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Introduction - The Cannabis Edition! Idon’tthinkI’dbealoneinconfessingthatIhavehadownersASKmeaboutcannabisoilfortheirdogs.Idon’tthinkI’dbealoneinsayingIhaveclientsthatareGIVINGtheirdogscannabisoil(somepurchasedproducts,somehome-made). Subsequently, Idon’t thinkI’dbealone insayingthat IwishIhadmoreinformationonthesubject. Well,Voilà!Thisnewsletterisdedicatedtoexactlythat! SearchingthroughPubMed,someinterestingarticleswerefound.Myfavouritehastobethe2016reviewpaper!Justcheckit out! Yep,more research is needed, but that holds true for somany things that are actually in usealready. I’mdeTinitely of the opinion that cannabis oil has an important future in humanand animalmedicine!Enjoytheread!Cheers,Laurie

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Cannabinoids in Vet

Medicine

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FOUR LEG NEWS

Cannabinoids and

Osteoarthritis

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CannabinoidsMisc.

Research

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Owners learning

about CBD

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Cannabinoids in Vet Medicine LandaL,SulcovaA,GbelecP.Theuseofcannabinoidsinanimalsandtherapeuticimplicationsforveterinarymedicine:areview.VeterinariMedicina61(3),2016:111-122.

AlittleCannabinoidhistory:Cannabinoidshavebeenusedintraditionalmedicineforthousandsofyears. ReportsofusegobacktoancientChina,medievalPersia,and 19th century Europe. Treatmentwas largely aimed at varioussomatic disorders such as headache, fever, bacterial infections,diarrhoea,rheumaticpain,ormalaria.

Cannabinoidclassi3ications:1. Endogenous cannabinoids – released in response to

increasesinintracellularcalcium.2. Herbal cannabinoids – chemical produced by the female

plants of Cannabis sativa and are found in the resin of theherb.

3. Synthetic cannabinoids – manufactured cannabinoids thatbind to cannabinoid receptors (originally created forresearch).

Nexttoknow–thebodyhascannabinoidreceptors! Thetwomainreceptorsareasfollows:

CB1receptorsarefoundinthecentralnervoussysteminregionsofthebrainresponsible forpainmodulation(partsof thespinalcord,the periaqueductal gray),movement (basal ganglia, cerebellum) ormemory processing (hippocampus& cerebral cortex). To a lesserextent,theycanalsobefoundinsomeperipheraltissuessuchasthepituitary gland, immune cells, reproductive tissues, gastrointestinaltissues, sympathetic ganglia, heart, lung, urinary bladder andadrenalglands.

CB2 receptors are primarily found in the periphery, and highestdensity on immune cells, especially B-cells and natural killer cellsand also in tonsils or spleen; nevertheless, their presence has alsobeendescribedintheCNS.

The psychotropic effects of cannabinoids aremediated only by theactivationofCB1receptorsandnotofCB2receptors

Cannabinoidsinhumans:Theirtherapeuticpotentialhasbeendemonstratedinthetreatmentof many disorders including pain, inTlammation, cancer, asthma,glaucoma, spinal cord injury, epilepsy, hypertension, myocardialinfarction, arrhythmia, rheumatoid arthritis, diabetes, multiplesclerosis, Parkinson’s disease, Alzheimer’s disease, depression orfeeding-relateddisorders,andmanyothers.

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Not just for hippies anymore!!

As of 2015, Bangladesh, Cambodia, Canada, Chile, Colombia, the Czech Republic, India, Jamaica, Mexico, Portugal, Spain, Costa Rica, Uruguay, Germany, the Netherlands, some U.S. states, Native American Indian reservations, and cities as well as some territories of Australia have the least restrictive cannabis laws.

THE BASICS:

THC =tetrahydrocannabinol =psychotropic

CBD =cannabidiol =medicinal / therapeutic

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Cannabinoidsandanimals:Theeffectsof cannabinoidsonanimalscanbe foundon theexperimentallevel and were obtained during the pre-clinical testing of individualsubstancesinmice,ratsandguineapigs(i.e.laboratoryrodents).BeneTicialeffects of cannabinoids in these animals have been reported e.g. fordisorders of the cardiovascular system, cancer treatment, pain treatment, disorders of the respiratorysystemormetabolicdisorders.

Ithasbeenshownthatthemechanismofactionofcannabinoidsisverycomplex.

TheactivationofcannabinoidCB1receptorsresults inretrograde inhibitionof theneuronalreleaseofacetylcholine, dopamine, GABA, histamine, serotonin, glutamate, cholecystokinin, D-aspartate, glycineandnoradrenaline.

CB2receptorslocalizedmainlyincellsassociatedwiththeimmunesystemareinvolvedinthecontrolofinTlammatoryprocesses.Theiractivationresultsin,amongothereffects,inhibitionofpro-inTlammatorycytokineproductionandincreasedreleaseofanti-inTlammatorycytokines.

Some cannabinoids were shown to act not only at cannabinoid receptors but also at vanilloid orserotonin5-HT3receptors.

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Non-Rodentpapers& 3indings are less abundant. Promisingresearchisneverthelessavailable!• Research dating back to the 1950’s in Czechoslovakiashowed antibiotic properties of cannabinoids. More recentresearchbacksthisupaswell!• The most frequently reported companion animal use ofcannabinoidsisforglaucoma.• Promising results shown for inTlammation and painapplications in dermatology (healing of lesions, reducing mastcell hyperactivity, and reducing allergic skin reaction) andoncology (inhibitor of angiogenesis in osteosarcoma cells,stimulationofeating,andantiemeticactivity). Note-worthy• Cannabis-basedmedicalproductswereintroducedtohumanmedicine in the last years in many countries (among othersAustria,Canada,CzechRepublic,Finland,Germany,Israel,Italy).• Preparations approved for use in human medicine includeCesamet, Dronabinol, Sativex, Bedrocan, Bedrobinol, Bediol,BedicaorBedrolite. • For dogs and cats, the veterinarian-recommended, readymade hempbased supplement Canna-Pet is presently available(containingnon-psychoactivecannabidiol-CBD).• The reluctant attitude of veterinarians towards the use ofcannabinoids/medicalmarijuanainanimalscouldbeassociatedwith the risk that owners will make attempts to treat theiranimals using cannabis-based products, which can lead tointoxication.• Legislative regulations may differ in various countries andthe use of cannabinoids/ medical marijuana must be inaccordancewiththerespectiverules.

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FUN FACTS!

Cannabis is the largest cash crop in the U.S., exceeding corn and wheat combined – Source

 In Colorado, medical marijuana dispensaries outnumber Starbucks locations 3 to 1 – Source

Rastafarians are legally allowed to possess marijuana in Italy due to it being a ‘sacrament’ to the religion. – Source

During Prohibition, Pharmacies sold “Medicinal Whiskey,” much like today’s Medicinal Marijuana. – Sourcehttp://www.kickassfacts.com/25-kickass-interesting-facts-about-marijuana/

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What about Osteoarthritis? Injection (intra-peritoneal) or oral administration of cannabidiol (CBD) at onset of clinicalsymptomsofinducedarthritisinmiceresultedinablockingofprogressionofarthritis. Bothmethodsofadministrationwereequallyeffective.Dosedependencyshowedabellcurvewhenadministered: 2.5mg/kg and 20mg/kg (highest and lowest doses tested) were ineffectivewhengiveni.p.,whereas5mg/kgwas‘justright’!Orally,25mg/kgwasmosteffective(againadosenotthehighestorlowesttested).

• Evaluation of the biochemical events following administering of CBD in this modelshowthatthereisacombinedimmunosuppressiveandanti-inTlammatoryactionsthatresultinanti-arthriticeffectsininduced-OA.

One study engaged in looking at the importance of CB2 receptors in the progression of OAcreatedbydestabilizationof themedialmeniscus inmice. They found thatmice thatwerelacking in CB2 receptors had amore severe OA sequelea than ‘normalmice’ who had CB2receptors.

• Thus,CB2pathwaysseemtoplayaroleinthepathophysiologyofOAinmice,andshowthatpharmacologicalactivationofCB2hasaprotectiveeffect.

Useofasyntheticnonpsychoactivecannabinoidacid(ajulemicacid)was testedonratswithinduced arthritis. Synthetic cannabinoid was found to suppress production of matrixmetalloproteinases(asubstance found in joint tissueofpatientswith inTlammatoryarthritissignifyingcartilagedegradationandboneerosion).

• Syntheticcannabinoidacid(AjA)maybeusefulinbothrheumatoidandosteoarthritis.

References:1. Malfait AM, Gallily R, Sumariwalla PF, et al. The

nonpsychoactive cannabis constituent cannabidiol isan oral anti-arthritic therapeutic in murine collagen-induced arthritis. ProcNatlAcad SciUSA. 2000,Aug15;97(17):9561-6.

2. Sophocleous A, Borjesson AE, Salter DM, Ralston SH.The type 2 cannabinoid receptor regulatessusceptibility toosteoarthritis inmice. OsteoarthritisCartilage.2015,Sep;23(9):1586-1594.

3. JohnsonDR,StebulisJA,RossettiRG,etal.Suppressionof Tibroblas metalloproteinases by ajulemic acid, anonpsychoactivecannabinoidacid.2007,Jan1;100(1):184-90.

Description of puri3ication of CBD from theMalfaitstudymentionedabove: GaoniY&MechoulamR.J.Am.Chem.Soc., 1971, 93 (1),pp217–224http://pubs.acs.org.cyber.usask.ca/doi/pdf/10.1021/ja00730a036

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More Nuggets of Goodness

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GastroesophagealreTluxdisease(GERD)maybetreatedbyactivationofCB1receptorsintheperiphery. A range of compounds demonstrated a dose-dependent inhibition of transientloweresophagealsphincterrelaxationinadogmodel.

Claims of clinical efTicacy in epilepsy of CBD-predominant cannabis or medical marijuanacomemostlyfromlimitedstudies,surveys,orcasereports.Themechanismremainsunclear.

Cannabinoid ligands regulate bone mass. Cannabidiol (CBD) enhances the biomechanicalpropertiesofhealingratmid-femoralfractures.

Effectofcannabidiolintradiscalinjectionwasstudiedincoccygealintervertebraldiscsofratswithinduceddiscdegeneration.120nmolofcannabidiolsigniTicantlyminimizedtheeffectsofthediscdamage.

References:1. PlowrightAT,NilssonK,AntonssonMetal. Discoveryofagonistsofcannabinoidreceptor1restricted

centralnervoussystempenetrationaimedfortreatmentofgastroesophagealreTluxdisease.JMedChem.2013,Jan10,56(1):220-40.

2. ReddyDS,GolubVM.Thepharmacologicalbasisofcannabistherapyforepilepsy. JPharmacolExpTher.2016,Apr;357(1):45-55.

3. Kogan NM, Melamed E, Wasserman E. Cannabidiol, a major non-psychotropic cannabis constituentenhances fracture healing and stimulates Lysl Hydroxylase activity in osteoblasts. J Bone Miner Res.2015,Oct;30(10):1905-13.

4. SilveiraJW,IssyAC,CastaniaVA,etal.Protectiveeffectsofcannabidiolonlesion-inducedintervertebral

Don’t leave your Marijuana baked goods out where Fido can find them!

Meola et al, 2012, J Vet Emerg Crit Care (San Antonio) found a signiTicant correlationbetween thenumberofmedicalmarijuana licenses andmarijuana toxicosis cases seen intwoveterinaryhospitals inColorado. Ingestionofbakedgoodsmadewithmedicalgradetetrahydrocannabinolbutterresultedintwodeaths.

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Dog Owners are Learning More about Cannabis Dogs Naturally Magazine had an article recently, Cannabis for your dog: How it can help.

http://www.dogsnaturallymagazine.com/cannabis-dog-can-help/

ThearticletalksmoreaboutHempratherthanMarijuana.

Both hemp and marijuana come from the plant Cannabis sativia(however,marijuanacanalsocomefromCannabisindica).Accordingto the articlemarijuana has a THC content between 10 – 15%; buthemphasonly0.3%orless.Hemphowever,ishigherinCBD.

Veterinarians are Tinding CBD hemp to be useful in treating acuteailments like sprains and strains, torn ligaments, bone breaks andevenduringpost-operativecaretoreduceswelling,painandstiffness.Apparently, as with any herbal medicine, you may not see animmediateeffect. Perhaps itwillhelpwithpainwithina fewhours,butinTlammationcouldtakelongertorespond.

CBDhempmaymakeyourdogalittledrowsy.Onrareoccasions,sideeffectshaveincludedexcessiveitchinessormildvomiting.

Where to buy CBD Hemp? The article suggested the followingsuppliers:

Canna-Pet Canna4Pets Treat Well CannaCompanion Auntie Dolores Treatibles

Dosing?Start low andwork up. 1 drop of CBD oil per 10lbs of dog’s bodyweightperday. Ifthatgoeswell,thenmoveuptotwiceadaydosing.Youcouldincreasethedoseevery4–5daysuntiltherapeuticbeneTitsare seen (without side effects). Watch out for disorientation,hyperactivity, vomiting,orexcessive sedation. If anyof these thingshappen,thearticleisclear,thatoneshouldtaketheiranimaltotheirveterinarian.

MORE FUN FACTS!

In Bhutan, marijuana grows wild and is more common than regular grass. However, virtually no one smokes it. Instead it is the number one source of feed for pigs. – Source

US, Canadian and Australian consumption of cannabis per capita is more than double that of the Dutch, despite it being legal in Netherlands. – Source

Cannabis grew rampantly in Brooklyn around 1951 before being eradicated by the Sanitation Department – Source

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Did you know: China, Egypt, France, Indonesia, Japan, Malaysia, Nigeria, Norway, the Philippines, Poland, Saudi Arabia, Singapore, South Korea, Thailand, Turkey, Ukraine, the United Arab Emirates and Vietnam have the strictest cannabis laws.

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Source:

https://en.wikipedia.org/wiki/Legality_of_cannabis_by_country

See what else is available to learn: Visit www.fourleg.com Drop me a line! Send me your questions!

Four Leg Rehab Inc PO Box 1581,

Cochrane, AB T4C 1B5 Canada

Laurie@Fourleg.com