SCHEDULING CANNABIS: A PREPARATORY DOCUMENT FOR FDA’S 8-FACTOR ANALYSIS ON CANNABIS A SCIENTIFIC APPROACH FOR CONGRESS, DRUG ENFORCEMENT ADMINISTRATION, AND DEPARTMENT OF JUSTICE Prepared by Americans for Safe Access (2016) Reviewed by Jahan Marcu, Ph.D., Ethan Russo MD, Lumir Hanus, Ph.D., Roger Pertwee, Ph.D., Steph Sherer, and Jason Schechter, Ph.D. ASA | Scheduling Cannabis: A PreparaTory DocumenT for FDA’s 8-FacTor Analysis on Cannabis The research and analysis in this report was conducted by Americans for Safe Access Foundation, a 501(c)(3) non-profit organization. Publication date July 2016 With over 100,000 active members in all 50 states, Americans for Safe Access (ASA) is the largest national member-based organization of patients, medical professionals, scientists and concerned citizens promoting safe and legal access to cannabis for therapeutic use and research. ASA works to overcome political and legal barriers by creating policies that improve access to medical cannabis for patients and researchers through legislation, education, litigation, grassroots actions, advocacy and services for patients and their caregivers, the medical cannabis industry, and governments. Copyright © 2016 Americans for Safe Access Foundation™ All rights reserved. No part of this publication may be reproduced in any form by any electronic or mechanical means without permission in writing from Americans for Safe Access. Learn more about ASA at AmericansForSafeAccess.org. 1624 U Street NW, Suite 200, Washington, D.C. 20009 Phone: 1-888-929-4367 fax: 202.857.4273 2 | Americans for Safe Access A Scientific Approach for Congress, Drug Enforcement Administration, and Department of Justice TABLE OF CONTENTS I. InTroducTion .......................................................................................................................................................... 5 II. Background ......................................................................................................................................................... 6 III. EvaluaTing Cannabis Under The 8 FacTors ................................................................................................ 9 Factor 1: Cannabis’ Actual or Relative Potential for Abuse ............................................................................................. 9 a. Individuals are not taking the substance in amounts sufficient to create a hazard to their health or to the safety of other individuals or to the community. ............................................................................................................................ 10 b. There is no significant diversion of the drug or substance from legitimate drug channels. ................. 26 c. Individuals are not taking the substance on their own initiative, rather on the basis of medical advice from a practitioner licensed by law to administer such substances. .................................................................................. 27 d. The substance is not so related in its action to a substance already listed as having a potential for abuse to make it likely that it will have the same potential for abuse as such substance, thus it is not reasonable to assume that there may be significant diversions from legitimate channels, significant use contrary to or without medical advice, or that it has a substantial capability of creating hazards to the health of the user or to the safety of the community. 28 Factor 2: Scientific Evidence of the Pharmacological Effects and General Pharmacology of Cannabis .... 28 Basic Pharmacology ................................................................................................................................................................... 29 Central Nervous System Effects ........................................................................................................................................... 30 Human Behavioral Effects ....................................................................................................................................................... 31 Cardiovascular ............................................................................................................................................................................. 31 Respiratory .................................................................................................................................................................................... 32 Endocrine Systems ..................................................................................................................................................................... 32 Immune System ........................................................................................................................................................................... 34 Factor 3: The State of Current Scientific Knowledge Regarding the Drug or Other Substance ..................... 34 Chemistry ....................................................................................................................................................................................... 34 Human Pharmacokinetics ....................................................................................................................................................... 35 Metabolism .................................................................................................................................................................................... 35 Distribution ................................................................................................................................................................................... 36 Excretion ........................................................................................................................................................................................ 36 Absorption and Bioavailability ............................................................................................................................................. 36 Inhalation ....................................................................................................................................................................................... 36 Oral Administration ................................................................................................................................................................... 37 Opthalmic Administration ...................................................................................................................................................... 38 Sublingual Administration ...................................................................................................................................................... 38 Dermal Administration ............................................................................................................................................................ 38 Rectal Administration ............................................................................................................................................................... 38 Plasma Levels vs. Administration Routes ........................................................................................................................ 38 Americans for Safe Access 3 ASA | Scheduling Cannabis: A PreparaTory DocumenT for FDA’s 8-FacTor Analysis on Cannabis Medical Uses for Marijuana/Cannabis ............................................................................................................................... 39 List of Medical and Scientific Organizations that have Issued Letter of Support for Medical Cannabis57 Factors 4 & 5: Its History and Current Pattern of Abuse & the Scope, Duration, and Significance of Abuse 59 Use and Abuse .............................................................................................................................................................................. 59 Abuse of Cannabis ...................................................................................................................................................................... 62 Cannabis and Dronabinol ........................................................................................................................................................ 68 Cannabis as Gateway Drug ..................................................................................................................................................... 70 Side Effects of the Legal Situation ........................................................................................................................................ 71 Factor 6: What, if any, Risk there is to the Public Health ................................................................................................ 71 Overview Prenatal and Adolescent Exposure to Cannabis ....................................................................................... 71 Children (Development Pre- and Post-Natal) ................................................................................................................ 72 Emergency Room Admissions ............................................................................................................................................... 74 Cannabis Drug Testing and Impairment in Driving and at the Workplace ......................................................