Ephedrine hydrochloride (ephedrine HCl) is the hydrochloride salt of ephedrine, a stimulant alkaloid that occurs naturally in ma huang (Ephedra sinica) and other Ephedra plants and can also be made synthetically. It acts on the sympathetic (“fight or flight”) nervous system. It raises heart rate and blood pressure, widens the airways and increases energy expenditure.
In the US, ephedrine HCl is legal as an over-the-counter (OTC) bronchodilator for mild intermittent asthma, at 12.5–25 mg per dose. A different salt, ephedrine sulfate, is a prescription injection for low blood pressure during anesthesia. Outside medicine, ephedrine products have been marketed for weight loss, athletic performance and energy. The most important regulatory fact: FDA has stated that synthetic ephedrine HCl cannot legally be sold as a dietary supplement, and it banned supplements containing ephedra alkaloids in 2004.
This page summarizes what the FDA labels and rules, the clinical trials and the regulators report. It is for education only and is not medical advice.
| Property | Detail |
|---|---|
| Drug class | Sympathomimetic amine: direct α- and β-adrenergic agonist plus norepinephrine releaser |
| US products | OTC bronchodilator tablets (e.g. Primatene tablets, 12.5 mg); prescription injection as ephedrine sulfate (e.g. Akovaz) |
| Route | Oral (HCl tablets); intravenous (sulfate injection) |
| OTC labeled dose | 12.5–25 mg every 4 h as needed, max 150 mg in 24 h (adults and children 12 and over) |
| Ephedrine content | About 82% of the HCl salt’s weight (12.5 mg HCl ≈ 10.2 mg ephedrine base) |
| Half-life | About 6 h after oral dosing (Akovaz label); longer when urine is alkaline |
| Elimination | Excreted in urine as ephedrine and its metabolite norephedrine |
| US status | OTC drug (21 CFR 341.16); DEA List I chemical with retail sales limits; not a legal dietary ingredient |
| WADA | Prohibited in-competition (S6.B specified stimulant) when urine concentration is over 10 µg/mL |
What it is
Ephedrine is (1R,2S)-2-(methylamino)-1-phenylpropan-1-ol, formula C₁₀H₁₅NO, molecular weight 165.23 g/mol (PubChem). The hydrochloride salt, C₁₀H₁₆ClNO, weighs 201.69 g/mol (PubChem). The salt only makes the drug stable and water-soluble; once dissolved, the active molecule is the same ephedrine.
The salt matters when comparing products, because labels state the salt weight, not the base:
| Form | Molecular weight | Ephedrine base per labeled mg | Example product |
|---|---|---|---|
| Ephedrine base | 165.23 g/mol | 100% | — |
| Ephedrine hydrochloride | 201.69 g/mol | ≈ 82% | OTC tablets, 12.5 mg |
| Ephedrine sulfate | 428.5 g/mol (2:1 salt) | ≈ 76% (50 mg = 38 mg base, per label) | IV injection, 50 mg/mL |
Ephedrine is one of several “ephedrine alkaloids” that occur in Ephedra species, alongside pseudoephedrine, norephedrine, methylephedrine and others (FDA final rule, 2004). FDA notes that ephedrine hydrochloride was approved as a human drug as early as the late 1940s.
Mechanism
The ephedrine sulfate label describes two actions (Akovaz label):
- Direct: it activates α- and β-adrenergic receptors.
- Indirect: it releases norepinephrine from sympathetic nerve endings.
The result is a faster heart rate, higher cardiac output and usually higher blood pressure. β-receptor activation in the lungs causes bronchodilation, the basis of its asthma use. α-receptor activation at the bladder neck can make urination harder. Unlike clenbuterol, a selective β₂-agonist, ephedrine acts broadly across receptor types. Exercise researchers attribute part of its effect to central nervous system stimulation (Bell et al., MSSE 2001).
Pharmacokinetics
The Akovaz label states that the plasma elimination half-life after oral dosing is about 6 hours. Ephedrine and its metabolite norephedrine are excreted in urine, and the label warns that kidney impairment is likely to prolong the half-life.
| Study | Design | Key findings |
|---|---|---|
| Persky et al., Br J Clin Pharmacol 2004 | 8 overweight adults; 0.25, 0.5 and 1.0 mg/kg oral ephedrine sulfate vs placebo, crossover | One-compartment kinetics; pooled apparent clearance 0.45 L/h/kg and volume 4.2 L/kg, which corresponds to a half-life of ≈ 6.5 h; clearance tracked creatinine clearance |
| Haller et al., Clin Pharmacol Ther 2002 | 8 adults; single supplement dose with 20 mg ephedrine alkaloids + 200 mg caffeine | Half-lives similar to drug formulations; the half-life was prolonged in the subject with the most alkaline urine |
| Haller et al., Clin Pharmacol Ther 2004 | 16 adults; 25 mg ephedrine, 200 mg caffeine, both, or placebo, crossover | No clinically significant pharmacokinetic interaction between ephedrine and caffeine |
Two points follow from these data. First, because the kidneys clear ephedrine, urine pH and kidney function change how long it lasts. Second, the blood pressure effect fades faster than the drug itself: in the Persky study, tolerance to the rise in systolic blood pressure developed with a half-life of about 15 minutes, while the heart rate rise tracked the plasma level.
Approved medical use
OTC bronchodilator (ephedrine HCl)
The FDA OTC monograph lists ephedrine, ephedrine hydrochloride, ephedrine sulfate and racephedrine hydrochloride as permitted oral bronchodilators (21 CFR 341.16). The required labeling (21 CFR 341.76) sets:
- Use: temporary relief of mild symptoms of intermittent asthma (wheezing, chest tightness, shortness of breath);
- Dose: 12.5–25 mg every 4 hours as needed, not more than 150 mg in 24 hours, for adults and children 12 and over;
- Do not use: unless a doctor has diagnosed asthma, or with a monoamine oxidase inhibitor (MAOI) or within 2 weeks of stopping one.
The current Primatene tablet contains 12.5 mg ephedrine HCl, and its label notes it will not relieve asthma as quickly as an inhaled bronchodilator (Primatene label). Several other OTC tablets combine ephedrine HCl with the expectorant guaifenesin.
Hypotension during anesthesia (ephedrine sulfate)
Injectable ephedrine sulfate (Akovaz, first approved 2016, and generics) is indicated for clinically important hypotension in the setting of anesthesia. The labeled dose is a 5–10 mg IV bolus, repeated as needed, up to a total of 50 mg, given by trained providers (Akovaz label).
Ephedrine was long the standard vasopressor for spinal anesthesia at cesarean delivery. A systematic review of 7 randomized trials (n = 292) found it no better than phenylephrine at managing maternal hypotension (RR 1.00, 95% CI 0.96–1.06). Babies of mothers given ephedrine had slightly lower umbilical artery pH (mean difference 0.03), but true fetal acidosis was not more common (Lee et al., Anesth Analg 2002).
What the research shows
Weight loss
The most complete review is a meta-analysis by the RAND Southern California Evidence-based Practice Center (Shekelle et al., JAMA 2003). No trial lasted more than 6 months. Pooled extra weight loss compared with placebo:
| Treatment | Trials | Extra weight loss vs placebo (95% CI) |
|---|---|---|
| Ephedrine alone | 5 | 0.6 kg/month (0.2–1.0) |
| Ephedrine + caffeine | 12 | 1.0 kg/month (0.7–1.3) |
| Ephedra (herbal) | 1 | 0.8 kg/month (0.4–1.2) |
| Ephedra + caffeine-containing herbs | 4 | 1.0 kg/month (0.6–1.3) |
The authors concluded the effect is modest, about 0.9 kg per month more than placebo, and that there are no data on long-term weight loss.
The best-known single trial randomized 180 obese adults on a 4.2 MJ/day (≈ 1,000 kcal) diet to ephedrine 20 mg, caffeine 200 mg, both, or placebo, three times a day for 24 weeks (Astrup et al., Int J Obes 1992); 141 completed it:
| Arm (three times daily) | Mean weight loss at 24 weeks |
|---|---|
| Ephedrine 20 mg + caffeine 200 mg | 16.6 kg |
| Placebo | 13.2 kg |
| Ephedrine 20 mg alone | Similar to placebo |
| Caffeine 200 mg alone | Similar to placebo |
Tremor, insomnia and dizziness were more common early on but fell to placebo levels after 8 weeks.
“Ephedrine burns fat on its own.” In the Astrup trial, ephedrine alone did not produce significantly more weight loss than placebo; only the ephedrine–caffeine combination did. In the RAND meta-analysis, ephedrine alone added about 0.6 kg per month. The effects are real but small, and the trials were short and done under dietary supervision.
Ephedrine raises energy expenditure (thermogenesis). In a small study of 5 overweight women, the extra oxygen use after a 1 mg/kg dose was larger after 4 and 12 weeks of 20 mg three times daily than before treatment, suggesting the thermogenic response does not fade with regular use (Astrup et al., Am J Clin Nutr 1985).
Exercise performance
RAND judged the evidence that ephedrine alone improves athletic performance insufficient; the 7 ephedrine trials were too different to pool (Shekelle et al., JAMA 2003). A group of small Canadian defence-research studies, each with 8–16 participants taking a single dose 90 minutes before exercise, reported short-term effects:
| Study | Doses | Outcome |
|---|---|---|
| Bell et al., MSSE 2001 | Ephedrine 1 mg/kg, caffeine 5 mg/kg, both, or placebo | Ephedrine raised early power output in a 30-second Wingate cycle sprint |
| Bell et al., MSSE 2002 | Ephedrine 0.8 mg/kg, caffeine 4 mg/kg, both, or placebo; n = 12 | 10-km loaded run: 45.5 min (ephedrine) and 45.7 min (both) vs 46.8 min (placebo) |
| Jacobs et al., MSSE 2003 | Same doses; n = 13 | Leg-press reps in the first set: 16 (ephedrine) and 19 (both) vs 13 (placebo); no difference in later sets |
In both the run and the lifting study, the benefit came mainly from ephedrine, with no clear added effect of caffeine. The lifting study also found higher pre-exercise systolic blood pressure with ephedrine: 150 mm Hg (ephedrine) and 156 mm Hg (both) vs 138 mm Hg (placebo). These are single-dose laboratory studies in small groups of healthy volunteers; they do not show effects on training adaptations, muscle gain or competition results.
Cardiovascular and metabolic effects of a single dose
In a placebo-controlled crossover study of 16 healthy adults (Haller et al., Clin Pharmacol Ther 2004):
- 25 mg ephedrine alone raised heart rate, blood glucose and insulin, but not systolic blood pressure;
- ephedrine plus 200 mg caffeine raised systolic blood pressure by a peak of 11.7 mm Hg and heart rate by 5.9 beats/min over placebo, and raised glucose, insulin, free fatty acids and lactate;
- the combined effect came from pharmacodynamics (the drugs acting together), not from one raising the other’s blood level.
Side effects and risks
Common effects in trials
Across 50 controlled trials, ephedrine or ephedra (with or without caffeine) was linked to a 2.2- to 3.6-fold increase in the odds of psychiatric symptoms, autonomic symptoms, gastrointestinal symptoms and heart palpitations (Shekelle et al., JAMA 2003). The trials were too small to measure events rarer than about 1 in 1,000. The injectable label lists nausea, vomiting and tachycardia as the most common reactions, along with palpitations, reactive hypertension, dizziness and restlessness.
Serious cardiovascular and neurological events
The concern that led to the 2004 ban came from adverse event reports for ephedra-containing supplements:
- An FDA-requested review of 140 reports (1997–1999) rated 31% as definitely or probably related to ephedra and another 31% as possibly related. Among these, 47% involved the heart or circulation and 18% the central nervous system. There were 10 deaths and 13 cases of permanent disability (Haller and Benowitz, NEJM 2000).
- In 2001 US poison center data, ephedra products accounted for 64% of adverse reactions to herbal products but only 0.82% of herbal product sales (Bent et al., Ann Intern Med 2003).
- A case-control study of hemorrhagic stroke found no overall association with ephedra use (OR 1.00, 95% CI 0.32–3.11). At more than 32 mg/day, the odds ratio was 3.59, but the confidence interval was wide (0.70–18.35) (Morgenstern et al., Neurology 2003).
Case reports and poison center data cannot prove cause or give a true rate. They mostly involve botanical supplements, often combined with caffeine. The required OTC label nevertheless warns that ephedrine can raise blood pressure or heart rate and increase the risk of heart attack or stroke, “which may cause death” (21 CFR 341.76). The Primatene label adds that the risk is higher with a history of heart disease or high blood pressure or with more frequent or higher-than-recommended doses, and it tells users to avoid caffeine-containing foods and drinks and stimulant supplements (Primatene label).
Tolerance
Repeated injections cause tachyphylaxis, a quick loss of the blood-pressure response, and the label advises having another vasopressor ready (Akovaz label). The oral study by Persky and colleagues showed the same pattern within a single dose.
Interactions
From the ephedrine labels:
| Interacting drug | Effect |
|---|---|
| MAOIs | OTC label: do not use with an MAOI or within 2 weeks of stopping one; MAOIs augment the pressor effect |
| Oxytocic drugs (e.g. methylergonovine) | Serious postpartum hypertension, including stroke, has been described |
| Clonidine, propofol, atropine | Augment the rise in blood pressure |
| α- and β-blockers, reserpine | Antagonize the pressor effect |
| Cardiac glycosides (digoxin) | May increase the risk of arrhythmias |
| Theophylline | More nausea, nervousness and insomnia |
| Guanethidine | Ephedrine may reverse its blood-pressure-lowering effect |
| Caffeine, phenylephrine, pseudoephedrine | OTC label: ask a doctor or pharmacist first; caffeine adds to the cardiovascular effects |
Who should be cautious
The OTC monograph tells people to ask a doctor before use if they have any of the following (21 CFR 341.76):
- heart disease or high blood pressure;
- diabetes or thyroid disease;
- seizures or a psychiatric condition;
- narrow-angle glaucoma;
- trouble urinating due to an enlarged prostate;
- a past hospitalization for asthma.
Ephedrine crosses the placenta. The injectable label notes reports of metabolic acidosis in newborns after maternal exposure, and that kidney impairment can prolong its effects.
Legal status and use outside medicine
Dietary supplements
On February 11, 2004, FDA declared all dietary supplements containing ephedrine alkaloids adulterated because they present an unreasonable risk of illness or injury, effective April 12, 2004 (69 FR 6788). The rule addressed botanical sources such as ma huang. On synthetic ephedrine, FDA was explicit:
- ephedrine hydrochloride is not a constituent or extract of a botanical, so it cannot be a dietary ingredient;
- products with synthetic ephedrine therefore “cannot be legally marketed as dietary supplements”;
- FDA had already seized ephedrine HCl products labeled as supplements in 2001.
The rule does not cover OTC or prescription drugs, so ephedrine HCl remains legal as an OTC asthma product.
Controlled-chemical rules
Ephedrine is not a scheduled controlled substance, but its salts are DEA List I chemicals because ephedrine can be used to make methamphetamine (21 CFR 1310.02). Under 21 CFR part 1314, retail sale of OTC ephedrine products requires:
- behind-the-counter placement or a locked cabinet;
- photo identification and a logbook entry for each sale;
- a limit of 3.6 g of ephedrine base per purchaser per day.
Sport
WADA lists ephedrine as a specified stimulant (S6.B), prohibited in-competition when the urine concentration exceeds 10 µg/mL (WADA 2026 Prohibited List). Methylephedrine has the same threshold and pseudoephedrine a threshold of 150 µg/mL. Detecting any amount of ephedrine together with a diuretic or masking agent counts as an adverse finding unless the athlete holds a therapeutic use exemption. Related stimulants in this library include DMAA, synephrine (on WADA’s monitoring program, not prohibited) and yohimbine.
Key takeaways
- A legal OTC asthma drug, not a supplement. Ephedrine HCl is sold as a 12.5–25 mg bronchodilator with a 150 mg daily cap; FDA says synthetic ephedrine cannot legally be sold as a dietary supplement.
- Mixed-acting stimulant. It activates adrenergic receptors directly and releases norepinephrine, raising heart rate, blood pressure and energy expenditure.
- Roughly 6-hour half-life. It is cleared mainly through the kidneys, so alkaline urine or kidney impairment prolongs it.
- Modest, short-term weight loss. Trials show about 0.6 kg/month alone and 1.0 kg/month with caffeine over placebo, with no trial longer than 6 months.
- Cardiovascular risk drove the ban. Trials show 2–3.6-fold higher odds of palpitations and psychiatric, autonomic and digestive symptoms, and adverse event reports included strokes, seizures and deaths.
- Regulated as a precursor and in sport. It is a DEA List I chemical with retail limits and is prohibited in-competition by WADA above 10 µg/mL in urine.
Sources
- Foundation Consumer Brands. Primatene (ephedrine hydrochloride) tablet, 12.5 mg, Drug Facts label. DailyMed.
- Food and Drug Administration. 21 CFR 341.16, Bronchodilator active ingredients; 21 CFR 341.76, Labeling of bronchodilator drug products. eCFR 341.16; eCFR 341.76.
- Exela Pharma Sciences. Akovaz (ephedrine sulfate injection), prescribing information. DailyMed.
- National Center for Biotechnology Information. Ephedrine, PubChem CID 9294; Ephedrine hydrochloride, PubChem CID 65326. PubChem; PubChem.
- Food and Drug Administration. Final rule declaring dietary supplements containing ephedrine alkaloids adulterated because they present an unreasonable risk. Federal Register. February 11, 2004;69(28):6788–6854 (FR Doc 04-2912). govinfo.
- Drug Enforcement Administration. 21 CFR 1310.02, Substances covered; 21 CFR part 1314, Retail sale of scheduled listed chemical products. eCFR 1310.02; eCFR part 1314.
- World Anti-Doping Agency. The 2026 Prohibited List. WADA 2026 Prohibited List.
- Shekelle PG, Hardy ML, Morton SC, et al. Efficacy and safety of ephedra and ephedrine for weight loss and athletic performance: a meta-analysis. JAMA. 2003;289(12):1537–1545. PubMed.
- Astrup A, Breum L, Toubro S, Hein P, Quaade F. The effect and safety of an ephedrine/caffeine compound compared to ephedrine, caffeine and placebo in obese subjects on an energy restricted diet. A double blind trial. Int J Obes Relat Metab Disord. 1992;16(4):269–277. PubMed.
- Astrup A, Lundsgaard C, Madsen J, Christensen NJ. Enhanced thermogenic responsiveness during chronic ephedrine treatment in man. Am J Clin Nutr. 1985;42(1):83–94. PubMed.
- Persky AM, Berry NS, Pollack GM, Brouwer KL. Modelling the cardiovascular effects of ephedrine. Br J Clin Pharmacol. 2004;57(5):552–562. PubMed; PMC.
- Haller CA, Jacob P 3rd, Benowitz NL. Pharmacology of ephedra alkaloids and caffeine after single-dose dietary supplement use. Clin Pharmacol Ther. 2002;71(6):421–432. PubMed.
- Haller CA, Jacob P 3rd, Benowitz NL. Enhanced stimulant and metabolic effects of combined ephedrine and caffeine. Clin Pharmacol Ther. 2004;75(4):259–273. PubMed.
- Lee A, Ngan Kee WD, Gin T. A quantitative, systematic review of randomized controlled trials of ephedrine versus phenylephrine for the management of hypotension during spinal anesthesia for cesarean delivery. Anesth Analg. 2002;94(4):920–926. PubMed.
- Bell DG, Jacobs I, Ellerington K. Effect of caffeine and ephedrine ingestion on anaerobic exercise performance. Med Sci Sports Exerc. 2001;33(8):1399–1403. PubMed.
- Bell DG, McLellan TM, Sabiston CM. Effect of ingesting caffeine and ephedrine on 10-km run performance. Med Sci Sports Exerc. 2002;34(2):344–349. PubMed.
- Jacobs I, Pasternak H, Bell DG. Effects of ephedrine, caffeine, and their combination on muscular endurance. Med Sci Sports Exerc. 2003;35(6):987–994. PubMed.
- Haller CA, Benowitz NL. Adverse cardiovascular and central nervous system events associated with dietary supplements containing ephedra alkaloids. N Engl J Med. 2000;343(25):1833–1838. PubMed.
- Bent S, Tiedt TN, Odden MC, Shlipak MG. The relative safety of ephedra compared with other herbal products. Ann Intern Med. 2003;138(6):468–471. PubMed.
- Morgenstern LB, Viscoli CM, Kernan WN, et al. Use of Ephedra-containing products and risk for hemorrhagic stroke. Neurology. 2003;60(1):132–135. PubMed.