OJPsych  Vol.5 No.3 , July 2015
Cerebral Bioavailability of Silexan—A Quantitative EEG Study in Healthy Volunteers
Abstract: Background: A quantitative EEG (qEEG) study was performed to investigate the cerebral bioavailability of Silexan. Method: Twenty-four male and female healthy volunteers between 20 and 62 years of age were eligible for participation and received 160 or 80 mg/day Silexan or placebo in randomised order according to a 3-way crossover design. Treatment phases of 14 days were separated by 14-day washout periods. qEEG recordings in conditions “eyes open”, “eyes closed”, as well as during performance of 3 different cognitive tasks, were performed at 0, 1, 2, 3, and 4 h after drug administration on the first (single-dose assessment) and last day of each treatment period (repetitive dose assessment). Result: Compared with placebo, qEEG analysis revealed a significant increase of spectral power within two hours in the alpha1 range (7.0 - 9.5 Hz), particularly in the fronto-temporal region, where it was more pronounced after administration of Silexan 160 mg/day than after the 80 mg/day dose. Changes in other frequency bands were mainly attributable to circadian rhythm. No EEG changes typically seen during the investigation of sedative drugs (general theta increase) were observed. Cognitive task performance under both doses of Silexan was not inferior compared with that in the placebo period. Conclusions: The study provides evidence that ingredients of the anxiolytic lavender oil preparation Silexan penetrate the blood-brain barrier and induce functional changes in the CNS. The types of changes observed in the qEEG are consistent with the anxiolytic clinical effect of the drug represented by increases of alpha1 spectral power. No sedative effects were observed. Silexan was well tolerated during repetitive administration of doses up to twice the marketed dose.
Cite this paper: Dimpfel, W. , Wedekind, W. and Dienel, A. (2015) Cerebral Bioavailability of Silexan—A Quantitative EEG Study in Healthy Volunteers. Open Journal of Psychiatry, 5, 285-297. doi: 10.4236/ojpsych.2015.53032.

[1]   Shukla, S.D., Bhatnagar, M. and Khurana, S. (2012) Critical Evaluation of Ayurvedic Plants for Stimulating Intrinsic Antioxidant Response. Frontiers in Neuroscience, 6, 112.

[2]   Bhattaram, V.A., Graefe, U., Kohlert, C., Veit, M. and Derendorf, H. (2002) Pharmacokinetics and Bioavailability of Herbal Medicinal Products. Phytomedicine, 9, 1-33.

[3]   Jobert, M., Wilson, F.J., Ruigt, G.S., Brunovsky, M., Prichep, L.S., Drinkenburg, W.H. and Committee, I.P.-E.G. (2012) Guidelines for the Recording and Evaluation of Pharmaco-EEG Data in Man: The International Pharmaco-EEG Society (IPEG). Neuropsychobiology, 66, 201-220.

[4]   Saletu, B., Grünberger, J. and Linzmayer, L. (1983) Quantitative Pharmaco-EEG and Performance after Administration of Brotizolam to Healthy Volunteers. British Journal of Clinical Pharmacology, 16, 333S-345S.

[5]   Fink, M. and Shapiro, D.M. (1969) EEG Patterns as an Index of Clinical Activity of Psychoactive Drugs. Electroencephalography and Clinical Neurophysiology, 27, 710.

[6]   Itil, T.M., Ulett, G.A. and Fukuda, T. (1971) Quantitative Pharmaco-Electroencephalography in Early Evaluation of Psychotropic Drugs. Folia Psychiatrica et Neurologica Japonica, 25, 195-202.

[7]   Dimpfel, W., Hofmann, H.C., Prohaska, A., Schober, F. and Schellenberg, R. (1996) Source Density Analysis of Functional Topographical EEG: Monitoring of Cognitive Drug Action. European Journal of Medical Research, 1, 283-290.

[8]   Schober, F., Schellenberg, R. and Dimpfel, W. (1995) Reflection of Mental Exercise in the Dynamic Quantitative Topographical EEG. Neuropsychobiology, 31, 98-112.

[9]   Dimpfel, W. (2003) Preclinical Data Base of Pharmaco-Specific Rat EEG Fingerprints (Tele-Stereo-EEG). European Journal of Medical Research, 8, 199-207.

[10]   Dimpfel, W. (2013) Pharmacological Classification of Herbal Extracts by Means of Comparison to Spectral EEG Signatures Induced by Synthetic Drugs in the Freely Moving Rat. Journal of Ethnopharmacology, 149, 583-589.

[11]   Dimpfel, W., Koch, K. and Weiss, G. (2011) Early Effect of NEURAPAS? Balance on Current Source Density (CSD) of Human EEG. BMC Psychiatry, 11, 123.

[12]   Hamilton, M. (1976) Hamilton Anxiety Scale (HAMA). In: Guy, W., Ed., ECDEU Assessment Manual for Psychopharmacology, US National Institute of Health, Psychopharmacology Research Branch, Rockville, 193-197.

[13]   Kasper, S., Gastpar, M., Müller, W.E., Volz, H.P., M?ller, H.J., Dienel, A. and Schl?fke, S. (2010) Silexan, an Orally Administered Lavandula Oil Preparation, Is Effective in the Treatment of “Subsyndromal” Anxiety Disorder: A Randomized, Double-Blind, Placebo Controlled Trial. International Clinical Psychopharmacology, 25, 277-287.

[14]   Kasper, S., Anghelescu, I. and Dienel, A. (2010) Efficacy of Silexan (WS? 1265) in Patients with Restlessness and Sleep Disturbance. Annual Congress of the German Society for Psychiatry and Psychotherapy (DGPPN), Berlin.

[15]   Kasper, S., Gastpar, M., Müller, W.E., Volz, H.-P., M?ller, H.-J., Schl?fke, S. and Dienel, A. (2014) Lavender Oil Preparation Silexan Is Effective in Generalized Anxiety Disorder—A Randomized, Double-Blind Comparison to Placebo and Paroxetine. The International Journal of Neuropsychopharmacology, 17, 859-869.

[16]   Woelk, H. and Schl?fke, S. (2010) A Multi-Center, Double-Blind, Randomised Study of the Lavender Oil Preparation Silexan in Comparison to Lorazepam for Generalized Anxiety Disorder. Phytomedicine, 17, 94-99.

[17]   Brickenkamp, R. (1994) d2-Test. Hogrefe, G?ttingen.

[18]   Düker, H. and Lienert, G.A. (1965) Der Konzentrations-Leistungstest (KLT). Hogrefe, G?ttingen.

[19]   Cantero, J.L., Atienza, M., Salas, R.M. and Gomez, C.M. (1999) Brain Spatial Microstates of Human Spontaneous Alpha Activity in Relaxed Wakefulness, Drowsiness Period, and REM Sleep. Brain Topography, 11, 257-263.

[20]   Hardt, J.V. and Kamiya, J. (1978) Anxiety Change through Electroencephalographic Alpha Feedback Seen Only in High Anxiety Subjects. Science, 201, 79-81.

[21]   Rice, K.M., Blanchard, E.B. and Purcell, M. (1993) Biofeedback Treatments of Generalized Anxiety Disorder: Preliminary Results. Biofeedback and Self-Regulation, 18, 93-105.

[22]   Kasper, S., Dienel, A. and Kieser, M. (2004) Continuation and Long-Term Maintenance Treatment with Hypericum Extract WS? 5570 after Successful Acute Treatment of Mild to Moderate Depression—Rationale and Study Design. International Journal of Methods in Psychiatric Research, 13, 176-183.

[23]   Saletu, B., Anderer, P. and Saletu-Zyhlarz, G.M. (2006) EEG Topography and Tomography (LORETA) in the Classification and Evaluation of the Pharmacodynamics of Psychotropic Drugs. Clinical EEG and Neuroscience, 37, 66-80.

[24]   Takahashi, M., Iwamoto, K., Kawamura, Y., Nakamura, Y., Ishihara, R., Uchiyama, Y., Ebe, K., Noda, A., Noda, Y., Yoshida, K., Iidaka, T. and Ozaki, N. (2010) The Effects of Acute Treatment with Tandospirone, Diazepam, and Placebo on Driving Performance and Cognitive Function in Healthy Volunteers. Human Psychopharmacology, 25, 260-267.