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Saoirse Elizabeth O'Sullivan

Saoirse Elizabeth O'Sullivan
CanPharmaConsulting

BA Mod Hons (Physiology) PhD

About

117
Publications
26,851
Reads
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4,661
Citations
Citations since 2017
48 Research Items
3220 Citations
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20172018201920202021202220230200400600800
20172018201920202021202220230200400600800
20172018201920202021202220230200400600800
Additional affiliations
September 2007 - February 2015
University of Nottingham
Position
  • Lecturer, Associate professor
October 1998 - October 2002
Trinity College Dublin
Position
  • PhD
October 1998 - September 2002
Trinity College Dublin
Position
  • PhD
Education
September 1998 - September 2001
Trinity College Dublin
Field of study
  • Physiology (Cardiovascular)
October 1994 - June 1998
Trinity College Dublin
Field of study
  • Physiology

Publications

Publications (117)
Article
Full-text available
The cannabinoid 1 (CB1) receptor regulates appetite and body weight; however, unwanted central side effects of both agonists (in wasting disorders) or antagonists (in obesity and diabetes) have limited their therapeutic utility. At the peripheral level, CB1 receptor activation impacts the energy balance of mammals in a number of different ways: inh...
Article
Full-text available
Introduction: Cannabidiol (CBD) can be isolated from Cannabis sativa L. or synthetically produced. The aim of this study was to compare the in vitro effects of purified natural and synthetic CBD to establish any pharmacological differences or superiority between sources. Methods: Six purified samples of CBD were obtained, 4 of these were natural...
Article
Full-text available
Background: Animal models of stroke have been criticised as having poor predictive validity, lacking risk factors prevalent in an aging population. This pilot study examined the development of comorbidities in a combined aged and high-fat diet model, and then examined the feasibility of modelling stroke in such rats. Methods: Twelve-month old male...
Article
Knowledge about the therapeutic potential of medical cannabis has greatly improved over the past decade, with an ever-increasing range of developments in human clinical applications. A growing body of scientific evidence supports the use of medical cannabis products for some therapeutic indications, whilst for others, the evidence base remains disp...
Article
Full-text available
Background and Objectives: Preclinical studies have shown cannabidiol is protective in models of ischemic stroke. Based on results from our recent systematic review, we investigated the effects of two promising neuroprotective phytocannabinoids, cannabigerol (CBG) and cannabidivarin (CBDV), on cells of the blood-brain barrier (BBB), namely human br...
Article
Full-text available
Background: Pharmacological management of chronic neuropathic pain (CNP) still represents a major clinical challenge. Collective harnessing of both the scientific evidence base and clinical experience (of clinicians and patients) can play a key role in informing treatment pathways and contribute to the debate on specific treatments (e.g., cannabino...
Article
Full-text available
Paediatric brain tumours are the second most common cancer after haematological malignancies. Intermittent dosing regimens are typical for chemotherapy drugs in order to avoid excessive damage to organs and avoid the onset of late effects. Cannabidiol (CBD) has been shown to have cytotoxic properties on paediatric brain tumour cell lines. Although...
Article
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Brain tumours are the leading cause of cancer related death in children with limited treatment options and high recurrence rates. Recent evidence suggests there may be anti-tumoral properties of cannabinoids, and of cannabidiol (CBD) in particular. We evaluated the effect of CBD on paediatric brain tumour cell lines in 2D and 3D spheroids; pHGG (SF...
Article
Full-text available
Coronavirus disease-19 (COVID-19)-related anxiety and post-traumatic stress symptoms (PTSS) or post-traumatic stress disorder (PTSD) are likely to be a significant long-term issue emerging from the current pandemic. We hypothesize that cannabidiol (CBD), a chemical isolated from Cannabis sativa with reported anxiolytic properties, could be a therap...
Article
Full-text available
Background and purpose Remote ischaemic per‐conditioning (RIC) is neuroprotective in experimental ischaemic stroke. Several neurohumoral, vascular and inflammatory mediators are implicated. The effect of RIC on plasma biomarkers was assessed using clinical data from the REmote ischaemic Conditioning After Stroke Trial (RECAST‐1). Methods RECAST‐1...
Article
Full-text available
Emerging evidence suggests that dysregulated lipid signaling is a key factor in prostate cancer (PC), through fatty acid activation of the nuclear receptors peroxisome proliferator-activated receptors (PPARs), leading to the upregulation of protumoral genes. Fatty acid-binding proteins (FABPs) are intracellular lipid-binding proteins that transport...
Article
Full-text available
Undercarboxylated osteocalcin (ucOC) improves glucose metabolism; however, its effects on endothelial cell function are unclear. We examined the biological effect of ucOC on endothelial function in animal models ex vivo and human cells in vitro. Isometric tension and immunohistochemistry techniques were used on the aorta of male New Zealand white r...
Article
Full-text available
Cannabidiol (CBD) has substantial therapeutic potential, but its development as an effective drug by the pharmaceutical industry is hindered by intrinsic characteristics such as low bioavailability, low water solubility, and variable pharmacokinetic profiles. Importantly, lack of patentability of the drug substance also limits the likelihood of an...
Article
Full-text available
Embase and Pubmed were systematically searched for articles addressing the neuroprotective properties of phytocannabinoids, aside from cannabidiol and Δ9‐tetrahydrocannabinol, including Δ9‐tetrahydrocannabinolic acid (Δ9‐THCA), Δ9‐tetrahydrocannabivarin (Δ9‐THCV), cannabidiolic acid (CBDA), cannabidivarin (CBDV), cannabichromene (CBC), cannabichrom...
Article
Full-text available
IntroductionWhile the beneficial effects of sodium-glucose cotransporter-2 (SGLT-2) inhibitors on cardiovascular and renal outcomes are recognized, their direct effects on endothelial function remain unclear. We, therefore, undertook a systematic review to evaluate the current literature in this area. Methods Electronic databases (PubMed, EMBASE, a...
Article
Remote ischaemic conditioning (RIC) is achieved by repeated transient ischaemia of a distant organ/limb and is neuroprotective in experimental ischaemic stroke. However, the optimal time and methods of administration are unclear. Systematic review identified relevant preclinical studies; two authors independently extracted data on infarct volume, n...
Article
Full-text available
Osteocalcin (OCN) is a bone-derived protein that is detected within human calcified vascular tissue. Calcification is particularly prevalent in chronic kidney disease (CKD) patients but the role of OCN in calcification, whether active or passive, has not been elucidated. Part 1: The relationship between OCN, CKD and vascular calcification was asses...
Article
Many psychiatric illnesses have a multifactorial etiology involving genetic and environmental risk factors that trigger persistent neurodevelopmental impairments. Several risk factors have been individually replicated in rodents, to understand disease mechanisms and evaluate novel treatments, particularly for poorly-managed negative and cognitive s...
Article
Introduction: Over-the-counter cannabidiol (CBD) products have seen unprecedented recent growth in the United Kingdom. However, analysis of these predominantly unregulated products from other countries tells us that they are often mislabeled or contain unlabeled and potentially dangerous chemicals. Thus, the aim of the present study was to analyze...
Article
Full-text available
Objective The primary aim was to determine endocannabinoid (EC) concentrations of 2-arachidonoylglycerol (2-AG), oleoylethanolamine (OEA), palmitoylethanolamine (PEA) and anandamide (AEA) in the aqueous humour of patients, and to investigate any differences in gender and diabetic or ocular disease status. Methods and Analysis Adult participants (a...
Article
Full-text available
Background: In vivo studies show that cannabidiol (CBD) acutely reduces blood pressure (BP) in men. The aim of this study was to assess the effects of repeated CBD dosing on haemodynamics. Methods: Twenty-six healthy males were given CBD (600 mg) or placebo orally for seven days in a randomised, placebo-controlled, double-blind, parallel study (...
Article
Full-text available
Background Repeated episodes of limb ischemia and reperfusion (remote ischemic conditioning [ RIC ]) may protect the brain from ischemic reperfusion injury. Methods and Results We performed a phase II b blinded dose‐escalation sham‐controlled trial in patients with hyperacute stroke, randomized 1:1 to receive RIC (four 5‐minute cycles) or sham to...
Article
Full-text available
Some human observational studies have suggested an anti‐inflammatory role of osteocalcin (OCN). An inflammatory protocol using interferon‐γ and tumor necrosis factor‐α (10 ng/ml) was employed to examine the acute (24 hr) and chronic (144 hr) effects of uncarboxylated OCN (ucOCN) in commercial, primary, subcultured human aortic endothelial cells (HA...
Article
Full-text available
Bone-derived factors that demonstrate extra-skeletal functions, also termed osteokines, are fast becoming a highly interesting and focused area of cross-disciplinary endocrine research. Osteocalcin (OCN), fibroblast growth factor-23 (FGF23) and lipocalin-2 (LCN-2), produced in bone, comprise an important endocrine system that is finely tuned with o...
Article
Background and purpose: We have previously reported that endocannabinoids modulate permeability in Caco-2 cells under inflammatory conditions and hypothesised in the present study that endocannabinoids could also modulate permeability in ischemia/reperfusion. Experimental approach: Caco-2 cells were grown on cell culture inserts to confluence. T...
Article
Full-text available
Aims: Cannabidiol is a cannabis-derived medicinal product with potential application in a wide-variety of contexts, however its effective dose in different disease states remains unclear. This review aimed to investigate what doses have been applied in clinical populations, in order to understand the active range of cannabidiol in a variety of med...
Article
Full-text available
Structural alterations and breakdown of the blood brain barrier (BBB) is often a primary or secondary consequence of disease, resulting in brain oedema and the transport of unwanted substances into the brain. It is critical that effective in vitro models are developed to model the in vivo environment to aid in clinically relevant research, especial...
Conference Paper
Full-text available
Introduction Vascular calcification (VC), the progressive deposition of calcium within the vasculature, is a major risk factor for morbidity, mortality and cardiovascular disease, particularly within chronic kidney disease (CKD) patients. Accurate and reliable in vitro models are essential to allow for investigation into the complex mechanisms behi...
Article
Full-text available
The purpose of this study was to characterize the direct effects of uncarboxylated osteocalcin (ucOCN) on vascular cell biology in vitro, to assess its potential function in pathophysiological conditions such as atherosclerosis. Human aortic endothelial cells (HAECs) and smooth muscle cells (HASMCs) were treated with ucOCN (0.1-50 ng/ml) and change...
Article
Background and aims We aimed to examine, for the first time, the effect of cannabidiol (CBD) and palmitoylethanolamide (PEA) on the permeability of the human gastrointestinal tract in vitro, ex vivo, and in vivo. Methods Flux measurements of fluorescein-labeled dextrans 10 (FD10) and fluorescein-labeled dextrans 4 (FD4) dextran across Caco-2 cultu...
Article
Full-text available
Background: Cannabidiol is being pursued as a therapeutic treatment for multiple conditions, usually by oral delivery. Animal studies suggest oral bioavailability is low, but literature in humans is not sufficient. The aim of this review was to collate published data in this area. Methods: A systematic search of PubMed and EMBASE (including MEDLINE...
Article
Full-text available
The euphoric feeling described after running is, at least in part, due to increased circulating endocannabinoids (eCBs). eCBs are lipid signaling molecules involved in reward, appetite, mood, memory and neuroprotection. The aim of this study was to investigate whether activities other than running can increase circulating eCBs. Nine healthy female...
Article
Full-text available
The euphoric feeling described after running is, at least in part, due to increased circulating endocannabinoids. Endocannabinoids are lipid signalling molecules involved in reward, appetite, mood, memory and neuroprotection. The aim of this study was to investigate whether activities other than running can increase circulating endocannabinoids. 9...
Article
Full-text available
The endocannabinoid system (ECS) is involved in many physiological processes including fertility, pain and energy regulation. The aim of this systematic review was to examine the contribution of single nucleotide polymorphisms (SNPs) of the ECS to adiposity and glucose metabolism. Database searches returned 734 articles, of which 65 were included c...
Conference Paper
Background: Remote ischaemic per-conditioning (RIC) in experimental ischaemic stroke is neuroprotective. Several neurohumoral, vascular and inflammatory mediators are implicated. Methods: The REmote ischaemic Conditioning After Stroke Trial (RECAST) was a pilot blinded sham-controlled trial in patients with ischaemic stroke, randomised to receive f...
Article
Full-text available
9-Tetrahydrocannabinol (THC) has complex effects on the cardiovascular system. We aimed to systematically review studies of THC and haemodynamic alterations. PubMed, Medline, and EMBASE were searched for relevant studies. Changes in blood pressure (BP), heart rate (HR), and blood flow (BF) were analysed using the Cochrane Review Manager Software. T...
Article
Full-text available
Background Clinical trials investigating the use of cannabinoid drugs for the treatment of intestinal inflammation are anticipated secondary to preclinical literature demonstrating efficacy in reducing inflammation. Methods We systematically reviewed publications on the benefit of drugs targeting the endo-cannabinoid system in intestinal inflammat...
Article
Objective: We sought to quantify the anti-inflammatory effects of two cannabinoid drugs, cannabidiol (CBD) and palmitoylethanolamide (PEA), in cultured cell lines and compared this effect with experimentally inflamed explant human colonic tissue. These effects were explored in acutely and chronically inflamed colon, using inflammatory bowel diseas...
Article
Full-text available
Background Osteocalcin (OC) is an intriguing hormone, concomitantly being the most abundant non-collagenous peptide found in the mineralized matrix of bone, and expanding the endocrine function of the skeleton with far-reaching extra-osseous effects. A new line of enquiry between OC and vascular calcification has emerged in response to observations...
Poster
Full-text available
Abstract: Cardiovascular disease is the number one killer worldwide. Osteocalcin (OCN) is an intriguing, unique hormone having established roles throughout the body emigrating beyond its origin of the bone extra cellular matrix. A new line of enquiry between OCN and vascular calcification has emerged in response to observations that the mechanism o...
Article
Background: Cannabidiol (CBD) is a nonpsychoactive phytocannabinoid used in multiple sclerosis and intractable epilepsies. Preclinical studies show CBD has numerous cardiovascular benefits, including a reduced blood pressure (BP) response to stress. The aim of this study was to investigate if CBD reduces BP in humans. Methods: Nine healthy male...
Chapter
Since the early 2000s, evidence has been accumulating that most cannabinoid compounds interact with the nuclear hormone family peroxisome proliferator-activated receptors (PPARs). This can be through direct binding of these compounds to PPARs, metabolism of cannabinoid to other PPAR-activating chemicals, or indirect activation of PPAR through cell...
Article
Full-text available
Background and purpose: We have shown that in vitro treatment with cannabidiol (CBD, 2 h) enhances endothelial function in arteries from Zucker diabetic fatty (ZDF) rats, partly due to a cyclooxygenase (COX)-mediated mechanism. The aim of the present study was to determine whether treatment with CBD in vivo would also enhance endothelial function....
Article
Full-text available
The endocannabinoid system has previously been shown to play a role in the permeability and inflammatory response of the human gut. The goal of our study was to determine the effects of endogenous anandamide (AEA) and 2-arachidonoyl glycerol (2-AG) on the permeability and inflammatory response of intestinal epithelium under normal, inflammatory, an...
Article
Full-text available
Despite cannabidiol (CBD) having numerous cardiovascular effects in vitro, its haemodynamic effects in vivo are unclear. Nonetheless, the clinical use of CBD (Epidiolex) is becoming more widespread. The aim of this systematic review was to establish whether CBD is associated with changes in haemodynamics in vivo. Twenty-five studies that assessed t...
Article
Full-text available
Background and purpose: Repeated episodes of limb ischemia and reperfusion (remote ischemic conditioning [RIC]) may improve outcome after acute stroke. Methods: We performed a pilot blinded placebo-controlled trial in patients with acute ischemic stroke, randomized 1:1 to receive 4 cycles of RIC within 24 hours of ictus. The primary outcome was...
Presentation
Introduction: The bone hormone osteocalcin (OCN) has been recently connected to a number of extra-osseous functions, particular its undercarboxylated (ucOCN) form. Research into the effects of both ucOCN and the carboxylated (cOCN) form in the vasculature has resulted in a number of revelations including increased Akt phosphorylation and nitric oxi...
Poster
Abstract: Introduction: The bone hormone osteocalcin (OCN) has been recently connected to a number of extra-osseous functions, particular its undercarboxylated (ucOCN) form. Research into the effects of both ucOCN and the carboxylated (cOCN) form in the vasculature has resulted in a number of revelations including increased Akt phosphorylation and...
Article
Full-text available
Cannabinoids modulate intestinal permeability through CB1 The endocannabinoid-like compounds oleoylethanolamine (OEA) and palmitoylethanolamine (PEA) play an important role in digestive regulation, and we hypothesized they would also modulate intestinal permeability. Transepithelial electrical resistance (TEER) was measured in human Caco-2 cells to...
Article
Full-text available
The endocannabinoid anandamide (AEA) causes vasorelaxation in animal studies. Although circulating AEA levels are increased in many pathologies, little is known about its vascular effects in humans. The aim of this work was to characterise the effects of AEA in human arteries. Ethical approval was granted to obtain mesenteric arteries from patients...
Article
Full-text available
Objective: Cannabidiol (CBD) and Δ(9)-tetrahydrocannabivarin (THCV) are nonpsychoactive phytocannabinoids affecting lipid and glucose metabolism in animal models. This study set out to examine the effects of these compounds in patients with type 2 diabetes. Research design and methods: In this randomized, double-blind, placebo-controlled study,...
Article
Some cannabinoids activate the different isoforms of peroxisome proliferator-activated receptors (PPARs; α, β and γ), as shown through the use of reporter gene assays, binding studies, selective antagonists and knockout studies. Activation of all isoforms, but primarily PPARα and γ, mediate some (but not all) of the analgesic, neuroprotective, neur...
Article
Full-text available
Background: Acute Kidney Injury (AKI) is a common and serious with no specific treatment. An episode of AKI may affect organs distant to the kidney, further increasing the morbidity associated with AKI. The mechanism of organ cross-talk after AKI is unclear. The renal and immune systems of pigs and humans are alike. Using a preclinical animal (por...
Article
Full-text available
Background and purpose: In vivo and in vitro studies have demonstrated a protective effect of cannabidiol (CBD) in reducing infarct size in stroke models, and against epithelial barrier damage in numerous disease models. We aimed to investigate whether CBD also affects blood-brain barrier (BBB) permeability following ischaemia. Experimental appro...
Article
Full-text available
The endocannabinoid system is expressed in bone, although its role in the regulation of bone growth is controversial. Many studies have examined the effect of endocannabinoids directly on osteoclast function, but few have examined their role in human osteoblast function, which was the aim of the present study. Human osteoblasts were treated from se...
Article
The endocannabinoid system is widely distributed throughout the cardiovascular system. Endocannabinoids play a minimal role in the regulation of cardiovascular function in normal conditions, but are altered in most cardiovascular disorders. In shock, endocannabinoids released within blood mediate the associated hypotension through CB1 activation. I...
Article
Full-text available
The protective effects of cannabidiol (CBD) have been widely shown in preclinical models and have translated into medicines for the treatment of multiple sclerosis and epilepsy. However, the direct vascular effects of CBD in humans are unknown. Using wire myography, the vascular effects of CBD were assessed in human mesenteric arteries, and the mec...
Article
Background and Purpose Endocannabinoids alter permeability at various epithelial barriers, and cannabinoid receptors and endocannabinoid levels are elevated by stroke, with potential neuroprotective effects. We therefore explored the role of endocannabinoids in modulating blood–brain barrier (BBB) permeability in normal conditions and in an ischaem...
Article
Full-text available
Aim: We examined endocannabinoids (ECs) in relation to bariatric surgery and the association between plasma ECs and markers of insulin resistance. Methods: A study of 20 participants undergoing bariatric surgery. Fasting and 2-hour plasma glucose, lipids, insulin, and C-peptide were recorded preoperatively and 6 months postoperatively with plasm...
Article
Full-text available
Background and purpose: Endocannabinoids alter permeability at various epithelial barriers, and cannabinoid receptors and endocannabinoid levels are elevated by stroke, with potential neuroprotective effects. We therefore explored the role of endocannabinoids in modulating blood-brain barrier (BBB) permeability in normal conditions and in an ischa...
Conference Paper
Full-text available
Reductions in plasma endocannabinoids following bariatric surgery in morbidly obese females with impaired glucose homeostasis: A non-randomized prospective study • Endocannabinoids (ECs) are bioactive lipid mediators − N-arachidonyl ethanolamine (AEA) − N-palmitoyl ethanolamine (PEA) − N-oleoyl ethanolamine (OEA) − related N-acylethanolamine (NAE)...
Article
Full-text available
Endothelial dysfunction is a key initiating event in vascular disease in chronic kidney disease (CKD) patients and haemodialysis (HD) patients exhibit significant vascular abnormalities. To understand this further, we examined how ex vivo intrinsic function in isolated arteries correlates with in vivo assessments of cardiovascular status in HD pati...
Article
Full-text available
Cannabinoids (CBs) show promise as neuroprotectants with some agents already licensed in humans for other conditions. We systematically reviewed CBs in preclinical stroke to guide further experimental protocols. We selected controlled studies assessing acute administration of CBs for experimental stroke, identified through systematic searches. Data...
Article
Cannabinoids (CBs) show promise as neuroprotectants with some agents already licensed in humans for other conditions. We systematically reviewed CBs in preclinical stroke to guide further experimental protocols. We selected controlled studies assessing acute administration of CBs for experimental stroke, identified through systematic searches. Data...