Greater Celandine

Chelidonium majus L. was published by Linnaeus in Species Plantarum in 1753 and is the accepted name in Kew’s Plants of the World Online (POWO). It belongs to Papaveraceae, the poppy family; Grieve’s A Modern Herbal (1931) notes that its four petals arranged in a cross suggest the cabbage family, but the dense mass of stamens at the center marks it as a poppy relative. Zielińska and colleagues (Frontiers in Pharmacology 2018) explain that the genus was long treated as having a single species, and describe a 1982 proposal by Krahulcová to separate an East Asian plant as C. asiaticum; Kew’s data portal lists two subspecies, subsp. majus and subsp. grandiflorum. POWO gives the native range as Macaronesia, Europe to western Siberia, and the Mediterranean to northern Iran, with native records reaching China, Korea, and the Russian Far East. It is introduced in New Zealand, parts of South America, and much of North America, from Nova Scotia and Ontario to North Carolina and west to Colorado, Utah, Montana, Washington, and British Columbia. In Britain the Botanical Society of Britain and Ireland (BSBI) treats it as an archaeophyte, an ancient introduction, with fossil evidence of its presence since Roman times.

It is a short-lived perennial, described by BSBI as winter-green, rising to about a meter from a short taproot with many long side roots (Zielińska). The stems are branched and sparsely hairy, and Grieve notes that they are swollen at the joints and snap easily. The thin leaves are deeply divided into lobed, round-toothed leaflets, green above and pale bluish-gray beneath, and they droop almost as soon as they are picked. From April to October, loose umbels of two to six flowers open, each with four bright yellow petals and two whitish sepals that fall early. They are followed by slender pods about 3 cm long that split into two valves to release shiny dark seeds, each carrying an elaiosome, a small fleshy appendage. Every part of the plant contains latex, described by Zielińska as yellow to orange and by Austria’s medicines regulator (BASG) as orange-red. Grieve writes that it stains the hands strongly, has a nauseous taste and a disagreeable smell, and is acrid and a powerful irritant.

Greater celandine is a plant of human settlements. BSBI records it on pavements, roadsides, old walls, waste ground, and hedge bottoms, mostly near houses, and notes that it was once cultivated as a medicinal plant; EMA calls it a typical ruderal plant of nitrogen-rich ground. Its chemistry is dominated by isoquinoline alkaloids. EMA’s assessment report lists more than 20, at 0.01–1% of the herb, including the benzophenanthridines chelidonine, sanguinarine, chelerythrine, and isochelidonine; the protoberberines berberine, coptisine, dihydrocoptisine, and stylopine; and protopine. Alongside them are chelidonic, caffeic, and other plant acids, flavonoids, carotenoids, and a protein called chelidocystatin. The European Pharmacopoeia requires the dried flowering herb to contain at least 0.6% total alkaloids, calculated as chelidonine. Content is not stable: Zielińska notes that several alkaloids rise during the day and fall at night, and EMA notes that sanguinarine sits mainly in the roots rather than the aerial parts. Lesser celandine (Ficaria verna, formerly Ranunculus ficaria) is a different plant: LiverTox places it in the buttercup family, and Grieve wrote that it has nothing in common with greater celandine except the color of its flowers.

The plant has been tied to swallows for about two thousand years. Zielińska and colleagues recount that Dioscorides, in the first century, wrote that it begins to flower when the swallows arrive and withers when they leave, and repeated a story that swallows restore sight to their blind nestlings with it; Pliny the Elder told the same tales. The Greek chelidon means swallow, Pliny recorded the Latin chelidonia, and Grieve explains that the English celandine is simply a corruption of the Greek. The German Schöllkraut descends from the same root. Grieve adds that the sap was used to clear films from the cornea, a property Pliny credited to the swallows, which gave the plant a double claim to the bird’s name. Other names describe the latex or its uses. EMA lists devil’s milk, rock poppy, tetterwort, and swallow-wort in English, and Zielińska records names meaning wart herb in Spanish (hierba de las verrugas) and German (Warzenkraut), and the Polish glistnik, from the plant’s use against roundworms.

For most of its early history celandine was an eye medicine. Dioscorides advised boiling the juice with honey in a brass vessel for failing sight, Pliny named an eye lotion after the plant, and Gerard’s herbal, quoted by Grieve, said the juice was ‘good to sharpen the sight.’ Medieval writers, including the author of the eleventh-century herbal poem Macer floridus and Hildegard of Bingen, recommended it for the eyes, skin ulcers, and liver complaints (Zielińska). The liver use is also ancient, since Dioscorides recommended the plant soaked in wine with anise for jaundice, but its color amplified it. Zielińska dates its use for jaundice and liver disease under Paracelsus’s doctrine of signatures, the idea that a plant’s appearance reveals its purpose, to the sixteenth century, and Grieve recorded that the old alchemists held it good against jaundice ‘because of its intense yellow colour.’ In 1931 Grieve still listed it for jaundice and eczema, as an infusion, tincture, or fresh juice for a sluggish liver, and in milk as an eye lotion for opaque spots on the cornea.

Folk medicine kept the plant busy. Across Central and Eastern Europe, Zielińska and colleagues found it among the most widespread wild remedies: fresh sap rubbed on warts, infusions for jaundice and gallbladder complaints, decoctions against roundworms, and, in parts of Poland, babies with jaundice bathed in celandine water. Grieve noted that it was very popular in Russia, where it was said to have helped in cancer, and that the sap was used on warts, ringworm, and corns but kept off healthy skin. In Germany celandine moved into pharmacy: EMA records Panchelidon, a single-herb product on the market before 1977, and old formulas such as Tinctura Cholagoga that paired celandine tincture with milk thistle and nux vomica tinctures. Then came the case reports. From the late 1990s German physicians described acute hepatitis in people taking celandine products, Germany restricted oral products in 2008, and EMA’s herbal committee declined to issue a monograph in 2011. In 2018 BfArM pressed Bayer into adding liver warnings to Iberogast, now sold as Iberogast Classic, after new reports that included a fatal case of liver failure.

The traditional digestive uses rest on laboratory work on muscle and bile. In isolated tissue, EMA’s assessment report describes antispasmodic (muscle-relaxing) activity from coptisine, chelidonine, and (+)-caffeoylmalic acid, acting both directly on smooth muscle and through nerves, and effects on GABA receptors that might contribute to mild pain relief. A bile-promoting (choleretic) effect was seen with the whole extract but not with the alkaloid fraction alone, which suggests that, if real, it depends on the full mixture. Test-tube studies have found activity against herpes simplex virus, adenoviruses, bacteria including MRSA, and skin fungi, and several alkaloids, sanguinarine above all, kill cancer cells in culture, partly by binding DNA. EMA notes that anticancer activity seen in cells was not confirmed in animal experiments. None of these findings has been shown to translate into benefit in people, and EMA records no pharmacodynamic studies in humans.

How much of the plant reaches the body is unclear. EMA reports that the alkaloids are poorly absorbed and heavily metabolized in rats, rabbits, and pigs, and that there are no pharmacokinetic data in humans. The liver injury is also unexplained. LiverTox states that none of the plant’s components has been shown to be specifically toxic to the liver and describes the cases as idiosyncratic, meaning they strike a susceptible minority rather than everyone who takes a given dose; Teschke and colleagues (Annals of Hepatology 2012) classify it as idiosyncratic injury of the metabolic type and say the responsible compound is uncertain. Animal studies do not reproduce it. Rats given an extract for four weeks at up to 1,820 mg/kg a day showed no liver changes, and another rat study at 50 to 100 times usual human doses found no loss of liver function (both summarized by EMA). In cell culture, however, human liver cells appeared more sensitive to celandine extracts than those of dogs, rats, or monkeys (EMA, citing Runge 2009), one possible reason animal tests miss the problem.

Whether dose matters is debated. Germany’s 2008 limit assumed that risk rises with alkaloid intake, and an expert analysis cited by EMA found that, where intake could be estimated in the more convincing cases, daily alkaloid doses exceeded 9 mg. Yet Moro and colleagues (Journal of Ethnopharmacology 2009), reviewing 16 published cases, found that onset seemed independent of dose, and EMA said it was not reassured that a limit of 2.5 mg a day makes oral use safe. Interactions are another hypothesis: a majority of the patients in Moro’s review were also taking other herbal or conventional medicines, and Zielińska notes suggestions that interactions rather than intrinsic toxicity may explain some cases. In cancer cell lines, chelidonine lowered the expression of genes for drug transporters and for CYP3A4, a liver enzyme that clears many medicines, but whether this happens in people is unknown. Finally, the fresh plant differs from the dried herb: EMA notes that the latex makes the fresh plant acutely toxic and that drying considerably reduces this toxicity.

Indigestion and gallbladder-type pain are the uses with the most human data, and the data are old and few. In the best trial, Ritter and colleagues (1993, summarized by EMA) randomized 60 people with functional upper abdominal complaints to celandine tablets standardized to 4 mg of alkaloids, two tablets three times a day, or placebo for six weeks. Symptom scores fell significantly more with celandine, and physicians rated 18 of 30 patients improved or symptom-free, against 8 of 30 on placebo. That regimen supplied 24 mg of alkaloids a day, almost ten times the ceiling Germany imposed in 2008. Niederau and Göpfert (Medizinische Klinik 1999) gave 76 people with right upper abdominal pain blamed on bile-duct dysfunction a capsule of celandine and turmeric extracts or placebo for three weeks; cramping pain eased faster in the first week, but the main outcome narrowly missed statistical significance (p = 0.069), and other symptoms improved equally in both groups. Open studies of the product Panchelidon in gallstone and bile-duct patients, and a 608-patient post-marketing survey of a celandine extract, reported good results without control groups.

EMA’s assessors called these studies heterogeneous, mixing single herbs and combinations, different conditions, and different outcomes, with controlled trials that were small and lacked power calculations. Their 2011 conclusion was that evidence of efficacy is lacking, so a well-established use could not be accepted, and that the documented traditional use did not outweigh the large number of liver and bile-duct reports and the withdrawal of products in several countries. Germany’s 2008 decision, as summarized by EMA, noted that no valid efficacy studies existed for the low doses, between 2.5 µg and 2.5 mg of alkaloids a day, that it still allowed. The result is an uncomfortable mismatch: the doses with some trial support are doses regulators judged unsafe, and the doses regulators tolerated have no proof of benefit. In 2012 BASG summed up that the efficacy of celandine extracts could not be proven in controlled clinical trials, while the risk of severe liver side effects after internal use is documented by a large number of case reports, so that medical use cannot be recommended.

Most people who swallow greater celandine today do so in Iberogast Classic, also known as STW 5, a Bayer liquid that combines extracts of nine herbs: bitter candytuft, angelica root, chamomile flower, caraway fruit, milk thistle fruit, lemon balm leaf, peppermint leaf, licorice root, and greater celandine, which makes up 10 ml of every 100 ml. In Germany it is licensed for functional dyspepsia, irritable bowel syndrome, and as supportive treatment for gastritis symptoms. Melzer and colleagues (Alimentary Pharmacology and Therapeutics 2004) pooled three placebo-controlled trials in functional dyspepsia: 138 people on STW 5 did better than 135 on placebo on their most bothersome symptom (odds ratio 0.22), with similar rates of side effects. Those results belong to the nine-herb product, not to celandine, and Zielińska notes there is no proof that celandine is the essential ingredient. A six-herb version without celandine, angelica, or milk thistle (STW 5-II), sold in Germany as Iberogast Advance, has its own trials: a 2024 pooled analysis by Andresen and colleagues (Digestion) found it improved dyspepsia symptoms more than placebo at four and eight weeks. The Iberogast sold as a dietary supplement in the United States is also a six-herb blend with no celandine.

Warts are celandine’s most enduring folk use. Zielińska and colleagues found fresh sap rubbed onto warts in Poland, Ukraine, Russia, and the Balkans. EMA’s survey of the European market found celandine in wart products mostly as part of combinations, such as a Belgian solution with thuja tincture and salicylic acid and Spanish preparations with salicylic acid and iodine, plus a Hungarian single-herb solution sold since 1999 for warts and corns. We found no controlled trials of celandine sap or extract for warts. EMA concluded that skin use was not sufficiently supported by market information on single-herb products, and BASG states that the traditional use of the fresh latex against warts is not scientifically proven. Because the combination products also contained salicylic acid, any benefit from them cannot be credited to celandine. The sap is an irritant, and contact dermatitis, with severe itching and a red, bumpy rash, has been reported in a woman who used it on warts (Etxenagusia and colleagues, Contact Dermatitis 2000, cited by EMA).

Cancer is the most troubling claim. Ukrain (NSC-631570), an injectable product created in 1978 by a Ukrainian-born chemist and sold through his Austrian company, Nowicky Pharma, was described as a semisynthetic compound of celandine alkaloids and the chemotherapy drug thiotepa, and promoted for cancer, HIV, and hepatitis. Ernst and Schmidt (BMC Cancer 2005) found seven randomized trials, all reporting benefit but mostly of poor methodological quality, and concluded that numerous caveats prevented a positive conclusion. Habermehl and colleagues (BMC Cancer 2006) could not detect the claimed molecule and found ordinary celandine alkaloids such as chelidonine, sanguinarine, and chelerythrine instead. Memorial Sloan Kettering Cancer Center (MSKCC) says Ukrain has not been shown to prevent or treat cancer and is not FDA-approved. BASG reports that national approval and European orphan-drug status were both refused, and in September 2012 Austrian authorities seized the company’s stock. The inventor went on trial in Vienna in 2015 accused of fraud (The Local), and Ukrainian media reported in 2017 that he had been convicted. Laboratory research on celandine alkaloids continues, but no celandine product is an established cancer treatment.

Greater celandine has been used as dried flowering herb for tea, as tinctures, fluid and dry extracts, fresh juice, and homeopathic mother tinctures. EMA’s assessment report lists 1.2–3.6 g of herb as a tea infusion (from the 2003 ESCOP monograph), tinctures of 2–4 ml, and dry extracts of 100–200 mg three times a day, and Grieve gave an ounce of dried herb to a pint of boiling water, taken by the wineglass. These figures are recorded here as history, not guidance. Because alkaloid content varies with plant part, season, and even time of day, a home tea has an unknown dose. EMA summarizes the case of an 82-year-old man who developed toxic hepatitis after drinking a tea of self-collected celandine that he admitted was probably too concentrated (Bichler 2009), and that of a 65-year-old man who drank a daily decoction for a month for heartburn and was admitted with jaundice and an ALT, a liver enzyme, more than 100 times the upper limit of normal (Moro 2009). Both recovered after stopping.

Licensed medicines are regulated by alkaloid content. Under BfArM’s 2008 decision, oral products supplying more than 2.5 mg of total alkaloids a day lost their authorization, and those supplying 2.5 µg to 2.5 mg had to state that they must not be used with current or past liver disease, with other liver-damaging medicines, or in pregnancy and breastfeeding, and that liver tests should be done if use exceeds four weeks. Iberogast Classic’s current German professional information (September 2023) contraindicates it in liver disease, with medicines whose leaflets list liver damage as a side effect, under age 3, and in pregnancy and breastfeeding; it lists liver damage, including hepatitis and liver failure, as a side effect of unknown frequency and tells users to stop at once for yellow skin or eyes, dark urine, or pale stools. It contains 240 mg of alcohol per 20 drops. Iberogast Advance carries no liver warning, is not recommended under age 12, and contains no celandine. The US Iberogast supplements are for adults 18 and older and also contain no celandine.

Practical points: there is no form of greater celandine we can suggest swallowing. If you use Iberogast Classic or any product listing Chelidonium, Chelidonii herba, Schöllkraut, or celandine, follow the label, do not exceed it, tell your doctor, and ask whether a celandine-free alternative would suit you. Check multi-herb and imported products, because LiverTox records celandine in herbal tablets for veins, in insomnia drops, and in weight-loss products linked to liver injury. Do not make tea from wild plants, which also risks confusing it with lesser celandine. For warts, leave the sap alone and ask a pharmacist or doctor about established treatments. When weeding, wear gloves, keep the latex away from your eyes and from children, and wash it off promptly; Grieve warned that it should not touch healthy skin. If you have used celandine and develop any sign of liver trouble, stop it, keep the package, and see a doctor.