“There have been significant advances in the treatment of cancer in the past decade. However, patients continue to suffer from significant side effects of antineoplastic agents that greatly affect their quality of life (QOL), including chemotherapy-induced nausea and vomiting (CINV), chemotherapy-induced peripheral neuropathy (CIPN), and chemotherapy-induced alopecia (CIA). This review aims to provide an updated overview of emerging strategies for the management and prevention of these immediate and long-lasting side effects. The use of integrative medicine including cannabis continues to evolve in the realm of CINV and cancer-related anorexia. Although no pharmaceutical agent has been approved for the prevention of CIPN, cryotherapy, compression therapy and, more recently, cryocompression therapy have shown benefit in small trials, but there are concerns with tolerability especially related to cryotherapy. More data are necessary to determine an effective and tolerable option to prevent CIPN in large, randomized studies. Scalp cooling (SC), which has a similar mechanism to cryotherapy and compression therapy for CIPN prevention, has proven to be an effective and tolerable approach in randomized studies and has significantly limited CIA, an entity that definitively affects the QOL of patients living with cancer. Taken together, cannabis, cryotherapy, compression and cryocompression therapy, and SC all strive to improve the QOL of patients living with cancer by minimizing the side effects of chemotherapeutic agents.”
“Non-melanoma skin cancer is one of the most common malignancies reported around the globe. Current treatment therapies fail to meet the desired therapeutic efficacy due to high degree of drug resistance. Thus, there is prominent demand in advancing the current conventional therapy to achieve desired therapeutic efficacy. To break the bottleneck, nanoparticles have been used as next generation vehicles that facilitate the efficient interaction with the cancer cells. Here, we developed combined therapy of 5-fluorouracil (5-FU) and cannabidiol (CBD)-loaded nanostructured lipid carrier gel (FU-CBD-NLCs gel). The current investigation has been designed to evaluate the safety and efficacy of developed 5-Flurouracil and cannabidiol loaded combinatorial lipid-based nanocarrier (FU-CBD NLCs) gel for the effective treatment of skin cancer. Initially, confocal microscopy study results showed excellent uptake and deposition at epidermal and the dermal layer. Irritation studies performed by IR camera and HET cam shows FU-CBD NLCs was much more tolerated and less irritant compared to conventional treatment. Furthermore, gamma scintigraphy evaluation shows the skin retention behavior of the formulation. Later, in-ovo tumor remission studies were performed, and it was found that prepared FU-CBD NLCs was able to reduce tumor volume significantly compared to conventional formulation. Thus, obtained results disclosed that permeation and disposition of 5-FU and CBD into different layers of the skin FU-CBD NLCs gel could be more potential carrier than conventional gel. Furthermore, prepared formulation showed greater tumor remission, better survival rate, reduction in tumor number, area, and volume with improved biochemical profile. Thus, prepared gel could serve as a promising formulation approach for the skin cancer treatment.”
“Aging is usually considered a key risk factor associated with multiple diseases, such as neurodegenerative diseases, cardiovascular diseases and cancer. Furthermore, the burden of age-related diseases has become a global challenge. It is of great significance to search for drugs to extend lifespan and healthspan. Cannabidiol (CBD), a natural nontoxic phytocannabinoid, has been regarded as a potential candidate drug for antiaging. An increasing number of studies have suggested that CBD could benefit healthy longevity. Herein, we summarized the effect of CBD on aging and analyzed the possible mechanism. All these conclusions may provide a perspective for further study of CBD on aging.”
“CBD is a potential antiaging candidate. CBD possesses antioxidant, anti-inflammatory and autophagy-inducing properties. CBD has potentially beneficial therapeutic effects for several age-related diseases.”
“Cannabinoids are compounds found in the cannabis sativa plant. Cannabinoids, such as delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), have potential therapeutic benefits in various medical conditions. Some can activate the cannabinoid receptors type-1 and -2 (CB1 and CB2), that are part of the endocannabinoid system (ECS), alongside the endocannabinoids and their metabolic enzymes.
The ECS regulates physiological and cognitive processes and is a potential therapeutic target for a wide range of health conditions like chronic pain, anxiety, and neurodegenerative diseases. Synthetic cannabinoids, are associated with serious health risks, including addiction, psychosis, and death. Nonetheless, some of these molecules are also being explored for pharmacological applications.
Angiogenesis is the process of forming new blood vessels from existing ones, crucial for growth, repair, and tissue maintenance. Dysregulation of this process is associated with several diseases, including cancer, diabetic retinopathy and reproductive pathologies, such as preeclampsia. Recent data suggests that cannabinoids may affect angiogenesis.
Here, we reviewed their impact on pro-angiogenic factors, extracellular matrix enzymes and inhibitors, immune-inflammatory responses, angiogenic pathways and functional assays, focusing on the main compounds for each cannabinoid class: THC and CBD for phytocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2-AG) for endocannabinoids and WIN-55, JWH-133, XLR-11, LYR-7 and LYR-8, for the synthetic cannabinoids.
Despite conflicting reports about the actions of phytocannabinoids and endocannabinoids on angiogenesis, the ability to modulate the angiogenic process is undoubtedly confirmed. This may open a new therapeutical route for angiogenesis-related pathologies. In addition, synthetic cannabinoids present anti-angiogenic actions in several cell models, hinting their potential as anti-angiogenic drugs.”
“Introduction: Taste alteration is a common adverse effect of chemotherapy. This study aimed to investigate the effect of cannabidiol (CBD) on Lean Body Mass (LBM), and taste alterations during oxaliplatin- or paclitaxel-based chemotherapy.
Methods: LBM was estimated by bioelectrical impedance analysis (BIA), and taste perception was evaluated by a randomized sensory test of six samples: sweet, salt, and umami, all in weak and strong concentrations. Taste perceptions were scored on visual analog scales. Patients in the intervention group received oral CBD 300 mg/day for 8 days; patients in the control group did not. Patients were followed for three cycles of chemotherapy.
Results: Twenty-two/ten patients (intervention/control group) were eligible. No effects on LBM were demonstrated. At baseline, the control group was able to differentiate between weak and strong saltiness and weak and strong sweetness but lost this ability after three cycles of chemotherapy. At baseline, the intervention group was unable to differentiate between the concentrations but gained the ability to significantly differentiate between weak and strong sweetness (p = 0.03) and weak and strong saltiness (p = 0.04) after three cycles of chemotherapy and treatment with CBD.
Conclusions: CBD may improve patients’ ability to differentiate taste strengths during chemotherapy.”
“Background: Targeting protein kinase B (Akt) and its downstream signaling proteins are promising options in designing novel and potent drug candidates against hepatocellular carcinoma (HCC). The present study explores the anti-HCC potentials of Cannabis sativa (C. sativa) extract via the involvement of Akt using both in silico and in vivo animal models of HCC approaches.
Methods: Phytoconstituents of C. sativa extract obtained from Gas Chromatography Mass-spectrometry (GCSM) were docked into the catalytic domain of Akt-2. The Diethylnitrosamine (DEN) model of HCC was treated with C. sativa extract. The effects of C. sativa extract treatments on DEN model of hepatocellular carcinoma were assessed by One-way analysis of variance (ANOVA) of the treated and untreated groups RESULT: The lead phytoconstituents of C. sativa extract, Δ-9-tetrahydrocannabinol (Δ-9-THC) and cannabidiol form stable hydrophobic and hydrogen bond interactions within the catalytic domain of Akt-2. C. sativa extract (15 mg/kg and 30 mg/kg) respectively gives a 3-fold decrease in the activities of liver function enzymes when compared with the positive control (group 2). It also gives a 1.5-fold decrease in hepatic lipid peroxidation and elevates serum antioxidant enzymes’ activities by 1-fold in HCC treated Wistar rats when compared with the positive control (group 2). In an animal model of hepatocellular carcinoma, C. sativa extract significantly downregulated Akt and HIF mRNAs in groups 3, 4, and 5 with 2, 1.5, 2.5-fold decrease relative to group 2. VEGF mRNA was downregulated by 1.5-fold decrease in groups 3-5 when compared to group 2. The expression of XIAP mRNA was downregulated by 1.5, 2, and 1.25-folds in groups 3, 4, and 5 respectively, in comparison with group 2. In comparison to group 2, COX-2 mRNA levels were downregulated by 1.5, 1, and 1-folds in groups 3-5. In groups 3-5, CRP mRNA was downregulated by 2-fold in comparison with group 2. In groups 3-5, p21 mRNA was upregulated by 2, 2.5, and 3-folds, respectively when compared with group 2. It upregulated p53 mRNA by 2.5, 3.5, and 2.5-folds in groups 3-5 in comparison with group 2. It downregulated AFP mRNA by 3.5, 2.5, .2.5-folds in groups 3, 4, and 5 respectively when compared with group 2. Histologic analysis showed that C. sativa extract reduced necrosis and inflammation in HCC.
Conclusion: C. sativa demonstrates anti-hepatocellular carcinoma potentials in an animal model of HCC and with the involvement of Akt. Its anticancer potential is mediated through antiangiogenic, proapoptotic, cycle arrest, and anti-inflammatory mechanisms. In future studies, the mechanisms of anti-HCC effects of Δ-9-tetrahydrocannabinol (Δ-9- THC) and cannabidiol via the PI3K-Akt signaling pathways should be explored.”
“We established that C. sativa demonstrates anti-hepatocellular carcinoma potentials in an animal model of HCC and with the involvement of Akt. THC and cannabidiol form stable hydrophobic and hydrogen bond interactions within the catalytic domain of Akt-2. C. sativa extract reduced the activities of liver function enzymes. It ameliorates lipid peroxidation and increases the antioxidant enzymes’ activities. It shows anti-angiogenic, proapoptotic, and anti-inflammatory effects. It also demonstrates cell cycle arrest. C. sativa extract further demonstrates its anti-HCC effects by moderating necrosis and reduce inflammation in HCC. In future studies, the mechanisms of anti-HCC effects of Δ-9-tetrahydrocannabinol (Δ-9- THC) and cannabidiol via the PI3K-Akt signaling pathways should be explored. Although preclinical trials have demonstrated the clinical efficacy of C. sativa, clinical trials with cancer patients are lacking. It is imperative to review the results of prospective and randomized studies on the use of C. sativa in cancer treatment before drawing any conclusions.”
“During solid tumor progression, the tumor microenvironment (TME) evolves into a highly immunosuppressive milieu. Key players in the immunosuppressive environment are regulatory myeloid cells, including myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs), which are recruited and activated via tumor-secreted cytokines such as colony-stimulating factor 1 (CSF-1). Therefore, the depletion of tumor-secreted cytokines is a leading anticancer strategy. Here, we found that CSF-1 secretion by melanoma cells is decreased following treatment with Cannabis extracts. Cannabigerol (CBG) was identified as the bioactive cannabinoid responsible for the effects. Conditioned media from cells treated with pure CBG or the high-CBG extract reduced the expansion and macrophage transition of the monocytic-MDSC subpopulation. Treated MO-MDSCs also expressed lower levels of iNOS, leading to restored CD8+ T-cell activation. Tumor-bearing mice treated with CBG presented reduced tumor progression, lower TAM frequencies and reduced TAM/M1 ratio. A combination of CBG and αPD-L1 was more effective in reducing tumor progression, enhancing survival and increasing the infiltration of activated cytotoxic T-cells than each treatment separately. We show a novel mechanism for CBG in modulating the TME and enhancing immune checkpoint blockade therapy, underlining its promising therapeutic potential for the treatment of a variety of tumors with elevated CSF-1 expression.”
“Our findings have immediate practical implications; current treatment protocols that are already in combination with medical Cannabis as palliative care can select the CBG-rich chemovars in combination with immune checkpoint blockade therapy, making it more effective, and providing patients with antitumor properties in addition to the palliative ones.”
“Exosomes are extracellular vesicles (EVs) originating from endosomes that play a role in cellular communication. These vesicles which mimic the parental cells that release them are promising candidates for targeted drug delivery and therapeutic applications against cancer because of their favorable biocompatibility, specific targeting, low toxicity, and immunogenicity.
Currently, Delta-9-tetrahydrocannabinol (THC), cannabidiol (CBD) and other cannabinoids (e.g., CBG, THCV, CBC), are being explored for their anticancer and anti-proliferative properties. Several mechanisms, including cell cycle arrest, proliferation inhibition, activation of autophagy and apoptosis, inhibition of adhesion, metastasis, and angiogenesis have been proposed for their anticancer activity. EVs could be engineered as cannabinoid delivery systems for tumor-specificity leading to superior anticancer effects.
This review discusses current techniques for EV isolation from various sources, characterization and strategies to load them with cannabinoids. More extensively, we culminate information available on different sources of EVs that have anticancer activity, mechanism of action of cannabinoids against various wild type and resistant tumors and role of CBD in histone modifications and cancer epigenetics. We have also enumerated the role of EVs containing cannabinoids against various tumors and in chemotherapy induced neuropathic pain.”
“Objectives: The study sought to assess factors contributing to the demand for MC among patients with cancer.
Methods: Patients applying for a permit to receive MC at a pain and palliative clinic of a university-affiliated cancer center in Israel in 2020-2021 were asked to complete self-report questionnaires assessing attitudes, knowledge, and expectations regarding MC use. Findings were compared between first-time and repeat applicants. Repeat applicants were asked to report their indications for requesting MC, patterns of use, and treatment effect.
Results: The cohort included 146 patients: 63 first-time applicants and 83 repeat applicants. First-time applicants were more likely to consult sources other than their oncologist for MC-related information (p <.01) and expressed more concern about addiction (p <.001) and side effects (p <.05). They often erroneously assumed the treatment was subsidized (p <.001). Repeat applicants were younger (p <.05) and included more smokers (p <.05) and recreational cannabis users (p <.05); 56.6% were cancer survivors and 78% used high-potency MC. Most patients believed to some degree that MC is more effective than conventional medications for symptom control, and over half thought that MC helps to cure cancer.
Conclusion: Misconceptions regarding the effectiveness of MC for symptom management and treatment may explain the motivation of patients with cancer to apply for a permit. There seems to be an association of young age, cigarette smoking, and recreational cannabis use with ongoing use of MC among cancer survivors.”
“Cannabis sativa is a multipurpose plant that has been used in medicine for centuries. Recently, considerable research has focused on the bioactive compounds of this plant, particularly cannabinoids and terpenes. Among other properties, these compounds exhibit antitumor effects in several cancer types, including colorectal cancer (CRC). Cannabinoids show positive effects in the treatment of CRC by inducing apoptosis, proliferation, metastasis, inflammation, angiogenesis, oxidative stress, and autophagy. Terpenes, such as β-caryophyllene, limonene, and myrcene, have also been reported to have potential antitumor effects on CRC through the induction of apoptosis, the inhibition of cell proliferation, and angiogenesis. In addition, synergy effects between cannabinoids and terpenes are believed to be important factors in the treatment of CRC. This review focuses on the current knowledge about the potential of cannabinoids and terpenoids from C. sativa to serve as bioactive agents for the treatment of CRC while evidencing the need for further research to fully elucidate the mechanisms of action and the safety of these compounds.”
“Data suggest that cannabinoids exert advantages in the treatment of CRC, mostly by inducing apoptosis, although some evidence also points out that they may target other key therapeutic events, such as proliferation, metastasis, inflammation, angiogenesis, oxidative stress, and autophagy. The currently available data on this subject refer mostly to the C. sativa major cannabinoids, i.e., CBD, THC, and CBG, but several pieces of evidence suggest that minor cannabinoids and other bioactive compounds such as terpenes also may hold potential as therapeutic agents for CRC. Data also suggest that certain combinations of cannabinoids and terpenes in C. sativa extracts can lead to a synergistic action known as the “entourage effect,” which has been linked to certain pharmacological benefits. The potential therapeutic benefits of the cannabinoids and terpenes from this plant make them key candidates for further drug development.”
