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Cannabis sativa CBD Extract Exhibits Synergy with Broad-Spectrum Antibiotics against Salmonella enterica subsp. Enterica serovar typhimurium

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“New generation antibiotics are needed to combat the development of resistance to antimicrobials. One of the most promising new classes of antibiotics is cannabidiol (CBD). It is a non-toxic and low-resistance chemical that can be used to treat bacterial infections.

The antibacterial activity of Cannabis sativa L. byproducts, specifically CBD, has been of growing interest in the field of novel therapeutics. As research continues to define and characterize the antibacterial activity that CBD possesses against a wide variety of bacterial species, it is important to examine potential interactions between CBD and common therapeutics such as broad-spectrum antibiotics.

In this study it is demonstrated that CBD-antibiotic (combination of CBD and antibiotic) co-therapy can effectively fight Salmonella typhimurium (S. typhimurium) via membrane integrity disruption. This research serves to examine the potential synergy between CBD and three broad-spectrum antibiotics (ampicillin, kanamycin, and polymyxin B) for potential CBD-antibiotic co-therapy. In this study, it is revealed that S. typhimurium growth is inhibited at very low dosages of CBD-antibiotic.

This interesting finding demonstrates that CBD and CBD-antibiotic co-therapies are viable novel alternatives to combating S. typhimurium.”

https://pubmed.ncbi.nlm.nih.gov/36557613/

“The decrease in antibiotic development over the 21st century has exacerbated the need for new antibacterial agents as well as new methodologies designed to retain the efficacy of current antibiotics. CBD extract from C. sativa has been presented as a promising antibacterial agent with in vitro efficacy against several relevant bacterial pathogens including Staphylococcus aureus, Streptococcus pneumoniae, Salmonella spp. Clostridium difficile, Neisseria spp., Moraxella catarrhalis, and Legionella pneumophila. This antibacterial activity achieved through membrane disruption of both Gram-positive and Gram-negative bacterial species presents CBD as a unique and particularly effective class of antibacterial agents.”

https://www.mdpi.com/2076-2607/10/12/2360

Anti-Bacterial Effect of Cannabidiol against the Cariogenic Streptococcus mutans Bacterium: An In Vitro Study

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“Dental caries is caused by biofilm-forming acidogenic bacteria, especially Streptococcus mutans, and is still one of the most prevalent human bacterial diseases. The potential use of cannabidiol (CBD) in anti-bacterial therapies has recently emerged.

Here we have studied the anti-bacterial and anti-biofilm activity of CBD against S. mutans. We measured minimum inhibitory concentration (MIC) and minimum biofilm inhibitory concentration (MBIC). The bacterial growth and changes in pH values were measured in a kinetic study. The biofilm biomass was assessed by Crystal Violet staining and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) metabolic assay. Spinning Disk Confocal Microscopy (SDCM) was used to assess biofilm structure, bacterial viability and extracellular polysaccharide (EPS) production.

CBD inhibited S. mutans planktonic growth and biofilm formation in a dose-dependent manner, with similar MIC and MBIC values (5 µg/mL). CBD prevented the bacteria-mediated reduction in pH values that correlated with bacterial growth inhibition. SDCM showed a decrease of 50-fold in live bacteria and EPS production. CBD significantly reduced the viability of preformed biofilms at 7.5 µg/mL with an 80 ± 3.1% reduction of metabolic activity. At concentrations above 20 µg/mL, there was almost no bacterial recovery in the CBD-treated preformed biofilms even 48 h after drug withdrawal.

Notably, precoating of the culture plate surfaces with CBD prior to incubation with bacteria inhibited biofilm development. Additionally, CBD was found to induce membrane hyperpolarization in S. mutans. Thus, CBD affects multiple processes in S. mutans including its cariogenic properties.

In conclusion, we show that CBD has a strong inhibitory effect against cariogenic bacteria, suggesting that it is a potential drug adjuvant for reducing oral pathogenic bacterial load as well as protecting against dental caries.”

https://pubmed.ncbi.nlm.nih.gov/36555519/

“We have shown that the mode of action of CBD against S. mutans is multifactorial and attributed to: inhibition of bacterial growth and subsequently hindrance of biofilm formation, diminished biofilm metabolic activity and prevention of bacterial recovery within the biofilms following CBD treatment. Some of these effects can be attributed to the membrane hyperpolarization caused by CBD. The combined anti-bacterial and anti-metabolic effects of CBD contribute to the prevention in pH drop with implications for being a potential adjuvant drug in protecting against dental caries.”

https://www.mdpi.com/1422-0067/23/24/15878

Phytocannabinoids Act Synergistically with Non-Steroidal Anti-Inflammatory Drugs Reducing Inflammation in 2D and 3D In Vitro Models

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“Lung inflammation is associated with elevated pro-inflammatory cytokines and chemokines. Treatment with FCBD:std (standard mix of cannabidiol [CBD], cannabigerol [CBG] and tetrahydrocannabivarin [THCV]) leads to a marked reduction in the inflammation of alveolar epithelial cells, but not in macrophages.

In the present study, the combined anti-inflammatory effect of FCBD:std with two corticosteroids (dexamethasone and budesonide) and two non-steroidal anti-inflammatory drugs (NSAID; ibuprofen and diclofenac), was examined. Enzyme-linked immunosorbent assay (ELISA) was used to determine protein levels. Gene expression was determined by quantitative real-time PCR. Inhibition of cyclo-oxygenase (COX) activity was determined in vitro.

FCBD:std and diclofenac act synergistically, reducing IL-8 levels in macrophages and lung epithelial cells. FCBD:std plus diclofenac also reduced IL-6, IL-8 and CCL2 expression levels in co-cultures of macrophages and lung epithelial cells, in 2D and 3D models. Treatment by FCBD:std and/or NSAID reduced COX-1 and COX-2 gene expression but not their enzymatic activity. FCBD:std and diclofenac exhibit synergistic anti-inflammatory effects on macrophages and lung epithelial cells, yet this combined activity needs to be examined in pre-clinical studies and clinical trials.”

https://pubmed.ncbi.nlm.nih.gov/36559009/

“We have shown that FCBD:std and diclofenac have synergistic anti-inflammatory effects on macrophages and lung epithelial cells, which involve the reduction of COX and CCL2 gene expression and IL levels. FCBD:std, when combined with diclofenac, can have considerably increased anti-inflammatory activity by several fold, suggesting that in an effective cannabis-diclofenac combined treatment, the level of NSAIDs may be reduced without compromising anti-inflammatory effectivity.”

https://www.mdpi.com/1424-8247/15/12/1559

Cannabinoid Compounds as a Pharmacotherapeutic Option for the Treatment of Non-Cancer Skin Diseases

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“The endocannabinoid system has been shown to be involved in various skin functions, such as melanogenesis and the maintenance of redox balance in skin cells exposed to UV radiation, as well as barrier functions, sebaceous gland activity, wound healing and the skin’s immune response.

In addition to the potential use of cannabinoids in the treatment and prevention of skin cancer, cannabinoid compounds and derivatives are of interest as potential systemic and topical applications for the treatment of various inflammatory, fibrotic and pruritic skin conditions. In this context, cannabinoid compounds have been successfully tested as a therapeutic option for the treatment of androgenetic alopecia, atopic and seborrhoeic dermatitis, dermatomyositis, asteatotic and atopic eczema, uraemic pruritis, scalp psoriasis, systemic sclerosis and venous leg ulcers. This review provides an insight into the current literature on cannabinoid compounds as potential medicines for the treatment of skin diseases.”

https://pubmed.ncbi.nlm.nih.gov/36552866/

“Based on the current publications, it can be summarised that cannabinoid compounds have great potential in the treatment of skin diseases, both as topical applications and as systemic medications.”

https://www.mdpi.com/2073-4409/11/24/4102

Cannabidiol and Beta-Caryophyllene in Combination: A Therapeutic Functional Interaction

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“Cannabis contains over 500 distinct compounds, which include cannabinoids, terpenoids, and flavonoids. However, very few of these compounds have been studied for their beneficial effects. There is an emerging concept that the constituents of the cannabis plant may work in concert to achieve better therapeutic benefits. This study is aimed at determining if the combination of a minor cannabinoid (cannabidiol, CBD) and a terpene (beta-caryophyllene, BCP) works in concert and if this has any therapeutic value. We used an inflammatory pain model (formalin) in mice to test for any functionality of CBD and BCP in combination. First, we determined the analgesic effect of CBD and BCP individually by establishing dose-response studies. Second, we tested the analgesic effect of fixed-ratio combinations and monitored any adverse effects. Finally, we determined the effect of this combination on inflammation. The combination of CBD and BCP produces a synergistic analgesic effect. This effect was without the cannabinoid receptor-1 side effects. The analgesic effect of CBD and BCP in combination involves an inflammatory mechanism. The combination of these two constituents of the cannabis plant, CBD and BCP, works in concert to produce a therapeutic effect with safety profiles through an inflammatory mechanism.”

https://pubmed.ncbi.nlm.nih.gov/36555111/

“In summary, the present data support the concept that cannabinoids and terpenes work synergistically with therapeutical value. In particular, the CBD and BCP in combination produce a synergistic analgesic effect without CB1-associated side effects. Finally, scientific investigation of the interactive effects of CBD and BCP on a therapeutic target has not been undertaken. Therefore, our present data set the stage for future studies on the therapeutic value of this combination in other diseases and testing other terpenes in combination with other cannabinoids or terpenes.”

https://www.mdpi.com/1422-0067/23/24/15470

Inhibiting Human and Leishmania Arginases Using Cannabis sativa as a Potential Therapy for Cutaneous Leishmaniasis: A Molecular Docking Study

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“Cutaneous leishmaniasis (CL), a vector-borne parasitic disease caused by the Leishmania protozoan, is a serious public health problem in Morocco. The treatment of this disease is still based on pentavalent antimonials as the primary therapy, but these have associated side effects. Thus, the development of effective, risk-free alternative therapeutics based on natural compounds against leishmaniasis is urgent. Arginase, the key enzyme in the polyamine biosynthetic pathway, plays a critical role in leishmaniasis outcome and has emerged as a potential therapeutic target.

The objective of this study was to test Cannabis sativa‘s phytochemical components (cannabinoids and terpenoids) through molecular docking against Leishmania and human arginase enzymes.

Our results showed that delta-9-tetrahydrocannabinol (THC) possessed the best binding energies of -6.02 and -6.35 kcal/mol with active sites of Leishmania and human arginases, respectively. Delta-9-THC interacted with Leishmania arginase through various amino acids including His139 and His 154 and linked to human arginase via His 126. In addition to delta-9-THC, caryophyllene oxide and cannabidiol (CBD) also showed a good inhibition of Leishmania and human arginases, respectively.

Overall, the studied components were found to inhibit both arginases active sites via hydrogen bonds and hydrophobic interactions. These components may serve as therapeutic agents or in co-administrated therapy for leishmaniasis.”

https://pubmed.ncbi.nlm.nih.gov/36548655/

“Since CL is still a public health problem in low-income and developing countries, the discovery of an efficient, less toxic, and accessible therapy is a necessity. The present in silico study was the first to investigate C. sativa’s selected constituents as selective inhibitory agents for parasitic as well as host arginases, which play an important role in this parasitic infection pathology. Interestingly, THC showed a great inhibitory potential for both species’ enzymes and will allow a better control of leishmaniasis.”

https://www.mdpi.com/2414-6366/7/12/400

Cannabis sativa L. alleviates loperamide-induced constipation by modulating the composition of gut microbiota in mice

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“MaZiRenWan (MZRW) is the most frequently used Traditional Chinese Medicine formula to treat chronic constipation, Cannabis sativa L. is regarded as a monarch drug in MZRW. However, the targets of Cannabis sativa L. that enhance colonic motility and improve constipation symptoms remain unknown.

This study was designed to investigate the laxative effect and underlying mechanism of the water extract of Cannabis sativa L. (WECSL) using a loperamide-induced constipation mouse model.

We found that WECSL treatment significantly improved intestinal motility and water-electrolyte metabolism, decreased inflammatory responses, prevented gut barrier damage, and relieved anxiety and depression in constipated mice. WECSL also structurally remodeled the composition of the gut microbiota and altered the abundance of bacteria related to inflammation, specifically Butyricicoccus and Parasutterella. Moreover, WECSL failed to relieve constipation symptoms following intestinal flora depletion, indicating that WECSL alleviates constipation symptoms depending on the gut microbiota.

Our research provides a basis for WECSL to be further investigated in the treatment of constipation from the perspective of modern medicine.”

https://pubmed.ncbi.nlm.nih.gov/36532754/

“In conclusion, this study demonstrated that WECSL can improve constipation symptoms, reduce anxiety and depression behaviors, and inhibit intestinal inflammation. WECSL also structurally remodeled the composition of the gut microbiota, altering the abundance of bacteria related to inflammation.

Our research provides a basis for WECSL to be further investigated in the treatment of constipation from the perspective of modern medicine. Constipation may be prevented and improved by targeting these possible gut bacteria.”

https://www.frontiersin.org/articles/10.3389/fphar.2022.1033069/full


Topical Cannabidiol in the Treatment of Digital Ulcers in Patients with Scleroderma: Comparative Analysis and Literature Review

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“Objective: To explore the effect of topical cannabidiol (CBD) in treating digital ulcers in patients with systemic sclerosis (SSc).

Methods: In total, 45 patients with SSc who had digital ulcers were consecutively enrolled between January 2019 and December 2019. Of the participants, 25 were treated with CBD during surgical debridement and 20 were treated with standard local therapy. A numeric rating scale for pain and Health Assessment Questionnaire Disability Index were administered at the baseline and at the end of treatment.

Results: Local treatment with CBD was significantly associated with lower pain scores, higher health assessment scores, and an increase in participants’ total hours of sleep. Patients in the control group more frequently required additional analgesic therapy.

Conclusions: Topical CBD may be a valuable tool to treat pain related to digital ulcers in patients with SSc.”

https://pubmed.ncbi.nlm.nih.gov/36537770/

“Topical administration of CBD is a safe, effective, noninvasive tool that is associated with improved wound-related pain, DU healing, and QoL of patients with SSc.”

https://journals.lww.com/aswcjournal/Fulltext/2023/01000/Topical_Cannabidiol_in_the_Treatment_of_Digital.4.aspx

The Modulation of Blue-Light-Induced Inflammation, Intracellular Lipid Secretion, and Oxidative Stress in Sebocytes with Cannabidiol

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“Light-induced skin damage leads to cellular or molecular dysfunction, thus potentially causing different skin issues (e.g., skin aging, seborrheic dermatitis and pigmentation). Blue light, a potent visible light that was previously adopted for promoting skin regeneration, draws considerable concerns in the past several years due to their potential damage to the skins. In this work, we investigated the roles of blue light in skewing the functions of sebocytes – the major cells that compose the sebaceous gland – an important “active” neuro-immuno-endocrine organ in maintaining skin functions.

For therapeutically purposes, we employed cannabidiol (CBD), a clinically used non-psychotropic phytocannabinoid, to revert blue-light-induced sebocytes dysfunctions, including intracellular lipid secretion, inflammation, reactive oxygen species (ROS) secretion, and cell cycles. At the cellular level, CBD reduced the blue-light-enhanced intracellular lipid secretion, decreased inflammation, down-regulated intracellular ROS production, and restored the skewed cell cycles in the sebocytes. In the intracellular mechanism, CBD inhibited the blue-light-induced pro-apoptotic activity through rebalance BCL-2/BAX expression and down-regulated the NF-κB p65 pathway.

Collectively, this study demonstrated that CBD was a potent therapeutic agent for maintaining normal sebocytes functions, thus is a promising drug for skincare purposes, especially considering its effectiveness in restoring the twisted sebocytes behaviors.”

https://pubmed.ncbi.nlm.nih.gov/36524438/

https://onlinelibrary.wiley.com/doi/10.1111/php.13764

Receptor-mediated effects of Δ9 -THC & CBD on the inflammatory response of alveolar macrophages

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“Δ9 -tetrahydrocannabinol (Δ9 -THC) and cannabidiol (CBD) are cannabinoids found in Cannabis sativa. While research supports cannabinoids reduce inflammation, the consensus surrounding receptor(s) mediated effects has yet to be established.

Here, we investigated the receptor-mediated properties of Δ9 -THC and CBD on alveolar macrophages, an important pulmonary immune cell in direct contact with cannabinoids inhaled by cannabis smokers.

MH-S cells, a mouse alveolar macrophage cell line, were exposed to Δ9 -THC and CBD, with and without lipopolysaccharide (LPS). Outcomes included RNA-sequencing and cytokine analysis. Δ9 -THC and CBD alone did not affect the basal transcriptional response of MH-S cells.

In response to LPS, Δ9 -THC and CBD significantly reduced the expression of numerous pro-inflammatory cytokines including TNF-α, IL-1β and IL-6, an effect that was dependent on CB2 . The anti-inflammatory effects of CBD- but not Δ9 -THC- were mediated through a reduction in signaling through NF-κB and ERK1/2.

These results suggest that CBD and Δ9 -THC have potent immunomodulatory properties in alveolar macrophages, a cell type important in immune homeostasis in the lungs. Further investigation into the effects of cannabinoids on lung immune cells could lead to the identification of therapies that may ameliorate conditions characterized by inflammation.”

https://pubmed.ncbi.nlm.nih.gov/36510483/

https://onlinelibrary.wiley.com/doi/10.1111/imcb.12614