This experiment utilized a dual-blind, randomized controlled trial design, which is difficult to perform in clinical OMT studies. Osteopathic manipulative treatment is notoriously difficult to blind in controlled studies.
35,36 The novel approach to subject blinding that we chose to use in our study (ie, dual-blinding) required that we use a calculated deception protocol. In this protocol, we described our two-arm study to subjects as a four-arm study. We found this approach to be somewhat effective, as reported.
As noted, the standard methodology for use in randomized controlled trials is termed “double blinding” in the majority of publications. However, we feel that the most appropriate and accurate terminology when investigating the clinical effectiveness of OMT and certain other treatment modalities (eg, surgery, psychotherapy, acupuncture, and chiropractic) is better described as “dual-blind” to reflect the inability of researchers and clinical investigators to blind practitioners and caregivers working in these modalities.
37
Blinding subjects in the control intervention (sham BOCF) group was more effective than blinding subjects in the OMT group. Sham manipulative treatment, in this case sham BOCF, may be intrinsically easier to blind, because the sham BOCF practitioner applies a very light touch and follows the subject's inherent rhythms (eg, respiratory excursions), so no movement in the practitioner may be perceived by the subject.
19 Thus, sham BOCF can be quite plausible.
Control interventions must be plausible to the subject yet remain clinically ineffective (ie, carry little or no therapeutic effect). Sham manipulative treatment is notoriously difficult to render ineffectively because even the slight application of human touch and attention may evoke physiologic responses in subjects.
32,35
Rather than conduct an uncontrolled study to maximize the physiologic effects of OMT, we chose to conduct a controlled study with sham manipulative treatment—with the known pitfall of potentially diminishing the differences between OMT and sham manipulative treatment. We chose this option as preferable to the known pitfalls of conducting an uncontrolled study, which is vulnerable to detractors as it is not considered evidence-based medicine.
Laboratory personnel who performed the DRS evaluations and the endocannabinoid measurements were fully blinded. As noted, blinding practitioners who delivered OMT and the sham manipulative treatment protocols was not possible.
Osteopathic manipulative treatment elicited changes in subjects' responses to the DRS questionnaire, especially in cannabimimetic descriptors previously linked with THC administration, such as
high, light-headed, hungry, and
stoned.
16,33,34 These psychotropic alterations may explain why OMT, like THC, has been used to treat depression,
38 to improve appetite,
39 and to treat anxiety and provide an improved sense of health and well-being.
18,19
Control subjects recorded a mix of DRS responses, with a decrease in score for the cannabimimetic descriptor high, and an increase in score for the noncannabimimetic descriptors rested and relaxed. The latter descriptors seemed to reflect effects of the control intervention itself (ie, lying comfortably on a treatment table in a warm, quiet room).
Although the serum endocannabinoid assays fell short of statistical significance (α<.05) because of large variances, data trends suggested that OMT selectively increased AEA levels and decreased OEA levels, rather than influence a general elevation of circulating endocannabinoid concentrations. Serum AEA levels more than doubled in post-OMT subjects, and OEA levels decreased 27% in post-OMT subjects.
Aspects of the experimental design may have biased toward a beta error: a small study population was used and there was insufficient homogenization of subjects (ie, too wide an age range and use of both male and female subjects).
Additionally, the fact that we obtained serum samples from 8:30 am to 7:30 pm may have been a confounding variable in light of recently discovered circadian fluctuations in AEA and 2-AG.
40 Interestingly, a previous OMT study based on the CCP model showed greatest physiologic changes in subjects who underwent OMT during the late afternoon.
30 Anandamide has a short half-life in the serum, so small differences in collection and processing of samples could result in large variations between samples.
The effects from AEA administration have not been measured in humans. In rodent studies, administration of AEA
13 or metabolically stable AEA analogs
41,42 produced subtly different effects than THC.
13 If post-OMT changes in DRS scores are assumed to be the result of elevations in AEA, then AEA's effects on subjects' DRS scores were different than THC's effects on subjects' DRS scores, as reported in previous DRS studies.
16,33,34 Increased AEA levels correlated best with an increase in subjects' DRS scores in the
rational and
cold descriptors, and with decreased subject-reported scores among the descriptors
paranoid, bad, and
warm. Increased subject DRS scores in
cold and decreased subject scores for
warm were similar to physiologic results in rodent studies, where AEA produced hypothermia.
12,43
The increase in subject scores for
rational and the decrease in subject scores for
paranoid were intriguing because increased AEA levels have correlated with decreased psychotic symptoms in schizophrenic patients.
44 Osteopathic manipulative treatment has long been noted to show improvements in patients with schizophrenia,
45 and an increase in AEA levels could conceivably provide a therapeutic mechanism for this patient population. Osteopathic manipulative treatment decreased serum OEA levels, and this result correlated with decreased feelings of the descriptor
rational. Thus, the effects of OMT on AEA and OEA may produce additive effects to subjects in the
rational category. Paradoxically, decreases in OEA correlated with increases in incidence of
nausea as well as
hunger, although the correlation with
nausea was twice as strong as that with
hunger.
As OMT has long been noted to improve appetite,
17 a decrease in OEA could conceivably provide a mechanism for decreasing the sense of satiety.
11
The common mechanism by which OMT maintained health, according to Dr Still, was improved cardiovascular circulation, “The rule of the artery must be absolute, universal, and unobstructed, or disease will be the result. I proclaimed that all nerves depended wholly on the arterial system for their qualities....”
2 Salamon et al
46 lend additional support to Still's principle by suggesting that OMT augments blood flow and vasodilatation by stimulating the release of nitric oxide. Anandamide causes release of nitric oxide from vascular endothelial cells,
47 thus OMT's release of AEA links OMT to Salamon et al's nitric oxide hypothesis.
We plan to extend our investigations of AEA with nitric oxide, using a larger, more homogenized subject population. Measuring AEA in cerebrospinal fluid, which is more sensitive than measuring serum levels,
44 has been considered. Perhaps OMT's effects on endocannabinoids are amplified in symptomatic subjects or correlate with somatic dysfunctions documented in specific body regions. Testing different OM techniques would be interesting (eg, indirect myofascial release versus direct high-velocity, low-amplitude thrust), and perhaps more than one treatment with OMT is needed to generate significant differences.