Excessive Cocoa can be Problematic…

To add to the list of complains, I found that too much cocoa causes pain (strain) in my heart. It makes sense, given that theobromine is a heart stimulant. Another problem is that high cocoa consumption often triggers migraines for me, which I find to be quite anti-nootropic. I attribute this problem to theobromine once again.

Finally, too much theobromine causes negative mood & dysphoria. I experience this in high doses of cocoa, and studies also show that other people do experience this as well[2].

So to re-iterate, I have decided to remove cocoa from my nootropic stack and keep coffee instead, given that coffee is just plain more effective. Although I do have a word of warning, don’t take too much coffee. Not only will it cause you anxiety, but caffeine also metabolizes into theobromine so that you run into the same problem (albeit to a lesser degree) for high caffeine consumption.

I suppose the dose makes the poison, after all.

The Benefits & Problems with Turmeric and Black Pepper as Nootropics

In my previous stack, I used turmeric and Black Pepper. Turmeric worked great to clear my mind, given that turmeric is an anti-inflammatory and blood thinner. Turmeric may also affect cognition by inhibiting the monoamine oxidase (MAO) A & B enzymes[3][4][5]; increasing norepinephrine, serotonin, and dopamine levels in the brain. I suppose a little MAO inhibition can benefit cognition by the increase in brain neurotransmitters, but you’ve got to be careful when taking a MAOI with certain drugs in order to avoid serotonin syndrome.

Now there is a reason why I added black pepper to my previous smart drug stack. Black pepper has a substance called piperine, which is usually taken with curcumin derived from the turmeric root. Piperine in not only an anti-depressant MAO inhibitor[6] like fluoxetine, but also increases the bio-availability of curcumin. Increasing the absorption of curcumin is desirable:

Due to various effects of curcumin, such as decreased Beta-amyloid plaques, delayed degradation of neurons, metal-chelation, anti-inflammatory, antioxidant and decreased microglia formation, the overall memory in patients with AD has improved.[7]

With so many benefits, you’d think I would keep both turmeric and black pepper in my stack. Well the problem for me was that chewing and consuming the raw-fresh rhizome of curcuma longa and black pepper really messed up my stomach. It’s less damaging when consumed with food, but still irritates my digestive system.

I’ve thought about switching from the raw-original sources for turmeric and black pepper with a curcumin-piperine supplement. But there are a few problems here as well; first the supplements are not properly regulated. Either there are heavy metals[8][9][10] like lead to worry about, or toxic solvents[11] that can harm the body. I suppose this simply means you need to carefully research which supplements to take. It looks like NatureWise’s Curcumin supplement is the best one out there.

Furthermore, (excessive) curcumin-piperine supplements inhibits the absorption of certain minerals in the diet, like iron which would lead to anemia. Meaning that curcumin-piperine supplementation may require cycling.

So taking all of this information into account, I suppose I’ll leave raw turmeric & black pepper as additives to cook into curries. It works for the Indians for staving off dementia, so why not?

So What’s My Current Stack?

Finally, you must be wondering what I am using for my current stack, yes? It’s simply a small list of what I’ve found to work without complication, after experimenting with various different substances that I could get my hands on. To list them out, they are:

Coffee as a Cognitive Enhancer

You should already know that coffee is a pretty great cognitive enhancer. Coffee also has neuroprotective[12] effects on the brain in the long run, reducing the risk for contracting Dementia and Alzheimer’s disease by 65 percent[13]. There are even more cognitive benefits that coffee bestows upon its drinker- I’ll go ahead and list them out here[13]:

In mice genetically engineered to be prone to Alzheimer’s Disease (AD), caffeine was found to protect against, and even reverse, memory loss and AD pathology.

Caffeine and/or caffeinated coffee (but not decaffeinated coffee) decreased the levels of amyloid-beta plaques in the brains of mice and humans with AD

The phytochemicals in coffee have a high anti-oxidant activity, which clean up free radicals within the body. Antioxidants are valuable for the elderly, given that age-related cognitive decline happens partially because of the falling capacity to handle oxidative stress and inflammation with age.

Coffee high in a substance called pyroglutamate was found to partially reverse scolopamine induced amnesia in mice, showing that coffee can singificantly enhances a organism’s ability to learn

But the beneficial effects of coffee aren’t due to caffeine alone.

In one study, they showed that 19 month old rats (the human equivalent of senior citizens) showed improvements in psychomotor (voluntary movement) skills and working memory (perceptual & linguistic short-term memory) after being administered coffee for 8 weeks. However, the same cognitive benefits were absent in the rats supplemented with pure caffeine[13].

Another study[14] indicates that there is a synergy between caffeine and other coffee phytochemicals that benefit cognition. Specifically, whole coffee causes a substance called granulocyte-colony stimulating factor (GCSF) to increase in early blood plasma, which isn’t observed with decaffeinated coffee or pure caffeine alone. An increase in GCSF is attributed to coffee’s ability to enhance working memory, and enhancing cognitive performance in AD mice by improving the “recruitment of microglia from bone marrow, synaptogenesis, and neurogenesis”.

In fact, caffeine all by itself can be harmful with studies[15] showing that it shortens the length of DNA telomeres. Whereas coffee lengthens DNA telomeres[15][16], showing that coffee has other substances that benefit the body and/or synergize with caffeine. That the length of a telomere indicates how long our cells live- and longer telomeres indicate cells that age slower. Know that scientists look at telomere length as a biomarker for human aging and that telomere shortening can be accelerated by oxidative stress.

My personal anecdote with pure caffeine tablets is pretty negative. With caffeine tablets, I found that low doses didn’t give me a significant cognitive boost. At a higher dose like 200mg of caffeine, I feel a strong buzz. But in 1 to 2 hours I feel worse than baseline, mentally and physically fatigued and with the cognitive boost mostly gone. Whereas 40mg of caffeine in the form of coffee gives me a substantial cognitive boost, leaving me feeling pretty good & motivated throughout the day. At this low dose of caffeine, I don’t feel a crash.

Some people may think that more is better. But in the case of caffeine, too much can negatively affect cognition (whether it be pure or in coffee form). Specifically, caffeine reduces blood flow to the brain by constricting cerebral blood vessels. Although overtime our bodies can adapt to the vasoconstriction caused by caffeine, thereby returning blood vessels to near-original size, it is only for low to moderate doses of caffeine. High amounts of caffeine end up constricting blood vessels regardless, and therefore reducing blood flow to the brain[17].

Another point I want to talk about from my anecdote is the dynamic effectiveness of caffeine. Obviously 200mg of caffeine is much more than 40mg. But the question is, why would pure caffeine require more supplementation than caffeine in the form of coffee?

The answer may be that coffee is also a mild MAO inhibitor[18]. Not only do MAO inhibitors improve the effectiveness of caffeine, but also cause the level of dopamine, norepinephrine, serotonin, and other monoamine neurotransmitters in the brain to stay elevated in neuronal synapses for longer. This explains coffee’s ability to boost cognition with vaster implications. Boosting dopamine may increase a person’s motivation and willingness to get work done. Increasing norepinephrine also improves motivation, arousal, attention, memory, and executive function. Finally, an increase in serotonin levels improves the function of the hippocampus to form new memories, and may act as an anti-depressant[19].

To summarize caffeine dosing, I advise not to use pure caffeine, but to use coffee in moderation. The best way to drink coffee is in small amounts, throughout the day. Taking a lot of caffeine all at once harms cognition, but distributed in small amount throughout the day is beneficial to cognition.

Ginger to Lift Brain Fog

So I decided to add ginger to my stack as a blood thinner and anti-inflammatory. Mildly thinning the blood improve cerebral blood flow, and lowering inflammation[20] (in the correct way) reduces oxidation stress. Lowering inflammation also allows you to think clearer by reducing brain fog.

I believe that brain fog is cause by inflammation, because inflammation lowers the amount of the serotonin neurotransmitter in the brain. You see, the brain cannot directly take serotonin from outside the blood brain barrier. However, tryptophan can still get past the blood brain barrier. Once tryptophan reaches the brain, it can then be converted to serotonin.

But the problem is that if there is too much inflammation in the body, much of the tryptophan gets destroyed by the immune system, leading to a decline in brain serotonin levels and therefore affecting our cognition. High or sufficient levels of serotonin in the CNS have an anti-depressant effect, increasing neurogenesis in the hippocampus thereby improving memory formation, as well as improving memory consolidation. And vice versa when serotonin levels are too low.

Other than raising serotonin levels in the hippocampus, ginger can enhance learning and memory formation by raising the level of Nerve Growth Factor (NGF) in the hippocampus. An increase in hippocampal NGF is associated with an increase of the phosphorylation/activation of extracellular-signal-regulated kinase (ERK) and cyclic AMP response element-binding protein (CREB). The activation of ERK and CREB causes an increase of cellular development & division, as well as an increase in synapse formation in the hippocampus[21].

Lion’s Mane for Improving memory

One reason why I chose to add Lion’s Mane to my stack is to improve my long-term memory and my short term memory. With a better ability to remember, it helps with almost any task- especially work that requires a lot of analysis (like this article :P). I’ve already extensively talked about how Lions’ Mane benefits the brain in a separate article; specifically by promoting neuronal growth & development as well as decreasing the apoptosis rate of neurons. I also talk about how Lion’s Mane improved the myelination of neurons.

All of these brain enhancing effects already justify adding Lion’s Mane to my stack. But Lion’s Mane has even more beneficial properties as an:

… antibiotic, anticarcinogenic, antidiabetic, antifatigue, antihypertensive, antihyperlipodemic, antisenescence, cardioprotective, hepatoprotective, nephroprotective, and neuroprotective properties and improvement of anxiety, cognitive function, and depression. The described anti-inflammatory, antioxidative, and immunostimulating properties in cells, animals, and humans seem to be responsible for the multiple health-promoting properties[22].

Orange and Elemi as Short-Term Cognitive Boosters

Finally, I frequently use a drop or two of cold-pressed orange oil (Citrus sinensis) and thereafter 1 to 2 drops of elemi (Canarium luzonicum) essential oil rubbed into the palm of my hands whenever I need a quick boost in mental energy and clarity within 5 to 15 minutes. After topical application, I find that I can type faster, think clearer, and feel a boost in motivation, wakefulness, and positive mood. I sometimes even get a slight cold sweat, which is the same thing I feel when playing intense video games. I usually get cold sweats during an adrenaline rush, while I am completely focused on what I am doing.

(Mind you, I would only recommend other people to try aromatherapy with essential oils. If you not careful, you can harm yourself).

From my experience, it seems that Orange Oil and Elemi oil may be more than a placebo. But what does does science have to say about these two essential oils?

How Orange Oil Improves Brain Function

For starters, it looks like orange oil used in aromatherapy has a significant anti-stress property, lowering the body’s cortisol levels[23][24]. I can definitely see how this can be useful; too much (and too little) stress can impair learning. Although Pavlovian conditioning benefits from high stress situations, our spatial or explicit information processing suffers- particularly for chronic stress[25].

Orange oil also contains a substance called “nobiletin“. Nobiletin is a substance that is shown to improve cognitive impairment, reduce beta amyloid levels, and reverse the impairment of short-term memory and recognition memory in mice with Alzheimer’s Disease (AD). Additionally, nobiletin is shown to reduce the levels of Reactive Oxygen Species in the hippocampus of AD mice[26], indication that nobiletin is an anti-oxidant[27][28][29]. Nobiletin is also shown to have anti-cancer properties[30][31][32].

Finally, I would like to mention that nobiletin is also reported to upregulate “the expression of muscarinic acetylcholine receptor subtype M1, choline acetyltransferase, and cAMP response element-binding protein genes in the cells“[33].

Up-regulating a receptor makes the associated binding molecule more effective. That means the up-regulation of the M1 muscarinic acetylcholine receptor results in increased levels of the acetylcholine molecule in the body and brain where the receptor is located- improving those area’s function. In fact, the muscarinic acetylcholine receptor M1 it is common found in exocrine glands and the CNS, being especially abundant in the cerebal cortex and hippocampus. M1 receptors are involved in mediating higher cognitive processes, such as learning and memory[34].

Choline acetyltransferase is an enzyme that speeds up the conversion of choline to acetylcholine via acetylation. Increasing this enzyme also increases the amount of acetylcholine in the body.

How Elemi Oil Improves Brain Function

So I wanted to really expand on how elemi oil can affect cognitive function. But the number of authentic sources, like scientific studies, were very sparse concerning elemi oil. So I decided to start by analyze the components of essential oil. So elemi essential oil is composed of 57.61% Limonene, 11.73% Alpha Phellandrene, 10.24% Elemol, 4.19% Sabinene, 3.81 % Elemicin, 2.15% Alpha Terpineol, 2.05% Beta Phellandrene, and other chemicals in smaller amounts[35].

Limonene (orange oil is also high in this component) shows anti-cancer properties[36], anti-inflammatory and anti-oxidant properties[37], and anti-stress action[38].

Alpha Phellandrene shows to stimulate an immune response[39], but there are studies that show that this substance could be bad for cells[40][41]. The studies aren’t too clear, and they don’t test on healthy cells.

Elemol seems to have insecticidal properties, but there currently aren’t any studies that I could find showing how it could affect brain function.

Sabinene is what gives in part some of the spiciness that you taste in black pepper. Sabinene also may have an anticholineresterase effect[42]. That means it would inhibit the enzyme that helps break down acetylcholine. In other words, sabinene may increase acetylcholine levels in the brain.

Elemicin also has very few studies done on it, and I couldn’t find information on how it affects cognition.

If you have any information on elemi oil and/or its constituents, I’d be happy if you could share it in the comments below. Thanks!

Video Summary of Article

Sources

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