Melissa oil is the essential oil extracted from the leaves of Melissa officinalis L. (Lamiaceae). Melissa is used in traditional aromatherapy to alleviate depression, anxiety, stress and insomnia. We have identified Melissa oil as an effective depressant of neurotransmission, with a proposed mechanism involving voltage-gated sodium channels (VGSCs)(1). Melissa essential oil (Mo) reversibly blocks 750 ms bursts of sustained repetitive firing in cultured forebrain cells from E16-18 Sprague-Dawley rats without any effect on the primary spike. Voltage-clamp experiments in N1E 115 neuroblastoma cells confirmed that Mo (0.1-1mg/ml) was able to block VGSCs and exert hyperpolarising shifts in the fast inactivation curves which were significantly greater than those evoked by supra-clinical concentrations of carbamazepine (100 µM). High frequency stimulation and depolarisation both facilitated the blocking action of Mo, and Mo reversibly reverses ictal-like epileptiform activity in a 4-AP (4-aminopyridine)-induced brain slice model for epilepsy(2). Based on a [3H] batrachotoxinin A 20-α-benzoate binding assay (3), Mo was confirmed to modulate VGSCs, but the 12 most common components within the oil appeared not to modulate VGSCs. Essential oils are characterized by a very complex mixtures whose components belong to different classes of compounds including hydrocarbons, aldehydes, ketones, esters, and alcohols that range widely in concentration and variability among different plant species. A solid phase extraction protocol (SPE) was developed as an initial step for identifying the neuroactive components in Mo. 100 μL of the essential oils was loaded onto a 4g silica cartridge (SF10-4g) that had previously been conditioned with pentane. The elution of the SPE cartridge was performed using a vacuum manifold at a velocity of 3 ml/sec with the following solvent sequence: Fraction I: pentane 100% Fraction II: pentane/ethyl ether 90:10 and Fraction III: ethyl ether 100%. Gas chromatography mass spectroscopy (GC-MS) analysis was carried out on Melissa essential oil and the three fractions. Fraction A contained all hydrocarbons; fraction B carbonyl compounds, ethers, esters and tertiary alcohols; Fraction C primary alcohols, acids and diols. This method was successful in fractionating Essential oils into three distinct fractions in one simple step easily, quickly and using small amounts of organic solvents. Protocols have been modified to further improve the fractionation profiles, and the fractions are now being tested using our electrophysiological and binding assays.