Autumn Crocus
Scientific Name(s): Bulbocodium vernum L. Ker-Gawl, Colchicum autumnale L., Colchicum speciosum Steven
Common Name(s): Autumn crocus, Crocus, Fall crocus, Gowri gedde, Meadow saffron, Mysteria, Naked lady, Vellorita, Wild saffron, Wonder bulb
Medically reviewed by Drugs.com. Last updated on May 1, 2024.
Clinical Overview
Use
Due to its main active constituent colchicine, autumn crocus plant and its extracts have traditionally been used to treat gout and related inflammatory disorders. Autumn crocus may have benefit in conditions such as cirrhosis or hyperthyroidism. However, the plant is considered toxic and no clinical trials are available to support the use of autumn crocus for any indication.
Dosing
Data are lacking to provide dosing recommendations for any indication. The entire autumn crocus plant is toxic. The main component colchicine has a narrow therapeutic index; use of colchicine (whether from a plant-based extract or a purified form) requires medical supervision.
Contraindications
Contraindications have not been identified.
Pregnancy/Lactation
Avoid use. Information regarding safety and efficacy in pregnancy and lactation is contradictory. The entire autumn crocus plant is toxic, primarily due to colchicine content.
Interactions
Avoid use in patients taking colchicine. Colchicine is listed as a substrate of CYP3A4 hepatic metabolism. Monitor therapy when patients are receiving CYP3A4 substrates/inhibitors (especially if renal and/or hepatic dysfunction is demonstrated) and ingesting autumn crocus, as colchicine metabolism can be inhibited. Caution is warranted in patients taking cyclosporine, gemfibrozil, macrolide antibiotics, and St. John's wort.
Adverse Reactions
GI disturbances (eg, diarrhea, steatorrhea, reversible malabsorption syndrome) are common following acute therapeutic use of colchicine.
Toxicology
All parts of autumn crocus are highly toxic. Severe gastric distress, shock, and inhibition of normal cell growth may occur with use.
Scientific Family
- Liliaceae (lily)
Botany
Crocus plants are members of the lily family and often are cultivated for their long, ornamental flowers. This perennial herb grows to approximately 0.3 m in height and has pale purple flowers and a fleshy conical root (corm). The corm has a bitter, acrid taste and radish-like odor.(Liu 2001) Low-lying leaves are arranged around the base of the plant, growing from the bulb. In the spring, the plant has leaves but no blossoms.(Gabrscek 2004) The plant is native to grassy meadows, woods, and riverbanks in Ireland, England, and portions of Europe and has been cultivated throughout much of the world. Some plant databases classify C. autumnale as belonging to the Colchicaceae family, and multiple synonyms exist for the plant.(WCSP 2020)
History
The name Colchicum is derived from the district of Colchis, located on the ancient eastern shore of the Black Sea.(Rodnan 1970) The plant and its extracts have been used for centuries in the treatment of gout, rheumatism, dropsy, prostate enlargement, and gonorrhea.(Morton 1977) Extracts have been used to treat cancers. The first official Pharmacopeia of the United States (1820) listed a Colchicum preparation.(Rodnan 1970) Today the plant is a primary source of colchicine, which is used therapeutically to treat gout and experimentally in cellular chromosomal studies. Aside from its Food and Drug Administration (FDA)-approved uses (gout and familial Mediterranean fever), colchicine has been used (either alone or adjunctively) in the following conditions: neurologic disability caused by chronic progressive multiple sclerosis, hepatic cirrhosis, primary biliary cirrhosis, primary amyloidosis,(Kyle 1997) Behçet disease,(Russell 2001) pseudogout,(Alvarellos 1986) skin manifestations of scleroderma,(Guttadauria 1977) psoriasis,(Wahba 1980) palmoplantar pustulosis,(Wong 2001) and dermatitis herpetiformis.(Silvers 1980)
Chemistry
Colchicine is the main active constituent found in autumn crocus and is present in a concentration of approximately 0.6% in the corm; concentrations may exceed 1% in the seeds.(Cortez-Pinto 2002) Dried leaves and flowers contain the same concentration of colchicine as fresh parts; however, dried flowers and seeds contain 15 times as much colchicine as leaves.(Malichova 1979) A variety of other related alkaloids have been isolated from the plant, including colchicerine, colchamine, colchicoside, demethyl-3-colchicine, cornigerine, and 2-demethylcolchifoline.(Danel 2001, Malichova 1979) Colchicine is not destroyed by heat or boiling and is highly soluble in water.(Morton 1977) Colchysat is a hydroethanolic extract of fresh C. autumnale blossoms.(Poulev 1994)
Uses and Pharmacology
Colchicine inhibits normal cell division, specifically by interfering with microtubule growth and mitosis during cell division. It also may interfere with the normal function of cyclic adenosine monophosphate (cAMP) or the cellular membrane.(Gutman 1973)
Gout
The autumn crocus plant and its extracts have been traditionally used to treat gout and related inflammatory disorders.
Animal data
Animal studies have evaluated disease-modifying activity of the related Colchicum luteum in experimental arthritis.(Nair 2011)
Hyperthyroidism
Clinical data
An observational study (N=24) reported positive findings among participants with subclinical hyperthyroidism given dilutions of extracts of C. autumnale plant bulb.(Scheffer 2016)
Dosing
Data are lacking to provide dosing recommendations for any indication. The entire autumn crocus plant is toxic. The main component colchicine has a narrow therapeutic index; use of colchicine (whether from a plant-based extract or a purified form) requires medical supervision.
Pregnancy / Lactation
Avoid use. Information regarding safety and efficacy in pregnancy and lactation is contradictory. The entire autumn crocus plant is toxic, primarily due to colchicine content.
One text lists autumn crocus as a mutagen and teratogen.(Lewis 1977) Although no mutagenic effects were reported in a small number of colchicine-exposed human fetuses, sperm abnormalities have been reported in men treated with the pharmaceutical form of colchicine. Effects included azoospermia and abnormal numbers of chromosomes (including trisomy 21), which causes Down syndrome.(Briggs 1994)
Interactions
Autumn crocus should be avoided in patients taking colchicine because of the potential for additive adverse and therapeutic effects. Due to colchicine content, any precautions regarding prescription colchicine drug products are likely applicable to the use of autumn crocus.
Colchicine is listed as a substrate of CYP3A4 hepatic metabolism.(Tateishi 1997) Monitor therapy when patients are receiving CYP3A4 substrates/inhibitors (especially if renal and/or hepatic dysfunction is demonstrated) and ingesting autumn crocus, as colchicine metabolism can be inhibited.(Atmaca 2002, Tateishi 1997)
Colchicine is a substrate of CYP3A4, which St. John's wort induces. Coadministration increases drug metabolism (see St. John’s Wort monograph).(Tateishi 1997) This interaction warrants close observation or discontinuation of autumn crocus (colchicine).
Adverse Reactions
GI disturbances (eg, diarrhea, steatorrhea, reversible malabsorption syndrome) are common after acute therapeutic use of colchicine.(Longstreth 1975, Race 1970)
Toxicology
Veterinary poisonings have been associated with autumn crocus; these often are observed in grazing animals. There have been reports of calves becoming intoxicated after drinking milk from cows that ingested the plant.(James 1977)
There are reports of children becoming intoxicated after drinking milk from cows that ingested the autumn crocus plant.(James 1977) Human intoxications have occurred after corms were mistaken for onions, wild garlic (Allium ursinum), Japanese domestic allium (Allium victorialis platyphyllum), or leeks, and have also occurred from overdosages of seed- or corm-derived natural medicinals.(Arellano 1991, Brenner 1990, Brncic 2001, Flesch 2001, Klintschar 1999, Kritikos 2017, Sannohe 2002) A 20-year retrospective case series of 16 adults 38 to 76 years of age (median age, 53.5 years) in Slovenia reviewed patients who were accidentally poisoned with C. autumnale. In all cases, the crocus leaves used in salads, soups, sauces, and meals had been misidentified as wild garlic (Allium usinum). The 25% mortality rate occurred within 3 days of ingestion and was associated with an onset of vomiting within 2 hours after the meal, multiorgan failure, and an older age (median, 72.5 years). Combining these cases with 58 others reported in the literature, the authors reported an overall mortality rate of 35% for C. autumnale accidental poisonings.(Razinger 2021) Consider differential diagnosis of C. autumnale poisoning in unexplained extensive GI symptoms after ingestion of wild plants used as spices or in salads.(Brncic 2001, Klintschar 1999) Toxicity has been observed when colchicine was mistaken for methamphetamine and accidentally taken by nasal insufflation.(Baldwin 1990)
Cases of attempted suicide by self-poisoning with C. autumnale L. flowers have been reported. A 16-year-old girl who ingested more than a dozen flowers (calculated at about colchicine 270 mg) experienced convulsions and subsequently died.(Ellwood 1971) A 44-year-old man ingested 40 flowers (calculated at up to colchicine 102 mg [1.5 mg/kg]) but survived after gastric lavage and aggressive treatment.(McMillian 1997) A fatal case of intentional poisoning was reported in a 24-year-old man who presented with vomiting, watery diarrhea, epigastric burning sensation, tachycardia, tachypnea, and hypotension. He died on day 3 after ingestion of C. autumnale due to cardiovascular and respiratory distress that manifested as multiorgan congestion. Colchicine poisoning was detected in postmortem samples of the kidney, liver, and blood.(Nagesh 2011)
Signs and symptoms of colchicine poisoning follow 3 phases: Phase 1 (0 to 24 hours) includes GI symptoms (eg, nausea, vomiting, diarrhea), volume depletion, and peripheral leukocytosis; phase 2 (day 2 through 7) includes life-threatening respiratory distress, cardiovascular shock, thrombocytopenia, metabolic acidosis, rhabdomyolysis, bone marrow suppression, and renal and hepatic failure; phase 3 (day 7 and later) includes rebound leukocytosis, neruopathy, and alopecia. Death may follow in the first 24 to 48 hours but may be delayed up to 14 days.(Ellwood 1971, Hood 1994, Razinger 2021, Sannohe 2002) Fluid loss may lead to hypovolemic shock, and renal impairment with oliguria has been reported.(Hood 1994, Lampe 1985) Because of the slow elimination of colchicine from the body, intoxication follows a long course. Fluid replacement and supportive therapy are recommended.(Lampe 1985) Because no specific antidote is available for colchicine poisoning, emesis followed by gastric lavage, with or without oral activated charcoal, has also been of value along with supportive therapy for shock.(Danel 2001, Duke 1985) Patients with cardiac disease, hepatic disease, and/or renal insufficiency have a worse prognosis because they may have a more severe clinical presentation.(Brvar 2004, Finger 1963) Fab fragment antibodies produced in rabbits or goats have been effective in treating colchicine poisoning when tested in mice and rabbits. Colchicine-specific fab fragments have been successfully used to treat a life-threatening, intentional overdose of colchicine tablets in a 25-year-old woman.(Baud 1995) However, fab fragments of anticolchicine antibody are not commercially available.(Flanagan 2004) Pancytopenia in patients surviving the initial stages of autumn crocus poisoning has been successfully treated with granulocyte colony-stimulating factor, which may help prevent life-threatening sepsis.(Critchley 1997, Folpini 1995)
The entire autumn crocus plant is toxic, primarily because of the colchicine content. After ingestion, immediate burning of the mouth and throat is followed by intense thirst, nausea, and vomiting. Abdominal pain and persistent diarrhea attributed to disturbances of water and electrolyte balance develop because of small and large intestine mucosal lining damage.(Yamada 1998) An experimental study in cattle reported that autumn crocus not only arrests mitosis in GI tract tissue but also causes apoptosis.(Yamada 1999) One study found a species difference: Orally administered toxic amounts of autumn crocus caused guinea pigs to develop diarrhea but did not affect mice in the same way.(Yamada 2000)
Prolonged therapeutic use of colchicine may cause agranulocytosis, aplastic anemia, thrombocytopenia, peripheral neuritis, and epithelial atypia.(Finger 1963, Hood 1994) Colchicine-induced myopathy and neuropathy have been diagnosed in patients taking usual doses for gout; however, patients also had renal dysfunction, causing increased colchicine plasma levels(Kuncl 1987, Wilbur 2004). One case of colchicine-induced neuromyopathy has been reported in a patient with normal renal function. If myopathy is suspected, monitor muscle strength and creatine phosphokinase levels.(Pirzada 2001) The volatile oils emitted during commercial slicing of the fresh corm may irritate the nostrils and throat, and the fingertips holding the corm may become numb.(Morton 1977) The lowest reported human lethal dose is 186 mcg in 4 days.(Duke 1985) Although ingestion of colchicine 7 mg has been reported to be lethal to humans, the more typical lethal dose is 65 mg.(Hood 1994, Klintschar 1999, Morton 1977)
References
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