Article
Multidisciplinary Sciences
Kyle R. Jensen, Coralie Berthoux, Kaoutsar Nasrallah, Pablo E. Castillo
Summary: Recurrent excitatory neural networks in the hippocampus involving excitatory mossy cells (MCs) can promote epilepsy. Physiologically relevant activity patterns of MCs induce robust presynaptic long-term potentiation (LTP) of MC-GC transmission. Type-1 cannabinoid receptors (CB1Rs) at MC axon terminals play a crucial role in modulating presynaptic metaplasticity and excitatory transmission onto granule cells (GCs).
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemical Research Methods
Marie H. Deventer, Katleen Van Uytfanghe, Inge M. J. Vinckier, Fabiano Reniero, Claude Guillou, Christophe P. Stove
Summary: In recent years, countries have implemented measures to control the increase of new synthetic cannabinoid receptor agonists (SCRAs) in the recreational drug market. China implemented a new legislation in July 2021, banning SCRAs with seven core scaffolds. This study reports on the potency and efficacy of five members of a new class of SCRAs, providing important information for public health officials, law enforcement agencies, and clinicians.
DRUG TESTING AND ANALYSIS
(2022)
Article
Pharmacology & Pharmacy
Wen-Qiang Ge, Ou-Yang Zhan-Mu, Chao Chen, Hong Zhang, Xiao-Yu Wang, Xin Liu, Li Li, Yu-Ye Lan, Chen-Nan Li, Jia-Can Sun, Run-Lin Shi, Zi-Yue Dou, Hui-Lin Pan, Hong-Ping Li, Xiang-Hong Jing, Man Li
Summary: Electroacupuncture (EA) reduces chronic itch by activating CB1 receptors on glutamatergic neurons and inhibiting CB1 receptors on GABAergic neurons in the vlPAG, thereby reducing the release of 5-HT in the medulla oblongata and GRPR signaling in the spinal cord. This study advances our understanding of the therapeutic mechanisms of EA on chronic itch and guides the selection of optimal parameters and acupoints for treatment.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Chemistry, Medicinal
George Amato, Scott Runyon, Vineetha Vasukuttan, Ann M. Decker, Elaine A. Gay, Lucas Laudermilk, Rangan Maitra
Summary: Partial agonists of peripheral cannabinoid receptors (CBRs) have potential therapeutic applications in several medical conditions. However, the principal active component of marijuana, THC, penetrates the central nervous system and produces adverse effects. Peripherally restricted partial agonists of CBRs, particularly of CB1, can be used to treat illnesses safely and effectively with a better therapeutic index. The lead compound 40, a pyrazole partial CBR agonist with peripheral selectivity, shows promising potential for optimization with its high plasma biodistribution over the brain.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Pharmacology & Pharmacy
Dalal AlKhelb, Emily L. Burke, Alexander Zvonok, Christos Iliopoulos-Tsoutsouvas, Markos-Orestis Georgiadis, Shan Jiang, Thanh C. Ho, Spyros P. Nikas, Alexandros Makriyannis, Rajeev I. Desai
Summary: This study aimed to compare the behavioral effects of different cannabinoid (CB) ligands using drug discrimination methods. The results showed that AM411 and AM4089 exhibit better pharmacological profiles compared to A9-THC, including higher potency and in vivo partial agonist-like actions mediated via CB1 receptors.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Neurosciences
Milad Afrasiabi, Akshay Gupta, Huaying Xu, Bogumila Swietek, Vijayalakshmi Santhakumar
Summary: This study reveals that fast-spiking parvalbumin interneurons (PV-INs) contribute minimally to basal synaptic inhibition but selectively mediate sustained feedback inhibition in a subtype of dentate projection neurons called semilunar granule cells (SGCs). The blunting of activity-driven sustained inhibitory gating in SGCs may play a crucial role in their preferential and persistent recruitment during behavioral tasks.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Eduardo Molina-Holgado, Beatriz Paniagua-Torija, Angel Arevalo-Martin, Rafael Moreno-Luna, Pedro F. Esteban, Minh Quynh Uyen Le, Maria del Mar Del Cerro, Daniel Garcia-Ovejero
Summary: CB1 cannabinoid receptor is widely expressed in the central nervous system of animals and its appropriate activation and signaling are crucial during perinatal/postnatal and adolescent stages, influencing long-lasting changes in brain activity that could lead to adult brain disorders. The signaling complexes of CB1 show differences between maturation stages, with enrichment in mitochondrial associated proteins and metabolic molecular functions in immature stages, and an increase in maturation and synaptic-associated proteins in more mature stages. Interacting partners specifically immunoprecipitated with N-terminal or C-terminal CB1 directed antibodies were also described, highlighting new players in postnatal cortical development potentially affected by altered cannabinoid signaling.
JOURNAL OF NEUROCHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Irene B. Maroto, Carlos Costas-Insua, Coralie Berthoux, Estefania Moreno, Andrea Ruiz-Calvo, Carlos Montero-Fernandez, Andrea Macias-Camero, Ricardo Martin, Nuria Garcia-Font, Jose Sanchez-Prieto, Giovanni Marsicano, Luigi Bellocchio, Enric I. Canela, Vicent Casado, Ismael Galve-Roperh, Angel Nunez, David Fernandez de Sevilla, Ignacio Rodriguez-Crespo, Pablo E. Castillo, Manuel Guzman
Summary: The interaction between CB1R and GAP43 affects the signaling of excitatory synapses in the brain, thereby inhibiting the anti-convulsant activity of cannabinoids.
NATURE COMMUNICATIONS
(2023)
Article
Biochemical Research Methods
Marie H. Deventer, Mattias Persson, Caitlyn Norman, Huiling Liu, Matthew J. Connolly, Niamh Nic Daeid, Craig McKenzie, Henrik Green, Christophe P. Stove
Summary: Following the generic ban in China in 2021, the synthetic cannabinoid market has seen the emergence of compounds with wider structural diversity. This study investigated the cannabinoid receptor activation potential of different analogs, including tail-less compounds and those with a brominated core. The results showed that both tail-less and tailed analogs exhibited cannabinoid activity, albeit with varying potency and efficacy. The study also assessed the CB activity of mixtures of different reference standards and confirmed the presence of ADB-5'Br-INACA and MDMB-5'Br-INACA in seized powders.
DRUG TESTING AND ANALYSIS
(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)
Review
Clinical Neurology
Carlos A. Lafourcade, Fraser T. Sparks, Angelique Bordey, Ursula Wyneken, Michael H. Mohammadi
Summary: The hippocampal formation is crucial in the development of temporal lobe epilepsy (TLE), a disease characterized by recurrent, unprovoked epileptic discharges. The hippocampal dentate gyrus (DG) acts as a filter to prevent excessive excitation and is considered critical in the progression of epileptogenesis. Endogenous cannabinoids (endocannabinoids) play a central role in regulating neuronal activity in the DG circuit. This review summarizes recent findings on the role of the DG in controlling hyperexcitability and discusses the potential therapeutic interventions using cannabinoids.
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
Pharmacology & Pharmacy
Yousif Aldabbagh, Anam Islam, Weicong Zhang, Paul Whiting, Afia B. Ali
Summary: In this study, the researchers investigated the alteration of astrocyte-specific GABA transporter 3/4 (GAT3/4) in a mouse model of Alzheimer's disease (AD) and its correlation with changes in excitability of principal cells. They found increased expression of GAT3/4 in reactive astrocytes in the hippocampus of AD mice, which was correlated with enhanced tonic inhibition. Blocking GAT3/4 resulted in increased excitability of principal cells in both wild-type and AD mice, exacerbating synaptic hyperactivity. This suggests that reducing tonic inhibition through GAT3/4 may not be an effective therapeutic strategy for AD.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Neurosciences
Sai Varshini Magham, Praveen Thaggikuppe Krishnamurthy, Neenu Shaji, Lalithkumar Mani, Shivaramakrishnan Balasubramanian
Summary: The endocannabinoid system, particularly the CB2 receptor, has unique neuroprotective properties in neuroinflammation, making it a significant focus of research in neurodegenerative disorders like Alzheimer's disease.
JOURNAL OF NEUROSCIENCE RESEARCH
(2021)
Article
Neurosciences
Yu-Ting Wei, Jei-Wei Wu, Chia-Wei Yeh, Hung-Chang Shen, Kun-Pin Wu, Imre Vida, Cheng-Chang Lien
Summary: VIP+ INs in the DG region of the hippocampus exhibit a high degree of morpho-physiological diversity, with their axons branching in different layers. These INs display variable intrinsic properties and discharge patterns without clear correlation with their morphologies. They show a long latency response to cortical inputs and selectively regulate inhibitory INs over glutamatergic principal neurons through disinhibition mechanisms.
JOURNAL OF COMPARATIVE NEUROLOGY
(2021)