Fabrizio Benedetti

Last updated
Fabrizio Benedetti
Scientific career
Fields Neuroscience, Placebo studies.
Institutions University of Turin Medical School

Fabrizio Benedetti is professor of physiology and neuroscience at the University of Turin Medical School in Turin, Italy and a researcher in the field of placebo studies. [1] He is known for his research into the placebo and nocebo effects. [2] [3]

Contents

Placebo and nocebo research

Benedetti began studying placebos in the 1990s while researching pain. [4] His research has found that "the promise of treatment activates areas of the brain involved in weighing the significance of events and the seriousness of threats." [4] Another of Benedetti's studies examined the effectiveness of placebos in the treatment of Parkinson's disease, and the effect of this treatment on neurons that control movement. He found that giving these patients a placebo led to a decrease in the rate at which these neurons fired of about 40%, and that this enabled the patients to move more easily. [5] In 2007, Benedetti published a study in which he and his co-authors gave subjects morphine during a hand-squeezing exercise, and later replaced the morphine with a placebo without the subjects' knowledge. In this study, the subjects who received morphine and then a placebo endured significantly more pain than did patients in any of the control groups. [6] [7] In a 2011 paper, Benedetti and co-authors argued that there exist many different placebo effects, "with different mechanisms and in different diseases, systems, and therapeutic interventions." [8]

He has also published research on the nocebo effect, in which adverse events are produced as a result of negative expectations. In some of these studies, he found that cholecystokinin is responsible for the transmission of pain by the nocebo effect. This research also found that drugs used to block this chemical, such as proglumide, can also stop nocebo pain. [9] [10] [11] Another of Benedetti's studies found that when individuals were told about a possible link between high altitudes and headaches before going on a high-altitude hike in the Italian Alps, it led to an enhancement of the cyclooxygenase-prostaglandin pathway in those individuals, and that they developed significantly more headaches than the control group did. [12] [13]

Impact

Benedetti has been credited as being partly responsible for the increasing respectability of research into the placebo effect. [14] A review of his book Placebo Effects: Understanding the mechanisms in health and disease in the New England Journal of Medicine stated that he runs "the foremost laboratory for the study of placebo effects in the world." [15]

Awards and honors

Benedetti is a member of the Academy of Europe and the European Dana Alliance for the Brain. Additionally, his book Placebo Effects: Understanding the mechanisms in health and disease won the British Medical Association's Highly Commended Book Award. [16]

Books

Related Research Articles

<span class="mw-page-title-main">Aspirin</span> Medication

Aspirin, also known as acetylsalicylic acid (ASA), is a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and/or inflammation, and as an antithrombotic. Specific inflammatory conditions which aspirin is used to treat include Kawasaki disease, pericarditis, and rheumatic fever.

<span class="mw-page-title-main">Nonsteroidal anti-inflammatory drug</span> Class of therapeutic drug for relieving pain and inflammation

Non-steroidal anti-inflammatory drugs (NSAID) are members of a therapeutic drug class which reduces pain, decreases inflammation, decreases fever, and prevents blood clots. Side effects depend on the specific drug, its dose and duration of use, but largely include an increased risk of gastrointestinal ulcers and bleeds, heart attack, and kidney disease.

<span class="mw-page-title-main">Transcranial magnetic stimulation</span> Form of brain stimulation using magnetic fields

Transcranial magnetic stimulation (TMS) is a noninvasive form of brain stimulation in which a changing magnetic field is used to induce an electric current at a specific area of the brain through electromagnetic induction. An electric pulse generator, or stimulator, is connected to a magnetic coil connected to the scalp. The stimulator generates a changing electric current within the coil which creates a varying magnetic field, inducing a current within a region in the brain itself.

<span class="mw-page-title-main">Placebo</span> Substance or treatment of no therapeutic value

A placebo is a substance or treatment which is designed to have no therapeutic value. Common placebos include inert tablets, inert injections, sham surgery, and other procedures.

<span class="mw-page-title-main">Diclofenac</span> Nonsteroidal anti-inflammatory drug


Diclofenac, sold under the brand name Voltaren, among others, is a nonsteroidal anti-inflammatory drug (NSAID) used to treat pain and inflammatory diseases such as gout. It is taken by mouth or rectally in a suppository, used by injection, or applied to the skin. Improvements in pain last for as much as eight hours. It is also available in combination with misoprostol in an effort to decrease stomach problems.

<span class="mw-page-title-main">Opioid</span> Psychoactive chemical

Opioids are substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, replacement therapy for opioid use disorder, reversing opioid overdose, and suppressing cough. Extremely potent opioids such as carfentanil are approved only for veterinary use. Opioids are also frequently used non-medically for their euphoric effects or to prevent withdrawal. Opioids can cause death and have been used for executions in the United States.

Anti-inflammatory is the property of a substance or treatment that reduces inflammation or swelling. Anti-inflammatory drugs, also called anti-inflammatories, make up about half of analgesics. These drugs remedy pain by reducing inflammation as opposed to opioids, which affect the central nervous system to block pain signaling to the brain.

COX-2 inhibitors are a type of nonsteroidal anti-inflammatory drug (NSAID) that directly targets cyclooxygenase-2, COX-2, an enzyme responsible for inflammation and pain. Targeting selectivity for COX-2 reduces the risk of peptic ulceration and is the main feature of celecoxib, rofecoxib, and other members of this drug class.

A nocebo effect is said to occur when negative expectations of the patient regarding a treatment cause the treatment to have a more negative effect than it otherwise would have. For example, when a patient anticipates a side effect of a medication, they can experience that effect even if the "medication" is actually an inert substance. The complementary concept, the placebo effect, is said to occur when positive expectations improve an outcome. The effect is also said to occur in someone who falls ill owing to the erroneous belief that they were exposed to a toxin, or to a physical phenomenon they believe is harmful, such as EM radiation.

<span class="mw-page-title-main">Hyperalgesia</span> Abnormally increased sensitivity to pain

Hyperalgesia is an abnormally increased sensitivity to pain, which may be caused by damage to nociceptors or peripheral nerves and can cause hypersensitivity to stimulus. Prostaglandins E and F are largely responsible for sensitizing the nociceptors. Temporary increased sensitivity to pain also occurs as part of sickness behavior, the evolved response to infection.

<span class="mw-page-title-main">Indometacin</span> Anti-inflammatory drug

Indometacin, also known as indomethacin, is a nonsteroidal anti-inflammatory drug (NSAID) commonly used as a prescription medication to reduce fever, pain, stiffness, and swelling from inflammation. It works by inhibiting the production of prostaglandins, endogenous signaling molecules known to cause these symptoms. It does this by inhibiting cyclooxygenase, an enzyme that catalyzes the production of prostaglandins.

An adverse effect is an undesired harmful effect resulting from a medication or other intervention, such as surgery. An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. The term complication is similar to adverse effect, but the latter is typically used in pharmacological contexts, or when the negative effect is expected or common. If the negative effect results from an unsuitable or incorrect dosage or procedure, this is called a medical error and not an adverse effect. Adverse effects are sometimes referred to as "iatrogenic" because they are generated by a physician/treatment. Some adverse effects occur only when starting, increasing or discontinuing a treatment. Adverse effects can also be caused by placebo treatments . Using a drug or other medical intervention which is contraindicated may increase the risk of adverse effects. Adverse effects may cause complications of a disease or procedure and negatively affect its prognosis. They may also lead to non-compliance with a treatment regimen. Adverse effects of medical treatment resulted in 142,000 deaths in 2013 up from 94,000 deaths in 1990 globally.

A prostaglandin antagonist is a hormone antagonist acting upon one or more prostaglandins, a subclass of eicosanoid compounds which function as signaling molecules in numerous types of animal tissues.

<span class="mw-page-title-main">Proglumide</span> Chemical compound

Proglumide (Milid) is a drug that inhibits gastrointestinal motility and reduces gastric secretions. It acts as a cholecystokinin antagonist, which blocks both the CCKA and CCKB subtypes. It was used mainly in the treatment of stomach ulcers, although it has now been largely replaced by newer drugs for this application.

<span class="mw-page-title-main">Mechanism of action of aspirin</span>

Aspirin causes several different effects in the body, mainly the reduction of inflammation, analgesia, the prevention of clotting, and the reduction of fever. Much of this is believed to be due to decreased production of prostaglandins and TXA2. Aspirin's ability to suppress the production of prostaglandins and thromboxanes is due to its irreversible inactivation of the cyclooxygenase (COX) enzyme. Cyclooxygenase is required for prostaglandin and thromboxane synthesis. Aspirin acts as an acetylating agent where an acetyl group is covalently attached to a serine residue in the active site of the COX enzyme. This makes aspirin different from other NSAIDs, which are reversible inhibitors. However, other effects of aspirin, such as uncoupling oxidative phosphorylation in mitochondria, and the modulation of signaling through NF-κB, are also being investigated. Some of its effects are like those of salicylic acid, which is not an acetylating agent.

The word placebo was used in a medicinal context in the late 18th century to describe a "commonplace method or medicine" and in 1811 it was defined as "any medicine adapted more to please than to benefit the patient". Although this definition contained a derogatory implication, it did not necessarily imply that the remedy had no effect.

Tor D. Wager is the Diana L. Taylor Distinguished Professor in Neuroscience at Dartmouth College, as well as the director of the Cognitive and Affective Neuroscience Laboratory at this university. He is known for his research into the placebo effect and into the way the brain processes pain.

Placebo analgesia occurs when the administration of placebos leads to pain relief. Because placebos by definition lack active ingredients, the effect of placebo analgesia is considered to result from the patient's belief that they are receiving an analgesic drug or other medical intervention. It has been shown that, in some cases, the endogenous opioid system is critical for mediating placebo analgesia, as evidenced by the ability of such analgesia to be reduced by the opioid antagonist naloxone. However, it is also possible for placebo analgesia to be mediated by non-opioid mechanisms, in which case it would not be affected by naloxone. Other research has indicated that the human spinal cord, prefrontal cortex, and rostral anterior cingulate cortex also play a role in placebo analgesia.

Prostaglandin inhibitors are drugs that inhibit the synthesis of prostaglandin in human body. There are various types of prostaglandins responsible for different physiological reactions such as maintaining the blood flow in stomach and kidney, regulating the contraction of involuntary muscles and blood vessels, and act as a mediator of inflammation and pain. Cyclooxygenase (COX) and Phospholipase A2 are the major enzymes involved in prostaglandin production, and they are the drug targets for prostaglandin inhibitors. There are mainly 2 classes of prostaglandin inhibitors, namely non- steroidal anti- inflammatory drugs (NSAIDs) and glucocorticoids. In the following sections, the medical uses, side effects, contraindications, toxicity and the pharmacology of these prostaglandin inhibitors will be discussed.

<span class="mw-page-title-main">Sonlicromanol</span> Chemical compound

Sonlicromanol (KH176) is a clinical-stage oral drug compound developed by Khondrion as a potential treatment for inherited mitochondrial diseases, such as Leigh's Disease, MELAS and LHON. Due to dysfunctional mitochondria, an increased level of cellular reactive oxygen species (ROS) is observed in these patients, causing a wide range of symptoms. The active metabolite of Sonlicromanol has several mechanisms of action, acting both as antioxidant and as reactive oxygen species (ROS)-redox modulator. Through selective suppression of microsomal prostaglandin E synthase-1 (mPGES-1), Sonlicromanol even has potency as anti-cancer drug for mPGES-1 overexpressing cancer like prostate cancer. Currently, Sonlicromanol is in phase II clinical trial in the KHENERGYZE, KHENEREXT and KHENERGYC studies as potent candidate in treatment for mitochondrial diseases.

References

  1. ↑ "Placebo Effects in Psychology". Oxford Bibliographies. Retrieved 17 March 2022.
  2. ↑ Planès, Sara; Villier, Céline; Mallaret, Michel (17 March 2016). "The nocebo effect of drugs". Pharmacology Research & Perspectives. 4 (2): e00208. doi:10.1002/prp2.208. ISSN   2052-1707. PMC   4804316 . PMID   27069627.
  3. ↑ Benedetti, Fabrizio (3 March 2022). "The science of placebos is fuelling quackery". Knowable Magazine. doi:10.1146/knowable-030222-3. S2CID   247265071 . Retrieved 17 March 2022.
  4. 1 2 Silberman, Steve (24 August 2009). "Placebos Are Getting More Effective. Drugmakers Are Desperate to Know Why". Wired. Retrieved 25 October 2014.
  5. ↑ Neergaard, Lauren (28 November 2005). "Expecting benefit really can help healing". USA Today. Retrieved 25 October 2014.
  6. ↑ Benedetti, F.; Pollo, A.; Colloca, L. (31 October 2007). "Opioid-Mediated Placebo Responses Boost Pain Endurance and Physical Performance: Is It Doping in Sport Competitions?". Journal of Neuroscience. 27 (44): 11934–11939. doi: 10.1523/JNEUROSCI.3330-07.2007 . PMC   6673345 . PMID   17978033.
  7. ↑ "How to cheat without cheating". The Economist. 1 November 2007. Retrieved 3 August 2015.
  8. ↑ Benedetti, Fabrizio; Carlino, Elisa; Pollo, Antonella (30 June 2010). "How Placebos Change the Patient's Brain". Neuropsychopharmacology. 36 (1): 339–354. doi:10.1038/npp.2010.81. PMC   3055515 . PMID   20592717.
  9. ↑ Benedetti, F.; Amanzio, M.; Vighetti, S.; Asteggiano, G. (15 November 2006). "The Biochemical and Neuroendocrine Bases of the Hyperalgesic Nocebo Effect". Journal of Neuroscience. 26 (46): 12014–12022. doi: 10.1523/JNEUROSCI.2947-06.2006 . PMC   6674855 . PMID   17108175.
  10. ↑ Sarchet, Penny (13 November 2011). "The nocebo effect: Wellcome Trust science writing prize essay". The Guardian. Retrieved 25 October 2014.
  11. ↑ Scudellari, Megan (1 July 2013). "Worried Sick". The Scientist. Retrieved 26 October 2014.
  12. ↑ Benedetti, Fabrizio; Durando, Jennifer; Vighetti, Sergio (May 2014). "Nocebo and placebo modulation of hypobaric hypoxia headache involves the cyclooxygenase-prostaglandins pathway". Pain. 155 (5): 921–928. doi:10.1016/j.pain.2014.01.016. PMID   24462931. S2CID   207310855.
  13. ↑ Robson, David (11 February 2015). "The contagious thought that could kill you". BBC. Retrieved 11 February 2015.
  14. ↑ Vance, Erik (27 July 2010). "Get to Know the Placebo Effect". Chicago Tribune. Retrieved 25 October 2014.
  15. ↑ Brody, Howard A. (9 April 2009). "Book Review Placebo Effects: Understanding the Mechanisms in Health and Disease By Fabrizio Benedetti. 295 pp., illustrated. New York, Oxford University Press, 2009. $59.95. 978-0-19-955912-1". New England Journal of Medicine. 360 (15): 1576–1577. doi:10.1056/NEJMbkrev0810817.
  16. ↑ Benedetti, Fabrizio (May 2011). "Ask the Experts: Is there a place for placebo analgesia in everyday clinical practice?". Pain Management. 1 (3): 211–212. doi:10.2217/pmt.11.16. ISSN   1758-1869. PMID   24646386.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.