“We present a novel, multicomponent nanoparticulate carrier system based on superparamagnetic iron oxide nanoparticles with a designed hydrophilic/hydrophobic balance based on oleic acid and TWEEN 80 to incorporate hydrophobic cannabinoids-cannabigerol and cannabidiol-as well as the hydrophilic anthracycline drug epirubicin, forming a conjugate anticancer system.
Additionally, the superparamagnetic iron oxide-based nanoparticles formed the core of the system, thus providing it with magnetic hyperthermia capabilities with a specific absorption rate comparable to the corresponding systems in the literature. The interaction of the conjugate with the cell membrane was studied using the Langmuir monolayers at the air/water interface formed of selected lipids modeling the healthy and cancerous cell membranes.
Finally, cytotoxicity tests were carried out against the SKOV-3 cell line in vitro. A synergistic effect was observed when both the cannabinoid and epirubicin were present in the conjugate, as compared to the cannabinoid or epirubicin alone, making our system advantageous for further development for tentative therapeutic use.”
“This work examines the anticancer activity, the anti-inflammatory nature, and the cytotoxicity of the ethanol extract obtained from the female flowers of Cannabis sativa L using molecular methods in vitro, animal testing in vivo, as well as computational methods and simulations in silico.
From the GC-MS analysis, the following bioactive compounds were found: cannabidiol (CBD), tetrahydrocannabinol (THC), and humulene. The antiproliferative activities of the extract were determined on HeLa cells by using MTT, Crystal Violet, and Trypan Blue assays with an IC50 value suggesting 51%-77.6% lethality.
The bioinformatics analysis of molecular docking proved significant ligand-protein interactions of CBD, THC, and humulene with cancer-associated proteins such as PD-1/PD-L1, TNF-α, and MMP-9. In vivo, breast cancer was first established in female Sprague-Dawley rats with 7,12-dimethylbenz(a)anthracene (DMBA) then treated with cannabinoids either singularly or in combination.
Detailed treatment demonstrated that the use of the three cannabinoids simultaneously yielded the best anticancer and anti-inflammatory outcomes together with the best tumor reduction. The concentration of serum biomarkers of inflammation and tumor progression was substantially reduced in treated groups compared to the control group, which proves the synergistic effects of these cannabinoids in breast cancer therapy.
This study emphasizes the importance of medical Cannabis sativa derivatives in cancer treatment.”
“Cancer still has no known treatment, and research is being conducted to create lead compounds and precursors that could be used as anticancer medications for 1 day. The goal of this study was to identify natural compounds with anticancer properties.
The MTT assay showed that cannabinoids retain anti-proliferative, anti-invasion, and apoptotic effects. IC50 upregulates 51%–77.6% of carcinoma cell death. The synergistic effects of cannabidiol, tetrahydrocannabinol, and humulene significantly suppressed PD-1/PD-L1 expression and oxidative stress, suggesting a possible approach for targeting breast cancer resistance. The greatest effect was obtained when all three compounds were combined, suggesting that the immunosuppressive and oxidative stress-modulatory effects of the compounds occurred synergistically.
Herein, we report comprehensive findings that may be helpful in designing new combinatory therapeutic strategies for breast cancer via the PD-1/PD-L1 pathway and oxidative stress markers. Further studies and trials are needed to identify more cannabinoid-based treatments and to combine pharmacological and cannabinoid drugs to gain remarkable effects against various cancer treatments.”
“Cannabis sativa is the oldest cultivated plant and contains a lot of naturally useful components used by humans. It is used as a source of fuel, food, herbal body care products, and medicines to cure different diseases. It is a plant of the Cannabaceae family. “
“Commonly known as marijuana or hemp, Cannabis sativa L. (Cannabaceae), contains numerous active compounds, particularly cannabinoids, which have been extensively studied for their biological activities. Among these, cannabidiol (CBD) stands out for its therapeutic potential, especially given its non-psychotropic effects.
This review evaluates the antitumor properties of CBD, highlighting its various mechanisms of action, including the induction of apoptosis, autophagy, and necrosis.
By synthesizing findings from in vitro studies on the cell death mechanisms and signaling pathways activated by CBD in various human tumor cell lines, this literature review emphasizes the therapeutic promise of this natural antineoplastic agent. We conducted a comprehensive search of articles in PubMed, Scopus, Springer, Medline, Lilacs, and Scielo databases from 1984 to February 2022.
Of the forty-three articles included, the majority (68.18%) reported that CBD activates apoptosis, while 18.18% observed simultaneous apoptosis and autophagy, 9.09% focused on autophagy alone, and 4.54% indicated necrosis. The antitumor effects of CBD appear to be mediated by transient receptor potential cation channels (TRPVs) in endometrial cancer, glioma, bladder cancer, and myeloma, with TRPV1, TRPV2, and TRPV4 playing key roles in activating apoptosis.
This knowledge paves the way for innovative therapeutic strategies that may enhance cancer treatment outcomes while minimizing the toxicity and side effects associated with conventional therapies.”
“This review underscores the therapeutic potential of CBD as a promising antitumor agent across various cancer types, particularly through its interaction with transient receptor potential cation channels (TRPVs) and endocannabinoid CB receptors.
Our findings suggest that CBD primarily activates the apoptosis pathway while also engaging autophagy and necrosis, offering a multifaceted strategy for inducing cancer cell death. Moreover, the potential for combination therapies that integrate CBD with established chemotherapeutics highlights the importance of further research to investigate these synergies and optimize therapeutic regimens.
Although regulatory challenges persist, robust scientific evidence demonstrating CBD’s safety and efficacy of CBD will be crucial for advancing its clinical application in oncology.”
“Cannabinoids are widely recognized for their potential therapeutic effects, making them significant and valuable candidates for medical research and applications across various fields.
This review aims to analyze the pharmacokinetics of Cannabidiol (CBD), Cannabigerol (CBG), and Cannabichromene (CBC), along with their corresponding acidic forms, Cannabidiolic acid (CBDA), Cannabigerolic acid (CBGA), and Cannabichromenic acid (CBCA).
Among these cannabinoids, CBD is the most extensively studied. Nevertheless, research involving all the mentioned cannabinoids has shown that their pharmacokinetic parameters are highly variable, depending significantly on factors such as dose, formulation, route of administration, and diet. Furthermore, challenges such as brain penetration and first-pass metabolism have been highlighted.
In conclusion, this review demonstrates significant progress in understanding the pharmacokinetics of non-psychotropic cannabinoids. However, it also underscores the need for further research, particularly on CBG, CBC, and their respective acidic forms, with the most significant gap being in clinical investigations. Expanding these studies is essential to facilitate their optimized use in medical treatments.”
“Background/Objectives: Current inflammatory bowel disease (IBD) treatments focus on symptomatic relief, highlighting the need for innovative approaches. Dysregulation of the cannabinoid 1 (CB1) receptor, part of the endocannabinoid system, is linked to colitis. While tetrahydrocannabinol (THC) alleviates colitis via CB1 activation, its psychotropic effects limit clinical use. ZCZ011, a CB1R allosteric modulator, and cannabidiol (CBD), a non-psychoactive cannabinoid, offer alternatives. This study investigated combining sub-therapeutic THC doses with ZCZ011 or CBD in a murine model of dextran sodium sulphate (DSS)-induced colitis.
Methods: Acute colitis was induced with 4% DSS for 7 days, followed by 3 days of water. Chronic colitis was modelled over 24 days with alternating DSS concentrations. The combination of 2.5 mg/kg THC with 20 mg/kg ZCZ011 or 10 mg/kg CBD was evaluated. Key markers were assessed to determine efficacy and safety, including disease activity index (DAI), inflammation, cytokine levels, GLP-1, and organ health.
Results: DSS-induced colitis resulted in increased DAI scores, cytokines, organ inflammation and dysregulation of GLP-1 and ammonia. THC at 10 mg/kg significantly improved colitis markers but was ineffective at 2.5 and 5 mg/kg. ZCZ011 alone showed transient effects. However, combining 2.5 mg/kg THC with either 20 mg/kg ZCZ011 or 10 mg/kg CBD significantly alleviated colitis markers, restored colon integrity and reestablished GLP-1 homeostasis. This combination also maintained favourable haematological and biochemical profiles, including a notable reduction in colitis-induced elevated ammonia levels.
Conclusions: This study demonstrates the synergistic potential of low-dose THC combined with CBD or ZCZ011 as a novel, effective and safer therapeutic strategy for ulcerative colitis.”
“This study provides compelling evidence that sub-therapeutic doses of THC combined with ZCZ011 or CBD offer a safe and effective strategy for managing both the inflammatory and metabolic components of IBD. Notably, the normalisation of GLP-1 and ammonia levels underscores the dual benefits of these treatments in alleviating colitis while addressing associated metabolic dysregulation and extraintestinal complications. This dual-action approach addresses key limitations of current therapies and emphasizes ECS modulation as a promising avenue for IBD treatment.”
“In the scenario of fighting bacterial resistance to antibiotics, natural products have been extensively investigated for their potential antibacterial activities. Among these, cannabinoids-bioactive compounds derived from cannabis-have garnered attention for their diverse biological activities, including anxiolytic, anti-inflammatory, analgesic, antioxidant, and neuroprotective properties.
Emerging evidence suggests that cannabinoids may also possess significant antimicrobial properties, with potential applications in enhancing the efficacy of conventional antimicrobial agents. Therefore, this review examines evidence from the past five years on the antimicrobial properties of cannabinoids, focusing on underlying mechanisms such as microbial membrane disruption, immune response modulation, and interference with microbial virulence factors. In addition, their synergistic potential, when used alongside standard therapies, underscores their promise as a novel strategy to address drug resistance, although further research and clinical trials are needed to validate their therapeutic use.
Overall, cannabinoids offer a promising avenue for the development of innovative treatments to combat drug-resistant infections and reduce the reliance on traditional antimicrobial agents.”
“The unique chemical properties of cannabinoids, combined with their interactions with existing therapies, contribute to their antimicrobial effects against a wide range of microorganisms, including bacteria, fungi, and viruses.The data collected support the conclusion that cannabinoids exert their effects through multiple pathways, including the disruption of microbial membranes, modulation of immune responses, and interference with microbial virulence factors.
The use of cannabinoids as alternative therapeutic options has demonstrated their potential to overcome the limitations of conventional antibiotics, offering a potential new approach to combating drug-resistant microorganisms, potentially reducing dependence on traditional antimicrobial agents that have become less effective. It also appears that the use of combinations of cannabinoids with other conventional drugs can potentially lead to a synergistic effect with improved therapeutic capabilities.”
“Introduction: Individuals living with Sickle Cell Disease (SCD) are subject to numerous chronic complications, including disabling chronic pain, often dependent on opioids and with important repercussions on quality of life. The use of Medicinal Cannabis in this scenario may be a promising strategy for mitigating this impact.
Areas covered: This work compiled current knowledge regarding the endocannabinoid system in humans and the role of this system in various organic functions. Articles were retrieved through a comprehensive search of the PubMed NCBI database, covering relevant studies up to 2024. These data bring important speculations on the potential role of the use of medicinal cannabis in modulating SCD chronic complications, and the preliminary results of clinical trials carried out in this condition are discussed.
Expert opinion: The search for understanding the role of cannabis-derived products in the management of chronic complications of sickle cell disease could add resources to the serious challenge of dealing with the multiple aspects of the disease faced by patients. They range from the management of chronic pain itself, the risks of opioid dependence, in addition to other difficult scenarios, such as leg ulcers and chronic inflammation and its consequences.”
“Human epidermal growth factor receptor 2 (HER2) is a transmembrane receptor within the ErbB family that plays a pivotal role in the progression of various aggressive cancers. HER2-positive tumors often develop resistance to standard therapies, necessitating the exploration of innovative treatment options.
Cannabinoids, bioactive compounds from Cannabis sativa such as cannabidiol (CBD), cannabigerol (CBG), and cannabinol (CBN), have gained attention for their potential anticancer properties.
This study evaluates the efficacy of CBD, CBG, and CBN in targeting HER2-positive ovarian cancer through kinase inhibition assays, surface plasmon resonance (SPR), molecular docking, and cell viability assessments.
SPR analysis revealed that cannabinoids bind strongly to HER2-tyrosine kinase (HER2-TK), with CBD showing the highest affinity (KD = 6.16 μM), significantly better than afatinib (KD = 26.30 μM), and CBG demonstrating moderate affinity (KD = 17.07 μM). In kinase inhibition assays, CBG was the most potent inhibitor (IC50 = 24.7 nM), followed by CBD (IC50 = 38 nM), suggesting their ability to disrupt HER2-mediated signaling pathways. Molecular docking studies highlighted critical interactions between cannabinoids and essential HER2 residues (Leu796, Thr862, Asp863). In cell viability assays, CBD and CBG effectively inhibited the growth of HER2-positive SKOV3 cells (IC50 = 13.8 μM and 16.6 μM, respectively), comparable to traditional tyrosine kinase inhibitors.
These findings underscore the therapeutic potential of cannabinoids, particularly CBD and CBG, as alternative or adjunct therapies for HER2-positive cancers, with the promise of mitigating resistance and adverse effects associated with existing treatments.”
“This study provides compelling evidence for the potential of cannabinoids, particularly CBD and CBG, as effective inhibitors of HER2-TK in HER2-positive ovarian cancer. The significant binding affinities and potent inhibitory effects observed in kinase assays and cell viability experiments highlight cannabinoids as promising candidates for alternative or adjunctive therapies, especially in patients facing challenges with conventional treatments.
The findings not only indicate that cannabinoids can disrupt HER2-mediated signaling pathways but also suggest that they may enhance the therapeutic efficacy of existing TKIs while potentially mitigating associated side effects. The molecular docking analysis reinforces the understanding of how cannabinoids interact with critical residues in HER2-TK, revealing a detailed mechanism of action that warrants further exploration. Given the rising concerns regarding resistance to standard HER2-targeted therapies and their adverse effects, the incorporation of cannabinoids into treatment regimens may offer a novel and beneficial strategy for managing HER2-positive ovarian cancer.”
“Background: The therapeutic use of cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) to treat migraine has been understudied. Using three mouse models, we examined the impact of CBD and THC on migraine-relevant behaviors triggered by: 1) calcitonin gene-related peptide (CGRP), 2) sodium nitroprusside (SNP), and 3) cortical spreading depolarization (CSD).
Methods: Both male and female CD1 mice were treated with CBD (100 mg/kg) or THC (1 mg/kg) alone or in combinations of CBD (1, 30 or 100 mg/kg) and THC (1 mg/kg) prior to injection of CGRP or SNP. The mice were assessed for light aversion (photophobia), squint (non-evoked pain), and periorbital tactile hypersensitivity, as well as possible adverse effects. In a separate set of experiments, CSD events were optogenetically induced in familial hemiplegic migraine 1 (FHM1) mutant and wildtype littermates (WT) mice (C57BL/6 background), followed by grimace and motor assessments with and without combinations of CBD (30 or 100 mg/kg) and THC (1 mg/kg).
Results: In CD1 mice, a 100:1 CBD:THC combination mitigated light aversion induced by CGRP and SNP in males and females. Rescue of CGRP- and SNP-induced squint was observed only in male mice with 100:1 CBD:THC. None of the treatments rescued periorbital tactile hypersensitivity in either sex. In FHM1 mutant and WT mice, the 100:1 CBD:THC ratio did not affect CSD characteristics but did reduce CSD-induced grimace features (i.e., head pain mimic). No adverse effects of any of the cannabinoid treatments were observed using cognitive, emotional, or motor tests.
Conclusions: A 100:1 ratio of CBD:THC has a beneficial effect on some of the most bothersome migraine-related symptoms in three mouse models. Our findings support a potential therapeutic efficacy of combined CBD and THC treatments.”
“Our preclinical findings suggest that cannabinoids may have therapeutic potential for treating migraine symptoms without causing adverse effects. These findings are in line with previous studies that have suggested that cannabinoids may be effective in treating pain and migraine.”
“Despite extensive research on insulin resistance, which is associated with type 2 diabetes and obesity, there remains a lack of effective and safe methods to treat it. Thus, we hypothesized that cannabidiol (CBD), which influences lipid accumulation and inflammatory response, may interact with sphingolipid metabolism and insulin signaling.
To investigate the effects of CBD, male Wistar rats were fed a standard rodent chow or high-fat diet for 7 weeks to induce IR and were treated with CBD or its vehicle administered intraperitoneally for the last two weeks of the experiment. High-Performance Liquid Chromatography (HPLC) was used to assess sphingolipid concentration in the liver, while multiplex assay and western blotting were used to investigate the level or expression of proteins in the insulin signaling pathway and sphingolipid metabolism.
Our results revealed that CBD prevented ceramide deposition in the liver of high-fat-fed rats through inhibition of the ceramide de novo synthesis pathway. Moreover, the accumulation of sphingosine-1-phosphate was notably increased with impaired catabolic pathway. Observed changes in the sphingolipid pathway coincided with improved insulin signaling after CBD treatment in animals fed a high-fat diet.
Considering the presented evidence, CBD exerted a beneficial effect on insulin sensitivity in a state of lipid overload through the modification of sphingolipid deposition.
Our study reveals the importance of broadening IR treatment methods, especially with natural substances that lack serious side effects such as CBD.”
