Many essential oils (EOs) have anticonvulsant activity and might benefit people with epilepsy. Lemongrass, lavender, clove, dill, and other EOs containing constituents such as asarone, carvone, citral, eugenol, or linalool are good candidates for evaluation as antiepileptic drugs. On the other hand, some EOs have convulsant effects and may trigger seizures in both epileptic and healthy individuals. Internal use of EOs like sage, hyssop, rosemary, camphor, pennyroyal, eucalyptus, cedar, thuja, and fennel can cause epileptic seizures because they contain thujone, 1,8-cineole, camphor, or pinocamphone, which have been identified as convulsive agents. While more research is needed to confirm their mechanisms of action, it appears that the convulsant or anticonvulsant properties of essential oils are largely due to (1) their ability to modulate the GABAergic system of neurotransmission and (2) their capacity to alter ionic currents through ion channels. This review presents a systematic analysis of the current research on EOs and epilepsy, including human case studies, animal models, and
Approximately 20-30% percent of patients with epilepsy suffer from seizures that cannot be controlled using any antiepileptic drugs (AEDs) that are currently available [
Essential oils (EOs) are one particular class of natural medicines obtained by distillation of plant material to obtain a volatile, hydrophobic extract. EOs have been used as anticonvulsants in traditional medicine in many cultures worldwide, especially in the Middle East, India, China, and Brazil. It is no surprise that much of the research on EOs and their antiepileptic effects has been produced by institutions in these regions. Even today, some herbal remedies are often more accessible than synthetic drugs for individuals in developing communities located in these parts of the world [
EOs have been documented for anxiolytic, sedative, neuroprotective, and anticonvulsive properties by academic research groups worldwide [
Compounds found in EOs have been shown to interact with and exert pharmacological action on central nervous system targets involved in epilepsy. Structures involved in neurotransmitter release and metabolism such as NMDA,
EOs and their constituent compounds have unique chemical properties that make them good candidates for drug design. Since the plant enzymes that produce terpenes are stereoselective, many EOs contain only one enantiomer of a compound. This can be advantageous in cases where one enantiomer has pronounced effects while the other is inactive or affects a different target. Another key property of EOs in the context of epilepsy is their ability to cross the blood-brain barrier (BBB). Drug candidates likely to cross the BBB are usually of small size (<400 Da) and high lipid solubility [
The present review employed a systematic search of the National Institute of Health PubMed database for all articles containing the keyword “essential oils,” together with either of the three keywords “epilepsy,” “epileptic,” or “seizure.” Only primary research articles published in the English language between 1900 and 2017 with relevant information on EOs and epilepsy were included in the review. Publications documenting the activity of methanolic or aqueous extracts but not EOs were excluded, as were articles describing the activity of EOs in the context of diseases other than epilepsy.
Of the 122 research articles identified in the initial search, fifty-eight were excluded. Of these fifty-eight, thirty-three did not contain information about essential oils in the context of epilepsy or seizures and were excluded for being irrelevant to the subject at hand. Eight were excluded because they were published in a language other than English, and sixteen others were excluded because they were review articles, commentaries, or other publications which are not considered original research. A total of sixty-four articles meeting the inclusion criteria were systematically reviewed and classified into two categories depending on whether the research documented positive or negative outcomes. Of the articles included in this review, fifty-four of the publications (84%) reported positive outcomes and ten of the publications (16%) reported negative outcomes.
Two main types of animal models emerged in this review: models of acute seizure and models of chronic epilepsy. Animal models of chronic epilepsy aim to simulate spontaneous seizure, neurological insult that results from seizure, and lasting changes in the epileptic brain. Animal models of acute seizure aim to simulate the hyperexcitation of neural circuitry that causes convulsions and neurological lesion.
The majority of the studies that investigated the effects of EOs on chronic epilepsy used the pilocarpine or electric kindling models. Pilocarpine is a muscarinic acetylcholine receptor agonist used to mimic complex human partial seizures. The pilocarpine model shares many similarities to human temporal lobe epilepsy in terms of neurochemistry and its effects on cerebral networks [
The two main models used to study acute seizure were pentylenetetrazole (PTZ) and maximal electroshock (MES) models. PTZ is thought to be a
Some authors in the present review used other drugs to induce acute seizures. Above-threshold doses of pilocarpine and kainic acid, which are also used to model chronic epilepsy, can be effective models of acute seizure. Picrotoxin and strychnine are two other less common proconvulsants. Picrotoxin (PCTX) antagonistically binds to the
In the majority of the studies, EOs or their isolated compounds were administered via intraperitoneal injection and the dosage was standardized across all test animals by milliliters or milligrams per kilogram body weight. The animal studies included in this review were not screened for their inclusion or exclusion of controls.
No clinical trials have been conducted on EOs as antiepileptic drugs. Eight case studies of adverse events in humans were the only source of human clinical research data in this review. Generally, these were peer-reviewed publications produced by physicians or by researchers using data from hospital records.
Many EOs and their isolated constituents have been documented for their anticonvulsive properties. Oils high in monoterpenes and monoterpenoids such as a-pinene, limonene, myrcene, asarone, carvone, citral, eugenol, and linalool predominate. This data is consolidated in Table
Essential oils with anticonvulsant activity.
EO or Constituent | Study Type | Dosage | Effects | Reference |
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alpha-Asarone | animal (mice) PTZ, MES | 200 mg/kg | Little effect on acute PTZ, MES model animals | [ |
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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. | [ |
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alpha-Asarone | animal (mice) MES | 25 mg/kg | Protected against MES seizures. Interacted competitively with chlorpromazine. | [ |
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beta-Asarone | animal (mice) MES | 25 mg/kg | Slightly increased susceptibility and mortality. No effect on chlorpromazine activity. | [ |
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| 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. | [ |
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| 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. | [ |
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| animal (mice) MES, PTZ | 400 mg/kg | 83% protection, 16% mortality from PTZ seizures | [ |
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| animal (mice) MES, PTZ | 500 mg/kg | 100% protection from MES seizures, no mortality; duration reduced 20-fold, latency increased four-fold | [ |
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| 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. | [ |
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| animal (mice) PTZ, MES model | 0.84 mL / kg | ED50 for MES animals | [ |
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| animal (mice) PTZ, MES | 0.26 mL/kg | ED50 for PTZ animals | [ |
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| animal (mice) PTZ, MES | 1 mL / kg | 0% of convulsive movements compared to PTZ-only control | [ |
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| animal (mice) PTZ, MES | 1.25 mL / kg | 0% of convulsive movements compared to MES only control | [ |
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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. | [ |
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| 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. | [ |
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| animal (mice) PTZ | 100 mg/kg | 75% reduction in seizure duration, latency period 22.2 times longer than controls | [ |
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| animal (mice) PTZ | 42.3 mg/kg | ED50 for PTZ clonic seizures | [ |
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| animal (mice) PTZ | 97.6 mg/kg | ED50 for PTZ tonic seizure | [ |
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R-Carvone | animal (mice) PTZ, PCTX | 200 mg/kg | no effect | [ |
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S-Carvone | animal (mice) PTZ, PCTX | 200 mg/kg | Significantly increased latency of convulsions | [ |
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| animal (rats) PTZ | 0.8 mL/kg | Prevention of all convulsions and mortality. Some slight sedative effects were observed. | [ |
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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. | [ |
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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. | [ |
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| 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. | [ |
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| animal (mice) MES, PTZ | 1g/kg | Increased latency period for MES and PTZ | [ |
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| in vitro neurons, PTZ | 1% v/v | Decreased spontaneous activity induced by PTZ in a concentration dependent manner | [ |
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Curzerene | animal (mice) PTZ | 0.4 mg/kg | 100% prevention of PTZ convulsions and mortality | [ |
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Curzerene | animal (mice) PTZ | 0.25 mg/kg | ED50 | [ |
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| 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. | [ |
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| animal (mice) PTZ | oral dose of 200 mg/kg | No effect | [ |
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| 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. | [ |
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| 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). | [ |
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p-Cymene | animal (mice) MES | 970 mg/kg | ED50 for MES seizures | [ |
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p-Cymene | animal (mice) PTZ | 393 mg/kg | ED50 for PTZ seizures | [ |
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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. | [ |
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| 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. | [ |
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| 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. | [ |
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(-)-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. | [ |
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(+)-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. | [ |
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| 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. | [ |
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Eugenol | animal (mice) pilocarpine | - | No difference in seizure latency, but decreased duration and intensity of pilocarpine-induced seizures about threefold each. | [ |
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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. | [ |
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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. | [ |
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| 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. | [ |
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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. | [ |
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| 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 | [ |
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| 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. | [ |
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| 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. | [ |
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| 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. | [ |
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Linalool | in vitro snail neurons | 0.1 mM | supressed spontaneous activity and PTZ induced epileptiform activity | [ |
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Linalool | in vitro snail neurons | 0.4 mM | Induced epileptiform activity. This epileptiform was reversed by calcium channel blockers. | [ |
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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. | [ |
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Linalool | animal (mice) MES, PTZ, STRN | - | Increased latency period and decreased mortality in all models | [ |
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Linalool oxide | animal (mice) MES, PTZ | 150 mg/kg | Moderately reduced duration of tonic seizures induced by MES and increased latency to PTZ seizures. | [ |
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| animal (mice) PTZ | 100 mg/kg | Increased seizure latency and percentage of survival | [ |
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| animal (mice) PTZ | 200 mg/kg | Increased seizure latency and percentage of survival | [ |
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| animal (mice) PTZ | 200 mg/kg | Increased seizure latency and percentage of survival | [ |
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| animal (mice) PTZ | 1.6 mL/kg | Completely prevented all seizures at all and produced a rate of 100% survival. | [ |
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| animal (mice) PTZ | 1.6 mL/kg | 12-fold increase in seizure latency | [ |
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| 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. | [ |
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| animal (mice) MES, PTZ | 1g/kg | Average of about 30 percent protection from MES convulsions. Little effect on PTZ convulsions | [ |
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| 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. | [ |
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| 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. | [ |
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alpha-Pinene | animal (mice) PTZ | 440 mg/kg | ED50 for PTZ seizures | [ |
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| 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. | [ |
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| 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. | [ |
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| 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. | [ |
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| animal (mice) PTZ | 223 mg/kg | ED50 | [ |
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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. | [ |
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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. | [ |
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Terpinen-4-ol | animal (mouse) MES, PTZ, PCTX | 200 mg/kg | Significantly increased latency of convulsions and inhibited PCTX induced seizures | [ |
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Terpinen-4-ol | animal (mouse) MES, PTZ, PCTX | 300 mg/kg | Decreased tonic convulsions at 300 mg/kg. | [ |
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Terpineol | animal (mice) MES, PTZ, STRN | - | Increased latency period and decreased mortality in all models | [ |
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| animal (mice) leptazol | 0.4 mL | Protected 78% of animals at a dose of 0.4 mL. | [ |
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Thymoquinone | animal (mice) PTZ | 93 mg/kg | ED50 for PTZ seizures | [ |
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1S-(-)-Verbenone | animal (mice) PTZ | 200 mg/kg | Increased seizure latency more than ten-fold. Upregulated COX-2, BDNF and c-fos. | [ |
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| animal (mice) PTZ, MES | 0.35 mL/kg | Significantly increased latency period for tonic convulsions and completely prevented tonic convulsions. | [ |
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| animal (mice) MES, PTZ | 0.26 mL/kg | ED50 for PTZ and MES induced convulsions | [ |
EOs containing alpha-pinene and other monoterpenes show anticonvulsant effects in animal models.
Asarone is a compound found in the rhizomes of plants of the genus
Carvone is a monoterpene ketone found in mint plants and some Mediterranean spices. The S (+) enantiomer is the primary chemical constituent of
EOs obtained from plants of the genus
Like citronellol, eugenol also has a depressive action on action potentials. It activity as a sodium channel blocker has been confirmed using whole-cell electrophysiology. Isolated eugenol depressed transient and late components of the sodium current. It also decreased L-type calcium currents and delayed rectifier potassium currents at higher concentrations [
Eugenol is the primary constituent in
Linalool is a monoterpene alcohol proven to potentiate
In addition, it is possible that linalool may have neuroprotective effects by modulating NMDA receptors. NMDA-mediated calcium toxicity is one major mechanism of injury from epileptic seizures. In vitro assays showed that linalool displaced an NMDA antagonist, MK801, which directly interacts with NMDA receptors [
Lavender and other EOs high in linalool demonstrate strong anticonvulsive effects in animal models of seizure.
Many other EOs and their isolated constituents have demonstrated anticonvulsive activity in animal models. Cumin EOs of the species
Certain sesquiterpene compounds have positive effects on animal models of epilepsy. Trans-caryophyllene has protective effects on kainic acid-induced seizure by inhibiting malondialdehyde synthesis and maintaining healthy catalase, superoxide dismutase, and glutathione peroxidase activity [
Monoterpene alcohols may have potential as AEDs. Terpineol prolonged narcotic effects of hexobarbital, ethyl alcohol, and chloral hydrate and protected against MES- and PTZ- but not STRN-induced convulsions [
Other monoterpenoids are documented for similar activity. The monoterpene ketone verbenone increased seizure latency more than tenfold and upregulated COX-2, BDNF and c-fos in PTZ animals [
Only a few EOs with nonterpene constituents have been found to inhibit seizures. These include
Some EOs contain constituents with convulsant activity. Reports of adverse events in humans are the primary source of research on these EOs. EOs of the species
Essential oils with proconvulsive activity.
EO or Constituent | Study Type | Dosage | Effects | Reference |
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1,8-Cineole (isolated constituent) | animal | 0.5 mL/kg | Induced tonic-clonic seizures | [ |
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Blend (rosemary EO and camphor constituent) | human adult man | unknown, applied topically | Breakthrough (relapse) seizure in an epileptic patient after 8 years free of seizures | [ |
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Blend (eucalyptus, pine, and thyme EOs) | human (12 months) | unknown, applied topically | Three episodes of tonic convulsions lasting one minute each. Hundreds of similar seizures the next day. As a result, the patient developed long-term status epilepticus and showed developmental delay for at least 4 years following the event. | [ |
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Camphor (isolated constituent) | animal | 0.5 mL/kg | Induced tonic-clonic seizures | [ |
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Camphor oil | human (3 years) | about 1 teaspoon taken internally | Generalized tonic-clonic seizure and respiratory depression within 20 minutes | [ |
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Camphor oil | human (15 months) | about 20 mL | Generalized tonic-clonic seizure after 10 minutes | [ |
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Fennel oil | human adult woman | unknown but large amount | Tonic-clonic seizure lasting 45 minutes | [ |
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Hyssop oil | animal | 0.13 g/kg; 1.25 g/kg | Caused convulsions; lethal dose | [ |
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Pennyroyal oil | human infant | 25 ng/mL blood pulegone content and 41 ng/mL blood menthofuran content | Epileptic encephalopathy in and liver failure | [ |
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Sage oil | animal | 0.5g/kg; 3.2 g/kg intraperitoneally | Caused convulsions; lethal dose | [ |
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Sage oil | human (53 yrs) | 10 drops taken internally | Tonic-clonic seizure followed by 15-minute coma | [ |
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Sage oil | human (54 yrs) | mouthful-sized amount taken internally | Tonic-clonic seizure, unconscious for 1/2 hour following the seizure | [ |
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Sage oil | human (33 days) | unknown, taken internally | 33-day old boy experienced tonic-clonic convulsions lasting 20 minutes | [ |
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Sage oil | human (5 1/2 yrs) | 5 mL taken internally | Generalized tonic-clonic seizure lasting 10 minutes | [ |
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Sage, cedar, thuja, hyssop | human (multiple cases) | unknown, taken internally | Tonic-clonic convulsions in humans | [ |
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Thuja (arborvitae) oil | human (7-months) | unknown, applied topically | 8 tonic-clonic seizures at different times | [ |
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Thujone (isolated constituent) | animal | 25 mg/kg; 50 mg/kg | All animals experienced seizures; all animals died | [ |
Thujone is the primary chemical constituent in sage oil, although sage oil also contains significant levels of 1,8-cineole and camphor. The ingestion of small quantities of sage EO has caused tonic-clonic seizures in humans, especially in children [
Like sage oil, thuja and cedar EOs are high in thujone and are also known to cause convulsions, sometimes even when used topically [
EOs of camphor, rosemary, and eucalyptus which are high in 1,8-cineole and camphor (note that camphor is the name of the EO
Topical application of these EOs can also cause seizures, especially in people with epilepsy. Another patient with a history of epilepsy experienced a breakthrough (relapse) seizure after a massage with a blend of sea fennel, maritime pine, sea-buckthorn, and rosemary EOs. The camphor content in rosemary EO was thought to be the cause of the seizure. The patient had not had a seizure in 8 years and did not experience any seizures again for at least a year following the incident [
Paradoxically, oils high 1,8-cineole have produced some positive results in animal models of seizure.
Some other EOs that do not contain thujone, 1-8-cineole, or camphor can cause seizures. Hyssop EO, predominantly composed of the compound pinocamphone, can cause tonic-clonic convulsions in humans [
In this review, we find that many EOs demonstrate anticonvulsant activity and might benefit people with epilepsy. Plants of the genus
Some of the research studies in this review described EOs that were composed of multiple constituent compounds, but many described EOs that were predominantly composed of one compound. When many oils containing the same major constituent had similar effects, it was inferred that that specific constituent was the active component responsible for the oils’ anticonvulsive effects. However, further research is needed to confirm that these compounds are in fact the active components of the EOs.
While more research is needed to confirm their mechanisms of action, it appears that one mechanism for the anticonvulsant properties of EOs is their ability to modulate GABAergic neurotransmission. Alpha-asarone and SuHeXiang Wan oil, for instance, both inhibit the GABA transaminase enzyme, increasing brain GABA levels and decreasing brain glutamate levels in animal models of chronic epilepsy. The constituents linalool, alpha-pinene, thymoquinone, and terpinen-4-ol either potentiated GABA activity or were found to bind the
A second mechanism explaining the anticonvulsive action of EOs is their capacity to block ionic currents. Eugenol, the principal component of clove oil, inhibits action potential generation by blocking sodium channels. Citronellol depresses the depolarization phase of action potentials in nerve fibers, probably by the same mechanism. Terpinen-4-ol also decreased sodium currents in electrophysiology experiments.
Blending is a popular practice among people who use EOs. Traditionally, mixtures and formulations of two or more EOs were believed to sometimes exhibit synergy. At this time however, no blends have been studied for their anticonvulsive potential except for SuHeXiang Wan oil, which did show significant effects on brain GABA levels in a model of chronic epilepsy. From these and other results discussed in this review, it is possible that a blend of anticonvulsive oils might serve as a multitarget pharmacological approach to controlling epilepsy and could be more effective than any single oil alone. For example, a combination of acorus EO high in asarone, lemongrass EO high in citronellol and citral, lavender EO high in linalool, and clove EO high in eugenol would simultaneously suppress action potentials, potentiate
Another chemical that has recently become popular in the world of natural products and is undergoing investigation for possible benefits in regard to seizures and epilepsy is cannabidiol (CBD). CBD itself has been shown anecdotally and clinically to provide benefit and significant relief to epileptic patients [
This review has limitations. The publications included in this review were gathered exclusively from PubMed; other scientific databases were not searched for relevant publications. Poison databases were not searched for reports of potential EO-induced seizures. Furthermore, the animal studies included in this review were not screened for their inclusion or exclusion of controls.
Because of their lipophilic nature, EO compounds can easily cross the blood-brain barrier. This property, combined with the aforementioned pharmacology of their constituents, makes EOs excellent candidates for investigation into their potential as AEDs. That said, certain EOs should be used with caution due to case reports and animal studies demonstrating that they may induce seizures, specifically EOs of sage, thuja, cedar, hyssop, eucalyptus, camphor, pennyroyal, and fennel, as well as the constituents 1,8-cineole, camphor, thujone, and pinocamphone. Future research will be necessary to determine the pharmacological action of these compounds, but
Together, these results suggest that many EOs may be promising for treating people with epilepsy. While some EOs have convulsive properties, these observations cannot be generalized to all EOs. Many EOs have had positive effects on animal models of chronic and acute epilepsy. Because different EOs affect different targets, blends and formulations of EOs should be considered. Future experiments including human clinical trials should also be considered as a next step in verifying whether EOs might be used as AEDs in people with epilepsy.
Tyler A. Bahr, Damian Rodriguez, Cody Beaumont, and Kathryn Allred are employees of dōTERRA, a company that manufactures essential oils.
Tyler A. Bahr interpreted the data and wrote the paper. Damian Rodriguez, Cody Beaumont, and Kathryn Allred participated in the writing and revision of the paper.
This study was funded by dōTERRA Intl. (Pleasant Grove, UT, USA). Estee Crenshaw, Casey Harding, and Devin Martinez participated in the revision of the paper.