Investigating the Placebo Effect

Behavioral, Subjective, and Physiological Dimensions

This research initiative is an exploration of the placebo effect, with a focus on its manifestation across behavioral, subjective, and physiological domains. We are committed to elucidating the multifaceted nature of placebo responses and their underlying mechanisms.

The placebo effect occurs when a person's symptoms are alleviated by an otherwise inert treatment, due to other factors than spontaneous improvement or regression to the mean. Current theoretical frameworks explain the effect in terms of the patient’s beliefs and/or learning. As such, the placebo effect is a phenomenon addressing the relation of mental states and physiological processes.

The placebo effect represents a unique intersection between cognition, emotion, perception, behavior and somatic response. Our project aims to dissect the various external and psychological factors that contribute to the elicitation of placebo responses. We are examining environmental variables, patient-practitioner dynamics, and the cognitive constructs that shape the therapeutic context.

A critical aspect of our inquiry involves delineating the neural correlates of the placebo effect. Through neuroimaging and neurophysiological techniques, we are identifying the specific brain structures and networks implicated in the modulation of both conscious and unconscious placebo-induced changes.

Our methodological framework aims to separate the placebo effect on overt behavior and self-reported experiences from its impact on autonomic and physiological processes. By employing a combination of behavioral assays, subjective assessments, and objective physiological measurements, we aim to parse out the discrete contributions of these components.

The findings from our research have the potential to inform clinical practice by optimizing the use of placebo mechanisms to augment therapeutic outcomes or by contributing to developing optimal designs for clinical trials. A deeper understanding of the placebo effect can lead to more effective patient care strategies, minimizing unnecessary interventions while maximizing treatment benefits.

Publications

Laursen, D. R. T., Nejstgaard, C. H., Bjørkedal, E., Frost, A. D., Hansen, M. R., Paludan-Müller, A. S., Prosenz, J., Werner, C. P., & Hróbjartsson, A. (2023). Impact of active placebo controls on estimated drug effects in randomised trials: a systematic review of trials with both active placebo and standard placebo. Cochrane Database of Systematic Reviews(3). https://doi.org/10.1002/14651858.MR000055.pub2

Aslaksen, P. M., Forsberg, J. T., & Gjerstad, J. (2018). The opioid receptor mu 1 (OPRM1) rs1799971 and catechol-O-methyltransferase (COMT) rs4680 as genetic markers for placebo analgesia. PAIN, 159(12), 2585-2592. https://doi.org/10.1097/j.pain.0000000000001370

Flaten, M. A., Bjørkedal, E., Lyby, P. S., Figenschau, Y., & Aslaksen, P. M. (2018). Failure to Find a Conditioned Placebo Analgesic Response. Frontiers in Psychology, 9, 1198. https://doi.org/10.3389/fpsyg.2018.01198

Forsberg, J. T., Gjerstad, J., Flaten, M. A., & Aslaksen, P. M. (2018). Influence of catechol-O-methyltransferase Val158Met on fear of pain and placebo analgesia. PAIN, 159(1), 168-174. https://doi.org/10.1097/j.pain.0000000000001081

Turi, Z., Bjørkedal, E., Gunkel, L., Antal, A., Paulus, W., & Mittner, M. (2018). Evidence for Cognitive Placebo and Nocebo Effects in Healthy Individuals. Scientific Reports, 8(1), 17443. https://doi.org/10.1038/s41598-018-35124-w

Turi, Z., Mittner, M., Paulus, W., & Antal, A. (2017). Placebo Intervention Enhances Reward Learning in Healthy Individuals. Scientific Reports, 7, 41028. https://doi.org/10.1038/srep41028

Vambheim, S. M., & Flaten, M. A. (2017). A systematic review of sex differences in the placebo and the nocebo effect. Journal of Pain Research, 10, 1831-1839. https://doi.org/10.2147/JPR.S134745

Aslaksen, P. M., Åsli, O., Øvervoll, M., & Bjørkedal, E. (2016). Nocebo hyperalgesia and the startle response. Neuroscience, 339, 599-607. https://doi.org/10.1016/j.neuroscience.2016.10.040

Aslaksen, P. M., & Lyby, P. S. (2015). Fear of pain potentiates nocebo hyperalgesia. Journal of Pain Research, 8, 703-710. https://doi.org/10.2147/JPR.S91923

Aslaksen, P. M., Zwarg, M. L., Eilertsen, H.-I. H., Gorecka, M. M., & Bjørkedal, E. (2015). Opposite effects of the same drug: reversal of topical analgesia by nocebo information. Pain, 156(1), 39-46. https://doi.org/10.1016/j.pain.0000000000000004

Aslaksen, P. M., Vasylenko, O., & Fagerlund, A. J. (2014). The effect of transcranial direct current stimulation on experimentally induced heat pain. Experimental Brain Research, 232(6), 1865-1873. https://doi.org/10.1007/s00221-014-3878-0

Bjørkedal, E., & Flaten, M. A. (2012). Expectations of increased and decreased pain explain the effect of conditioned pain modulation in females. Journal of Pain Research, 5, 289-300. https://doi.org/10.2147/JPR.S33559

Lyby, P. S., Forsberg, J. T., Åsli, O., & Flaten, M. A. (2012). Induced fear reduces the effectiveness of a placebo intervention on pain. PAIN, 153(5), 1114-1121. https://doi.org/10.1016/j.pain.2012.02.042

Mueller, M., Bjørkedal, E., & Kamping, S. (2012). Manipulation of Expectancy and Anxiety in Placebo Research and Their Effects on Opioid-Induced Analgesia. Journal of Neuroscience, 32(41), 14051-14052. https://doi.org/10.1523/JNEUROSCI.3756-12.2012

Aslaksen, P. M., Bystad, M., Vambheim, S. M., & Flaten, M. A. (2011). Gender differences in placebo analgesia: event-related potentials and emotional modulation. Psychosomatic Medicine, 73(2), 193-199. https://doi.org/10.1097/PSY.0b013e3182080d73

Bjørkedal, E., & Flaten, M. A. (2011). Interaction between expectancies and drug effects: an experimental investigation of placebo analgesia with caffeine as an active placebo. Psychopharmacology, 215(3), 537-548. https://doi.org/10.1007/s00213-011-2233-4

Flaten, M. A., Aslaksen, P. M., Lyby, P. S., & Bjørkedal, E. (2011). The relation of emotions to placebo responses. Philosophical Transactions of the Royal Society B: Biological Sciences, 366(1572), 1818-1827. https://doi.org/10.1098/rstb.2010.0407

Lyby, P. S., Aslaksen, P. M., & Flaten, M. A. (2011). Variability in placebo analgesia and the role of fear of pain--an ERP study. PAIN, 152(10), 2405-2412. https://doi.org/10.1016/j.pain.2011.07.010

Lyby, P. S., Aslaksen, P. M., & Flaten, M. A. (2010). Is fear of pain related to placebo analgesia? Journal of Psychosomatic Research, 68(4), 369-377. https://doi.org/10.1016/j.jpsychores.2009.10.009

Aslaksen, P. M., & Flaten, M. A. (2008). The roles of physiological and subjective stress in the effectiveness of a placebo on experimentally induced pain. Psychosomatic Medicine, 70(7), 811-818. https://doi.org/10.1097/PSY.0b013e31818105ed

Flaten, M. A., Aslaksen, P. M., Finset, A., Simonsen, T., & Johansen, O. (2006). Cognitive and emotional factors in placebo analgesia. Journal of Psychosomatic Research, 61(1), 81-89. https://doi.org/10.1016/j.jpsychores.2005.12.004

Flaten, M. A., Aasli, O., & Blumenthal, T. D. (2003). Expectations and placebo responses to caffeine-associated stimuli. Psychopharmacology, 169(2), 198-204. https://doi.org/10.1007/s00213-003-1497-8

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