Standalone hordenine 50-100 mg oral:

• Onset: 30-60 min, gentle.
• Peak feel: ~1-1.5 hours post-dose.
• Subjective effect: Mild stimulation — most users describe it as "there but not pronounced." Slight appetite suppression. Light mood lift. Modest "warming" sensation, mild increase in alertness without strong cognitive sharpening. Some users report nothing at all at 50 mg.
• Duration: 2-4 hours subjective; tapers gently rather than crashing.
• Cardiovascular: Modest HR rise (3-8 bpm typical at 100 mg), small BP rise. CV-healthy adults rarely notice it; pre-existing CV-sensitive users may feel it.
• Honest assessment: As a standalone tool, hordenine is the kind of supplement where double-blinding it against placebo would likely produce a small, non-significant effect. Most of its supplement-industry presence is downstream of the PEA-potentiator stack rationale, not independent merit.

Hordenine 50-75 mg + PEA 500 mg (the canonical stack, taken 30-45 min apart):

• Onset: 15-45 min after PEA dose (hordenine pre-load already partial).
• Subjective effect: Noticeably more focus, euphoria, energy, and motivation than either compound alone. Effect feels closer to a low-dose ADHD stimulant or amphetamine analog, but cleaner and shorter. "Get-shit-done" feel, mood lift, appetite suppression, mild body warmth.
• Duration: 1-3 hours of usable effect; tapers without the hard crash of caffeine.
• CV signal: More pronounced than either alone, but still modest at standard doses. Avoid the stack with other strong sympathomimetics.

Pre-workout context (hordenine + caffeine + PEA + N-methyl-tyramine + tyrosine + B-vitamins):

• The "pre-workout stack" subjective effect is dominated by caffeine; hordenine + PEA contribute a layered focus/motivation feel on top. Effect is real but small magnitude relative to caffeine itself.

Honest variability: Some users find hordenine produces palpable effects at 50-75 mg; others report nothing even at 150 mg. Variance is large and not well-characterized pharmacogenomically. MAO-B activity polymorphisms likely contribute (slow MAO-B = stronger effect of any MAO-B substrate or inhibitor).

• Tolerance buildup: Mild and slow at supplement doses. The MAO-B competitive interaction is reversible and competitive — it doesn't produce the kind of receptor downregulation seen with chronic adenosine antagonism (caffeine) or chronic dopamine release (amphetamines). However, repeated daily dosing of any sympathomimetic-leaning compound produces some tachyphylaxis.
• Recommended cycle: PRN use is the dominant pattern; daily use is uncommon. For pre-workout use, 4-5 days/week is reasonable. For PEA + hordenine PRN focus stack, 1-3 days/week.
• Reset protocol: 7-14 days off restores any modest tolerance.
• Cross-tolerance: Likely some cross-tolerance with other phenethylamine sympathomimetics (tyramine, synephrine, N-methyl-tyramine) and weakly with amphetamine-class compounds. Probably no cross-tolerance with adenosine-class stimulants (caffeine, paraxanthine).

Synergistic with

• phenylethylamine: The canonical hordenine stack. Hordenine's reversible MAO-B competition extends PEA's 5-15 min half-life to 1-3 hours, producing a smoother, longer focus/euphoria pulse. Pre-load hordenine 30-45 min before PEA. The single most popular practical use of hordenine.
• caffeine: Common pre-workout pairing. Caffeine's adenosine antagonism + hordenine's sympathomimetic + dopaminergic feel layer cleanly. Not synergistic in a special way; just additive within a tolerable CV envelope at standard doses.
• l-tyrosine: Trace-amine + dopamine-precursor pairing. Tyrosine supplies the substrate for trace-amine biosynthesis and dopamine; hordenine modulates the trace-amine system. Mild theoretical synergy; not breakthrough.
• N-methyl-tyramine (NMT): Often co-formulated in pre-workouts. Both are phenethylamine derivatives with similar pharmacology; effect is additive.

Avoid stacking with

• Non-selective MAOIs (phenelzine, tranylcypromine): Hypertensive crisis risk through tyramine-pressor mechanism. Hordenine itself is structurally similar to tyramine and full MAOI blockade can produce serious BP spikes.
• Selegiline at antidepressant-range doses (10+ mg): Same logic. At MAO-B-selective low-dose selegiline (5 mg) the risk is lower but still present, especially with tyramine-rich diet.
• Tyramine-rich foods + selegiline: Established cheese-effect interaction; adding hordenine on top compounds risk.
• High-dose other sympathomimetics (synephrine + yohimbine + ephedrine + caffeine megadose): Cumulative CV load. Many "extreme" pre-workouts stack 5+ stimulants and produce real CV events in susceptible users.
• Stimulant medications (amphetamine, methylphenidate) at therapeutic doses: Additive sympathomimetic load.
• PM dosing past 6h pre-bed: Sleep onset delay risk.
• Drug-tested elite athletes during competition windows: Hordenine itself is not WADA-prohibited, but pre-workout blends containing hordenine often contain banned stimulants; check labels carefully.

Neutral / safe co-administration

• The user's V4/V5 baseline supplements (Mg, NAC, citicoline, alpha-GPC, PS, DHA, curcumin, rhodiola, glycine/tryptophan, D3/K2, beta-alanine, vitamin C) — no interactions of concern.
• Most peptides (BPC-157, TB-500, Semax, Selank) — neutral.
• Paraxanthine — likely neutral/additive in the same way caffeine + hordenine is. No specific RCT of the combination.

• MAOIs (non-selective and selective MAO-B at high doses): primary clinically relevant interaction — covered in Stacking.
• Sympathomimetics (pseudoephedrine, phenylephrine, ephedrine, amphetamines, high-dose synephrine, yohimbine): additive pressor / CV load.
• Antihypertensives: modest theoretical antagonism via the small pressor effect; not clinically meaningful at supplement doses but worth noting.
• SSRIs: theoretical additive serotonergic load if combined with strong MAOI; no concern at supplement doses without that potentiator.
• Stimulant medications (Adderall, methylphenidate): additive CV / sympathomimetic effect.

• MAO-B activity polymorphisms affect both endogenous PEA/dopamine clearance and the practical impact of MAO-B substrates like hordenine. Slow MAO-B carriers may experience stronger subjective effects from hordenine + PEA stacks; fast MAO-B carriers may notice nothing.
• COMT Val/Val vs Met/Met affects dopamine clearance; high-COMT-activity (Val/Val) users may benefit slightly more from compounds that prolong dopamine signaling.
• No actionable pharmacogenomic test currently available for predicting hordenine response.

For users in this archetype: standalone hordenine is rarely worth ordering as a dedicated bottle. If experimenting with the PEA + hordenine stack, Bulk Supplements hordenine HCl powder + Bulk Supplements PEA HCl powder + a milligram-scale is the cleanest path (~$20-30 total). Otherwise, exposure happens organically through any standard pre-workout that lists it on the panel.

Baseline (before starting)

• Resting HR + BP (3-day morning average) — hordenine adds 3-8 bpm at 100 mg, modest BP rise.
• Subjective mood / focus VAS for 5-7 days pre-dose if using for PRN focus.
• Anxiety baseline (GAD-7 or daily 1-10 VAS).
• Body composition / weight if using for appetite-suppression context.

During use

• First 2 weeks: post-dose HR/BP at 60 and 120 min to characterize personal response.
• Subjective focus / mood VAS on use-days vs rest-days.
• Sleep tracker (Oura/equivalent) — flag any sleep onset delay or REM/deep sleep degradation if dosing afternoon.
• Body composition if appetite suppression is the primary use case.

Post-cycle (rarely needed; PRN use dominant)

• Note any subjective rebound (rare with hordenine; mostly absent at supplement doses).