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[Transepithelial transport in vivo and in vitro and anti-inflammatory activity of cannabidiol]

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“This study used Caco-2 cells and normal rats to investigate the in vitro absorption characteristics and in vivo pharmacokinetic characteristics of cannabidiol(CBD) and explore the anti-inflammatory mechanism of CBD. The safe concentration range of CBD was determined by the CCK-8 assay, and then the effects of time, concentration, temperature, endocytosis inhibitors, and transport inhibitors on the transepithelial absorption and transport of CBD were assessed. The blood drug concentration was measured at different time points after oral administration in rats for pharmacokinetic profiling, and the pharmacokinetic parameters were calculated. The Caco-2 cell model of inflammation injury was established with lipopolysaccharide(LPS). The effects of CBD on lactate dehydrogenase(LDH) activity, transendothelial electrical resistance(TEER), and levels of inflammatory cytokines of the modeled cells were exami-ned, on the basis of which the anti-inflammatory mechanism of CBD was deciphered.

The results showed that within the concentration range tested in this study, the CBD uptake by Caco-2 cells reached saturation at the time point of 2 h. Moreover, the CBD uptake was positively correlated with concentration and temperature and CBD could be endocytosed into the cells. CBD could penetrate Caco-2 cells through active transport pathways involving multidrug resistance-associate protein 2(MRP2) and breast cancer resistance protein(BCRP), while the addition of P-gp inhibitors had no effect on CBD transport. Rats exhibited rapid absorption of CBD, with the peak time(t_(max)) of(1.00±0.11) h, and fast elimination of CBD, with a half-life(t_(1/2)) of only(1.86±0.16) h. In addition, CBD significantly ameliorated the increased LDH activity and decreased TEER that were caused by inflammatory response. It maintained the intestinal barrier by down-regulating the expression of pro-inflammatory cytokines interleukin-8(IL-8), interleukin-1 beta(IL-1β) and tumor necrosis factor-α(TNF-α), thus exerting anti-inflammatory effects.”

https://pubmed.ncbi.nlm.nih.gov/39307812/

Unleashing the therapeutic role of cannabidiol in dentistry

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“Cannabidiol (CBD) found in Cannabis sativa is a non-psychoactive compound which is capable of binding to CB1 and CB2 receptors. CBD has recently gained interest in dentistry although it has not been explored sufficiently yet.

The therapeutic effects of CBD include anti-inflammatory, analgesic, antioxidant, biological and osteoinductive properties. The aim of this review is to highlight these effects with respect to various oral conditions and shed light on the current limitations and prospects for the use of CBD in maintaining oral health.”

https://pubmed.ncbi.nlm.nih.gov/39296277/

“CBD are potent non-psychoactive drug which when used in appropriate proportions under proper guidelines hold the potential to drastically change the current state of dental sciences. However, future researches are imperative focusing on the nature, mechanism, formulations as well as modes of administration to understand this drug thoroughly. Nonetheless, due to its properties such as anti-inflammation, antioxidation, biological nature, analgesia as well as osteoinduction; it is a drug with promising future in dentistry.”

https://www.sciencedirect.com/science/article/pii/S2212426824001258?via%3Dihub

Cannabidiol for the Treatment of Cervical Spondyloarthritis-Related Pain: A Case Report

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“Spondyloarthritis (SA) is a chronic inflammatory disease that predominantly affects the spinal column. SA-related pain can be intense, persistent, and disabling. Studies with cannabis have been conducted involving patients with refractory epilepsy, multiple sclerosis, Parkinson’s disease, sleep disorders, and chronic pain.

Cannabidiol is the major non-psychotropic component of cannabis, has anti-inflammatory and analgesic properties, and exerts anxiolytic and mood-stabilizing effects. This paper reports a case of a 72-year-old male with SA, with mild stenoses of the spinal canal at C4-C5 and C5-C6 and stenoses of the left neural foramina at C3-C4, C4-C5, C5-C6, and C6-C7.

The use of cannabidiol in our patient achieved satisfactory results in the control of pain related to cervical spondyloarthritis.”

https://pubmed.ncbi.nlm.nih.gov/39295690/

https://www.cureus.com/articles/278440-cannabidiol-for-the-treatment-of-cervical-spondyloarthritis-related-pain-a-case-report#!/

Therapeutic potential of cannabis for surgical wound healing in rats

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“This study was conducted to evaluate the wound-healing activities of a Cannabis sativa L. plant extract and cannabidiol on incision wounds.

An incision was created and sutured in rats under anaesthesia. Routine wound care procedures were applied for 10 days, followed by histological wound examinations. The cellular bioactivities of the hemp extract and CBD were assessed for MCP-1, EGF, BFGF, IL-8, and COL-1 using ELISA on the rat skin wound healing activity. A one-way ANOVA was used for the data analysis.

The EGF values in the plasma were similar in the povidone-iodine, hemp seed oil, and hemp essential oil groups (P > 0.05). However, the EGF levels were lower in the CBD group compared to the other groups (P < 0.001, P < 0.005). The MCP-1 values in the hemp seed oil, hemp essential oil, and CBD were similar (P > 0.05), whereas povidone iodine exhibited lower MCP-1 levels compared to the other groups (P < 0.001, P < 0.005). It was determined that the plasma BFGF, IL-8, and COL 1 values of the groups were similar (P > 0.05).

To our knowledge, this study is the first to evaluate the effects of CBD, seed oil, and hemp leaf extract on incision wound healing. It demonstrates that hemp extract holds greater potential benefits for wound healing compared to CBD.”

https://pubmed.ncbi.nlm.nih.gov/39296630/

http://vetmed.agriculturejournals.cz/artkey/vet-202408-0002_therapeutic-potential-of-cannabis-for-surgical-wound-healing-in-rats.php

Bidirectional Effect of Long-Term Δ9-Tetrahydrocannabinol Treatment on mTOR Activity and Metabolome

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“Brain aging is associated with cognitive decline, reduced synaptic plasticity, and altered metabolism. The activity of mechanistic target of rapamycin (mTOR) has a major impact on aging by regulating cellular metabolism. Although reduced mTOR signaling has a general antiaging effect, it can negatively affect the aging brain by reducing synaptogenesis and thus cognitive functions. Increased mTOR activity facilitates aging and is responsible for the amnestic effect of the cannabinoid receptor 1 agonist Δ9-tetrahydrocannabinol (THC) in higher doses.

Long-term low-dose Δ9-THC had an antiaging effect on the brain by restoring cognitive abilities and synapse densities in old mice.

Whether changes in mTOR signaling and metabolome are associated with its positive effects on the aging brain is an open question. Here, we show that Δ9-THC treatment has a tissue-dependent and dual effect on mTOR signaling and the metabolome.

In the brain, Δ9-THC treatment induced a transient increase in mTOR activity and in the levels of amino acids and metabolites involved in energy production, followed by an increased synthesis of synaptic proteins. Unexpectedly, we found a similar reduction in the mTOR activity in adipose tissue and in the level of amino acids and carbohydrate metabolites in blood plasma as in animals on a low-calorie diet.

Thus, long-term Δ9-THC treatment first increases the level of energy and synaptic protein production in the brain, followed by a reduction in mTOR activity and metabolic processes in the periphery.

Our study suggests that a dual effect on mTOR activity and the metabolome could be the basis for an effective antiaging and pro-cognitive medication.”

https://pubmed.ncbi.nlm.nih.gov/39296258/

https://pubs.acs.org/doi/10.1021/acsptsci.4c00002

Cannabidiol modulation of immune cell function: in vitro insights and therapeutic implications for atopic dermatitis

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“Introduction: Cannabidiol (CBD) exhibits neuroprotective, anti-inflammatory, and immunomodulatory properties, making it a promising candidate for addressing inflammatory skin disorders like atopic dermatitis.

Aim: This study aimed to (i) investigate CBD’s impact on lymphocyte proliferation and lymphocyte viability; (ii) assess in vitro cytotoxicity U937 cells (a human promonocytic cell line) of CBD/cytotoxicity of CBD on U937 cells; (iii) provide insights into CBD immunomodulatory potential, and (iv) evaluate suitability of CBD for treating inflammatory skin conditions.

Material and methods: To this aim PBMCs from healthy donors were cultured with mitogen and two different CBD doses (0.1 and 1 mg/ml), assessing B and T cell proliferation through flow cytometry. CBD inhibited mitogen-induced lymphocyte proliferation, reducing the percentage of proliferating T and B cells. Notably, both CBD doses did not exhibit cytotoxicity on lymphocytes as revealed by viability assessment. We also analysed the effect of CBD on U937 cells using an optical microscopy approach. Interestingly, the higher dose of CBD exerted a cytotoxic effect on U937 cells, while the lower dose was well tolerated.

Results: We analysed the effect of an adjuvant treatment for atopic dermatitis with a CBD-containing cleansing cream in reducing itch. Notably, the treatment with the CBD-containing cleansing cream significantly reduced itch in patients suffering from atopic dermatitis.

Conclusions: These findings affirm CBD’s immunomodulatory characteristics, emphasizing its potential therapeutic application in inflammatory skin disorders.”

https://pubmed.ncbi.nlm.nih.gov/39290893/

https://www.termedia.pl/Cannabidiol-modulation-of-immune-cell-function-in-vitro-insights-and-therapeutic-implications-for-atopic-dermatitis,7,54606,0,1.html

Measuring the Impact of Medical Cannabis Law Adoption on Employer-Sponsored Health Insurance Costs: A Difference-in-Difference Analysis, 2003-2022

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“Introduction: Recent studies suggest that medical cannabis laws may contribute to a relative reduction in health insurance costs within the individual health insurance markets at the state level. We investigated the effects of adopting a medical cannabis law on the cost of employer-sponsored health insurance in the United States.

Methods: We analyzed state-level data from the Medical Expenditure Panel Survey-Insurance Component (MEPS-IC) Private Sector spanning from 2003 to 2022. The outcomes included log-transformed average total premium costs per employee for single, employee-plus-one, and family coverage plans. We utilized the Sun and Abraham (J Econometr 225(2):175-199, 2021) difference-in-difference (DiD) method, looking at the overall DiD and event-study DiD. Models were adjusted for various state-level demographics and dichotomous policy variables, including whether a state later adopted recreational cannabis, as well as time and unit fixed effects and population weights.

Results: For states that adopted a medical cannabis law, there was a significant decrease in the log average total premium per employee for single (-0.034, standard error [SE] 0.009 (-$238)) and employee-plus-one (-0.025, SE 0.009 (-$348)) coverage plans per year considering the first 10 years of policy change compared with states without such laws. Looking at the last 5 years of policy change, we saw increases in effect size and statistical significance. In-time placebo testing suggested model robustness. Under a hypothetical scenario where all 50 states adopted medical cannabis in 2022, we estimated that employers and employees could collectively save billions on healthcare coverage, potentially reducing healthcare expenditure’s contribution to GDP by 0.65% in 2022.

Conclusion: Adoption of a medical cannabis law may contribute to decreases in healthcare costs. This phenomenon is likely a secondary effect and suggests positive externalities outside of medical cannabis patients.”

https://pubmed.ncbi.nlm.nih.gov/39287774/

Phytochemistry and pharmacological activities of Cannabis sativa fruit (Cannabis Fructus)

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“Cannabis sativa fruit (Cannabis Fructus) refers to the dried and ripe fruit of Cannabis sativa L. It is widely distributed in the northeast, North, and South China. It has medicinal, ecological, and economic values.

This study aimed to review the chemical constituents and pharmacological activities of Cannabis Fructus, providing a reference for further exploration of Cannabis Fructus. Comprehensive information on Cannabis Fructus was collected via electronic searches (e.g., Google Scholar, PubMed, Sci Finder, and Web of Science) and from books on phytochemistry.

Cannabis Fructus contains various compounds such as phenylpropanoids, flavonoids, steroids and terpenoids, cannabinoids, fatty acids, alkaloids, phenanthrenes, proteins, and polysaccharides. Its active ingredients exhibit anti-inflammatory, anti-oxidant, anti-bacterial, anti-aging, anti-fatigue, anti-tumor, anti-constipation, neuroprotective, lipoid-regulating, hepatoprotective, and immunomodulatory properties.”

https://pubmed.ncbi.nlm.nih.gov/39278423/

“Highlights

  • •Cannabis Fructus is the dried and ripe fruit of Cannabis sativa L, it has a long history of medicinal and edible use.
  • •Compounds in Cannabis Fructus include phenylpropanoids, flavonoids, steroids and terpenoids, cannabinoids, fatty acids, alkaloids, phenanthrenes, proteins and polysaccharides.
  • •Cannabis Fructus and its active ingredients have anti-inflammatory, antioxidant, antibacterial, anti-aging, anti-fatigue, anti-tumor, anti-constipation, neuroprotection, lipoid-regulating and liver-protecting activities and immunomodulatory activities.
  • •Cannabis Fructus can be used as the main raw material in the development of food, medicine, cosmetics, health products industry.”

https://www.sciencedirect.com/science/article/abs/pii/S0367326X24003976?via%3Dihub

Cannabinol modulates the endocannabinoid system and shows TRPV1-mediated anti-inflammatory properties in human keratinocytes

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“Cannabinol (CBN) is a secondary metabolite of cannabis whose beneficial activity on inflammatory diseases of human skin has attracted increasing attention. Here, we sought to investigate the possible modulation by CBN of the major elements of the endocannabinoid system (ECS), in both normal and lipopolysaccharide-inflamed human keratinocytes (HaCaT cells).

CBN was found to increase the expression of cannabinoid receptor 1 (CB1) at gene level and that of vanilloid receptor 1 (TRPV1) at protein level, as well as their functional activity. In addition, CBN modulated the metabolism of anandamide (AEA) and 2-arachidonoylglicerol (2-AG), by increasing the activities of N-acyl phosphatidylethanolamines-specific phospholipase D (NAPE-PLD) and fatty acid amide hydrolase (FAAH)-the biosynthetic and degradative enzyme of AEA-and that of monoacylglycerol lipase (MAGL), the hydrolytic enzyme of 2-AG.

CBN also affected keratinocyte inflammation by reducing the release of pro-inflammatory interleukin (IL)-8, IL-12, and IL-31 and increasing the release of anti-inflammatory IL-10. Of note, the release of IL-31 was mediated by TRPV1. Finally, the mitogen-activated protein kinases (MAPK) signaling pathway was investigated in inflamed keratinocytes, demonstrating a specific modulation of glycogen synthase kinase 3β (GSK3β) upon treatment with CBN, in the presence or not of distinct ECS-directed drugs.

Overall, these results demonstrate that CBN modulates distinct ECS elements and exerts anti-inflammatory effects-remarkably via TRPV1-in human keratinocytes, thus holding potential for both therapeutic and cosmetic purposes.”

https://pubmed.ncbi.nlm.nih.gov/39275884/

“Taken together, our data suggest that CBN may hold true therapeutic potential to treat different human skin diseases. Such a biological activity of CBN occurs through engagement of selected elements of the endocannabinoid system—in particular TRPV1—a finding that paves the way to the development of distinct formulations of cannabis extracts for selected therapeutic applications.”

https://iubmb.onlinelibrary.wiley.com/doi/10.1002/biof.2122

Design, Synthesis, and Characterization of Novel Cannabidiol-Based Derivatives with Potent Antioxidant Activities

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“In recent years, extensive research has focused on cannabidiol (CBD), a well-studied non-psychoactive component of the plant-derived cannabinoids. CBD has shown significant therapeutic potential for treating various diseases and disorders, including antioxidants and anti-inflammatory effects. Due to the promising therapeutic effect of CBD in a wide variety of diseases, synthetic derivatization of this compound has attracted the attention of drug discovery in both industry and academia.

In the current research, we focused on the derivatization of CBD by introducing Schiff base moieties, particularly (thio)-semicarbazide and aminoguanidine motifs, at the 3-position of the olivetolic ring. We have designed, synthesized, and characterized new derivatives based on CBD’s framework, specifically aminoguanylhydrazone- and (thio)-semicarbazones-CBD-aldehyde compounds. Their antioxidant potential was assessed using FRAP and DPPH assays, alongside an evaluation of their effect on LDL oxidation induced by Cu2+ and AAPH. Our findings suggest that incorporating the thiosemicarbazide motif into the CBD framework produces a potent antioxidant, warranting further investigation.”

https://pubmed.ncbi.nlm.nih.gov/39273525/

https://www.mdpi.com/1422-0067/25/17/9579