PC SPES

1. 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)

2. PC SPES for Prostate Cancer

3. Identification of PC SPES-Regulated Genes in Prostate Epithelial Cells Nelson, 2001

4. Dietary Supplement Research • Effectiveness • Mechanisms • Interactions

5. 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

6. 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

7. 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

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

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

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

11. 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

12. 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)

13. ‘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

14. ‘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

15. “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

16. 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

17. 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

18. 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

19. 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

20. The Placebo Effect • Relieves pain • Works through the opioid system • Anatomically specific • Shares the same neuronal pathways as narcotics

21. RFAs • Elucidation of the Underlying Mechanisms of Placebo Effect • The Placebo Effect in Clinical Practice BMJ Books March 6, 2002 Edited by: Harry A. Guess Arthur Kleinman John W. Kusek Linda W. Engel

22. Evidence Leads to Understanding Potential benefits of dietary supplements may be offset by untoward drug interactions.

23. Evidence Leads to Understanding The mind-body dialogue yields powerful, even surprising, physiological responses.

24. Understanding Leads to Acceptance CAM will be integrated with conventional medicine as science affords a fuller understanding of its benefits and risks.

29. 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

30. 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