Cited by 984Cannabis and Cannabinoid ResearchNeuroscience and Neuropharmacology ResearchPain Mechanisms and Treatments

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Cannabinoids and the expanded endocannabinoid system in neurological disorders

Cristino, Luigia, Bisogno, Tiziana, Di Marzo, Vincenzo·2020·Nature Reviews Neurology

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Abstract

Anecdotal evidence that cannabis preparations have medical benefits together with the discovery of the psychotropic plant cannabinoid Δ 9-tetrahydrocannabinol (THC) initiated efforts to develop cannabinoid-based therapeutics. These efforts have been marked by disappointment, especially in relation to the unwanted central effects that result from activation of cannabinoid receptor 1 (CB1), which have limited the therapeutic use of drugs that activate or inactivate this receptor. The discovery of CB2 and of endogenous cannabinoid receptor ligands (endocannabinoids) raised new possibilities for safe targeting of this endocannabinoid system. However, clinical success has been limited, complicated by the discovery of an expanded endocannabinoid system - known as the endocannabinoidome - that includes several mediators that are biochemically related to the endocannabinoids, and their receptors and metabolic enzymes. The approvals of nabiximols, a mixture of THC and the non-psychotropic cannabinoid cannabidiol, for the treatment of spasticity and neuropathic pain in multiple sclerosis, and of purified botanical cannabidiol for the treatment of otherwise untreatable forms of paediatric epilepsy, have brought the therapeutic use of cannabinoids and endocannabinoids in neurological diseases into the limelight. In this Review, we provide an overview of the endocannabinoid system and the endocannabinoidome before discussing their involvement in and clinical relevance to a variety of neurological disorders, including Parkinson disease, Alzheimer disease, Huntington disease, multiple sclerosis, amyotrophic lateral sclerosis, traumatic brain injury, stroke, epilepsy and glioblastoma.

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Authors: Cristino, L., Bisogno, T., & Di Marzo, V.
Affiliations: Istituto di Chimica Biomolecolare (IT)
Istituto di Farmacologia Traslazionale (IT)
ORCID: Cristino, Luigia
Bisogno, Tiziana
Di Marzo, Vincenzo
Venue: Nature Reviews Neurology
Publisher: Springer Science and Business Media LLC
Published: 2019-12-12
Volume: 16
Issue: 1
Pages: 9-29
ISSN: 1759-4758 (ISSN-L)
1759-4766
DOI: 10.1038/s41582-019-0284-z
OpenAlex: W2996080671
Cited by: 970
References: 351
Citations by year: 2026: 79 · 2025: 126 · 2024: 173 · 2023: 185 · 2022: 183 · 2021: 142 · 2020: 82
FWCI: 13.33
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Nature Reviews Neurology (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Pharmacology (medical) › Cannabis and Cannabinoid Research
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
Keywords: cannabinoids, endocannabinoid system, endocannabinoidome, neurological disorders, CB1 receptor, CB2 receptor, nabiximols, cannabidiol, THC, multiple sclerosis, spasticity, neuropathic pain, pediatric epilepsy, Parkinson's disease, Alzheimer's disease, Huntington's disease, amyotrophic lateral sclerosis, traumatic brain injury, stroke, glioblastoma
MeSH terms: Analgesics, Animals, Cannabidiol, Cannabinoids, Drug Combinations, Humans, Nervous System Diseases, Dronabinol, Receptor, Cannabinoid, CB1, Receptor, Cannabinoid, CB2, Endocannabinoids

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Cannabinoids and the expanded endocannabinoid system in neurological disorders

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