Medical Efficacy of Cannabis Therapeutics: Focus on Pain Management PAINWeek-End 2018

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1 Medical Efficacy of Cannabis Therapeutics: Focus on Pain Management PAINWeek-End 2018 Theresa Mallick-Searle, MS, ANP-BC Stanford Health Care, Division Pain Medicine ("")*+,,---.%&/012&/.'3#,&/,"(141*$5#$%%&'05*1$4%1 Disclosure Speakers bureau Allergan, Amgen & Pernix Pharmaceuticals Any unlabeled/unapproved uses of drugs or products referenced will be disclosed.!

2 Condition of the times!why is this lecture being presented at PWEnd 2018?!Why is it a timely topic in pain management?!what are the three key take a ways today:! Where to start the discussion! How to counsel patient s about dosing! The best resources to provide Learning Objectives!Define the endocannabinoid system.!discuss evidence for cannabinoids in pain management.!review practical clinical basics. $

fda just approved EPIDIOLEX (cannabidiol) oral solution, pending DEA scheduling action.!federally illegal! Major confusion?! Background! USP 1850-1942!

3 Is this really a big deal?!29 states, as well as DC, Guam & Puerto Rico, that have legislation for the legal use of medicinal marijuana.!8 states & DC legalized recreational use.!global financial impact!canada = Cannabis Act!UK = Legalize medicinal marijuana!fda just approved EPIDIOLEX (cannabidiol) oral solution, pending DEA scheduling action.!federally illegal! Major confusion?! Background! USP ! 1930s U.S. Federal Bureau of Narcotics sought to portray marijuana gate-way drug to narcotics addiction.! 1937 Marijuana Tax Act! The Controlled Substances Act of 1970! Agriculture Act 2014 Hemp Farming Act 2018 &

2-arachidonylglycerol (2AG) identified Endogenous cannabinoid ligands shown to be analgesic 1994-97 1995 1964 1992 94-97 1998 Synthetic cannabinoids 1980 s 1988 2000+ Discovery of

4 Milestones in Cannabinoid Science!9-THC structure identified & synthesized Raphael Mechoulam Discovery of the CB2 Receptor site & the first endocannabinoid Anandamide (Raphael Mechoulam) Receptor antagonists 2-arachidonylglycerol (2AG) identified Endogenous cannabinoid ligands shown to be analgesic Synthetic cannabinoids 1980 s Discovery of the CB1 receptor St. Louis University Medical Center, Howlett & Devane! 2001 Noladin ether identified! "#$%&'%()*)+$$+,($-(./! 0.1+$)'.*/%2.#*.(/)-1'3#*4* 5+$(627+%(-$*-8*'$.-)+$$+,($-(.* /#/%'5*9,(-/#$%&'/(/:*.';3+.+%(-$<! =-1'7*.'7(1'3#*/#/%'5/ Endocannabinoid System (ECS)!""#$%%!&'()*+%,-./%-0%,1%&23+*4224( "&963:995&7% &

5 Endocannabinoid System Endogenous - homeostatic regulatory system "!"#$%&%"$'(')*)"+, inherited by all mammals. " -..*&%&*'('/%#*0&%"$ " 1&+*00'+*0."$0* " 2$345))5&%"$'!"#$% Includes: " 6"&"+'7"$&+"4 "$& " 14**.!CB1 & CB2 receptor sites {CBx Receptor & VR1 Receptor} " 89.4"+5&%"$:'0"7%54' '#""(!Endocannabinoids {anandamide, 2AG, Nolan ether, ;*<5=%"+:'('5$9%*&, )*!+"&,, virodhamine, NADA} " 2))>$*?8$/"7+%$*' (!*&"-&!Synthesizing and degrading enzymes 3>$7&%"$ " ->&"$")%7'$*+=">0' 0,0&*) " -$&%$"7%7*.&%"$ Synthesis Endogenous Cannabinoid System O R Cellular uptake Endocannabinoids Metabolism CB2 Receptor CB1 Receptor CBx Receptor VR1 Receptor Signal Transduction Immune function Cell proliferation Inflammation PAIN Appetite Immune function Muscle control PAIN IOP Cognition Emesis Neuroexcitability Reward Thermoregulation PAIN Vaso-dilation PAIN Inflammation &

@A0%BCDEFG Clinical Endocannabinoid Deficiency Ethan Russo, MD

!lack of sufficient endocannabinoids/ dysregulation of the ECS.

syndrome, depression, anxiety, migraine).

6 !"#$#%&'( )*++*%,+",-'.&/&01"23'( 4"2,5"+6')*++*%,3'( $7&'89,:';&&- Clinical Endocannabinoid Deficiency Ethan Russo, MD (2004)!The ECS theory of disease.!lack of sufficient endocannabinoids/ dysregulation of the ECS.!Result in higher susceptibility (fibromyalgia, irritable bowel syndrome, depression, anxiety, migraine).!phytocannabinoids (THC, CBD) can bind to the cannabinoid receptor sites (CB1, CB2), and mimic the physiological processes seen with binding of the endocannabinoids. &

What is Marijuana? It is a Plant w/over 400 different chemicals:!>60 types of cannabinoids!delta-9-tetrahydrocannabinol(thc)!

Terpenes, Terpenoids!Fungus? Bacteria? Pesticides? Research! Center for Medicinal Cannabis Research!

National Institute on Drug Abuse (NIDA)!

7 What is Marijuana? It is a Plant w/over 400 different chemicals:!>60 types of cannabinoids!delta-9-tetrahydrocannabinol(thc)!cannabidiol (CBD)!Cannabinol (CBN)!Cannabichromene (CBC)!Cannabigerol (CBG)!Tetrahydrocannabivarin (THCV)!Flavinoids!Terpenes, Terpenoids!Fungus? Bacteria? Pesticides? Research! Center for Medicinal Cannabis Research!National Center for Natural Products Research (NCNPR) at the University of Mississippi! National Institute on Drug Abuse (NIDA)! National Institutes of Health (NIH) " Canadian Institutes of Health Research " Canadian Consortium for the Investigation of Cannabinoids (CCIC) Europe o The Medicinal Cannabis Research Foundation (MCRF): UK o Spain, Germany, Italy o ICRS: &

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8 !!"#$%&'$()*&+,'-.$/,#$01$.2*33"%'.*2$."4.1&00&5,0",#2.,0.16%"0,1.3&,0. &#/$%2$.$44$1'28!"#$%&!"'() *+,-.,*/0,1234/*5!!"#"$%&'"($)**)+&*,&-.(/0,'&-"-()(.1)##(+"*"2&%(&*($30,*&$(*"40,/)%3&$( /)&*5!6&73(-"70""(,2(3"%"0,7"*"&%8()1,*7.%(&*$#4-"-(/4+#&$)%&,*.5!9""-(2,0()--&%&,*)#:(;"##(-".&7*"-<(#)07"<(=>?(%,(+"%%"0().."..( %

9 !"#$ %&'()*+,-&./012&314510&60-,57&4'8 A13+5&4'0<,&40&4.146&./! A1<=>.60=B0;=31>,.10<,&40>1-&1B! C;<>=21;14.0&406-11<! C;<>=21;14.0&40<6/5(=-='&5,-03&6.>166! D-=:,-0&;<>=21;14.!"#$ %&&'()**)+,-.+)-/0'1/0,(,*/'233&/0'435/46/7'8/7/'9:'+/44/7'46)*' F37/'2/32&/'7/2374/0'-&//2,*/--G'0,HH,*/--G'(35*,4,=/'273+&/1-')*0' 07322/0'3A4'3B'-4A0,/-'+/()A-/'3B'-,0/'/BB/(4-'8,46')&&'()**)+,-.+)-/0' 1/0,(,*/-'233&/0'435/46/7'=/7-A-'2&)(/+3I &

@<,(G,"'#<(2//,*#.(%/(>"&&"H$.("&+(>"&&"H$&%$+.?(>I44,&#(0#"#,( %/(2J$+,&*,("&+(K,*%--,&+"#$%&.(/%4(K,.

! Adults with chronic pain are more likely to experience clinically significant pain relief.

(%/(0*$,&*,.1(2&3$&,,4$&31("&+( 5,+$*$&,6(789:6(!"#$"#%&'"$#((#)'*$+($)%,,%-.*$%,/$)%,,%-.,+./*0$1233#,'$ *'%'#$+($#4.

10 @<,(G,"'#<(2//,*#.(%/(>"&&"H$.("&+(>"&&"H$&%$+.?(>I44,&#(0#"#,( %/(2J$+,&*,("&+(K,*%--,&+"#$%&.(/%4(K,.,"4*<(L789:M! In adults with chemotherapy induced N/V, oral cannabinoids are effective antiemetics.! Adults with chronic pain are more likely to experience clinically significant pain relief.! Adults with MS related spasticity reported improvement of spasticity symptoms.!"##$%&$'()*&+&*,-.(!"#$%&"'()*"+,-$,.(%/(0*$,&*,.1(2&3$&,,4$&31("&+( 5,+$*$&,6(789:6(!"#$"#%&'"$#((#)'*$+($)%,,%-.*$%,/$)%,,%-.,+./*0$1233#,'$ +,-./ !"

Opioid-Sparing Effect of Cannabinoids: A Systematic Review and Meta-Analysis (2017) Purpose: Determine the opioid-sparing potential of cannabinoids.

11 Opioid-Sparing Effect of Cannabinoids: A Systematic Review and Meta-Analysis (2017) Purpose: Determine the opioid-sparing potential of cannabinoids. Results: Studies included in qualitative synthesis (n = 28)! Median effective dose of morphine administered in combination with delta-9- tetrahydrocannabinol (delta-9-thc) is 3.6 times lower than the of morphine alone.! For codeine administered in combination with delta-9-thc was 9.5 times lower than of codeine alone. Pre-clinical studies provide robust evidence of the opioid-sparing effect of cannabinoids.!"#$%&'()*%&*+$,+)%-%.(/ #.67189:;34<1=34></! From 2010 to 2015 there were million daily doses of any opioid dispensed per year in the average state under Medicare Part D.! Prescriptions for all opioids! by 2.11 million daily doses per year, when a state instituted medical cannabis law.! Prescriptions for all opioids! by million daily doses per year, when medical dispensaries opened. Medical cannabis policies may be one mechanism that can encourage lower prescription opioid use & service as a harm abatement tool in the opioid crisis.!"#"$%&'()&$#(*+$$,-./0.1/ ,+!!

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12 !Population-based, cross-sectional study using the all-capture Medicaid opioid prescription data for 2011 to 2016.!Medical marijuana laws & adult-use marijuana laws were associated with lower opioid prescribing rates (5.88% & 6.38% lower, respectively).!"#"$%&'()&$#(*+$,-./$#01$.2.3/ :83;!!"#$#%&'()#%($*+$,(&(#-./#$)#/.'.%&0$)&1.23&%&$0&-,$.,$&,,*'.&(#/$ -.("$,.4%.+.'&%(05$0*-#1$,(&(#60#7#0$*8.*./$*7#1/*,#$)*1(&0.(5$1&(#,9$ D#,#&1'"#1,$1#8*1(#/9$EF(&(#,$-.("$)#/.'&0$'&%%&:.,$0&-,$"&/$&$ <?CGH$0*-#1$)#&%$&%%3&0$*8.*./$*7#1/*,#$)*1(&0.(5$1&(#$'*)8&1#/$ -.("$,(&(#,$-.("*3($)#/.'&0$'&%%&:.,$0&-,CI!$

The National Institutes of Health recently awarded a 5-year $3.8 million grant to Albert Einstein College of Medicine and Montefiore Health System!

13 The National Institutes of Health recently awarded a 5-year $3.8 million grant to Albert Einstein College of Medicine and Montefiore Health System!To determine if medical marijuana reduced opioid consumption in specific patient groups.! There is a lack of information about the impact of medical marijuana on opioid use in those with chronic pain. We hope this study will fill in the gaps and provide doctors and patients with some much-needed guidance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

I know nothing about cannabis! Important Talking Points! Encourage open dialogue.! Driving under the influence.! Recommend obtaining medical marijuana card issued by state.

14 I know nothing about cannabis! Important Talking Points! Encourage open dialogue.! Driving under the influence.! Recommend obtaining medical marijuana card issued by state.! Traveling considerations.! Share the extend of the research that is known.! Provide website resources.! Discuss drug to plant interactions, side effects, risk of addiction.! Do Not:! Recommend products & dispensaries!&

15 Mental Health!Cannabinoids appear to effect the same reward system as alcohol, cocaine, opioids.!evidence for cannabis dependence from epidemiological studies (Miller & Plant 1996; Malhotra & Biswas 2006).!irritability, anxiety, disturbed sleep, craving! Mental wellness!worsen sub-clinical, stable mental illness!effective motivation!psychosis in genetically susceptable individuals Tolerance & Adverse Effects (AEs)! Tolerance! Mood, sleep! Psychomotor performance! Arterial pressure! Antiemetic properties! Common AEs! Anticholinergic effects (dry mouth, blurry vision, urinary retention, tachycardia, constipation, hypertension).! CNS effects (ataxia, cognitive dysfunction, hallucination)! Cannabis Hyperemesis Syndrome!&

16 Stirring the Pot: Potential Drug Interactions!CYP450 Enzymes: 1A2, 3A4, 2C9, 2C19!CNS depressants, antidepressants, central nervous system drugs potentiate effects of THC.!Smoking more than two joints weekly is likely to increase the risk of drug-related interactions. (Horn & Hansten, 2014) Pharmacokinetics delta-9-tetrahydrocannabinol!thc psychoactive cannabinoid!highly lipophilic!rapidly absorbed through lungs after inhalation, quickly reaching high serum concentration!systemic bioavailability is ~23-27% for daily users, ~10-14% occasional users! Extensive liver (first pass) metabolism!>65% excreted in the feces, ~20% urine!t1/2 occasional users is 1-2 days, daily users up to 2 weeks!&

Inhaled versus Oral INHALED ORALLY INGESTED Peak Blood Levels (min) 3-10 60-120 Bioavailability (%) 10-40 <15 Time to peak psychoactive activity (min) 20 120-240 Varieties/Strains Though cannabis is

17 Inhaled versus Oral INHALED ORALLY INGESTED Peak Blood Levels (min) Bioavailability (%) <15 Time to peak psychoactive activity (min) Varieties/Strains Though cannabis is biologically classified as the single species Cannabis Sativa, there are at least three distinct plant varieties:! Cannabis Sativa! Cannabis Indica! Cannabis Ruderalis using_medical_cannabis!&

18 Practical Dosing (Thank you to Mariavittoria Mangini, PhD, FNP) Regardless of the specific physiological system, the effects of cannabis are dependent on many factors:!dose, variety!route (Inhalation, oral, transmucosal, trandsdermal, topical)!timing!general health (medical co-morbidities), Age!Use of other substances/medications!chronic user of cannabis versus naive!""#$%&&'''()*+*,-.*(/*0&#-)121)&$1"3$&.32-4+"&21+3$& Practical Dosing (Thank you to Mariavittoria Mangini, PhD, FNP) Average adult dosing of THC for:!cannabis-naïve individuals!daily to weekly users!daily mg mg 25 mg+ To convert % cannabinoids & terpenoids/gram to milligrams, move the decimal one place to the right " 20% THC = 200 mg THC/gram of cannabis " 2% CBD = 20 mg CBD/gram of cannabis " 0.20%!-caryophyllene = 2.0 mg/gram of cannabis!%

19 Lack of standardization makes dosing a challenge for patients & clinicians Overconsumption:!Re-dosing too soon!delayed on-set with oral dosing (>120 minutes)!hostile behavior/erratic speech/mild psychosis The L.E.S.S. Method: A measured approach to oral cannabis dosing!start Low!Establish potency!go slow!supplement as needed (Erowid & Erowid, 2011) Practical Dosing: RX dronabinol (Marinol/Syndros) Schedule III drug A synthetic version of THC & does not contain CBD (cannabidiol) or other cannabinoids. Recommended dosing oral mg twice daily nabiximols (Sativex) Not available in US!An oromucosal spray! fixed dose of 2.7mg THC & 2.5mg CBD.!Muscle stiffness/spasm due to multiple sclerosis. nabilone (Cesamet) Schedule II drug A synthetic cannabinoid agonist (an analog of dronabinol) & does not contain CBD (cannabidiol) or other cannabinoids. Recommended dosing oral 1-2 mg twice daily. cannabidiol (Epidiolex) Approved FDA!CBD pure-plant-derived product for epilepsy.!2.5mg/kg 10mg/kg taken twice daily.!&

Resources!"#$%&#'()*+&,-(.'/"-&0*!"#$%&#'()*+,%-'.

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20 Resources!"#$%&#'()*+&,-(.'/"-&0*!"#$%&#'()*+,%-'.%/#$0$*"#$)& >)&)6/"21 1##2344*">*-B"*-*>5*"4 $"

21 Resources!"#"$%"#&!'#(')*%+,&-')&*./&0#1/(*%2"*%'#&'-&!"##"3%#'%$(&4!!0!5!!""#$%&'$%(")**)+&*,&%($%-")'&,*(.!/01(2#,3#)45! 6*7,#4$%(+8(*$$%5()55$554$*'59($:2$#'(7)"-;'8 <<<=""&"=*$' 0#*/)#"*%'#"6&<(('8%"*%'#&-')&!"##"3%#'%$&=/$%8%#/&40<!=5; <<<=")**)+&5B4$%=,#3 MediHuanna - Medicinal Cannabis Education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`V $!

22 ! New York: Physician/Clinician Training Florida: All licensed MDs/DOs some states require specialty practice (e.g. pain management, palliative care, etc.) NPs: CA, OR, WA, NY, MA, NM Tips!Familiarize yourself with THC, CBD dosing.!familiarize yourself with drug : drug (plant) interactions, side effects, withdrawal.!familiarize yourself with local dispensaries and refer patient to accordingly.!consider The Treatment Agreement.!Continue to remember Federally illegal.!mindful of addiction, abuse, mental health issues. $$

$refractory chronic pain management.$ !cannabinoid-opioid synergy deserves attention.

23 Conclusion!Cannabinoids emerging as valid option for refractory chronic pain management.!innovative solutions to opioid crises needed.!cannabinoid-opioid synergy deserves attention.!clinical trials challenging to design but necessary to conduct.!can no longer refuse to discuss. THANK YOU Questions? $&

24 Selected References 1. Abrams D, Couey P, Shade S, et al. Cannabinoid-opioid interaction in chronic pain. Clin Pharmacol Ther 2011;90(6): Abrams D, Jay C, Shade S, et al. Cannabis in painful HIV-associated sensory neuropathy: a randomized placebo-controlled trial. Neurology 2007;68(7): Carter G, Weydt P, Kyashna- Tocha M, Abrams D. Medicinal Cannabis: Rational guidelines for dosing. IDrugs: The Investigational Drugs Journal 2004;7(5): Croxford J. Therapeutic potential of cannabinoids in CNS disease. CNS Drugs 2003;17(3): Di Marzo V. The endocannabinoid system: its general strategy of action, tools for its pharmacological manipulation and potential therapeutic exploration. Pharmacol Res 2009;60(2): Downer E and Finn D. Cannabinoids: clearing the smoke on pain, inflammation and neurodegeneration. Br J Pharmacol 2014;171(6): Ellis R, Toperoff W, Vaida, et al. Smoked medicinal cannabis for neuropathic pain in HIV: a randomized, crossover clinical trial. Neuropsychopharmacology 2009;34(3): Erowid E, Erowid F. "The L.E.S.S. Method: A Measured Approach to Oral Cannabis." Erowid Extracts Nov 2011;21: Guindon J & Hohmann A. The endocannabinoid system and pain. CNS Neurol Disord Drug Targets 2009;8: Selected References 10. Hazekamp A, & Fischedick J. Cannabis from cultivar to chemovar. Drug Testing and Analysis 2012;4(special issue): Hua T, Vemuri K, Pu M, et al. Crystal Structure of the Human Cannabinoid Receptor CB1. Cell 2016;167: Janero D & Makriyannis A. Cannabinoid receptor antagonists: pharmacological opportunities, clinical experieince, and translational prognosis. Expert Opinion On Emerging Drugs 2009;14(1): Malhotra A & Biswas P. Cannabis Use and Performance in Adolescents. Journal of Indian Association for Child and Adolescent Mental Health 2006;2(2): McPartland J. Phylogenomic and chemotaxonomic analysis of the endocannabinoid system. Brain Res Rev 2004;45(1): Miller P & Plant M. Drinking, smoking, and illicit drug use among 15 and 16 year olds in the United Kingdom. BMJ 1996 Aug 17;313(7054): Murry R, Quigley H, Quattrone D, et al. Traditional marijuana, high-potency cannabinoid and synthetic cannabinoids: increasing risk for psychosis. World Psychiatry 2016;15(3): Nugent S, Morasco B, O Neil M, et al. The effects of cannabis among adults with chronic pain and an overview of general harms. Annals of Internal Medicine 2017;167(5): Pacher P, Batkai S, & Kunos G. The endocannabinoid system as an emerging target of pharmacotherapy. Diabetes 2006;55(3): $&

25 Selected References 19. Price M, Baillie G, Thomas A, et al. Allosteric modulation of the cannabinoid CB1 receptor. Mol Pharmacol 2005;68(5): Rom S & Persidsky Y. Cannabinoid receptor 2: Potential role in immunomodulation and neuroimflammation. J Neuroimmune Pharmacol 2013;8: Russo E. Clinical endocannabinoid deficiency (CECD): Can this concept explain therapeutic benefits of cannabis in migraine, fibromyalgia, irritable bowel syndrome and other treatment resistant conditions? Neuroendocrinol Lett 2004;25(1-2): Russo E. Cannabinoids in the management of difficult to treat pain. Ther Clin Risk Manag 2008;4(1): Walsh Z, Gonzalez R, Crosby K, et al. Medical cannabis and mental health: a guided systematic review. Clin Psychol Rev 2017;51: Ware M, Wang T, Shapiro S, et al. Smoked cannabis for chronic neuropathic pain: a randomized controlled trial. CMAJ 2010:182(14):E Wilkerson J & Milligan E. The central role of glia in pathological pain and the potential of targeting the cannabinoid 2 receptor for pain relief. ISRN Anesthesiol : Wilsey B, Marcotte T, Tsodikov A, et al. A randomized, placebo-controlled, crossover trial of cannabis cigarettes in neuropathic pain. J Pain 2008;9(6): $&

Medical Efficacy of Cannabis Therapeutics: Focus on Pain Management PAINWeek-End 2018

Medical Efficacy of Cannabis Therapeutics: Focus on Pain Management PAINWeek-End 2018 Theresa Mallick-Searle, MS, ANP-BC Stanford Health Care, Division Pain Medicine Tmallick@stanfordhealthcare.org @tmallic