Skip to main content

Calabar Bean

Scientific Name(s): Physostigma venenosum Balf. f.
Common Name(s): Calabar bean, Chop nut, Esere nut, Faba calabarica, Ordeal bean, Physostigma

Medically reviewed by Drugs.com. Last updated on Mar 22, 2024.

Clinical Overview

Use

Calabar bean was originally consumed in African rituals, with its toxic constituents often resulting in death. Physostigmine, a main constituent of calabar bean, has been investigated for use in anticholinergic toxicity and in dementia. However, because of the bean's toxicity and lack of clinical trials using the crude plant material or extract, use cannot be supported or recommended for any indication.

Dosing

Calabar bean's constituent physostigmine has been widely studied as the pure alkaloid available as an approved medication. Clinical data relating to the crude plant material or to an extract are lacking; the bean is toxic and should not be used or ingested.

Contraindications

Contraindications have not yet been identified for calabar bean; however, physostigmine should be avoided in individuals with asthma, cardiovascular disease, diabetes, gangrene, and urinary and GI obstructions.

Pregnancy/Lactation

Avoid use. Adverse effects have been documented.

Interactions

None well documented.

Adverse Reactions

There are few reports regarding adverse reactions; calabar bean is toxic to humans, with cases of acute toxicity reported. Adverse effects of physostigmine include cramps, twitching, weakness, increased urination, sweating, increased heart rate, seizures, and convulsions.

Toxicology

Physostigmine is extremely toxic, affecting heart contractibility and inducing respiratory paralysis, which can result in death. Physostigmine can also be harmful to the liver.

Scientific Family

Botany

The calabar bean is the dried ripened seed of P. venenosum, a large, herbaceous perennial climbing plant with woody stems found on the banks of streams in Nigeria, West Africa. The base of the stem grows up to 5 cm in diameter and the plant can reach upwards of 15.25 m in height, bearing showy purple flowers and seed pods that grow to about 15 cm in length. Each pod contains 2 to 3 seeds. The thick dark brown seeds are about 2.5 cm wide and have an extremely hard shell. The beans ripen in all seasons but thrive in abundance during the rainy season (June through September).Aihiokhai 2019, Duke 2002, USDA 2020

History

The plant is native to an area of Nigeria once known as Calabar, and the seeds were historically used as an "ordeal poison" to determine if a person was a witch, possessed by evil spirits, or guilty of a crime. When used for this purpose, the accused was made to ingest several beans. If they regurgitated the beans and survived the "ordeal," their innocence was proclaimed. Western settlers captured by native tribes and made to undergo the "ordeal" learned not to chew the bean, but to swallow it intact, thereby avoiding release of the toxic constituents. The plant has been long recognized as a commercial source of the alkaloid physostigmine, a reversible cholinesterase inhibitor. The deadly potency of the extract was first noted by European missionaries as early as 1840; observations of the "trial by ordeal" ritual included a case in which a suspect developed cholinergic crisis after swallowing a physostigmine-containing calabar bean. In 1864, physostigmine was first isolated from calabar beans.Dawson 2016, Pope 2018 It was also used experimentally to counteract the effects of atropine and for miotic effects in the eyes.Andrade 2019, Calabrese 2008, Dawson 2016, Karczmar 1998, Nickalls 1988, Proudfoot 2006, Realini 2011

Chemistry

The seeds of P. venenosum contain the major alkaloid physostigmine (eserine), as well as the related alkaloids eseramine, physovenine, calabatine, geneserine, and others. These alkaloids are derived from a tryptophan precursor. Because physostigmine oxidizes to a reddish compound known as rubreserine when exposed to air, it should be protected from air and light.Zhao 2004

Uses and Pharmacology

Anticholinergic toxicity

Physostigmine alone is an acetylcholinesterase inhibitor that prolongs the neuronal activity of acetylcholine. Given its ability to cross the blood-brain barrier, it is used to reverse the CNS toxicity (eg, anxiety, delirium, disorientation, hyperactivity, hallucinations, and seizures) of anticholinergic drugs, including tricyclic antidepressants and scopolamine.Andrade 2019, Dawson 2016, Malamed 2018, Pakala 2019

Animal and in vitro data

Physostigmine-loaded liposomes have been evaluated in vitro and in pharmacokinetic studies in rats to determine the feasibility of prolonging the physostigmine half-life in order to extend protection against the effects of nerve gas exposure that lead to nerve-agent poisoning. The liposomes aided in maintaining constant plasma concentrations of physostigmine.Park 2018

Dementia

Clinical data

Physostigmine from the calabar bean has been investigated for its ability to increase cognition, particularly in patients with Alzheimer disease, but with minimal success.Howes 2011, Howes 2012

Dosing

Calabar bean's constituent physostigmine has been widely studied as the pure alkaloid available as an approved medication. Clinical data relating to the crude plant material or to an extract are lacking; the bean is toxic and should not be used or ingested.Duke 2002

Pregnancy / Lactation

Avoid use. Adverse effects have been documented.Ernst 2002

Interactions

None well documented.

Adverse Reactions

There are few reports regarding adverse reactions; calabar bean is toxic to humans, with cases of acute toxicity reported. A study of Wistar rats given P. venenosum extract ranging from 10 to 30 mg/kg/day for 2 weeks displayed signs of hepatic injury.Aihiokhai 2019 CNS effects of physostigmine, which include ataxia and convulsions, can eventually lead to coma.Andrade 2019 Other observed severe adverse reactions include tachycardia and tachyarrhythmia.Pinder 2019 More severe adverse reactions are typically due to overdose. Less severe adverse reactions include GI disturbances, dyspnea, miosis, sweating, hypertension, salivation, headache, and lacrimation.Andrade 2019, Dawson 2016, Effenberger-Neidnicht 2018, Malamed 2018, Pinheiro 2018

Toxicology

Physostigmine is extremely toxic, with an oral median lethal dose of 4.5 mg/kg in mice. Physostigmine affects heart contractility and induces respiratory paralysis, which can result in death; 2 to 3 beans are sufficient to be lethal.Duke 2002 Based on hepatic injury demonstrated in rats, a P. venenosum extract dose of 20 mg/kg/day should not be exceeded over an extended period of time.Aihiokhai 2019 In the event of physostigmine toxicity, atropine or oximes (eg, pralidoxime) are utilized as antidotes.Andrade 2019, Pakala 2019 Excessive administration of physostigmine can lead to cholinergic toxicity and should be used with caution. Signs of cholinergic toxicity include hypersecretion, salivation, lacrimation, bronchospasm, bradycardia, nausea, vomiting, diarrhea, neuromuscular weakness, coma, and seizures.Dawson 2016, Pakala 2019

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.

Aihiokhai MO, Idu M, Ovuakporie-Uvo O. Histopathological Studies of Physostigma venenosum Balf. on Wistar Rats. J Adv Bot Zool. 2019;7;1.
Andrade OA, Zafar Gondal A. Physostigmine. StatPearls. 2019.31424845
Calabrese EJ. Alzheimer's disease drugs: an application of the hormetic dose-response model. Crit Rev Toxicol. 2008;38(5):419-451.18568864
Dawson AH, Buckley NA. Pharmacological management of anticholinergic delirium - theory, evidence and practice. Br J Clin Pharmacol. 2016;81(3):516-524.26589572
Duke J, Bogenschutz-Godwin M, duCellier J, Duke P. Handbook of Medicinal Herbs. 2nd ed. Boca Raton, FL: CRC Press; 2002.
Effenberger-Neidnicht K, Jägers J, Verhaegh R, Kirsch M. Therapeutic effects of physostigmine during systemic inflammation. J Inflamm Res. 2018;11:465-475.30573986
Ernst E. Herbal medicinal products during pregnancy: are they safe? BJOG. 2002;109(3):227-235.11950176
Howes MJ, Houghton PJ. Ethnobotanical treatment strategies against Alzheimer's disease. Curr Alzheimer Res. 2012;9(1):67-85.22329652
Howes MJ, Perry E. The role of phytochemicals in the treatment and prevention of dementia. Drugs Aging. 2011;28(6):439-468.21639405
Karczmar A. Invited review: Anticholinesterases: dramatic aspects of their use and misuse. Neurochem Int. 1998;32(5-6):401-411.9676738
Malamed S. Physostigma venenosum: Pharmacology. In: Sedation: A Guide to Patient Management. 6th ed. St. Louis, MO: Elsevier; 2018.
Nickalls RW, Nickalls EA. The first use of physostigmine in the treatment of atropine poisoning. A translation of Kleinwachter's paper entitled 'Observations on the effect of Calabar bean extract as an antidote to atropine poisoning'. Anaesthesia. 1988;43(9):776-779.3052162
Pakala RS, Brown KN. Cholinergic Medications. StatPearls. 2019.30844190
Park JH, Lee JY, Kim KT, et al. Physostigmine-loaded liposomes for extended prophylaxis against nerve agent poisoning. Int J Pharm. 2018;553(1-2):467-473.30389473
Physostigma venenosum Balf. USDA, NRCS. 2020. The PLANTS database (http://plants.usda.gov, 20 February 2020). National Plant Data Team, Greensboro NC 27401-4901 USA.
Pinder N, Bruckner T, Lehmann M, et al. Effect of physostigmine on recovery from septic shock following intra-abdominal infection - Results from a randomized, double-blind, placebo-controlled, monocentric pilot trial (Anticholium per Se). J Crit Care. 2019;52:126-135.31035187
Pinheiro GKLO, Araújo Filho I, Araújo Neto I, et al. Nature as a source of drugs for ophthalmology. Arq Bras Oftalmol. 2018;81(5):443-454.30208150
Pope CN, Brimijoin S. Cholinesterases and the fine line between poison and remedy. Biochem Pharmacol. 2018;153:205-216.29409903
Proudfoot A. The early toxicology of physostigmine: a tale of beans, great men and egos. Toxicol Rev. 2006;25(2):99-138.16958557
Realini T. A history of glaucoma pharmacology. Optom Vis Sci. 2011;88(1):36-38.21131876
Zhao B, Moochhala SM, Tham SY. Biologically active components of Physostigma venenosum. J Chromatogr B Analyt Technol Biomed Life Sci. 2004;812(1-2):183-192.15556497

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.