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Proteomic and metabolomic analyses reveal the antibacterial mechanism of Cannabidiol against gram-positive bacteria

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“Cannabidiol (CBD), the primary non-psychoactive cannabinoid isolated from cannabis, exhibits promising antibacterial effects. However, the antibacterial mechanism of CBD remains poorly understood.

In this study, the mechanism was investigated using bacterial inhibition assays, label-free proteomics, and untargeted metabolomics, with Bacillus licheniformis (B. licheniformis), Staphylococcus aureus (S. aureus), and Enterococcus faecium (E. faecium) selected as representative Gram-positive bacteria.

The results revealed that CBD caused significant damage to bacterial cell walls and membranes, leading to notable changes in proteomic and metabolic profiles. Specifically, 437, 120, and 195 proteins, as well as 52, 153, and 94 metabolites, were differentially expressed in B. licheniformis, S. aureus, and E. faecium, respectively.

The antimicrobial mechanism of CBD shares similarities with previously known antibacterial agents, such as penicillin and cephalosporins, particularly in affecting the bacterial cell wall, but differs in its detailed mode of action. CBD disrupted the biosynthesis of primary and secondary metabolites and altered bacterial metabolism, contributing to its antibacterial activity.

This study provides valuable insights into the antibacterial mechanism of CBD, supporting its potential development as an antibiotic alternative and its application in food safety.

SIGNIFICANCE: It is crucial to find alternatives to antibiotics to mitigate the impact of pathogenic bacteria on food safety and reduce the use of antibiotics. CBD is the primary non-psychoactive cannabinoid derived from cannabis, and it has shown promising antibacterial effects. However, the antimicrobial mechanisms of CBD have not been well elucidated. This study provides a deep understanding of the antibacterial mechanism from the cellular to molecular level, which will contribute to the development of CBD as a novel antibacterial agent.”

https://pubmed.ncbi.nlm.nih.gov/39978755/

“CBD is a promising antibacterial agent for Gram-positive bacteria.”

https://www.sciencedirect.com/science/article/abs/pii/S1874391925000387?via%3Dihub

Medical Cannabis for Patients Over Age 50: A Multi-site, Prospective Study of Patterns of Use and Health Outcomes

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“Objective: Cannabis is being used as a therapeutic option by patients around the globe, and older patients represent a rapidly growing subset of this population. This study aims to assess the patterns of medical cannabis use in patients over 50 years of age and its effect on health outcomes such as pain, sleep, quality of life, and co-medication.

Method: The Medical Cannabis in Older Patients Study (MCOPS) is a multi-site, prospective observational study examining the real-world impact of medical cannabis use on patients over age 50 under the guidance of a health care provider. The study included validated instruments, with treating physicians collecting detailed data on participant characteristics, medical cannabis and co-medication use, and associated impacts on pain, sleep, quality of life, as well as adverse events.

Results: Inclusion criteria were met by 299 participants. Average age of participants was 66.7 years, and 66.2% of respondents identified as female. Approximately 90% of patients used medical cannabis to treat pain-related conditions such as chronic pain and arthritis. Almost all patients reported a preference for oral cannabis products (e.g., extracts, edibles) rather than inhalation products (e.g., flower, vapes), and most preferred oral formulations high in cannabidiol and low in tetrahydrocannabinol.

Over the six-month study period, significant improvements were noted in pain, sleep, and quality of life measures, with 45% experiencing a clinically meaningful improvement in pain interference and in sleep quality scores. Additionally, nearly 50% of patients taking co-medications at baseline had reduced their use by the end of the study period, and quality of life improved significantly from baseline to M3 and from baseline to M6, with an incremental cost per quality-adjusted life-year (QALY) of $25,357.20. No serious adverse events (SAEs) were reported.

Conclusions: In this cohort of older patients, most of whom suffered from pain-related conditions, medical cannabis seemed to be a safe and effective treatment. Most patients experienced clinically significant improvements in pain, sleep, and quality of life and reductions in co-medication. The cost per QALY was well below the standard for traditional pharmaceuticals, and no SAEs were reported, suggesting that cannabis is a relatively safe and cost-effective therapeutic option for adults dealing with age-related health conditions.”

https://pubmed.ncbi.nlm.nih.gov/39968489/

https://publications.sciences.ucf.edu/cannabis/index.php/Cannabis/article/view/239

Recreational Cannabis Laws and Fills of Pain Prescriptions in the Privately Insured

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“Objective: Almost half of U.S. states have passed recreational cannabis laws as of May 2024. While considerable evidence to date indicates cannabis may be a substitute for prescription opioids in the treatment of pain, it remains unclear if patients are treating pain with cannabis alone or concomitantly with other medications.

Method: Using data from a national sample of commercially insured adults, we examine the effect of recreational cannabis legalization (through two sequential policies) on prescribing of opioids, NSAIDS, and other pain medications by implementing synthetic control estimations and constructing case-study level counterfactuals for the years 2007-2020.

Results: Overall, we find recreational cannabis legalization is associated with a decrease in opioid fills among commercially insured adults in the U.S., and we find evidence of a compositional change in prescriptions of pain medications more broadly. Specifically, we find marginally significant increases in prescribing of non-opioid pain medications after recreational cannabis becomes legal in some states. Once recreational cannabis dispensaries open, we find statistically significant decreases in the rate of opioid prescriptions (13% reduction from baseline, p < .05) and marginally significant decreases in the average daily supply of opioids (6.3% decrease, p < .10) and number of opioid prescriptions per patient (3.5% decrease, p < .10).

Conclusions: These results suggest that substitution of cannabis for traditional pain medications increases as the availability of recreational cannabis increases. There appears to be a small shift once recreational cannabis becomes legal, but we see stronger results once users can purchase cannabis at recreational dispensaries. The decrease in opioids and marginal increase in non-opioid pain medication may reflect patients substituting opioids with cannabis and non-opioid pain medications, either separately or concomitantly. Reductions in opioid prescription fills stemming from recreational cannabis legalization may prevent exposure to opioids in patients with pain and lead to decreases in the number of new opioid users, rates of opioid use disorder, and related harms.”

https://pubmed.ncbi.nlm.nih.gov/39968486/

https://publications.sciences.ucf.edu/cannabis/index.php/Cannabis/article/view/268

Motherhood and medicinal cannabis

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“Introduction: Women are emerging as a key demographic for medicinal cannabis (MC) use in countries that have implemented MC reforms. However, research on mothers’ experiences of consuming MC remains limited beyond studies on perinatal outcomes. This study explores mothers’ diverse experiences of consuming MC in New Zealand under the legal MC scheme.

Methods: Interviews with 15 mothers using MC via prescriptions, the illegal market or both in the last 12 months. Thematic analysis focused on MC use in parenting, MC conversations with children, societal stigma and risks.

Results: Mothers reported MC as an important facilitator of their ability to positively parent their children, enabling them to manage their own health needs (i.e., anxiety, endometriosis and arthritis). High costs of legal products hindered access to MC. Participants expressed unique risks that mothers face accessing the unregulated market for MC like being deemed a ‘bad mother’ and losing custody of children. Stigma was countered with narratives of empowerment through proactive MC conversations with children and agency by self-medicating with MC despite the judgement they may face for being a parent that uses cannabis.

Discussion and conclusions: Mothers felt managing their health with MC allowed them to be more present parents and better tolerate the stressors of motherhood. In-depth exploration of discussing MC with children and anticipating these conversations was a novel finding. Most mothers tried to destigmatise MC in conversations by classifying it in the same category as other medications and discussing its therapeutic benefits. Few were cautious about having these conversations too early.”

https://pubmed.ncbi.nlm.nih.gov/39967064/

“This study has provided insights into MC use among mothers, highlighting perceived therapeutic benefits for managing the unique stressors of motherhood and health and wellbeing in general. The findings illustrate the global legalisation of MC as a possible catalyst for shifting attitudes towards cannabis use in parenting, and a trend of women exercising agency in their health using complementary alternative therapies.”

https://onlinelibrary.wiley.com/doi/10.1111/dar.14027

Cannabidiol reshapes the gut microbiome to promote endurance exercise in mice

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“Cannabidiol (CBD), a nonpsychoactive compound from Cannabis, has various bioactive functions in humans and animals.

Evidence suggests that CBD promotes muscle injury recovery in athletes, but whether and how CBD improves endurance performance remains unclear.

Here we investigated the effects of CBD treatment on exercise performance in mice and assessed whether this effect involves the gut microbiome.

CBD administration significantly increased treadmill running performance in mice, accompanied by an increase in oxidative myofiber composition. CBD also increased mitochondrial biogenesis and the expression of associated genes such as PGC-1α, phosphorylated CREB and AMPK in muscle tissue. Interestingly, CBD altered the composition of the gut microbiome, and antibiotic treatment reduced the muscle endurance-enhancing effects of CBD and mitochondrial biogenesis.

We isolated Bifidobacterium animalis, a microbe increased by CBD administration, and named it KBP-1. Treatment with B. animalis KBP-1 in mice resulted in improved running performance. Whole-genome analysis revealed that B. animalis KBP-1 presented high expression of genes involved in branched-chain amino acid biosynthesis, expression of branched-chain amino acid release pumps and metabolism of lactic acid.

In summary, our study identified CBD and B. animalis KBP-1 as potential endurance exercise-promoting agents.”

https://pubmed.ncbi.nlm.nih.gov/39966566/

“In summary, we propose that both CBD and the gut bacteria B. animalis KBP-1, which is increased by CBD treatment, could be used in strategies to promote endurance exercise performance.”

https://www.nature.com/articles/s12276-025-01404-5

The role of cannabinoid-mediated signaling pathways and mechanisms in brain disorders

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“Cannabinoids play significant roles in the central nervous system (CNS), but cannabinoid-mediated physiopathological functions are not elaborated. Cannabinoid receptors (CBRs) mediate functions that include the regulation of neuroinflammation, oxidative stress, apoptosis, autophagy, and neurogenesis.

Microglia are the primary immune cells responsible for mediating neuroinflammation in the CNS. Therefore, this article primarily focuses on microglia to summarize the inflammatory pathways mediated by cannabinoids in the CNS, including nuclear factor-κB (NF-κB), NOD-like receptor protein 3 (NLRP3) inflammasome, mitogen-activated protein kinase (MAPK), protein kinase B (Akt), and cAMP-dependent protein kinase (PKA) signaling pathways. Additionally, we provide a table summarizing the role of cannabinoids in various brain diseases.

Medical use of cannabinoids has protective effects in preventing and treating brain diseases; however, excessive and repeated use can be detrimental to the CNS. We propose that cannabinoids hold significant potential for preventing and treating brain diseases, including ferroptosis, lactate metabolism, and mitophagy, providing new insights for further research on cannabinoids.”

https://pubmed.ncbi.nlm.nih.gov/39952540/

“Cannabis plants were historically used by pharmacologists as drugs to treat diseases in ancient India and China. Cannabinoids are natural compounds extracted from the cannabis plant. The most well-known component of cannabis is delta-9-tetrahydrocannabinol (delta9-THC)”

“This article reviews the role of cannabinoids in signaling pathways, including NF-κB, the NLRP3 inflammasome, MAPK, and AKT. Cannabinoids primarily combat neuroinflammation through CB2R-mediated signaling. Additionally, we discuss the effects of cannabinoids on oxidative stress, apoptosis, autophagy, and neurogenesis. Numerous studies demonstrate the neuroprotective effects of cannabinoids”

https://www.sciencedirect.com/science/article/abs/pii/S089865682500066X?via%3Dihub

Cannabidiol restores hematopoietic stem cell stemness in mouse through Atf2-Lrp6 axis after acute irradiation

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“Bone marrow serves as the residence of hematopoietic stem cells and is recognized as one of the most radiosensitive tissues. Exposure to acute radiation leads to severe damage to bone marrow hematopoiesis which can be fatal, while few clinically applicable medication or specific therapeutic targets have been discovered.

In this study, we found that the administration of cannabidiol significantly enhanced individual survival and restored the reconstitution capacity of bone marrow hematopoietic stem cells within 14 days after irradiation.

Single-cell RNA sequencing analysis demonstrated that the expression levels of genes associated with stemness along with Wnt and BMP signaling pathways were restored by the cannabidiol treatment through the upregulation of Atf2, a transcription factor possessing multifunctional properties. Atf2 upregulation induced by cannabidiol treatment potentially upregulated the expression of Lrp6 to improve the stemness of hematopoietic stem cells. Further functional experiments validated the crucial role of Atf2 in regulating multilineage differentiation potential of bone marrow hematopoietic stem and progenitor cells.

Overall, our findings provide evidence for a promising radioprotective function of cannabidiol and Atf2 as a candidate therapeutic target for acute radiation-induced hematopoietic injury, thereby paving the way for future research in the field.”

https://pubmed.ncbi.nlm.nih.gov/39949985/

“Cannabidiol (CBD) is the primary non-psychoactive chemical from Cannabis Sativa and an important component of hemp seed, a traditional Chinese medicine with a long history of application. Based on its multiple function, CBD has been investigated in fields of nervous system diseases, analgesic therapy, aging, anti-tumor therapy, and so on.2 In this study, we first assessed the potential role of CBD in preventing and treating acute irradiation-induced hematopoietic injury in bone marrow. Using single-cell RNA sequencing and functional assay, we dissected molecular alterations and potential mediator under CBD-treatment which led to the facilitated recovery of the HSC function. Collectively, this work strongly supports the therapeutic application of CBD in irradiation-induced bone marrow hematopoietic injury and highlights Atf2 as a promising therapeutic target herein.”

https://onlinelibrary.wiley.com/doi/10.1002/mco2.70092

The Presence of the Endocannabinoid System in an In Vitro Model of Gorham-Stout Disease and Its Possible Role in the Pathogenesis

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“Gorham-Stout syndrome (GSD), also known as disappearing bone disease, is an extremely rare bone disorder, characterized by a huge bone loss, which is followed by a lack of new matrix deposition and an excessive proliferation of both blood vessels and lymphatics. Unfortunately, the biological causes of GSD are still unknown. Recent studies that have tried to understand the etiopathogenesis of GSD have been principally focused on the vascular and osteoclastogenic aspects, not considering the possibility of a lack of osteoblast function. Nowadays, a diagnosis is still difficult, and is often made by exclusion of the presence of other pathologies, as well as on radiological evidence, and finally confirmed by histological examination. Treatment also remains a critical issue for clinicians today, who mostly try to control the progression of the disease.

Over the last two decades, clear evidence has emerged that the endocannabinoid system plays an important role in bone metabolism, leading scientists to hypothesize that it could be involved in physiological and pathological bone processes. In this work, we analyzed the presence of the ES in a primary cell line of human mesenchymal stem cells derived from a GSD patient for the first time, to understand if and how this complex network may play a role in the pathogenesis of the syndrome.

Our preliminary results demonstrated that the ES is also present in the pathological tissue. Moreover, the qRT-PCR analysis showed an altered expression of the different ES components (i.e., CNR1, CNR2, TRPV1, and GPR55). We observed an upregulation of CNR1 and TRPV1 expression, while the opposite trend was noticed for CNR2 and GPR55 expression. Thus, these results could lead us to speculate that possible deregulation of the ES may play an important role in the lack of bone regeneration in GSD patients. However, further studies will be necessary to confirm the role of the ES in the progression of GSD and understand whether the natural components of Cannabis Sativa could play a therapeutic role in the treatment of the disease.”

https://pubmed.ncbi.nlm.nih.gov/39940911/

“In conclusion, this is only a preliminary study, and further future analyses are needed to understand the role of the ES during osteogenic differentiation better and to try to comprehend what the molecular mechanisms involved in GSD pathogenesis are. In addition to this, the demonstration that the ES is present in our GSD in vitro model could pave the way to a study of the effects of the natural components of Cannabis Sativa as possible future new molecules that could be useful in the treatment of GSD and other bone diseases.”

https://www.mdpi.com/1422-0067/26/3/1143

Acute and prolonged toxicity assessment of Cannabis sativa extract in rodents and lagomorphs

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“Cannabinoids offer a novel pharmacotherapeutic approach and can complement other medications to address unmet clinical needs in numerous patients, which has led to a global increase in the use of these products.

No significant safety concerns have been identified in preclinical studies involving CBD and THC. However, the available data on the toxicity of combined CBD and THC are still inconclusive. Evaluating full-spectrum Cannabis sativa extracts is even more complex since whole extracts and isolated phytomolecules do not act in the same way.

Given the growing interest in cannabinoid-containing products for human use and the fact that most cannabis treatments utilize entire inflorescence rather than isolated compounds, the current studies aim to evaluate the preclinical safety of a full-spectrum composition (THC, CBD, minor cannabinoids, terpenes, and flavonoids) Cannabis sativa extract (CSE).

This research includes acute (single dose, with animals monitored for 14 days to assess potential effects) and long-term treatments (6 months for rodents and 9 months for rabbits) to assess safety and tolerance.

This study demonstrates that a full-spectrum Cannabis sativa extract has a favorable safety profile in both acute and prolonged toxicity studies in rodents and rabbits.

In acute toxicity tests, the extract did not show any significant behavioral or physiological changes after oral or intraperitoneal administration. Additionally, administering the extract acutely to rabbits had minimal impact on the central nervous, cardiovascular, and respiratory systems, with only a temporary reduction in motor activity at the highest dose.

Prolonged administration of 6 months in rats and 9 months in rabbits did not lead to significant changes in organ histopathology, body weight, or behavior.

Although liver enzymes were elevated at the highest doses, other biochemical and hematological parameters remained unchanged. CSE was well-tolerated, as no serious adverse effects were observed; however, a reduction in motor activity was noted in the highest dose group, highlighting the need for further investigation, which is proposed for future studies.”

https://pubmed.ncbi.nlm.nih.gov/39917037/

https://www.sciencedirect.com/science/article/pii/S2214750025000368?via%3Dihub

Cannabidiol protects lung against inflammation and apoptosis in a rat model of blunt chest trauma via Bax/Bcl-2/Cas-9 signaling pathway

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“Purpose: This study aimed to investigate the hypothesis that cannabidiol (CBD), with known anti-inflammatory and anti-apoptotic effects, would reduce the severity of acute lung injury in pulmonary contusion following blunt chest trauma.

Methods: Forty male Wistar Albino rats were randomly divided into four groups, each consisting of 10 rats: Sham, Trauma, Trauma + CBD, and CBD. The rats were treated with a single dose of 5 mg/kg CBD intraperitoneally 30 min before trauma. Then, the trauma were exposed to a weight of 200 g and a height of 1 m. After sacrifice, the lung tissues were removed for histopathological, immunohistochemical, biochemical, and genetic analyses.

Results: Pulmonary injury of trauma group led to increases in tumor necrosis factor α, caspase-3, caspase-9, Bcl-2-associated X protein expressions, total oxidant status, oxidative stress index levels, and decreases in B-cell lymphoma expression and total antioxidant levels. Additionally, inflammatory cell infiltration, damage-related emphysema, pronounced hyperemia, and increased septal tissue thickness were observed histopathologically. CBD treatment ameliorated all these findings.

Conclusion: CBD reduces lung damage in lung contusions caused by blunt chest trauma through its anti-inflammatory and antiapoptotic effects. More detailed studies investigating other important intracellular pathways are needed.”

https://pubmed.ncbi.nlm.nih.gov/39918746/

“In conclusion, it has been observed that CBD reduces lung damage in lung contusions caused by blunt chest trauma through its anti-inflammatory and antiapoptotic effects. In addition, the effects of a single dose of CBD were examined in this study, and more detailed molecular studies are needed in which longer-term use or higher doses are preferred, in addition to this study, which highlights the acute effects of CBD. The ability to perform analyses at the gene level at the protein level via the western blot method will increase the effectiveness of the study.”

https://link.springer.com/article/10.1007/s00068-025-02767-0