Medical Marijuana Kent W. Peterson, MD, FACOEM Occupational Health Strategies, Inc. Charlottesville, VA Speaker Disclosure Requirements 1. Do not dispense, prescribe, refer or recommend MMJ 2. Have no financial interest in any entity that grows, procures, processes, sells or dispenses MMJ 3. Not receiving financial sponsorship for this presentation Share with a Partner 1
Agenda Medical Marijuana History Types of Cannabinoids Pharmaceutical Preparations, Administration Physiological Actions, Medical Uses and Indications Side Effects, Contraindications Workplace and Policy Issues What have we learned??? Ancient History Cannabis sativa plant origin in Central Asia/Himalayas 36 million years ago China Emperor Shen Nung described therapeutic properties 2737 BCE India widespread medicinal use 1000 BCE Spread throughout Asia, Middle East, Africa through 18 th Century Early Use in Western Medicine 1839 Publication by O Shaughnessy: effective analgesic, appetite stimulant, antiemetic, muscle relaxant, anticonvulsive 1854 Entered US Dispensary, usually available as tincture 1860 Ohio State Medical Society conference on cannabis, 1900 >100 scientific pubs. in US, Europe Marketed by Merck, Burroughs Wellcome, Bristol Myers Squibb, Parke Davis, Eli Lilly 2
20 th Century Challenges Difficulty with standardized dosing, water solubility, delayed onset when taken orally Other medications introduced for primary indications 1937: Federal Marijuana Tax Act severely burdened use by high taxes (AMA opposed) 1942: Removed from US Pharmacopoeia (AMA opposed) 1970: Controlled Substance Act banned use 1971: Nixon declared War on Drugs As result, research difficult & funding plummeted Recent Movement to Legalize 1964: chemical structure of THC identified 1996: medical marijuana legalized in California 1999: Institute of Medicine reported scientific and clinical basis for medical use 2015: legalized in 22 states & DC (15 pending) 2015: 11 states approved use of CBD oil for Tx of childhood epilepsy 2014 15: recreational use legalized in CO, WA, AK, DC with expected and unexpected effects 3
California Medical Marijuana 1996: intended to aid terminally ill: Chronic, persistent med conditions that limit a person s ability to perform one or more major life activities as defined by the ADA in 1990, or, if not alleviated may cause harm to the person s safety, physical or mental health Currently: any illness for which marijuana provides relief Question?? Can doctors in medical marijuana states actually prescribe medical marijuana? No. Because MJ is still Schedule 1 drug it cannot be prescribed. A licensed physician can only recommend or refer someone for medical marijuana. Patient can then get medical cannabis ID card or license at a registry, and/or go to dispensary to obtain (varies by state). 4
Medical Marijuana Cannabinoids 1. Endogenous Endocannabinoids 2. Plant based Phytocannabinoids 3. Synthetic or Pharmaceutical Exogenous cannabinoids 1. Endogenous Cannabinoid System Components: receptors, receptor ligands, synthesizing and degrading enzymes ECS promotes relax, eat, sleep, forget, and protect Mediates runner s high, effects of electroacupuncture, osteopathic manipulation, etc. CB1 Receptors most abundant in brain CB2 Receptors activate immune cell migration; inhibit inflammatory cytokine production/release 5
2. PhytoCannabinoids Delta 9 Tetrahydrocannabinol (THC) Greatest psychoactive effect and analgesic activity 11 Hydroxy THC Immediate metabolite; 4 times greater psychoactive and immunosuppressive effects Cannabidiol (CBD) Non psychoactive; modulates ion channel, receptor and enzyme targets Anti inflammatory, antiemetic, anti psychotic, antiischemic, anxioytic, and anti epileptiform effects Others: e.g., Cannabinol, Cannabigerol, Tetrahydro cannabivarian, Canabichromene Cannabis Components Cannabis contains >450 distinct compounds in 18 chemical classes Pyrolysis yields >2000 compounds THC is primary psychoactive ingredient THC and cannabidiol most abundant cannabinoids. THC/CBD ratios vary by strain, preparation (Charlotte s Web: CBD, THC). Agricultural Hybridization THC content of cultivated cannabis has risen dramatically ~3% in 1980s ~12% in 2013 Overdoses responsible for growing number of ED visits over last decade 6
3. Pharmaceutical Preparations Dronabinol (Marinol) isomer of THC Schedule 3 1985 nausea and vomiting (chemotherapy induced) 1992 anorexia and cachexia (AIDS) Nabilone (Cesamet) Schedule 3 More potent than synthetic THC Nausea and vomiting Nabiximols (Sativex) Approved in 20 countries, including Canada U.S. Phase III trials for cancer pain Cannador Orally administered cannabis extract with 2:1 THC:CBD Current research by European Institute for Clinical Research Pharmaceutical grade smoked or vaporized Cannabis Netherlands, Canada (NOT U.S.) Pharmaceutical Costs Dronabinol 1 po bid x 30 days = $715 Nabilone 1 po bid x 30 days = $2010 Thanks to Mark Upfal, MD, FACOEM 2014 Routes of Administration Pulmonary Smoking (high temp.) Vaporization (lower temp.) Oral Medication, e.g., capsules, tinctures, oral spray Edible, e.g., brownies, cookies, pastries Tea 7
Challenges of Administration Smoking dosage inconsistencies depth of inhalation time before exhalation variance in side effects, duration of action and drug interactions Ingestion slower onset, longer duration of effects variable absorption majority of ED visit for intoxication unintentional ingestion More difficult with nausea Thanks to Bernyce Peplowsky, DO, FACOEM Current Medical Use Not primary drug of choice for any condition Recommended where standard therapies have been ineffective or intolerable Often used as adjunct with other medications or therapy (e.g., to lower opiate doses) Medical indications formalized by states (e.g., NY, CA, MI), Health Canada, Netherlands 8
Indications for Medical Use 1 Disorders of pain and spasticity (intractable spasticity, multiple sclerosis, spinal cord damage or injury, ALS) Nausea/vomiting from chemotherapy, radiation therapy, or medications for HIV and hepatitis C Pain and palliative Rx for Cancer, HIV/AIDS (stimulate appetite, avoid weight loss, reduce debilitation and wasting syndrome) Indications for Medical Use 2 Chronic neuropathic pain (nerve damage, phantom limb, facial neuralgia, post herpetic neuralgia) Neuropsychiatric disorders (childhood epilepsy,* tics of Tourette syndrome, neuropathy, Parkinson s disease, PTSD) Autoimmune disease (arthritis, lupus, Chrohn s/inflammatory bowel disease) Treatment resistant glaucoma * Five upcoming clinical trials Acute Side Effects* Respiratory irritation/cough (if smoked) Cognitive: attention, memory, reaction time Lightheadedness or dizziness (30 60%) Sedation/fatigue (5 40%) Dry mouth (10 25%) Muscle weakness (10 25%) Palpitations: tachycardia/hypotenstion (20%) *Dose dependent; rapidly reversible 9
Risks (dose related) No established lethal dose Slower reaction time, diminished estimation of time and distance impaired motor skills and vehicle operation (especially with alcohol) Impaired thinking and memory Anxiety/panic attacks Exacerbation of underlying psychological/ psychiatric conditions (acute psychosis?, schizophrenia?) Adolescents: poorer educational outcomes Contraindications and Precautions Hypersensitivity to cannabinoids or smoke Psychosis personal or family history Age <18 years Severe cardio pulmonary disease Severe liver or renal disease Pregnancy or breastfeeding History of substance abuse Current CNS depressant Rx Mentally demanding work Safety sensitive jobs (e.g., motor tasks; operating machinery, vehicles) Addictive Potential 32% nicotine 23% heroin 17% cocaine 15% alcohol 9% recreational marijuana?? medical marijuana 10
Cannabinoids Unproven Myths Gateway drug theory Most MJ users do not use hard drugs 25% lower opioid OD mortality in states with MMJ laws (2014 JAMA). Is MJ substitute? Adjunct? Pulmonary harm 2014 JAMA: nl. FEV1, FVC over 20 yr. w small sample Adverse Immune effects Cognitive Impairment beyond acute use Addiction (dependence vs. addiction) American Psychiatric Association There is no current scientific evidence that marijuana is in any way beneficial for the treatment of any psychiatric disorder. Medical treatment should be evidence based and determined by professional standards of care; it should not be authorized by ballot initiatives. Further research on the use of cannabis derived substances as medicine should be encouraged and facilitated by the federal government. Position Statement on Marijuana as Medicine, 2013 Workplace Issues Impact on Corporate culture Work quality and productivity Safety sensitive work functional impairment Even where medical MJ or recreational MJ legalized, most employers have right to ban Some states upheld firing MMJ users with + UDS (CA, MI, OR, WA) Other states prohibit discrimination against MMJ users with + UDS (AZ, DE, IL, MN) unless used or impaired on job Important not to discriminate against underlying disability 11
Policy Issues Illegal under federal law, even where legal under state law (generally federal law not enforced) Shift from Schedule 1 to Schedule 2 long urged by IOM, ACP, AMA (11/09) Bona Fide Physician Patient Relationship Mandatory CME for prescribers? Parallel to mandatory opiate education Research Exploring other active components, e.g., CBD Randomized controlled clinical trials Social research What Have We Learned????? 12