Durban Poison (Pure Indica) Hindu Kush (Pure Sativa) Northern Lights (Ruderalis-Indica Hybrid) Royal Dwarf (Ruderalis-Sativa Hybrid)

11 Adapted from Figure 1. The endocannabinoid System in the Nervous system as presented in Information for health care professionals cannabis and the cannabinoids

Glycerol Esters 72 2-arachidonoylglycerol (2- AG) retrograde neurotransmitter Greater potency/efficacy relative to anandamide 1,2

Dronabinol tablet (MARINOL) Schedule III Dronabinol liquid (SYNDROS) Schedule II synthetic delta-9-tetrahydrocannabinol FDA approved: nausea and vomiting a/w chemotherapy Anorexia and weight loss a/w AIDS Nabilone (CESAMET) Schedule II THC analog FDA approved: nausea and vomiting a/w chemotherapy Nabiximol (SATIVEX) sublingual spray Whole cannabis extract Each spray delivers a dose of ~2.7 mg THC and 2.5 mg CBD. Approved in Europe and Canada for MS related spasticity and cancer pain Currently in phase three trials in the US for cancer pain

Photo: http://www.huffingtonpost.ca/2014/05/22/medical-marijuana-clinical-trial-canada_n_5373658.html

Benefits may Outweigh Risks Palliative Care 41,42,43 Chemo related nausea and vomiting 11,15, 59 Cachexia 11,15 Multiple Sclerosis 44,59 Chronic pain 40,59,71 Neuropathic pain 33,44,59 Rheumatoid Arthritis 39,59,67 Glaucoma 11,15,59 Irritable bowel syndrome 64 Crohn s 11,15 Ulcerative Colitis 11,15 HIV 32,59,69 Unclear Role Anorexia Nervosa 11,15 ALS 11,15 Epilepsy 59 Migraine 64 Fibromyalgia 64 Dystonia 44 Sleep Disorders 59 PTSD 57,65,66 Anxiety 3,8,24,2731,54,58 Depression 24,38,58,59,65,68 Schizophrenia Alzheimer s 45,46,47,48 Risks may Outweigh Benefits Post operative pain 11,15 Osteoporosis 11 Huntington s 11 Parkinson s 7 Tourette s 11 Asthma 59 As a chemotherapy 11,15 Acute pain 44,59 Addiction 49,59

Benefits may Outweigh Risks Palliative Care 41,42,43 Chemo related nausea/vomiting 59 Cachexia 11,15 Multiple Sclerosis 44 Chronic pain 40,59,70,71 Neuropathic pain 44,59 Rheumatoid Arthritis 39,59,67 Glaucoma 11,15 Alzheimer s 45,46,47,48 IBS 64 Crohn s 11,15 Ulcerative Colitis 11,15 Unclear Role Anorexia Nervosa 15 ALS 11,15 Epilepsy 59 Migraine 64 Fibromyalgia 64 Dystonia 44 Sleep Disorders 11,15 PTSD 57,58,65,66 Depression 38,58,59,65,68 Anxiety Addiction 49,59 3,8,24,27,31,35, 54,58,59 Risks may Outweigh Benefits Post operative pain 11,15 Osteoporosis 11 Huntington s 11 Parkinson s 11 Tourette s 11 Asthma 59 As a chemotherapy 11,15 Schizophrenia 63 Acute pain 44

Benefits may Outweigh Risks Multiple Sclerosis 11,15 Chronic pain 40,44,59,71 Neuropathic pain 40,44,59 Rheumatoid Arthritis 39,53,59,67 Glaucoma 11,15 Alzheimer s 45,46,47,48 IBS 64 Crohn s 11,15 Ulcerative Colitis 11,15 Anxiety 34,37,55,56,58,59 Depression 38,58,59,65 Schizophrenia 36,60,61,62 Addiction 49,50,51,52,59 Epilepsy 59 Palliative Care 41,42,43 Unclear Role Anorexia Nervosa 11 ALS 11 Acute pain 44 Migraine 64 Fibromyalgia 64 Dystonia 44 Sleep Disorders 11,15 Chemo related nausea and vomiting 11,15 Palliative Care 11,15 Cachexia 11,15 PTSD 57,58,59,65,66 Risks may Outweigh Benefits Post operative pain 11,15 Osteoporosis 11 Tourette s 11 Asthma 11 As a chemotherapy 11,15

33 Abram, S. (2011). Smoked cannabis for chronic neuropathic pain: a randomized controlled trial. Yearbook of Anesthesiology and Pain Management, 2011, 366-367. doi:10.1016/j.yane.2011.01.030 C<Aj/ 182: E694-E701 34 Bergamaschi, M. M., Queiroz, R. H., Chagas, M. H., Oliveira, D. C., Martinis, B. S., Kapczinski, F.,... Crippa, J. A. (2011). Cannabidiol Reduces the Anxiety Induced by Simulated Public Speaking in Treatment-Naïve Social Phobia Patients. Neuropsychopharmacology, 36(6), 1219-1226. 35 Fusar-Poli, P., Crippa, J.A., Bjattacharyya, S., Borgwardt, S.J. and other. (2009) Distinct effect of delta 9- tetrathydrocannabinol and cannabidiol on neural activating during emotional processing Arch. Gen. Psychiatry. 66; 95-105) 36 Zuardi, A., Crippa, J., Hallak, J., Moreira, F., & Guimarães, F. (2006). Cannabidiol, a Cannabis sativa constituent, as an antipsychotic drug. Brazilian Journal of Medical and Biological Research, 39(4), 421-429. 37 Guimaraes, F. S., De Aguiar, K.C., Mechiulam, R. and Breuer, A. (1994) Anxiolytic effect of cannabidiol derivatives in the elevated plus-maze. Gen. Pharmacol. 25: 4170426 38 Bambico, F. R., Katz, N., Debonnel, G., & Gobbi, G. (2007). Cannabinoids Elicit Antidepressant-Like Behavior and Activate Serotonergic Neurons through the Medial Prefrontal Cortex. Journal of Neuroscience, 27(43), 11700-11711. 39 Blake, D. R. (2006). Preliminary assessment of the efficacy, tolerability and safety of a cannabis-based medicine (Sativex) in the treatment of pain caused by rheumatoid arthritis. Rheumatology, 45(1), 50-52. 40 Aggarwal, S. K. (2013). Cannabinergic Pain Medicine. The Clinical Journal of Pain, 29(2), 162-171 41 Carter, G. T., Flanagan, A. M., Earleywine, M., Abrams, D. I., Aggarwal, S. K., & Grinspoon, L. (2011). Cannabis in Palliative Medicine: Improving Care and Reducing Opioid- Related Morbidity. American Journal of Hospice and Palliative Medicine, 28(5), 297-303. 42 Wale, J. (2014). Exploring key topics in palliative care: pain and palliative care for older people. Clinical Medicine, 14(4), 416-418 43 Mccarberg, B. H. (2007). Cannabinoids. Journal of Pain & Palliative Care Pharmacotherapy, 21(3), 19-28. 44 Karst, M., Wippermann, S., & Ahrens, J. (2010). Role of Cannabinoids in the Treatment of Pain and (Painful) Spasticity. Drugs, 70(18), 2409-2438. 45 Ahmed, A. I., Geke A. H. Van Den Elsen, Marck, M. A., & Rikkert, M. G. (2014). Cannabinoids for Pain in Dementia: The Good, the Bad, and the Ugly. Journal of the American Geriatrics Society, 62(5), 1001-1002. 46 Marchalant, Y., Brothers, H. M., & Wenk, G. L. (2008). Inflammation and aging: Can endocannabinoids help? Biomedicine & Pharmacotherapy, 62(4), 212-217. 47 Volicer, L., Stelly, M., Morris, J., Mclaughlin, J., Volicer, B., & Rogers, E. (1996). 292 Effects of dronabinol on anorexia and disturbed behavior in patients with Alzheimer's disease. Neurobiology of Aging, 17(4). 48 Pazos, M., Núñez, E., Benito, C., Tolón, R., & Romero, J. (2004). Role of the endocannabinoid system in Alzheimer's disease: New perspectives. Life Sciences, 75(16), 1907-1915. 49 Hurd, Y. L., Yoon, M., Manini, A. F., Hernandez, S., Olmedo, R., Ostman, M., & Jutras-Aswad, D. (2015). Early Phase in the Development of Cannabidiol as a Treatment for Addiction: Opioid Relapse Takes Initial Center Stage. Neurotherapeutics, 12(4), 807-815. 50 Katsidoni, V., Anagnostou, I., & Panagis, G. (2012). Cannabidiol inhibits the reward-facilitating effect of morphine: involvement of 5-HT 1A receptors in the dorsal raphe nucleus. Addiction Biology, 18(2), 286-296.

Cannabis helps with my anxiety. Photo credit: http://www.huffingtonpost.com/2013/12/20/kinds-of-psychotherapy-try_n_4466536.html

Effects of WIN 55212-2 on % open time (a), absolute open time (b), % open arm entries (c), and number of total arm entries (d) during a 5-min exposure to the elevated-plus maze. *, p < 0.05; **, p < 0.01, significantly different from vehicle control. 12 Sachin Patel, and Cecilia J. Hillard J Pharmacol Exp Ther 2006;318:304-311 The American Society for Pharmacology and Experimental Therapeutics