Whole Genome Sequencing feels like quite an obvious step for me given what I have already done. it fits the My Eternal Golden Braid path well, another strand in the braid where Neuropharmacology, Quantified Self, Computational Neuroscience, and Self Configuration fold back into each other.
Beyond extended Health/Longevity data, there are some uses for experiment loops involving Neuropharmacology.
- current neuropharmacology project is mostly inference from mechanisms, subjective logs, and sparse biomarkers.
- this would give us priors: how my body clears compounds, how receptors might differ from the population default, and what baseline neurochemical tendencies I may have been modulating without knowing it.
Reminiscent of Gödel, Escher, Bach self-reference. system is reading a low level description of itself, then using it to modify higher level behavior.
Some Starting Pharmacogenomics Ideas
CYP450 Clearance
cytochrome P450 system an the obvious first pass as its effects tolerability of many compounds. If I am an ultra-rapid, normal, intermediate, or poor metabolizer on specific CYP pathways, that changes the interpretation of almost every Self Reported medication.
Genes of interest:
- CYP2D6
- CYP2C19
- CYP2C9
- CYP3A4 / CYP3A5
- CYP1A2
- CYP2B6
- UGTs and other conjugation pathways if the report is broad enough
Some Specific Substances Worth Investigating
- Tropisetron: HTR3A / HTR3B variants may alter 5-HT3 receptor response. CHRNA7 variation could matter for α7 nicotinic signaling.
- Bromantane and other dopaminergic agents: DRD2, DRD4, SLC6A3/DAT1, TH, and dopamine pathway variants could explain differences in drive, side effects, or lack of felt stimulation.
- TAK-653: AMPAR subunit genes and glutamatergic baseline may matter for whether AMPA potentiation feels like cleaner cognition or overstimulation.
- Neboglamine: NMDA glycine-site response may depend on glutamatergic architecture and glycine/D-serine related pathways.
- serotonergic compounds: HTR variants and SLC6A4 could explain differential anxiolytic, compulsive, or affective response.
Baseline Neurochemistry
A lot of stack design assumes a baseline state, but the baseline is exactly what is missing. Genetics can make the baseline less invisible.
Almost all compounds ( in this case lets look at the example of Citicoline ) are usually only showing improvement in RCTs for non-healthy people who have some deficiency. Citicoline will show little to no cognitive benefit if at a normal level, and maybe even cause negative effects if you already operate at a high level. I should only really be taking something like Citicoline if I have a deficiency OR am taking another substance that causes my base Acetylcholine levels to deplete faster.
High priority Neurotransmitters/etc to investigate
- BDNF Val66Met: activity-dependent BDNF secretion. Crucial for interpreting ACD-856, BPN14770, NSI-189, Cerebrolysin-adjacent ideas, and anything framed as neurotrophic repair.
- COMT Val158Met: prefrontal dopamine clearance. Directly relevant for executive function, working memory, stress response, and stimulant/dopaminergic sensitivity.
- MAO-A / MAO-B: monoamine degradation baseline. Relevant to dopaminergic and serotonergic tone, Selegiline, and mood/drive interpretation.
- SLC6A4 / HTR genes: serotonergic tone, SSRIs, 5-HT3 antagonism, anxiety/OCD-ish circuitry.
- DRD2 / DRD4 / SLC6A3: dopamine receptor/transporter architecture.
- GRIN / GRIA genes: NMDA and AMPA receptor architecture, relevant to TAK-653 and Neboglamine.
- MTHFR / methylation genes: one-carbon metabolism, methylfolate/B12 relevance, fatigue, mood, homocysteine.
- APOE: longevity and neurodegeneration risk, but interpret carefully because it has psychological load.