Brain Scans Reveal that Mindfulness Meditation to Reduce Pain Is Not a Placebo Effect

Mindfulness meditation, which has been used for centuries for pain management in various cultures, has long been speculated to work by activating processes supporting the placebo response. However, scientists have now shown that this is not the case. A new study opens in new tab/window in Biological Psychiatry opens in new tab/window, published by Elsevier, has revealed that mindfulness meditation engages distinct brain mechanisms to reduce pain, compared to those of the placebo response.

John Krystal, MD, Editor of Biological Psychiatry, says, “Pain is a complex, multifaceted experience shaped by various factors beyond physical sensation, such as a person’s mindset and their expectations of pain. This study highlights the complexity of psychological modulation of pain. The placebo effect, the tendency for a person’s symptoms to improve in response to inactive treatment, is a well-known example of how expectations can significantly alter a person’s experience."

The study included 115 healthy participants and consisted of two separate clinical trials. Participants were randomly placed into groups to receive four interventions:

• A mindfulness meditation that was practiced by focusing on the breath without judgement

• A sham-mindfulness meditation that only consisted of deep breathing

• A placebo cream (petroleum jelly) that participants were trained to believe reduces pain

• As a control, one group listened to an audiobook

The researchers applied a very painful, but harmless heat stimulus to the back of the leg and scanned the participants’ brains while they meditated, had placebo cream applied, or just rested (depending on the group).

To analyze the participants’ brain activity patterns, the researchers used functional MRI and a novel approach called multivariate pattern analysis (MVPA) developed by co-author Tor D. Wager, PhD, Department of Psychological and Brain Science, Dartmouth College, which uses machine learning to disentangle the many complex neural mechanisms underlying the experience of pain, including those stemming from specific heat stimulus, negative emotions, and pain responses that are driven by the placebo effect. The researchers were then able to identify if mindfulness meditation and placebo engage similar and/or separate brain processes.

Although placebo cream and sham-mindfulness meditation lowered pain, the researchers found that mindfulness meditation was significantly more effective at reducing pain when compared to placebo cream, sham-mindfulness meditation, and the controls.

Lead investigator Fadel Zeidan, PhD, Department of Anesthesiology, University of California San Diego, notes, “It has long been assumed that the placebo effect overlaps with brain mechanisms triggered by active treatments, such as mindfulness meditation, but these results suggest that when it comes to pain, this may not be the case. Instead, these two brain responses are completely distinct, which supports the use of mindfulness meditation as a direct intervention for chronic pain rather than as a way to engage the placebo effect. The mind is extremely powerful, and we’re still working to understand how it can be harnessed for pain management by studying the brain. By separating pain from the self and relinquishing evaluative judgment, mindfulness meditation is able to directly modify how we experience pain in a way that uses no drugs, costs nothing, and can be practiced anywhere.”

Researchers also found that mindfulness-based pain relief reduced synchronization between brain areas involved in introspection, self-awareness, and emotional regulation. These parts of the brain together comprise the Neural Pain Signal (NPS), a documented pattern of brain activity thought to be common to pain across different individuals and different types of pain. In contrast, the placebo cream and sham-mindfulness meditation did not show a significant change in the NPS when compared to controls. Instead, these other interventions engaged entirely separate brain mechanisms with little overlap.

In modern medicine, new therapies are generally deemed effective and reliable if they outperform placebo. Since the present study found that mindfulness meditation is more powerful than placebo and does not engage in the same neurobiological processes as placebo, the findings have important implications for the development of new treatments for chronic pain. However, it will take more research to demonstrate these effects in people living with chronic pain as opposed to healthy participants.

In the long term, the researchers hope that by understanding the distinct brain mechanisms underlying mindfulness meditation, they can design more effective and accessible interventions that harness the power of mindfulness to reduce pain in people with various health conditions.

Dr. Zeidan concludes, "Millions of people are living with chronic pain every day, and there may be more these people can do to reduce their pain and improve their quality of life than we previously understood. We are excited to continue exploring the neurobiology of mindfulness and how we can leverage this ancient practice in the clinic.”

Notes for editors

The article is "Mindfulness Meditation and Placebo Modulate Distinct Multivariate Neural Signatures to Reduce Pain,” by Gabriel Riegner, Jon Dean, Tor D. Wager, and Fadel Zeidan (https://doi.org/10.1016/j.biopsych.2024.08.023 opens in new tab/window). It appears online in advance of volume 97, issue 1 (January 2025) of Biological Psychiatry, published by Elsevier.

The article is openly available for 30 days at https://www.biologicalpsychiatryjournal.com/article/S0006-3223(24)01556-7/fulltext opens in new tab/window.

Copies of this paper and additional information are also available to credentialed journalists upon request; please contact Rhiannon Bugno at [email protected] opens in new tab/window. Journalists wishing to interview the authors should contact Miles Martin, Senior Communications and Media Relations Manager, UC San Diego Health Sciences, at +1 858 255 1195 (mobile) or [email protected] opens in new tab/window.

This work was funded by the National Center for Complementary and Integrative Health.

The authors’ affiliations and disclosures of financial and conflicts of interests are available in the article.

John H. Krystal, MD, is Chairman of the Department of Psychiatry at the Yale University School of Medicine, Chief of Psychiatry at Yale-New Haven Hospital, and a research psychiatrist at the VA Connecticut Healthcare System. His disclosures of financial and conflicts of interests are available here opens in new tab/window.

About Biological Psychiatry

Biological Psychiatry opens in new tab/window is the official journal of the Society of Biological Psychiatry opens in new tab/window, whose purpose is to promote excellence in scientific research and education in fields that investigate the nature, causes, mechanisms, and treatments of disorders of thought, emotion, or behavior. In accord with this mission, this peer-reviewed, rapid-publication, international journal publishes both basic and clinical contributions from all disciplines and research areas relevant to the pathophysiology and treatment of major psychiatric disorders.

The journal publishes novel results of original research which represent an important new lead or significant impact on the field, particularly those addressing genetic and environmental risk factors, neural circuitry and neurochemistry, and important new therapeutic approaches. Reviews and commentaries that focus on topics of current research and interest are also encouraged.

Biological Psychiatry is one of the most selective and highly cited journals in the field of psychiatric neuroscience. It is ranked 6th^th out of 279 Psychiatry titles and 15^th out of 309 Neurosciences titles in Journal Citation Reports^TM published by Clarivate. The 2023 Impact Factor score for Biological Psychiatry is 9.6. www.biologicalpsychiatryjournal.com opens in new tab/window

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