Minding the Mind in Photobiomodulation: It Matters!

T his journal's editorials have considered a variety of topics as they relate to the science and practice of medicine. We have discussed the need for well-controlled studies at the laboratory research level and have opined about the condition of the scientific literature as it pertains to clinical trials. We have considered randomized controlled trials as well as the need for more attention to these tools, both from the perspective of the study organizers and sponsors and of the scientific and lay community, who are judging the worth of particular interventions based on published details. Issues such as bias in the organization of the trial, and recording and reporting of trial data are topics that are relevant to our discipline as well as to clinical medicine at large. We have also considered the concept of placebos and controls in such trials. ¹

Our analysis has revealed that placebos are quite often not “inert,” which has been a source of concern for pharmaceutical trials. We have also considered the possibility that the so-called placebos in photobiomodulation studies could actually have biological effects, and have suggested that rigorous laboratory investigation of the proposed parameters for treatment and control groups is critically important as trials are designed and results are interpreted. ¹

We now will consider another potential confounding issue, namely, the nocebo and the nocebo effect. A nocebo effect was originally defined as being the negative counterpart of the placebo phenomenon. ² “Nocebo” was a word that was coined as a way to distinguish the negative or adverse effects of placebos in contrast to the beneficial effects of a placebo. A nocebo is an inert substance or procedure that is intended to create negative expectations. An example would be orally suggesting that a placebo might cause worsening of a symptom or condition.

A so-called “nocebo effect” refers to “the negative psychosocial context around the patient and the treatment” being rendered and the neurobiological basis for it. ² The nocebo response is the actual expectancy-induced changes in the patient's brain or body as a result of the nocebo. ²

These concepts are important because nocebo effects and nocebo responses can occur in a clinical or research scenario irrespective of whether the treatment or procedure is an inert placebo or the active therapy. The actual oral communication and other details of a clinical encounter can produce nocebo responses in patients, leading to worsening outcomes. ²

It has often been observed that patients in clinical trials who were given a purportedly inert placebo report experiencing the negative side effects that are associated with the real drugs. ² This should come as no surprise, as the concept of mind over matter is something that is quite familiar in our daily and professional lives. We are comfortable with the power of suggestion and have likely experienced it personally relative to the perceived pain, nausea, or various other effects we associate with a particular procedure, drug, or intervention, especially if we perceive that it will “hurt” or produce nausea. The phenomenon is not unlike the medical student syndrome, which was exhibited by one of my roommates when I was a medical student. Tom (not his real name) was an extremely bright individual and a voracious reader, who delighted in the obscure, often having contests with two other roommates as to who could predict what disease was being represented on the most popular television medical dramas of the day. As we navigated our way through our clinical medicine lectures and readings, Tom would actually begin to experience symptoms of some of the entities we were studying. This was somewhat amusing at the time, as he was more likely to experience complaints of the more exotic or rare diseases we studied. We are thankful that he grew out of it, and is now a highly successful medical subspecialist today. The power of suggestion was quite strong in Tom's case. This is not unlike the patient who begins reporting a wide array of symptoms after having read the side effects and warnings provided with the insert and directions for the prescription drug that patient is receiving.

It would be a good idea to consider the potential influence of nocebo effects and nocebo responses in the clinical and investigational applications of light in so-called low-level laser therapy (LLLT). There are numerous positive outcomes reported in the literature, as well as others that either demonstrated no effect or an effect that was indistinguishable from the control or placebo. We would be foolish to presume that all of the negative reports were caused by nocebo effects or responses. However, we should always be circumspect and vigilant as we describe the anticipated effects, outcomes, and responses to a particular treatment, light-based or not. It would be unethical not to provide accurate information to the patient or to withhold information from the patient during the informed consent process.

The words we use to describe a procedure and the expectations, side effects, and outcomes should be accurate. However, it is wise not to over-sell or disparage a treatment by our oral communication. The former suggestion could overly inflate positive results for a treatment. The latter could produce negative outcomes. For example, indicating that a treatment is sometimes effective could indeed produce a different response than stating that the treatment is not often effective. How the details, benefits, and consequences of treatment are described and discussed is arguably as important as the design of the study or therapy itself. Our words are indeed powerful tools. What we instill in someone's mind does indeed matter.