Placebo studies and ritual theory: a comparative analysis of Navajo, acupuncture and biomedical healing

Using a comparative analysis of Navajo healing ceremonials, acupuncture and biomedical treatment, this essay examines placebo studies and ritual theory as mutually interpenetrating disciplines. Healing rituals create a receptive person susceptible to the influences of authoritative culturally sanctioned 'powers'. The healer provides the sufferer with imaginative, emotional, sensory, moral and aesthetic input derived from the palpable symbols and procedures of the ritual process-in the process fusing the sufferer's idiosyncratic narrative unto a universal cultural mythos. Healing rituals involve a drama of evocation, enactment, embodiment and evaluation in a charged atmosphere of hope and uncertainty. Experimental research into placebo effects demonstrates that routine biomedical pharmacological and procedural interventions contain significant ritual dimensions. This research also suggests that ritual healing not only represents changes in affect, self-awareness and self-appraisal of behavioural capacities, but involves modulations of symptoms through neurobiological mechanisms. Recent scientific investigations into placebo acupuncture suggest several ways that observations from ritual studies can be verified experimentally. Placebo effects are often described as 'non-specific'; the analysis presented here suggests that placebo effects are the 'specific' effects of healing rituals.     

Effectiveness and tolerance of selected Polish antacids in the therapy of duodenal ulcer disease. A placebo- and ranitidine-controlled study

In a randomized, open clinical trial we compared the efficiency of selected Polish antacids Alugastrin, Gastrin and Wikalina with ranitidine and placebo in the healing of duodenal ulcer, pain relief and drug toleration. One hundred and ten outpatients completed the study. The trial showed that antacids and ranitidine had similar rates of duodenal ulcer healing which were significantly better than placebo. After 4 weeks of treatment with Alugastrin, Gastrin, Wikalina and ranitidine the healing rates were 70%, 76%, 71% and 81%, respectively, compared to placebo 44%. Efficiency of antacids in pain relief was similar to placebo and slightly lower than ranitidine. Antacids were well tolerated, except for hypermagnezemia and urine alkalization caused by Gastrin and Wikalina. We conclude that studied antacids are as effective as ranitidine in promoting healing of duodenal ulcer, but because of side effects they are not recommended for maintenance therapy.     

Healing of gastric ulcers after one,two, and three months of ranitidine.

Ranitidine (150 mg twice daily) was compared with placebo in 42 patients with gastric ulcer. The study was conducted as a double-blind trial for one month, followed by an open assessment of one, two, and three months of ranitidine in the patients with persistent ulceration. Thirty-eight patients completed the double-blind trial. Repeat endoscopy confirmed complete healing in 16 of the 21 who had received ranitidine and five of the 17 who had received placebo (p less than 0.01). The remaining 17 patients with persistent ulceration participated in the open assessment. The combined cumulative healing rates of ranitidine at four, eight, and 12 weeks were 73%, 88%, and 97%. There were no adverse effects or unusual reasons for withdrawal from the study (four patients). Ranitidine appears to be a safe and highly effective treatment of gastric ulceration, with about 90% of ulcers healed after eight weeks.     

Are All Placebo Effects Equal? Placebo Pills,Sham Acupuncture,Cue Conditioning and Their Association

Placebo treatments and healing rituals have been used to treat pain throughout history. The present within-subject crossover study examines the variability in individual responses to placebo treatment with verbal suggestion and visual cue conditioning by investigating whether responses to different types of placebo treatment, as well as conditioning responses, correlate with one another. Secondarily, this study also examines whether responses to sham acupuncture correlate with responses to genuine acupuncture. Healthy subjects were recruited to participate in two sequential experiments. Experiment one is a five-session crossover study. In each session, subjects received one of four treatments: placebo pills (described as Tylenol), sham acupuncture, genuine acupuncture, or no treatment rest control condition. Before and after each treatment, paired with a verbal suggestion of positive effect, each subject''s pain threshold, pain tolerance, and pain ratings to calibrated heat pain were measured. At least 14 days after completing experiment one, all subjects were invited to participate in experiment two, during which their analgesic responses to conditioned visual cues were tested. Forty-eight healthy subjects completed experiment one, and 45 completed experiment two. The results showed significantly different effects of genuine acupuncture, placebo pill and rest control on pain threshold. There was no significant association between placebo pills, sham acupuncture and cue conditioning effects, indicating that individuals may respond to unique healing rituals in different ways. This outcome suggests that placebo response may be a complex behavioral phenomenon that has properties that comprise a state, rather than a trait characteristic. This could explain the difficulty of detecting a signature for “placebo responders.” However, a significant association was found between the genuine and sham acupuncture treatments, implying that the non-specific effects of acupuncture may contribute to the analgesic effect observed in genuine acupuncture analgesia.     

Does treatment with cimetidine extended beyond initial healing of duodenal ulcer reduce the subsequent relapse rate?

Cimetidine 1 g daily is often continued for a fixed period beyond the time of healing of duodenal ulcer on the assumption that it might reduce the subsequent relapse rate. To test this, 194 patients whose ulcers had healed after one month of cimetidine 1 g daily were allocated at random to three groups for further treatment with cimetidine 1 g daily for two months (n = 63) or five months (n = 66) or placebo (n = 65). Thereafter all patients received placebo. Endoscopy was done routinely every three months, or earlier if symptoms recurred. During follow-up in the placebo phase, which lasted for up to 25 months, the estimated total proportions of patients in the three groups with symptomatic recurrences of ulcer were 80%, 90%, and 77%, respectively; the corresponding proportions with silent plus symptomatic relapses were 92%, 90%, and 100%. The relapse rates were also similar in all three groups. Statistical analysis showed a significant variation in relapse rate but the differences were regarded as clinically unimportant. These findings show that full-dose cimetidine continued for several months beyond the time of healing of duodenal ulcer dose not decrease the risk of subsequent relapse.     

Body condition, growth rates and diet of Skylark Alauda arvensis nestlings on lowland farmland

Factors affecting the diet, body condition and growth rates of Skylark chicks were assessed to examine their relationship to their agricultural environment during a critical period in the life cycle of this rapidly declining species. Rainfall explained the greatest amount of variation in body condition and growth rates and had a negative effect on both. Body condition indices were a good predictor of the likelihood of future partial brood loss to starvation. Low body condition in grass fields was related to a low diversity in the diet. Chicks fed insect larvae had higher body condition indices than those not fed larvae. Larger broods tended to have higher growth rates than smaller ones, whereas smaller broods tended to have higher body condition indices. Natural brood size reduction through the non-hatching of eggs resulted in higher body condition indices than were found in nests with the same number of chicks where all eggs hatched, this effect being independent of absolute brood size. There was no significant difference between crop types in the distance adult birds flew to forage for food for nestlings and foraging crop destination had no effect on chick development. Differences between crop types in chick diet could be related to the documented effects of pesticides on different prey species. We suggest that recent agricultural changes have affected diet and possibly body condition, but that these effects are unlikely to have been an important factor in recent population declines.     

Habitat quality, nestling diet, and provisioning behaviour in great tits Parus major

Variation in early nutrition is often a strong predictor of offspring condition and fitness. In the case of woodland passerine birds, nestling diet is determined by the spatiotemporal distribution of prey items such as caterpillars during the nestling period, and is usually quantified as differences in provisioning behaviour between habitats. However, the habitat level does not account for variation between individual territories, the level at which competition and selection are assumed to operate. Here we use nestbox cameras and Radio Frequency Identification technology (RFID) to simultaneously assess variation in both nestling diet (components) and provisioning rates (quantity) among a sample (n=22) of different quality great tit Parus major territories selected from a larger breeding population (n=310 fledged broods) in a single year. Caterpillars were by far the most numerous item provisioned to nestlings (mean=75% of prey items), as expected given the known importance of this food source for this species. Broods raised close to an oak tree, or far from the woodland edge, were provisioned the highest proportion of caterpillars. Provisioning rates declined seasonally and there was a weak association between low provisioning rates and caterpillar rich diets. During the first week of the nestling stage, nestling condition was unrelated to the proportion of caterpillars in the diet, provisioning rates and oak proximity. Condition at fledging was slightly improved in broods fed a higher proportion of caterpillars in the diet and in broods raised close to an oak tree. However, in our data early breeding was the only predictor of recruitment success, although power was low for this test. Analyses of long‐term data (41 years) from the same population confirmed a relationship between oak proximity and fledgling mass, but not recruitment success. Our results suggest that territory level environmental variation can affect offspring condition, probably through observed changes in nestling diet, but that such variation does not necessarily produce discernable effects on offspring fitness.     

A Human Model of Small Fiber Neuropathy to Study Wound Healing

The aim of this study was to develop a human model of acute wound healing that isolated the effects of small fiber neuropathy on the healing process. Twenty-five healthy subjects had the transient receptor vanilloid 1 agonist capsaicin and placebo creams topically applied to contralateral areas on the skin of the thigh for 48 hours. Subjects had shallow (1.2 millimeter) and deep (>3 millimeter) punch skin biopsies from each thigh on days 1 and 14. Biopsy wound healing was monitored photographically until closure. Intra-epidermal and sweat-gland nerve fiber densities were measured for each biopsy. Shallow wounds in capsaicin-treated sites healed more slowly than in placebo treated skin with biopsies taken on day 1 (P<0.001) and day 14 (P<0.001). Deep biopsies in the capsaicin and placebo areas healed at similar rates at both time points. Nerve fiber densities were reduced only in capsaicin treated regions (P<0.01). In conclusion, topical application of capsaicin causes a small fiber neuropathy and is associated with a delay in healing of shallow, but not deep wounds. This novel human model may prove valuable in the study of wound healing in patients with neuropathy.     

Randomised,double blind placebo controlled trial of pentoxifylline in the treatment of venous leg ulcers

ObjectiveTo determine whether pentoxifylline 400 mg (Trental 400) taken orally three times daily, in addition to ambulatory compression bandages and dressings, improves the healing rate of pure venous ulcers.DesignRandomised, double blind placebo controlled trial, parallel group study of factorial design, permitting the simultaneous evaluation of alternative pharmaceutical, bandaging, and dressings materials.SettingLeg ulcer clinics of a teaching and a district general hospital in southern Scotland.Participants200 patients with confirmed venous ulcers and in whom other major causal factors were excluded.InterventionsPentoxifylline 400 mg three times daily or placebo.ResultsComplete healing occurred in 65 of the 101 (64%) patients receiving pentoxifylline and 52 of the 99 (53%) patients receiving placebo.ConclusionsThe difference in the healing rates between patients taking pentoxifylline and those taking placebo did not reach statistical significance.

Key messages

• Leg ulcers cost the NHS around £400 million per annum
• 50%-75% of venous leg ulcers can be succesfully treated with dressings and compression bandages but take many months to heal
• A drug that reduced the healing time of venous ulcers would be useful, although no agent has been proved to be effective to date
• Trials with pentoxifylline, a vasoactive drug used in the treatment of peripheral vascular diseases, as an adjunct to the treatment of venous ulcers have been inconclusive
• At the 5% level, pentoxifylline had a non-significant effect on healing rates of pure venous ulcers

     

Migration,ethnicity and psychoses: evidence,models and future directions

There is a large body of research reporting high rates of psychotic disorders among many migrant and minority ethnic groups, particularly in Northern Europe. In the context of increasing migration and consequent cultural diversity in many places worldwide, these findings are a major social and public health concern. In this paper, we take stock of the current state of the art, reviewing evidence on variations in rates of psychoses and putative explanations, including relevant theories and models. We discuss in particular: a) the wide variation in reported rates of psychotic disorders by ethnic group, and b) the evidence implicating social risks to explain this variation, at ecological and individual levels. We go on to set out our proposed socio‐developmental model, that posits greater exposure to systemic social risks over the life course, particularly those involving threat, hostility and violence, to explain high rates of psychoses in some migrant and minority ethnic groups. Based on this analysis, the challenge of addressing this social and public health issue needs to be met at multiple levels, including social policy, community initiatives, and mental health service reform.     

The placebo effect: how the subconscious fits in

The placebo effect is very well known, being replicated in many scientific studies. At the same time, its exact mechanisms still remain unknown. Quite a few hypothetical explanations for the placebo effect have been suggested, including faith, belief, hope, classical conditioning, conscious/subconscious expectation, endorphins, and the meaning response. This article argues that all these explanations may boil down to autosuggestion, in the sense of "communication with the subconscious." An important implication of this is that the placebo effect can in principle be used effectively without the placebo itself, through a direct use of autosuggestion. The benefits of such a strategy are clear: fewer side effects from medications, huge cost savings, no deception of patients, relief of burden on the physician's time, and healing in domains where medication or other therapies are problematic.     

Lessons learned from placebo groups in antidepressant trials

This comprehensive review provides an overview about placebo and nocebo phenomena in antidepressant trials. Improvements in the placebo groups may partly be explained through methodological issues such as natural course of depression and regression to the mean, but also fundamentally reflect investigators' and participants' expectations. A meta-analysis by our group of 96 randomized placebo-controlled trials showed large placebo responses to antidepressant medication. Moderator analyses revealed substantially larger placebo responses in observer ratings compared with self-report. Effect sizes in observer ratings showed strong increase with publication year while this effect was not found for patients' self-ratings. This reflects the strong influence of investigators' expectations. The analysis of 'nocebo effects', e.g. adverse effects in placebo groups of antidepressant trials also confirms the impact of expectations: nocebo symptoms reflected the typical side-effect patterns expected in the drug group, with higher symptoms rates in the placebo groups of tricyclic antidepressant trials compared with placebo groups of trials testing selective serotonin reuptake inhibitors. While the placebo response seems to be similar for women and men, gender differences were found for nocebo rates. In the conclusion, we discuss potential implications for clinical trial designs and argue for interventions aimed at optimizing positive expectations of treatment benefit while minimizing the impact of adverse effects.     

Oral nutritional supplementation accelerates skin wound healing: a randomized, placebo-controlled, double-arm, crossover study

Nutritional therapy is critical for wound healing in people with severe malnutrition or specific metabolic deficiencies. Medical claims from manufacturers of many oral supplements are marketed to surgical patients for decreasing edema, bruising, and discomfort. The effect of supplementing nutrients on soft-tissue wound healing in otherwise normal, healthy adults is an area of clinical importance, but little information is available. Proteolytic enzymes have been reported to moderate the inflammatory cycle and may up-regulate the healing process. The goal of this study was to perform a clinical trial in normal, healthy adults that examined the effects of an oral nutritional supplement (InflammEnz, Enzymes, Inc., Parkville, Mo.) on soft-tissue healing times. Twenty-six normal, healthy volunteers were recruited into a randomized, crossover, placebo-controlled, clinical trial consisting of two phases, each lasting 21 days. In phase I, subjects were subjected to a 3-mm forearm skin biopsy and randomly received a placebo or oral supplement (four capsules per day for 7 days). After a 2-week washout period, a second biopsy was performed to start phase II, with each subject receiving the respective placebo or supplement capsules. Digital photographs were taken during wound healing in both phases and analyzed for wound areas (in square millimeters) and perimeters (in millimeters). Twenty-two subjects completed the clinical trial. On the basis of wound surface areas, 17 subjects had improved wound healing and five subjects did not respond or responded only slightly to the supplement treatment. The mean +/- SD healing time of the subjects responding to supplement-treated wounds was 15 +/- 2.2 days, compared with 18 +/- 2.5 days for the placebo group. The 17 percent acceleration of wound-healing time was significant (p < 0.005). In subjects responding to oral supplements, less redness in the wounds was observed that may have been associated with less inflammation. The authors' results demonstrate that InflammEnz oral supplementation accelerated soft-tissue wound healing in 77 percent of normal, healthy subjects studied. The authors' study validates observations made that this supplement modulates the wound-healing process and suggests that many patients with minor soft-tissue wounds may benefit from treatment.     

An enactive account of placebo effects

Placebos are commonly defined as ineffective treatments. They are treatments that lack a known mechanism linking their properties to the properties of the condition on which treatment aims to intervene. Given this, the fact that placebos can have substantial therapeutic effects looks puzzling. The puzzle, we argue, arises from the relationship placebos present between culturally meaningful entities (such as treatments or therapies), our intentional relationship to the environment (such as implicit or explicit beliefs about a treatment’s healing powers) and bodily effects (placebo responses). How can a mere attitude toward a treatment result in appropriate bodily changes? We argue that an ‘enactive’ conception of cognition accommodates and renders intelligible the phenomenon of placebo effects. Enactivism depicts an organism’s adaptive bodily processes, its intentional directedness, and the meaningful properties of its environment as co-emergent aspects of a single dynamic system. In doing so it provides an account of the interrelations between mind, body and world that demystifies placebo effects.     

A Visual ERP Study of Impulse Inhibition following a Zaleplon-Induced Nap after Sleep Deprivation

The side effects of a zaleplon-induced nap as a countermeasure in the reduction of impulse inhibition function decline following 30 h of sleep deprivation (SD) were examined by event-related brain potentials. Sixteen adult participants performed a Go/NoGo task at five time points: (1) baseline; (2) after 30 h of SD; (3) upon sudden awakening, also called 2 h post-drug; (4) 4 h post-drug; and (5) 6 h post-drug. Behavior results show an increase in both reaction time and false alarm rates after SD and sudden awakening, and a marked decrease at 4 h and 6 h post-drug in zaleplon and placebo conditions. However, no difference was observed between the zaleplon condition and the placebo condition. In event-related potential (ERP) reults compared with results obtained under control conditions, NoGo-P3 latencies significantly increased, whereas the Nogo-P3 amplitude decreased after 30 h of SD and sudden awakening in both the zaleplon condition and the placebo condition. These results indicate that SD attenuates resource allocation and error monitoring for NoGo stimuli. In addition, NoGo-P3 latencies were longer in the zaleplon condition compared with the placebo condition at sudden awakening. Additionally, the NoGo-P3 latencies were shorter in the zaleplon condition than in the placebo condition at 4 h and 6 h post-drug. These results indicate that zaleplon at a dose of 10 mg/day may help subjects achieve a better recovery or maintain better impulse inhibition function, although the side effects of zaleplon last at least 2 h post-drug.     

Introduction to placebo effects in medicine: mechanisms and clinical implications

The field of placebo research has made considerable progress in the last years and it has become a major focus of interest. We know now that the placebo effect is a real neurobiological phenomenon and that the brain's 'inner pharmacy' is a critical determinant for the occurrence of psychobiological and behavioural changes relevant to healing processes and well-being. However, harnessing the advantages of placebo effects in healthcare is still a challenge. The first part of the theme issue summarizes and discusses the various kinds of placebo mechanisms across medical fields, thereby not only focusing on two main explanatory models-expectation and conditioning theory-but also taking into account empathy and social learning, emotion and motivation, spirituality and the healing ritual. The second part of the issue focuses on questions related to transferring knowledge from placebo research into clinical practice and discusses implications for the design and interpretation of clinical trials, for the therapeutic settings in daily patient care, and for future translational placebo research.     

Effects of male group size,parity, and cycle stage on female chimpanzee copulation rates at Ngogo,Kibale National Park,Uganda

Chimpanzees have complex and variable mating strategies, but most copulations occur when females with full sexual swellings are in parties with multiple males and mate with most or all of those males. Daily copulation rates for fully swollen females vary at different times of a female’s cycle, among females, and across communities and populations. Variation in female age, parity, and cycle stage underlie some of this variation, but possible demographic effects on copulation rates have not been systematically investigated. Demographic variation can affect many aspects of behavior and ecology, including the frequency and success of different mating tactics. Analysis of data from the unusually large chimpanzee community at Ngogo produces two results that are consistent with the hypothesis that demographic variation affects female copulation rates. Copulation rates were high compared with those reported from other research sites, where females had fewer potential mates available. Daily copulation rates of fully swollen females were also positively related to the number of males with whom they associated. Ngogo data also re-confirm results from other studies, of both wild and captive populations, showing that female copulation rates increase during periovulatory periods. This is consistent with the hypothesis that sexual swellings and extended receptivity and proceptivity help to protect females against infanticide by helping to ensure they mate with all potential sires. As at some other sites, parous females at Ngogo copulated at higher rates than nulliparous females. Possible effects of demography on sexual behavior should be considered in assessments of differences between chimpanzees and bonobos and of variation across chimpanzee populations.     

The effects of fluoxetine and buspirone on self-injurious and stereotypic behavior in adult male rhesus macaques

The effects of two serotonergic agents--fluoxetine, a serotonin (5-HT) reuptake inhibitor, and buspirone, a 5-HT 1a agonist--on rates of self-injurious and stereotypic behavior were examined in 15 adult male Macaca mulatta. All animals received a placebo for 2 weeks followed by either buspirone or fluoxetine for 12 weeks. Behavior was monitored using a focal sampling technique throughout the study and for 2 weeks post-study. Cerebrospinal fluid (CSF) samples and body weights were obtained pre-study, at the ends of placebo and treatment phases, and post-study. Fluoxetine and buspirone were significantly effective in reducing rates of self-biting during treatment weeks 1 to 8 and self-directed stereotypic behavior during weeks 5 to 12 and post-treatment. No significant effect of either treatment on hair-plucking, stereotypic pacing, saluting, or head tossing was identified. The duration of neutral behavior increased, and rates of scratching and yawning decreased in the buspirone-treated condition. In the fluoxetine-treated condition, rates of yawning, scratching, and self-directed grooming were higher overall compared with those of buspirone-treated animals, and rates of scratching increased significantly (P < 0.05) in weeks 9 to 12; these findings suggest that animals in the fluoxetine-treated condition experienced higher levels of anxiety throughout the study. In both treatment conditions, concentrations of CSF 5-HIAA (5-HT metabolite) were significantly lower (P < 0.05) than placebo concentrations. Fluoxetine and buspirone may be efficacious for treatment of self-injurious and self-directed stereotypic behavior in macaques. Further studies are required to determine the optimal dosages and treatment length.     

Identifying innovation in laboratory studies of cultural evolution: rates of retention and measures of adaptation

In recent years, laboratory studies of cultural evolution have become increasingly prevalent as a means of identifying and understanding the effects of cultural transmission on the form and functionality of transmitted material. The datasets generated by these studies may provide insights into the conditions encouraging, or inhibiting, high rates of innovation, as well as the effect that this has on measures of adaptive cultural change. Here we review recent experimental studies of cultural evolution with a view to elucidating the role of innovation in generating observed trends. We first consider how tasks are presented to participants, and how the corresponding conceptualization of task success is likely to influence the degree of intent underlying any deviations from perfect reproduction. We then consider the measures of interest used by the researchers to track the changes that occur as a result of transmission, and how these are likely to be affected by differing rates of retention. We conclude that considering studies of cultural evolution from the perspective of innovation provides us with valuable insights that help to clarify important differences in research designs, which have implications for the likely effects of variation in retention rates on measures of cultural adaptation.     

Longevity and metabolism in Drosophila melanogaster: genetic correlations between life span and age-specific metabolic rate in populations artificially selected for long life

We measured age-specific metabolic rates in 2861 individual Drosophila melanogaster adult males to determine how genetic variation in metabolism is related to life span. Using recombinant inbred (RI) lines derived from populations artificially selected for long life, resting metabolic rates were measured at 5, 16, 29, and 47 days posteclosion, while life spans were measured in the same genotypes in mixed-sex population cages and in single-sex vials. We observed much heritable variation between lines in age-specific metabolic rates, evidence for genotype x age interaction, and moderate to large heritabilities at all ages except the youngest. Four traits exhibit evidence of coordinate genetic control: day 16 and day 29 metabolic rates, life span in population cages, and life span in vials. Quantitative trait loci (QTL) for those traits map to the same locations on three major chromosomes, and additive genetic effects are all positively correlated. In contrast, metabolic rates at the youngest and oldest ages are unrelated to metabolic rates at other ages and to survival. We suggest that artificial selection for long life via delayed reproduction also selects for increased metabolism at intermediate ages. Contrary to predictions of the "rate of living" theory, we find no evidence that metabolic rate varies inversely with survival, at the level of either line means or additive effects of QTL.