**6. Neurological toxicity of essential oils**

Essential oils could easily pass the blood-brain barrier, reaching the central nervous system after a systemic absorption. In an experimental setting, essential oils from *Salvia officinalis* and *Hyssopus officinalis* evoked convulsions after intraperitoneal administration in rats at doses of 0.5 g/kg and 0.13 g/kg, respectively [29].

In humans, essential oils from *Salvia officinalis*, *Thuja plicata*, *Cedrus* spp., *Hyssopus officinalis*, *Eucalyptus* spp., *Mentha pulegium*, *Cinnamonum camphora* and *Anethum graveolens* produced tonic-clonic convulsions, particularly in children and especially in those with a history of epileptic syndromes, according to several reports [30, 31].

#### **Figure 4.**

*Chemical structure of terpenes with epileptogenic potential.*

The identified chemical constituents responsible for convulsions were usually 1,8-cineole, camphor, thujone, pulegone and pinocamphone (**Figure 4**) [29, 30].

Molecular mechanisms of the convulsant effect of essential oils and their constituents were investigated in laboratory animals. According to a study, some essential oils resemble pentylentetrazole, a powerful convulsive agent, modifying tissue gradients of Na and K and leading to increased cellular excitability in the brain [32]. In another experimental study, thujone one of the frequently incriminated pro-convulsant terpenes, suppressed GABA-induced peak currents in rat dorsal root ganglion neurons, with the subsequent apparition of convulsions, terminated by diazepam or phenobarbital [33]. On the contrary, other research proved that different terpenes could have an anticonvulsant effect. Menthol, another terpene derivative found in the chemical composition of some essential oils enhanced electric currents induced by low concentrations of GABA and directly activated GABAA receptors in laboratory animals [34].

In the context of potential neurological toxicity of essential oils, European Medicines Agency (EMA) reviewed the safety of suppositories containing terpenes used in seven European countries (France, Belgium, Portugal, Spain, Italy, Luxembourg and Finland) for the treatment of respiratory diseases. The report concluded that terpenes could induce convulsions in children less than 30 months, recommending they should be contraindicated in this particular segment of patients [35].
