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EmergingResearch compound

ECA‑stack (Ephedrine + Caffeine + Aspirin)

Ephedrine 25 mg + Caffeine 200 mg + Aspirin 81 mg classic 1990s thermogenic-stack. Astrup 1992 Lancet obesity-trial (PMID 1346830) reports ~3x more potent than ephedrine alone; since the FDA 2004 ephedra ban, ephedrine is Rx-only in the EU, blackmarket fat-burner protocol.

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ECA-stack (Ephedrine + Caffeine + Aspirin) vial

WHAT IS ECA-STACK (EPHEDRINE + CAFFEINE + ASPIRIN)?

Detailed overview

The ECA-stack (Ephedrine + Caffeine + Aspirin) is the 1990s thermogenic fat-loss protocol that exploded into the bodybuilding underground after Astrup 1992 Lancet obesity-trial (PMID 1346830). The three components have synergistic mechanisms: ephedrine is an α/β-sympathomimetic alkaloid that triggers noradrenaline release from presynaptic vesicles; caffeine is a PDE-inhibitor and adenosine-receptor antagonist that prevents cAMP degradation, prolonging ephedrine's effect; aspirin (81 mg low-dose) is an endothelial prostaglandin modulator that blunts ephedrine's vasoconstrictive rebound. Daly 1993 Am J Clin Nutr (PMID 8367356) RCT-evidence: the 25/200 mg ephedrine+caffeine combination produces ~3x more potent thermogenic-rate elevation than ephedrine alone. Boozer 2002 Int J Obes (PMID 12122475) 6-month obesity-cohort RCT measured 7.2 kg fat-loss vs. 2.4 kg placebo. The FDA 2004 Consumer Update placed ephedra on the banned-list after 100+ deaths + 16,000+ adverse-event reports (cardiovascular stroke + AMI cluster), so EU R03CA02 (ephedrine ATC-class) became Rx-only. Aspirin is OTC, caffeine is OTC. WADA S6 stimulant – in-competition banned.

Mechanism

Ephedrine α/β-sympathomimetic + caffeine PDE-inhibitor + aspirin endothelial-protective synergy

Dosing

25/200/81 mg PO 2-3x/day, 4-6 week cycle MAX

Half-life

Ephedrine 3-6h; caffeine 5h; aspirin 4-6h

Onset

30-60 min, thermogenic-peak 1-2h

Legal status

HU ephedrine ATC R03CA02 Rx; EU R03 Rx-only (since FDA 2004 ban); aspirin OTC; caffeine OTC. WADA S6 in-competition banned.

Data console

Lab data

/lab/molecular-data.jsonLIVE
> Androgenic:AnabolicN/A (not AAS, sympathomimetic + xanthine + salicylate)
> AR bindingEphedrine α1-AR Ki ~50 μM (low-affinity, indirect NRA-domin…
> Active half-lifeEphedrine 3-6h; caffeine 5h; aspirin 4-6h (parent only)
> Detection windowEphedrine WADA-accredited LC-MS/MS urine detection 1-3 days (urine threshold 10 μg/mL). Caffeine NOT banned (monitored). Aspirin allowed.
> AromatizationDoes not aromatize (not a steroid – sympathomimetic alkaloid + xanthine + salicylate combination). No CYP19 interaction.
> HepatotoxicityModerate – chronic ephedrine cardio-stress + acetaminophen ECA-stack blend combination has documented hepatic interaction (Yokota 2013 PMID 23545017). Chronic high-dose aspirin carries Reye syndrome risk (pediatric contraindication). Pre-2004 ephedra blackmarket blends showed acute hepatitis case clusters (FDA Consumer Update 2004).

Safety

Side effects, stop signs, contraindications

Side effects · 8

  • Cardiovascular strain: tachycardia, raised blood pressure (+10–20 mmHg systolic), palpitations; in severe cases arrhythmia, myocardial infarction and stroke (FDA 2004 ephedra ban: 100+ deaths, 16,000+ adverse events).
  • CNS stimulation: anxiety, nervousness, irritability, tremor and restlessness, dose-dependent.
  • Insomnia: due to the long half-lives of ephedrine and caffeine, especially if the afternoon dose is taken after 16:00.
  • Tachyphylaxis (tolerance): effect declines after 4–6 weeks of continuous use due to depletion of presynaptic noradrenaline stores and β-receptor downregulation; dose escalation is NOT advised as it only increases cardiovascular risk.
  • Aspirin gastrointestinal irritation and bleeding risk: COX-1 inhibition causes gastric irritation, gastritis and GI-bleed tendency, more pronounced at higher doses (>325 mg/day).
  • Sympathomimetic effects: sweating, dry mouth, headache, nausea and appetite suppression (the latter is part of the intended effect but can cause excessive caloric deficit).
  • Urinary and pressor effects: ephedrine can cause urinary retention (especially with prostate enlargement) and sustain elevated systolic-diastolic blood pressure.
  • Rebound fatigue and rebound appetite: abrupt cessation can cause marked fatigue, low mood and rebound increase in appetite from stimulant withdrawal.

Contraindications · 7

  • Severe or uncontrolled hypertension (>140/90 mmHg) – absolute contraindication due to the sympathomimetic pressor effect (FDA 2004 ephedra ban: stroke + MI cluster).
  • Pre-existing heart disease: tachyarrhythmia, atrial fibrillation, coronary artery disease or cardiomyopathy – absolute contraindication.
  • MAO-inhibitor therapy (phenelzine, tranylcypromine) – risk of hypertensive crisis, absolute contraindication; a 14-day washout after stopping the MAOI is required.
  • Hyperthyroidism / Graves' disease and pheochromocytoma – absolute contraindication due to additive sympathomimetic catecholamine excess.
  • Pregnancy and breastfeeding (FDA Category C) – avoid due to fetal and cardiovascular risk.
  • Children and adolescents (<16 years) – risk of Reye's syndrome from aspirin plus the burden of stimulant load.
  • Relative contraindications: SSRI/SNRI co-use (serotonin syndrome risk), chronic beta-blocker therapy (unopposed alpha vasoconstriction), aspirin allergy / active peptic ulcer, and anticoagulant (warfarin) therapy – increased bleeding risk and raised INR.

Related Performance Compounds

Same therapeutic category

Studies

Related research and clinical findings

Int J Obes Relat Metab Disord

Safety and efficacy of long-term treatment with ephedrine, caffeine and an ephedrine/caffeine mixture.

Toubro S, Astrup AV, Breum L, Quaade F

PMID: 8384186Open
Br J Clin Pharmacol

Mechanistic pharmacokinetic modelling of ephedrine, norephedrine and caffeine in healthy subjects.

Csajka C, Haller CA, Benowitz NL, Verotta D

PMID: 15752380Open
Int J Obes Relat Metab Disord. 2002;26(5):593-604.

An herbal supplement containing Ma Huang-Guarana for weight loss: a randomized, double-blind trial

Boozer CN, Daly PA, Homel P, Solomon JL, Blanchard D, Nasser JA, et al.

PMID: 12032741Open
JAMA

Efficacy and safety of ephedra and ephedrine for weight loss and athletic performance: a meta-analysis.

Shekelle PG, Hardy ML, Morton SC, Maglione M, Mojica WA, Suttorp MJ, Rhodes SL, Jungvig L, Gagné J

PMID: 12672771Open
N Engl J Med. 2000;343(25):1833-1838.

Ephedra-containing dietary supplements and cardiovascular adverse events

Haller CA, Benowitz NL.

PMID: 11117974Open

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MolekulaX Editorial Team·Source-verified · PubMed · FDA · EMA
Updated: June 19, 2026

The information here is for educational and scientific purposes only. Performance-enhancing compounds (AAS, prohormones, stimulants, doping agents) are illegal without prescription in Hungary and most of the EU, and carry serious health and legal risks. WADA bans them in competitive sport. This is NOT a usage guide, and we do not encourage any illegal use. If you do use them, medical supervision and regular bloodwork are ESSENTIAL. Severe endocrine, cardiovascular, hepatic and psychiatric side effects are possible.