Original Editor - Lucinda hampton

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Introduction[edit | edit source]

Placebos are typically inert tablets, such as sugar pills

A placebo is a substance that has positive effects as a result of a patient's perception that it is beneficial rather than as a result of a causative ingredient. The Placebo effect is a phenomenon where, with the usage of certain substances, a “perceived” beneficial impact is created. A placebo can be eg a saline solution, sterile water or a sham surgery. It is not known to have any medical significance hence is considered as a “fake” treatment. In some cases they tend to produce real responses. The expectations of the patient plays a large part here, with higher the belief in the treatment the greater chances of it being beneficial.[1]

Placebos have been in use since antiquity and may have been significant in improving health and quality of life when little was known about the etiology of most illnesses. The emergence of placebo-controlled clinical trials in the 1940s reintroduced the placebo effect to the modern day[2]. Over the past 30 years there has been an increase in research on the placebo effect using a neuroscientific approach, with an interest in the identification of several biological mechanisms of the placebo. An important contribution of neuroscience has been to highlight the important role of psychobiological factors in therapeutic outcomes, be they drug related or not[3].

Mechanism[edit | edit source]

An individual who receives a placebo is convinced that the treatment will help, This conviction in turn makes the individual more likely to get better.

Two theories have been proposed to explain the placebo effect:

  1. Conditioning theory: that the placebo effect is a conditioned response
  2. Mentalistic theory: sees the patient's expectation as the primary cause of the placebo effect.

The mechanisms involved in these processes are beginning to be understood through new techniques of investigation in neuroscience.

  • Dopamine and the endorphins have been clearly shown to be mediators of placebo effects.
  • Brain imaging has demonstrated that placebos can mimic the effect of the active drugs and activate the same brain areas.

This is the case for placebo-dopamine in Parkinson's disease, for placebo-analgesics or antidepressants, and for placebo-caffeine in the healthy subject. It remains to be understood how conditioning and expectation are able to activate memory loops in the brain that reproduce the expected biological responses[4].

Manual Therapy[edit | edit source]

Manual therapy as applied by physiotherapists in the rehabilitation setting are a part of rehabilitation rather than applied in isolation. The context of the treatment including the technique, the provider, the participant, the environment, and the interaction between these factors may contribute to patient outcomes. The effects of manual therapy are likely related to multiple mechanisms, including the placebo effect. Many of the neurophysiological responses associated with manual therapy and considered pertinent in the clinical outcomes are also observed in placebo studies unrelated to manual therapy. Placebo responses may account for some of the changes in clinical outcomes observed in response to manual therapy[5].

  • Placebo-related hypoalgesia may be enhanced by factors related to negative mood, expectation, and conditioning, and manual therapists should be aware of these influences and take steps to maximize their benefits during treatment (not meaning that we should purposefully deceive our patients by knowingly promoting the benefits of inert or ineffective interventions).
  • Manual therapists may strengthen the treatment effects of evidence-based interventions when they embrace the placebo response.[5]

Sham Surgery[edit | edit source]

Sham Surgery or real?

Meniscal Repair: The New England Journal of Medicine published a trial showing that sham surgery can be as good as the real thing. The subjects were candidates for knee surgery, with a torn meniscus and debilitating pain. They underwent surgery in the operating room with surgeons who performed either a meticulous repair of the torn cartilage, or a charade. Incisions were made, and closed, with no other intervention. In the operating theatre the doctors and nurses passed instruments, made surgical sounds, and pretended to do surgery for as long as the procedure would normally take.

Both surgeries worked, with subjects who underwent the fake procedure experiencing just as much improvement in pain and activity as those whose meniscus was actually repaired.[6]

Tendinopathy: Sham surgery (placebo) trials are the gold standard against which to judge the effect of surgery on clinical conditions (eg tendinopathy). In 12 eligible randomised controlled trials in patients with various tendinopathies, surgery was not superior to sham surgery in patients with tendinopathy in the midterm and long term. Studies advocate that healthcare professionals who treat patients with tendinopathies should reserve surgery for selected cases and only after a sufficiently long course (12 months) of evidence-based loading exercise has failed[7].

Parkinson's[edit | edit source]


Studies have shown people with Parkinson’s experience a significant placebo effect. Patient characteristics that affect placebo include patients' expectations of good outcomes, genetic variants, and personality. Exactly how placebos work and why they may have a potentially larger impact in Parkinson’s isn’t clear. But it likely has to do with dopamine, the brain chemical that decreases in Parkinson’s. Brain imaging studies show that placebos stimulate the release of dopamine, which plays a role in the brain’s reward system[8].

A Little Irrelevancy[edit | edit source]

  • I'm addicted to placebos. I could quit but it wouldn't matter.
  • In my whole life I’ve only ever been to two concerts. I’ve seen Placebo, and I’ve seen The Cure. They were just as good as each other
  • On my way home from work today I was listening to Placebo. I thought I was listening to something else, but obviously I was the control group.

References[edit | edit source]

  1. Byjus Placebo effect Available: (accessed 21.4.2022)
  2. Munnangi S, Sundjaja JH, Singh K, Dua A, Angus LD. Placebo effect. Available: 21.4.2022)
  3. Benedetti F, Frisaldi E, Shaibani A. Thirty years of neuroscientific investigation of placebo and nocebo: the interesting, the good, and the bad. Annual review of pharmacology and toxicology. 2022 Jan 6;62:323-40.Available: (accessed 21.4.2022)
  4. Haour F. Mechanisms of the placebo effect and of conditioning. Neuroimmunomodulation. 2005;12(4):195-200. Available: (accessed 21.4.2022)
  5. 5.0 5.1 Bialosky JE, Bishop MD, George SZ, Robinson ME. Placebo response to manual therapy: something out of nothing?. Journal of Manual & Manipulative Therapy. 2011 Feb 1;19(1):11-9.Available: (accessed 21.4.2022)
  6. Sihvonen R, Paavola M, Malmivaara A, Itälä A, Joukainen A, Nurmi H, Kalske J, Järvinen TL. Arthroscopic partial meniscectomy versus sham surgery for a degenerative meniscal tear. N Engl J Med. 2013 Dec 26;369:2515-24. Available: 21.4.2022)
  7. Challoumas D, Clifford C, Kirwan P, Millar NL. How does surgery compare to sham surgery or physiotherapy as a treatment for tendinopathy? A systematic review of randomised trials. BMJ open sport & exercise medicine. 2019 Apr 1;5(1):e000528.Available: 21.4.2022)
  8. Lou JS. Placebo responses in Parkinson's disease. International Review of Neurobiology. 2020 Jan 1;153:187-211.Available: (accessed 21.4.2022)