Article
Neurosciences
Xiao Han, Ying Liang, Briana Hempel, Chloe J. Jordan, Hui Shen, Guo-Hua Bi, Jin Li, Zheng-Xiong Xi
Summary: Cannabinoids modulate dopamine transmission and behavior through activation of CB1 receptors. This study found that CB1 receptors are expressed in a subset of dopamine neurons and are involved in cannabinoid modulation of dopamine release and behavior. Deletion of CB1 receptors from dopamine neurons attenuated the effects of cannabinoids on dopamine release, locomotion, and anxiety.
JOURNAL OF NEUROSCIENCE
(2023)
Article
Chemistry, Analytical
Christian Ieritano, Patrick Thomas, W. Scott Hopkins
Summary: With the increasing global legalization of cannabis, there is a need for accurate quantification of cannabinoids in commercial products. However, the isobaric nature of many cannabinoids, variations in extraction methods and product formulations pose challenges for mass spectrometry (MS) quantitation. In this study, the use of differential mobility spectrometry (DMS) and tandem-MS was demonstrated to distinguish a set of seven cannabinoids, including five isobaric ones. The addition of DMS to the tandem-MS workflow enabled the resolution of each cannabinoid and accurate quantitation of cannabinoid levels in cannabis extracts.
ANALYTICAL CHEMISTRY
(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
Pharmacology & Pharmacy
Ismail Nurul Iman, Nur Aimi Zawami Ahmad, Nurul Aiman Mohd Yusof, Ummi Nasrah Talib, Anwar Norazit, Jaya Kumar, Muhammad Zulfadli Mehat, Zurina Hassan, Christian P. Mueller, Mustapha Muzaimi
Summary: The study suggests that high-dose exposure to mitragynine may lead to cognitive deficits, which can be reversed with a CB1 receptor antagonist. Long-term use of kratom/mitragynine may affect the reward system and cognitive abilities in the brain.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Multidisciplinary Sciences
D. Kostic, M. Nowakowska, J. Freundt Revilla, F. Attig, K. Rohn, F. Gualtieri, W. Baumgaertner, H. Potschka, A. Tipold
Summary: Canine drug-resistant epilepsy is a common problem in veterinary neurology. Treatment with cannabinoids shows promising results, and understanding the distribution of cannabinoid receptor type 1 (CB1R) in the epileptic brain can contribute to better disease understanding and application of cannabinoids in dogs with epilepsy. This study found decreased CB1R expression in the CA1 region of the hippocampus in dogs with idiopathic epilepsy, while dogs with structural epilepsy showed increased CB1R signal intensity. The distinct disease-associated CB1R expression should be considered in the development of new treatments for dogs with epilepsy.
SCIENTIFIC REPORTS
(2023)
Article
Pharmacology & Pharmacy
Xue-Fei Hu, Hong Zhang, Ling-Ling Yu, Wen-Qiang Ge, Ou-Yang Zhan-mu, Yan-Zhen Li, Chao Chen, Teng-Fei Hou, Hong-Chun Xiang, Yuan-Heng Li, Yang-Shuai Su, Xiang-Hong Jing, Jie Cao, Hui-Lin Pan, Wei He, Man Li
Summary: The therapeutic effects of electroacupuncture (EA) on visceral pain and anxiety comorbidity in patients with inflammatory bowel disease (IBD) is well known. This study investigated the involvement of the ventral hippocampus (vHPC) and the cannabinoid type 1 receptors (CB1R) in the mechanism of EA's effects on anxiety and pain. The results demonstrated that EA alleviated visceral hyperalgesia and anxiety in IBD mice by reducing the expression of CB1R in GABAergic neurons and activating CB1R in glutamatergic neurons in the vHPC.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Mary K. Piscura, Diana E. Sepulveda, Malabika Maulik, Josee Guindon, Angela N. Henderson-Redmond, Daniel J. Morgan
Summary: This study demonstrates that further deletion of fi-arrestin2 does not enhance the delay in cannabinoid tolerance observed in CB1R S426A/S430A mutant mice.
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
(2023)
Review
Pharmacology & Pharmacy
Raphael Mechoulam
Summary: After experiencing a traumatic childhood in Europe during the Second World War, the author discovers the joy of scientific research in Israel. Over the past 65 years, the author has focused on studying the chemistry and pharmacology of natural products, particularly plant cannabinoids and endogenous anandamide-like compounds. Despite the approval of certain cannabinoids as drugs, the effects of endogenous cannabinoids and anandamide-like compounds in humans remain poorly researched. Intellectual freedom, the ability to pursue scientific interests, has been the most fulfilling aspect of the author's career. Looking back on their 91 years of life, the author considers themselves fortunate both personally and scientifically.
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY
(2023)
Article
Endocrinology & Metabolism
Mylene Potier, Marlene Maitre, Thierry Leste-Lasserre, Giovanni Marsicano, Francis Chaouloff, Aline Marighetto
Summary: This study investigated the age-dependent effects of acute 17 beta-estradiol (E2) on temporal memory and CA3 to dCA1 synaptic efficacy in male mice. The results showed that E2 reduced memory and synaptic efficacy in young mice, while tending to improve memory without affecting synaptic efficacy in aged mice. The study suggests a key role of CB1-R in mediating E2's deleterious effects in young adulthood and reveals the age-related effects of E2 on memory and synaptic efficacy.
PSYCHONEUROENDOCRINOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Almudena Robledo-Menendez, Maria Vella, Pedro Grandes, Edgar Soria-Gomez
Summary: Hippocampal circuits play a crucial role in cognitive performance and are deeply affected in pathological conditions. Cannabinoid receptors regulate different cell types within hippocampal circuitries. Understanding the precise mechanisms triggered by cannabinoid receptor activation at a cellular and subcellular level helps in grasping hippocampal pathophysiological states.
Article
Behavioral Sciences
Waldo Lucas Luz, Mateus Santos-Silva, Patrick Bruno Cardoso, Nadyme Assad, Edinaldo Rogerio da Silva Moraes, Alan Barroso Araujo Grisolia, Danielle Valente Braga, Luana Ketlen Reis Leao, Suellen Alessandra Soares de Moraes, Adelaide da Conceicao Passos, Evander de Jesus Oliveira Batista, Amauri Gouveia, Karen R. H. Matos Oliveira, Anderson Manoel Herculano
Summary: Acute stress can induce anxiety-like behavior, increased lipid peroxidation, and decreased GABA levels in the brains of zebrafish. Stimulation of CB1 receptors can prevent stress-induced anxiety and oxidative stress, as well as maintain GABA levels in the brain. This suggests that CB1 receptors may be a potential target for treating anxiety disorders triggered by acute stress.
FRONTIERS IN BEHAVIORAL NEUROSCIENCE
(2021)
Article
Endocrinology & Metabolism
Guichang Zou, Jing Xia, Heyi Luo, Dan Xiao, Jin Jin, Chenjian Miao, Xin Zuo, Qianqian Gao, Zhi Zhang, Tian Xue, Yezi You, Ye Zhang, Li Zhang, Wei Xiong
Summary: The combined use of cannabis and alcohol leads to greater psychoactive toxicity than using either substance alone, and the underlying mechanisms behind this worsened outcome are still unclear. This study reveals that the synergistic effect of THC and ethanol on motor incoordination in mice is achieved by activating CB1R and potentiating GlyR within cerebellar PCs. Ethanol enhances THC actions by increasing its permeability across the blood-brain barrier and enriching THC in the cell membrane.
Article
Neurosciences
Devan M. Gomez, Thomas J. Everett, Lindsey R. Hamilton, Ajit Ranganath, Joseph F. Cheer, Erik B. Oleson
Summary: Synthetic cannabinoids, a commonly abused drug in the US, may lead to blunted dopamine response and cross-tolerance to heroin. Chronic exposure to synthetic cannabinoids in rats resulted in reduced dopamine releasing effects of both cannabinoids and heroin.
Article
Clinical Neurology
Xia Li, Briana J. Hempel, Hong-Ju Yang, Xiao Han, Guo-Hua Bi, Eliot L. Gardner, Zheng-Xiong Xi
Summary: The study found that activation of the CB1 receptor is rewarding, while activation of the CB2 receptor is aversive, leading to differential effects of cannabinoids; the release of dopamine in the NAc is regulated by CB1 and CB2 receptors, with CB2 activation inhibiting dopamine release; Δ(9)-THC induces decreased locomotion through both CB1 and CB2 receptor mechanisms.
EUROPEAN NEUROPSYCHOPHARMACOLOGY
(2021)
Article
Psychiatry
Shani Poleg, Emad Kourieh, Angela Ruban, Guy Shapira, Noam Shomron, Boaz Barak, Daniel Offen
Summary: This study investigates the effects of long-term oral treatment with CBD-enriched medical cannabis oil on a human mutation-based Shank3 mouse model of ASD. The treatment was found to alleviate anxiety and decrease repetitive grooming behavior in mutant mice. The involvement of CB1 receptor signaling in the mechanism of Avidekel oil, alongside a decrease in cerebrospinal fluid glutamate concentrations, was uncovered. RNA sequencing of cerebellar brain samples post-treatment revealed changes in mRNA expression of neurotransmission-related genes. The relevance of CBD enrichment and the importance of the THC component in treating core symptoms of ASD were highlighted.
TRANSLATIONAL PSYCHIATRY
(2021)
Review
Pharmacology & Pharmacy
Beltran Alvarez-Perez, Herve Poras, Rafael Maldonado
Summary: Dual enkephalinase inhibitors (DENKIs) provide an innovative strategy to activate opioid receptors and treat opioid use disorders by protecting endogenous opioid peptides. They have the potential to be a safe and effective treatment for acute opioid withdrawal and a promising alternative to opioid substitution therapy with minimized side effects.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Editorial Material
Neurosciences
Arnau Busquets-Garcia, Miriam Melis, Luigi Bellocchio, Giovanni Marsicano
Summary: This article introduces the wide expression and regulatory functions of the endocannabinoid system in both the brain and the periphery. It discusses the distribution of cannabinoid receptors in different cell types and compartments, and highlights the different cellular or molecular effects mediated by these receptors. The article also mentions the expression of the endocannabinoid system throughout the body and its role in modulating the connection between the brain and the periphery. Lastly, it emphasizes the importance of understanding the cannabinoid receptors structure and pharmacology for the development of novel allosteric modulators.
EUROPEAN JOURNAL OF NEUROSCIENCE
(2022)
Article
Neurosciences
Carla Ramon-Duaso, Ana Rocio Conde-Moro, Arnau Busquets-Garcia
Summary: In neuroscience, innovative and advanced technical accomplishments are crucial for understanding brain functioning. The discovery of functional presence of type-1 cannabinoid receptors in astroglial cells has revealed their important role in behavioral control.
Editorial Material
Behavioral Sciences
Arnau Busquets-Garcia, Nathan M. Holmes
FRONTIERS IN BEHAVIORAL NEUROSCIENCE
(2022)
Article
Pharmacology & Pharmacy
Laura Vidal-Palencia, Carla Ramon-Duaso, Jose Antonio Gonzalez-Parra, Arnau Busquets-Garcia
Summary: This study aims to expand our knowledge of the ECS status in a presymptomatic period by using the AD mouse model APP/PS1 mice. The research found that at 3 months of age, the expression of ECS in different brain regions showed differences depending on sex, indicating ECS alterations in APP/PS1 mice at the presymptomatic stage.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Neurosciences
Laura Cutando, Emma Puighermanal, Laia Castell, Pauline Tarot, Morgane Belle, Federica Bertaso, Margarita Arango-Lievano, Fabrice Ango, Marcelo Rubinstein, Albert Quintana, Alain Chedotal, Manuel Mameli, Emmanuel Valjent
Summary: The study demonstrates that the dopamine D2 receptors in cerebellar Purkinje cells play a role in regulating synaptic efficacy and are involved in social behaviors, without affecting motor functions.
NATURE NEUROSCIENCE
(2022)
Article
Neurosciences
Sara Martinez-Torres, Araceli Bergada-Martinez, Jorge E. Ortega, Lorena Galera-Lopez, Arnau Hervera, Lucia de los Reyes-Ramirez, Antonio Ortega-Alvaro, Floortje Remmers, Emma Munoz-Moreno, Guadalupe Soria, Jose Antonio del Rio, Beat Lutz, Jose Angel Ruiz-Ortega, J. Javier Meana, Rafael Maldonado, Andres Ozaita
Summary: Peripheral CB1R plays an important role in memory persistence, modulating the adrenergic system and being relevant for cognition. Inhibition of peripheral CB1R can improve memory performance but has transient effects on contextual fear memory extinction.
NEUROPSYCHOPHARMACOLOGY
(2023)
Correction
Cell Biology
Roman Serrat, Ana Covelo, Vladimir Kouskoff, Sebastien Delcasso, Andrea Ruiz-Calvo, Nicolas Chenouard, Carol Stella, Corinne Blancard, Benedicte Salin, Francisca Julio-Kalajzic, Astrid Cannich, Federico Massa, Marjorie Varilh, Severine Deforges, Laurie M. Robin, Diego De Stefani, Arnau Busquets-Garcia, Frederic Gambino, Anna Beyeler, Sandrine Pouvreau, Giovanni Marsicano
Review
Biochemistry & Molecular Biology
Ignacio Fernandez-Moncada, Giovanni Marsicano
Summary: Astrocytes play a crucial role in brain homeostasis and function, responding to neuronal signals and modulating synaptic activity through gliotransmission. The cannabinoid type-1 (CB1) receptor has emerged as a critical player in the control of glio-transmission and metabolic cooperation between astrocytes and neurons. This review discusses the known and newly discovered properties of astroglial CB1 receptors and their impact on brain function and behavior, highlighting the interconnected relationship between energy metabolism and gliotransmission.
ESSAYS IN BIOCHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Margaret Haney, Monique Vallee, Sandy Fabre, Stephanie Collins Reed, Marion Zanese, Ghislaine Campistron, Caroline A. Arout, Richard W. Foltin, Ziva D. Cooper, Tonisha Kearney-Ramos, Mathilde Metna, Zuzana Justinova, Charles Schindler, Etienne Hebert-Chatelain, Luigi Bellocchio, Adeline Cathala, Andrea Bari, Roman Serrat, David B. Finlay, Filippo Caraci, Bastien Redon, Elena Martin-Garcia, Arnau Busquets-Garcia, Isabelle Matias, Frances R. Levin, Francois-Xavier Felpin, Nicolas Simon, Daniela Cota, Umberto Spampinato, Rafael Maldonado, Yavin Shaham, Michelle Glass, Lars Lykke Thomsen, Helle Mengel, Giovanni Marsicano, Stephanie Monlezun, Jean-Michel Revest, Pier Vincenzo Piazza
Summary: Cannabis use disorder (CUD) is a widespread problem with no current pharmacological treatment options. AEF0117, a signaling-specific inhibitor of the cannabinoid receptor 1, has shown promise in reducing self-administration of cannabis and THC-related behavioral impairment without significant adverse effects in animal studies. Clinical trials involving healthy volunteers and individuals with CUD found that AEF0117 was safe, well tolerated, and significantly reduced the positive subjective effects of cannabis.
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.
Review
Biochemistry & Molecular Biology
Armin Kouchaeknejad, Gunter Van Der Walt, Maria Helena De Donato, Emma Puighermanal
Summary: As CNS-related disorders become a growing concern worldwide, there is an urgent need for new insights and treatment options. The endocannabinoid system (ECS), consisting of endogenous compounds, receptors, and enzymes, plays a critical role in CNS development and regulation. Despite significant progress in understanding the ECS's role in the CNS, its complex architecture and interaction with other biological systems present challenges for research and clinical advancements. To address these challenges, various molecular-genetic tools have been developed to unlock the therapeutic potential of ECS interventions in CNS-related disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Ignacio Fernandez-Moncada, Rui S. Rodrigues, Unai B. Fundazuri, Luigi Bellocchio, Giovanni Marsicano
Summary: The brain requires a large amount of energy and has developed specialized mechanisms to control and fulfill its energy needs. The endocannabinoid system, particularly the CB1 receptor, plays a significant role in regulating brain functions and behavior. The mtCB1 receptors in neurons and astrocytes impair mitochondrial functions and specifically influence behavioral outputs. Understanding the potential implications of (mt)CB1 receptors on oligodendrocytes and microglia metabolic functions can provide insights into the role of these receptors in brain function and behavior.
JOURNAL OF NEUROCHEMISTRY
(2023)
Article
Endocrinology & Metabolism
Arnau Busquets-Garcia, Juan P. Bolanos, Giovanni Marsicano
Summary: Busquets-Garcia et al. provide a historical perspective on the discovery of endocannabinoid signaling and summarize recent findings on the role of endocannabinoids in regulating intracellular metabolism and maintaining whole-body homeostasis. The central and peripheral control of body energy metabolism appears to be the main function of type-1 cannabinoid receptors. Recent advances have revealed the mechanisms through which endocannabinoids control cell metabolism by modulating specific organelle functions. This short review highlights past discoveries and proposes future research questions in this rapidly evolving field.