Placebo

Key Insights

• Power of expectation: Can our expectations shape the reality we experience? Experiences and expectations may be more connected and dependent than we currently understand. Our mind may determine our health, future, and our psychedelic trips. Can placebos create psychedelic-like experiences?
• Placebo and nocebo, where and how? Cutting-edge fMRI research is what we need to understand where placebos and nocebos take place. How can my body undergo changes to fit my expectations?
• Placebo ethics and future of research: Placebo research needs ethical considerations. Future needs more placebo research. Can my mind become a machine which determines my future?

Author: Zeynep Beril Sinanoglu. Neuroscience graduate from University College London. Scientific writer on psychedelic research, hallucinations, effects of music/meditation on the brain.  Placebo is a powerful tool created by our minds. It can shape your reality and can change your life. When the mind becomes its own scenarist, it becomes important to write a good scenario. Email [email protected] for enquiries. 

What is the placebo effect?

Can our expectations shape the reality we experience?

The placebo effect occurs when a patient’s symptom gets relieved after taking a drug without any therapeutic value (e.g. a sugar pill). Hence, the treatment becomes effective solely due to the patient’s mindset.

For example, imagine having severe pain in your leg. When you go to the hospital, your doctor prescribes a new effective medicine and tells you to take a pill. Soon after taking the pill, your leg pain disappears, and the treatment becomes successful. Later, you discover that the medicine prescribed to you was ineffective (no actual ‘active’ drug in the pill, or a sham procedure was done) and had nothing to do with managing pain. Therefore, not the drug but your expectations regarding pain relief that reduces your pain and causes a physiological change in your body.

Placebo studies have repeatedly shown us how incredibly powerful our expectations are for our experiences [1]. The mind is a powerful tool that we merely know how to use.

Placebo and Pain

Can our mind become a machine which determines our pain experience?

Our experience of pain depends on both psychological and physiological factors. Psychological factors may include one’s expectations or beliefs. If one believes that a treatment will be successful, the treatment becomes more likely to be successful, whereas if one believes that the treatment will fail, the treatment becomes more likely to fail.

Similarly, the belief that receiving an analgesic treatment may reduce pain perception during placebo analgesia. Since our brain modulates the perception of pain, and our brain can create placebos, placebos may be able to alter our pain perception.

In a study by Wager and colleagues, the placebo-induced changes in fMRI were studied in the anticipation and the experience of pain [2]. They hypothesised that placebo treatments without therapeutic effects may result in analgesia solely by altering expectations. If a placebo decreases pain perception, it should also reduce fMRI blood-oxygen-level dependent (BOLD) signal in pain-responsive brain regions (e.g., somatosensory cortex, thalamus, insula, anterior cingulate cortex) during pain.

Their second hypothesis was that placebos can inhibit activity in pain-processing regions by creating expectations for pain relief. Since evidence suggests that the prefrontal cortex and the dorsolateral aspect (DLPFC) maintains and updates internal representations of expectations, and these regions in turn modulate the activity of other brain areas, placebo-induced pain relief should correlate with stronger PFC/DLPFC activation during the anticipation of pain.

In one fMRI study on placebo analgesia, decreased brain activity in pain-sensitive brain regions such as the thalamus, insula, and the anterior cingulate cortex was observed. In another fMRI study on the anticipation of pain, increased brain activity in the prefrontal cortex was observed. Hence, the study provided evidence for physiological changes in the brain following an expectation for pain relief, and for the anticipation of pain. Therefore, placebos and nocebos (negative placebo effect) have substantial effects on altering pain experience.

Can placebos create psychedelic-like experiences?

Psychedelic drugs often alter the perception of the reality we experience on a day-to-day basis in a matter of minutes. Psilocybin is a powerful mind-altering compound found in psychedelic mushrooms and has been recreationally used by people for centuries. A study by Olson and colleagues asked participants to consume a new drug resembling the effects of psilocybin. However, the drug they administered to the participants was an inert substance and did not have any psychoactive effect in reality. During this 4-hour study in a psychedelic-like setting, 61% of participants verbally reported some effect of the drug. Some felt heavier, as if gravity had a stronger hold on them, while some saw paintings move.

The study highlighted two distinct types of effect; the placebo and the nocebo. When asked for verbal reports, one participant reported feeling light-headed, relaxed, and warm. She felt as if she was using less effort to move her head. She enjoyed staring at the paintings, felt high, and didn’t feel like she could talk to anybody else. She was amazed that the drug was a placebo at the end of the study.

On the other hand, other participants felt nauseated, heavier, and sweaty. Some felt a headache and had low energy. One participant reported seeing the colours of a painting move and reshape itself, while another participant had difficulties understanding what people were saying for approximately 20 minutes of the study.

Others reported no change in their perception. Since people had varying expectations regarding the placebo drug, each one experienced different effects. This not only highlighted the importance of placebo-controlled drug studies while exploring a new drug but also showed that a good-trip and a bad-trip may depend on our expectations regarding our future trip.

The Importance of Placebo-Controlled Studies

Can the placebo effect increase the effectiveness of treatment?

Researchers have used placebo-controlled studies to minimize the placebo effect in statistical analysis. Since the placebo effect creates considerable psychological and physiological effects on people, placebo-controlled studies attempt to solve this issue by randomly allocating patients into two groups. The first group is the experimental group which receives the investigated drug, while the second group gets an inert placebo substance. This procedure allows comparison between the placebo group and the experimental group and thus, minimizes the effect of placebo in statistical analysis. By minimizing the placebo effect, researchers hope to get a better understanding of the investigated drug’s effects.

However, placebo-controlled studies do come with ethical issues. Participants willing to join drug studies often hope for some level of treatment. Some scientists argue that giving a placebo treatment to a patient seeking an experimental drug can be considered misguidance [3]. Balancing ethical considerations with cutting-edge scientific research is a delicate task requiring careful thought and reflection.

Future Directions for Research

The placebo effect has shown that our mind and beliefs can powerfully impact our physical bodies. However, it’s important to note the limitations as well. The placebo effect can help manage symptoms, especially those that are subjective like pain, fatigue, or stress, but it can’t cure diseases or repair physical damage. For example, a placebo might improve the symptoms of someone with arthritis by reducing perceived pain, but it won’t be able to reverse the joint damage caused by the disease. Understanding both the power and the limitations of the placebo effect is crucial for its effective and ethical application in medicine and health.

The Intersection of Psychedelics and the Placebo Effect

The Role of Expectation in Psychedelic Experiences

Despite the ethical concerns, fMRI data has shown us how powerful the placebo effect can be. Hence, placebo-controlled studies are required for exposing the true impact of a given drug.

Psychedelic drugs can present people with good trips or bad trips. How much of that is due to our expectations about the trip, and how powerful of a placebo or a nocebo we create for ourselves is extremely important to understand the power of our thoughts. Thus, the intersection of the placebo effect and psychedelics is a promising field for future research.

Can a positive expectation from a psychedelic drug create a placebo effect and result in a good trip? Similarly, can a negative expectation from the same drug create a nocebo effect and result in a bad trip? If so, we would be able to show just how interconnected expectations and experiences are. Expectations can shape experiences, and experiences can shape our expectations.

Food For Thought

Doctors often tell their patients how long they may live after their diagnosis. Suppose a doctor wrongfully told their patient they have three months to live. Considering that our expectations are compelling, and our minds can alter our future, can this person’s expectation of death create a nocebo which will lead to their death in three months? Conversely, can a placebo effect increase the effectiveness of any given treatment?

External references for Placebo and Psychedelics

All resources available on Blossom are directly linked on this topic page. Find even more background about this topic with these external references.

1. Colloca, L., & Barsky, A. J. (2020). Placebo and nocebo effects. New England Journal of Medicine, 382(6), 554-561.

2. Wager, T. D., Rilling, J. K., Smith, E. E., Sokolik, A., Casey, K. L., Davidson, R. J., … & Cohen, J. D. (2004). Placebo-induced changes in FMRI in the anticipation and experience of pain. Science, 303(5661), 1162-1167.

3. Gupta, U., & Verma, M. (2013). Placebo in clinical trials. Perspectives in clinical research, 4(1), 49.