Review
Pharmacology & Pharmacy
Carmen Rodriguez-Cueto, Laura Garcia-Toscano, Irene Santos-Garcia, Marta Gomez-Almeria, Claudia Gonzalo-Consuegra, Francisco Espejo-Porras, Javier Fernandez-Ruiz, Eva de Lago
Summary: Cannabinoids have therapeutic effects by targeting different elements of the endocannabinoid system, with potential as neuroprotective agents in ALS. The focus is on the activation of the CB2 receptor to limit glial reactivity, and there is a need for clinical trials to confirm the potential of cannabinoid-based medicines in ALS.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Chemistry, Medicinal
Florian Mohr, Thomas Hurrle, Lindsey Burggraaff, Lukas Langer, Martijn P. Bemelmans, Maximilian Knab, Martin Nieger, Gerard J. P. van Westen, Laura H. Heitman, Stefan Braese
Summary: The study reports the development and evaluation of structure-activity relationship of a series of modified coumarins as cannabinoid receptor ligands. The most potent coumarins showed a CB2 selective agonistic profile with low nanomolar affinities, and several crucial structural requirements were identified through the research.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Neurosciences
Beth M. Wiese, Angelica Alvarez Reyes, Todd W. Vanderah, Tally M. Largent-Milnes
Summary: Recent changes in cannabis accessibility have led to the need for understanding the interaction between cannabinoids and the endocannabinoid system with other physiological structures. The endocannabinoid system plays a critical role in respiratory homeostasis and pulmonary functionality. This review focuses on the influence of the endocannabinoid system on the central and peripheral respiratory functionality, and discusses the potential therapeutic applications and safety profile expansion of opioids in respiratory diseases.
FRONTIERS IN NEUROSCIENCE
(2023)
Article
Neurosciences
Robin Visvanathar, Maria Papanikolaou, Diana Aline Noga, Marina Padua-Reis, Adriano Bretanha Lopes Tort, Martina Blunder
Summary: The field of cannabinoid research is gaining increasing interest, with a focus on the function of cannabinoids within the CNS. While Cb-1 receptors have been extensively studied, recent attention has shifted towards Cb-2 receptors in the brain, which remain largely unexplored. Through studies on hippocampal Cb(2)Rs, significant progress has been made in understanding their role in modulating cellular properties and network excitability, challenging prior notions of the endocannabinoid system. Targeting hippocampal Cb(2)Rs may offer novel therapies for memory and adult neurogenesis deficits.
REVIEWS IN THE NEUROSCIENCES
(2022)
Review
Chemistry, Medicinal
Martina Rabino, Sara Mallia, Elisa Castiglioni, Davide Rovina, Giulio Pompilio, Aoife Gowran
Summary: The endocannabinoid system is a complex and diverse regulatory network, with alterations and dysfunctions observed in almost every category of disease. Shifting attitudes toward cannabis not only bring new therapeutic prospects, but also raise other issues.
Review
Biochemistry & Molecular Biology
Ivona Maria Tudorancea, Mitica Ciorpac, Gabriela Dumitrita Stanciu, Catalin Caratasu, Alina Sacarescu, Bogdan Ignat, Alexandra Burlui, Elena Rezus, Ioana Creanga, Teodora Alexa-Stratulat, Ionut Tudorancea, Bogdan Ionel Tamba
Summary: The endocannabinoid system (ECS) plays a significant role in regulating various aspects of mammalian physiology and has potential therapeutic effects in age-related diseases. This comprehensive review explores the complex interaction between the cannabinoid system (CS) and neurodegenerative, oncological, skeletal, and cardiovascular disorders, highlighting the potential of cannabinoids to ameliorate these conditions. The role of the ECS in improving aging-associated immune system dysregulation is also discussed.
Review
Neurosciences
Christopher Martinez-Aguirre, Resat Cinar, Luisa Rocha
Summary: Epilepsy is a common neurological disorder worldwide. Recent studies have shown that the use of cannabinoids and activation of the endocannabinoid system (ECS) can be a therapeutic strategy for controlling epilepsy. However, there are controversial findings regarding the effects of ECS activation.
Article
Chemistry, Medicinal
Daniel Gundel, Winnie Deuther-Conrad, Lea Ueberham, Sarandeep Kaur, Elina Otikova, Rodrigo Teodoro, Magali Toussaint, Thu Hang Lai, Oliver Clauss, Matthias Scheunemann, Guy Bormans, Michael Bachmann, Klaus Kopka, Peter Brust, Rares-Petru Moldovan
Summary: The cannabinoid receptor type 2 (CB2R) is an ideal target for the diagnosis and therapy of neurodegenerative diseases and cancer. This study introduces a novel F-18-labeled radioligand that can efficiently image upregulated CB2R expression.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Kangtai Xu, Yifei Wu, Zhuangzhuang Tian, Yuanfan Xu, Chaoran Wu, Zilong Wang
Summary: Pain, especially chronic pain, has a significant impact on patients' quality of life. Cannabinoids have shown potent analgesic effects in preclinical pain models by acting as agonists of CB1 and CB2 receptors. While the activation of CB1 receptors is associated with psychotropic adverse effects, the promising target for pain treatment is the CB2 receptors primarily expressed in immune cells. Microglia, as resident immune cells in the central nervous system, play a critical role in chronic pain, and CB2 receptors regulate their activity and function. This review focuses on the role of microglial CB2 receptors in spinal nociceptive circuitry and their implications for selective CB2 receptor agonist-mediated analgesia.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Bashir Bietar, Sophie Tanner, Christian Lehmann
Summary: The endocannabinoid system offers a promising avenue for therapeutic interventions, but the presence of cannabinoid receptors in various organs and tissues can complicate targeted treatments. Injuries to the central nervous system can induce neuroinflammation and potentially affect the immune system. Exploring immunomodulatory therapies provides a hopeful alternative in the face of challenges in traditional preventive treatments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Clinical Neurology
Carmen Rodriguez-Cueto, Marta Gomez-Almeria, Laura Garcia Toscano, Julian Romero, Cecilia J. Hillard, Eva de Lago, Javier Fernandez-Ruiz
Summary: The activation of the cannabinoid receptor type-2 (CB2) has neuroprotective effects in ALS models, while the inactivation of CB2 receptor leads to accelerated deterioration and premature mortality in TDP-43 transgenic mice. Pharmacological inactivation of CB2 receptor also showed subtle trends towards worsening ALS symptoms. These findings suggest the potential of CB2 receptor agonists as a neuroprotective therapy for ALS.
Review
Biochemistry & Molecular Biology
Barbara Vuic, Tina Milos, Lucija Tudor, Marcela Konjevod, Matea Nikolac Perkovic, Maja Jazvinscak Jembrek, Gordana Nedic Erjavec, Dubravka Svob Strac
Summary: Neurodegenerative diseases, characterized by protein aggregation in the brain, can be influenced by the activation of CB2 receptors in the endocannabinoid system. Studies suggest that activating CB2 receptors has potential benefits in reducing protein aggregation-based pathology, attenuating inflammation, and alleviating dementia-related symptoms.
Article
Chemistry, Medicinal
Toni Kline, Cong Xu, Faith R. Kreitzer, Dow P. Hurst, Khalil M. Eldeeb, Jim Wager-Miller, Kathleen Olivas, Seon A. Hepburn, John W. Huffman, Ken Mackie, Allyn C. Howlett, Patricia Reggio, Nephi Stella
Summary: The author synthesized fourteen novel alkylindole analogues and evaluated their activities at alkylindole-sensitive GPCRs. They found three characteristics that favor binding to alkylindole-sensitive GPCRs versus CB1R/CB2R and identified novel chemical tools for studying alkylindole-sensitive GPCRs.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Medicine, Research & Experimental
Hebaallah Mamdouh Hashiesh, Charu Sharma, Sameer N. Goyal, Bassem Sadek, Niraj Kumar Jha, Juma Al Kaabi, Shreesh Ojha
Summary: BCP is a natural compound with selective agonist properties that activate CB2R and have various pharmacological effects. BCP shows protective effects in the heart, liver, nervous system, kidneys, gastrointestinal tract, cancer, with antioxidant, anti-inflammatory, and immunomodulatory actions.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Chemistry, Medicinal
Malliga R. Iyer, Resat Cinar, Casey M. Wood, Charles N. Zawatsky, Nathan J. Coffey, Kyu Ah Kim, Ziyi Liu, Alexis Katz, Jasmina Abdalla, Sergio A. Hassan, Yong-Sok Lee
Summary: This report describes the synthesis and structure-activity relationships of novel four-arm dihydropyrazoline compounds designed as peripherally restricted antagonists of the cannabinoid-1 receptor (CB1R). These compounds showed high affinity for CB1R and potent in vitro CB1R antagonist activities. Some compounds with potent CB1R activity exhibited limited brain penetrance, indicating their peripheral restriction. In vivo studies suggested that these compounds could serve as potential leads for developing selective CB1R antagonists with improved potency and peripheral restriction.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Neurosciences
Sonia Burgaz, Concepcion Garcia, Maria Gomez-Canas, Carmen Navarrete, Adela Garcia-Martin, Alain Rolland, Carmen del Rio, Maria J. Casarejos, Eva Munoz, Claudia Gonzalo-Consuegra, Eduardo Munoz, Javier Fernandez-Ruiz
Summary: The quinone derivative VCE-003.2 showed significant neuroprotective effects in both in vitro and in vivo models of Parkinson's disease, while the CBGA-Q and CBGA-Q-Salt derivatives exhibited lower activity at the PPAR-gamma receptor, indicating potential differences in their mechanisms of action.
MOLECULAR AND CELLULAR NEUROSCIENCE
(2021)
Article
Biochemical Research Methods
Yolanda Gomez-Galvez, Monte A. Gates
Summary: This research developed a new method for controlling astrocyte division in primary VM cultures by treating them with different doses of the anti-mitotic drug paclitaxel. The study found that reducing astrocyte density did not affect the survival of dopamine neurons when exposed to the toxin 6-OHDA. These findings suggest that astrocytes may not play a significant role in enhancing the survival of dopamine neurons under toxin challenge.
JOURNAL OF NEUROSCIENCE METHODS
(2021)
Article
Neurosciences
Valentina Satta, Cristina Alonso, Paula Diez, Soraya Martin-Suarez, Marta Rubio, Juan M. Encinas, Javier Fernandez-Ruiz, Onintza Sagredo
Summary: The study validated a new mouse model of Dravet syndrome that exhibited seizuring susceptibility and several comorbidities similar to patients, and identified contributions of the endocannabinoid system, inflammatory events, and impaired neurogenesis in the pathology of the disease.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2021)
Article
Clinical Neurology
Carmen Rodriguez-Cueto, Marta Gomez-Almeria, Laura Garcia Toscano, Julian Romero, Cecilia J. Hillard, Eva de Lago, Javier Fernandez-Ruiz
Summary: The activation of the cannabinoid receptor type-2 (CB2) has neuroprotective effects in ALS models, while the inactivation of CB2 receptor leads to accelerated deterioration and premature mortality in TDP-43 transgenic mice. Pharmacological inactivation of CB2 receptor also showed subtle trends towards worsening ALS symptoms. These findings suggest the potential of CB2 receptor agonists as a neuroprotective therapy for ALS.
Article
Pharmacology & Pharmacy
Isabel Gonzalez-Mariscal, Beatriz Carmona-Hidalgo, Matthias Winkler, Juan D. Unciti-Broceta, Alejandro Escamilla, Maria Gomez-Canas, Javier Fernandez-Ruiz, Bernd L. Fiebich, Silvana-Yanina Romero-Zerbo, Francisco J. Bermudez-Silva, Juan A. Collado, Eduardo Munoz
Summary: Natural cannabidiol and its derivatives, particularly the enantiomer (+)-CBD-HPE, showed enhanced binding and functional activities on cannabinoid receptors CB1R and CB2R. The compound demonstrated potential in preventing hyperglycemia and its complications in a mouse model, with promising pharmacological profile for metabolic and immune-related disorders.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Neurosciences
M. Galan-Ganga, C. Rodriguez-Cueto, J. Merchan-Rubira, F. Hernandez, J. avila, M. Posada-Ayala, J. L. Lanciego, E. Luengo, M. G. Lopez, A. Rabano, J. Fernandez-Ruiz, I. Lastres-Becker
Summary: The study revealed an increase in CB2 receptor expression in hippocampal neurons in Tauopathies, contributing to neurodegeneration, and providing a novel therapeutic strategy for investigation.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Sonia Burgaz, Concepcion Garcia, Maria Gomez-Canas, Alain Rolland, Eduardo Munoz, Javier Fernandez-Ruiz
Summary: This study confirmed the neuroprotective potential of VCE-004.8 in 6-OHDA-lesioned mice, and in vitro studies indicated a greater relevance for PPAR-gamma receptors rather than CB2 receptors in these effects.
Article
Biochemistry & Molecular Biology
Marta Gomez-Almeria, Sonia Burgaz, Carlos Costas-Insua, Carmen Rodriguez-Cueto, Irene Santos-Garcia, Ignacio Rodriguez-Crespo, Concepcion Garcia, Manuel Guzman, Eva de Lago, Javier Fernandez-Ruiz
Summary: This study suggests that dysregulation of the chaperone protein BiP may contribute to the pathogenesis of ALS, with a possible link to CB1 receptor function and the neuroprotective effects of cannabinoids.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Sonia Burgaz, Concepcion Garcia, Claudia Gonzalo-Consuegra, Marta Gomez-Almeria, Francisco Ruiz-Pino, Juan Diego Unciti, Maria Gomez-Canas, Juan Alcalde, Paula Morales, Nadine Jagerovic, Carmen Rodriguez-Cueto, Eva de Lago, Eduardo Munoz, Javier Fernandez-Ruiz
Summary: This study investigated the neuroprotective potential of VCE-006.1 in murine models of neurodegenerative diseases, showing promising results in reversing motor defects caused by Parkinson's disease but no significant effects in amyotrophic lateral sclerosis. The findings suggest the specificity of targeting GPR55 in the development of cannabinoid-based therapies for different neurodegenerative disorders.
Article
Neurosciences
Cristina Alonso, Valentina Satta, Paula Diez-Gutierrez, Javier Fernandez-Ruiz, Onintza Sagredo
Summary: This study suggests that beta-caryophyllene (BCP) could be a promising therapy for Dravet Syndrome. It shows efficacy against seizures and associated comorbidities, and reduces glial reactivity in the brain.
Article
Biochemistry & Molecular Biology
Isabel Lastres-Becker, Eva de Lago, Ana Martinez, Javier Fernandez-Ruiz
Summary: This study provides evidence that the NRF2 signaling pathway is differently affected in ALS and FTD, suggesting a distinct regulatory mechanism for cellular homeostasis in these neurodegenerative disorders.
Article
Chemistry, Medicinal
Laura Figuerola-Asencio, Paula Morales, Pingwei Zhao, Dow P. Hurst, Sommayah S. Sayed, Katsuya L. Colon, Maria Gomez-Canas, Javier Fernandez-Ruiz, Mitchell P. Croatt, Patricia H. Reggio, Mary E. Abood, Nadine Jagerovic
Summary: This study focused on the exploration of GPR55 receptor and identified a thienopyrimidine scaffold-based GPR55 antagonist. The GPR55 activity of newly synthesized compounds was evaluated, and some derivatives with functional efficacy and selectivity against CB1 and CB2 cannabinoid receptors were discovered.
ACS MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Immunology
Irene Santos-Garcia, Carmen Rodriguez-Cueto, Patricia Villegas, Fabiana Piscitelli, Anna Lauritano, Che-Kun J. Shen, Vincenzo Di Marzo, Javier Fernandez-Ruiz, Eva de Lago
Summary: This study used a mouse model of frontotemporal dementia (FTD) and found that increasing endocannabinoid levels can improve the neuropathology caused by FTD, reduce glial reactivity, protect neuronal integrity, and improve cognitive, emotional, and social deficits.
JOURNAL OF NEUROINFLAMMATION
(2023)
Article
Neurosciences
Cristina Alonsoa, Valentina Sattaa, Ines Hernandez-Fisac, Javier Fernandez-Ruiz, Onintza Sagredo
Summary: Cannabidiol (CBD) has been approved as an antiseizure agent in Dravet Syndrome (DS), and it could also potentially relieve associated comorbidities. This study compared the efficacy of CBD and beta-caryophyllene (BCP) and explored the possible additive effect of combining both compounds on these comorbidities. The results showed that BCP and CBD both partially attenuated the behavioral disturbances and glial reactivities, with a potential superior effect when combined.
Article
Neurosciences
Santiago Rodriguez-Carreiro, Elisa Navarro, Eduardo Munoz, Javier Fernandez-Ruiz
Summary: This study found that VCE-003.2 demonstrated neuroprotective effects in experimental Parkinson's disease, while L-DOPA/benserazide only provided symptom relief. This finding reinforces the interest in clinical development of VCE-003.2 for this disease.