Entries by Michelle Smith

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Real-World evidence on the use of cannabidiol for the treatment of drug resistant epilepsy not related to Lennox-Gastaut syndrome, Dravet syndrome or Tuberous Sclerosis Complex

Highly purified cannabidiol (CBD) has a broad spectrum of action and could be useful for the treatment of drug resistant epilepsy regardless of etiology or syndrome. Multicenter retrospective study that evaluated the efficacy and safety of CBD for the treatment of drug resistant epilepsy of different etiologies in patients >2 years of age.

September 20, 2023 by
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Increased Hippocampal Blood Flow in People at Clinical High Risk for Psychosis and Effects of Cannabidiol

Hippocampal hyperperfusion has been observed in people at Clinical High Risk for Psychosis (CHR), is associated with adverse longitudinal outcomes and represents a potential treatment target for novel pharmacotherapies. Whether cannabidiol (CBD) has ameliorative effects on hippocampal blood flow (rCBF) in CHR patients remains unknown. Using a double-blind, parallel-group design, 33 CHR patients were randomised to a single oral 600mg dose of CBD or placebo; 19 healthy controls did not receive any drug. Hippocampal rCBF was measured using Arterial Spin Labelling. We examined differences relating to CHR status (controls vs placebo), effects of CBD in CHR (placebo vs CBD) and linear between-group relationships, such that placebo>CBD>controls or controls>CBD>placebo, using a combination of hypothesis-driven and exploratory wholebrain analyses.

September 20, 2023 by
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Cannabidiol in Sports: Insights on How CBD could improve performance and recovery

Damage caused by physical exertion (anti-inflammatory) (Gamelin et al., 2020;Kennedy, 2017;Stone et al., 2023;Villanueva et al., 2022), and reduce pain caused by high physical demands (pain and soreness reliever) (see figure 1) (Gamelin et al., 2020;Henson et al., 2022;Kennedy, 2017). substances promote sleep controlled by the endocannabinoid system, which we can activate by consuming CBD (McCartney et al., 2020;Rojas-Valverde, 2021).Sleep management requires a precise balance of neurotransmitters, and CBD’s actions on the endocannabinoid system contribute to this balance. CBD interacts with adenosine receptors, which is significant since adenosine is a neurotransmitter that promotes sleep and relaxation.CBD promotes tranquillity and preparedness for sleep by boosting adenosine signalling.Furthermore, CBD’s effect on GABAergic neurotransmission adds to its sleep-enhancing properties (Kaul et al., 2021;Kesner & Lovinger, 2020). GABA is an inhibitory neurotransmitter that promotes relaxation and drowsiness by lowering neuronal excitability.CBD’s effect on GABA receptors can promote deeper, more comfortable sleep. Furthermore, CBD’s ability to relieve anxiety and stress, which are significant causes of sleep disruption, indirectly supports greater sleep quality (Blessing et al., 2015;Moltke & Hindocha, 2021;Ortiz Rios et al., 2022). CBD provides a biological foundation for its action via modifying endocannabinoid system signalling, increasing adenosine effects, and regulating GABAergic neurotransmission (Martinez Naya et al., 2023;Yarar, 2020;Zou & Kumar, 2018).

September 16, 2023 by
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Cannabidiol alters mitochondrial bioenergetics via VDAC1 and triggers cell death in hormone-refractory prostate cancer

In spite of the huge advancements in both diagnosis and interventions, hormone refractory prostate cancer (HRPC) remains a major hurdle in prostate cancer (PCa). Metabolic reprogramming plays a key role in PCa oncogenesis and resistance. However, the dynamics between metabolism and oncogenesis are not fully understood. Here, we demonstrate that two multi-target natural products, cannabidiol (CBD) and cannabigerol (CBG), suppress HRPC development in the TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model by reprogramming metabolic and oncogenic signaling. Mechanistically, CBD increases glycolytic capacity and inhibits oxidative phosphorylation in enzalutamide-resistant HRPC cells. This action of CBD originates from its effect on metabolic plasticity via modulation of VDAC1 and hexokinase II (HKII) coupling on the outer mitochondrial membrane, which leads to strong shifts of mitochondrial functions and oncogenic signaling pathways. The effect of CBG on enzalutamide-resistant HRPC cells was less pronounced than CBD and only partially attributable to its action on mitochondria. However, when optimally combined, these two cannabinoids exhibited strong anti-tumor effects in TRAMP mice, even when these had become refractory to enzalutamide, thus pointing to their therapeutical potential against PCa.

September 16, 2023 by
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Cannabidiol Inhibits the Proliferation and Invasiveness of Prostate Cancer Cells

Prostate cancer is the fifth leading cause of cancer death in men, responsible for over 375,000 deaths in 2020. Novel therapeutic strategies are needed to improve outcomes. Cannabinoids, chemical components of the cannabis plant, are a possible solution. Preclinical evidence demonstrates that cannabinoids can modulate several cancer hallmarks of many tumor types. However, the therapeutic potential of cannabinoids in prostate cancer has not yet been fully explored. The aim of this study was to investigate the antiproliferative and anti-invasive properties of cannabidiol (CBD) in prostate cancer cells in vitro. CBD inhibited cell viability and proliferation, accompanied by reduced expression of key cell cycle proteins, specifically cyclin D3 and cyclin-dependent kinases CDK2, CDK4, and CDK1, and inhibition of AKT phosphorylation. The effects of CBD on cell viability were not blocked by cannabinoid receptor antagonists, a transient receptor potential vanilloid 1 (TRPV1) channel blocker, or an agonist of the G-protein-coupled receptor GPR55, suggesting that CBD acts independently of these targets in prostate cancer cells. Furthermore, CBD reduced the invasiveness of highly metastatic PC-3 cells and increased protein expression of E-cadherin. The ability of CBD to inhibit prostate cancer cell proliferation and invasiveness suggests that CBD may have potential as a future chemotherapeutic agent.

September 16, 2023 by
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The clinical and pathological significance of increased expression of the cannabinoid receptors CB-1R and CB-2R in patients with papillary thyroid carcinomas compared to benign thyroid lesions

Phytocannabinoids have been shown to inhibit the aggregation and neurotoxicity of the neurotoxic Alzheimer’s disease protein beta amyloid (Aβ). We characterised the capacity of six phytocannabinoids: cannabichromene, cannabigerol, cannabinol, cannabidivarin, cannabidiol and Δ9-tetrahydrocannabinol, to disrupt Aβ aggregation and protect against Aβ-evoked neurotoxicity in PC12 cells. Neuroprotection against lipid peroxidation and Aβ-induced cytotoxicity was assessed using the MTT assay. Transmission electron microscopy was used to visualise phytocannabinoid effects on Aβ aggregation and fluorescence microscopy, with morphometrics and principal component analysis to assess PC12 cell morphology.

September 16, 2023 by

The structurally diverse phytocannabinoids cannabichromene, cannabigerol and cannabinol significantly inhibit amyloid β-evoked neurotoxicity and changes in cell morphology in PC12 cells

Phytocannabinoids have been shown to inhibit the aggregation and neurotoxicity of the neurotoxic Alzheimer’s disease protein beta amyloid (Aβ). We characterised the capacity of six phytocannabinoids: cannabichromene, cannabigerol, cannabinol, cannabidivarin, cannabidiol and Δ9-tetrahydrocannabinol, to disrupt Aβ aggregation and protect against Aβ-evoked neurotoxicity in PC12 cells. Neuroprotection against lipid peroxidation and Aβ-induced cytotoxicity was assessed using the MTT assay. Transmission electron microscopy was used to visualise phytocannabinoid effects on Aβ aggregation and fluorescence microscopy, with morphometrics and principal component analysis to assess PC12 cell morphology.

September 16, 2023 by

Pharmacological Aspects and Biological Effects of Cannabigerol and Its Synthetic Derivatives

Cannabigerol (CBG) is a cannabinoid from the plant Cannabis sativa that lacks psychotomimetic effects. Its precursor is the acidic form, cannabigerolic acid (CBGA), which is, in turn, a biosynthetic precursor of the compounds cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC). CBGA decarboxylation leads to the formation of neutral cannabinoid CBG, through a chemical reaction catalyzed by heat. On the basis of the growing interest in CBG and with the aim of highlighting scientific information on this phytocannabinoid, we focused the content of this article on its pharmacokinetic and pharmacodynamic characteristics and on its principal pharmacological effects. CBG is metabolized in the liver by the enzyme CYP2J2 to produce hydroxyl and di-oxygenated products. CBG is considered a partial agonist at the CB1 receptor (R) and CB2R, as well as a regulator of endocannabinoid signaling. Potential pharmacological targets for CBG include transient receptor potential (TRP) channels, cyclooxygenase (COX-1 and COX-2) enzymes, cannabinoid, 5-HT1A, and alpha-2 receptors. Pre-clinical findings show that CBG reduces intraocular pressure, possesses antioxidant, anti-inflammatory, and anti-tumoral activities, and has anti-anxiety, neuroprotective, dermatological, and appetite-stimulating effects. Several findings suggest that research on CBG deserves to be deepened, as it could be used, alone or in association, for novel therapeutic approaches for several disorders.

September 16, 2023 by

Relative Risk of Cannabis, Alcohol, and Their Combination on Driver Behavior in Fatal Crashes in Washington State

Self-dosing of off-the-shelf cannabidiol (CBD) for a myriad of health conditions is common in the USA. These CBD products are often mislabeled, suggesting that much less or much more CBD is being consumed than indicated on the label. This study examined the relationship between long-term self-dosing of CBD and (a) indications and, when a verified concentration of CBD is being consumed, (b) the daily CBD dosage, (c) the impact on general health and symptoms, and (d) over-the-counter (OTC) and prescription (Rx) drug usage.

September 6, 2023 by

Long-Term, Self-Dosing CBD Users: Indications, Dosage, and Self-Perceptions on General Health/Symptoms and Drug Use

Self-dosing of off-the-shelf cannabidiol (CBD) for a myriad of health conditions is common in the USA. These CBD products are often mislabeled, suggesting that much less or much more CBD is being consumed than indicated on the label. This study examined the relationship between long-term self-dosing of CBD and (a) indications and, when a verified concentration of CBD is being consumed, (b) the daily CBD dosage, (c) the impact on general health and symptoms, and (d) over-the-counter (OTC) and prescription (Rx) drug usage.

September 6, 2023 by
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Recreational cannabis use over time in individuals at clinical high risk for psychosis: Lack of associations with symptom, neurocognitive, functioning, and treatment patterns

Recreational cannabis use has recently gained considerable interest as an environmental risk factor that triggers the onset of psychosis. To date, however, the evidence that cannabis is associated with negative outcomes in individuals at clinical high risk (CHR) for psychosis is inconsistent. The present study tracked cannabis usage over a 2-year period and examined its associations with clinical and neurocognitive outcomes, along with medication rates. CHR youth who continuously used cannabis had higher neurocognition and social functioning over time, and decreased medication usage, relative to non-users. Surprisingly, clinical symptoms improved over time despite the medication decreases.

September 6, 2023 by

Quality of Life in Patients Receiving Medical Cannabis

Medical cannabis has been used to relieve the symptoms of people with various chronic diseases. Despite of this, it has been stigmatized, even after its legalization in many countries. The purpose of this study was to investigate the quality of life of patients receiving medical cannabis. One hundred patients receiving medical cannabis were given (a) a socio-demographic and clinical questionnaire, and (b) the SF-36 Health Survey scale for assessing quality of life.

September 6, 2023 by