Ephedra

Ma huang appears across the classical Chinese materia medica ^{24,29Reference 24Tang et al. · 2023ReviewEphedrae Herba: a review of its phytochemistry, pharmacology, clinical application and alkaloid toxicity — reviewView study →Reference 29Yang et al. · 2013Introduction to Chinese Materia Medica (3rd ed.). (Pg}.

The dried stem is classified as acrid and slightly bitter in taste and warm in nature, entering the Lung and Bladder channels ^{24,29,30Reference 24Tang et al. · 2023ReviewEphedrae Herba: a review of its phytochemistry, pharmacology, clinical application and alkaloid toxicity — reviewView study →Reference 29Yang et al. · 2013Introduction to Chinese Materia Medica (3rd ed.). (PgReference 30Wu · 2005An Illustrated Chinese Materia Medica}.

It is used to promote sweating and disperse wind-cold, to diffuse the lungs and relieve wheezing, to promote the flow of lung Qi, and to reduce oedema by increasing urination. It is given classically for wind-cold colds without sweating, chest oppression, cough and wheezing from excess, and wind oedema ^{29Reference 29Yang et al. · 2013Introduction to Chinese Materia Medica (3rd ed.). (Pg}.

Traditional practice cautions against it in people who sweat easily, in deficiency-type asthma or weak constitutions, and in high blood pressure or heart disease, and warns against large doses ^{29,30Reference 29Yang et al. · 2013Introduction to Chinese Materia Medica (3rd ed.). (PgReference 30Wu · 2005An Illustrated Chinese Materia Medica}.

Several Kampo formulas containing ephedra are common first treatments for infections in Japan ^{17Reference 17Odaguchi et al. · 2025RCTSafety and efficacy of ephedrine alkaloids-free Ephedra Herb extract (EFE) for mild COVID-19: a randomised controlled trial — randomised controlled trialView study →}. The best known is maoto (ma-huang-tang), a four-herb formula given for influenza and feverish colds, including in children ^{12,13,14Reference 12Nabeshima et al. · 2012RCTA randomised, controlled trial comparing traditional herbal medicine (maoto) and neuraminidase inhibitors in influenza — randomised controlled trialView study →Reference 13Yoshino et al. · 2019Meta-analysisThe use of maoto (Ma-Huang-Tang) to alleviate flu symptoms: a systematic review and meta-analysis — systematic review, meta-analysisView study →Reference 14Kubo et al. · 2007ObservationalAntipyretic effect of Mao-to, a Japanese herbal medicine, for treatment of type A influenza infection in children — cohort/observationalView study →}.

Western medicine took up ephedra mainly through its isolated alkaloid ephedrine, used as a bronchodilator for asthma and wheezing and as a nasal decongestant ^{6Reference 6Abourashed et al. · 2003ReviewEphedra in perspective — a current review — reviewView study →}. Ephedrine alkaloids were also used to treat the low blood pressure caused by spinal anaesthesia, and urinary incontinence ^{7Reference 7Ibragic et al. · 2015Chemical composition of various Ephedra species — analyticalView study →}.

In the late twentieth century ephedra was sold in the United States as a caffeine-paired weight-loss and stimulant supplement. That use led to the 2004 ban ^{6,7Reference 6Abourashed et al. · 2003ReviewEphedra in perspective — a current review — reviewView study →Reference 7Ibragic et al. · 2015Chemical composition of various Ephedra species — analyticalView study →}.

This indication has the most human trial data. A 6-month double-blind RCT (n=167) tested a ma huang and kola-nut supplement delivering 90 mg ephedrine alkaloids plus 192 mg caffeine daily. It produced greater loss of body weight (−5.3 vs −2.6 kg) and body fat than placebo ^{2Reference 2Boozer et al. · 2002RCTHerbal ephedra/caffeine for weight loss: a 6-month randomised, double-blind, placebo-controlled trial — randomised controlled trialView study →}.

The 2003 JAMA meta-analysis concluded that ephedra or ephedrine promotes short-term weight loss of roughly 0.9 kg a month more than placebo. It found no data supporting long-term use, and a 2.2- to 3.6-fold increase in the odds of psychiatric, autonomic and gastrointestinal symptoms and heart palpitations ^{1Reference 1Shekelle et al. · 2003Meta-analysisEfficacy and safety of ephedra and ephedrine for weight loss and athletic performance: a meta-analysis — meta-analysisView study →}.

A 2024 meta-analysis of 16 RCTs found significant reductions in BMI, body weight and waist circumference, with no difference in adverse events between groups ^{3Reference 3Cho et al. · 2024Meta-analysisEfficacy and safety of ephedra-containing oral medications for weight reduction: a systematic review, meta-analysis and dose-response analysis — systematic review, meta-analysisView study →}.

The effect comes from adrenergic stimulation of metabolic rate and thermogenesis, and is consistently larger when ephedrine is combined with caffeine ^{4Reference 4Diepvens et al. · 2007ReviewObesity and thermogenesis related to the consumption of caffeine, ephedrine, capsaicin and green tea — reviewView study →}.

The US FDA banned ephedra-containing dietary supplements in 2004, judging that they posed an unacceptable risk ^{7Reference 7Ibragic et al. · 2015Chemical composition of various Ephedra species — analyticalView study →}.

Gap: The benefit is small, was almost never shown for the herb alone (ephedrine + caffeine was the usual combination), and comes with a documented signal for serious cardiovascular and CNS adverse events.

Ephedra’s classical use for asthma and wheezing rests on ephedrine, a mixed α- and β-adrenergic agonist that relaxes bronchial smooth muscle and opens the airways. Modern β-agonist inhalers work through the same receptors, but ephedrine is far less selective and is active by mouth ^{6,24Reference 6Abourashed et al. · 2003ReviewEphedra in perspective — a current review — reviewView study →Reference 24Tang et al. · 2023ReviewEphedrae Herba: a review of its phytochemistry, pharmacology, clinical application and alkaloid toxicity — reviewView study →}.

This bronchodilator pharmacology is well established for the isolated alkaloid. Ephedrine was replaced in asthma care by selective, inhaled β2-agonists because its non-selective action causes cardiac and CNS side effects ^{6Reference 6Abourashed et al. · 2003ReviewEphedra in perspective — a current review — reviewView study →}.

There are essentially no contemporary RCTs of standardised whole-herb ephedra for asthma.

The stem’s second major alkaloid, pseudoephedrine, is a proven oral decongestant. It constricts the blood vessels of the nasal lining through α-adrenergic agonism, and has extensive human trial support as a standalone drug and in combination products for allergic rhinitis and the common cold ^{7,23Reference 7Ibragic et al. · 2015Chemical composition of various Ephedra species — analyticalView study →Reference 23Corren et al. · 1997RCTEfficacy and safety of loratadine plus pseudoephedrine in patients with seasonal allergic rhinitis and mild asthma — randomised controlled trialView study →}.

A double-blind RCT of loratadine plus pseudoephedrine, for example, showed significant relief of nasal congestion versus placebo in seasonal allergic rhinitis ^{23Reference 23Corren et al. · 1997RCTEfficacy and safety of loratadine plus pseudoephedrine in patients with seasonal allergic rhinitis and mild asthma — randomised controlled trialView study →}.

Ephedrine and pseudoephedrine are the main alkaloids of the genus; in some species ephedrine makes up as much as 90% of the total alkaloids, and in others pseudoephedrine as much as 99% ^{7Reference 7Ibragic et al. · 2015Chemical composition of various Ephedra species — analyticalView study →}. The human evidence is for the purified alkaloid at a controlled dose, not for a tea or tincture of variable alkaloid content.

Gap: Efficacy is shown for isolated pseudoephedrine; the whole herb delivers an unstandardised and variable dose of the same molecule, so the trial data do not transfer directly to herbal preparations.

Ephedrine is a central nervous system stimulant that activates adrenergic receptors, raising alertness, heart rate and energy expenditure. This is the basis for its use as a pre-workout and study aid, and for its potential for abuse ^{4,6Reference 4Diepvens et al. · 2007ReviewObesity and thermogenesis related to the consumption of caffeine, ephedrine, capsaicin and green tea — reviewView study →Reference 6Abourashed et al. · 2003ReviewEphedra in perspective — a current review — reviewView study →}.

The 2003 meta-analysis found no trials of ephedra for athletic performance. The seven trials of ephedrine were too varied to combine, and the authors judged the evidence insufficient ^{1Reference 1Shekelle et al. · 2003Meta-analysisEfficacy and safety of ephedra and ephedrine for weight loss and athletic performance: a meta-analysis — meta-analysisView study →}.

The stimulant effect is the same one that drives the herb’s cardiovascular risk.

Two lines of evidence support an antiviral role. The first is the ephedra-containing Kampo formula maoto (ma-huang-tang). A randomised trial (n=28) found maoto comparable to oseltamivir and zanamivir for shortening influenza fever, and a 2019 meta-analysis reported it reduced flu symptom duration when added to neuraminidase inhibitors ^{12,13Reference 12Nabeshima et al. · 2012RCTA randomised, controlled trial comparing traditional herbal medicine (maoto) and neuraminidase inhibitors in influenza — randomised controlled trialView study →Reference 13Yoshino et al. · 2019Meta-analysisThe use of maoto (Ma-Huang-Tang) to alleviate flu symptoms: a systematic review and meta-analysis — systematic review, meta-analysisView study →}.

An observational study in children showed an antipyretic effect in type A influenza ^{14Reference 14Kubo et al. · 2007ObservationalAntipyretic effect of Mao-to, a Japanese herbal medicine, for treatment of type A influenza infection in children — cohort/observationalView study →}.

Because maoto is a four-herb formula, these results cannot be attributed to ephedra alone.

The second line is the ephedrine-alkaloids-free extract (EFE). In vitro it cut SARS-CoV-2 titres by more than 99% and inhibited respiratory syncytial virus, with condensed tannins identified as the active macromolecule ^{15,16Reference 15Uema et al. · 2023In vitroAntiviral effect of ephedrine alkaloids-free Ephedra Herb extract against SARS-CoV-2 in vitro — in vitroView study →Reference 16Fujikane et al. · 2024In vitroAntiviral effect of alkaloids-free Ephedra Herb extract on respiratory syncytial virus infection — in vitroView study →}. A randomised trial (n=81) in mild COVID-19 found EFE safe, but no better than placebo, except that nausea resolved faster ^{17Reference 17Odaguchi et al. · 2025RCTSafety and efficacy of ephedrine alkaloids-free Ephedra Herb extract (EFE) for mild COVID-19: a randomised controlled trial — randomised controlled trialView study →}.

Gap: The strongest human data are for a multi-herb formula, not ephedra alone; the ephedra-specific antiviral work is largely in vitro, and the one human EFE trial is small.

Ephedra carries anti-inflammatory activity in constituents other than the stimulant alkaloids. From the roots, the compounds ephedrannin A and ephedrannin B inhibited LPS-induced inflammatory mediators in macrophages by suppressing NF-κB signalling in vitro ^{9Reference 9Kim et al. · 2010In vitroEphedrannin A and B from roots of Ephedra sinica inhibit lipopolysaccharide-induced inflammatory mediators — in vitroView study →}.

Separately, an acidic stem polysaccharide (ESP-B4) reduced pro-inflammatory cytokines and NF-κB p65 nuclear translocation via TLR4 in cultured cells, and improved adjuvant-induced arthritis in rats ^{10Reference 10Wang et al. · 2016In vitroA pure polysaccharide (ESP-B4) from Ephedra sinica treating arthritis and inhibiting cytokine expression via TLR4/NF-κB — animal model, in vitroView study →}.

The alkaloid-free extract also shows anti-inflammatory and analgesic activity, including prevention of paclitaxel-induced neuropathic pain in mice, attributed to non-alkaloid macromolecules ^{11,18Reference 11Hyuga et al. · 2016In vitroEphedrine alkaloids-free Ephedra Herb extract: a safer alternative to ephedra with comparable analgesic, anticancer and anti-influenza activity — in vitro, animal modelView study →Reference 18Huang et al. · 2025AnimalPreventive and therapeutic effects of ephedrine alkaloids-free Ephedra Herb extract on paclitaxel-induced peripheral neuropathic pain — animal modelView study →}.

The evidence is entirely animal and cell-based, much of it from root or isolated-fraction material rather than the whole medicinal stem.

Antioxidant activity is concentrated in the non-alkaloid, water-soluble fractions. Polysaccharides isolated from Ephedra alata stems showed concentration-dependent radical-scavenging activity in standard in-vitro assays (DPPH, reducing power) ^{21Reference 21Soua et al. · 2020In vitroWater-soluble polysaccharides from Ephedra alata stems: structural characterisation, functional properties and antioxidant activity — in vitroView study →}.

In animal models, methanolic E. alata extract restored glutathione, superoxide dismutase and catalase and lowered lipid peroxidation in cisplatin-treated rats, and E. pachyclada extract showed DPPH and β-carotene bleaching activity in vitro ^{19,20Reference 19Ghasemi et al. · 2014AnimalProtective effects of Ephedra pachyclada extract on mouse models of carbon tetrachloride-induced chronic and acute liver failure — animal modelView study →Reference 20Sioud et al. · 2020AnimalMethanolic extract of Ephedra alata ameliorates cisplatin-induced nephrotoxicity and hepatotoxicity through reducing oxidative stress and genotoxicity — animal modelView study →}.

The findings are in-vitro or animal, use other species (E. alata, E. pachyclada) rather than E. sinica, and include no human antioxidant data.

Ephedra extracts protect the liver in chemically induced injury models. Ephedra pachyclada extract reduced markers of both acute and chronic carbon-tetrachloride liver damage in mice ^{19Reference 19Ghasemi et al. · 2014AnimalProtective effects of Ephedra pachyclada extract on mouse models of carbon tetrachloride-induced chronic and acute liver failure — animal modelView study →}, and E. alata methanolic extract lessened cisplatin-induced liver toxicity and genotoxicity in rats by lowering oxidative stress ^{20Reference 20Sioud et al. · 2020AnimalMethanolic extract of Ephedra alata ameliorates cisplatin-induced nephrotoxicity and hepatotoxicity through reducing oxidative stress and genotoxicity — animal modelView study →}.

The effect is ascribed to free-radical scavenging by non-alkaloid constituents rather than to ephedrine. All of it comes from rodent toxicant models in species other than E. sinica, with no clinical liver data.

The glycans ephedrans A–E, isolated from Ephedra distachya, lowered blood glucose in animals in the 1985 study that named them ^{8Reference 8Konno et al. · 1985AnimalIsolation and hypoglycemic activity of ephedrans A, B, C, D and E, glycans of Ephedra distachya herbs — animal modelView study →}. Later reviews list hypoglycemic activity among the herb’s non-alkaloid actions, but the primary data trace back largely to that single early report ^{22Reference 22Zhang et al. · 2018ReviewPhytochemistry and pharmacology of the genus Ephedra — reviewView study →}. It is one old animal study, in another species, and has not been replicated in humans.

Heart and nervous system. Controlled trials of ephedra or ephedrine linked them to 2.2- to 3.6-fold higher odds of psychiatric, autonomic and gastrointestinal symptoms and heart palpitations ^{1Reference 1Shekelle et al. · 2003Meta-analysisEfficacy and safety of ephedra and ephedrine for weight loss and athletic performance: a meta-analysis — meta-analysisView study →}. Case reports describe myocardial infarction, arrhythmia, stroke and death ^{1,5Reference 1Shekelle et al. · 2003Meta-analysisEfficacy and safety of ephedra and ephedrine for weight loss and athletic performance: a meta-analysis — meta-analysisView study →Reference 5Haller et al. · 2000ObservationalAdverse cardiovascular and central nervous system events associated with dietary supplements containing ephedra alkaloids — cohort/observational case seriesView study →}.

US adverse-event reports. In a review of 140 reports submitted to the FDA in 1997–1999, high blood pressure was the most frequent problem, followed by palpitations or a fast heart rate, stroke and seizures. Ten events ended in death and thirteen in permanent disability ^{5Reference 5Haller et al. · 2000ObservationalAdverse cardiovascular and central nervous system events associated with dietary supplements containing ephedra alkaloids — cohort/observational case seriesView study →}. The FDA banned ephedra dietary supplements in 2004 ^{7Reference 7Ibragic et al. · 2015Chemical composition of various Ephedra species — analyticalView study →}.

Contraindications. Ephedra is contraindicated in cardiovascular disease, high blood pressure, thyroid disease, diabetes and prostate enlargement, and it is not for use in children ^{5,6Reference 5Haller et al. · 2000ObservationalAdverse cardiovascular and central nervous system events associated with dietary supplements containing ephedra alkaloids — cohort/observational case seriesView study →Reference 6Abourashed et al. · 2003ReviewEphedra in perspective — a current review — reviewView study →}.

Interactions. It must not be combined with monoamine oxidase inhibitors, where it can precipitate fatal hypertension, or with cardiac glycosides ^{5,6Reference 5Haller et al. · 2000ObservationalAdverse cardiovascular and central nervous system events associated with dietary supplements containing ephedra alkaloids — cohort/observational case seriesView study →Reference 6Abourashed et al. · 2003ReviewEphedra in perspective — a current review — reviewView study →}. The most relevant interaction in practice is added heart and nervous-system stimulation with caffeine, the combination used in nearly all the weight-loss products implicated in adverse events. Guanethidine can enhance ephedra’s effect, and use with halothane may provoke arrhythmias ^{5,6Reference 5Haller et al. · 2000ObservationalAdverse cardiovascular and central nervous system events associated with dietary supplements containing ephedra alkaloids — cohort/observational case seriesView study →Reference 6Abourashed et al. · 2003ReviewEphedra in perspective — a current review — reviewView study →}. These interactions act through the drugs’ effects on the body, not on how drugs are broken down.

Drug metabolism. In people, most of a dose of ephedrine leaves the body unchanged in the urine, with only a minor share broken down in the liver ^{37Reference 37Sever et al. · 1975Clinical trialThe metabolism of (-)-ephedrine in man — human studyView study →}. In rats, two weeks of ephedra water decoction induced the liver enzyme CYP1A2 and lowered blood levels of the asthma drug theophylline, which has not been tested in people ^{36Reference 36Tang et al. · 2012AnimalEffects of ephedra water decoction and cough tablets containing ephedra and liquorice on CYP1A2 and the pharmacokinetics of theophylline in rats — animal modelView study →}.

Product quality. Commercial ephedra products have been spiked with synthetic ephedrine alkaloids ^{7Reference 7Ibragic et al. · 2015Chemical composition of various Ephedra species — analyticalView study →}.

Short-term, supervised use. Use should be short-term only and under expert supervision. An ephedrine-alkaloid-free extract has been developed to keep therapeutic activity while removing these adrenergic hazards ^{11,17Reference 11Hyuga et al. · 2016In vitroEphedrine alkaloids-free Ephedra Herb extract: a safer alternative to ephedra with comparable analgesic, anticancer and anti-influenza activity — in vitro, animal modelView study →Reference 17Odaguchi et al. · 2025RCTSafety and efficacy of ephedrine alkaloids-free Ephedra Herb extract (EFE) for mild COVID-19: a randomised controlled trial — randomised controlled trialView study →}.

Contraindications

• Cardiovascular conditions and hypertension
• Thyroid conditions
• Enlarged prostate
• Diabetes
• Pregnancy & lactation
• Not for use in children