Cannabidiol for neurodegenerative disorders: important new clinical applications for this phytocannabinoid?

Authors

  • Javier Fernández-Ruiz,

    Corresponding author
    1. Departamento de Bioquímica y Biología Molecular III, Instituto Universitario de Investigación en Neuroquímica, Facultad de Medicina, Universidad Complutense, 28040-Madrid
    2. Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED)
    3. Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS)
      Professor Javier Fernández-Ruiz PhD, Departamento de Bioquímica y Biología Molecular III, Facultad de Medicina, Universidad Complutense, Ciudad Universitaria s/n, 28040-Madrid, Spain. Tel.: +34 91 394 1450, Fax: +34 91 394 1691, E-mail: jjfr@med.ucm.es
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  • Onintza Sagredo,

    1. Departamento de Bioquímica y Biología Molecular III, Instituto Universitario de Investigación en Neuroquímica, Facultad de Medicina, Universidad Complutense, 28040-Madrid
    2. Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED)
    3. Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS)
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  • M. Ruth Pazos,

    1. Unidad Experimental, Fundación para la Investigación Biomédica, Hospital Universitario Puerta de Hierro, 28222-Majadahonda, Madrid, Spain
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  • Concepción García,

    1. Departamento de Bioquímica y Biología Molecular III, Instituto Universitario de Investigación en Neuroquímica, Facultad de Medicina, Universidad Complutense, 28040-Madrid
    2. Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED)
    3. Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS)
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  • Roger Pertwee,

    1. School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, UK
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  • Raphael Mechoulam,

    1. Institute for Drug Research, Medical Faculty, Hebrew University, Jerusalem 91120, Israel
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  • José Martínez-Orgado

    1. Unidad Experimental, Fundación para la Investigación Biomédica, Hospital Universitario Puerta de Hierro, 28222-Majadahonda, Madrid, Spain
    2. Servicio de Neonatología, Departamento de Pediatría, Hospital Universitario Puerta de Hierro, 28222-Majadahonda, Madrid, Spain
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Professor Javier Fernández-Ruiz PhD, Departamento de Bioquímica y Biología Molecular III, Facultad de Medicina, Universidad Complutense, Ciudad Universitaria s/n, 28040-Madrid, Spain. Tel.: +34 91 394 1450, Fax: +34 91 394 1691, E-mail: jjfr@med.ucm.es

Abstract

Cannabidiol (CBD) is a phytocannabinoid with therapeutic properties for numerous disorders exerted through molecular mechanisms that are yet to be completely identified. CBD acts in some experimental models as an anti-inflammatory, anticonvulsant, anti-oxidant, anti-emetic, anxiolytic and antipsychotic agent, and is therefore a potential medicine for the treatment of neuroinflammation, epilepsy, oxidative injury, vomiting and nausea, anxiety and schizophrenia, respectively. The neuroprotective potential of CBD, based on the combination of its anti-inflammatory and anti-oxidant properties, is of particular interest and is presently under intense preclinical research in numerous neurodegenerative disorders. In fact, CBD combined with Δ9-tetrahydrocannabinol is already under clinical evaluation in patients with Huntington's disease to determine its potential as a disease-modifying therapy. The neuroprotective properties of CBD do not appear to be exerted by the activation of key targets within the endocannabinoid system for plant-derived cannabinoids like Δ9-tetrahydrocannabinol, i.e. CB1 and CB2 receptors, as CBD has negligible activity at these cannabinoid receptors, although certain activity at the CB2 receptor has been documented in specific pathological conditions (i.e. damage of immature brain). Within the endocannabinoid system, CBD has been shown to have an inhibitory effect on the inactivation of endocannabinoids (i.e. inhibition of FAAH enzyme), thereby enhancing the action of these endogenous molecules on cannabinoid receptors, which is also noted in certain pathological conditions. CBD acts not only through the endocannabinoid system, but also causes direct or indirect activation of metabotropic receptors for serotonin or adenosine, and can target nuclear receptors of the PPAR family and also ion channels.

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