“The management of orofacial pain to alleviate the quality of life of affected patients is becoming increasingly challenging for scientific research and healthcare professionals. From this perspective, in addition to conventional therapies, new alternatives are being sought, increasingly looking at the use of both natural and synthetic products.
Cannabis sativa L. represents an interesting source of bioactive compounds, including non-psychoactive cannabinoids, flavonoids, and terpenes, many of which are effective in improving pain intensity.
Here, we aim to analyze the possible mechanisms of action of the bioactive natural and synthetic hemp-derived compounds responsible for the modulatory effects on pain-related pathways. The ability of these compounds to act on multiple mechanisms through a synergistic effect, reducing both the release of inflammatory mediators and regulating the response of the endocannabinoid system, makes them interesting agents for alternative formulations to be used in orofacial pain.”
“Non-Alcoholic Steatohepatitis (NASH) is the progressive form of Non-Alcoholic Fatty Liver Disease (NAFLD). NASH is distinguished by severe hepatic fibrosis and inflammation. The plant-derived, non-psychotropic compound cannabigerol (CBG) has potential anti-inflammatory effects similar to other cannabinoids. However, the impact of CBG on NASH pathology is still unknown. This study demonstrated the therapeutic potential of CBG in reducing hepatic steatosis, fibrosis, and inflammation.
Methods: 8-week-old C57BL/6 male mice were fed with methionine/choline deficient (MCD) diet or control (CTR) diets for five weeks. At the beginning of week 4, mice were divided into three sub-groups and injected with either a vehicle, a low or high dose of CBG for two weeks. Overall health of the mice, Hepatic steatosis, fibrosis, and inflammation were evaluated.
Results: Increased liver-to-body weight ratio was observed in mice fed with MCD diet, while a low dose of CBG treatment rescued the liver-to-body weight ratio. Hepatic ballooning and leukocyte infiltration were decreased in MCD mice with a low dose of CBG treatment, whereas the CBG treatment did not change the hepatic steatosis. The high dose CBG administration increased inflammation and fibrosis. Similarly, the expression of cannabinoid receptor (CB)1 and CB2 showed decreased expression with the low CBG dose but not with the high CBG dose intervention in the MCD group and were co-localized with mast cells. Additionally, the decreased mast cells were accompanied by decreased expression of transforming growth factor (TGF)-β1.
Conclusions: Collectively, the low dose of CBG alleviated hepatic fibrosis and inflammation in MCD-induced NASH, however, the high dose of CBG treatment showed enhanced liver damage when compared to MCD only group. These results will provide pre-clinical data to guide future intervention studies in humans addressing the potential uses of CBG for inflammatory liver pathologies, as well as open the door for further investigation into systemic inflammatory pathologies.”
“Objectives: Cannabis has been proposed as a potential treatment for Parkinson’s disease (PD) due to its neuroprotective benefits. However, there has been no rigorous review of preclinical studies to evaluate any potential treatment effect. This systematic review was undertaken to provide evidence in support or against a treatment effect of cannabinoids in animal models of PD.
Methods: Databases were searched for any controlled comparative studies that assessed the effects of any cannabinoid, cannabinoid-based treatment or endocannabinoid transport blocker on behavioural symptoms in PD animal models.
Results: A total of 41 studies were identified to have met the criteria for this review. 14 of these studies were included in meta-analyses of rotarod, pole and open field tests. Meta-analysis of rotarod tests showed a weighted mean difference of 31.63 s for cannabinoid-treated group compared with control. Meta-analysis of pole tests also showed a positive treatment effect, evidenced by a weighted mean difference of -1.51 s for cannabinoid treat group compared with control. However, meta-analysis of open field test demonstrated a standardised mean difference of only 0.36 indicating no benefit.
Conclusion: This review demonstrates cannabinoid treatment effects in alleviating motor symptoms of PD animal models and supports the conduct of clinical trials of cannabis in PD population. However, there is no guarantee of successful clinical translation of this outcome because of the many variables that might have affected the results, such as the prevalent unclear and high risk of bias, the different study methods, PD animal models and cannabinoids used.”
“Overall, this systematic review and meta-analysis provides evidence of the benefit of cannabinoid treatment in PD animal models, which warrants further investigations. This review supports clinical trial of cannabis or cannabis-based treatments in humans with PD.”
“Oxidative stress, neurodegeneration, neuroinflammation, and vascular leakage are believed to play a key role in the early stage of diabetic retinopathy (ESDR). The aim of this study was to investigate the blockade of cannabinoid receptor 1 (CB1R) and activation of cannabinoid receptor 2 (CB2R) as putative therapeutics for the treatment of the early toxic events in DR. Diabetic rats [streptozotocin (STZ)-induced] were treated topically (20 μL, 10 mg/mL), once daily for fourteen days (early stage DR model), with SR141716 (CB1R antagonist), AM1710 (CB2R agonist), and the dual treatment SR141716/AM1710. Immunohistochemical-histological, ELISA, and Evans-Blue analyses were performed to assess the neuroprotective and vasculoprotective properties of the pharmacological treatments on diabetes-induced retinal toxicity. Activation of CB2R or blockade of CB1R, as well as the dual treatment, attenuated the nitrative stress induced by diabetes. Both single treatments protected neural elements (e.g., RGC axons) and reduced vascular leakage. AM1710 alone reversed all toxic insults. These findings provide new knowledge regarding the differential efficacies of the cannabinoids, when administered topically, in the treatment of ESDR. Cannabinoid neuroprotection of the diabetic retina in ESDR may prove therapeutic in delaying the development of the advanced stage of the disease.”
“In closing, our findings suggest that topical administration of the three cannabinoid treatments, such as eye drops, provides protection to the diabetic retina in a differential manner against the four pathologies of ESDR. The actions of both CB2R activation and CB1R blockade in restoring ganglion cell axons (NFL-IR) in ESDR suggest that both agents may be effective in retarding RGC death. AM1710 is efficacious as an antioxidant, anti-inflammatory, neuroprotective and vasculoprotective agent and, thus, a promising new therapeutic for ESDR. Further advancement of retinal imaging to screen and identify the early events in DR, such as neurodegeneration in diabetic patients, is crucial for selecting neuroprotective drugs and implementing personalized treatments. As our findings clearly implicate the endocannabinoid system, the therapeutic benefits of this class of compounds should also extend to patients with diabetic nephropathy and cardiopathy/stroke since DR has been associated with the development of these diseases.”
“Melanoma is deadly, physically impairing, and has ongoing treatment deficiencies. Current treatment regimens include surgery, targeted kinase inhibitors, immunotherapy, and combined approaches. Each of these treatments face pitfalls, with diminutive five-year survival in patients with advanced metastatic invasion of lymph and secondary organ tissues. Polyphenolic compounds, including cannabinoids, terpenoids, and flavonoids; both natural and synthetic, have emerging evidence of nutraceutical, cosmetic and pharmacological potential, including specific anti-cancer, anti-inflammatory, and palliative utility. Cannabis sativa is a wellspring of medicinal compounds whose direct and adjunctive application may offer considerable relief for melanoma suffers worldwide. This review aims to address the diverse applications of C. sativa‘s biocompounds in the scope of melanoma and suggest it as a strong candidate for ongoing pharmacological evaluation.”
“In conclusion, there is a complex array of effects that polyphenolic and cannabinoid compounds elicit in relation to melanoma. Multiple biochemical and genetic cascades are regulated through the presence of these natural substances. Polyphenolic compounds emergingly demonstrate a significant capacity to mediate many of the impacts of cancer, including pain, inflammation and invasiveness. Combined administration of polyphenol compounds has shown existing promise for improvement of potency and bioactivity of these substances. To combat the complexity of cancer, new pharmacological perspectives are necessary. Accordingly, plant polyphenols, particularly those of cannabis provide a deep well of structural potential for the emergence of novel drugs with multi-applicability to the total sphere of cancer treatment. This is merely the budding tip of biocompounds available for exploration in plant-based medicine and is a substantive base for future research.”
“Since its medical legalization, cannabis preparations containing the major phytocannabinoids (cannabidiol (CBD) and δ9-tetrahydrocannabinol (THC)) have been used by patients with rheumatoid arthritis (RA) to alleviate pain and inflammation. However, minor cannabinoids such as cannabigerol (CBG) also demonstrated anti-inflammatory properties, but due to the lack of studies, they are not widely used. CBG binds several cellular target proteins such as cannabinoid and α2-adrenergic receptors, but it also ligates several members of the transient potential receptor (TRP) family with TRPA1 being the main target. TRPA1 is not only involved in nnociception, but it also protects cells from apoptosis under oxidative stress conditions. Therefore, modulation of TRPA1 signaling by CBG might be used to modulate disease activity in RA as this autoimmune disease is accompanied by oxidative stress and subsequent activation of pro-inflammatory pathways. Rheumatoid synovial fibroblasts (RASF) were stimulated or not with tumor necrosis factor (TNF) for 72 h to induce TRPA1 protein. CBG increased intracellular calcium levels in TNF-stimulated RASF but not unstimulated RASF in a TRPA1-dependent manner. In addition, PoPo3 uptake, a surrogate marker for drug uptake, was enhanced by CBG. RASF cell viability, IL-6 and IL-8 production were decreased by CBG. In peripheral blood mononuclear cell cultures (PBMC) alone or together with RASF, CBG-modulated interleukin (IL)-6, IL-10, TNF and immunoglobulin M and G production which was dependent on activation stimulus (T cell-dependent or independent). However, effects on PBMCs were only partially mediated by TRPA1 as the antagonist A967079 did inhibit some but not all effects of CBG on cytokine production. In contrast, TRPA1 antagonism even enhanced the inhibitory effects of CBG on immunoglobulin production. CBG showed broad anti-inflammatory effects in isolated RASF, PBMC and PBMC/RASF co-cultures. As CBG is non-psychotropic, it might be used as add-on therapy in RA to reduce IL-6 and autoantibody levels.”
“Cannabidiol (CBD) is a biologically active compound present in the plants of the Cannabis family, used as anticonvulsant, anti-inflammatory, anti-anxiety, and more recently, anticancer drug. In this work, its use as a new self-assembly inducer in the formation of nanoparticles is validated. The target conjugates are characterized by the presence of different anticancer drugs (namely N-desacetyl thiocolchicine, podophyllotoxin, and paclitaxel) connected to CBD through a linker able to improve drug release. These nanoparticles are formed via solvent displacement method, resulting in monodisperse and stable structures having hydrodynamic diameters ranging from 160 to 400 nm. Their biological activity is evaluated on three human tumor cell lines (MSTO-211H, HT-29, and HepG2), obtaining GI50 values in the low micromolar range. Further biological assays were carried out on MSTO-211H cells for the most effective NP 8B, confirming the involvement of paclitaxel in cytotoxicity and cell death mechanism.”
“Acute and chronic pain management remains an ongoing challenge for hand surgeons. This has been compounded by the ongoing opioid epidemic in the United States.
With the increasing legalization of medical and recreational cannabis throughout the United States and other countries, previous societal stigmas about this substance keep evolving, and recognition of medical cannabis as an opioid-sparing pain management alternative is growing. A review of the current literature demonstrates a strong interest from patients regarding the use of medical cannabis for pain control.
Current evidence demonstrates its efficacy and safety for chronic musculoskeletal and neuropathic pain. However, definitive conclusions regarding the efficacy of cannabis for pain control in hand and upper extremity conditions require continued investigation.
The purpose of this article is to provide a general review of the mechanism of medical cannabis and a scoping review of the current evidence for its efficacy, safety, and potential applicability in hand and upper extremity conditions.”
“Purpose: Appropriate preoperative screening techniques are needed to safely provide anesthesia to increasing numbers of cannabis using surgical patients.
Design: This was a quasi-experimental quality improvement project.
Methods: Preoperative identification of cannabis users by registered nurses (RNs) and certified registered nurse anesthetists (CRNAs) was compared to baseline identification rates. CRNAs’ compliance with evidenced base guidelines was recorded. Perioperative medication requirements were recorded and compared between cannabis-users and non-cannabis users.
Findings: Identification of cannabis users by CRNAs conducting preanesthetic assessments increased from 4.08% to 14.36% while RN identification improved from 11.22% to 13.81%. Compliance with identification guidelines was 69.2% among CRNAs.
There were no differences in anesthetic requirements, complications, or postanesthesia care unit (PACU) length of stay between cannabis users and non-users.
Conclusion: Preoperative identification of cannabis users allows for safer, more effective perioperative care by CRNAs, registered nurses, and surgical staff.”
“Non-melanoma skin cancer is one of the most common malignancies reported with high number of morbidities, demanding an advanced treatment option with superior chemotherapeutic effects. Due to high degree of drug resistance, conventional therapy fails to meet the 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 NLCs were optimized using central composite design that showed an average particle size of 206 nm and a zeta potential of -34 mV. In addition, in vitro and ex vivo drug permeations studies demonstrated the effective delivery of both drugs in the skin layers via lipid structured nanocarriers.
Also, the prepared FU-CBD-NLCs showed promising effect in-vitro cell studies including MTT assays, wound healing and cell cycle as compared to the conventional formulation. Moreover, dermatokinetic studies shows there was superior deposition of drugs at epidermal and the dermal layer when treated with FU-CBD-NLCs.
In the end, overall study offered a novel combinatorial chemotherapy that could be an option for the treatment of non-melanoma skin cancer.”
