PC SPES

Dietary supplement of chrysanthemum, licorice, ginseng, saw palmetto, scutellaria, and three other herbs

Used for advanced prostate cancer Small Phase I/II studies suggest safety,

improved quality of life, reduction of pain, and lower PSA levels (Pfeifer, BJU Int., 2000)

Loss of libido, breast tenderness, and lower PSA levels associated with potent estrogenic activity (DiPaola, NEJM, 1998)

PC SPES for Prostate Cancer

P.I. Adrian S. Dobs, MD, MHS, Johns Hopkins University

Background Multiple, small pre-clinical and clinical studies

Enrollment 100 men with hormone-refractory disease, rising PSAs

Design Double-blind, randomized controlled trial vs. estradiol

Sites Johns Hopkins and Singapore

Endpoints Disease progression, PSA, quality of life, safety

Identification of PC SPES-Regulated Genes in Prostate Epithelial Cells

Nelson, 2001

Dietary Supplement Research

Effectiveness

Mechanisms

Interactions

CAM Domains

Biologically Based Systems

Manipulative and Body-Based Systems

Mind-Body Medicine

Alternative Medical Systems

Energy Therapies

Diets Herbals

Homeopathy Naturopathy

Yoga Prayer

Meditation

Massage Chiropractic

Reiki Magnets Qi qong

CommonCAM

Practices

What Is Hypnosis?

Intense focus on a suggested response leads to involuntary changes in perception, mood, memory, or physiology

Subject of great controversy and popular misunderstandings since developed by Mesmer in 18th C. France

Hypnosis Alters Color Processing in the Brain

8 hypnotizable subjects viewed identical patterns in color or gray scale during PET scanning

Randomly told to see color or gray scale

Blood flow to cortical color processing regions increased when asked to perceive color and decreased when told to see gray scale, regardless of what they were actually shown

Kosslyn SM, Thompson, WL, Spiegel D, et al. Am J Psychiatry 2000;157:1279-84

Kosslyn SM, Thompson, WL, Spiegel D, et al. Am J Psychiatry 2000;157:1279-84

Kosslyn SM, Thompson, WL, Spiegel D, et al. Am J Psychiatry 2000;157:1279-84

Kosslyn SM, Thompson, WL, Spiegel D, et al. Am J Psychiatry 2000;157:1279-84

The Placebo

Historically, an inactive or innocent management contrivance to encourage healing in the absence of specific therapeutics

Relied upon to “control” for nonspecific effects that might confound calculation of the true benefits of a novel intervention

The Placebo – A ‘Pious Fraud’

“One of the most successful physicians I have ever known has assured me that he used more bread pills, drops of coloured water, and powders of hickory ashes, than all other medicines put together.”

Thomas Jefferson (1743-1826)

‘The Powerful Placebo’

Analysis of the aggregate percentage of patients satisfactorily relieved by a placebo across multiple clinical trials

1082 patients in 15 controlled trials

35.2 ± 2.2% “average significant effectiveness”

HK Beecher, JAMA, 1955

‘The Powerless Placebo’

Systematic review of outcomes for 8525 subjects in 116 controlled trials

No overall benefit attributable to placebo

Significant differences only for continuous subjective outcomes

27% (95% CI of 15-40%) reduction in pain associated with placebo

Hrobjartsson & Gotzche, NEJM, 2001

“Such a report can hardly negate an experienced physician’s awe at a phenomenon that might impress even a dispassionate biometrician, should he ever venture within the range of a real patient.”

S.B. Nuland, The American Scholar, 2001

Placebo Analgesia: Spatially Specific and Mediated by

Endogenous Opioid Systems

Pain induced in all 4 limbs with capsaicin

Patients told they were to receive a powerful local anesthetic

Placebo cream applied to 1 limb

Analgesia achieved only in the treated limb

Analgesia abolished by IV naloxone

Benedetti et al., J Neurosci, 1999

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This Is Your Brain on Placebo

Petrovic, PP et al. February 7 2002; 10.1126/science.1068836, Science Express Reports

Placebo and Opioid Analgesia - Imaging a Shared Neuronal Network

rostral anterior

cingulate cortex

The Placebo Effect

Relieves pain

Works through the opioid system

Anatomically specific

Shares the same neuronal pathways as narcotics

BMJ BooksMarch 6, 2002

Edited by:Harry A. GuessArthur KleinmanJohn W. KusekLinda W. Engel

RFAs Elucidation of the Underlying

Mechanisms of Placebo Effect

The Placebo Effect in Clinical Practice

Evidence Leads to Understanding

Potential benefits of dietary supplements may be offset by untoward drug interactions.

The mind-body dialogue yields powerful, even surprising, physiological responses.

Evidence Leads to Understanding

Understanding Leads to Acceptance

CAM will be integrated with conventional medicine as science affords a fuller understanding of its benefits and risks.

Charles Rosenberg, Ph.D.Professor of the History of Science

Harvard University July 18, 2002

Alternative to What? Complementary to Whom? On Some Aspects of Medicine's Scientific Identity

Arthur Kleinman, M.D.Professor of Social Anthropology

Harvard UniversityLillian Presley Professor of Medical

Anthropology and PsychiatryHarvard Medical School

November 7, 2002The Global Transformation of Health Care: Cultural and Ethical Challenges to Medicine

N a t i o n a l C e n t e r f o r C o m p l e m e n t a r y a n d A l t e r n a t i v e M e d i c i n e