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Levant Berry

Scientific Name(s): Anamirta cocculus Wight & Arn.
Common Name(s): Cocculus fructus, Cocculus indicus, Fish killer, Fishberry, Hockle elderberry, Indian berry, Kockel-lian, Levant berry, Levantnut, Louseberry, Poisonberry, Tuba biji

Medically reviewed by Drugs.com. Last updated on Oct 1, 2019.

Clinical Overview

Use

Levant berry has traditionally been used to relieve malaria, treat lice, stun or kill fish and game, and manage epilepsy. Clinical use of levant berry has largely been abandoned in the United States and Europe because there are no studies supporting its use. The constituent picrotoxin has been evaluated in limited clinical studies for vertigo.

Dosing

No clinical evidence supports any clinical applications of levant berry. In a small clinical study, picrotoxin suppositories (1 mg 3 times per week) were more effective than betahistine in reducing the frequency and intensity of vertigo attacks.

Contraindications

Toxicity of the constituent picrotoxin has been established.

Pregnancy/Lactation

Avoid use. Adverse effects have been documented.

Interactions

None well documented.

Adverse Reactions

Picrotoxin stimulates the CNS and is a GI irritant.

Toxicology

High doses can cause salivation, vomiting, purging, rapid shallow respiration, palpitations or heart slowing, stupor, loss of consciousness, and death. Death from doses of 2 to 3 g of the fruit has been reported.

Scientific Family

  • Menispermaceae (moonseed)

Botany

A. cocculus, known as levant berry, is a climbing woody shrub native to India, Burma, and other parts of Malaysia. It has wide thick leaves and rootlets that ooze a white milky latex. The fragrant flowers produce U-shaped seeds. The fruit dries to a bitter, nearly black wrinkled shape.Duke 2002, Morton 1977, USDA 2015

History

The fruit of levant berry is gathered from the wild and sun dried for export. In India, the leaves have been inhaled as a snuff to relieve malaria, and the leaf juice used in combination with other natural products as a vermifuge.Morton 1977 Extracts of the plant have been applied topically for lice, but the toxic nature of the components (in particular picrotoxin) makes this application dangerous, especially in cases of abraded or irritated skin. For centuries, fishermen in Asia used the seeds to produce a poison to stun fish,Bause 2013 and in some societies, ground whole dried fruit has been used to kill birds or dogs, and to stupefy game as well as fish.Jablonski 2008 Picrotoxin has been used as a stimulant for the management of morphine and barbiturate poisoning and was considered an official remedy for epilepsy at the turn of the 19th century into the 20th in the United States; however, it is no longer used for this condition because of severe toxicity.Duke 2002, Morton 1977 Use as a biological weapon has been suggested for picrotoxin because of the ease of chemical isolation and purification.Jablonski 2008

Chemistry

The fruit flesh and seed shells contain the nontoxic alkaloids menispermine and paramenispermine.Morton 1977, Verpoorte 1981 The seed, however, contains the bitter, toxic principle picrotoxin (1.5% to 5%); this compound can be separated into picrotoxinin and picrotin, which are oxygenated sesquiterpene derivatives.Duke 1992 The tasteless compounds anamirtin and cocculin are also present, along with a fixed oil (11% to 24% of the seed).Morton 1977 The seed is also rich in fatty acids. The stem and roots of the plant contain quaternary alkaloids (eg, berberine, palmatine).Verpoorte 1981

Uses and Pharmacology

CNS effects

Animal data

Picrotoxin acts as gamma-aminobutyric acid (GABA) receptors, blocking conductance enhancement of agonists such as propofol and barbiturates, hence its historical application as an antidote to barbiturate poisoning.Bause 2013, Belcher 2013 Studies conducted in rodents have shown improved sexual behavior in adult rats and their offspring due to possible action of picrotoxin on GABA receptors.Baso 2003, Bernardi 2013, Teodorov 2005

Clinical data

Clinical studies of picrotoxin use in Meniere disease, as well as in combination with other natural remedies for vertigo, have been limited because of toxicity concerns.Heinle 2010, Weikert 2008 In a small clinical study, picrotoxin suppositories (1 mg 3 times per week) were more effective than betahistine in reducing the frequency and intensity of vertigo attacks.Weikert 2008

Other uses

Picrotoxin, not levant berry itself, has been studied for effect on acute hypoxic states, potentially via activity on GABA receptors, in ratsSanotskaya 2008 and on cognitive decline in mice.Yoshiike 2008

Dosing

No clinical evidence supports any clinical applications of levant berry. In a small clinical study, picrotoxin suppositories (1 mg 3 times per week) were more effective than betahistine in reducing the frequency and intensity of vertigo attacks.Weikert 2008

Pregnancy / Lactation

Avoid use. Adverse effects have been documented. Exposure to picrotoxin has been shown to induce demasculinization of male offspring.Baso 2003

Interactions

None well documented.

Adverse Reactions

Picrotoxin stimulates the CNS and is a GI irritant.Morton 1977

Toxicology

High doses can cause salivation, vomiting, purging, rapid shallow respiration, palpitations or heart slowing, stupor, loss of consciousness, and death.Belcher 2013, Duke 2002 Death from doses of 2 to 3 g of the fruit have been reported.Duke 2002

References

Baso AC, Goulart FC, Teodorov E, Felicio LF, Bernardi MM. Effects of maternal exposure to picrotoxin during lactation on physical and reflex development, square crossing and sexual behavior of rat offspring. Pharmacol Biochem Behav. 2003;75(4):733-740.12957213
Bause GS. From fish poison to Merck picrotoxin. Anesthesiology. 2013;118(6):1263.23695089
Belcher SF, Morton TR. Tutu toxicity: three case reports of Coriaria arborea ingestion, review of literature and recommendations for management. N Z Med J. 2013;126(1370):103-109.23474518
Bernardi MM, Scanzerla KK, Chamlian M, Teodorov E, Felicio LF. Maternal treatment with picrotoxin in late pregnancy improved female sexual behavior but did not alter male sexual behavior of offspring. Behav Pharmacol. 2013;24(4):282-290.23838964
Duke JA, Bogenschutz-Godwin M, duCellier J, Duke PK. Handbook of Medicinal Herbs. 2nd ed. Boca Raton, FL: CRC Press; 2002.
Duke JA. Handbook of Biologically Active Phytochemicals and Their Activities. Boca Raton, FL: CRC Press Inc; 1992.
Heinle H, Tober C, Zhang D, Jäggi R, Kuebler WM. The low-dose combination preparation Vertigoheel activates cyclic nucleotide pathways and stimulates vasorelaxation. Clin Hemorheol Microcirc. 2010;46(1):23-35.20852360
Jablonski JE, Jackson LS. Stability of picrotoxin during yogurt manufacture and storage. J Food Sci. 2008;73(8):T121-T128.19019133
Morton JF. Major Medicinal Plants: Botany, Culture, and Uses. Springfield, IL: Thomas; 1977.
Sanotskaya NV, Matsievskii DD, Lebedeva MA. Effect of picrotoxin on organism's resistance to acute severe hypoxia. Bull Exp Biol Med. 2008;145(2):177-180.19023962
Teodorov E, Moraes AP, Felicio LF, Varolli FM, Bernardi MM. Perinatal maternal exposure to picrotoxin: effects on sexual behavior in female rat offspring. Pharmacol Biochem Behav. 2005;81(4):935-942.16098570
USDA. NRCS. 2015. The PLANTS Database (http://plants.usda.gov, 2015). National Plant Data Center, Baton Rouge, LA 70874-4490 USA.
Verpoorte R, Siwon J, Tieken MEM, Svendsen AB. Studies on Indonesian medicinal plants. V. The alkaloids of Anamirta cocculus. J Nat Prod. 1981;44(2):221-224.
Weikert S, Rotter A, Scherer H, Hölzl M. Picrotoxin in the treatment of Menière's disease. Laryngorhinootologie. 2008;87(12):862-866.18720328
Yoshiike Y, Kimura T, Yamashita S, et al. GABA(A) receptor-mediated acceleration of aging-associated memory decline in APP/PS1 mice and its pharmacological treatment by picrotoxin [published online August 21, 2008]. PLoS One. 2008;3(8):e3029.1871665610.1371/journal.pone.0003029

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