About a year ago, I fought for control of my life. Not over a threat to my flesh and bone, but a threat to my relationships and perceived needs. I was consumed by fear and blind to what was in front of me, gazing instead at an unchangeable history of anger. The pain of lonliness pushed me to reflect on my past, understand my decisions and change the way I process emotions. If I was going to live a life of meaningful relationships and endless learning, I had to get rid of the fear.

The central amygdala, part of the temporal lobe, master of fight or flight, surfaced as public enemy number one in my battle to eliminate stress[1]. Running away from my past and fighting possibility felt no different than running away from a rabid dog or fighting someone that bullied me. Rationalizing that one is a threat to my life and the other is a faulty perception of reality did not comfort me so I constantly felt fear which, over time, develops into stress.

In software development terms, I wanted to deprecate the central amygdala to disconnect the power of fear and hopefully eliminate stress.

I hypothesized that chemical alterations would recalibrate my brain so that, over time, my mind would advance an optimal state of consciousness free of stress. Like muscles in the body, each functional area of the brain can be challenged or suppressed to strengthen or weaken its influence on how we think. Why is chemistry limited to solving problems like depression, insomnia and anxiety? Shifting perspective away from the determined to the potential, there is an opportunity to balance compassion and order through scientific rigor for the founding design principles of effective cognitive tools that advance the human potential.

Targeting the amygdala as the root cause of stress and by making commonly found chemical influences effective in vivo, I controlled my central amygdala and suppressed my fight or flight instinct with a drink that I call “Plusfour”.

Formulation

To ensure my safety and wellbeing, I created the following requirements for the ingredients of Plusfour:

Legal for consumption and distribution in all 50 US states Readily available toxicology information Separability of effective compounds into isolates for evaluation

Research led me to evaluate the following ingredients further:

Vague and stringent rules governing the use of Kratom prevent me from exploring its effects based on my personal principles. People report a wide range of experiences with Kratom because the plant and it’s various species contain hundreds of different alkaloids that contribute various pharmacokinetic effects. It seems that the plant is totally safe to consume but I could not find a single vendor who would tell me what was actually in Kratom, so forget about even testing the isolated compounds.

Most dietary supplements fail to meet their statement of identification claims, particularly in the essential oil space. Fortunately, there are labs that use an HPLC to verify the potency of individual compounds. For about $75, I was able to ensure that what I was putting into my body was what I wanted to be putting into my body.

A lot of nootropics and essential oils in raw form are ineffective in vivo. It took $15 worth of hemp oil to get remotely close to a desired effect, and caused a slight discomfort in my stomach and chest. I consumed 5g of GABA and though I certainly felt slightly intoxicated, I also had a growing pain in my stomach and digestive track that didn’t go away until I woke the next day. I’m fairly certain that the effects I experienced were more like a poison than a therapy, acting like alcohol instead of an intelligently designed tool. Attention turned to making the compounds more bioavailable.

Enhancement

The human body has an immune system that is built to fight foreign objects. Drinking works so well because we overpower the livers defenses by flooding 14g of alcohol for every wine or beer. You get a hangover because CYP450’s metabolize alcohol into a carcinogen called acetaldehyde that alters the ph of the blood and the ability to carry oxygen throughout the body. Essential oils and isolated neurotransmitters are consumed at quantities 3–4 orders of magnitude less than beer and wine. Unlike ethanol, they are hydrophobic and extremely wide relative to the gap in the blood brain barrier. Stomach acid and enzymatic soldiers of the liver eradicate my hopeful offensive against stress on the shores of digestion.

The effectiveness of coffee gave me a clue on how to make Plusfour work. The neuro-pharmacokinetic compound in coffee is a xanthine alkaloid affectionately known as caffeine. Caffeine passes through digestion and the liver quickly, causing noticeable, mostly harmless, cognitive effects in 10 minutes with as little as 50mg. The insights from the pharmacokinetic effects caused by the chemical structure of caffeine led me to experiment with different methods that combined to make Plusfour 800% more bioavailable.

To make Plusfour a reality, I collected extracted hemp oil, terpenes, vitamins, minerals and nootropics in my at home temple devoted to the study of chemistry. The first step was to make the hydrophobic compounds evenly dispersed in water. I observed that the essential oils floated on top, while the nootropics dispersed unevenly in water. The Coca-cola Co. emulsified flavonoids extracted from essential oils over 100 years ago and used root powder to uniformly distribute the dozens of flavors into a coca and sugarcane concentrate. Formulating a similar gum arabic solution, I was able to make the ingredients of Plusfour disperse evenly in water. Even so, drinking Plusfour did not cause an effect that I could distinguish from placebo.

The ingredients of Plusfour were moving through the stomach faster but the sub gram quantity was easily broken down in digestion. Encasing the compounds into a phospho-lipid bilayer seemed to be a promising way to protect the ingredients from processing. I bought an ultrasound, designed to clean jewelry, to sonicate the compounds into a long chain lipid. A method widely used by hobby chemists everywhere to improve the effectiveness of Vitamin C turned Plusfour into a much more effective solution. At this point, I didn’t need a prohibitively costly amount of Plusfour to feel calm. However, it still took 30–45 minutes to remove my stress. I found that the risk of ingesting too much of a compound increases on a log scale for every 10 minutes it takes for the effects to kick in.

Encapsulated and emulsified Plusfour compounds needed to be shrunk from a micrometer to a nanometer level to effectively slip through digestion and cross the blood brain barrier. Compressing a compound carrier down to the nanoscale is very difficult. Unfortunately, Amazon doesn’t sell an at home nano-encapsulator. Thanks to Bezos, Gates and Allen — my adopted hometown Seattle is full of people who know a lot about cancer research. I had a chance encounter with a young scientist working to cure cancer who told me, hesitantly, about the process they used to make their therapeutic effective. She stopped short of telling me the chemical structures, but the solution to my problem became clear. To get Plusfour to cross the blood brain barrier and effectively agonize neurons, I outsourced the processing of its core ingredients to a cancer researcher.

Think about a chemical molecule as a too-small-to-see with the naked eye sphere and think about a liquid as enough of these spheres holding hands close together to be seen by our eyes. The purpose of nano-encapsulation is to increase the distinct population of molecule containing carriers in the same space by decreasing the diameter of the carriers. Packing more carriers into the same space increases the surface area potential so that a drop of liquid that normally can’t stretch itself past the area of a dime is able to become a drop of liquid that can stretch over multiple football fields. Expanding the drop of liquid in the body to cover more surface area makes the molecules smear over most of the intestinal tissue where it can be pulled into the blood stream faster. In telecommunication terms, the effect would be equivalent to decreasing the bit error rate thereby allowing the body to read more information from a chemical formulation.

A high quality nano-encapsulation has more spheres that look alike in the nanometer scale. Nano-formulators measure success with a tool that shoots light across the liquid where the spheres, being rough and clear, reflect and bend the light to change the visible color of the light. The tool produces a graph that shows the quality of nano-encapsulation by what is called the Kurtosis. The goal is to see a Kurtosis chart that shows a tree in the nanometer scale, not a bunch of rolling hills in the micrometer scale. Looking at the graph and seeing a tree means that the spheres in the liquid are about the same size and have a greater potential to expand over a greater surface area.

Here is an example of what a good Kurtosis, good nano-encapsulation looks like:

Here is an example of what a bad Kurtosis, bad nano-encapsulation looks like:

On a particularly sunny Seattle afternoon in January, a package arrived at my door that carried an unmarked vial containing 5 ml of a white, slightly bitter aqueous solution. I dropped the dram of Plusfour into 8 ounces of carbonated rose water and took a drink.

Within ten minutes, my pulse slowed and my muscles relaxed with a feeling of warmth around my shoulders. I felt my soul cool as the troubles of the past and unknowns about the future grew distant. As I drank more, the euphoria and sedation increased ever so slightly. After 4 or 5 drinks, I experienced the point of diminishing returns and my state of relaxation did not intensify into impaired judgement or motor function. The effects extended in time but not in intensity. I felt euphoric, not from intoxication, but from serenity.

Adjusting the ratio of materials in Plusfour allowed me to balance the effects based on my various goals in learning, socializing and relaxing. Ingesting too much GABA made Plusfour more like a sedative. Too little, and I wouldn’t feel calm. The hemp oil suppressed the fear so that I didn’t feel stress, but to feel socially confident or more curious I needed to adjust the dopamine agonization in the prefrontal cortex and GABA agonization globally.

When I wanted to read, I increased dopamine and decreased GABA by increasing caffeine and lowering l-theanine and phenyl-GABA. When I wanted to work, I increase caffeine and l-theanine while lowering phenyl-GABA. When I wanted to open my ideas to criticism, I increased caffeine and increased hemp oil. When I wanted a dreamless sleep, I increased phenyl-GABA. When I wanted to experience vivd dreams, I lowered the hemp oil and the caffeine and added acetylcholine. In all of these various forms I did not experience any anxious thoughts or physical strain because Plusfour controled the source of stress by suppressing the amygdala.

Certain vitamins and minerals in Plusfour function to prevent any tolerance. Humans are efficient at turning raw nutrients into the right chemicals for our mind and body. But if it can’t get the right nutrients, the brain will run on fumes and cause discomfort and pain. Tolerance is a result of the brain adjusting to scarcity. By supplying the proper building blocks and nutrition for my body to replenish the reservoir of biochemicals, tolerance is effectively prevented. After 2 months of consuming Plusfour on a regular basis, each new drink is the same as the first.

Continuation

Self-help books and spiritual guides espouse the virtues of the sober minds ability to control itself. Dissatisfaction with perplexing meditations that failed to remove my apathy in the presence of “beautiful” and “amazing” pleasures, pushed me to look for a more effective remedy. I found that most drugs sledge hammer the mind into total numbness. They only mask pain and force dependence so that the mind doesn’t get better, it gets worse! People are wallowing in addiction, dying from overdose and costing society billions from the shortsighted attempts of the few to impose injustice on the many.

Mammals developed a taste for alcohol because it is an efficient energy source readily available in the jungle. Metabolization of 1 gram of carbohydrates or proteins renders 4 kcals, lipids 9kcals and alcohol 7kcals. Affinity for chemicals of rotting fruits became a significant source of fuel to survive but it was the euphoric feelings gained from indulgence that inspired human invention of agriculture. Unfortunately, alcohol replaces GABA activity in the amygdala and forces a chemical dependence. It takes 2 weeks for the dependence to completely wear off and the mind to be able to suppress fear without alcohol. I decided that I cannot consciously consume alcohol knowing what I know now.

Over 54 days in January and February, I tested the safety of Plusfour by consuming it regularly. The long term sustainability is important as I do not want to consume something that is more harmful than alcohol and prescription drugs. In a month where I set out to test the safety of my relief from feeling stressed, I found that the absence of stress eliminated my stress.

In my next post, I’ll share the results of my experiment.

Edit 3–16–17: The explanation regarding the purpose of nano-encapsulation incorrectly stated that the molecule was being shrunk when in fact it is the carriers of the molecules that are being shrunk. The paper has been updated with the proper explanation