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, Levant nut, Louseberry, Poisonberry, Tuba biji
Medically reviewed by Drugs.com. Last updated on Feb 20, 2023.
Clinical Overview
Use
Levant berry has traditionally been used topically as a parasiticide to treat lice, while the ground whole dried fruit has been used to stun or kill fish and game. Picrotoxin, a major toxic constituent of levant berry seeds, has historically been used to manage epilepsy and has been evaluated in studies for various nervous system disorders, including limited clinical studies of vertigo. Clinical use of levant berry has largely been abandoned in the United States and Europe due to toxicity and a lack of studies supporting use. Due to toxicity concerns and a lack of clinical trial data, use cannot be recommended for any indication.
Dosing
Clinical studies are lacking to support any clinical applications of levant berry; toxicity of the constituent picrotoxin has been established.
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 the respiratory system. It is also a GI irritant.
Toxicology
High doses can cause convulsions, delirium, depression, diaphoresis, disturbed coordination, dizziness, dyspnea, headache, nausea, and spastic twitching. Death from doses of 2 to 3 g of the fruit has been reported.
Scientific Family
- Menispermaceae (moonseed)
Botany
A. cocculus 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
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 has been 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 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. Picrotoxin was considered an official remedy for epilepsy at the turn of the 19th century into the 20th century in the United States; however, it is no longer used for this condition because of severe toxicity.Duke 2002, Morton 1977 Use of picrotoxin as a biological weapon has been suggested because of the ease of chemical isolation and purification.Jablonski 2008
Chemistry
The fruit flesh and seed shells contain nontoxic alkaloids, such as menispermine and paramenispermine.Morton 1977, Verpoorte 1981 The seeds contain the bitter, toxic principle picrotoxin (1.5% to 5%); this compound can be separated into picrotoxinin and picrotin, both of 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 seeds are also rich in fatty acids. The stem and roots of the plant contain quaternary alkaloids, such as berberine and palmatine.Verpoorte 1981
Uses and Pharmacology
Antibacterial activity
In vitro data
Antibacterial activity has been noted; for example, methanolic extracts obtained from the seeds of A. cocculus showed remarkable antibacterial activity against Escherichia coli at a concentration of 3 mcg/mL using agar disc diffusion methods.Qadir 2015
CNS effects
Picrotoxin acts on gamma-aminobutyric acid A (GABAA) receptors as an antagonist. It also blocks conductance enhancement of agonists such as propofol and barbiturates, hence its historical application as an antidote to barbiturate poisoning.Bause 2013
Animal data
Studies conducted in rodents have shown improved sexual behavior in adult rats and their offspring due to possible action of picrotoxin on GABAA receptors.Baso 2003, Bernardi 2013, Teodorov 2005
In a study in mice evaluating whether behavioral changes accompany the effects of picrotoxin on the prefrontal dopaminergic system (ie, increased prefrontal dopamine release), picrotoxin caused anxiety and anhedonia.Hasebe 2017 In another study, picrotoxin treatment improved cognitive function in adult mice expressing amyloid precursor protein (APP) and presenilin 1 (PS1) mutations.Yoshiike 2008
Clinical data
Clinical studies of picrotoxin use in Ménière disease, alone and in combination with other natural remedies for vertigo, have been limited because of toxicity concerns.Heinle 2010, Weikert 2008 In a small clinical study (N=41), picrotoxin suppositories (1 mg inserted 3 times per week) (n=23) were more effective than betahistine (n=18) in reducing the frequency and intensity of vertigo attacks. The authors concluded that the clinical benefit and lack of adverse effects at this picrotoxin dose make it a reasonable alternative in the long-term treatment of Ménière disease.Weikert 2008
Hypoxia
Animal data
In a study evaluating effects of picrotoxin on acute hypoxic states, increased resistance to hypoxia was observed in anesthetized rats, potentially via activity on GABAA receptors.Sanotskaya 2008
Dosing
Clinical studies are lacking to support any clinical applications of levant berry; toxicity of the constituent picrotoxin has been established. In a small clinical study, picrotoxin suppositories (1 mg inserted 3 times per week) were used to reduce the frequency and intensity of vertigo attacks.Weikert 2008
Pregnancy / Lactation
Avoid use. Adverse effects have been documented. In rats, maternal exposure to picrotoxin has been shown to induce demasculinization of male offspring.Baso 2003
Interactions
None well documented. Picrotoxin is a potent inducer of rat hepatic CYP-450 (ie, CYP2B1 and CYP2B2); therefore, drug interactions are possible.Yamada 1993
Adverse Reactions
Picrotoxin stimulates the CNS and respiratory system. It is also a GI irritant.Morton 1977
Toxicology
The dried fruit of A. cocculus is highly toxic. Death from doses of 2 to 3 g of the fruit have been reported. Overdose results in convulsions, delirium, depression, diaphoresis, disturbed coordination, dizziness, dyspnea, headache, nausea, and spastic twitching.Duke 2002
References
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