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Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5200_Библиотеки_им_академика_М_И_Перельмана

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Schedule 1 classification. In accordance with the state law, physicians are only able to certify or recommend patients for medical marijuana treatment. As of July 2020, there were four states where marijuanaremainscompletelyillegal:Idaho,Kansas,Nebraska,andSouthDakota.
PATHOPHYSIOLOGY
RefresheronthePathophysiologyofPain
Painitselfistheendresultofthecentralnervoussystem’sprocessingstimuli.Paincanbeclassifiedas eithernociceptiveorneuropathic.Nociceptivepainisthepainsecondarytoaninsult(chemical,thermal, ormechanical)tothebody,resultinginnervereceptorstimulation.Thiscanbeeithersomaticorvisceral, dependingonthepain’s origin.Inflammatorypain,anothernociceptive subtype, isa result ofcytokine release secondary to tissue injury and is often seen in chronic pain syndromes such as rheumatoid arthritis. Neuropathic pain, either peripheral or central, is caused by damage to the somatosensory nervoussystem. Theabnormalpainsignalingoccurringduetothedamagednerves either increasesthe excitatoryactionordecreasestheinhibitoryaction,andthisleadstovariationinthewaypainmessages aremodulatedinthecentralnervoussystem.
Themolecularandbiochemicalprocessesinvolvedinthetransmissionofpainsignalstoandfromthe centralnervoussystemareoftenthetargetofdrugtherapy,sincemanydrugscanenhanceinhibitorypain signals or block excitatory pain signals. For more information, please see Chapter 9, “Principles of PharmacologyinPainManagement.”
TheEndocannabinoidSystemandItsRelationshiptoPain
TheECSisabiologicalsystemrecentlydiscovered(intheearly1990s)andiscomposedoflipid-based endogenousneurotransmitters. Two such transmitters, anandamide and 2-arachidonoylglycerol (2-AG), havebeenfairlywellcharacterized.Theseneurotransmittersactinaretrogradefashion;theyarecreated inthepostsynapticneuronandbind toreceptors on the presynaptic neuron.This mechanism creates a feedbacklooptothesendingneuron,thusregulatingthereleaseofneurotransmittersfromthepresynaptic neuron.Theendocannabinoidsarecreated“ondemand”—thatis,theyarecreatedinresponsetoaneed andthendestroyed in the synapse once the needfor them is abated. TheECS is foundthroughoutthe central and peripheral nervous systems, is found in most vertebrates, and is involved in maintaining homeostasis.AlterationsintheECShavebeenimplicatedina varietyofdiseasestates,fromimmune­regulateddiseases(e.g.,rheumatoidarthritis)toneurologicaldisorderssuchasepilepsyandMS.
WithintheECSarecannabinoid(CB)receptorslocatedthroughoutthebody.Thetworeceptorsmost characterizedaretheCB1andCB2receptors.Thesereceptorsreceivesignalsfromtheendocannabinoids andinturntransmitmessagestothepresynapticneuron,regulatingthereleaseofotherneurotransmitters. These receptors are of the G-coupled protein type andare the mostcommonly found receptors in the human body. The CB1 receptors are primarily located in the central nervous system, while the CB2 receptorsareprimarilylocatedintheperiphery,especiallyintheimmunecells(Figure11.2).
Activation of the CB1 receptor is linked to a decrease in the release of glutamate (an excitatory neurotransmitter)oradecreaseingamma-aminobutyricacid(GABA),aninhibitoryneurotransmitter.The overallneteffectis typicallya reductionintheexcitationofthepostsynaptic neuron.Activationofthe CB1 receptor has been associated with changes in pain perception, appetite stimulation, and
memory/cognitionchanges.AnandamideappearstobetheprimaryendogenousagonistofCB1receptors. TheexogenouscannabinoidTHCinteractswiththeCB1receptorbuthasamuchloweraffinityforthe receptorthananandamide.Inthisrespect,THCmaybeconsideredapartialagonistoftheCB1receptor. CBDhasalowaffinityforthisreceptorandmayevenactasanantagonist.Thus,THCmaydecreasethe releaseofneurotransmitterspresynapticallywhileCBDmayincreasethem.Thespecificneurotransmitter islocationandfunctiondependent.
CB2receptorsarefoundmoreintheperipheralnervoussystemthaninthecentralnervoussystembut havesimilarpharmacologicpropertiesas theCB1receptors. Thatis,theytooareG-coupledreceptors andregulatethereleaseofneurotransmittersfrompresynapticneurons.ActivationoftheCB2receptors, dependingontheperipheralorgan,canhavepositiveeffectsonpain,theimmunesystem,andneurological disorderssuchasepilepsy.AnandamidehasahighaffinityfortheCB2receptor,buttheendocannabinoid 2-AGhasahigheraffinityandtheseendogenousligandsserveasagonistsatthisreceptor.Similartothe CB1receptor,THCactsasapartialagonisttotheCB2receptorandCBDactsasanantagonist.
FIGURE11–2Structureandfunctionoftheendocannabinoidsystem.
CB1,cannabinoid1;CB2,cannabinoid2;CBD,cannabidiol.
ThecomponentsoftheECScanbefoundallalongthepainpathway,fromperipherytothebrain.The ECS receptors are involved in the modulation of pain thresholds through inhibition or release of
neurotransmittersinvolvedinpain.
DIAGNOSTICCRITERIA
AsnotedinChapter9,thediagnosisandassessmentofpainisacomplexprocess.Oncethepainhasbeen classifiedasnociceptiveorneuropathic,thetreatmentmodalitycanbebetterselected.
DiscussionofDiseaseStatesWhereCannabisMayBeEffective
Cannabis and cannabinoid derivatives are becoming more accepted in the treatment of disease or alleviationofsymptoms.However,thedatasupportingtheirefficacyforspecificindicationsarenotwell established.In2011,LynchandCampbellpublisheda systematic review of18 randomized,controlled trialsinvestigatingtheuseofcannabinoidsinthetreatmentofnoncancerchronicpainsuchasneuropathic pain, fibromyalgia, and rheumatoid arthritis (Lynch & Campbell, 2011). The cannabinoids included smoked cannabis, oral cannabis-based medicine, nabilone, dronabinol, anda THCanalogue,ajulemic acid. Fifteen of the 18 included trials demonstrated a significant analgesic effect of cannabinoids compared with the placebo. Cannabinoid use was generally well tolerated; adverse effects most commonlyreportedweremildtomoderateinseverity.
TheNationalAcademiesofSciences,EngineeringandMedicine(NASEM)conductedareviewofthe literaturesurroundingtheuseofcannabis (NASEM,2017).TheNASEMreportconcludedthatthereis substantialorconclusiveevidenceregardingtheefficacyofcannabisorcannabinoidsinthetreatmentof chronicpaininadults,chemotherapy-inducednauseaand/orvomiting,andspasticitysymptomsinpatients withMS.Thereportfurther assertedthatthereismoderateevidencethattheseagentsare effectivefor short-termsleepdisturbancesinpatientswithfibromyalgia,sleepapneasyndrome,chronicpain,andMS. Therewaslimitedevidencereportedornonereportedontheefficacyofcannabisorcannabinoidsinthe treatmentofallotherdiseases.
INITIATINGDRUGTHERAPY
Sincemarijuana/cannabisisaSchedule1drug,thefocusoftherestofthischapterwillbeontheFood andDrugAdministration(FDA)–approvedcannabinoids.Table11.1showstheFDA-approvedcannabis products.
TABLE11.1
OverviewofCannabisDrugsApprovedbytheU.S.FoodandDrugAdministration
Generic(Trade)Name andAdultDosage
SelectedAdverse Effects
Contraindications SpecialConsiderations
Cannabidiol(Epidiolex): Theinitialdoseforthe treatmentofLGSorDS inpatients≥2yearsof ageis2.5mg/kgBID. Maybeincreasedto5 mg/kgafter1week,up toamaximumof10
Drowsiness,sedation, fatigue,sleep disturbances, includinginsomnia. GIdisturbances,such asdiarrheaandlossof appetitemayoccur.
Hypersensitivityto cannabidiol,sesameoil,or dehydratedalcohol. Individualswithsevereliver diseasemayalsobeatrisk foradverseeffects.
Hepaticinjurymayoccur(increased ALT/AST~10%),typicallyinthe first2monthsbuthasbeenseenin patients18monthsafterinitiationof treatment.Treatmentshouldbe discontinuediftransaminaselevels exceed3timestheupperlimitof normalorbilirubinlevelsare2times
mg/kgBID. greaterthannormal Dronabinol(Marinol):
2.5mgbeforelunchand
2.5mgbeforesupper; chemotherapy-induced nauseaandvomiting;an initialdoseofMarinolis
5mg/m21–3hoursprior totheadministrationof chemotherapy. Syndros:2.1mgbefore lunchanddinner; chemotherapy-induced nauseaandvomiting;4.2
mg/m2,1to3hours priortothe administrationof chemotherapy.
Mostcommon adversereactions (≥3%)areabdominal pain,dizziness, euphoria,nausea, paranoidreaction, somnolence,thinking abnormal,and vomiting.
Contraindicatedinany patientwithahypersensitivity totheactiveingredientorany cannabinoid. ForMarinol,patientswith sensitivitytosesameoiland patientswitha hypersensitivitytoalcoholor takingdisulfiramor metronidazoleshouldnot takeSyndrosbecausealcohol isusedinitsformulation.
Patientsshouldbeinstructednotto crush,break,orchewtheMarinol capsule.
Nabilone(Cesamet): Usualstartingdoseis1– 2mgBIDandcanbe increasedto2mgTID, withamaximumdoseof 6mgdaily(2mgTID).
Euphoria, hypotensionimpaired cognition. Delayedadverse reactionsinclude depressionandataxia. Lesssevereadverse reactionsinclude drowsiness,headache, vertigo/dizziness, insomniaand/or fatigue,asthenia,and drymouth.
Contraindicatedinany patientwithacannabinoid hypersensitivity.Patientswith psychiatricconditions(e.g., bipolardisorder, schizophrenia)shouldnot receivethisagentunless necessarybecauseoftherisk forexacerbatingthe psychoticdisorder.
Cautioninpatientswithcardiac conditionsduetothetachycardia andorthostatichypotension.
ALT,alanineaminotransferase;AST,aspartateaminotransferase;DS,Dravetsyndrome;GI,gastrointestinal;LGS,Lennox-Gastautsyndrome.
Oneofthekeymantras usedwhen treatingpatientswithcannabis productsis“startlow,goslow.” Dependingontheproductandthedose, theadverseeffectsoftoohighadosemaydetertheuserfrom adheringtotreatment.
GoalsofDrugTherapy
Giventhefocusofthischapterisonpainmanagementusingcannabinoids,itmustbementionedthatthe goalsofdrugtherapyusingtheseagentsarethesameasthoseofanyotheragentusedtotreatpain.With chronicpain,thegoalsoftherapyaretodecreasethepaintoatolerablelevelandimprovefunctionusing acombinationofvarioustypesoftherapiestoultimatelyenhancequalityoflife.
Dronabinol
Dronabinol(Marinol,Syndros)isasyntheticTHCproductthatisindicatedforthetreatmentofanorexia associatedwithweightlossinpatientswithAIDSandforthetreatmentofchemotherapy-inducednausea
andvomiting.
MechanismofAction
Dronabinol,asasyntheticversionofTHC,hascomplexeffectsonthecentralnervoussystem,whichmay includepartialagonismoftheCB1andCB2receptors.
Dosage
Marinolisavailablein2.5-mg,5-mg,and10-mgcapsules.Thesecapsulescontainsesameoilaspartof theformulation.Syndrosisformulatedasa5-mg/mLoralsolution,with50%dehydratedalcohol.
Forappetitestimulationandantiemeticeffects,dosingofMarinolstartsat2.5mgbeforelunchand2.5 mg before supper. Syndros is administered at 2.1 mg before lunch and dinner. The maximum recommendeddoseofSyndrosis8.4mgtwicedaily.
Fortreatmentofchemotherapy-inducednauseaandvomiting,theinitialdoseofMarinolis5mg/m2and thatofSyndrosis4.2mg/m2,1to3hourspriortotheadministrationofchemotherapy,thenevery2to4
hoursafterchemotherapy.Inbothcases,thedosemaybeincreasedordecreaseddependingonthedesired effectorundesiredsideeffects,respectively.
Patientsshouldbeinstructednottocrush,break,orchewtheMarinolcapsule.
TimeFrameforResponse
Dronabinol has an onset of action of 0.5 to1 hour with a peakeffectoccurring at 2 to4 hours. The appetitestimulationeffectmaycontinuefor24 hoursafteradministrationwhile thepsychoactiveeffect lastsonlyabout4to6hours.
Contraindications
Marinoliscontraindicatedinanypatientwithahypersensitivitytotheactiveingredient,anycannabinoid, orsesameoil,whichisusedintheproduct’sformulation.Patientswithahypersensitivitytoalcohol,or takingdisulfiramormetronidazole,shouldnottakeSyndrosbecausealcoholisusedinitsformulation.
Patientstakingdronabinolshouldbewarnednottodriveor operatemachineryuntiltheyare able to toleratethedrugandtoperformsuchtaskssafely.
AdverseEvents
Most common adverse reactions (≥3%) are abdominal pain, dizziness, euphoria, nausea, paranoid reaction,somnolence,thinkingabnormally,andvomiting.
Interactions
DronabinolisprimarilymetabolizedbytheCYP2C9and3A4systems,andthusonecouldpresumedrug– druginteractionswithagentsusingoneormoreofthesemetabolicpathways.Thus,inhibitorsorinducers oftheseenzymescanalterthesystemicconcentrationofdronabinol,andcautionmustbetakenwhenused
concomitantly.However,dronabinolisnotcurrentlyconsideredaninhibitororinducerofeitherofthese enzymesystems.
The Syndros formulation contains 50% (w/w) alcohol, and this formulation should be avoided in patientstaking disulfiram(Antabuse) ormetronidazole (Flagyl) since these agents inhibit thealdehyde dehydrogenase enzyme and can cause severe reactions (disulfiram-like reactions—cramps, nausea/vomiting,flushing).
Nabilone
Nabilone(Cesamet)isasyntheticderivativeofTHC,approvedbytheFDAforthetreatmentofnausea andvomitingassociatedwithcancerchemotherapyinpatientswhohavefailedtorespondadequatelyto conventionalantiemetictreatments. Similar to dronabinol, nabilone haspsychotomimetic reactions that arenotnormallyobservedwithotherantiemeticagents.
MechanismofAction
AsasyntheticanaloguetoTHC,nabiloneexertsitseffectsontheCB1andCB2receptors similarly. It actsasapartialagonistoftheCB1andCB2receptorsandthuswouldhavesimilareffects.
Dosage
Nabiloneisavailableorallyasa1-mgcapsule.Theusualstartingdoseis1to2mgtwicedaily,which can be increased to 2 mg thrice daily, with a maximum dose of 6 mg daily (2 mg thrice daily). For childrenunder18kg,thedoseis0.5mgtwicedailyandforchildren18to30kg,thedoseis1mgtwice daily.Forthoseover30kg,thedosewouldbe1mgthricedaily.Themanufacturerdoesnotreportany adjustmentforolderadultsorpatientsrenallyorhepaticallyimpaired.
TimeFrameforResponse
Afteroraladministration,thepeakplasmaleveloccursinabout2hours.Theparentcompoundhasahalf­life of about 2 hours, while the half-life of the metabolites is about 35 hours. The activity of the metaboliteshasnotbeencompletelyestablished,butitisspeculatedthattheymayplayaroleinthelong durationofactionoftheagent.
Contraindications
Nabiloneiscontraindicatedinanypatientwithacannabinoidhypersensitivity.Further,itshouldbeused with caution in patients with cardiac conditions because of tachycardia and the adverse effects of orthostatic hypotension associated with its use. In addition, patients with psychiatric conditions (e.g., bipolar disorder, schizophrenia) should notreceive this agentunless necessary because of the riskof exacerbatingthepsychoticdisorder.
AdverseEvents
Earlyintreatment,euphoriaandhypotensionmayoccur,aswellasimpairedcognition.Delayedadverse
reactionsincludedepression,ataxia,andorthostatichypotension.Lesssevereadversereactionsinclude drowsiness,headache,vertigo/dizziness,insomniaand/orfatigue,asthenia,anddrymouth.
Interactions
Nabilone is similar to THC; thus, the mechanism of metabolism is similar to that of THC and other cannabinoids. The nabilone prescribing information states that nabilone is extensively metabolized by multiplecytochromeP450enzymes,includingCYP3A4,CYP2E1,CYP2C9.
Cannabidiol(Epidiolex)
Cannabidiol (Epidiolex) is a 98% pure plant-derived oral CBD solution with an FDA-approved indication for the treatment of seizures associated with Lennox-Gastaut syndrome (LGS) or Dravet syndrome(DS)inpediatricpatients2yearsofageandolder.Itisthefirstplant-derivedcannabisproduct approvedbytheFDAandisconsideredanon-psychoactivecannabinoid.
Although it has not been evaluated in depth for the treatment of pain (as monotherapy), its antiinflammatory,anti-spasmodicbenefitsandgoodsafetyprofilesuggestthatitcouldbeaneffectiveand safeanalgesic.Duetothefarmbillof2018,theover-the-countermarketforCBDhasexploded.SeeBox
11.1formoreinformation.
Box11.1 CautionUsingUnregulatedCannabidiol
The 2018 farm bill is the firstpiece of federal legislation legalizing hemp and removing its DEA Schedule1controlledsubstancedesignation.However,theFDAnotesthatalthoughhempandproducts derivedfromhemparenolongerillegalsubstancesunderfederallaw,itremainsaregulatedproduct undertheFood,Drug,andCosmeticAct(FD&CAct).Theagencybasestheirauthorityonthefactthat CBDisanactiveingredientinFDA-approveddrugsandissubjecttotheFD&CAct.Therefore,any marketed cannabis product,including CBDderived from hemp, with a claimof therapeutic benefit mustbeapprovedbytheFDAbeforeitcanbesoldlegally.
TheFDAalsostatesthataddingCBDtofoodproductsordietarysupplementswouldbeunlawful.
Despitetheserestrictions,manyCBDproductsarebeingsoldonlineandinpharmacies,foodstores, healthstores,andspecialtycannabisshops.BecausetherearesomanyCBDproductsbeingproduced andsoldthroughouttheUnitedStates,andnoneofthemarefederallyregulatedbytheFDA,someof theseproducts maybe ofquestionable qualityandsafety. Further,theremaybe variabilitybetween productsandbatcheswithrespecttoquantityofactiveingredient.Bonn-Millerandcolleagues(2017) examined84CBDproductsfrom31companies.Theyfoundthatnearly43%contained10%ormore CBD than labeled (under-labeled), 31% were accurately labeled, and 26% were over-labeled. Therefore,theclinicianmustadviseapatientusingCBDfromthesesourcesthatheorshecannotknow forsurethattheproductpurchasedhastheactiveingredientsaslistedonthelabelandmustadvisethat theproductmaycontainother,insomecases,unknownelements.
Further, the clinician should inquire with the patient regarding his or her use of CBD products. Untold drug interactions and adverse effects may occur in the patient using these products without supervisionandguidance.
CBD,cannabidiol;DEA,drugenforcementagency;FDA,FoodandDrugAdministration.
MechanismofAction
CBDisthoughttohavesignificantanalgesic,antiinflammatory,anti-convulsant,andanxiolyticactivities withoutthepsychoactiveeffectofTHC.CBDhasverylittleaffinityfortheCB1andCB2receptorsasan agonistbutmayserveasanantagonist,particularlyinthepresenceofTHC.CBDisthoughttoregulatethe perceptionofpainbyaffectingtheactivityofothertargetreceptorsfoundintheECS.
Dosage
Epidiolexcomesina105-mLbottleofa100-mg/mLsolution.TheinitialdoseforthetreatmentofLGSor DSinpatients≥2yearsofageis2.5mg/kgtwicedaily.Thisdosemaybeincreasedto5mg/kgafter1 week,uptoamaximumof10mg/kgtwicedaily.Therearenodoseadjustmentsforpatientswithrenalor mildhepaticimpairment.However,forthosepatientswithmoderatetoseverehepaticimpairment(Child­PughclassificationofBorC),thedoseisadjustedto1.25mg/kgand0.5mg/kgtwicedaily,respectively.
TimeFrameforResponse
Anoral dosepeaksin2.5to5hoursandthedrug hasahalf-lifeofapproximately56to61hours.Full responsefortreatingLGSorDSisapproximately4weeks.However,forthereliefofpain,littleclinical datais available. Animalmodels suggestthatpainrelief occurs afterrepeated dosing,andoneexpert suggestsatimeframeofuptoaweekbeforearesponseisseen(McNamara,2018).
Contraindications
EpidiolexiscontraindicatedinpatientswithhypersensitivitytoCBDoranyoftheinactiveingredients (sesame oil, dehydrated alcohol). Hypersensitivity reactions, including angioedema, erythema, and pruritusrequiringantihistamines,havebeenreported.Individualswithsevereliverdiseasemayalsobe atriskforadverseeffects.
AdverseEvents
Drowsiness,sedation,fatigue,andlethargyarecommoninpatientstakingCBD.Othersleepdisturbances, includinginsomnia,mayoccur.Gastrointestinal(GI)disturbances,suchasdiarrheaandlossofappetite, may occur. Hepatic injury may occur (increased alanine aminotransferase [ALT]/aspartate aminotransferase [AST]~10%),typicallyinthefirst2 monthsbuthasbeenseeninpatients18months afterinitiationoftreatment.Treatmentshouldbediscontinuediftransaminaselevelsexceed3timesthe upperlimitofnormalorifbilirubinlevelsare2timesgreaterthannormal.
Interactions
CBD is metabolized by the CYP2C9, CYP2C19, CYP2D6, and CYP3A4 enzyme systems. CBD can inhibitthemetabolismof medicationsmetabolizedbythese systemsandthus mayincrease theriskfor adverse events. A reduction in the dose of medications metabolized by these systems should be
consideredwhenusedconcomitantly.Similarly,drugsinhibitingorinducingtheseenzymesmayincrease ordecreasethelevelofCBDinthebody,andthusdosageadjustmentsforCBDmaybenecessary.
CombinationTreatmentofTetrahydrocannabinolandCannabidiol(Sativex [Nabiximols])
Sativex, nabiximols, is available as a 1:1 combination of THC and CBD. It is a plant-derived oral mucosalsprayformulationnotyetavailableintheUnitedStates.OutsideoftheUnitedStates,nabiximols is indicated forthe“symptomimprovement inadultpatientswithmoderate tosevere spasticitydueto multiplesclerosis(MS)whohavenotrespondedadequatelytootheranti-spasticitymedication”(Sativex PrescribingInfo,2010).
TerpenesandOtherChemicalsinPainManagement
Terpenesarethemainconstituentsofessentialoilsandarecommonlyfoundincannabisplants.Essential oilsextracted fromplantsare thecompounds thattypically produce the plant’sfragrance.The oil can comefromanypartoftheplant,andsometimesdifferentoilscomefromthesameplant,justfromdifferent parts.Terpenesarethevolatilehydrocarbonsfoundintheseoilsandaretheactualmolecularcompounds thatgivetheplantitscharacteristic odor.Forexample,mentholis aterpenefromthepeppermintplant, andlimonenecanbefoundinorangepeelandothercitrusfruits.
Cannabiscontainsavarietyofterpenesthatcontributetothenamingvernacularcommonlyreferredto
asstrain names.Strainsof cannabis oftenrelateto the fragranceconferred byterpenes. However, the growing conditionsandlarge genetic variabilityamong strains thwart the creation of an accurate and reproducible chemotaxic classification based on terpene content. Nonetheless, many practitioners and patientsrelyontheterpenecontentofcannabistoconferthedesiredtherapeuticeffect.
TheFDAhasnotedthatmanyterpenesaregenerallyrecognizedassafe(Smithetal.,2005).Terpenes canbe pharmacologically active. They are lipophilicandinteractwith many differentparts of a cell. Terpenesinteractwithcellmembranes,neuronalandmuscleionchannels,G-protein-coupledreceptors, neurotransmitterreceptors,andsecondarymessengersystemsandenzymes(Russo,2019).Theseterpenes include,butarenotlimitedto,limonene,pinene,andmyrcene.Cannabisproductscontainingterpenesin concentrationsabove0.05%areconsideredofpharmacologicalinterest(Russo,2011).Box11.2liststhe mostcommonterpenesfoundincannabisplantsatpharmacologicallyrelevantconcentrations.Whenseen inthese concentrations,terpenes canhaveanxiolytic, antiinflammatory,analgesic, andsedative effects. TerpenesarethoughttohaveasynergisticeffectwithTHCand/orCBD.Thissynergisticeffectisoften referredtoastheentourageeffect(Russo,2011).Thetheoryissupportedbytheevidencethatisolated, non-plant-derived THC-basedproducts(e.g.,dronabinolornabilone)maynothavethesameeffectsas thefullplant(Russo,2019).
SelectingtheMostAppropriateDrug
Asoftheyear 2020, use ofmarijuana—or any cannabis plantcontaining more than0.3% THC—is illegalintheUnitedStatesperfederallaw.Whilemorethan50%ofthestateshavesomeformofmedical marijuanalawallowingpatientsaccesstoit,primarycarepractitionersshouldconsidercannabis-based paintreatmentonlyaftersufficienttrialsofapproved,proventreatmentshavebeentried.Andoncethat point has arrived, the patient needs to be certified by a medical practitioner (in most states, it is a
physician)thatthepatienthasanunderlyingconditionthatisonthestate’slistofapprovedconditionsfor medicalmarijuanause.Afterthatcertification,apatientmayaccessaproductbygoingtoadispensary.
Box11.2 CommonPharmacologicallyActiveTerpenesFoundinCannabisPlants
Alpha-pinene Beta-caryophyNene Beta-myrcene Limonene Linalool
TheproductselectedclearlydependsontheconditionandthetheoreticalneedforCBD,THC,and/or terpenes.Inallcases,themantrastartlow,goslowshouldalwaysbekeptinmind.
SpecialConsiderations
Pediatric
CBD is used in pediatric patients 2 years or older. It is FDA approved for the treatment of seizures associatedwithLGSandDS.Themostcommonadversereactionsareinfection,somnolence,decreased appetite,diarrhea, fatigue,andelevatedtransaminases. Serumtransaminases (ALTandAST) andtotal bilirubinlevelsshouldbemonitoredinallpediatricpatients.
Geriatric
Medical marijuanashouldbe usedcautiouslyingeriatric populationsduetothesedativepropertiesof certainmarijuanastrainsandshouldbeinitiatedatthelowerendofthedosingrange.
Women
Although there is limited evidence regarding the use of marijuana during pregnancy, it is strongly recommendedthatwomenavoiditsusewhilepregnant.Infantswhoarebornfrommotherswhohavebeen exposedtocannabisduringpregnancytendtohavelowerbirthweight.
Ethnic
Cannabis dependence was found to be the greatest among blacks, mixed-race adults, and Native Americans(Wuetal.,2016).
Genomics
Minimal evidence hasbeenpublishedregardingpharmacogenomicsandthe association with cannabis.
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