Effects of Silexan on the Serotonin-1A Receptor and Microstructure of the Human Brain: A Randomized, Placebo-Controlled, Double-Blind, Cross-Over Study with Molecular and Structural Neuroimaging

Abstract

Background:Recently, Silexan, a patented active substance comprised of an essential oil produced from Lavandula angustifolia flowers, has been authorized in Germany as a medicinal product for the treatment of states of restlessness related to anxious mood. Its efficacy has been shown in several forms of anxiety disorders. Findings from preclinical and clinical studies attribute a major role to the serotonin-1A receptor in the pathogenesis and treatment of anxiety.Methods:To elucidate the effect of Silexan on serotonin-1A receptor binding, 17 healthy men underwent 2 positron emission tomography measurements using the radioligand [carbonyl-11C]WAY-100635 following the daily intake of 160mg Silexan or placebo for a minimum of 8 weeks (randomized, double-blind, cross-over design). Additionally, structural magnetic resonance imaging and voxel-based morphometry analysis was performed to determine potential effects on gray matter microstructure.Results:Serotonin-1A receptor binding potential was shown to be significantly reduced following the intake of Silexan compared with placebo in 2 large clusters encompassing the temporal gyrus, the fusiform gyrus and the hippocampus on one hand as well as the insula and anterior cingulate cortex on the other hand. No effects of Silexan on gray matter volume could be detected in this investigation.Conclusion:This positron emission tomography study proposes an involvement of the serotonin-1A receptor in the anxiolytic effects of Silexan.The study was registered in the International Standard Randomized Controlled Trial Number Register as ISRCTN30885829 ().

Silexan in anxiety disorders: Clinical data and pharmacological background

“…Based on their findings, Silenieks et al (2013) also conclude there is little likelihood of a benzodiazepine-like anxiolytic action of Silexan via interaction with GABA A receptors, which supports the findings reported by Schuwald et al (2013). Baldinger et al (2015) provided supportive information on the anxiolytic mode of action of Silexan by reporting data from a placebo-controlled clinical trial with a cross-over design. In order to elucidate the effect of Silexan on 5-HT 1A receptor binding, 17 healthy men underwent positron emission tomography measurements using the radioligand [carbonyl-11 C]WAY-100635 following a daily intake of 160 mg Silexan or placebo for a minimum of 8 weeks.…”

“…Summarizing the nonclinical findings and the results obtained from the human pharmacological study by Baldinger et al (2015), it must be noted that, despite some similarities to the anxiolytic action of benzodiazepines, SSRIs or the gabapentinoid pregabalin, Silexan does not interact with typical targets of these standard anxiolytics (Schuwald et al 2013). Instead, Silexan is reported to inhibit different types of VOCCs and to modulate serotonergic neurotransmitter systems.…”

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].…”

The relevance of ‘mixed anxiety and depression’ as a diagnostic category in clinical practice

“…Consequently, SSRIs, that were originally developed as antidepressants [46], are now also recommended as first-line treatment for anxiety disorders [e.g., 47], and there is also evidence that SSRIs are efficacious in MADD where studies have been performed for sertraline [48], fluvoxamine [49], and citalopram [50]. Comparable results were also found for Silexan, a herbal active substance acting on the serotonin-1A receptor subtype [51], which was shown to be efficacious in anxiety disorders [52, 53] as well as in MADD [54]. …”