Clinical indications for herbal drugs very often only rely on traditional knowledge. Single plant-derived preparations are used for many purposes and cannot be classified to belong to a single category like calming or stimulating drugs. With respect to the brain a unique possibility exists to analyze drug effects by recording the EEG. It is common knowledge that many drugs change the frequency content of electric brain activity. Quantitative analysis of the EEG by Fast Fourier Transformation reveals parameters like spectral power, which can be processed further (CATEEM ®). Source density was determined from 17 channels of the quantitative EEG from 10 clinical studies recorded in a relaxed state with open eyes. Linear discriminant analysis was used to differentiate the effects of Placebo (circadian rhythm) from CNS-active herbal drugs in comparison to Valium ®. Calmvalera ®, L-Theanine, Lasea ®, Neurapas ®, Neuravena ®, Neurexan ®, Nutrifin Relax ®, Pascoflair ® (herbal calming drugs) as well as memoLoges ®, Zembrin ® (herbal stimulating drugs) induced different changes of the frequency content of brain electric activity. Discriminant analysis revealed that Nutrifin Relax ®, Pascoflair ® and Suntheanine ® could not be separated well from each other indicating a similar mechanism of action. The effect of Valium ® was projected at a very isolated position far away from the herbal preparations indicating a totally different mechanism of action. Zembrin ® and memoLoges ® grouped together with respect to the first three discriminant functions, but were different with respect to the 4th to 6th discriminant function. Lasea ® as anxiolytic drug and Neurapas ® as antidepressive drug were projected at isolated positions indicating their different clinical indications. The results indicate that discriminant analysis of human quantitative EEG data allows for unique pharmacological description of individual effect profiles of herbal drugs.
Widespread clinical use of behavior-modifying drugs having defined biochemical actions has provided observations and generated hypotheses that relate neurochemical findings to normal and abnormal behaviors in man [
In day-night converted rats recording of field potentials from the depth of the brain revealed significant changes in the presence of drugs in comparison to placebo. Quantitative analysis of these data by frequency analysis using Fast Fourier Transformation (FFT) documented time and dose dependent changes of spectral power in four brain areas (frontal brain, hippocampus, striatum and reticular formation). Results from frequency analysis were documented according to 6 specifically defined ranges (frequency bands). In order to discriminate effects of 40 drugs with known clinical indications from each other, 24 parameters (spectral power from 4 brain areas × 6 frequency bands) were fed into linear discriminant analysis. Surprisingly, drugs with similar indication clustered together (could not be discriminated well from each other) and were clearly separated from drugs with other indications [
Data from 10 clinical studies were reanalyzed. Quantitative EEG data were obtained by Fast Fourier Transformation of analog data [
All experiments were performed under identical conditions as published earlier [
Electric activity of the human brain changes with time and follows a circadian rhythm [
Calmvalera® tablets are prescribed for nervous restlessness and better coping with stress. This homeopathic remedy has been tested within a clinical study in young subjects suffering from examination anxiety. Clinical efficacy was demonstrated [
Ingredients | Dosage | |
---|---|---|
Calmvalera® | Cimicifuga Trit. D3 20 mg, Cocculus Trit. D4 20 mg Cypripedium pubescens Trit. D4 10 mg, Ignatia Trit. D6 40 mg Lilium tigrinum Trit. D6 20 mg, Passiflora incarnata Trit. D3 40 mg Platinum metallicum Trit. D8 20 mg, Valeriana Trit. D2 20 mg Zincum valerianicum Trit. D3 20 mg Other ingredients: lactose-monohydrate (35 mg), magnesium stearate (Ph.Eur.), corn starch | 6 tab. |
Lasea® | Lavender oil 80 mg Gelatin polysuccinate Glycerol 85% Rapeseed oil, refined sorbitol Carminic acid, aluminum salts Patent Blue V, aluminum salt Titanium dioxide | 2 cap. |
memoLoges® | 120 mg Bacopa monnieri extract + 380 mg Sideritis scardica extract plus 20 mg of vitamin B6, 500 μg of Vitamin B12, 400 μg of folic acid, 18 mg of Vitamin B5 and 1.5 mg of Zinc | 2 cap. |
Neurapas® balance | Passionflower herb dry extract (6.2-7.1: 1) 32 mg native extract Extraction Agent: Ethanol 60% (m/m) equivalent to 68% (v/v) Valerian root dry extract (3.8-5.6: 1) 28 mg native extract Extraction Agent: Ethanol 40% (m/m) equivalent to 48% (v/v) The extracts used are extract preparations of native extract and excipients St. John’s wort dry extract preparation (80 mg/day): (75% native extract + 5% silica, colloidal anhydrous + 20% lactose monohydrate) Passionflower herb dry extract preparation (40 mg/tablet): (80% native extract + 20% maltodextrin) Valerian Root Dry Extract Preparation (40 mg/tablet): (70% native extract + 26% glucose, spray dried + 4% silica, colloidal anhydrous) | 6 tab. |
Neuravena® | Wild Green Oat Extract 400 mg (Neuravena®* Special Extract 3.5:1) 1; Vitamin B6 1.5 mg; Vitamin B12 2.5 μg; Pantothenic acid 6 mg | 2500 mg |
Neurexan® | 0.6 mg Dil. D2 Passiflora incarnata 0.6 mg Dil. D2 Avena sativa 0.6 mg Dil. D12 Coffea arabica 0.6 mg Dil. D4 Zincum isovalerianicum Magnesiumstearat (1.5 mg), Lactose-Monohydrat (300 mg) | 4 tab. |
Nutrifin Relax® | 3 mg Lavender oil, 67.5 mg Lemon balm extract, 11.25 Oat extract and 11.25 mg Hops extract | 2 × 1 lozenge |
Pascoflair® | Passionflower herb dry extract (5-7:1) 425 mg native extract Extraction Agent: Ethanol 50% (v/v) equivalent to 42% (m/m) The extract used is an extract preparation of native extract and excipients Passionflower Dried Dry Extract Preparation (607.1 mg/tablet): (70% native extract + 27% maltodextrin + 3% silica, colloidal anhydrous) | 3 tab. |
Suntheanine® | L-Theanine | 250 mg |
Valium® | Diazepam 5 mg magnesium stearate corn starch Iron (III) oxide hydrate (E 172) Lactose monohydrate | 5 mg |
Zembrin® | 25 mg Zembrin® (Sceletium tortuosum extract), microcrystalline cellulose, cellulose (capsule), silicon dioxide, magnesium stearate | 50 mg |
Nervous restlessness | Anxiety | Depression | Sleep disorder | Stress | Cognition | |
---|---|---|---|---|---|---|
Calmvalera® | X | X | X | X | ||
Lasea® | X | X | X | X | ||
memoLoges® | X | |||||
Neurapas® balance | X | X | ||||
Neuravena® | X | |||||
Neurexan® | X | X | ||||
Nutrifin Relax® | X | |||||
Pascoflair® | X | X | X | |||
Suntheanine® | X | |||||
Valium® | X | X | X | X | ||
Zembrin® | X | X | X | X |
Lasea® is an herbal drug prescribed to treat general anxiety [
MemoLoges® has been clinically tested in subjects suffering from mild cognitive impairment [
Neurapas® balance has been developed to fight stress, anxiety and depression. The effect of this drug has been successfully characterized within a clinical study [
The next herbal drug, which has been analyzed, was Neuravena® (2500 mg).
This drug has been tested and found to have positive effects on cognition [
Neurexan® is sold as a homeopathic drug for the treatment of nervousness. A double-blind, randomized clinical trial proved efficacy [
Another relaxing drug is Nutrifin Relax®. EEG was recorded after intake of 2 lozenges. Results have been published earlier [
Pascoflair® is used to treat anxiety, nervousness and generalized anxiety disorder. In preoperative surgery patients it reduced anxiety [
was also shown by a combination of psychometry and quantitative EEG [
An herbal calming drug is Suntheanine®. Its active constituent is L-Theanine, a compound found in green tea [
Valium® is one of the best-known drugs with a strong sedative, anxiolytic and anticonvulsive action [
Zembrin® (a special extract of Sceletium tortuosum, which has been consumed by original inhabitants in South Africa for a long time) is a food supplement marketed also in the USA and Canada for improvement of cognitive performance [
Statistically significant changes of single frequencies in the presence of drugs at any of the brain regions are listed in
Delta | Theta | Alpha 1 | Alpha 2 | Beta 1 | Beta 2 | |
---|---|---|---|---|---|---|
Calmvalera® | + | + | + | + | (+) | |
Lasea® | (+) | (+) | + | + | + | (+) |
memoLoges® | − | (−) | + | + | + | − |
Neurapas® balance | − | (−) | (−) | (−) | ||
Neuravena® | + | + | + | |||
Neurexan® | − | − | − | − | − | (−) |
Nutrifin Relax® | (+) | + | ||||
Pascoflair® | (−) | − | ||||
Suntheanine® | + | + | + | + | + | + |
Valium® | (−) | − | − | − | (+) | + |
Zembrin® | + | + | + | + |
“+” or “−” indicate the direction of changes. Brackets indicate p < 0.10, otherwise change of the frequency is statistically significantly different from circadian rhythm at least at the level of p < 0.05.
Another way to document the results from quantitative EEG recording is to construct a brain map. This approach allows an overview on the involvement of different brain regions during the action of drugs. However, there is an influence of the circadian rhythm on electric brain activity during relaxation, which is recognized when placebo is given (
The pattern of frequency changes in the brain in the presence of drugs seems to be very specific and can be differentiated from each other by looking at the spectral power in 17 regions. Nevertheless, it would be desirable to find an approach to compress the information for individual characterization and classification of the drug effects. This can be achieved by using discriminant analysis. This type of analysis is based on all 102 parameters (spectral power in 17 brain regions) and separates the effects of all drugs from each other best (
far away from the synthetic strongly sedative drug Valium®. Two drugs acting positively on cognition (Zembrin® and memoLoges®) are not very far from each other, but show a different colour due to the result of the 4th to 6th discriminant function. Furthermore, the unique efficacy of Lasea® and Neurapas® is documented by their isolated position as shown in
Quantitative EEG data have been used extensively to characterize drug effects on the brain in the past under the term Pharmaco-EEG [
Individual patterns of frequency changes in the presence of different drugs also give hints on their mechanism of action since changes of particular frequencies
have been related to neurotransmitter action. Extensive animal studies have revealed that delta waves are influenced by the activity of acetylcholine. Theta activity seems to be controlled by norepinephrine, whereas alpha 1 activity reflects serotonergic actions. Changes in dopaminergic activity are represented by alpha 2 spectral power [
A methodological approach is now presented, which allows evaluation of all experimental parameters at the same time: discriminant analysis [
After successful application in preclinical research [
In conclusion, discriminant analysis is not only used successfully in the pharmacological characterization of drug effects in rats, but proves to be a very convenient tool in describing the unique effects of herbal drugs in humans. This is a major progress and should be used in the future for characterization and classification of pharmacological effects of herbal drugs on the brain.
The author declares no conflicts of interest regarding the publication of this paper.
Dimpfel, W. (2019) Classification of Herbal Drug Effects by Discriminant Analysis of Quantitative Human EEG Data. Neuroscience & Medicine, 10, 101-117. https://doi.org/10.4236/nm.2019.102007