Entries by Michelle Smith

The role of cannabinoids in neurodevelopmental disorders of children and adolescents

Neurodevelopmental disorders have a multifactorial etiology that results from the interaction between biological and environmental factors. The biological basis of many of these disorders is only partially understood, which makes therapeutic interventions, especially pharmacological ones, particularly difficult. The impact of medical cannabis on neurological and psychiatric disorders has been studied for a long time. This study aimed to review the currently available clinical and pre-clinical studies regarding the use of cannabinoids in pediatric neurodevelopmental disorders and to draw attention to the potential therapeutic role of cannabidiol in this field.

Proapoptotic RECS1: a requisite gateway to lysosomal dysfunction and death

For a long time since their discovery by Christian de Duve in the 1950s, lysosomes have been referred to almost exclusively as passive garbage bags; the endpoint in the degradation of intra- and extracellular cargo. The catabolic function of lysosomes is accomplished by an array of more than 60 acid hydrolases, which together break down a wide variety of biological macromolecules, including proteins, lipids, carbohydrates, and nucleic acids, for reutilization in the metabolic processes of the cell. For their optimal function, these enzymes require an acidic intraluminal pH of ~4.5, which is maintained by the joint action of a proton pump, the vacuolar H+-ATPase, and several ion channels embedded in the lysosomal limiting membrane. Nowadays, lysosomes are envisioned as complex signaling hubs, integrating diverse stimuli about the cell’s metabolic status to coordinate different adaptive responses (Ballabio and Bonifacino, 2020). The lysosome can also induce cell death signals in response to certain conditions, such as infections and treatment with lysosomotropic drugs, which leads to lysosomal membrane permeabilization (LMP) and the release of cathepsins, resulting in lysosomal-mediated cell death.

Cannabinol inhibits oxytosis/ferroptosis by directly targeting mitochondria independently of cannabinoid receptors

The oxytosis/ferroptosis regulated cell death pathway recapitulates many features of mitochondrial dysfunction associated with the aging brain and has emerged as a potential key mediator of neurodegeneration. It has thus been proposed that the oxytosis/ferroptosis pathway can be
used to identify novel drug candidates for the treatment of age-associated neurodegenerative diseases that act by preserving mitochondrial function. Previously, we identified cannabinol (CBN) as a potent neuroprotector. Here, we demonstrate that not only does CBN protect nerve cells from oxytosis/ferroptosis in a manner that is dependent on mitochondria and it does so independently of cannabinoid receptors

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Cannabidiol in the treatment and prevention of Alzheimer’s disease – a comprehensive

Dementia is a major public health problem. Alzheimer’s disease (AD) accounts for 60% of dementia cases. However, AD is currently considered as an incurable disorder and the only few drugs available for its treatment are mostly symptomatic. In the quest for novel drugs for this devastating disease, cannabidiol (CBD) has been recently gaining attention due to its multiple properties, such as an ability to interact with various receptors, anti-inflammatory and antioxidative effects and many more. The aim of this review article was to summarize findings on the effect of CBD on AD with a focus on molecular mechanisms of CBD’s action and therapeutic effects which it exerts.

The Impact of Cannabis Decriminalization and Legalization on Road Safety Outcomes: A Systematic Review

There is substantial debate concerning the impact of cannabis decriminalization and legalization on road safety outcomes. Seven databases were systematically searched: Embase, MEDLINE, and PsycINFO through Ovid as well as Web of Science Core Collection, SafetyLit, Criminal Justice Database (ProQuest), and Transport Research International Documentation (from inception to June 16, 2021). Eligible primary studies examined group-level cannabis decriminalization or legalization and a road safety outcome in any population

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Cannabidiol exerts anti-proliferative activity via a cannabinoid receptor 2-dependent mechanism in human colorectal cancer cells

Colorectal cancer is the third leading cause of cancer incidence and mortality in the United States. Cannabidiol (CBD), the second most abundant phytocannabinoid in Cannabis sativa, has potential use in cancer treatment on the basis of many studies showing its anti-cancer activity in diverse types of cancer, including colon cancer. However, its mechanism of action is not yet fully understood. In the current study, we observed CBD to repress viability of different human colorectal cancer cells in a dose-dependent manner. CBD treatment led to G1-phase cell cycle arrest and an increased sub-G1 population (apoptotic cells); it also downregulated protein expression of cyclin D1, cyclin D3, cyclin-dependent kinase 2 (CDK2), CDK4, and CDK6. CBD further increased caspase 3/7 activity and cleaved poly(ADP-ribose) polymerase, and elevated expression of endoplasmic reticulum (ER) stress proteins including binding immunoglobulin protein (BiP), inositol-requiring enzyme 1α (IRE1α), phosphorylated eukaryotic initiation factor 2α (eIF2α), activating transcription factor 3 (ATF3), and ATF4.

Systematic literature review of human studies assessing the efficacy of cannabidiol for social anxiety

The current review evaluates the potential of cannabidiol (CBD) as a promising pharmacotherapy for social anxiety disorder (SAD). Although a number of evidence-based treatments for SAD are available, less than a third of affected individuals experience symptom remission after one year of treatment. Therefore, improved treatment options are urgently needed, and CBD is one candidate medication that may have certain benefits over current pharmacotherapies, including the absence of sedating side effects, reduced abuse liability, and rapid course of action.

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Use of Medicinal Cannabis for Palliative Care Patients: A Systematic Review

Medical cannabis is a rapidly growing area of medicine. In this sense, due to the numerous benefits associated with its use, it has been increasingly proposed for patients in palliative care, in which the improvement of debilitating symptoms is directly associated with better quality of life. However, due to the complexity of treatments for these individuals, further studies are needed to determine the best possible prescription for them.

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Raising awareness: The implementation of medical cannabis and psychedelics used as an adjunct to standard therapy in the treatment of advanced metastatic breast cancer

A 49-year-old woman was diagnosed with an ER + , PR-, HER2 + , BRCA- invasive ductal carcinoma which progressed metastatically to include bone, liver, and lymph node involvement. Standardised care included a 26-month treatment period with targeted chemotherapy and a ketogenic diet. The patient also began a course of cannabinoid-based therapy, consisting initially of a titrated high-dose protocol of mixed cannabidiol (CBD) and d9-tetrahydrocannabinol (THC) chemotypes, as well as psilocybin-assisted psychotherapy at macro and intermittent micro-doses. At the end of the five-month treatment period PET/CT investigations revealed no evidence of metastatic disease and chemotherapy was withdrawn.

Inhaled Marijuana and the Lung

Although vaping has recently increased as a mode of inhaling marijuana and has been associated with numerous and sometimes fatal cases of acute severe lung injury, smoking remains the most common method of inhaling marijuana and has been studied more extensively. Smoking marijuana has been shown to produce modest but significant short-term bronchodilation both in healthy subjects and in those with asthma. Long-term effects of habitual marijuana smoking include the following: (1) symptoms of chronic bronchitis (increased cough, sputum production, and wheezing); (2) modest effects on lung function in cross-sectional studies (no significant decrease in FEV1 but mild reductions in FEV1/forced vital capacity ratio, an increase in forced vital capacity and other lung volumes, reductions in specific airway conductance, and variable effects of maximal midexpiratory flow rates and diffusing capacity); and (3) variable effects on age-related decline in FEV1 in longitudinal studies. Most cohort and case-control studies have failed to show that marijuana smoking is a significant risk factor for lung cancer despite the presence of procarcinogenic components in marijuana smoke, although further study is warranted. The question whether marijuana smoking is associated with asthma is unclear and requires further investigation.

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A Case Series of the Role of Cannabis Based Medicine in the Palliative Care Setting

Complex refractory pain is highly prevalent in the palliative care setting. Opioid therapies play a pivotal role in pain management, but have an extensive side effect profile and frequently fail to provide sufficient relief, despite dose optimisation or concurrent use of standard adjuvant analgesics.(1) Therefore, identification of novel analgesics to alleviate pain would be very beneficial.(2)Currently, there is equipoise within the available clinical evidence of the efficacy and safety of cannabis-based medications in the management of pain.(3) This is a case series of three patients with complex pain, with inadequate pain relief with standard multimodal analgesia. Each of these patients were commenced on Sativex, an oromucosal spray composed of two cannabis extracts, delta-9- tetrahydrocannabinol and cannabidiol, and the dose was titrated until therapeutic benefit was
achieved. All three cases demonstrated a positive analgesic effect without any adverse symptoms.