“Antimicrobial resistance (AMR) poses a serious threat to human, animal, and plant health on a global scale. Search and elimination techniques should be used to effectively counter the spread of methicillin-resistant Staphylococcus aureus (MRSA) infections. With only a few novel drugs in clinical development, the quest for plant-based alternatives to prevent the spread of antibiotic resistance among bacteria has accelerated. Treatment of MRSA infections is challenging owing to rapidly emerging resistance mechanisms coupled with their protective biofilms. In the present research, we examined the antibacterial properties of ten plant-derived ethanolic leaf extracts.
The most effective ethanolic leaf extract against MRSA in decreasing order of zone of inhibition, Cannabis sativa L. > Syzygium cumini > Murraya koenigii > Eucalyptus sp. > while Aloe barbadensis, Azadirachta indica, had very little impact. Mangifera indica, Curcuma longa, Tinospora cordifolia, and Carica papaya did not exhibit inhibitory effects against MRSA; hence, Cannabis was selected for further experimental study. The minimal inhibitory concentration (MIC) of Cannabis sativa L. extract was 0.25 mg ml-1 with 86% mortality. At a sub-MIC dosage of 0.125 mg ml-1, the biofilm formation was reduced by 71%.
The two major cannabinoids detected were cannabidiol and delta-9-tetrahydrocannabinol (Δ9-THC), which were majorly attributed to substantial inhibitory action against MRSA. The time-kill kinetics demonstrated a bactericidal action at 4 MIC over an 8-20-h time window with a 90% reduction in growth rate. The results from SEM, and light microscopy Giemsa staining revealed a reduction in cells in the treated group with increased AKP activity, indicating bacterial cell membrane breakdown.
These findings suggested cannabinoids may be a promising alternative to antibiotic therapy for bovine biofilm-associated MRSA.”
“Objective: To assess the use of cannabis as a symptom management strategy for patients with fibromyalgia.
Patients and methods: An electronic, cross-sectional survey was conducted among patients diagnosed with fibromyalgia and treated in Integrative Medicine & Health at Mayo Clinic, Rochester, Minnesota. The survey was constructed with the Symptom Management Theory tool and was sent anonymously via web-based software to patients with a diagnosis of fibromyalgia.
Results: Of 5234 patients with fibromyalgia sent the online survey, 1336 (25.5%) responded and met the inclusion criteria. Survey respondents had a median age of 48 (Q1-Q3: 37.5-58.0) years, and most identified as female. Nearly half of respondents (49.5%, n=661) reported cannabis use since their fibromyalgia diagnosis. The most common symptoms for which respondents reported using cannabis were pain (98.9%, n=654); fatigue (96.2%; n=636); stress, anxiety, or depression (93.9%; n=621); and insomnia (93.6%; n=619). Improvement in pain symptoms with cannabis use was reported by 82.0% (n=536). Most cannabis-using respondents reported that cannabis also improved symptoms of stress, anxiety, and depression and of insomnia.
Conclusion: Considering that cannabis is a popular choice among patients for managing fibromyalgia symptoms, clinicians should have adequate knowledge of cannabis when discussing therapeutic options for fibromyalgia with their patients.”
“Objective: The purpose of this study is to comparatively analyze the anticancer properties of Tetrahydrocannabinol (THC), Cannabidiol (CBD), and Tetrahydrocannabivarin (THCV) using In silico tools.
Methods: Using SwissADME and pkCSM, the physicochemical and pharmacokinetics properties of the cannabinoids were evaluated. Protox-II was utilized for the assessment of their cytotoxicity. The chemical-biological interactions of the cannabinoids were also predicted using the Way2Drug Predictive Server which comprises Acute Rat Toxicity, Adver-Pred, CLC-Pred, and Pass Target Prediction.
Results: Both physicochemical and drug-likeness analysis using SwissADME favored THCV due to high water solubility and lower MLOGP value. On the other hand, ADMET assessment demonstrated that THC and CBD have good skin permeability while both THC and THCV exhibited better BBB permeability and have low inhibitory activity on the CYP1A2 enzyme. Furthermore, toxicity predictions by Protox-II revealed that CBD has the lowest probability of hepatotoxicity, carcinogenicity, and immunotoxicity. Contrarily, it has the highest probability of being inactive in mutagenicity and cytotoxicity. Additionally, CLC results revealed that CBD has the highest probability against lung carcinoma. The rat toxicity prediction showed that among the cannabinoids, THCV had the lowest LD50 concentration in rat oral and IV.
Conclusion: Overall, in silico predictions of the three cannabinoid compounds revealed that they are good candidates for oral drug formulation. Among the three cannabinoids, THCV is an excellent anticancer aspirant for future chemotherapy with the most favorable results in drug-likeness and ADMET analysis, pharmacological properties evaluation, and cytotoxicity assessment results. Further study on bioevaluation of compounds is needed to elucidate their potential pharmacological activities.”
“Background: The elevation of endocannabinoid levels through inhibiting their degradation afforded neuroprotection in CaMKIIα-TDP-43 mice, a conditional transgenic model of frontotemporal dementia. However, which cannabinoid receptors are mediating these benefits is still pending to be elucidated.
Methods: We have investigated the involvement of the CB1 and the CB2 receptor using chronic treatments with selective ligands in CaMKIIα-TDP-43 mice, analysis of their cognitive deterioration with the Novel Object Recognition test, and immunostaining for neuronal and glial markers in two areas of interest in frontotemporal dementia.
Results: Our results confirmed the therapeutic value of activating either the CB1 or the CB2 receptor, with improvements in the animal performance in the Novel Object Recognition test, preservation of pyramidal neurons, in particular in the medial prefrontal cortex, and attenuation of glial reactivity, in particular in the hippocampus. In addition, the activation of both CB1 and CB2 receptors reduced the elevated levels of TDP-43 in the medial prefrontal cortex of CaMKIIα-TDP-43 mice, an effect exerted by mechanisms that are currently under investigation.
Conclusions: These data reinforce the notion that the activation of CB1 and CB2 receptors may represent a promising therapy against TDP-43-induced neuropathology in frontotemporal dementia. Future studies will have to confirm these benefits, in particular with one of the selective CB2 agonists used here, which has been thoroughly characterized for clinical development.”
“Cannabis sativa is one of the oldest medicinal plants in human history. Even ancient physicians from hundreds of years ago used Cannabis sativa to treat several conditions like pain.
In the modern era, the research community, including health-care providers, have witnessed wide-scale changes in cannabis policy, legislation, and marketing, with a parallel increase in patient interest. A simple search in PubMed using “cannabis and pain” as keywords provides more than 2,400 articles, about 80% of which were published in the last 8-10 years. Several advancements have been achieved in understanding the complex chemistry of cannabis along with its multiple pharmacological activities.
Preclinical data have demonstrated evidence for the promising potential of cannabis for pain management, and the continuous rise in the prevalence of pain increases the urgency to translate this into clinical practice. Despite the large body of cannabis literature, researchers still need to find rigorous answers for the questions about the efficacy and safety of cannabis in treatment of certain disorders such as pain. In the current chapter, we seek to present a critical overview about the current knowledge on cannabis with special emphasis on pain-related disorders.”
“Introduction: A significant gap exists in the understanding and utilization of medical marijuana and its effects on a patient’s quality of life. This is largely attributed to Cannabis’ sp. Schedule 1 classification, which has impeded the scientific investigation of its effects on the endocannabinoid system (ECS) and quality of life. Additionally, conflicting results from previous studies highlight the need for more research to provide guidance to both patients and clinicians regarding the therapeutic potential of medical marijuana.
Methods: Patients over 18 years of age who were members of the Pennsylvania Medical Marijuana Program (PAMMP) were recruited from regulated Pennsylvania medical marijuana dispensaries. Eligible patients were enrolled through informed consent, following a study design that received approval from the LECOM Institutional Review Board (IRB). Over 90 days, participants were remotely administered an electronic survey every 30 days to collect medical marijuana use patterns and assess changes in quality of life.
Results: Of the 103 participants who completed the study, significant improvements were observed in physical and social functioning, emotional well-being, and energy levels within the first 30 days. Participants reported significant decreases in emotional limitations, fatigue, and pain levels. Notably, participants who used inhaled or vaped products (defined as vape cartridges and concentrates) were younger and exhibited a significantly higher increase in emotional well-being scores compared to those who used flower products (defined as dry leaf only). Participants who consumed medical marijuana for opioid use demonstrated significantly higher THC consumption compared to those seeking treatment for anxiety, chronic pain, or inflammatory bowel disease (IBD). Improvements in the first 30 days also remained constant for the remainder of the study.
Discussion: This study contributed valuable insights into the effects of medical marijuana on quality of life and highlighted potential benefits associated with its use. Moreover, ongoing research aims to assess the observed sustained improvements beyond 90 days, investigating potential long-term trends. While further research is needed to explore the underlying mechanisms of action and long-term effects of medical marijuana, clinicians and patients can gain a better understanding of medical marijuana’s therapeutic potential, enabling more informed decisions regarding its use in clinical settings.”
“This research looks at the effects of medical marijuana on a patient’s quality of life. The study involved 103 participants from Pennsylvania who were using medical marijuana for various health conditions. They answered four surveys over 90 days, reporting on their experiences with marijuana and their well-being.
The results showed that many participants experienced improvements in their physical and social functioning, energy levels, and emotional well-being within the first 30–60 days of using medical marijuana.
Interestingly, the study found that how often someone used medical marijuana could affect their overall health. Those who used it once a day tended to have better general health scores compared to those who used it more frequently. Alcohol use seemed to have an impact too. People who used both alcohol and medical marijuana had lower energy levels and emotional well-being, suggesting that the combination might not be ideal. The study also looked at how people consumed medical marijuana, whether by inhaling it or using it as a flower, and found differences in THC consumption and emotional well-being. However, the study had some limitations, like relying on self-reported data and having a small sample size. Still, it provides valuable insights into how medical marijuana can affect people’s lives and highlights the need for personalized approaches to its use.”
“Human pancreatic ductal adenocarcinoma (PDAC) is a highly malignant and lethal tumor of the exocrine pancreas.
Cannabinoids extracted from the hemp plant Cannabis sativa have been suggested as a potential therapeutic agent in several human tumors. However, the anti-tumor effect of cannabinoids on human PDAC is not entirely clarified. In this study, the anti-proliferative and apoptotic effect of cannabinoid solution (THC:CBD at 1:6) at a dose of 1, 5, and 10 mg/kg body weight compared to the negative control (sesame oil) and positive control (5-fluorouracil) was investigated in human PDAC xenograft nude mice model.
The findings showed that cannabinoids significantly decreased the mitotic cells and mitotic/apoptotic ratio, meanwhile dramatically increased the apoptotic cells. Parallelly, cannabinoids significantly downregulated Ki-67 and PCNA expression levels. Interestingly, cannabinoids upregulated BAX, BAX/BCL-2 ratio, and Caspase-3, meanwhile, downregulated BCL-2 expression level and could not change Caspase-8 expression level.
These findings suggest that cannabinoid solution (THC:CBD at 1:6) could inhibit proliferation and induce apoptosis in human PDAC xenograft models. Cannabinoids, including THC:CBD, should be further studied for use as the potent PDCA therapeutic agent in humans.”
“Herbal medicinal plants and their derivatives have been discovered and used as potential sources for the treatment of human cancers for decades. Of these, cannabinoids extracted from the hemp plant Cannabis sativa have been remarkably noted as a potential therapy for the treatment of several human tumors.”
“In summary, this study revealed that cannabinoids (THC:CBD) (1:6) could inhibit the proliferation and induce apoptosis in human PDAC xenograft nude mice models.”
“Anastasis cascade including induction of Epithelial to Mesenchymal Transition (EMT), DNA repair, and stimulation of pro-survival mediators collectively exaggerate therapy resistance in cancer prognosis. The extensive implications of DNA-damaging agents are clinically proven futile for the rapid development of disease recurrence during treatment regime.
Herein we report a glycosidic derivative of Δ9-tetrahydrocannabinol (THC-9-OG) abrogates sub-toxic doses of 5-Fluorouracil (5FU) induced EMT in colon cancer cells nullifying DNA repairing mechanism. Our in vitro and in vivo data strongly proclaims that THC-9-OG could not only abrogated 5FU mediated background EMT activation through stalling matrix degradation as well as murine 4T1 lung metastasis but also strongly diminished Rad-51 repairing mediator along with stimulation of γ-H2AX foci formation.
The combinatorial treatment (5FU + THC-9-OG) in Apc knockout colorectal carcinoma model conferred remission of the crypt progenitor phenotype which was prominently identified in 5FU treatment. Mechanistically, we demonstrated that 5FU plus THC-9-OG significantly attenuated major EMT inducer Vimentin via extensive ROS generation along with autophagy induction via LC3B I-II conversion and p62 degradation in a p-ATM dependent manner. Additionally, Cannabinoid receptor CB1 was responsible for abrogation of Vimentin since we found increase in the expression of γH2AX and decrease in vimentin expression in CB1 agonist (ACEA) plus 5FU treated cells.
Nutshell, our results unveil a new direction of Cannabinoid based combinatorial approach to control background EMT along with robust enhancing of DNA damage potential of sub-toxic concentration of 5FU resulting immense inhibition of distant metastasis coupled with triggering cell death in vitro and in vivo.”
“Background: Several studies have described a potential anti-tumour effect of cannabinoids (CNB). CNB receptor 2 (CB2) is mostly present in hematopoietic stem cells (HSC). The present study evaluates the anti-leukaemic effect of CNB.
Methods: Cell lines and primary cells from acute myeloid leukaemia (AML) patients were used and the effect of the CNB derivative WIN-55 was evaluated in vitro, ex vivo and in vivo.
Results: We demonstrate a potent antileukemic effect of WIN-55 which is abolished with CB antagonists. WIN-treated mice, xenografted with AML cells, had better survival as compared to vehicle or cytarabine. DNA damage-related genes were affected upon exposure to WIN. Co-incubation with the PARP inhibitor Olaparib prevented WIN-induced cell death, suggesting PARP-mediated apoptosis which was further confirmed with the translocation of AIF to the nucleus observed in WIN-treated cells. Nicotinamide prevented WIN-related apoptosis, indicating NAD+ depletion. Finally, WIN altered glycolytic enzymes levels as well as the activity of G6PDH. These effects are reversed through PARP1 inhibition.
Conclusions: WIN-55 exerts an antileukemic effect through Parthanatos, leading to translocation of AIF to the nucleus and depletion of NAD+, which are reversed through PARP1 inhibition. It also induces metabolic disruptions. These effects are not observed in normal HSC.”
“Dronabinol has preferential antileukemic activity in acute lymphoblastic and myeloid leukemia with lymphoid differentiation patterns. Our study provides rigorous data to support clinical evaluation of THC as a low-toxic therapy option in a well defined subset of acute leukemia patients.”
“Background: The survey of Copeia captured early 2022 patient-reported outcomes (PRO) in Germany under cannabis medicinal product (CAM) therapy, with particular attention to symptoms, symptom changes, indications, side effects, dosages, and cost bearers.
Goal: This study investigated the question of whether associations emerge from the results that could play a role in the indication and treatment monitoring of CAM in chronically ill patients.
Materials and methods: A standardized questionnaire was administered online nationwide in dialogue form over a 15-week period to collect itemized symptoms and PRO. Recruitment was supported by pharmacies, prescribing physicians, and patient associations. Inclusion criteria included physician-prescribed CAM therapy.
Results and discussion: Of 1582 participants, 1030 data sets (65%) could be completely analyzed. There was a heterogeneous patient population, whose common feature was disease chronicity. The frequency distribution of symptoms showed a homogeneous pattern for the respective indications, in which the most frequent six (pain 71%, sleep disturbance 64%, stress/tension 52%, inner restlessness 52%, depressive mood 44% and muscle tension 43%) seem to have a special significance.
According to subjective assessment, quality of life improved significantly in 84% of all participating patients.
Conclusion: A symptom matrix (SMX) composed of different symptoms seems to play a special role in CAM therapy to improve the quality of life of chronically ill patients, regardless of the underlying disease. The SMX could contribute to the identification of an indication and to targeted treatment monitoring.”
