Category Archives: Uncategorized

The Development and Therapeutic Potential of Classical and Next-Generation Cannabinoid Ligands

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“The endogenous cannabinoid system (ECS) is a complex network that plays a crucial role in various physiological processes, and its modulation through cannabinoid ligands has garnered significant interest in pharmacological research.

Cannabinoid receptors, primarily CB1 and CB2, are G-protein-coupled receptors that can interact with many different types of ligands, including orthosteric agonists and antagonists and allosteric and biased modulators.

This review provides an updated perspective on cannabinoid receptor ligand development, beginning with natural ligands such as phytocannabinoids and endocannabinoids. These compounds provided the initial inspiration for the design of the first synthetic classical cannabinoids which were later refined into structurally distinct non-classical cannabinoids.

Beyond these traditional orthosteric ligands, we explore the expanding field of allosteric and biased modulators, which offer refined control over receptor signaling and present opportunities to reduce side effects associated with direct receptor activation. We also highlight the significance of covalent ligands and labeled chemical probes in elucidating cannabinoid receptor structure, localization, and function.

Advances in imaging and chemoproteomic techniques have further enhanced our ability to visualize receptor dynamics and identify novel interaction partners. Finally, we examine the clinical landscape of cannabinoid-based therapeutics, from approved drugs to ongoing clinical trials, and discuss the remaining challenges and future directions in ECS-targeted drug development.

This review aims to provide a comprehensive overview of current trends and emerging strategies in cannabinoid ligand research.”

https://pubmed.ncbi.nlm.nih.gov/41192631/

“The endogenous cannabinoid system has broad therapeutic relevance. “

“Natural and synthetic cannabinoids finely regulate the endogenous cannabinoid system.”

https://www.sciencedirect.com/science/article/pii/S1043661825004475?via%3Dihub

Therapeutic Potential of Cannabidiol in Dentistry: A Systematic Review From Cellular Mechanisms to Clinical Trials

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“Background: CBD holds substantial promise in medical applications. This review aims to comprehensively analyse the current status of cannabidiol (CBD) in dentistry.

Methods: A systematic search of databases including PubMed-MEDLINE, Scopus, Embase, Cochrane Library, World Intellectual Property Organization (WIPO), European Patent Office (EPO), and the United States Patent and Trademark Office (USPTO) was conducted. Peer-reviewed journal manuscripts focusing on cell studies, clinical trials, and registered patents related to CBD and its derivatives in dentistry were summarised. Inclusion criteria were studies on CBD in dentistry, including original research and patents, published in English between 2013 and mid-2023 (articles) or early 2024 (patents), with full-text availability. Excluded were non-dentistry studies, unpublished or non-peer-reviewed reports, and duplicates using Microsoft Excel. The risk of bias was evaluated using the Cochrane RoB 2 tool. Two observers independently screened the articles for inclusion in the present study to mitigate bias. Cohen’s kappa was used to measure inter-rater agreement.

Results: The total number of included studies was 57. Cell-based studies demonstrated CBD’s effectiveness in modulating cellular responses and anti-inflammatory properties, especially in oral-origin cells, and its impact on osteogenic differentiation. Research, including clinical trials and patents, has shown CBD’s benefits in treating pain and inflammation in the maxillofacial area, notably in conditions such as radiation-induced mucositis. CBD research in dental pain and inflammation is advanced, but studies on CBD’s role in regenerative dentistry remain limited.

Conclusion: More studies on the mineralisation of oro-facial structures are necessary to fully understand CBD’s role in regenerative dentistry. This study was supported by the Faculty of Dentistry, Chulalongkorn University. This study was registered in the PROSPERO (ID: CRD4201055832) and Open Science Framework (OSF) database (osf.io/z3bd8). The PRISMA guideline was followed to include the relevant full-text papers.”

https://pubmed.ncbi.nlm.nih.gov/41194764/

https://onlinelibrary.wiley.com/doi/10.1111/jop.70081

History of cannabis use and cognitive function in older adults: findings from the UK biobank

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“Background: Cannabis is a commonly used psychoactive drug, but its cognitive effects remain unclear, particularly in older adults. This study examined associations between past and present cannabis use and cognitive function among dementia-free older adults.

Methods: Cross-sectional and longitudinal data were drawn from the UK Biobank, including adults aged ≥60 years. Cannabis use patterns were self-reported, and cognitive function was assessed via computerized tests of attention, executive function, processing speed, visual memory and working memory. Multivariable linear regression models adjusted for demographic, health and lifestyle-related covariates.

Results: Cross-sectional analyses included 67 713 participants; longitudinal analyses included 52 002 participants with two cognitive assessments (mean age 67.2 ± 4.4 years; 46.1% male). Lifetime cannabis users (17%) performed better across all cognitive domains: attention (B = 0.071), executive function (B = 0.047), processing speed (B = 0.363), visual (B = 0.062) and working memory (B = 0.181). Current use was associated with better working memory (B = 0.169). Mixed and contradictory results were found for early onset, duration and frequency of use with cognitive outcomes. Longitudinally, past use was associated with less decline in executive function, while longer duration of use predicted steeper decline in processing speed.

Conclusions: Cannabis use is not uniformly harmful to cognition in older adults. Past use was linked to better performance and slower decline in some cognitive domains. However, specific usage patterns, such as longer duration, were associated with poorer outcomes in other domains. These findings highlight the need for further research to clarify underlying mechanisms and guide evidence-based recommendations regarding cannabis use in aging populations.”

https://pubmed.ncbi.nlm.nih.gov/41189327/

“Cannabis use in older adults is not uniformly associated with cognitive decline; former users showed better cognitive perform.”

“These results offer preliminary evidence that cannabis use may not be uniformly detrimental to cognitive health in aging.”

https://academic.oup.com/ageing/article/54/11/afaf319/8313927?login=false

The Therapeutic Potential of Cannabidiol in Skin Conditions

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“Background: Dermatological disorders can have a negative impact on quality of life. Cannabidiol (CBD) is a phytocannabinoid found in the Cannabis sativa L. plant. It has multiple molecular targets, many of which are expressed in the skin, and may have therapeutic potential in several skin conditions.

Aims: This review aims to provide an overview of preclinical and clinical studies of CBD in dermatological disorders.

Methods: Literature searches were conducted using databases including PubMed and Google Scholar using the search terms: (‘cannabidiol’ OR ‘CBD’) AND ‘skin’, ‘acne’, ‘psoriasis’, ‘dermatitis’, and ‘wound healing’. Studies were included if they were original research articles focused on CBD and skin conditions.

Results: Preclinical evidence suggests that CBD may have therapeutic potential for the treatment of a variety of skin conditions, while evidence for skin moisturizing properties suggests possible cosmetic benefits. To date, there is limited clinical evidence that CBD may be beneficial in the treatment of acne, dermatitis, and psoriasis, as well as for cosmetic purposes including improving skin hydration, elasticity, and protection against skin aging.

Conclusions: There is some evidence indicating the therapeutic potential of CBD for a variety of skin conditions, including acne, dermatitis, and psoriasis, and possible utility for cosmetic purposes. Several clinical trials involving the topical application of CBD for skin conditions are currently ongoing, and the results of these trials will be important in determining the therapeutic potential of CBD.”

https://pubmed.ncbi.nlm.nih.gov/41178006/

“CBD may have therapeutic potential for the treatment of a variety of skin conditions such as acne, psoriasis, and dermatitis, with its anti-inflammatory, antimicrobial and potential anti-pruritic effects.”

https://onlinelibrary.wiley.com/doi/10.1111/jocd.70527

Selective activation of cannabinoid receptors by cannabis terpenes

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“Terpenes are aromatic compounds abundantly present in plants, including cannabis. Emerging preclinical and clinical evidence indicates that certain terpenes exhibit pharmacological effects in various physiological and psychological conditions. Yet, their molecular mechanisms of action, particularly in cannabis preparations, remain poorly understood.

We have previously reported results of activating cannabinoid receptor type 1 (CB1R) by several terpenes that are most common in cannabis. Here we employed the same Xenopus oocytes functional heterologous expression system to complement the CB1R data and to study the activation of the cannabinoid receptor type 2 (CB2R) by sixteen individual cannabis terpenes and by terpene mixtures.

Employing receptor- induced GIRK currents as a measure for receptor activation, dose-dependent responses were found for many of these terpenes, reaching a maximal response of about 10-60 % the activation elicited by THC. Terpenes’ apparent EC50 at CB1R and CB2R were similar to, or lower than those obtained for THC at the same apparatus, suggesting lower efficacy but equivalent or even improved potency. At CB2R, multiple terpenes reach ‘clinical effect level’ at concentration equivalent or lower than those of THC (≥ 0.1 µM). Per a given receptor, terpenes differ in their activation level. Additionally, terpenes act differently at the two receptors, giving room for receptor selectivity.

Our results support the role of cannabis terpenes as partial agonists at CB1R and CB2R and provide the basis for selecting terpenes or terpene mixture for affecting physiological functions involving these receptors. These results may further contribute to our understanding of terpenes’ medicinal effects.”

https://pubmed.ncbi.nlm.nih.gov/41173057/

“Terpenes, a vast and chemically diverse class of organic compounds, are widely recognized for imparting characteristic aromas and flavors to plants, including Cannabis sativa. More than 200 terpenes have been identified in the cannabis plant, with approximately 20 being the most prevalent, including myrcene, limonene, pinene, linalool, terpinolene, β-caryophyllene, and humulene.”

“Collectively, these findings suggest a pharmacological basis for incorporating specific terpenes into ECS-focused product design and warrant further research into their tissue-specific activity, and synergistic potential when used in combination with cannabinoids or other therapeutic agents. The broad availability and favorable safety profiles of many terpenes further support their potential as accessible, scalable, and customizable tools in the modulation of endocannabinoid signaling.”

https://www.sciencedirect.com/science/article/pii/S0006295225007634?via%3Dihub

Hemp seed protein exerts its hypoglycemic and hypolipidemic effects through degradation into short peptides

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“This study aimed to investigate the effects of hemp seed protein (HSP) on glucose and lipid metabolism and its possible mechanisms.

In a high-fat-induced mouse obesity model, HSP supplementation significantly reduced serum TC (Total cholesterol), TG (Triglycerides), and LDL-C (Low-density lipoprotein cholesterol) levels by 28 % (P < 0.001), 34 % (P < 0.001), and 40 % (P < 0.001) respectively, compared to the model group, while HDL-C (High-density lipoprotein cholesterol) increased by 77 % (P < 0.001).

Hepatic lipid accumulation was alleviated, and glucose tolerance and insulin sensitivity improved. In vitro, HSP hydrolysates exhibited stronger inhibitory activity against pancreatic α-amylase and lipase than HSP itself. Network pharmacology and molecular docking identified three hemp seed peptides from HSP hydrolysates, which interacted with AKT1, PPARG, and HMGCR.

These findings suggest that the metabolic regulatory effects of HSP are mediated by bioactive peptides that inhibit digestive enzymes and regulate AMPK-AKT1/PPARG/HMGCR metabolism pathway, providing insights into its potential as a functional health food.”

https://pubmed.ncbi.nlm.nih.gov/40279904/

https://www.sciencedirect.com/science/article/pii/S0308814625016577?via%3Dihub

Phytochemical Profile, Extraction and Characterization of Bioactive Compounds from Industrial Hemp (Cannabis sativa L.) Felina 32 Variety

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“An efficient method for the simultaneous extraction of cannabinoids and terpenes from the leaves and flowers of Cannabis sativa L. (var. Felina 32) was developed.

Extraction parameters, including solvent type, temperature, and pressure, were optimized, revealing that hexane enables high-yield cannabinoid recovery. Moreover, terpene composition was influenced by the extraction temperature. Two extracts with the highest cannabinoid content were selected for further study, Feli1 (64.76%) and Feli2 (61.32%), both obtained using hexane. Feli1, extracted at -55 °C, had a monoterpene-to-sesquiterpene ratio of 16.7% to 83.3%, while Feli2, extracted at 25 °C, showed a higher monoterpene content (25.2%) and lower sesquiterpene content (74.8%).

Both extracts demonstrated selective antiproliferative activity against cancer cell lines, with reduced toxicity toward normal breast epithelial cells (MCF-10A). Feli2 showed slightly stronger antiproliferative effects, likely due to its higher monoterpene content. At low concentrations, both extracts stimulated the growth of MV4-11 leukemia and MDA-MB-468 triple-negative breast cancer (TNBC) cells, while higher concentrations led to growth inhibition. These stimulatory effects were weaker than those observed for pure Δ9-THC or CBD.”

https://pubmed.ncbi.nlm.nih.gov/41157165/

https://www.mdpi.com/1420-3049/30/20/4148

Venous Thromboembolism and Coagulation Biomarker Changes in Trauma Patients Using Cannabis

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“Prior studies showed contradictory results regarding the impact of cannabinoids on thromboembolic events in trauma patients. The goal of the study was to investigate the association of cannabinoids to venous thromboembolism (VTE).

Records for all trauma patients admitted to the level one trauma center aged 14 years and above between October 18, 2019 and December 29, 2023 with urine drug screening (UDS) and blood alcohol concentration (BAC) results were included for collection. Patients testing positive for cannabinoids and patients testing negative for cannabinoids that were also negative for other illicit drugs and for alcohol were included in the final analysis primarily examining VTE occurrence, along with secondary outcomes in mortality, hospital length of stay, discharge disposition, and coagulation-related biomarkers. One-to-one propensity score matching analysis was performed.

Patient population was mostly white (78.8%), mostly male (71.5%), had a median age of 46, and a median ISS of 17. Out of 302 patients, 226 tested negative and 76 tested positive for cannabinoids. In the matched analysis, no difference was observed in rates of VTE (7.4% vs 4.4%, P = .683) or in platelet count (median [IQR], 260 [215-304] vs 260 [211-306], P = .790). No significant differences were found between the groups on coagulation profiles, complications, or other outcomes.

This study failed to identify significant differences between coagulation-related biomarkers and VTE incidence of adolescent and adult, trauma patients who tested positive for cannabinoids vs those that tested negative for cannabinoids.”

https://pubmed.ncbi.nlm.nih.gov/41160914/

https://journals.sagepub.com/doi/10.1177/00031348251393925

Acute and Subchronic Exposure to Hemp (Cannabis sativa L.) Leaf Oil: Impacts on Vital Organs in Sprague-Dawley Rats

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“Background/Objectives: Hemp (Cannabis sativa L. subsp. sativa) is a plant within the Cannabis sativa species and utilized for several applications, including antioxidation, antihypertension, and anti-inflammation. To our knowledge, no prior study has assessed the acute and sub-chronic oral safety of hemp leaf oil in Sprague-Dawley rats under Thailand-compliant THC levels. This study investigates the acute and sub-chronic effects of Hemp leaf oil (HLO) on the heart, liver, and kidneys of male and female Sprague-Dawley rats. 

Methods: Six-week-old male and female Sprague-Dawley rats were administered HLO (1.5 mL/kg) intragastrically, either as a single dose or a repeat dose over 28 days. 

Results: No changes in body or organ weights were observed following acute and sub-chronic HLO administration in sex-matched groups. Moreover, blood pressure and heart rate remained comparable across groups after acute and sub-chronic HLO treatment. Both acute and sub-chronic administration of HLO did not influence electrolyte balance, liver enzymes, total protein, albumin, blood urea nitrogen, or creatinine levels. Hematoxylin and eosin staining revealed the normal morphology of the heart, liver, and kidneys in rats subjected to HLO, during both acute and sub-chronic treatment. 

Conclusions: In conclusion, our data suggested that both acute and sub-chronic administration of HLO at 1.5 mL/kg could be safe for the vital organs. These findings support the potential use of HLO in therapeutic applications, particularly in scenarios when the safety of essential organs is at stake.”

https://pubmed.ncbi.nlm.nih.gov/41155551/

“These results support the safety effect of HLO treatment and the prospective application of HLO in preclinical research or clinical settings. This safety profile supports the extension of research into many domains, including dose-escalation studies and extended chronic toxicity assessments. This will strengthen the evidence base for any future clinical development of HLO.”

https://www.mdpi.com/1424-8247/18/10/1437

Unlike Tobacco Users, Documented Cannabis Users Are Not at an Increased Risk of Adverse Events After Total Hip Arthroplasty

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“Background: Perioperative tobacco use has been identified as an independent risk factor for adverse events after total hip arthroplasty (THA). It is unknown if perioperative cannabis users share similar levels of risk for adverse events after THA.

Methods: Patients undergoing THA were identified from the 2010 to 2021 PearlDiver M151 administrative data set. Patient subcohorts were categorized based on presence or absence of cannabis and/or tobacco use, as determined by coding. These subcohorts were equally matched based on patient age, sex, and Elixhauser Comorbidity Index scores to form groups of nonusers, tobacco users, tobacco and cannabis users, as well as cannabis users. The incidences of adverse events within 90 days postoperatively were obtained and compared using univariate and multivariate analyses that controlled for age, sex, and Elixhauser Comorbidity Index. Bonferroni correction was applied.

Results: Of 494,431 THA patients, nonusers were 442,000 (89.40%), tobacco users 46,925 (9.50%), tobacco and cannabis users 3,390 (0.69%), and cannabis users 2,116 (0.43%). After matching, there were 1,897 in each group. By multivariate analyses, tobacco-only users were at significantly greater risk of severe adverse events, sepsis, and pneumonia (P < 0.001 for each). Tobacco and cannabis users were at significantly greater risk of severe adverse events, myocardial infarction, pneumonia, and readmission (P < 0.001 for each). Conversely, cannabis-only users were not at significantly greater risk for any of the combined or individual adverse events assessed.

Discussion: This study confirmed that THA patients with tobacco-only use were at greater risk of perioperative adverse events and that these were relatively similar to those with concurrent tobacco and cannabis use. However, cannabis-only users were not at greater risk, a finding that is of clinical interest given the evolving access and increasing use of this agent.”

https://pubmed.ncbi.nlm.nih.gov/41144882/

https://journals.lww.com/jaaos/abstract/9900/unlike_tobacco_users,_documented_cannabis_users.1503.aspx