The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research Committee on the Health Effects of Marijuana: An Evidence Review and Research Agenda Board on Population Health and Public Health Practice Health and Medicine Division A Report of PREPUBLICATION COPY—UNCORRECTED PROOFS Copyright © National Academy of Sciences. All rights reserved. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research THE NATIONAL ACADEMIES PRESS 500 Fifth Street, NW Washington, DC 20001 This activity was supported by Grant No. ADHS16-113368 from the Arizona Department of Health Services, Grant No. 910-16-SC from the CDC Foundation, Grant No. 200-2011-38807, Task Order #47 from the Centers for Disease Control and Prevention, Grant No. HHSN263201200074I, Task Order #91 from the National Institutes of Health, and Grant No. 151027 from Oregon Health Authority. Additional support was received by Alaska Mental Health Trust Authority; California Department of Public Health; Mat-Su Health Foundation; National Highway Traffic Safety Administration; National Institutes of Health/National Cancer Institute; National Institutes of Health/National Institute on Drug Abuse; The Colorado Health Foundation; The Robert W. Woodruff Foundation; Truth Initiative; U.S. Food and Drug Administration; and Washington State Department of Health. Any opinions, findings, conclusions, or recommendations expressed in this publication do not necessarily reflect the views of any organization or agency that provided support for the project. International Standard Book Number-13: 978-0-309-XXXXX-X International Standard Book Number-10: 0-309-XXXXX-X Digital Object Identifier: 10.17226/24625 Library of Congress Control Number: Additional copies of this publication are available for sale from the National Academies Press, 500 Fifth Street, NW, Keck 360, Washington, DC 20001; (800) 624-6242 or (202) 334-3313; http://www.nap.edu. Copyright 2017 by the National Academy of Sciences. All rights reserved. Printed in the United States of America Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2017. The health effects of cannabis and cannabinoids: The current state of evidence and recommendations for research. Washington, DC: The National Academies Press. doi: 10.17226/24625. PREPUBLICATION COPY—UNCORRECTED PROOFS Copyright © National Academy of Sciences. All rights reserved. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research The National Academy of Sciences was established in 1863 by an Act of Congress, signed by President Lincoln, as a private, nongovernmental institution to advise the nation on issues related to science and technology. Members are elected by their peers for outstanding contributions to research. Dr. Marcia McNutt is president. The National Academy of Engineering was established in 1964 under the charter of the National Academy of Sciences to bring the practices of engineering to advising the nation. Members are elected by their peers for extraordinary contributions to engineering. Dr. C. D. Mote, Jr., is president. The National Academy of Medicine (formerly the Institute of Medicine) was established in 1970 under the charter of the National Academy of Sciences to advise the nation on medical and health issues. Members are elected by their peers for distinguished contributions to medicine and health. Dr. Victor J. Dzau is president. The three Academies work together as the National Academies of Sciences, Engineering, and Medicine to provide independent, objective analysis and advice to the nation and conduct other activities to solve complex problems and inform public policy decisions. The National Academies also encourage education and research, recognize outstanding contributions to knowledge, and increase public understanding in matters of science, engineering, and medicine. Learn more about the National Academies of Sciences, Engineering, and Medicine at www.national- academies.org. PREPUBLICATION COPY—UNCORRECTED PROOFS Copyright © National Academy of Sciences. All rights reserved. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research Reports document the evidence-based consensus of an authoring committee of experts. Reports typically include findings, conclusions, and recommendations based on information gathered by the committee and committee deliberations. Reports are peer reviewed and are approved by the National Academies of Sciences, Engineering, and Medicine. Proceedings chronicle the presentations and discussions at a workshop, symposium, or other convening event. The statements and opinions contained in proceedings are those of the participants and have not been endorsed by other participants, the planning committee, or the National Academies of Sciences, Engineering, and Medicine. For information about other products and activities of the Academies, please visit nationalacademies.org/whatwedo. PREPUBLICATION COPY—UNCORRECTED PROOFS Copyright © National Academy of Sciences. All rights reserved. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research COMMITTEE OF THE HEALTH EFFECTS OF MARIJUANA: AN EVIDENCE REVIEW AND RESEARCH AGENDA MARIE McCORMICK (Chair), Professor, Harvard T. H. Chan School of Public Health, Harvard University, Boston, MA DONALD I. ABRAMS, Professor of Medicine, University of California, San Francisco, and Chief of Hematology–Oncology Division, Zuckerberg San Francisco General Hospital, San Francisco, CA MARGARITA ALEGRÍA, Chief, Disparities Research Unit, Department of Medicine, Massachusetts General Hospital, Boston WILLIAM CHECKLEY, Associate Professor of Medicine, Division of Pulmonary and Critical Care, Johns Hopkins University, Baltimore, MD R. LORRAINE COLLINS, Associate Dean for Research, School of Public Health and Health Professions and Professor, Department of Community Health and Health Behavior, State University of New York at Buffalo–South Campus, Buffalo, NY ZIVA COOPER, Assistant Professor of Clinical Neurobiology, Department of Psychiatry, Columbia University Medical Center, New York, NY ADRE J. DU PLESSIS, Director, Fetal Medicine Institute; Division Chief of Fetal and Transitional Medicine; and Director, Fetal Brain Program, Children’s National Health System, Fetal Medicine Institute, Children’s National Health System, Washington, DC SARAH FELDSTEIN EWING, Professor, Department of Child and Adolescent Psychiatry, Oregon Health & Science University, Portland SEAN HENNESSY, Professor of Epidemiology, Systems Pharmacology, and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia KENT HUTCHISON, Professor, Department of Psychology and Neuroscience, University of Colorado Boulder NORBERT E. KAMINSKI, Professor, Pharmacology and Toxicology, and Director, Institute for Integrative Toxicology, Department of Pharmacology and Toxicology, Michigan State University, East Lansing SACHIN PATEL, Associate Professor and Director, Division of Addiction Psychiatry, Department of Psychiatry and Behavioral Sciences, Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, TN DANIELE PIOMELLI, Professor, Anatomy and Neurobiology, School of Medicine and Louise Turner Chair in Neurosciences, Department of Anatomy and Neurobiology, University of California, Irvine STEPHEN SIDNEY, Director of Research Clinics, Division of Research, Kaiser Permanente Northern California, Oakland, CA ROBERT B. WALLACE, Irene Ensminger Stecher Professor of Epidemiology and Internal Medicine, Department of Epidemiology, University of Iowa College of Public Health, Iowa City JOHN WILEY WILLIAMS, Professor of Medicine, Duke University Medical Center, Durham, NC Study Staff LEIGH MILES JACKSON, Study Director JENNIFER A. COHEN, Program Officer KELSEY GEISER, Research Associate (from July 2016) R. BRIAN WOODBURY, Research Associate SARA THARAKAN, Research Associate (until July 2016) HOPE R. HARE, Administrative Assistant v PREPUBLICATION COPY—UNCORRECTED PROOFS Copyright © National Academy of Sciences. All rights reserved. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research MATTHEW MASIELLO, Research Assistant (from June 2016) MARJORIE PICHON, Senior Program Assistant (from August 2016) KATHLEEN STRATTON, Scholar ROSE MARIE MARTINEZ, Senior Board Director, Board on Population Health and Public Health Practice Norman F. Grant/American Board of Obstetrics and Gynecology Fellow BROWNSYNE TUCKER EDMONDS, Assistant Professor of Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis Consultants STEVEN DAVENPORT, BOTEC Analysis Corporation TAMAR LASKY, MIE Resources, Maryland LEANN LOCHER, LeAnn Locher and Associates GUILLERMO MORENO-SANZ, University of California, Irvine BRYCE PARDO, BOTEC Analysis Corporation vi PREPUBLICATION COPY—UNCORRECTED PROOFS Copyright © National Academy of Sciences. All rights reserved. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research Reviewers This report has been reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise. The purpose of this independent review is to provide candid and critical comments that will assist the institution in making its published report as sound as possible and to ensure that the report meets institutional standards for objectivity, evidence, and responsiveness to the study charge. The review comments and draft manuscript remain confidential to protect the integrity of the deliberative process. We wish to thank the following individuals for their review of this report: Eric Bass, Johns Hopkins University Jonathan P. Caulkins, Carnegie Mellon University Mary D’Alton, Columbia University Medical Center Raul Gonzalez, Florida International University Frank F. Furstenberg, Jr., University of Pennsylvania Eden Evins, Massachusetts General Hospital Mark A. Ware, McGill University Mark Helfand, Oregon Health and Science University Larry A. Walker, The University of Mississippi Medical Center Donald P. Tashkin, University of California, Los Angeles David Geffen School of Medicine David A. Kessler, University of California, San Francisco Igor Grant, University of California, San Diego School of Medicine Robin Mermelstein, University of Illinois at Chicago Aron Lichtman, Virginia Commonwealth University John H. Krystal, Yale University School of Medicine Although the reviewers listed above have provided many constructive comments and suggestions, they were not asked to endorse the conclusions or recommendations nor did they see the final draft of the report before its release. The review of this report was overseen by Eric B. Larson, Group Health Research Institute, and Bobbie A. Berkowitz, Columbia University Medical Center. They were responsible for making certain that an independent examination of this report was carried out in accordance with institutional procedures and that all review comments were carefully considered. Responsibility for the final content of this report rests entirely with the authoring committee and the institution. vii PREPUBLICATION COPY—UNCORRECTED PROOFS Copyright © National Academy of Sciences. All rights reserved. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research Copyright © National Academy of Sciences. All rights reserved. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research Acknowledgments This report reflects contributions from a number of individuals and groups. The committee takes this opportunity to recognize those who so generously gave their time and expertise to inform its deliberations. To begin, the committee would like to thank the sponsors of this study for their guidance and support. Support for the committee’s work was generously provided by the Alaska Mental Health Trust Authority; Arizona Department of Health Services; California Department of Public Health; CDC Foundation; Centers for Disease Control and Prevention; Mat-Su Health Foundation; National Highway Traffic Safety Administration; National Institutes of Health/National Cancer Institute; National Institutes of Health/National Institute on Drug Abuse; Oregon Health Authority; The Colorado Health Foundation; The Robert W. Woodruff Foundation; Truth Initiative; U.S. Food and Drug Administration; and Washington State Department of Health. The committee greatly benefited from the opportunity for discussion with individuals who attended and presented at their open session meetings (see Appendix D). The committee is thankful for the many contributions of these individuals. The committee could not have done its work without the support and guidance provided by the National Academies project staff: Leigh Miles Jackson, study director; Jennifer Cohen, program officer; Kelsey Geiser, research associate; R. Brian Woodbury, research associate; Sara Tharakan, research associate; Matthew Masiello, research assistant; and Marjorie Pichon, senior program assistant. The committee is also grateful to Hope R. Hare and Doris Romero for their administrative and financial assistance on this project, and gratefully acknowledges Kathleen Stratton and Rose Marie Martinez of the Board on Population Health and Public Health Practices for the guidance they provided throughout this important study. Many other staff within the National Academies provided support to this project in various ways. The committee would like to thank the executive office staff of the Health and Medicine Division (HMD), as well as Lauren Shern, Janice Mehler, and the staff in the HMD Office of Reports and Communication for the management of the report review process. We would like to thank Rebecca Morgan and the National Academies Research Center staff for their assistance in the committee’s research efforts, and the National Academies Press staff. We thank Steven Davenport, Tamar Lasky, Guillermo Moreno-Sanz, and Bryce Pardo for their valuable commissioned work, and we are grateful to LeAnn Locher for her creative efforts in our graphic design projects. Finally, Robert Pool is to be credited for his superb editorial assistance in preparing this report. ix PREPUBLICATION COPY—UNCORRECTED PROOFS Copyright © National Academy of Sciences. All rights reserved. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research Copyright © National Academy of Sciences. All rights reserved.