Acute electroencephalographic effects from repeated olfactory administration of homeopathic remedies in individuals with self-reported chemical sensitivity.

BACKGROUND: Homeopaths report that individuals with heightened self-reported environmental chemical intolerance (CI) exhibit increased reactivity to homeopathic remedies. Persons high in CI sensitize their electroencephalographic (EEG) alpha responses to repeated intermittent chemical exposures. PRIMARY STUDY OBJECTIVE: The present feasibility study explored interactions between CI and one of two specific homeopathic remedies over time (Sulphur or Pulsatilla nigricans [Pulsatilla]). DESIGN: This study used a two-arm, double-blind, placebo-controlled repeated measures design. Intervention Participants underwent a series of three once-weekly sessions during which they repeatedly sniffed one remedy (6c, 12c, 30c; one potency per week) matched to their Homeopathic Constitutional Type Questionnaire (CTQ) type and two solvent controls (distilled water and a waterethanol [95%] solution). Within sessions, remedies and control solvents were administered via 2-second sniffs (eight sniffs of each of four different succussion levels per potency, in randomized order). PARTICIPANTS: Participants were college student volunteers (N = 96, ages 18-30, both sexes), screened for good health and relatively elevated Sulphur or Pulsatilla symptom pattern scores on the Homeopathic Constitutional Type Questionnaire (CTQ). Participants also completed a validated trait CI scale. PRIMARY OUTCOME MEASURES: Average 19-lead relative EEG alpha power (alpha 1 8-10 Hz; alpha 2 10-12 Hz). RESULTS: Trait CI interacted significantly with time factors for each remedy (both over visit weeks and over sniff cycles during sessions). The patterns were nonlinear and differed between the two remedies. Individuals high in CI showed greater variability over time in remedy EEG alpha effects than did those low in CI. CONCLUSION: The data suggest that CI, with an underlying susceptibility to time-dependent sensitization and oscillatory responses, could contribute to nonlinear dose-response patterns and inconsistent reproducibility of homeopathic clinical care and research.

Nonlinear dynamical systems effects of homeopathic remedies on multiscale entropy and correlation dimension of slow wave sleep EEG in young adults with histories of coffee-induced insomnia.

BACKGROUND: Investigators of homeopathy have proposed that nonlinear dynamical systems (NDS) and complex systems science offer conceptual and analytic tools for evaluating homeopathic remedy effects. Previous animal studies demonstrate that homeopathic medicines alter delta electroencephalographic (EEG) slow wave sleep. The present study extended findings of remedy-related sleep stage alterations in human subjects by testing the feasibility of using two different NDS analytic approaches to assess remedy effects on human slow wave sleep EEG. METHODS: Subjects (N=54) were young adult male and female college students with a history of coffee-related insomnia who participated in a larger 4-week study of the polysomnographic effects of homeopathic medicines on home-based all-night sleep recordings. Subjects took one bedtime dose of a homeopathic remedy (Coffea cruda or Nux vomica 30c). We computed multiscale entropy (MSE) and the correlation dimension (Mekler-D2) for stages 3 and 4 slow wave sleep EEG sampled in artifact-free 2-min segments during the first two rapid-eye-movement (REM) cycles for remedy and post-remedy nights, controlling for placebo and post-placebo night effects. RESULTS: MSE results indicate significant, remedy-specific directional effects, especially later in the night (REM cycle 2) (CC: remedy night increases and post-remedy night decreases in MSE at multiple sites for both stages 3 and 4 in both REM cycles; NV: remedy night decreases and post-remedy night increases, mainly in stage 3 REM cycle 2 MSE). D2 analyses yielded more sporadic and inconsistent findings. CONCLUSIONS: Homeopathic medicines Coffea cruda and Nux vomica in 30c potencies alter short-term nonlinear dynamic parameters of slow wave sleep EEG in healthy young adults. MSE may provide a more sensitive NDS analytic method than D2 for evaluating homeopathic remedy effects on human sleep EEG patterns.

Short-term effects of repeated olfactory administration of homeopathic sulphur or pulsatilla on electroencephalographic alpha power in healthy young adults.

INTRODUCTION: Homeopathic pathogenetic trials usually rely on symptom self report measures. Adding objective biomarkers could enhance detection of subtle initial remedy effects. The present feasibility study examined electroencephalographic (EEG) effects of repeated olfactory administration of two polycrest remedies. METHODS: College student volunteers (ages 18-30, both sexes) from an introductory psychology course were screened for good health and relatively elevated Sulphur or Pulsatilla symptom scores on the Homeopathic Constitutional Type Questionnaire (CTQ). Subjects underwent a series of 3 once-weekly double-blind sessions during which they repeatedly sniffed the remedy matched to their CTQ type and solvent controls. Each remedy was given in a 6c, 12c, and 30c potency, one potency per week, in randomly assigned order. Solvent controls included both plain distilled water and a water-ethanol (95%) solution. All sniff test solutions were further diluted just prior to laboratory sessions (0.5 ml test solution in 150 ml distilled water). Within a session, remedies and control solvents were administered via 2-s sniffs (8 sniffs of each of 4 different succussion levels for the potency in randomized order). Primary outcome variable was relative EEG power (alpha 1 8-10 Hz; alpha 2 10-12 Hz) averaged over 19 electrode sites, including all succussions for a given potency. RESULTS: Mixed-effect models revealed significant main effects for remedy type (Sulphur >Pulsatilla) in both alpha bands, controlling for gender, baseline resting EEG alpha, and solvent control responses. Additional analyses showed significant nonlinear interactions between dilution and time (weekly session) in alpha 2 for both remedies and alpha 1 for Sulphur. CONCLUSION: EEG alpha offers an objective biomarker of remedy effects for future studies and potential method for distinguishing time-dependent effects of specific remedies and remedy potencies from one another.

Clear Tinnitus, middle-ear pressure, and tinnitus relief: a prospective trial.

GOAL: Our goal was to establish the efficacy, in a 12-week period, of Clear Tinnitus for tinnitus relief in patients with tinnitus of the severe, disabling type. HYPOTHESIS: We hypothesized that tinnitus relief with Clear Tinnitus reflects improvement in the sensory component of the tinnitus complaint by controlling the factor of aeration of the middle ears and improving eustachian tube function. METHOD: In a prospective clinical trial of a homeopathic preparation--Clear Tinnitus--we attempted to identify in 15 tinnitus patients (14 male, 1 female; mean age, 47.6 years) its clinical efficacy for establishing tinnitus relief for a 3-month period. We employed a descriptive data analysis method across dimensions of risk to evaluate a base of multidimensional evidence and establish support for our hypothesis. A medical-audiological tinnitus patient protocol completed by each patient identified the clinical type of tinnitus as predominantly cochlear, with a central and middle-ear component bilaterally. We identified fluctuation in middle-ear pressure (MEP) via patients' clinical history, supported by physical examination and established with tympanometry, as a factor influencing the clinical course of the tinnitus in each patient. RESULTS: Eleven of 15 patients completed the study. Seven responders reported tinnitus relief; four did not respond. Descriptive data analysis failed to detect any trends in a change in response with audiometric tests across the hearing spectrum; thus, we could derive no coefficients of hearing change. Evaluation revealed high-frequency tinnitus in 11 patients. The Feldmann masking curve comparison at the start and end of the study showed no significant change in the 11 patients. There was no significant alteration in the minimum masking levels or loudness discomfort levels before and after the study. Tympanometry and MEP measurement indicated a significant difference in MEP with an improvement on average of -58.18 in the right ear and -40.90 in the left ear for the 11 patients. Quantitative electroencephalography analysis revealed a marked difference in the number of significant abnormal recordings between the different frequency bands, with the delta band significantly higher than the theta, alpha, and beta bands for both the overall cohort of patients (n = 11) and those reporting tinnitus relief (n = 7). The tinnitus outcome questionnaires--the tinnitus intensity index, the tinnitus annoyance index, and the tinnitus reaction questionnaire--revealed a significant difference for the patients (7 of 11) obtaining tinnitus relief. Results of the tinnitus stress test, the tinnitus handicap index, and the measurement of depression scale before and after the study were not statistically significant. CONCLUSIONS: Patients who completed the study demonstrated with tympanometry a statistical and clinical significance in MEP improvement or maintenance of MEP (or both). Patients with tinnitus of the severe disabling type selected for this study and responding to Clear Tinnitus reported tinnitus relief accompanied by improvement in or maintenance of MEP of the middle ears. The statistical and clinical significance of Clear Tinnitus for establishing tinnitus relief remains to be established with a larger cohort of tinnitus patients.

Monitoring of anaesthesia in neurophysiological experiments.

Cortical activity can be substantially changed by the type of anaesthetic used, and by its dose level. For easy monitoring of depth of anaesthesia we describe the changes in electroencephalogram and electrocardiogram accompanying changes in depth of anaesthesia in the cat. Anaesthesia was induced by the volatile anaesthetic isoflurane. The high-frequency components (around 30 Hz) in the electroencephalogram disappear in deep anaesthesia. The electrocardiogram also shows substantial changes in contamination due to muscle fasciculations with anaesthesia level. Fasciculations appear as noise in the electrocardiogram. The amplitude of the electrical muscle activity contaminating the ECG can be easily used for the maintainance of a constant level of anaesthesia during a neurophysiological experiment.

Electroencephalographic cordance patterns distinguish exceptional clinical responders with fibromyalgia to individualized homeopathic medicines.

OBJECTIVES: To characterize initial central nervous system responses to olfactory administration of homeopathic remedies as biomarkers for subsequently exceptional, simillimum-like clinical outcomes at a systemic level (i.e., both locally and globally). DESIGN: Double-blinded, randomized, placebo-controlled clinical trial. SETTING: A private homeopathic clinic in Phoenix, AZ, and a university laboratory in Tucson, AZ. PATIENTS: Sixty-two (62) persons with physician-confirmed fibromyalgia (FM) (mean age, 49 years; 94% women) enrolled; 53 completed the 3-month assessment visit. Exceptional responders (n = 6, 23% of active treatment group; none on placebo) were those with improvements in the top one-third for both tender point pain and global health ratings after 3 months. INTERVENTION: Patients took daily oral doses of treatment solution in LM (1/50,000 dilution) potency (active group received individualized remedy; placebo group received plain solvent). Dependent measures: Baseline and 3-month difference scores for initial prefrontal electroencephalographic alpha frequency cordance (EEG-C, a correlate of functional brain activity) during 16 pairs of randomized, double-blinded bottle sniffs (treatment minus control solutions). RESULTS: Exceptional responders versus other patients exhibited significantly more negative initial EEG-C difference scores at prefrontal sites. Right prefrontal cordance findings correlated with subsequently reduced pain (r = 0.85, p = 0.03), better global health (r =-0.73, p = 0.10), and trait absorption (genetically determined ability to focus attention selectively and fully) (r = 0.91, p = 0.012). CONCLUSIONS: These observations suggest prefrontal EEG-C as an early biomarker of individualized homeopathic medicine effects in patients with FM who later exhibit exceptional outcomes. Prefrontal cortex controls executive function, including ability to redirect attention. Interactions between executive function, absorption, and the simillimum remedy could facilitate exceptional responses.

Effects of muscle relaxants on EEG, ABR and EMG in rabbits.

The effects of baclofen and pancuronium bromide on evoked electromyogram (EMG), cortical electroencephalogram (EEG) and auditory brainstem responses (ABR) were studied in pentobarbital anesthetized normal rabbits. Evoked EMG was measured in the gastrocnemius muscle by electrical stimulation of the sciatic nerve. Intravenous injection of baclofen decreased EEG and arterial blood pressure and light reflex, however, it had no significant influence on EMG or ABR at doses of 10 and 20 mg/kg/h. Pancuronium bromide immediately inhibited respiration, decreased EEG and EMG, however, it had no significant influence on arterial blood pressure, ABR, or light reflex, at doses of 0.4 and 1.0 mg/kg/h in anesthetized rabbits. ABR waves were observed until just before cardiac arrest with both of the muscle relaxants. It is suggested that ABR are not influenced by central or peripheral muscle relaxants, or by pentobarbital.

Slow EEG-power spectra correlate with haemodynamic changes during laryngoscopy and intubation following induction with fentanyl or sufentanil.

We studied nociception-associated arousal following laryngoscopy and intubation in patients scheduled for elective open heart surgery, using EEG power spectra and hemodynamics. Either fentanyl (7 micrograms/kg; n = 30) or sufentanil (1 microgram/kg; n = 30) were given in a randomized fashion to induce anesthesia in heavily premedicated patients, followed by pancuronium bromide (100 micrograms/kg). EEG-power spectra (delta, theta, alpha, beta) as well as mean arterial blood pressure (MAP) and heart rate (HF) were measured at the following end-points: before the induction of anesthesia (control), 1 and 10 minutes after laryngoscopy and intubation (L & I). Linear regression analysis was computed to determine which of the EEG power spectra was most sensitive to detect insufficient blockade of nociceptive-related arousal when correlated with haemodynamics. In the fentanyl group the change in HF closely correlated with the decrease of power in the slow delta- and theta-domain (r2 = 0.98 and r2 = 0.89 respectively) of the EEG. The change in MAP also closely correlated with a decrease in the slow delta- and theta-domain (r2 = 0.97 and r2 = 0.99 respectively). There was little correlation in regard to spectral edge frequency (SEF) and HF and MAP changes (r2 = 0.36 and r2 = 0.12 respectively). In the sufentanil group the change in HF correlated closely with an increase of power in the fast alpha and a decrease in the slow theta-domain (r2 = 0.91 and r2 = 0.98 respectively) of the EEG. The changes in MAP closely correlated with an increase in the fast alpha-band a decrease in the slow theta-domain (r2 = 0.98 and r2 = 0.73 respectively). Also there was little correlation of SEF with HF and MAP changes (r2 = 0.09 and r2 = 0.02 respectively). Among the EEG-spectra, reduction of power in the slow delta- and theta-bands are the most sensitive parameters to determine insufficient antinociception of opioids commonly used for the induction in cardiac anesthesia. Increase of power in the alpha-band seems to be closely correlated with cortical reactivation and reduction of hypnosis, while a reduction of power especially in the deltabut more so in the theta-band of the EEG reflects nociception related arousal.

Pancuronium increases the duration of electroencephalogram burst suppression in dogs anesthetized with isoflurane.

Earlier studies have demonstrated both a decrease as well as no effect on halothane MAC after administration of nondepolarizing neuromuscular relaxants. To clarify further the relationship between neuromuscular blocking agents and anesthetic potency, the authors studied the effect of pancuronium on steady-state electroencephalogram (EEG) burst suppression produced by isoflurane in dogs. Anesthesia was induced using isoflurane and oxygen via mask without the administration of other drugs. The trachea was intubated, and isoflurane was administered at a concentration sufficient to produce EEG burst suppression. Thereafter, end-tidal isoflurane concentration, temperature, and end-tidal PCO2 were meticulously maintained at constant values. Dogs in group 1 (n = 6) received pancuronium 0.1 mg.kg-1. The percent of the EEG that was isoelectric increased from 21 +/- 9% (mean +/- SD) to 35 +/- 11% (P less than 0.01). After the return of single-twitch response to train-of-four stimulation, neostigmine 0.05 mg.kg-1 and glycopyrrolate 0.01 mg.kg-1 were administered. This resulted in a reduction in EEG isoelectricity to 19 +/- 8% (P less than 0.01), similar to the value before pancuronium administration. In group 2 dogs (n = 6), the percent isoelectricity of the EEG prior to pancuronium was 25 +/- 10%. After administration of pancuronium 0.02, 0.04, and 0.2 mg.kg-1 sequentially, the percent isoelectricity of the EEG was 29 +/- 11, 37 +/- 15, and 43 +/- 9%, respectively. This represents a dose-related increase in isoelectricity for the 0.04- and 0.2-mg.kg-1 doses (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Comparative effect of Coffea cruda potencies on rats.

The effects of Coffea cruda 30 and 200c and caffeine on the sleep pattern of rats were investigated. Treatments were administered orally at the beginning of the sleeping period. EEG from the parietal region was recorded. Delta (0.5-2.5 Hz) and slow (< 1 Hz) waves are two of the major oscillation types that characterize neocortical electrical activity. The spectral power in these bands and the power ratio between 0.32-0.48 Hz and the delta band (slow/delta power ratio) for control and treatment groups were analyzed blind. Power in the delta band was significantly higher than baseline for Coffea 30c and caffeine (15.5mg/kg). An increase in the slow/delta power ratio between control and treatment was detected for Coffea cruda 30 and 200c. Coffea 30c and caffeine have similar effects on sleep pattern, enhancing delta power; Coffea cruda 200c appears to affect only the synchronization.

An evaluation of Coffea cruda effect on rats.

To investigate the effect of the homeopathic medicine Coffea cruda on sleep pattern, it was orally administered to rats at the beginning of their waking period. EEG from the parietal region was recorded during their next sleep cycle. Applying an FFT algorithm, spectral in the delta band, 0.5-2.5 Hz, was chosen as a marker parameter, evaluated for control and verum groups using a double-blind protocol. Power in the verum group was statistically higher than baseline value, it was not statistically different in the control group. The results indicate that an enhancement in EEG slow delta activity is associated with Coffea cruda.

Peripheral acting muscle relaxants alter the effects of baclofen on the electrocorticograms in the rat.

The effects of intraperitoneally administered baclofen on behavior and electrocorticograms (ECoG) were studied in freely moving and paralyzed rats. In the freely moving rats, 10 mg/kg of baclofen suppressed ECoGs with behavioral sedation, and 20 mg/kg caused whole body twitching accompanied with spike discharges in low voltage slow waves background. In the freely moving rats, baclofen acted as depressant in low dose and convulsant in high dose. In the paralyzed rat, 10 mg/kg of baclofen first suppressed ECoGs. Though fast waves components recovered with slow waves background in the ECoGs of rats paralyzed with gallamine (50 mg/kg) 3 hours after the baclofen injection, fast waves activities were not observed in the ECoG of rats paralyzed with succinylcholine (50 mg/kg), d-tubocurarine (3 mg/kg) or pancuronium (1 mg/kg). Under paralysis with d-tubocurarine, baclofen suppressed ECoG first, and then spike discharges started 90 min after the injection. These results suggest that the effects of baclofen on ECoG were different depending on the muscle relaxant used.

A kinetic approach to caffeine--Coffea cruda interaction.

The biological effect of Coffea cruda 30c was investigated in rats pre and post treated with caffeine. The experimental subjects were male Wistar rats. Caffeine was administered intraperitoneally at the beginning of a sleep period. Coffea cruda 30c (0.1 ml) was administered orally, a contemporaneous control group was tested. The Electroencephalogram (EEG) was recorded in the parietal region during the following sleep cycle. The effect was evaluated by three EEG parameters: the spectral power in delta (0.5-2.5 Hz) and slow 0.32-0.48 Hz bands and the slow/delta power ratio. These markers were analyzed vs time for control and homeopathic groups, blind. In the pretreated set, a similar pattern was identified for control and verum groups up to the 4th hour. From the 5th hour on, power in the delta band was statistically higher in the verum. Spectral power in the slow band and power ratio for the verum group was smaller than the control group from the 6th hour on. In the post-treated set, two verum sub-groups were identified: Post v-A: did not exhibit significant differences from control; Post v-B: displayed an opposite tendency than pre-treatment verum. We conclude that Coffea cruda 30c modifies sleep pattern increasing sleep intensity with pre-treatment. In a subset of the post-treated animals Coffea 30c appeared to reinforce the effects of caffeine.