Psychoactive Botanical Products: A Workshop Sponsored by NIDA and ODS

1. Psychoactive Botanical Products:A Workshop Sponsored by NIDA and ODS Paul M. Coates, Ph.D. Director, Office of Dietary Supplements National Institutes of Health Department of Health and Human Services

2. DSHEA(Dietary Supplement Health and Education Act - 1994) • Amended the FD & C Act • Defined dietary supplements • Established regulatory framework • Food and Drug Administration (FDA) • As foods, not as drugs • Established rules for what a label should contain • Gave FDA authority to write GMP • Called for creation of the Office of Dietary Supplements at the NIH

3. Definition of Dietary Supplement • A product (other than tobacco) intended to supplement the diet that bears or contains one or more of the following dietary ingredients: • A vitamin, mineral,amino acid, herb or other botanical; OR • A dietary substance for use to supplement the diet by increasing the total dietary intake; OR • A concentrate, metabolite, constituent, extract, or combination of any ingredient described above.

4. Dietary Supplement • Intended for ingestion in the form of a capsule, powder, softgel, or gelcap • Not represented as a conventional food or as a sole item of a meal or the diet • Excludes items that are smoked or administered sublingually • Label claims generally limited to effects on a structure or function of the body

5. Examples of Ingredients in the Dietary Supplement Category • Vitamins, minerals • Antioxidants • Creatine, carnitine • Lutein, lycopene, phytoestrogens • Soy, garlic • Omega-3 fatty acids • St. John’s wort, echinacea, ephedra • Androstenedione, DHEA • Combinations

7. Herbs: Myths and Reality • Natural  safe • Used for thousands of years  effective and safe • Herb as a plant  capsule or tablet • All brands of herbs are not the same

8. THE OFFICE OF DIETARY SUPPLEMENTS

9. ODS Mission Statement The mission of the ODS is to strengthen knowledge and understanding of dietary supplements by evaluating scientific information, stimulating and supporting research,disseminating research results, and educating the public to foster an enhanced quality of life and health for the U.S. population.

10. Much Research Is Needed • Surveys to understand and characterize use • Basic research on most supplements • Botanical supplements - mechanisms of action • Intervention studies • Clinical trials where appropriate • Effectiveness

11. Issues in Dietary Supplement Research • Safety • Efficacy • Quality

12. RESEARCH AGENDA: Analytical Methods and Reference Materials

13. Analytical Methods and Reference Materials Program • Establish priorities (botanicals and others) • Identify potential research partners • Academic, government, private sector • Initiated collaborations with USDA, FDA, NIST • Develop and validate analytical methods • Produce reference materials • Share methods and reference materials

14. RESEARCH AGENDA: Dietary Supplement Ingredient Database

15. Database of DS Ingredients • ODS held 2 workshops with other Federal agencies, academic researchers, and the private sector to explore the feasibility of developing a database of DS ingredients • Considerable research funded by NIH and other agencies on dietary supplement use • Depends on accurate measures of intake • Emerging opportunities for public-private partnership in meeting research needs • Published in J Nutrition 133: 573S – 634S, 2003

16. RESEARCH AGENDA: Evidence-Based Review

17. Evidence-Based Review Program • Systematic review of the literature, with meta-analysis as appropriate, on DS efficacy and safety • Major reason for conducting these reviews is to assist NIH in the development of an appropriate research agenda

18. Ephedra sinica Copyright Steven Foster 2003

19. Ephedra Efficacy and Safety • Ephedra efficacy and safety for weight management and athletic performance enhancement • Review included relevant reports in all languages, both published and unpublished • Released by Secretary of DHHS, Feb 2003 • Shekelle P et al, JAMA 289:1537-1545, 2003 • Conclusions: • Modest effect on weight in short term and no evidence of effect on athletic performance • Some side effects seen in trials, some very serious adverse events filed with FDA and to a major ephedra manufacturer

20. Omega-3 Fatty Acids or Photo of Menhaden courtesy of National Oceanic and Atmospheric Administration (NOAA)

21. Health Effects of Omega-3 Fatty Acids • Systematic review of the literature, with meta-analysis as appropriate, on omega-3 fatty acid supplementation for a number of health indications (prevention of heart disease, immune function enhancement, others) • A series of evidence reports will be developed over 2 years; first ones to be released in Fall 2003 • The major reason for conducting this review is to assist NIH in the development of an appropriate clinical research agenda that will address future questions

22. Solid Research on the Efficacy and Safety of Dietary Supplements • Is variable • Stronger for nutrient supplements • Diversity of available botanical supplements makes task difficult • Only passive adverse event reporting

23. Botanicals Research at NIH • Several ongoing clinical trials (e.g., ginkgo, SJW, garlic) • Not all clinical investigators have been successful in meeting recruitment projections of their clinical trials • Some trials had to be terminated, e.g. because of potential toxicity (kava) or contamination (PC SPES) • Formidable challenge of obtaining quality products for use in trials

24. Issues in Conducting Efficacy Research on Dietary Supplements • Cost • Federal investment, partnership • Quality of Product/Intervention • Characterization, reliability • Endpoints/Markers • Supplement vs. drug • Generalizability of Results • Diseased vs. healthy population