Medicinal Marijuana: The Canadian Journey

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1 Medicinal Marijuana: The Canadian Journey Nady el-guebaly MD Professor & Head, Addiction Division, UofC Research Director, Alberta Gambling Research Institute Chief Examiner, ISAM Certification

2 Disclosures: none related TOPICS 1. The North American context 2. Cannabinoids & therapeutic properties 3. Current foci of debate 4. Government & medical policies 5. Research needs

3 Ebers Papyrus 1552 BCE Scientific American 2004, pp.70-75

4 The North American Context 2000 s: Failed War on Drugs & 25% of the world s incarcerated in US!! 2003: US Gov patents cannabinoids as antioxidant & neuroprotectant 2012 Nov: Washington & Colorado legalize production, sale & use of marijuana for adults Dec: Uruguay passes full legalization for adults : 20 states & DC have legalized medical marijuana & 12 pending; range of regulations & enforcement (Texas 5-99y!) Legalization of all drugs? Medical hallucinogens & stimulants?

5 Defining the cannabinoid system Exogenous compounds Phytocannabinoids THC, CBD, combinations Synthetic cannabinoids Nabilone, dronabinol K2, spice Endogenous cannabinoids Anandamide eternal bliss/joy 2-arachidonyl glycerol Receptor targets CB1, CB2, TRPV1, PPAR, 5-HT, other

6 Cannabinoid mechanisms

7 Components of Cannabis Plant Cannabis used centuries ago possessed a 1:1 CBD:THC ratio THC (tetrahydrocannabinol) CBD (cannabidiol) is analgesic, antispasmodic, anti-tremor, anti-inflammatory, appetite stimulant, anti-emetic is anti-inflammatory, analgesic, anti-convulsant, anti-psychotic, anti-oxidant, neuroprotective Both compounds are in Nabiximols (2.7% THC, 2.5% cannabinoids) unlike other cannabinoid medicines (e.g. dronabinol, nabilone) does not bind to cannabinoid receptors binds to other receptors reduces the negative effects of THC ( dullness > High ) has been bred out of modern herbal cannabis! CBN & CBL: degradative products of THC through light THCV & CBC: enhance High! Terpenes & Phenols

8 Adapted from Izzo et al, Trends Pharmacol. Sci Potential Therapeutic Properties

9 Prescription cannabinoids Dronabinol (Δ-9 tetrahydrocannabinol THC) (2.5-10mg) Oral capsule (off market in Canada) Approved for chemotherapy-induced nausea & vomiting & anorexia associated with HIV/AIDS Nabilone ( mg) Oral capsule Approved for chemotherapy-induced nausea & vomiting Nabiximols (2.7% THC + 2.5% CBD) Oromucosal spray Approved in Canada for multiple sclerosis-associated neuropathic pain, spasticity & advanced cancer pain Herbal cannabis (varying THC levels) State programs (USA) Federal programs (Canada, Holland) No formal approval

10 Why is cannabinoid prescribing so hard? Multiple symptoms are affected by cannabis Pain Spasticity Sleep Anxiety Itch Doses used are hard to quantify Data on risks/benefits do not meet regulatory standards Not much taught in training programs A recreational drug with a great deal of stigma Risks of recreational use spill over into medical use

11 Adolescent Marijuana Use Increases While Alcohol and Cigarette Use Continue to Decline Percentage of U.S. 12 th Grade Students Reporting Past Month Use of Alcohol, Cigarettes, and Marijuana, 1975 to % 50% Alcohol Alcohol 25% Marijuana Marijuana Cigarettes Cigarettes 0% '75 '76 '77 '78 '79 '80 '81 '82 '83 '84 '85 '86 '87 '88 '89 '90 '91 '92 '93 '94 '95 '96 '97 '98 '99 '00 '01 '02 '03 '04 '05 '06 '07 '08 '09 '10 '11 '12 '13 Source: University of Michigan: 2013 Monitoring the Future Study

12 Increased Marijuana Treatment Admissions: 1993 and 2007 Emergency Department Visits Involving Selected Drugs: 2008 % of admissions Source: SAMHSA, TEDS 1993 & Source: SAMHSA, 2008 DAWN.

13 Source of Marijuana* among 12 th Graders in 2012 and 2013, by State Policy *Categories not mutually exclusive ** Statistically significant difference SOURCE: University of Michigan, 2013 Monitoring the Future Study

14 How does Marijuana Use in Adolescents Influence Brain Development? Persistent Cannabis Users Show IQ Decline from Childhood to Midlife Early (<18y) Long-Term Cannabis Use Decreases Axonal Fiber Connectivity 0.4 Adolescent Vulnerability 1 Diagnosis 2 Diagnoses 3 Diagnoses 0.2 Change in Full-Scale IQ (in standard deviation units) p=.44 p=.09 p=.02 Cannabis Dependent Before Age 18 (n=17) Not Cannabis Dependent Before Age 18 (n=57) Cannabis Dependent Before Age 18 (n=12) Not Cannabis Dependent Before Age 18 (n=21) Cannabis Dependent Before Age 18 (n=23) Not Cannabis Dependent Before Age 18 (n=14) Dunedin prospective study of 1037 Ss born 1972/73, Tested for IQ at age 13 and 38y. Tested THC use ages 18, 21, 26, 32 and 38y Source: Meier MH et al., PNAS Axonal paths with reduced connectivity (measured with diffusion-weighted MRI) in cannabis users (n=59) than in controls (N=33). Zalesky et al Brain 2012.

15 Adolescent Use

16 The Yale MBAs Are Here Health Canada: 400 applications, 13 licensed so far; cost $6-9/gm Colorado: estimated $134M taxes for July /20 rule: 1/5 past year users consume 20+ days/month & account for 80% of consumption

17 Big Alcohol-Tobacco-Gambling Big Marijuana Model? Can we really trust companies and Big Corporations not to target youth and the vulnerable? World s first cannabis vending machine unveiled in Colorado

18 The Marihuana for Medical Purposes Regulations (MMPR) Canada June 2013 Medical document, no Rx No formal indication : cannabis can be prescribed to anyone No guidelines for screening or monitoring Licensed producers ship directly to patient (not pharmacies) Cost - $6-9/gm taxable expense Medicolegal issues lawsuits re: Access USA: Approval of medicines through States & local ballot initiatives! Role of FDA vs Consumer drives? Right to try? AZ Medical Certification (& Renewals); Distribution Centres

19 1-3?

20 Physicians should only sign medical documents when they have the necessary clinical knowledge to engage in a meaningful consent discussion with patients. Discuss with the patient the lack of information available to date. All consent-related discussions should be documented in the patient s medical record, including: what is known, and not known. CMPA no longer advises physicians to ask patients to sign a release. Colleges: - Registration - Risk of Addiction - Physicians cannot dispense or become producers. No weed clinics; 20 min. or Skype interviews

21 Intern. Assoc. of Cannabinoid Medicine

22 Research Required I. The impact of Research Prohibition; opium as precedent? II. III. IV. The Canary Study, UBC Prospective Longitudinal Studies in Youth 12+ to assess effects of substances on developing brain & behavior - NIAAA s Cohort 800+, age 12-24, $3.65 M/yr/5yrs Clinical Trials: Roles of academia & industry - Efficacy; effectiveness; doses; duration; strains Bubba Kush, Thai Fire ; environment - Novel deliveries: vaporization in balloons heat, don t burn ; e-cigarettes; speed of delivery V. Education & Training: Optimal, cost effective interventions; National & international cannabinoid societies Can J Addiction ( Spec Edition 4(3), Sept 2013 Acknowledgements: Dr. Jag Khalsa (NIDA); Dr. Mark Ware (McGill s Pain Centre)

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