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22 pages, 1793 KiB  
Article
Formulation and Functional Characterization of a Cannabidiol-Loaded Nanoemulsion in Canine Mammary Carcinoma Cells
by Francisca J. Medina, Guillermo Velasco, María G. Villamizar-Sarmiento, Cristian G. Torres and Felipe A. Oyarzun-Ampuero
Pharmaceutics 2025, 17(8), 970; https://doi.org/10.3390/pharmaceutics17080970 - 26 Jul 2025
Viewed by 783
Abstract
Background/Objectives: Mammary carcinoma is a common disease in female dogs. Cannabidiol (CBD) can inhibit cell proliferation and induce apoptosis in human cancer cells. However, its low solubility in aqueous media requires solvents such as ethanol or dimethylsulfoxide that limit their dosage. Incorporating [...] Read more.
Background/Objectives: Mammary carcinoma is a common disease in female dogs. Cannabidiol (CBD) can inhibit cell proliferation and induce apoptosis in human cancer cells. However, its low solubility in aqueous media requires solvents such as ethanol or dimethylsulfoxide that limit their dosage. Incorporating CBD into oil-in-water nanoemulsions (Nem) can improve its aqueous dispersibility. This study aimed to develop a CBD-Nem formulation and evaluate its effects on canine mammary cancer cell lines (CF41.Mg and IPC366) and non-cancer cells (MDCK). Methods: CBD-Nem was prepared with Miglyol 812 oil and Epikuron 145 V as the surfactant, and was characterized by analyzing size, morphology, zeta potential, release profile, and uptake/internalization. Moreover, the antitumor effects of CBD-Nem were evaluated in cancer cells through viability, proliferation, cell cycle, and migration–invasion assays. Results: CBD-Nem exhibited a monodisperse nanometric population (~150 nm), spherical shape, and negative zeta potential (~−50 mV). The in vitro release kinetics showed slow and sustained delivery at both pH 5.5 and pH 7.4. Rhodamine-Nem, as a fluorescent model of CBD-Nem, was taken up and homogenously internalized in CF41.Mg cells. CBD-Nem decreased the viability of cancer cells with a maximum effect at 50 µM and showed a lower toxicity in MDCK cells. Long-term efficacy (20 days) was evidenced by CBD-Nem at inhibiting colony formation in cancer cells. Furthermore, CBD-Nem reduced the proportion of cells in the G2-M phase, induced apoptosis, and inhibited the migration and invasion of CF41.Mg cells. Conclusions: CBD-Nem exhibited an in vitro antitumor effect, which supports its study in dogs with mammary carcinoma. Full article
(This article belongs to the Topic Cannabis, Cannabinoids and Its Derivatives)
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20 pages, 2175 KiB  
Article
Evaluation of Cannabidiol Oil’s Effects on Sedation, Behavioral Responses to Handling, and Nociceptive Thresholds in Healthy Cats
by Kannika Wanapinit, Sirirat Niyom, Panisara Suriyawongpongsa, Sakunrat Khathatip, Kaittisak Tancharoen, Sittiruk Roytrakul and Sekkarin Ploypetch
Animals 2025, 15(13), 1987; https://doi.org/10.3390/ani15131987 - 6 Jul 2025
Viewed by 572
Abstract
This study explored the effects of cannabidiol (CBD) on clinically relevant parameters, including sedation, compliance, and temperament, as well as mechanical nociceptive thresholds in healthy cats. Nine client-owned cats (3.44 ± 2.35 years, mean ± standard deviation) were assessed prior to (baseline) and [...] Read more.
This study explored the effects of cannabidiol (CBD) on clinically relevant parameters, including sedation, compliance, and temperament, as well as mechanical nociceptive thresholds in healthy cats. Nine client-owned cats (3.44 ± 2.35 years, mean ± standard deviation) were assessed prior to (baseline) and 30 min, 1, 2, 4, 8, 12, and 24 h after oral administration of 8 mg/kg CBD oil via capsule. Sedation scores increased significantly 2, 4, and 8 h post administration compared to baseline (all medians = 1 vs. 0 at baseline; p < 0.001). Compliance and temperament scores were significantly reduced 2 and 4 h post dosing, with median scores decreasing from 1 at baseline to 0 after 2 and 4 h for both parameters (p < 0.001 and p = 0.012, respectively). Mechanical nociceptive thresholds and sensitivity, assessed using an algometer and von Frey filaments, respectively, along with physiological parameters (heart rate, respiratory rate, and body temperature), remained unchanged across timepoints. These results indicate that 8 mg/kg CBD induces mild sedation and reduces handling resistance in healthy cats without affecting nociceptive thresholds or physiological stability. Therefore, CBD may facilitate non-painful procedures requiring animal cooperation; further controlled studies are warranted to confirm these findings. Full article
(This article belongs to the Section Companion Animals)
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38 pages, 1316 KiB  
Review
Unveiling the Antioxidant Role of Hemp Oils in Cancer Prevention and Treatment
by Marios C. Christodoulou, Panagiotis Rodosthenous and Christiana M. Neophytou
Cancers 2025, 17(13), 2128; https://doi.org/10.3390/cancers17132128 - 25 Jun 2025
Viewed by 2316
Abstract
The global incidence of cancer continues to rise at an alarming rate, with annual cases projected to increase by 47% from 19.3 million in 2020 to 28.4 million by 2025. Cannabis sativa L. was among the earliest plants investigated for potential anticancer therapies, [...] Read more.
The global incidence of cancer continues to rise at an alarming rate, with annual cases projected to increase by 47% from 19.3 million in 2020 to 28.4 million by 2025. Cannabis sativa L. was among the earliest plants investigated for potential anticancer therapies, due to its more than 100 bioactive constituents that confer notable antioxidant properties. Hemp-derived extracts, particularly those rich in cannabidiol (CBD), exhibit notable synergistic biological effects, including the inhibition of cancer cell proliferation, angiogenesis, and metastasis, alongside the promotion of apoptosis. These pharmacological attributes suggest that hemp oils may serve as promising alternatives or adjuncts to conventional chemotherapy, offering potential therapeutic benefits with a reduced risk of severe adverse effects. This review discusses the current literature on hemp oils, with emphasis on their roles in cancer prevention, therapeutic efficacy, and potential toxicity in humans. Furthermore, it explores the various extraction methods employed in hemp oil production and examines their chemical compositions, offering a comprehensive understanding of the principal antioxidant constituents responsible for their bioactivity to the readers. Full article
(This article belongs to the Special Issue Natural Compounds in Cancers: 2nd Edition)
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17 pages, 1675 KiB  
Article
Assisted Extraction of Hemp Oil and Its Application to Design Functional Gluten-Free Bakery Foods
by Noemi Baldino, Mario F. O. Paleologo, Mariateresa Chiodo, Olga Mileti, Francesca R. Lupi and Domenico Gabriele
Molecules 2025, 30(12), 2665; https://doi.org/10.3390/molecules30122665 - 19 Jun 2025
Viewed by 559
Abstract
Cannabis sativa L. is known for its high-value compounds, like Cannabidiol (CBD) and Cannabidiolic Acid (CBDA). It is widely used in the pharmaceutical and food industries. Different extraction methods, like Soxhlet and maceration, are commonly employed to obtain its extracts. High temperature and [...] Read more.
Cannabis sativa L. is known for its high-value compounds, like Cannabidiol (CBD) and Cannabidiolic Acid (CBDA). It is widely used in the pharmaceutical and food industries. Different extraction methods, like Soxhlet and maceration, are commonly employed to obtain its extracts. High temperature and long extraction time can influence the yield and the purity of the extracts, affecting the quality of the final product. This study focused on optimizing CBD oil extraction from hemp inflorescences and its incorporation into a gluten-free bakery product for functionalization. Dynamic maceration (DME), assisted by ultrasound and microwave irradiation, was used. Our study explored the impact of varying sonication times (three distinct durations) and microwave powers (three levels, applied for two different irradiation times) on the resulting extracts. HPLC analysis was performed on these extracts. Subsequently, we used hemp flour and hemp oil to bake gluten-free cupcakes, which were fortified with the extracted CBD oil. Rheological characterization was used to investigate the cupcake properties, along with stereoscopic, color and puncture analysis performed on the baked samples. The most effective extraction parameters identified were 30 s of microwave irradiation at 700 W, yielding 45.2 ± 2.0 g of CBD extract, and 15 min of sonication, which resulted in 53.2 ± 2.5 g. Subsequent rheological characterization indicated that the product exhibited mechanical properties and a temperature profile comparable to a benchmark, evidenced by a height of 4.1 ± 0.2 cm and a hardness of 1.9 ± 0.2 N. These promising values demonstrate that hemp oil and hemp flour are viable ingredients for traditional cakes and desserts, notably contributing increased nutritional value through the CBD-enriched hemp oil and the beneficial profile of hemp flour. Full article
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15 pages, 1287 KiB  
Article
Potency Analysis of Semi-Synthetic Cannabinoids in Vaping Oils Using Liquid Chromatography Diode Array Detector with Electrospray Ionization Time-of-Flight Mass Spectrometry for Confirmation of Analyte Identity
by Shaozhong Zhang, Md Mahmud Alam, Brent D. Chandler, Jocelyn P. Lanorio, Caitlin Deskins and Liguo Song
Molecules 2025, 30(12), 2597; https://doi.org/10.3390/molecules30122597 - 15 Jun 2025
Viewed by 1530
Abstract
Since the 2018 Farm Bill legalized hemp, semi-synthetic cannabinoids, typically derived from hemp-extracted CBD, have been marketed as offering a “legal high”, raising concerns about consumer safety, labeling, and regulation. Consequently, the potency analysis of these compounds has become increasingly important. To address [...] Read more.
Since the 2018 Farm Bill legalized hemp, semi-synthetic cannabinoids, typically derived from hemp-extracted CBD, have been marketed as offering a “legal high”, raising concerns about consumer safety, labeling, and regulation. Consequently, the potency analysis of these compounds has become increasingly important. To address this need, an LC-DAD method was developed for the quantification of seventeen cannabinoids, selected based on the synthetic pathways of semi-synthetic cannabinoids. These included naturally occurring compounds, semi-synthetic derivatives, and byproducts (CBC, CBD, CBDV, CBG, CBN, CBN-O-acetate, CBT, 9(R)-HHC, 9(S)-HHC, 9(R)-HHC-O-acetate, 9(S)-HHC-O-acetate, Δ8-THC, Δ9-THC, Δ9,11-THC, Δ8-THC-O-acetate, Δ9-THC-O-acetate, and Δ9-THCV), using abnormal CBD as an internal standard. The method was validated according to ISO 17025 guidelines, demonstrating a linear calibration range from 0.1 to 50 µg/mL. The method was further applied to the potency analysis of one Δ8-THC, two THC-O-acetate, two HHC, and one HHC-O-acetate vaping oil sample. Using an innovative method to recover the contents of vaping cartridges, cannabinoids were extracted using methanol, diluted to a concentration of 50 µg/mL, and analyzed using the validated LC-DAD method, which provided a quantifiable range of 0.1 to 100% (w/w). Method specificity was evaluated using ESI/TOFMS and showed minimal interference, despite the presence of other isomers of the semi-synthetic cannabinoids in the samples. Full article
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7 pages, 168 KiB  
Brief Report
Possible Anxiolytic Effects of Cannabidiol (CBD) Administration on Feline Responses to a Fear Response Test
by Nobuo Masataka
Animals 2025, 15(11), 1642; https://doi.org/10.3390/ani15111642 - 3 Jun 2025
Viewed by 839
Abstract
In humans, cannabidiol (CBD), the primary non-addictive component of cannabis, is known to possess considerable therapeutic potential. The purpose of this study was to investigate the effects of CBD administration on reducing sound-induced fear in healthy domestic cats in a laboratory model of [...] Read more.
In humans, cannabidiol (CBD), the primary non-addictive component of cannabis, is known to possess considerable therapeutic potential. The purpose of this study was to investigate the effects of CBD administration on reducing sound-induced fear in healthy domestic cats in a laboratory model of thunderstorm simulation. A total of 40 cats, each naïve to the current testing, were randomly assigned into either of two administration groups (CBD and placebo). Each group was then exposed to the thunderstorm test twice; once at the beginning of the administration (the administration of CBD at 4.0 mg/kg/day over a 2-week-period or the administration of the same amount of sunflower oil as a placebo) and once after the end of the administration. When undesirable urination was observed, occurrences of this behaviour were found to decrease significantly when CBD was administered. However, no such changes were recorded when the placebo was administered. These results indicate that CBD could be an effective option for the treatment of noise-induced fear. Full article
(This article belongs to the Section Companion Animals)
14 pages, 515 KiB  
Article
Pharmacokinetic Characteristics of a Single Cannabidiol Dose in Oil and Treat Forms and Health Impacts After 30 Days of Administration in Dogs
by Phattharakan Kamutchat, Sasithorn Limsuwan, Nattaya Leewichit and Natthasit Tansakul
Animals 2025, 15(10), 1470; https://doi.org/10.3390/ani15101470 - 19 May 2025
Viewed by 874
Abstract
Cannabidiol (CBD) has garnered significant interest in veterinary therapeutics, yet the pharmacokinetic and safety profiles of its various formulations remain incompletely characterized. This study compared the pharmacokinetics (PK) and health effects of CBD administered as oil (OG, 5 mg/kg) and treats (TG, 50 [...] Read more.
Cannabidiol (CBD) has garnered significant interest in veterinary therapeutics, yet the pharmacokinetic and safety profiles of its various formulations remain incompletely characterized. This study compared the pharmacokinetics (PK) and health effects of CBD administered as oil (OG, 5 mg/kg) and treats (TG, 50 mg) in 16 healthy mixed-breed dogs over 30 days. Plasma CBD concentrations were measured using liquid chromatography–tandem mass spectrometry (LC-MS/MS), and the PK parameters were analyzed using non-compartmental methods. The CBD-infused rice bran oil formulation (OG) achieved a significantly higher dose-normalized maximum plasma concentration (Cmax, 58.40 vs. 21.29 kg·ng/mL/mg) and area under the curve (AUC0-inf, 305.85 vs. 141.75 h·kg·ng/mL/mg) compared to the treats (TG). The treat formulation exhibited relative reductions in bioavailability, with AUC and Cmax values approximately 2.2- and 2.7-fold lower than the oil group. The terminal half-life (~9.66 h OG vs. 8.52 h TG) and time to peak (2.38 h OG vs. 3.63 h TG) did not differ significantly. CBD accumulation occurred with repeated dosing but declined rapidly post-cessation. The hematological and biochemical analyses revealed no clinically adverse effects, though minor erythrocyte and eosinophil fluctuations were noted. The oil formulation demonstrated superior absorption, while both forms were well-tolerated. These findings highlight the impact of formulation on CBD absorption and support further research into optimized delivery methods for veterinary applications. Full article
(This article belongs to the Section Companion Animals)
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20 pages, 3919 KiB  
Article
Effects of Cannabidiol Oil on Anesthetic Requirements in Cats: MAC Determination and Serum Profiling via Nanoscale Liquid Chromatography–Tandem Mass Spectrometry
by Panisara Suriyawongpongsa, Sirirat Niyom, Kannika Wanapinit, Monchanok Vijarnsorn, Sittiruk Roytrakul and Sekkarin Ploypetch
Animals 2025, 15(10), 1393; https://doi.org/10.3390/ani15101393 - 12 May 2025
Cited by 1 | Viewed by 981
Abstract
Cannabidiol (CBD), a non-psychotropic cannabinoid derived from Cannabis plants, is increasingly explored for its potential therapeutic applications in veterinary medicine. This study aimed to evaluate the impact of CBD oil on the minimum alveolar concentration of isoflurane (MACiso) in cats. Sixteen [...] Read more.
Cannabidiol (CBD), a non-psychotropic cannabinoid derived from Cannabis plants, is increasingly explored for its potential therapeutic applications in veterinary medicine. This study aimed to evaluate the impact of CBD oil on the minimum alveolar concentration of isoflurane (MACiso) in cats. Sixteen healthy cats underwent isoflurane anesthesia, and the MACiso was determined using the tail-clamping technique both at baseline and 30 min after the administration of CBD oil (2 mg/kg) via a stomach tube. CBD administration resulted in a significant 11% reduction in the MACiso, from 1.77 ± 0.14% to 1.62 ± 0.21% (p < 0.001). Following CBD administration, heart and respiratory rates were elevated at the time of MACiso determination compared to baseline whereas other physiological parameters remained unchanged. Serum biochemical analysis conducted two weeks post administration revealed a significant decrease in blood urea nitrogen (BUN) levels while one cat exhibited a mild increase in alanine aminotransferase (ALT). Proteomic analysis identified 12 CBD-associated proteins in feline serum 30 min post administration, with CBDA and THCA synthases demonstrating significant upregulation. These findings indicate that CBD oil reduces anesthetic requirements in cats without inducing significant physiological disturbances. Further research is warranted to elucidate the underlying mechanisms of CBD’s anesthetic-sparing effects and its implications in veterinary anesthesia. Full article
(This article belongs to the Section Companion Animals)
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17 pages, 751 KiB  
Article
Efficacy of Cannabis Oil in Improving Subjective Sleep Quality in Systemic Sclerosis: A Prospective Placebo-Controlled Study
by Apichart So-ngern, Bungon Sripanichkulchai, Ajanee Mahakkanukrauh, Siraphop Suwannaroj, Patnarin Pongkulkiat, Tippawan Onchan, Somdej Kanokmedhakul and Chingching Foocharoen
Life 2025, 15(5), 727; https://doi.org/10.3390/life15050727 - 30 Apr 2025
Cited by 1 | Viewed by 1319
Abstract
Objective: We aimed to investigate the efficacy of cannabis oil in improving sleep quality, as evaluated using the Pittsburgh Sleep Quality Index (PSQI), in patients with systemic sclerosis (SSc) compared to placebo. Methods: An experimental investigation was conducted in patients with SSc aged [...] Read more.
Objective: We aimed to investigate the efficacy of cannabis oil in improving sleep quality, as evaluated using the Pittsburgh Sleep Quality Index (PSQI), in patients with systemic sclerosis (SSc) compared to placebo. Methods: An experimental investigation was conducted in patients with SSc aged 18–70 years. The treatment group received a cannabis preparation containing 2.7 mg/mL tetrahydrocannabinol (THC) and 2.5 mg/mL cannabidiol (CBD) sublingually for 4 weeks. Results: Twenty-seven participants were included in the study. One case was withdrawn due to a serious adverse event, leaving 13 participants in each group. The mean difference in PSQI scores decreased more in the treatment group than in the placebo group from baseline to post-treatment, but this difference was not statistically significant (p = 0.09). Increases in sleep duration were more frequently observed in the treatment group than in the placebo group, along with decreases in sleep disturbance, sleep medication use, and daytime dysfunction; however, these were not statistically significant. Conclusions: Cannabis oil showed some positive trends; however, our study did not provide conclusive evidence supporting the efficacy of cannabis oil in improving sleep quality. More rigorous studies are needed to confirm these findings and expand the clinical applicability of cannabinoids for sleep disorders. Full article
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15 pages, 1838 KiB  
Article
A Preliminary Evaluation of the Comparative Efficacy of Gel-Based and Oil-Based CBD on Hematologic and Biochemical Responses in Dogs
by Wassana Puttharaksa, Rangsun Charoensook, Rongdej Tungtrakanpoung, Niramon Hoidokhom, Saowaluk Rungchang, Bertram Brenig and Sonthaya Numthuam
Vet. Sci. 2025, 12(4), 342; https://doi.org/10.3390/vetsci12040342 - 7 Apr 2025
Cited by 1 | Viewed by 955
Abstract
Cannabidiol (CBD) has gained popularity in veterinary medicine for its potential to alleviate stress, pain, and inflammation in dogs. However, its oral administration is limited by hydrophobicity, variable absorption, and extensive first-pass metabolism, which requires optimized delivery methods to enhance efficacy. This study [...] Read more.
Cannabidiol (CBD) has gained popularity in veterinary medicine for its potential to alleviate stress, pain, and inflammation in dogs. However, its oral administration is limited by hydrophobicity, variable absorption, and extensive first-pass metabolism, which requires optimized delivery methods to enhance efficacy. This study investigated the effects of daily oral supplementation of CBD oil and CBD gel (each at 4 mg/kg), compared to a placebo, over 14 days in shelter dogs subjected to solitary confinement-induced stress. Both CBD formulations appeared safe under the study conditions, with no adverse effects on hematological and biochemical parameters. Post-stress cortisol levels were significantly lower in CBD-treated groups compared to controls, with CBD-infused gel showing a pattern toward greater attenuation. Multivariate analysis revealed distinct blood profile shifts in CBD-treated dogs, with PCA loadings indicating associations between CBD supplementation and lymphocyte percentages and IgG levels. These findings support gel-based CBD as a promising strategy for stress modulation in dogs. Further studies should explore its pharmacokinetics and long-term immune effects to optimize veterinary applications. Full article
(This article belongs to the Section Veterinary Biomedical Sciences)
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13 pages, 227 KiB  
Article
The Effectiveness of Amitriptyline and Gabapentin in Treating Pomeranians with Chiari-like Malformation and/or Syringomyelia
by Ramona ter Maat, Kathelijn van Heusden, Larissa Hoogervorst-Spek, Marta Płonek and Paul J. J. Mandigers
Animals 2025, 15(7), 992; https://doi.org/10.3390/ani15070992 - 29 Mar 2025
Cited by 1 | Viewed by 1849
Abstract
Background: Chiari-like malformation (CM) and syringomyelia (SM) are commonly observed disorders in the Pomeranians. Both disorders can lead to pain and diminish quality of life to varying extents. In veterinary medicine, affected dogs are often treated with gabapentin or pregabalin, which contrasts with [...] Read more.
Background: Chiari-like malformation (CM) and syringomyelia (SM) are commonly observed disorders in the Pomeranians. Both disorders can lead to pain and diminish quality of life to varying extents. In veterinary medicine, affected dogs are often treated with gabapentin or pregabalin, which contrasts with human medicine, where the tricyclic antidepressants amitriptyline and nortriptyline are the first-choice treatments. Methods: affected dogs were treated with either amitriptyline or gabapentin. If a pre-syrinx was present, furosemide was also added. Owners were asked to score the clinical signs they observed (ORCS). Results: 90 Pomeranians were included, of which 62 received amitriptyline and 28 received gabapentin. Adding furosemide did not have an influence on the outcome. A logistic regression analysis with the number of ORCS, duration of ORCS, treatment (amitriptyline or gabapentin), and outcome (responder or non-responder) as the dependent variable revealed that the number of ORCS had an Odds of 1123 (p = 0.03). Duration of the ORCS (Odds 1.027; p = 0.45) and treatment group had a low influence (Odds 1.258; p = 0.65). Conclusions: In this study, amitriptyline demonstrated a moderate, though not statistically significant, more favorable effect on CM/SM pain compared to gabapentin. Adding furosemide to either of these two treatments did not influence the outcome. The outcome for dogs affected by CM/SM is not influenced by MRI grading; however, the number of ORCS and a longer duration negatively impact the outcome. A dose of 1 to 2 mg/kg body weight of amitriptyline administered twice daily proved to be more effective in several dogs. Full article
(This article belongs to the Section Veterinary Clinical Studies)
28 pages, 6588 KiB  
Article
Formulation and Evaluation of Solid Self-Nanoemulsifying Drug Delivery System of Cannabidiol for Enhanced Solubility and Bioavailability
by Fengying Wu, Qing Ma, Guanghui Tian, Kaixian Chen, Rulei Yang and Jingshan Shen
Pharmaceutics 2025, 17(3), 340; https://doi.org/10.3390/pharmaceutics17030340 - 6 Mar 2025
Cited by 2 | Viewed by 2521
Abstract
Background/Objectives: This study aims to develop a solid self-nanoemulsifying drug delivery system (SNEDDS) to enhance the solubility and oral bioavailability of cannabidiol (CBD). Methods: According to the solubility of CBD and pseudo-ternary phase diagrams of the different ingredients, an oil (medium-chain triglyceride, MCT), [...] Read more.
Background/Objectives: This study aims to develop a solid self-nanoemulsifying drug delivery system (SNEDDS) to enhance the solubility and oral bioavailability of cannabidiol (CBD). Methods: According to the solubility of CBD and pseudo-ternary phase diagrams of the different ingredients, an oil (medium-chain triglyceride, MCT), mixed surfactants (Labrasol, Tween 80), and a co-surfactant (Transcutol) were selected for the SNEDDS. CBD-loaded SNEDDS formulations were prepared and characterized. The optimal SNEDDS was converted into solid SNEDDS powders via solid carrier adsorption and spray drying techniques. Various evaluations including flowability, drug release, self-emulsifying capacity, X-ray diffraction (XRD), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), morphology, and pharmacokinetic characteristics were conducted. Subsequently, the solid powders with fillers, disintegrants, and lubricants were added to the capsules for accelerated stability testing. Results: The investigations showed that the two S-SNEDDS formulations improved the CBD’s solubility and in vitro drug release, with good storage stability. The pharmacokinetic data of Sprague Dawley rats indicated that a single oral dose of L-SNEDDS and spray drying SNEDDS led to a quicker absorption and a higher Cmax of CBD compared to the two oil-based controls (CBD-sesame oil (similar to Epidiolex®) and CBD-MCT), which is favorable for the application of CBD products. Conclusions: SNEDDS is a prospective strategy for enhancing the solubility and oral bioavailability of CBD, and solid SNEDDS offers flexibility for developing more CBD-loaded solid formulations. Moreover, SNEDDS provides new concepts and methods for other poorly water-soluble drugs. Full article
(This article belongs to the Section Physical Pharmacy and Formulation)
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16 pages, 17418 KiB  
Article
Incomplete Decarboxylation of Acidic Cannabinoids in GC-MS Leads to Underestimation of the Total Cannabinoid Content in Cannabis Oils Without Derivatization
by Martina Franzin, Rebecca Di Lenardo, Rachele Ruoso and Riccardo Addobbati
Pharmaceutics 2025, 17(3), 334; https://doi.org/10.3390/pharmaceutics17030334 - 5 Mar 2025
Viewed by 1033
Abstract
Background: Cannabis oil titration consists of quantification of the acidic precursors tetrahydrocannabinolic acid (THCA) and cannabidiolic acid (CBDA) and their decarboxylated products, the active neutral cannabinoids delta-9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD), and is recommended to ensure galenic preparation quality through gas and [...] Read more.
Background: Cannabis oil titration consists of quantification of the acidic precursors tetrahydrocannabinolic acid (THCA) and cannabidiolic acid (CBDA) and their decarboxylated products, the active neutral cannabinoids delta-9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD), and is recommended to ensure galenic preparation quality through gas and liquid chromatography coupled with mass spectrometry (GC-MS; LC-MS). Analyses by LC-MS and GC-MS involving derivatization allow for detection of acidic and neutral cannabinoids; on the contrary, GC-MS without derivatization determines only neutral cannabinoids due to high temperature-decarboxylation occurring in the injection system. However, it is not clear if decarboxylation is complete. Methods: Different GC-MS methods with (BSTFA: TMCS and pyridine; incubation at 60 °C for 25 min) or without derivatization and an LC-MS method were developed for cannabinoid quantification. The total Δ9-THC and CBD yield of recovery were compared between the methods by testing laboratory samples with known concentrations of THCA and CBDA (total Δ9-THC and CBD: 175–351–702 ng/mL) and real cannabis oil samples (n = 6). Results: The total Δ9-THC and CBD yield of recovery were determined using LC-MS and GC-MS with derivatization, but not using GC-MS without derivatization (decarboxylation conversion rate of about 50–60%). No high deviation (<10%) in the total neutral cannabinoid concentrations in real cannabis oil samples was noticed, probably due to the low content of acidic forms in the original galenic preparation. Conclusions: This study raised awareness about the potential underestimation of the total Δ9-THC and CBD content in cannabis oils when quantification is performed by GC-MS without derivatization. The advice for pharmacists is to perform complete decarboxylation to convert all acidic precursors in neutral cannabinoids. Full article
(This article belongs to the Special Issue Recent Advances in Oral Pharmaceutical Forms)
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25 pages, 9259 KiB  
Article
Formulation of W/O/W Emulsion-Based Chitosan-Alginate Microcapsules for Encapsulation of Cannabidiol and A. annua L. Extract Containing Luteolin and Apigenin: A Response Surface Optimization Approach
by Emilija Nemickaite, Ugne Zlabiene, Agne Mazurkeviciute, Mindaugas Marksa and Jurga Bernatoniene
Pharmaceutics 2025, 17(3), 309; https://doi.org/10.3390/pharmaceutics17030309 - 28 Feb 2025
Cited by 1 | Viewed by 1436
Abstract
Background/Objectives: Chitosan–alginate microcapsules were produced to encapsulate bioactive compounds from Artemisia annua L. extract (apigenin, luteolin) and cannabidiol (CBD). The study aimed to optimize emulsion composition and encapsulation parameters for potential applications in food supplements and pharmaceuticals. Methods: A water-in-oil-in-water (W/O/W) emulsion and [...] Read more.
Background/Objectives: Chitosan–alginate microcapsules were produced to encapsulate bioactive compounds from Artemisia annua L. extract (apigenin, luteolin) and cannabidiol (CBD). The study aimed to optimize emulsion composition and encapsulation parameters for potential applications in food supplements and pharmaceuticals. Methods: A water-in-oil-in-water (W/O/W) emulsion and a modified coacervation extrusion technique were employed. The study was conducted in two phases using response surface methodology. Key metrics included encapsulation efficiency (EE), yield (EY), cumulative release in vitro, and physicochemical and morphological properties, analyzed via scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), high-performance liquid chromatography with a diode array detector (HPLC-DAD), and gas chromatography with flame ionization detection (GC-FID). Results: The optimal conditions were identified as 0.1% Tween 20, 3.8% Span 80, 3.8% CBD, 19.9% A. annua L. extract, 1.5% outer-phase Tween 20, 48.5% sodium alginate, 200 rpm stirring for 30 min, and a 0.05 mL/min flow rate. The EE values were 80.32 ± 4.11% for CBD, 88.13 ± 3.13% for apigenin, and 88.41 ± 4.17% for luteolin, with respective cumulative releases of 77.18 ± 4.4%, 75.12 ± 4.81%, and 75.32 ± 4.53%. Conclusions: The developed microcapsules demonstrated high encapsulation efficiency and controlled release, highlighting their potential for further development in food supplements and pharmaceuticals. Future studies should focus on refining the formulation for improved bioavailability and stability. Full article
(This article belongs to the Special Issue Natural Pharmaceuticals Focused on Anti-inflammatory Activities)
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21 pages, 1339 KiB  
Article
Evaluation of the Effectiveness of a Mouthwash Containing Spilanthol and Cannabidiol on Improving Oral Health in Patients with Gingivitis—Clinical Trial
by Maksymilian Kiełbratowski, Anna Kuśka-Kiełbratowska, Anna Mertas, Elżbieta Bobela, Rafał Wiench, Małgorzata Kępa, Agata Trzcionka, Rafał Korkosz and Marta Tanasiewicz
J. Clin. Med. 2025, 14(5), 1641; https://doi.org/10.3390/jcm14051641 - 28 Feb 2025
Cited by 1 | Viewed by 2681
Abstract
Background/Objectives: Plaque-associated gingivitis is widely regarded as a local inflammatory condition initiated by the accumulation of a non-specific dental biofilm in the interaction with the host immune system. The initial symptom noticed by the patient is bleeding gums. The use of mouthwash [...] Read more.
Background/Objectives: Plaque-associated gingivitis is widely regarded as a local inflammatory condition initiated by the accumulation of a non-specific dental biofilm in the interaction with the host immune system. The initial symptom noticed by the patient is bleeding gums. The use of mouthwash can serve to supplement mechanotherapy. However, there is an increasing interest in mouthwashes comprising natural ingredients, including cannabidiol (CBD) and spilanthol. The objective of this study was to evaluate the effect of an oral rinse containing spilanthol and CBD oil compared to a rinse containing tea tree oil on the oral microbiota and the values of selected oral status indicators in patients with gingivitis. Methods: The study included 40 patients treated with a rinse containing tea tree oil (TTO)/TTO + spilanthol + CBD for a period of 42 days. Patients rinsed their mouth twice daily for 30 s. The patients’ oral microbiome was assessed before and after treatment, and bleeding on probing (BOP) and approximal plaque index (API) were assessed. The study was double-blind. Results: API and BOP were reduced in all groups, both the test and control. The most significant decrease in baseline BOP-1 scores was observed in test groups A and D (p = 0.005062 and p = 0.005062, respectively). A significant difference in API improvement was observed between the initial and final visits in the test (A, D) and control (B, C) groups (p = 0.012516, p = 0.005062, p = 0.004028, p = 0.003172, respectively). Conclusions: Firstly, the use of a mouthwash containing cannabidiol (CBD) and spilanthol was demonstrated to be efficacious in the maintenance of oral microbiota homeostasis. Secondly, the combination of TTO with spilanthol and CBD in the rinse was shown to result in a more significant reduction in selected oral health parameters (BOP and API) and anti-inflammatory effects when compared to a rinse with TTO alone. It should be noted that this is a pilot study and will continue. Full article
(This article belongs to the Special Issue Clinical Advances in Dental Medicine and Oral Health)
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