Kelay Trentham MS RDN CSO FAND Oncology Dietitian MultiCare Regional Cancer Center Tacoma WA What well talk about today History of medical cannabis use Does it work If so for what ID: 1041399
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1. Medical Cannabis: What you Need to KnowKelay Trentham, MS, RDN, CSO, FAND Oncology DietitianMultiCare Regional Cancer CenterTacoma, WA
2. What we’ll talk about todayHistory of medical cannabis useDoes it work? If so, for what?Pros and cons of forms of useReasons not to use it & adverse effects
3. What Cannabis is…(Russo 2007)A plant From the Cannabaceae family: HopsHackberryCannabis by any other name: AKA: “grass”, “weed”, “ganja”, “marijuana”, “hash”, “bhang”, etc. Is still Cannabis!
4. Cannabis History “Tour”Medicinal use = before written historyEarly written history:>3500 yrs ago in Egypt1st-2nd century ChinaIntro to modern Western medicine: 1840’sUS ban via taxation: 1937Schedule 1 classification (US): 1970 “high risk for abuse, … no accepted medical use”(Russo 2007; NIH-NCI; Backes 2014)
5. (Map source: National Conference of State Legislatures)
6. Our Endocannabinoid SystemReceptors: CB1 (nervous system) & CB2 (immune cells)EndocannabinoidsEnzymes(Battista 2012, Vemuri & Makriyannis 2015)
7. What’s so special about Cannabis?Phytocannabinoids:“…any plant-derived natural product capable of either directly interacting with cannabinoid receptors or sharing chemical similarity with cannabinoids, or both.”110+ in cannabisProperties:Pain-relieving Anti-anxietyAnti-seizure Anti-nausea And the list goes on!Anti-inflammatoryAnti-oxidantAnti-tumorNeuroprotective(Pacher et al. 2006; Gertsch et al. 2010; Russo 2011; Ahmed et al. 2015)
8. Courtesy Steep Hill Halent(NIH-NCI; Backes 2014)
9. The “Most Studied” CannabinoidsCannabinoid:ReceptorActivity:Major Effects:Associated Rx drug:THC:CB1: nervous system (strong)CB2: immune cells (weak)PsychoactiveAnti-nauseaPain reliefAnti-spasmodicAnti-inflammatoryMarinol (dronabinol)Cesamet (nabilone)Sativex (nabiximols)LevonantradolCBD:CB1: nervous system (weak)CB2: immune cells (weak)Pain reliefNeuroprotectiveAnti-seizureAnti-anxietyAnti-nauseaSativex (nabiximols)Epidiolex (cannabidiol)(Russo 2011)
10. Terpenoids in CannabisEssential oil componentsCharacteristic aromaPharma effectsLimoneneMyrcenePineneLinaloolCaryophyllene(s)NerolidolPhytol(Russo 2011)
11. Some Terpenoid ActivitiesTerpenoid: Noted Effects: Limonene anti-anxiety, anti-depressantMyrcene anti-inflammatory, sedativePinene anti-inflammatory, bronchodilatorLinalool anti-anxiety, anti-convulsantCaryophyllenes anti-inflammatory, anti-fungalNerodilol sedative, anti-protozoal (Russo 2011)
12. The “Entourage Effect”
13. Noted “entourage” effectsWhen THC:CBD @ ~ 1:1 ↓ anxiety, memory issuesMay ↑ pain controlTerpenoidsCaryophyllene: ↓ pain, inflammationLinalool, limonene: ↓ anxietyMyrcene: sedating, ↓ pain Pinene: ↓ memory issues(Russo & Guy 2006; Morgan et al. 2010; Russo 2011, Nielsen et al. 2017)
14. Indica? Sativa? Strains?“New speak” = ChemovarsType I: THC predominantType II: THC & CBDType III: CBD predominantAdditional distinctions: terpenoid profile(Lewis et al. 2018)
15. Terpenoid Analysis
16. Reviewing the EvidenceAvailable studies will include:Synthetic THC (dronabinol, nabilone) Extracted THC +/- CBDLess often: “whole cannabis”
17. Nausea/VomitingCannabinoidControlResultsReferenceDronabinolLevonantradolNabiloneAnti-nausea meds &PlaceboMore effectivePreferredTramer et al. 2001DronabinolNabiloneLevonantradolAnti-nausea medsDronabinol: decreased nausea, was preferredNSNSRocha et al. 2008NabiloneAnti-nausea meds80%: ↓ nausea78%: people: preferredWare et al. 2008DronabinolOndansetron&PlaceboDronabinol: 71%Ondansetron: 64%Placebo: 15%Parker et al. 2011
18. AppetiteDronabinol vs. Megestrol acetate (Jatoi et al. 2002)Improved appetite: Megace 75% vs. Dronabinol 49%Advanced cancer patients
19. AppetiteTHC+CBD vs. THC vs. Placebo (Strasser et al. 2006)No Difference*Very low dose studied (2.5 mg THC)
20. Taste and SmellTHC vs. placebo (Brisbois et al. 2011)Chemosensory response: Significant improvement: 36% THC vs. 15% placebo“Food tastes better”: 55% THC, 10% placebo (p = 0.04) Pre-meal Appetite score: THC > placeboPilot study: n= 11 (THC), 10 placebo
21. Pain/neuropathyCannabinoidPainResultsNotesRefMixedCA, otherCanna > Effective than placeboSignificant Adverse effects1MixedNeuro, other15/18 trials: sig, modest effectNo severe AEs, no dropouts; placebo or active control2MixedCA, other27/38 RCTs: sig reliefPlacebo or active control3CannabisNeuro6 RCTs: All = sig relief3 studies: clinically meaningful relief45, 53, 61% C vs.18, 24, 26% p4(1: Martin-Sanchez 2009; 2: Lynch & Campbell 2011; 3: Aggarwal 2013; 4: Deshpande 2015)
22. Cannabis (smoked)Prospective, observational study: n = 131P>0.001 for trend (after 6-8 wks)SymptomGradeChangeNauseaNoneModSevere+37%-38%+1%VomitingNoneMod+23%-23%AnorexiaNoneModSevere+36%-38%+2%Weight lossNoneModSevere+35%-32%-5%(Bar-Sela et al. 2013)
23. Cannabis (smoked)Prospective, observational study: n = 131P>0.001 for trend (after 6-8 wks)SymptomGradeChangePainNoneModSev+23%+3%-26%(Bar-Sela et al. 2013)
24. Cannabis a “Cancer Cure”?Limited Preclinical Evidence:In vitro, In vivo1 small human study: GBMPotential? maybeCertainty? NoNeeds more research!!
25. Cannabis Administration Routes
26. Inhalation (Smoking & Vaping)Onset: 5 – 10 minutesDuration: 2-4 hoursBioavailability: 10-35%Vaping: less toxic byproduct (than smoking)(Grotenhermen 2003; Huestis 2007; MacCallum & Russo 2018)
27. Caution…What is a “dab”?Volatile “concentrate”Extracted via solvents, liquid gas, CO2 Safety concerns:Residual solvents: >80% samplesPesticides: 33% samplesPaclobutrazol: not listed with EPA for use on food cropsIncreased in adverse effects*Best avoided as medicine(Raber et al. 2015, MacCallum & Russo 2018)
28. Caution…Risk to the severely immunocompromised patient…Bacteria, molds on green budFew case reports: aspergillus via inhaled cannabis *can be fatalTesting?Sterilization?(Ruchlemer 2015)
29. Oral Ingestion: Edibles, CapsulesOnset: 1 - 3 hours Duration: 6 - 8 hoursBioavailability: variable, 4-20%*First-pass metabolism: 11-OH-THCPotent psychoactiveReduces bioavailability THCMore difficult to determine dose(Grotenhermen 2003; Huestis 2007; MacCallum & Russo 2018)
30. Caution…Labeling inaccuracies… Content analysis:17% accurately labeled23% under-labeled (had >THC content!)60% over-labeledContributes to:OverdosingDifficulty dosing(Vandrey et al. 2015)
31. Oromucosal: Sprays, TincturesOnset: ~15 – 45 minutes (average)Duration: 6 - 8 hoursBioavailability: Highly variable Inhaled > OM >/= oral Increases with food *Less first-pass metabolism(Guy & Robson 2003, MacCallum & Russo 2018)
32. RectalSuppositories Favored for absorption, no first-pass metabolismPeak concentration: 1-8 hoursBioavailability : ~2 X that of oralAvailability?*Best to avoid during chemo(Huestis 2007; Grotenhermen 2003)
33. SkinCreams, Ointments Few StudiesLocal effect onlyTransdermal PatchPreclinical researchAnimal model → plasma for 48 hrsMore research needed(www.hc-sc.gc.ca/dhp-mps/marihuana)
34. ContraindicationsAllergyPregnancy & breastfeedingHeart, RespiratoryHepatic, Renal Mental health hxschizophrenia, bipolar d/o, depression(Kahan 2014, Sachs 2015, Health Canada)
35. Use with CautionHistory of: Heart, AnginaHigh Blood PressureAsthma, COPD (inhaled)(Kahan 2014, Sachs 2015, Health Canada)
36. Adverse EffectsMost Common:Drowsiness/fatigueDizziness AnxietyNauseaCognitive effects (confusion, disorientation, hallucination, impaired memory)Cough/phlegm/bronchitis (with smoking)Common:Euphoria (adverse?)Blurred visionHeadacheRare:HypotensionPsychosis/paranoiaRapid heart rate HyperemesisDiarrheaLoss of coordination(MacCallum & Russo 2018)
37. Cannabis-Drug InteractionsDrug effects increased by cannabis:THC:AlcoholBenzodiazepines (Ativan, Valium, Xanax, Restoril, etc.)Opiates: codeine, fentanyl, morphine CBD (high dose):Clobazapam – will need dose reduction(MacCallum & Russo 2018)
38. About Dosing…“Start low, go slow, stay low”Helps limit fatigue, high heart rate, dizzinessAids tolerance to psychoactive effectsConsider Type II (THC+ CBD) or III (CBD)CBD tempers unwanted THC effectsChronic issues: oral product = “mainstay”Acute/breakthrough symptoms: vaporization useful(MacCallum & Russo 2018, Ware et al. 2015*)
39. Don’t Drive!!!
40. In SummaryCannabis has a long history of medical usemay be effective for some conditions Pros/cons include: Mode of use: difference in effects, contaminants, variabilityIndividual medical historyBest dose: lowest for relief, good tolerance
41. ResourcesInternational Association for Cannabis as Medicinecannabis-med.org – database of studiesAmericans for Safe AccessSafeaccessnow.org“Cannabis Pharmacy” by Michael Backes“Chronic Relief” by Nishi Whitely