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  • Cardiovascular, Pain, Safety
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Cannabis for chronic pain: cardiovascular safety in a nationwide Danish study

Abstract Background and aims: A rising number of countries allow physicians to treat chronic pain with medical cannabis. However, recreational cannabis use has been linked with cardiovascular side effects, necessitating investigations concerning the safety of prescribed medical cannabis. Methods: Using nationwide Danish registers, patients with chronic pain initiating first-time treatment with medical cannabis during 2018-21 were identified and matched 1:5 to corresponding control patients on age, sex, chronic pain diagnosis, and concomitant use of other pain medication. The absolute risks of first-time arrhythmia (atrial fibrillation/flutter, conduction disorders, paroxysmal tachycardias, and ventricular arrhythmias) and acute coronary syndrome were reported comparing medical cannabis use with no use. Results: Among...
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Cumulative Deleterious Effects of Tetrahydrocannabinoid (THC) and Ethanol on Mitochondrial Respiration and Reactive Oxygen Species Production Are Enhanced in Old Isolated Cardiac Mitochondria

Abstract Delta 9 tetrahydrocannabinol (THC), the main component of cannabis, has adverse effects on the cardiovascular system, but whether concomitant ethanol (EtOH) and aging modulate its toxicity is unknown. We investigated dose responses of THC and its vehicle, EtOH, on mitochondrial respiration and reactive oxygen production in both young and old rat cardiac mitochondria (12 and 90 weeks). THC dose-dependently impaired mitochondrial respiration in both groups, and such impairment was enhanced in aged rats (−97.5 ± 1.4% vs. −75.6 ± 4.0% at 2 × 10−5 M, and IC50: 0.7 ± 0.05 vs. 1.3 ± 0.1 × 10−5 M, p < 0.01, for old and young rats, respectively). The...
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Marijuana use and coronary artery disease in young adults

Abstract Background Marijuana is the most popular drug of abuse in the United States. The association between its use and coronary artery disease has not yet been fully elucidated. This study aims to determine the frequency of coronary artery disease among young to middle aged adults presenting with chest pain who currently use marijuana as compared to nonusers. Methods In this retrospective study, 1,420 patients with chest pain or angina equivalent were studied. Only men between 18 and 40 years and women between 18 and 50 years of age without history of cardiac disease were included. All patients were queried about current or prior...
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Vasodilatory effects of cannabidiol in human pulmonary and rat small mesenteric arteries: modification by hypertension and the potential pharmacological opportunities

Abstract Objective:  Cannabidiol (CBD) has been suggested as a potential antihypertensive drug. The aim of our study was to investigate its vasodilatory effect in isolated human pulmonary arteries (hPAs) and rat small mesenteric arteries (sMAs). Methods:  Vascular effects of CBD were examined in hPAs obtained from patients during resection of lung carcinoma and sMAs isolated from spontaneously hypertensive (SHR); 11-deoxycorticosterone acetate (DOCA-salt) hypertensive rats or their appropriate normotensive controls using organ bath and wire myography, respectively. Results:  CBD induced almost full concentration-dependent vasorelaxation in hPAs and rat sMAs. In hPAs, it was insensitive to antagonists of CB1 (AM251) and CB2 (AM630) receptors but it was reduced...
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Cannabidiol Ameliorates Monocrotaline-Induced Pulmonary Hypertension in Rats

Abstract Cannabidiol (CBD) is known for its vasorelaxant (including in the human pulmonary artery), anti-proliferative and anti-inflammatory properties. The aim of our study was to examine the potential preventive effect of chronic CBD administration (10 mg/kg/day for three weeks) on monocrotaline (MCT)-induced pulmonary hypertension (PH) rats. PH was connected with elevation of right ventricular systolic pressure; right ventricle hypertrophy; lung edema; pulmonary artery remodeling; enhancement of the vasoconstrictor and decreasing vasodilatory responses; increases in plasma concentrations of tissue plasminogen activator, plasminogen activator inhibitor type 1 and leukocyte count; and a decrease in blood oxygen saturation. CBD improved all abovementioned changes induced by PH except...
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Cannabidiol inhibits multiple cardiac ion channels and shortens ventricular action potential duration in vitro

Please use this link to access this publication. Abstract Cannabidiol (CBD) is a non-psychoactive component of Cannabis which has recently received regulatory consideration for the treatment of intractable forms of epilepsy such as the Dravet and the Lennox-Gastaut syndromes. The mechanisms of the antiepileptic effects of CBD are unclear, but several pre-clinical studies suggest the involvement of ion channels. Therefore, we have evaluated the effects of CBD on seven major cardiac currents shaping the human ventricular action potential and on Purkinje fibers isolated from rabbit hearts to assess the in vitro cardiac safety profile of CBD. We found that CBD inhibits with comparable micromolar potencies the peak and late...
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The electrophysiological effect of cannabidiol on hERG current and in guinea-pig and rabbit cardiac preparations

Abstract Interest is increasing regarding use of Cannabidiol (CBD) in companion animals due to anecdotal evidence of beneficial behavioral and health effects. The purpose of this investigation was to evaluate the influence of CBD on behavioral responses to fear-inducing stimuli in dogs. Sixteen dogs (18.1 ± 0.2 kg) were utilized in a replicated 4 × 4 Latin square design experiment with treatments arranged in a 2 × 2 factorial, consisting of control, 25 mg CBD, trazodone (100 mg for 10–20 kg BW, 200 mg for 20.1–40 kg BW), and the combination of CBD and trazodone. A fireworks model of noise-induced fear was used to...
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The The Effect of Delta-9-Tetrahydrocannabinol and Cannabidiol on Blood Flow

Abstract   Background: This study is based on the premise that while consumption of cannabis has increased for medicinal and recreational purposes there has also been an increase in adverse events seemingly associated with cannabis usage.   Objective: This study was designed to investigate the effect of different concentrations of Delta-9-Tetrahydrocannabinol (THC) and Cannabidiol (CBD) separately and in combination on blood flow.   Method: Forty male Sprague-Dawley rats were randomly divided into eight groups consisting of five rats each. Six of the test groups received different concentrations of THC and CBD (1 and 2 mg/kg body weight) respectively, while the seventh group received an extract with a...
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The TRPV2 channel mediates Ca2+ influx and the Δ9-THC-dependent decrease in osmotic fragility in red blood cells

Abstract Water and ionic homeostasis of red blood cells (RBC) is regulated by various active and passive transport mechanisms in the RBC membrane, including channels like aquaporins, 1 the mechanically activated non-selective cation channel Piezo12 and the Ca2+-activated potassium channel KCa3.1.3 The human genome contains 27 genes that code for transient receptor potential (TRP) channels. The only TRP channel protein that has been detected in circulating mouse RBC is TRPC6,4 which might be associated with basal Ca2+ leakage and stress-stimulated Ca2+ entry.4 TRPC2 and TRPC3 are expressed by murine erythroid precursors and splenic erythroblasts, and in these cells, erythropoietin stimulates an increase in intracellular...
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Exposure to Δ9-tetrahydrocannabinol during rat pregnancy leads to impaired cardiac dysfunction in postnatal life

Abstract Background Cannabis use in pregnancy leads to fetal growth restriction (FGR), but the long-term effects on cardiac function in the offspring are unknown, despite the fact that fetal growth deficits are associated with an increased risk of developing postnatal cardiovascular disease. We hypothesize that maternal exposure to Δ9-tetrahydrocannabinol (Δ9-THC) during pregnancy will impair fetal development, leading to cardiac dysfunction in the offspring. Methods Pregnant Wistar rats were randomly selected and administered 3 mg/kg of Δ9-THC or saline as a vehicle daily via intraperitoneal injection from gestational days 6 to 22, followed by echocardiogram analysis of cardiac function on offspring at postnatal days 1 and...
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