Evaluating the Metabolomic Profile and Anti-Pathogenic Properties of Cannabis Species

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“The Cannabis species is one of the potent ancient medicinal plants acclaimed for its medicinal properties and recreational purposes. The plant parts are used and exploited all over the world for several agricultural and industrial applications. For many years Cannabis spp. has proven to present a highly diverse metabolomic profile with a pool of bioactive metabolites used for numerous pharmacological purposes ranging from anti-inflammatory to antimicrobial. Cannabis sativa has since been an extensive subject of investigation, monopolizing the research. Hence, there are fewer studies with a comprehensive understanding of the composition of bioactive metabolites grown in different environmental conditions, especially C. indica and a few other Cannabis strains. These pharmacological properties are mostly attributed to a few phytocannabinoids and some phytochemicals such as terpenoids or essential oils which have been tested for antimicrobial properties. Many other discovered compounds are yet to be tested for antimicrobial properties. These phytochemicals have a series of useful properties including anti-insecticidal, anti-acaricidal, anti-nematicidal, anti-bacterial, anti-fungal, and anti-viral properties. Research studies have reported excellent antibacterial activity against Gram-positive and Gram-negative multidrug-resistant bacteria as well as methicillin-resistant Staphylococcus aureus (MRSA). Although there has been an extensive investigation on the antimicrobial properties of Cannabis, the antimicrobial properties of Cannabis on phytopathogens and aquatic animal pathogens, mostly those affecting fish, remain under-researched. Therefore, the current review intends to investigate the existing body of research on metabolomic profile and anti-microbial properties whilst trying to expand the scope of the properties of the Cannabis plant to benefit the health of other animal species and plant crops, particularly in agriculture.”

https://pubmed.ncbi.nlm.nih.gov/38786730/

“Cannabis extracts and their phytochemicals have so far been demonstrated to be a solution.”

https://www.mdpi.com/2218-1989/14/5/253

Cannflavin A inhibits TLR4-induced chemokine and cytokine expression in human macrophages

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“Cannflavin A (CFL-A), a flavonoid present in the hemp plant Cannabis sativa L. (C. sativa), has anti-inflammatory and neuroprotective capacity.

Research continues to elucidate the anti-inflammatory effects of components of C. sativa, with evidence that plant-derived cannabinoids and terpenes can mediate anti-inflammatory activity by targeting toll-like receptor (TLR) signalling, the sensors of pathogen-associated molecules.

This study set out to determine if TLR-mediated inflammatory signalling is a CFL-A target using the endotoxin lipopolysaccharide (LPS) to induce TLR4 signalling in human THP-1-derived macrophages. TLR4 activation promoted the production of the chemokine CXCL10 and cytokines IL-1β and TNFα. Treatment with CFL-A dose-dependently attenuated TLR4-induced CXCL10 and IL-1β secretion, with our findings also indicating that the inhibitory effects of CFL-A on chemokine/cytokine secretion are in line with an NF-κB inhibitor.

This study highlights TLR4 signalling as a cannflavin target in macrophages.”

https://pubmed.ncbi.nlm.nih.gov/38780010/

“This study highlights TLR4-induced inflammatory signalling as a cannflavin target. TLR4 is a key player in controlling innate immune responses to infection, and targeted TLR4 immunotherapies are under investigation for chronic inflammatory disorders. This study indicates that CFL-A warrants further study to decipher its anti-inflammatory potential in terms of regulating innate immune inflammatory signalling. Our findings also suggest that the therapeutic value of components of the hemp plant C. sativa should be broadened to include cannflavins.”

https://www.tandfonline.com/doi/full/10.1080/14786419.2024.2358382

The Potential of Cannabichromene (CBC) as a Therapeutic Agent

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“There is a growing interest in the use of medicinal plants to treat a variety of diseases, and one of the most commonly used medicinal plants globally is Cannabis sativa 

The two most abundant cannabinoids (Δ9-tetrahydrocannabinol and cannabidiol) have been governmentally approved to treat selected medical conditions; however, the plant produces over 100 cannabinoids, including cannabichromene (CBC). While the cannabinoids share a common precursor molecule, cannabigerol, they are structurally and pharmacologically unique. These differences may engender differing therapeutic potentials.

In this review, we will examine what is currently known about CBC with regards to pharmacodynamics, pharmacokinetics, and receptor profile. We will also discuss the therapeutic areas that have been examined for this cannabinoid, notably antinociceptive, antibacterial, and anti-seizure activities. Finally, we will discuss areas where new research is needed and potential novel medicinal applications for CBC. 

Significance Statement Cannabichromene (CBC) has been suggested to have disparate therapeutic benefits such as anti-inflammatory, anticonvulsant, antibacterial, and antinociceptive effects. Most of the focus on the medical benefits of cannabinoids has been focused on THC and CBD. The preliminary studies on CBC indicate that this phytocannabinoid may have unique therapeutic potential that warrants further investigation. Following easier access to hemp, CBC products are commercially available over-the-counter and are being widely utilized with little or no evidence of their safety or efficacy.”

https://pubmed.ncbi.nlm.nih.gov/38777605/

https://jpet.aspetjournals.org/content/early/2024/05/22/jpet.124.002166

[Cannabinoid Drugs in the Treatment of Psychiatric Disorders – Data from the German Federal Institute for Drugs and Medical Devices]

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“Background: Since 2017 physicians in Germany can prescribe cannabis based medicines or medical cannabis with subsequent funding by the statutory health insurance system.

Methods: Physicians prescribing cannabinoid drugs were legally required to take part in a survey conducted by the Federal Institute for Drugs and Medical Devices. This study analyses data from 16.809 case reports that were collected from 30.3.2017 to 31.12.2021.

Results: There were 5582 cases documenting the use of cannabinoid drugs in psychiatric disorders. More than half of the prescriptions were Dronabinol. 80% of the treatments concerned somatoform disorders. Most of the treatments for other psychiatric disorders also targeted pain. Doctors reported a positive effect on symptoms in at least 75% of the cases.

Discussion: Most patients with psychiatric disorders received cannabinoid drugs for pain. The evidence from randomized controlled clinical trials for the use of cannabinoid drugs in psychiatric indications is weak.”

https://pubmed.ncbi.nlm.nih.gov/38749455/

https://www.thieme-connect.de/products/ejournals/abstract/10.1055/a-2296-1358

The Use of Cannabidiol in Treating Psychiatric Disorders: A Systematic Review

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“Cannabidiol (CBD) has been used as a pharmacological treatment for psychiatric disorders in many studies, but few of good quality at the moment. Our objective was to assess the effect of CBD in mono/add-on therapy on symptom severity in psychiatric disorders. We performed a systematic review of clinical trials and randomized controlled trials that used CBD as treatment for psychiatric disorders. PRISMA criteria have been used for methodological purposes. Two assessors individually examined the results based on title and abstract, and decided which papers warranted full read. We included studies in English that measured disease severity as primary outcome. Out of 226 studies returned from the search, 9 warranted full read. There were 4 studies using CBD in schizophrenia, 3 studies of substance use disorder and 2 studies of social anxiety. CBD has a good safety profile even in higher doses, but results are inconclusive regarding improvements in disease severity.”

https://pubmed.ncbi.nlm.nih.gov/38765233/

https://psychiatry-psychopharmacology.com/en/the-use-of-cannabidiol-in-treating-psychiatric-disorders-a-systematic-review-133107

Perioperative Cannabinoids Significantly Reduce Postoperative Opioid Requirements in Patients Undergoing Coronary Artery Bypass Graft Surgery

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“Background Opioids, commonly used to control pain associated with surgery, are known to prolong the duration of mechanical ventilation and length of hospital stay. A wide range of adjunctive strategies are currently utilized to reduce postoperative pain, such as local and regional nerve blocks, nerve cryoablation, and adjunctive medications. We hypothesized that dronabinol (a synthetic cannabinoid) in conjunction with standard opioid pain management will reduce opioid requirements to manage postoperative pain. Methods Sixty-eight patients who underwent isolated first-time coronary artery bypass graft surgery were randomized to either the control group, who received only standard opioid-based analgesia, or the dronabinol group, who received dronabinol (a synthetic cannabinoid) in addition to standard opioid-based analgesia. Dronabinol was given in the preoperative unit, before extubation in the ICU, and after extubation on the first postoperative day. Preoperative, intraoperative, and postoperative parameters were compared under an IRB-approved protocol. The primary endpoints were the postoperative opioid requirement, duration of mechanical ventilation, and ICU length of stay, and the secondary endpoints were the duration of inotropic support needed, left ventricular ejection fraction (LVEF), and the change in LVEF. This study was undertaken at Northwest Medical Center, Tucson, AZ, USA. Results Sixty-eight patients were randomized to either the control group (n = 37) or the dronabinol group (n = 31). Groups were similar in terms of demographic features and comorbidities. The total postoperative opioid requirement was significantly lower in the dronabinol group [39.62 vs 23.68 morphine milligram equivalents (MMEs), p = 0.0037], representing a 40% reduction. Duration of mechanical ventilation (7.03 vs 6.03h, p = 0.5004), ICU length of stay (71.43 vs 63.77h, p = 0.4227), and inotropic support requirement (0.6757 vs 0.6129 days, p = 0.7333) were similar in the control and the dronabinol groups. However, there was a trend towards lower durations in each endpoint in the dronabinol group. Interestingly, a significantly better preoperative to postoperative LVEF change was observed in the dronabinol group (3.51% vs 6.45%, p = 0.0451). Conclusions Our study found a 40% reduction in opioid use and a significantly greater improvement in LVEF in patients treated with adjunctive dronabinol. Mechanical ventilation duration, ICU length of stay, and inotropic support requirement tended to be lower in the dronabinol group, though did not reach statistical significance. The results of this study, although limited by sample size, are very encouraging and validate our ongoing investigation.”

https://pubmed.ncbi.nlm.nih.gov/38765405/

https://www.cureus.com/articles/243644-perioperative-cannabinoids-significantly-reduce-postoperative-opioid-requirements-in-patients-undergoing-coronary-artery-bypass-graft-surgery#!/

Cannabidiol prevents LPS-induced inflammation by inhibiting the NLRP3 inflammasome and iNOS activity in BV2 microglia cells via CB2 receptors and PPARγ

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“Neuroinflammation stands as a critical player in the pathogenesis of diverse neurological disorders, with microglial cells playing a central role in orchestrating the inflammatory landscape within the central nervous system.

Cannabidiol (CBD) has gained attention for its potential to elicit anti-inflammatory responses in microglia, offering promising perspectives for conditions associated with neuroinflammation.

Here we investigated whether the NLRP3 inflammasome and inducible nitric oxide synthase (iNOS) are involved in the protective effects of CBD, and if their modulation is dependent on cannabinoid receptor 2 (CB2) and PPARγ signalling pathways.

We found that treatment with CBD attenuated pro-inflammatory markers in lipopolysaccharide (LPS)-challenged BV2 microglia in a CB2- and PPARγ-dependent manner. At a molecular level, CBD inhibited the LPS-induced pro-inflammatory responses by suppressing iNOS and NLRP3/Caspase-1-dependent signalling cascades, resulting in reduced nitric oxide (NO), interleukin-1β (IL-1β), and tumour necrosis factor-alpha (TNF-α) concentrations.

Notably, the protective effects of CBD on NLRP3 expression, Caspase-1 activity, and IL-1β concentration were partially hindered by the antagonism of both CB2 receptors and PPARγ, while iNOS expression and NO secretion were dependent exclusively on PPARγ activation, with no CB2 involvement. Interestingly, CBD exhibited a protective effect against TNF-α increase, regardless of CB2 or PPARγ activation.

Altogether, these findings indicate that CB2 receptors and PPARγ mediate the anti-inflammatory effects of CBD on the NLRP3 inflammasome complex, iNOS activity and, ultimately, on microglial phenotype. Our results highlight the specific components responsible for the potential therapeutic applications of CBD on neuroinflammatory conditions.”

https://pubmed.ncbi.nlm.nih.gov/38761855/

https://www.sciencedirect.com/science/article/abs/pii/S0197018624000962?via%3Dihub

Structurally Diverse Phenylpropanamides from Cannabis Fructus and Their Potential Neuroprotective Effects

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“This study aimed to investigate the chemical components and potential health benefits of the fruits of Cannabis sativa L.

Fourteen new phenylpropanamides designated as cannabisin I-XIV (114) and 40 known analogs were isolated and characterized via nuclear magnetic resonance spectroscopy, high-resolution electrospray ionization mass spectrometry, and electronic circular dichroism.

In vitro bioassay using H2O2-induced PC12 cell damage models demonstrated that hempseeds extract and compounds 131526303641, and 48 exhibited neuroprotective properties. 3,3′-Demethylgrossamide (30) displayed encouraging protection activity, which was further investigated to relieve the oxidative stress and apoptosis of PC12 cells treated with H2O2.

The isolation and characterization of these neuroprotective phenylpropanamides from the fruits of C. sativa provide insights into its health-promoting properties as a healthy food and herbal medicine for preventing and treating neurodegenerative diseases, especially Alzheimer’s disease.”

https://pubmed.ncbi.nlm.nih.gov/38748649/

https://pubs.acs.org/doi/10.1021/acs.jafc.4c00242

Extraction, purification and in vitro assessment of the antioxidant and anti-inflammatory activity of policosanols from non-psychoactive Cannabis sativa L

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“Policosanols (PCs) are bioactive compounds extracted from different natural waxes.

In this work, the purification, characterization and assessment of the antioxidant and anti-inflammatory activity was carried out on PCs from an innovative source, i.e. a waxy material from supercritical-fluid extraction (SFE) of non-psychoactive Cannabis sativa L. (hemp) inflorescences.

Starting from this material, PCs were obtained by microwave-assisted trans-esterification and hydrolysis, followed by preparative liquid chromatography under normal phase conditions. The purified product was characterized using high-performance liquid chromatography (HPLC) with an evaporative light scattering detector (ELSD). In vitro cell-free and cell-based antioxidant and anti-inflammatory assays were then performed to assess their bioactivity. HPLC-ELSED analysis of the purified mixture from hemp wax revealed C26OH and C28OH as the main compounds. 

In vitro assays indicated an inhibition of intracellular reactive oxygen species (ROS) production, a reduction of nuclear factor kappa B (NF-κB) activation and of the activity of the neutrophil elastase. Immunoblotting assays allowed us to hypothesize the mechanism of action of the compounds of interest, given the higher levels of MAPK-activated protein kinase 2 (MK2) and heme oxygenase-1 (HO-1) protein expression in the PC pretreated HaCaT cells.

In conclusion, even if more research is needed to unveil other molecular mechanisms involved in hemp PC activity, the results of this work suggest that these compounds may have potential for use in oxinflammation processes.”

https://pubmed.ncbi.nlm.nih.gov/38737258/

“A new extraction method for policosanols from hemp wax was developed. This new product may be useful against oxinflammation processes.”

https://www.cell.com/heliyon/fulltext/S2405-8440(24)06322-9?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2405844024063229%3Fshowall%3Dtrue

“Policosanol suppresses tumor progression in a gastric cancer xenograft model”

https://pubmed.ncbi.nlm.nih.gov/36277362/

Hemp Seeds (Cannabis sativa L.) as a Valuable Source of Natural Ingredients for Functional Foods-A Review

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“Hemp (Cannabis sativa L.) has experienced a significant resurgence in popularity, and global interest in diversifying its use in various industries, including the food industry, is growing. Therefore, due to their exceptional nutritional value, hemp seeds have recently gained increasing interest as a valuable ingredient for obtaining high-quality foods and dietary supplements.

Hemp seeds stand out for their remarkable content of quality proteins, including edestin and albumin, two distinct types of proteins that contribute to exceptional nutritional value. Hemp seeds are also rich in healthy lipids with a high content of polyunsaturated fatty acids, such as linoleic acid (omega-6), alpha-linolenic acid (omega-3), and some vitamins (vitamins E, D, and A). Polyphenols and terpenoids, in particular, present in hemp seeds, provide antimicrobial, antioxidant, and anti-inflammatory properties.

This review examines the scientific literature regarding hemp seeds’ physicochemical and nutritional characteristics. The focus is on those characteristics that allow for their use in the food industry, aiming to transform ordinary food products into functional foods, offering additional benefits for the body’s health. Innovating opportunities to develop healthy, nutritionally superior food products are explored by integrating hemp seeds into food processes, promoting a balanced and sustainable diet.”

https://pubmed.ncbi.nlm.nih.gov/38731588/

“Cannabis sativa L. hemp seeds represent a valuable resource for the food industry, offering versatility and nutritional quality.”

https://www.mdpi.com/1420-3049/29/9/2097