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Antimicrobial, Probiotic, and Immunomodulatory Potential of Cannabis sativa Extract and Delivery Systems

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“The compounds present in hemp show multidirectional biological activity. It is related to the presence of secondary metabolites, mainly cannabinoids, terpenes, and flavonoids, and the synergy of their biological activity. The aim of this study was to assess the activity of the Henola Cannabis sativae extract and its combinations with selected carriers (polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer, magnesium aluminometasilicate, and hydroxypropyl-β-cyclodextrin) in terms of antimicrobial, probiotic, and immunobiological effects.

As a result of the conducted research, the antimicrobial activity of the extract was confirmed in relation to the following microorganisms: Clostridium difficile, Listeria monocytogenes, Enterococcus faecalis, Staphylococcus aureus, Staphylococcus pyrogenes, Escherichia coli, Klebsiella pneumoniae, Salmonella typhimurium, Pseudomonas aereuginosa, and Candida albicans (microorganism count was reduced from ~102 CFU mL-1 to <10 CFU mL-1 in most cases). Additionally, for the system with hydroxypropyl-β-cyclodextrin, a significant probiotic potential against bacterial strains was established for strains Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus plantarum, Lactobacillus brevis, Lactobacillus rhamnosus, Lactobacillus reuteri, Pediococcus pentosaceus, Lactococcus lactis, Lactobacillus fermentum, and Streptococcus thermophilus (microorganism count was increased from ~102 to 104-107). In terms of immunomodulatory properties, it was determined that the tested extract and the systems caused changes in IL-6, IL-8, and TNF-α levels.”

https://pubmed.ncbi.nlm.nih.gov/38667045/

“This study investigated the antimicrobial potential of Cannabis sativa extract, Henola variety, and systems with carriers. The extract showed antimicrobial activity against pathogenic microorganisms, suggesting its possible application as support in combating infections. Additionally, the system with hydroxypropyl-β-cyclodextrin may possess prebiotic properties, stimulating the growth of probiotic microorganisms. Furthermore, the investigated systems exhibit immunomodulatory and immunostimulatory effects, with potential therapeutic implications for modulating inflammatory responses. Overall, these findings underscore the multifaceted therapeutic potential of Cannabis sativa extracts. The delivery systems might be used as powder-based food additives, but they might also be subjected to formulation studies for the development of an oral dietary supplement.”

https://www.mdpi.com/2079-6382/13/4/369

Antibiofilm and Immune-Modulatory Activity of Cannabidiol and Cannabigerol in Oral Environments-In Vitro Study

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“Objective: To evaluate the in vitro antimicrobial and antibiofilm properties and the immune modulatory activity of cannabidiol (CBD) and cannabigerol (CBG) on oral bacteria and periodontal ligament fibroblasts (PLF).

Methods: Cytotoxicity was assessed by propidium iodide flow cytometry on fibroblasts derived from the periodontal ligament. The minimum inhibitory concentration (MIC) of CBD and CBG for S. mutans and C. albicans and the metabolic activity of a subgingival 33-species biofilm under CBD and CBG treatments were determined. The Quantification of cytokines was performed using the LEGENDplex kit (BioLegend, Ref 740930, San Diego, CA, USA).

Results: CBD-treated cell viability was greater than 95%, and for CBG, it was higher than 88%. MIC for S. mutans with CBD was 20 µM, and 10 µM for CBG. For C. albicans, no inhibitory effect was observed. Multispecies biofilm metabolic activity was reduced by 50.38% with CBD at 125 µg/mL (p = 0.03) and 39.9% with CBG at 62 µg/mL (p = 0.023). CBD exposure at 500 µg/mL reduced the metabolic activity of the formed biofilm by 15.41%, but CBG did not have an effect. CBG at 10 µM caused considerable production of anti-inflammatory mediators such as TGF-β and IL-4 at 12 h. CBD at 10 µM to 20 µM produced the highest amount of IFN-γ.

Conclusion: Both CBG and CBD inhibit S. mutans; they also moderately lower the metabolic activity of multispecies biofilms that form; however, CBD had an effect on biofilms that had already developed. This, together with the production of anti-inflammatory mediators and the maintenance of the viability of mammalian cells from the oral cavity, make these substances promising for clinical use and should be taken into account for future studies.”

https://pubmed.ncbi.nlm.nih.gov/38667018/

“The role of bacteria, together with the production of anti-inflammatory mediators and the maintenance of the viability of mammalian cells from the oral cavity, make these substances promising for clinical use and should be considered for future in vivo studies. In the near future, it will be useful to study Cannabis derivatives uses on biofilm formation as well as to functionalize different regeneration biomaterials with cannabinoids, which could be a useful approach to improve clinical outcomes after periodontal therapy.”

https://www.mdpi.com/2079-6382/13/4/342

Anti-Inflammatory Properties of Cannabidiol and Beta-Caryophyllene Alone or Combined in an In Vitro Inflammation Model

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“Cannabis contains over 500 different compounds, including cannabinoids, terpenoids, and flavonoids. Cannabidiol (CBD) is a non-psychoactive constituent, whereas beta-caryophyllene (BCP) is one of most the well-known terpenoids of Cannabis sativa.

In recent years, there has been an emerging idea that the beneficial activities of these compounds are greater when they are combined.

The aim of this study was to evaluate the anti-inflammatory effect of CBD and BCP using the in vitro model of lipopolysaccharide (LPS)-stimulated human keratinocytes (HaCaT) cells. The vitality of the cells was quantified using LDH and MTT assays. The levels of the following pro-inflammatory proteins and genes were quantified: IL-1β, COX-2, and phospho-NF-κB p65 (p-p65) through Western blotting (WB) and interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNFα) through quantitative real-time polymerase chain reaction (RT-qPCR).

When present in the incubation medium, CBD and BCP reduced the increased levels of pro-inflammatory proteins (IL-1β, COX-2, and p-NF-kB) induced by LPS. The anti-inflammatory effects of CBD were blocked by a PPARγ antagonist, whereas a CB2 antagonist was able to revert the effects of BCP. Selected concentrations of CBD and BCP were able to revert the increases in the expression of pro-inflammatory genes (IL-1β, IL-6, and TNFα), and these effects were significant when the drugs were used in combination.

Our results suggest that CBD and BCP work in concert to produce a major anti-inflammatory effect with good safety profiles.”

https://pubmed.ncbi.nlm.nih.gov/38675427/

“Our data suggest that the topical use of a combination of CBD and BCP should be efficacious for treating skin inflammation and/or other inflammatory disorders.”

https://www.mdpi.com/1424-8247/17/4/467

Phytocannabinoids: Exploring Pharmacological Profiles and Their Impact on Therapeutical Use

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“Phytocannabinoids, a diverse group of naturally occurring compounds extracted from the Cannabis plant, have attracted interest due to their potential pharmacological effects and medicinal uses.

This comprehensive review presents the intricate pharmacological profiles of phytocannabinoids while exploring the diverse impacts these substances have on biological systems. From the more than one hundred cannabinoids which were identified in the Cannabis plant so far, cannabidiol (CBD) and tetrahydrocannabinol (THC) are two of the most extensively studied phytocannabinoids.

CBD is a non-psychoactive compound, which exhibits potential anti-inflammatory, neuroprotective, and anxiolytic properties, making it a promising candidate for a wide array of medical conditions.

THC, known for its psychoactive effects, possesses analgesic and antiemetic properties, contributing to its therapeutic potential.

In addition to THC and CBD, a wide range of additional phytocannabinoids have shown intriguing pharmacological effects, including cannabichromene (CBC), cannabigerol (CBG), and cannabinol (CBN).

The endocannabinoid system, made up of the enzymes involved in the production and breakdown of endocannabinoids, cannabinoid receptors (CB1 and CB2), and endogenous ligands (endocannabinoids), is essential for preserving homeostasis in several physiological processes. Beyond their effects on the endocannabinoid system, phytocannabinoids are studied for their ability to modify ion channels, neurotransmitter receptors, and anti-oxidative pathways.

The complex interaction between phytocannabinoids and biological systems offers hope for novel treatment approaches and lays the groundwork for further developments in the field of cannabinoid-based medicine. This review summarizes the state of the field, points out information gaps, and emphasizes the need for more studies to fully realize the therapeutic potential of phytocannabinoids.”

https://pubmed.ncbi.nlm.nih.gov/38673788/

“Phytocannabinoids offer diverse therapeutic applications, ranging from pain management to neurological disorders and inflammatory diseases. Their antimicrobial and anti-inflammatory properties make them valuable candidates for combating antibiotic resistance and modulating inflammatory pathways. By leveraging the synergistic effects of combination therapies and targeting multiple disease pathways, phytocannabinoids hold immense potential to revolutionize the future of pharmacotherapy and improve human health outcomes. “

https://www.mdpi.com/1422-0067/25/8/4204

Medicinal cannabis in neurodegenerative disorders: an open label, dose finding, safety and efficacy study

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“Aim: Currently, there exist no curative treatments for neurodegenerative disorders. Recently, there has been a resurgence of interest in the use of medicinal cannabis to improve neurological conditions. 

Methods: A 12-month, open label, dose-finding, safety and efficacy study was conducted including 48 subjects with a variety of neurodegenerative disorders. 

Results: In our participants, we observed a reduction in pain, improved sleep, enhanced well-being and less agitation. 

Conclusion: Our findings suggest that medicinal cannabis might be useful in patients with neurodegenerative disorders in controlling pain, enhancing sleep, reducing difficult behaviors, controlling unusual and complex symptoms when other treatments have failed – this offers medicinal cannabis a role in palliation.”

https://pubmed.ncbi.nlm.nih.gov/38639578/

Investigating the Impact of Cannabis Consumption on Hospital Outcomes in Patients With Primary Spontaneous Pneumothorax: A Nationwide Analysis

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“Introduction Existing data suggest an association between primary spontaneous pneumothorax (PSP) and cannabis consumption, although evidence remains controversial.

Methods This study used the 2016-2019 National Inpatient Sample Database to examine inpatients with PSP, categorizing them as cannabis users and non-users. Multivariate regression analyzed continuous variables, chi-square assessed categorical variables, and logistic regression models were built. Propensity score matching (PSM) mitigated the confounding bias.

Results A total of 399,495 patients with PSP were admitted during the study period (13,415 cannabis users and 386,080 non-cannabis users). Cannabis users were more likely to be younger (p<0.001) and male (p<0.001) with a lower risk of baseline comorbidities than non-users. Cannabis users had a lower risk of sudden cardiac arrest, vasopressor use, the development of acute kidney injury, venous thromboembolism, the requirement for invasive and non-invasive mechanical ventilation, hemodialysis, ventilator-associated pneumonia, and the need for a tracheostomy. Cannabis use was associated with a 3.4 days shorter hospital stay (p<0.001), as confirmed by PSM analysis (2.3 days shorter, p<0.001). Additionally, cannabis users showed a lower risk of in-hospital mortality (p<0.001), a trend maintained in the PSM analysis (p<0.001).

Conclusions Our study revealed correlations suggesting that cannabis users with PSP might experience lower in-hospital mortality and fewer complications than non-cannabis users.”

https://pubmed.ncbi.nlm.nih.gov/38586642/

“Our study makes a significant contribution to understanding the association between cannabis use and PSP outcomes. It reveals correlations suggesting that cannabis users with PSP might experience lower in-hospital mortality and fewer complications compared to non-cannabis users.”

https://www.cureus.com/articles/226735-investigating-the-impact-of-cannabis-consumption-on-hospital-outcomes-in-patients-with-primary-spontaneous-pneumothorax-a-nationwide-analysis#!/

Nutrition, endocannabinoids, and the use of cannabis: An overview for the nutrition clinician

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“The endocannabinoid system (ECs) is composed of multiple signaling compounds and receptors within the central and peripheral nervous system along with various organs, including the gut, liver, and skeletal muscle.

The ECs has been implicated in metabolism, gut motility, and eating behaviors. The ECs is altered in disease states such as obesity. Recent studies have clarified the role of the gut microbiome and nutrition on the ECs. Exogenous cannabinoid (CB) use, either organic or synthetic, stimulates the ECs through CB1 and CB2 receptors. However, the role of CBs is unclear in regard to nutrition optimization or to treat disease states.

This review briefly summarizes the effect of the ECs and exogenous CBs on metabolism and nutrition. With the increased legalization of cannabis, there is a corresponding increased use in the United States. Therefore, nutrition clinicians need to be aware of both the benefits and harm of cannabis use on overall nutrition status, as well as the gaps in knowledge for future research and guideline development.”

https://pubmed.ncbi.nlm.nih.gov/38555505/

https://aspenjournals.onlinelibrary.wiley.com/doi/10.1002/ncp.11148

Cannabinoids for the treatment of autoimmune and inflammatory skin diseases: A systematic review

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“In recent years, the medical use of cannabinoids has attracted growing attention worldwide. In particular, anti-inflammatory properties of cannabinoids led to their emergence as potential therapeutic options for autoimmune and inflammatory disorders.

Recent studies have also shown that cannabinoid receptors are widely expressed and have endogenous ligands in the skin, suggesting that the skin has its own endocannabinoid system. The aim of this review is to discuss the potential therapeutic effects of cannabinoids in autoimmune and inflammatory skin diseases.

Following an overview of cannabinoids and the endocannabinoid system, we describe the cellular and molecular mechanisms of cannabinoids in skin health and disease. We then review the clinical studies of cannabinoids in autoimmune and inflammatory skin diseases including systemic sclerosis (SSc), dermatomyositis (DM), psoriasis (Pso) and atopic dermatitis (AD). A primary literature search was conducted in July 2023, using PubMed and Web of Science. A total of 15 articles were included after excluding reviews, non-human studies and in vitro studies from 389 non-duplicated articles.

Available evidence suggests that cannabinoids may be beneficial for SSc, DM, Pso and AD. However, further studies, ideally randomized controlled trials, are needed to further evaluate the use of cannabinoids in autoimmune and inflammatory skin diseases.”

https://pubmed.ncbi.nlm.nih.gov/38532572/

“The available data support the safety and efficacy of cannabinoids in SSc, DM, Pso and AD, as well as highlight the need for further studies to confirm their therapeutic use. In conclusion, available evidence suggests that cannabinoids have the potential therapeutic benefit with good tolerability in SSc, DM, Pso and AD. “

https://onlinelibrary.wiley.com/doi/10.1111/exd.15064

Observational Analysis of the Influence of Medical Marijuana Use on Quality of Life in Patients

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“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.”

https://pubmed.ncbi.nlm.nih.gov/38500669/

“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.”

https://karger.com/mca/article/7/1/44/895874/Observational-Analysis-of-the-Influence-of-Medical

[Patient-reported outcomes in chronic diseases under treatment with cannabis medicines : Analysis of the results of the Copeia survey]

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“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.”

https://pubmed.ncbi.nlm.nih.gov/38451340/

https://link.springer.com/article/10.1007/s00482-024-00802-4