Permeability of active ingredients of cannabis and possibility for further antituberculosis drug development

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“Background

Cannabis is presently legalized in several countries owing to its medicinal property. The antibacterial properties of active ingredients of cannabis have been mentioned. Their usefulness in the management of tuberculosis is very interesting.

Materials and methods 

The authors performed a bioinformatics analysis to assess the possibility of important active ingredients of cannabis.

Results 

Based on the present analysis, it can be seen that the studied active ingredients of cannabis can effectively pass through the cell wall of Mycobacterium tuberculosis, indicating the possibility of further pharmacological actions.

Conclusion 

The active ingredients of cannabis are the possible new targets for further antituberculosis drug development.”

“Cannabis is presently legalized in several countries owing to its medicinal properties[3]. The antibacterial property of active ingredients of cannabis is mentioned. Their usefulness in management of tuberculosis is very interesting. In the present study, the authors studied the permeability of active ingredients detectable in cannabis. The studied ingredients are the important main ingredients including tetrahydrocannabinol (THC) and cannabidiol (CBD)[4]. The study is a useful basic study for further antituberculosis drug search.”

“Here, it can be shown that the studied active ingredients of cannabis have the possibility to pass into the mycobacterial cell. Difference in permeability based on the size of the ingredients can be observed. Of interest, it can confirm the previous reports that the Mycobacteria can cause biotransformation of CBD[9], delta-8-THC[9], and delta-9 THC[10]. This observation can show that CHD, delta-8-THC, and delta-9 THC can be a further target for antituberculosis drug development. The three studied main active ingredients of cannabis are reported for bactericidal activity for some gram-positive bacteria.”

“The present study is a medical pharmacoinformatics study. It can confirm that the active ingredients of cannabis are the possible new targets for further antituberculosis drug development.”

https://journals.lww.com/ecdt/fulltext/2021/70030/permeability_of_active_ingredients_of_cannabis_and.3.aspx

Molecular Mechanisms Underlying Neuroinflammation Intervention with Medicinal Plants: A Critical and Narrative Review of the Current Literature

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“Neuroinflammation is a key factor in the progression of neurodegenerative diseases, driven by the dysregulation of molecular pathways and activation of the brain’s immune system, resulting in the release of pro-inflammatory and oxidative molecules. This chronic inflammation is exacerbated by peripheral leukocyte infiltration into the central nervous system.

Medicinal plants, with their historical use in traditional medicine, have emerged as promising candidates to mitigate neuroinflammation and offer a sustainable alternative for addressing neurodegenerative conditions in a green healthcare framework.

This review evaluates the effects of medicinal plants on neuroinflammation, emphasizing their mechanisms of action, effective dosages, and clinical implications, based on a systematic search of databases such as PubMed, SCOPUS, and Web of Science.

The key findings highlight that plants like Cleistocalyx nervosum var. paniala, Curcuma longa

Cannabis sativa,

and Dioscorea nipponica reduce pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β), inhibit enzymes (COX-2 and iNOS), and activate antioxidant pathways, particularly Nrf2. NF-κB emerged as the primary pro-inflammatory pathway inhibited across studies. While the anti-inflammatory potential of these plants is significant, the variability in dosages and phytochemical compositions limits clinical translation.

Here, we highlight that medicinal plants are effective modulators of neuroinflammation, underscoring their therapeutic potential. Future research should focus on animal models, standardized protocols, and safety assessments, integrating advanced methodologies, such as genetic studies and nanotechnology, to enhance their applicability in neurodegenerative disease management.”

https://pubmed.ncbi.nlm.nih.gov/39861194/

“Addressing neuroinflammation to reduce disease severity and improve patient outcomes is a promising strategy against neurodegeneration. From a molecular perspective, there are several conventional drug targets for neuroinflammation, such as enzymes, receptors, and ion channels. However, the high cost of synthetic drugs presents a challenge, emphasizing the need for alternative approaches. This has heightened interest in naturally occurring medicinal plants known for their antioxidant, anti-inflammatory, and neuroprotective properties. These plants are often more cost-effective and have been safely utilized in treatments for thousands of year.”

https://www.mdpi.com/1424-8247/18/1/133

Optimization and Evaluation of Cannabis-Based Magistral Formulations: A Path to Personalized Therapy

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“Introduction: The official implementation of pharmaceutical-grade cannabis raw materials for medicinal use has permitted doctors to prescribe and pharmacists to prepare cannabis-based formulations. The objective of the pharmaceutical development and manufacturing process optimization work was to propose a suppository formulation containing doses of 25 mg and 50 mg of tetra-hydrocannabinol (∆-9-THC) as an alternative to existing inhalable or orally administered formulations. The formulation could be used for rectal or vaginal administration, thereby providing dosage control in the treatment of endometriosis and other conditions involving pain. In this study, two substrates from suppositories with standardized Cannabis extractum normatum (CEX) were used: cocoa butter and Witepsol® H15.

Materials and methods: The long-term stability of CEX was investigated over a period of up to 24 months. The concentrations of ∆-9-THC, cannabidiol (CBD), and cannabinol (CBN) were determined using an HPLC method. Furthermore, the water content of the extract, the ethanol residue, and the microbiological purity were determined. The pharmaceutical properties of CEX-incorporated suppositories, namely content uniformity, hardness, softening time, total deformation time, disintegration time, and the release profile of ∆-9-THC, CBD, and CBN, were evaluated in order to develop optimal preparation procedures for pharmacists.

Results and discussion: Following a 24-month stability study on CEX, no significant alterations in component content were observed beyond the specified requirements. The disintegration time, total deformation time, and hardness of the suppositories based on Witepsol® H15 with CEX were found to be longer and higher, respectively, than those of suppositories formulated with cocoa butter. In vitro studies demonstrated that suppositories prepared with Witepsol® H15 exhibited superior release of ∆-9-THC compared to those prepared with cocoa butter.

Conclusions: We suggest that pharmacists making prescription drugs in a pharmacy setting in the form of medical marijuana suppositories will receive a better release profile of the drug by choosing Witepsol® H15 as a substrate.”

https://pubmed.ncbi.nlm.nih.gov/39861136/

https://www.mdpi.com/1424-8247/18/1/73

Anti-Inflammatory Effects of Cannabigerol In Vitro and In Vivo Are Mediated Through the JAK/STAT/NFκB Signaling Pathway

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“Cannabinoid compounds have potential as treatments for a variety of conditions, with cannabigerol (CBG) being known for its anti-inflammatory properties.

In this study, we investigated the effects of CBG in a cellular model of 1-chloro-2,4-dinitrobenzene (DNCB)-induced atopic dermatitis (AD).

In the cellular model, we confirmed the cytotoxicity of CBG and downregulated the expression of inflammatory markers CCL26IL1BIL6, and TNF (p < 0.001). In the mouse model, clinical, histological, and immunological changes were analyzed.

The results showed that CBG improved dermatitis severity score, epidermal thickness, and mast cell count and reduced inflammatory cytokines (TslpIl1bIl4Il6Il13Il17Il18Il22, and Il33) by qRT-PCR (p < 0.001). Western blot results showed modulated changes in JAK1, JAK2, TYK2, STAT1, STAT2, STAT3, p-STAT3, STAT6, and p-STAT6 (p < 0.05). Subsequently, p-IκBα, NF-κB, and p-NF-κB signaling factors were also reduced (p < 0.05), with corresponding changes in skin barrier factors.

The results of this study indicate that CBG effectively alleviates AD-like symptoms and suggest the potential of CBG as a therapeutic agent.”

https://pubmed.ncbi.nlm.nih.gov/39851511/

https://www.mdpi.com/2073-4409/14/2/83

Unveiling Cannabinoids and Terpenes Diversity in Cannabis sativa L. from Northern India for Future Breeding Strategies

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“Cannabis sativa L. is an important medicinal plant with high commercial value.

In recent years, the research interest in cannabidiol (CBD) and terpene-rich cannabis has been rapidly expanding due to their high therapeutic potential.

The present study aims to explore the phytocannabinoids and terpenes diversity in Cannabis sativa collected from different parts of northern India.

Our findings revealed that the cannabinoids and terpenes synthesize together in capitate stalked and capitate sessile glandular trichomes, whereas bulbous glands synthesize only terpenes. The North Indian C. sativa is mainly dominated by tetrahydrocannabinol (THC). The CBD-rich plant diversity is nominal (1.11%) in studied north Indian C. sativa. The essential oil profiling reveals (E)-caryophyllene (10.30-36.80%) as the major constituent, followed by α-humulene (0.50-15.29%) and α-bisabolol (0.00-16.40%) in the North Indian population.

The cannabinoids and terpenes content showed significant diversity among and within the five studied populations. The correlation analysis between cannabinoids and terpenes indicates that α-pinene, β-pinene, and limonene positively correlated with CBD content. Similarly, α- and β-selinene correlate positively with tetrahydrocannabinolic acid (THCA) content. This study could help to identify the key cultivars from India and establish a consistent chemotype for future breeding programs.”

https://pubmed.ncbi.nlm.nih.gov/39853702/

https://onlinelibrary.wiley.com/doi/10.1002/cbdv.202402278

Oral cannabidiol did not impair learning and memory in healthy adults

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“Background: The effect of oral Cannabidiol (CBD) on interference during learning and memory (L&M) in healthy human volunteers has not been studied.

Method: A two-arm crossover, randomized, double-blind, placebo-controlled trial was conducted at Colorado State University Pueblo (CSU Pueblo) to evaluate the effects of 246 mg oral CBD on L&M in healthy adults. Among 57 healthy volunteers enrolled, 35 were included in the analyses. For assessment of L&M, Montreal Cognitive Assessment (MOCA) was used to evaluate verbal baseline cognitive function; RAVLT-R tests (List A and List B recalls, Proactive and Retroactive Interference ratios, and Forgetting Speed ratio) were used to evaluate verbal declarative memory; and total prose recall was used to evaluate verbal logical memory. Linear Mixed Models with Bonferroni Corrections were used to compare L&M results between primary outcomes (CBD vs. placebo) and secondary demographic outcomes, with a two-tailed statistical significance of P < 0.05.

Results: CBD administration did not affect any of the dependent variables measured compared to the placebo group. There were no effects of THC, history of CBD use, or sex on CBD’s modulation of L&M. However, a highly significant interaction effect between treatment groups (CBD vs. placebo) and age of subjects was observed for the PI ratio (P = 0.008; n = 35).

Conclusions: The results of this study suggest that administration of oral CBD alone does not significantly impair L&M in healthy adults. However, age might influence CBD related modulation of proactive interference during human L&M. Future research involving a larger group of older adults is needed to confirm this potential effect.”

https://pubmed.ncbi.nlm.nih.gov/39849639/

https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-025-00262-2

Mechanisms and strategic prospects of cannabinoids use: Potential applications in antimicrobial food packaging-A review

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“This review focuses on antimicrobial packaging for food safety, critically examining the activity and efficacy of cannabinoids against commonly found microorganisms and exploring their antimicrobial mechanisms.

Specifically, the review considers cannabinoids derived from industrial hemp plants, which are characterized by low levels of psychoactive components. It also outlines viable strategies to control the sustained release of cannabinoids from the packaging, enabling extended storage and enhanced safety of food products.

Research demonstrates that cannabinoids are effective against both foodborne bacteria and fungi, with their antimicrobial action primarily attributed to microbial membrane instability.

Cannabinoids can be utilized to prepare effective antimicrobial films and edible coatings; however, the number of studies in this area remains limited.

The potential of cannabinoids to contribute to intelligent packaging systems is also discussed, with an emphasis on the regulatory aspects and challenges associated with incorporating cannabinoids into food packaging. Finally, the review identifies future research directions to address current limitations and advance hemp-based antimicrobial food packaging solutions.”

https://pubmed.ncbi.nlm.nih.gov/39840610/

https://ift.onlinelibrary.wiley.com/doi/10.1111/1541-4337.70113

Therapeutic potential of cannabidiol polypharmacology in neuropsychiatric disorders

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“Cannabidiol (CBD), the primary non-intoxicating compound in cannabis, is currently approved for treating rare, treatment-resistant seizures.

Recent preclinical research suggests that CBD’s multifaceted mechanisms of action in the brain, which involve multiple molecular targets, underlie its neuroprotective, anti-inflammatory, anxiolytic, and antipsychotic effects. Clinical trials are also exploring CBD’s therapeutic potential beyond its current uses.

This review focuses on CBD’s polypharmacological profile and discusses the latest preclinical and clinical findings regarding its efficacy in neuropsychiatric disorders.

Existing evidence suggests that CBD’s ability to modulate multiple signaling pathways may benefit neuropsychiatric disorders, and we propose further research areas to clarify its mechanisms, address data gaps, and refine its therapeutic indications.”

https://pubmed.ncbi.nlm.nih.gov/39837749/

https://www.cell.com/trends/pharmacological-sciences/fulltext/S0165-6147(24)00271-2?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0165614724002712%3Fshowall%3Dtrue

Exploring the antifungal potential of Cannabis sativa-derived stilbenoids and cannabinoids against novel targets through in silico protein interaction profiling

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“Cannabinoid and stilbenoid compounds derived from Cannabis sativa were screened against eight specific fungal protein targets to identify potential antifungal agents.

The proteins investigated included Glycosylphosphatidylinositol (GPI), Enolase, Mannitol-2-dehydrogenase, GMP synthase, Dihydroorotate dehydrogenase (DHODH), Heat shock protein 90 homolog (Hsp90), Chitin Synthase 2 (CaChs2), and Mannitol-1-phosphate 5-dehydrogenase (M1P5DH), all of which play crucial roles in fungal survival and pathogenicity.

This research evaluates the binding affinities and interaction profiles of selected cannabinoids and stilbenoids with these eight proteins using molecular docking and molecular dynamics simulations. The ligands with the highest binding affinities were identified, and their pharmacokinetic profiles were analyzed using ADMET analysis. The results indicate that GMP synthase exhibited the highest binding affinity with Cannabistilbene I (-9.1 kcal/mol), suggesting hydrophobic solid interactions and multiple hydrogen bonds. Similarly, Chitin Synthase 2 demonstrated significant binding with Cannabistilbene I (-9.1 kcal/mol). In contrast, ligands such as Cannabinolic acid and 8-hydroxycannabinolic acid exhibited moderate binding affinities, underscoring the variability in interaction strengths among different proteins.

Despite promising in silico results, experimental validation is necessary to confirm therapeutic potential. This research lays a crucial foundation for future studies, emphasizing the importance of evaluating binding affinities, pharmacokinetic properties, and multi-target interactions to identify promising antifungal agents.”

https://pubmed.ncbi.nlm.nih.gov/39834844/

“This study provides a comprehensive assessment of how selected cannabinoid and stilbenoid compounds interact with eight different fungal proteins, highlighting the promising potential of these compounds as antifungal agents. In conclusion, this study highlights the therapeutic potential of cannabinoids and stilbenoids and provides a solid foundation for the development of new antifungal therapies.”

https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2024.1515424/full

Investigation of Cannabidiol’s Protective Effects on Cadmium-Induced Toxicity in Mice

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“Current chelation treatments used for cadmium poisoning may cause some serious side effects. Thus, safer novel treatments could be promising for clinical use.

This study evaluated the effects of cannabidiol on Cd toxicity.

Four groups of 10 mice were formed: Groups I and III were cadmium-free, while groups II and IV received 50 mg/L cadmium in drinking water. Groups III and IV received daily cannabidiol (25 mg/kg) via intragastric gavage. After 30 days, the animals were killed, and blood and tissue samples were collected. Oxidative stress and inflammation markers, including glutathione, catalase, myeloperoxidase, TNF-α, IL-1β and IL-6, were analysed using ELISA. Additionally, histological evaluations of the liver, kidney and testis were performed. Cadmium exposure reduced glutathione and catalase levels in the blood, liver, kidney and testis, while increasing myeloperoxidase.

Cannabidiol mitigated these effects on oxidative stress markers. Cannabidiol also reduced the increase in proinflammatory cytokines. Histopathological analysis revealed reduced liver and kidney damage in cannabidiol-treated groups compared to cadmium-only groups. In addition, histopathological evaluation showed CBD had no protective effect on the testicular tissue against Cd toxicity.

Our results indicate that cannabidiol protects against some toxic effects of cadmium. If confirmed by future studies, cannabidiol may be proposed as a novel treatment for cadmium toxicity.”

https://pubmed.ncbi.nlm.nih.gov/39832793/

“Cadmium (Cd) is a heavy metal that can have toxic effects on multiple organs. Chelation treatments that are used for treating Cd toxicity can have serious side effects, which limit their use. This study aimed to investigate cannabidiol (CBD), a non-psychoactive compound derived from hemp, for its potential to reduce Cd toxicity.

Our experiments on mice showed CBD had significant protective effects against Cd-induced tissue damage in the liver and the kidneys by reducing oxidative stress and inflammation. These findings suggest that CBD can be explored as a safer treatment option for Cd toxicity in a clinical setting.”

https://onlinelibrary.wiley.com/doi/10.1111/bcpt.14131