Exploring the Scientific Basis of Complementary and Alternative Medicine. Part I

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. Background Enrollment Design Sites Adrian S. Dobs, MD, MHS, Johns Hopkins University Multiple, small pre-clinical and clinical studies 100 men with hormone-refractory disease, rising PSAs Double-blind, randomized controlled trial vs. estradiol 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 Massage Chiropractic Manipulative and Body-Based Systems Energy Therapies Reiki Magnets Qi qong Common CAM Practices Yoga Prayer Meditation Mind-Body Medicine Homeopathy Naturopathy Alternative Medical Systems 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 pain 10 pain 0 0 minutes 15 0 0 minutes 15 Left Hand Right Hand Left Foot 10 pain pain Right Foot 10 0 0 minutes 15 0 0 Benedetti et al. 1999 minutes 15 10 pain 10 pain 0 0 minutes 15 0 0 minutes 15 Left Hand Right Hand Left Foot 10 pain pain Right Foot 10 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