“Growing evidence suggests that stress may contribute to the pathophysiology of depression. The alleviation of depressive symptoms is one of the most attractive medical applications of cannabis. Here, we investigated the antidepressant-like actions of synthetic cannabinoid-HU210 in acute despair response and explored the possible underlying mechanisms. Acute stress, induced by forced-swimming, induced depression-like behavior in the sucrose preference test (SPT). HU-210 (50 μg/kg) displayed anti-depressant like effect in the forced swim test in naïve mice and decreased depression-like behavior in the SPT, induced by forced swim stress. Pretreatment with AM251, an inhibitor of CB1R or inhibition of long-term depression (LTD) at hippocampal CA3-CA1 synapses by Tat-GluR2 attenuated the antidepressant like action of HU-210. These results indicate that HU210 produces antidepressant-like effects in acute stress and its underlying mechanism may be related to CB1R activation and hence hippocampal LTD production invivo. Synthetic cannabis or cannabis-related drugs may be used as an early intervention after acute stress exposure to prevent or at least reduce depression-like behaviors.”
“(1) Background: Hemp seeds are a source of plant-based protein, making them an appropriate supplement to a plant-based diet. The current work was focused on the preparation of the protein isolate from the hemp seeds with eco-friendly and cheap technology. Moreover, it evaluated the physicochemical and functional properties of hemp protein isolate for its potential application in food manufacturing.
(2) Methods: The protein content of hemp seeds has been isolated through two main steps: (1) extraction of the protein content of an alkaline pH (10-12); (2) precipitation of the extracted protein on an acidic pH as an isoelectric point (pH = 4.5).
(3) Results: The edastin protein is the most predominant protein in the protein profile with a molecular weight of 58.1 KDa beside albumin with a molecular weight of 31.5 KDa. The FTIR spectrum detected the absorption peaks of the amide I at 1750 and 1600 cm-1, which pointed to C=O stretching while N-H stretching at 1650-1580 cm-1. The peak at 3250 is found to be related to N-H stretching of the aliphatic primary amine (3400-3300 cm-1) and the N-H stretching for the secondary (II) amine appeared at 3350-3310 cm-1. The Hemp protein isolate (HPI) showed a high content of arginine (15.52 g/100 g), phenylalanine + tyrosine (9.63 g/100 g), methionine + cysteine (5.49 g/100 g), leucine + isoleucine (5.21 g/100 g), and valine (4.53 g/100 g). It contains a moderate level of threonine (3.29 g/100 g) and lysine (2.50 g/100 g) with tryptophan as the limiting amino acid (0.22 g/100 g). The HPI showed an appropriate water-and-oil holding capacity (4.5 ± 2.95 and 2.33 ± 1.88 mL/g, respectively). The foaming capacity of the HPI was increased with increasing the pH values to reach the maximum value at pH 11 (67.23 ± 3.20%). The highest emulsion ability index of the HPI was noted at pH 9 (91.3 ± 2.57 m2/g) with low stability (19.15 ± 2.03).
(4) Conclusions: A strong positive correlation (r = 0.623) was shown between protein concentration and solubility. The current easy-to-use, cheap, and eco-friendly technology provides the industrial sector with a cheap protein isolate for manufacturing protein-rich diet and beverages. The HPI showed a good nutritional quality and functional properties that might be helpful in utilizing it in different food products such as beverages and bakery products.”
“It could be concluded that the hemp protein isolate (HPI) of the variety “Cannabis sativa ssp. Sativs” showed adequate nutritional and functional properties that encourage food technologists to use it as a promising alternative protein source for developing/ formulation of rich protein foods and fortification of some food products with a good protein isolate for improving their nutritional quality and technological properties.”
“Emotionally unstable personality disorder (EUPD) is a common mental health disorder, manifesting with a range of chronic and debilitating symptoms, including impaired social functioning, unstable mood, and risky impulsive or self-injurious behaviour. Whilst the exact aetiology has not been fully elucidated, implicated factors seem to include genetic factors, environmental causes such as trauma, and neurotransmitter deficits.
The literature suggests that impaired functioning of the endocannabinoid system in key brain regions responsible for emotional processing and stress response may underlie the manifestation of EUPD symptoms. The National Institute for Health and Care Excellence (NICE) 2009 guidelines state that “no drugs have established efficacy in treating or managing EUPD”, and yet, patients are commonly prescribed medication which includes antipsychotics, antidepressants, and mood stabilisers.
Here we present a case series of seven participants diagnosed with EUPD and treated with cannabis-based medicinal products (CBMPs). Participants were given an initial assessment and followed up one month after CBMPs prescription. Improvement in symptoms was assessed by the completion of ratified rating scales by the participant and psychiatrist.
Our results indicate that CBMPs were effective and well tolerated, as six participants reported a noticeable improvement in their symptoms and functioning. Although promising, further research is needed to ascertain the long-term tolerability, efficacy, and dosing strategy for CBMPs in EUPD.”
“To our knowledge, this case series represents the first medical evidence of the use of CBMPs for the clinical management of patients with a diagnosis of EUPD, who are met with limited pharmacological options typically based on the off-label use of psychiatric medications.
Cannabinoids may represent a novel, efficacious, and safe treatment alternative for EUPD patients.
The neuro- and immune-modulatory effects of THC and CBD seem theoretically well-aligned with cellular and molecular deficits that are currently being investigated as key features underlying the pathogenesis of EUPD. Although preliminary, our results suggest that, when deployed in a rigorously controlled clinical environment, CBMPs can provide substantial improvement in symptoms associated with EUPD thus warranting the need for further research on this therapeutical strategy.”
“Colorectal cancer (CRC) is one of the diseases with the highest rates of prevalence and mortality despite therapeutic methods in the world. In particular, there are not enough methods to treat metastasis of CRC cells to distant organs. Cannabis sativa Linne (C. sativa) is a popular medicinal plant used by humans to treat many diseases. Recently, extracts of C. sativa have shown diverse pharmacological effects as a result of choosing different extraction methods. In this study, we performed experiments to confirm the inhibitory effect and related mechanisms of supercritical extract of C. sativa on metastatic CRC cells. The effect of SEC on the viability of CRC cell lines, CT26 and HCT116, was determined using CCK reagent. Flow cytometry was performed to confirm whether SEC can promote cell cycle arrest and apoptosis. Additionally, SEC reduced proliferation of CT26 and HCT116 cells without causing toxicity to normal colon cell line CCD-18Co cells. SEC treatment reduced colony formation in both CRC cell lines, promoted G0/G1 phase arrest and apoptosis in CT26 and HCT116 cells through AMPK activation and MAPKs such as ERK, JNK, and p38 inactivation. Moreover, oral administration of SEC decreased pulmonary metastasis of CT26 cells. Our research demonstrates the inhibitory effect of SEC on CRC cell proliferation and metastasis. Thus, SEC might have therapeutic potential for CRC treatment.”
“Ovarian cancer (OC) is the single most lethal gynecologic malignancy. Cannabis sativa is used to treat various medical conditions, and is cytotoxic to a variety of cancer types. We sought to examine the effectiveness of different combinations of cannabis compounds against OC. Cytotoxic activity was determined by XTT assay on HTB75 and HTB161 cell lines. Apoptosis was determined by flow cytometry. Gene expression was determined by quantitative PCR and protein localization by confocal microscopy. The two most active fractions, F5 and F7, from a high Δ9-tetrahydrocannabinol (THC) cannabis strain extract, and their standard mix (SM), showed cytotoxic activity against OC cells and induced cell apoptosis. The most effective phytocannabinoid combination was THC+cannabichromene (CBC)+cannabigerol (CBG). These fractions acted in synergy with niraparib, a PARP inhibitor, and were ~50-fold more cytotoxic to OC cells than to normal keratinocytes. The F7 and/or niraparib treatments altered Wnt pathway-related gene expression, epithelial-mesenchymal transition (EMT) phenotype and β-catenin cellular localization. The niraparib+F7 treatment was also effective on an OC patient’s cells. Given the fact that combinations of cannabis compounds and niraparib act in synergy and alter the Wnt signaling pathway, these phytocannabinoids should be examined as effective OC treatments in further pre-clinical studies and clinical trials.”
“We suggest that cannabis might be regarded as a complementary and effective anti-cancer treatment for OC. Given the favorable safety profile of phytocannabinoids, compared to standard pharmacotherapies, we propose that clinical trials with cannabis-based products are desperately needed for OC patients.”
“There is an increasing medical need for the development of new materials that could replace damaged organs, improve healing of critical wounds or provide the environment required for the formation of a new healthy tissue. The three-dimensional (3D) printing approach has emerged to overcome several of the major deficiencies of tissue engineering. The use of Cannabis sativa as a therapy for some diseases has spread throughout the world thanks to its benefits for patients. In this work, we developed a bioink made with gelatin and alginate that was able to be printed using an extrusion 3D bioprinter. The scaffolds obtained were lyophilized, characterized and the swelling was assessed. In addition, the scaffolds were loaded with Cannabis sativa oil extract. The presence of the extract provided antimicrobial and antioxidant activity to the 3D scaffolds. Altogether, our results suggest that the new biocompatible material printed with 3D technology and with the addition of Cannabis sativa oil could become an attractive alternative to common treatments of soft-tissue infections and wound repair.”
“In summary, herein we show that the new biomaterial loaded with Cannabis sativa oil and printed with 3D technology could be a promising alternative to conventional treatments for wound healing.”
“Opportunities for developing innovative and intelligent drug delivery technologies by targeting the endocannabinoid system are becoming more apparent. This review provides an overview of strategies to develop targeted drug delivery using the endocannabinoid system (ECS). Recent advances in endocannabinoid system targeting showcase enhanced pharmaceutical therapy specificity while minimizing undesirable side effects and overcoming formulation challenges associated with cannabinoids. This review identifies advances in targeted drug delivery technologies that may permit access to the full pharmacotherapeutic potential of the ECS. The design of optimized nanocarriers that target specific tissues can be improved by understanding the nature of the signaling pathways, distribution in the mammalian body, receptor structure, and enzymatic degradation of the ECS. A closer look at ligand-receptor complexes, endocannabinoid tone, tissue distribution, and G-protein activity leads to a better understanding of the potential of the ECS toolkit for therapeutics. The signal transduction pathways examine the modulation of downstream effector proteins, desensitization, signaling cascades, and biased signaling. An in-depth and overall view of the targeted system is achieved through homology modeling where mutagenesis and ligand binding examine the binding site and allow sequence analysis and the formation of libraries for molecular docking and molecular dynamic simulations. Internalization routes exploring receptor-mediated endocytosis and lipid rafts are also considered for explicit signaling. Furthermore, the review highlights nanotechnology and surface modification aspects as a possible future approach for specific targeting.”
“Specific targeting of the endocannabinoid system seems to be a good starting point towards developing a sophisticated cannabinoid drug design void of undesirable side effects but the future of commercialized ECS products calls for exploration from a broader perspective. Further study into the complexity of the expanded endocannabinoidome is required to consider the dynamics and interconnections it has with other regulatory systems. As the ECS is interconnected with other lipid-based signaling systems and cannabinomimetic compounds have been identified in a variety of foods, research into the link between diet and the synthesis and release of endocannabinoids and related mediators will do well to guide a better understanding of the endocannabinoidome and epigenetics of the ECS.”
“Introduction: Patients and healthcare practitioners are increasingly interested in using cannabis and cannabinoids to address unmet clinical needs. Although we have clinical evidence on the medical use of cannabinoids, a significant portion of the data is not based on randomized clinical trials, which are considered the gold standard in clinical research. We have reviewed the registered clinical trials on cannabis and cannabinoids for therapeutic or drug development purposes to underline the past and current attempts to generate robust clinical evidence and identify existing knowledge gaps.
Methods: We reviewed four clinical trial registries (International Clinical Trials Registry Program [ICTRP], ClinicalTrials.gov, European Clinical Trial Registry [EUCTR], Australian New Zealand Clinical Trial Registry [ANZCTR]) to identify clinical trials on cannabinoids (phyto- or synthetic) or cannabis-based medications between January 1, 2000, and December 31, 2021. All interventional clinical trials on cannabinoids and other compounds interacting with the endocannabinoid system, regardless of the investigated medical condition, assessed health outcomes, or choice of comparator, were included, provided they had a therapeutic or drug development purpose. Data on the primary sponsor, type of sponsor, date of registration, recruitment status, number of participants, study design, the phase of the study, country, medical conditions, investigated cannabinoids, and the route of administration were extracted. The therapeutic area and class of cannabinoids were identified based on the details of each trial.
Results: We included 834 out of 2966 reviewed clinical trials. The number of registered clinical trials has constantly increased from 30 in 2013 to 103 in 2021. More than 40% of registered clinical trials in 2021 were phase II and phase III clinical trials. The mean number of trial enrollments for completed, ongoing, and terminated studies were 128, 156, and 542, respectively. Clinical research on Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), and the oral routes of administration dominate the field. Approximately two-thirds of clinical trials were conducted in five therapeutic areas (i.e., ‘Chronic pain,’ ‘Mental, behavioral or neurodevelopmental disorders,’ ‘Nervous system diseases,’ ‘Endocrine, nutritional or metabolic diseases,’ and ‘Neoplasms’). Pharmaceutical companies sponsored 39% of all clinical trials. However, trial sponsorships vary noticeably in different jurisdictions, likely due to, in part, different regulatory frameworks.
Conclusion: Our review highlights the diversification of clinical trials on cannabinoid-based medications in the past 21 years. This review underlines the increased interest in conducting clinical studies on new cannabinoid administration methods such as topical applications and on the investigation of emerging phyto- and synthetic cannabinoids. Moreover, more clinical trials have been designed to explore the potential therapeutic benefits of cannabinoids in areas such as mental, behavioral, or neurodevelopmental disorders and skin diseases. There is a need for granular analyses of clinical trials on more commonly studied therapeutic areas such as chronic pain, nervous system diseases, and mental and behavioral disorders to generate more actionable information and insight for all stakeholders.”
“This work reports for the first time on the synthesis, characterization, and photodynamic therapy effect of a novel water-soluble zinc (II) 2(3), 9(10), 16(17), 23(24)-tetrakis-(sodium 2-mercaptoacetate) phthalocyanine (ZnPcTS41), on metastatic melanoma cells (A375) combined with cannabidiol (CBD). The ZnPcTS41 structure was confirmed using FTIR, NMR, MS, and elemental analysis while the electronic absorption spectrum was studied using UV-VIS. The study reports further on the dose-dependent effects of ZnPcTS41 (1-8 µM) and CBD alone (0.3-1.1 µM) at 636 nm with 10 J/cm2 on cellular morphology and viability. The IC50 concentrations of ZnPcTS41 and CBD were found to be 5.3 µM and 0.63 µM, respectively. The cytotoxicity effects of the ZnPcTS41 enhanced with CBD on A375 cells were assessed using MTT cell viability assay, ATP cellular proliferation and inverted light microscopy. Cell death induction was also determined via Annexin V-FITC-PI. The combination of CBD- and ZnPcTS41-mediated PDT resulted in a significant reduction in cell viability (15%***) and an increase in the late apoptotic cell population (25%*). These findings suggest that enhancing PDT with anticancer agents such as CBD could possibly obliterate cancer cells and inhibit tumor recurrence.”
“There is currently a growing interest in the use of cannabidiol (CBD) to alleviate the symptoms caused by cancer, including pain, sleep disruption, and anxiety. CBD is often self-administered as an over-the-counter supplement, and patients have reported benefits from its use. However, despite the progress made, the mechanisms underlying CBD’s anti-cancer activity remain divergent and unclear. Herein, we provide a comprehensive review of molecular mechanisms to determine convergent anti-cancer actions of CBD from pre-clinical and clinical studies. In vitro studies have begun to elucidate the molecular targets of CBD and provide evidence of CBD’s anti-tumor properties in cell and mouse models of cancer. Furthermore, several clinical trials have been completed testing CBD’s efficacy in treating cancer-related pain. However, most use a mixture of CBD and the psychoactive, tetrahydrocannabinol (THC), and/or use variable dosing that is not consistent between individual patients. Despite these limitations, significant reductions in pain and opioid use have been reported in cancer patients using CBD or CBD+THC. Additionally, significant improvements in quality-of-life measures and patients’ overall satisfaction with their treatment have been reported. Thus, there is growing evidence suggesting that CBD might be useful to improve the overall quality of life of cancer patients by both alleviating cancer symptoms and by synergizing with cancer therapies to improve their efficacy. However, many questions remain unanswered regarding the use of CBD in cancer treatment, including the optimal dose, effective combinations with other drugs, and which biomarkers/clinical presentation of symptoms may guide its use.”
“CBD has great potential to improve the lives of cancer patients both by alleviating the symptoms of pain, sleep disturbance, and anxiety, but also by synergistic activity with anti-cancer treatments to reverse or eliminate the growth of tumors causing these symptoms. Pre-clinical evidence in cell and mouse models supports the use of CBD as an anti-cancer therapy; however, clinical knowledge is currently lacking in this area. The effectiveness of CBD has been demonstrated in models of lung, breast, and colon cancer, as well as leukemia and glioblastoma. CBD has been shown to be toxic to cancer cells in vitro, and it is also generally well tolerated in the clinic.”
