The anti-biofilm activity of cannabinoids against methicillin-resistant Staphylococcus aureus

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“Aims: Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of hospital-acquired pneumonia with resistance against beta-lactam antibiotics. New, potent antibiotics against MRSA with other mechanisms of action are thus urgently needed. Recently, cannabinoids have been evaluated for antimicrobial activity in the ongoing search for new anti-infective agents, but their anti-biofilm effect has not been extensively studied. In this study, five main phytocannabinoids – canndibidiol (CBD), delta-9-tetrahydrocannabinol (THC), cannabinol (CBN), cannabigerol (CBG), and cannabichromene (CBC) were examined for their activity against a MRSA biofilm.

Methods and results: The anti-biofilm activity was assessed by crystal violet staining, resazurin metabolic assay, reactive oxygen species (ROS) assay, and propidium iodide membrane integrity test. The minimum inhibitory concentrations of all tested cannabinoids were between 1-2 µg/mL. CBN showed the most potent anti-MRSA biofilm activity, significantly reducing biofilm biomass and bacterial viability. It also induced the highest intracellular ROS levels. In contrast, CBD was the least effective among the tested cannabinoids in most of the anti-biofilm assays, yet it caused the greatest membrane damage to bacteria within the biofilm.

Conclusions: This study showed that despite being chemically similar, the cannabinoids demonstrated different potency and potentially different mechanisms of action against MRSA. More research is needed to investigate how they act on this pathogen and its biofilm.”

https://pubmed.ncbi.nlm.nih.gov/40844832/

https://academic.oup.com/jambio/advance-article/doi/10.1093/jambio/lxaf214/8239790?login=false

Acute cannabidiol (CBD), tetrahydrocannabinol (THC) and their mixture (THC:CBD) exert differential effects on brain activity and blood flow in rats: A translational neuroimaging study

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“Background: Cannabis constituents, including Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), show distinct pharmacological profiles with therapeutic relevance for neurological and psychiatric conditions. THC exerts euphoric effects primarily via CB1 receptor activation, while CBD displays non-euphoric properties affecting various pathways.

Aims: This study evaluated the effects of THC, CBD, and their combination on brain functional connectivity (FC) and cerebral blood flow (CBF) using multimodal neuroimaging.

Methods: Adult male Sprague Dawley rats received intraperitoneal doses of 10 mg/kg THC, 150 mg/kg CBD, 10.8:10 mg/kg THC:CBD, or vehicle. Resting-state blood oxygenation level dependent magnetic resonance imaging and arterial spin labelling assessed FC and CBF, approximately 2 h after drug administration. Graph-theory metrics and seed-based analyses identified connectivity and perfusion alterations, while plasma analyses determined cannabinoid concentrations.

Results: THC increased whole-brain FC and clustering coefficient, with elevated CBF in cortical and subcortical regions. CBD decreased FC metrics without affecting CBF, while THC:CBD induced moderate increases in both. Seed-based analysis revealed THC-driven increases in cortical-hippocampal and cortical-striatal connectivity, attenuated in the THC:CBD group. A multivariate combined analysis of FC and CBF revealed a divergent pattern of changes induced by each drug.

Conclusions: In conclusion, we show that THC and CBD induce distinct neurophysiological profiles in rats, with THC increasing both connectivity and perfusion, moderated by CBD when combined. These findings corroborate existing knowledge about the effects of cannabinoids on the brain, while also supporting the potential of preclinical functional neuroimaging to delineate cannabinoid-induced endophenotypes, offering insights for therapeutic development.”

https://pubmed.ncbi.nlm.nih.gov/40838351/

“Growing evidence supports the therapeutic potential of cannabis and its constituent phytocannabinoids in treating a range of neurological and psychiatric conditions.”

“In summary, we have demonstrated that acute THC administration resulted in increases in FC and regional CBF, acute CBD administration resulted in an overall reduction in FC with negligible effect on CBF, and the combination drug THC:CBD resulted in effects similar to, but lower than THC alone. Our application of functional neuroimaging has thus identified differential pharmacodynamic signatures for THC and CBD in anaesthetised adult male rats. Further work should encompass an investigation of the effects of sub-chronic administration of phytocannabinoids on brain activity in animal models with relevance to selected disease indications to investigate changes on FC in a perturbed system, more applicable to the disease state. “

https://journals.sagepub.com/doi/10.1177/02698811251360745

Release of delta-9-tetrahydrocannabinol from polyvinyl alcohol hydrogels and its safe interaction with human skin fibroblasts

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“This study aimed to design a THC-rich hydrogel to deliver cannabis derivatives topically. We developed hydrogels using polyvinyl alcohol (PVA) mixed with propylene glycol (PG), vegetable glycerin (VG), or both to facilitate the dissolution of delta-9-tetrahydrocannabinol (THC).

The hydrogels showed a brown color, confirming the presence of the cannabinoid. They exhibit a porous structure and better mechanical properties than PVA alone. Indeed, the hydrogel containing PG, VG, or both showed elastic deformation behaviors with lower water content. FTIR analysis demonstrated the presence of THC with two specific peaks at 1,575 and 1,619 cm-1, confirming the presence of THC in the hydrogels.

Human dermal fibroblast cultures onto the surface of all hydrogels confirmed the safety of the THC-rich hydrogel as the cell adhesion was comparable to the control (no THC). Furthermore, cells adhering to the hydrogels could proliferate, showing increased cell viability at 48 and 72 h, with a higher proliferation obtained with the THC-rich PVA-PG-VG hydrogels.

Such cell behavior could be due to the release of the THC in the culture medium, as demonstrated by ultra-high performance liquid chromatography (UPLC), showing the presence of THC in the culture medium, ranging from 203 to 290 μg after 24 h of incubation of the hydrogels containing PG and VG or both. In comparison, the released THC from the PVA hydrogel was higher, reaching 852 μg. It is interesting to note that the THC release at 24, 48, and 72 h was slower with the hydrogels containing PG, VG, and both, compared to PVA alone.

Overall, the present study has designed safe THC-rich PVA-PG-VG hydrogels as a functional delivery system for the topical use of cannabinoids to control tissue diseases, such as inflammation.”

https://pubmed.ncbi.nlm.nih.gov/40836986/

“Cannabis has long been used to relieve symptoms such as pain, fever, anxiety, and diarrhea in the context of numerous diseases. Furthermore, cannabis products were reported to reduce inflammatory diseases. Over the past decades, it has been demonstrated that cannabinoids have anti-inflammatory effects, as ascertained by the decrease in the secretion of inflammatory mediators. The human body is subjected to various conditions (stress, autocrine/endocrine changes, exposure to exogenous stimuli, etc.) leading to organ and tissue inflammatory disorders, such as those in the skin and the oral cavity. Such tissue inflammation could be controlled using cannabis products.”

“Altogether, our results demonstrated the possible combination of PVA with PG and VG to generate useful THC-rich hydrogels for cannabinoid delivery. Because THC is lipophilic, our study suggests the possible delivery of THC when in topical contact with the tissues, including skin and oral mucosa, as the cells have lipid-rich membranes. Our THC-rich PVA-PG-VG hydrogels, therefore, may have the potential as a drug carrier for topical use to treat tissue inflammation.”

https://www.frontiersin.org/journals/drug-delivery/articles/10.3389/fddev.2024.1303812/full

Therapeutic potential of cannabinoids for treating atopic dermatitis

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“This review aims to assess the therapeutic potential of cannabinoids as complementary treatments for atopic dermatitis. Atopic dermatitis (AD) is a skin disease characterized by the loss of skin barrier function that promotes subsequent symptoms such as intense itching, xerosis and inflammation. Several treatments are available, particularly topical approaches, which are crucial for both acute and chronic management of the disease.

The main objectives of topical treatments are to promote skin hydration and reduce itching and immune responses, typically through lotions and topical medications such as glucocorticoids. However, the long-term use of glucocorticoids presents certain disadvantages, highlighting the need for new therapeutic options to minimize adverse effects and providing a broader range of choices for both physicians and patients to find the best alternative for each case.

Research involving cannabinoids, which can be endogenous, plant-based or synthetic, has intensified in recent years to evaluate the therapeutic potential of these compounds for skin conditions, including AD. Studies suggest that phytocannabinoids such as cannabidiol (CBD) and Δ-9-tetrahydrocannabinol (THC), along with endogenous and synthetic compounds such as palmitoyletanolamide (PEA) and dronabinol, can improve AD symptoms, primarily because of their anti-inflammatory, antipruritic and antioxidant properties. Additionally, some cannabinoids exhibit antimicrobial effects.

Despite these promising results, the use of cannabinoids in AD treatment requires further investigation to better understand their efficiency and safety, necessitating high-accuracy clinical and preclinical trials.”

https://pubmed.ncbi.nlm.nih.gov/40818974/

“Cannabinoids, whether of plant, endogenous, or synthetic origin, clearly possess significant therapeutic potential and should be further explored as complementary treatments for AD. The development of cannabinoid-based formulations for skin conditions is not limited to products classified as medicines by pharmaceutical regulatory agencies, but also includes their use as active ingredients in cosmetic formulations, such as soaps, shampoos, and especially moisturizing lotions and creams, for individuals with AD and other conditions requiring enhanced skin hydration.

Beyond the therapeutical potential of the classical phytocannabinoids CBD and THC, other components such as CBG and CBC have also been investigated for their dermatological benefits, including anti-inflammatory, antibacterial, and antioxidant properties that may contribute to skin health and the treatment of various skin disorders, including AD .”

https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-025-00317-4

Cannabis for female orgasmic disorder/difficulty: a systematic review

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“Background: Cannabis is increasingly recommended to treat female orgasmic disorder/difficulty (FOD/difficulty), a condition that affects up to 41% of women worldwide with no conventional medications.

Aim: To systematically review the existing literature on cannabis and its impact on female orgasm function.

Methods: A systematic review based on the PRISMA model evaluated the effects of cannabis on orgasm function in females with or without FOD/difficulty. Risk of bias was assessed for randomized and nonrandomized studies. Searches were conducted in PubMed, Google Scholar, Cochrane, and Embase.

Outcomes: Primary outcomes focused on the impact of cannabis on female orgasm function.

Results: Sixteen studies met inclusion criteria: 1 randomized controlled trial and 15 observational studies, including data from 8849 females. Most were nonrandomized designs without comparator groups and high risk of bias. Most included both sexes and reported dichotomized outcomes by sex. None excluded females with self-reported orgasm difficulty; 1 controlled for its prevalence; 1 dichotomized females by the presence or absence of orgasm difficulty; and no studies used a clinical diagnosis of FOD. Nine studies investigated cannabis use prior to sexual activity. All 9 studies cited improvements in female orgasm function, including increases in frequency, ease, intensity, quality, and/or multiorgasmic capacity. However, 1 study found cases of situational anorgasmia, and 1 reported that women had more difficulty with focus, potentially leading to orgasm difficulty. Two studies assessed general cannabis use and sexual function: 1 found no association between the frequency of cannabis use and female sexual problems, while the other noted improved orgasm and reduced dysfunction with more frequent use. Five studies examined cannabis alongside other substances, before sex or not: 1 linked inhibited orgasm to combined cannabis and alcohol use, 1 to noncannabis substances, 2 found improved orgasm function with cannabis, and 1 reported improved orgasm function and cases of inability to orgasm due to a lack of focus.

Clinical implications: Cannabis appears to be a promising treatment option for FOD/difficulty.

Strengths and limitations: This review found consistent evidence that cannabis improves orgasm function in females with or without FOD/difficulty. Limitations include insufficient high-quality studies and limited reporting on cannabis dosage and timing.

Conclusion: FOD/difficulty should be recognized as a qualifying condition for medical cannabis use. Given the existing evidence supporting its potential efficacy, medical cannabis warrants consideration as a first-line treatment. More randomized controlled trials are needed to clarify optimal dosing, routes of administration, strain specificity, timing of use, and differential effects across FOD subtypes.”

https://pubmed.ncbi.nlm.nih.gov/40808870/

“Cannabis appears to be a promising treatment for FOD/difficulty, with the majority of studies reviewed reporting improvements in orgasm function and satisfaction among women who use cannabis. These benefits were observed across diverse study designs, populations, and cannabis use contexts. Given this growing body of evidence, FOD/difficulty should be considered a qualifying condition for medical cannabis, and medical cannabis should be evaluated as a potential first-line treatment. These findings suggest a strong association between cannabis use and improved orgasm function, but further RCTs are needed to establish causality and better define key parameters, such as dosage, route of administration, timing of use, strain specificity, and the differential effects on FOD subtypes.”

https://academic.oup.com/smoa/article/13/4/qfaf061/8232583?login=false

The Endocannabinoid System in PTSD: Molecular Targets for Modulating Fear and Anxiety

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“Fear and anxiety perform essential protective roles, yet when they become dysregulated, they can trap trauma survivors in persistent hypervigilance and distress. Post-traumatic stress disorder (PTSD) manifests as intrusive memories, avoidance, and heightened arousal long after the precipitating event. Although current pharmacotherapies – including selective serotonin reuptake inhibitors, adrenergic blockers, benzodiazepines, and atypical antipsychotics – provide relief for some, many patients contend with residual symptoms or intolerable adverse effects.

Recent discoveries position the endocannabinoid system as a pivotal regulator of fear acquisition, consolidation, and extinction. Clinical observations of altered anandamide levels and cannabinoid receptor CB₁ upregulation in individuals with severe PTSD underscore the therapeutic potential of restoring endocannabinoid tone.

Preclinical studies demonstrate that direct CB₁ agonists, fatty acid amide hydrolase (FAAH) inhibitors, and phytocannabinoids such as tetrahydrocannabinol (THC) and cannabidiol (CBD) can facilitate extinction learning and attenuate anxiety-like behaviours.

Preliminary human trials report that nabilone alleviates trauma-related nightmares and that acute cannabinoid administration modulates amygdala reactivity to a threat. Yet optimal dosing strategies, sex-specific responses, and ideal THC:CBD ratios remain to be defined. Self-medication with cannabis can offer transient relief but carries a risk of cannabis use disorder and potential worsening of PTSD symptoms. By elucidating molecular targets – including CB₁, CB₂, FAAH, and monoacylglycerol lipase – this review outlines a strategic framework for next-generation cannabinoid-based interventions.

Harnessing the endocannabinoid system promises to expand the therapeutic arsenal for PTSD, offering hope for more effective and better-tolerated treatments.”

https://pubmed.ncbi.nlm.nih.gov/40789309/

https://www.thieme-connect.de/products/ejournals/abstract/10.1055/a-2647-8030

α-Glucosidase Inhibitors from the Leaves of Cannabis sativa: Structure-Activity Relationship, Kinetic Investigation, and Molecular Docking

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“Cannabis sativa L. is a valuable agricultural crop, extensively utilized in various fields and comprising diverse chemical constituents. In preliminary experiments for rat intestinal α-glucosidase inhibition, the methanolic extract of Cannabis sativa demonstrated potential for inhibiting maltase and sucrase. Bioassay-guided isolation led to 30 metabolites, including five new cannabinoids (123430) and four new spiroindans (561011). Their structures were elucidated using spectroscopic techniques such as NMR, and absolute configurations were determined by Mosher’s method. Cannabinoids were the main contributors to inhibitory potency (IC50: 0.09-0.8 mM), while spiroindans and simple phenolics showed lower activity (IC50: 1.0-2.2 mM). 8-Hydroxycannabinol (18) was the most potent inhibitor retarding the enzymes through a noncompetitive mechanism. Molecular dynamics simulations of compounds 15 and 18 showed that hydrogen bonding between phenolic hydroxyl groups and specific amino acid residues at the allosteric site was essential for strong α-glucosidase binding.”

https://pubmed.ncbi.nlm.nih.gov/40788893/

“Cannabis sativa L., a member of the Cannabaceae family derived from Western Asia, has been grown for centuries for food, fiber, and medicine.”

“This study reveals that the leaves of Cannabis sativa are a prolific source of α-glucosidase inhibitors with cannabinoids, particularly cannabinol derivatives exhibiting the most pronounced bioactivity.

Among 30 isolated compounds, 8-hydroxycannabinol demonstrated the strongest inhibitory effect, outperforming other cannabinoids through an uncompetitive inhibition mechanism. Structure–activity relationship analysis indicated that additional phenolic hydroxyl groups and extended aromatic rings substantially enhance inhibitory potency.

Molecular docking and molecular dynamics simulations confirmed that active cannabinol derivatives bind stably to an allosteric site on the α-glucosidase enzyme, supported by favorable binding energies and consistent hydrophobic interactions. However, the limited structural diversity of the isolated compounds restricts the full elucidation of SAR trends, underscoring the need for broader analog libraries.

These findings not only highlight the therapeutic potential of C. sativa leaf cannabinoids as natural antidiabetic agents but also lay a foundation for future research. In particular, the semisynthesis of novel cannabinol derivatives via rational modifications such as halogenation or esterification represents a promising strategy to enhance α-glucosidase inhibitory activity and to systematically probe the structure–activity relationship of this pharmacophore class.”

https://pubs.acs.org/doi/10.1021/acs.jafc.5c08443

“Alpha-glucosidase inhibitors are a class of medications used to treat type 2 diabetes by slowing down the digestion and absorption of carbohydrates from the small intestine.”

Lifetime Cannabis Use and Incident Hypertension: The Coronary Artery Risk Development in Young Adults (CARDIA) Study

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“Background: Observational evidence investigating associations between cannabis use and hypertension is inconsistent.

Methods: The association between cumulative lifetime cannabis use (cannabis-years) and incident hypertension was examined over 35 years in a sample of CARDIA study (Coronary Artery Risk Development in Young Adults) participants free of hypertension at baseline. Marginal structural models with inverse probability weighting were used to adjust for potential time-dependent confounding and censoring. Hazard ratios and 95% CIs were estimated using Cox proportional hazards regression. Sensitivity analyses included modeling cannabis-years using restricted cubic splines, stratifying the primary analyses by sex, race, alcohol and cigarette smoking, and evaluating an additional exposure measure (days of use in the past month).

Results: The analytic sample consisted of 4328 participants at baseline and 64.9% (n=2810) at year 35. Median cannabis-years increased minimally and remained low across visits: 0.0 (Q1-Q3, 0.0-0.3) at baseline and 0.2 (Q1-Q3, 0.0-0.7) by year 35. There were 2478 cases of incident hypertension over 88 292 person-years (28.1 cases per 1000 person-years). Cannabis-years were not significantly associated with incident hypertension (adjusted hazard ratio, 0.99 [95% CI, 0.97-1.00]; P=0.18). The association remained unchanged in sensitivity analyses.

Conclusions: In a cohort of Black and White young adults with 35 years of follow-up, no association was found between cumulative lifetime use of cannabis and risk of incident hypertension. This finding was robust to restricted cubic spline analyses, analyses stratified by sex, race, alcohol use and tobacco cigarette smoking, and an additional measure of exposure (days of use in the past month).”

https://pubmed.ncbi.nlm.nih.gov/40785536/

“No association was found between cumulative lifetime use of cannabis, measured as cannabis-years, and incident hypertension over 35 years of follow-up in a cohort of relatively young Black and White adults free of hypertension at baseline. This finding was consistent across sensitivity analyses, including post hoc RCS analyses, analyses stratified by sex, race, alcohol use, and tobacco cigarette smoking, and an alternative measure of cannabis exposure (days of use in the past month).”

“Our findings suggest that cannabis use, even when accumulated over decades, may not independently elevate hypertension risk.”

https://www.ahajournals.org/doi/10.1161/HYPERTENSIONAHA.125.25005

Medical cannabis for the management of pain in chronic pancreatitis with recurrent exacerbations: a case report

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“Introduction: Control of pain in patients affected by chronic pancreatitis with recurrent exacerbations is a challenging condition, with conventional therapies often providing limited relief. This case report describes the use of medical cannabis as a novel approach in a patient with refractory chronic pancreatitis, contributing to the growing interest in alternative treatments for pain and inflammation in similar complex cases.

Case presentation: A 54-year-old woman with a 24-year history of chronic pancreatitis caused by recurrent acute pancreatitis presented with persistent, severe abdominal pain and recurrent exacerbations despite undergoing numerous conventional interventions, including cholecystectomy, enzyme supplementation, repeated endoscopic retrograde cholangiopancreatographies (ERCPs), and stent placements. Imaging and laboratory findings confirmed chronic pancreatitis, with evidence of Oddi sphincter stenosis and microlithiasis. The patient was initially managed with standard pain relief therapy, digestive enzymes, and endoscopic interventions, all of which failed to provide lasting relief. In February 2024, she began treatment with a medical cannabis formulation rich in Cannabidiol, under the supervision of her healthcare provider. This intervention led to substantial pain reduction, cessation of acute episodes, improved appetite, and enhanced quality of life.

Conclusion: This case illustrates that medical cannabis may offer a promising alternative for managing chronic pancreatitis, especially when conventional treatments prove ineffective. This outcome underscores the need for further research on cannabinoids as a therapeutic option in chronic pain and inflammation management for pancreatitis and other challenging conditions.”

https://pubmed.ncbi.nlm.nih.gov/40781340/

“This case illustrates the potential of medical cannabis as an effective treatment option for chronic, treatment-resistant pancreatitis, a condition notoriously difficult to manage with conventional therapies. The patient’s experience demonstrates how cannabinoids can provide substantial pain relief, reduce inflammation, and improve quality of life, even when standard interventions fail to yield lasting benefits. Her case underscores the importance of exploring alternative therapies for complex, chronic conditions like pancreatitis, suggesting that medical cannabis may offer a transformative option for patients with few viable treatment paths.”

https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-025-00303-w

Changes in Local Community Spatial Trends of Motor Vehicle Accidents Near Cannabis Dispensaries after Recreational Cannabis Legalization

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“Introduction: In recent years, the impact of recreational cannabis legalization (RCL) on road safety and motor vehicle accidents (MVAs) has become a growing area of research, given increasing cannabis legalization and the impact of cannabis on motor control and attention. In 2023, Connecticut legalized recreational cannabis, and this study explored changes in MVAs both in a statewide analysis and in the local vicinity of recreational cannabis dispensaries. 

Materials and Methods: We conducted an ecological study to assess the impact of recreational cannabis dispensaries on MVAs in Connecticut after legalization on January 10, 2023. Using crash data from Connecticut and Maryland (as a control) for two 24-week periods before and after legalization, we performed a difference-in-differences analysis with negative binomial regression, controlling confounders. At the dispensary level, we compared MVAs within an 800-m radius 8 weeks before and after opening, employing interrupted time series analysis with negative binomial mixed-effects regression models. 

Results: In the statewide analysis comparing Connecticut with Maryland over two 24-week periods before and after RCL in Connecticut, no significant effect on MVAs was found after adjusting for autocorrelation and seasonal variations (interaction term coefficient = -0.0391, p = 0.0696). In the local analysis, examining accident rates within an 800-m radius of 13 dispensaries over 8 weeks before and after their openings, the negative binomial mixed-effects model showed no significant change (incidence rate ratio = 1.10, 95% confidence interval: 0.74-1.64, p = 0.63). 

Discussion: These findings suggest that cannabis legalization and dispensary openings did not significantly impact motor vehicle accident rates during the study period.”

https://pubmed.ncbi.nlm.nih.gov/40779507/