INFORMATION FOR HEALTH CARE PROFESSIONALS

1 INFORMATION FOR. HEALTH care . PROFESSIONALS . Cannabis (marihuana, marijuana) and the cannabinoids Dried or fresh plant and oil administration by ingestion or other means Psychoactive agent HEALTH Canada is the federal department responsible for helping the people of Canada maintain and improve their HEALTH . HEALTH Canada is committed to improving the lives of all of Canada 's people and to making this country's population among the healthiest in the world as measured by longevity, lifestyle and effective use of the public HEALTH care system.

2 Galement disponible en fran ais sous le titre : RENSEIGNEMENTS DESTIN S AUX PROFESSIONNELS DE LA SANT . Le cannabis (marihuana, marijuana) et les cannabino des Plante s ch e ou fra che et huile destin es l'administration par ingestion ou par d'autres moyens Agent pyschoactif To obtain additional INFORMATION , please contact: HEALTH Canada Address Locator 0900C2. Ottawa, ON K1A 0K9. Tel.: 613-957-2991. Toll free: 1-866-225-0709. Fax: 613-941-5366. TTY: 1-800-465-7735. E-mail: Her Majesty the Queen in Right of Canada, as represented by the Minister of HEALTH , 2018.

3 Publication date: October 2018. This publication may be reproduced for personal or internal use only without permission provided the source is fully acknowledged. Cat.: H129-19/2018E-PDF. ISBN: 978-0-660-27828-5. Pub.: 180312. INFORMATION for HEALTH care PROFESSIONALS Cannabis (marihuana, marijuana) and the cannabinoids Dried or fresh plant and oil for administration by ingestion or other means Psychoactive agent This document has been prepared by the Cannabis Legalization and Regulation Branch at HEALTH Canada to provide INFORMATION on the use of cannabis (marihuana) and cannabinoids for medical purposes.

4 This document is a summary of peer-reviewed literature and international reviews concerning potential therapeutic uses and harmful effects of cannabis and cannabinoids. It is not meant to be comprehensive and should be used as a complement to other reliable sources of INFORMATION . This document is not a systematic review or meta-analysis of the literature and has not rigorously evaluated the quality and weight of the available evidence nor has it graded the level of evidence. Despite the similarity of format, it is not a Drug Product Monograph, which is a document which would be required if the product were to receive a Notice of Compliance authorizing its sale in Canada.

5 This document should not be construed as expressing conclusions or opinions from HEALTH Canada about the appropriate use of cannabis (marihuana) or cannabinoids for medical purposes. Cannabis is not an approved therapeutic product, unless a specific cannabis product has been issued a drug identification number (DIN) and a notice of compliance (NOC). The provision of this INFORMATION should not be interpreted as an endorsement of the use of this product, or cannabis and cannabinoids generally, by HEALTH Canada. Prepared by HEALTH Canada Date of latest version: Spring 2018.

6 Iii Reporting Adverse Reactions to Cannabis (marihuana, marijuana) Products Reporting adverse reactions associated with the use of cannabis and cannabis products is important in gathering much needed INFORMATION about the potential harms of cannabis and cannabis products for medical purposes. When reporting adverse reactions, please provide as much complete INFORMATION as possible including the name of the licensed producer, the product brand name, the strain name, and the lot number of the product used in addition to all other INFORMATION available for input in the adverse reaction reporting form.

7 Providing HEALTH Canada with as much complete INFORMATION as possible about the adverse reaction will help HEALTH Canada with any follow-ups or actions that may be required. Any suspected adverse reactions associated with the use of cannabis and cannabis products (dried, oils, fresh) for medical purposes should be reported to the Canada Vigilance Program by one of the following three ways: 1. Report online 2. Call toll-free at 1-866-234-2345. 3. Complete a Canada Vigilance Reporting Form and: o Fax toll-free to 1-866-678-6789, or o Mail to: Canada Vigilance Program HEALTH Canada Postal Locator 0701D.

8 Ottawa, Ontario K1A 0K9. Postage paid labels, Canada Vigilance Reporting Form and the adverse reaction reporting guidelines are available on the MedEffect Canada Web site. iv TABLE OF CONTENTS. Page List of figures and tables .. 1. List of abbreviations .. 2. Authorship and acknowledgements .. 7. Overview of summary statements .. 11. The Endocannabinoid 18. Cannabis .. 22. Chemistry and 22. Other constituents .. 22. Stability and storage .. 22. Clinical 24. Pharmacodynamics .. 24. Pharmacokinetics .. 29. Absorption .. 30. Smoked cannabis.

9 30. Vapourized cannabis .. 30. Oral .. 31. Oro-mucosal and intranasal .. 33. Rectal .. 33. Topical .. 33. Distribution .. 34. Metabolism .. 34. Inhalation .. 35. Oral .. 35. Excretion .. 36. Pharmacokinetic-pharmacodynamic relationships .. 36. Tolerance, dependence, and withdrawal symptoms .. 39. Special populations .. 43. Dosing .. 46. Smoking .. 48. Oral .. 51. Oro-mucosal .. 52. 52. Potential Therapeutic 54. Palliative 56. Quality of life .. 57. Chemotherapy-induced nausea and vomiting .. 59. Wasting syndrome (cachexia, , from tissue injury by infection or tumour) and loss of appetite (anorexia) in AIDS and cancer patients, and anorexia nervosa.

10 62. To stimulate appetite and produce weight gain in AIDS patients .. 62. To stimulate appetite and produce weight gain in cancer patients .. 63. Anorexia nervosa .. 64. Multiple sclerosis, amyotrophic lateral sclerosis, spinal cord injury and disease .. 64. Multiple sclerosis .. 65. Amyotrophic lateral sclerosis .. 70. Spinal cord injury (or spinal cord disease) .. 71. Epilepsy .. 72. Pain .. 78. Acute pain .. 80. Experimentally-induced acute pain .. 81. Post-operative pain .. 82. Chronic pain .. 82. v Experimentally-induced inflammatory and chronic neuropathic pain.