K2, Spice, and Everything Nice? Synthetic Cannabinoids, Marijuana & Medicine

Transcription

1 K2, Spice, and Everything Nice? Synthetic Cannabinoids, Marijuana & Medicine Hakique Virani, MD FRCPC ABAM Occupational and Environmental Medical Association of Canada 32 nd Annual Scientific Conference

2 Disclosures Public Health & Preventive Medicine Specialist, First Nations and Inuit Health Branch Health Canada

3 Outline Neurobiology of cannabinoids Addiction and Mental Health considerations Other adverse impacts (the low side) Synthetic cannabinoids Marijuana as medicine (the high side) Public health and safety considerations Regulatory considerations

4 The incarnations of Mary J Hash oil (15 70%) Sinsemilla (7.5 14%) Cannabis sativa (0.5 5%) Hashish (2 8%)

5 Trends in marijuana use 2013 National Institute on Drug Abuse. Monitoring the Future Study.

6 Trends in marijuana use 2013 National Institute on Drug Abuse. Monitoring the Future Study.

7 What s in it? 400 some hydrocarbons in the smoke of marijuana cannabinoids Δ 9 tetrahydrocannabinol (THC)

8 Endocannabinoids and CB receptors Anandamide CB1 and CB2 receptors THC Howlett AC Pharmacol Rev. Classification of cannabinoid receptors

9 Endocannabinoids and CB receptors

10 Endocannabinoids and CB receptors CB1 receptors are located on PREsynaptic neuron terminals and act to attenuate neurotransmission in a retrograde fashion

11 Non psychoactive cannabinoids in marijuana Izzo et al. Trends in Pharmacol Sci Oct;30(10): Non psychotropic plant cannabinoids: new therapeutic opportunities from an ancient herb.

12 Is marijuana addictive? CA Proposition 19: The Regulate, Control, and Tax Cannabis Act of 2010 Section 2: Findings, Intent, and Purposes A. Findings (5) Cannabis has fewer harmful effects than either alcohol or cigarettes, which are both legal for adult consumption. Cannabis is not physically addictive, does not have long term toxic effects on the body, and does not cause its consumers to become violent.

13 Is marijuana addictive? (the epidemiologic argument) 2008 NSDUH (SAMHSA) All Americans >12 y.o High School Seniors Lifetime Use 42.4% 42% Annual Use 10.6% 32.4% Daily Use 1.3% 5% 8 9% of all lifetime users develop dependence 17% of those using before age 18 develop dependence

14 Is marijuana addictive? (the clinical argument) Moderate to severe cannabis use disorder (DSM V) (4+ criteria in a 12) Withdrawal [day 1 or 2 to day 7 14] Irritability/anger/aggression Nervousness/anxiety Sleep disturbance Decreased appetite/weight loss Restlessness Depressed mood At least one physical symptom causing significant discomfort Stomach pain/tremors/sweating/ fever/chills/headache Tolerance Larger amount than intended Unsuccessful attempts to reduce Time spent Craving Use despite social consequences Use despite physical consequences Abandonment of activities Use in hazardous situations

15 Withdrawal syndrome Is marijuana addictive? (the clinical argument) American Journal of Psychiatry Nov;161(11): Review of the validity and significance of cannabis withdrawal syndrome. Budney AJ et al

16 Withdrawal syndrome Is marijuana addictive? (the clinical argument) American Journal of Psychiatry Nov;161(11): Review of the validity and significance of cannabis withdrawal syndrome. Budney AJ et al

17 Is marijuana addictive? (the neurobiological argument) Activity in the reward pathway and stimulation of dopaminergic neurons

18 Is marijuana addictive? (the neurobiological argument) Chronic THC exposure Control Brain Res Mol Brain Res Jun;46(1 2): Effects of chronic exposure to delta9 tetrahydrocannabinol on cannabinoid receptor binding and mrna levels in several rat brain regions. Romero J et al

19 Neurocognitive effects of marijuana Dunedin Study Proceedings of the National Academy of Sciences of the USA Aug. Persistent cannabis users show neuropsychological decline from childhood to midlife. Meier MH et al.

20 Neurocognitive effects of marijuana

21 Specific functional and anatomic changes associated with marijuana in the adolescent brain Functional deficits Problem solving Executive Function Attention Processing speed Reaction time Memory (verbal and nonverbal) Loss aversion Cognitive efficiency Anatomic changes Gray matter volume/density White matter volume/density Fronto parietal white matter volume Hippocampal volume Amygdala reactivity Jacobus J. et al. Functional consequences of marijuana use in adolescents. Pharmacol Biochem Behav June ; 92(4):

22 Psychiatric risks associated with marijuana Moore THM et al. Cannabis use and risk of psychotic or affective mental health outcomes: a systematic review. Lancet 2007:370:

23 Impairment Asbridge M, Hayden JA, Cartwright JL. Acute cannabis consumption and motor vehicle collision risk: systematic review of observational studies and meta analysis. BMJ 2012; 344:e536.

24 Other potential adverse impacts of marijuana Lung Cancer Heart Liver Reproductive

25 Synthetic Cannabinoids (synthetic CB1 agonists)

26 Synthetic CB1 agonists Potent CB receptor agonists like THC, but better (ie. worse) Cannot detect with standard urine toxicology testing (such as immunoassay) **** Legal pot it s NOT US Synthetic Drug Abuse Prevention Act 2012 specifically outlaws any substance demonstrated to be a CB1 agonist Products containing ingredients that are similar synthetic preparations of cannabis are regulated under the Controlled Drugs and Substances Act (CDSA). All activities associated with them (e.g., production, distribution, import, export, etc.) are illegal in Canada. Law enforcement is authorized to seize these products at points of entry and/or remove them from retail outlets. (Health Canada 2013) Young people and current cannabis users (24%) Rapidly changing popular molecules JWH 018, 073; AM 2201 HU 210; the list goes on

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28 Synthetic CB1 agonists Intoxication syndrome onset usually rapid (1 2h peak) Cannabinoid tetrad analgesia, catalepsy, hypothermia, hypomotility Psychosis, panic, sedation, seizure HTN, MI, CVA ATN, AIN

29 But on the bright side

30 What can Aunt Mary cure?

31 What can Aunt Mary cure? if you ask her nieces and nephews Reported condition for which marijuana is being used Proportion citing this condition as reason for marijuana use Chronic pain 58.2 Mental health disorders 22.9 Sleep disorders 21.3 Neurological disorders 16.6 HIV 1.6 Cancer 1.5 Glaucoma 1.3 Reinarman C et al. Who are medical marijuana patients? Population characteristics from nine California assessment clinics. Journal of Psychoactive Drugs Apr Jun; 43(2):

32 Safety and efficacy on the whole HIV Associated Neuropathic Pain Chemotherapy associated toxicity MS spasticity/pain Chronic neuropathic pain (Accessed Sept 12, 2014) Nausea/vomiting NOS Appetite/Cachexia FMA Non MS spasticity Seizure disorders Intraocular pressure Inflammatory conditions Myofascial pain Migraine Tension Headache Bostwick JM. Blurred boundaries: the therapeutics and politics of medical marijuana. Mayo Clinic Proceedings. 87(2) Feb 2012: pf72.

33 Pharmacologic challenges dronabinol (Marinol) synthetic THC Late onset/peak, poor bioavailability nabilone (Cesamet) synthetic dimethylheptyl analog of THC Higher potency and half life than THC Late onset/peak nabiximols (Sativex) botanical extract of THC, CBD, minor cannabinoids, terpinoids, flavinoids Quicker onset (15 40 min), but shorter duration. Only on NS formulary. Wide individual variation in peak concentrations and time to onset/peak

34 Pharmacologic challenges Burning something and inhaling it isn t great medicine Institute of Medicine Marijuana and Health

35 Pharmacologic challenges DI Abrams et al. Vaporization as a smokeless cannabis delivery system: a pilot study. Nature. 11 April 2007

36 Pharmacologic challenges

37 Current Regulatory Framework (Marihuana for Medical Purposes Regulations MMPR) No more Health Canada authorization process or federal monitoring of patient access No more license to possess No more personal production (pending Allard v. the Crown) Licensed producers instead, who comply with QC requirements, record keeping, inventory management, and security Producer direct courier to patient more choices of marijuana strains and commercial suppliers

38 Current Regulatory Framework (Marihuana for Medical Purposes Regulations MMPR) sc.gc.ca/dhp mps/marihuana/info/list eng.php

39 Current Regulatory Framework (Marihuana for Medical Purposes Regulations MMPR)

40 Current Regulatory Framework (Marihuana for Medical Purposes Regulations MMPR) Patient provides the original medical document to the licensed producer of their choice, and then orders the variety of their choice Order is shipped directly by the licensed producer to the patient Maximum amount is the lesser of 30x daily dose OR 150g

41 Public Health/Safety considerations Substanial proportions of adolescent patients attending for addiction treatment obtain marijuana from a medical user Thurstone C, Lieberman SA, Schmiege SJ. Medical marijuana diversion and associated problems in adolescent substance treatment. Drug and Alcohol Dependence Nov 1;118(2 3): Changes in social norms Particularly in adolescent populations The opioid example

42 CPSA, CMPA, and C.Y.A. CPSA Standard of Practice Marihuana for Medical Purposes (April 3, 2014) Register with the College as an authorizer Trial and failure of conventional therapies Assess addiction risk with standard addiction risk tool INFORMED CONSENT Review PIN and TPP Fill Medical Document (and provide a copy to CPSA within one week of completing it) Assess regularly for risks and benefits with respect to the condition being treated (and at least every 3 months after stabilization ) You MUST NOT apply to become a licensed producer

43 CPSA, CMPA, and C.Y.A. CMPA Guidance ( acpm.ca/ /medical marijuana new regulations new college guidance for canadian doctors) Know and abide by your College s policy/guidelines You are not obligated to complete a medical document for medical marijuana if you re unfamiliar with it s therapeutic use or feel it is medically inappropriate Only sign the medical document if you have the necessary clinical knowledge to have a meaningful consent discussion Capture the consent discussion in the medical record Document attempts at conventional therapies (and that they were unsuccessful) Call CMPA for advice

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