Autumn Crocus Uses, Benefits & Dosage - Drugs.com Herbal Database

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# 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 11, 2021.

## 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

## Disclaimer

This information relates to an herbal, vitamin, mineral or other dietary supplement. This product has not been reviewed by the FDA to determine whether it is safe or effective and is not subject to the quality standards and safety information collection standards that are applicable to most prescription drugs. This information should not be used to decide whether or not to take this product. This information does not endorse this product as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this product. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this product. This information is not specific medical advice and does not replace information you receive from your health care provider. You should talk with your health care provider for complete information about the risks and benefits of using this product.

This product may adversely interact with certain health and medical conditions, other prescription and over-the-counter drugs, foods, or other dietary supplements. This product may be unsafe when used before surgery or other medical procedures. It is important to fully inform your doctor about the herbal, vitamins, mineral or any other supplements you are taking before any kind of surgery or medical procedure. With the exception of certain products that are generally recognized as safe in normal quantities, including use of folic acid and prenatal vitamins during pregnancy, this product has not been sufficiently studied to determine whether it is safe to use during pregnancy or nursing or by persons younger than 2 years of age.

Alvarellos A, Spilberg I. Colchicine prophylaxis in pseudogout. JRheumatol. 1986;13(4):804-805.3772928
Arellano F, Krupp P. Muscular disorders associated with cyclosporine. Lancet. 1991;337:915.1672991
Atmaca J, Sayarlioglu H, Kulah E, Demircan N, Akpolat T. Rhabdomyolysis associated with gemfibrozil-colchicine therapy. Ann Pharmacother. 2002;36(11):1719-1721.12398566
Baldwin LR, Talbert RL, Samples R. Accidental overdose of insufflated colchicine. Drug Saf. 1990;5(4):305-312. doi:10.2165/00002018-199005040-000062375835
Baud FJ, Sabouraud A, Vicaut E, et al. Brief report: treatment of severe colchicine overdose with colchicine-specific Fab fragments. N Eng J Med. 1995;332(10):642-645. doi:10.1056/NEJM1995030933210047845428
Brenner DA, Alcorn JM. Therapy for hepatic fibrosis. Semin Liver Dis. 1990;10(1):75-83. doi:10.1055/s-2008-10404592186490
Briggs GG, Freeman ED, Yaffe SJ. Drugs in Pregnancy and Lactation. 4th ed. Williams & Wilkins; 1994:218c-221c.
Brncic N, Viskovic I, Peric R, Dirlic A, Vitezic D, Cuculic D. Accidental plant poisoning with Colchicum autumnale: report of two cases. Croat Med J. 2001;42(6):673-675.11740853
Brvar M, Ploj T, Kozelj G, Mozina M, Noc M, Bunc M. Case report: fatal poisoning with Colchicum autumnale. Crit Care. 2004;8(1):R56-R59. doi:10.1186/cc242714975056
Cortez-Pinto H, Alexandrino P, Camilo ME, et al. Lack of effect of colchicine in alcoholic cirrhosis: final results of a double blind randomized trial. Eur J Gastroenterol Hepatol. 2002;14(4):377-381. doi:10.1097/00042737-200204000-0000711943949
Critchley JA, Critchley LA, Yeung EA, et al. Granulocyte-colony stimulating factor in the treatment of colchicine poisoning. Hum Exp Toxicol. 1997;16(4):229-232. doi:10.1177/0960327197016004139154449
Danel VC, Wiart JF, Hardy GA, Vincent FH, Houdret NM. Self-poisoning with Colchicum autumnale L. flowers. J Toxicol Clin Toxicol. 2001;39(4):409-411. doi:10.1081/clt-10010516311527237
Duke JA. Handbook of Medicinal Herbs. CRC Press; 1985.
Ellwood MG, Robb GH. Self-poisoning with colchicine. Postgrad Med J. 1971;47 (544):129-131. doi:10.1136/pgmj.47.544.1295576148
Finger JE, Headington JT. Colchicine-induced epithelial atypia. Am J Clin Pathol. 1963;40:605-609.14100663
Flanagan RJ, Jones AL. Fab antibody fragments: some applications in clinical toxicology. Drug Saf. 2004;27(14):1115-1133. doi:10.2165/00002018-200427140-0000415554746
Flesch F, Kintz P, Krencker E, Ihadadene N, Sauder P, Jaeger A. Food mistake: a case of poisoning by ingesting autumn crocus. Eur J Emerg Med. 2001;8:73-74.
Folpini A, Furfori P. Colchicine toxicity—clinical features and treatment. Massive overdose case report. J Toxicol Clin Toxicol. 1995;33(1):71-77. doi:10.3109/155636595090202197530779
Gabrscek L, Lesnicar G, Krivec B, et al. Accidental poisoning with autumn crocus. J Toxicol Clin Toxicol. 2004;42(1):85-88. doi:10.1081/clt-12002875015083942
Gutman AB. The past four decades of progress in the knowledge of gout, with an assessment of the present status. Arthritis Rheum. 1973;16(4):431-445. doi:10.1002/art.17801604024147308
Guttadauria M, Diamond H, Kaplan D. Colchicine in the treatment of scleroderma. J Rheumatol. 1977;4(3):272-276.926103
Hood RL. Colchicine poisoning. J Emerg Med. 1994;12(2):171-177. doi:10.1016/0736-4679(94)90695-58207152
James LF. Plant-induced congenital malformations in animals. World Rev Nutr Diet. 1977;(26):208-224. doi:10.1159/000428539324142
Klintschar M, Beham-Schmidt C, Radner H, Henning G, Roll P. Colchicine poisoning by accidental ingestion of meadow saffron (Colchicum autumnale): pathological and medicolegal aspects. Forensic Sci Int. 1999;106(3):191-200. doi:10.1016/s0379-0738(99)00191-710680067
Kritikos A, Spertini O. Reversible granulocyte abnormalities after accidental ingestion of Colchicum autumnale. Blood. 2017;130(1):95. doi:10.1182/blood-2017-02-76641028684450
Kuncl RW, Duncan G, Watson D, Alderson K, Rogawski MA, Peper M. Colchicine myopathy and neuropathy. N Engl J Med. 1987;316(25):1562-1568. doi:10.1056/NEJM1987061831625023035372
Kyle RA, Gertz MA, Greipp PR, et al. A trial of three regimens for primary amyloidosis: colchicine alone, melphalan and prednisone, and melphalan, prednisone, and colchicine. N Engl J Med. 1997;336(17):1202-1207. doi:10.1056/NEJM1997042433617029110907
Lampe KF, McCann MA. AMA Handbook of Poisonous and Injurious Plants. American Medical Association; Chicago Review Press; 1985.
Lewis WH, Elvin-Lewis MP. Medical Botany: Plants Affecting Man's Health. John Wiley & Sons Inc; 1977:92.
Liu JH, Yang MH, Fan FS, et al. Tamoxifen and colchicine-modulated vinblastine followed by 5-fluorouracil in advanced renal cell carcinoma: a phase II study. Urology. 2001;57(4):650-654. doi:10.1016/s0090-4295(00)01096-711306370
Longstreth GF, Newcomer AD. Drug-induced malabsorption. Mayo Clinic Proc. 1975;50(5):284-293.1127993
Malichova V, Potesilova H, Preininger V, Santavy F. Alkaloids from leaves and flowers of Colchicum autumnale L. Planta Med. 1979;36(2):119-127. doi:10.1055/s-0028-1097251461564
McMillian R. Therapy for adults with refractory chronic immune thrombocytopenic purpura. Ann Intern Med. 1997;126:307-314.
Morton JF. Major Medicinal Plants. Thomas Books; 1977.
Nagesh KR, Menezes RG, Rastogi P, et al. Suicidal plant poisoning with Colchicum autumnale. J Forensic Leg Med. 2011;18(6):285-287. doi:10.1016/j.jflm.2011.04.00821771560
Nair V, Singh S, Gupta YK. Evaluation of the disease modifying activity of Colchicum luteum Baker in experimental arthritis. J Ethnopharmacol. 2011;133(2):303-307. doi:10.1016/j.jep.2010.09.02720920569
Pirzada NA, Medell M, Ali II. Colchicine induced neuromyopathy in a patient with normal renal function. J Clin Rheumatol. 2001;7(6):374-376. doi:10.1097/00124743-200112000-0000517039178
Poulev A, Dues-Neumann B, Bombardelli E, Zenk MH. Immunoassays for the quantitative determination of colchicine. Planta Med. 1994;60(1):77-83. doi:10.1055/s-2006-9594138134420
Race TF, Paes IC, Faloon WW. Intestinal malabsorption induced by oral colchicine. Comparison with neomycin and cathartic agents. Am J Med Sci. 1970;259(1):32-41. doi:10.1097/00000441-197001000-000055416781
Razinger G, Kozelj G, Gorjup V, Grenc D, Brvar M. Accidental poisoning with autumn crocus (Colchicum autumnale): a case series. Clin Toxicol (Phila). 2021;59(6):493-499.33156711
Rodnan GP, Benedek TG. The early history of antirheumatic drugs. Arthritis Rheum. 1970;13(2):145-165. doi:10.1002/art.17801302074912138
Russell AI, Lawson WA, Haskard DO. Potential new therapeutic options in Behçet's syndrome. BioDrugs. 2001;15(1):25-35. doi:10.2165/00063030-200115010-0000311437673
Sannohe S, Makino Y, Kita T, Kuroda N, Shinozuka T. Colchicine poisoning resulting from accidental ingestion of meadow saffron (Colchicum autumnale). J Forensic Sci. 2002;47(6):1391-1396.12455670
Scheffer C, Debus M, Heckmann C, Cysarz D, Girke M. Colchicum autumnale in patients with goitre with euthyroidism or mild hyperthyroidism: indications for a therapeutic regulative effect-results of an observational study. Evid Based Complement Alternat Med. 2016;2016:2541912. doi:10.1155/2016/254191226955394
Silvers DN, Juhlin EA, Berczeller PH, McSorley J. Treatment of dermatitis herpetiformis with colchicine. Arch Dermatol. 1980;116(12):1373-1384.7458365
Tateishi T, Soucek P, Caraco Y, Guengerich FP, Wood AJ. Colchicine biotransformation by human liver microsomes. Identification of CYP3A4 as the major isoform responsible for colchicine demethylation. Biochem Pharmacol. 1997;53(1):111-116. doi:10.1016/s0006-2952(96)00693-48960070
Wahba A, Cohen H. Therapeutic trials with oral colchicine in psoriasis. Acta Derm Venereol. 1980;60(6):515-520.6162337
WCSP (Colchicum autumnale). World Checklist of Selected Plant Families. Facilitated by the Royal Botanic Gardens, Kew. Accessed January 2020. http://wcsp.science.kew.org
Wilbur K, Makowsky M. Colchicine myotoxicity: case reports and literature review. Pharmacotherapy. 2004;24(12):1784-1792. doi:10.1592/phco.24.17.1784.5233415585444
Wong SS, Tan KC, Goh CL. Long-term colchicine for recalcitrant palmoplantar pustulosis: treatment outcome in 3 patients. Cutis. 2001;68(3):216-218.11579788
Yamada M, Kobayashi Y, Furuoka H, Matsui T. Comparison of enterotoxicity between autumn crocus (Colchicum autumnale L.) and colchicine in the guinea pig and mouse: enterotoxicity in the guinea pig differs from that in the mouse. J Vet Med Sci. 2000;62(8):809-813. doi:10.1292/jvms.62.80910993176
Yamada M, Matsui T, Kobayashi Y, et al. Supplementary report on experimental autumn crocus (Colchicum autumnale L.) poisoning in cattle: morphological evidence of apoptosis. J Vet Med Sci. 1999;61(7):823-825. doi:10.1292/jvms.61.82310458107
Yamada M, Nakagawa M, Haritani M, Kobayashi M, Furuoka H, Matsui T. Histopathological study of experimental acute poisoning of cattle by autumn crocus (Colchicum autumnale L.). J Vet Med Sci. 1998;60(8):949-952. doi:10.1292/jvms.60.9499764409

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