Placebo-induced expectancies have been shown to decrease pain in a manner reversible by opioid antagonists, but little is known about the central brain mechanisms of opioid release during placebo treatment. This study examined placebo effects in pain by using positron-emission tomography with [11C]carfentanil, which measures regional μ-opioid receptor availability in vivo. Noxious thermal stimulation was applied at the same temperature for placebo and control conditions. Placebo treatment affected endogenous opioid activity in a number of predicted μ-opioid receptor-rich regions that play central roles in pain and affect, including periaqueductal gray and nearby dorsal raphe and nucleus cuneiformis, amygdala, orbitofrontal cortex, insula, rostral anterior cingulate, and lateral prefrontal cortex. These regions appeared to be subdivided into two sets, one showing placebo-induced opioid activation specific to noxious heat and the other showing placebo-induced opioid reduction during warm stimulation in anticipation of pain. These findings suggest that a mechanism of placebo analgesia is the potentiation of endogenous opioid responses to noxious stimuli. Opioid activity in many of these regions was correlated with placebo effects in reported pain. Connectivity analyses on individual differences in endogenous opioid system activity revealed that placebo treatment increased functional connectivity between the periaqueductal gray and rostral anterior cingulate, as hypothesized a priori, and also increased connectivity among a number of limbic and prefrontal regions, suggesting increased functional integration of opioid responses. Overall, the results suggest that endogenous opioid release in core affective brain regions is an integral part of the mechanism whereby expectancies regulate affective and nociceptive circuits.
We conducted randomized clinical trials to examine the impact of direct-to-consumer advertisements on the efficacy of a branded drug. We compared the objectively measured, physiological effect of Claritin (Merck & Co.), a leading antihistamine medication, across subjects randomized to watch a movie spliced with advertisements for Claritin or advertisements for Zyrtec (McNeil), a competitor antihistamine. Among subjects who test negative for common allergies, exposure to Claritin advertisements rather than Zyrtec advertisements increases the efficacy of Claritin. We conclude that branded drugs can interact with exposure to television advertisements.
For over 20 years, Linda Buonanno lived in fear that her irritable bowel syndrome (IBS) would suddenly interrupt her daily routine with frequent trips to the bathroom and unbearable cramping. Buonanno, now a 71-year-old medical assistant and hairdresser from Methuen, Mass., tried everything from drugs to dairy-free diets. Nothing worked. She remembers a particularly tough period over 10 years ago, when she was working on the factory floor of a medical-device company for up to 10 hours a day, six days a week. When an IBS episode would strike, her co-workers would cover for her as she huddled in a corner, keeled over in pain. If she wanted to go dancing with friends at the local club on Sunday, Buonanno would stop eating on Friday so there wouldn’t be anything in her system to interrupt her plans. “It was a horrible way to live,” she says. One day in 2009, she saw a TV ad looking for people with IBS to enroll in a study. She signed up and was thrilled when she was among about 80 people selected to take part in a first-of-its-kind clinical trial.
Background: Placebo treatment can significantly influence subjective symptoms. However, it is widely believed that response to placebo requires concealment or deception. We tested whether open-label placebo (non-deceptive and non- concealed administration) is superior to a no-treatment control with matched patient-provider interactions in the treatment of irritable bowel syndrome (IBS). Findings: Open-label placebo produced significantly higher mean (6SD) global improvement scores (IBS-GIS) at both 11- day midpoint (5.261.0 vs. 4.061.1, p,.001) and at 21-day endpoint (5.061.5 vs. 3.961.3, p = .002). Significant results were also observed at both time points for reduced symptom severity (IBS-SSS, p = .008 and p = .03) and adequate relief (IBS-AR, p=.02 and p=.03); and a trend favoring open-label placebo was observed for quality of life (IBS-QoL) at the 21-day endpoint (p = .08). Conclusion: Placebos administered without deception may be an effective treatment for IBS. Further research is warranted in IBS, and perhaps other conditions, to elucidate whether physicians can benefit patients using placebos consistent with informed consent.
Randomized placebo-controlled trials are recognized as the gold-standard of evidence-based medicine but when it comes to psychotherapy research all that g litters is not gold. Translation of this standard from medicine to clinical psychology is fraught with difficulties. While a wealth of robust evidence shows that psychotherapy is effective for a range of mental health conditions the use of placebo controls to assess the effectiveness of specific psychological interventions faces serious conceptual and methodological challenges (Gaab et al., 2018). In this Opinion article we identify two under-appreciated placebo-related problems which substantially risk the validity of clinical trials in psychotherapy. The first is a common misconception about the nature of placebos; the second is the problem of double-blinding. We review current solutions and future prospects for the gold-standard in psychotherapy research.
BY: PAUL ENCK & SIBYLLE KLOSTERHALFEN | DECEMBER 6, 2018 In comparison to Henry Beecher’s much-cited paper, “The Powerful placebo,” of 1955 (1), Stewart Wolf’s paper, “The pharmacology of placebos,” of 1959 (2) is today almost forgotten; it came along less spectacularly but more scientifically solid, hiding its implicit provocation (there is a biology underlying the placebo effects) behind a seemingly …