Subjects suffering from anxiety during examinations often take drugs with considerable side effects. As alternative, homeopathic preparations virtually lack side effects in general. However, clinical efficacy has to be demonstrated. This experimental series was initiated to provide evidence, that Calmvalera Hevert tablets, marketed for treatment of nervous restlessness and better coping with stress, have an influence on brain electric activity. In order to test this, a new clinical design was used: “EnkephaloVision”. It consists of the combination of quantitative EEG recording with time epochs of 364 ms (Neurocode-Tracking) with conventional Eye-Tracking. Seventeen channels of EEG and one channel EOG were recorded. After frequency analysis (FFT) current source density was calculated. Recording was performed in the presence of a video clip, which contained several different cognitive and emotional challenges in series. Twenty-four male and female subjects having a score >60 in an anxiety questionnaire (Prüfungsangstfragebogen PAF-S) were recruited to participate. A correlation between the Hamilton anxiety score and spectral alpha1 power during the recording condition “eyes open” before drug intake was detected. Spectral power was averaged including C z, F 3 and F 4 electrode positions. Audiovisual challenges induced spectral changes with respect to delta, theta and beta power, not in the alpha ranges, to a different but statistically significant degree. Intake of Calmvalera Hevert tablets resulted in statistically significant increases of alpha1 and alpha2 spectral power during most of the recording conditions within the left hemisphere. Increases of alpha activity have been related to relaxation and calmness as reported in the literature. Discriminant analysis of the whole data set revealed a clear difference between verum and placebo and a projection of the data into the vicinity of other plant-derived calming preparations. Performance of psychometric tasks was not disturbed. Efficacy of Calmvalera Hevert tablets points to active molecules contained due to low triturations (D2 - D8).
Anxiety during examinations and similar conditions is a widespread phenomenon that very often leads to intake of drugs with considerable side effects. An alternative therapy might consist in using complex homeopathic medicines with a better tolerability. Among these, one preparation is based on nine mainly plant derived homeopathic triturations (potencies D2 to D8) and is marketed in Germany under the name of Calmvalera Hevert tablets for the treatment of nervous restlessness and sleep disorders including better coping with stress.
Many other preparations from herbal origin have been tested using neurophysiological techniques [
There is convincing evidence that emotional states directly relate to brain electric activity in terms of spectral frequency changes [
Twenty-four healthy male and female subjects aged 18 - 40 years were recruited by advertisements in newspapers. Using an anxiety questionnaire (Prüfungsangstfragebogen PAF-S from Hogrefe Verlag, Göttingen, Germany [
Acute or chronic disease with an impact on the study, which becomes obvious by case history or clinical examination (i.e. also Hamilton depression scale).
Clinically relevant pathological findings from clinical and laboratory findings.
Clinically relevant allergic symptoms.
Detection of alcohol at the time of initial examination (screening day SC) or on study day A (positive alcohol test) or by case history. Detection of drugs (positive drug test) at the time of initial examination (screening day SC).
Consumption of clinically relevant medication during last fourteen days before and during the active study period based on the notification of the subject or his case history.
Consumption of medication with primarily central action (i.e. psychotropic drugs or centrally acting antihypertensives). Known intolerance/hypersensitivity (allergy) to plant derived extracts (Cimicifuga, Cocculos, Passiflora, Valeriana etc.) or any of the ingredients of the investigational product (anamnestic). Presence of a rare genetic disease such as fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase deficiency (anamnestic).
BMI (Body Mass Index) <18 or >32.
Consumption of unusual quantities or misuse of coffee (more than 4 cups a day), tea (more than 4 cups a day) or tobacco (more than 20 cigarettes per day).
Smoking on study day A.
Participation in another clinical trial within the last 60 days.
Positive pregnancy test (study day A).
Lactation.
Cancellation of informed consent.
Ingredients of Calmvalera Hevert tablets and placebo tablets are listed in
Each subject was asked for intake of 6 tablets (daily dosage) at a time. The subjects selected for the study had a normal physical examination, electrocardiogram (ECG) and blood count for safety reasons. Laboratory tests for safety are listed in
EnkephaloVision is the term for the entirely new combination of quantitative EEG (Neurocode-Tracking) and Eye-Tracking.
In this study a 17-channel EEG recording was combined with Eye-Tracking. Details
Composition | ||
---|---|---|
1 tablet contains active ingredients: | ||
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.
Composition | |
---|---|
Lactose/62% Ethanol Trit. | 105,00 mg |
Lactose/43% Ethanol Trit. | 110,00 mg |
Lactose/Lactose Trit. D3 | 2000 mg |
Lactose/Glycerin/Ethanol 43% Trit. | 1000 mg |
Other ingredients: | |
Corn starch | 750 mg |
Magnesium stearate | 100 mg |
Final product doesn’t contain anymore Excipient (s): | |
Purified water | 3500 mg |
Ethanol 96% (V/V) | 500 mg |
Laboratory Tests for safety | Screening day SC | Study day A | Final Examination day FE |
---|---|---|---|
Clinical Examination | x | x | |
Vital Signs (pulse rate, temperature, respiration rate, and blood pressure) | x | x | x |
ECG for safety | x | x | |
Alcohol Test | x | x | x |
Drug-Test (MAHSHAN-KOMBI/ DOA 10 quick test) | x | ||
Pregnancy Test for female (BioSign-HCG-quick test) | x | ||
Laboratory Tests for safety* (Na+, GOT, GPT, GGT, Kreatinin, Glucose in serum, blood count) | x | x | |
Urine (Status, Sediment) | x | x |
of the EEG recording have been published earlier [
EEG recording was performed in the presence of a video clip, which contained several different cognitive and emotional challenges in series. At the beginning, after a gong for synchronization purposes, one minute was recorded under relaxation (eyes open) as reference, followed by presentation of a fixation cross. After this several cognitive and emotional challenges were presented: The total video was presented before and after intake of 6 tablets with some changes of cognitive tasks for prevention of memorized results. Between baseline recording and intake of Calmvalera Hevert or placebo tablets subjects had a pause for 90 minutes in the restroom. The time line of consecutive scenes is documented in the following
EnkephaloVision Neurocode-Tracking in Combination with Eye-Tracking Audio-visual Presentations | ||
---|---|---|
Elements | Time | |
1 | Instructions of volunteers in the Neurocode-Tracking method | 5 min. 00 s |
2 | Gong (for synchronization Neurocode-Tracking (qEEG and Eye-Tracking)) | 21 s |
3 | Black screen (Eyes open) | 1 min. 00 s |
4 | Fix Cross (Eyes open) | 1 min. 00 s |
5 | Picture Comparison (n = 1 foil) with 8 errors including instructions | 1 min. 15 s |
6 | Stroop-Test (n = 1 foil) including instructions | 1 min. 00 s |
7 | Memory-Test (n = 4 tasks) including instructions | 1 min. 35 s |
8 | CPT-Test (concentration performance test) (n = 4 tasks) including instructions | 2 min. 20 s |
9 | Brain Teaser (n = 10 foils) including instructions | 5 min. 15 s |
10 | Emotional Pictures | 1 min. 19 s |
11 | Video “Exam Anxiety” | 1 min. 55 s |
12 | Video “Dentist Pain” | 52 s |
13 | Video “Emergency-OP” (Horror-OP) | 52 s |
14 | Video “Horror” | 1 min. 33 s |
Total Time | 20 min. 17 s |
Eye-Tracking (equipment and software from Tobii Technology GmbH, Frankfurt, Germany), was performed concomitantly with Neurocode-Tracking (fast dynamic quantitative EEG recording). All mental and emotional challenges were presented as a single video clip. Single challenges were first constructed as a power point file and then converted into a final video clip (by Adobe Captivate software). For offline analysis and synchronization with the eye-track data a screen grabber (Adobe Captivate software) was used to produce a video containing all successively calculated EEG maps of 364 ms duration. A second video was obtained from the eye-tracker software running on a separate computer. It is called a “gaze overlay” movie depicting the presented pictures, tasks or video film. In this gaze overlay video the momentary gaze of the subject is documented by a red spot. Data from the whole group are depicted as so-called heat maps. The presentation always started with an audio signal (gong). This audio signal was registered by screen capture of the EEG computer and was used for synchronization of both videos by means of a video cut software (Adobe Premiere Pro). Due to the processing time of the brain (300 to 400 ms) plus that of the computer (depends individually on the type and number of active processors!) the gaze overlay video is shifted in our case (quad core, 3.4 Giga-Hz) for one second in order to obtain synchronized images between gaze and the particular EEG epoch of 364 ms. For detailed offline documentation a movie was exported and analyzed image by image. Single representative images containing the gaze and corresponding EEG map were cut from the screen by a software tool available on all computers.
On the experimental day (Day A), subjects started with a standardized breakfast. After this two questionnaires had to be filled out: Hamilton depression scale (HAMD) [
EEG data from the first recording session before intake of the capsules are given as ab-
solute numbers (µV2). For explorative statistical evaluation the nonparametric Wilcoxon test was used. For mathematical differentiation of the different mental loads the linear discriminant analysis according to Fischer was used. Results from the first three discriminant functions were projected into space (X, Y and Z coordinates), whereas results from the fourth to sixth discriminant functions were coded into red, green and blue color, respectively, followed by an additive color mixture (so-called RGB-mode). In order to document statistically the different electric reaction of the brain to various cognitive and emotional loads, data from each part of the presentation were divided by the data obtained during recording of a relaxed state with eyes open (1 minute) at the beginning. Comparison of Calmvalera Hevert tablets versus placebo was accomplished by evaluation of the second recording of the day 90 minutes after intake. Data from the first recording (baseline) were set to 100% and electrophysiological changes produced by placebo or Calmvalera Hevert tablets are depicted as %-changes thereof. Sample size was defined according to several earlier studies performed under identical conditions.
The study was conducted according to the protocol after approval by the BfArM (Bonn, Germany) and Ethikkommission (Landesärztekammer Frankfurt, Germany) (PP_5014 _HEVERT_FINAL V1.0_23042015) and “Amendment 1 for PP_5014_HEVERT_FIN AL V1.0 _23042015”.
Twenty-four subjects were recruited for this study on the base of filling out a questionnaire dealing with examination anxiety. Concomitant presentation of a series of mental and emotional challenges during recording of the EEG was performed before and 90 minutes after intake of 6 Calmvalera Hevert tablets or placebo. The absolute starting values of spectral power in the six frequency ranges (delta to beta2) are given in
In order to relate the result from the anxiety questionnaire “HAMA” with EEG parameters a correlation was searched based on the first recordings before administration of the drug. The result indicates that absolute spectral alpha power from all 24 subjects during the recording condition “eyes open” in a relaxed state before drug administration correlated with the score values of the questionnaire.
Next step in the analysis was to find out if the different cognitive and visually presented
Absolute Spectral Power during relaxation (eyes open) 0 h before acute intake at day A | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Delta | Theta | Alpha 1 | Alpha 2 | Beta 1 | Beta 2 | |||||||
Subjects | n = 12 | n = 12 | n = 12 | n = 12 | n = 12 | n = 12 | n = 12 | n = 12 | n = 12 | n = 12 | n = 12 | n = 12 |
Electrode | Placebo | Verum | Placebo | Verum | Placebo | Verum | Placebo | Verum | Placebo | Verum | Placebo | Verum |
Cz | 1.21 | 1.21 | 0.77 | 0.85 | 0.34 | 0.62 | 0.51 | 0.47 | 0.38 | 0.42 | 0.57 | 0.59 |
Fz | 2.12 | 2.55 | 1.30 | 1.70 | 0.77 | 1.17 | 1.13 | 0.71 | 0.62 | 0.61 | 0.75 | 0.84 |
F3 | 1.78 | 1.24 | 1.24 | 0.86 | 0.71 | 0.60 | 0.85 | 0.61 | 0.93 | 0.57 | 1.32 | 0.95 |
C3 | 1.10 | 0.76 | 0.77 | 0.55 | 0.53 | 0.48 | 0.49 | 0.52 | 0.65 | 0.76 | 1.39 | 1.00 |
P3 | 0.72 | 0.59 | 0.47 | 0.39 | 0.47 | 0.42 | 0.44 | 0.43 | 0.56 | 0.41 | 0.62 | 0.48 |
Pz | 0.95 | 0.96 | 0.71 | 0.71 | 0.48 | 0.54 | 0.50 | 0.51 | 0.63 | 0.64 | 0.69 | 0.70 |
P4 | 0.80 | 0.75 | 0.54 | 0.50 | 0.44 | 0.51 | 0.52 | 0.60 | 0.50 | 0.54 | 0.58 | 0.64 |
C4 | 0.97 | 0.88 | 0.72 | 0.71 | 0.49 | 0.64 | 0.55 | 0.72 | 0.55 | 0.75 | 1.06 | 0.90 |
F4 | 1.80 | 1.47 | 1.20 | 1.09 | 0.59 | 0.79 | 0.89 | 0.59 | 0.67 | 0.60 | 0.80 | 1.02 |
F7 | 5.67 | 5.45 | 3.29 | 2.95 | 1.48 | 1.60 | 1.92 | 1.22 | 1.56 | 1.31 | 3.32 | 2.39 |
T3 | 3.26 | 2.50 | 1.92 | 1.75 | 0.95 | 1.22 | 1.35 | 0.91 | 1.95 | 1.44 | 3.85 | 2.48 |
T5 | 1.75 | 1.89 | 1.21 | 1.48 | 1.00 | 1.40 | 1.15 | 1.39 | 1.78 | 1.47 | 1.54 | 1.48 |
O1 | 1.93 | 1.66 | 1.28 | 1.05 | 0.64 | 0.72 | 0.79 | 0.65 | 1.05 | 0.84 | 2.19 | 1.38 |
O2 | 1.88 | 1.58 | 1.26 | 0.99 | 1.04 | 0.83 | 0.89 | 0.91 | 0.94 | 0.86 | 1.33 | 1.40 |
T6 | 2.46 | 2.00 | 1.27 | 1.41 | 1.08 | 1.37 | 0.93 | 1.47 | 1.87 | 1.46 | 1.82 | 1.84 |
T4 | 2.25 | 2.64 | 1.38 | 1.42 | 1.09 | 1.19 | 1.23 | 0.97 | 1.84 | 1.35 | 3.27 | 2.38 |
F8 | 5.56 | 5.46 | 2.68 | 2.54 | 1.37 | 1.50 | 1.69 | 1.10 | 1.51 | 1.35 | 2.65 | 2.47 |
Med | 1.71 | 1.57 | 1.22 | 0.97 | 0.80 | 0.77 | 0.81 | 0.67 | 0.93 | 0.79 | 1.32 | 1.25 |
emotional challenges lead to consistent changes of spectral power. For this purpose, data from each challenge were averaged over the presentation time in order to follow each of the brain regions with respect to the pattern of spectral power changes with respect to each frequency. In order to evaluate challenge specific changes of spectral power each challenge was calculated against the “eyes open” condition in order to eliminate unspecific responses. As expected, highly statistically significant increases of spectral power in the delta, theta and beta range were observed during all challenges. An overview on the statistical significance of the regional distribution of spectral power enhancement in comparison to the recording condition “eyes open” is documented in
There is wide believe that the two brain hemispheres can function independently from each other. We therefore have analyzed the frequency changes in the presence of all challenges for each hemisphere in separate. The result is documented in
First impressions of the effectiveness of Calmvalera Hevert tablets are obtained during single scenes of the presented challenges like emotional images (example:
Electrodes [µV2] F3,7 T3,5 P3 C3 O1 (n = 24) | Delta | Theta | Alpha 1 | Alpha 2 | Beta 1 | Beta 2 |
---|---|---|---|---|---|---|
Eyes Open | 1.78 | 1.17 | 0.82 | 0.70 | 0.98 | 1.49 |
Fix Cross | 1.92 | 1.36 | 0.88 | 0.82 | 1.04 | 1.61 |
0.064 | ||||||
Emotional Pictures | 2.14 | 1.41 | 0.88 | 0.84 | 1.11 | 2.15 |
0.007 | 0.064 | 0.064 | 0.023 | |||
Exam Anxiety | 1.90 | 1.38 | 0.95 | 0.76 | 1.13 | 2.10 |
0.007 | 0.064 | 0.007 | 0.023 | |||
Dentist Pain | 2.00 | 1.20 | 0.82 | 0.85 | 1.07 | 1.90 |
0.007 | 0.064 | 0.023 | ||||
Horror-OP | 1.88 | 1.27 | 0.91 | 0.80 | 1.20 | 1.83 |
0.002 | 0.007 | |||||
Horror-Video | 2.14 | 1.42 | 1.06 | 0.91 | 1.30 | 2.10 |
0.002 | 0.023 | 0.064 | 0.0003 | |||
Picture Comparison | 2.28 | 1.53 | 1.02 | 0.77 | 1.06 | 1.89 |
0.0003 | 0.007 | 0.064 | ||||
Stroop-Test | 2.49 | 1.57 | 0.95 | 0.78 | 1.19 | 2.35 |
0.000003 | 0.0003 | 0.007 | 0.023 | |||
Memory-Test | 2.35 | 1.48 | 0.93 | 0.79 | 1.05 | 2.13 |
0.002 | ||||||
CPT-Test | 2.36 | 1.57 | 0.96 | 0.70 | 1.02 | 2.33 |
0.0003 | 0.002 | 0.002 | ||||
Brain Teaser | 2.36 | 1.42 | 0.91 | 0.79 | 1.10 | 2.26 |
0.00004 | 0.002 | 0.064 | 0.007 |
mented before and after intake of the drug. The spectral power of all regions was looked at in terms of possible changes. A first impression was that alpha1 as well as alpha2 spectral power had increased in regions like the temporal lobe (yellow bars in
Quantitative analysis of frequency changes induced by Calmvalera Hevert tablets with respect to different brain regions revealed a statistically significant increase of apha1
Electrodes [µV2] F4,8 T4,6 P4 C4 O2 (n = 24) | Delta | Theta | Alpha 1 | Alpha 2 | Beta 1 | Beta 2 |
---|---|---|---|---|---|---|
Eyes Open | 1.66 | 1.17 | 0.88 | 0.87 | 0.97 | 1.25 |
Fix Cross | 1.94 | 1.38 | 0.91 | 0.89 | 1.02 | 1.39 |
0.002 | ||||||
Emotional Pictures | 2.20 | 1.39 | 1.07 | 0.95 | 1.13 | 1.89 |
0.0003 | 0.023 | 0.023 | 0.002 | |||
Exam Anxiety | 2.23 | 1.49 | 1.03 | 0.90 | 1.18 | 1.70 |
0.002 | 0.023 | 0.002 | 0.007 | |||
Dentist Pain | 2.22 | 1.27 | 0.91 | 0.76 | 1.09 | 1.71 |
0.002 | 0.064 | |||||
Horror-OP | 2.09 | 1.28 | 1.00 | 0.84 | 1.17 | 1.71 |
0.023 | 0.023 | |||||
Horror-Video | 2.24 | 1.51 | 1.16 | 0.93 | 1.34 | 1.54 |
0.0003 | 0.002 | 0.00004 | 0.023 | |||
Picture Comparison | 2.79 | 1.69 | 1.03 | 0.82 | 1.02 | 1.90 |
0.0003 | 0.002 | 0.007 | ||||
Stroop-Test | 2.37 | 1.51 | 0.87 | 0.83 | 1.27 | 1.91 |
0.000003 | 0.002 | 0.007 | 0.00004 | |||
Memory-Test | 2.36 | 1.47 | 0.97 | 0.90 | 1.07 | 1.59 |
0.002 | 0.064 | 0.023 | ||||
CPT-Test | 2.59 | 1.61 | 0.97 | 0.79 | 1.16 | 2.15 |
0.00004 | 0.0003 | 0.002 | ||||
Brain Teaser | 2.42 | 1.51 | 0.96 | 0.85 | 1.27 | 2.21 |
0.0003 | 0.002 | 0.064 | 0.064 | 0.002 |
and alpha2 spectral power at electrode positions F3, C3, P3, T3 and O1 already under the recording condition “eyes open” as depicted in
When subjects were concentrating their attention on a fixation cross for one minute again alpha1 and alpha2 spectral power increases emerged nearly at the same electrode positions plus at F4 and F8 on the right hemisphere in a significant manner in comparison to placebo. An overview is given in
A very similar pattern was observed when watching the video “at the dentist”. Highest increases of alpha spectral power appeared at electrode position C3, followed by F3 and O1. Under this recording condition also Pz and T6 showed very slight, but statistically significant increases as documented in
Analysis of the spectral power changes during watching the video dealing with an emergency surgery in the bush (Horror-OP) again revealed largest increases of alpha2 power at electrode positions C3 and O1. Minor but still significant increases were seen at C4, O2 and T6. An overview on changes with respect to all brain areas is given in
During performance of a cognitive task like the “Picture Comparison” again electrode positions C3 and O1 showed high statistically significant increases of alpha power. In addition, some increase of beta power emerged at electrode positions C3, T3 and O1. Data are documented in
observed in frontal parts of the brain at interpolated regions indicated by predominating yellow and/or green color (more in the left hemisphere).
Since right and left hemisphere reacted in a somewhat quantitatively different way to several challenges, they were analyzed separately with respect to an action of Calmvalera Hevert tablets in comparison to placebo. Regarding spectral delta and theta spectral activity virtually no effects were seen except for a tiny increase of theta power when watching emergency surgery (Horror-OP). Strongest statistically significant changes were observed in the alpha frequencies during several challenges as depicted in
nificant increases of beta1 power and one result in beta2 power. Statistically significant spectral changes within the right hemisphere were only observed in the alpha1 range during watching the fix cross (p < 0.1), in the alpha2 range during watching the fix cross (p < 0.05) and the horror video (p < 0.05). Finally, beta1 spectral power had increased again during looking at the fix cross (p < 0.1).
Finally, all 102 parameters (17 electrode positions × 6 frequency ranges) were fed into a linear discriminant analysis for comparison with other drugs. As documented in
after intake. Interestingly, another homeopathic drug (Neurexan®) and a plant derived preparation (Neuravena®), both prescribed for the same indication as Calmvalera Hevert tablets, are projected into close vicinity of Calmvalera Hevert tablets (verum in
Analysis of the performance of the psychometric tests did not reveal an influence of Calmvalera Hevert tablets when comparing to baseline values or after intake of placebo or verum as documented in
The present investigation contained an entirely new approach with respect to drug studies by using a combination of fast dynamic EEG analysis named “Neurocode-Trac- king” in combination with Eye-Tracking [
Interpretation of spectral EEG changes depends on the recording conditions. For example, general increases of delta activity during relaxation indicate sleepiness and usually are observed during sleep [
Increases of alpha activity have been related to relaxation and calmness in the past as reported in the literature [
Comparing now the electric brain patterns before and 90 minutes after intake of six tablets of Calmvalera Hevert there was no influence on spectral delta, theta or beta ac tivity, in general. Calmvalera Hevert did not disturb psychometric performance. However, a statistical significant increase of alpha1 and alpha2 activity was observed in the presence of Calmvalera Hevert during several of the challenges, especially within the left hemisphere. Prevalence of alpha activity is regarded as a safe indicator of higher relaxation and less anxiety as mentioned above. This means that the brain is protected by a disconnection of the electrical circuits between these brain areas. Thus, increases of alpha power induced by Calmvalera Hevert tablets speak in favor of a calming and protective effect and provides objective proof of the action against nervousness and stress Interpretation of such biological surrogate parameters has been supported and reported also by others [
Performance of Picture Comparison | |||
---|---|---|---|
Placebo | Verum | ||
0 h | Mean | 64.79 | 65.63 |
SD | 15.28 | 12.67 | |
SEM | 4.41 | 3.48 | |
1.5 h | Mean | 73.96 | 78.13 |
SD | 18.24 | 9.42 | |
SEM | 5.21 | 2.72 | |
Performance of Stroop-Test | |||
Placebo | Verum | ||
0 h | Mean | 100.00 | 100.00 |
SD | 0.00 | 0.00 | |
SEM | 0.00 | 0.00 | |
1.5 h | Mean | 100.00 | 100.00 |
SD | 0.00 | 0.00 | |
SEM | 0.00 | 0.00 | |
Performance of Memory-Test | |||
Placebo | Verum | ||
0 h | Mean | 87.83 | 93.75 |
SD | 12.76 | 1.54 | |
SEM | 3.68 | 4.49 | |
1.5 h | Mean | 89.58 | 97.92 |
SD | 16.71 | 7.22 | |
SEM | 4.83 | 2.08 | |
Performance of Calculation (CPT) | |||
Placebo | Verum | ||
0 h | Mean | 52.08 | 27.08 |
SD | 31.00 | 22.51 | |
SEM | 8.95 | 6.50 | |
1.5 h | Mean | 62.83 | 37.50 |
SD | 33.02 | 34.54 | |
SEM | 9.53 | 9.97 | |
Performance of Brain Teaser | |||
Placebo | Verum | ||
0 h | Mean | 77.50 | 72.50 |
SD | 9.65 | 16.58 | |
SEM | 2.79 | 4.79 | |
1.5 h | Mean | 86.67 | 83.33 |
SD | 10.73 | 13.03 | |
SEM | 3.10 | 3.76 |
herbal preparations. Projection of the EEG data of Calmvalera Hevert tablets into the close vicinity of Neurexan® (a homeopathic drug with proven relaxing properties) and Neuravena® (a plant-derived drug marketed for its relaxing property) point to a similar calming action.
A limitation of the study might be seen in the fact that results from the psychometric testing only revealed a positive tendency in the presence of Calmvalera tablets in comparison to placebo. Possibly, statistical significances would have been obtained by including higher numbers of subjects. Due to the low triturations (D2 to D8) of the ingredients of Calmvalera tablets, their efficacy points to the content of highly active molecules in one or more of the single ingredients. Evidence for this hypothesis stems from the preclinical in vivo and in vitro pharmacological characterization of other low homeopathic triturations like for example obtained from Gelsemium and Veratrum [
Using the new clinical design “EnkephaloVision”, experiments provide evidence, that the homeopathic Calmvalera Hevert tablets are obviously able to change the electric activity of the brain in a statistically significant manner in comparison to placebo. Ninety minutes after intake of 6 tablets (daily dosage) increases of spectral alpha power were observed during relaxation and most of audiovisual challenges in comparison to baseline. Since increases of alpha power are related to higher calmness, efficacy of the homeopathic Calmvalera Hevert tablets is shown by a biological surrogate parameter for relaxation. Comparison to other drugs using discriminant analysis shows, that present data obtained for Calmvalera tablets are projected into the vicinity of other plant-deri- ved calming preparations. Efficacy of Calmvalera tablets point to highly active molecules contained in low triturations (D2 - D8) of this preparation.
Mrs. Ingrid K. Keplinger-Dimpfel is thanked for performance of the logistics of the study and quality control. We greatly appreciate the experimental work as well as the data documentation performed by Mrs. Leonie Schombert.
Dimpfel, W., Tau- send, S., Suliman, S. and Dipah, G.N.C. (2016) Psychophysiological Effectiveness of Calmvalera Hevert Tablets as Measured by EnkephaloVision in Anxious Subjects during Audio-Visual Cognitive and Emotional Chal- lenges: A Double-Blind, Randomized, Placebo-Controlled, 2-Armed, Phase IV Study in Parallel Design. Journal of Behavioral and Brain Science, 6, 404-431. http://dx.doi.org/10.4236/jbbs.2016.610039