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 SPESRegulated Genes in Prostate
Epithelial Cells
Nelson, 2001
Dietary Supplement Research
Effectiveness
Mechanisms
Interactions
CAM Domains
Biologically
Based Systems
Diets
Herbals
Energy
Therapies
Reiki
Magnets
Qi qong
Massage
Chiropractic
Common
CAM
Practices
Manipulative and
Body-Based
Systems
Yoga
Prayer
Meditation
Homeopathy
Naturopathy
Alternative Medical Systems
Mind-Body
Medicine
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
10
10
pain
pain
0
0
0
0
15
minutes
minutes
15
Right Hand
Left Hand
Right Foot
Left Foot
10
10
pain
pain
0
0
minutes
0
0
15
Benedetti et al. 1999
minutes
15
10
10
pain
pain
0
0
15
minutes
Left Hand
0
0
15
Right Hand
Right Foot
Left Foot
10
minutes
10
pain
pain
0
0
minutes
15
0
0
minutes
15
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.10688
36, Science Express
Reports
The Placebo Effect
Relieves pain
Works through the opioid
system
Anatomically specific
Shares the same neuronal
pathways as narcotics
BMJ Books
March 6, 2002
Edited by:
Harry A. Guess
Arthur Kleinman
John W. Kusek
Linda 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.
Evidence Leads to
Understanding
The mind-body dialogue yields
powerful, even surprising,
physiological responses.
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 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
National Center for Complementary and Alternative Medicine