Modulation of Mood and Cognitive Performance Following Acute Administration of Single Doses of Melissa Officinalis (Lemon Balm) with Human CNS Nicotinic and Muscarinic Receptor-Binding Properties

Abstract

Melissa officinalis (Lemon balm) is a herbal medicine that has traditionally been attributed with memory-enhancing properties, but which is currently more widely used as a mild sedative and sleep aid. In a previous study it was demonstrated that a commercial Melissa extract led to dose-specific increases in calmness, and dose-dependent decrements in timed memory task performance. However, the extract utilized in that study did not exhibit in vitro cholinergic receptor-binding properties. The current study involved an initial screening of samples of M. officinalis for human acetylcholinesterase inhibition and cholinergic receptor-binding properties. The cognitive and mood effects of single doses of the most cholinergically active dried leaf were then assessed in a randomized, placebo-controlled, double-blind, balanced crossover study. Following the in vitro analysis, 20 healthy, young participants received single doses of 600, 1000, and 1600 mg of encapsulated dried leaf, or a matching placebo, at 7-day intervals. Cognitive performance and mood were assessed predose and at 1, 3, and 6 h postdose using the Cognitive Drug Research computerized assessment battery and Bond-Lader visual analog scales, respectively. In vitro analysis of the chosen extract established IC(50) concentrations of 0.18 and 3.47 mg ml(-1), respectively, for the displacement of [(3)H]-(N)-nicotine and [(3)H]-(N)-scopolamine from nicotinic and muscarinic receptors in the human cerebral cortex tissue. However, no cholinesterase inhibitory properties were detected. The most notable cognitive and mood effects were improved memory performance and increased 'calmness' at all postdose time points for the highest (1600 mg) dose. However, while the profile of results was overwhelmingly favorable for the highest dose, decrements in the speed of timed memory task performance and on a rapid visual information-processing task increased with decreasing dose. These results suggest that doses of Melissa officinalis at or above the maximum employed here can improve cognitive performance and mood and may therefore be a valuable adjunct in the treatment of Alzheimer's disease. The results also suggest that different preparations derived from the same plant species may exhibit different properties depending on the process used for the sample preparation.

Effects of Cholinesterase Inhibiting Sage (Salvia officinalis) on Mood, Anxiety and Performance on a Psychological Stressor Battery

“…As an example, while extracts of M. officinalis (also a member of the Labiatae family) have been shown to bind directly to both muscarinic and nicotinic receptors in human brain tissue (eg Kennedy et al, 2003), potential receptor-binding properties (in any neurotransmitter system) have not, as yet, been investigated in extracts of S. officinalis. It therefore seems premature to attribute any effects to a specific mechanism simply on the basis that it has been demonstrated.…”

Transdermal Absorption of (−)-Linalool Induces Autonomic Deactivation but has No Impact on Ratings of Well-Being in Humans

“…Since these drugs are associated with serious adverse effects, for example, rebound and hang-over effects, reduced alertness and efficiency during the day as well as physical and psychic addiction, chronic intake of these substances is somewhat problematic. Recent studies demonstrated that herbal preparations containing lemon balm (Melissa officinalis, L.) (Ballard et al, 2002;Kennedy et al, 2003), valerian (Valeriana officinalis, L.) (Cerny and Schmid, 1999) or St John's wort (Kommission E Monograph, 1989) proved as alternatives with satisfying efficacy and tolerability. Also lavender (Lavandula angustifolia, Mill.)…”

Effects of Ncl. Basalis Meynert volume on the Trail‐Making‐Test are restricted to the left hemisphere

“…Studies on AChE inhibitor application in healthy participants showed a cognitive impairment rather than an enhancement and a bell‐shaped dose‐response curve has been proposed for the effects of several cholinergic receptor agonists on cognition (Kennedy et al. 2003; Kitagawa et al. 2003; Beglinger et al.…”