“Innovative topical drug delivery systems, such as film forming systems, aim, among other objectives, to offer new application possibilities, enhance patient compliance, and provide prolonged therapeutic effects.
This study presents the development and comprehensive characterization of a novel chitosan-based film-forming system incorporating cannabidiol for antimicrobial topical treatment.
While chitosan and cannabidiol have been separately explored for their pharmaceutical properties, their combination within an in situ film-forming matrix remains largely unreported. Chitosan was chosen for its film-forming, mucoadhesive, and inherent antimicrobial properties. Ethanol-water ratios enabling optimal solubilization of chitosan were determined, and a suitable cannabidiol solubilizer was identified to ensure its homogeneous incorporation into the polymer matrix. The resulting films were characterized using differential scanning calorimetry, rheological analysis, Raman spectroscopy, optical microscopy, and scanning electron microscopy.
In vitro studies demonstrated sustained cannabidiol release, favorable mechanical properties, and excellent antimicrobial efficacy against both Gram-positive and Gram-negative bacteria, as well as fungi.
These results highlight the developed film-forming system as a novel and promising platform for the localized treatment of bacterial and fungal skin infections.”
“Wound healing in old mice is characterized by disturbed tissue homeostasis, manifested by delayed immune cell infiltration and reduced growth factor secretion, leading to a delayed onset and prolonged duration of the inflammatory phase.
The endocannabinoid system (ECS) is an important regulator of tissue homeostasis and cell migration and is also considered to be subject to aging processes, which may contribute to observable aging phenomena. Therefore, stimulating the aged ECS could represent a therapeutic option to support tissue regeneration in aging.
Female old mice received a low-dose of medical THC daily for 3 weeks, before four excisional full skin wounds were created. At day 1, 3 and 7 post-surgery, the wound closure rate was analyzed and wound samples were examined immunohistochemically for the numbers of granulocytes, M1-macrophages and mesenchymal stem cells (MSCs). The concentrations of inflammatory cytokines and regenerative growth factors were determined by ELISA.
Administration of THC improved the wound healing rate of old mice between day 1 and 7, which was associated with an altered timing and quantity of infiltrating immune cells and decreased levels of inflammatory cytokines in wound tissue on days 1 and 3 post-injury.
THC treatment significantly increased MSC infiltration but had no effect on the growth factor release.
The present study confirmed the anti-inflammatory activity of THC in vivo.
The THC-treatment improved wound healing in old mice by coordinating the temporal sequence of immune cell infiltration and cytokine release. Thus, restoration of ECS signaling could be an effective strategy to support age-related skin regeneration.”
“Introduction: Among diverse chemical profile of Cannabis sativa L., over 100 phytocannabinoids have been identified. The major cannabinoids ΔΔ -9-THC and CBD are well-studied, with approved palliative and therapeutic applications such as appetite stimulation, antiemetic therapy, pain management and epilepsy treatment. However, ΔΔ -9-THC’s psychotropic effects limit its broader use. Minor cannabinoids exhibit therapeutic promise for a variety of conditions, potentially offering therapeutic potential without the adverse effects of ΔΔ -9-THC.
Methods: We explored 14 cannabinoids with an inverse molecular docking approach, docking each cannabinoid into >50000>50000 human protein structures from the ProBiS-Dock database. We validated our inverse molecular docking protocol using retrospective metrics (ROC AUC, BEDROC, RIE, enrichment factors, total gain). We apply the novel inverse molecular docking fingerprint method to better analyze the binding patterns of different cannabinoids and extend the methodology to include hierarchical clustering of fingerprints.
Results: Our analysis of the inverse molecular docking results identified high scoring targets with potential as novel protein targets for minor cannabinoids, the majority associated with cancer, while others have connections with neurological disorders and inflammation. We highlighted GTPase KRas and hematopoietic cell kinase (HCK) as very promising potential targets due to favorable docking scores with almost all investigated cannabinoids. We also find multiple matrix metalloproteinases among the top targets, suggesting possible novel therapeutic opportunities in rheumatic diseases. An analysis of inverse molecular docking fingerprints shows similar binding patterns for cannabinoids with similar structures, minor structural differences still suffice to change the affinity to specific targets. Hierarchical clustering of inverse molecular docking fingerprints revealed two main clusters in protein binding pattern similarity, the first encompassing THC-class and similar cannabinoids, as well as CBL-class cannabinoids, while the second contained CBD, CBC, and CBG-class cannabinoids. Notably, CBL-class cannabinoids exhibited binding patterns more similar to THC-class cannabinoids than their CBC-class precursors, possibly offering potential therapeutic benefits akin to THC with fewer psychotropic effects.
Discussion: This study highlights the therapeutic potential of minor cannabinoids and identifies their potential novel protein targets. Moreover, we demonstrate the utility of inverse molecular docking fingerprinting with clustering to identify compounds with similar binding patterns as well as identify pharmacophore-related compounds in a structurally agnostic manner, paving the way for future drug discovery and development.”
“We firmly believe that this study provides a springboard paving the way for experimental validations in vitro and in vivo, hopefully leading to novel therapies with cannabinoids.”
“Shrimp aquaculture plays a crucial role in global food production but is increasingly threatened by viral and microsporidian pathogens such as White Spot Syndrome Virus (WSSV), Enterocytozoon hepatopenaei (EHP) and Infectious Hypodermal and Haematopoietic Necrosis Virus (IHHNV). Conventional reliance on antibiotics to combat these infections has raised serious concerns regarding antimicrobial resistance, environmental contamination and food safety. Additionally, environmental stressors such as salinity shifts and poor water quality exacerbate disease outbreaks, leading to severe production losses across Asia and Latin America.
To explore eco-friendly therapeutic alternatives, this study assessed the antiviral potential of cannabidiol (CBD), a bioactive compound extracted from Cannabis sativa seed oil, identified through GC-MS analysis.
Using molecular docking techniques, we evaluated CBD’s interactions with key viral proteins: VP28 of WSSV, the tubulin β-chain of EHP and the capsid protein of IHHNV. The docking results revealed strong binding affinities of -6.61 kcal/mol (EHP), -6.72 kcal/mol (IHHNV) and -5.38 kcal/mol (WSSV), indicating stable and potentially inhibitory interactions. Structural models were retrieved from RCSB PDB and SwissModel, while ligand preparation and docking were performed using AutoDock 4.2.
CBD also demonstrated favourable pharmacokinetic and safety profiles, with predictions indicating no mutagenicity, hepatotoxicity or cardiotoxicity, and acceptable drug-likeness characteristics.
Compared to other plant-derived compounds previously tested in shrimp disease models, CBD exhibited superior binding stability, more interaction residues and better bioavailability scores.
These findings highlight CBD as a promising dual-function agent, capable of both modulating shrimp immunity and directly inhibiting key viral pathogens.
These findings highlight cannabidiol (CBD) as a promising dual-action compound, with the potential to both enhance shrimp immune responses and exert direct antiviral effects against key pathogens. This study lays a robust groundwork for future in vivo validations, formulation strategies and regulatory frameworks, ultimately supporting the development of sustainable, precision-based aquaculture health management.”
“Introduction: On May 21, 2024, the Drug Enforcement Administration (DEA) published a proposed rule to reschedule marijuana from schedule I to III under the Controlled Substance Act (CSA), followed by a 60-day open comment period. The purpose of this study was to analyze the public attitudes regarding the proposed rule and identify trends based on time of comment submission and recurring arguments throughout the comments.
Methods: This was an observational, cross-sectional, mixed-methods study. Comments from the proposal were stratified according to the submission date as early (May 21 to June 11), mid- (June 12 to July 2), and late (July 3-22) respondents. Investigators were assigned an equal number of comments to code as in favor of, against, or no clear position on rescheduling. Comments were further coded based on type of comment (form letters, personal anecdotes), rationale for comment (racism, decriminalization, safety, and economic factors), and whether descheduling was favored. Chi-square tests were used to analyze categorical data. A random sample of comments was selected to assure a 5% margin of error.
Results: More than 42,000 comments were submitted. Of these, 380 comments were selected and coded, with 42% (n = 158) in support of rescheduling, 55% (n = 211) against rescheduling, and 2.9% (n = 11) with no clear position. Of all comments coded, 71% wanted to go further and were in support of descheduling. The early responses consisted of a majority in favor of rescheduling, while the mid- and late responses consisted of more comments against rescheduling (X2 [2, N = 369] = 35.8, p < 0.00001). Of the comments against rescheduling, a large majority supported descheduling (X2 [2, N = 265] = 32.0, p < 0.0001). As for comment structure, 69% (n = 263) of all comments coded were form letters, while 8.4% (n = 32) were personal anecdotes.
Conclusion: The number of comments in support of rescheduling decreased with time, only dominating the early respondent wave. Despite a larger number of negative attitudes toward the DEA’s proposed rule of rescheduling marijuana from schedule I to III, a majority of comments supported taking a step further to deschedule marijuana all together.”
“The study’s findings suggest that future cannabis policy discussions may need to address not just rescheduling, but potentially more far-reaching reforms to align with evolving public sentiment. As the conversation around marijuana regulation continues, policymakers will need to carefully balance public health and safety concerns with growing calls for increased access and reduced criminalization.”
“The rapid emergence of multidrug-resistant (MDR) bacterial pathogens poses a critical threat to global health, creating an urgent need for novel antimicrobial agents.
In this study, we evaluated a small library of natural and semisynthetic phytocannabinoids against a broad panel of MDR Gram-positive bacterial strains, evidencing very good activity in the low µM range.
We provide evidence of the antibacterial activity of the two separated enantiomers of cannabidiol, offering novel insights into the stereochemical aspects of their bioactivity.
To investigate the possible molecular targets and clarify the mechanism of action, we employed Inverse Virtual Screening (IVS), a computational approach optimized for predicting potential protein-ligand interactions, on three selected MDR bacterial species. Interestingly, key targets belonging to important bacterial metabolic pathways and defense mechanisms were retrieved, and the results were used to rationalize the observed biological activities.
To the best of our knowledge, this study marks the first application of IVS to microorganisms, offering a novel strategy for identifying bacterial protein targets. The results pave the way for future experimental validation, structure-based drug design, and the development of novel antibacterial agents.”
“These findings suggest that these phytocannabinoids likely exert their antibacterial effects via multi-target inhibition, interfering with multiple essential bacterial pathways.”
“Recent advances in cannabinoid-based therapies identified the natural CB2 receptor agonist β-caryophyllene (BCP) as a promising anti-inflammatory and neuroprotective agent. To further explore its therapeutic potential on the management of neurodegenerative disorders, in the present study we investigated the ability of BCP to prevent neuroinflammation and promote neuroprotection by using both in vitro and ex vivo models of β-amyloid induced neurotoxicity.
Our data showed that BCP significantly protected human microglial HMC3 cells from Aβ25-35-induced cytotoxicity, reducing the release of pro-inflammatory cytokines (TNF-α, IL-6) while enhancing IL-10 secretion. These effects were associated with a reduced activation of the NF-κB pathway, which emerged as a central mediator of BCP action.
Notably, the use of CB2R- or PPARγ-selective antagonists revealed that the observed NF-κB inhibition by BCP may involve the coordinated activation of both canonical (e.g., CB2R) and non-canonical (e.g., PPARγ) receptors. Moreover, BCP restored the expression of SIRT1, PGC-1α, and BDNF, indicating the involvement of neurotrophic pathways.
Clear neuroprotective properties for BCP have been highlighted in Aβ1-42-treated brain slice preparations, where BCP demonstrated the rescue of both the amyloid-dependent depression of BDNF expression and long-term synaptic potentiation (LTP) impairment.
Overall, our results suggest that BCP constitutes an attractive natural molecule for the treatment of Aβ-induced neuroinflammation and synaptic dysfunction, warranting further exploration for its clinical application.”
“In conclusion, the results of our study suggest a pleiotropic mechanism of action for the development of BCP neuroprotective effects in relation to amyloid-induced neuroinflammation and synaptic impairment, encouraging further investigations into an in vivo model of amyloid-dependent cognitive damage to clarify the exact mechanism of action of BCP and confirm whether this natural molecule may represent a novel option for the treatment of NDDs.
Furthermore, the potent anti-inflammatory effects exerted by BCP through the interaction of CB2 and PPARγ receptors support the therapeutic potential of BCP in a broad range of conditions, including neurodegenerative and metabolic diseases, neuropathic pain, and cancer. Taking into consideration the safety of BCP in humans, dietary use, and its efficacy in various experimental models of disease, BCP may be further explored as co-supplementary drug in experimental studies.”
“β-caryophyllene (BCP) is a common constitute of the essential oils of numerous spice, food plants and major component in Cannabis.” http://www.ncbi.nlm.nih.gov/pubmed/23138934
“Alcohol use disorder (AUD) remains a pervasive public health issue with limited effective treatments. Cannabidiol (CBD), a non-psychotropic constituent of cannabis, shows promise in modulating addictive behaviors.
This study investigated the effects of chronic CBD administration on alcohol dependence, withdrawal symptoms, and neurodegeneration using two complementary rodent models: chronic intermittent ethanol (CIE) exposure, which models established alcohol dependence, and ethanol vapor self-administration (EVSA), which captures the volitional aspects of alcohol intake. In the CIE model, CBD reduced alcohol self-administration during acute withdrawal without affecting alcohol metabolism or locomotor activity.
CBD decreased motivation for alcohol, somatic withdrawal signs, withdrawal-induced anxiety-like behaviors, and mechanical sensitivity. During extinction, CBD attenuated alcohol-seeking behavior and stress-induced reinstatement. Electrophysiological recordings revealed that CBD reversed alcohol-induced decreases in neuronal excitability in the basolateral amygdala, suggesting a mechanism involving normalization of neural function. In the EVSA model, CBD reduced voluntary alcohol intake during the escalation phase, impacting voluntary alcohol intake. This effect was specific to alcohol-related behaviors, as it did not affect saccharin self-administration.
Immunohistochemical analyses showed that CBD prevented alcohol-induced neurodegeneration in the nucleus accumbens shell and dorsomedial striatum, regions implicated in the volitional control of alcohol consumption. These findings indicate that chronic CBD administration attenuates both behavioral and neurobiological facets of alcohol dependence by modulating neuronal excitability and preventing neurodegeneration, supporting its therapeutic potential for AUD and providing mechanistic insights for future research.”
“In conclusion, chronic CBD administration mitigates key behavioral and neurobiological features of alcohol dependence by reducing withdrawal symptoms, lowering relapse risk, restoring BLA neuronal excitability, and preventing neurodegeneration in striatal regions. Together, these findings highlight CBD’s capacity to preserve functional integrity in neural circuits underlying emotional regulation, reward processing, and habit formation.”
“Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age, with an estimated prevalence of 10%–15%.1 In addition to its reproductive features, that is, hyperandrogenism, anovulation, and polycystic ovarian morphology, PCOS is strongly associated with metabolic disturbances, including obesity, insulin resistance and an elevated risk of metabolic associated steatotic liver disease (MASLD).1 These complications not only worsen the quality of life but also increase long-term morbidity and mortality of women living with PCOS. The coexistence of these metabolic traits complicates clinical management and increases the risk of developing type-2 diabetes and cardiovascular diseases.
Lifestyle modifications are considered first-line interventions in PCOS, but they frequently fail to achieve sustained weight loss or ideal metabolic control, particularly in patients with pronounced hormonal perturbations (e.g., persistent hyperandrogenism) or psychological distress. Pharmacological approaches, such as metformin and GLP-1 receptor agonists, are currently used to handle metabolic complications, but they have limitations regarding efficacy, tolerability and/or accessibility, and are not universally approved for management of PCOS. Moreover, these treatments might overlook the inflammatory and fibrotic dimensions of PCOS, which are increasingly recognized as central contributors to its pathogenesis.
Cannabidiol (CBD), a non-psychotropic phytocannabinoid from Cannabis sativa,5 has garnered attention due to its anti-inflammatory, antioxidant and metabolic regulatory properties. Preclinical studies suggest that CBD acts as a negative allosteric modulator of the cannabinoid CB1 receptor (CB1R),6 and engages additional targets, such as PPARγ7 and the Nrf2 signalling pathway.8 Given these pleiotropic actions, CBD represents an attractive candidate for addressing the complex metabolic profile of PCOS. In this study, we evaluated the metabolic and hepatic effects, including proteomic profiles, of CBD in a validated murine model of PCOS associated with androgenic obesity (AO),9 aiming to provide insights into its therapeutic potential and underlying mechanisms of action.”
“This study provides compelling preclinical evidence that CBD exerts broad metabolic benefits in a murine model of PCOS with androgenic obesity. Treatment with CBD led to significant reductions in weight gain, adiposity, insulin resistance, indices of hepatic fibrosis and systemic inflammation, with prominent favourable actions on MASLD traits. Liver proteomic and circulating biomarker analyses strongly supported the reprogramming of disease-associated molecular pathways caused by CBD, underscoring its potential to mitigate the multifactorial pathophysiology of PCOS.”
“Endocannabinoid system is an important contributor to body’s immune responses which are significantly impaired by chronic sleep deprivation (cSD). Although cannabinoids can modulate the endocannabinoid system, most are understudied, especially regarding cSD.
To investigate the therapeutic potential of CBD, CBG, CBC and their combinations, current study analyzed cSD-induced memory impairment, depression, microglial responses, cytokine profile and therapeutic effects of cannabinoid treatments using behavioral test and ELISA. Furthermore, molecular docking of these cannabinoids was performed to deduce the binding affinity with cannabinoid receptors and possible entrouge effects.
The results showed that memory impairment and depression were more evident in cSD groups. Moreover, microglial activation and pro-inflammatory polarization was also more evident and was supported by increased pro-inflammatory cytokine concentrations in cSD groups.
These changes were significantly reversed the cannabinoid groups but the combination of CBD + CBC was more effective than other treatments in reversing these cSD-induced behavioral and neuroinflammatory changes. Whereas, the molecular docking results also corroborated with the neuroimmunological changes observed in the current study, pointing towards the possible therapeutic role.
SIGNIFICANCE STATEMENT: Chronic SD employs microglial activation/polarization, to exert behavioral impairments and neuroinflammation.
This study signifies the therapeutic potential of proper sleep and cannabinoid intake.”
“This study demonstrates the therapeutic efficacy of cannabinoid treatments in ameliorating cSD-induced behavioral and neuroinflammatory alterations. Notably, a multiple-compound treatment of CBD and CBC exhibited superior effectiveness compared to single-compound treatments. These findings suggest potential avenues for developing effective interventions against cSD-induced detrimental changes.”
