Monthly Archives: May 2024

Use of cannabidiol in the treatment of drug-refractory epilepsy in children and young adults: A systematic review

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“Objectives: Epilepsy poses a significant challenge in pediatric and adolescent populations, impacting not only seizures but also psychological and cognitive comorbidities, leading to higher mortality rates than the general population. Drug-refractory epilepsy, resistant to conventional treatments, affects a range of 7-20% of pediatric patients. The search for alternative therapies has led to exploring the therapeutic potential of Cannabis sativa L. compounds, particularly cannabidiol (CBD). Examine the use of CBD for treating drug-refractory epilepsy in children and young adults, summarizing existing evidence on its efficacy.

Materials and methods: A systematic review, following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, assessed studies from 2018 to 2023, focusing on CBD’s efficacy and safety for treatment-resistant epilepsy in pediatric and juvenile populations. The search spanned seven databases, and the studies underwent rigorous screening and data extraction.

Results: Out of 6351 identified articles, eight were selected for review. The included studies reported positive outcomes, with CBD leading to a reduction in seizure frequency ranging from 50% to complete seizure freedom. Adverse effects were mostly mild and reversible, including drowsiness, diarrhea, and loss of appetite.

Conclusion: The CBD emerges as a promising tool for refractory epilepsy in pediatric patients, showing efficacy in reducing seizure frequency and improving overall quality of life. Despite mild and reversible adverse effects, CBD’s benefits outweigh the risks. However, more research on long-term effects is needed to fully understand its implications.”

https://pubmed.ncbi.nlm.nih.gov/38746511/

“The use of cannabis is a tool for refractory epilepsy when first-line therapies do not have the expected efficacy. The benefits of the crisis are clear, in the reduction and even elimination or blocking of seizures, impacting positively their quality of life such as sleep, behavior, and cognitive functions. There is great efficacy against different types of epileptic seizures, such as tonic, tonic-clonic, epileptic encephalopathy, focal seizures, and generalized seizures, making its use advisable for patients, without forgetting that more information is still required regarding its long-term use. As for the adverse effects, it can be noted that, despite being almost constant, these mainly appear due to the interaction of CBD with the medications used by these patients, although it is clear that none of these adverse effects turned out to be a reason not to stop the treatment that was presented during the different studies.”

https://ruralneuropractice.com/use-of-cannabidiol-in-the-treatment-of-drug-refractory-epilepsy-in-children-and-young-adults-a-systematic-review/

Unraveling the Endocannabinoid System: Exploring Its Therapeutic Potential in Autism Spectrum Disorder

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“The salient features of autism spectrum disorder (ASD) encompass persistent difficulties in social communication, as well as the presence of restricted and repetitive facets of behavior, hobbies, or pursuits, which are often accompanied with cognitive limitations.

Over the past few decades, a sizable number of studies have been conducted to enhance our understanding of the pathophysiology of ASD. Preclinical rat models have proven to be extremely valuable in simulating and analyzing the roles of a wide range of established environmental and genetic factors.

Recent research has also demonstrated the significant involvement of the endocannabinoid system (ECS) in the pathogenesis of several neuropsychiatric diseases, including ASD. In fact, the ECS has the potential to regulate a multitude of metabolic and cellular pathways associated with autism, including the immune system. Moreover, the ECS has emerged as a promising target for intervention with high predictive validity.

Particularly noteworthy are resent preclinical studies in rodents, which describe the onset of ASD-like symptoms after various genetic or pharmacological interventions targeting the ECS, providing encouraging evidence for further exploration in this area.”

https://pubmed.ncbi.nlm.nih.gov/38744725/

https://link.springer.com/article/10.1007/s12017-024-08781-6

Extraction, purification and in vitro assessment of the antioxidant and anti-inflammatory activity of policosanols from non-psychoactive Cannabis sativa L

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“Policosanols (PCs) are bioactive compounds extracted from different natural waxes.

In this work, the purification, characterization and assessment of the antioxidant and anti-inflammatory activity was carried out on PCs from an innovative source, i.e. a waxy material from supercritical-fluid extraction (SFE) of non-psychoactive Cannabis sativa L. (hemp) inflorescences.

Starting from this material, PCs were obtained by microwave-assisted trans-esterification and hydrolysis, followed by preparative liquid chromatography under normal phase conditions. The purified product was characterized using high-performance liquid chromatography (HPLC) with an evaporative light scattering detector (ELSD). In vitro cell-free and cell-based antioxidant and anti-inflammatory assays were then performed to assess their bioactivity. HPLC-ELSED analysis of the purified mixture from hemp wax revealed C26OH and C28OH as the main compounds. 

In vitro assays indicated an inhibition of intracellular reactive oxygen species (ROS) production, a reduction of nuclear factor kappa B (NF-κB) activation and of the activity of the neutrophil elastase. Immunoblotting assays allowed us to hypothesize the mechanism of action of the compounds of interest, given the higher levels of MAPK-activated protein kinase 2 (MK2) and heme oxygenase-1 (HO-1) protein expression in the PC pretreated HaCaT cells.

In conclusion, even if more research is needed to unveil other molecular mechanisms involved in hemp PC activity, the results of this work suggest that these compounds may have potential for use in oxinflammation processes.”

https://pubmed.ncbi.nlm.nih.gov/38737258/

“A new extraction method for policosanols from hemp wax was developed. This new product may be useful against oxinflammation processes.”

https://www.cell.com/heliyon/fulltext/S2405-8440(24)06322-9?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2405844024063229%3Fshowall%3Dtrue

“Policosanol suppresses tumor progression in a gastric cancer xenograft model”

https://pubmed.ncbi.nlm.nih.gov/36277362/

Hemp Seeds (Cannabis sativa L.) as a Valuable Source of Natural Ingredients for Functional Foods-A Review

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“Hemp (Cannabis sativa L.) has experienced a significant resurgence in popularity, and global interest in diversifying its use in various industries, including the food industry, is growing. Therefore, due to their exceptional nutritional value, hemp seeds have recently gained increasing interest as a valuable ingredient for obtaining high-quality foods and dietary supplements.

Hemp seeds stand out for their remarkable content of quality proteins, including edestin and albumin, two distinct types of proteins that contribute to exceptional nutritional value. Hemp seeds are also rich in healthy lipids with a high content of polyunsaturated fatty acids, such as linoleic acid (omega-6), alpha-linolenic acid (omega-3), and some vitamins (vitamins E, D, and A). Polyphenols and terpenoids, in particular, present in hemp seeds, provide antimicrobial, antioxidant, and anti-inflammatory properties.

This review examines the scientific literature regarding hemp seeds’ physicochemical and nutritional characteristics. The focus is on those characteristics that allow for their use in the food industry, aiming to transform ordinary food products into functional foods, offering additional benefits for the body’s health. Innovating opportunities to develop healthy, nutritionally superior food products are explored by integrating hemp seeds into food processes, promoting a balanced and sustainable diet.”

https://pubmed.ncbi.nlm.nih.gov/38731588/

“Cannabis sativa L. hemp seeds represent a valuable resource for the food industry, offering versatility and nutritional quality.”

https://www.mdpi.com/1420-3049/29/9/2097

Clinical outcome analysis of patients with multiple sclerosis – Analysis from the UK Medical Cannabis Registry

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“Introduction: Whilst disease-modifying therapies are the cornerstone for treatment of multiple sclerosis (MS), there is a need to develop novel therapeutics for the symptomatic sequalae of the disease. Cannabis-based medicinal products (CBMPs) have been suggested as a potential therapy for the associated pain, spasticity, and mental health disorders. However, there is a paucity of clinical evidence on CBMPs in MS. The aim of this study is to assess changes in MS-specific and general health-related quality of life (HRQoL) outcomes alongside adverse event incidence in patients prescribed CBMPs for MS from the UK Medical Cannabis Registry (UKMCR).

Method: Patients prescribed CBMPs for MS symptoms for longer than one month were identified from the UKMCR. The primary outcomes were changes from baseline in MS Quality of Life-54 (MSQoL-54), Generalised Anxiety Disorder-7 (GAD-7), Single-Item Sleep Quality Scale (SQS), and EQ-5D-5L scales at one month, three months and six months. p < 0.050 was defined as statistically significant.

Results: 141 patients met the inclusion criteria for the study. There was an improvement in the following subscales of the MSQoL-54 at 6 months: change in health scale, cognitive function, mental health composition, physical health, role limitations due to physical limitation and due to emotional problems, as well as social and sexual function (p < 0.050). There were also improvements in the EQ-5D-5L index value, GAD-7 and SQS (p < 0.050). 146 (103.55 %) adverse events were reported in total. Most were considered mild (n = 47; 33.33 %) and moderate (n = 72; 51.06 %).

Conclusions: This preliminary analysis demonstrates a possible association with improved general health-related quality of life in those prescribed CBMPs for MS. Moreover, the results suggest that CBMPs are well-tolerated in the first 6 months of treatment. However, this must be interpreted with caution considering the limitations of the observational study design.”

https://pubmed.ncbi.nlm.nih.gov/38728958/

“Cannabis-based medicinal products were prescribed to those with multiple sclerosis.•Significant improvements were observed in health-related quality of life. •Treatment was well-tolerated over the course of 6 months.”

https://www.msard-journal.com/article/S2211-0348(24)00242-6/fulltext


The Potential Antinociceptive Effect and Mechanism of Cannabis sativa L. Extract on Paclitaxel-Induced Neuropathic Pain in Rats Uncovered by Multi-Omics Analysis

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“Cannabis sativa L. (hemp) is a herbaceous plant rich in cannabinoids with a long history of use in pain treatment.

The most well-characterized cannabinoids, cannabidiol (CBD) and Δ9-tetrahydrocannabinol (Δ9-THC), garnered much attention in chemotherapy-induced peripheral neuropathy (CIPN) treatment. However, few studies have investigated the biological benefits and mechanism of hemp extract on CIPN.

In the present study, hemp extract (JG) rich in cannabinoids was extracted by supercritical fluid carbon dioxide extraction (SFCE). The antinociceptive efficacy was evaluated using a paclitaxel-induced peripheral neuropathy (PIPN) rat model based on behavioral tests. Further omics-based approaches were applied to explore the potential mechanisms.

The results showed that JG decreased mechanical allodynia, thermal hyperalgesia, and inflammatory cytokines in PIPN rats significantly. Transcriptome analysis identified seven key genes significantly regulated by JG in PIPN model rats, mainly related to the neuroactive ligand-receptor interaction pathway, PPAR signaling pathway, and cAMP signaling pathway. In metabolomic analysis, a total of 39 significantly altered metabolites were identified, mainly correlated with pentose and glucuronate interconversions and the glycerophospholipid metabolism pathway.

Gut microbiota analysis suggested that increased community Lachnoclostridium and Lachnospiraceae_UCG-006 in PIPN rats can be reversed significantly by JG.

In conclusion, hemp extract exhibited antinociceptive effects on PIPN. The analgesic mechanism was probably related to the regulation of inflammation, neuroactive ligand-receptor interaction pathway, sphingolipid metabolism, etc. This study provides novel insights into the functional interactions of Cannabis sativa L. extract on PIPN.”

https://pubmed.ncbi.nlm.nih.gov/38731449/

“In conclusion, the antinociceptive effects and mechanism of Cannabis sativa L. extract rich in cannabinoids in PIPN rats were evaluated by using pharmacological methods integrated with transcriptomic analysis, metabolomic analysis, and gut microbiota analysis. 

Cannabis sativa L. extract effectively alleviated neuropathic pain induced by PTX, mainly by the identified 7 key genes, 39 metabolic biomarkers, and 2 bacterial genera.

Related pathways may be involved in the inflammatory response, regulating neuroactive ligand–receptor interaction pathway, PPAR signaling pathway, inflammatory mediator regulation of TRP channels, glycerophospholipid metabolism, pentose and glucuronate interconversions, etc.

Our study provides novel insights into the functional interactions of Cannabis sativa L. extract on PIPN, which offers key information for new strategies in PIPN treatment and provides a reference for the medicinal development of hemp.”

https://www.mdpi.com/1420-3049/29/9/1958

Research Progress on the Mechanism of the Antitumor Effects of Cannabidiol

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“Cannabidiol (CBD), a non-psychoactive ingredient extracted from the hemp plant, has shown therapeutic effects in a variety of diseases, including anxiety, nervous system disorders, inflammation, and tumors. CBD can exert its antitumor effect by regulating the cell cycle, inducing tumor cell apoptosis and autophagy, and inhibiting tumor cell invasion, migration, and angiogenesis. This article reviews the proposed antitumor mechanisms of CBD, aiming to provide references for the clinical treatment of tumor diseases and the rational use of CBD.”

https://pubmed.ncbi.nlm.nih.gov/38731434/

“The antitumor effects of CBD in different types of cancer have attracted widespread attention, and the number of relevant research results is steadily increasing. The studies published to date all point to the obvious antitumor effects of CBD and that its mechanisms include the induction of cell cycle arrest and autophagy, the promotion of apoptosis, the modulation of angiogenesis, and the inhibition of tumor cell migration and invasion. In addition, CBD has good synergistic effects with other medicines, and several clinical reports show CBD being used to treat cancer. The results presented in this review indicate that CBD has extremely promising potential for clinical use in the treatment of cancer patients.”

https://www.mdpi.com/1420-3049/29/9/1943

CBD in the Treatment of Epilepsy

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“It has been several years since highly purified cannabidiol (CBD) was registered as a medication that can be used in children of at least 2 years of age to treat different types of seizures related to Lennox-Gastaut syndrome (LGS), Dravet syndrome (DS), and more recently tuberous sclerosis complex (TSC).

During this time, 39 randomized clinical trials (RCTs) and 13 meta-analyses on the efficacy and safety of CBD treatment have been published. Each of the meta-analyses had its own criteria for the RCTs’ inclusion and, therefore, slightly different interpretations of the analyzed data.

Each of them contributed in its own way to the understanding of CBD pharmacology, mechanisms of therapeutic action, development of adverse reactions, and drug-drug interactions. Hence, it seemed reasonable to gather the most relevant data in one article and present all the current knowledge on the use of CBD in epilepsy.

The results of the 13 meta-analyses presented herein confirmed the effectiveness and safety of CBD in children and adolescents with DREs. In adults, reliable conclusions cannot be drawn due to insufficient data.”

https://pubmed.ncbi.nlm.nih.gov/38731471/

https://www.mdpi.com/1420-3049/29/9/1981

Cannabidiol-Loaded Solid Lipid Nanoparticles Ameliorate the Inhibition of Proinflammatory Cytokines and Free Radicals in an In Vitro Inflammation-Induced Cell Model

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“Cannabidiol (CBD) is a non-psychoactive compound derived from Cannabis sativa. It has demonstrated promising effects in combating inflammation and holds potential as a treatment for the progression of chronic inflammation. However, the clinical application of CBD is limited due to its poor solubility and bioavailability.

This study introduces an effective method for preparing CBD-loaded solid lipid nanoparticles (CBD-SLNs) using a combination of low-energy hot homogenization and ultrasonication. We enhanced this process by employing statistical optimization with response surface methodology (RSM). The optimized CBD-SLN formulation utilizes glyceryl monostearate as the primary lipid component of the nanocarrier. The CBD-SLN formulation is screened as a potential tool for managing chronic inflammation. Stable, uniformly dispersed spherical nanoparticles with a size of 123 nm, a surface charge of -32.1 mV, an encapsulation efficiency of 95.16%, and a drug loading of 2.36% were obtained.

The CBD-SLNs exhibited sustained release properties, ensuring prolonged and controlled CBD delivery, which could potentially amplify its therapeutic effects. Additionally, we observed that CBD-SLNs significantly reduced both reactive oxygen and nitrogen species and proinflammatory cytokines in chondrocyte and macrophage cell lines, with these inhibitory effects being more pronounced than those of free CBD.

In conclusion, CBD-SLNs demonstrated superiority over free CBD, highlighting its potential as an effective delivery system for CBD.”

https://pubmed.ncbi.nlm.nih.gov/38731964/

https://www.mdpi.com/1422-0067/25/9/4744

Mitochondrial calcium overload contributes to cannabinoid-induced paraptosis in hormone-responsive breast cancer cells

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“Studies have shown that natural products can induce paraptosis in tumour cell lines. Paraptosis is characterized by cytoplasmic vacuolation arising from the endoplasmic reticulum (ER) and mitochondria. The mechanism of paraptosis is unclear; however, dysregulation of Ca2+ homeostasis is believed to affect paraptosis induction.

This study investigated the mechanism of cell death induced by a phytocannabinoid ratio in the MCF7 breast cancer cell line.

The crystal violet assay was used to detect changes in viability and morphology changes were investigated using light and transmission electron microscopy. Various inhibitors, fluorescent staining with high-content screening, and Western blot analysis were used to investigate different cell death mechanisms.

The phytocannabinoid ratio induced significant cell death and cytoplasmic vacuolation in MCF7 cells; however, no apoptosis, necrosis, autophagy, or ferroptosis was detected. Vacuolation induced by phytocannabinoid treatment was inhibited by cycloheximide, suggesting paraptosis induction. The mechanism of paraptosis induction was investigated, and it was found that treatment (1) induced ER dilation and mitochondrial swelling, (2) induced significant ER stress and mitochondrial Ca2+ overload and dysfunction, which appeared to be mediated by the voltage-dependent anion channel, and (3) significantly impaired all mitochondrial metabolic pathways.

The data demonstrated that paraptosis induced by the cannabinoid ratio was mediated by Ca2+ flux from the ER to the mitochondria.

These findings highlight a novel mechanism of cannabinoid-induced cell death and emphasize the anti-cancer potential of cannabinoid ratios, which exhibited enhanced effects compared to individual cannabinoids.”

https://pubmed.ncbi.nlm.nih.gov/38721827/

” In the context of cancer, cannabinoids have primarily been used for their palliative effects to treat the side effects of chemotherapy; however, their tumour-suppressive properties have been known since the first observation of their antitumor effects in 1975.”

https://onlinelibrary.wiley.com/doi/10.1111/cpr.13650