Tag Archives: Hemp
Cannabinoids.
“Cannabinoids, broadly speaking, are a class of biological compounds that bind to cannabinoid receptors. They are most frequently sourced from and associated with the plants of the Cannabis genus, including Cannabis sativa, Cannabis indica, and Cannabis ruderalis.
The earliest known use of cannabinoids dates back 5,000 years ago in modern Romania, while the documentation of the earliest medical dates back to around 400 AD. However, formal extraction, isolation, and structural elucidation of cannabinoids have taken place rather recently in the late 19th and early 20th centuries. Since then, numerous advancements have been made in further isolating naturally occurring cannabinoids, synthesizing artificial equivalents, and discovering the endogenous the endocannabinoid system in mammals, reptiles, fish, and birds.”
Promising in vitro antioxidant, anti-acetylcholinesterase and neuroactive effects of essential oil from two non-psychotropic Cannabis sativa L. biotypes.
“The aim of this study was to compare the micro-morphological features of two different non-drug Cannabis sativa L. biotypes (Chinese accession G-309 and one fibrante variety) and to evaluate the phytochemical profile as well as some biological properties of the essential oils (EOs) obtained by hydrodistillation of dried flowering tops. After a micro-morphological evaluation by scanning electron microscopy, the phytochemical composition was analysed by GC-FID and GC-MS analyses.
Antioxidant and anti-acetylcholinesterase properties were investigated by several in vitro cell-free assays, while neuroactive effects were evaluated on mouse cortical neuronal as well as human iPS cell-derived central nervous system cells grown on MEA chips. Both EOs showed strong antioxidant properties mainly attributable to the high content of hydroxylated compounds as well as significant anti-acetylcholinesterase activities (IC50 74.64 and 57.31 μg/ml for Chinese accession and fibrante variety, respectively).
Furthermore, they showed a concentration-dependent inhibition of spontaneous electrical activity of human and mouse neuronal networks, with the fibrante variety, which showed the best activity (MFR, IC50 0.71 and 10.60 μg/ml, respectively). The observed biological activities could be due to a synergic effect between terpenes and phytocannabinoids, although in vivo studies, which clarify the molecular mechanism, are still lacking.”
Cannabidiol (CBD).
“Cannabis sativa or Indian hemp (subfamily Cannaboideae of family Moraceae) is an annual herbaceous plant, native to central and western Asia, cultivated for medicinal properties and for hemp, which is a natural textile fiber. The plant contains over 400 chemical compounds, of which approximately 80 biologically active chemical molecules. The most important cannabis compounds are cannabinoids formed by a terpene combined with resorcinol, or, according to a different nomenclature, by a benzopyranic ring system. There are about sixty cannabinoids, of which the most important psychoactive compound is tetrahydrocannabinol (TCH), in particular the isomer delta (Δ9-THC). Other identified compounds are cannabidiol (CBD), cannabigerol (CBG), cannabinol (CBN), cannabichromene (CBC), and olivetol. In addition to cannabinoids, the plant contains terpenoids such as beta-myrcene, beta-caryophyllene, d-limonene, linalool, piperidine, and p-cymene, as well as flavonoids such as quercetin.”
Epigenetic regulation of the cannabinoid receptor CB1 in an activity-based rat model of anorexia nervosa.
“Both environmental and genetic factors are known to contribute to the development of anorexia nervosa (AN), but the exact etiology remains poorly understood.
Herein, we studied the transcriptional regulation of the endocannabinoid system, an interesting target for body weight maintenance and the control of food intake and energy balance.
Among the evaluated endocannabinoid system components, we observed a selective and significant down-regulation of the gene encoding for the type 1 cannabinoid receptor (Cnr1) in ABA rats’ hypothalamus and nucleus accumbens and, in the latter area, a consistent, significant and correlated increase in DNA methylation at the gene promoter.
Our findings support a possible role for Cnr1 in the ABA animal model of AN. In particular, its regulation in the nucleus accumbens appears to be triggered by environmental cues due to the consistent epigenetic modulation of the promoter.
These data warrant further studies on Cnr1 regulation as a possible target for treatment of AN.”
Possible Enhancement of Photodynamic Therapy (PDT) Colorectal Cancer Treatment when Combined with Cannabidiol.
“Colorectal cancer (CRC) has a high mortality rate and is one of the most difficult diseases to manage due to tumour resistance and metastasis. The treatment of choice for CRC is reliant on the phase and time of diagnosis. Despite several conventional treatments available to treat CRC (surgical excision, chemo-, radiation- and immune-therapy), resistance is a major challenge, especially if it has metastasized. Additionally, these treatments often cause unwanted adverse side effects and so it remains imperative to investigate, alternative combination therapies.
Photodynamic Therapy (PDT) is a promising treatment modality for the primary treatment of CRC, since it is non-invasive, has few side effects and selectively damages only cancerous tissues, leaving adjacent healthy structures intact. PDT involves three fundamentals: a Photosensitizer (PS) drug localized in tumour tissues, oxygen and light. Upon PS excitation using a specific wavelength of light, an energy transfer cascade occurs, that ultimately yields cytotoxic species, which in turn induces cell death.
Cannabidiol (CBD) is a cannabinoid compound derived from the Cannabis sativa plant, which is found to exert anticancer effects on CRC through different pathways, inducing apoptosis and so inhibits tumour metastasis and secondary spread.
This review paper highlights current conventional treatment modalities for CRC and their limitations, as well as discusses the necessitation for further investigation into unconventional active nanoparticle targeting PDT treatments for enhanced primary CRC treatment. This can be administered in combination with CBD, to prevent CRC secondary spread and so enhance the synergistic efficacy of CRC treatment outcomes, with less side effects.”
Synergistic cytotoxic activity of cannabinoids from cannabis sativa against cutaneous T-cell lymphoma (CTCL) in-vitro and ex-vivo.
“Cannabis sativa produces hundreds of phytocannabinoids and terpenes.
Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma (CTCL), characterized by patches, plaques and tumors. Sézary is a leukemic stage of CTCL presenting with erythroderma and the presence of neoplastic Sézary T-cells in peripheral blood.
This study aimed to identify active compounds from whole cannabis extracts and their synergistic mixtures, and to assess respective cytotoxic activity against CTCL cells.
This mixture induced cell cycle arrest and cell apoptosis. Significant cytotoxic activity of the corresponding mixture of pure phytocannabinoids further verified genuine interaction between S4 and S5.
We suggest that specifying formulations of synergistic active cannabis compounds and unraveling their modes of action may lead to new cannabis-based therapies.”
https://www.ncbi.nlm.nih.gov/pubmed/32284791
“Cannabis sativa has been used by humanity for thousands of years. Various phytocannabinoids exhibit antitumor effects in a wide array of cell lines and animal models. We have shown that a certain synergistic mixture of phytocannabinoids derived from C. sativa extracts have significant cytotoxic activity against My-La and HuT-78 cell lines and against SPBL.
To conclude, active cannabis extract fractions and their synergistic combinations were cytotoxic to CTCL cell lines in in-vitro and to SPBL in ex-vivo studies. The defined S4+S5 formulation of synergistic phytocannabinoids induced cell cycle arrest and cell apoptosis, and affected multiple biological pathways, including those associated with cancer. Based on this pre-clinical study new cannabis-based products that are based on precise composition of synergistically interacting compounds may be developed.”
Cannabidiol (CBD) Inhibited Rhodamine-123 Efflux in Cultured Vascular Endothelial Cells and Astrocytes Under Hypoxic Conditions.
“Despite the constant development of new antiepileptic drugs (AEDs), more than 30% of patients develop refractory epilepsy (RE) characterized by a multidrug-resistant (MDR) phenotype. The “transporters hypothesis” indicates that the mechanism of this MDR phenotype is the overexpression of ABC transporters such as P-glycoprotein (P-gp) in the neurovascular unit cells, limiting access of the AEDs to the brain.
Recent clinical trials and basic studies have shown encouraging results for the use of cannabinoids in RE, although its mechanisms of action are still not fully understood. Here, we have employed astrocytes and vascular endothelial cell cultures subjected to hypoxia, to test the effect of cannabidiol (CBD) on the P-gp-dependent Rhodamine-123 (Rho-123) efflux.
Results show that during hypoxia, intracellular Rho-123 accumulation after CBD treatment is similar to that induced by the P-gp inhibitor Tariquidar (Tq). Noteworthy, this inhibition is like that registered in non-hypoxia conditions. Additionally, docking studies predicted that CBD could behave as a P-gp substrate by the interaction with several residues in the α-helix of the P-gp transmembrane domain.
Overall, these findings suggest a direct effect of CBD on the Rho-123 P-gp-dependent efflux activity, which might explain why the CBD add-on treatment regimen in RE patients results in a significant reduction in seizure frequency.”
https://www.ncbi.nlm.nih.gov/pubmed/32256321
“Interestingly, for several thousand years, humanity has given medicinal use to Cannabis sativa (Marijuana), even for the treatment of epileptic patients. Our results indicate that, in addition to the various effects previously described by CBD, this drug can also inhibit the active efflux of Rho-123, a known P-gp substrate, in two types of cells of the NVU, in a similar (though less potent) manner to TQ. Consistently, our in silico study indicates that CBD may bind the transmembrane domain of P-gp, possibly acting as a competitive inhibitor. CBD could thus be used as an adjuvant therapy to reverse the MDR phenotype as observed in patients with RE, which could explain its recent approval as an add-on therapy to treat severe refractory childhood epilepsies.”
https://www.frontiersin.org/articles/10.3389/fnbeh.2020.00032/full
Cannabinoids as anticancer therapeutic agents.
“The recent announcement of marijuana legalization in Canada spiked many discussions about potential health benefits of Cannabis sativa. Cannabinoids are active chemical compounds produced by cannabis, and their numerous effects on the human body are primarily exerted through interactions with cannabinoid receptor types 1 (CB1) and 2 (CB2). Cannabinoids are broadly classified as endo-, phyto-, and synthetic cannabinoids. In this review, we will describe the activity of cannabinoids on the cellular level, comprehensively summarize the activity of all groups of cannabinoids on various cancers and propose several potential mechanisms of action of cannabinoids on cancer cells.”
https://www.ncbi.nlm.nih.gov/pubmed/32249682
“Endocannabinoids and phytocannabinoids can be used for cancer therapy. Cannabis extracts have stronger anti-tumor capacity than single cannabinoids. Combination of several cannabinoids may have more potent effect on cancer.”
https://www.tandfonline.com/doi/abs/10.1080/15384101.2020.1742952?journalCode=kccy20
CBD Reverts the Mesenchymal Invasive Phenotype of Breast Cancer Cells Induced by the Inflammatory Cytokine IL-1β.
“Cannabidiol (CBD) has been used to treat a variety of cancers and inflammatory conditions with controversial results. In previous work, we have shown that breast cancer MCF-7 cells, selected by their response to inflammatory IL-1β cytokine, acquire a malignant phenotype (6D cells) through an epithelial-mesenchymal transition (EMT).
We evaluated CBD as a potential inhibitor of this transition and inducer of reversion to a non-invasive phenotype. It decreased 6D cell viability, downregulating expression of receptor CB1. The CBD blocked migration and progression of the IL-1β-induced signaling pathway IL-1β/IL-1RI/β-catenin, the driver of EMT.
Cannabidiol reestablished the epithelial organization lost by dispersion of the cells and re-localized E-cadherin and β-catenin at the adherens junctions. It also prevented β-catenin nuclear translocation and decreased over-expression of genes for ∆Np63α, BIRC3, and ID1 proteins, induced by IL-1β for acquisition of malignant features.
Cannabidiol inhibited the protein kinase B (AKT) activation, a crucial effector in the IL-1β/IL-1RI/β-catenin pathway, indicating that at this point there is crosstalk between IL-1β and CBD signaling which results in phenotype reversion.
Our 6D cell system allowed step-by-step analysis of the phenotype transition and better understanding of mechanisms by which CBD blocks and reverts the effects of inflammatory IL-1β in the EMT.”