Entries by Michelle Smith

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Cannabidiol Inhibits Tumorigenesis in Cisplatin-Resistant Non-Small Cell Lung Cancer via TRPV2

Drug resistance is the key factor contributing to the therapeutic failure of lung cancer and the deaths related to lung cancer. Our study demonstrated that small molecular weight non-psychotropic phytochemical, cannabidiol (CBD), inhibits growth and metastasis of drug-resistant non-small cell lung cancer cells (NSCLC) cells in-vitro and in-vivo. We further discovered that CBD mediates its anti-cancer effects in part via an ion channel receptor, TRPV2, present on lung adenocarcinoma. Moreover, we showed that CBD induces apoptosis of cisplatin-resistant cells by modulating oxidative stress pathways. Overall, these studies indicate that CBD could be used as a promising therapeutic strategy in TRPV2 expressing cisplatin-resistant NSCLC.

Cannabidiol goes nuclear: The role of PPARγ

Cannabidiol (CBD) is one of the main phytocannabinoids found in Cannabis sativa. In contrast to Δ9-tetrahydrocannabinol, it has a low affinity for cannabinoid receptors CB1 and CB2, thereby it does not induce significant psychoactive effects. However, CBD may interact with other receptors, including peroxisome proliferator-activated receptor gamma (PPARγ). CBD is a PPARγ agonist and changes its expression. There is considerable evidence that CBD’s effects are mediated by its interaction with PPARγ. So, we reviewed studies related to the interaction of CBD and PPARγ.

Cannabidiol and Cannabigerol, Nonpsychotropic Cannabinoids, as Analgesics that Effectively Manage Bone Fracture Pain and Promote Healing in Mice

Bone fractures are among the most prevalent musculoskeletal injuries, and pain management is an essential part of fracture treatment. Fractures heal through an early inflammatory phase, followed by repair and remodeling. Nonsteroidal anti‐inflammatory drugs (NSAIDs) are not recommended for fracture pain control as they potently inhibit the inflammatory phase and, thus, impair the healing. Opioids do not provide a better alternative for several reasons, including abuse potential. Accordingly, there is an unmet clinical need for analgesics that effectively ameliorate postfracture pain without impeding the healing. Here, we investigated the analgesic efficacy of two nonpsychotropic cannabinoids, cannabidiol (CBD) and cannabigerol (CBG), in a mouse model for tibial fracture.

Cannabidiol Oil Ingested as Sublingual Drops or Within Gelatin Capsules Shows Similar Pharmacokinetic Profiles in Healthy Males

Cannabidiol (CBD) is a nonintoxicating phytocannabinoid used in clinical treatments and sold widely in consumer products. CBD products may be designed for sublingual or oral delivery, but it is unclear whether either is advantageous for CBD absorption. This study compared CBD pharmacokinetics after providing CBD oil as sublingual drops and within orally ingested gelatin capsules, at a dose relevant to consumer products.

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Cannabidiol (CBD) inhibits glioblastoma progression through regulation of tumor microenvironment in a murine model

Glioblastoma multiforme (GBM) is the most common invasive brain tumor composed of diverse cell types with poor prognosis. The highly complex tumor microenvironment (TME) and its interaction with tumor cells play important roles in the development, progression, and durability of GBM. Angiogenic and immune factors are two major components of TME of GBM, their interplay is a major determinant of tumor vascularization, immune profile, as well as immune unresponsiveness of GBM. Given the ineffectiveness of current standard therapies (surgery, radiotherapy, and concomitant chemotherapy) in managing patients with GBM, it is necessary to develop new ways of treating these lethal brain tumors. Targeting TME, altering tumor ecosystem may be a viable therapeutic strategy with beneficial effects for patients in their fight against GBM.

Cannabichromene and Δ9-Tetrahydrocannabinolic Acid Identified as Lactate Dehydrogenase-A Inhibitors by in Silico and in Vitro Screening

Cannabis sativa contains >120 phytocannabinoids, but our understanding of these compounds is limited. Determining the molecular modes of action of the phytocannabinoids may assist in their therapeutic development. Ligand-based virtual screening was used to suggest novel protein targets for phytocannabinoids. The similarity ensemble approach, a virtual screening tool, was applied to target identification for the phytocannabinoids as a class and predicted a possible interaction with the lactate dehydrogenase (LDH) family of enzymes. In order to evaluate this in silico prediction, a panel of 18 phytocannabinoids was screened against two LDH isozymes (LDHA and LDHB) in vitro.

Biosynthetic Pathway and Medical Role of Cannabigerolic Acid

Nowadays, the application of cannabinoids in various fields is gradually increasing, and more and more studies have
been conducted on cannabigerolic acid, the basic compound produced by cannabis plants, which is produced by the
reclamation of olivine acid and isopentenyl catalyzed by cannabis isopentenyl transferase. They are isoprenylated
polyketone compounds derived from fatty acids and isoprenoid precursors. They are common receptors for all
cannabinoid synthetases and have important effects on the production of cannabinoids. At the same time, CBGA also
has certain medicinal value, which has certain efficacy in the treatment of diabetes, and glioblastoma, reducing
neuroinflammation of neurodegenerative diseases and treating the side effects of chemotherapy, and will not produce
psychotoxic side effects. This paper will describe the synthesis pathway and medical effects of cannabigerolic acid.

Binge and Cannabis Co-Use Episodes in Relation to White Matter Integrity in Emerging Adults

Growing evidence suggests that cannabis and alcohol (and especially binge alcohol drinking) use independently alters neural structure and functioning, particularly during sensitive developmental time periods (e.g., emerging adulthood). However, few studies have investigated the effects of same-day use of these two substances. Here, white matter (WM) integrity was investigated in relation to binge alcohol drinking, cannabis, and same-day binge and cannabis co-use in adolescents and emerging adults.

Behavioural and molecular effects of cannabidiolic acid in mice

Cannabidiolic acid (CBDA) is one of the most abundant phytocannabinoid acids in the Cannabis sativa plant. It has been shown that it is able to exert some therapeutic effects such as antiemetic, anti-inflammatory, anxiolytic or antidepressant, although some of them remain under debate. In the present study we aim to assess the potential behavioural effects of CBDA as well as its modulation of neuroinflammatory markers in the prefrontal cortex (PFC).

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Autism Spectrum Disorder and Medical Cannabis: Review and Clinical Experience

Autism spectrum disorder (ASD) is a multifactorial, pervasive neurodevelopmental disorder defined by the core symptoms of significant impairment in social interaction and communication as well as restricted, repetitive patterns of behavior. In addition to these core behaviors, persons with ASD frequently have associated noncore behavioral disturbance (ie, self-injury, aggression), as well as several medical comorbidities. Currently, no effective treatment exists for the core symptoms of ASD. This review reports the available preclinical and clinical data regarding the use of cannabis and cannabidiol in the treatment of core symptoms, noncore symptoms and comorbidities associated with ASD. Additionally, we describe our clinical experience working with children and young adults with ASD who have used cannabis or cannabidiol. At present, preclinical and clinical data suggest a potential for therapeutic benefit among some persons with ASD and that it is overall well tolerated. Further research is required to better identify patients who may benefit from treatment without adverse effects.

At the heart of microbial conversations: endocannabinoids and the microbiome in cardiometabolic risk

Cardiometabolic syndrome encompasses intertwined risk factors such as hypertension, dyslipidemia, elevated triglycerides, abdominal obesity, and other maladaptive metabolic and inflammatory aberrations. As the molecular mechanisms linking cardiovascular disease and metabolic disorders are investigated, endocannabinoids have emerged as molecules of interest. The endocannabinoid system (ECS) of biologically active lipids has been implicated in several conditions, including chronic liver disease, osteoporosis, and more recently in cardiovascular diseases. The gut microbiome is a major regulator of inflammatory and metabolic signaling in the host, and if disrupted, has the potential to drive metabolic and cardiovascular diseases. Extensive studies have unraveled the impact of the gut microbiome on host physiology, with recent reports showing that gut microbes exquisitely control the ECS, with significant influences on host metabolic and cardiac health. In this review, we outline how modulation of the gut microbiome affects host metabolism and cardiovascular health via the ECS, and how these findings could be exploited as novel therapeutic targets for various metabolic and cardiac diseases.