CliffMadHoneyIndex

This is a reference index of the terms used in grayanotoxin and mad honey research. Each entry defines the term and links to the page on this site that carries the sources and the caveats. Definitions describe what the published literature reports. They are not consumption guidance.

Medical disclaimer: This page is for educational purposes only and is not medical advice. Mad honey contains grayanotoxin, which can cause serious adverse effects.

What this glossary covers

Compounds and chemistryWhat grayanotoxins are, which isoforms matter, and where they come fromMechanismHow the compounds act, and the clinical picture that followsMeasurementUnits, laboratory methods, certificates and concentration bandsClaims and regulationMedicinal benefit, dosage, lab results and the regulatory position

Compounds and chemistry

Grayanotoxins are a compound class, not a single molecule. Almost every confused claim about mad honey traces back to that distinction.

Grayanotoxin (GTX)

A class of diterpenoid polyols: organic compounds built on a tetracyclic diterpene carbon skeleton carrying multiple hydroxyl groups. Grayanotoxins occur exclusively in the plant family Ericaceae. Roughly 50 structurally distinct variants have been characterised and numbered. They are the compounds responsible for the physiological effects of mad honey. They are not psychedelics and they do not act on serotonergic receptors. They act on ion channels.

What are grayanotoxins

Grayanotoxins (plural usage)

Used when referring to the compound class as a whole, or to the mixture actually present in a given honey. A laboratory result for a real sample is almost always a mixture rather than a single isoform, which is why analytical reports quantify individual grayanotoxins separately and then report a total. A figure quoted without saying which isoforms it includes cannot be compared to another figure.

Grayanotoxin I (GTX I)

One of the two isoforms that dominate Rhododendron nectar and therefore mad honey, and one of the two most biologically active. GTX I is the isoform most often quantified in analytical studies of commercial and confiscated honey, so it is the figure most frequently seen on a laboratory report.

Grayanotoxin III (GTX III)

The other dominant and highly active isoform. GTX III is the 10-O-acetyl derivative of GTX I. Both bind receptor site 2 on voltage-gated sodium channels with comparable potency, which is why safety frameworks sum the two rather than treating either alone as the measure of a honey.

GTX honey

An informal shorthand for mad honey, used mainly in laboratory, import and trade contexts where the honey is described by the compound it contains rather than by its folk name. The term carries no separate technical meaning: GTX honey and mad honey are the same material. Because the shorthand says nothing about which isoforms or what concentration are present, it should not be read as a grade or a quality claim.

Diterpenoid polyol

The chemical class grayanotoxins belong to. Diterpenoids are built from four isoprene units; a polyol carries several hydroxyl groups. The structural feature that defines grayanotoxins is a bicyclo[3.2.1] ring system with particular oxygenation patterns, and those patterns determine biological activity.

Ericaceae

The heath family, the only plant family in which grayanotoxins are found. It includes rhododendrons, azaleas, pieris, leucothoe and related genera. A plant outside Ericaceae is not a grayanotoxin source, which is why provenance claims about mad honey reduce to claims about which Ericaceae species the bees foraged.

Rhododendron

The genus that supplies the nectar behind almost all mad honey. Botanists recognise roughly 700 Rhododendron species. Not all produce grayanotoxins, and among those that do, concentrations vary by species. This is the first of several reasons two honeys described identically by origin can differ substantially in laboratory results.

Distribution across Rhododendron species

Mad honey

Honey containing grayanotoxins at concentrations sufficient to produce physiological effects, produced where bees forage predominantly on grayanotoxin-bearing Ericaceae. Regional names include deli bal in Turkey. The term describes a compositional fact about a honey, not a product grade, and carries no implication about concentration.

Deli bal

The Turkish name for mad honey, most closely associated with the Black Sea provinces. The term appears throughout the clinical literature because the largest published case series on mad honey poisoning come from emergency departments in that region.

Mechanism

One binding event explains the entire clinical picture. The effects are consistent across cases; only their severity varies.

Voltage-gated sodium channel (VGSC)

The membrane protein that opens to admit sodium ions when a cell depolarises, then closes again through a process called inactivation. Grayanotoxins act here. Because these channels are central to nerve and cardiac muscle signalling, effects appear in heart rate, blood pressure and sensation rather than in mood or perception.

Sodium channel modulation by GTX I

Receptor site 2

The specific binding site on the voltage-gated sodium channel that grayanotoxin I occupies, shared with other lipophilic toxins. Binding here holds the channel open by interfering with inactivation. That failure of channels to close normally is the single mechanism underlying the whole clinical picture.

Mad honey toxidrome

The recognisable cluster of findings that appears together in grayanotoxin exposure: bradycardia, hypotension, nausea and vomiting, dizziness, and in some cases atrioventricular block. Naming it as a toxidrome matters clinically, because the combination points toward a cause a patient may not have volunteered.

Mad honey toxidrome

Bradycardia

A slower than normal heart rate. It is the cardinal finding in mad honey presentations, reported in more than 90 percent of symptomatic cases in the Black Sea case series literature.

Hypotension

Low blood pressure. In grayanotoxin exposure it typically accompanies bradycardia rather than occurring alone, and the pairing is part of what makes the presentation recognisable.

Atrioventricular (AV) block

A conduction delay or failure between the atria and the ventricles, graded by degree. High-grade AV block is the finding that separates the minority of hospitalised presentations needing temporary pacing from the majority managed with atropine and observation.

ECG changes in mad honey poisoning

Atropine

The antimuscarinic drug used as first-line treatment for symptomatic bradycardia in mad honey poisoning. Published reviews report it as effective in the majority of cases. Temporary cardiac pacing is reported in roughly 5 to 10 percent of hospitalised presentations, those with high-grade AV block. This entry records what the treatment literature reports. It is not first aid guidance.

Atropine: systematic review

LD50

The lethal dose 50 percent: the amount of a substance required to kill half a test population under specified experimental conditions. Published grayanotoxin LD50 values exist in rodent models. A single quoted number is close to meaningless without four accompanying facts: which isoform, which species, which route of administration, and what extrapolation caveats apply before an animal figure says anything about a person eating honey.

Grayanotoxin LD50 data

Measurement and laboratory reporting

Concentration describes the honey. Dose describes the exposure. Conflating the two is the most common reading error on a certificate of analysis.

The only formula that matters

delivered dose (mg) = concentration (mg/kg) x serving (kg)

Honey at 20 mg/kg in a 20 g serving delivers 0.4 mg of grayanotoxin. Honey at 50 mg/kg in the same serving delivers 1.0 mg. The concentration on a certificate describes the honey; only the serving decides the exposure. Use the dose calculator.

Concentration bands at a glance

BandTotal GTX I + III (mg/kg)Grayanotoxin in a 20 g serving
Traceunder 1under 0.02 mg
Low1 to 100.02 to 0.2 mg
Moderate10 to 300.2 to 0.6 mg
Highover 30over 0.6 mg

Serving column is concentration multiplied by a 20 g serving, shown to make the difference between concentration and delivered dose concrete. Bands are documented ranges drawn from the clinical and laboratory literature. They are not safe-versus-unsafe categories, and no concentration is safe for everyone.

mg/kg

Milligrams of grayanotoxin per kilogram of honey: the unit in which concentration is normally reported. It describes the honey, not the exposure. Two people eating the same honey receive different doses if they eat different amounts.

Micrograms per gram

An equivalent unit to mg/kg: one microgram per gram is one milligram per kilogram. Analytical papers often report in micrograms per gram while consumer-facing material uses mg/kg. The two are directly comparable without conversion, and checking which unit a figure uses is the first step in comparing two results.

Serving dose

The quantity of grayanotoxin actually delivered by a given amount of honey, which is concentration multiplied by serving size. This is the number that determines exposure, and it is the reason concentration alone cannot be read as strength.

Dose calculator

Concentration band

A documented range rather than a verdict. The Cliff Mad Honey Safety Standard sorts honey by total grayanotoxin, GTX I plus GTX III, in mg/kg, into the four bands shown above. The ranges are drawn from the clinical and laboratory literature. They are explicitly not safe-versus-unsafe categories, and no concentration is safe for everyone.

Concentration bands explained

Batch variation

The difference in grayanotoxin content between batches that are otherwise described identically. It is large enough to be the defining analytical fact about this material. In the largest published quantitative study of Nepalese mad honey, 60 samples analysed by LC-MS/MS showed GTX I concentrations spanning 0.75 to 64.86 micrograms per gram, an 86-fold difference. A result for one jar does not describe the next jar.

Batch variation data

LC-MS/MS

Liquid chromatography tandem mass spectrometry: the highest-sensitivity validated method for detecting and quantifying grayanotoxins, and the method used in the 60-sample Nepalese study. Where a report names its method, LC-MS/MS results carry the most analytical weight.

HPLC-UV

High performance liquid chromatography with ultraviolet detection: an older and more widely available approach. Grayanotoxins lack a strong chromophore, which makes ultraviolet detection harder for them than for many compounds and constrains how low a concentration a method can reliably quantify.

HPLC-UV methodology

Certificate of Analysis (CoA)

The laboratory document accompanying a tested batch. A CoA is only as informative as what it names: which isoforms were measured, by which method, with what limits of detection and quantification, on which batch, and on what date. A CoA that omits the batch identifier cannot be matched to the jar in front of you.

How to read a lab report

Limit of detection and limit of quantification

The lowest concentration a method can reliably detect, and the lowest it can reliably put a number on. The two are different, and the gap matters when reading a result. Not detected means the method found nothing above its own detection threshold, which is not the same statement as contains none.

Claims, regulation and terms that recur in search

These phrases drive most of the search demand around grayanotoxin, and each needs a careful answer rather than a yes or no.

Medicinal benefits of grayanotoxin

Grayanotoxins have a documented pharmacological mechanism, and mad honey has a long ethnographic record of traditional medicinal use, particularly in Anatolia. Neither of those facts establishes a clinical benefit. Traditional use records what people did; a mechanism records how a compound acts. What is missing is the part that would justify a health claim: controlled trials in humans showing benefit at a defined dose with an acceptable safety margin. The therapeutic-potential literature that exists is preclinical and exploratory. Anyone citing grayanotoxin benefits should be asked which study, in which model, at what dose.

Therapeutic potential: what the review says

Mad honey lab testing results

What a laboratory reports for a specific batch, normally as a concentration in mg/kg or micrograms per gram for named isoforms. Reading a result means reading four things together: the isoforms measured, the analytical method, the detection and quantification limits, and the batch the sample came from. Because of batch variation, a result is a statement about one batch on one date and cannot be generalised to a producer or a region.

Concentration reference tool

Mad honey dosage

A phrase that appears constantly in search, and one this site treats as a measurement question rather than a recommendation. Because delivered dose is concentration multiplied by serving size, and because concentration varies by batch, a serving described in spoons carries no fixed grayanotoxin content. EFSA in 2023 found that all commercially available mad honey concentrations raise health concerns under realistic consumption scenarios, and singled out children as a group of particular concern.

What the dosage evidence supports

EFSA

The European Food Safety Authority. Its 2023 assessment of grayanotoxins in food is the most substantial regulatory-science treatment of the compound class to date, and its conclusion that commercially available concentrations raise health concerns under realistic consumption is the reference point most often cited in European regulatory discussion.

Cliff Mad Honey Safety Standard

This site’s framework for describing a honey by its documented grayanotoxin concentration band rather than by marketing language. It is a descriptive scheme drawn from published ranges, maintained so two honeys can be compared on the same basis. It does not certify products and it does not designate any concentration as safe.

The Safety Standard

Who should not consume mad honey

A separate question from concentration, and the one most often skipped. Published guidance identifies groups for whom any exposure carries elevated risk, including people with cardiac conduction disease or on rate-limiting medication. EFSA singled out children.

Who should not consume it

How to use this glossary

Entries here are deliberately short. Each links to the page on this site that carries the full treatment, the sources and the caveats. Where a figure appears in an entry, it is reproduced from the study or assessment named in the linked page rather than restated independently.

Research referencesThe annotated primary literature behind every figure on this site.Content integrityHow sourcing, review and correction are handled here.ToolsDose calculator and concentration reference.

Scope note. This glossary defines terminology. It is not medical advice, it is not a dosing guide, and no entry should be read as an endorsement of consumption. Anyone who suspects mad honey poisoning should seek emergency medical care rather than consult a reference page.