Isolating and Tasting Resiniferatoxin—The Hottest Known Substance

The Scoville scale is used to measure the “heat” of chili peppers, hot sauces made from them, and other foods containing capsaicin and capsaicinoid molecules which stimulate the heat receptors in the tissue of mammals (but not, interestingly, birds) and give hot food its kick. The Scoville scale was originally defined as an organoleptic test in which the heat was defined as the dilution of an extract from the pepper by sugar water at which five trained testers could not detect the presence of the pepper extract. Today, the test is usually performed with high-performance liquid chromatography (HPLC) measurement of the capsaicin content of the pepper or food.

On the Scoville scale, Tabasco sauce comes in at 2500, Jalapeño peppers between 2500 and 8000, Habanero peppers between 100,000 and 350,000, and the Carolina Reaper pepper above 1.5 million. Police grade pepper spray is between 2.5 and 3.5 million, and pure capsaicin (dissolved in oil, as it is insoluble in water) scores 16 million Scoville heat units.

But these are all capsaicin-based heat. Are the other molecules that are hotter? You bet there are! Resiniferatoxin, a molecule produced by the resin spurge (Euphorbia resinifera) plant found in Morocco, has a Scoville rating of 16 billion, a thousand times hotter than pure capsaicin. What happens if you purify it from plant’s sap and give it the old taste test?


Euphorbia resinifera contains a milky fluid or latex, which in its dried form is called Euphorbium. It has high concentration of resiniferatoxin, an analog of capsaicin, the primary vanilloid compound found in hot peppers. It can interact with a vanilloid receptor on primary sensory neurons mediating pain (nociception) and neurogenic inflammation. The pain sensing cation channel is TRPV1.[3] Resiniferatoxin has been used as a starting point in the development of a novel class of analgesics. Desensitization to topical resiniferatoxin has been tested in clinical trials to evaluate its potential to relieve neuropathic pain, as in diabetic polyneuropathy and postherpetic neuralgia.[3] Resiniferatoxin injected subcutaneously into a rat hind paw several minutes before a surgical incision reduced postsurgical pain for 10 days in a NIH study published March 2018.[4] It has been tested to treat pain with advanced cancer.[5]

Resiniferatoxin was isolated in 1975.[3] Euphorbium has been used since at least its first written record from the time of Roman Emperor Augustus.[3]


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