Ephedra gerardiana · PhytoNexus

01 Identity and provenance

Accepted binomial: Ephedra gerardiana
Common names: Himalayan Ephedra
Family (APG IV): Ephedraceae
Part used: Stem
Verification tier: Tier 2 · Verified Clinical columns reviewed and a source is on record.
Reviewer note (2026 audit): Shekelle PG et al. RAND/AHRQ Evidence Report No. 76, 2003 | Haller CA & Benowitz NL. N Engl J Med 2000;343:1833-8 | LiverTox NBK548711 | VERIFIED 2026 (batch 3) - synthetic analogue, application, interactions, side effects and references populated from retrieved primary/regulatory sources. Interactions labelled CLINICAL vs THEORETICAL. Marketed-formulation column intentionally blank. | COMPOSITION

02 Constituent chemistry

Chemical class	Marker compound	Synthetic analogue in use
Alkaloid	Ephedrine Stem	Pseudoephedrine,Phenylephrine

The analogue column is what makes the interaction reasoning tractable: where a constituent has a marketed structural counterpart, the counterpart's interaction profile is the starting hypothesis for the plant.

Looking up structures and physicochemical properties from PubChem…

03 Stated application

Reported activity: Traditional bronchodilator, nasal decongestant and CNS stimulant. NOTE: most safety data derive from E. sinica (ma huang, entry 54); species-specific human data for E. gerardiana are sparse but the alkaloid is the same.
Reported adverse effects: BANNED AS A SUPPLEMENT INGREDIENT. FDA concluded in 2004 that ephedrine-alkaloid dietary supplements pose a risk of heart attack, stroke and death, and prohibited their sale. Ephedra was associated with more reports of death, MI, arrhythmia, hypertension, stroke and seizure than all other dietary supplements combined. RAND review: no serious adverse events in 52 RCTs (trial populations were pre-screened and low-risk), but sentinel case reports included deaths, MIs, strokes, seizures and psychiatric events - the trial-versus-real-world gap is the whole point here. Also idiosyncratic hepatotoxicity up to acute liver failure. Nervousness, palpitations, insomnia, tachycardia at lower doses.

04 Interaction matrix

Source column, verbatim: CLINICAL: MAO inhibitors (hypertensive crisis), tricyclic antidepressants, other sympathomimetics, caffeine (most adverse events involved combination stimulant products), antihypertensives (antagonised), cardiac glycosides and general anaesthetics (arrhythmia risk).
Normalised onto 6 canonical drug classes below.

Curated from the reviewed source

Drug class	Severity	Mechanism type	Provenance	Expected effect
Antihypertensives Cardiovascular	4Contraindicated	PD-additive	curated A	Orthostatic hypotension, dizziness, syncope and falls; or loss of blood-p…	why ▾
Chemistry of this pair. Phenethylamine and methylxanthine constituents release noradrenaline and block adenosine receptors, producing direct sympathomimetic drive. Class mechanism. Vasodilator, diuretic, ACE-inhibitory and calcium-antagonist activity in botanical extracts adds to prescribed blood-pressure lowering. A minority (ephedrine-, glycyrrhizin- and caffeine-bearing) act in the opposite direction and antagonise control. Expected Orthostatic hypotension, dizziness, syncope and falls; or loss of blood-pressure control with pressor botanicals. Management Home BP log for 2 weeks after any change. Warn about postural symptoms; review in the elderly and in those on multiple agents. Onset rapid Evidence A - human data with a cited source Matched on “antihypertensives” Find evidence for this pair Map this mechanism
Cardiac glycosides (digoxin, digitoxin) Cardiovascular	4Contraindicated	PD-additive + PK-transporter + assay interference	curated A	Nausea, xanthopsia, bradyarrhythmia, AV block, ventricular tachycardia an…	why ▾
Class mechanism. Cardenolide- and bufadienolide-bearing plants are themselves Na+/K+-ATPase inhibitors, so co-administration is pharmacological overdose. Several also inhibit intestinal P-glycoprotein, raising digoxin exposure, and cross-react with digoxin immunoassays so that serum levels become uninterpretable. Expected Nausea, xanthopsia, bradyarrhythmia, AV block, ventricular tachycardia and death; falsely reassuring or falsely high assay results. Management Treat as an absolute contraindication. If exposure has occurred, manage on ECG and clinical grounds, not on assay values, and consult toxicology about digoxin-specific Fab. Onset rapid Evidence A - human data with a cited source Matched on “cardiac glycosides” Find evidence for this pair Map this mechanism
CNS stimulants and sympathomimetics CNS	4Contraindicated	PD-additive	curated A	Tachycardia, hypertension, arrhythmia, insomnia, anxiety, stroke and myoc…	why ▾
Chemistry of this pair. Phenethylamine and methylxanthine constituents release noradrenaline and block adenosine receptors, producing direct sympathomimetic drive. Class mechanism. Ephedrine, pseudoephedrine, caffeine, synephrine and cathine-type constituents add to prescribed stimulant and decongestant sympathomimetic drive. Expected Tachycardia, hypertension, arrhythmia, insomnia, anxiety, stroke and myocardial infarction in susceptible people. Management Avoid in cardiovascular disease, hyperthyroidism and pregnancy. Ask about weight-loss and sports supplements by brand. Onset rapid Evidence A - human data with a cited source Matched on “sympathomimetics” Find evidence for this pair Map this mechanism
Monoamine oxidase inhibitors CNS	4Contraindicated	PD-additive	curated A	Hypertensive crisis, hyperpyrexia, serotonin syndrome, intracranial haemo…	why ▾
Class mechanism. Beta-carboline (harmine, harmaline) and related botanical alkaloids are themselves reversible MAO-A inhibitors. Combined with a prescribed MAOI, or with tyramine-rich food or sympathomimetics, the pressor and serotonergic reserve is abolished. Expected Hypertensive crisis, hyperpyrexia, serotonin syndrome, intracranial haemorrhage. Management Absolute contraindication. Apply the full MAOI dietary and drug restriction list to the botanical as well. Onset rapid Evidence A - human data with a cited source Matched on “mao inhibitors” Find evidence for this pair Map this mechanism
Antidepressants (SSRI, SNRI, TCA) CNS	3Major	PD-additive serotonergic + PK-CYP2D6	curated A	Serotonin syndrome (agitation, clonus, hyperthermia, autonomic instabilit…	why ▾
Class mechanism. Hypericin- and hyperforin-type constituents inhibit monoamine reuptake and induce CYP3A4/2C19 and P-glycoprotein; others inhibit CYP2D6, raising tricyclic and SSRI concentrations. Expected Serotonin syndrome (agitation, clonus, hyperthermia, autonomic instability) or loss of antidepressant effect on withdrawal of an inducer. Management Screen for serotonergic burden before adding. Taper rather than stop abruptly. Consider therapeutic drug monitoring for tricyclics. Onset rapid Evidence A - human data with a cited source Matched on “tricyclic antidepressants” Find evidence for this pair Map this mechanism
General and local anaesthetics (perioperative) Perioperative	3Major	PD-additive + PK-CYP	curated A	Prolonged emergence, intraoperative haemodynamic instability, excess surg…	why ▾
Class mechanism. Botanical CNS depressants prolong anaesthetic recovery, antiplatelet and coumarin constituents raise surgical bleeding, and sympathomimetics destabilise intraoperative haemodynamics. CYP modulation changes opioid and muscle-relaxant handling. Expected Prolonged emergence, intraoperative haemodynamic instability, excess surgical bleeding, delayed neuraxial haematoma. Management Ask about all botanicals at pre-anaesthetic assessment and stop them 1-2 weeks before surgery unless there is a reason not to. Onset rapid Evidence A - human data with a cited source Matched on “anaesthetics” Find evidence for this pair Map this mechanism

Predicted from constituent chemistry

These edges are not clinical findings. Each one is a rule inference: a constituent class in this plant is known to act on a target that the drug class also acts on. They are shown because a blank cell reads as “safe”, and for a Tier 1 entry a blank cell only means “not yet looked at”. Treat them as a literature-search agenda, not as a warning.

Drug class	Severity	Mechanism type	Provenance	Expected effect
Antiarrhythmics Cardiovascular	4Contraindicated	PD-additive + electrolyte-mediated	predicted D	Proarrhythmia, QT prolongation, torsade de pointes, ventricular arrhythmi…	why ▾
Chemistry of this pair. Phenethylamine and methylxanthine constituents release noradrenaline and block adenosine receptors, producing direct sympathomimetic drive. Class mechanism. Botanicals that shift potassium or magnesium, block sodium or potassium channels, or prolong repolarisation add to class I and class III antiarrhythmic effects on an already unstable myocardium. Expected Proarrhythmia, QT prolongation, torsade de pointes, ventricular arrhythmia. Management Avoid. If unavoidable, baseline and follow-up ECG with QTc measurement plus potassium and magnesium correction. Onset rapid Evidence D - in silico rule prediction only Find evidence for this pair Map this mechanism
Cardiotoxic drugs Organ toxicity	4Contraindicated	Organ-toxicity additive	predicted D	Arrhythmia, reduced ejection fraction, myocarditis-like presentation.	why ▾
Chemistry of this pair. Phenethylamine and methylxanthine constituents release noradrenaline and block adenosine receptors, producing direct sympathomimetic drive. Class mechanism. Aconitine-type alkaloids, cardenolides and high-dose ephedrine add to anthracycline, trastuzumab and antiarrhythmic myocardial toxicity. Expected Arrhythmia, reduced ejection fraction, myocarditis-like presentation. Management Avoid during cardiotoxic chemotherapy. Baseline and follow-up echocardiography where exposure has occurred. Onset unspecified Evidence D - in silico rule prediction only Find evidence for this pair Map this mechanism
Narrow-therapeutic-index CYP3A4 substrates Pharmacokinetic	4Contraindicated	PK-CYP3A4	predicted D	Toxic accumulation or subtherapeutic failure of the co-prescribed drug, s…	why ▾
Chemistry of this pair. Alkaloidal bases have pH-dependent absorption and commonly interact with hepatic CYP isoenzymes and efflux transporters. Class mechanism. Furanocoumarins, bergamottin, piperine, glabridin and berberine inhibit CYP3A4; hyperforin, andrographolide and several diterpenes induce it through PXR. Because CYP3A4 handles roughly half of marketed drugs, the affected list is broad and the direction is product-specific. Expected Toxic accumulation or subtherapeutic failure of the co-prescribed drug, sometimes fatal for antiarrhythmics, immunosuppressants and oncology agents. Management Screen the full regimen for 3A4 substrates. Where the substrate has a narrow index, avoid rather than monitor. Onset unspecified Evidence D - in silico rule prediction only Find evidence for this pair Map this mechanism
Antacids, PPIs and H2 blockers Gastrointestinal	2Moderate	PK-absorption	predicted D	Reduced or erratic absorption of alkaloids; heartburn and reflux from pre…	why ▾
Chemistry of this pair. Alkaloidal bases have pH-dependent absorption and commonly interact with hepatic CYP isoenzymes and efflux transporters. Class mechanism. Gastric pH elevation alters the dissolution and ionisation of alkaloidal and enteric-coated botanical products; menthol- and peppermint-oil products lose their enteric protection at high pH and can be released prematurely. Expected Reduced or erratic absorption of alkaloids; heartburn and reflux from premature release of volatile-oil preparations. Management Separate administration by 2 hours. Avoid non-enteric peppermint oil in reflux disease. Onset unspecified Evidence D - in silico rule prediction only Find evidence for this pair Map this mechanism

05 Hazard register

product variability - trial populations were pre-screened; real-

06 Confusable material

These entries could be mistaken for this one in trade, in the herbarium, or in a prescription. Powdered material is often indistinguishable, so the check is macroscopic, microscopic and chromatographic rather than nominal.

Ephedra sinica

Ephedra

Ephedraceae

Same genus (Ephedra)

07 Mechanism map

Chemistry sorts to the left, pharmacology to the right. Dashed edges are predicted. Drag nodes, scroll to zoom, export at 3× for a figure.

species

chemical class

marker compound

drug class

expected effect

hazard

08 Open literature

Abstract-scoped query built from this binomial, its common names and its marker compounds, run live against Europe PMC, PubMed and OpenAlex, then ranked locally against an evidence hierarchy.

Checking openFDA spontaneous reports…

09 Isomechanistic neighbours

Species whose interaction profile overlaps this one, ranked by shared severity weight rather than by count — a shared contraindication counts for more than a shared minor signal. Practical use: these are the plants you should not stack with this one, because the mechanisms summate.

Species	Family	Shared classes	Jaccard
Ephedra sinica Ephedra	Ephedraceae	8	0.80
Citrus aurantium Bitter Orange	Rutaceae	6	0.55
Strychnos nux-vomica Nux Vomica	Loganiaceae	6	0.46
Camellia sinensis Green Tea	Theaceae	5	0.31
Peganum harmala Syrian Rue	Nitrariaceae	6	0.50
Aconitum napellus Monkshood	Ranunculaceae	5	0.45

10 References and notes

Source column: FDA final rule, 2004 (ephedrine alkaloid supplements)

FDA final rule, 2004 (ephedrine alkaloid supplements)

2004 manual

BibTeX for all 1 records

@article{anon2004,
  title = {FDA final rule, 2004 (ephedrine alkaloid supplements)},
  year = {2004},
}

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