Time-dependent vascular actions of cannabidiol in the rat aorta

O’Sullivan, Saoirse E.; Sun, Yan; Bennett, Andrew J.; Randall, Michael D.; Kendall, David A.

doi:10.1016/j.ejphar.2009.03.010

Cited by 149 publications

(131 citation statements)

References 42 publications

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“…Here, the protective effects of CBD in an Aβ-induced neuroinflammatory mouse model were abolished by a PPARγ antagonist, but no evidence was given as to whether this was a direct or indirect effect [198]. CBD can also positively modulate COX via increased mRNA and protein expression of PPARγ and COX2, which also suggests that a COX2-generated increase in PGD 2 and 15d-PGJ 2 could underlie PPARγ activation in addition to any direct activation of PPARγ by CBD [18,54,93]. A possible mechanism for this is suggested by the observation that NRF2 can increase PPARγ expression as CBD can activate NRF2 [79,199,200].…”

Section: Cbd Receptor Targets In Neurodegenerationmentioning

confidence: 91%

“…CBD can bind to PPARγ, and PPARγ activation is becoming an important target in neurodegeneration, as it is antiinflammatory and its activation improves mitochondrial function and resistance to oxidative stress [54,140]. Here, the protective effects of CBD in an Aβ-induced neuroinflammatory mouse model were abolished by a PPARγ antagonist, but no evidence was given as to whether this was a direct or indirect effect [198].…”

Section: Cbd Receptor Targets In Neurodegenerationmentioning

confidence: 94%

“…These results do not confirm a direct effect of CBD upon PPARγ but the extant data warrants its inclusion for completeness. Furthermore, CBD was shown to displace a fluorescent ligand of PPARγ (Fluormone PPAR Green, Life Technologies, Paisley, UK) at a relatively low IC 50 (5 μM) in a fluorescence polarization assay, indicating that CBD may bind to this protein [54]. In addition, CBD may be directly involved in PPARγ activation as 10 μM CBD stimulates activity of the luciferase reporter gene in HEK293 cells transiently overexpressing retinoid X receptor and PPARγ [54].…”

Section: Peroxisome Proliferator-activated Receptorsmentioning

confidence: 99%

“…CBD has been shown to upregulate and activate PPARγ [18,54], and therefore it may be able to replicate the effects of pioglitazone.…”

Section: Cbd Ion Channel Targets In Movement Disordersmentioning

confidence: 99%

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Molecular Targets of Cannabidiol in Neurological Disorders

Bih

Chen

Nunn³

et al. 2015

Neurotherapeutics

462

323

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Cannabis has a long history of anecdotal medicinal use and limited licensed medicinal use. Until recently, alleged clinical effects from anecdotal reports and the use of licensed cannabinoid medicines are most likely mediated by tetrahydrocannabinol by virtue of: 1) this cannabinoid being present in the most significant quantities in these preparations; and b) the proportion:potency relationship between tetrahydrocannabinol and other plant cannabinoids derived from cannabis. However, there has recently been considerable interest in the therapeutic potential for the plant cannabinoid, cannabidiol (CBD), in neurological disorders but the current evidence suggests that CBD does not directly interact with the endocannabinoid system except in vitro at supraphysiological concentrations. Thus, as further evidence for CBD's beneficial effects in neurological disease emerges, there remains an urgent need to establish the molecular targets through which it exerts its therapeutic effects. Here, we conducted a systematic search of the extant literature for original articles describing the molecular pharmacology of CBD. We critically appraised the results for the validity of the molecular targets proposed. Thereafter, we considered whether the molecular targets of CBD identified hold therapeutic potential in relevant neurological diseases. The molecular targets identified include numerous classical ion channels, receptors, transporters, and enzymes. Some CBD effects at these targets in in vitro assays only manifest at high concentrations, which may be difficult to achieve in vivo, particularly given CBD's relatively poor bioavailability. Moreover, several targets were asserted through experimental designs that demonstrate only correlation with a given target rather than a causal proof. When the molecular targets of CBD that were physiologically plausible were considered for their potential for exploitation in neurological therapeutics, the results were variable. In some cases, the targets identified had little or no established link to the diseases considered. In others, molecular targets of CBD were entirely consistent with those already actively exploited in relevant, clinically used, neurological treatments. Finally, CBD was found to act upon a number of targets that are linked to neurological therapeutics but that its actions were not consistent withmodulation of such targets that would derive a therapeutically beneficial outcome. Overall, we find that while >65 discrete molecular targets have been reported in the literature for CBD, a relatively limited number represent plausible targets for the drug's action in neurological disorders when judged by the criteria we set. We conclude that CBD is very unlikely to exert effects in neurological diseases through modulation of the endocannabinoid system. Moreover, a number of other molecular targets of CBD reported in the literature are unlikely to be of relevance owing to effects only being observed at supraphysiological concentrations. Of interest and after excludin...

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Section: Cbd Receptor Targets In Neurodegenerationmentioning

confidence: 91%

Section: Cbd Receptor Targets In Neurodegenerationmentioning

confidence: 94%

Section: Peroxisome Proliferator-activated Receptorsmentioning

confidence: 99%

“…CBD has been shown to upregulate and activate PPARγ [18,54], and therefore it may be able to replicate the effects of pioglitazone.…”

Section: Cbd Ion Channel Targets In Movement Disordersmentioning

confidence: 99%

See 2 more Smart Citations

Molecular Targets of Cannabidiol in Neurological Disorders

Bih

Chen

Nunn³

et al. 2015

Neurotherapeutics

462

323

View full text Add to dashboard Cite

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“…A PPAR-gamma-agonizmust 3T3 L1 fi broblastok segítségével és patkány-aorta időfüggő relaxációjának csökkentésével sikerült bizonyítani. A vazorelaxáció Ca 2+ -csatorna-gátláson keresztül volt mérsékelhető [16].…”

Section: A Kannabidiol Jelentősége Obesitásbanunclassified

The potential use of cannabidiol in the therapy of metabolic syndrome

Kleiner

Ditrói

2012

Orvosi Hetilap

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A kannabidiol kannabinoid-és szerotoninreceptor-antagonista, de a rimonabantra jellemző depresszív, illetve csök-kent inzulinérzékenység mellékhatásoktól mentesen mérsékelheti a hiperfágiát. Emellett, mint a peroxiszómaprolife-rátor-aktivált receptor-gamma-agonisták, segítheti az adipocyták differenciálódását. A kannabidiol immunmoduláns hatása miatt mérsékelheti a magas glükózszint indukálta atherosclerosis progresszióját. A metabolikus szindróma legveszélyesebb szövődményével, az elzáródásos kórképekkel szemben is hatásos. A kannabidiol gyenge receptorkötődése révén csak az adjuváns terápia része lehet. A citokróm P450 enzimrendszert gátló hatása szintén óvatos-ságra int, azonban a kannabidiol kiegészítő alkalmazása gyenge mellékhatásprofi lja miatt hasznossá válhat. Orv. Hetil., 2012, 153, 499-504. Kulcsszavak: kannabidiol, metabolikus szindróma, lipidmetabolizmus, ischaemiaThe potential use of cannabidiol in the therapy of metabolic syndrome Cannabidiol, a cannabinoid and serotonin receptor antagonist, may alleviate hyperphagia without the side effects of rimonabant (for example depression and reduced insulin sensitivity). Similar to the peroxisome proliferator-activated receptor-gamma agonists, it may also help the differentation of adipocytes. Cannabidiol has an immunomodulant effect as well that helps lessen the progression of atherosclerosis induced by high glucose level. It may also be effective in fi ghting ischaemic diseases, the most harmful complications of metabolic syndrome. However, it can only be administered as an adjuvant therapy because of its low binding potency, and its inhibiting effect of cytochrome P450 enzymes should also be considered. Nevertheless,,it may be benefi cially used in adjuvent therapy because of its weak side-effect profi le. Orv. Hetil., 2012, 153, 499-504. Keywords: cannabidiol, metabolic syndrome, lipid metabolism, ischemia (Beérkezett: 2011. december 14.; elfogadva: 2012. január 15.) Rövidítések CB-R = kannabinoidreceptor; CBD = kannabidiol, GPR55 = G-protein-kapcsolt receptor; 5-HT 1A = 1A típusú szerotoninreceptor; HMGB1 = (high mobility group box1) nagy mozgékonyságú csoport: citokinszerű mediátor; iNOS = indukálható nitrogén-monoxid-szintáz; MPO = mieloperoxidáz; NADPH = nikotinamid-adenin-dinukleotid-foszfát redukált forma; NF-кB = nukleáris faktor кB; p38 MAPK = mitogén-aktivált proteinkináz; PPAR-gamma = (peroxisome proliferator-activated receptor gamma) peroxiszómaproliferátor-aktivált r eceptor-gamma; ROS = (reactive oxygen substances) reaktív oxigéngyökök; STAT = (signal transducer and activator of transcription) szignalizációs transzducer és transzkripcióaktivátor; TNF-alfa = tumornekrózis-faktor-alfa; THC = d9-tetrahidro-kannabinol; TRP = tranziens receptorpotenciál A kannabidiol a kender nem pszichoaktív fő ható-anyaga, sokrétű farmakológiai hatásából több előnyös lehet a metabolikus szindróma terápiájában.A metabolikus szindróma összetettségénél fogva nehezen kezelhető gyógyszerrel, mert egyaránt csök-kenteni kell a vérnyomást, a vércukor-, a triglicer...

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Cannabis Use and Sinonasal Symptoms in US Adults

Orozco

Lin

Hur

2022

JAMA Otolaryngol Head Neck Surg

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IMPORTANCE Cannabis is the most commonly used illicit substance in the US and worldwide. Understanding the association between cannabis use and sinonasal symptoms may help clinicians and patients better understand the symptomatology associated with cannabis use. OBJECTIVE To assess the association between frequency of cannabis use and presence of sinonasal symptoms in a nationally representative sample of US adults. DESIGN, SETTING, AND PARTICIPANTS This population-based, retrospective cross-sectional study included adults aged 20 to 69 years who had completed data on sinonasal symptoms and substance use for the 2013 to 2014 National Health and Nutrition Examination Survey. The data were analyzed in February 2022. EXPOSURES Cannabis use frequency.MAIN OUTCOMES AND MEASURES Presence of sinonasal symptoms, demographic information, and medical history were obtained from National Health and Nutrition Examination Survey questionnaires. Presence of any sinonasal symptoms was defined as responding yes to any of a series of questions assessing rhinologic symptoms. Regular cannabis users were defined as using cannabis 15 or more times within the last 30 days. Nonregular users were defined as using cannabis fewer than 15 times within the last 30 days. Multivariable models were used to examine the association between frequency of cannabis use and presence of sinonasal symptoms while adjusting for demographic characteristics and medical comorbidities. RESULTSThe study included 2269 adults with a mean (SD) age of 36.5 (12.4) years (1207 women [53.2%]; 330 Asian [14.5%], 739 Black [32.6%], 461 Hispanic [20.3%], and 656 White [28.9%] individuals). The prevalence of sinonasal symptoms among regular cannabis users (45.0%; 95% Cl, 38.9%-51.1%) was lower than the prevalence among never users (64.5%; 95% Cl, 58.3%-68.8%). Compared with adults who had never used cannabis, regular cannabis users were less likely to have sinonasal symptoms (odds ratio, 0.22, 95% CI, 0.10-0.50). Current tobacco smokers were more likely to have sinonasal symptoms (odds ratio, 1.96; 95% CI, 1.17-3.28). The most common sinonasal symptoms reported were nasal congestion (62.8%; 95% Cl, 60.2%-65.4%) and change in smell (17.8%; 95% Cl, 15.2%-20.9%). CONCLUSIONS AND RELEVANCEThis cross-sectional study found that the prevalence of sinonasal symptoms was lower among regular cannabis users. Further research is needed to elucidate the mechanisms underlying the association between cannabis use and sinonasal symptoms.

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Time-dependent vascular actions of cannabidiol in the rat aorta

Cited by 149 publications

References 42 publications

Molecular Targets of Cannabidiol in Neurological Disorders

Molecular Targets of Cannabidiol in Neurological Disorders

The potential use of cannabidiol in the therapy of metabolic syndrome

Cannabis Use and Sinonasal Symptoms in US Adults

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