“HIV infection leads to blood-brain barrier (BBB) dysfunction that does not resolve despite viral suppression on antiretroviral therapy and is associated with adverse clinical outcomes.
In preclinical models, cannabis restores BBB integrity.
“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.
“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.”
“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.”
“Exemestane is one of the aromatase inhibitors (AI) used as first line treatment for estrogen-receptor positive breast cancer in post-menopausal women. Exemestane acts by inhibiting aromatase, the enzyme responsible for the conversion of androgens to estrogens and also by promoting apoptosis of breast cancer cells. Nevertheless, despite its therapeutic success, this AI, after prolonged treatment, can induce acquired resistance, which causes tumor relapse. Therefore, it is important to find new strategies to overcome resistance in order to improve breast cancer treatment.
Considering that the development of resistance is the main reason for endocrine treatment failure, our group decided to explore the ability of three cannabinoids, Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD) and anandamide (AEA), to reverse resistance to exemestane. The THC and CBD are phytocannabinoids derived from the plant Cannabis sativa (marijuana) whereas AEA is an endocannabinoid. For that, it was used LTEDaro cells, a long-term estrogen deprived ER+ breast cancer cell line that mimics resistance to exemestane. These cells were treated with exemestane in combination with two phytocannabinoids, CBD and THC, and the endocannabinoid AEA.
The presence of CB1 and CB2 in LTEDaro cells was confirmed by Western blot analysis and the effects of the combination of cannabinoids with exemestane were evaluated by MTT and LDH assays. Cell morphology was analyzed by Giemsa and Hoechst staining.
Results: Our results demonstrate that all the cannabinoids induce a decrease in viability of exemestane-resistant cells, in a dose- and time-dependent manner, without LDH release. These results indicate that the studied cannabinoids, mainly THC and AEA, revert the resistance to exemestane, probably by inducing apoptosis, as observed in Giemsa/Hoechst stain by the presence of typical morphological features of apoptosis.
Conclusion: This study highlights the efficacy of using cannabinoids as a potential adjuvant treatment to revert resistance to AIs.”
https://www.ncbi.nlm.nih.gov/pubmed/32258721
https://journals.lww.com/pbj/fulltext/2017/09000/The_effects_of_cannabinoids_in.118.aspx
“From June 2019 to January 2020, over 2500 cases of electronic cigarette (e-cigarette)– or vaping–associated lung injury (EVALI) were reported to the Centers for Disease Control and Prevention (CDC).
Some states have legalized marijuana and THC-containing products for recreational use. Many other states allow purchases for qualifying medical purposes. In remaining states, all forms of consumption and distribution are illegal, and individuals who use THC likely obtain it from the black market. If black-market THC products are responsible for EVALI, then case rates may be lower in recreational marijuana states.
The goal of this cross-sectional study was to measure whether states where marijuana is legal have lower rates of EVALI compared with states where it is illegal.
Recreational marijuana states had among the lowest EVALI rates of all states.
The data suggest that EVALI cases were concentrated in states where consumers do not have legal access to recreational marijuana dispensaries. This association was not driven by state-level differences in e-cigarette use, and EVALI case rates were not associated with state-level prevalence of e-cigarette use.
One possible inference from our results is that the presence of legal markets for marijuana has helped mitigate or may be protective against EVALI.”
https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2763966
“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
“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
“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.”
“Many epilepsy patients are refractory to conventional antiepileptic drugs.
Resurgent and persistent currents can be enhanced by epilepsy mutations in the Nav1.2 channel, but conventional antiepileptic drugs inhibit normal transient currents through these channels, along with aberrant resurgent and persistent currents that are enhanced by Nav1.2 epilepsy mutations.
Pharmacotherapies that specifically target aberrant resurgent and/or persistent currents would likely have fewer unwanted side effects and be effective in many patients with refractory epilepsy.
This study investigated the effects of cannbidiol (CBD) and GS967 (each at 1 μM) on transient, resurgent, and persistent currents in human embryonic kidney (HEK) cells stably expressing wild-type hNav1.2 channels.
We found that CBD preferentially inhibits resurgent currents over transient currents in this paradigm; and that GS967 preferentially inhibits persistent currents over transient currents.
Therefore, CBD and GS967 may represent a new class of more targeted and effective antiepileptic drugs.”