Cannabidiol inhibits lung proliferation in monocrotaline-induced pulmonary hypertension in rats

Krzyżewska, Anna; Baranowska-Kuczko, Marta; Kasacka, Irena; Kozłowska, Hanna

doi:10.1016/j.biopha.2023.114234

Cited by 4 publications

(2 citation statements)

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“…More specifically, research in various species has evaluated its efficacy in treating diseases such as diabetes mellitus ( 29–31 ), osteoarthritis ( 21 , 28 , 32 ), and neurologic diseases (e.g., Alzheimer’s, Parkinson’s) ( 33–37 ). In addition, CBD has been proposed to treat symptoms associated with stress ( 38 ), gastrointestinal disturbances ( 39 , 40 ), orofacial pain ( 41 , 42 ), hypertension ( 43–45 ), and neoplastic processes ( 46 ). Prior to cisplatin chemotherapy in the house musk shrew ( Suncus murinus ; n = 20), intraperitoneal CBD demonstrated a biphasic response—low doses (5 mg/kg) reduced emesis and higher doses (40 mg/kg) potentiated it ( 22 ); similarly, prior to lithium chloride administration ( n = 36), intraperitoneal CBDA significantly reduced the incidence of emesis at low doses (0.1–0.5 mg/kg) but increased dosing (5 mg/kg) did not significantly reduce emesis compared to the control ( 47 ).…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics of cannabidiol-/cannabidiolic acid-rich hemp oil in juvenile cynomolgus macaques (Macaca fascicularis)

Johns,

Wakshlag,

Lyubimov

et al. 2023

Front. Vet. Sci.

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IntroductionCannabinoids are increasingly popular in human and veterinary medicine and have been studied as an alternative treatment for a wide range of disorders. The goal of this study was to perform a pharmacokinetic analysis of oral cannabidiol (CBD)-/cannabidiolic acid (CBDA)-rich hemp oil (CBD/ArHO) in juvenile cynomolgus macaques (Macaca fascicularis).MethodsAfter a 2 mg/kg CBD/ArHO pilot study, 4 and 8 mg/kg direct-to-mouth CBD/ArHO were administered (n = 4 per dose) once daily for 14 days and blood was collected at 0-, 0.5-, 1-, 2-, 4-, 8-, 12-, and 24-h, and on Days 7 and 14, to quantify serum cannabinoid concentrations by high-performance liquid chromatography–tandem mass spectrometry. Serum biochemistries and complete blood counts were performed on Days 0, 1, and 14.ResultsThe maximum mean serum concentration (Cmax) of CBDA was 28.6–36.2 times that of CBD at 4 and 8 mg/kg. At 8 mg/kg, the Cmax of CBD was 1.4 times higher (p = 0.0721), and CBDA was significantly 1.8 times higher (p = 0.0361), than at 4 mg/kg. The maximum mean serum concentration of ∆9-tetrahydrocannabinol (THC) was 4.80 ng/mL at 8 mg/kg. Changes in serum biochemistries and complete blood counts over time were not clinically significant.DiscussionGiven the low serum CBD concentrations, the doses and frequency used in this study may be insufficient for a therapeutic effect of CBD in particular; therefore, clinical studies are needed to determine the therapeutic dose of CBD and CBDA for macaques, which may differ based on the disorder targeted.

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Section: Introductionmentioning

confidence: 99%

Pharmacokinetics of cannabidiol-/cannabidiolic acid-rich hemp oil in juvenile cynomolgus macaques (Macaca fascicularis)

Johns,

Wakshlag,

Lyubimov

et al. 2023

Front. Vet. Sci.

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“…Monocrotaline has inhibitory effect on a variety of experimental tumors, and it is mainly used in skin phosphorous cell carcinoma and basal cell carcinoma [4]. At the same time, it can cause pulmonary hypertension and right ventricular hypertrophy and other toxic side effects [5][6][7][8]. It is used as an inducer of pulmonary hypertension model in medical research.…”

Section: Introductionmentioning

confidence: 99%

Determination of monocrotaline and usaramine in rat plasma by UPLC-MS/MS and their pharmacokinetics

Chen,

Wang,

Xia

et al. 2023

AChrom

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An ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed for the determination of monocrotaline and usaramine in rat plasma, to study the plasma drug concentration and pharmacokinetics, and to calculate the absolute bioavailability. The plasma was treated with acetonitrile and methanol (9:1, v/v) protein precipitation method. The chromatographic column was UPLC HSS T3 (50 mm × 2.1 mm, 1.7 μm), the mobile phase was methanol-water (containing 0.1% formic acid with 10 mM ammonium acetate in water), and the elution time was 4 min at a flow rate of 0.4 mL min−1. Electrospray ionization (ESI) positive ion mode was used for detection and multiple reaction monitoring (MRM) mode was used for quantitative analysis. Monocrotaline and usaramine were administered sublingual intravenously (iv) 1 mg kg−1 and orally (po) 5 mg kg−1, respectively, with 6 rats in each group, for a total of 24 rats. Then the pharmacokinetic differences in rats were evaluated. For the UPLC-MS/MS method, the calibration curve showed good linearity in the range of 2–2,000 ng mL−1, where r was greater than 0.99. The precision, accuracy, recovery, matrix effect and stability results were all consistent with the requirements of biological sample detection methods. to provide scientific experimental basis for the basic research The bioavailability of monocrotaline and usaramine in rat plasma was calculated, which was 43.5 and 19.5%, respectively.

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Dissecting the role of cannabinoids in vascular health and disease

Guo,

Wei,

Pei

et al. 2024

Journal Cellular Physiology

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Cannabis, often recognized as the most widely used illegal psychoactive substance globally, has seen a shift in its legal status in several countries and regions for both recreational and medicinal uses. This change has brought to light new evidence linking cannabis consumption to various vascular conditions. Specifically, there is an association between cannabis use and atherosclerosis, along with conditions such as arteritis, reversible vasospasm, and incidents of aortic aneurysm or dissection. Recent research has started to reveal the mechanisms connecting cannabinoid compounds to atherosclerosis development. It is well known that the primary biological roles of cannabinoids operate through the activation of cannabinoid receptor types 1 and 2. Manipulation of the endocannabinoid system, either genetically or pharmacologically, is emerging as a promising approach to address metabolic dysfunctions related to obesity. Additionally, numerous studies have demonstrated the vasorelaxant properties and potential atheroprotective benefits of cannabinoids. In preclinical trials, cannabidiol is being explored as a treatment option for monocrotaline‐induced pulmonary arterial hypertension. Although existing literature suggests a direct role of cannabinoids in the pathogenesis of atherosclerosis, the correlation between cannabinoids and other vascular diseases was only reported in some case series or observational studies, and its role and precise mechanisms remain unclear. Therefore, it is necessary to summarize and update previously published studies. This review article aims to summarize the latest clinical and experimental research findings on the relationship between cannabis use and vascular diseases. It also seeks to shed light on the potential mechanisms underlying these associations, offering a comprehensive view of current knowledge in this evolving field of study.

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Cannabidiol inhibits lung proliferation in monocrotaline-induced pulmonary hypertension in rats

Cited by 4 publications

References 53 publications

Pharmacokinetics of cannabidiol-/cannabidiolic acid-rich hemp oil in juvenile cynomolgus macaques (Macaca fascicularis)

Pharmacokinetics of cannabidiol-/cannabidiolic acid-rich hemp oil in juvenile cynomolgus macaques (Macaca fascicularis)

Determination of monocrotaline and usaramine in rat plasma by UPLC-MS/MS and their pharmacokinetics

Dissecting the role of cannabinoids in vascular health and disease

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