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Updated: Nov 9, 2025
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
The cannabinoid system and microglia in health and disease
Samuel S Duffy1, Jessica P Hayes1, Nathan T Fiore1
1Translational Neuroscience Facility, School of Medical Sciences, University of New South Wales, UNSW Sydney, NSW, 2052, Australia.
Abstract:
Recent years have yielded significant advances in our understanding of microglia, the immune cells of the central nervous system (CNS). Microglia are key players in CNS development, immune surveillance, and the maintenance of proper neuronal function throughout life. In the healthy brain, homeostatic microglia have a unique molecular signature. In neurological diseases, microglia become activated and adopt distinct transcriptomic signatures, including disease-associated microglia (DAM) implicated in neurodegenerative disorders. Homeostatic microglia synthesise the endogenous cannabinoids 2-arachidonoylglycerol and anandamide and express the cannabinoid receptors CB1 and CB2 at constitutively low levels. Upon activation, microglia significantly increase their synthesis of endocannabinoids and upregulate their expression of CB2 receptors, which promote a protective microglial phenotype by enhancing their production of neuroprotective factors and reducing their production of pro-inflammatory factors. Here, we summarise the effects of the microglial cannabinoid system in the CNS demyelinating disease multiple sclerosis, the neurodegenerative diseases Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis, chronic inflammatory and neuropathic pain, and psychiatric disorders including depression, anxiety and schizophrenia. We discuss the therapeutic potential of cannabinoids in regulating microglial activity and highlight the need to further investigate their specific microglia-dependent immunomodulatory effects.
Insights
Microglia, the brain's immune cells, utilize the cannabinoid system to protect the central nervous system (CNS). Activating this system may offer therapeutic benefits for various neurological and psychiatric disorders.
Area of Science:
- Neuroimmunology
- Neuropharmacology
- Cellular Neuroscience
Background:
- Microglia are the primary immune cells of the central nervous system (CNS), crucial for development, immune surveillance, and neuronal health.
- In neurological diseases, microglia transition from a homeostatic state to an activated phenotype, such as disease-associated microglia (DAM).
- Microglia synthesize endocannabinoids and express cannabinoid receptors (CB1 and CB2), which are modulated during activation.
Purpose of the Study:
- To review the role of the microglial cannabinoid system in various CNS disorders.
- To explore the therapeutic potential of cannabinoids in modulating microglial activity.
- To highlight the immunomodulatory effects of cannabinoids on microglia.
Main Methods:
- Literature review and synthesis of existing research on microglia and the endocannabinoid system.
- Analysis of microglial transcriptomic signatures in health and disease.
- Examination of cannabinoid receptor expression and endocannabinoid synthesis in activated microglia.
Main Results:
- Activated microglia upregulate endocannabinoid synthesis and CB2 receptor expression, promoting a neuroprotective phenotype.
- The microglial cannabinoid system is implicated in multiple sclerosis, Alzheimer's disease, Parkinson's disease, ALS, chronic pain, depression, anxiety, and schizophrenia.
- Cannabinoid receptor 2 (CB2) activation enhances neuroprotective factor production and reduces pro-inflammatory factors in microglia.
Conclusions:
- The microglial cannabinoid system represents a promising therapeutic target for a range of neurological and psychiatric conditions.
- Modulating microglial activity via cannabinoids could offer novel treatment strategies for CNS disorders.
- Further research is needed to elucidate the specific microglia-dependent immunomodulatory effects of cannabinoids.
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