PLACEBO - Mind-Body Medicine

Forensic Psychiatry & Medicine - Dec. 9, 2002

The placebo effect baffles patients, confounds clinicians and frustrates drug developers. Until now, relatively little empirical evidence existed for the biological mechanisms that underlie the effect. But recently, researchers have begun approaching the challenge with methodological rigor. Understanding the biological basis of the placebo effect has potentially wide-ranging implications.

PAIN AND PLACEBO

Researchers have already reported intriguing findings. For years, opioids were known to play a significant role in the placebo effect in some contexts. In 1978, scientists demonstrated that an opioid blocker called naloxone could abolish the placebo effect in a pain experiment. A 2001 study demonstrated that the simple interaction between patient and practitioner has measurable effects in the brain. Researchers in Italy, led by Fabrizio Benedetti, found that "open" injections of analgesics (patient-witnessed) were significantly more effective and less variable than "hidden" injections (patients were ignorant of injections). Furthermore, they showed that by blocking the opioids, naloxone greatly reduces this open-injection placebo effect, suggesting that the therapist-patient interaction activates the endogenous opioid systems. "We are beginning to understand what happens in the patient's brain when he or she interacts with his or her therapist," says Benedetti, a physiology professor at the University of Turin Medical School.

In 2002, a Swedish research group caught the relationship of pain and placebo in action using positron emission tomography (PET), and showed that placebo and opioid analgesia may have a common neural mechanism. Nine subjects were exposed to standardized, brief, nonharmful, painful experiences. They received either no treatment or an injection of either placebo or analgesic. Subsequent PET scans indicated activation of the rostral anterior cingulate cortex for both treatments, though analgesic did provide more pain relief.


PLACEBO AND DEPRESSION

Researchers gave 17 severely depressed men either placebo or fluoxetine (Prozac). Scans taken at one and six weeks showed that both groups exhibited increased activity in the cortex and decreased activity in limbic regions, but only patients given fluoxetine experienced changes in brain stem, striatum, and hippocampus. "Drug is placebo plus," explains lead author Helen Mayberg, a psychiatry and neurology professor, University of Toronto.


http://www.forensic-psych.com/articles/artPlaceboeffect12.02.html When you open this link you will see three PET Scan images (upper left) for comparison showing the height of opioid treatment (left image), high-placebo responders (middle image) and nonresponders (right image).

National Institutes of Health

Physiology of Expectancy (Placebo Response)

Placebo effects are believed to be mediated by both cognitive and conditioning mechanisms. Until recently, little was known about the role of these mechanisms in different circumstances. Now, research has shown that placebo responses are mediated by conditioning when unconscious physiological functions such as hormonal secretion are involved, whereas they are mediated by expectation when conscious physiological processes such as pain and motor performance come into play, even though a conditioning procedure is carried out.

Positron emission tomography (PET) scanning of the brain is providing evidence of the release of the endogenous neurotransmitter dopamine in the brain of Parkinson's disease patients in response to placebo. Evidence indicates that the placebo effect in these patients is powerful and is mediated through activation of the nigrostriatal dopamine system, the system that is damaged in Parkinson's disease. This result suggests that the placebo response involves the secretion of dopamine, which is known to be important in a number of other reinforcing and rewarding conditions, and that there may be mind-body strategies that could be used in patients with Parkinson's disease in lieu of or in addition to treatment with dopamine-releasing drugs.


National Center for Complementary and Alternative Medicine article: http://nccam.nih.gov/health/backgrounds/mindbody.htm (scroll down)

2002 Nov 15;136(2):359-63.

Dopamine release in human ventral striatum and expectation of reward.

de la Fuente-Fernandez R, Phillips AG, Zamburlini M, Sossi V, Calne DB, Ruth TJ, Stoessl AJ.

Pacific Parkinson's Research Centre, Vancouver Hospital and Health Sciences Center, University of British Columbia, Purdy Pavilion, 2221 Westbrook Mall, Vancouver, BC, Canada V6T 2B5.

Using the ability of <11C>raclopride to compete with dopamine for D(2)/D(3) receptors, we investigated by positron emission tomography the effect of placebo (saline) injection on dopamine release in the ventral striatum of patients with Parkinson's disease. We found evidence for placebo-induced dopamine release of similar magnitude to that reported in healthy volunteers after amphetamine administration. However, in contrast to the dorsal striatum, there were no differences in <11C>raclopride binding potential changes between patients who experienced the reward (those who reported placebo-induced clinical benefit) and those who did not. We conclude that the release of dopamine in the ventral striatum (nucleus accumbens) is related to the expectation of reward and not to the reward itself. These observations have potential implications for the treatment of drug addiction. Copyright 2002 Elsevier Science B.V.

Publication Types:
PMID: 12429397

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12429397&query_hl=1&itool=pubmed_docsum

Swedish study leader Martin Ingvar says his research is partially motivated by shortcomings in patient care and a troubled drug industry. "In spite of more and more effective medicines, patients are complaining about less and less effects," says Ingvar, a cognitive neurophysiology professor. "Explaining all drug effects by pure molecular mechanisms will underexpose the effects of drugs."

http://www.forensic-psych.com/articles/artPlaceboeffect12.02.html

My thinking is that expectancy could potentiate the benefit of the drug. As you point out, the use of placebo effect can get into a paternalistic assumption. But, if the drug is being prescribed anyway, it seems like a good questionnaire and screening could avoid this trap by uncovering the patient's true goals thereby allowing allopathic medicine access to a powerful tool.

http://www.democraticunderground.com/discuss/duboard.php?az=view_all&address=222x4850#4883