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Keywords = cannabidiol extract

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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 2287
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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22 pages, 1017 KiB  
Article
Development of a Validated LC-MS Method for the Determination of Cannabinoids and Evaluation of Supercritical CO2 vs. Ultrasound-Assisted Extraction in Cannabis sativa L. (Kompolti cv.)
by Vasileios A. Ioannidis, Varvara Sygouni, Sotirios Giannopoulos, Konstantinos Sotirianos, Theophilos Ioannides, Christakis A. Paraskeva and Fotini N. Lamari
Antioxidants 2025, 14(7), 777; https://doi.org/10.3390/antiox14070777 - 24 Jun 2025
Viewed by 1501
Abstract
Cannabis (Cannabis sativa L.) contains numerous secondary metabolites with different bioactivities. Extraction methods differ in their efficiency in recovering metabolites from plant material, and thus cannabis extracts vary significantly in their composition and activity. We aimed to develop a repeatable and accurate [...] Read more.
Cannabis (Cannabis sativa L.) contains numerous secondary metabolites with different bioactivities. Extraction methods differ in their efficiency in recovering metabolites from plant material, and thus cannabis extracts vary significantly in their composition and activity. We aimed to develop a repeatable and accurate HPLC-MS method for the determination of nine common cannabinoids and compare two widely used extraction techniques: ultrasound-assisted extraction (UAE) with methanol and supercritical CO2 extraction (SFE). Inflorescences of the Kompolti cultivar were used as the plant material. On a polar C18 column, more than thirty compounds were well separated within 25 min; thirteen cannabinoids were identified and eight of them were quantified, with cannabidiol and its acidic precursor being the most abundant. Additionally, three spectrophotometric assays were employed for extract characterization: the total phenolic content, total flavonoid content, and DPPH radical scavenging capacity. The SFE extract, obtained using ethanol as a co-solvent under low pressure (<100 bar) and temperature (<45 °C), was more enriched than the UAE extract (181.62 ± 2.90 vs. 140.64 ± 13.24 mg quercetin equivalents/g of dry extract) and cannabinoids (446.29 ± 22.66 vs. 379.85 ± 17.16 mg/g of dry extract), especially cannabinoid acids. However, UAE achieved greater recovery from the plant material (cannabinoids: 83.42 ± 5.15 vs. 68.84 ± 3.49 mg/g of plant material) and showed superior antioxidant capacity (DPPH IC50: 2.50 ± 0.18 vs. 3.37 ± 0.07 mg/mL). Notwithstanding the observed partial decarboxylation, the high repeatability (RSD < 15%, n = 11) of the entire analytical workflow involving UAE extraction and LC-MS analysis renders it suitable for routine analyses. This study contributes to the ongoing efforts toward the quality control and valorization of C. sativa. Full article
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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 558
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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31 pages, 6448 KiB  
Article
Nanoemulsions of Cannabidiol, Δ9-Tetrahydrocannabinol, and Their Combination Similarly Exerted Anticonvulsant and Antioxidant Effects in Mice Treated with Pentylenetetrazole
by Pedro Everson Alexandre de Aquino, Francisco Josimar Girão Júnior, Tyciane de Souza Nascimento, Ítalo Rosal Lustosa, Geanne Matos de Andrade, Nágila Maria Pontes Silva Ricardo, Débora Hellen Almeida de Brito, Gabriel Érik Patrício de Almeida, Kamilla Barreto Silveira, Davila Zampieri, Marta Maria de França Fonteles, Edilberto Rocha Silveira, Giuseppe Biagini and Glauce Socorro de Barros Viana
Pharmaceuticals 2025, 18(6), 782; https://doi.org/10.3390/ph18060782 - 23 May 2025
Viewed by 731
Abstract
Background/Objectives: The main biologically active molecules of Cannabis sativa L. are cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC). Both exert anticonvulsant effects when evaluated as single drugs, but their possible interaction as components of C. sativa extracts has been scarcely studied. For this reason, we [...] Read more.
Background/Objectives: The main biologically active molecules of Cannabis sativa L. are cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC). Both exert anticonvulsant effects when evaluated as single drugs, but their possible interaction as components of C. sativa extracts has been scarcely studied. For this reason, we evaluated CBD and THC, combined or not, in two seizure models in mice, using an improved vehicle formula. Methods: Firstly, acute seizures were induced by intraperitoneal (i.p.) pentylenetetrazole (PTZ, 80 mg/kg), and mice received CBD or THC at 1, 3, 6, and 10 mg/kg, or a CBD/THC 1:1 combination at 1.5, 3, and 6 mg/kg, per os (p.o.), one hour before PTZ administration. Secondly, mice received p.o. CBD (10 mg/kg), CBD/THC (1.5, 3, and 6 mg/kg), valproic acid (50 mg/kg), or vehicle (nanoemulsions without CBD or THC), one hour before PTZ (30 mg/kg, i.p.) every other day for 21 days. Behavioral, biochemical, and immunohistochemical analyses were performed to assess the response to PTZ, oxidative stress, and astroglial activation. Results: In the acute model, CBD and THC at 3–10 mg/kg, and their combinations, significantly increased latency to generalized seizures and death, and improved survival rates. In the chronic model, similarly to valproic acid, CBD 10 mg/kg and CBD/THC at 1.5 and 3 mg/kg delayed kindling acquisition, while CBD/THC 6 mg/kg had no effect. CBD and CBD/THC treatments reduced oxidative and nitrosative stress and attenuated astrogliosis, as indicated by decreased glial fibrillary acidic protein and GABA transporter 1 expression and increased inwardly rectifying potassium channel 4.1 expression in hippocampal regions. However, no cannabinoid treatment prevented the impairment in novel object recognition and Y maze tests. Conclusions: These findings support the potential role of cannabinoids in counteracting seizures, possibly by reducing oxidative stress and astrogliosis. The study also highlights the importance of nanoemulsions as a delivery vehicle to enhance cannabinoid effectiveness while considering the risks associated with direct cannabinoid receptor activation. Full article
(This article belongs to the Section Pharmacology)
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25 pages, 2665 KiB  
Article
Chemical Profiling of Polyphenolic Fraction of Cannabis sativa L. vr. Kompolti Industrial Inflorescences: Insights into Cannabidiol Neuroprotective Effects in a Cellular Model of Parkinson’s Disease
by Francesca Fantasma, Gilda D’Urso, Noemi Martella, Alessandra Capuano, Eleonora Boccia, Vadym Samukha, Vincenzo De Felice, Gabriella Saviano, Federico Trombetta, Gianluigi Lauro, Marco Segatto, Maria Giovanna Chini, Giuseppe Bifulco, Agostino Casapullo and Maria Iorizzi
Plants 2025, 14(10), 1473; https://doi.org/10.3390/plants14101473 - 14 May 2025
Viewed by 842
Abstract
The ultra-high-performance liquid chromatography high-resolution mass spectrometry (LC-ESI-HR-MS/MS) technique was used to characterize the polyphenolic fraction of the hot water infusion (WI) of inflorescences of Cannabis sativa L. Kompolti variety, commercially used for food preparations or cosmetic purposes. On water infusion extract, we [...] Read more.
The ultra-high-performance liquid chromatography high-resolution mass spectrometry (LC-ESI-HR-MS/MS) technique was used to characterize the polyphenolic fraction of the hot water infusion (WI) of inflorescences of Cannabis sativa L. Kompolti variety, commercially used for food preparations or cosmetic purposes. On water infusion extract, we applied a multidisciplinary approach, where NMR, MS, in vitro cell-free and cell-based assays coupled with in silico studies, were used to rationalize at the molecular level the effects of the major component Cannabidiol (CBD), in a model of Parkinson’s disease (PD). The phytochemical analysis by LC-MS/MS led to the tentative identification of many components belonging to different classes of polyphenols, such as phenolic acids, flavonoids, and their glycosides. CBD and cannabidiolic acid (CBDA) were also detected in good amounts in the infusion, together with several minor cannabinoids. In addition, the water infusion WI was evaluated for mineral content, total phenolic content, flavonoid content, and antioxidant capacity by DPPH and FRAP methods. Notably, our results in a cellular model of PD highlight that CBD protects against rotenone-induced cell death without recovering neuronal morphology. These biological outcomes were rationalized by an in silico approach, where we hypothesize that CBD could influence the cellular response to oxidative stress via its interaction with the Keap1/Nrf2 pathway. In summary, these results enriched the nutraceutical profile of the water infusion of the inflorescences of the Kompolti cultivar, which demonstrated a high CBD content. This study could lead to the development of dietary supplements that could help in the management of clinical symptoms related to the antioxidant activity of CBD in the pathophysiology of PD, which remains poorly characterized. Full article
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11 pages, 1678 KiB  
Article
Utilization of Industrial Hemp Biomass Waste (I): Stability of Cannabidiol in Pre and Post- Encapsulation States
by Jerel Crew, Ying Wu, Richard Mu and Ankit Patras
Molecules 2025, 30(10), 2116; https://doi.org/10.3390/molecules30102116 - 10 May 2025
Viewed by 849
Abstract
After cannabidiol was extracted from the hemp biomass using supercritical CO2 extraction, the residual could be utilized as a source of other valuable ingredients. The stability of the extracted CBD in pre- and post- encapsulation states were evaluated. Dynamic macerations with ethanol [...] Read more.
After cannabidiol was extracted from the hemp biomass using supercritical CO2 extraction, the residual could be utilized as a source of other valuable ingredients. The stability of the extracted CBD in pre- and post- encapsulation states were evaluated. Dynamic macerations with ethanol and hexane were compared for CBD extraction. The ethanol extract yielded 0.11% ± 0.10 CBD and 1.83% ± 0.00 cannabidiolic acid (CBDA), while the hexane extraction yielded 0.08% ± 0.04 CBD, 1.06% ± 0.04 CBDA, and 0.30% ± 0.04 delta-9-tetrahydrocannabinol (Δ9-THC). Ethanol extraction was selected due to the low THC detection in the extract. The CBD extract was encapsulated using water soluble yellow mustard mucilage (WSM), maltodextrin (MD), gum Arabic (GA), and protein extracted from the hemp biomass waste (HBP) via freeze drying. The WSM-MD-GA 1:5 particle formulation exhibited superior thermal stability over 72 h, whereas the WSM-HBP-GA 1:5 formulation offered the most protection against UVa-induced degradation within the same duration. Incorporating hemp biomass protein as an encapsulation material enhanced protection against light exposure through UV absorption, although it did not grant thermal protection. These findings indicated that encapsulation significantly protects against CBD degradation when subjected to thermal and light conditions compared to non-encapsulated CBD. Full article
(This article belongs to the Special Issue Extraction and Analysis of Natural Products in Food—2nd Edition)
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15 pages, 3050 KiB  
Article
The Anticonvulsant Effects of Different Cannabis Extracts in a Zebrafish Model of Epilepsy
by Karen Jackson, Maytal Shabat-Simon, Jonathan Bar-On, Rafi Steckler, Soliman Khatib, Snait Tamir and Paula Adriana Pitashny
Biomolecules 2025, 15(5), 654; https://doi.org/10.3390/biom15050654 - 1 May 2025
Viewed by 803
Abstract
Epilepsy is a widespread neurological disorder that remains a critical global public health challenge. While numerous antiepileptic drugs (AEDs) are available, many patients either fail to achieve adequate seizure control or experience significant side effects. One promising alternative is pure cannabidiol (CBD), but [...] Read more.
Epilepsy is a widespread neurological disorder that remains a critical global public health challenge. While numerous antiepileptic drugs (AEDs) are available, many patients either fail to achieve adequate seizure control or experience significant side effects. One promising alternative is pure cannabidiol (CBD), but using a whole cannabis extract may be equally effective and preferred for some patients. In the current study, we employed the pentylenetetrazole (PTZ)-induced hyperactivity model in zebrafish to compare the effects of CBD with various cannabis extracts. We evaluated three cannabis strains, each subjected to three different extraction methods, and benchmarked the results against the commercially available AED valproic acid (VPA). Our findings revealed that 5.7 µg/mL of CBD and 10 µg/mL of different extracts significantly reduced movement compared to PTZ and VPA. In addition, effective extracts produced effects similar to pure CBD despite containing much lower molecule levels. These results reinforced and expanded previous evidence supporting the clinical potential of both CBD and whole cannabis extracts for seizure control while suggesting a possible entourage effect. Further research is necessary to determine which patients may benefit more from pure CBD versus those who might prefer whole cannabis extracts. Full article
(This article belongs to the Section Bio-Engineered Materials)
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14 pages, 2998 KiB  
Article
In Vitro Immunomodulatory Effects of Equine Adipose Tissue-Derived Mesenchymal Stem Cells Primed with a Cannabidiol-Rich Extract
by Lorena Battistin, Luís Felipe Arantes Moya, Lucas Vinícius de Oliveira Ferreira, Aline Márcia Marques Braz, Márcio de Carvalho, Marjorie de Assis Golim and Rogério Martins Amorim
Int. J. Mol. Sci. 2025, 26(9), 4208; https://doi.org/10.3390/ijms26094208 - 29 Apr 2025
Viewed by 512
Abstract
Cell-based therapy using mesenchymal stem cells (MSCs) shows promise for treating several diseases due to their anti-inflammatory and immunomodulatory properties. To enhance the therapeutic potential of MSCs, in vitro priming strategies have been explored. Cannabidiol (CBD), a non-psychoactive compound derived from cannabis, may [...] Read more.
Cell-based therapy using mesenchymal stem cells (MSCs) shows promise for treating several diseases due to their anti-inflammatory and immunomodulatory properties. To enhance the therapeutic potential of MSCs, in vitro priming strategies have been explored. Cannabidiol (CBD), a non-psychoactive compound derived from cannabis, may influence MSC proliferation, differentiation, and immunomodulatory properties. This study evaluates the immunomodulatory potential of equine adipose tissue-derived MSCs (EqAT-MSCs) primed with a CBD-rich cannabis extract. EqAT-MSCs (P3) were primed with CBD concentrations of 5 µM and 7 µM for 24 h. Morphological analysis, MTT assay, β-galactosidase activity, apoptosis assays, and gene expression of interleukins IL-1β, IL-6, IL-10, interferon-gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α) were conducted. Additionally, cannabinoid receptor 1 (CB1) and 2 (CB2) expression were evaluated in naïve EqAT-MSCs (P2–P5). The naïve EqAT-MSCs expressed CB1 and CB2 receptors. Priming with 5 µM significantly increased the expression of IL-10, TNF-α, and IFN-γ, while 7 µM decreased IL-1β and IL-6 expression. No significant changes were observed in other cytokines, MTT, β-galactosidase activity, or apoptosis. These findings demonstrate that naïve EqAT-MSCs express CB1 and CB2 receptors and priming with the extract modulates the expression of pro- and anti-inflammatory cytokines, highlighting its potential immunomodulatory role in EqAT-MSC-based therapies. Full article
(This article belongs to the Special Issue Biomedical Applications of Mesenchymal Stem Cells)
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13 pages, 1731 KiB  
Article
Beyond Cannabidiol: The Contribution of Cannabis sativa Phytocomplex to Skin Anti-Inflammatory Activity in Human Skin Keratinocytes
by Marco Fumagalli, Giulia Martinelli, Giuseppe Paladino, Nora Rossini, Umberto Ciriello, Vincenzo Nicolaci, Nicole Maranta, Carola Pozzoli, Safwa Moheb El Haddad, Elisa Sonzogni, Mario Dell’Agli, Stefano Piazza and Enrico Sangiovanni
Pharmaceuticals 2025, 18(5), 647; https://doi.org/10.3390/ph18050647 - 28 Apr 2025
Viewed by 1717
Abstract
Background: Cannabis sativa L. (C. sativa) has a long history of medicinal use. Its inflorescences contain bioactive compounds like non-psychotropic cannabidiol (CBD), which is well known for its anti-inflammatory potential in skin conditions such as psoriasis, and psychotropic Δ-9-tetrahydrocannabinol (THC). [...] Read more.
Background: Cannabis sativa L. (C. sativa) has a long history of medicinal use. Its inflorescences contain bioactive compounds like non-psychotropic cannabidiol (CBD), which is well known for its anti-inflammatory potential in skin conditions such as psoriasis, and psychotropic Δ-9-tetrahydrocannabinol (THC). Keratinocytes, the main cells in the epidermis, are crucial for regulating skin inflammation by producing mediators like IL-8 when stimulated by agents like TNFα. Methods: This study explores the anti-inflammatory effects of a standardized C. sativa extract (CSE) with 5% CBD and less than 0.2% THC in human keratinocytes challenged by TNFα. The aim of this study is to analyze the specific contributions of the main constituents of CSE to inflammatory responses in human keratinocytes by fractionating the extract and examining the effects of its individual components. Results: MTT assays showed that CSE was non-toxic to HaCaT cells up to 50 μg/mL. CSE inhibited NF-κB activity and reduced IL-8 secretion in a concentration-dependent manner, with mean IC50 values of 28.94 ± 10.40 μg/mL and 20.06 ± 2.78 μg/mL (mean ± SEM), respectively. Fractionation of CSE into four subfractions revealed that the more lipophilic fractions (A and B) were the most effective in inhibiting NF-κB, indicating that cannabinoids and cannflavins are key contributors. Pure CBD is one of the most active cannabinoids in reducing NF-κB-driven transcription (together with THC and cannabigerol), and due to its abundance in CSE, it is primarily responsible for the anti-inflammatory activity. Conclusions: This study highlights CBD’s significant role in reducing inflammation in human keratinocytes and underscores the need to consider the synergistic interactions of several molecules within C. sativa extracts for maximum efficacy. Standardized extracts are essential for reproducible results due to the variability in responses. Full article
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21 pages, 904 KiB  
Review
Cannabinoids: Therapeutic Perspectives for Management of Orofacial Pain, Oral Inflammation and Bone Healing—A Systematic Review
by Maria Domenica Campana, Giulio de Paolis, Gilberto Sammartino, Paolo Bucci, Angelo Aliberti and Roberta Gasparro
Int. J. Mol. Sci. 2025, 26(8), 3766; https://doi.org/10.3390/ijms26083766 - 16 Apr 2025
Cited by 2 | Viewed by 1904
Abstract
Cannabinoids, particularly cannabidiol (CBD) and tetrahydrocannabinol (THC), have been increasingly studied for their therapeutic applications in various medical fields. This systematic review aims to explore their role in oral surgery, focusing on pain management, inflammation control, and bone regeneration. A systematic review was [...] Read more.
Cannabinoids, particularly cannabidiol (CBD) and tetrahydrocannabinol (THC), have been increasingly studied for their therapeutic applications in various medical fields. This systematic review aims to explore their role in oral surgery, focusing on pain management, inflammation control, and bone regeneration. A systematic review was conducted using the PRISMA framework to identify relevant studies from the PubMed, Scopus, and Web of Science databases published up to November 2024. The review included clinical and preclinical studies investigating the effects of cannabinoids on orofacial pain, oral inflammation, and bone healing. Data on study design, cannabinoid types, and relevant outcomes were extracted and analyzed. CBD was the most commonly studied compound, with other studies evaluating CB1/CB2 receptor agonists, THC, and cannabis smoke. Clinical trials showed mixed results: some studies found CBD effective in reducing dental or myofascial pain, while others found limited or non-superior outcomes compared to standard treatments (e.g., NSAIDs, corticosteroids). Among the four RCTs, three had a low risk of bias, and one moderate; all nine animal studies had a high risk of bias. in conclusion, preclinical and clinical studies suggest that cannabinoids represent a promising non-opioid alternative for pain management and for oral inflammation. Although some evidence suggests potential benefits of cannabinoids, particularly CBD, in oral health contexts, findings are derived from heterogeneous studies—many with high risk of bias. More high-quality, standardized clinical trials are necessary before recommending cannabinoids for routine dental practice. Full article
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21 pages, 2109 KiB  
Article
Maximizing Cannabinoid and Polyphenol Extraction from Industrial Hemp (Cannabis sativa L. cv. Helena) Areal Parts: A Comparative Study of Ultrasound-Assisted and Conventional Methods at Two Harvest Stages
by Zorica Lazarević, Anamarija Koren, Tijana Zeremski, Aleksandra Mišan, Nataša Nastić, Nadežda Stojanov and Senka Vidović
Plants 2025, 14(5), 816; https://doi.org/10.3390/plants14050816 - 5 Mar 2025
Viewed by 1342
Abstract
In this work, two extraction techniques, conventional and ultrasound-assisted extraction (UAE) techniques, were employed for the extraction of natural bioactive compounds (NBCs) from the areal parts of industrial hemp (Cannabis sativa L. cv. Helena) at two harvesting stages: (i) the beginning of [...] Read more.
In this work, two extraction techniques, conventional and ultrasound-assisted extraction (UAE) techniques, were employed for the extraction of natural bioactive compounds (NBCs) from the areal parts of industrial hemp (Cannabis sativa L. cv. Helena) at two harvesting stages: (i) the beginning of flowering and (ii) the full flowering of the hemp plants. In the conventional extraction, the effect of different extraction solvents on the extraction yield and the content of NBCs was examined. The extraction temperature, extraction time, and ultrasonic power were chosen for the process parameters in UAE. The highest value of the investigated responses in UAE-obtained extracts was higher compared to extract obtained with conventional extraction techniques when the same solvent was used (50% ethanol): extraction yield (17.54 compared to 15.28%), content of total phenols and total flavonoids (1.7795 compared to 1.0476 mg GAE/mL and 0.6749 compared to 0.3564 mg CE/mL, respectively) and cannabidiol (0.8752 compared to 0.4310 mg/mL). Comparing the plant material in different developmental stages, it can be concluded that hemp aerial parts at the beginning of the flowering stage represent a good source of the phenolic compound with sinapic acid and apigenin being dominant, while hemp aerial parts in the full flowering stage represent a good source of cannabinoids. Full article
(This article belongs to the Section Phytochemistry)
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20 pages, 3112 KiB  
Article
Anti-Inflammatory Activity of Cannabis sativa L. Extract in 2,4-Dinitrochlorobenzene-Induced Dermatitis in Rats
by Renata Wolińska, Maria Zalewska, Piotr Poznański, Agata Nawrocka, Agnieszka Kowalczyk, Mariusz Sacharczuk and Magdalena Bujalska-Zadrożny
Pharmaceuticals 2025, 18(3), 370; https://doi.org/10.3390/ph18030370 - 5 Mar 2025
Cited by 1 | Viewed by 1345
Abstract
Background: Cannabis sativa L. and its products are becoming popular for the treatment of inflammatory diseases. One of the main phytocannabinoids contained in cannabis is cannabidiol (CBD), which is a component of numerous cosmetic preparations used to treat inflammatory skin diseases such [...] Read more.
Background: Cannabis sativa L. and its products are becoming popular for the treatment of inflammatory diseases. One of the main phytocannabinoids contained in cannabis is cannabidiol (CBD), which is a component of numerous cosmetic preparations used to treat inflammatory skin diseases such as atopic dermatitis (AD) and psoriasis. However, current data regarding the efficacy and safety of CBD for dermatological indications are limited. Therefore, the aim of the present study was to evaluate the anti-inflammatory effect of high-CBD Cannabis sativa L. extract (eCBD) in a model of AD. Methods: Dermatitis was induced by repeated application of 2,4-dinitrochlorobenzene (DNCB) to the skin of the rats’ ears. The therapeutic effect of eCBD was evaluated in behavioral, histopathological, and hematological studies following topical application as an ointment containing 2% CBD. Results: Application of the ointment containing eCBD resulted in attenuation of DNCB-induced inflammation. Interestingly, an anti-edematous effect was more pronounced in rats treated with the eCBD than in rats treated with 1% hydrocortisone ointment. However, eCBD did not reduce the frequency of DNCB-induced scratching, while there was a visible antipruritic effect of 1% hydrocortisone application. Histopathological analysis revealed that both eCBD and 1% hydrocortisone ointments significantly decreased mast cell count compared with the Vaseline control group. Furthermore, treatment with an ointment containing eCBD resulted in a decrease in the number of leukocytes in the blood. Conclusions: Topically administered eCBD had a stronger anti-edematous effect than glucocorticosteroid and differently affected hematological parameters. It is suggested that eCBD has therapeutic potential for the treatment of AD. Full article
(This article belongs to the Section Natural Products)
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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 1430
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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14 pages, 870 KiB  
Article
Optimized Extraction Method for Neutral Cannabinoids Quantification Using UHPLC-HRMS/MS
by João Victor Meirelles, Débora Cristina Diniz Estevam, Vanessa Farelo dos Santos, Henrique Marcelo Gualberto Pereira, Tatiana D. Saint Pierre, Valdir F. Veiga-Junior and Monica Costa Padilha
Biomolecules 2025, 15(2), 246; https://doi.org/10.3390/biom15020246 - 8 Feb 2025
Viewed by 1056
Abstract
The Cannabis market is experiencing steady global growth. Cannabis herbal extracts (CHE) are interesting and sought-after products for many clinical conditions. The medical potential of these formulations is mainly attributed to neutral cannabinoids, such as cannabidiol (CBD), tetrahydrocannabinol (THC), and cannabinol (CBN), and [...] Read more.
The Cannabis market is experiencing steady global growth. Cannabis herbal extracts (CHE) are interesting and sought-after products for many clinical conditions. The medical potential of these formulations is mainly attributed to neutral cannabinoids, such as cannabidiol (CBD), tetrahydrocannabinol (THC), and cannabinol (CBN), and their non-standardized content poses a significant fragility in these pharmaceutical inputs. High-resolution mass spectrometry portrays a powerful alternative to their accurate monitoring; however, further analytical steps need to be critically optimized to keep up with instrumental performance. In this study, Full Factorial and Box–Behnken designs were employed to achieve a multivariate optimization of CBD, THC, and CBN extraction from human and veterinary commercial CHE using a minimum methanol/hexane 9:1 volume and short operational times. A predictive model was also constructed using the Response Surface Methodology and its accuracy was validated. Agitation and sonication times were identified as the most significant operational extraction parameters, followed by the extraction mixture volume. The final setup of the optimized method represented a significantly faster and cheaper protocol than those in the literature. The selected neutral cannabinoids quantification was conducted using ultra high-performance liquid chromatography coupled to high-resolution tandem mass spectrometry (UHPLC-HRMS/MS) with a precision of <15%, accuracy of 69–98%, sensitivity of 23–39 ng kg−1, and linearity regarding pharmaceutical requirements. State-of-the-art levels of analytical sensitivity and specificity were achieved in the target quantification due to high-resolution mass spectrometry. The developed method demonstrated reliability and feasibility for routine analytical applications. As a proof-of-concept, it enabled the efficient processing of 16 samples of commercial CHE within a three-hour timeframe, showcasing its practicality and reproducibility, and highlighting its potential for broader adoption in similar scenarios for both human and veterinary medicines. Full article
(This article belongs to the Special Issue Biomolecules and Materials from Agro-Industrial Wastes, 2nd Edition)
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Article
Optimization and Evaluation of Cannabis-Based Magistral Formulations: A Path to Personalized Therapy
by Bożena Grimling, Magdalena Fast, Magdalena Okoniewska, Artur Owczarek and Bożena Karolewicz
Pharmaceuticals 2025, 18(1), 73; https://doi.org/10.3390/ph18010073 - 9 Jan 2025
Viewed by 1853
Abstract
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 [...] Read more.
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. Full article
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