Antibacterial, antioxidant, and haemolytic potential of silver nanoparticles biosynthesized using roots extract of Cannabis sativa plant

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“In this study, Cannabis sativa roots extract has been employed for the biosynthesis of silver nanoparticles (AgNPs). The appearance of reddish-brown colour followed by absorption peak of AgNPs at 408 nm through UV-vis spectrophotometry suggested biosynthesis of AgNPs. The size of the particles ranged from 90-113 nm, confirmed using DLS and TEM along with zeta potential of -25.3 mV. The FTIR provided information regarding the phytochemical capping. The study was further elaborated for determining AgNPs antibacterial, antioxidant, and cellular toxicity using MIC, DPPH, MTT, and haemolytic assays, respectively. The AgNPs were significantly effective against Staphylococcus aureus (Gram-positive), as compared to that of Pseudomonas aeruginosaKlebsiella pneumoniae, and Escherichia coli (Gram-negative). AgNPs also exhibited remarkable antioxidant potential wherein 58.01 ± 0.09% free radical scavenging was observed at a concentration of 100 µg/ml. AgNPs revealed lower cytotoxicity where cell viability was observed to be 52.38 ± 0.6% at a very high concentration of 500 µg/ml in HEK 293 cells. Further, very low toxicity was seen in RBCs i.e. 6.47 ± 0.04% at a high concentration of 200 µg/ml. Thus, the current study beholds anticipation that Cannabis sativa ethanolic root extract-mediated AgNPs may play a vital role in therapeutic.”

https://pubmed.ncbi.nlm.nih.gov/36519372/

“The study demonstrates the efficient biosynthesis of silver nanoparticles using Cannabis sativa ethanolic root extract. The potency of the plant extract and phytochemically fabricated silver nanoparticles were analysed over certain parameters such as antimicrobial, antioxidant and cellular toxicity tests. The study concludes the significant effectiveness of silver nanoparticles, thus prognosticating theirs use henceforth.”

https://www.tandfonline.com/doi/full/10.1080/21691401.2022.2149543

Phytocannabinoids Stimulate Rejuvenation and Prevent Cellular Senescence in Human Dermal Fibroblasts

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“In light of the increased popularity of phytocannabinoids (pCBs) and their appearance in beauty products without rigorous research on their rejuvenation efficacy, we decided to investigate the potential role of pCBs in skin rejuvenation.

Utilizing healthy and stress-induced premature senescent (SIPS) CCD-1064Sk skin fibroblasts, the effects of pCBs on cellular viability, functional activity, metabolic function, and nuclear architecture were tested. Both delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) within the range of 0.5 µM to 2.0 µM increased cell growth in a dose-dependent manner while significantly decreasing senescence as measured by beta-galactosidase activity.

Utilizing a scratch assay, both THC and CBD (2.0 µM) significantly improved wound healing in both healthy and SIPS fibroblasts. THC and CBD altered nuclear architecture and mRNA levels of cell cycle regulators and genes involved in ECM production. Subsequently, we found ELN, Cyclin D1, PCNA, and BID protein levels altered by SIPS but ameliorated after pCBs exposure in human dermal fibroblasts.

Lastly, we compared the efficacy of THC and CBD with common anti-aging nutrient signaling regulators in replicative senescent adult human dermal fibroblasts, CCD-1135Sk.

Both THC and CBD were found to improve wound healing better than metformin, rapamycin, and triacetylresveratrol in replicative senescent CCD-1135Sk fibroblasts. Therefore, pCBs can be a valuable source of biologically active substances used in cosmetics, and more studies using clinical trials should be performed to confirm the efficacy of phytocannabinoids.”

https://pubmed.ncbi.nlm.nih.gov/36497198/

“THC and CBD stimulated fibroblasts’ ability to close damaged wounds, while THC induced wound healing better than common nutrient signaling regulators,”

https://www.mdpi.com/2073-4409/11/23/3939

In Silico Binding Analysis of Cannabinoids with Eph Receptors for Therapeutic Use in Gliomas

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“Background: Accumulating evidence suggests overexpression of Eph receptors is associated with malignant human gliomas. Inhibiting interactions of Eph receptors with their ephrin ligands may improve clinical outcomes in glioma patients. The present study investigated the potential of cannabinoids to bind Eph receptors and block Eph/ephrin interactions.

Methods: Twelve major cannabinoids were computationally docked with ligand binding domains from six glioma-associated Eph receptors through Auto Dock Vina to measure their potential binding affinities. The molecular structures and residue interactions of the most favorable poses for each receptor binding domain were further visually examined.

Results: Cannabichromene (CBC) exhibited the most favorable binding with EphA2, EphA3, and EphB4 receptor ligand binding domains while tetrahydrocannabinol (THC) was predicted to bind favorably with EphB2 and EphB3 receptor ligand binding domains. EphA4 showed the best potential binding affinity with cannabidivarin (CBDV). Further analysis revealed that these cannabinoids bind to specific locations on Eph receptors required for Eph/ephrin interactions.

Conclusion: The findings suggest that certain cannabinoids can effectively bind to hydrophobic pockets required for ephrin binding and thereby be used to block subsequent Eph/ephrin interactions.”

https://pubmed.ncbi.nlm.nih.gov/36468933/

Cannabinoids inhibit ethanol-induced activation of liver toxicity in rats through JNK/ERK/MAPK signaling pathways

“Cannabinoids (CBs) are psychoactive compounds, with reported anticancer, anti-inflammatory, and anti-neoplastic properties. The study was aimed at assessing the hepatoprotective effects of CB against ethanol (EtOH)-induced liver toxicity in rats. The animals were divided into seven groups: control (Group I) and Group II were treated with 50% ethanol (EtOH 5 mg/kg). Groups III, IV, and VI were treated with (EtOH + CB 10 mg/kg), (EtOH + CB 20 mg/kg), and (EtOH + CB 30 mg/kg), respectively. Groups V and VII consisted of animals treated with 20 and 30 mg/kg, of CB, respectively. Biochemical analysis revealed that Group IV (EtOH + CB 20 mg/kg) had reduced levels of ALT-alanine transferase, AST-aspartate aminotransferase, ALP-alanine peroxidase, MDA-malondialdehyde and increased levels of GSH-reduced glutathione. Histopathological analysis of liver and kidney tissues showed that EtOH + CB (20 and 30 mg/kg) treated animal groups exhibited normal tissue architecture similar to that of the control group. ELISA revealed that the inflammatory markers were reduced in the animal groups that were treated with EtOH + CB 20 mg/kg, in comparison to the animals treated only with EtOH. The mRNA expression levels of COX-2, CD-14, and MIP-2 showed a remarkable decrease in EtOH + CB treated animal groups to control groups. Western blot analysis revealed that CB downregulated p38/JNK/ERK thereby exhibiting its hepatoprotective property by inhibiting mitogen-activated protein kinase pathways. Thus, our findings suggest that CB is a potential candidate for the treatment of alcohol-induced hepatotoxicity.”

https://pubmed.ncbi.nlm.nih.gov/36453646/

https://onlinelibrary.wiley.com/doi/10.1002/jbt.23260

Antitumor Effects of Delta (9)-Tetrahydrocannabinol and Cannabinol on Cholangiocarcinoma Cells and Xenograft Mouse Models

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“Cholangiocarcinoma (CCA) is a very aggressive tumor. The development of a new therapeutic drug for CCA is required.

This study aims to evaluate the antitumor effect of ∆9-tetrahydrocannabinol (THC), the major psychoactive component of marijuana (Cannabis sativa), and cannabinol (CBN), a minor, low-psychoactive cannabinoid, on CCA cells and xenograft mice.

THC and CBN were isolated, and their identities were confirmed by comparing 1H- and 13C-NMR spectra and mass spectra with a database. Cell proliferation, cell migration, and cell apoptosis assays were performed in HuCCT1 human CCA cells treated with THC or CBN. The phosphorylation of signaling molecules in HuCCT1 cells was detected. To determine the effects of THC and CBN in an animal model, HuCCT1 cells were inoculated subcutaneously into nude mice. After the tumors reached an appropriate size, the mice were treated with THC or CBN for 21 days. Tumor volumes were monitored and calculated. The 1H- and 13C-NMR data of THC and CBN were almost identical to those reported in the literature.

THC and CBN significantly inhibited cell proliferation and migration and induced apoptosis in HuCCT1 cells. The phosphorylation of AKT, GSK-3α/β, and ERK1/2 decreased in HuCCT1 cells treated with THC or CBN. CCA xenograft mice treated with THC showed significantly slower tumor progression and smaller tumor volumes than control mice. THC and CBN induced apoptosis in CCA by inhibiting the AKT and MAPK pathways.

These findings provide a strong rationale for THC and CBN as therapeutic options for CCA.”

https://pubmed.ncbi.nlm.nih.gov/36452140/

“THC and CBN induced apoptosis in CCA by inhibiting the AKT and MAPK pathways, leading to a decrease in cell proliferation in vitro and tumor volume in vivo. In addition, in this animal model, THC appeared to be superior in potency to CBN. These findings provide a strong rationale for THC and CBN as therapeutic options for CCA.”

https://www.hindawi.com/journals/ecam/2022/6477132/

A Systemic Review of Medical Cannabinoids Dosing in Human

“Purpose: This systemic review assesses currently available clinical information on which cannabinoids and what range of doses have been used to achieve positive effects in a diversity of medical context.

Methods: The data were collected according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol guidelines. Inclusion criteria were articles that assessed administration of any cannabinoid to any clinical population, reported in the ClinicalTrials.gov or PubMed databases, that involved a comparison with other treatment or placebo and a result measurement to assess the effectiveness or ineffectiveness of the cannabinoid. Exclusion criteria were review or letter; articles not in the English language; not full-text articles; not a clinical trial, case report, case series, open-label trial, or pilot study; administration in animals, in vitro, or in healthy participants; cannabinoids administered in combination with other cannabinoids (except for cannabidiol [CBD] or tetrahydrocannabinol [THC]) or as whole cannabis extracts; no stated concentration; inhalation or smoke as a route of administration; and no results described. The articles were assessed by the risk of bias.

Finding: In total, 1668 articles were recovered, of which 55 studies met the inclusion criteria for 21 diseases. Positive effects were reported in clinical studies: 52% with THC (range, 0.01-0.5 mg/kg/d [0.62-31 mg/d]), 74% with CBD (range, 1-50 mg/kg/d [62-3100 mg/d]), 64% with THC-CBD (mean, 1:1.3 mg/kg/d [ratio, 1:1]), and 100% with tetrahydrocannabivarin (THCV) (0.2 mg/kg/d).

Implications: THC, CBD, and THCV can regulate activity in several pathologies. New studies of cannabinoids are highly encouraged because each patient is unique and requires a unique cannabinoid medication.”

https://pubmed.ncbi.nlm.nih.gov/36411116/

https://www.clinicaltherapeutics.com/article/S0149-2918(22)00349-6/fulltext

Alleviation of opioid withdrawal by cannabis and delta-9-tetrahydrocannabinol: A systematic review of observational and experimental human studies

Drug and Alcohol Dependence

“Background: While six U.S. states have already officially authorized cannabinoids to substitute opioids and treat opioid use disorder, the therapeutic benefits of cannabinoids remain unclear, especially when weighted against their adverse effects.

Methods: We conducted a systematic review of studies examining the association between opioid withdrawal and cannabis use or delta-9-tetrahydrocannabinol (THC) administration. We searched multiple databases from inception to July 30, 2022, and assessed study quality.

Results: Eleven studies were identified, with a total of 5330 participants, of whom 64 % were male. Nine observational studies examined the association between cannabis use and opioid withdrawal. Two randomized, placebo-controlled clinical trials (RCTs) investigated the withdrawal-alleviating effects of dronabinol, a synthetic form of THC. Four observational studies found an association between cannabis use and the alleviation of opioid withdrawal; one reported exacerbation of opioid withdrawal symptoms; and four reported no association. RCTs reported that THC alleviated opioid withdrawal, albeit with dose-dependent increases in measures of abuse liability, dysphoria, and tachycardia. There was high heterogeneity in measurements of opioid withdrawal and the type and dose of opioid at baseline.

Conclusions: Although there is preliminary evidence that cannabis and its main psychoactive constituent, THC, may alleviate opioid withdrawal, these effects are likely to have a narrow therapeutic window. Further, the potential of cannabinoids to alleviate opioid withdrawal is determined by complex interactions between patient characteristics and pharmacological factors. Collectively, these findings have clinical, methodological, and mechanistic implications for treating opioid withdrawal during cannabinoid use, and for efforts to alleviate opioid withdrawal using non-opioid therapeutics.”

https://pubmed.ncbi.nlm.nih.gov/36434879/

https://www.sciencedirect.com/science/article/abs/pii/S0376871622004392?via%3Dihub

Pharmacognosy and Effects of Cannabinoids in the Vascular System

Go to ACS Pharmacology & Translational Science

“Understanding the pharmacodynamics of cannabinoids is an essential subject due to the recent increasing global acceptance of cannabis and its derivation for recreational and therapeutic purposes. Elucidating the interaction between cannabinoids and the vascular system is critical to exploring cannabinoids as a prospective therapeutic agent for treating vascular-associated clinical conditions.

This review aims to examine the effect of cannabinoids on the vascular system and further discuss the fundamental pharmacological properties and mechanisms of action of cannabinoids in the vascular system. Data from literature revealed a substantial interaction between endocannabinoids, phytocannabinoids, and synthetic cannabinoids within the vasculature of both humans and animal models. However, the mechanisms and the ensuing functional response is blood vessels and species-dependent. The current understanding of classical cannabinoid receptor subtypes and the recently discovered atypical cannabinoid receptors and the development of new synthetic analogs have further enhanced the pharmacological characterization of the vascular cannabinoid receptors.

Compelling evidence also suggest that cannabinoids represent a formidable therapeutic candidate for vascular-associated conditions.

Nonetheless, explanations of the mechanisms underlining these processes are complex and paradoxical based on the heterogeneity of receptors and signaling pathways. Further insight from studies that uncover the mechanisms underlining the therapeutic effect of cannabinoids in the treatment of vascular-associated conditions is required to determine whether the known benefits of cannabinoids thus currently outweigh the known/unknown risks.”

https://pubmed.ncbi.nlm.nih.gov/36407955/

https://pubs.acs.org/doi/10.1021/acsptsci.2c00141

The value of real world evidence: The case of medical cannabis

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“Randomised controlled trials (RCTs) have long been considered the gold standard of medical evidence. In relation to cannabis based medicinal products (CBMPs), this focus on RCTs has led to very restrictive guidelines in the UK, which are limiting patient access. There is general agreement that RCT evidence in relation to CBPMs is insufficient at present. As well as commercial reasons, a major problem is that RCTs do not lend themselves well to the study of whole plant medicines.

One solution to this challenge is the use of real world evidence (RWE) with patient reported outcomes (PROs) to widen the evidence base. Such data increasingly highlights the positive impact medical cannabis can have on patients’ lives.

This paper outlines the value of this approach which involves the study of interventions and patients longitudinally under medical care. In relation to CBMPs, RWE has a broad range of advantages. These include the study of larger groups of patients, the use of a broader range and ratio of components of CBMPs, and the inclusion of more and rarer medical conditions. Importantly, and in contrast to RCTs, patients with significant comorbidities-and from a wider demographic profile-can also be studied, so providing higher ecological validity and increasing patient numbers, whilst offering significant cost savings. We conclude by outlining 12 key recommendations of the value of RWE in relation to medical cannabis.

We hope that this paper will help policymakers and prescribers understand the importance of RWE in relation to medical cannabis and help them develop approaches to overcome the current situation which is detrimental to patients.”

https://pubmed.ncbi.nlm.nih.gov/36405915/

“Cannabis has an excellent safety profile and is a historically established medicine. We hope that this paper will aid policymakers and prescribers understand the value of RWE in relation to medical cannabis and help them develop approaches to overcome the current situation, which is ultimately harmful to patients, restricting access to medicines that could bring relief.”

https://www.frontiersin.org/articles/10.3389/fpsyt.2022.1027159/full

Examining the role of cannabinoids on osteoporosis: a review

SpringerLink

“Purpose: Prior research studies have shown that the endocannabinoid system, influenced by CBD and THC, plays a role in bone remodeling. As both the research on cannabis and use of cannabis continue to grow, novel medicinal uses of both its constituents as well as the whole plant are being discovered. This review examines the role of cannabinoids on osteoporosis, more specifically, the endocannabinoid system and its role in bone remodeling and the involvement of the cannabinoid receptors 1 and 2 in bone health, as well as the effects of Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), and synthetic cannabinoids on bone.

Methods: A comprehensive literature search of online databases including PUBMED was utilized.

Results: A total of 29 studies investigating the effects of cannabis and/or its constituents as well as the activation or inactivation of cannabinoid receptors 1 and 2 were included and discussed.

Conclusion: While many of the mechanisms are still not yet fully understood, both preclinical and clinical studies show that the effects of cannabis mediated through the endocannabinoid system may prove to be an effective treatment option for individuals with osteoporosis.”

https://pubmed.ncbi.nlm.nih.gov/36401719/

https://link.springer.com/article/10.1007/s11657-022-01190-x