Medical Marijuana Martin P. Eason MD, JD Associate Chief of Staff for Education Mountain Home VA Medical Center. Disclosure.

Transcription

1 Medical Marijuana Martin P. Eason MD, JD Associate Chief of Staff for Education Mountain Home VA Medical Center Controversies in Pain Management Conference Johnson City, TN November 13, 2015 Disclosure I have no financial interest in the presentation or the products discussed therein Cannabis 1

2 Cannabis flower A little history Chinese Pharmacopoeia of Emperor Shen Nung circa 2700 BC 2

3 WB Shaughnessy Used as an analgesic, sedative, antiinflammatory, antispasmodic, and anti-convulsant. producing as sometimes a heavy, lazy state of agreeable reverie, from which the individual may be easily roused to discharge any simple duty sometimes in a cheerful active of inebriation causing him to dance, sing and laugh, provoking the venereal appetite, and increasing the desire for food and sometimes a quarrelsome drunkenness, leading to acts of violence Christison, R. A Dispensary and Commentary on the Pharmacopoeais of Great Britain,

4 Pure Food and Drug Act 1906 Harrison Narcotics Tax Act 1914 Marihuana Tax Act 1937 Narcotics Control Act 1956 Comprehensive Drug Abuse Prevention and Control Act

5 Why are mores changing? Tax revenue Job creation Burden of criminalization Increasing public support ( % of Americans used MJ) Endocannabinoid System Endogenous cannabinoids - principle molecule is anandamide Two principle receptors: CB1 and CB2 Discovered in 1988 and 1993 Found throughout the body 5

6 Endocannabinoids 6

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8 CB2 activity Mechanism of Action 8

9 Putative mechanisms in analgesia Modulator of rostral ventromedial medulla neuronal activity Anti-nociception effect in descending pain pathways Anti-inflammatory effects through decreased prostaglandin production Phytocannabinoids Over 80 cannabinoids in cannabis Two most common substances are THC and Cannabidiol (CBD) THC agonist for CB1 and CB2 THC most psychotropic of cannabinoids CBD no psychotropic properties and does not work via receptor Cannabidiol Tetrahydrocannabinol Smoked, vaporized, oil extract, submucosal spray, eaten Variable concentrations (strains, preparations) Psychotropic properties Unlawful in most states THC 9

10 Pharmacokinetics Terminal ½ life is approximately 30 hrs. Highly lipophilic Vaporization becoming more popular Smoked bioavailability is between 0.1 and.25% Oral bioavailability is b/w 5 and 20% Inhaled levels similar to IV Metabolized by several enzyme systems (cytochrome P450) THC Clinical effects Euphoria, intoxication Inc. HR, dec. alertness, motor stability, sedation Decreased processing speed, attention, learning, recall; altered perception of time and velocity Anxiety, panic attack, paranoia, dysphoria, depressed mood, and possible latent risk of psychosis in adolescents Tolerance can develop in as little 4 days of use Effects last longer than serum levels Long term use No evidence of increased lung disease (if cig use is accounted for) No increased lung or GI cancers Possibility increase in MI incidence in pts. with CV disease No neurocognitive dysfunction with long term use 10

11 Abstinence syndrome After continuous use of 5-21 days Begins after 12 hours, decreases after 24, and terminates by hours Anxiety, irritability, insomnia, abdominal pain, and decreased appetite Cannabidiol Low affinity for CB1 and CB2 No psychotropic activity Increases activity of CB receptors via a variety of mechanisms Not FDA approved Has shown effectiveness for analgesia, neuroprotection, anti-epileptic Used in mixture of THC and CBD (nabiximols, Sativex) Cannabinoid preparations Cannabis Cannibidiol (hemp oil,not FDA approved) Dronabinol Nabilone Nabiximols (THC and CBD, Sativex) Oral Cannabis extract (OCE) Ribonabant (CB1 antagonist) no longer approved 11

12 Dronabinol (Marinol) Synthetic THC Approved for HIV associated anorexia and chemotherapy N/ V Schedule III Nabilone (Cesamet) Synthetic derivative of THC Approved for chemotx assoc. N/V who failed conventional tx Schedule II drug Combination of THC and CBD in equal concentrations Approved for use in Canada, NZ, and some EU countries for chemotx N/V Nabiximols 12

13 Putative benefits of Cannabinoids Analgesia Anti-convulsant Anti-emetic Anxiolytic Neuroprotection Anti-inflammatory Anti-tumor The evidence JAMA June 2015; Whiting et al. Meta analysis of high quality RCTs Efficacy of cannabinoids for 28 databases Looked at N/V, appetite stimulation, chronic pain, spasticity from MS, GAD, sleep disorder, glaucoma, depression 79 trials, 6462 participants Chronic pain 28 studies, 2454 patients Drugs studied: nabiximols, smoked THC, nabilone, THC spray, dronabinol, vaporized THC, oral THC Types of pain: neuropathic, cancer, diabetic neuropathic, fibromyalgia, HIV neuropathy, pain from MS Average number of people reporting >30% reduction was better with CNB Results for cancer and neuropathic pain were similar Nabiximols associate with greater average reduction in pain compared to placebo Smoked THC reported greatest beneficial effect Studies generally suggested improvement in pain measures but most individual studies did not reach statistical difference. 13

14 Spasticity No clear difference between CNBs Studies generally suggested CNBs associated with improvement in spasticity but most did not reach statistical significance Nausea and Vomiting CNBs better than placebos and comparators but did not reach statistical significance High risk of bias Low quality evidence Anxiety One study with high risk of bias Greater improvement in anxiety analog mood scale versus placebo on simulated speaking test 14

15 Adverse effects Asthenia, balance problems, confusion, dizziness, dry mouth, fatigue, hallucinations, nausea, somnolence, nausea Weaknesses in the trials Failure to handle withdrawals Selective outcome reporting Inadequate description of randomization Difficulty with blinding Conclusion Moderate quality evidence that CNBs are effective in treating neuropathic pain and spasticity Low quality evidence that CNBs effective in treating chemotx N/V and sleep disorders Very low quality evidence that CNBs effective in treating anxiety 15

16 Review Lynch et al., British Journal of Clinical Pharmacology, trials, 766 participants Effective treatment of neuropathic pain with cannabis, oromucosal THC extract, nabilone, and dronabinol Review American Academy of Neurology systemic review Pain: cannabis extract effective, (strong evidence), THC or nabiximols effective (moderate evidence), smoked THC (unclear) Spasm: oral THC effective (strong evidence), THC and nabiximols effective (moderate evidence) So you want to recommend cannabinoids things to consider Inconsistent concentration of THC in cannabis Legal liabilities of prescribing Risk benefit ratio compared to traditional treatment What is the condition you are treating and will it be responsive? Have alternative approaches been tried? What are potential medical and psychiatric risks (particularly in elderly patients)? What is the potential for misuse, abuse, and addiction? What preparation do you want to use? 16

17 What to do? So here we are 23 states allow medical MJ; 4 states and DC allow recreational Legalization versus decriminalization No prescription for cannabis (schedule I remember?); can only recommend. Medical Marijuana Statutes Process of recommendation (may be oral or written Conditions where MJ can be used (HIV/AIDS, MS, glaucoma, chronic pain) May require ID card Allows use, growing, and possession up to certain limits May require dispensaries 17

18 Marijuana ID cards Provider issues Who gets to recommend? How much? What are professional practice guidelines (AAFP does not endorse MM laws)? What are malpractice issues? Social issues Who regulates quality? What is quality? Does health department check cookies? How do businesses handle money? Do they pay taxes? Children in homes of MM users child endangerment Drug tests at work and MM use 18

19 The future Removal as a scheduled I drug More rigorous studies particularly with CBD Should be considered as adjunctive therapy in multi-modal approach Avenues for research: glucose metabolism, anti-inflammatory, anti-tumor, neuroprotection Thank you! 19