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The Endocannabinoid System in the Central Nervous System: Emphasis on the Role of the Mitochondrial Cannabinoid Receptor 1 (mtCB1R)

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NeuroPsychopharmacotherapy

Abstract

The study of the endocannabinoid system (ECS) emerges formally from the chemical characterization of the psychoactive component of Cannabis sativa, Δ9-tetrahydrocannabinol (Δ9-THC). The ECS consists of genes encoding two well-characterized cannabinoid receptors (CB1Rs and CB2Rs), endocannabinoids (eCBs), and metabolic enzyme machinery responsible for their synthesis and degradation. The study of the ECS is of great interest for understanding CNS function due to its role in the regulation of several physiological functions. Furthermore, ECS implication in antiexcitotoxic, antioxidant, anti-inflammatory, and neuroprotective mechanisms suggests therapeutic potential for some neurological and psychiatric disorders. It is noteworthy that the presence of CB1R in the outer membrane of mitochondria seems to modulate mitochondrial energy metabolism. The high-energy demand of neurons is needed to maintain cellular homeostasis, the membrane potential, and synaptic transmission; therefore, a broad distribution of mitochondria can be found throughout the neuronal body. In addition, ATP synthesis is necessary for axonal growth and regulation of axonal transport. The characterization of a CB1R-regulated Gi/Go signaling pathway at the mitochondrial level has led to a controversial and yet not well understood finding in terms of the physiological significance and the regulated reduction in ATP levels. Although the precise physiological role that cannabinoids play in mitochondria is to be elucidated, some reports using isolated mitochondria suggest that cannabinoids may prevent the mitochondrial damage through this pathway. Here we review, update, and discuss evidence collected on the relevance of the ECS to optimal CNS function and specifically the role that mtCB1R and cannabinoids play in the regulation of mitochondrial/neuronal function.

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Acknowledgments

E.S.O is supported by William Paterson University and NIAAA-NIH grant AA027909. M.A. was supported by the National Institute of Environmental Health Sciences’ grants R01ES03771 and R01ES10563.

Declaration of Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this chapter. The authors are responsible for content and writing of the manuscript and do not necessarily reflect the position of the US Food and Drug Administration nor do mention of trade names and commercial products constituting endorsement or recommendation for use and do not represent agency position or policy.

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Authors and Affiliations

  1. Posgrado en Ciencias Biológicas y de la Salud, DCBS, Universidad Autónoma Metropolitana-Iztapalapa, Ciudad de México, Mexico

    Marisol Maya-López

  2. Laboratorio de Aminoácidos Excitadores, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Ciudad de México, Mexico

    Marisol Maya-López & Abel Santamaría

  3. Departamento de Biomedicina Cardiovascular, Instituto Nacional de Cardiología Ignacio Chávez, Ciudad de México, Mexico

    Cecilia Zazueta

  4. Departamento de Biología de Reproducción, Universidad Autónoma Metropolitana-Iztapalapa, Ciudad de México, Mexico

    Socorro Retana-Márquez

  5. Division of Neurotoxicology, National Center for Toxicological Research, United States Food and Drug Administration, Jefferson, AR, USA

    Syed F. Ali

  6. Cellular Stress Response and Signal Transduction Research Laboratory, Faculty of Medicine, Department of Medical Pharmacology, Gazi University, Ankara, Turkey

    Cimen Karasu

  7. Department of Biology, William Paterson University, Wayne, NJ, USA

    Emmanuel S. Onaivi

  8. Albert Einstein College of Medicine, Bronx, NY, USA

    Michael Aschner

  9. IM Sechenov First Moscow State Medical University, Moscow, Russia

    Michael Aschner

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  1. Marisol Maya-López
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Correspondence to Abel Santamaría .

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Editors and Affiliations

  1. Dept Psychiatry , Psychosomatics & Psychotherapy, University of Würzburg, Medical School Clinical Neurochemistry, Würzburg, Germany

    Peter Riederer

  2. Inst für Psychologische Medizin, Haag, Bayern, Germany

    Gerd Laux

  3. Fujita Health University School Medicine, Toyoake, Aichi, Japan

    Toshiharu Nagatsu

  4. Center Translational Res Neurol Diseases, Dalian Med Uni Shanghai Inst Health Sc Center Translational Res Neurol Diseases, Dalian, China

    Weidong Le

  5. Würzburg, Bayern, Germany

    Christian Riederer

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  1. Clinic and Policlinic for Psychiatry, Psychosomatics and Psychotherapy, University of Hospital Würzburg, Würzburg, Germany

    Peter Riederer

  2. Department of Psychiatry, University of South Denmark, Odense, Denmark

    Peter Riederer

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Maya-López, M. et al. (2021). The Endocannabinoid System in the Central Nervous System: Emphasis on the Role of the Mitochondrial Cannabinoid Receptor 1 (mtCB1R). In: Riederer, P., Laux, G., Nagatsu, T., Le, W., Riederer, C. (eds) NeuroPsychopharmacotherapy. Springer, Cham. https://doi.org/10.1007/978-3-319-56015-1_461-1

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  • DOI: https://doi.org/10.1007/978-3-319-56015-1_461-1

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  • Print ISBN: 978-3-319-56015-1

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