Understanding The Nocebo Effect

» Posted by on Jul 8, 2013

Dave Berman, C.Ht.

The Scientist Magazine recently published an article called “Worried Sick” that looks at research into the neuroscience of the nocebo effect. The word “nocebo” comes from the Latin “I shall harm” and superficially appears to be the flip side of the coin to the more familiar placebo effect (from the Latin “I shall please”). Both refer to ways we are influenced by information or substances, one to our detriment and the other to our benefit.

I say they appear superficially related because recent research suggests these two phenomena have very different biochemical mechanisms. According to the article, nocebo first appeared in scientific literature in 1961. Since then it has only been studied a tiny fraction as much as placebo because it is controversial among bioethicists and ethics committees don’t easily approve research in this area.

Nonetheless, The Scientist quotes Ted Kaptchuk, director of Harvard’s Program in Placebo Studies at Beth Israel Deaconess Medical Center in Boston: “Nocebo is at least as important as the placebo effect and may be more widespread…In places like primary care, people are swimming in placebo and nocebo effects.”

That means what doctors and nurses are telling people about their conditions, treatments and medications are having both positive and negative effects. I noted this in my earlier article “What The Thinker Thinks, The Prover Proves.”

The Scientist points out “fear and distress before an operation has been associated with slow postoperative recovery and delayed wound healing.” Now we’re getting to the beginning of how this relates to hypnosis, which of course has been shown to speed post-op recovery and wound healing, reduce the need for medications and even anesthesia during surgery, and in the most basic of ways help people relax and calm fears or distress. (Click the News and Research tab for more evidence.)

In addition to Kaptchuk, another important figure in this field is Fabrizio Benedetti, an Italian neurophysiologist. In 1997, Benedetti became the first to demonstrate the biochemistry of the nocebo effect, as well as showing how to block it. This is where it becomes most interesting because if it can be blocked one way, perhaps it can be blocked in other ways. And let’s not be surprised that again it is hypnosis that has that ability.

Despite the disproportionate amount of effort put into placebo research, since Benedetti’s 1997 discovery there’s been an uptick in the funding and time devoted to investigating the mechanisms behind nocebo, with impressive results. “Without a doubt, there’s been a level of research and a sophistication of research that has made a quantum jump in the last decade or so,” says [chair of family medicine and director of the Institute for the Medical Humanities at the University of Texas Medical Branch in Galveston, Howard] Brody.

In 2007, for example, Benedetti discovered that the hypothalamic-pituitary-adrenal axis in the brain, an important part of the body’s “stress system,” is activated during a nocebo response, as detected by an increase in the secretion of the hormones ACTH, from the pituitary gland, and cortisol, from the adrenal gland, both markers of anxiety.8

Then, in 2008, Kaptchuk and colleagues at Harvard performed the first brain-imaging study of the nocebo effect. After conditioning healthy volunteers to expect pain on their right forearm, they watched as the hippocampus lit up when people experienced pain from a sham acupuncture device.

Through Benedetti’s and Kaptchuk’s work, it is now clear that a person’s expectation of pain can induce anticipatory anxiety, triggering the activation of cholecystokinin, the hormone that Benedetti blocked with proglumide. Cholecystokinin-mediated pathways in turn facilitate pain transmission, which occurs in specific areas of the brain. The finding does not coincide with what is know [sic] about the biochemistry of the placebo effect—which seems to be at least partly regulated by opioid release—suggesting the two phenomena have distinct mechanisms.

8: F. Benedetti et al., “The biochemical and neuroendocrine bases of the hyperalgesic nocebo effect,” J Neurosci, 26:12014-22, 2006.

This expectation of pain plays a big role in childbirth. I recently completed Teresa Van-Zeller’s training “Birthing As Nature Intended,” and this fall will begin offering birthing education classes. The point of the program is teaching pregnant women how to relax and use self-hypnosis for drug-free, pain-free deliveries of their babies.

In other words, natural childbirth!

The biggest reason this isn’t more common is the prevailing childbirth education and indoctrination women currently receive. They are told to expect lots of pain. No wonder their experiences often match such predictions.

The tragedy of this lack of investigation, researchers assert, is that controlled trials about the nocebo effect are needed to further understand and prevent nocebo’s insidious effects on medicine and research. “In clinical drug trials, the placebo effect—and now we know the nocebo effect—can be really, really large,” says Manfred Schedlowski, a clinical researcher at the University Hospital Essen in Germany. “This hinders the development of new drugs.”

Beyond acknowledging the scope of the nocebo effect, this quote is telling about how doctors are thinking about “nocebo’s insidious effects,” – in terms of drug development. Consider the possibility that the important ethical debates and research into nocebo’s mechanisms may ultimately have less practical value than thinking in terms of mitigation via new communication strategies, including techniques explored in the book “Hope Is Realistic,” by Michael Ellner and Kelley T. Woods, which I reviewed here last year.

“Most doctors don’t know what nocebo means,” agrees Y. M. Barilan, a practicing physician and associate professor of medical education at Tel Aviv University in Israel. That’s not to say that they don’t recognize the phenomenon. “They all know that the way you talk to a patient has enormous influence on side effects, mood, and state of mind,” Barilan notes—but without guidelines on how to deal with the problem or even to recognize it, the nocebo effect remains a specter of illness haunting our health-care system.

As medical hypnotists, all we have is the way we talk to our clients. We don’t get to prescribe drugs or run brain scans on sophisticated equipment. As research on nocebo becomes more widely reported, I hope doctors will allow a place for us in that discussion. I am particularly interested in exploring the link between nocebo and somatoform disorders, which are being reclassified as “somatic symptoms and related disorders” in the controversial new DSM-5. More on this in a future article…

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UPDATE 10/24/13: This article has also been published in the Fall 2013 Newsletter of the North Coast Association of Mental Health Professionals (.pdf).

UPDATE 11/19/13: This article has also been published in the November/December 2013 issue of The Isis Scrolls magazine available free throughout Northern California and Southern Oregon.

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Dave Berman, C.Ht. practices Clinical and Medical Hypnosis, Neuro-Linguistic Programming (NLP) and Life Coaching. He is certified by the International Medical and Dental Hypnotherapy Association and an affiliate member of the North Coast Association of Mental Health Professionals. Dave offers private and confidential sessions on a sliding scale in his Arcata, CA office and remotely via Skype. Referrals and inquiries are welcome. Learn more at www.HumboldtHypnosis.com or call (707) 845-3749 for a free consultation.

Posted: 7/8/13
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