Category Archives: Cardiovascular Disease

Chemical Composition and Antioxidant Activity of the Stembark Essential Oils of Two Cannabis sativa L. Cultivars from Komga, South Africa

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“Cannabis sativa L. is an aromatic medicinal plant with various biologically active classes of compounds such as cannabinoids, polyphenols, and terpenes.

Unlike the widely investigated inflorescence and leaf, the stembark of C. sativa has been overlooked regarding its medicinal potential. This study, therefore, was aimed at determining the chemical composition and antioxidant activity of the essential oils (EOs) obtained from the fresh and dried stembark of two C. sativa cultivars, Lifter and Cherrywine, grown in Komga, South Africa, with a view to ascertaining the more promising cultivar.

The chemical profiles of the hydro-distilled EOs were analyzed by gas chromatography-mass spectrometry (GC-MS), while an in vitro antioxidant activity assessment of the EOs was performed using DPPH and H2O2 spectrophotometric methods. The identified constituents from the EOs were molecularly docked against NOX2, a protein implicated in oxidative stress. The afforded EOs were colorless with a mild skunk-like odor. A total of thirty-two constituents were identified in both fresh and dry oils from the Lifter cultivar while the Cherrywine cultivar contained a total of forty-two constituents.

The EOs of both cultivars contained twenty compounds, notably Cannabidiol (0.25-85.03%), Caryophyllene oxide (1.27-19.58%), Caryophyllene (0.64-16.61%), Humulene (0.37-8.15%), Octacosane (3.37-6.55%), Humulene-1,2-epoxide (0.45-5.78%), Nerolidol (0.32-4.99%), Palmitic acid (1.45-4.45%), Tetracosane (1.75-2.91%), Dronabinol (0.86-2.86%), Cannabinol (0.54-1.64%), 7-epi-γ-eudesmol (0.53-1.00%), Guaiol (0.37-0.66%), Linoleic acid (0.22-0.60%), γ-Selinene (0.15-0.48%), β-Eudesmol (0.34-0.50%), and Linalool (0.24-0.30%).

The dried Lifter stembark oil (DLSO) gave the best antioxidant activity among the four investigated cannabis oils, exhibiting the lowest IC50 values of 21.68 ± 1.71 and 26.20 ± 1.34 µg/mL against DPPH and H2O2 radicals, respectively. The notable antioxidant activity of the DLSO may be attributed to the higher number (30) of constituents compared to the fresh Lifter stembark oil (LSO) with 11 constituents. Additionally, the DLSO showed a unique chemical profile comprising monoterpenes, oxygenated and hydrocarbon sesquiterpenes. Further in silico studies on the putative constituents in the Lifter cultivar revealed Cannabinol, Cannabidiol, and Linalool as the promising constituents based on their higher binding energy scores of -9.7, -8.5, and -6.5 kcal/mol, respectively, compared to L-Ascorbic acid (-5.7 kcal/mol).

It can be inferred from this study that the EOs from the stembark of C. sativa contain promising compounds, such as Cannabinol, Cannabidiol, and Linalool, which might be responsible for the displayed antioxidant activity of the oils. Thus, the study findings underscore the biological importance of C. sativa stembark in the management of oxidative stress-related conditions.”

https://pubmed.ncbi.nlm.nih.gov/40943472/

https://www.mdpi.com/1422-0067/26/17/8552

Effect of Preoperative Cannabis Use on Postoperative Pain and Outcomes Following Cardiothoracic Surgery

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“Cannabis use has grown both recreationally and medicinally in the United States over the past decades, alongside increased legalization and social acceptance. However, there remains little research investigating the effects of preoperative cannabis use on postoperative pain in patients undergoing surgery.

We conducted a single-center prospective study in adults undergoing cardiac surgery via sternotomy. Patients seen for preoperative consultation in clinic were asked a standardized survey about cannabis use. Clinical data was collected via chart review. Primary outcomes were morphine equivalents in the first 48 hours postoperatively and Visual Analog Scale (VAS) scores. Secondary outcomes were time to extubation, postoperative nausea/vomiting, ICU length of stay (LOS), reoperation, and in-hospital mortality. The non-cannabis user group had 50 patients, and the cannabis user group had 23 patients.

Average morphine equivalents in the first 48 hours were similar between cannabis users and non-users (60.98 vs 59.90; P = 0.93), as were VAS scores at 24 hours (5.52 vs 4.84; P = 0.414) and 48 hours (4.74 vs 3.90; P = 0.23). Average time to extubation (minutes) was nearly identical between cannabis users and non-users (718.41 vs 718.67; P = 0.99). There was also no significant difference in average LOS (days) between cannabis users and non-users (2.91 vs 3.48; P = 0.26). There were no differences in postoperative nausea/vomiting, reoperation, or in-hospital mortality.

In patients undergoing cardiac surgery via sternotomy, there was no effect of cannabis use on any outcomes, including morphine equivalents, Visual Analog Scale scores, time to extubation, ICU length of stay, postoperative nausea or vomiting, reoperation, or in-hospital mortality.”

https://pubmed.ncbi.nlm.nih.gov/40905360/

https://journals.sagepub.com/doi/10.1177/10892532251374952

Cannabinoid effective targeting of atherosclerotic plaquesin vivoby optimized-PLGA nanoparticles

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“Aim: While selective CB2 receptor agonists hold significant promise for mitigating inflammation and atherosclerosis, their poor physicochemical properties have hampered clinical translation. To overcome this, we engineered a sophisticated, nanoparticle-based delivery system designed for precise cannabinoid deposition at atheromatous plaque sites. Our approach utilized PEGylated PLGA nanoparticles (NPs), functionalized with a peptide ligand specifically targeting vascular cell adhesion molecule-1 (VCAM-1), a well-established biomarker of atherosclerotic lesions.

Methods: PEGylated PLGA NPs were synthesized via nanoprecipitation using a blend of PLGA, PLGA-PEG, and PLGA-PEG-Mal polymers. Peptide conjugation was then achieved through a maleimide-click reaction. The resulting functionalized nanoparticles were characterized for their physicochemical properties and evaluated both in vitro (using human vascular endothelial cells), and in vivo (in apolipoprotein E-deficient, ApoE-/-, mice).

Results: Optimal NP functionalization with the VBP peptide was achieved using a 1:1 maleimide-to-ligand molar ratio in 10 mM HEPES / 0.4 mM EDTA buffer after a 2-hour incubation. In vitro assays demonstrated that these functionalized NPs significantly downregulated the expression of adhesion molecules, inflammatory cytokines, and chemokines, while also successfully restoring oxidative balance in human endothelial cells. Importantly, in vivo experiments demonstrated efficient and site-specific delivery of the functionalized NPs to atheroprone regions in ApoE⁻/⁻ mice, resulting in a significant reduction of atherosclerotic plaque formation in the aortic sinus.

Conclusion: These findings indicate that this developed nanosystem represents a highly promising strategy for targeted cannabinoid delivery. This breakthrough could significantly contribute to the advancement of novel anti-atherogenic therapies, offering a new avenue for treating atherosclerosis.”

https://pubmed.ncbi.nlm.nih.gov/40858005/

“Collectively, these results suggest that VBP-functionalized nanoparticles loaded with CB2 agonists represent a promising therapeutic strategy for atherosclerosis. By selectively targeting VCAM-1-expressing inflammatory regions and effectively delivering cannabinoids, these nanocarriers offer a potential approach to mitigate endothelial dysfunction and reduce plaque progression. Future studies should focus on further evaluating their efficacy and safety in preclinical and clinical settings.”

https://www.sciencedirect.com/science/article/pii/S0927776525005648?via%3Dihub

Acute cannabidiol (CBD), tetrahydrocannabinol (THC) and their mixture (THC:CBD) exert differential effects on brain activity and blood flow in rats: A translational neuroimaging study

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“Background: Cannabis constituents, including Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), show distinct pharmacological profiles with therapeutic relevance for neurological and psychiatric conditions. THC exerts euphoric effects primarily via CB1 receptor activation, while CBD displays non-euphoric properties affecting various pathways.

Aims: This study evaluated the effects of THC, CBD, and their combination on brain functional connectivity (FC) and cerebral blood flow (CBF) using multimodal neuroimaging.

Methods: Adult male Sprague Dawley rats received intraperitoneal doses of 10 mg/kg THC, 150 mg/kg CBD, 10.8:10 mg/kg THC:CBD, or vehicle. Resting-state blood oxygenation level dependent magnetic resonance imaging and arterial spin labelling assessed FC and CBF, approximately 2 h after drug administration. Graph-theory metrics and seed-based analyses identified connectivity and perfusion alterations, while plasma analyses determined cannabinoid concentrations.

Results: THC increased whole-brain FC and clustering coefficient, with elevated CBF in cortical and subcortical regions. CBD decreased FC metrics without affecting CBF, while THC:CBD induced moderate increases in both. Seed-based analysis revealed THC-driven increases in cortical-hippocampal and cortical-striatal connectivity, attenuated in the THC:CBD group. A multivariate combined analysis of FC and CBF revealed a divergent pattern of changes induced by each drug.

Conclusions: In conclusion, we show that THC and CBD induce distinct neurophysiological profiles in rats, with THC increasing both connectivity and perfusion, moderated by CBD when combined. These findings corroborate existing knowledge about the effects of cannabinoids on the brain, while also supporting the potential of preclinical functional neuroimaging to delineate cannabinoid-induced endophenotypes, offering insights for therapeutic development.”

https://pubmed.ncbi.nlm.nih.gov/40838351/

“Growing evidence supports the therapeutic potential of cannabis and its constituent phytocannabinoids in treating a range of neurological and psychiatric conditions.”

“In summary, we have demonstrated that acute THC administration resulted in increases in FC and regional CBF, acute CBD administration resulted in an overall reduction in FC with negligible effect on CBF, and the combination drug THC:CBD resulted in effects similar to, but lower than THC alone. Our application of functional neuroimaging has thus identified differential pharmacodynamic signatures for THC and CBD in anaesthetised adult male rats. Further work should encompass an investigation of the effects of sub-chronic administration of phytocannabinoids on brain activity in animal models with relevance to selected disease indications to investigate changes on FC in a perturbed system, more applicable to the disease state. “

https://journals.sagepub.com/doi/10.1177/02698811251360745

Lifetime Cannabis Use and Incident Hypertension: The Coronary Artery Risk Development in Young Adults (CARDIA) Study

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“Background: Observational evidence investigating associations between cannabis use and hypertension is inconsistent.

Methods: The association between cumulative lifetime cannabis use (cannabis-years) and incident hypertension was examined over 35 years in a sample of CARDIA study (Coronary Artery Risk Development in Young Adults) participants free of hypertension at baseline. Marginal structural models with inverse probability weighting were used to adjust for potential time-dependent confounding and censoring. Hazard ratios and 95% CIs were estimated using Cox proportional hazards regression. Sensitivity analyses included modeling cannabis-years using restricted cubic splines, stratifying the primary analyses by sex, race, alcohol and cigarette smoking, and evaluating an additional exposure measure (days of use in the past month).

Results: The analytic sample consisted of 4328 participants at baseline and 64.9% (n=2810) at year 35. Median cannabis-years increased minimally and remained low across visits: 0.0 (Q1-Q3, 0.0-0.3) at baseline and 0.2 (Q1-Q3, 0.0-0.7) by year 35. There were 2478 cases of incident hypertension over 88 292 person-years (28.1 cases per 1000 person-years). Cannabis-years were not significantly associated with incident hypertension (adjusted hazard ratio, 0.99 [95% CI, 0.97-1.00]; P=0.18). The association remained unchanged in sensitivity analyses.

Conclusions: In a cohort of Black and White young adults with 35 years of follow-up, no association was found between cumulative lifetime use of cannabis and risk of incident hypertension. This finding was robust to restricted cubic spline analyses, analyses stratified by sex, race, alcohol use and tobacco cigarette smoking, and an additional measure of exposure (days of use in the past month).”

https://pubmed.ncbi.nlm.nih.gov/40785536/

“No association was found between cumulative lifetime use of cannabis, measured as cannabis-years, and incident hypertension over 35 years of follow-up in a cohort of relatively young Black and White adults free of hypertension at baseline. This finding was consistent across sensitivity analyses, including post hoc RCS analyses, analyses stratified by sex, race, alcohol use, and tobacco cigarette smoking, and an alternative measure of cannabis exposure (days of use in the past month).”

“Our findings suggest that cannabis use, even when accumulated over decades, may not independently elevate hypertension risk.”

https://www.ahajournals.org/doi/10.1161/HYPERTENSIONAHA.125.25005

Association of Smoking Cannabis With Cardiovascular Events Among Veterans With Coronary Artery Disease

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“Background: Whether cannabis is a risk factor for cardiovascular events is unknown. We examined the association between smoking cannabis and cardiovascular events in a cohort of older veterans (66 to 68 years of age) with coronary artery disease.

Methods: The THC Cohort (Heart and Cannabis) comprised 4285 veterans (mean [SD] age, 67.5 [1.01] years; 2% female) with coronary artery disease who were born in 1950 to 1952. Participants were recruited between April 5, 2018, and March 12, 2020, interviewed about health behaviors, and then classified according to their self-reported cannabis smoking status in the previous 30 days. In a separate analysis, we classified participants according to any form of cannabis use (smoking, vaping, or edible use) versus nonuse in the past 30 days. Data on demographic, behavioral, and clinical characteristics were collected by telephone interview and from national Department of Veterans Affairs and Medicare data sources. The primary outcome included a composite of fatal and nonfatal stroke, fatal and nonfatal acute myocardial infarction, and cardiovascular death. The follow-up period for each patient extended from the date of their initial interview until the end of study (June 14, 2022). All participants were followed until they experienced an outcome or until the end of the follow-up period. Survey nonresponse weights and propensity score-based weights were used to reduce bias and confounding. Hazard ratios were estimated using cause-specific hazard models.

Results: The cohort included 1015 veterans with coronary artery disease who reported smoking cannabis in the previous 30 days and 3122 veterans who did not smoke cannabis in the previous 30 days. Mean follow-up was 3.3 years, and 563 events occurred. Compared with veterans who did not smoke cannabis, smoking cannabis (past 30 days) was not associated with the composite outcome of acute myocardial infarction, stroke, and cardiovascular death (adjusted hazard ratio, 0.87 [95% CI, 0.61-1.24]). Similarly, use of any form of cannabis (smoking, vaping, dabbing, edibles) in the past 30 days was not associated with the composite outcome.

Conclusions: In this cohort of older veterans with coronary artery disease, self-reported cannabis use was not independently associated with increased cardiovascular events over a mean of 3.3 years of follow-up.”

https://pubmed.ncbi.nlm.nih.gov/40686207/

“In this older cohort of veterans with coronary artery disease, both recent and lifetime smoking of cannabis were not associated with risk for having a CVD event, defined as heart attack, stroke, or cardiovascular death.”

“Beyond established CVD risk factors, we could not detect an association of cannabis use with CVD events, so it may not be an important contributor in this population.”

https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.124.073193

Short-Term Incubation of H9c2 Cardiomyocytes with Cannabigerol Attenuates Diacylglycerol Accumulation in Lipid Overload Conditions

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“Fatty acids (FAs) play a crucial role in human physiology, including energy production and serving as signaling molecules. However, a dysregulation in their balance can lead to multiple disorders, such as obesity and metabolic syndrome. These pathological conditions alter the balance between the heart’s energetic substrates, promoting an increased reliance on FAs and decreased cardiac efficiency.

A therapeutic application of a non-psychotropic phytocannabinoid, cannabigerol (CBG), seems to be a promising target since it interacts with different receptors and ion channels, including cannabinoid receptors-CB1 and CB2, α2 adrenoceptor, or 5-hydroxytryptamine receptor.

Therefore, in the current study, we evaluated a concentration-dependent effect of CBG (2.5 µM, 5 µM, and 10 µM) on H9c2 cardiomyocytes in lipid overload conditions. Gas-liquid chromatography and Western blotting techniques were used to determine the cellular lipid content and the level of selected proteins involved in FA metabolism, glucose transport, and the insulin signaling pathway. The glucose uptake assay was performed using a colorimetric method.

Eighteen-hour CBG treatment in the highest concentration (10 µM) significantly diminished the accumulation of diacylglycerols (DAGs) and the saturation status of this lipid fraction. Moreover, the same concentration of CBG markedly decreased the level of FA transporters, namely fatty acid translocase (CD36) and plasma membrane fatty acid-binding protein (FABPpm), in the presence of palmitate (PA) in the culture medium.

The results of our experiment suggest that CBG can significantly modulate lipid storage and composition in cardiomyocytes, thereby protecting against lipid-induced cellular dysfunction.”

https://pubmed.ncbi.nlm.nih.gov/40643519/

“In our research, we presented evidence suggesting that CBG treatment, especially in higher concentrations (10 µM), may offer substantial benefits in the states associated with excessive lipid availability, which was demonstrated in the H9c2 cell model. The results obtained in our experiment suggest that CBG possesses the ability to alter the metabolism of H9c2 cells by influencing FA storage and utilization while also attenuating the inflammatory pathways activated in a high-lipid environment. These findings indicate that CBG may represent a promising therapeutic candidate for further investigation concerning lipotoxicity and insulin resistance development. Moreover, CBG is predisposed to be a metabolic modulator by altering the levels and cellular location of CD36, a major regulator of myocardial lipid metabolism and a therapeutic target for metabolic disturbances.”

https://www.mdpi.com/2073-4409/14/13/998

Cannabidiol Prevents Heart Failure Dysfunction and Remodeling Through Preservation of Mitochondrial Function and Calcium Handling

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“Heart failure (HF) is characterized by energy deprivation, calcium (Ca2+) handling alterations, and inflammation: effects associated with mitochondrial dysfunction.

Cannabidiol previously prevented mitochondrial dysfunction. Thus, it may prevent HF progression.

In mice with HF, subcutaneous cannabidiol attenuated cardiac fibrosis, hypertrophy, loss of ejection fraction, and inflammation; isolated cardiomyocytes preserved cell shortening, Ca2+ handling, mitochondrial function and redox balance. Hypertrophied ventricular cardiomyoblasts suggested cannabidiol-mediated effects through peroxisome proliferator-activated gamma receptors.

Therefore, cannabidiol in HF limited cardiac hypertrophy and preserved contractile function by sustaining cardiomyocyte and mitochondrial function through redox balance maintenance, supporting cannabidiol role as a cardioprotective therapy in HF.”

https://pubmed.ncbi.nlm.nih.gov/40562493/

“This study demonstrated that cannabidiol offers cardioprotection in a HF mouse model induced by L-NAME and ANGII administration. The results showed improved cardiac function and reduced cardiac hypertrophy, remodeling, inflammation, and cell death. In cardiomyocytes from the HF model, cannabidiol restored cell shortening, which was linked to improved calcium Ca2+ handling.

Additionally, it helped preserve cellular oxidative status, mitochondrial bioenergetics, and notably, modulated mCa2+ overload by affecting MCU expression. This suggests that the cardioprotective effects of cannabidiol are caused by the preservation of excitation-contraction-energetic coupling. The identified cellular mechanisms through which cannabidiol exerts its cardioprotective effects include reducing oxidative stress and the activation of PPAR-γ, which helps prevent mitochondrial dysfunction by decreasing MCU hyperactivity.”

“TRANSLATIONAL OUTLOOK: This study contributes to the knowledge of a novel therapy based on cannabidiol on the pathophysiology of HF, which is supported by preclinical data. Here, we described that cardioprotection exerted by cannabidiol on a HF mouse model was caused by the attenuation of cardiac fibrosis and hypertrophy along with improved ejection fraction and cardiac output. This was achieved, in the cardiomyocyte, by preservation of cell shortening, sarcoplasmic reticulum Ca2+ uptake, mitochondrial function, and redox balance, with data supporting the role of a PPAR-γ–dependent mechanism. This study suggests promising therapeutic results of cannabidiol used in the clinical field of HF treatment. In this regard, these results have inspired a translational effort to assess its effects in HF and cardiac dysfunction.”

https://www.jacc.org/doi/10.1016/j.jacbts.2024.12.009

Cannabis sativa L. Leaf Oil Displays Cardiovascular Protective Effects in Hypertensive Rats

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“Hemp (Cannabis sativa L.) leaf oil (HLO) contains several bioactive compounds such as phenolics, flavonoids, and quercetin. However, the effects of HLO on hypertensive conditions have not yet been investigated.

This study investigated the cardiovascular protective effects of HLO in a nitric oxide (NO) synthase inhibitor-induced hypertensive rat model.

Five weeks of HLO administration significantly prevented blood pressure elevation, improved cardiac function, and mitigated cardiac hypertrophy. Furthermore, HLO ameliorated vascular dysfunction by reducing sympathetic nerve stimulation-induced vasoconstriction, increasing endothelium-dependent vasorelaxation, as well as decreasing vascular wall thickness and vascular smooth muscle cell proliferation. HLO inhibited renin-angiotensin system (RAS) activation and downregulated angiotensin II type 1 (AT1) receptor and NADPH oxidase expression. Additionally, HLO normalized the circulating NO metabolites, decreased oxidative stress, and enhanced antioxidant status.

These findings suggest that HLO protects against cardiovascular dysfunction and preserves its morphology. The mechanism of action might involve the suppression of RAS overactivity and oxidative stress through the Ang II/AT1 receptor/NOX2 pathway in NO-deficient hypertension.”

https://pubmed.ncbi.nlm.nih.gov/40076524/

“In conclusion, HLO possesses a total phenolic content that demonstrates cardiovascular-protective effects against NOS inhibitor-induced hypertension. HLO exhibits an ACE inhibitory action and inhibits the Ang II/AT1 receptor/NOX2 pathway, alleviating cardiovascular hypertrophy and oxidative stress in a hypertensive rat model. Our findings suggest that HLO displays beneficial effects under a hypertensive condition.”

https://www.mdpi.com/1422-0067/26/5/1897

Cannabidiol Ameliorates Doxorubicin-Induced Myocardial Injury via Activating Hippo Pathway

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“Background: Doxorubicin (DOX) is a chemotherapeutic agent widely used for cancer treatment and has non-negligible cardiotoxicity. Some previous studies have reported that cannabidiol (CBD) has cardioprotective effects. In this study, we evaluated the protective effects of CBD against DOX-induced cardiomyocyte injury, and explored the downstream molecular mechanism.

Methods and materials: GSE193861, containing healthy myocardial tissues and myocardial tissues with DOX-induced injury, was analyzed to screen for the involved proteins and pathways. Molecular docking was performed to identify candidate drugs. After H9c2 cells were treated with DOX and CBD, their viability, oxidative stress, and apoptosis were assessed. After YAP depletion, the role of the Hippo pathway in CBD function was investigated. C57BL/6 mice were treated with DOX to establish an in vivo model, and CBD and verteporfin (VP) were used to treat the mice. Histological analyses and immunofluorescence were used to evaluate myocardial tissue injury, and apoptosis and oxidative stress of the myocardial tissues were also analyzed. Western blotting was used to investigate the regulatory effects of CBD on the Hippo and apoptosis-related pathways.

Results: Bioinformatic analysis suggested that the Hippo pathway was a crucial pathway involved in DOX-induced myocardial injury. Molecular docking showed that CBD targeted multiple regulators of the Hippo pathway. CBD showed cardioprotective effects against DOX-induced myocardial injury both in vitro and in vivo and regulated Hippo pathway activity in cardiomyocytes. After inactivation of the Hippo pathway by YAP knockdown or VP intervention, the protective effects of CBD were reversed.

Conclusion: For the first time, we revealed that CBD is likely to reduce DOX-induced myocardial injury by regulating the Hippo signaling pathway.”

https://pubmed.ncbi.nlm.nih.gov/39876987/

“Overall, this study reports that CBD alleviates DOX-induced myocardial injury by regulating the Hippo pathway.”

https://www.dovepress.com/cannabidiol-ameliorates-doxorubicin-induced-myocardial-injury-via-acti-peer-reviewed-fulltext-article-DDDT