Cinchona

Cinchona (Cinchona spp.): A Comprehensive Reference

1. Identity and Botanical Description

1.1 Taxonomy and Botanical Names

Cinchona is a genus of about 23 species of plants, mostly trees, in the madder family (Rubiaceae), native to the Andes of South America. There are at least 24 species of Cinchona recognized by botanists. The most pharmacologically significant species include Cinchona calisaya, C. ledgeriana, and C. succirubra, all of which were historically cultivated for alkaloid yield. Another species frequently cited in medicinal contexts is Cinchona officinalis, and the genus as a whole is often referred to simply as "cinchona" or by the common names applied to its bark.

The bark is also known as Peruvian Bark or Jesuit's Bark and is renowned for its medicinal properties. Other synonyms recorded in historical and contemporary literature include Bois aux Fièvres, Chinarinde, Écorce du Pérou, Écorce de Quina, Fieberrinde, Kina-Kina, Poudre des Jésuites, Quina, Quino, Quinquina, Quinquina Gris, and Quinquina Rouge. The name "cinchona" probably derives from the Quechua word "kina-kina," meaning "bark of the barks."

1.2 Natural Source and Habitat

The cinchona is a large shrub or small tree indigenous to South America; in the 19th century it could be found along the west coast from Venezuela in the north to Bolivia in the south. The cinchonas are evergreen shrubs and trees that grow to heights of 15 to 31 meters, native to the mountainous areas of tropical Central and South America, including regions of Bolivia, Costa Rica, and Peru.

The trees were introduced widely throughout the tropics during the 19th century to secure quinine supplies, leading to massive plantations in Java, India, and East Africa. After centuries of export of barks from South America to Europe, the threat of overharvesting along with the desire to control quality and quantity of supply led to attempts by the British, Dutch, and French empires to start Cinchona plantations in other tropical regions, taking this Andean tree as far as India and Indonesia.

1.3 The Medicinal Part: The Bark

The bark — gray-brown and deeply fissured in older specimens — is the plant's most valuable part, rich in quinoline alkaloids including quinine, cinchonine, and quinidine. Cinchona cortex contains between 5 and 15% bitter-tasting cinchona alkaloids, with a minimum of 30% and a maximum of 60% quinine; further ingredients include catechin tanning agents and triterpene-type bitter substances. A minimum content of 6.5% total alkaloids is required by the European Pharmacopoeia. Alongside the alkaloids, many cinchona barks contain cinchotannic acid, a particular tannin, which by oxidation rapidly yields a dark-coloured phlobaphene called red cinchonic, cinchono-fulvic acid, or cinchona red.

1.4 Common Forms and Preparations

Cinchona is available and has historically been used in several distinct forms:

• Crude bark (dried, ground, or chopped): Before 1820, the bark of the cinchona tree was first dried, ground to a fine powder, and then mixed into a liquid (commonly wine) before being drunk.
• Infusion (tea): The longstanding traditional remedy calls for a cup of boiling water poured over approximately 1–2 g of ground or chopped bark and allowed to steep for ten minutes; a cupful of this infusion is drunk half an hour before meals to stimulate the appetite, or after meals to treat digestive disorders. Traditionally, cinchona has been prepared as a tea.
• Tincture: Cinchona tincture is a preparation noted in both traditional pharmacopoeias and early modern formularies, including 19th-century bitter tonic mixtures combining cinchona tincture with gentian, calumba, and rhubarb tinctures.
• Purified alkaloid salts: In 1820, quinine was extracted from the bark, isolated, and named by Pierre Joseph Pelletier and Joseph Caventou. Purified quinine then replaced the bark as the standard treatment for malaria. Today, quinine sulfate capsules (e.g., Qualaquin) are the pharmaceutical form for clinical use.
• Flavoring agent in beverages: Products made from cinchona bark, such as spices or teas, have a characteristically extremely bitter taste; cinchona bark is used in many refreshing (e.g., tonic water) and alcoholic drinks for flavoring.
• Homeopathic preparations: Cinchona is used in homeopathic preparations — its role in the genesis of homeopathy as a system is notable, as Samuel Hahnemann's 1790 experiments with cinchona bark are credited with inspiring the foundational principle of "like cures like."
• Topical preparations: Cinchona is used in eye lotions to numb pain, kill germs, and as an astringent; cinchona extract is also applied to the skin for hemorrhoids, stimulating hair growth, and managing varicose veins.

2. Traditional and Historical Use

2.1 Pre-Colonial and Andean Use

From its first documented use by the Spanish in Peru around 1630, the history of Cinchona bark is a mixture of facts and legends. Although the bark was not included in the Inca pharmacopeia, it appears to have been used by Andean populations to combat shivering. The indigenous Quechua-speaking peoples of the Andean region are the earliest recorded users of the bark.

2.2 Introduction to Europe (17th Century)

The therapeutic potential of cinchona bark was first documented in 1633 by a Jesuit missionary in Peru, marking the beginning of its global use in managing febrile illnesses, most notably malaria, from the 17th century onward. The medicine became known, among other names, as Cortex peruanus, or Jesuit's powder, since it had been imported into Europe from Latin America by the Loyola Order. By the 1630s (or 1640s, depending on the reference), the bark was being exported to Europe.

Bark extracts had been used to treat malaria since at least 1632 and were introduced to Spain as early as 1636 by Jesuit missionaries returning from the New World. In the late 1640s, the method of use of the bark was noted in the Schedula Romana. During the 300 years between its introduction into Western medicine and its medical use during World War I, quinine from cinchona was the only effective remedy for malaria.

2.3 Use as a Fever Remedy and Antimalarial

During the second half of the 17th century, the bark was used increasingly to treat fevers — and intermittent fevers in particular, which were shown 200 years later to be caused by malarial parasites. During the 18th century, malaria gradually became accepted as a defined set of intermittent fevers responding to "therapeutic tests" using Cinchona bark, or, from the 1820s, by using quinine.

Quinine, a bitter-tasting, short-acting alkaloid drug extracted from cinchona bark, was the first drug used widely for malaria chemoprophylaxis from the 19th century. Treatment of malaria with quinine marks the first known use of a chemical compound to treat an infectious disease.

2.4 Use as a Digestive Bitter and General Tonic

Beyond malaria, cinchona bark was used as a digestive aid and a general tonic. Its bitter compounds were known to stimulate appetite and were thought to strengthen overall health. This use as a tonic eventually influenced aperitivo culture, where bitter botanicals are prized for their digestive benefits. The German Commission E monograph for cinchona bark lists loss of appetite, dyspeptic complaints, flatulence, and bloating as approved indications; in empirical medicine, it remains in use as a bitter substance for loss of appetite and digestive complaints.

2.5 Cardiac Use

Jean-Baptiste Senac, a French physician, is the first to describe the use of cinchona extract for cardiac irregularities. A well-documented anecdote describes a ship's captain with atrial fibrillation who showed cardiologist Karl Friedrich Wenckebach how cinchona bark could control cardiac irregularity; following this, Wenckebach popularized the use of cinchona extract for arrhythmia therapy. The recognition of quinidine's antiarrhythmic potential likely stemmed from a clinical observation in which a patient receiving quinine for malaria exhibited arrhythmic episodes that resolved without recurrence during therapy.

2.6 Colonial Plantation History

In the middle of the 19th century, seeds of Cinchona calisaya and Cinchona pubescens were smuggled out of South America by the British and the Dutch. The calisaya species was planted and cultivated in Java by the Dutch and the pubescens species was cultivated in India and Ceylon by the British. Cinchona calisaya, with a total alkaloid content up to 6.5% of which around 80% is quinine, provided the most readily available bioactive alkaloid with barks in reliable supply. Quinine was supplied by the first global pharmaceutical cartel, which discouraged competition resulting in a near monopoly of cinchona plantations on the island of Java — plantations that were closed to Allied use when the Japanese Imperial Army captured Indonesia in 1942.

2.7 Chemical Isolation and Standardization

In 1820, two French chemists, Joseph Pelletier and Pierre Caventou, first extracted two active constituents of cinchona — quinine and cinchonine. In 1820, the first quinine alkaloids were extracted and described, and it finally became possible to associate the various Cinchona species with their alkaloid concentrations. In 1934, efforts to make malaria drugs cheap and effective for use across countries led to the development of a standard called "totaquina" proposed by the Malaria Commission of the League of Nations. Totaquina required a minimum of 70% crystallizable alkaloids, of which at least 15% was to be quinine, with not more than 20% amorphous alkaloids.

The first FDA approval of a quinine formulation for the treatment of malaria took place only in 2005 with Qualaquin (quinine sulfate capsules), indicated for the treatment of uncomplicated P. falciparum malaria.

3. Key Constituents and Active Compounds

3.1 Major Alkaloids

Cinchona bark produces a number of alkaloids, namely cinchonine, cinchonidine, quinine, quinidine, and quinamine. By far the most valuable of these is quinine, a drug used to treat malaria; all the alkaloids, with the exception of sulphate of cinchonine, are known for their febrifugal properties.

• Quinine: The most familiar alkaloid, an antipyretic (antifever) agent especially useful in treating malaria. The class of chemical compounds to which it belongs is called the cinchona alkaloids.
• Quinidine: Quinidine is a stereoisomer of quinine, derived from the bark of the South American cinchona tree, and serves as a class Ia antiarrhythmic drug and an antimalarial agent.
• Cinchonine and cinchonidine: Quinine and other cinchona alkaloids including quinidine, cinchonine, and cinchonidine are all effective against malaria.

3.2 Non-Alkaloid Constituents

Further ingredients in the bark include catechin tanning agents and triterpene-type bitter substances. Many cinchona barks also contain cinchotannic acid, a particular tannin, which by oxidation rapidly yields a dark-coloured phlobaphene called red cinchonic, cinchono-fulvic acid, or cinchona red. These tannins contribute to the bark's astringent properties.

4. Mechanisms of Action

4.1 Antimalarial Mechanism of Quinine and Related Alkaloids

Quinoline-containing antimalarial drugs such as chloroquine, quinine, and mefloquine are mainstays of chemotherapy against malaria. The molecular basis of their action is not completely understood, but they are thought to interfere with hemoglobin digestion in the blood stages of the malaria parasite's life cycle. The parasite degrades hemoglobin in an acidic food vacuole, producing free heme and reactive oxygen species as toxic by-products; the heme moieties are normally neutralized by polymerization into hemozoin.

Quinine interferes with this detoxification process; specifically, it is believed to bind to heme, preventing its conversion into hemozoin. This leads to an accumulation of toxic heme within the parasite, causing oxidative damage and ultimately killing the parasite. By disrupting the detoxification pathway, quinine effectively halts the development and proliferation of the malaria parasite within the red blood cells. Moreover, quinine affects the parasite's DNA replication and protein synthesis, interrupting its ability to replicate and transcribe its genetic material, further hindering its capacity to reproduce and spread within the host.

Quinoline antimalarial drugs were studied as inhibitors of β-hematin formation; the most potent inhibitors were quinacrine, chloroquine, and amodiaquine, followed by quinidine, mefloquine, and quinine.

4.2 Antiarrhythmic Mechanism of Quinidine

Quinidine is a class IA antiarrhythmic agent used to treat heart rhythm disturbances. It is a diastereomer of antimalarial agent quinine, originally derived from the bark of the cinchona tree. The drug causes increased action potential duration, as well as a prolonged QT interval. Quinidine prolongs the QT interval on the electrocardiogram in a very heterogeneous way, creating a predisposition to the development of cardiac arrhythmias, especially Torsade de pointes, a rapid ventricular tachycardia.

4.3 Bitter Digestive Mechanism

Cinchona bark stimulates saliva and stomach (gastric) juice secretion. The alkaloids and bitter substances contained in the bark have a beneficial effect on gastric secretion and are therefore mainly used today as a remedy to stimulate the appetite and for digestive complaints. This effect is consistent with the established pharmacology of bitter substances (bitters), which interact with bitter taste receptors (TAS2Rs) in the gastrointestinal tract, triggering cephalic-phase digestive reflexes.

4.4 Muscle-Relaxant Properties

Quinine has analgesic and muscle-relaxant properties and has been shown to decrease the excitability of the motor end plate to nerve stimulation and increase the muscle refractory period. This latter property has led to the widespread use of quinine in the treatment of muscle cramps.

5. Scientific Evidence by Area of Use

5.1 Malaria Treatment

Evidence level: Strong for quinine-derived pharmaceutical preparations; weak for crude bark or supplement forms.

Cinchona bark is defined as the source of quinine, an alkaloid compound isolated in the 19th century that was widely used as an antimalarial agent, marking the first successful treatment of malaria with a pure chemical compound. Cinchona is the only economically practical source of quinine, a drug that is still recommended for the treatment of falciparum malaria.

The efficacies of the four major cinchona alkaloids were evaluated in one of the earliest clinical trials, conducted from 1866 to 1868 in 3,600 patients using prepared sulfates of the alkaloids. Comparative trials were subsequently organized internationally: the British Medical Research Council's Cinchona Derivatives and Malaria Committee made arrangements for "confirmative trials" in Khartoum, El-Obeid, Lagos, Port of Spain, Georgetown, Dar-es-Salaam, Nairobi, Entebbe, and Kuala Lumpur, using the disappearance of parasites from the peripheral blood as the principal measure of effect.

The cinchona alkaloids have been important antimalarial drugs for more than 350 years. The principal alkaloid, quinine, still remains effective against chloroquine-resistant falciparum malaria and is widely used. Development of quinine resistance in Plasmodium falciparum has been relatively slow and incomplete compared with the other principal antimalarial drugs. In areas with multidrug-resistant strains, 7-day regimens of quinine and tetracycline still provide cure rates well over 90% in patients with uncomplicated falciparum malaria.

In severe pediatric malaria, a major comparative trial (AQUAMAT) provided landmark data: the AQUAMAT study provides conclusive evidence of the superiority of intravenous artesunate over quinine in children under 15 years, with a relative reduction of 23% in mortality associated with the use of artesunate. This has shifted WHO guidelines, with artesunate now preferred for severe cases, while quinine remains a critical second-line option. Quinine is on the World Health Organization's List of Essential Medicines.

Importantly, many consumer websites promote natural ways to prevent or treat malaria using quinine from the cinchona tree, but official guidance strongly urges patients to follow official recommendations, including the use of malaria chemoprophylaxis, and not to rely on unproven natural approaches to prevent or treat such a serious disease. Crude cinchona bark preparations are not standardized for alkaloid content and are not recommended as a substitute for pharmaceutical quinine.

5.2 Cardiac Arrhythmia (Quinidine)

Evidence level: Historically established for quinidine as a pharmaceutical; safety concerns limit current use.

In 1918, Walter Frey demonstrated the high efficacy of quinidine in converting atrial fibrillation to sinus rhythm. Quinidine is occasionally used as a class I antiarrhythmic agent to prevent ventricular arrhythmias, particularly in Brugada Syndrome, although its safety in this indication is uncertain. A number of studies have indicated that patients taking quinidine are at a higher risk for death than those not taking quinidine. In 1991, the FDA approved the introduction of a new indication for quinidine gluconate injection, adding life-threatening P. falciparum malaria therapy to cardiac arrhythmia therapy.

There is one study supporting the use of a novel combination of dextromethorphan and low-dose quinidine in alleviating symptoms of pseudobulbar affect in neurological conditions such as ALS and multiple sclerosis. The dose of quinidine used (10 mg twice daily) is about 1/40th of a low antiarrhythmic dose. The authors did not observe significant safety risks at this low dose but urged caution, noting that quinidine interacts with a large number of other medications in dangerous or unpredictable ways. A meta-analysis was published referencing only that one study.

5.3 Muscle Cramps / Nocturnal Leg Cramps

Evidence level: Weak to negative; formally contraindicated for this use by the FDA.

A 2006 FDA advisory warned against the use of quinine in the treatment of nocturnal muscle cramps. Quinine is not approved for the treatment or prevention of night-time leg cramps. It can cause serious and life-threatening blood disorders, such as a severe drop in platelets (thrombocytopenia), which can lead to permanent kidney damage or death. Although quinine had historically been used for leg cramps based on anecdotal data from the 1930s, the risk-benefit profile has been judged unfavorable for this indication by regulatory authorities.

5.4 Digestive and Appetite Uses

Evidence level: Traditional/empirical; supported by pharmacological plausibility (bitter tonic reflex) but lacking robust modern clinical trials.

The German Commission E monograph for cinchona bark lists loss of appetite, dyspeptic complaints, flatulence, and bloating as recognized indications. Cinchona is used for increasing appetite, promoting the release of digestive juices, and treating bloating, fullness, and other stomach problems. Modern research supporting its efficacy and safety for non-malarial uses is limited, with most studies being observational or in vitro.

5.5 Other Putative Uses Lacking Clinical Evidence

People use cinchona for cancer, hemorrhoids, malaria, muscle cramps, varicose veins, and many other conditions, but there is no good scientific evidence to support these uses. It is also used for blood vessel disorders including hemorrhoids, varicose veins, and leg cramps, though these indications remain without well-designed clinical trial support.

6. Body Systems and Health Areas Associated with Cinchona

• Immune and Infectious Disease: Primary historical and pharmaceutical use. Quinine targets the malarial parasite (Plasmodium spp.) in the bloodstream.
• Cardiovascular System: Quinidine is used as a class Ia antiarrhythmic; both quinine and quinidine can prolong the QT interval and affect cardiac conduction. Some of the chemicals in cinchona can slow the heart, cause constipation, and affect the central nervous system.
• Gastrointestinal System: Cinchona can increase stomach acid. Its bitter alkaloids stimulate gastric juice and saliva secretion, supporting its use as a digestive tonic and appetite stimulant.
• Musculoskeletal System: Quinine's muscle-relaxant and motor end-plate properties have been applied to cramp treatment, though regulatory bodies have withdrawn approval for this use due to the risk profile.
• Nervous System / Sensory Organs: Cinchonism is a collection of symptoms stemming from the ingestion of quinoline derivatives and their subsequent neural, retinal, and auditory toxicity.
• Hematological System: Quinine can cause immune-mediated thrombocytopenia and hemolytic anemia, particularly in G6PD-deficient individuals.

7. Dosage Forms and Dosages Reported in Studies

Traditionally, cinchona has been prepared as a tea. However, there is not enough reliable information to know what an appropriate dose of cinchona (as crude bark) might be.

The following dosages come from specific clinical and regulatory sources:

• Crude bark infusion (traditional): Approximately 1–2 g of ground or chopped bark steeped in a cup of boiling water for ten minutes, drunk before or after meals.
• Quinine sulfate for uncomplicated falciparum malaria (FDA-approved pharmaceutical): Antimalarial doses of 600 mg or greater of quinine may inhibit the metabolism of other drugs that are CYP2D6 substrates. The Qualaquin prescribing information describes dosing at 648 mg three times daily for 7 days in combination with other antimalarials.
• Quinine for malaria prophylaxis (historical): "Prophylactic rations" of quinine were used widely from the 19th century, though compliance was difficult to enforce.
• Quinidine (antiarrhythmic, low-dose experimental): The dose of quinidine used in pseudobulbar affect studies (10 mg twice daily) is about 1/40th of a relatively low antiarrhythmic dose (400 mg twice or three times daily).
• Quinine (overdose threshold): An oral quinine dose of 2–8 g may be fatal for adults.
• Tonic water (regulated beverage use): There is a federal standard for the use of quinine in carbonated beverages, specifically that it cannot exceed 83 parts per million in the final tonic water (21 CFR 172.575).

8. Safety Considerations and Drug Interactions

8.1 Cinchonism

Cinchonism is a pathological condition caused by an overdose of quinine or its natural source, cinchona bark. Cinchonism can occur from therapeutic doses of quinine, either from one or several large doses. Quinidine, a Class 1A anti-arrhythmic, can also cause cinchonism symptoms to develop with as little as a single dose. Signs and symptoms of mild cinchonism include flushed and sweaty skin, ringing of the ears (tinnitus), blurred vision, impaired hearing, confusion, reversible high-frequency hearing loss, headache, abdominal pain, rashes, drug-induced lichenoid reaction, vertigo, dizziness, nausea, vomiting, and diarrhea.

Mild intoxication produces nausea, vomiting, and cinchonism (tinnitus, deafness, vertigo, headache, and visual disturbances). Severe intoxication may cause ataxia, confusion, obtundation, convulsions, coma, and respiratory arrest.

8.2 Serious Hematological Reactions

Quinine may cause unpredictable serious and life-threatening hematologic reactions including thrombocytopenia and hemolytic-uremic syndrome/thrombotic thrombocytopenic purpura (HUS/TTP) in addition to hypersensitivity reactions, QT prolongation, serious cardiac arrhythmias including torsades de pointes, and other serious adverse events requiring medical intervention and hospitalization.

Quinine-induced thrombocytopenia is an immune-mediated disorder. Severe cases of thrombocytopenia that are fatal or life-threatening have been reported, including cases of HUS/TTP. Chronic renal impairment associated with the development of TTP has also been reported. Thrombocytopenia usually resolves within a week upon discontinuation of quinine. If quinine is not stopped, a patient is at risk for fatal hemorrhage. Upon re-exposure to quinine from any source, a patient with quinine-dependent antibodies could develop thrombocytopenia that is more rapid in onset and more severe than the original episode.

8.3 Cardiac Toxicity

In cinchona tree bark, beyond quinine, the other natural alkaloids quinidine, cinchonine, and cinchonidine can have impacts on the heart called Prolonged QTc Syndrome. Quinidine can have serious impacts on heart rhythm, particularly in those with "prolonged QTc." Most people will not know if they have this condition, which can be exacerbated by medications including antibiotics and psychiatric medications. The number of people with prolonged QTc can be greater than 1 in 100. In people with atrial fibrillation, conduction defects, or heart block, quinine can cause heart arrhythmias and should be avoided.

8.4 G6PD Deficiency

Hemolysis can occur in patients with G6PD deficiency receiving quinine. Quinine can cause hemolysis in G6PD deficiency (an inherited deficiency), but this risk is small and the physician should not hesitate to use quinine in people with G6PD deficiency when there is no alternative.

8.5 Hypoglycemia

Other toxic effects of quinine include hypokalemia, hypoglycemia, hemolysis (in patients with glucose-6-phosphate dehydrogenase [G6PD] deficiency), and congenital malformations when used in pregnancy. Adverse effects associated with quinine sulfate include hypersensitivity reactions, cinchonism, high-frequency hearing loss, impaired vision including blindness, nausea, vomiting, epigastric pain, thrombocytopenia, granulomatous hepatitis, cardiovascular effects including cardiac conduction abnormalities, vascular instability with postural hypotension, and hyperinsulinemia with hypoglycemia.

8.6 Pregnancy and Lactation

Cinchona is likely unsafe when taken by mouth during pregnancy. It might stimulate the uterus and cause birth defects. Use should be avoided. Quinine has historically been used as an abortifacient, and this uterotonic property underlies the concern about its use in pregnancy at non-therapeutic doses.

8.7 Special Populations and Contraindications

Myasthenia gravis is listed as a contraindication for quinine, as quinine has neuromuscular blocking activity and may exacerbate muscle weakness. Stomach or intestinal ulcers represent a relative contraindication, as cinchona might increase the risk of bleeding. Cinchona might slow blood clotting, increasing the risk of extra bleeding during and after surgery; it is recommended to stop using cinchona at least 2 weeks before a scheduled surgery.

8.8 Drug Interactions

Cinchona alkaloids, including quinine, may have the potential to depress hepatic enzyme synthesis of vitamin K-dependent coagulation pathway proteins and may enhance the action of warfarin and other oral anticoagulants. Quinine may also interfere with the anticoagulant effect of heparin. Cinchona (quinine) has been reported to increase, through various mechanisms, the risk of bleeding when used concomitantly with warfarin.

At antimalarial doses (≥600 mg), quinine may inhibit the metabolism of other drugs that are CYP2D6 substrates (e.g., flecainide, debrisoquine, dextromethorphan, metoprolol, paroxetine). Patients taking CYP2D6 substrates concurrently should be monitored closely for adverse reactions. Quinine is a P-gp substrate and is primarily metabolized by CYP3A4; other enzymes including CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP2E1 may also contribute to quinine metabolism.

Carbamazepine, phenobarbital, and phenytoin are CYP3A4 inducers and may decrease quinine plasma concentrations if used concurrently. Cinchona can increase stomach acid; therefore, taking cinchona might decrease the effects of proton pump inhibitors. Numerous drugs should not be used concomitantly with quinine, including neuromuscular blocking agents, rifampin, class IA and III antiarrhythmic agents, astemizole, cisapride, erythromycin, and other medications known to cause QT prolongation.

8.9 Regulatory Status

Cinchona products sold as over-the-counter (OTC) medicines are required to carry the warning: "Caution — discontinue use if ringing in the ears, deafness, skin rash, or visual disturbances occur." Cinchona contains quinine, which was banned by the US FDA due to serious side effects. As more predictable and effective synthetic antimalarial drugs began to be developed in the 1930s, the use of quinine to treat and/or prevent malaria declined. The crude bark's quality is specified in the European Pharmacopoeia, providing standardized requirements for its alkaloid content.

References

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