Article
Pharmacology & Pharmacy
Luis Gustavo A. Patrone, Gustavo D. D. Ferrari, Rodrigo Moreira da Silva, Luciane C. C. Alberici, Norberto Peporine Lopes, Angelita M. M. Stabile, Wilfried Klein, Kenia C. Bicego, Luciane H. H. Gargaglioni
Summary: Cannabis legalization has led to increased cannabis use during pregnancy. This study found that prenatal exposure to synthetic cannabinoid WIN can affect the respiratory control system of neonatal and juvenile rats, with greater CO2 sensitivity in males and breathing and brainstem changes. In females, it leads to increased apnea and reduced serotonin neurons. These findings demonstrate long-term and sex-specific consequences of excessive stimulation of the endocannabinoid system during gestation.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Neurosciences
Urszula Skupio, Julia Welte, Roman Serrat, Abel Eraso-Pichot, Francisca Julio-Kalajzi, Doriane Gisquet, Astrid Cannich, Sebastien Delcasso, Isabelle Matias, Unai B. Fundazuri, Sandrine Pouvreau, Antonio C. Pagano Zottola, Gianluca Lavanco, Filippo Drago, Inigo Ruiz de Azua, Beat Lutz, Luigi Bellocchio, Arnau Busquets-Garcia, Francis Chaouloff, Giovanni Marsicano
Summary: Corticosteroid-mediated stress responses involve complex brain circuits and mitochondrial activity, and the endocannabinoid system plays a role in regulating these processes. The study shows that corticosterone impairs novel object recognition (NOR) task performance in mice through the activation of mitochondrial CB1 receptors and the regulation of neuronal mitochondrial calcium levels. Different brain circuits are modulated by this mechanism to mediate the effects of corticosterone during specific phases of the task.
Article
Neurosciences
Rafael Appel Flores, Renata Steinbach, Joao A. B. Pedroso, Martin Metzger, Jose Donato, Marta Aparecida Paschoalini
Summary: The study aimed to evaluate the effects of pharmacological manipulation of alpha-adrenergic agonists in the dorsal raphe nucleus on food intake in satiated rats. Administration of noradrenaline, adrenaline, and clonidine into the DR increased food intake and decreased latency to start consumption in satiated rats. The data suggest that the hyperphagia induced by noradrenaline or adrenaline treatment depends on alpha-2 adrenoceptors activation and that clonidine injections impact neuronal activity in the arcuate nucleus.
Review
Nutrition & Dietetics
Nicholas DiPatrizio
Summary: The gut-brain signaling system, particularly the endocannabinoid system in the upper gastrointestinal tract, plays a crucial role in controlling food intake and the dysregulation of this system is associated with obesity. Direct and indirect interactions between endocannabinoids and vagal afferent neurons are key mechanisms in this control, with a focus on how diet-induced obesity impacts these pathways.
Article
Agriculture, Multidisciplinary
Alba Miguens-Gomez, Marta Sierra-Cruz, Helena Segu, Raul Beltran-Debon, Esther Rodriguez-Gallego, Ximena Terra, Maria Teresa Blay, Anna Maria Perez-Vendrell, Montserrat Pinent, Anna Ardevol
Summary: This study found that acutely ingesting insect Alphitobius diaperinus protein increases food intake in rats and modifies the ex vivo enterohormone secretory profile differently than beef or almond proteins. However, these effects cannot be maintained for a longer period. The results suggest that consuming insect protein increases food intake by reducing ghrelin secretion in the small intestine.
JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE
(2023)
Article
Pharmacology & Pharmacy
David B. Finlay, Thuy Nguyen, Thomas F. Gamage, Shuli Chen, Daniel G. Barrus, Purvi R. Patel, Brian F. Thomas, Jenny L. Wiley, Yanan Zhang, Michelle Glass
Summary: This study compared the synthetic cannabinoid receptor agonist EG-018 and its analogues with existing putative neutral antagonists of CB1 receptor. The results showed highly variable signaling outcomes for EG-018 analogues, with some compounds demonstrating potential as neutral antagonists. These findings provide important insights for the development of CB1 neutral antagonists.
PHARMACOLOGY RESEARCH & PERSPECTIVES
(2022)
Article
Biochemistry & Molecular Biology
Diego A. Rodriguez-Soacha, Sophie A. M. Steinmueller, Ali Isbilir, Julia Fender, Marie H. Deventer, Yesid A. Ramirez, Anna Tutov, Christoph Sotriffer, Christophe P. Stove, Kristina Lorenz, Martin J. Lohse, James N. Hislop, Michael Decker
Summary: This study synthesized new agonist ligands for hCB1R through the design of different classes of photoswitchable molecules, evaluated their mechanisms of action and pharmacological properties through various experimental methods, providing a new molecular tool for studying the role of cannabinoid receptors in related diseases.
ACS CHEMICAL NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Diego A. Rodriguez-Soacha, Sophie A. M. Steinmueller, Ali Isbilir, Julia Fender, Marie H. Deventer, Yesid A. Ramirez, Anna Tutov, Christoph Sotriffer, Christophe P. Stove, Kristina Lorenz, Martin J. Lohse, James N. Hislop, Michael Decker
Summary: This study designed a series of photoswitchable molecules based on an indole core for synthesizing new agonist ligands for the human cannabinoid receptor type 1 (hCB1R). Compound 27a showed high affinity for CB1R and exhibited marked affinity difference compared to its inactive form. The novel agonist 27a can be used to optically modulate cannabinoid receptors and investigate disorders associated with the endocannabinoid system.
ACS CHEMICAL NEUROSCIENCE
(2022)
Article
Multidisciplinary Sciences
Ayat Zagzoog, Asher L. Brandt, Tallan Black, Eunhyun D. Kim, Riley Burkart, Mikin Patel, Zhiyun Jin, Maria Nikolaeva, Robert B. Laprairie
Summary: This study assessed select SCRAs recently identified as potential CB1R and CB2R agonists, finding several SCRAs displaying high bias for cAMP inhibition or beta arrestin2 recruitment and receptor subtype selectivity between CB1R and CB2R.
SCIENTIFIC REPORTS
(2021)
Article
Neurosciences
Edgar Soria-Gomez, Antonio C. Pagano Zottola, Yamuna Mariani, Tifany Desprez, Massimo Barresi, Itziar Bonilla-del Rio, Carolina Muguruza, Morgane Le Bon-Jego, Francisca Julio-Kalajzic, Robyn Flynn, Geoffrey Terral, Ignacio Fernandez-Moncada, Laurie M. Robin, Jose F. Oliveira da Cruz, Simone Corinti, Yasmine Ould Amer, Julia Goncalves, Marjorie Varilh, Astrid Cannich, Bastien Redon, Zhe Zhao, Thierry Leste-Lasserre, Peggy Vincent, Tarson Tolentino-Cortes, Arnau Busquets-Garcia, Nagore Puente, Jaideep S. Bains, Etienne Hebert-Chatelain, Gabriel Barreda-Gomez, Francis Chaouloff, Alexander W. Lohman, Luis F. Callado, Pedro Grandes, Jerome Baufreton, Giovanni Marsicano, Luigi Bellocchio
Summary: Recent neuroscience advances have identified brain circuits as key players in controlling behavior, with evidence showing that activation of specific receptors at different subcellular locations can lead to distinct behavioral outcomes.
Article
Medicine, Legal
Marie H. Deventer, Caitlyn Norman, Robert Reid, Craig McKenzie, Niamh Nic Daeid, Christophe P. Stove
Summary: The enactment of the 2021 class-wide generic SCRA ban in China has led to important changes in the synthetic cannabinoid receptor agonist (SCRA) market. New compounds with new structural features have entered the recreational drug market to bypass this ban. This study investigated the activation potential of these compounds and found that they were mostly inactive at the CB1 and CB2 receptors, indicating that they are unlikely to pose a major health threat.
FORENSIC SCIENCE INTERNATIONAL
(2023)
Article
Pharmacology & Pharmacy
Jamie J. Manning, Gabriel Rawcliffe, David B. Finlay, Michelle Glass
Summary: This study investigated the impact of phosphorylation modifications in a specific sequence of the CB1 receptor C-terminus on the translocation of Arrestin-2 and Arrestin-3. The results showed that these modifications partially contributed to the translocation of Arrestin, but complete inhibition was only achieved when all phosphorylation sites were mutated. Additionally, the dissociation of G proteins was also impaired proportionally to the extent of Arrestin translocation.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Maria Victoria Bariani, Fernando Correa, Ana Paula Dominguez Rubio, Manuel Luis Wolfson, Julieta Aylen Schander, Maximiliano Cella, Julieta Aisemberg, Ana Maria Franchi
Summary: Maternal overnutrition can negatively impact offspring's health, increasing the risk of chronic diseases or metabolic syndrome in adulthood. This study evaluated the transgenerational effect of maternal obesity on cannabinoid receptor 1 knock-out animals in developing metabolic disturbances in their offspring.
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
(2021)
Article
Pharmacology & Pharmacy
Martina Di Bartolomeo, Tibor Stark, Oriana Maria Maurel, Fabio Arturo Iannotti, Martin Kuchar, Jana Ruda-Kucerova, Fabiana Piscitelli, Samuele Laudani, Vladimir Pekarik, Salvatore Salomone, Beatrice Arosio, Raphael Mechoulam, Mauro Maccarrone, Filippo Drago, Carsten T. Wotjak, Vincenzo Di Marzo, Matteo Vismara, Bernardo Dell'Osso, Claudio D'Addario, Vincenzo Micale
Summary: Perinatal exposure to THC affects brain development and increases the risk of psychopathology in adulthood, possibly due to dysregulation of endocannabinoid and dopaminergic systems. Cannabidiol treatment may normalize these abnormalities by modulating altered dopaminergic activity.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Neurosciences
Catharine A. Mielnik, Kim S. Sugamori, David B. Finlay, Hayley H. A. Thorpe, Matthieu Schapira, Nirunthan Sivananthan, Chun Kit Li, Vincent M. Lam, Sean Harrington, Mostafa H. Abdelrahman, Laurent A. Trembleau, W. McIntyre Burnham, Jibran Y. Khokhar, Ali Salahpour, Amy J. Ramsey, Michelle Glass, Iain R. Greig, Ruth A. Ross
Summary: The endocannabinoid system plays a significant role in various psychiatric disorders, including schizophrenia. A CB1 receptor allosteric modulator, ABM300, has shown the ability to reduce behavioral deficits in transgenic models, particularly those with hyperdopaminergia.
NEUROPSYCHOPHARMACOLOGY
(2021)
Article
Chemistry, Medicinal
Michael S. Malamas, Manjunath Lamani, Shrouq Farah, Khadijah A. Mohammad, Christina Yume Miyabe, Girija Rajarshi, Simiao Wu, Nikolai Zvonok, Honrao Chandrashekhar, JodiAnne Wood, Alexandros Makriyannis
Summary: Fine-tuning 2-arachidonoylglycerol (2-AG) metabolism in the brain through inhibition of a/b-hydrolase domain containing 6 (ABHD6) shows promise in the treatment of epilepsy, neuropathic pain, and inflammation. ABHD6 inhibitors may also have implications in Type-2 diabetes, metabolic syndrome, and other diseases in the periphery.
Article
Chemistry, Medicinal
Tao Hu, Guoxun Zheng, Dongxiang Xue, Simeng Zhao, Fei Li, Fang Zhou, Fei Zhao, Linshan Xie, Cuiping Tian, Tian Hua, Suwen Zhao, Yueming Xu, Guisheng Zhong, Zhi-Jie Liu, Alexandros Makriyannis, Raymond C. Stevens, Houchao Tao
Summary: The study investigates the rational remodeling of atypical scaffolds for introducing azobenzene in the development of photoswitchable ligands for the cannabinoid receptor 2 (CB2). By optimizing spacer length and attachment position, AzoLig 9 exhibits excellent thermal bistability, decent photopharmacological switchability between configurations, and high subtype selectivity. This structure-guided approach provides new impetus for expanding chemical spaces for customization in diverse photopharmacological studies and beyond.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Clinical Neurology
Mauro Congiu, Laura Micheli, Michele Santoni, Claudia Sagheddu, Anna Lisa Muntoni, Alexandros Makriyannis, Michael S. Malamas, Carla Ghelardini, Lorenzo Di Cesare Mannelli, Marco Pistis
Summary: The study showed that NAAA inhibition with the novel brain permeable NAAA inhibitor AM11095 can enhance the analgesic effects of morphine, delay the development of tolerance to morphine, and reduce neuroinflammation in the spinal cord.
Article
Clinical Neurology
Pauline Bottemanne, Owein Guillemot-Legris, Adrien Paquot, Julien Masquelier, Michael Malamas, Alexandros Makriyannis, Mireille Alhouayek, Giulio G. Muccioli
Summary: The study reveals that NAAA inhibition significantly reduces pathological changes in a multiple sclerosis model, while FAAH inhibition is less effective, and simultaneous inhibition of NAAA and FAAH does not provide additional benefits.
Review
Behavioral Sciences
Jenny L. Wilkerson, Joshua A. Bilbrey, Jasmine S. Felix, Alexandros Makriyannis, Lance R. McMahon
Summary: The endogenous cannabinoid system plays crucial roles in regulating homeostasis and diseases, with efforts towards understanding its mechanisms and developing novel therapeutics. However, drug discovery in the cannabinoid field has been slower than expected, raising questions about the validity of developing new ligands targeting the endocannabinoid system. Current research focuses on exploring the role of the endocannabinoid system in various pathological conditions and developing effective treatments.
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
(2021)
Article
Biochemistry & Molecular Biology
Shrouq I. Farah, Samantha Hilston, Ngan Tran, Nikolai Zvonok, Alexandros Makriyannis
Summary: The interaction profiles of 2-AG, 1-AG, and 3-AG with endocannabinoid enzymes and CB1 receptor show differences in affinity and potency. The stereochemistry is crucial for the MGL enzyme, with 3-AG being the best substrate and 1-AG demonstrating the worst substrate profile. Both 1-AG and 3-AG are efficiently hydrolyzed by hABHD6 without preference.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Neurosciences
Jenny L. Wilkerson, Lauren B. Alberti, Ganesh A. Thakur, Alexandros Makriyannis, Erin D. Milligan
Summary: CB2R agonists can impact the expression of TRPV1 in the spinal cord and DRG, critical for combating allodynia.
Article
Pharmacology & Pharmacy
Barbara Romano, Ester Pagano, Fabio A. Iannotti, Fabiana Piscitelli, Vincenzo Brancaleone, Giuseppe Lucariello, Maria Francesca Nani, Ferdinando Fiorino, Rosa Sparaco, Giovanna Vanacore, Federica Di Tella, Donatella Cicia, Ruggero Lionetti, Alexandros Makriyannis, Michael Malamas, Marcello De Luca, Giovanni Aprea, Maria D'Armiento, Raffaele Capasso, Bernardo Sbarro, Tommaso Venneri, Vincenzo Di Marzo, Francesca Borrelli, Angelo A. Izzo
Summary: The research shows the functional importance of N-acyl ethanolamine acid amidase (NAAA) in colorectal cancer (CRC) progression, with its inhibition counteracting tumor growth and affecting the composition of tumor secretome. NAAA is proposed as a valid drug target for the treatment of CRC growth and development.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Chemistry, Medicinal
Ioannis P. Papanastasiou, Markos-Orestis Georgiadis, Christos Iliopoulos-Tsoutsouvas, Carol A. Paronis, Christina A. Brust, Ngan K. Tran, Lipin Ji, Xiaoyu Ma, JodiAnne T. Wood, Nikolai Zvonok, Fei Tong, Laura M. Bohn, Spyros P. Nikas, Alexandros Makriyannis
Summary: This study merged the features of nabilone and AM2389 and optimized the C3 side chain. Among the nabilone analogs, AM8936 exhibited balanced and potent agonist activity on the CB1 receptor, making it a potential candidate for further development.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Arman A. Sadybekov, Anastasiia Sadybekov, Yongfeng Liu, Christos Iliopoulos-Tsoutsouvas, Xi-Ping Huang, Julie Pickett, Blake Houser, Nilkanth Patel, Ngan K. Tran, Fei Tong, Nikolai Zvonok, Manish K. Jain, Olena Savych, Dmytro S. Radchenko, Spyros P. Nikas, Nicos A. Petasis, Yurii S. Moroz, Bryan L. Roth, Alexandros Makriyannis, Vsevolod Katritch
Summary: Structure-based virtual ligand screening using V-SYNTHES method is effective in rapidly identifying high-scoring compounds from a large chemical space, with experimental results demonstrating successful hit rates and potencies. This approach shows promise for lead discovery and is easily scalable for use with diverse docking algorithms.
Article
Anesthesiology
Xiaoyan Lin, Zhili Xu, Lawrence Carey, Julian Romero, Alexandros Makriyannis, Cecilia J. Hillard, Elizabeth Ruggiero, Marilyn Dockum, George Houk, Ken Mackie, Phillip J. Albrecht, Frank L. Rice, Andrea G. Hohmann
Summary: This study investigated the cell types expressing CB2 receptor and found that CB2 expressed in previously unrecognized populations of skin cells may serve as a potential target for suppressing chemotherapy-induced neuropathic pain.
Article
Multidisciplinary Sciences
Othman Benchama, Sergiy Tyukhtenko, Michael S. Malamas, Mark K. Williams, Alexandros Makriyannis, Hava Karsenty Avraham
Summary: This study found that the use of MAGL inhibitor AM9928 can effectively block the adhesion and migration of TNBC cells, reduce the secretion of pro-inflammatory factors by cells, and inhibit the activation of HBMECs and cytokine secretion caused by TNBC. Animal experiments showed that AM9928 can inhibit the growth of mammary tumors in the mammary fat pads and reduce the permeability changes of the blood brain barrier, thus reducing the metastasis of TNBC in the brain. These findings suggest that MAGL inhibitors have the potential to be a novel strategy for TNBC treatment.
SCIENTIFIC REPORTS
(2022)
Correction
Chemistry, Medicinal
Thanh C. Ho, Joseph J. Mullins, Marcus A. Tius, Spyros P. Nikas, Ngan K. Tran, Fei Tong, Nicolai Zvonok, Alexandros Makriyannis
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Endocrinology & Metabolism
Sherri Osborne-Lawrence, Connor Lawrence, Nathan P. Metzger, Julia Klavon, Hassan R. Baig, Corine Richard, Salil Varshney, Deepali Gupta, Omprakash Singh, Sean B. Ogden, Kripa Shankar, Subhojit Paul, Ryan K. Butler, Jeffrey M. Zigman
Summary: This study explored whether housing PWS mouse models in a thermoneutral environment could induce hyperphagia and obesity. The results showed that Snord116del mice housed in a thermoneutral environment had lower body weight, fat content, and food intake compared to wild-type mice housed at room temperature. However, the thermoneutral environment did not significantly affect the obesity level and food intake of Snord116del mice.
Article
Cell Biology
Suthakar Ganapathy, Jian Liu, Tianqi Yu, Rui Xiong, Qiang Zhang, Alexandros Makriyannis, Changyan Chen
Summary: Hexavalent chromium (Cr(VI)) pollution is a serious environmental and health concern. This study reveals the role of protein kinase C (PKC) in Cr(VI)-induced carcinogenesis and drug resistance, and suggests that PKC can be a potential biomarker for early detection of health damages and a therapeutic target for developing new treatments for diseases caused by Cr(VI).