Because the user archetype (healthy 20yo) is not phenelzine's target population, the subjective profile that follows describes the standard clinical experience of treatment-responsive patients with social anxiety, atypical depression, or panic disorder.

Onset (Week 1-2)

• Sedation often noticeable immediately. GABA-T inhibition + monoaminergic shift. "Feels like the volume on anxiety got turned down before the antidepressant effect kicked in."
• Mild orthostatic hypotension. Dizziness on standing, especially first 1-3 weeks.
• Sleep changes. Some users report initial insomnia (DA/NE elevation); more report sleepier than baseline.
• GI upset, dry mouth.
• Sexual side effects can emerge early. Anorgasmia is common across MAOIs and can be a discontinuation trigger.

Peak therapeutic (Week 3-6)

• Anxiety reduction often dramatic in social anxiety patients. "First time I've ever been able to make a phone call without rehearsing."
• Mood lift in atypical depression. Resolution of mood reactivity + hypersomnia + leaden paralysis + rejection sensitivity.
• Reduced panic frequency.
• Steady-state tyramine vigilance. Patients describe "constant low-grade dietary anxiety" — restaurants become calculations, sauces become unknowable. Lifestyle constraint is real and persistent.
• B6 deficiency symptoms emerge in users not supplementing. Paresthesias (especially hands), pedal edema, occasional myoclonic jerks at sleep onset.

Steady-state (Week 6+)

• Continued anxiolytic + antidepressant effect.
• Weight gain often ~5-15 lbs over months (mechanism: GABA-T-mediated appetite stimulation + atypical-depression resolution + monoamine effects).
• Sexual dysfunction often persists.
• Lifestyle commitment becomes routine — patients learn the diet, learn to ask about ingredients, carry a list. For some this is manageable; for others it's the breaking point.

What it does NOT do

• Doesn't have nootropic/cognitive-enhancement character. Sedating, not activating.
• Doesn't acutely "feel like" anything in the recreational sense. No euphoria, no rush.
• Doesn't reverse rapidly — once started, you're committed for at least the 2-3 weeks of washout if you ever discontinue.

• Tolerance: Generally minimal at therapeutic doses. The mechanism (irreversible enzyme inhibition + GABA-T inhibition + B6 sequestration) doesn't lend itself to receptor-level downregulation. Tachyphylaxis (loss of antidepressant effect) is reported in a minority of long-term users — sometimes managed by brief drug holiday + reinitiation.
• Cycling: Not a typical practice. Phenelzine is a chronic-use medication. Once you've established the lifestyle constraints + dose response, the goal is sustained use, not cycling.
• Reset protocol: 2-3 week washout for full MAO regeneration. NOT a fast-reversible intervention — this is a feature (sustained efficacy) and a constraint (slow reversal of any decision).
• Frequency ceiling: N/A — daily continuous use is the design.

Synergistic with (clinical practice)

• Pyridoxine (B6) 50-100 mg/day. ESSENTIAL prophylactic — reverses the deficiency syndrome.
• Lithium augmentation for treatment-resistant cases. Standard depression-augmentation strategy. Lithium 600-900 mg/day.
• Trazodone for insomnia. Low-dose trazodone (50-100 mg HS) is one of the few hypnotics safely combinable with MAOIs (technically a serotonin antagonist + reuptake inhibitor — SARI — with low serotonin syndrome risk at hypnotic doses). Caution still warranted; watch for serotonin syndrome signs.
• CBT for SAD. Combined treatment > monotherapy in SAD. Phenelzine + exposure therapy is the canonical treatment-resistant SAD protocol.

Avoid stacking with (absolute contraindications)

• All other MAOIs. Tranylcypromine, isocarboxazid, selegiline (any dose), rasagiline, safinamide, linezolid, methylene blue. Redundant + dangerous.
• All SSRIs. Sertraline, fluoxetine (especially — long t½ → 5 week washout needed), paroxetine, citalopram, escitalopram, fluvoxamine. Serotonin syndrome.
• All SNRIs. Venlafaxine, duloxetine, desvenlafaxine, levomilnacipran, milnacipran. Serotonin syndrome.
• All TCAs. Imipramine, amitriptyline, clomipramine especially, nortriptyline. Some old psychopharmacology specialists do combine TCA + MAOI in deeply refractory cases — this requires specialist supervision, not casual practice.
• Bupropion. NDRI; raises NE → hypertensive risk on MAOI.
• Tramadol. Serotonin syndrome.
• Meperidine (Demerol), methadone, fentanyl-class. Serotonin syndrome / fatal interactions. Tell ER/anesthesiology immediately if taking phenelzine.
• Dextromethorphan (DXM). Cough syrups containing DXM must be avoided. Use guaifenesin-only or codeine-only alternatives.
• MDMA, methamphetamine, amphetamines high-dose. Hypertensive crisis + serotonin syndrome.
• Triptans (sumatriptan, rizatriptan, etc.). Serotonin syndrome.
• St. John's Wort, 5-HTP, L-tryptophan high-dose. Serotonin syndrome.
• Sympathomimetics (pseudoephedrine, ephedrine, phenylephrine OTC). Hypertensive risk.
• L-DOPA / carbidopa/levodopa. Hypertensive risk + serotonin syndrome.
• Buspirone. Theoretical serotonin syndrome risk; avoid.

Caution / monitor (relative — clinical judgment)

• Alcohol. Tap beer + red wine specifically banned (tyramine). Other alcohol — clear spirits, white wine, distilled spirits — generally safe in moderation. Heavy drinking still risky for hepatotoxicity stacking.
• Caffeine. Generally fine in moderation; very high doses theoretical pressor risk.
• Decongestants of any kind. Avoid OTC cold/flu products without screening ingredients.
• Anesthetics. Disclose to anesthesiologist. Some opioids (morphine, oxycodone, hydromorphone) generally OK; meperidine and serotonergic opioids contraindicated.

Neutral / safe co-administration (for the rare healthy 20yo on phenelzine for SAD)

• Most peptides (BPC-157, TB-500, GHK-Cu) — no documented interaction; no monoaminergic mechanism overlap
• Most racetams (piracetam, aniracetam) — no documented interaction
• Creatine, beta-alanine, electrolyte supplements — fine
• Vitamin/mineral supplements — fine (and B6 is mandatory)
• Magnesium glycinate — fine
• NAC — fine
• Caffeine in moderation — fine
• Cannabis — generally tolerated though can amplify orthostatic hypotension; not formally contraindicated

Absolute contraindications (do not combine)

See exhaustive list above. The MAOI interaction matrix is one of the worst in modern pharmacology — wider and more dangerous than benzodiazepines, opioids, or anticoagulants.

Tyramine — full restriction always required

Unlike selegiline at low-oral dose (no restriction) or Emsam 6 mg (no restriction), phenelzine ALWAYS requires full dietary tyramine restriction. There is no "low-dose phenelzine" tier where the cliff disappears.

Strict avoid:

• All aged/fermented cheeses (>2 months aging): cheddar, blue, parmesan, brie, camembert, gouda, gruyère, swiss aged, feta in some cases
• All aged/cured meats: salami, pepperoni, prosciutto, dry sausage, soppressata, salt-cured fish, smoked fish
• Fermented soy: soy sauce in quantity, miso, tempeh, aged tofu
• Fermented vegetables: sauerkraut, kimchi, pickles in vinegar are OK but lacto-fermented restricted
• Tap/draft beer (any), red wine (especially Chianti, Burgundy, port, sherry), bottled beer in moderation (some sources allow 1-2 bottled beers, others restrict all)
• Fava beans (broad beans)
• Marmite, Vegemite, Bovril (yeast extracts in concentration)
• Overripe / spoiled food of any kind — fruits with bruising, leftover meat >24 hr
• Banana peel (banana flesh is fine, peel restricted) — relevant if drinking banana smoothies with peel

Generally safe in moderation:

• Fresh meat, fresh fish, fresh poultry
• Fresh cheese (cottage, cream, ricotta, mozzarella)
• Eggs, milk, yogurt
• Fresh produce (most)
• White wine, clear spirits (vodka, gin, tequila), bottled beer in moderation (1-2 max)
• Caffeine in moderation
• Chocolate (older guidance restricted; modern consensus minimal-tyramine — small amounts OK)

CYP / metabolism interactions

• NAT2 (N-acetyltransferase 2) is the primary metabolizer. Slow acetylators (~50% of US population, varies by ancestry) clear phenelzine more slowly → higher exposure → potentially greater efficacy AND greater side effects. Fast acetylators may need higher doses.
• CYP interactions are minor — phenelzine is not a major CYP substrate or inhibitor. Most drug interactions are pharmacodynamic (serotonin syndrome, hypertensive crisis), not pharmacokinetic.

NAT2 polymorphism — primary clinical genetic factor

N-acetyltransferase 2 (NAT2) polymorphism produces a bimodal phenotype:

• Slow acetylators (~50% Caucasians, ~50% African ancestry, ~10% East Asian). Reduced phenelzine clearance → 2-3× higher exposure at given dose. May respond at lower doses. Higher risk of dose-dependent side effects (orthostasis, sedation, B6 deficiency, hepatotoxicity).
• Fast acetylators. May require higher doses for same therapeutic effect. May tolerate higher doses with less side effect.
• 23andMe markers: rs1801279 (NAT214), rs1041983 (NAT25/6/7 detection), rs1799930 (NAT26), rs1799931 (NAT27) — all on standard 23andMe v5 chip.
• Clinical implication: Pharmacogenomic-guided dosing is plausible but rarely formally implemented. Some specialty psychiatry practices use NAT2 testing for MAOI dosing decisions.

Other relevant SNPs

• MAOA-uVNTR (the "warrior gene") — affects baseline MAO-A activity. Theoretical dose-response modifier; not formally validated for phenelzine.
• MAOB intron 13 (rs1799836) — affects MAO-B expression; theoretical relevance; not validated.
• *HLA-B1502, 5701* — important for some other psychotropics (carbamazepine, abacavir) but not specifically validated for phenelzine hepatotoxicity. The hydrazine hepatotoxicity is generally idiosyncratic without strong HLA association.
• 5-HTTLPR (SLC6A4 promoter VNTR) — affects 5-HT transporter expression; speculative MAOI response modifier; not formally validated for phenelzine specifically.

For the user specifically (23andMe results pending June 2026)

SNPs to flag if user ever considers phenelzine:

1. NAT2 acetylator status (rs1801279, rs1041983, rs1799930, rs1799931) — primary dosing predictor
2. MAOA-uVNTR — theoretical
3. 5-HTTLPR — theoretical

These are mostly research-grade — not actionable in the same robust way that CYP2D6 status guides codeine dosing. If user develops treatment-resistant SAD and is considering phenelzine, NAT2 status is the highest-priority pharmacogenomic check.

For the user (if ever indicated): in-person psychiatrist Rx is the realistic path. This is not a telehealth-friendly drug — the prescriber will want a documented diagnosis (treatment-resistant SAD, atypical depression), failed prior trials of safer alternatives, and ongoing monitoring (BP, liver enzymes, weight, B6 status). Most general psychiatrists are uncomfortable prescribing MAOIs given the interaction list; specialty mood-disorder programs are the typical referral. Cost is not the gating factor — willingness to commit to the lifestyle and monitoring is.

Baseline (before starting)

• Resting BP + orthostatic BP delta — establish baseline before MAOI initiation
• HR resting + standing
• Weight — track for the typical 5-15 lb gain
• Mood (PHQ-9), anxiety (GAD-7, LSAS for SAD specifically) — symptom severity
• Liver panel (ALT/AST, alk phos, bilirubin) — baseline for hepatotoxicity surveillance
• CBC, CMP — general baseline
• B6 (PLP) level — baseline, retest at 4-8 weeks
• 23andMe NAT2 status (if available) — pharmacogenomic dosing input
• Comprehensive medication review — confirm no serotonergic interactions, document washout if discontinuing prior SSRI

During use

• BP weekly first month, monthly thereafter — both for orthostatic (tracking acclimation) and for tyramine-event surveillance
• Liver enzymes at 1 month, 3 months, 6 months, then yearly
• B6 level at 6-8 weeks — verify supplementation adequate
• Symptoms questionnaire monthly — paresthesias, edema, weight, sexual function, mood/anxiety self-report
• Patient education check-ins — confirm dietary compliance, OTC medication awareness

Post-discontinuation

• 2-week tyramine vigilance
• 2-week washout from any other serotonergic agent before initiation
• BP monitoring during taper