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

Javier Fernandez-Ruiz*, Onintza Sagredo, M. Ruth Pazos, Concepcion Garcia, Roger Pertwee, Raphael Mechoulam, Jose Martinez-Orgado

*Corresponding author for this work

Research output: Contribution to journalArticle

148 Citations (Scopus)

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 ?9-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 ?9-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.

Original languageEnglish
Pages (from-to)323-333
Number of pages11
JournalBritish Journal of Clinical Pharmacology
Volume75
Issue number2
Early online date10 Jan 2013
DOIs
Publication statusPublished - Feb 2013

Keywords

  • cannabidiol
  • cannabinoid signalling system
  • Huntington's disease
  • neonatal ischaemia
  • neuroprotection
  • Parkinson's disease

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