Lavender Oil-Potent Anxiolytic Properties via Modulating Voltage Dependent Calcium Channels

Abstract

Recent clinical data support the clinical use of oral lavender oil in patients suffering from subsyndromal anxiety. We identified the molecular mechanism of action that will alter the perception of lavender oil as a nonspecific ingredient of aromatherapy to a potent anxiolytic inhibiting voltage dependent calcium channels (VOCCs) as highly selective drug target. In contrast to previous publications where exorbitant high concentrations were used, the effects of lavender oil in behavioral, biochemical, and electrophysiological experiments were investigated in physiological concentrations in the nanomolar range, which correlate to a single dosage of 80 mg/d in humans that was used in clinical trials. We show for the first time that lavender oil bears some similarities with the established anxiolytic pregabalin. Lavender oil inhibits VOCCs in synaptosomes, primary hippocampal neurons and stably overexpressing cell lines in the same range such as pregabalin. Interestingly, Silexan does not primarily bind to P/Q type calcium channels such as pregabalin and does not interact with the binding site of pregabalin, the α2δ subunit of VOCCs. Lavender oil reduces non-selectively the calcium influx through several different types of VOCCs such as the N-type, P/Q-type and T-type VOCCs. In the hippocampus, one brain region important for anxiety disorders, we show that inhibition by lavender oil is mainly mediated via N-type and P/Q-type VOCCs. Taken together, we provide a pharmacological and molecular rationale for the clinical use of the oral application of lavender oil in patients suffering from anxiety.

Exploring Pharmacological Mechanisms of Lavender (Lavandula angustifolia) Essential Oil on Central Nervous System Targets

“…LEO was able to displace CGP39653 binding in a dose-dependent mode, which means that this oil may exert nerve-calming effects via modulating NMDA receptors. This is the first time that this affinity is reported and this fact could explain the anti-agitation properties that have been found for these products in animal and some clinical studies (Bradley et al, 2009; Faturi et al, 2010; Kasper et al, 2010; Tsang and Ho, 2010; Woelk and Schlaefke, 2010; Chioca et al, 2011; Goes et al, 2012; Hritcu et al, 2012; Schuwald et al, 2013). NMDA-receptor activation by glutamate is also involved in neurotoxicity so our essential oil might exert neuroprotection through the blockade of this ionotropic receptor.…”

Efficacy of orally administered Silexan in patients with anxiety-related restlessness and disturbed sleep – A randomized, placebo-controlled trial

“…In contrast to initial speculations that the anxiolytic action of lavender oil is caused by a benzodiazepine-like effect on the GABA A receptors (Huang et al, 2008) a recent study performed by Schuwald et al (2013) did not identify any interaction of Silexan to known targets of other anxiolytic drugs such as the GABA A -receptor, norepinephrine, serotonin, or dopamine transporters, or monoamine-oxidase-A (MAO-A). Instead, Silexan caused a potent inhibition of voltage dependent calcium channels (VOCCs) in synaptosomes, primary hippocampal neurons and stably overexpressing cell lines comparable to pregabalin.…”

Phytopharmaceutical treatment of anxiety, depression, and dementia in the elderly: evidence from randomized, controlled clinical trials

“…The HMP is approved as a drug in Germany for the treatment of restlessness related to anxious mood, with a recommended dose of 1 × 80 mg/day. The anxiolytic effect of silexan can be explained by a potent inhibition of voltage-dependent calcium channels (VOCCs), however, without binding to the gabapentin binding site at the 2-1 and -2 subunits of the presynaptic VOCCs of the P/Q-type [19] as well as by a significant reduction the serotonin-1 A receptor (5-HT1A) binding potential in several brain clusters [20]. In adult patient populations, the drug has been demonstrated to be superior to placebo in subsyndromal anxiety disorder and generalized anxiety disorder (GAD) as well as comparably efficacious as paroxetine and lorazepam in GAD [21][22][23][24].…”