Onset: 30-60 min after oral dose (peak plasma 1-2 hr). Duration: ~5 hr half-life → 6-8 hr functional duration with smooth taper. Character (first 1-3 doses): clean, prefrontal-feeling motivation lift + mild euphoria + reduced friction starting tasks. Often described as "I want to do my work" rather than "I'm focused on my work" — drive precedes cognition. No jitter, no peripheral stimulation, no appetite suppression. Very different feel from caffeine (no peripheral activation), from modafinil (less wake/alertness, more drive), from amphetamine (no euphoria spike, no rebound crash). Character (dose 4-7, daily): noticeably blunter. The "extra drive" feels more like baseline. No paradoxical sedation in most users, but a few report unexpected drowsiness ("paradoxical fatigue"). Character (dose 8-14, daily): typically null response. Some users report mild anhedonia / blunting on cessation that resolves within days. Reset: 1-2 weeks fully off restores most/all sensitivity for most users.

Variability: a minority of users (~10-15% in Reddit reports) get little to no effect even on first dose. Whether this is genetic (thiamine transporter polymorphism, COMT, DRD1?) is unstudied.

• Tolerance buildup: fast — 1-2 weeks of daily dosing is the typical tolerance window. Some users report 4-5 days. This is the defining liability of the compound and the reason daily use is not recommended for any nootropic indication. Mechanism: D1 receptor desensitization/downregulation in response to sustained agonist drive (mirror image of the chronic-dosing upregulation that produces the original effect).
• Recommended cycle (Dylan-archetype): 2-3 doses per week, never 2 days in a row, with 400 mg AM as standard. Rotates through often enough to stay useful; spaced enough that D1 sensitivity stays close to baseline.
• Reset protocol: 1-2 weeks fully off restores sensitivity in most users. There is no documented permanent down-regulation. If tolerance happens during a 5-on-2-off cycle, escalate to 14 days off rather than dose-bumping.
• Asthenia / chronic-fatigue-archetype context: in a deficient/asthenic baseline, the tolerance phenomenon may be less limiting because the underlying CNS thiamine elevation contributes more of the clinical effect than the dopaminergic component. This is consistent with the French "2-4 week course" pattern. In healthy adults already replete in thiamine, the dopaminergic component dominates → tolerance dominates.

Synergistic with

• caffeine + L-theanine (PRN combo): functional pairing — caffeine adds peripheral arousal + adenosine block; theanine smooths edge; sulbutiamine adds drive/motivation. Three different mechanisms, no overlap, low risk. Reasonable PRN heavy-cognitive-day stack: 400 mg sulbutiamine + 100 mg caffeine + 200 mg theanine AM.
• alpha-gpc (300-600 mg): cholinergic substrate — sulbutiamine's chronic ACh-release effect is substrate-limited; alpha-GPC supplies the choline. Logical pairing on the rare day both are used.
• l-tyrosine (1-2 g): tyrosine is the rate-limiting precursor for dopamine synthesis. Under cognitive stress, tyrosine prevents DA depletion; sulbutiamine raises D1 sensitivity to whatever DA is around. Theoretically synergistic; not formally studied. Useful pairing for high-stress cognitive days where tolerance allows.
• phenylpiracetam: another PRN-only dopaminergic with even faster tolerance (~3 days). Not literally synergistic but they share the "PRN drawer" use case and don't conflict mechanistically. Probably best to use one or the other on a given day, not both.
• modafinil: mechanistically distinct (DAT, orexin, histamine vs D1 receptor density). Plausibly additive on motivation. Reddit anecdotes suggest the combination feels "clean" with no significant added side effects. No formal interaction studies. Reasonable on rare PRN days.

Avoid stacking with

• selegiline (oral or Emsam): Caution. Selegiline at nootropic doses (1-2.5 mg) is selective MAO-B but loses selectivity at higher exposures (Emsam 9-12 mg patch reaches MAO-A inhibition). Sulbutiamine is not a direct dopamine releaser, but its D1 upregulation amplifies the response to whatever DA is around — combined with MAO-B inhibition (which raises tonic DA), this is a theoretical hypertensive / over-stimulation setup. No documented case reports of sulbutiamine + selegiline crisis, but the mechanism makes it the most concerning single interaction. Skip the combo or space it out widely.
• bromantane: both work on dopaminergic systems (bromantane via TH/AADC enzyme upregulation increasing DA synthesis; sulbutiamine via D1 receptor density increasing sensitivity). Theoretical strong synergy → over-activation, anxiety, insomnia. Plus both are PRN-tolerance-prone. Not literally dangerous but redundant — pick one PRN dopaminergic for a given day.
• Other strong DA agents (amphetamine, methylphenidate, bupropion at high dose): stacking sulbutiamine on top of a DA-releaser is over-determined and likely not additive for benefit (D1 saturated) but is additive for jitter/anxiety/sleep disruption.
• In bipolar I/II or family history of bipolar: avoid entirely (manic switch risk per case reports).

Neutral / safe co-administration

• V4 stack (DHA, magnesium, NAC, citicoline, PS, curcumin, rhodiola, theanine, glycine, D3+K2, beta-alanine, vitamin C, creatine): no conflicts.
• B-complex / standalone thiamine: redundant but not harmful. Sulbutiamine itself adds CNS-active thiamine, so additional B1 isn't gaining much.
• L-tryptophan / pre-bed sleep stack: different system, different time of day, no conflict.
• Cerebrolysin, Adamax, Semax, Selank, Apigenin, Taurine, Astaxanthin, ALCAR: no documented conflicts.
• BPC-157, TB-500, GHK-Cu (peptide healing stack): no overlap.

• CYP enzymes: no documented significant induction or inhibition of CYP1A2/2C9/2C19/2D6/3A4. Sulbutiamine is metabolized to thiamine via reduction/hydrolysis (non-CYP).
• Alcohol: alcohol depletes thiamine; sulbutiamine partially offsets this. Not a clinical-grade rescue but biologically real. Dylan zero-alcohol → not relevant.
• Loop diuretics (furosemide), high-dose metformin: both deplete thiamine. Sulbutiamine could be supportive in those contexts. Not relevant to Dylan.
• 5-FU chemotherapy, cisplatin: thiamine status concerns; not relevant to Dylan.
• Hormonal contraceptives: no interaction (irrelevant for Dylan).

• SLC19A2 (THTR-1) and SLC19A3 (THTR-2) variants: rare loss-of-function variants cause Wernicke-like syndromes responsive to high-dose thiamine. Common variants may modulate baseline brain thiamine status and could plausibly affect sulbutiamine responsiveness, but no published pharmacogenomics studies link sulbutiamine response to specific transporter SNPs. Flagged speculative.
• DRD1 polymorphisms: could theoretically modulate D1 upregulation response. Unstudied.
• COMT Val/Met: theoretical relevance via PFC dopamine clearance kinetics. Unstudied for sulbutiamine specifically.
• 23andMe coverage: Dylan should look at SLC19A2/A3 (low-coverage on consumer arrays), DRD1, COMT when results land June 2026 — but assume minimal interpretive power for sulbutiamine specifically.

Dylan's expected path: Double Wood from Amazon — already on standard sourcing, easy add. Estimated $15-25/month at 2-3 doses/week × 400 mg = ~24-32 caps/month. Dirt cheap relative to value if used PRN.

• Baseline (before starting):
  • RBC thiamine or whole-blood thiamine pyrophosphate (TPP-effect erythrocyte transketolase activation) — only if asthenia is the indication; uninformative for healthy users.
  • Fasting glucose + HbA1c — sulbutiamine's TPP-elevation supports glucose metabolism; relevant only in dysglycemia context.
  • TSH/free T3/free T4 — rule out thyroid causes of fatigue before reaching for sulbutiamine.
  • Mood screen (PHQ-9 informally) — establish baseline before any dopaminergic compound.
• During use:
  • Subjective dose-response journal: dose / day-of-week / subjective effect (1-10) / next-morning energy. Track whether tolerance is creeping in on the user's actual cycle.
  • If using >2 weeks daily: re-check sleep onset/quality, mood baseline.
• Post-cycle (if cycled):
  • Subjective return-to-baseline (1-2 weeks should fully reset).
  • Watch for transient mild anhedonia/blunting in first 2-3 days off; if persists >1 week investigate.