Cascara Sagrada

What Is Cascara Sagrada?

Cascara sagrada is a small deciduous tree of the Pacific Northwest whose dried, aged bark is one of the classic stimulant laxatives. The name is Spanish for “sacred bark” ^{20Reference 20European Medicines Agency · 2020Assessment report on Rhamnus purshiana DC., cortex, final, revision 1 — regulatory assessmentView study →}.

The tree grows from British Columbia to northern California, mostly west of the Cascades ^{22,23Reference 22NesomNesom, G. L. (n.d.). Frangula purshiana (de Candolle) A. Gray ex J. G. Cooper — species description, subspecies, habitat and distribution — flora. In Flora of North America Editorial Committee (eds.), Flora of North America North of Mexico, Vol. 12. http://www.efloras.org/florataxon.aspx?flora_id=1&taxon_id=250101357View study →Reference 23Habeck · 1992Frangula purshiana, cascara buckthorn — distribution, botanical and ecological characteristics — species databaseView study →}. Its bark entered medicine in 1877 and was in European use by 1880 ^{20Reference 20European Medicines Agency · 2020Assessment report on Rhamnus purshiana DC., cortex, final, revision 1 — regulatory assessmentView study →}. It is still an official drug in the European Pharmacopoeia, and the EU herbal monograph accepts it for short-term use in occasional constipation ^{19,20Reference 19European Medicines Agency · 2020ReviewEuropean Union herbal monograph on Rhamnus purshiana DC., cortex, final, revision 1 — regulatory monographView study →Reference 20European Medicines Agency · 2020Assessment report on Rhamnus purshiana DC., cortex, final, revision 1 — regulatory assessmentView study →}.

Its laxative action comes from the cascarosides. These glycosides pass the small intestine largely unabsorbed, and bacteria in the colon convert them into the active compound, mainly emodin-9-anthrone ^{19Reference 19European Medicines Agency · 2020ReviewEuropean Union herbal monograph on Rhamnus purshiana DC., cortex, final, revision 1 — regulatory monographView study →}. The bowel moves eight to twelve hours after a dose ^{19Reference 19European Medicines Agency · 2020ReviewEuropean Union herbal monograph on Rhamnus purshiana DC., cortex, final, revision 1 — regulatory monographView study →}.

The plant is listed under two names. Rhamnus purshiana is the older one and is still used in pharmacopoeias; Frangula purshiana is the name most floras now accept ^{19,22Reference 19European Medicines Agency · 2020ReviewEuropean Union herbal monograph on Rhamnus purshiana DC., cortex, final, revision 1 — regulatory monographView study →Reference 22NesomNesom, G. L. (n.d.). Frangula purshiana (de Candolle) A. Gray ex J. G. Cooper — species description, subspecies, habitat and distribution — flora. In Flora of North America Editorial Committee (eds.), Flora of North America North of Mexico, Vol. 12. http://www.efloras.org/florataxon.aspx?flora_id=1&taxon_id=250101357View study →}.

How Is Cascara Sagrada Used?

• Dried, aged bark — taken as a tea or decoction, usually as a single evening dose. Fresh bark causes vomiting and is not used ^{17,20Reference 17A Modern Herbal · 1931Buckthorn (Californian). https://www.botanical.com/botanical/mgmh/b/buckth80.htmlView study →Reference 20European Medicines Agency · 2020Assessment report on Rhamnus purshiana DC., cortex, final, revision 1 — regulatory assessmentView study →}.
• Standardised preparations — tablets, capsules and liquid extracts dosed by their content of hydroxyanthracene derivatives, calculated as cascaroside A ^{19Reference 19European Medicines Agency · 2020ReviewEuropean Union herbal monograph on Rhamnus purshiana DC., cortex, final, revision 1 — regulatory monographView study →}.
• Liquid extract — the traditional form in British and American pharmacy, alongside an aromatic syrup ^{17Reference 17A Modern Herbal · 1931Buckthorn (Californian). https://www.botanical.com/botanical/mgmh/b/buckth80.htmlView study →}.
• Small doses as a bitter — before meals, as a stomachic ^{20Reference 20European Medicines Agency · 2020Assessment report on Rhamnus purshiana DC., cortex, final, revision 1 — regulatory assessmentView study →}.

Traditional Uses

Cascara is first a medicine of the Indigenous peoples of the Pacific Northwest, who took the bark as a laxative from British Columbia to northern California ^{25Reference 25Moerman et al. · 1973Turner et al. and other ethnobotanies — ethnobotanical database. http://naeb.brit.org/uses/search/?string=purshianaView study →}. Settler medicine took it up in the late nineteenth century, as a laxative and, in small doses, as a bitter ^{17,20Reference 17A Modern Herbal · 1931Buckthorn (Californian). https://www.botanical.com/botanical/mgmh/b/buckth80.htmlView study →Reference 20European Medicines Agency · 2020Assessment report on Rhamnus purshiana DC., cortex, final, revision 1 — regulatory assessmentView study →}.

Native American Medicine

The bark was one of the most widely used laxatives of the Pacific Northwest. A laxative or purgative use of the bark, as an infusion, a decoction or simply chewed, is recorded for more than twenty peoples, among them the Bella Coola, Cowlitz, Flathead, Haisla, Hesquiat, Klallam, Kutenai, Kwakiutl, Lummi, Makah, Nitinaht, Okanagan-Colville, Quileute, Quinault, Sanpoil, Shuswap, Skagit, Squaxin, Swinomish and Thompson, and in California the Karok, Tolowa and Yurok ^{25Reference 25Moerman et al. · 1973Turner et al. and other ethnobotanies — ethnobotanical database. http://naeb.brit.org/uses/search/?string=purshianaView study →}.

It was dosed by the tree. The Hesquiat held that the bigger the tree, the stronger the medicine, and took thick bark from large trees for a strong dose and thin bark from young trees for a mild one ^{25Reference 25Moerman et al. · 1973Turner et al. and other ethnobotanies — ethnobotanical database. http://naeb.brit.org/uses/search/?string=purshianaView study →}. The Nitinaht took an infusion of spring or early-summer bark as a mild but effective laxative and as a tonic for bowel regularity ^{25Reference 25Moerman et al. · 1973Turner et al. and other ethnobotanies — ethnobotanical database. http://naeb.brit.org/uses/search/?string=purshianaView study →}. The Makah mixed it with crab-apple bark to stop the crab apple from constipating ^{25Reference 25Moerman et al. · 1973Turner et al. and other ethnobotanies — ethnobotanical database. http://naeb.brit.org/uses/search/?string=purshianaView study →}.

The bark served the gut more widely. The Kwakiutl drank a decoction of the dried bark for biliousness, the Paiute for “any trouble in the stomach”, the Skagit took the inner bark for dysentery, and the Hesquiat gave it to children for worms ^{25Reference 25Moerman et al. · 1973Turner et al. and other ethnobotanies — ethnobotanical database. http://naeb.brit.org/uses/search/?string=purshianaView study →}. The Thompson took it with red elderberry root for liver disease and with flowering dogwood bark for ulcers ^{25Reference 25Moerman et al. · 1973Turner et al. and other ethnobotanies — ethnobotanical database. http://naeb.brit.org/uses/search/?string=purshianaView study →}.

Other uses reached beyond digestion. The Okanagan-Colville took it for rheumatism and arthritis and as a blood purifier, and the Quileute and other west-coast peoples for gonorrhoea ^{25Reference 25Moerman et al. · 1973Turner et al. and other ethnobotanies — ethnobotanical database. http://naeb.brit.org/uses/search/?string=purshianaView study →}. On the skin, it was used as a poultice for wounds (Clallam), a wash for cuts and sores (Nitinaht, Squaxin) and a salve of bark ash and grease for swellings (Skagit) ^{25Reference 25Moerman et al. · 1973Turner et al. and other ethnobotanies — ethnobotanical database. http://naeb.brit.org/uses/search/?string=purshianaView study →}.

The fresh plant and large doses were known to be harsh. The Klamath used the berries, or an infusion of the leaves, twigs and bark, as an emetic, the Flathead considered the fruit poisonous, and a west-coast record notes that large doses of the bark infusion caused death ^{25Reference 25Moerman et al. · 1973Turner et al. and other ethnobotanies — ethnobotanical database. http://naeb.brit.org/uses/search/?string=purshianaView study →}.

The wood was used for tool handles, and the Skagit boiled the bark into a green dye ^{25Reference 25Moerman et al. · 1973Turner et al. and other ethnobotanies — ethnobotanical database. http://naeb.brit.org/uses/search/?string=purshianaView study →}.

Western Herbal Medicine

The bark entered American medicine in 1877, introduced by Dr J. H. Bundy, and was in European use as a purgative by 1880 ^{20Reference 20European Medicines Agency · 2020Assessment report on Rhamnus purshiana DC., cortex, final, revision 1 — regulatory assessmentView study →}. It appears in the British Pharmaceutical Codex of 1911 and in the United States Dispensatory as a vegetable cathartic ^{20Reference 20European Medicines Agency · 2020Assessment report on Rhamnus purshiana DC., cortex, final, revision 1 — regulatory assessmentView study →}.

As a laxative it was considered mild enough for delicate and elderly people, and was given for chronic constipation ^{17Reference 17A Modern Herbal · 1931Buckthorn (Californian). https://www.botanical.com/botanical/mgmh/b/buckth80.htmlView study →}. It was also given to soften the stool where straining was the problem, for instance with hemorrhoids ^{18Reference 18Bone · 2003A Clinical Guide to Blending Liquid Herbs}.

In small doses before meals it was used as a bitter stomachic, to promote appetite and digestion ^{17,20Reference 17A Modern Herbal · 1931Buckthorn (Californian). https://www.botanical.com/botanical/mgmh/b/buckth80.htmlView study →Reference 20European Medicines Agency · 2020Assessment report on Rhamnus purshiana DC., cortex, final, revision 1 — regulatory assessmentView study →}. The Eclectic physicians gave it for “sick headache” caused by a sluggish bowel, for gastric and duodenal catarrh with jaundice, and for chronic diarrhoea with a sluggish liver ^{20Reference 20European Medicines Agency · 2020Assessment report on Rhamnus purshiana DC., cortex, final, revision 1 — regulatory assessmentView study →}. Other old texts add rheumatic complaints, and external use for scabies ^{20Reference 20European Medicines Agency · 2020Assessment report on Rhamnus purshiana DC., cortex, final, revision 1 — regulatory assessmentView study →}.

The bark must be stored before use. It is stripped in spring and early summer, when it peels easily, and dried in the shade. Grieve records that bark three years old was preferred, because keeping makes it milder and less emetic ^{17Reference 17A Modern Herbal · 1931Buckthorn (Californian). https://www.botanical.com/botanical/mgmh/b/buckth80.htmlView study →}. During drying, the anthrones in fresh bark that cause vomiting are oxidised to milder forms ^{20Reference 20European Medicines Agency · 2020Assessment report on Rhamnus purshiana DC., cortex, final, revision 1 — regulatory assessmentView study →}.

In Western herbal practice cascara is combined with boldo for constipation, flatulence and abdominal fullness, and with rhubarb, boldo and gentian for dyspepsia ^{18Reference 18Bone · 2003A Clinical Guide to Blending Liquid Herbs}.

Indications

• Occasional constipation [aged bark; EU well-established use] ⚠Caution: No controlled trial has tested cascara on its own. The EU monograph bases its efficacy on the pharmacology and on trial data for senna and aloe, and limits use to one week ^19,20.
• Constipation [bark infusion or decoction; Native American medicine]
• Chronic constipation and a sluggish bowel [bark; Western herbal medicine]
• Straining at stool, including with hemorrhoids [bark; Western herbal medicine]
• Dyspepsia and poor appetite [bark in small doses; Western herbal medicine]
• Headache from a sluggish bowel [bark; Eclectic medicine]
• Gastric and duodenal catarrh with jaundice [bark; Eclectic medicine]
• Rheumatic complaints [bark; European materia medica]
• Scabies [bark, external; European materia medica]
• Biliousness and stomach upset [bark decoction; Native American medicine]
• Worms in children [bark; Hesquiat medicine]
• Rheumatism and arthritis [bark infusion; Okanagan-Colville medicine]
• Wounds, sores and swellings [bark poultice, wash or salve, external; Native American medicine]

Botany

Cascara sagrada is a deciduous shrub or small tree in the buckthorn family, Rhamnaceae ^{22Reference 22NesomNesom, G. L. (n.d.). Frangula purshiana (de Candolle) A. Gray ex J. G. Cooper — species description, subspecies, habitat and distribution — flora. In Flora of North America Editorial Committee (eds.), Flora of North America North of Mexico, Vol. 12. http://www.efloras.org/florataxon.aspx?flora_id=1&taxon_id=250101357View study →}. It usually reaches 1–12 m ^{22Reference 22NesomNesom, G. L. (n.d.). Frangula purshiana (de Candolle) A. Gray ex J. G. Cooper — species description, subspecies, habitat and distribution — flora. In Flora of North America Editorial Committee (eds.), Flora of North America North of Mexico, Vol. 12. http://www.efloras.org/florataxon.aspx?flora_id=1&taxon_id=250101357View study →}. West of the Cascades it grows a single trunk 20–30 cm thick and 6–10.7 m tall, and it becomes smaller and bushier toward the south of its range ^{23Reference 23Habeck · 1992Frangula purshiana, cascara buckthorn — distribution, botanical and ecological characteristics — species databaseView study →}.

The leaves are alternate and oblong to elliptic, usually 5–15 cm long ^{22Reference 22NesomNesom, G. L. (n.d.). Frangula purshiana (de Candolle) A. Gray ex J. G. Cooper — species description, subspecies, habitat and distribution — flora. In Flora of North America Editorial Committee (eds.), Flora of North America North of Mexico, Vol. 12. http://www.efloras.org/florataxon.aspx?flora_id=1&taxon_id=250101357View study →}. Each has 9–12 pairs of prominent, parallel side veins ^{22,23Reference 22NesomNesom, G. L. (n.d.). Frangula purshiana (de Candolle) A. Gray ex J. G. Cooper — species description, subspecies, habitat and distribution — flora. In Flora of North America Editorial Committee (eds.), Flora of North America North of Mexico, Vol. 12. http://www.efloras.org/florataxon.aspx?flora_id=1&taxon_id=250101357View study →Reference 23Habeck · 1992Frangula purshiana, cascara buckthorn — distribution, botanical and ecological characteristics — species databaseView study →}. The leaf buds have no scales ^{23Reference 23Habeck · 1992Frangula purshiana, cascara buckthorn — distribution, botanical and ecological characteristics — species databaseView study →}.

The small flowers are greenish-yellow, with petals 3–4 mm long, and are borne in stalked umbels of 10–25 ^{22,23Reference 22NesomNesom, G. L. (n.d.). Frangula purshiana (de Candolle) A. Gray ex J. G. Cooper — species description, subspecies, habitat and distribution — flora. In Flora of North America Editorial Committee (eds.), Flora of North America North of Mexico, Vol. 12. http://www.efloras.org/florataxon.aspx?flora_id=1&taxon_id=250101357View study →Reference 23Habeck · 1992Frangula purshiana, cascara buckthorn — distribution, botanical and ecological characteristics — species databaseView study →}. The fruit is a black, rounded drupe 5–10 mm across, holding three stones ^{22Reference 22NesomNesom, G. L. (n.d.). Frangula purshiana (de Candolle) A. Gray ex J. G. Cooper — species description, subspecies, habitat and distribution — flora. In Flora of North America Editorial Committee (eds.), Flora of North America North of Mexico, Vol. 12. http://www.efloras.org/florataxon.aspx?flora_id=1&taxon_id=250101357View study →}.

Flora of North America recognises three subspecies. Subspecies purshiana is the widespread, usually tree-like form. The other two are confined to California and Oregon, and one of them, ultramafica, is a small shrub of mafic and ultramafic soils ^{22Reference 22NesomNesom, G. L. (n.d.). Frangula purshiana (de Candolle) A. Gray ex J. G. Cooper — species description, subspecies, habitat and distribution — flora. In Flora of North America Editorial Committee (eds.), Flora of North America North of Mexico, Vol. 12. http://www.efloras.org/florataxon.aspx?flora_id=1&taxon_id=250101357View study →}.

The plant was long catalogued as Rhamnus purshiana, and pharmacopoeias still use that name ^{19Reference 19European Medicines Agency · 2020ReviewEuropean Union herbal monograph on Rhamnus purshiana DC., cortex, final, revision 1 — regulatory monographView study →}. Floras now place it in Frangula, as Frangula purshiana ^{22,23Reference 22NesomNesom, G. L. (n.d.). Frangula purshiana (de Candolle) A. Gray ex J. G. Cooper — species description, subspecies, habitat and distribution — flora. In Flora of North America Editorial Committee (eds.), Flora of North America North of Mexico, Vol. 12. http://www.efloras.org/florataxon.aspx?flora_id=1&taxon_id=250101357View study →Reference 23Habeck · 1992Frangula purshiana, cascara buckthorn — distribution, botanical and ecological characteristics — species databaseView study →}. It is a different plant from the European buckthorns Rhamnus cathartica and Frangula alnus.

Distribution

Cascara sagrada grows from British Columbia south through Washington and Oregon to northern California. It is mostly found west of the Cascades, but reaches east to northern Idaho and northwestern Montana ^{23Reference 23Habeck · 1992Frangula purshiana, cascara buckthorn — distribution, botanical and ecological characteristics — species databaseView study →}.

It grows in coniferous forests, forest edges, deciduous woodland and along stream banks, from sea level to 2,000 m ^{22Reference 22NesomNesom, G. L. (n.d.). Frangula purshiana (de Candolle) A. Gray ex J. G. Cooper — species description, subspecies, habitat and distribution — flora. In Flora of North America Editorial Committee (eds.), Flora of North America North of Mexico, Vol. 12. http://www.efloras.org/florataxon.aspx?flora_id=1&taxon_id=250101357View study →}. It favours lower mountain slopes and moist sites, and is often found with red alder on moist bottomland, though it is rarely abundant ^{23Reference 23Habeck · 1992Frangula purshiana, cascara buckthorn — distribution, botanical and ecological characteristics — species databaseView study →}.

Sourcing: cascara is on United Plant Savers’ At-Risk list ^{24Reference 24United Plant SaversUnited Plant Savers. (n.d.). Cascara Sagrada – Frangula purshiana (Rhamnus) — At-Risk species profile. https://unitedplantsavers.org/cascara-sagrada-frangula-purshiana/View study →}. Bark harvest kills the stem, although a tree that has been stripped and cut down can sprout again from the stump ^{23Reference 23Habeck · 1992Frangula purshiana, cascara buckthorn — distribution, botanical and ecological characteristics — species databaseView study →}. Before its removal from US over-the-counter laxatives in 2002, more than 5 million pounds of bark were processed in a single year; demand has fallen since, but the bark is still sold in supplements ^{3,24Reference 3Food et al. · 2002Status of certain additional over-the-counter drug category II and III active ingredients (cascara sagrada reclassified as not GRASE)View study →Reference 24United Plant SaversUnited Plant Savers. (n.d.). Cascara Sagrada – Frangula purshiana (Rhamnus) — At-Risk species profile. https://unitedplantsavers.org/cascara-sagrada-frangula-purshiana/View study →}. The IUCN Red List assesses the species as Least Concern ^{24Reference 24United Plant SaversUnited Plant Savers. (n.d.). Cascara Sagrada – Frangula purshiana (Rhamnus) — At-Risk species profile. https://unitedplantsavers.org/cascara-sagrada-frangula-purshiana/View study →}.

Some cascara is now farmed ^{24Reference 24United Plant SaversUnited Plant Savers. (n.d.). Cascara Sagrada – Frangula purshiana (Rhamnus) — At-Risk species profile. https://unitedplantsavers.org/cascara-sagrada-frangula-purshiana/View study →}. When buying the bark, it is worth asking whether it came from cultivated or managed trees, and whether it has been properly dried and aged.

Growing Conditions

Cultivation snapshot for Cascara Sagrada

LifeperennialZoneUSDA 4–9

• Deciduous, cold-hardy tree (roughly USDA zones 4–9); full sun to light woodland shade; a moist-site species.

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Pharmacology & Research

Cascara’s laxative action is well described pharmacologically, but no controlled trial has tested cascara on its own. The EU monograph accepts it for occasional constipation on the strength of its long medical use, its pharmacology, and trial data for the related laxatives senna and aloe ^{20Reference 20European Medicines Agency · 2020Assessment report on Rhamnus purshiana DC., cortex, final, revision 1 — regulatory assessmentView study →}.

The same hydroxyanthracene derivatives that produce the laxative effect are the ones EFSA treats as a genotoxicity concern ^{2,26Reference 2EFSA Panel on Food Additives et al. · 2018ReviewSafety of hydroxyanthracene derivatives for use in food — pharmacopoeial standard and genotoxicity reviewView study →Reference 26EFSA Panel on Nutrition et al. · 2024ReviewScientific Opinion on additional scientific data related to the safety of preparations of Rheum palmatum L., Rheum officinale Baill. and their hybrids, Rhamnus purshiana DC., Rhamnus frangula L. and Cassia senna L., submitted pursuant to Article 8(4) of Regulation (EC) No 1925/2006 — reviewView study →}. Potency also depends on drying and ageing the bark, which turns the emetic anthrones of fresh bark into milder forms ^{20Reference 20European Medicines Agency · 2020Assessment report on Rhamnus purshiana DC., cortex, final, revision 1 — regulatory assessmentView study →}.

The largest body of primary research on its constituents concerns the anthraquinone emodin in cancer cell lines. Isolated emodin and extracts of other Rhamnus and Frangula species are different materials from the aged bark taken as a laxative.

1. Laxative

The bark’s laxative glycosides are the cascarosides A–F, which make up 60–70% of its hydroxyanthracene derivatives ^{14,20Reference 14Rho et al. · 2020Isolation of six anthraquinone diglucosides from cascara sagrada bark by high-performance countercurrent chromatographyView study →Reference 20European Medicines Agency · 2020Assessment report on Rhamnus purshiana DC., cortex, final, revision 1 — regulatory assessmentView study →}. The European Pharmacopoeia requires at least 8.0% hydroxyanthracene glycosides, of which at least 60% must be cascarosides, calculated as cascaroside A ^{20Reference 20European Medicines Agency · 2020Assessment report on Rhamnus purshiana DC., cortex, final, revision 1 — regulatory assessmentView study →}.

The cascarosides are largely not split by human digestive enzymes and are not absorbed in the upper gut. Bacteria in the large intestine convert them into the active metabolite, mainly emodin-9-anthrone ^{19Reference 19European Medicines Agency · 2020ReviewEuropean Union herbal monograph on Rhamnus purshiana DC., cortex, final, revision 1 — regulatory monographView study →}.

The active compound works in two ways. It speeds the movement of the colon, and it reduces the absorption of water and salts from the bowel while increasing their secretion into it ^{19Reference 19European Medicines Agency · 2020ReviewEuropean Union herbal monograph on Rhamnus purshiana DC., cortex, final, revision 1 — regulatory monographView study →}. The bowel moves eight to twelve hours after a dose ^{19Reference 19European Medicines Agency · 2020ReviewEuropean Union herbal monograph on Rhamnus purshiana DC., cortex, final, revision 1 — regulatory monographView study →}.

The EU assessment found no controlled clinical studies of cascara alone for constipation. The clinical studies that exist tested it in combinations. In bowel cleansing before examination, a cascara and magnesium sulphate combination did less well than a polyethylene glycol solution ^{20Reference 20European Medicines Agency · 2020Assessment report on Rhamnus purshiana DC., cortex, final, revision 1 — regulatory assessmentView study →}.

In 2002 the FDA reclassified cascara as not generally recognised as safe and effective for over-the-counter use, a regulatory judgement rather than a finding about efficacy ^{3Reference 3Food et al. · 2002Status of certain additional over-the-counter drug category II and III active ingredients (cascara sagrada reclassified as not GRASE)View study →}.

Gap: no placebo-controlled trial of cascara itself for constipation, and no dose-finding study ^{20Reference 20European Medicines Agency · 2020Assessment report on Rhamnus purshiana DC., cortex, final, revision 1 — regulatory assessmentView study →}.

2. Anticancer

The bark’s most studied single molecule, the anthraquinone emodin, shows anti-proliferative and pro-apoptotic activity in cancer cell lines. Synthetic emodin rhamnosides were about ten times more potent than emodin itself against a panel of human cancer cell lines, acting through the mitochondrial (intrinsic) apoptosis pathway ^{7Reference 7Xing et al. · 2015In vitroAntitumor effects and mechanism of novel emodin rhamnoside derivatives against human cancer cells in vitroView study →}.

A study of cascarosides isolated from cascara bark found that the sugar groups on the molecule reduced its toxicity to cells. The authors recommended cascaroside-enriched extracts for laxative use ^{5Reference 5Demarque et al. · 2018In vitroCytotoxicity of structurally diverse anthranoids and correlation with mechanism of action and side effects — in vitroView study →}.

Whole-extract work compares the effects of single hydroxyanthracene molecules with those of whole plant extracts in intestinal cells ^{15Reference 15Tinti et al. · 2023In vitroHydroxyanthracene derivatives cytotoxicity: a differential evaluation between single molecule and whole plant extract — in vitroView study →}.

Gap: no animal tumour studies with the bark and no clinical data. The activity belongs to isolated or synthetic molecules, not to the laxative bark.

3. Antiviral

Hot glycerin extracts of cascara and four other anthraquinone-bearing plants inactivated herpes simplex virus type 1 in vitro. Purified aloe-emodin inactivated herpes simplex, varicella-zoster, pseudorabies and influenza viruses, but not adenovirus or rhinovirus. Electron microscopy showed the virus envelopes partly disrupted ^{6Reference 6Sydiskis et al. · 1991In vitroInactivation of enveloped viruses by anthraquinones extracted from plants — in vitroView study →}.

In a separate study, anthraquinones derived from cascaroside A were tested in a short-term Epstein–Barr virus activation assay used to screen for anti-tumour-promoting activity ^{16Reference 16Koyama et al. · 2001In vitroInhibitory effects of anthraquinones and bianthraquinones on Epstein-Barr virus activation — in vitroView study →}.

Gap: both are direct-contact laboratory findings, with no animal or human data.

Mechanisms

The cascarosides are glycosides of anthrones, and their sugar groups keep them from being absorbed until they reach the colon. There, bacteria release the active anthrone, mainly emodin-9-anthrone, which acts on the wall of the large bowel ^{19Reference 19European Medicines Agency · 2020ReviewEuropean Union herbal monograph on Rhamnus purshiana DC., cortex, final, revision 1 — regulatory monographView study →}.

The free anthraquinones, emodin and aloe-emodin, have been studied separately in cancer cells and against viruses. EFSA considers them genotoxic in vitro ^{2Reference 2EFSA Panel on Food Additives et al. · 2018ReviewSafety of hydroxyanthracene derivatives for use in food — pharmacopoeial standard and genotoxicity reviewView study →}.

Pharmacokinetics

The cascarosides are not split by human digestive enzymes and are not absorbed in the upper gut. Colon bacteria convert them to the active anthrone, emodin-9-anthrone, which acts on the bowel wall ^{19Reference 19European Medicines Agency · 2020ReviewEuropean Union herbal monograph on Rhamnus purshiana DC., cortex, final, revision 1 — regulatory monographView study →}. The bowel moves eight to twelve hours after a dose ^{19Reference 19European Medicines Agency · 2020ReviewEuropean Union herbal monograph on Rhamnus purshiana DC., cortex, final, revision 1 — regulatory monographView study →}.

No pharmacokinetic study of cascara itself has been done in people. The nearest data are for senna: in ten healthy volunteers given therapeutic doses, aloe-emodin was undetectable in plasma, while rhein peaked at 150–160 ng/mL, at 3–5 hours and again at 10–11 hours, the later peak probably from rhein released in the colon by bacteria ^{27Reference 27Krumbiegel G · 1993Clinical trialRhein and aloe-emodin kinetics from senna laxatives in man — human study (healthy volunteers)View study →}.

Anthraquinones as a class are absorbed mainly in the intestine, the free aglycones faster than their glycosides, and often show two blood peaks from recirculation through the liver and gut. They are cleared mainly by glucuronidation and sulfation ^{28Reference 28Wang D et al. · 2021ReviewPharmacokinetics of Anthraquinones from Medicinal Plants — reviewView study →}. In rat liver microsomes, emodin is oxidised by CYP enzymes, partly CYP1A2, to 2-hydroxyemodin, which was more genotoxic than emodin in a cell test ^{29Reference 29Mueller SO et al. · 1998In vitroBiotransformation of the anthraquinones emodin and chrysophanol by cytochrome P450 enzymesView study →}.

Rhein passes into breast milk in small amounts ^{19Reference 19European Medicines Agency · 2020ReviewEuropean Union herbal monograph on Rhamnus purshiana DC., cortex, final, revision 1 — regulatory monographView study →}.

Clinical Trials

No registered trial has tested cascara sagrada on its own. ClinicalTrials.gov entries for “cascara” are coffee-cherry pulp, unrelated studies, or a multi-ingredient cleanse supplement that includes cascara bark among a dozen ingredients.

Last checked: October 2026.

Phytochemistry

The bark’s active constituents are hydroxyanthracene derivatives. The European Pharmacopoeia requires at least 8.0% hydroxyanthracene glycosides in the dried bark, of which at least 60% must be cascarosides, calculated as cascaroside A ^{20Reference 20European Medicines Agency · 2020Assessment report on Rhamnus purshiana DC., cortex, final, revision 1 — regulatory assessmentView study →}.

Of the total hydroxyanthracene complex, 60–70% is cascarosides, 10–30% is the aloins and chrysaloins, and 10–20% is a mixture of O-glycosides and free aglycones ^{20Reference 20European Medicines Agency · 2020Assessment report on Rhamnus purshiana DC., cortex, final, revision 1 — regulatory assessmentView study →}. Six cascarosides, A to F, have been isolated from the bark ^{14Reference 14Rho et al. · 2020Isolation of six anthraquinone diglucosides from cascara sagrada bark by high-performance countercurrent chromatographyView study →}.

The cascarosides form three pairs. Cascaroside A and cascaroside B are built on the aloins (barbaloin), which are aloe-emodin anthrone glycosides. Cascaroside C and cascaroside D are built on the chrysaloins, from chrysophanol anthrone. Cascarosides E and F are built on emodin anthrone ^{20Reference 20European Medicines Agency · 2020Assessment report on Rhamnus purshiana DC., cortex, final, revision 1 — regulatory assessmentView study →}.

The O-glycoside fraction includes glucosides of aloe-emodin, chrysophanol, emodin and physcion, along with the free aglycones ^{20Reference 20European Medicines Agency · 2020Assessment report on Rhamnus purshiana DC., cortex, final, revision 1 — regulatory assessmentView study →}. The bark also contains tannic acid ^{17Reference 17A Modern Herbal · 1931Buckthorn (Californian). https://www.botanical.com/botanical/mgmh/b/buckth80.htmlView study →}.

Fresh bark is chemically different. It holds mono-anthrones and their O-glycosides, which cause vomiting. During drying these are oxidised to dianthrone and anthraquinone glycosides, which do not ^{20Reference 20European Medicines Agency · 2020Assessment report on Rhamnus purshiana DC., cortex, final, revision 1 — regulatory assessmentView study →}.

Constituent Summary

Figures are shares of the dried bark or of its total hydroxyanthracene derivatives ^{20Reference 20European Medicines Agency · 2020Assessment report on Rhamnus purshiana DC., cortex, final, revision 1 — regulatory assessmentView study →}.

Dosage

Cascara is dosed by its content of hydroxyanthracene derivatives, calculated as cascaroside A. The EU herbal monograph dose for adults and adolescents over 12 is 10–30 mg, taken once at night, using the smallest dose that gives a comfortable soft stool. It is not for use for more than one week, and two or three doses in that week are usually enough ^{19Reference 19European Medicines Agency · 2020ReviewEuropean Union herbal monograph on Rhamnus purshiana DC., cortex, final, revision 1 — regulatory monographView study →}.

As a tea, the monograph uses an amount of bark giving no more than 30 mg hydroxyanthracene derivatives, infused in 150 mL of boiling water ^{19Reference 19European Medicines Agency · 2020ReviewEuropean Union herbal monograph on Rhamnus purshiana DC., cortex, final, revision 1 — regulatory monographView study →}.

The dried-bark equivalent assumes the Ph. Eur. minimum of 8% hydroxyanthracene derivatives. Bark with a higher content needs less.

Traditional Dosage

Safety & Pregnancy

Cascara is a stimulant laxative for short courses, no more than a week ^{19Reference 19European Medicines Agency · 2020ReviewEuropean Union herbal monograph on Rhamnus purshiana DC., cortex, final, revision 1 — regulatory monographView study →}. The problems come from long or heavy use.

Full Safety Detail

Short courses only. Long-term use of stimulant laxatives can impair bowel function and lead to dependence on laxatives. If a laxative is needed every day, the cause of the constipation should be looked into. Cascara is for use after a change of diet or a bulk-forming laxative has not worked ^{19Reference 19European Medicines Agency · 2020ReviewEuropean Union herbal monograph on Rhamnus purshiana DC., cortex, final, revision 1 — regulatory monographView study →}.

Common effects. Cascara can cause abdominal pain, spasm and liquid stools, especially in people with an irritable colon; these usually mean the dose is too high. Hypersensitivity reactions such as itching, hives and rash can occur. Urine may turn yellow or red-brown, which is not clinically significant ^{19Reference 19European Medicines Agency · 2020ReviewEuropean Union herbal monograph on Rhamnus purshiana DC., cortex, final, revision 1 — regulatory monographView study →}.

Long-term use. Prolonged use can upset the balance of water and electrolytes, and may cause protein and blood in the urine. People with kidney disease should be aware of the risk of electrolyte imbalance ^{19Reference 19European Medicines Agency · 2020ReviewEuropean Union herbal monograph on Rhamnus purshiana DC., cortex, final, revision 1 — regulatory monographView study →}.

Pigmentation of the colon. Chronic use pigments the colon lining (pseudomelanosis coli). The pigment usually fades once the laxative is stopped ^{19Reference 19European Medicines Agency · 2020ReviewEuropean Union herbal monograph on Rhamnus purshiana DC., cortex, final, revision 1 — regulatory monographView study →}. In one large series, people with melanosis coli had more polyps detected at colonoscopy but fewer colorectal cancers than controls, which the authors put down to the pigment making polyps easier to see ^{11Reference 11Abu Baker et al. · 2018ReviewMelanosis coli: a helpful contrast effect or a harmful pigmentation? — reviewView study →}. A second study linked severe melanosis from anthranoid use with a higher rate of adenomas ^{12Reference 12Katsumata et al. · 2022ObservationalSevere grade of melanosis coli is associated with a higher detection rate of colorectal adenoma — observationalView study →}.

Colorectal cancer. A 2022 meta-analysis of observational studies found a trend toward more colorectal cancer with anthraquinone laxatives, but the association was not statistically significant ^{1Reference 1Lombardi et al. · 2022Meta-analysisAnthraquinone laxatives use and colorectal cancer: systematic review and meta-analysis of observational studiesView study →}.

Genotoxicity. EFSA concluded in 2018 that emodin and aloe-emodin are genotoxic in vitro, and that hydroxyanthracene derivatives in food should be treated as genotoxic and carcinogenic unless shown otherwise ^{2Reference 2EFSA Panel on Food Additives et al. · 2018ReviewSafety of hydroxyanthracene derivatives for use in food — pharmacopoeial standard and genotoxicity reviewView study →}. In 2021 the EU banned emodin and aloe-emodin in foods and placed cascara bark preparations under scrutiny ^{21Reference 21European Commission · 2021Commission Regulation (EU) 2021/468 of 18 March 2021 amending Annex III to Regulation (EC) No 1925/2006 as regards botanical species containing hydroxyanthracene derivatives — regulationView study →}. In 2024 EFSA reviewed new genotoxicity studies of cascara and related bark, root and leaf preparations. All were negative, but the preparations were too poorly characterised to settle the question, and because they contained a compound known to be genotoxic in animals, their safety could not be established ^{26Reference 26EFSA Panel on Nutrition et al. · 2024ReviewScientific Opinion on additional scientific data related to the safety of preparations of Rheum palmatum L., Rheum officinale Baill. and their hybrids, Rhamnus purshiana DC., Rhamnus frangula L. and Cassia senna L., submitted pursuant to Article 8(4) of Regulation (EC) No 1925/2006 — reviewView study →}.

A plant-cell test of two cascara bark extracts found they slowed cell division and damaged chromosomes in lettuce root cells, with the drying method changing the effect ^{4Reference 4Silva Souza et al. · 2025In vitroPhytotoxicity and cytogenotoxic effects of extracts from the medicinal bark of Rhamnus purshiana DC. — in vitroView study →}. The EU monograph notes that genotoxicity was seen in vitro but not proven in vivo, and that cascara bark did not induce precancerous lesions (aberrant crypt foci) in rats treated for 13 weeks. At the higher of two dietary doses, cascara glycosides did increase the number of these lesions caused by a known carcinogen ^{19Reference 19European Medicines Agency · 2020ReviewEuropean Union herbal monograph on Rhamnus purshiana DC., cortex, final, revision 1 — regulatory monographView study →}.

Liver. Case reports describe cholestatic hepatitis with portal hypertension after three days of cascara capsules, severe toxic hepatitis after four weeks, and acute liver injury after large quantities ^{8,9,10Reference 8Nadir et al. · 2000Case reportCascara sagrada-induced intrahepatic cholestasis causing portal hypertension: case report and review of herbal hepatotoxicityView study →Reference 9Nakasone et al. · 2015A case of cholangiocarcinoma identified incidentally after acute liver injury due to cascara sagradaView study →Reference 10Jacobsen et al. · 2009Case reportToxic hepatitis following consumption of the herbal medicinal product cascara sagrada — case reportView study →}. Chronic overdose of anthranoid laxatives may lead to toxic hepatitis ^{19Reference 19European Medicines Agency · 2020ReviewEuropean Union herbal monograph on Rhamnus purshiana DC., cortex, final, revision 1 — regulatory monographView study →}.

Who should not take it. Cascara is contraindicated in bowel obstruction or narrowing, bowel atony, appendicitis, inflammatory bowel disease (Crohn’s disease, ulcerative colitis), abdominal pain of unknown cause, and severe dehydration ^{19Reference 19European Medicines Agency · 2020ReviewEuropean Union herbal monograph on Rhamnus purshiana DC., cortex, final, revision 1 — regulatory monographView study →}. It should not be taken with faecal impaction, or with unexplained abdominal pain, nausea or vomiting, which can signal a blocked bowel ^{19Reference 19European Medicines Agency · 2020ReviewEuropean Union herbal monograph on Rhamnus purshiana DC., cortex, final, revision 1 — regulatory monographView study →}.

Interactions. Potassium lost through long-term use strengthens the effect of cardiac glycosides such as digoxin and interacts with antiarrhythmic drugs. Diuretics, corticosteroids and liquorice root add to the potassium loss, and people on QT-prolonging drugs should take advice first ^{19Reference 19European Medicines Agency · 2020ReviewEuropean Union herbal monograph on Rhamnus purshiana DC., cortex, final, revision 1 — regulatory monographView study →}.

Drug metabolism. No human interaction study of cascara has been done. In liver cells, an infusion of the bark raised CYP3A4 gene expression, apparently by activating the pregnane X receptor, and it changed P-glycoprotein activity in gut cells; the authors recommend pharmacovigilance ^{30Reference 30Mazzari ALDA et al. · 2022In vitroIn vitro effects of European and Latin-American medicinal plants in CYP3A4 gene expression, glutathione levels, and P-glycoprotein activity — in vitroView study →}. In rat liver microsomes, emodin is oxidised partly by CYP1A2 to a more genotoxic metabolite ^{29Reference 29Mueller SO et al. · 1998In vitroBiotransformation of the anthraquinones emodin and chrysophanol by cytochrome P450 enzymesView study →}. Neither finding has been confirmed in people.

Children and incontinent adults. The EU herbal monograph does not allow cascara under 12 years. In incontinent adults, pads should be changed often to prevent long skin contact with stool ^{19Reference 19European Medicines Agency · 2020ReviewEuropean Union herbal monograph on Rhamnus purshiana DC., cortex, final, revision 1 — regulatory monographView study →}.

Overdose. Overdose causes griping pain and severe diarrhoea, with loss of fluid and electrolytes. Potassium should be monitored, especially in the elderly ^{19Reference 19European Medicines Agency · 2020ReviewEuropean Union herbal monograph on Rhamnus purshiana DC., cortex, final, revision 1 — regulatory monographView study →}.

Quality. Cascara bark is a good medium for aflatoxin-producing moulds. In one survey aflatoxin was found in 2 of 9 raw-bark samples and 1 of 10 tablet lots, and the authors call for aflatoxin testing of the bark ^{31Reference 31Rizzo I et al. · 1999In vitroMycotoxicological control on raw material and tablets of cascara sagrada (Rhamnus purshiana) — in vitro (aflatoxin survey)View study →}. Fresh, unaged bark causes vomiting and is not used ^{20Reference 20European Medicines Agency · 2020Assessment report on Rhamnus purshiana DC., cortex, final, revision 1 — regulatory assessmentView study →}.

References

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