Special Issues

Cannabinoids and the Endocannabinoid System in Neurological Disorders
Editor: Álvaro Llorente Berzal

Submission Deadline: 15 December 2023 (Status: Open)

Special Issue Editor

Dr. Álvaro Llorente Berzal      Email   |   Website
Department of Physiology, Faculty of Medicine, Autonomous University of Madrid, Madrid, Spain
Interests: endocannabinoid system; sex differences; neuropathic pain; cognition; chemotherapeutic drugs; neurodevelopment; drug addiction

Special Issue Information

Dear Colleagues,

The endocannabinoid system (ECS) is a complex lipidic signalling system that modulates neural activity and network function in the central nervous system (CNS). This system plays a crucial role maintaining the correct homeostasis, not only by modulating neural function, but also by controlling immunological and inflammatory responses of the CNS. The ECS is comprised of cannabinoid receptors (CB1 and CB2), endocannabinoid ligands that bind and activate these receptors (anandamide and 2-arachidonoylglycerol; AEA and 2-AG, respectively), and an enzymatic machinery that synthetises and catabolises these ligands.

Since ECS discovery, cannabinoid drugs (i.e., drugs modulating the ECS) have been isolated from the Cannabis sp. plant (phytocannabinoids) or chemically developed (synthetic cannabinoids). These drugs may act as direct agonists, antagonists, indirect agonists among others of cannabinoid receptors. During several years, preclinical and clinical studies have observed interesting changes in the components of this system in neurological disorders such as Alzheimer′s disease, neuropathic pain, brain tumours, or even schizophrenia. Even more, pharmacological administration of cannabinoids in preclinical models of neurological disease have shown promising results alleviating, or even reverting, some of the most severe symptoms of the mentioned diseases. Thus, ECS has become an important potential therapeutic target for the pharmacological treatment of these diseases.

Based on the above information, we encourage all researchers interested in this topic to present research articles or reviews on different aspects of cannabinoids and endocannabinoid system. This special issue will include state-of-the-art reviews and original articles on basic or clinical research on the endocannabinoid system, cannabinoid or cannabis preparations in neurological disorders, either from a pathophysiological or from a therapeutic perspective.

Álvaro Llorente Berzal
Guest Editor


endocannabinoid system; neurological disorders; cannabinoid drugs; cannabis plant; therapeutic approaches; basic research; clinical research

Manuscript Submission Information

Manuscripts should be submitted via our online editorial system at https://www.biolifesas.org/journalx_brha/authorLogOn.action by registering and logging in to this website. Once you are registered, click here to start your submission. Manuscripts can be submitted now or up until the deadline. All papers will go through peer-review process. Accepted papers will be published in the journal (as soon as accepted) and meanwhile listed together on the special issue website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts will be thoroughly refereed through a double-blind peer-review process. Please visit the Instruction for Authors page before submitting a manuscript. Submitted manuscripts should be well formatted in good English.

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  • Article
    Rosario Licitra, Devid Damiani, Valentina Naef, Baldassare Fronte, Stefania Della Vecchia, Chiara Sangiacomo, Maria Marchese, Filippo M. Santorelli
    Journal of Biological Regulators and Homeostatic Agents. 2023, 37(9): 4935-4946. https://doi.org/10.23812/j.biol.regul.homeost.agents.20233709.480
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    Background: Valproic acid (VPA), an anticonvulsant used in epilepsy, has deleterious effects on embryonic development and is considered an environmental risk factor for autism spectrum disorders. There is a growing need for easy and rapid ways to study its effects on embryonic development. The zebrafish model is a cost- and time-effective tool able to facilitate mechanistic studies and high-throughput drug screening. Epileptic patients are increasingly looking to natural compounds to avoid the strong side effects of synthetic drugs, and cannabinoids appear promising. We evaluated the potential of cannabidiol to mitigate the negative effects of VPA on developing zebrafish embryos.

    Methods: Wild-type AB embryos, untreated or exposed to VPA (5, 10 or 20 μM) and/or cannabidiol (1, 2 or 3 μM), were evaluated at up to 120 hours post-fertilization. Developmental endpoints: survival, hatching, heart rate, morphology, and locomotor behavior (tail coiling and visual motor response test). Three replicates were evaluated per group, for a total of 120 larvae per treatment.

    Results: Although VPA-treated groups showed significantly reduced survival rates compared to control group fish (p ≤ 0.01), zebrafish simultaneously treated with VPA (5 and 10 μM) and cannabidiol (3 μM) displayed survival rates similar to those of untreated controls. Hatching rate, body length and eye area were not influenced by any treatment, but the highest VPA dose and all cannabidiol doses caused a significant increase in burst activity (p ≤ 0.0001). Compared with controls, the pericardial area was larger only in larvae treated with VPA at the highest concentration (p ≤ 0.01). Each VPA treatment caused tachycardia (p ≤ 0.0001), while cannabidiol 3 μM induced bradycardia (p ≤ 0.01). Finally, simultaneous treatment with VPA 5 μM and cannabidiol 3 μM avoided almost all the adverse effects of the two compounds administered individually, stabilizing heart rate and locomotor behavior at control levels.

    Conclusions: This study adds further information on the embryotoxic effect of VPA in the zebrafish model and offers new insights into the use of cannabidiol as an alternative natural drug able to mitigate the deleterious effects of VPA. Multi-laboratory large-scale validation and new genomic and molecular analyses are required to clarify the mechanism of action of VPA on developing embryos and the role of cannabidiol as a potential natural protective agent against its toxic effects.