Pharmacologic and Clinical Effects of Cannabis (Medical Marijuana)

Transcription

1 Pharmacologic and Clinical Effects of Cannabis (Medical Marijuana) 1 MARY LYNN MCPHERSON, PHARM.D., MA, BCPS, CPE PROFESSOR MMCPHERS@RX.UMARYLAND.EDU

2 History of Medical Marijuana Ancient cultures used marijuana to relieve a variety of symptoms William O Shaughnessy first described the use of MJ in medical literature (1839) 1854 marijuana listed in US Dispensary with purported benefits of: Analgesic, sedaron TherapeuRc effects against inflammaron, nausea and spasm 1937 criminal fine imposed for marijuana possession CSA (high potenral for abuse, no medical use, and not safe to use without medical supervision) - CI

3 Reefer Madness: Marijuana is Medically Useful Whether PoliRcians Like it or Not 3 If marijuana were unknown, and bio-prospectors were suddenly to find it in some remote mountain crevice, its discovery would no doubt be hailed as a medical breakthrough. ScienRsts would praise its potenral for trearng everything from pain to cancer, and marvel at its rich pharmacopoeia many of whose chemicals mimic vital molecules in the human body. In reality, marijuana has been with humanity for thousands of years and is considered by many governments (notably America s) to be a dangerous drug without urlity. Any suggesron that the plant might be medically useful is polircally controversial, whatever the science says. The Economist, April 27, 2006

4 What s the deal today One of the most popular recrearonal drugs worldwide 178 million people aged years of age used cannabis at least 1x in There s a growing trend of older Americans who are using marijuana in their rerrement. That makes sense because old people are always talking about their joints. Jimmy Fallon

5 What s the deal today Medical cannabis refers to the use of cannabis or cannabinoids as medical therapy to treat disease or alleviate symptoms Can be given orally, sublingually, topically Can be smoked, inhaled, mixed with food, made into tea Can be given in herbal form, extracted naturally from the plant, gained by isomerizaron of cannabidiol, or manufactured synthercally 5

6 What s the deal today Prescribed cannabinoids include: Dronabinol capsules (Marinol) AppeRte srmulant in AIDS parents Cancer chemotherapy induced nausea and vomirng Nabilone capsules (Cesamet) Cancer chemotherapy induced nausea and vomirng Oromucosal spray nabiximols (SaHvex) not in US SpasRcity or neuropathic pain associated with mulrple sclerosis, cancer pain 23 states and Washington permit medical use 2009 DOJ said would not prosecute medical MJ users 6

7 Let s get that prescripron pad out Survey of 520 members of the Colorado Academy of Family Physicians (2013) 19% believed physicians should recommend medical cannabis 80% agreed it should be incorporated into medical school educaron 82% agreed that it should be included in residency training 92% agreed it should be a topic of CME for pracrcing MDs 7 Majority agreed that there are significant mental and physical health risks associated with marijuana Kondrad E, Reid A. J Am Board Fam Med 2013;26: Abstract.

8 Inquiring HCP minds want to know Regarding medical cannabis: Is it safe? Is there adequate evidence for its efficacy? If so, for what condirons is it effecrve? If it is sold in dispensaries rather than on street corners, should it be considered medical? If it is medical can it srll be abused? Is marijuana medical, or do certain components of marijuana have medical benefit and are they safe? 8 Michael A. Schatman, Medical Marijuana: The State of the Science. Medscape, Feb 06, 2015.

9 Am J Health-Syst Pharm May 15;64: Anaesthesia Nov;56: Marijuana (MJ) MJ = crude product (e.g., dried leaves and flowers of the plant Cannabis sa(va) AcRve chemicals: > 460 Cannabinoids: > 100 δ-9-tetrahydrocannabinol (THC): major ingredient responsible for therapeurc and psychoacrve effects. Dronabinol, nabilone - syntherc THC Cannabidiol: Liole or no psychoacrve properres. May reduce psychoacrve effects of THC. Possibly of therapeurc value. 9

10 Role of Endocannabinoid System 10 To maintain homeostasis in health and disease Results in increased endocannabinoid release or up-regularon of receptors in parrcular cells and Rssues Provides autoprotecron or autoimpairment Pertwee RG. Br J Pharmacol, 2009; 156:

11 Cannabinoid Receptors 11 LocaRon Cannabinoid-1 (CB 1 ) Receptors Cannabinoid-2 (CB 2 ) Receptors CNS Peripheral nervous system Peripheral Rssues Peripheral Rssues Central immune cells Effects Neuromodulatory Analgesia Muscle relaxaron Increase apperte Hormonal acrvity Impair cogniron & memory Alter motor funcron Immunosuppressive AnR-inflammatory AnR-nocicepRve Am J Health-Syst Pharm May 15;64: ; Anaesthesia Nov;56: ; Ann Pharmacother. 2006; Feb;40:

12 Effects 12 System CNS Cardiorespiratory System Eye Immune System ReproducRve System Effects Euphoria, dysphoria, anxiety, heightened sensory percepron, drowsiness, sleep, memory impairment, increased apperte Tachycardia (acute use), bradycardia (chronic use), vasodilaron, orthostarc hypotension, coughing, airway obstrucron Decreased intraocular pressure Impaired bactericidal acrvity Decreased sperm count and sperm mobility, suppression of ovularon

13 PharmacokineRcs InhalaHon Oral AbsorpHon Rapid Variable Bioavailability 20-45% 25-30% Onset Within minutes hours Peak Within 15 minutes 1 hour DuraRon of acron 2-4 hours 5-6 hours DistribuHon Metabolism ExcreHon 13 Highly lipid soluble Crosses the placenta, enters fetal circularon HepaRc AcRve metabolite (11-hydroxy-delta-9-THC) First pass (oral) Slow due to storage in adipose, can take days Enters breast milk

14 Non-Opioids: Acetaminophen (Tylenol), NSAIDs (Ibuprofen) Adjuvants: AnRdepressants, AnRconvulsants, CorRcosteroids, AnestheRcs, [Cannabinoid?] World Health OrganizaRon Pain Ladder

15 Clinical Effects of Marijuana 15 Symptom Relief AddicRon Anxiety, tension, stress Depression DigesRve problems InflammaRon Nausea and vomirng Pain Spasms and Convulsions Disease Management ArthriRs ADHD, PTSD Cancer treatments GastrointesRnal Disorders HIV/AIDS Insomnia Migraine Movement disorders MulRple sclerosis

16 JAMA 2015;313(24):

17 SystemaRc Review IndicaHon Cannabinoids TherapeuHc Outcome Chemotherapy NV AppeRte srmularon in HIV/ AIDS InfecRon Chronic Pain JAMA 2015;313(24): Nabilone Dronabinol Nabiximols THC (vs. placebo, tradironal comparators) Dronabinol (3 studies vs. megestrol; 1 study vs. placebo) Nabiximols THC (smoked, oral) Nabilone THC oromucosal spray Dronabinol Vaporized cannabis All studies showed a greater benefit with cannabinoids than placebo or comparators; did not achieve SS May have increased apperte, % body fat. Did not achieve SS. % of parents with > 30% reducron in pain was greater than placebo (especially with neuropathic pain)

18 SystemaRc Review IndicaHon Cannabinoids TherapeuHc Outcome SpasRcity due to MS or paraplegia Nabiximols Dronabinol Nabilone THC/CBD Smoked THC Cannabis improved spasrcity but failed to reach SS. More parents had global improvement Anxiety disorder Cannabidiol vs. placebo Greater improvement in anxiety on visual analogue mood scale (SS) Sleep disorder Nabilone Greater effect than placebo (SS) Psychosis Cannabidiol vs. placebo No difference in outcomes Glaucoma JAMA 2015;313(24): THC Cannabidiol, Cannabidiol oromucosal spray No difference when compared to placebo

19 Cannabis in Chronic Pain AddiRve effects with opioids Opioid-sparing effect No consrparon or respiratory depression Has not caused a single recorded fatal overdose Lethal dose is 40,000 Rmes typical human dose 19 No scienrfic basis that demonstrates MJ is a gateway drug Alternate routes of administraron (oral, transdermal, vaporizaron) Temporary mental impairment Less than alcohol

20 Medical Marijuana Laws Linked to Fewer Opioid Deaths Opioid analgesic overdose mortality rates in each state from from CDC 3 states (California, Oregon, Washington) had medical cannabis laws before addironal states introduced laws between States with medical cannabis laws had a 24.8% lower mean annual opioid overdose mortality rate compared with states without medical cannabis laws (95% CI, 37.5% to 9.5%; P =.003) 20 JAMA Intern Med. 2014;174(10): doi: /jamainternmed

21 Adverse Effects Meta-regression and analysis showed no evidence for a difference in the associaron of cannabinoids with the incidence of any AE based on: Type of cannabinoid, study design IndicaRon, comparator DuraRon of follow-up Cannabinoids were associated with a much greater risk of: Any AE, serious AE, withdrawal due to AE, many specific AE 21 JAMA 2015;313(24):

22 Adverse Events with Cannabinoid vs. Placebo Cannabinoid (vs. Placebo) Odds RaHo More Adverse Effects with Cannabinoid Dronabinol 3.01 Nabiximols 3.41 Nabilone 3.63 Levonantradol 4.84 THC capsules 3.16 THC oromucosal spray 2.0 THC/Cannabidiol capsules 3.03 JAMA 2015;313(24):

23 Nausea, fargue Increased weakness Most Common Adverse Events Behavioral or mood changes Suicidal idearons or hallucinarons (or both) Dizziness of vasovagal symptoms (or both) Feelings of intoxicaron Psychosis, dysphoria, anxiety 23 Koppel BS et al. American Academy of Neurology 2014

24 So who s with me? I would prescribe or recommend cannabis (medical marijuana) for a parent with a disease or symptom where cannabis has been shown to be helpful. 24 A. Absolutely, where do I sign? B. Maybe, I need more convincing C. Not in this liferme