Review
Chemistry, Medicinal
T. Srinivasa Reddy, Roby Zomer, Nitin Mantri
Summary: Medical cannabis has gained significant attention for its potential benefits in managing pain, anxiety, depression, and neurological disorders. The major phytocannabinoids derived from the cannabis plant, THC and CBD, have shown pharmacological and therapeutic properties. In particular, they have been studied for their use in cancer treatment due to their palliative effects and anticancer activities. However, their poor solubility and bioavailability limit their clinical application, thus nanotechnology-based drug delivery strategies are being developed to improve their efficacy.
PHYTOTHERAPY RESEARCH
(2023)
Article
Neurosciences
Vanessa A. Mitchell, Juliette Harley, Sherelle L. Casey, Arabella C. Vaughan, Bryony L. Winters, Christopher W. Vaughan
Summary: The study found that oral THC and CBD, either alone or in combination, have analgesic effects in an animal neuropathic pain model. However, unlike injection studies, the combination of THC:CBD lacks analgesic synergy when delivered orally. Furthermore, both oral THC and THC:CBD combination display a relatively poor therapeutic window, suggesting that CBD may provide a safer but less effective oral treatment for nerve injury-induced neuropathic pain than THC.
Article
Multidisciplinary Sciences
Samantha L. Baglot, Catherine Hume, Gavin N. Petrie, Robert J. Aukema, Savannah H. M. Lightfoot, Laine M. Grace, Ruokun Zhou, Linda Parker, Jong M. Rho, Stephanie L. Borgland, Ryan J. McLaughlin, Laurent Brechenmacher, Matthew N. Hill
Summary: Up to a third of North Americans report using cannabis in the prior month, most commonly through inhalation. Animal models that reflect human consumption are critical to study the impact of cannabis on brain and behaviour. The study found different pharmacokinetic profiles following inhalation versus injection of THC, with higher initial brain THC concentration following inhalation.
SCIENTIFIC REPORTS
(2021)
Review
Plant Sciences
Henry Lowe, Blair Steele, Joseph Bryant, Ngeh Toyang, Wilfred Ngwa
Summary: This article discusses the potential medicinal value of non-cannabinoid compounds in the cannabis plant, such as flavonoids and terpenes, and highlights one promising non-cannabinoid molecule, Caflanone, for clinical trials. The article suggests that many phytochemicals in cannabis have wide therapeutic potential.
Article
Medicine, General & Internal
C. Austin Zamarripa, Tory R. Spindle, Renuka Surujunarain, Elise M. Weerts, Sumit Bansal, Jashvant D. Unadkat, Mary F. Paine, Ryan Vandrey
Summary: This study compared the pharmacokinetics and pharmacodynamics of orally administered ?9-THC-dominant and CBD-dominant cannabis extracts at the same dose of ?9-THC (20 mg). The results showed that the use of CBD-dominant extract resulted in stronger adverse effects, contradicting the common claim that CBD attenuates the adverse effects of ?9-THC. These differences are likely due to the inhibition of ?9-THC and 11-OH-?9-THC metabolism by CBD. This study is important for understanding the clinical and regulatory decisions regarding the use of cannabis products and the interactions between cannabinoid compounds and drugs.
Article
Neurosciences
Markus Koestenberger, Gerhard Nahler, Trevor M. Jones, Stefan Neuwersch, Rudolf Likar
Summary: There is a growing interest in medical cannabis and cannabinoids treatments, with increasing research in the field. While medical cannabis plays a significant role in managing chronic pain, the existence of the entourage effect of other cannabis constituents remains controversial. CBD, a emerging cannabinoid, is gaining attention for its potential benefits, but further studies are needed to fully understand its effects.
JOURNAL OF NEUROIMMUNE PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Philip Wiredu Addo, Sai Uday Kumar Reddy Sagili, Samuel Eichhorn Bilodeau, Frederick-Alexandre Gladu-Gallant, Douglas A. MacKenzie, Jennifer Bates, Garnet McRae, Sarah MacPherson, Maxime Paris, Vijaya Raghavan, Valerie Orsat, Mark Lefsrud
Summary: This study evaluated the effects of different extraction techniques on cannabis extraction and optimized conditions for maximum yield and concentration of cannabinoids and terpenes. Ultrasound-assisted extraction outperformed microwave-assisted extraction, with sample-to-solvent ratio significantly influencing the secondary metabolite profiles in ultrasound-assisted extracts.
Article
Biochemistry & Molecular Biology
Philip Wiredu Addo, Sai Uday Kumar Reddy Sagili, Samuel Eichhorn Bilodeau, Frederick-Alexandre Gladu-Gallant, Douglas A. A. MacKenzie, Jennifer Bates, Garnet McRae, Sarah MacPherson, Maxime Paris, Vijaya Raghavan, Valerie Orsat, Mark Lefsrud
Summary: Efficient extraction of cannabinoids and terpenes from cannabis biomass using cold ethanol was optimized in this study. The optimal conditions for extraction at different temperatures were a cannabis-to-ethanol ratio of 1:15 and a 10 min extraction time. Terpene content decreased at -20 degrees C and room temperature compared to -40 degrees C extraction.
Article
Chemistry, Analytical
Yao Lin, Yuyang Li, Hongqi Chang, Simin Ye, Yi Ye, Lin Yang, Linchuan Liao, Hao Dai, Zeliang Wei, Yurong Deng, Jinyi Zhang, Chengbin Zheng
Summary: The excessive consumption of THC poses severe health risks and public safety concerns. However, the quantification of THC using simple and cost-effective tools remains challenging. In this study, researchers developed a label-free ratiometric fluorescent sensor based on THC1.2/ThT and red CdTe quantum dots for the instant monitoring of THC and its metabolite THC-COOH.
ANALYTICAL CHEMISTRY
(2023)
Article
Biochemical Research Methods
Sebastian Rzeppa, Joachim Grosse, Claudia Rautenberg, Detlef Thieme, Triin Lepp, Henn Vallimae, Annekathrin M. Keiler
Summary: Delta(8)-Tetrahydrocannabinol (Delta(8)-THC) is an isomer of Delta(9)-THC with a similar mode of action but lower potency. Despite low levels in plant material, formulations with high concentrations of Delta(8)-THC are becoming popular. It is classified as a prohibited substance by WADA.
DRUG TESTING AND ANALYSIS
(2021)
Review
Biochemistry & Molecular Biology
Rosario Licitra, Maria Marchese, Valentina Naef, Asahi Ogi, Marco Martinelli, Claudia Kiferle, Baldassare Fronte, Filippo Maria Santorelli
Summary: This article reviews the use of cannabis/cannabinoids in zebrafish and their potential application in neurological disorder models. Zebrafish have been proven to be a useful tool for testing the bioactivity of cannabinoids and providing important insights into the safety and efficacy of different cannabis extract-based products.
Review
Biochemistry & Molecular Biology
Cristina Ferreira Almeida, Natercia Teixeira, Georgina Correia-da-Silva, Cristina Amaral
Summary: Cannabinoids have shown promising potential for diverse pathological conditions such as multiple sclerosis, epilepsy, pain relief, and cancer treatment. Studies have demonstrated their ability to modulate cancer cell proliferation and death, as well as angiogenesis, making them attractive as agents for cancer therapy. Research on the effects of cannabinoids on breast cancer subtypes, particularly ER- and ER+ cells, has been increasing in recent years, showing potential for future therapeutic applications.
Review
Biochemistry & Molecular Biology
Kathleen Louis-Gray, Srinivasan Tupal, Louis S. Premkumar
Summary: The most common medicinal claims for cannabis are relief from chronic pain, stimulation of appetite, and as an antiemetic. Transient receptor potential vanilloid 1 (TRPV1) plays a crucial role in pain and nausea/vomiting perception and control. Chronic cannabis use can cause paradoxical cannabis-induced hyperemesis syndrome (HES), which can be treated with hot-water hydrotherapy and topical application of capsaicin.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Oncology
Herman J. Woerdenbag, Peter Olinga, Ellen A. Kok, Donald A. P. Brugman, Ulrike F. van Ark, Arwin S. Ramcharan, Paul W. Lebbink, Frederik J. H. Hoogwater, Daan G. Knapen, Derk Jan A. de Groot, Maarten W. Nijkamp
Summary: The use of cannabis products in oncology has generated interest, particularly among patients. However, the value of these products in cancer care and the associated risks are still a matter of debate despite the availability of research data. This review aims to provide a recommendation on the use of cannabis products in clinical oncology by assessing recent literature. The different types, characteristics, quality, and pharmacology of cannabis products are discussed. Standardization is crucial for ensuring reliable and reproducible quality. The oromucosal/sublingual route of administration is preferred over inhalation and drinking tea. Cannabinoids may interact with anticancer drugs and symptom management drugs, potentially enhancing or reducing their effects. Clinical research is needed to support the use, or refraining from use, of cannabis products in cancer patients.
Review
Chemistry, Organic
Abhinandan Banerjee, John J. Hayward, John F. Trant
Summary: THC and CBD, the major cannabinoids, face challenges in their incorporation into clinical and nutraceutical preparations due to limited bioavailability, low water solubility, and variable pharmacokinetic profiles. Derivatization offers potential solutions to these issues by providing labile pro-drugs with enhanced bioavailability or interesting pharmacological properties. This review explores advanced derivatization strategies for the major cannabinoids, using pure phytocannabinoids as starting materials to produce cannabinoid pro-drugs or novel pharmacoactive materials.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2023)
Article
Obstetrics & Gynecology
Camille Dugas, Laurence Laberee, Julie Perron, Gabrielle St-Arnaud, Veronique Richard, Veronique Perreault, Nadine Leblanc, Isabelle Marc, Vincenzo Di Marzo, Alain Doyen, Alain Veilleux, Julie Robitaille
Summary: This study compared the macronutrient and energy content of human milk between women with and without GDM. The results showed that protein, lactose, and energy content were similar between the two groups, but the concentration of TG was higher in women with GDM. Maternal age and fasting glucose level were associated with the composition of human milk, and TG in human milk was associated with infant growth in children without GDM.
BREASTFEEDING MEDICINE
(2023)
Article
Medicine, Research & Experimental
Hilal Kalkan, Ester Pagano, Debora Paris, Elisabetta Panza, Mariarosaria Cuozzo, Claudia Moriello, Fabiana Piscitelli, Armita Abolghasemi, Elisabetta Gazzerro, Cristoforo Silvestri, Raffaele Capasso, Andrea Motta, Roberto Russo, Vincenzo Di Marzo, Fabio Arturo Iannotti
Summary: This study found that there are changes in the gut microbiota composition, short-chain fatty acids (SCFAs) levels, and related metabolites in the mdx mouse model of Duchenne muscular dystrophy (DMD) compared to healthy controls. Supplementation with sodium butyrate (NaB) in mdx mice showed similar benefits as deflazacort (DFZ) in terms of muscle strength, autophagy, and inflammation. In LPS-stimulated C2C12 myoblasts, NaB reduced inflammation, promoted autophagy, and prevented dysregulation of microRNAs targeting the endocannabinoid CB1 receptor gene through the activation of GPR109A and PPAR gamma receptors. This suggests a potential disease-modifying approach for DMD and other muscular dystrophies.
EMBO MOLECULAR MEDICINE
(2023)
Article
Chemistry, Medicinal
Giovanni Graziano, Pietro Delre, Francesca Carofiglio, Jose Brea, Alessia Ligresti, Magdalena Kostrzewa, Chiara Riganti, Claudia Gioe-Gallo, Maria Majellaro, Orazio Nicolotti, Nicola Antonio Colabufo, Carmen Abate, Maria Isabel Loza, Eddy Sotelo, Giuseppe Felice Mangiatordi, Marialessandra Contino, Angela Stefanachi, Francesco Leonetti
Summary: CB2R, together with CB1R and endogenous cannabinoids, forms the ECS and plays a role in inflammatory diseases. The design of selective CB2R ligands is challenging due to the high sequence homology of CB1R and CB2R. In this study, a new class of N-adamantyl-anthranil amide derivatives as CB2R selective ligands were designed and synthesized, displaying high affinity for CB2R and excellent selectivity over CB1R. The compounds also exhibited modulation of the inflammatory cascade.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Cell Biology
Francesco Suriano, Claudia Manca, Nicolas Flamand, Matthias Van Hul, Nathalie M. Delzenne, Cristoforo Silvestri, Patrice D. Cani, Vincenzo Di Marzo
Summary: This study characterized the profile of endocannabinoidome and oxylipins in the intestines of obese and diabetic mice, and found correlations between these mediators and intestinal inflammation and gut microbiota composition. The results suggest that the altered eCBome and oxylipin signaling may contribute to obesity and diabetes-induced gut dysbiosis and inflammation.
Review
Pharmacology & Pharmacy
Alexandre Perez-Lopez, Ana Isabel Torres-Suarez, Cristina Martin-Sabroso, Juan Aparicio-Blanco
Summary: The blood-brain barrier (BBB) poses challenges for drug delivery to the central nervous system, resulting in unmet medical needs for brain diseases. Research on the three-dimensional structure of the BBB provides insights into its pathology and aids in the development of novel brain disease therapies. Various 3D models, including hydrogel, spheroid, organoid-based static models, and microfluidic-based BBB-on-a-chip models, have been developed to mimic the human neurovascular unit. This review discusses the development and application of these BBB models for permeability testing of nanomedicines, as well as their advantages and disadvantages, and the validation of their results with in vivo preclinical data.
ADVANCED DRUG DELIVERY REVIEWS
(2023)
Review
Biochemistry & Molecular Biology
Giovanni Graziano, Angela Stefanachi, Marialessandra Contino, Ruben Prieto-Diaz, Alessia Ligresti, Poulami Kumar, Antonio Scilimati, Eddy Sotelo, Francesco Leonetti
Summary: Multicomponent reactions (MCRs) are widely used in synthetic organic chemistry for drug discovery and development due to their flexibility in forming complex products with high efficiency. They are considered as an exploratory and evolutionary tool in medicinal chemistry, enabling sustainable and rapid synthesis of biologically active molecules. This review provides an overview of the approaches and applications of MCRs in the development of new anticancer drugs, showcasing their extensive use in this field.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Martina Di Bartolomeo, Tibor Stark, Serena Di Martino, Fabio Arturo Iannotti, Jana Ruda-Kucerova, Giovanni Luca Romano, Martin Kuchar, Samuele Laudani, Petr Palivec, Fabiana Piscitelli, Carsten T. Wotjak, Claudio Bucolo, Filippo Drago, Vincenzo Di Marzo, Claudio D'Addario, Vincenzo Micale
Summary: Adolescent exposure to cannabinoids, such as THC, may increase the risk of psychosis in individuals exposed to perinatal insult. In this study, the researchers examined the effects of peripubertal THC exposure on rats that were also exposed to prenatal methylazoxymethanol acetate (MAM) or perinatal THC (pTHC). They found that the rats exposed to MAM or pTHC exhibited adult phenotypes relevant to schizophrenia, including social withdrawal and cognitive impairment. The researchers also observed changes in gene expression and DNA methylation, suggesting potential molecular mechanisms underlying these effects.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Ali Mokhtar Mahmoud, Magdalena Kostrzewa, Viviana Marolda, Marianna Cerasuolo, Federica Maccarinelli, Daniela Coltrini, Sara Rezzola, Arianna Giacomini, Maria Pina Mollica, Andrea Motta, Debora Paris, Antonio Zorzano, Vincenzo Di Marzo, Roberto Ronca, Alessia Ligresti
Summary: Despite advancements in diagnosis and interventions, hormone refractory prostate cancer (HRPC) remains a challenge in prostate cancer. Metabolic reprogramming plays a crucial role in PCa oncogenesis and resistance. Cannabidiol (CBD) and cannabigerol (CBG) can suppress HRPC development and show anti-tumor effects in TRAMP mice, even when resistant to enzalutamide.
PHARMACOLOGICAL RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Analia Young Hwa Cho, Hery Chung, Javier Romero-Parra, Poulami Kumar, Marco Allara, Alessia Ligresti, Carlos Gallardo-Garrido, Hernan Pessoa-Mahana, Mario Faundez, Carlos David Pessoa-Mahana
Summary: The endocannabinoid system (ECS) is a broad-spectrum modulator of homeostasis in mammals, offering therapeutic opportunities for various pathologies. In this study, a new library of compounds targeting the CB2 receptor was synthesized by combining natural product motifs with a benzo[d]imidazole scaffold. SAR analysis revealed the importance of bulky aliphatic or aromatic natural product motifs in receptor recognition.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Claudia Mugnaini, Magdalena Kostrzewa, Marta Casini, Poulami Kumar, Valeria Catallo, Marco Allara, Laura Guastaferro, Antonella Brizzi, Marco Paolino, Andrea Tafi, Christelos Kapatais, Gianluca Giorgi, Federica Vacondio, Marco Mor, Federico Corelli, Alessia Ligresti
Summary: Selective CB2 receptor ligands, specifically 7-hydroxy-5-oxopyrazolo[4,3-b]pyridine-6-carboxamide derivatives, have shown potential as therapeutic agents for various diseases. This study synthesized and evaluated twenty-three new compounds in this class, along with seven previously synthesized analogs, to further understand their pharmacological profile and structure-activity relationship. Ten of the new compounds showed potent and selective binding to CB2 receptor, with high affinity and selectivity. The functional activity of these compounds depended on the substitution pattern of the pyrazole ring.
Article
Endocrinology & Metabolism
Hayatte-Dounia Mir, Giada Giorgini, Vincenzo Di Marzo
Summary: This review article focuses on the expanded endocannabinoid system (eCBome) and the gut microbiome, which are increasingly attracting attention as sources of chemical signals regulating food intake, energy metabolism, and body weight. The article describes the mechanisms through which these two systems, in interactions with other signaling systems, intervene in eating disorders, based on studies in experimental models or patients. Furthermore, the article discusses the possibility of the involvement of the eCBome-gut microbiome axis in eating disorders, considering the emerging multi-faceted cross-talk mechanisms between these complex systems.
PSYCHONEUROENDOCRINOLOGY
(2023)
Article
Cell Biology
Hilal Kalkan, Elisabetta Panza, Ester Pagano, Giuseppe Ercolano, Claudia Moriello, Fabiana Piscitelli, Monika Sztretye, Raffaele Capasso, Vincenzo Di Marzo, Fabio Arturo Iannotti
Summary: In this study, the researchers investigated the role of the endocannabinoid system in simvastatin-induced muscle toxicity. They found that the expression of endocannabinoids and specific miRNAs targeting the endocannabinoid CB1 gene increased in myoblasts exposed to simvastatin. Moreover, they discovered that the dysregulation of the CB1 receptor and its downstream signaling pathways contributed to statin-induced myopathy.
CELL DEATH & DISEASE
(2023)
Article
Instruments & Instrumentation
Ana Isabel Fraguas-Sanchez, Dolores Hernan, Consuelo Montejo, Justin L. Poklis, Aron H. Lichtman, Ana Isabel Torres-Suarez
Summary: This study evaluates the pharmacokinetics and release characteristics of CBD formulated in polymer microparticles for subcutaneous administration. Comparing the release of CBD from two microparticle formulations in vitro and in vivo, it was found that they had similar dissolution profiles in vitro but significant differences in blood and brain pharmacokinetics. Extended release of CBD was achieved after a single subcutaneous administration.
DRUG DELIVERY AND TRANSLATIONAL RESEARCH
(2023)
Article
Microbiology
Thomas Deschenes, Fred Wilfried Elom Tohoundjona, Pier-Luc Plante, Vincenzo Di Marzo, Frederic Raymond
Summary: This study compared the performance of machine learning approaches according to different types of data representations derived from shotgun metagenomics. Gene-based approaches provided similar or improved classification performances compared to taxonomic and functional profiles. Feature selection based on biological function also improved classification performance for some pathologies. This study proposes new approaches to represent microbiome data for machine learning.
Article
Biology
Nicola Forte, Charlene Roussel, Brenda Marfella, Anna Lauritano, Rosaria Villano, Elvira De Leonibus, Emanuela Salviati, Tina Khalilzadehsabet, Giada Giorgini, Cristoforo Silvestri, Fabiana Piscitelli, Maria Pina Mollica, Vincenzo Di Marzo, Luigia Cristino
Summary: N-oleoylglycine and N-oleoylalanine reduce the rewarding properties of palatable food, dopamine neuron firing, and the obesogenic effect of a high-fat diet by activating PPAR alpha. Olive oil-rich diets can also decrease weight gain by increasing oleoylglycine levels and enhancing gut microbial diversity.
COMMUNICATIONS BIOLOGY
(2023)