The present data support the homeopathic theory-based prediction of a differential remedy response when individuals are given their respective constitutional remedy. In this study Sulphur CTQ “types” exhibited greater relative EEG power remedy effects for both alpha 1 and alpha 2 than their Pulsatilla CTQ counterparts. The interaction between dilution and visit week was also more evident in the Sulphur CTQ types. Whether or not such findings would be replicable with subjects identified using individualized homeopathic case taking interviews rather than the CTQ is a valid, but as yet unanswered, question. These data in human subjects extend findings from controlled animal studies that previously demonstrated the short-term ability of single or combination homeopathic remedies to alter waking EEG alpha and delta29
and sleeping EEG delta wave activity.9,30
Although it would be preferable to have comparable proportions of men and women in subsequent studies with larger samples, the current analyses were controlled for gender differences between groups.
Future studies should also examine other designs, such as testing for differential effects of giving the constitutional remedy versus non-constitutional remedy to persons of a specific constitutional type. In a recent study of mood effects on sleep in which it was possible to evaluate the interaction of personality type and remedy received, Brooks et al.7
reported different effects of two remedies (Nux Vomica 30c and Coffea Cruda 30c), based on an interaction between the specific remedy given and the baseline personality type. In the present study, the design did not allow parsing the remedy effects apart from the baseline CTQ type.
The predictions concerning different main effects for dilution level and succussion level were, in general, minimally confirmed in this study. Dilution main effects were found only for Sulphur, with relative alpha 1 EEG power greater for the 6c dilution than either the 12c or 30c dilution. A contrasting trend was also observed in alpha 2, where dilution 12c produced greater effects than did 30c. An oscillatory response was observed for time, with relative alpha 1 EEG power greater at the second visit week than the first or third visit week for Sulphur only. These findings are additional examples of the nonlinear dose-response phenomena previously reported in a variety of living systems with homeopathic remedies.12,31
The effect of succussion level was found for alpha 2 relative EEG power in Pulsatilla only. In this case relative EEG power was significantly lower at 40 succussions than the other succussion levels. Subsequent studies using larger samples and focusing only on different levels of succussion for a single dilution, may clarify whether or not the Pulsatilla finding was a statistical anomaly or a hint of more meaningful succussion-related findings, also nonlinear in nature.
More notably, the minimal main effects for dilution or time were superseded by the significant interaction within subjects between dilution and time (visit week), significant in both bands in Sulphur and in the alpha 2 band in Pulsatilla. No consistent pattern emerged across the two remedies or the alpha frequency bands. The EEG response to a 6c dilution was greater at the second visit than at the first visit for both bands in Sulphur participants; while the reverse was true for the Pulsatilla participants, i.e., the 6c dilution response was greater at the first visit than the second visit. During the first visit week a 30c dilution produced a stronger alpha1 EEG response than 6c dilution, while the 12c dilution produced the strongest EEG response in alpha 2 that same visit week for Sulphur participants. In contrast, the 6c dilution produced a stronger response than the 12c dilution in alpha 2 for the Pulsatilla participants during the first visit week. Similarly, during the third visit week a 12c dilution was associated with a greater alpha 1 EEG response than 30c in Sulphur participants and alpha 2 EEG response for Pulsatilla participants. However, there was no difference in EEG response to dilution level during that same visit week in alpha 1 for the Sulphur participants.
Taken together, the findings suggest that remedy effects on relative EEG alpha power are complex, nonlinear, and dynamical, dependent on the nature of the specific remedy, dilution, and time, including the individual’s recent past history of remedy exposure in previous study week visits. Such data may relate to clinical claims that the same remedy at the same potency may act very differently in the same patient when administered under seemingly similar circumstances on two or more separate occasions over time.32
Articulating relevant hypotheses based on this conceptualization should assist in generating innovative and novel study designs. New study designs will need to accommodate the hypothesis that homeopathic remedies may modulate system dynamics at global and local levels of scale,33
rather than act like pharmaceutical drugs to consistently and linearly suppress local symptoms.18
The complexity of the findings is consistent with convergent models for homeopathic remedy effects that invoke complex adaptive systems and nonlinear dynamical systems (NDS) concepts. NDS may help account for the altered variability and response patterning within the host found in the current study and in previous research summarized above. Such models suggest that different remedies will mobilize changes in the host system not seen with placebos, but that the direction, magnitude, and time pattern of effects will not necessarily be reproducible or consistent over time for subjective or objective measures. Using research methods adapted from the field of complexity science18,33–36
could allow much better characterization of how remedies act in living systems. One example would be computer modeling of evolving systemic global and local changes during homeopathic remedy testing in pathogenetic trials or clinical treatment in patient care.
The findings require several caveats. This study is preliminary and mainly indicates the feasibility of using quantitative EEG as a biomarker for early remedy effects in human subjects participating in pathogenetic types of trials. The study extends findings from this laboratory’s prior investigation of EEG alpha changes during individualized homeopathy treatment in patients with fibromyalgia.6,11
The current data are not definitive in characterizing the nature of the EEG response to remedies.
On the one hand, the present study design may have captured some of the time-dependent and host state-dependent phenomenological processes underlying the variability of results from laboratory to laboratory or study to study. If remedies can set an initial destabilization of system dynamics into motion,34,37
the hypothesized result of remedy administration would be a transient period of less predictable nonlinear dynamical bidirectional fluctuations (oscillations31
), perhaps of greater than “usual” amplitude and irregular frequency. Eventually, without further external perturbation, e.g., from another remedy dose, a living system should restabilize into another dynamical pattern (i.e., an attractor). The nature of the evolving change over time would depend, in part, on sensitivity of the living system to small and subtle differences in initial conditions at the moment of remedy administration, i.e., the “butterfly” effect well-known from chaos theory and research.38,39
In such a model, if the remedy acted therapeutically, the net clinical outcome would be a healthier dynamical state characterized by greater resilience, flexibility, and adaptability to environmental change, i.e., flourishing.34,36
If the remedy did not exert a therapeutic benefit even though it initiated a temporary disturbance in system behavior, i.e., an active but therapeutically poorly-matched remedy for the individual, the outcome would end up manifesting as a return to roughly the same rigid and maladaptive dynamics (attractor) as before the remedy.36
The current data demonstrate, as have many previous studies, that specific verum homeopathic remedies trigger changes in outcome variables different in pattern from those seen with placebo. The paradoxical feature of such effects is their inherent variability and even bidirectionality. These observations would be consistent with NDS phenomena such as bifurcations of system dynamics at critical moments, along with unstable phase transitions in the evolutionary or developmental shift from one relatively stable pattern to a different stable pattern of dynamics.34,37
On the other hand, the study design was a trade off between scientific and practical considerations. The design was admittedly complicated and confounded by potential carryover effects between verum and controls within a given session. However, it permitted evaluation of timing and dilution effects within budgetary constraints, despite losing experimental sensitivity to detecting succussion effects and a thorough examination of possible dilution presentation order effects. These practical limitations precluded adding more arms to the study to parse out more factors in the variable outcomes. However, future research, informed by the preliminary findings of the current investigation, can pursue some of these additional questions.
Also, the primary outcome variable in this study was EEG alpha power. In contrast with typical pathogenetic trials, the current study did not ask participants for ratings of self reported symptoms after each sniff. The reason for this methodological choice was to minimize the otherwise high risk of confounding EEG changes with set shifting, mood, and motor task-related effects of giving symptom or mood ratings 96 times per session. In the future, researchers may be able to use other types of designs that would keep the duration of each session visit to an acceptable length and collect both moment-to-moment subjective and EEG data.40,41
The study examined only 3 weeks of effects during an unusually intensive regimen of olfactory remedy administration per session. Clinically, most chronically ill patients only sniff a remedy once per day, if they take their treatment via olfactory administration. In order to obtain averaged EEG effects, we gave the olfactory sniffs 8 times per experimental condition (where condition = a given dilution at a given succussion level). The methodological choice to use such an approach stemmed from empirical data and experience in earlier studies11,26
indicating that any single remedy exposure may or may not produce effects, but repeated exposures will generate a measurable average effect on a system.
In addition, future studies will need to explore the issue of succussion in greater detail. While the data hint at an isolated effect of 40 succussions for Pulsatilla, the present study cannot provide clarification of an important question, e.g., is there a threshold number of succussions above which effects plateau, with further succussion producing no additional change in the capacity of a remedy to alter the function or health of the host? Anecdotal statements by basic scientists suggest the possibility of a threshold and plateau process, rather than a progressive increase in remedy effects with a greater number of succussions. However, a proper design to assess succussion effects would require a larger sample testing only one dilution prepared with different numbers of succussions and tested on separate occasions and/or within separate arms of a study.
In conclusion, this study opens the door to further research on the nonlinear dynamical effects of homeopathic remedies on human EEG response patterns.42
It raises many questions that merit specific systematic study. Notably, these findings are consistent with the hypothesis that homeopathic remedy effects depend not only on the nature of the remedy, but also on the interaction of remedy with the continuously changing/evolving (dynamical) host system over time.18
Re-focusing research attention away from the remedy per se and over to the interaction of the remedy with the host and to the factor of time may be a key step toward advancing understanding of variability in remedy effects on living systems.43