PC%20SPES

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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)

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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
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Identification of PC SPES-Regulated Genes in
Prostate Epithelial Cells
Nelson, 2001
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Dietary Supplement Research

• Effectiveness
• Mechanisms
• Interactions

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CAM Domains
Manipulative and Body-Based Systems
Biologically Based Systems
Massage Chiropractic
Diets Herbals
Common CAM Practices
Yoga Prayer Meditation
Reiki Magnets Qi qong
Mind-Body Medicine
Energy Therapies
Homeopathy Naturopathy
Alternative Medical Systems
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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

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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 20001571279-84
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Kosslyn SM, Thompson, WL, Spiegel D, et al. Am J
Psychiatry 20001571279-84
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Kosslyn SM, Thompson, WL, Spiegel D, et al. Am J
Psychiatry 20001571279-84
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Kosslyn SM, Thompson, WL, Spiegel D, et al. Am J
Psychiatry 20001571279-84
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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

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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)
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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

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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

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Such a report can hardly negate an experienced
physicians 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
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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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10
10
pain
pain
0
0
0
15
0
15
minutes
minutes
Right Hand
Left Hand
Placebo
expectation
Placebo
expectation
Right Foot
Left Foot
10
10
pain
pain
0
0
0
15
0
15
minutes
minutes
Benedetti et al. 1999
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10
10
pain
pain
0
0
0
15
0
15
minutes
minutes
Right Hand
Left Hand
Placebo
expectation
Naloxone
Placebo
expectation
Right Foot
Left Foot
10
10
pain
pain
0
0
0
15
0
15
minutes
minutes
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This Is Your Brain on Placebo
rostral anterior cingulate cortex
Placebo and Opioid Analgesia - Imaging a Shared
Neuronal Network
Petrovic, PP et al. February 7 2002
10.1126/science.1068836, Science Express Reports
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The Placebo Effect

• Relieves pain
• Works through the opioid system
• Anatomically specific
• Shares the same neuronal pathways as narcotics

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BMJ Books March 6, 2002 Edited by Harry A.
Guess Arthur Kleinman John W. Kusek Linda W. Engel
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Evidence Leads to Understanding
Potential benefits of dietary supplements may be
offset by untoward drug interactions.
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Evidence Leads to Understanding
The mind-body dialogue yields powerful, even
surprising, physiological responses.
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Understanding Leads to Acceptance
CAM will be integrated with conventional medicine
as science affords a fuller understanding of its
benefits and risks.
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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 University Lillian Presley
Professor of Medical Anthropology and
Psychiatry Harvard Medical School November 7, 2002
The Global Transformation of Health Care
Cultural and Ethical Challenges to Medicine
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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