Pharmacodynamic Effects of two Different Hypericum Extracts in Healthy Volunteers Measured by Quantitative EEG

Abstract

A double-blind, randomized, placebo-controlled parallel-group trial (phase I) was performed to evaluate the central pharmacodynamic effects of two hypericum extracts with different contents of hyperforin (0.5 % and 5.0 %) but identical hypericin content. Three groups of 18 volunteers between 18 and 35 years of age participated in the trial. The volunteers receiving verum took 900 mg of the extract once a day for 8 consecutive days. The primary aim of this study was to observe the frequency bands, i.e., delta (1.25-4.5 Hz), theta (4.75-6.75 Hz), alpha-1 (7.0-9.5 Hz), alpha-2 (9.75-12.5 Hz), beta-1 (12.75-18.5 Hz), and beta-2 (18.75-35 Hz). This was the first study of its kind testing hypericum controlled on the basis of its hyperforin contents. A quantitative topographic EEG (qEEG) was performed on days 1 and 8 as an indicator of drug-induced pharmacological action. The volunteers' electrophysiological data were obtained prior to application and 2, 4, 6, 8, and 10 hours post administration. Plasma samples for evaluation of the pharmacokinetics of hyperforin were also obtained.

The qEEG results of the placebo group on days 1 and 8 showed no significant changes with regard to their physiological daily rhythm. In both verum groups (0.5 % and 5.0 % hyperforin content), reproducible central pharmacodynamic effects were apparent in comparison to placebo, in particular with the extract containing 5.0 % of hyperforin. A peak pharmacodynamic efficacy was observed between 4 and 8 hours post administration. These results were confirmed on day 8 of the trial. The extract containing 5.0 % hyperforin showed a marked tendency to produce higher increases in qEEG baseline power performances than the one containing 0.5 % hyperforin. These higher baseline outputs on day 8 were seen at the delta, theta, and alpha-1 frequency values. Compared to placebo there was a significant increase in qEEG power performance in the delta and beta-1 frequency values exclusively for the extract containing 5.0 % hyperforin. The theta and alpha-1 frequency values showed a noticeable tendency more emphasized on day 8 than on day 1. Preclinical trials in rats have been observed with similar changes in the frequency bands mentioned above, especially in the cholinergic (delta), noradrenergic (theta) and serotonergic (alpha) neurotransmitter systems.

These experimental findings suggest that hypericum extracts with a high hyperforin content have a shielding effect on the central nervous system.