Entries by Michelle Smith

,

The Endocannabinoid System and Physical Exercise

The endocannabinoid system (ECS) is involved in various processes, including brain plas- ticity, learning and memory, neuronal development, nociception, inflammation, appetite regulation, digestion, metabolism, energy balance, motility, and regulation of stress and emotions. Physical exercise (PE) is considered a valuable non-pharmacological therapy that is an immediately available and cost-effective method with a lot of health benefits, one of them being the activation of the endoge- nous cannabinoids. Endocannabinoids (eCBs) are generated as a response to high-intensity activities and can act as short-term circuit breakers, generating antinociceptive responses for a short and variable period of time. A runner’s high is an ephemeral feeling some sport practitioners experience during endurance activities, such as running. The release of eCBs during sustained physical exercise appears to be involved in triggering this phenomenon. The last decades have been characterized by an increased interest in this emotional state induced by exercise, as it is believed to alleviate pain, induce mild sedation, increase euphoric levels, and have anxiolytic effects. This review provides information about the current state of knowledge about endocannabinoids and physical effort and also an overview of the studies published in the specialized literature about this subject.

,

Reprogramming systemic and local immune function to empower immunotherapy against glioblastoma

The limited benefits of immunotherapy against glioblastoma (GBM) is closely related to the paucity of T cells in brain tumor bed. Both systemic and local immunosuppression contribute to the deficiency of tumor-infiltrating T cells. However, the current studies focus heavily on the local immunosuppressive tumor microenvironment but not on the co-existence of systemic immuno- suppression. Here, we develop a nanostructure named Nano-reshaper to co- encapsulate lymphopenia alleviating agent cannabidiol and lymphocyte recruiting cytokine LIGHT. The results show that Nano-reshaper increases the number of systemic T cells and improves local T-cell recruitment condition, thus greatly increasing T-cell infiltration. When combined with immune checkpoint inhibitor, this therapeutic modality achieves 83.3% long-term survivors without recurrence in GBM models in male mice. Collectively, this work unveils that simultaneous reprogramming of systemic and local immune function is critical for T-cell based immunotherapy and provides a clinically translatable option for combating brain tumors.

,

Antioxidant promotion and oxidative stress downregulation by β-caryophyllene oxide attenuate lung cancer A549 cell proliferation

One of the most common cancers that result in death is lung cancer. There is new hope in the ght against lung cancer thanks to the chemopreventive properties of natural dietary substances like β- caryophyllene oxide (CPO), and research is currently being done to test this theory. CPO, a sesquiterpene isolated from medicinal plant essential oils, inhibits carcinogenesis and has been effective in treating many cancers. This study examined how CPO affected proliferation of human lung cancer A549 cells. CPO was found to have an inhibitory concentration (IC50) of 124.1 g/ml.

,

Effects of Cannabidiol on Innate Immunity Experimental Evidence and Clinical Evidence

Cannabidiol (CBD) is the main non-psychotropic cannabinoid derived from cannabis (Cannabis sativa L., fam. Cannabaceae). CBD has received approval by the Food and Drug Administration (FDA) and European Medicines Agency (EMA) for the treatment of seizures associated with Lennox–Gastaut syndrome or Dravet syndrome. However, CBD also has prominent anti-inflammatory and immunomodulatory effects; evidence exists that it could be beneficial in chronic inflammation, and even in acute inflammatory conditions, such as those due to SARS-CoV-2 infection. In this work, we review available evidence concerning CBD’s effects on the modulation of innate immunity. Despite the lack so far of clinical studies, extensive preclinical evidence in different models, including mice, rats, guinea pigs, and even ex vivo experiments on cells from human healthy subjects, shows that CBD exerts a wide range of inhibitory effects by decreasing cytokine production and tissue infiltration, and acting on a variety of other inflammation-related functions in several innate immune cells. Clinical studies are now warranted to establish the therapeutic role of CBD in diseases with a strong inflammatory component, such as multiple sclerosis and other autoimmune diseases, cancer, asthma, and cardiovascular diseases

Cannabis Use and COVID-19 Hospitalization Outcomes. A Retrospective Study

In vitro studies have shown cannabinoids blocking SARS-CoV-2 cellular entry and affecting replication. There is a paucity of data assessing the effect of cannabis on patients hospitalized with COVID in the USA. The aim of our study was to assess mortality and complication rates in patients hospitalized with COVID stratified by cannabis use.

,

Cannabinol inhibits cell growth and triggers cell cycle arrest and apoptosis in cancer cells

Cannabinol (CBN) is a weak-psychoactive cannabinoid and has been shown to exert several bio-logical activities. At the same time, not much is known about the anti-cancer activities of CBN. In this report, we characterized the anti-tumor effects of CBN on the glioma A172, liver cancer HepG2 and breast cancer HCC1806 cell lines. We found that CBN reduces the proliferation of the analyzed cancer cells and modulates the level of cannabinoid receptors, including GPR18, CB2 and GPR55. Furthermore, CBN inhibits the ERK1/2 pathway in A172 and HepG2 cells, while suppressing the AKT pathway in HCC1086 cells. Moreover, CBN may cause apoptosis through downregulation of p21 and p27 as well as a cell cycle arrest at G1 or S-phase via decreasing the CDK1, CDK2, and cyclin E1 levels. Taken together, these results offer new insights into the anti-cancer properties of CBN.

,

Changes in Prescribed Opioid Dosages Among Patients Receiving Medical Cannabis for Chronic Pain, New York State, 2017-2019

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.

,

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.

,

Therapeutic and Supportive Effects of Cannabinoids in Patients with Brain Tumors (CBD Oil and Cannabis)

The potential medicinal properties of Cannabis continue to garner attention, especially in the brain tumor domain. This attention is centered on quality of life and symptom management; however, it is amplified by a significant lack of therapeutic choices for this specific patient population. While the literature on this matter is young, published and anecdotal evidence imply that cannabis could be useful in treating chemotherapy-induced nausea and vomiting, stimulating appetite, reducing pain, and managing seizures. It may also decrease inflammation and cancer cell proliferation and survival, resulting in a benefit in overall patient survival. Current literature poses the challenge that it does not provide standardized guidance on dosing for the above potential indications and cannabis use is dominated by recreational purposes. Furthermore, integrated and longitudinal studies are needed but these are a challenge due to arcane laws surrounding the legality of such substances. The increasing need for evidence-based arguments about potential harms and benefits of cannabis, not only in cancer patients but for other medical use and recreational purposes, is desperately needed.

Young Adults’ Attitudes Towards Marijuana Use

Marijuana is categorized as an addictive substance that increases the likelihood of substance abuse in the future and is one of the most used illicit drugs in the United States. Marijuana use at a younger age increases the likelihood of continued use into young adulthood (Feeney & Kampman, 2016; Keyes et al., 2016; Friese, 2017). Young adults that use marijuana are more likely to introduce other peers and family members to the drug due to peer pressure, curiosity, or as a socialization tool.