Therapeutic potentials of cannabidiol: Focus on the Nrf2 signaling pathway

pubmed logo

“Cannabidiol (CBD), a cannabinoid that does not create psychoactive activities, has been identified as having a multitude of therapeutic benefits.

This study delves into the chemical properties, pharmacokinetics, safety and toxicity, pharmacological effects, and most importantly, the association between the therapeutic potential of CBD and the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway.

The relationship between Nrf2 and CBD is closely linked to certain proteins that are associated with cardiovascular dysfunctions, cancers, and neurodegenerative conditions. Specifically, Nrf2 is connected to the initiation and progression of diverse health issues, including nephrotoxicity, bladder-related diseases, oral mucositis, cancers, obesity, myocardial injury and angiogenesis, skin-related inflammations, psychotic disorders, neuropathic pain, Huntington’s disease, Alzheimer’s disease, Parkinson’s disease, neuroinflammation, Amyotrophic Lateral Sclerosis, and Multiple Sclerosis.

The association between CBD and Nrf2 is a zone of great interest in the medical field, as it has the potential to significantly impact the treatment and prevention of wide-ranging health conditions. Additional investigation is necessary to entirely apprehend the mechanisms underlying this crucial interplay and to develop effective therapeutic interventions.”

https://pubmed.ncbi.nlm.nih.gov/39491419/

“CBD plays a protective role in cardiovascular dysfunctions, cancers, and neurodegenerative conditions by targeting the Nrf2 signaling pathway.”

https://www.sciencedirect.com/science/article/pii/S0753332223016037?via%3Dihub

A recent update on the antibacterial effects of distinct bioactive molecules derived from the Cannabis plant

pubmed logo

“The number of human infections with multidrug-resistant (MDR) bacteria is increasing worldwide and constitutes a serious threat to human health. Given the lack of novel antibiotic compounds worsening this dilemma, alternative antibiotic-independent treatment and prevention strategies of infectious diseases applying natural compounds appear highly appreciable.

Given the long-known health-beneficial and disease-alleviating properties of Cannabis, we performed a literature search summarizing current knowledge regarding the antibacterial effects of extracts from different parts of the Cannabis sativa plant and of defined Cannabis-derived molecules and their potential mode of action.

The included studies revealed that various extracts and essential oils of C. sativa as well as major cannabinoids exerted potent activities against a broad spectrum of Gram-positive bacteria and against some Gram-negative bacterial species including MDR strains. Particularly the disruption of the bacterial cytoplasmic membrane by some cannabinoids resulted in potent antibacterial effects against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus. Furthermore, defined cannabinoids inhibited the formation of and eradicated existing bacterial biofilms.

In conclusion, given their antibacterial properties distinct Cannabis-derived molecules expand the repertoire of antibiotics-independent treatment options in the combat of bacterial infectious diseases which should be further addressed in future studies including clinical trials.”

https://pubmed.ncbi.nlm.nih.gov/39470741/

“Collectively, results from the here reviewed studies open future perspectives for cannabis-derived molecules as alternative antibiotic-independent treatment and prevention strategies in the combat of bacterial infectious diseases which should be further addressed in future studies including clinical trials.”

https://akjournals.com/view/journals/1886/aop/article-10.1556-1886.2024.00098/article-10.1556-1886.2024.00098.xml

Harnessing Cannabis sativa Oil for Enhanced Skin Wound Healing: The Role of Reactive Oxygen Species Regulation

pubmed logo

“Cannabis sativa emerges as a noteworthy candidate for its medicinal potential, particularly in wound healing. This review article explores the efficacy of cannabis oil in reducing reactive oxygen species (ROS) during the healing of acute and chronic wounds, comparing it to the standard treatments.

ROS, produced from various internal and external sources, play a crucial role in wound development by causing cell and tissue damage. Understanding the role of ROS on skin wounds is essential, as they act both as signaling molecules and contributors to oxidative damage.

Cannabis oil, recognized for its antioxidant properties, may help mitigate oxidative damage by scavenging ROS and upregulating antioxidative mechanisms, potentially enhancing wound healing.

This review emphasizes ongoing research and the future potential of cannabis oil in dermatological treatments, highlighted through clinical studies and patent updates. Despite its promising benefits, optimizing cannabis oil formulations for therapeutic applications remains a challenge, underscoring the need for further research to realize its medicinal capabilities in wounds.”

https://pubmed.ncbi.nlm.nih.gov/39458608/

“Cannabis oil, especially its primary bioactive constituents, CBD and THC, demonstrates considerable potential in facilitating skin wound healing by modifying oxidative stress via the regulation of reactive oxygen species. CBD’s therapeutic effects in wound healing are largely attributed to its antioxidant, anti-inflammatory, and antimicrobial properties. Increased ROS levels can hinder wound healing by exacerbating inflammation and cellular damage; however, CBD’s antioxidant properties mitigate these effects, fostering a more conducive environment for tissue regeneration. Additionally, the antibacterial and analgesic properties of cannabis contribute to reducing the microbial load and minimizing the complications associated with chronic wounds, thereby enhancing the overall healing efficacy. Integrating cannabis oil into drug delivery systems for wound management represents a promising strategy for treating both acute and chronic wounds.”

https://www.mdpi.com/1999-4923/16/10/1277

Cannabis-Based Phytocannabinoids: Overview, Mechanism of Action, Therapeutic Application, Production, and Affecting Environmental Factors

pubmed logo

“This review provides an overview of cannabis-based phytocannabinoids, focusing on their mechanisms of action, therapeutic applications, and production processes, along with the environmental factors that affect their quality and efficacy.

Phytocannabinoids such as THC (∆9-tetrahydrocannabinol), CBD (cannabidiol), CBG (cannabigerol), CBN (cannabinol), and CBC (cannabichromene) exhibit significant therapeutic potential in treating various physical and mental health conditions, including chronic pain, epilepsy, neurodegenerative diseases, skin disorders, and anxiety.

The cultivation of cannabis plays a crucial role in determining cannabinoid profiles, with indoor cultivation offering more control and consistency than outdoor methods. Environmental factors such as light, water, temperature, humidity, nutrient management, CO2, and the drying method used are key to optimizing cannabinoid content in inflorescences.

This review outlines the need for broader data transfer between the health industry and technological production, especially in terms of what concentration and cannabinoid ratios are effective in treatment. Such data transfer would provide cultivators with information on what environmental parameters should be manipulated to obtain the required final product.”

https://pubmed.ncbi.nlm.nih.gov/39457041/

“Phytocannabinoids, including THC, CBD, CBG, CBN, and CBC, present broad therapeutic potential in a wide range of physical and mental conditions. They have shown efficacy in treating chronic pain, reducing seizure activity, slowing neurodegenerative processes, psoriasis, acne, loss of appetite, sleep disorders, and psychosis. Dose dependence was notable in most cases, and thus, this requires careful management.”

https://www.mdpi.com/1422-0067/25/20/11258

Cannabinoids-Multifunctional Compounds, Applications and Challenges-Mini Review

pubmed logo

“Cannabinoids represent a highly researched group of plant-derived ingredients. The substantial investment of funds from state and commercial sources has facilitated a significant increase in knowledge about these ingredients.

Cannabinoids can be classified into three principal categories: plant-derived phytocannabinoids, synthetic cannabinoids and endogenous cannabinoids, along with the enzymes responsible for their synthesis and degradation. All of these compounds interact biologically with type 1 (CB1) and/or type 2 (CB2) cannabinoid receptors.

A substantial body of evidence from in vitro and in vivo studies has demonstrated that cannabinoids and inhibitors of endocannabinoid degradation possess anti-inflammatory, antioxidant, antitumour and antifibrotic properties with beneficial effects. This review, which spans the period from 1940 to 2024, offers an overview of the potential therapeutic applications of natural and synthetic cannabinoids. The development of these substances is essential for the global market of do-it-yourself drugs to fully exploit the promising therapeutic properties of cannabinoids.”

https://pubmed.ncbi.nlm.nih.gov/39459291/

https://www.mdpi.com/1420-3049/29/20/4923

Cannabidiol exerts antipyretic effects by downmodulating inflammatory mediators in LPS-induced fever

pubmed logo

“Contrasting to tetrahydrocannabinol (THC), cannabidiol (CBD) has virtually no psychoactive effects and thus presents a minor risk for abuse. Furthermore, emerging preclinical and clinical evidence indicates that CBD exerts several beneficial pharmacological effects, including anti-inflammatory and antioxidant properties.

Even though fever is one of the responses associated with systemic inflammation, no previous study assessed the putative impact of CBD on lipopolysaccharide (LPS)-induced fever.

The present study aimed to evaluate whether CBD exerts effects on febrile responses, by modulating the hypothalamic-pituitary-adrenal (HPA) axis, and the inflammatory reflex, in this response. CBD caused no change in euthermic mice, indicating that it does not alter euthermia. Conversely, CBD blunted all the assessed systemic inflammation parameters including fever (a hallmark of infection), plasma pro-inflammatory cytokines and prostaglandin E2 (PGE2) surges, and hypothalamic PGE2 (the proximal mediator of fever) synthesis. Moreover, CBD also reduced LPS-induced increase in plasma corticosterone levels and spleen TNF-α.

These data are consistent with the notion that CBD has antipyretic effects, reducing peripheral febrigenic signaling (plasma pro-inflammatory cytokines levels), and eventually down-modulating hypothalamic PGE2 production, possibly in a corticosterone- and inflammatory reflex-dependent manner.”

https://pubmed.ncbi.nlm.nih.gov/39437961/

“Cannabidiol (CBD) reduces fever by downmodulating inflammatory mediators in mice.”

https://www.sciencedirect.com/science/article/abs/pii/S027858462400246X?via%3Dihub

“Antipyretic refers to a type of drug therapy that is used to reduce fever and enhance patient comfort.” https://www.sciencedirect.com/topics/neuroscience/antipyretic

Effect of cannabis use history on postoperative opioid utilization in lumbar fusion patients: an American retrospective study

pubmed logo

“Study design: A retrospective cohort study.

Purpose: To examine the effect of cannabis use history on postoperative opioid utilization in patients undergoing one- to three-level lumbar fusion for degenerative spine disease.

Overview of literature: Strategies to minimize dosing and chronic opioid use are needed for spine surgery given their widespread prescription for postsurgical pain management.

Methods: In this database study, medical coding was used to identify patients who had undergone one- to three-level lumbar fusions between 2012 and 2021. Propensity score matching was used to create two equal cohorts with respect to cannabis use history. Opioid utilization rates (morphine milligram equivalents [MME]/day) and overuse rates at 6 months post-index procedure were assessed. All pvalues <0.05 were considered statistically significant.

Results: Following examination of 153,500 patient records, 1,216 patients were matched into cannabis user and non-cannabis user cohorts. Cannabis users had lower rates of opioid utilization compared to non-cannabis users as early as 2 months after fusion (47.7% vs. 41.1%, p <0.05), a relationship which persisted at 6 months (46.2% vs. 37.7%, p <0.01). Additionally, cannabis users had lower rates of high-dose opioid utilization (≥100 MME per day) during the initial 14-30 days following surgery (6.91% vs. 3.79%, p <0.05).

Conclusions: Patients with a history of cannabis use were less likely to be using opioids as early as 2 months postoperatively and had lower rates of high-dose opioid utilization in the immediate postoperative period. Physicians operating on these patients should consider their cannabis use patterns to provide appropriate titration of pain medication over time.”

https://pubmed.ncbi.nlm.nih.gov/39434224/

https://www.asianspinejournal.org/journal/view.php?doi=10.31616/asj.2024.0194

An early economic analysis of medical cannabis for the treatment of chronic pain

pubmed logo

“Background: Cannabis-based medicinal products (CBMPs) are increasingly demonstrating effectiveness in treating a wide range of conditions, with a relatively high safety profile in clinical usage compared to other prescription pain medications and few contraindications. Consultation and other prescription-related costs are, at present, higher for CBMPs than for some other treatment options, leading to some concern around wider prescribing.

Research design and methods: An early cost-effectiveness model was developed to estimate the impact of prescribing CBMPs alone and/or in addition to analgesics, physiotherapy, and cognitive behavioral therapy for chronic pain in the UK for 1 year.

Results: Due to their comparative effectiveness, CBMPs were found to be cost saving. Various scenarios were model tested; in all scenarios where CBMPs decrease pain-level states, less resource use is required. Increased efficacy of 5% was conservatively assumed based on current Real-World Evidence. In this scenario, CBMPs were significantly more cost-effective, and as costs relating to the prescribing of these continue to fall, relative savings are predicted to increase.

Conclusion: These findings highlight the substantial cost saving that CBMPs may represent for the treatment of chronic pain patients, and the benefits for healthcare providers as a treatment for this often hard-to-treat population.”

https://pubmed.ncbi.nlm.nih.gov/39415537/

https://www.tandfonline.com/doi/full/10.1080/14737167.2024.2412248

Innovative active bio-based food packaging material with Cannabis sativa L. seeds extract as an agent to reduce food waste

pubmed logo

“In the present study, ethanolic extracts from the extract of unshelled seeds of Cannabis sativa L. were used to produce films in order not to generate additional waste, taking into view a circular economy. Combinations of apple pectin and citrus pectin in a ratio of 80:20 were used. Film samples containing 0.5, 1.0 and 2.5 [wt%] of the extract were extruded. Antimicrobial, mechanical and barrier properties of the obtained films were tested. Samples with 0.5 [wt%] showed a WVTR of 16.98 [g/m2d]. The water vapour barrier properties of the films decreased with an increase in the amount of extract used. As the amount of extract increased, the transparency of the films decreased linearly to 12.84 [%] (0.5 [wt%]), 4.90 [%] (1.0 [wt%]) and 4.99 [%] (2.5 [wt%]). It was observed that the brightness of the samples decreased with increasing concentration, due to the presence of higher levels of phenolic compounds. Tests carried out showed that the prepared films exhibited inhibitory activity against all micrograms tested. All prepared films had antibacterial activity against the Salmonella typhimurium strain. Similarly, in the case of L. monocytogenes.”

https://pubmed.ncbi.nlm.nih.gov/39418822/

“In this study, packaging films were developed based on bio-based ingredients, including pectin (a combination of apple and citrus pectin in a ratio of 80:20), tragacanth gum and ethanol extracts from unshelled cannabis seeds. Ethanolic extracts from unshelled cannabis seeds were used in this study to avoid waste generation, in relation to a circular economy. The use of higher amounts of extract resulted in lower TS and EB values. With increasing amounts of extract, the transparency of the film decreased linearly and was 12.84 [%] (0.5 wt%), 4.90 [%] (1.0 wt%) and 4.99 [%] (2.5 wt%), respectively. The film was observed to have a significant colour change, confirmed by examination under a stereoscopic microscope. This was confirmed by colour tests of L a b. The highest value of the L* parameter (89.91) was obtained for the film sample without extract. All prepared films had a lethal effect on the Salmonella typhimurium strain. The same was the case for L. monocytogenes bacteria. The high antimicrobial activity of the films seems to be due to the active effect of the phenolic compounds present in the films that were found in the extract.”

https://www.sciencedirect.com/science/article/pii/S0927776524005721?via%3Dihub

Effect of Cannabidiol (CBD), a cannabis plant derivative, against Candida albicans growth and biofilm formation

pubmed logo

“This study aimed to evaluate the antifungal activities of cannabidiol (CBD) against C. albicans.

Yeast cells were treated once or twice with different concentrations (from 0 to 20 mg/ml) of CBD, showing a significant (p < 0.05) decreased the growth of C. albicans, with cell concentrations ranging from 5.1 × 106 cell/mL in the control to 1.8 × 106 cell/mL after one exposure to 20 µg/mL CBD. This growth reduction was greater after two exposures to CBD. After two exposures to 20 µg/mL CBD, the cell concentration was only 1.1 × 106 cell/mL. Such a growth decrease in C. albicans was confirmed by a reduced number of CFUs and a lower MTT value compared to the control. The growth inhibition was supported by a significant (p < 0.001) decrease in the yeast-to-hyphae transition, ranging from 20 ± 0.2% in the control to 2 ± 0.5% after exposure to 20 µg/mL CBD. Biofilm formation was also significantly reduced following CBD exposure.

CBD at 10 and 20 µg/mL promoted the death of C. albicans through an apoptosis/necrotic pathway.

Altogether, our results suggest the possible use of CBD, a cannabis derivative, to control C. albicans infection, including oral candidiasis.”

https://pubmed.ncbi.nlm.nih.gov/39418672/

https://cdnsciencepub.com/doi/10.1139/cjm-2024-0034