The Effects of Various Essential Oils on Epilepsy and Acute Seizure: A Systematic Review

Table 1

Essential oils with anticonvulsant activity.

EO or Constituent	Study Type	Dosage	Effects	Reference
alpha-Asarone	animal (mice) PTZ, MES	200 mg/kg	Little effect on acute PTZ, MES model animals	[18]
alpha-Asarone	animal (rat) pilocarpine spontaneous recurrent seizures	200 mg / kg	Chronic daily treatment at this dose for 28 days abolished all convulsions and prevented mortality in 100% of animals. 100% of control animals experienced convulsions and mortality was 40% in the controls.	[18]
alpha-Asarone	animal (mice) MES	25 mg/kg	Protected against MES seizures. Interacted competitively with chlorpromazine.	[19]
beta-Asarone	animal (mice) MES	25 mg/kg	Slightly increased susceptibility and mortality. No effect on chlorpromazine activity.	[19]
Acorus gramineus rhizome	animal (mice) PTZ	30 days inhalation	Increased brain GABA levels and decreased glutamate content by inhalation of the oil. PTZ-seizure animals which inhaled the oil for 30 days had brain higher GABA levels and lower glutamate levels, close to the control animals which did not go through PTZ-induced seizures periodically. The mechanism was determined to be inhibition of the GABA transaminase enzyme.	[20]
Acorus tatarinowii Schott rhizome	animal (mice) PTZ, MES	1.25 g / kg;	ED50 for MES. No effect on PTZ induced seizures, but prolonged latency and decreased convulsive rate. Also decreased mortality.	[21]
Angelica archangelica Linn.	animal (mice) MES, PTZ	400 mg/kg	83% protection, 16% mortality from PTZ seizures	[22]
Angelica archangelica Linn.	animal (mice) MES, PTZ	500 mg/kg	100% protection from MES seizures, no mortality; duration reduced 20-fold, latency increased four-fold	[22]
Artemisia annua L.	animal (mice), PTZ, pilocarpine, PCTX, STRN	470 mg/kg	ED50 for PTZ seizures. Increased latency to pilocarpine and PCTX-induced convulsions. Prevented onset of PTZ and STRN-induced seizures. Motor inhibition was a side effect.	[23]
Artemisia dracunculus L.	animal (mice) PTZ, MES model	0.84 mL / kg	ED50 for MES animals	[24]
Artemisia dracunculus L.	animal (mice) PTZ, MES	0.26 mL/kg	ED50 for PTZ animals	[24]
Bunium persicum	animal (mice) PTZ, MES	1 mL / kg	0% of convulsive movements compared to PTZ-only control	[25]
Bunium persicum	animal (mice) PTZ, MES	1.25 mL / kg	0% of convulsive movements compared to MES only control	[25]
trans-Caryophyllene	animal (mice) kainic acid	60 mg/kg	Reduced mortality by 50% compared to kainic acid-only group. Significantly reduced seizure activity score around two-fold. Also lessened seizure severity by inhibiting malondialdehyde synthesis and preserving activity of GPx, SOD, and CAT. Reduced levels of the inflammatory cytokines TNF-a and IL-1B.	[26]
Calamintha officinalis	animal (mice) PTZ	50 mg/ kg	55% reduction in average duration of convulsions, latency period 21.7 times longer than controls and comparable to animals treated with 1 mg/kg diazepam.	[27]
Calamintha officinalis	animal (mice) PTZ	100 mg/kg	75% reduction in seizure duration, latency period 22.2 times longer than controls	[27]
Carum Carvi L.	animal (mice) PTZ	42.3 mg/kg	ED50 for PTZ clonic seizures	[28]
Carum Carvi L.	animal (mice) PTZ	97.6 mg/kg	ED50 for PTZ tonic seizure	[28]
R-Carvone	animal (mice) PTZ, PCTX	200 mg/kg	no effect	[29]
S-Carvone	animal (mice) PTZ, PCTX	200 mg/kg	Significantly increased latency of convulsions	[29]
Cinnamosma madagascariensis Danguy	animal (rats) PTZ	0.8 mL/kg	Prevention of all convulsions and mortality. Some slight sedative effects were observed.	[30]
Citronellol	animal (mice) PTZ, MES, PCTX	400 mg / kg	Increased seizure latency by around 50% and reduced the percent of animals with convulsions by 75% in PTZ model. For MES animals, the reduction in convulsions was identical at the same dosage of 400 mg/kg, with 75% protection from tonic convulsions.	[31]
Citronellol	In vitro nerve fibers	6.4 mM solution	Compound action potentials reduced by 90% in nerve bundle bathed in citronellol. There was no effect on repolarization, but only the initial depolarization.	[31]
Citrus aurantium blossom	animal (mice) PTZ, MES	40 mg / kg	Increased the clonic seizure threshold by 50%. The EO provided 92% seizure protection and 100% survival, compared to 0% protection and 30% surivival in controls. flumazenil reversed protection, indicating the involvement of GABA-ergic system.	[32]
Citrus aurantium peel	animal (mice) MES, PTZ	1g/kg	Increased latency period for MES and PTZ	[33]
Cuminum cyminum Linn	in vitro neurons, PTZ	1% v/v	Decreased spontaneous activity induced by PTZ in a concentration dependent manner	[34]
Curzerene	animal (mice) PTZ	0.4 mg/kg	100% prevention of PTZ convulsions and mortality	[35]
Curzerene	animal (mice) PTZ	0.25 mg/kg	ED50	[35]
Cymbopogon citratus	animal (mice) MES, PTZ	1 g/kg	Delayed clonic seizures induced by PTZ and blocked tonic extensions induced by MES. Prevented 40% of tonic convulsions in PTZ animals and 80% of tonic convuslions in MES animals. No significant effect on clonic convulsions.	[36]
Cymbopogon citratus	animal (mice) PTZ	oral dose of 200 mg/kg	No effect	[37]
Cymbopogon citratus & Cymbopogon winteranius	Animal (mice) PTZ, STRN	200 mg/kg	Increased seizure latency 8-fold and also increased latency to death in both PTZ and strychinine models. Effects blocked by flumazenil and potentiated by diazepam.	[38]
Cymbopogon winterianus	animal (mouse) PTZ, PCTX, phenytoin, STRN	200 mg/kg	Seizure latency increased nearly seven fold. Percent of animals experiencing convulsions was reduced by 50% and survival increased from 20% (control) to 70% (EO treatment group).	[39]
p-Cymene	animal (mice) MES	970 mg/kg	ED50 for MES seizures	[40]
p-Cymene	animal (mice) PTZ	393 mg/kg	ED50 for PTZ seizures	[40]
Dehydrofukinone	in vitro and animal (mice) PTZ	100 mg/kg	Delayed onset of generalized tonic-clonic seizures. Induced hyperpolarization of neurons via GABA activation. Decreased calcium mobilization from synapse. Activity could be reversed by flumazenil.	[41]
Denettia tripetala	animal (mice) PTZ, STRN	200 mg/kg	100% protection from PTZ and STRN-induced convulsions. Co-treatemnt with flumazenil, a GABA receptor antagonist, abolished the anticonvulsant effects on the EO and the constituent.	[42]
Elettaria cardamomum	animal (mice) PTZ, MES	1 mL/kg	Significantly delayed onset of clonic seizures, prevented all PTZ seizures and 62.5% of MES seizures at this dose. Showed some degree of movement toxicity.	[43]
(-)-Epoxycarvone	animal (mice) PTZ, pilocarpine, STRN	300 mg/kg	Only 12.5% inhibition of PTZ convulsions. No effect on STRN animals. Protected against pilocarpine seizures.	[44]
(+)-Epoxycarvone	animal (mice) PTZ, pilocarpine, STRN	300 mg/kg	Increased latency to PTZ-induced seizure onset with 100% survival. Prevented tonic seizures induced by MES. Exhibited 25% inhibition of PTZ convulsions. No effect on strychine animals. Protected against pilocarpine seizures.	[44]
Eugenia caryophyllata	animal (mice) MES, PTZ	0.1 mL/kg	Abolished all convulsions in MES mice and 100% survival. Nearly doubled PTZ seizure threshold, but only reduced convulsions by 20% in mice above the threshold.	[45]
Eugenol	animal (mice) pilocarpine	-	No difference in seizure latency, but decreased duration and intensity of pilocarpine-induced seizures about threefold each.	[16]
Eugenol	patch-clamp electrophysiology	-	Depressed transient and late components of sodium current. It also decreased L-type calcium currents and delayed rectifier potassium currents at higher concentrations.	[16]
Eugenol	animal (rats) pilocarpine	100 mg/kg for 7 days	55% reduction in average duration of convulsions. Latency period was 21.7 times longer than controls and comparable to animals treated with 1 mg/kg diazepam. Neuronal loss was prevented by eugenol treatment in epileptic animals in all hippocampal sub-regions including DG, CA3, and CA1. Seizure stage and mortaility were improved.	[46]
Gardenia lucida resin	animal (mice) MES, PTZ	300 mg/kg	For MES animals, the EO reduced convulsion time nearly tenfold and reduced recovery time six-fold. In PTZ animals, the EO increased latency fourfold and reduced number of convulsions twofold. Loss of motor function was a side effect.	[47]
Hydroxydihydrocarvone	animal (PTZ)	400 mg/kg	PTZ seizure latency increased two-fold. Side effects included palpebral ptosis, decreased response to touch, increased sedation. Decreased motor activity. Protected against PTZ-induced convulsions.	[48]
Laurus nobilis leaf	animal (mice) PTZ, MES	0.75 mL/kg	Prevented all convulsions in PTZ mice and 0% mortality. Also produced sedation and motor impairment at anticonvulsant doses	[49]
Laurus nobilis leaf	animal (mice) PTZ, MES	1 mL/kg	In MES animals, prevented 80% of convulsions. Only 10% mortality. Also produced sedation and motor impairment at anticonvulsant doses.	[49]
Lavandula angustifolia	in vitro human embryonic kidney cells	0.034 mg/mL	Lavender and rosemary essential oils both inhibit CaV3.2 T-type calcium channels. Linalool was determined to be the active component.	[50]
Lavandula angustifolia	animal (mice) PTZ, strychinine	Inhalation of 1 mL	Inhalation of 1 mL of lavender oil 15 minutes before treatment with 50 mg/kg PTZ prevented all convulsions in 100% of the animals and prevented mortality. All animals in the control group experienced seizures and there was a 100% mortality rate at this dose. In this experiment, lavender had no effect on STRN induced seizures.	[51]
Linalool	in vitro snail neurons	0.1 mM	supressed spontaneous activity and PTZ induced epileptiform activity	[52]
Linalool	in vitro snail neurons	0.4 mM	Induced epileptiform activity. This epileptiform was reversed by calcium channel blockers.	[52]
Linalool	in vitro	-	In vitro assays showed that linalool displaced an NMDA antagonist, MK801, which directly interacts with NMDA receptors. This suggests a direct interaction between linalool and NMDA receptors. There was no effect on muscimol binding, so no conclusive evidence was obtained about a GABAergic mechanism.	[53]
Linalool	animal (mice) MES, PTZ, STRN	-	Increased latency period and decreased mortality in all models	[54]
Linalool oxide	animal (mice) MES, PTZ	150 mg/kg	Moderately reduced duration of tonic seizures induced by MES and increased latency to PTZ seizures.	[55]
Lippia alba, citral chemotype	animal (mice) PTZ	100 mg/kg	Increased seizure latency and percentage of survival	[56]
Lippia alba, limonene chemotype	animal (mice) PTZ	200 mg/kg	Increased seizure latency and percentage of survival	[56]
Lippia alba, myrcene chemotype	animal (mice) PTZ	200 mg/kg	Increased seizure latency and percentage of survival	[56]
Mentha piperita	animal (mice) PTZ	1.6 mL/kg	Completely prevented all seizures at all and produced a rate of 100% survival.	[57]
Mentha spicata	animal (mice) PTZ	1.6 mL/kg	12-fold increase in seizure latency	[57]
Myristica fragrans	animal (mice) MES, STRN, bicuculline, PTZ	0.2 mL/kg	Increased latency to PTZ seizure and death 2-fold. 100% protection from convulsions induced by MES. Delayed onset of convuslions by STRN. At high doses, was a weak proconvulsant. No motor impariment was observed.	[58]
Ocimum gratissimum L.	animal (mice) MES, PTZ	1g/kg	Average of about 30 percent protection from MES convulsions. Little effect on PTZ convulsions	[59]
Pimpinella anisum fruit	animal (mice) MES, PTZ	1 mL/kg	Nearly doubled the PTZ seizure threshold. Protected against 80% of convulsions and prevented death in 90% of animals for both PTZ and MES conditions.	[60]
Pimpinella anisum fruit	animal (mice) PTZ	3 mL / kg	Latency increased five-fold with a treatment of 3 mL / kg. Inhibited production of dark neurons in different regions of brain in epileptic rats. Prolonged latency and reduced amplitude and duration of PTZ seizures.	[61]
alpha-Pinene	animal (mice) PTZ	440 mg/kg	ED50 for PTZ seizures	[40]
Psidium Guyanensis leaf	animal (mice) PTZ, PCTX, STRN	400 mg/kg	Reduced severity of PTZ seizures but not strychine or picroptoxin. Caffeine reversed the effect, suggesting that the mechanism involves the adenosine system.	[62]
Rosa damascena	animal (amygdala electrical kindling)	750 mg/kg	Number of stimulations necessary for first appearance of seizure was larger in animals treated with the EO. Seizure duration was shorter in the treatment groups.	[63]
Rosmarinus officinalis	in vitro human embryonic kidney (HEK) cells	0.054 mg/mL	Rosemary essential oil was found to inhibit CaV3.2 T-type calcium channels. Rosmarinic acid was found to be the active component.	[50]
Smyrnium cordifolium	animal (mice) PTZ	223 mg/kg	ED50	[35]
SuHeXiang Wan	animal (mice) PTZ	Inhalation for 3 hrs at a time, twice per day	3 hr inhalation twice per day doubled onset latency of PTZ-induced seizures and abolished lethality. Effects were minimal for pcrotoxin and strychinine treated animals. Inhalation of the oil inhibited the activity of GABA transaminase, increasing GABA content and decreasing glutamate content in the brain to levels similar to controls. EO inhibited the binding of a GABA ligand at the benzodiazepine site.	[64]
Terpinen-4-ol	animal (mice) PTZ	200 mg/kg	Increased latency period to PTZ-induced seizure 10 fold and latency to 2-MP induced seizure 5-fold, with activity comparable to 4 mg/kg DZP in both cases. Prevented 87% of seizures induced by PTZ. Alleviated 3-MP (a gaba antagonist) mediated convulsions. However, flumazenil didn't reverse the effect. Decreased I_Na through voltage-dependent sodium channels.	[65]
Terpinen-4-ol	animal (mouse) MES, PTZ, PCTX	200 mg/kg	Significantly increased latency of convulsions and inhibited PCTX induced seizures	[66]
Terpinen-4-ol	animal (mouse) MES, PTZ, PCTX	300 mg/kg	Decreased tonic convulsions at 300 mg/kg.	[66]
Terpineol	animal (mice) MES, PTZ, STRN	-	Increased latency period and decreased mortality in all models	[54]
Tetrapleura tetraptera	animal (mice) leptazol	0.4 mL	Protected 78% of animals at a dose of 0.4 mL.	[67]
Thymoquinone	animal (mice) PTZ	93 mg/kg	ED50 for PTZ seizures	[40]
1S-(-)-Verbenone	animal (mice) PTZ	200 mg/kg	Increased seizure latency more than ten-fold. Upregulated COX-2, BDNF and c-fos.	[68]
Zataria Multiflora	animal (mice) PTZ, MES	0.35 mL/kg	Significantly increased latency period for tonic convulsions and completely prevented tonic convulsions.	[69]
Zhumeria majdae	animal (mice) MES, PTZ	0.26 mL/kg	ED50 for PTZ and MES induced convulsions	[70]