Abstract
Cannabis and cannabinoids offer significant therapeutic benefits for a wide scope of pathological conditions. Among them, the clinical issues rooted in inflammation stand out, nonetheless, the underlying mechanisms are not yet plainly understood. Circumstantial evidence points to polymorphonuclear leukocytes (PMN) as targets for the anti-inflammatory effects of cannabis. Therefore, we conducted this study to assess the effects of CM5, a novel Cannabis sativa L. extract standardized in 5% cannabidiol (CBD), on human PMN functions, including cell migration, oxidative metabolism and production of tumour necrosis factor (TNF)-α. We then sought to investigate whether such effects could be ascribed to its content in CBD. Cell migration was assessed by the Boyden chamber assay, oxidative metabolism by means of spectrofluorimetric measurement of reactive oxygen species (ROS) production, and TNF-α was measured by real time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). Results show that both CM5 and CBD inhibit PMN migration, ROS and TNF-α production, indicating that CBD may be the main item responsible for the effects of CM5. CM5 is however more potent than CBD on cell migration and TNF-α production, and less effective on ROS production, suggesting that beyond CBD, other components of the cannabis plant may contribute to the biological effects of the extract. As a whole, such results support the use of cannabis standardized extract and CBD to stem inflammation; however, they also warrant in-depth investigation of the underlying cellular and molecular mechanisms to better exploit their therapeutic potential.
Highlights
The present study provides evidence that CM5, a standardized cannabis extract in CBD 5% and with THC
CBD alone was more effective than CM5 on PMN oxidative metabolism
This is the first study reporting the inhibitory effects of a cannabis extract rich in CBD and with a low level of THC on human PMN functions
Summary
Medical cannabis is available in many countries, a world of controversy still surrounds cannabis use in clinical practice in consideration of its mind-altering properties and addictive potential related to its ∆9-tetrahydrocannabinol (THC) content [3]. New varieties of cannabis have been developed which are poor in THC and rather rich in non-psychoactive cannabinoids [4]. Cannabidiol (CBD, Figure 1) is the major non-psychoactive cannabinoid and occurs naturally in appreciable amounts. CBD is devoid of any drug abuse liability [62]oafn1d1 carries no meaningful side effects across a wide dose range in humans (up to 6000 mg/day p.o.) [7,8,9]. CBD is devoid of any drug abuse liability [62]oafn1d1 carries no meaningful side effects across a wide dose range in humans (up to 6000 mg/day p.o.) [7,8,9]. pC.BoD.) [h7a–s9r]e. cCeBnDtlyhraescerievceednFtloyordecaenidveDdruFgooAddamnidniDstrrautgioAn d(FmDiAni)satrpaptiroonva(lFfDoAr s)eaizpuprreosvaaslsofocriasteedizuwrieths aLsesnoncioaxte-GdawstiathutLseynnndorxo-GmaesotaruDt sryavnedtrosymnedorormDera[v1e0t],syfunrdthroemrmeo[1re0]a, vfuariltahbelremeovriedaenvaceilasbulgegeevsitdsetnhcaet sCuBgDgemstisghtht abte CbeBnDefimciiaglhint abenubmenbeefricoiaf ldiisneaasensu, mincbleurdoinfgd: iAselzahseesim, ienrc’lsuddiisnega:seA, Plzahrekiimnseorn’s’sddiisseeaassee,, Pmaurkltiinpsloens’csledroisseisa,seep, imlepusltyi,pHleunsctlienrgotsoins,’sedpiisleeapssey,,hHypuonxtiian-gistochne’smdiaisienajuser,y,hpyapino,xaian-xisiechtye,mdeiapriensjsuiroyn,, pcaaninc,era,nnxaieutsye,ad, eipnflreasmsiomna,tocarnycderis, enaasuess,eain, fiencftliaomnms, arthoeruymdaistoeaidseas,rtihnrfietcist,ioinnsfl,armhemuamtoartyoidboawrtehlraitnisd, iCnrfolahmn’ms adtioseryasbeso,wcaerldainodvaCscruolhanr’ds idseisaesaesaens,dcdairadbioetvicasccoumlaprlidciasteioanses [a1n1d]. dPiraebliemticincaormy sptluicdaiteisonsusg[g1e1s].t Pthraetlimmoinstaoryf tshteudthieersaspuegugtiecstefftheacttsmofocsatnonfatbhies tahnedraCpBeDutmicaeyffbeectlsinokfecdatnontahbeiisr aabnidlitCyBtoDamffeacyt ibmemlinukneitdy taontdheinirflaabmilmityattioonaf[f1e2ct],imnomneutnhietyleassndthienuflnamdemrlaytiinognm[1e2c]h, nanoinsemthsealeressntohteyuent dpelarilnyilnygumndeecrhsatonoisdm. s are not yet plainly understood
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